"\n\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2015 Jul Vol 34\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. 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This category offers a means for rapid \ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation. \nThis category provides rapid publications and is meant to be a \nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in the \narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods , Results, Comment and \nReferences. A Structured Abstract of not more than 240 words \nmust be included. It should consist of four paragraphs, labelled \nBackground, Methods, Results, and Conclusions. It should \ndescribe the problem studies, how the study was performed, \nthe main results, and what the author(s) concluded from the \nresults. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and \nsummarizes the existing knowledge in a particular field. \nIt should not be an exhaustive review of the literature, and \nreferences should not exceed 100 in number. Tables, diagrams, \nand selected figures are often helpful. The length is left to the \njudgment of the author, although it generally should not exceed \n5000 words. Topics may include updates in clinically relevant \nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author who \nwill be responsible for reading the proofs must also be given on \nthe title page. The author(s) must also declare any affiliation or \nsignificant financial involvement in any organizations or entity \nwith a direct financial interest in the subject matter or materials \ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in \nthe manuscript. References from journals should include: (1) \nname(s) followed by the initials of the author(s), up to four \nauthors: if more than four authors, include the first three authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; (5) \nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A \nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) referred \nto. \n\n\n\nFor example: \nFoong HBB.  Transcontinental Dermatology: Virtual Grand \nRounds. In: Wootton R and Oakley A, editors. Teledermatology. \nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on \nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\nNotice to Authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY \n\n\n\n ORIGINAL ARTICLE\n2 Epidemiology and clinical features of \n paediatric patients with psoriasis in \n Malaysia: Evidence from the Malaysian \n psoriasis registry (2007-2012)\n Azura MA, Fatimah AA, Asmah J, Roshidah B\n\n\n\n QUIZ\n17 Multiple vesicular-like papules and plaques\n Yap FBB\n\n\n\n CASE REPORT\n11 Adherence to acne medication and its original \n relation to acne severity and quality of life\n Tan CL, Yang SS, Toh MPH, Aw DC\n\n\n\n20 Epidermodysplasia verruciformis in a pair\n of siblings\n Ling HN, Tagal JM, Lee BR, Leong KF\n\n\n\n23 Verrucous haemangioma in a 10-year-old \n girl\n         Lee S, Mohd Shariman MS, Teoh TZ,\n Choon SE\n\n\n\n26 Hypohydrotic ectodermal dysplasia: \n A case series\n Visuvanathan VV, Najeeb AMS\n\n\n\n29 Gorlin syndrome: A case report with \n clinical and radiological correlation\n Azura MA, Izzaty D\n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1MJD 2015 Jul Vol 34\n\n\n\nEditor-in-Chief \nAssociate Professor Dr Felix Yap Boon Bin \nMRCP Adv MDerm\nUniversiti Tunku Abdul Rahman\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCPI\nKuala Lumpur\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP\nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed, Penang\n\n\n\nDr Ng Ting Guan MRCP AdvMDerm\nKlang, Selangor\n\n\n\nDr Adawiyah Jamil MMed AdvMDerm\nKuala Lumpur\n\n\n\nDr Tang Jyh Jong MRCP AdvMDerm\nIpoh, Perak\n\n\n\nDr Tarita Taib AdvMDerm\nSelayang, Selangor\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nExecutive Staff\nHenry Foong Boon Bee, FRCP - President\nNajeed Ahmad Safdar, MRCP - Past President\nAgnes Heng Yoke Hui, MRCP - Vice President\nRohna Ridzwan, MRCP - Secretary\nNoor Zalmy Azizan, AdvMDerm - Treasurer\nChan Lee Chin, MMed\nKhor Guat Ee, MRCP\nSabeera Begum, MMed\nTan Wooi Chiang, AdvMDerm\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2014 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 MJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nEPIDEMIOLOGY AND CLINICAL FEATURES OF PAEDIATRIC \nPATIENTS WITH PSORIASIS IN MALAYSIA: EVIDENCE FROM \nTHE MALAYSIAN PSORIASIS REGISTRY (2007-2012)\nAzura MA1, Fatimah AA1, Asmah J1, Roshidah B2\n\n\n\nAbstract\n\n\n\nBackground: Psoriasis is a common dermatological condition affecting both adults and children. It \ncauses significant physical and psychological burden on patients and adversely affect their quality of \nlife.\n\n\n\nAim: To evaluate the clinical characteristics of paediatric patients with psoriasis in Malaysia.\n\n\n\nMaterials & Methods: Data were obtained from the Malaysian Psoriasis Registry (MPR). All paediatric \npatients aged <18 years notified to the registry from July 2007 to December 2012 were included in \nthis study.\n\n\n\nResults: A total of 677 patients were notified from 18 participating centres. There was a slight female \npreponderance (ratio 1.3:1). Malay accounted for 70.6%, followed by Chinese (8.9%), Indian (12.3%) \nand others (8.1%). Mean age of onset was 9.8 \u00b1 4.4 years. Positive family history was noted in 19.1%. \nPlaque psoriasis was the commonest type of psoriasis (79.6%), followed by guttate psoriasis (7.4%), \npustular psoriasis (1.6%), erythrodermic (1.2%) and flexural psoriasis (1.2%). Psoriatic arthropathy \nwas reported in only 2.2% of patients. Nail involvement is common, affecting 38.1%. Pitting was the \ncommonest (89.9%). Topical treatment remains the most popular choice of treatment and was given \nin 95.1% of our patients. Topical steroid was the commonest prescribed (81.4%), followed by tar \npreparations (78.7%) and emollients (51.6%). Only 1.2% of our patients received phototherapy. Of \nthe patients who had phototherapy, narrowband UVB (NBUVB) was the commonest used (87.5%). \nSystemic therapy was given in 5.3% of paediatric patients. The most frequently used systemic therapy \nwas methotrexate (50%) and acitretin (27.8%). The mean CDLQI score for paediatric patients with \npsoriasis was 7.7 \u00b1 5.5. \n\n\n\nConclusion: Data from the Malaysian Psoriasis Registry highlights the clinical features of paediatric \npatients with psoriasis in Malaysia. We hope to get more participation from other centres in the future, \nespecially from private sectors, so that our results can represent the Malaysian data more accurately.\n\n\n\nKeywords: psoriasis, paediatric, epidemiology\n\n\n\nCorresponding Author and Reprint Request \nDr Azura Mohd Affandi, MBChB (UK), MRCP (UK), \nAdv M Derm (UKM)\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586 Kuala Lumpur, Malaysia \nEmail: affandi_azura@yahoo.co.uk\n\n\n\n1 Department of Dermatology, Hospital Kuala Lumpur\n2 Department of Dermatology, Hospital Melaka\n\n\n\nIntroduction\nPsoriasis is a genetically determined chronic \ninflammatory disorder affecting the skin, nails \nand joints. It is characterized by well demarcated, \nerythematous, scaly plaques. It is common, affecting \n1 - 3% of the general population and can affect both \nadult and children.1 Both genetic and environmental \nfactors play an important role in triggering psoriasis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2015 Jul Vol 34\n\n\n\nLittle information is available on the prevalence \nof psoriasis in children. Previous studies found \nprevalence estimates of paediatric psoriasis ranging \nfrom 0.5% to 1.4%.2 Onset during the first 2 decades \nof life is reported in 31% to 45% of affected adults.3 \nAlthough a recent study suggested that childhood \nonset of psoriasis is not associated with disease \nseverity, early onset may result in longer exposure \nto a chronic inflammatory condition and, thus, may \naffect the morbidity and mortality risk.4 It carries \na significant physical and psychological burden on \npatients and adversely affect their quality of life.\n\n\n\nThus, we aim to evaluate the clinical characteristics \nof paediatric patients with psoriasis in Malaysia.\n\n\n\nMethology\nThis was a multicenter study involving 18 \ndermatology out-patient clinics participating in the \nMalaysian Psoriasis Registry (MPR). The MPR is a \nprospective, ongoing, systematic collection of data \non patients with psoriasis in Malaysia. Confirmation \nof diagnosis by histopathologic examination is \noptional. All paediatric patients aged <18 years \nnotified to the registry from July 2007 to December \n2012 were included in this study.\n\n\n\nData were collected on the patient\u2019s first visit and \nevery 6 months during follow-up visits. The impact \nof psoriasis on the quality of life of paediatric patients \nwas determined by using the 10-item Children\u2019s \nDermatology Life Quality Index (CDLQI). This \nCDLQI was designed for the paediatric patients from \nage 5 to 16 years old. Patients above the age of 16 \nwere assessed using the Dermatology Life Quality \nIndex (DLQI). The CDLQI contains 10 questions \nwhich measure how much the skin problem has \naffected the patients\u2019 life over the last week. Each \nquestion has five possible answers (very much, a lot, \na little, not at all or not relevant) with scores of 3, 2, \n1 or 0 respectively. The total score ranges between 0 \nand 30. A score of 0-1 means no effect on QoL, 2-5 \nsmall effect, 6-10 moderate effect, 11-20 very large \neffect and 21-30 extremely large effect.\n\n\n\nCollected data was tabulated using SPSS. \nCategorical data was presented as number and \npercentages whereas continuous data was presented \nas mean and standard deviation. \n\n\n\nResults\n\n\n\nClinical Features\nThere were a total of 677 paediatric patients notified \nto the registry between July 2007 and December \n2012. Hospital Tengku Ampuan Rahimah, Klang \nnotified the highest number of paediatric patients, \nfollowed by Hospital Sultanah Bahiyah and Hospital \nKuala Lumpur (Table 1). Majority of the paediatric \npatients (83.5%) were new cases and 16.5% were \nfollow-up cases. All patients were Malaysians. \nMalay accounted for 70.6% of the patients, followed \nby Indian (12.3%), Chinese (8.9%) and other ethnic \ngroups (8.1%). Slightly more than half of the \npatients were female (56.9%). There was a slight \nfemale preponderance, with male-to-female ratio of \n1:1.3.\n\n\n\nPsoriasis may first appear at any age. The mean \nage of onset in our cohort of patients was 9.8 \u00b1 \n4.4 years. Figure 1 illustrates the onset of psoriasis \naccording to different age groups. The mean age at \nwhich psoriasis was first diagnosed by clinician was \n11.2 \u00b1 4.3 years. Psoriasis is a skin disorder with \na polygenic mode of inheritance. In our registry, \nabout one-fifth (19.1%) of patients had at least \none family member with psoriasis. Of those with \na positive family history, 34.9% had either parents \naffected and 16.3% had positive family history in \ntheir siblings.\n\n\n\nAt least one or multiple factors caused aggravation \nof psoriasis in 38.1% of paediatric patients with \npsoriasis. Stress was the commonest aggravating \nfactor (57.0%), followed by sunlight (45.0%), \ninfection (20.5%) and trauma (9.3%). Drugs \naggravating psoriasis were less common and \nreported in only 1.2% of the patients. Analyzing the \nsubgroup of patients who reported infection as an \naggravating factor, upper respiratory tract infection \n(66.7%) appeared to be the commonest infective \ntrigger. Patients with psoriasis can have a number \nof other concomitant diseases and co-morbidities. \nIn children and adolescents aged below 18 years \nwith psoriasis, the most prevalent comorbidity was \noverweight or obesity (BMI \u2265 85th centile), in 27.0 \n% of patients. Other comorbid conditions were less \ncommon.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 MJD 2015 Jul Vol 34\n\n\n\nTable 1. Number of paediatric patients with psoriasis notified from each participating centres.\n\n\n\nFigure 1. Age of onset of paediatric patients with psoriasis. Figure 2.  Age of onset of paediatric patients with psoriasis.\n\n\n\nNo \n\n\n\n1 Hospital  Tengku Ampuan Rahimah \n\n\n\n2 Hospital Sultanah Bahiyah\n\n\n\n3 Hospital Kuala Lumpur\n\n\n\n4 Hospital  Tengku  Ampuan  Afzan\n\n\n\n5 Hospital  Umum  Sarawak\n\n\n\n6 Hospital Queen Elizabeth\n\n\n\n7 Hospital Melaka\n\n\n\n8 Hospital Raja Permaisuri Bainun\n\n\n\n9 Hospital Pulau Pinang\n\n\n\n10 Hospital  Sultanah  Fatimah\n\n\n\n11 Hospital  Sultanah  Aminah\n\n\n\n12 Hospital  Tuanku  Fauziah\n\n\n\n13 Hospital  Tuanku  Jaafar\n\n\n\n14 Hospital  Sungai  Buloh \n\n\n\n15 Gleneagles Medical Centre \n\n\n\n16 UM Medical Centre\n\n\n\n17 UKM Medical Centre \n\n\n\n18 Hospital Raja Perempuan Zainab II\n\n\n\nTOTAL\n\n\n\n2007\n\n\n\n0\n\n\n\n9\n\n\n\n10\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n4\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n31\n\n\n\nNo. of paediatric patients notified\n\n\n\n2009\n\n\n\n18\n\n\n\n15\n\n\n\n17\n\n\n\n10\n\n\n\n12\n\n\n\n17\n\n\n\n6\n\n\n\n11\n\n\n\n13\n\n\n\n0\n\n\n\n10\n\n\n\n4\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n134\n\n\n\n2011\n\n\n\n17\n\n\n\n10\n\n\n\n9\n\n\n\n20\n\n\n\n7\n\n\n\n8\n\n\n\n19\n\n\n\n5\n\n\n\n4\n\n\n\n7\n\n\n\n4\n\n\n\n5\n\n\n\n8\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n125\n\n\n\n2008\n\n\n\n10\n\n\n\n30\n\n\n\n21\n\n\n\n4\n\n\n\n15\n\n\n\n8\n\n\n\n0\n\n\n\n3\n\n\n\n8\n\n\n\n6\n\n\n\n2\n\n\n\n8\n\n\n\n5\n\n\n\n5\n\n\n\n4\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n129\n\n\n\n2010\n\n\n\n34\n\n\n\n11\n\n\n\n11\n\n\n\n14\n\n\n\n9\n\n\n\n12\n\n\n\n14\n\n\n\n2\n\n\n\n6\n\n\n\n3\n\n\n\n5\n\n\n\n7\n\n\n\n6\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n135\n\n\n\n2012\n\n\n\n10\n\n\n\n9\n\n\n\n13\n\n\n\n17\n\n\n\n17\n\n\n\n9\n\n\n\n13\n\n\n\n12\n\n\n\n0\n\n\n\n12\n\n\n\n7\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n123\n\n\n\nTotal\n\n\n\n89\n\n\n\n84\n\n\n\n81\n\n\n\n65\n\n\n\n61\n\n\n\n55\n\n\n\n52\n\n\n\n37\n\n\n\n31\n\n\n\n30\n\n\n\n28\n\n\n\n28\n\n\n\n19\n\n\n\n9\n\n\n\n4\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n677\n\n\n\nAge\n\n\n\n350\n300\n250\n200\n150\n100\n\n\n\n50\n0\n\n\n\n0-5 6-10 11-15 above15\n\n\n\nNo\n. o\n\n\n\nf p\nat\n\n\n\nie\nnt\n\n\n\nPlague\n\n\n\nGuttate\n\n\n\nPustular\n\n\n\nReythrodermic\n\n\n\nFlexural/inverse\n\n\n\nPalmoplantar \nnon-pustular\n\n\n\n0% 7% 2%1%\n1%\n2%\n\n\n\n7%\n\n\n\n80%\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2015 Jul Vol 34\n\n\n\nFigure 3. Nail changes in paediatric patients with psoriasis\n\n\n\nFigure 4.  Types of topical therapy used in paediatric patients with psoriasis\n\n\n\nPlaque psoriasis was the commonest type of psoriasis \nand accounted for 79.6% of patients, followed \nby guttate psoriasis in 7.4% of patients, pustular \npsoriasis in 1.6% of the patients, erythrodermic \npsoriasis and flexural psoriasis in 1.2% each. \nOther types of psoriasis were less common (Figure \n2). Majority of our patients had mild to moderate \nbody surface area involvement, with 34.3% of our \npatients having <5% Body Surface Area (BSA) \naffected, and 30.3% had 5-10% of BSA affected. \nSevere psoriasis with >10% BSA affected occurred \nin 11.7% patients, while 0.6% had erythrodermic \npsoriasis, with >90% BSA involved. A composite \nclinical scoring system was used to evaluate the \nseverity of psoriatic lesions in five body regions. \nA score of 0 to 3 was given for each body region \naccording to the degree of erythema, thickness and \nscaliness of the skin lesions. The total clinical score \nmay range from 0 to 15. Analysis on the severity \nof psoriasis in our patients noted that most of the \nmoderate to severe lesions (score 2 and 3) were seen \nmainly on the scalp region (36.5%), followed by the \ntrunk (24.2%). Almost half (47.3%) of the patients \n\n\n\ndid not have any lesion on the face and neck. If \npresent, lesions on face and neck were generally \nless severe (score 1 or 2).\n\n\n\nNail involvement is common in psoriasis, and was \nseen in 258 (38.1%) of our patients. Among patients \nwho had psoriatic nail disease, the commonest \nwas pitting (89.9%). Other common features were \nonycholysis (29.1%) and nail discoloration (15.1%). \nSubungual hyperkeratosis and total nail dystrophy \nwere not common and only noted in 3.5% and 1.9% \npatients respectively (Figure 3).\n\n\n\nPsoriatic arthropathy was reported in only 15 (2.2%) \nof our patients. The commonest psoriatic arthropathy \nwas oligo/monoarthropathy (6 patients) followed \nby distal hand joints arthropathy (4 patients) and \nrheumatoid-like symmetrical polyarthropathy (3 \npatients). Morning stiffness of > 30 minutes was \nreported in 13.3% of the patients. Most of the \npatients with psoriatic arthropathy experienced joint \npain at time of presentation (93.3%). Joint swelling \nand joint deformity were present in only 1 patient.\n\n\n\n250\n\n\n\n200\n\n\n\n150\n\n\n\n100\n\n\n\n50\n\n\n\n0\nPitting Onycholyis Discoloration Subungual\n\n\n\nhyperkeratosis\nTotal nail\ndystrophy\n\n\n\nNo\n. o\n\n\n\nf p\nat\n\n\n\nie\nnt\n\n\n\nNail features\n\n\n\n600\n\n\n\n500\n\n\n\n400\n\n\n\n300\n\n\n\n200\n\n\n\n100\n\n\n\n0\nTopical \nsteroids\n\n\n\nTar preparation Emollient Keratolytics Calcipotriol Dithranol\n(anthralin)\n\n\n\nCalcipotriol with\nbetamethasone\n\n\n\ndipropionate\n\n\n\nNo\n. o\n\n\n\nf p\nat\n\n\n\nie\nnt\n\n\n\nTypes of topical therapy\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 MJD 2015 Jul Vol 34\n\n\n\nTreatment\nMajority of the patients (95.1%) were on topical \ntreatment. Topical steroid was the commonest \ntreatment prescribed (81.4%), closely followed \nby tar preparations (78.7%). Both emollients and \nkeratolytics were prescribed in 51.6% and vitamin \nD analogue, such as calcipotriol were prescribed in \n25.9% of patients. Calcipotriol with betamethasone \ndipropionate and dithranol were least favoured and \nused in 3.1% and 1.9% % of patients, respectively \n(Figure 4). In the last six months prior to notification, \n1.2% of paediatric patients received phototherapy. \nOf the patients who had phototherapy, 87.5% had \nnarrowband UVB (NBUVB) and 12.5% had topical \nPUVA.  Systemic therapy was given in 5.3% of \nthe patients. The most frequently used systemic \ntherapy was methotrexate (50%), followed by \nacitretin (27.8%). Systemic corticosteroids were \nused in 8.3% patients. Other systemic agents such \nas suphasalazine, cyclosporine, hydroxyurea and \nbiologics were not prescribed in our paediatric \npatients.\n\n\n\nQuality of life\nPsoriasis can have a major psychological impact on \nthe patients and affect their quality of life. Out of \n677 paediatric patients with psoriasis, 260 patients \nwere investigated for their quality of life assessment \nwith the validated questionnaire, Children\u2019s \nDermatology Life Quality Index (CDLQI). The \nmean CDLQI score for our patients was 7.7 \u00b1 5.5. \nA CDLQI of more than 10, indicating very large or \nextremely large effect on their quality of life (QoL) \n\n\n\nwas reported in 18.4% of patients, and 4.6% of the \npatients had CDLQI of more than 20, reflecting \nextremely large effect on their QoL. On the other \nhand, 11.9% paediatric patients reported no effect at \nall on their QoL (Figure 5).\n\n\n\nDiscussion\nPsoriasis is a common inflammatory skin condition, \naffecting between 1-3% of the population.1 Despite \nbeing so common, there are sparse data regarding \nthe incidence of psoriasis in children. A Turkish \nstudy estimated the prevalence in children as high \nas 3.8%.4 A population case study in Minnesotta, \nUSA found the overall age- and sex adjusted annual \nincidence of pediatric psoriasis to be 40.8 per \n100,000, which was considerably lower than the \nadult incidence of 78.9 per 100,000 population.5-7 \nThere was a slight female preponderance in our \npatients, with male to female ratio of 1:1.3. This \nconcur with other studies which demonstrated a \nhigher incidence of psoriasis in girls compared to \nboys.4,8 However, Tollefson et al found that boys and \ngirls were equally affected during childhood.6\n\n\n\nSeveral prevalence studies have demonstrated that \napproximately one third of patients with psoriasis \ndevelop their symptoms sometime during childhood, \nalthough some of these may not be diagnosed until \nadulthood.9 The mean age of onset of psoriasis in \nour cohort of patients was 9.8 \u00b1 4.4 years. This was \nlower compared to other studies which reported \nmean age of onset of psoriasis between 10.6 - 11 \nyears old.6,8\n\n\n\nFigure 5.  Quality of life in paediatric patients with psoriasis.\n\n\n\nNo effect at all (0-1)\n\n\n\nSmall effect (2-6)\n\n\n\nModerate effect (7-12)\n\n\n\nVery large effect (13-18)\n\n\n\nExtremely large effect (19-30)\n\n\n\ncD\nLQ\n\n\n\nI\n\n\n\n0 4010 5020 60 8030 70 90 100\n\n\n\nNumber of patients\n\n\n\nDermatology Life Quality Index (DLQI) in Children with Psoriasis\nN=260\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2015 Jul Vol 34\n\n\n\nPsoriasis can be aggravated by several factors, \nincluding medications such as antimalarials, \nstress and infections such as streptococcal throat \ninfection.10,11 More than one third of our patients \n(38.1%) reported one or multiple factors aggravating \ntheir psoriasis, in which stress was the commonest, \nfollowed by sunlight and upper respiratory tract \ninfection. Drugs aggravating psoriasis were less \ncommon and reported in only 1.2% of the patients. \nObesity and being overweight has recently been \ndescribed as a risk factor for psoriasis in the adult \npopulation and it is likely that it plays a significant \nrole in children as well.12 Our cohort reported \n27% of the children were obese (BMI at or above \n85th centile). Several prevalence studies have also \ndemonstrated that paediatric patients with psoriasis \nmay be associated with significant comorbidities \nsuch as obesity, diabetes mellitus, hyperlipidemia, \nhypertension, cardiovascular disease, rheumatoid \narthritis and Crohn\u2019s disease.13\n\n\n\nMost of the children in our study have chronic \nplaque psoriasis (79.6%), followed by guttate \npsoriasis (7.4%). Pustular psoriasis was not very \ncommon and was found in only 1.6% of the \npatients. This is in concordance with other studies \nin children which found rates of plaque psoriasis \nin children ranging between 60.6% and 74%.6,8,14 \nScalp and face were the most frequently affected \nsites in paediatric population, followed by extensor \nsurfaces of the knees and elbows, trunk and groin.14 \nGuttate psoriasis is often the next most common \ntype of childhood psoriasis with proportions \n\n\n\nranging from 9.7% to 28.9%, and is often linked \nto an infectious trigger, particularly streptococcal \ninfection.6,8,14 Nail involvement are observed in \nup to 40% of children who have psoriasis.14 Most \ncommon nail changes are pitting, but other types of \nnail involvement such as discoloration, onycholysis, \nsubungual hyperkeratosis and onychodystrophy can \nbe observed. These concur with our results, which \nreported 38.1% of the paediatric patients with nail \ninvolvement, in which pitting was the commonest \n(89.9%). Although psoriatic arthropathy was \nreported in 8 - 20% of paediatric patients with \npsoriasis, our data showed that only 2.2% of our \npatients were affected.15\n\n\n\nPsoriasis in paediatric group is generally mild \nand easy to control, but in a few cases the disease \nmight be challenging.16 It is important to tailor \nthe treatment to reflect the patient\u2019s age, severity \nand location of the condition. In younger patients, \nparental involvement is required for compliance. \nDisease control is a more realistic objective than \nclearance for many children. Topical treatment is the \nmost favoured treatment in children and is usually \nwell tolerated. Our findings showed that topical \ntreatment was the most frequently used agent in \ntreating paediatric patients with psoriasis. Topical \nsteroid was the commonest treatment prescribed \n(81.4%),  followed by tar preparations in 78.7%, \nemollients in 51.6%, keratolytics in 51.6% and \nvitamin D analogue such as calcipotriol in 25.9% \nof the patients. \n\n\n\nFigure 5.  QoL impairment in paediatric patients with psoriasis based on category of DLQI.\n\n\n\nSymptoms &\nfeelings\n\n\n\nLeisure School or\nholidays\n\n\n\nPersonal\nrelationships\n\n\n\nSleep Treatment\n\n\n\nPe\nrc\n\n\n\nen\nta\n\n\n\nge\n\n\n\nCategory od cDLDI\n\n\n\n100%\n90%\n80%\n70%\n60%\n50%\n40%\n30%\n20%\n10%\n0%\n\n\n\nNot at all\nA little\nA lot\nVery much\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 MJD 2015 Jul Vol 34\n\n\n\nIn children, phototherapy is reserved for those with \nsevere widespread plaque or guttate psoriasis that is \nnot responding to topical therapy. There is concern \nabout the long-term effects of repeated courses \nof phototherapy because of photocarcinogenesis \nand photoaging.17 Parents and children should \ntherefore be fully informed of the potential risks. \nThere are also the practical considerations of \nsupervising young children in phototherapy cabins. \nOnly 1.2% of our patients received phototherapy. \nOf the patients who had phototherapy, 87.5% had \nnarrowband UVB (NBUVB) and 12.5% had topical \nPUVA. The low number could be due to under-\nreporting, as the notification to the registry is done \nevery 6 months, and patients would have completed \nthe phototherapy during this period. A systematic \nreview on the efficacy and safety of treatments for \nchildhood psoriasis by de Jager et al. concluded \nthat NBUVB should not be used in toddlers and \ninfants. In adolescents, it should be used carefully, \nespecially if they have fair skin.18\n\n\n\nTreatment with systemic agents, such as \nmethotrexate, acitretin and cyclosporin is usually \nreserved for more severe cases, such as pustular \npsoriasis, erythrodermic psoriasis, psoriatic \narthropathy or extensive plaque psoriasis, refractory \nto other treatment modalities.16,18 Methotrexate \nis an effective treatment option in moderate to \nsevere childhood psoriasis, and is the commonest \nsystemic agent used in our paediatric patients \n(50%). Retinoid is another systemic agent that can \nbe used in severe psoriasis. Retinoid is an effective \ntreatment for pustular and erythrodermic psoriasis. \nHowever, side effects are frequently seen. Acitretin \nis the second commonest systemic agent used in our \npatients and accounted for 27.8% of cases. Other \nsystemic agents such as suphasalazine, cyclosporin, \nhydroxyurea and biologics were not prescribed in \nour patients.\n\n\n\nStudies have shown that psoriasis may affect the \nquality of life of children.19,20 They may be absent \nfrom school due to clinic visits or hospitalization. \nThey may also suffer from embarrassment due to \n\n\n\nthe clinical appearance of the disease. The mean \nCDLQI score for our patients was 7.7. This was \nhigher than other studies which reported a mean \nCDLQI of 5.4-7.5.19,20 18.4% of our patients \nreported a CDLQI of more than 10 indicating very \nlarge or extremely large effect on their quality of \nlife (QoL), and 4.6% of the patients had CDLQI of \nmore than 20, reflecting extremely large effect on \ntheir QoL. The category of CDLQI most affected \nwas \u201csymptoms and feelings\u201d. 39.0% of our patients \nreported that psoriasis affected very much or a lot \nin the \u201csymptoms and feelings\u201d domain. This was \nsimilar to other study which reported itch and pain \nto be the most bothersome symptoms in children.21\n\n\n\nConclusion\nData from the Malaysian Psoriasis Registry reported \na slight female preponderance among paediatric \npatients with psoriasis in Malaysia. Plaque psoriasis \nis the commonest type of psoriasis and only a small \npercentage of the patients had psoriatic arthropathy.  \nTopical therapy, which is safer, with less side effects, \nremains the treatment of choice in our patients. \nIt is important to note the moderate impairment \nin the quality of life in paediatric patients with \npsoriasis. We hope to get more participation from \nother dermatology centres in Malaysia in the future, \nespecially from private sectors, so that our results \ncan represent the Malaysian data more accurately.\n\n\n\nConflict of interest \nThe Malaysian Psoriasis Registry received funding \nfrom the Dermatological Society of Malaysia, \nAbbvie Malaysia and LeoPharma Malaysia.\n\n\n\nAcknowledgement \nWe would like to thank the Director General of \nHealth, Malaysia for permission to publish this \npaper. We would also like to thank the doctors, \nallied health personnel and clerical staff from \nthe participating dermatology centres for their \ncontribution of data to the Malaysian Psoriasis \nRegistry. We also appreciate the support by the \nClinical Research Centre, Malaysia.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9MJD 2015 Jul Vol 34\n\n\n\nReferences\n \n1. Gelfand JM, Weinstein R, Porter SB, et al. Prevalence \n\n\n\nand treatment of psoriasis in the United Kingdom: a \npopulation-based study. Arch Dermatol 2005;141: 1537-\n41. \n\n\n\n2. Augustin M, Glaeske G, Radtke MA, et al. Epidemiology \nand comorbidity of psoriasis in children. Br J Dermatol \n2010; 162: 633-6.\n\n\n\n3. Raychaudhuri SP, Gross J. A comparative study of pediatric \nonset psoriasis with adult onset psoriasis. Pediatr Dermatol \n2000; 17: 174-8.\n\n\n\n4. Wu JJ, Black MH, Smith N, et al. Low prevalence of \npsoriasis among children and adolescents in a large \nmultiethnic cohort in southern California. J Am Acad \nDermatol 2011; 65: 957-64.\n\n\n\n5. Seyhan M, Coskun BK, Saglam H, et al. Psoriasis in \nchildhood and adolescence: evaluation of demographic \nand clinical features. Pediatr Int 2006; 48: 525-30.\n\n\n\n6. Tollefson MM, Crowson CS, McEvoy MT, Kremers HM. \nIncidence of psoriasis in children: A population-based \nstudy. J Am Acad Dermatol. 2010. 62(6): 979-987.\n\n\n\n7. Icen M, Crowson CS, McEvoy MT, et al. Trends in \nincidence of adult-onset psoriasis over three decades: a \npopulation-based study. J Am Acad Dermatol 2009; 60: \n394-401.\n\n\n\n8. Fan X, Xiao FL, Yanq S, et al. Childhood psoriasis: A study \nfrom China. J Eur Acad Dermatol. 2007; 6: 762-765.\n\n\n\n9. Raychaudhuri SP, Gross J. A comparative study of pediatric \nonset psoriasis with adult onset psoriasis. Pediatr Dermatol \n2000; 17: 174-8.\n\n\n\n10. Tsankov N, Angelova I, Kazandjieva J. Drug-induced \npsoriasis: recognition and management. Am J Clin \nDermatol 2000; 1: 159-65.\n\n\n\n11. Picardi A, Mazzotti E, Gaetano P, et al. Stress, social \nsupport, emotional regulation, and exacerbation of diffuse \nplaque psoriasis. Psychosomatics 2005; 46: 556-64.\n\n\n\n12. Murray ML, Bergstresser PR, Adams-Huet B, Cohen JB. \nRelationship of psoriasis severity to obesity using same-\ngender siblings as controls for obesity. Clin Exp Dermatol \n2009; 34: 140-4.\n\n\n\n13. Augustin, M., Glaeske, G., Radtke, MA, et al. Epidemiology \nand comorbidity of psoriasis in children. Br J Dermatol \n2010; 162: 633\u2013636. \n\n\n\n14. Benoit S, Hamm H. Childhood psoriasis. Clin Dermatol \n2007; 25: 555\u2013562.\n\n\n\n15. Southwood TR, Petty RE, Malleson PN, et al. Psoriatic \narthritis in children. Arthritis Rheum 1989;32:1007-13.\n\n\n\n16. Siddha SK and Burden AD. Recognition and treatment \nof psoriasis in children. Paediatrics and Child Health \n2007;17:10:390-394.\n\n\n\n17. Jury CS, McHenry P, Burden AD, et al. Narrowband \nultraviolet B phototherapy in children. Clin Exp Dermatol \n2006; 31: 196\u20139.\n\n\n\n18. de Jager ME, De Jong EG, Van de Kerkhof PC, Seyger \nMMB.  Efficacy and safety of treatments for childhood \npsoriasis: A systematic literature review. J Am Acad \nDermatol 2010; 62: 1013-30.\n\n\n\n19. Oostveen AM, de Jager ME, Van de Kerkhof, et al. The \ninfluence of treatments in daily clinical practice on the \nChildren\u2019s Dermatology Life Quality Index in juvenile \npsoriasis: A longitudinal study from the Child-CAPTURE \npatient registry. Br J Dermatol 2012; 167(1): 145-9.\n\n\n\n20. Lewis-Jones MS, Finlay AY. The Children\u2019s Dermatology \nLife Quality Index (CDLQI): Initial validation and \npractical use. Br J Dermatol 1995; 132: 942-949. \n\n\n\n21. Lin VW. Tough-skinned kids: Identifying psychosocial \neffects of psoriasis and helping pediatric patients and \nfamilies cope. J Pediatr Nursing 2012; 27(5): 563-72.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10 MJD 2015 Jul Vol 34\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1.  It is noted in this study that predominant ethnic group affected is Malay followed by Indian and \nChinese. This likely correspond to the clinic attendance among the participating centres, mostly \ncomprising of Dermatology Clinics in government hospitals. This composition might be different in the \nprivate setting and thus it is crucial to have data from both the public and private settings.\n\n\n\n2. The onset of psoriasis among the Malaysian children is approximately 9.8 years. Thus, it is essential \nfor clinicians to consider psoriasis for older children presenting with skin lesions to their clinics. Finding \ncharacteristics plaques on the extensor surfaces of the limbs, scalp, lower back and umbilicus points to the \ndiagnosis. Although eczema is more common in childhood, psoriasis must always be considered in older \nchildren.\n\n\n\n3. Only a fifth of the children have family history of psoriasis. Hence, clinicians should not rely on this \npointer to diagnose psoriasis in the paediatric population.\n\n\n\n4. Stress is the most common aggravating factor in psoriasis. This is the case not only in children but \nalso in adult. Determining stress level in children especially the younger ones is a challenge. Thus, stress \nas an aggravating factor might only apply for older children and more specifically adolescents.\n\n\n\n5. It is not surprising that this study found overweight children as a comorbidity in psoriasis. Studies \nin South East Asia shows that Malaysia is the most obese country in the region. Thus, it is essential for \nclinicians managing psoriasis to address the issue of obesity as to reduce the cardiovascular risks when \nthese children grow up.\n\n\n\n6. Joint disease is uncommon in children, accounting for 2.2% only. Nevertheless, development of \narthropathy needs to be frequently checked as to treat the disease early to prevent future complications.\n\n\n\n7. Malaysian children with psoriasis have moderate impairment in their quality of life. A CDLQI score \nof 7.7 points that these children are embarrassed and dismayed by their condition. Thus, optimal treatment \nof psoriasis is important to address this quality of life issue.\n\n\n\nYap FBB\nMD MRCP AdvMDerm\nEditor-in-Chief, MJD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11MJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nADHERENCE TO ACNE MEDICATION AND ITS RELATION\nTO ACNE SEVERITY AND QUALITY OF LIFE\nTan CL1, Yang SS1, Toh MPH2,3, Aw DC1 \n\n\n\nAbstract\n\n\n\nBackground: Acne vulgaris is a chronic condition which commonly affects adolescents and exerts a \npsychological burden on its sufferers. Non-adherence to acne treatment is believed to be a major factor \ncontributing to treatment failure. In this study, we characterize the profile of a non-adherent Asian \nacne patient, and evaluate the relationship between treatment adherence and acne severity and quality \nof life.\n\n\n\nMethods: A total of 53 acne patients were recruited from the Dermatology outpatient clinic of National \nUniversity Hospital, Singapore, and followed up over a 3 month period in this prospective observational \nstudy. The Elaboration d\u2019un outil d\u2019evaluation de l\u2019observance (ECOB) adherence assessment tool \nwas used to assess adherence to acne treatment, and acne severity was evaluated using the US Food \nand Drug Administration Center 5-point Acne Severity Score (ASS).  \n\n\n\nResults: Of the 53 study participants, 29 (54.7%) were non-adherent to acne treatment. There was \nno significant difference in gender, educational level or acne severity at time of presentation between \nadherent and non-adherent patients. Adherent patients had a significantly larger improvement in acne \nseverity scores compared to non-adherent patients (change in ASS: -1.33 \u00b1 0.64 vs -0.76 \u00b1 0.83, p = \n0.008), but this did not translate to a significant improvement in quality of life.\n\n\n\nConclusion: Adherence to acne treatment was not associated with demographic characteristics or \nacne severity. Factors contributing to adherence to acne treatment are complex and multi-faceted, and \nindividualized motivation and education of each patient may be the method of choice in encouraging \ntreatment adherence.\n\n\n\nKeywords: SAcne vulgaris, adherence, severity, quality of life, Asia\n\n\n\nCorresponding Author and Reprint Request \nSam Shiyao Yang, MBBS, MRCP (UK)\n6 East Coast Avenue, Singapore 459176\nEmail: samsyyang@gmail.com\n\n\n\n1 Department of General Medicine,\n University Medicine Cluster,\n National University Health System, Singapore\n2 Information Management, Regional Health,\n National Healthcare Group, Singapore\n3 Saw Swee Hock School of Public Health,\n National University of Singapore, Singapore\n\n\n\nIntroduction\nAcne vulgaris is a common skin condition that \nbegins in adolescence and has a far-ranging impact. \nIt affects up to 91% of male and 79% of female \nteenagers.1 Our local data from a community-based \nstudy in 2007 reported a prevalence of 88% (919 \nout of 1045) in teenagers 13 to 19 years of age, with \nacne.2\n\n\n\nThis represents a significant psychological burden \nof acne on society especially in adolescents3, who \nconstitute the largest proportion of patients with \nacne. Whilst at the age of psychosocial development, \ntheir social, vocational and academic functioning \nare further compromised by acne.4 \n\n\n\n\n\n\n\n\nAt the 3-month follow-up visit, demographic data \nand data on social history were collected by means \nof a questionnaire.\n\n\n\nAn adaptation of the Elaboration d\u2019un outil \nd\u2019evaluation de l\u2019observance (ECOB) adherence \nassessment tool was utilized to assess if a patient \nwas adherent or not to the prescribed treatment \nregime over the past 3 months6. Two questions were \nasked on adherence. Firstly, whether the patient \nhad forgotten to take his medications at any time \nduring the treatment period, and secondly, whether \nthe patient ever stopped taking these medications \nbecause he thought it would do more harm than \ngood. If the patient answered \u201cyes\u201d to either of \nthese questions, he would be classified into the non-\nadherent group.\n\n\n\nThe Cardiff Acne Disability Index (Table 2) by \nMotley and Finlay, 1992, was utilized to assess a \npatient\u2019s quality of life.\n\n\n\nFor each of the 5 questions, an answer of (a) was \nawarded 3 points, and an answer of (d) was awarded \n0 points. The responses for each patient were \ntotalled.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 MJD 2015 Jul Vol 34\n\n\n\nThis psychological effect compounds the issue of \nacne treatment adherence3, a universal challenge \nfor dermatologists. In general, clinicians tend to \nbelieve that treatment failure is largely the result \nof non-adherence to treatment, patients failing \nto understand the nature of the condition and the \ntreatment regime, or having unmet expectations5.\n\n\n\nOur study aims to characterize the profile of a \npatient who is non-adherent to acne medications, in \nthe Asian setting. We also aim to determine whether \nadherence to therapy impacts the clinical severity of \nacne, and if it affects quality of life. \n\n\n\nMethodology\nThis was a prospective observational study \nconducted on patients with acne who presented \nto the Dermatology clinic in National University \nHospital Singapore in the period of May 2012 to \nOct 2012 for their first visit. All patients who were \nat least 18 years of age and returned at 3 months for \na follow-up visit were included.\n\n\n\nAcne severity of each patient was evaluated by \na dermatologist using the US Food and Drug \nAdministration Center 5-point Acne Severity Score \n(Table 1) at the first visit and 3-month follow-up \nvisit.\n\n\n\nTable 1. Acne Global Severity Scale (ASS).\n\n\n\nRating\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\nDescription\n\n\n\nNormal, clear skin with no evidence of acne \nvulgaris\n\n\n\nSkin is almost clear. Rare non-inflammatory lesions \npresent, with non-inflamed papules.\n\n\n\nSome non-inflammatory lesions are present, with \nfew inflammatory lesions. Papules and pustules \nonly with no nodulocystic lesions.\n\n\n\nNon-inflammatory lesions predominate, with \nmultiple inflammatory lesions evident. Several to \nmany comedones and papules/pustules, and up to \none small nodulo-cystic lesion.\n\n\n\nInflammatory lesions are more apparent: many \ncomedones and papules/pustules; up to a few \nnodulo-cystic lesions\n\n\n\nHighly inflammatory lesions predominate: variable \nnumber of comedones, many papules/pustules \nnodulo-cystic lesions\n\n\n\nTable 2. Cardiff Acne Disability Index (CADI).\n\n\n\nAs a result of having acne, \nduring the last month \nhave you been aggressive, \nfrustrated or embarrassed?\n\n\n\nDo you think that having \nacne during the last month \ninterfered with your daily \nsocial life, social events \nor relationships with \nmembers of the opposite \nsex?\n\n\n\nDuring the last month, \nhave you avoided public \nchanging facilities or \nwearing swimming \ncostumes because of your \nacne?\n\n\n\nHow would you describe \nyour feelings about the \nappearance of your skin \nover the last month?\n\n\n\nPlease indicate how bad \nyou think your acne is \nnow:\n\n\n\n(a) Very much indeed \n(b) A lot \n(c) A little \n(d) Not at all\n\n\n\n(a) Severely, affecting all \n activities \n(b) Moderately, in most \n activities \n(c) Occasionally or in only \n some activities\n(d) Not at all\n\n\n\n(a) All of the time \n(b) Most of the time\n(c) Occasionally\n(d) Not at all\n\n\n\n(a) Very depressed and \n miserable \n(b) Usually concerned\n(c) Occasionally \n concerned \n(d) Not bothered\n\n\n\n(a) The worst it could \n possibly be \n(b) A major problem \n(c) A minor problem \n(d) Not a problem\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2015 Jul Vol 34\n\n\n\nSignificance testing of proportions was carried \nusing Fisher\u2019s exact test, where a probability (p) of \n<0.05 was considered statistically significant.\n\n\n\nResults\nOf the 110 patients with acne vulgaris identified at \nthe first visit, 75 patients returned for the 3-month \nfollow-up visit. Of these, 53 patients completed the \nquestionnaire.\n\n\n\nPatient characteristics\nDemographic Data \nDemographic data of the study participants \nis summarized in Table 3. Of the 53 study \nparticipants, the mean age was 23.4 years, with \na similar gender ratio. Chinese participants \nformed the majority (84.9%). In terms \nof educational background, 37.7% of the \nparticipants had a tertiary-level education.\n\n\n\nTreatment regime\nA larger proportion of the participants received \ncombinations of oral and topical treatment \n(66%) whilst the rest received either topical \ntreatment or oral treatment alone.\n\n\n\nOf the 46 patients who were on topical \nmedication, slightly less than half (47.8%) were \nprescribed a single agent, whereas the rest were \ngiven two or more agents. For the 40 patients \nwho had oral medications, almost all were \nprescribed a single oral agent (95%).\n\n\n\nPatient adherence\nOf the 53 study participants, 24 (45.3%) were \nadherent to their prescribed acne therapy and 29 \n(54.7%) were non-adherent. Demographic and \ntreatment data of the adherent and non-adherent \ngroups are presented in Table 4.\n\n\n\nNo significant difference in gender, educational \nlevel, smoking status and alcohol intake was \nfound between adherent and non-adherent. \nThere was also no significant association \nbetween treatment regime (oral, topical, or \nboth) and adherence. A higher percentage of \nnon-adherent patients were on combination \n(both topical and oral) therapies as compared to \nadherent patients, however this difference also \ndid not reach significance.\n\n\n\nPatient characteristic\n\n\n\nAge\n\n\n\nGender\n Male\n Female\n\n\n\nEthnicity\n Chinese\n Malay\n Indian\n Eurasian/Other ethnicity\n\n\n\nEducational level\n Tertiary-level\n Junior college/Polytechnic\n GCSE O-level and below\n\n\n\nTreatment route\n Topical only\n Oral only\n Topical and oral \n Topical and oral and chemical peel\n\n\n\nMean (\u00b1 SD)\n\n\n\n23.4 \u00b1 5.7\n\n\n\nNumber (%)\nN = 53\n\n\n\n 24 (45.3)\n 29 (54.7)\n\n\n\n 45 (84.9)\n 1 (1.9)\n 4 (7.5)\n 3 (5.7)\n\n\n\n 2\n 0 (37.7)\n 24 (45.3)\n 9 (17.0)\n\n\n\n 9 (17.0)\n 7 (13.2)\n 35 (66.0)\n 2 (3.8)\n\n\n\nTable 3. Patient demographics and treatment regimens.\n\n\n\nDemographics\n\n\n\nTreatment regime\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 MJD 2015 Jul Vol 34\n\n\n\nPatient characteristic\n\n\n\nGender - Female\n\n\n\nEducational level\n Tertiary\n Junior college/Polytechnic\n GCSE O-level and below\n\n\n\nSmoking status\n Smokers\n Non and Ex-smokers\n\n\n\nAlcohol-drinking status\n Drinkers\n Ex-drinkers and teetotallers         \n\n\n\nTreatment regime\n Topical only\n Oral only\n Topical and oral\n\n\n\nAdherent \npatients (%)\n\n\n\nn = 24\n\n\n\n14 (58.3)\n\n\n\n7 ( 29.2)\n11 (45.8)\n6 (25.0)\n\n\n\n3 (12.5)\n21 (87.5)\n\n\n\n9 (37.5)\n15 (62.5)\n\n\n\n5 (20.8)\n4 (16.7)\n15 (62.5)\n\n\n\nNon-adherent \npatients\nn = 29\n\n\n\n15 (51.7)\n\n\n\n13 (44.8)\n13 (44.8)\n3 (10.4)\n\n\n\n8 (27.6)\n21 (72.4)\n\n\n\n19 (60.5)\n10 (34.5)\n\n\n\n4 (13.8)\n3 (10.3)\n22 (75.9)\n\n\n\np value\n\n\n\n0.78 \n\n\n\n0.60\n\n\n\n0.47\n\n\n\n0.13\n\n\n\n0.64\n\n\n\nTable 4. Comparison of patient characteristics and treatment regimens between adherent and non-adherent patients.\n\n\n\nAcne Severity Score\n\n\n\nInitial Visit \n\n\n\nImprovement of ASS after 3 months\n\n\n\nCADI\n\n\n\nAdherent \npatients (%)\n\n\n\nn = 24\n\n\n\n3.63 \u00b1 0.82\n\n\n\n-1.33 \u00b1 0.64\n\n\n\n6.92 \u00b1 3.19\n\n\n\nNon-adherent \npatients\nn = 29\n\n\n\n3.31 \u00b1 0.85\n\n\n\n-0.76 \u00b1 0.83\n\n\n\n6.62 \u00b1 3.840\n\n\n\np value\n\n\n\n0.18\n\n\n\n0.008\n\n\n\n0.23\n\n\n\nTable 5. Comparison of ASS and CADI scores between adherent and non-adherent patients.\n\n\n\nTable 6. Comparison of ASS and CADI scores.\n\n\n\nCADI\n\n\n\nHigh (6-15) \n\n\n\nLow (0-5)\n\n\n\nClear & Almost Clear\n\n\n\n4 (7.5%)\n\n\n\n4 (7.5%)\n\n\n\nMild to Severe\n\n\n\n30 (56.6%)\n\n\n\n15 (28.3%)\n\n\n\nTotal\n\n\n\n34\n\n\n\n19\n\n\n\nP =0.144\n\n\n\nAcne Severity Score\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2015 Jul Vol 34\n\n\n\nComparison of Acne Severity Scale Scores and \nQuality of Life Scores\nAmongst the 53 participants, we found that there \nwas no correlation between acne severity at the \npoint of presentation and adherence to medication \n(Table 5). This was observed in spite of the fact \nthat improvement of acne severity scores was \nsignificantly better for the adherent patients as \ncompared to the non-adherent ones.\n\n\n\nThere was also no significant difference of the \nCardiff Acne Disability Index between the adherent \nand non-adherent groups (Table 5). This implies \nthat adherence to treatment does not correlate to \nhow much a patient\u2019s quality of life is affected by \nhis skin condition.\n\n\n\nThe 53 participants were subdivided into two \ngroups, based on intensity of CADI (Table 6). Of \nnote, there was lack of correlation between acne \nseverity (ASS) and quality of life (CADI).\n\n\n\nDiscussion\nTreatment for acne is characterized by a period of \nlatency - usually 6 to 8 weeks - until the appearance \nof definite clinical improvement2, which often \nprogresses slowly. The frequency of relapses also \ncontributes to poor adherence. In addition, the \npsychological effects of anger, sadness and social \navoidance is amplified by treatment failure and \nrelapses, which in turn results in a vicious cycle of \ncostlier treatment or high doses of medications. This \nalso leads to frustration and cessation of treatment \n- with the resultant psychological effects of under-\ntreated acne.7 A review on medical adherence \namongst patients with acne by Jones-Caballero et \nal. reported adherence rates of 38% to 57%8.\n\n\n\nOur study reproduces similar low acne treatment \nadherence rates in Singapore as well.\n\n\n\nMany studies on factors associated with poor \nadherence to acne treatment have proposed widely \nvarying factors. These include the use of complex \nregimes, the presence of side-effects, medication \nshelf-life, and preference for oral medications rather \nthan topical applications.7\n\n\n\nWe failed to demonstrate an influence of gender, \nsmoking history, drinking habits, educational level \nand treatment complexity on therapeutic adherence. \nThis is an important reminder to clinicians not to \ncast presumptions on likely adherence to therapy \nmerely based on these factors.\n\n\n\nWe also noted that acne severity at presentation does \nnot predict adherence to treatment. We believe this \nmay be explained by a lack of correlation between \nacne severity and quality of life. This important \nfinding debunks an assumption that many physicians \nwould make - that patients who are more affected by \nacne would naturally be more adherent to medication \nthan someone who is not. Thus, we postulate that \nthe most likely factor that determines adherence to \nacne treatment lies in the specific individual who is \ncorrectly motivated to comply with the treatment \nregime and has the correct expectations of treatment \nefficacy.\n\n\n\nWhilst there is an undeniable need for clinicians \nto provide patients with as simple a regime as their \nacne grade allows, our data also shows that simpler \nregimes do not correlate with increased adherence - \nand is also not the answer to therapeutic adherence.\nTherefore, further elaboration on individualized \neducation regarding acne treatment and the necessity \nof adherence must be emphasized. This may indeed \nbe the most important factor in the management of \nour patients with acne.\n\n\n\nNon-adherent patients should require closer follow-\nups and counseling. Published data of strategies \nto improve acne treatment adherence include text \nmessage reminders, parental reminders, phone \nreminders from physicians and nurses as well as \nskilled counseling of patients during clinic visits.9\n\n\n\nStudy Limitations\nOur study is conducted amongst patients attending \na tertiary care centre and is not reflective of patients \nwho receive treatment in the primary care setting. Its \nlimitations include patient recall bias and a lack of \naccurate objective measurements make assessment \nof adherence difficult. We also did not compare or \nassess how well-informed our patients were in terms \nof knowledge about acne therapy.\n\n\n\nConclusion\nAcne treatment adherence comprises multi-faceted \noverlapping factors, however, the motivation and \neducation of each individual patient is likely to be \nthe most effective method of encouraging treatment \nadherence.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16 MJD 2015 Jul Vol 34\n\n\n\nReferences\n \n1. Lello J, Pearl A, Arroll B et al. Prevalence of acne vulgaris \n\n\n\nin Auckland senior high school students. N Z Med J 1995; \n108:287\u20139.\n\n\n\n2. Tan HH, Tan AW, Barkham T et al. Community-based \nstudy of acne vulgaris in adolescents in Singapore.  Br J \nDermatol 2007; 157:547\u201351.\n\n\n\n3. Fried RG, Wechsler A. Psychological problems in the acne \npatient. Dermatol Ther 2006; 19:237-40.\n\n\n\n4. Motley RJ, Finlay AY. How much disability is caused by \nacne? Clin Exp Dermatol 1989; 14:194\u20138.\n\n\n\n5. Katsambas AD. Why and when the treatment of acne fails. \n\n\n\nWhat to do. Dermatology 1998; 196:158\u201361.\n6. Dr\u00e9no B, Thiboutot D, Gollnick H et al. Large-scale \n\n\n\nworldwide observational study of adherence with acne \ntherapy. Int J Dermatol 2010; 49:448-56.\n\n\n\n7. Lott R, Taylor SL, O\u2019Neill J et al. Medication adherence \namong acne patients: a review. J Cosmet Dermatol 2010; \n9:160-6.\n\n\n\n8. Jones-Caballero M, Pedrosa E, Pe\u00f1as PF. Self-reported \nadherence to treatment and quality of life in mild to \nmoderate acne. Dermatology 2008; 217:309\u201314.\n\n\n\n9. Baldwin HE. Tricks for improving compliance with acne \ntherapy. Dermatol Ther 2006; 19:224-36.\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Non adherence to treatment is common among patients with acne vulgaris. In this study, the non \nadherence rate was noted to be 54.7%. This is especailly common among adolescents who do not consider \nacne as a problem but consulted clinicians as a result of coercion form their caregivers.\n\n\n\n2. The rate of non adherence was higher in patients treated with combination of oral and topical treatment \n(59.5%) compared to those who are on topical (44.4%) and oral (42.9%) alone. This might be attributed \nby a few causes. Non compliance might be due to complicated regimen of oral and topical medications. \nIt might also be due to costlier medications. Alternatively, it might also be due to more severe disease at \nthe outset and slow response to treatment leading to anger, frustration and anxiety.\n\n\n\n3. In this study, it was noted that compliance to treatment leads to objective clinical improvement. \nHowever, this improvement did not translate to improvement in quality of life. Thus, the issue of adherence \nto treatment is not dependent on clinical improvement and severity of acne but it is multifaceted.\n\n\n\n4. The authors concluded that patient\u2019s education might be the single most important factor to ensure \ncompliance to treatment.\n\n\n\nYap FBB\nEditor-in-Chief, MJD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2015 Jul Vol 34\n\n\n\nQUIZ\n\n\n\nMULTIPLE VESICULAR-LIKE PAPULES AND PLAQUES\n\n\n\nQuestions\n1. What is the most likely diagnosis?\n a. Sweet\u2019s syndrome\n b. Subcutaneous fungal infection\n c. Pyoderma gangrenosum\n d. Behcet\u2019s disease\n e. Leukemia cutis\n\n\n\n2. What is the expected histological appearance in \n a classical case?\n a. Dense diffuse neutrophilic infiltrates in the \n  reticular dermis with leukocytoclasia \n b. Leukocytoclastic vasculitis\n c. Non-caesating granulomas in the dermis\n d. Infiltration of the dermis with leukemic \n  cells\n e. Epidermal necrosis and ulceration with \n  dense neutrophilic infiltrates\n\n\n\n3. The causes of this condition includes the \n following except\n a. Myelodysplasia\n b. Multiple myeloma\n c. Yersinia enterocolitica infection\n d. Granulocyte - colony stimulating factors \n  (G-CSF) administration\n e. Trauma\n\n\n\n4. The treatment of this condition includes the \n following except\n a. Corticosteroid\n b. Colchicine\n c. Antifungal\n d. Etanercept\n e. Dapsone\n\n\n\nFigure 1b. Erythematous nodule with erosion on the \ndorsum of the right hand.\n\n\n\nFigure 1a. Vesicular like firm plaque on the left upper \nback. \n\n\n\nA 47 year old Chinese lady presented with multiple \nvesicular-like firm papules and plaques on the \nbody. It first appeared on the left upper back and \nslowly increased in size over 3 weeks period. It \nlater involved the dorsum of the hands, face, neck, \nback and lower limbs. The skin lesions were painful \nand tender but not itchy. During this time she also \nhad fever and feeling unwell for a month. She has \nvisited few general practitioners and given multiple \ncourses of antibiotics without much improvement. \nFull blood count done showed an elevated total \nwhite cell count with predominant neutrophils with \nan elevated erythrocyte sedimentation rate and \nC-reactive protein.\n\n\n\nCorresponding Author and Reprint Request \nDr Felix Yap Boon Bin\nFaculty of Medicine and Health Sciences\nUniversiti Tunku Abdul Rahman, Sungai Long Campus, \nJalan Sungai Long, 43000 Kajang, Selangor DE\nE mail: woodzlamp@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 MJD 2015 Jul Vol 34\n\n\n\nDiscussion\nSweet\u2019s syndrome was first described by Robert Sweet \nin 1964 as an acute febrile neutrophilic dermatosis.1 \nIt is characterized by fever, tender erythematous \nskin lesions, neutrophilia, high serum inflammatory \nmarkers, and diffure mature neutrophils infiltration \nof the dermis.2 Table 1 outline the diagnostic criteria \nfor Sweet\u2019s syndrome.2 Patients must have 2 major \nand 3 minor criteria to fulfil the diagnosis.\n\n\n\nSweet\u2019s syndrome is seen from newborn to elderly \npatients. The mean age of reported cases is around \n50 years. Majority of patients are females with \nno specific racial predilection.2 The syndrome is \ndivided into 4 clinical types ie.\n\n\n\n1. Classical or idiopathic Sweet\u2019s syndrome\n Usually seen in women in their reproductive \n age and associated with infection (upper \n respiratory or gastrointestinal), inflammatory \n bowel disease or pregnancy.2,3,4\n\n\n\n2. Drug induced Sweet\u2019s syndrome\n Many drugs are implicated. The most \n commonly implicated drug is the G-CSF.2,3,4 \n Other implicated drugs include antibiotics, \n anti-epileptics, anti-hypertensives, oral   \n contraceptives and retinoids.\n3. Malignancy associated Sweet\u2019s syndrome\n Seen in 85% of hematologic malignancies, \n most commonly acute myeloblastic leukemia \n (AML) and 15% of solid neoplasia.2,3,4\n\n\n\n4. Neutrophilic dermatosis of the hands\n\n\n\nLocalized form and the most recently described \nmainly in women.2\n\n\n\nPatients with Sweet\u2019s syndrome classically present \nwith fever and characteristic skin lesions. The fever \nusually precedes the skin lesions by several days to \nweeks. Other symptoms include arthralgia, malaise, \nlethargy, headache and myalgia. The skin lesions \nis typically red or purple-red papules or nodules \nthat have a strong tendency to coalesce forming \nirregular plaques.4  These skin lesions are firm but \nhave transparent, vesicle like appearance due to \npronounced upper dermal edema.4 The lesions are \npainful and tender with tendency to enlarge over \nweeks and heal after weeks and months without \nscarring. They are usually seen on the upper limbs, \nface and neck. Cutaneous pathergy might be present. \nOral involvement is uncommon in classical type but \nmore common with Sweet\u2019s syndrome associated \nwith malignancy.4 Extracutaneous manifestations \ncan also be seen and include involvement of the \nbone, central nervous system, eyes, kidneys, liver, \nintestines, muscles, heart and lungs.3,4\n\n\n\nThe pathogenesis of Sweet\u2019s syndrome remains \nelusive. Inappropriate regulation of the cytokines \nleading to hypersensitivity reaction to infection, \ntumour and drugs is the most acceptable hypothesis.3\n\n\n\nThe classic histologic features are dense diffuse \nmature neutrophils infiltrate in the superficial \ndermis and dermal edema. Leukocytoclasia or \nfragmented neutrophil nuclei are common. However, \nleukocytoclastic vasculitis is absent in Sweet\u2019s \nsyndrome. Occasionally, leukemic cells can be seen \nin patients with hematologic malignancies.3,4 There \nis no significant changes in the epidermis but rarely \nthere will be neutrophilic infiltration of the subcutis \nin patients with underlying malignancies.3\n\n\n\nSweet\u2019s syndrome must be differentiated with \nother neutrophilic dermatoses, infections and \ninflammatory dermatoses. Clinically, erythema \nmultiforme and erythema nodosum resemble skin \nlesions of early Sweet\u2019s syndrome. The vesicular \nlike lesions can be confused with herpes simplex \nand zoster. Pyoderma gangrenosum can clinically \nand histologically resembles Sweet\u2019s syndrome. \nHistologically, Sweet\u2019s syndrome needs to be \ndifferentiated from other neutrophilic dermatoses \nlike pyoderma gangrenosum, neutrophilic eccrine \nhidradenitis and granuloma faciale. Leukocytoclastic \nvasculitis must be excluded.\n\n\n\nTable 1. Diagnostic criteria for Sweet\u2019s syndrome.\n\n\n\nMajor Criteria\n\n\n\nMinor criteria\n\n\n\n1. Rapid onset of characteristic skin \n lesions which are tender \n erythematous plaques and nodules\n2. Typical histological features: \n dense neutrophils infiltration \n without leukocytoclastic vasculitis\n\n\n\n1. Fever (> 38\u00baC), history of upper \n respiratory or gastrointestinal \n infection or immunization, the \n history of haematologic or solid \n neoplasia, inflammatory disorder, \n pregnancy, very good response to \n corticosteroids or potassium iodid\n2. ESR > 20mm/h\n3. WBC > 8 X 109/L \n4. Neutrophil > 70%\n5. High CRP\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2015 Jul Vol 34\n\n\n\nReferences\n \n1. Sweet RD. An acute febrile neutrophilic dermatosis. Br J \n\n\n\nDermatol 1964; 74: 349-56.\n2. Paydas S. Sweet\u2019s syndrome: a revisit for haematologists \n\n\n\nand oncologists. Critical Rev Oncol Hematol 2013; 86: 85-\n95.\n\n\n\n3. Cohen PR. Sweet\u2019s syndrome- a comprehensive review of \nan acute febrile neutrophilic dermatosis. Orphanet J Rare \nDis 2007; 34: 1-28.\n\n\n\n4. Cohen PR, Kurzrock R. Sweet\u2019s syndrome: a neutrophilic \ndermatosis classically associated with acute onset and \nfever. Clin Dermatol 2000; 18: 265-82.\n\n\n\n5. Cohen PR, Kurzrock R. Sweet\u2019s syndrome and cancer. Clin \nDermatol 1993; 11: 149-157.\n\n\n\nCorticosteroid is the gold standard treatment.4 \nHigh dose systemic steroid leads to dramatic \nresponse of the fever and skin lesions within \nhours. Other first line treatment includes colchicine \nand potassium iodide.3 Second line treatment \ninclude indomethacin, clofazimine, dapsone and \ncyclosporine. Other medications that can be used \nare thalidomide, cyclophosphamide, antimicrobials, \netretinate, etanercept and infliximab.4\n\n\n\nThe recurrence rate for classical Sweet\u2019s syndrome \nis 30%. Drug induced Sweet\u2019s syndrome has a \nrecurrence rate of 67%, hematologic malignancy \nassociated 69% and solid tumour associated 41%.5\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 MJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nEPIDERMODYSPLASIA VERRUCIFORMIS IN A PAIR\nOF SIBLINGS \nLing HN\u00b9, Tagal JM\u00b2,  Lee BR\u00b3, Leong KF4\n\n\n\nIntroduction\nEpidermodysplasia verruciformis (EV) described \nby Lewandowski & Lutz is a rare genodematosis, \ninherited mostly via autosomal recessive or X-linked. \nIt is characterized by increased susceptibility to \ninfection by specific human papillomavirus (HPV) \ngenotypes. There are more than 20 known EV-HPV \ntypes, including 3, 5, 8, 9, 10, 12, 14, 15, 17, 19-\n25, 28, 29, 36, 46, 47, 49, and 50.\u00b9 Classically, this \nviral infection leads to the development of tinea \nversicolor like macules on the trunk, neck, arms, \nand face during childhood.\u00b2 In EV patients, these \n\n\n\nCorresponding Author and Reprint Request \nDr Ling Hee Ninh, MD MRCP\nDepartment of Dermatology\nSarawak General Hospital, Jalan Hospital,\n93586 Kuching, Sarawak\nEmail: heeninh@yahoo.com.sg\n\n\n\n\u00b9 Department of Dermatology &\n\u00b2 Opthalmology, Sarawak General Hospital,\n Jalan Hospital, 93586 Kuching, Sarawak\n\u00b3 Department of Pathology &\n4 Paediatrics, Hospital Kuala Lumpur, Jalan Pahang, \n 50586 Kuala Lumpur\n\n\n\nHPV types have oncogenic potential, and over time, \n30% to 60% of affected individuals will develop \nsquamous cell carcinoma (SCC).\u00b3 This malignant \ntransformation is a slow process, with malignancies \nfirst appearing on sun exposed skin in the fourth \ndecade of life, usually 20 to 30 years after onset of \nthe disease. The term \u2018\u2019acquired epidermodysplasia \nverruciformis\u2019\u2019 was introduced to describe patients \nwith impaired cell mediated immunity acquiring \nsusceptibility to the EV-HPV types that are \ninnocuous for the general population. Herein, we \nreport a case of a 10 year old boy with acquired EV.\n\n\n\nCase Report\nA 10 years old boy presented with chronic cough & \nasymptomatic widespread truncal hyperpigmented \nand hypopigmented macules with pityriasiform \nscales associated with pedunculated warty lesions \non eyelids and chin for 1 year duration (Figure 1-B1 \nand B2).\n\n\n\nFigure 1. Presence of warty lesions in both siblings before (A1 & B1) and after treatment (A2 & B2).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2015 Jul Vol 34\n\n\n\nImmunology workup showed persistent leucopenia \nwith persistently low T-cells (CD4/CD8) and B \ncells. He was later diagnosed to have primary \nimmunodeficiency, Medellian Susceptibility to \nMycobacterial Disease (MSMD) and bronchiectasis \nsecondary to pulmonary tuberculosis. There was no \nfamily history of consanguinity.\n\n\n\nSimilar cutaneous lesions were seen in his older sister \nwho was his only sibling (Figure 1-A1 and A2), but \nnot in the father. His mother had passed away 8 year \nearlier from colon cancer. Skin biopsies taken from \npatient\u2019s chin and torso confirmed the diagnosis of \nviral wart. Histopathological examination showed \nenlarged cells in the granular and spinous layer with \nbluish gray cytoplasm suggesting HPV) infection. \nAddition features were enlarged keratohyaline \ngranules and koilocytes (Figure 2). HPV typing on \nthe skin biopsy specimens embedded in paraffin \nwere not available in our setting.\n\n\n\nLesions in both siblings were well controlled with \nregular cryotherapy and oral isotretinoin (Figure \n1-A3 and B3). Sunscreen usage and sun avoidance \nwas counseled to avoid malignant transformation. \n\n\n\nDiscussion\nIn EV patients, HPV infections have oncogenic \npotential. This malignant transformation is a slow \nprocess, with malignancies first appearing on sun \nexposed skin in the fourth decade of life, usually \n20 to 30 years after onset of the disease. In EV, \nHPV infections is necessary but not sufficient for \nmalignant transformation. Ultraviolet radiation \n(UVR) plays an important role in the induction of \nSCC in EV patients. The majority of skin cancers \nin EV patients develop on sun-exposed sites. The \noncogenic nature of EV-HPV and how it works \n\n\n\nsynergistically with UVR to induce carcinogenesis \nremain unclear. However, it is well known that UVR, \nspecifically UVB, damages keratinocyte DNA \nand suppresses the skin\u2019s immune system. UVB-\nspecific mutations in the p53 tumor suppressor \ngene, including formation of pyrimidine dimer \nphotoproducts, are seen in the majority of SCC.4\n\n\n\nA wide range of therapies have been tried with \nvariable success in the treatment of congenital \nEV and acquired EV. The treatments of common \nverrucae, including electrodesiccation, cryotherapy, \ntopical retinoids, contact sensitization, imiquimod, \n5-fluorouracil, podophyllotoxin and topical cidofovir \nhave all been found to be ineffective in the treatment \nof the lesions. In a case report of a patient with EV \ntreated with systemic retinoids (etretinate at 1 mg/kg \ndaily for 4 months), there was a temporary decrease \nin the number of lesions\u00b9.The combination of oral \nretinoids (acitretin 50 mg/day) and recombinant \ninterferon alfa-2a (subcutaneously at 3 million units \n3 days/wk), led to improvement in one case of EV \nreported after 9 months of treatment. At 3 months \npost treatment, there was a recurrence of lesions on \nthe hands, but at 1 year the face remained clear.5\n\n\n\nIn our patients, the warts were controlled with \ncombination of isotretinoin and cryotherapy. It must \nalso be stressed that patient education regarding \nphotoprotection and frequent skin surveillance is of \nutmost importance for early cancer detection.\n\n\n\nConclusion \nEV should be included in the differential diagnosis \nof any generalized warty lesions and work up for \ncauses of cell mediated immunodeficiency should \nbe performed in those with no obvious family \nhistory.\n\n\n\nFigure 2. Presence of keratohyaline granules and koilocytes suggesting HPV infection (H & E, magnification X4, X10 and X40).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 MJD 2015 Jul Vol 34\n\n\n\nReferences\n \n1. Lutzer M, Blacnchet-Bardon C, Orth G. Clinical \n\n\n\nobservations, virologic studies, treatment trials in patients \nwith epidermodysplasia  verruciformis, a disease induced \nby specific human papillomaviruses. J Invest Dermatol \n1984; 83: 18-25.\n\n\n\n2. Heather DR, Jennifer LM, Kristin MN, et al. Acquired \nepidermodysplasia verruciformis. J Am Acad Dermatol \n2009; 60: 315-20. \n\n\n\n3. Acquired epidermodysplasia verruciformis associated \nwith transplant related immunosuppression. J Am Acad \nDermatol 2011; 2: 2503\n\n\n\n4. Brash DE, Ponten J. Skin precancer. Cancer Surv 1998; 32: \n69-113.\n\n\n\n5. Anadolu R, Oskay T, Erdem C, et al. Treatment of \nepidermodysplasia verruciformis with a combination of \nacitretin and interferon alfa-2a. J Am Acad Dermatol 2001; \n45: 296-9.\n\n\n\nAcknowledgement \nThe authors would like to thank the Director General \nof Health Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23MJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nVERRUCOUS HAEMANGIOMA IN A 10-YEAR-OLD GIRL\nLee S1, Mohd Shariman MS2, Teoh TZ3, Choon SE3\n\n\n\nIntroduction\nVerrucous haemangioma (VH) is a rare vascular \nanomaly which may be mistaken as infantile \nhaemangioma or angiokeratoma. The characteristic \nclinicopathologic features of VH were first \nelaborated by Imperial and Helwig in 1967.1 \nHowever, its distinctive clinical and histopathologic \nfeatures may not be apparent at initial manifestation \nand only emerges with disease evolution. We \ndescribe a case of VH, which was initially diagnosed \nas infantile haemangioma, to highlight the clinical \nhistopathological features that distinguish it from \nother vascular anomalies.\n\n\n\nCorresponding Author and Reprint Request \nDr. Siew Eng Choon\nDepartment of Dermatology \nHospital Sultanah Aminah Johor Bahru\n80100, Johor, Malaysia\nEmail: choonse@yahoo.co.uk\n\n\n\n1 Medical student, School of Medicine and\n Health Sciences, University of Monash, Victoria, \n Australia\n3  Department of Dermatology and\n2 Pathology, Hospital Sultanah Aminah Johor Bahru,  \n Johor, Malaysia\n\n\n\nCase Report\nA 10-year-old girl presented with multiple purplish-\nred verrucous plaques on her right foot and ankle. \nThese lesions started as erythematous patches at \nbirth on the dorsum of her right foot and gradually \nbecame larger and more warty with new lesions \nappearing and spreading up her right leg. Bleeding \noccurred occasionally with minor trauma. Although \nnot painful, the lesions affected her shoe-wearing.  \nPhysical examination revealed multiple boggy \nswellings ranging from 1cm by 2cm to 5cm by 7 cm \nwith overlying erythematous or verrucous purplish- \nred plaques on the dorsum of her right foot, ankle \nand leg (Figs 1- 2).\n\n\n\nThe lower limbs were equal in length although the \nswelling on the right foot resulted in asymmetry of \nher feet. The rest of her skin was clear. No significant \nlymphadenopathy or organomegaly was detected. A \n4mm-punch biopsy revealed hyperplastic epidermis \nwith hyperkeratosis, papillomatosis and acanthosis \noverlying vascular proliferations in both the dermis \nand subcutaneous fat (Fig. 3a). The papillary dermis \nshowed dilated thin-walled vascular channels lined \nby flat endothelial cells (Fig. 3b). Foci of thick-\nwalled, round capillary-sized vessels lined by single \nlayer of plump protruding endothelial cells were \nconspicuous in the reticular dermis and subcutis \n(Fig. 3c, 3d).\n\n\n\nFigure 2. Boggy mass on lateral malleolus of right leg \nsurmounted by purplish red verrucous plaque.\n\n\n\nFigure 1. Multiple verrucous purplish- red plaques on \nthe dorsum of her right foot, ankle and leg.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24 MJD 2015 Jul Vol 34\n\n\n\nDiscussion\nVH is a rare vascular anomaly that classically \nmanifests at birth as a pinkish macule/patch that \ngrows proportionately with the child.1-4 Unilateral \nlocalization to a lower limb is characteristic \nbut lesions had been reported on other sites. \nNew lesions appear gradually with time. Initial \npinkish lesions evolve into reddish or purplish-red \nverrucous plaques with underlying soft masses. \nThe lesions are often distributed in a linear or \nserpiginous pattern. Bleeding and infection may \nsupervene. VH does not involute spontaneously. \nHistologically, it is characterized by irregular \nacanthosis, papillomatosis and hyperkeratosis \noverlying vascular proliferations in both dermis and \nsubcutis. The vessels in the papillary dermis are \ndiffusely distributed and composed of thin-walled \ndilated blood vessels lined by flat endothelial cells \nwhereas vascular proliferations in the deep dermis \nand subcutis consist of aggregates of round thick-\nwalled vessels with plump endothelial cells and \nmulti-lamellated basement membranes.\n\n\n\nThe nosologic status of VH is still unclear. The \nInternational Society for the Study of Vascular \nAnomalies (ISSVA) classified vascular anomalies \ninto vascular tumours and vascular malformations.5 \n\n\n\nVascular tumours grow by endothelial hyperplasia \nwhereas malformations are due to defects of \nvascular morphogenesis. Vascular tumours may \n\n\n\ninvolute spontaneously or persist depending on \ntheir type but vascular malformations persist for \nlife. Vascular malformations usually present at birth \nand have commensurate growth during childhood. \nIt is important to differentiate vascular tumors from \nmalformations because management is different. \nImmunohistochemical marker Wilms tumor 1 \n(WT1) is useful in distinguishing between vascular \ntumours and malformations, being positive in the \nformer and negative in the latter.6,7\n\n\n\nAlthough, VH behaves like a vascular malformation, \nbeing present at birth, exhibits proportionate \ngrowth without regression, it is WT1-positive.8 \n\n\n\nVH also expresses GLUT1 (Erythrocyte-\ntype glucose transporter protein-1), another \nimmunohistochemical marker, not found in vascular \nmalformations.8 GLUT1 is a marker of infantile \nhaemangioma which distinguishes it from other \nvascular tumours such as congenital haemangioma, \ntufted angioma, pyogenic granuloma and kaposiform \nhemangioendothelioma.8 Hence, ISSVA parked VH \nunder the category of \u201cprovisionally unclassified \nvascular anomalies\u201d. Both WT1 and GLUT1 are not \navailable in our laboratory.\n\n\n\nA close clinicopathologic correlation is essential \nto diagnose VH as its clinical features may mimic \nother vascular anomalies especially angiokeratoma \ncircumscriptum. Like VH, angiokeratoma \n\n\n\nFigure 3. (a) Hyperplastic epidermis with hyperkeratosis, \npapillomatosis and acanthosis overlying vascular proliferations in \nboth the dermis and subcutaneous fat; (b) Dilated thin-walled vascular \nchannels lined by flat endothelial cells in the papillary dermis with \nthicker walled vessels in reticular dermis; (c,d) Clusters of thick-walled, \nround capillary-sized vessels lined by single layer of plump protruding \nendothelial cells in reticular dermis and subcutis. Haemotoxylin and \neosin, original magnification (a) X 2; (b, c, d) X 10\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25MJD 2015 Jul Vol 34\n\n\n\ncircumscriptum usually presents at birth with a \ncluster of small reddish papules which are commonly \nlocated on lower limbs in a segmental distribution. \nWith time, existing papules become more warty \nwhile more papules develop. These papules may \ncoalesce to form a persistent hyperkeratotic vascular \nplaque which resembles verrucous haemangioma \nclinically. Histologically, hyperplastic epidermis \nis also seen in angiokeratoma circumscriptum but \nthe confinement of dilated vessels to the papillary \ndermis distinguishes it from VH which displays \nvascular proliferations in both papillary and deep \ndermis as well as the subcutis. Differentiating VH \nfrom angiokeratoma circumscriptum is important \nbecause angiokeratoma is easily treated with \nelectrocoagulation, cryotherapy or laser whereas \nVH requires deep excision with wide margins and \nfrequently recur due to incomplete excision.2,4,9 \nPrompt diagnosis and complete excision of an \nearly lesion provide a better prognosis.10 Staged \nexcisions may be necessary for multiple lesions.9 \nOther treatment options include cryotherapy, \ncautery, laser therapy and a combination of laser \nwith surgery. Although laser therapy is mainly \npalliative, a recent study showed that laser therapy \nusing carbon dioxide in combination with dual \npulsed dye and ND-YAG lasers may be a viable \ntreatment option. In this study, 7 out of 8 patients \ntreated had at least a 50% improvement in skin \nlesions.11 More importantly, all treated patients \nwere satisfied with the treatment with a satisfaction \nscore (from 1= poor to 10= excellent) of 8 to 10. A \nrecurrence rate of 30% following surgical excision \nhad been documented.9 Recurrence rate is high with \n\n\n\nother treatment modalities but reliable estimates are \nnot available due to paucity of reports. Our patient \nchose to try laser therapy first and was referred to \nKuala Lumpur for the treatment.\n\n\n\nVH may be mistaken as infantile haemangioma \nor port wine stain during its early phase when it \nis still flat and non-keratotic. However, infantile \nhaemangioma is a vascular tumour which presents \non the head and neck, with only 15% reported on the \nextremities.10 Histologically, infantile haemangioma \nresembles early stage of VH and diagnosis is often \nonly made with disease progression.7 Unlike VH \nwhich persists indefinitely, infantile haemangioma \nexhibits an initial rapid growth phase followed \nby involution.2,10 Treatment options for infantile \nhaemangioma include pharmacological treatment, \nlaser therapy and surgery.2,10 Port wine stain is a \ncapillary malformation that presents at birth on \nthe head and neck as pinkish patches and persists \nthroughout life. As it matures, the erythematous \npatches become violaceous and thicker with the \nappearance of angiomatous nodules or vascular \nblebs. In its advanced stage, the vascular plaque \ntends to appear nodular as opposed to verrucous.2 \nHistologically, it is characterized by ectatic vessels \nof variable size in the dermis. Port wine stain is best \ntreated early with pulsed dye laser.2\n\n\n\nIn conclusion, we describe a case of VH, diagnosed \nat 10 years of age, due to unfamiliarity with this \nrare condition. Early diagnosis and treatment is \nimportant to attain a better cosmetic result.\n\n\n\nReferences\n \n1. Imperial R, Helwig EB. Verrucous hemangioma; a \n\n\n\nclinicopathologic study of 21 cases. Arch Dermatol \n1967;96:247-253\n\n\n\n2. Moss C, Shahidullah H. Naevi and other developmental \ndefects. In: Textbook of Dermatology, In: Burns T, \nBreathnach S, Cox N, Griffiths C, editors. 8th ed. Oxford: \nBlackwell Science; 2010 chapter18 p.40-74\n\n\n\n3. Tennant LB, Mulliken JB, Perez-Atayde AR, et al. Verrucous \nhemangioma revisited. Pediatr Dermatol 2006;23:208-215\n\n\n\n4. Clairwood MQ, Bruckner AL, Dadras SS. Verrucous \nhemangioma: a report of two cases and review of the \nliterature. J Cutan Pathol 2011;38: 740-746.\n\n\n\n5. International Society for the Study of Vascular Anomalies. \nISSVA classification for vascular anomalies. http://issva.\norg/content.aspx?page_id=22&club_id=298433&module_\nid=152904 Last accessed March 12, 2015.\n\n\n\n6. Trindade F, Tellechea O, Torrelo A, et al. Wilms tumor \n1 expression in vascular neoplasms and vascular \nmalformation. Am J Dermatopathol 2011; 33: 569\n\n\n\n7. Al Dhaybi R, Powell J, McCuaig C, et al. Differentiation of \nvascular tumors from vascular malformations by expression \nof Wilms tumor 1 gene: evaluation of 126 cases. J Am Acad \nDermatol 2010; 63: 1052\n\n\n\n8. Trindade F, Torrelo A, Requena L, et al. An \nimmunohistochemical study of verrucous hemangiomas. J \nCutan Pathol 2013; 40: 472-476\n\n\n\n9. Mankani MH, Dufresne CR. Verrucous malformation: their \npresentation and management. AnnPlast Surg 2000; 45: 31-\n36\n\n\n\n10. Koc M, Kavala M, Kocat\u00fcrk E, et al. An unusual vascular \ntumor: Verrucous hemangioma. Dermatol Online J 2009; 15 \n(11): 7\n\n\n\n11. Segura Palacios JM, Boixeda P, Rocha J, et al. Laser \ntreatment for verrucous hemangioma. Lasers Med Sci 2012; \n27(3): 681-684\n\n\n\n12. Zimmermann AP, Wiegand S, Werner JA, et al. Propranolol \ntherapy for infantile haemangiomas: review of the literature. \nInt J Paediatr Otorhinolaryngol 2010; 74:338-342\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26 MJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nHYPOHYDROTIC ECTODERMAL DYSPLASIA: A CASE SERIES\nVisuvanathan VV1, Najeeb AMS2\n\n\n\nIntroduction\nThe ectodermal dysplasias (ED) are a rare group of \ninherited disorders characterised by hypohidrosis \n(reduced ability to sweat), hypotrichosis (sparseness \nof hair), hypodontia (decreased tooth development) \nand onychodysplasia (nail abnormalities).1 \nClinically, ectodermal dysplasia can be broadly \nclassified into hypohidrotic ectodermal dysplasia \n(HED) and the hidrotic ectodermal dysplasia.  \nX-linked hypohidrotic ectodermal dysplasia (XL-\nHED), which is also known as Christ-Siemens-\nTouraine, is the most classic subtype. Nguyen-\nNielsen and Skovbo found that in Denmark, the \nprevalence of XL-HED was 21.9 per 100,000 overall \nand 1.6 per 100,000 when restricted to molecularly-\nconfirmed XLHED cases.2 Herein, we report a case \nseries of 3 family members with XL-HED.\n\n\n\nCorresponding Author and Reprint Request \nDr Vaani Valerie Visuvanathan\nInternational Medical University,\nJalan Rasah, 70300 Seremban,\nNegeri Sembilan Darul Khusus, Malaysia.\nEmail: vaani_valerie@imu.edu.my\n\n\n\n1 International Medical University, Jalan Rasah,\n 70300 Seremban\n2 Department of Dermatology, Hospital Tuanku Jaafar, \n Jalan Rasah, 70300 Seremban\n\n\n\nCase Report\n\n\n\nPatient A\nA is a 6-month old child, who presented with perioral \npruritic erythematous, papules for 3 weeks (Figure \n1). His parents had noted that the infant had sparse \nhair and did not sweat even during exceptionally \nwarm weather. Thus far, the child has not had any \nrespiratory illness.\n\n\n\nClinical examination revealed erythematous, scaly, \npapules and macules over the perioral region. The \ninfant was edentulous and had a saddle-shaped nose.\nHe was prescribed a mild topical steroid \n(Clobetasone Butyrate) and emollients, which led \nto minimal residual papules one week later. Dental \nreferral was suggested.\n\n\n\nPatient B\nB, a 21-year-old male, is the younger maternal uncle \nof patient A. He had been noted to have abnormal \ndentition with sparse hair since birth, as illustrated \nin Figure 2. He claims to have minimal sweat but \nno problems with salivation and dry eyes. The \nabnormal dentition did not cause any problems nor \nlimit his diet. Occasionally, he did require water to \naid the swallowing of certain types of food.  He had \nrecurrent pruritic, erythematous papules on his face, \nespecially at the periorbital and perioral region. He \nhad a total of eight teeth, which were all peg-shaped \nwith significant gap between the teeth. He was \nprescribed some mild topical steroids and advised \nto keep cool during warm weather by having cold \nshowers and increasing fluid intake.\n\n\n\nPatient C\nThe elder brother of Patient B, C, has a similar facies \ni.e. depressed nasal bridge, prominent lips, sparse \nhair, oligodontia with increased gaps between the \nteeth. He has minimal sweat but denied dry eyes or \nfrequent respiratory illness as a child. He had been \nseen by a dentist who suggested dentures, but he is \nnot keen to wear them. He had no signs of eczema \nnor hyperpigmentation.\n\n\n\nFigure 1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27MJD 2015 Jul Vol 34\n\n\n\nFigure 3. Saddle nose, sparse hair, loss of \neyebrow, oligodontia and peg shaped teeth.\n\n\n\nFigure 2. Sparse hair and eyebrow, saddle nose, \noligodontia, peg shaped teeth and erythematous \nperiorbital papules.\n\n\n\nDiscussion\nAs illustrated in the case series above, patients with \nHED present with a myriad of symptoms. However, \nsome patients are asymptomatic and troubled by \ntheir appearance.  On the other extreme, some \npatients present with heat stroke and seizures due \nto thermo dysregulation. Other problems that may \nbe encountered by a child with HED are feeding \ndifficulties (deficiency of saliva), difficulty in \narticulation, recurrent respiratory infections (due \nto deficient mucus production by the respiratory \nepithelia in the trachea and bronchi) and dry eyes. \nAtopic eczema and hyperpigmentation would \n\n\n\nbring them to the attention of the dermatologist.  A \nthorough history and astute clinical skills would be \nrequired to suspect the diagnosis in a young patient \nwho presents with atopic eczema.\n\n\n\nMaking an early diagnosis has been found to improve \nthe outcome of boys with HED.4 Early fitting of \nartificial dentures, before the child attends school, \nhelps with speech, facial appearance and nutrition.  \nManagement of HED involves a multidisciplinary \nteam and should focus on thermoregulation, \ntreatment and prevention of infections, optimising \nfeeding, treatment of bronchial asthma and eczema, \nmonitoring of speech and genetic counselling.\n\n\n\nFigure 4. Genogram of the 3 patients illustrating the X-linked dominant genetic linkage.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28 MJD 2015 Jul Vol 34\n\n\n\nReferences\n \n1. Lamartine, J. Towards a new classification of ectodermal \n\n\n\ndysplasias. Clin Exp Dermatol 2003; 28: 351\u2013355.\n2. Nguyen-Nielsen M, Skovbo S, Svaneby D, et al. The \n\n\n\nprevalence of X-linked hypohidrotic ectodermal dysplasia \n(XLHED) in Denmark. 1995-2010. Eur J Med Genet 2013; \n56(5): 236-42.\n\n\n\n3. Pinheiro M, Freire- Maia N. Ectodermal Dysplasias: a \nclinical classification and causal review. Am. J. Med Genet \n1994; 53: 153-162.\n\n\n\n4.  Prasun, Pankaj, Karmarkar, et al. Unusual physical features \nand heat stroke presentation for hypohydrotic ectodermal \ndysplasia. Clin Dysmorphology 2012; 21(1): 24-26.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29MJD 2015 Jul Vol 34\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nGORLIN SYNDROME: A CASE REPORT WITH CLINICAL\nAND RADIOLOGICAL CORRELATION\nAzura MA, Izzaty D\n\n\n\nIntroduction\nGorlin syndrome is a condition characterized by \na wide range of developmental abnormalities and \na predisposition to skin cancer, namely basal cell \ncarcinoma (BCC). It is inherited as an autosomal \ndominant trait with complete penetrance and \nvariable expressivity, and caused by mutations in \n\n\n\nCorresponding Author and Reprint Request \nDr Azura Mohd Affandi \nMBChB(UK), MRCP(UK), Adv M Derm (UKM)\nDepartment of Dermatology, Hospital Kuala Lumpur\nJalan Pahang, 50586 Kuala Lumpur, Malaysia\nEmail: affandi_azura@yahoo.co.uk\n\n\n\nthe PTCH1 (Patched1) gene which is mapped to \nthe long arm of chromosome 9q22.3-q31.1 The \nsyndrome is also known as naevoid basal cell \ncarcinoma syndrome, Gorlin-Goltz syndrome, \nbasal cell naevus syndrome, fifth phacomatosis and \nmultiple basilioma syndrome.2 Diagnosis of Gorlin \nsyndrome is made by having two major criteria or \n\n\n\none major & two minor criteria.3 We report a case \nof Gorlin syndrome who presented with multiple \nbasal cell carcinoma, with clinical and radiological \ncorrelations.\n\n\n\nCase Report\nA 60 year old Malay lady with underlying \ndiabetes mellitus type II, hypertension and \nhypercholesterolemia, presented to our clinic in \n2003 with multiple hyperpigmented papules and \nplaques on the trunk, upper and lower limbs (Fig. \n1a-c). The lesions started to appear when she \nwas 46 years old and gradually increased in size \nand number. She is of medium built, with frontal \nbossing and high arched palate. There were also \npalmo-plantar pits (Fig. 1d-e).\n\n\n\nFigure 1a. Multiple pigmented basal cell carcinomas on \nthe chest.\n\n\n\nFigure 1b. Multiple pigmented basal cell carcinomas on \nthe back.\n\n\n\nFigure 1c. Multiple pigmented basal cell \ncarcinomas on the lower limbs.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30 MJD 2015 Jul Vol 34\n\n\n\nDermoscopy examination of the pigmented plaque \nshowed maple-leaf pattern, large ovoid nests and \narborizing telangectasias (Fig. 2), suggestive of basal \ncell carcinoma. Excision biopsies over 3 areas (left \nthigh, upper back and lower back) in 2003 confirmed \nbasal cell carcinoma. Throughout her follow-up, she \nhad multiple excisions of basal cell carcinoma over \ndifferent locations: left infra-mammary region and \nface (2011), right chest, left shoulder , left flank and \nlower back (2012), chest, right and left arm (2013). \nThe other smaller, multiple, superficial basal cell \ncarcinoma were treated with multiple sessions of \n\n\n\nliquid nitrogen cryotherapy. She denied any family \nhistory of skin malignancy and did not have history \nof prolonged exposure to sunlight.\n\n\n\nRadiological examination revealed macrocephaly, \ncalcification of the falx cerebri and two cysts in the \nmandible (Fig. 3a & 3b). There was also sprengel \ndeformity of the left scapula (elevation of the scapula \ncharacterised by medial rotation of the distal pole of \nthe scapula) and left 4th bifid rib evident from the \nchest radiography.\n\n\n\nFigure 2. Dermoscopy showing maple leaf pattern, \nlarge ovoid nests and arborizing telangiectasia.\n\n\n\nFigure 3b. X-ray showing multiple mandibular cysts.\n\n\n\nFigure 3a. Skull X-ray showing \nmacrocephaly and calcification of the falx \ncerebri.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31MJD 2015 Jul Vol 34\n\n\n\nShe was started on acitretin 25mg daily since May \n2013 to reduce the risk from getting recurrent \nnon-melanoma skin cancers. She is tolerating the \nmedication well. The last reported recurrence of \nbasal cell carcinoma was in September 2014, and \nthere was no recurrence of basal cell carcinoma \nsince then.\n\n\n\nDiscussion\nGorlin syndrome is a rare autosomal dominant \nsyndrome which is caused by mutations in the \nPCTH1 gene on chromosome 9q22.3-q31.1 The \nsyndrome is also known as naevoid basal cell \ncarcinoma syndrome, Gorlin-Goltz syndrome, \nbasal cell naevus syndrome, fifth phacomatosis \nand multiple basilioma syndrome.2 It was first \nreported by Jarish in 1894 who described a patient \nwith multiple basal cell carcinomas, scoliosis and \nlearning disability.2 In the 1960s, Gorlin and Goltz \ndescribed them as a triad of disorders including \nmultiple basal cell carcinoma, numerous keratocysts \nin the jaws and skeletal abnormalities, which gave \nrise to the Gorlin-Goltz syndrome.2,3\n\n\n\nAlthough its occurrence among family members is \nan important diagnosing criteria, it has been found \nthat between 20% and 40% of cases result from a \nde novo mutation of the PTCH1 gene.4 Our patient \nalso did not have a positive family history of Gorlin \nsyndrome. The prevalence range from 1:57,000 \n(in England) to 1:164,000, and even 1:256,000 \n(in Italy).3 There is equal predisposition in male \nand female, and it can occur in all ethnic groups, \nalthough the Caucasians are most often affected by \nit.5\n\n\n\nSkin manifestations in Gorlin Syndrome\nMultiple basal cell carcinoma of the skin constitutes \nthe most characteristic feature of the syndrome. The \nhighest incidence rate is observed in people between \npuberty and age 35.6 In general, the mean age of \nonset is about 25 years of age, although it was also \nobserved in children ages 3 to 4 years.7 The number \nof BCC varies from several to multiple, and their \ndiameter ranges from 1 mm to 10 mm, and they may \nhave various forms from skin-coloured nodules or \npapules, pigmented lesions to ulcerating plaques.8 \nThey are usually located on the face, back and chest, \nbut they may also be found on skin not exposed to \nthe sun.8 Aggressive forms of basal cell carcinomas, \nwhich infiltrate the facial bones, hardly ever occur. \nThe histopathology of naevoid BCC cannot be \ndifferentiated from that of ordinary sporadic BCC. \n\n\n\nBetween 30% and 65% of patients with the syndrome \nhave small asymmetric palmo-plantar pits by the \nage of 10 years.2,3 This percentage rises to 80% of \npatients by the age of 15, and 85% of patients over \nthe age of 20 years have palmo-plantar pits. They \nare small, with a diameter ranging from 2 to 3 mm \nand depth from 1 to 3mm. They increase in number \nwith age, are permanent, and are a strong diagnostic \nindicator whenever found in a child. They are found \nmore commonly on the palms (77%) than on the \nsoles (50%).2,3 They become more visible after the \npalms have been held in warm water for about 10 \nminutes.\n\n\n\nMultiple naevi are present in 30-50% of patients \nunder 20 years of age, rising to 70% in patients over \nthe age of 20 years. The naevi are flesh colored, \nreddish brown or pearly.  Some of them grow rapidly \nfor a few days (to a few weeks), then mostly remain \nstatic. Other skin signs are nodular or patch lesions, \nand benign dermal cysts. Small keratin-filled cysts \n(milia) can be found on the face in 30% of cases, \nmost commonly in the area below the eyes, but they \ncan also occur on the forehead.2 Epidermoid cysts \noccur on the limbs and the trunk in over 50% of \ncases. They are usually 1-2 cm in diameter and are \nparticularly common around the knee. \n\n\n\nKeratocystic odontogenic tumour (KCOT)\nThe most important manifestations of Gorlin \nsyndrome within the oral cavity are recurrent \nmultiple jaw tumours called keratocysts. The lesions \noccur in as many as 90% of patients above age 40.2 \nThey are most frequently located in the mandible - \n44% are found in the mandibular angles and 18% \nin the zones adjacent to incisor and canine teeth.2 In \nthe maxilla, they accompany canines and incisors \n(15%), as well as molars (14%). In spite of their less \nfrequent occurrence as compared to in the mandible, \nthey are more aggressive than those in the lower jaw \narea.\n\n\n\nThe KCOTs are divided into parakeratotic, \northokeratotic, and (rarely) mixed and solid \nlesions, and they are differentiated based on the \nhistological image of the cells lining them.3 The \ncavity of the tumour is filled with thick keratinous \nmaterial or a straw-coloured fluid. The tumours are \nusually diagnosed incidentally during routine x-ray \nexaminations performed in the course of a regular \ndental treatment. Other defects of the oral cavity \nare malocclusion, impacted teeth, mandibular \nprognathism, dental ectopy or heterotopy, and dental \nagenesis. Cleft palate and lip are rare, occurring in \n5% of patients.9\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32 MJD 2015 Jul Vol 34\n\n\n\nCentral nervous system\nCalcifications of the central nervous system \nhave been reported: lamellar calcification of \nthe falx cerebri (in 70-85% of patients) and \ntentorium cerebelli (in 20-40% of patients).10 The \ncalcification of the falx cerebri can appear very \nearly in life, and is often strikingly apparent from \nlate childhood. Other signs reported are cysts of \nthe choroid plexus, intraparenchymal brain cysts, \ncommunicating hydrocephalus, meningioma and \nmedulloblastoma.11,12 Seizures have occasionally \nbeen noted and mental retardation occurs in about \n5% of cases.13\n\n\n\nMusculo-skeletal system\nPatients with Gorlin syndrome have various skeletal \nmanifestations. They are usually much taller than the \nother family members, although in our case, she is \nof an average size. An abnormal skull configuration \n(characterized by frontal, biparetial or temporal \nbossing, and large calvaria) is frequent (70%).10\n\n\n\nMacrocephaly has been reported in 50% of cases. \nAs a result of the abnormal growth of the skull, \nabout 70% of patients affected by NBCCS have eyes \nwhich appear wider apart than usual. In our patient, \nalthough she is of normal stature, she had frontal \nbossing and macrocephaly. Other skeletal signs are \nscoliosis (40%), and abnormalities such as bifid, \nwide, fused, partially missing or underdeveloped \nribs (30-60%).10 Rib abnormalities may give rise to \na prominent or depressed sternum in about 30% - \n40% of patients. Spina bifida occulta of the cervical \nor thoracic vertebrae is found in 60% of cases. Bifid \nor fused vertebra and Sprengel anomaly (elevation \nof the scapula with rotation toward the spine with \nscoliosis) are observed in 10 to 40% of patients. Our \npatient had an evidence of bifid rib and sprengel \ndeformity on the chest radiograph. Extra digits on \nthe hands or feet can occur. \n\n\n\nOther systems involvement\nPatients with Gorlin syndrome may also have \ninvolvement of the other systems, such as the \nocular, genito-urinary, cardiovascular, respiratory, \nauditory and gastro-enteric systems (Table 1). \nApart from getting recurrent basal cell carcinoma, \nthey are also at risk of developing other tumours \nsuch as medulloblastoma,14 fibroma15 and \nrhabdomyosarcoma.16\n\n\n\nDiagnosis\nDiagnosis of Gorlin syndrome can be made by \nhaving two major criteria or one major & two minor \ncriteria, as shown in Table 2.1-3,6 Our patient fulfilled \n\n\n\nfive out of the six major criteria, namely multiple \noccurrence of basal cell carcinoma, odontogenic \nkeratocysts, palmo-plantar pits, calcification of the \nfalx cerebri and bifid ribs. She also had three minor \ncriteria, which are macrocephaly, frontal bossing \nand sprengel deformity. Direct mutation analysis of \nthe gene may be helpful. It was not done in our case \ndue to limited resources.  It is particularly helpful to \nfollow a specific clinical protocol in the examination \nof patients with suspected Gorlin syndrome (Table \n3). At least annual examination of the skin since \npuberty is recommended to detect the occurrence of \nbasal cell carcinoma. \n\n\n\nThe syndrome is a hereditary condition, thus \nreferral to a geneticist for counseling is mandatory. \nGorlin syndrome is caused when one copy of the \nPTCH1 gene pair contains a fault; this means that \nevery child of a person with the syndrome has a 1 \nin 2 (50:50) chance of inheriting the faulty gene. \nThe definitive diagnostic test is to demonstrate a \nmutation in the PTCH1 gene, although this is labor-\nintensive as there are 24 exons.\n\n\n\nManagement\nPatients with Gorlin syndrome are best managed by \nmulti-disciplinary team, depending on the organs \naffected. Keratocysts can be treated by surgical \nremoval. This requires exposure of the lesion by \nmaking an osteotomy in the jawbone under local or \ngeneral anaesthesia, finding the wall of the cyst and \nremoving this completely.\n\n\n\nWith regards to BCC, only a few of these tumours \nbecome invasive and the very rare cases of death \nresult from spread to the brain or lung. Results from \nseveral epidemiologic studies have indicated that \nthe risks of BCCs show a strong positive correlation \nwith ultraviolet (UV) exposure to UV. Thus, the \npatients with Gorlin syndrome are advised to avoid \nexcessive sun exposure, to use sunscreen (SPF30+), \nand to use UV protective sunglasses.\n\n\n\nTreatment of BCC can be divided into surgical and \nnon-surgical therapy. Surgical excision is the typical \napproach for a patient with BCC if the number of \nlesions is limited. Curretage and electrodessication \nis a simple and fast method, and can be used to treat \nsmall BCC. Cryosurgery and CO2 laser17 can also \nbe used to treat multiple, small, superficial BCC. \nMohs micrographic surgery allows radical excision \nof the lesions while minimizing the damage of \nhealthy tissue. However, due to its cost, it is mainly \nreserved for BCC on the face where normal tissue \npreservation is imperative.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33MJD 2015 Jul Vol 34\n\n\n\nAnother therapeutic option for BCC is photodynamic \ntherapy (PDT), a cancer treatment involving use of \na photosensitizing agent (given intravenously or \ntopically) that preferentially accumulates within \nmalignant cells. BCCs are then treated with red \nlight that leads to dye activation and, eventually to \ndeath of these cells.18\n\n\n\nTopical treatment for BCC includes 5% imiquimod \ncream or topical 5-fluorouracil. 5% imiquimod cream \nappears to be an effective treatment for nodular basal \ncell carcinoma alone or if combined with curettage \nprior to its application.19 5% imiquiomod cream is \napplied five times a week for a total of six weeks, \nand provides clinical and histological remission in \nall cases.19 5-fluorouracil cream is usually applied \ntwice a day for a period of 6-12 weeks. The cure rate \nranges from 80% to 95%.20 However, it is effective \nonly in the case of superficial BCC.20\n\n\n\nOral retinoid (Isotretinoin) has been used as a \nchemoprevention or delaying the development \nof recurrent BCC. Some authors indicated that \ndoses of 0.5-1.0 mg/kg/day cause regression of \nlesions of less than 1.0 cm and prevent new lesions \nformation.21 However, a study of high-dose oral \nisotretinoin (mean daily dose: 3 mg/kg/day) found \nthat only 8% of BCCs underwent complete clinical \nand histological regression, while all patients \ndeveloped moderate-to-severe acute toxicity.22 Our \npatient was started on acitretin 25mg daily, and she \nseems to be tolerating the medication well, and had \nno recurrence of BCC since September 2014. \n\n\n\nThe hedgehog signaling pathway is a key regulator \nof cell growth and differentiation.23 Somatic \nmutations in this pathway are present in the vast \nmajority of sporadic BCCs and Gorlin syndrome. In \n\n\n\nJanuary 2012, vismodegib became the first selective \ninhibitor of the Hedgehog signaling pathway to be \napproved by the US Food and Drug Administration \nfor the treatment of locally advanced and metastatic \nbasal cell carcinoma. The drug selectively binds to \nSmoothened, a transmembrane receptor, thereby \nsuppressing tumor proliferation and growth.23 \nIn a phase II study on vismodegib in 42 Gorlin \nsyndrome patients, the patients were randomized \nto two groups, one group received vismodegib and \nthe other group received placebo only. The results \nshowed reduction in the number of BCC (2 vs 29) \nand less surgery (0.31 vs 4.4) in the vismodegib \ngroup, compared to the placebo group.24\n\n\n\nConclusion\nThis case highlights the multitude of clinical \nfindings that can be encountered in patients with \nGorlin syndrome. Diagnosis is challenging, and \nthe geneticist and radiologist can play a role in \ndiagnosis, by detecting chromosomal abnormalities \nand radiological features associated with Gorlin \nsyndrome. Multidisciplinary team, comprising of \ndermatologist, dentist, radiologist, neurologist and \nophthalmologist are essential in managing this \nchallenging syndrome. Patients should be taught on \nhow to examine their skin and to report any changes \nto the doctor. \n\n\n\nAcknowledgement\nWe acknowledge the support of the pathologist, \nplastic surgeon and radiologist in Hospital Kuala \nLumpur in the diagnosis and management of this \nchallenging case. We would also like to thank the \nDirector General of Health, Malaysia for permission \nto publish this report.\n\n\n\nReferences\n\n\n\n1. Mohan R.V.S, Vemanna N.S, Narayanappa S.M, et.al. \nGorlin-Goltz syndrome: A clinico radiological illustrative \ncase report. Ind J Dentistry 2013; 4: 165-9.\n\n\n\n2. Lo Muzio L. Nevoid basal cell carcinoma syndrome \n(Gorlin syndrome). Orphanet J Rare Dis 2008; 3: 32.\n\n\n\n3. Kiwilsza M, Sporniak-Tutak K. Gorlin-Goltz syndrome \u2013 a \nmedical condition requiring a multidisciplinary approach. \nMed Sci Monit 2012; 18(9): RA145-153.\n\n\n\n4. Huang YF, Chen YJ, Yang HW. Nevoid basal cell carcinoma \nsyndrome \u2013 case report and genetic study. J Dent Sciences \n2010; 5: 166\u201370.\n\n\n\n5. Manfredi M, Vescovi P, Bonanini M, Porter S. Nevoid \nbasal cell carcinoma syndrome: a review of the literature. \nInt J Oral and Maxillofac Surg 2004; 33: 117\u201324.\n\n\n\n6. Gorlin R.J. Nevoid basal cell carcinoma syndrome. \nDermatol Clin 1995; 13: 113-125.\n\n\n\n7. Shanley S, Ratcliffe J, Hockey A, et.al. Nevoid basal cell \ncarcinoma syndrome: review of 118 affected individuals. \nAm J Med Genet 1994; 50: 282-290.\n\n\n\n8. Pratt MD, Jackson R. Nevoid basal cell carcinoma \nsyndrome. A 15-year follow-up of cases in Ottawa and the \nOttawa Valley. J Am Acad Dermatol 1987; 16: 964-970.\n\n\n\n9. Ruprecht A, Austermann KH, Umstadt H. Cleft lip and \npalate, seldom seen features of the Gorlin-Goltz syndrome. \nDentomaxillofac Radiol 1987; 16: 99-103.\n\n\n\n10. Lo Muzio L, Nocini PF, Savoia A, et.al. Nevoid basal \ncell carcinoma syndrome. Clinical findings in 37 Italian \naffected individuals. Clin Genet 1999; 55: 34-40.\n\n\n\n11. Fukushima Y, Oka H, Utsuki S, et.al. Nevoid Basal\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34 MJD 2015 Jul Vol 34\n\n\n\n12. Mortimer PS, Geaney DP, Liddell K, Dawber RP. Basal \ncell naevus syndrome and intracranial meningioma. J \nNeurol Neurosurg Psychiatry 1984; 47: 210-212.\n\n\n\n13. Hogan RE, Tress B, Gonzales MF, et.al. Epilepsy in the \nnevoid basal-cell carcinoma syndrome (Gorlin syndrome): \nreport of a case due to a focal neuronal heterotopia. \nNeurology 1996, 46: 574-576.\n\n\n\n14. Amlashi SF, Riffaud L, Brassier G, Morandi X. Nevoid \nbasal cell carcinoma syndrome: relation with desmoplastic \nmedulloblastoma in infancy. A population-based study and \nreview of the literature. Cancer 2003; 98:618-624.\n\n\n\n15. Pirschner F, Bastos P.M, Contarato G.L et.al. Gorlin \nsyndrome and bilateral ovarian fibroma. Int J Surg Case \nReports 2012; 3: 477\u2013 480.\n\n\n\n16. Cajaiba MM, Bale AE, Alvarez-Franco M, et.al. \nRhabdomyosarcoma, Wilms tumor, and deletion of the \npatched gene in Gorlin syndrome. Nat Clin Pract Oncol \n2006; 3:575-580.\n\n\n\n17. Doctoroff A, Oberlender SA, Purcell SM. Full-face carbon \ndioxide laser resurfacing in the management of a patient \nwith the nevoid basal cell carcinoma syndrome. Dermatol \nSurg 2003; 29:1236-1240.\n\n\n\n18. Madan V, Loncaster JA, Allan D et al. Nodular basal cell \ncarcinoma in Gorlin\u2019s syndrome treated with systemic \nphotodynamic therapy and interstitial optical fiber diffuser \nlaser. J Am Acad Dermatol 2006; 55: S86-89.\n\n\n\n19. Neville JA, Williford PM, Jorizzo JL. Pilot study using \ntopical imiquimod 5% cream in the treatment of nodular \nbasal cell carcinoma after initial treatment with curettage. \nJ Drugs Dermatol 2007; 6: 910-914.\n\n\n\n20. Walter AW: Gorlin Syndrome. www.emedicine.com/PED/\ntopic890.html.\n\n\n\n21. Sanchez-Conejo-Mir J, Camacho F. Nevoid basal cell \ncarcinoma syndrome: combined etretinate and surgical \ntreatment. J Dermatol Surg Oncol 1989; 15: 868-871.\n\n\n\n22. Peck GL, DiGiovanna JJ, Sarnoff DS, et.al. Treatment and \nprevention of basal cell carcinoma with oral isotretinoin. J \nAm Acad Dermatol 1988; 19:176-185.\n\n\n\n23. V. Ruiz-Salas, M. Alegre, A. L\u00f3pez-Ferrer, J.R. Garc\u00e9s. \nVismodegib. A Review. Actas Dermosifiliogr 2014; \n105(8): 744-751.\n\n\n\n24. Tang JY, Mackay-Wiggan J, Aszterbaum M, et al. Inhibiting \nthe Hedgehog pathway in patients with the basal cell nevus \nsyndrome. N Engl J Med 2012; 366: 2180-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35MJD 2014 Dec Vol 33\n\n\n\n\n\n\n\n\n\n\n\n\n\n"
"\n\niiMJD 2009 June Vol 22\n\n\n\nJURNAL DERMATOLOGI MALAYSIA\n\n\n\nVOLUME 22  |  JUNE 2009  |  ISSN: 1511-5356\n\n\n\nContents\n\n\n\nPAEDIATRIC DERMATOLOGY\n\n\n\nReview Article\n1 Recognising cutaneous signs and \n\n\n\ntreatment in paediatric connective tissue \ndiseases \nTang SP, MRCP (Paeds) UK\n\n\n\nDERMATO-ONCOLOGY\n\n\n\nOriginal Article\n7 Pattern of cutaneous malignancies in a \n\n\n\ntertiary hospital in Sarawak\nYap FBB, MRCP, Pubalan M, MRCP\n\n\n\nAUTOIMMUNE DISORDERS\n\n\n\nOriginal Article\n11 Henoch - Sch\u00f6nlein Purpura:\n\n\n\nRelationship between cutaneous clinical \nmanifestations with severity outcomes:\nA 5-year retrospective study \nTarita T, M Med, Lee CE, MBBS, Rohna R, MRCP\n\n\n\nCase Report\n19 Acute cardiac failure in a young atopic \n\n\n\npatient\nPan JY, MRCP, Yong WH, FAMS (Rheumatology), \nAudrey TWH, FAMS (Dermatology)\n\n\n\nCase Reports\n25 Mucous membrane pemphigoid\n\n\n\nLee CK,MRCP, Zuraiza MZ, MBBS,\nRokiah I, MRCP \n\n\n\nGRANULOMATOUS DISEASES\n\n\n\nOriginal Article\n29 Risk factors for type 1 leprosy reaction in \n\n\n\na tertiary skin clinic in Sarawak \nYap FBB, MRCP, Pubalan M, MRCP\n\n\n\nCase Report\n33 A lady with complicated erythema \n\n\n\nnodosum leprosum\nYap FBB, MRCP, Pubalan M, MRCP \n\n\n\nShort Communication\n35 Post vaccination lupus vulgaris\n\n\n\nMasliza Hanuni, MD, Ong CL, MRCP, Zamri MD, \nNor Azura, MD\n\n\n\nGENERAL DERMATOLOGY\n\n\n\nOriginal Article\n38 An outbreak of Rove Beetle dermatitis in \n\n\n\nPenang Hospital: A report of 37 cases\nTan WC MRCP, Chan LC, MMed\n\n\n\nShort Communication\n43 Twin psoriasis\n\n\n\nZaigham M, MD\n\n\n\nSelf Assessment\n44 Clinical Diagnostic Skill Testing\n\n\n\nRohna R, MRCP\n\n\n\nDERMATOSURGERY\n\n\n\nSurgical Tips\n46 Surgical lines\n\n\n\nGangaraam H, FRCP\n\n\n\nMalaysian Journal of  Dermatology\n\n\n\n\n\n\n\n\niii MJD 2009 June Vol 22\n\n\n\nTHERAPEUTICS\n\n\n\nOriginal Article\n47 Efficacy and safety of tacrolimus \n\n\n\nointment in patients with moderate to \nsevere atopic dermatitis - Malaysian \nexperience\nNg TG, M Adv Derm, Mardziah A, M Med, \nRoshidah BB, MRCP, Heng A, MRCP,\nNajeeb A, MRCP, Lo Kang SC, M Adv. Derm, \nPubalan M, MRCP, Loh LC, MRCP, \nSuraiya HH, FRCP\n\n\n\nOriginal Article\n55 A 5-yr retrospective study on the outcome \n\n\n\nof patients with acne vulgaris treated \nwith oral isotretinoin in Ipoh Hospital  \nTang JJ, MRCP, Chan LC, MMed, Heng A, MRCP\n\n\n\nShort Communication\n60 Penicillin-treated plaque psoriasis:\n\n\n\nReport of 2 cases from Taiwan\nAng XX, Wong SM, MRCP\n\n\n\nNURSING\n\n\n\nQuiz\n62 Dermatology Care Plan Quiz for nurses\n\n\n\nRohna R, MRCP\n\n\n\nShort Communication\n63 Nursing challenges in a teenager with \n\n\n\npemphigus vulgaris and toxic epidermal \nnecrolysis \nHazfaneza AH, MBBS, Kasmahwati T, SRN, \nNoradiah J, SRN, Norhasmie R, SRN\n\n\n\nANNOUNCEMENT\n\n\n\nAdministrative Update\n24 Pain as a vital sign\n\n\n\nMary SC, FRCS (Anaes)\n\n\n\n67 Guidelines to diagnosis of occupational \ndermatoses and its compensation\nMohammed AAM, LFOMRCP, Zainul AMH, \nM SC (OM)\n\n\n\nContinuous Professional Development\n18 Malaysian Dermatology Congress\n\n\n\n18 Regional Congress of Dermatology\n(Asian - Australasian)\n\n\n\n28 Satellite Meeting 2009\n\n\n\nANSWERS TO QUIZES\n\n\n\n68 Answers to Clinical Diagnostic Skill Test\n\n\n\n70 Answers to Dermatology Care Plan Quiz\n\n\n\n\n\n\n\n\nKeywords Juvenile systemic lupus erythematosus,\njuvenile dermatomyositis treatment\n\n\n\nIntroduction\nPaediatric rheumatology is an emerging field in\npaediatrics which deals with both inflammatory and\nnon inflammatory conditions of the connective\ntissue and joints in children. In paediatric\nrheumatology, the skin remains one of the most\nimportant organs which can be involved especially\nwith respect to the group of inflammatory\nconnective tissue diseases. In children with these\ndiseases, the cutaneous signs are often important\ndiagnostic clues of the underlying disease.\n\n\n\nHowever, due to the rarity of these conditions and\nthe relative inexperience by many, these cutaneous\nsigns can sometimes be mistakenly diagnosed. This\nnot only leads to a delay in diagnosis but also\ninstitution of appropriate therapy and a detrimental\nlong term outcome. In this review, the focus will be\non cutaneous signs in the two main paediatric\nconnective tissue disorders and its current\nmanagement.\n\n\n\nJuvenile Systemic Lupus Erythematosus (JSLE)\nJuvenile systemic lupus erythematosus (JSLE) or\nchildhood lupus is a chronic multisystem\nautoimmune disease that accounts for 15-20% of all\nlupus patients. In the paediatric population,\ncutaneous manifestations remain one of the\ncommon organ systems to be involved and are\npresent in an estimated 50-80% of children at initial\npresentation1. In a Malaysian study of 38 children\nwith JSLE, 89% had cutaneous symptoms and signs\nat initial presentation of which only 55% had malar\nrash, 45% mucosal ulceration and 42% alopecia2.\n\n\n\n1MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nPAEDIATRIC DERMATOLOGY - Review Article\n\n\n\nRecognising cutaneous signs and the management in \n\n\n\npaediatric connective tissue diseases\n\n\n\nTang SP, MRCP(Paeds) UK\n\n\n\nCutaneous involvement in JSLE can be either due\nto lupus specific interface dermatitis or non\nspecific manifestations of lupus like\n(photosensitivity, vasculitis, erythema or Raynaud\u2019s\nphenomenon). Lupus specific cutaneous disease\ncan be further divided into acute cutaneous lupus,\nsubacute cutaneous lupus (SCLE) and chronic\ncutaneous (discoid) lupus (CCLE). As a result of\nthis, the presentation of skin disease in lupus can be\nvery varied. Whilst lupus specific skin lesions serve\nprimarily as an important diagnostic clue to the\nunderlying disease, the presence non specific lupus\nlesions has been associated with more active SLE\nand hence may warrant more intensive therapy and\ndisease monitoring3.\n\n\n\nThe malar rash or \u2018butterfly\u2019 rash which is the\ntypical rash of SLE unfortunately only occurs in\nabout 50-70% of childhood lupus. One needs to\nremember that although it is pathognomonic of\nSLE, it is not a diagnostic rash and can be present\nin other conditions like juvenile dermatomyositis.\nSubacute cutaneous lesions are rare in children and\noften begin as papules that evolve to annular lesions\nwith raised edges which can then crust, become\nhyperpigmented and atrophied. Discoid skin lesions\nare also relatively rare in children and characterized\nby sharply demarcated papulosquamous lesions\nwhich are often photosensitive and heal with\natrophy and scarring. It is important to note that\ndiscoid lesions in children tend to have a higher\nchance of being associated or transitioning to\nsystemic lupus erythematosus as compared to\nadults, and hence a careful search for systemic\nsymptoms is warranted once a diagnosis of discoid\nLE is made4. Children with lupus can also present\nwith various non specific rashes like maculopapular\nrashes, petechiae, purpura or urticaria. The fingers\nand nails need to be checked carefully looking for\nnailfold infarcts and periungual erythema.\nPeriungual erythema which is the result of nail fold\ncapillary dilatation and tortuosity is not a finding\nwhich is specific to lupus and can be found in other\nconnective tissue diseases like juvenile\ndermatomyositis\n\n\n\nCorrespondence\nDr Tang Swee Ping\nDepartment of Paediatrics\nSelayang Hospital, Selangor, Malaysia\nEmail : tang@selayanghospital.gov.my\n\n\n\n\n\n\n\n\n2 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ndermatomyositis, juvenile scleroderma and\nundifferentiated connective tissue disease. In lupus,\nnailfold capillary abnormalities appear to be related\nto disease activity as well as the presence of various\ndifferent autoantibodies like anti-cardiolipin,\nanti-Sm and also the presence and higher titres of\nanti-dsDNA antibodies5. Livedo reticularis is also\nsometimes seen in children and one needs to\ninvestigate for associated presence of\nantiphospholipid antibodies6. Diffuse alopecia is\ncommon in active lupus while scarring alopecia is\nnot common in children. Rare presentations include\nvesicobullous lesions, nodules, lupus profundus and\nchilblain lupus. Oral mucosal lesions are also\ncommon and there can either be palate erythema or\nclassically a shallow, ragged painless ulcer on the\nhard palate. On some occasions, there can also be\nnasal septum ulceration.\n\n\n\nAs in adult patients, skin disease can sometimes be\none of the most refractory clinical manifestations of\nJSLE. The standard therapy consists of sun\nprotection, topical corticosteroids and\nantimalarials. In addition, children are advised to\navoid direct sun exposure, wear lightweight tightly\nwoven clothing and use broad-spectrum, water\nresistant sunscreens. Sun avoidance in particular is\ndifficult for children and ensuring compliance is a\nchallenge as this often limits their physical\nactivities or play especially at school or with\nfriends. In addition, children generally do not like\napplying sunscreens for reasons of stickiness, smell\nor colour especially in those who have pigmented\nskin. Skin lesions of acute LE often resolve with\ntreatment of the systemic disease in particular the\naddition of oral steroids but management of more\npersistent skin lesions remain a challenge. Some\nadditional suggested treatments include\nmethotrexate, intravenous immunoglobulin,\nmycophenolate mofetil and more recently anti-CD\n20 monoclonal antibody rituximab.\n\n\n\nLow dose methotrexate given in weekly dosages has\nbeen reported in various uncontrolled case series to\nbe of benefit for adults with active cutaneous and/or\narticular disease7,8,9. However the efficacy of\nmethotrexate for skin disease in the paediatric\npopulation is not so clear with two studies yielding\nconflicting results. Abud- Mendoza et al treated 10\nchildren with various manifestations including 7\nwith cutaneous symptoms and found in this group,\npositive response in 80% (5 excellent, 3 good) with\nonly 1 patient having a poor response10. However\n\n\n\nRavielli et al in his cohort of 11 paediatric onset\nlupus of which majority had nephritis, found no\nresponse for the cutaneous symptoms (3 malar rash\nand 2 skin vasculitis) and also that methotrexate did\nnot show any major corticosteroid sparing\npotential11. \n\n\n\nMycophenolate mofetil (MMF), an\nimmunosuppressive agent initially used for\ntransplantation has proven to be beneficial in lupus\nnephritis in both adults and children. However the\nevidence for refractory skin disease has been\nconflicting. Several adult case reports and case\nseries have shown good response to MMF and this\nincluded patients with refractory discoid lupus,\nSCLE, lupus profundus, lupus pernio, lupus\ntumidus and chilblain lupus12, 13, 14, 15. However in\nanother adult case series of 7 patients who had\npreviously failed to respond to a median of 4 drugs,\nresponse to MMF was poor with only one patient\nshowing a partial response and another showing an\ninitial response but flared subsequently even whilst\non MMF16. Currently, most available MMF data in\nchildren relates to its efficacy as either an induction\nor maintenance agent for lupus nephritis but there is\nsuggestion that MMF may be of benefit especially\nin non-renal lupus although there are no specific\nreports on the response of refractory cutaneous\ndisease in children17,18,19.\n\n\n\nRituximab, a chimeric monoclonal anti-CD20 IgG1\nantibody has shown promising results in paediatric\npatients with severe or refractory SLE mainly\ninvolving lupus nephritis, severe vasculitis or\ncytopenias20, 21. There is inadequate experience of its\nuse in isolated skin disease. There is a recent case\nreport of successful use of rituximabf22 or refractory\nlupus skin disease in an adult. An 11 year old\npaediatric patient with recurrent skin flares with\nsystemic manifestations has also been successfully\ntreated with rituximab and remained in remission 9\nmonths after initiating therapy23.\n\n\n\nOral thalidomide has also been reported to be a very\nuseful agent in inducing remission for refractory\nlupus skin lesions in adults but its use is limited by\npotential teratogenicity as well as peripheral\nneuropathy24,25,26. Although the response may be\ngood, the effect of thalidomide appears not to be\nsustained and a relapse rate of as high as 67% was\nreported upon cessation of the drug in one study26.\nIn children, data on thalidomide is scarce and is\ncurrently reserved only for those with severe\nautoimmune\n\n\n\n\n\n\n\n\n3MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nautoimmune pathologies. A major difficulty\nconcerning the use of thalidomide in children is the\nmonitoring for peripheral neuropathy. The\nperipheral neuropathy unlike in adults, has been\nshown to be dose-dependent especially cumulative\ndosages; age dependent and also occurs at a\nsignificantly high frequency of 53.8%, and thus has\nto be used with much caution27. Children may not be\nable to verbalise symptoms of clinical neuropathy\nand it is difficult to perform nerve conduction test\nin small children frequently. There is promise of\nsafer thalidomide analogues on the horizon which\nmay then make this an appropriate choice in the\nfuture.\n\n\n\nTopical pimecrolimus 1% cream, an ascomycin\nmacrolactam which inhibits calcineurin and has no\natrophogenic potential has been reported to be safe\nand efficacious in small cases series in adults but no\navailable data in children28,29.\n\n\n\nIn our experience managing childhood lupus, most\ncutaneous lesions respond to topical\ncorticosteroids, antimalarials and sometimes\nrequire low dose prednisolone. However second\nline agents like methotrexate and azathioprine do\nnot seem to have beneficial effects in improving\nrefractory skin lesions. Intravenous\nimmunoglobulin has been tried in 3 patients with\nrefractory cutaneous symptoms but we did not see\nany improvement. Mycophenolate mofetil has been\nused successfully in two patients with chronic\ndiscoid lupus with skin vasculitis - one who had\npreviously failed oral prednisolone and monthly\nintravenous pulse methylprednisolone,\nantimalarials, azathioprine, intravenous\nimmunoglobulin and 6 months of intravenous\ncycophosphamide. The other had failed\nantimalarials, azathioprine and six months of\nmonthly intravenous immunoglobulin. The\nimprovement in the skin rash was seen as early as 2\nmonths after initiation of MMF therapy. Currently,\nRituximab has been reserved for children with more\nsevere major organ involvement of lupus.\n\n\n\nJuvenile Dermatomyositis\nJuvenile Dermatomyositis (JDM) is a rare disease\nbut remains the commonest of all the idiopathic\ninflammatory myopathies of childhood. It\ncharacteristically affects the proximal muscles\nresulting in weakness and also the skin with\npathognomonic rashes. However, the cutaneous\ndisease does not always parallel the muscle disease\n\n\n\nin terms of onset, activity or response to therapy.\nAlthough both these organ systems can be affected\nsimultaneously at presentation, at times the\nmanifestation of one organ system may precede the\nother and often the skin rashes may be undiagnosed\nfor months before the clinical muscle weakness sets\nin. In an unpublished study of 20 Malaysian\nchildren with JDM, the initial presentation in 50%\nof the patients was cutaneous alone with only 20%\npresenting simultaneously with skin rashes and\nmuscle disease. In this cohort, facial rash was the\ncommonest presentation present in 90% of the\npatients whilst Gottron papules was reported in\n75% of patients. The mean delay between onset of\nskin disease to diagnosis was 15 months indicating\na significant delay in diagnosis30.\n\n\n\nJuvenile dermatomyositis has typical skin rash\nwhich include the heliotrope rash and Gottron\npapules. Heliotrope rash is a purplish\ndiscolouration of the upper eyelids whilst Gottron\npapules are erythematous scaly lesions often found\nover the metacarpophalangeal and proximal\ninterphalangeal joints as well as over the elbows\nand knees. In our experience, the Gottron papules\nmay sometimes just be non-discrete erythema and\noften in our population especially those with\npigmented skin, the rash can appears as non-\nerythematous hyperpigmented lesions. Lesions over\nthe elbows are more common than over the knees\nand Gottron papules are also seen on occasions over\nthe distal interphalangeal joints although it is\nusually associated with lesions elsewhere. Children\nwith JDM can also present with a malar rash which\nis often well demarcated although the area of\ninvolvement can be quite small and sometimes be\nmissed. In some children, an extensive\nerythematous rash can also occur over the whole\nbody whilst others can present with vasculitic or\nulcerative skin lesions and these often signify a\nmore aggressive disease and a poor prognosis.\nPeriungual erythema due to nailfold capillary loop\ndilatations is common and can affect both finger\nand toe tips. In some instances in acute JDM, there\ncan also be periorbital oedema or diffuse oedema of\nthe whole face whether erythematous or not. This is\nsometimes mistaken as an allergic reaction to\nvarious drugs administered. Photosensitivity is also\na feature in these patients and sun exposure can\nprecipitate a flare. Calcinosis and lipodystrophy are\nconsidered complications of inadequately or\nprolonged untreated disease.\n\n\n\n\n\n\n\n\n4 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSmith et al in a study of 60 newly diagnosed,\npreviously untreated children with JDM found that\nthe cutaneous manifestations were associated with\nend row capillary loss which indicated a\nvasculopathy. As such, they proposed that the\ncutaneous manifestations of JDM are associated\nwith vascular disease and hence warrant aggressive\ntherapy31. The presence of a persistent rash and the\nduration of untreated disease have also been\nassociated with one of the dreaded complications of\nJDM which is calcifications32. As such, cutaneous\nlesions of JDM need to be diagnosed accurately and\ngiven prompt and perhaps systemic therapy.\n\n\n\nAs in JSLE, the standard therapy for skin lesions in\nJDM include sun protection, topical cortiosteroids\nand sometimes antimalarials. More resistant skin\nlesions sometimes require the addition of low dose\noral corticosteroids. The use of topical\nimmunosuppressive agents has largely been\ndisappointing. In an unblinded observational study\nof 5 adults with dermatomyositis and 1 child with\nJDM, topical tacrolimus was reported to be a useful\nadjunct in patients for refractory cutaneous\nlesions33. However this beneficial effect was not\nobserved in another study whereby none of the 5\npatients treated with topical tacrolimus showed any\nimprovement34. Oral tacrolimus on the other hand,\nhas been reported to be of benefit for severe\ncutaneous manifestations in a total of 9 children in\n2 different case series but its role in controlling\nmuscle disease is conflicting in these 2 studies35,36. \n\n\n\nIntravenous immunoglobulin has been proven\neffective as an adjunctive treatment for myositis in\nsevere JDM with improvement in disease activity as\nwell as permitting steroid reduction37,38. In addition,\nLang et al also reported 5 children who not only\nshowed improvement in their muscle strength but\nalso their skin rash39. Two adult patients treated with\nintravenous immunoglobulin for their skin disease\nin dermatomyositis have also been reported to show\nresponse - one complete and one partial40.\n\n\n\nRiley et al reviewed the efficacy of intravenous\npulse Cyclophosphamide in 12 patients with severe\nrefractory JDM and of these 8 had ulcerative skin\nlesions. Two patients died of underlying pulmonary\ninsufficiency early in the disease, but the remaining\n10 showed improvement after 6 months of\ntreatment in both muscular and extra-muscular\ndisease including skin scores. Although all the\nulcerative skin disease was successfully treated,\n\n\n\nother skin disease was also one of the main\npersistent features41.\n\n\n\nOther drugs which have been tried include the\nfollowing. Infliximab has also recently been\nreported to be of benefit for 5 children with\nrefractory JDM but the positive effect was mainly\nnoted for muscle disease, contractures and\ncalcinosis whilst skin disease was less well\ncontrolled42. As in JSLE, Rituximab, a chimeric\nmonoclonal anti - CD20 IgG1 antibody has also\nbeen reported to be potentially useful for JDM in an\nobservational study of 4 children of which 3 showed\nclinical benefit regardless of status of myositis\nspecific antibodies43.\n\n\n\nIn our experience, monthly intravenous\nimmunoglobulin (IVIg) at 1g/kg/day for 2 days has\nbeen used in six children with severe JDM with\nmoderate success. One patient with only severe\ncutaneous disease who had failed prior therapy with\noral and topical corticosteroids, antimalarials,\nmethotrexate and topical tacrolimus showed a\ndramatic response and went into complete\nremission only after 2 doses of IVIg and has\nremained in remission since then. Four other\nchildren showed improvement in both their\ncutaneous and muscle disease whilst one child did\nnot show any response despite having had a\nprolonged 12 month course of intravenous\nimmunoglobulin. We postulate that the poor\nresponse in this child is due to long term damage\nfrom uncontrolled inflammation which is\nirreversible.\n\n\n\nConclusion\nThe prognosis of common paediatric connective\ntissue diseases like juvenile systemic lupus\nerythematosus and juvenile dermatomyositis has\nimproved tremendously over the recent decades\nwith better understanding of the disease as well as\nmore aggressive therapy. However, the treatment for\ncutaneous manifestations in these diseases has\nlargely remained the same and resistant skin\nmanifestations continue to be a therapeutic\nchallenge. The emergence and ongoing research of\nnew drugs including biologic therapy have offered\npromise in these situations but more research has to\nbe conducted before they can be widely applied\nespecially in children.\n\n\n\n\n\n\n\n\n5MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nReferences\n\n\n\n1. Wananukul S, Watana D, et al, Cutaneous\nmanifestations of childhood lupus erythematosus.\nPediatr Dermatol 1998; 15(5): 342-6\n\n\n\n2. Hii KC, Tang SP. Clinical and laboratory features of\njuvenile systemic lupus erythematosus at initial\npresentation. (unpublished) - personal communication\n\n\n\n3. Zecevic RD, Vojvodic D, et al. Skin lesions - an\nindicator of disease activity in systemic lupus\nerythematosus. Lupus 2001; 10(5): 364-7\n\n\n\n4. Fenniche S, Triki S, Benmously R et al. Lupus\nerythematosus in children: a report of six cases.\nDermatol Online J 2005; 11(2): 11\n\n\n\n5. Riccieri V, Spadaro A et al. Nailfold capillaroscopy\nchanges in systemic lupus erythematosus : correlations\nwith disease activity and autoantibody profile. Lupus\n2005; 14(7): 521-5\n\n\n\n6. Weinstein C, Miller MH, et al. Livedo reticularis\nassociated with increased titres of anticardiolipin\nantibodies in systemic lupus erythematosus. Arch\nDermatol 1987; 123(5) 596-600\n\n\n\n7. Sato E I. Methotrexate therapy in systemic lupus\nerythematosus. Lupus 2001; 10(3) 162-4\n\n\n\n8. Asherson RA, Schatten S, Hughes GRV. Methotrexate\nin systemic lupus erythematosus. J Rheumatol 1997;\n24: 610-611\n\n\n\n9. Wise CM, Vuyyuru S, Roberts WN. Methotrexate in\nnonrenal lupus and undifferentiated connective tissue\ndisease - a review of 36 patients. J Rheumatol 1996;\n23(6) : 1005-10\n\n\n\n10. Abud-Mendoza C, Sturbaum AK, Vasquez-Compean E\net al. Methotrexate therapy in childhood systemic lupus\nerythematosus. J Rheumatol 1993;20:731-733\n\n\n\n11. Ravelli A, Ballardini G, Viola S et al. Methotrexate\ntherapy in refractory pediatric onset systemic lupus\nerythematosus. J Rheumatol 1998; 25(3): 572-5\n\n\n\n12. Goyal S, Nousari HC. Treatment of resistant discoid\nlupus erythematosus of the palsm and soles with\nmycophenolate mofetil. J Am Acad Dermatol\n2001;45:142-4\n\n\n\n13. Boehm I, Bieber T. Chilblain lupus erythematosus :\nsuccessful treatment with mycophenolate mofetil.\nArch Dermatol 2001; 137: 235-6\n\n\n\n14. Schanz S, Ulmer A, Rassner G et al, Successful\ntreatment of subacute lupus erythematosus with\nmycophenolate mofetil. Br J Dermatol 2002; 147:174-\n8\n\n\n\n15. Hanjani NM, Nousari CH. Mycophenolate mofetil for\nthe treatment of cutaneous lupus erythematosus with\nsmoldering systemic involvement. Arch Dermatol\n2002; 138:1616-18\n\n\n\n16. Pisoni CN, Obermoser G, Cuadrado MJ et al, Skin\nmanifestations of systemic lupus erythematosus\nrefractory to multiple treatment modalities: poor\nresults with mycophenolate mofetil. Cin Exp\nRheumatol 2005; 23: 393-6\n\n\n\n17. Lau KK, Ault BH, Jones DP et al. Induction therapy\nfor pediatric focal proliferative lupus nephritis:\ncyclophosphamide versus mycophenolate mofetil. J\nPediatr Health Care 2008; 22(5): 282-8\n\n\n\n18. Fujinaya S, Ohtomo Y, Hara S et al. Maintenance\ntherapy with mycophenolate mofetil for children with\nsevere lupus nephritis after low-dose intravenous\ncyclophosphamide regimen. Pediatr Nephrol. 2008;\n23(10):1877-82\n\n\n\n19. Falcini F, Capannini S, Martini G et al. Mycophenolate\nmofetil for the treatment of juvenile onset SLE: a\nmulticenter study. Lupus 2009;18 (2): 139-43\n\n\n\n20. Nwobi O, Abitbol CL, Chandar J et al, Rituximab\ntherapy for juvenile onset systemic lupus\nerythematosus. Pediatr Nephrol 2008; 23: 413-9\n\n\n\n21. Willems M, Haddad E, Niaudet P et al, French\nPaediatric - Onset SLE study group. Rituximab therapy\nfor childhood onset systemic lupus erythematosus. J\nPediatr 2006; 148:623-7\n\n\n\n22. Uthman I, Taher A et al. Successful treatment of\nrefractory skin manifestations of systemic lupus\nerythematosus with rituximab: report of a case.\nDermatology 2008; 216(3): 257-9\n\n\n\n23. Menon S. Hari P, Bagga A. Beneficial effects of\nrituximab therapy for systemic lupus erythematosus.\nIndian J Pediatr 2007; 74(1): 79-82\n\n\n\n24. Sato E I, Assis LS et al, Long term thalidomide use in\nrefractory cutaneous lesions of systemic lupus\nerythematosus. Rev Assoc Med Bras 1998; 44(4):\n289-93\n\n\n\n25. Coelho A, Souto MI, Cardoso CR et al. Long term\nthalidomide use in refractory cutaneous lesions of\nlupus erythematosus; a 65 series of Brazilian patients.\nLupus 2005; 14(6) ; 434-9\n\n\n\n26. Cuadrado MJ, Karim Y, Sanna G et al Thalidomide for\nthe treatment of resistant cutaneous lupus: efficacy\nand safety of different therapeutic regimes. Am J Med\n2005; 118(3); 246-50\n\n\n\n27. Priolo T, Lamda LD, Giribaldi G et al. Childhood\nthalidomide neuropahty: a clinical and\nneurophysiologic study. Pediatr Neurol 2008; 38:196-9\n\n\n\n28. Tlacuilo-Parra A, Guevara-Gutierrez E, Guiterrez-\nMurillo F et al, Pimecrolimus 1% cream for the\ntreatment of discoid lupus erythematosus.\nRheumatology (Oxford) 2005; 44(12):1564-8\n\n\n\n29. Kreuter A, Gambicher T, Breuckmann F et al.\nPimecrolimus 1% cream for cutaneous lupus\nerythematosus. J Am Acad Dermatol 2004; 51(3): 407-\n10\n\n\n\n30. TangSP, Lingesh S, Mathan RN et al. Clinical features\nof Juvenile Dermatomyositis at diagnosis. Unpublished\nstudy - personal communication\n\n\n\n31. Smith RL, Sundberg J, Shamiyah E, et al. Skin\ninvolvement in juvenile dermatomyositis is associated\nwith loss of end row nailfold capillary loops. J\nRheumatol 2004; 31(8) : 1644-9\n\n\n\n32. Seshadri R, Feldman BM, Ilowite N et al. The role of\naggressive corticosteroid therapy in patients with\njuvenile dermatomyositis: a propensity score analysis.\nArthritis Rheum 2008; 59(7): 989-95\n\n\n\n33. Hollar CB, Jorizzo JL. Topical tacrolimus 0.1% for\nrefractory skin disease in dermatomyositisL a pilot\nstudy. J Dermatolog Treat 2004;15:35-39\n\n\n\n34. Garcia-Doval I, Cruces M. Topical tacrolimus in\ncutaneous lesions of dermatomyositis: lack of effect in\nside-by-side comparison in five patients. Dermatology\n2004; 209: 247-248\n\n\n\n\n\n\n\n\n6 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35. Hassan J, van der Net JJ, van Royen-Kerkhof A.\nTreatment of refractory juvenile dermatomyositis with\ntacrolimus. Clin Rheumatol 2008; 27(11):1467-71\n\n\n\n36. Martin Nalda A, Modesto Caballero C, Arnal Guimeral\nC et al. Efficacy of tacrolimus in the treatment of\nrecalcitrant juvenile dermatomyositis. Med Cin (Barc)\n2006; 127 (18): 697-701\n\n\n\n37. Sansome A, Dubowitz V. Intravenous immunoglobulin\nin juvenile dermatomyositis : four year review of nine\ncases. Arch Dis Child 1995; 75: 25-28\n\n\n\n38. Al-Mayouf SM, Laxer RM, Schneider R, et al.\nIntravenous immunoglobulin therapy for juvenile\ndermatomyositis: efficacy and safety. J Rheumatol\n2000; 27: 2498-2503\n\n\n\n39. Lang B, Murphy G. Treatment of dermatomyositis\nwith intravenous globulin. Am J Med 1991;91:169-72\n\n\n\n40. Wtter DA, Davis MD, Yiannias JA, et al. Effectiveness\nof intravenous immunoglobulin therapy in skin disease\nother than toxic epidermal necrolysis: a retrospective\nreview of Mayo clinic experience. Mayo Clin Proc\n2005; 80 (1): 41-7\n\n\n\n41. Riley P, Maillard SM, Wedderburn R et al. Intravenous\ncycophosphamide pulse therapy in juvenile\ndermatomyositis: a review of efficacy and safety.\nRheumatology (Oxford) 2004; 43: 491-496\n\n\n\n42. Riley P, McCann LJ, Malillard SM et al. Effectiveness\nof infliximab in the treatment of refractory juvenile\ndermatomyositis with calcinosis. Rheumatology\n(Oxford) 2008; 47(6): 877-80\n\n\n\n43. Cooper MA, Willingham DL, Brown DE et al.\nRitximab for the treatment of juvenile\ndermatomyositis: a report of four paediatric patients.\nArthritis Rheum 2007; 56(9) : 3107-11\n\n\n\n\n\n\n\n\n7MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDERMATO-ONCOLOGY - Original Article\n\n\n\nPattern of cutaneous malignancies in a tertiary hospital\n\n\n\nin Sarawak\n\n\n\nYap FBB, MRCP, Pubalan M, MRCP\n\n\n\nAbstract\n\n\n\nBackground Most Asian studies have determined that basal cell carcinoma (BCC) is the commonest\nskin cancer followed by squamous cell carcinoma (SCC), malignant melanoma (MM) and others.\nThe pattern of cutaneous malignancies has never been determined in Sarawak. Thus, this\nretrospective study was performed to determine the pattern among patients attending the skin clinic\nin Sarawak General Hospital.\n\n\n\nMaterials and Methods The clinic notes of 87 patients diagnosed to have skin cancer\nhistopathologically between 2000 and 2008 were retrieved and subjected to descriptive analysis.\nAnalysis for the pattern of disease and demographics was performed.\n\n\n\nResults BCC constituted the main skin cancer with 49.4% (n=43) followed by SCC with 26.4%\n(n=23), cutaneous lymphomas (CL) with 9.2% (n=8), MM with 4.6% (n=4) and other cutaneous\nmalignancies with 10.3% (n=9). The number of cases detected steadily increased over the 8 year\nperiod, with most BCC and SCC diagnosed after 2003. The mean age of presentation was highest in\npatients suffering from SCC at 62.7 years followed by BCC 60.9 years, MM 59 years, CL 54.3 years\nand other malignancies 40.6 years. Female predominance was noted in all the malignancies except\nsquamous cell carcinoma. Chinese constituted the majority of cases (50.6%) followed by Malays\n(29.9%),  Bidayuhs (9.2%), Ibans (8.0%) and other indigenous people of Sarawak (2.3%). This\npattern of distribution corresponds with the racial distribution of the clinic attendance.\n\n\n\nConclusion Cutaneous malignancies in Sarawak differ from regional pattern in that CL is ranked as\nthe third commonest skin cancer and that female predominance was seen in BCC, CL, MM and other\nskin cancers.\n\n\n\nKeywords skin cancer, pattern of disease, demographics\n\n\n\nCorrespondence\nDr Yap Felix Boon Bin, MRCP\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak, Malaysia\nEmail : woodzlamp@yahoo.com\nConflict of interest : Nil\n\n\n\nIntroduction\nCutaneous malignancy is estimated to occur in 20%\nto 30% of all malignancies in Caucasians, 2% to 4%\nof all neoplasm in Orientals, and 1% to 2% of all\ncancers in Africans and Indians1. It has been\nrecognized as the most common malignancy among\nCaucasian population2,3. In neighbouring Singapore,\nskin cancer is ranked seventh in their cancer\nregistry4.\n\n\n\nBasal cell carcinoma (BCC) is the most common\nskin malignancy in Orientals, Caucasians,\nHispanics1,4,5. However, among Indians and\nAfricans, squamous cell carcinoma (SCC) is\nrecognized as the most common skin cancer6,7.\n\n\n\nMalignant melanoma (MM) is seen as the third\nmost common cutaneous malignancy among\nAsians, Caucasians, Hispanics and Africans4,7,8. In\nJapan, cutaneous T cell lymphoma is seen as the\nfourth commonest skin malignancy, representing\napproximately 5% of the skin cancer9. Kaposi\u2019s\nsarcoma is seen as a common cancer in Africans,\nrepresenting around 10% of their cancer load10. The\npattern of skin cancer in Sarawak has never been\nreported. Sarawak is unique as it is inhabited by the\nnative tribes. In Kuching where the Sarawak\nGeneral\n\n\n\n\n\n\n\n\n8 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGeneral Hospital is situated, Bidayuhs and Ibans are\nthe major ethnic tribes served. Skin clinic in\nSarawak General Hospital is the only skin referral\ncentre for the whole state of Sarawak. This tertiary\ncentre caters mainly for the Chinese, Malays,\nBidayuhs and Ibans. A retrospective study is\nundertaken to determine the pattern of skin\nmalignancy seen in the Sarawak General Hospital\nbetween 2000 and 2008.\n\n\n\nMaterials and methods\nAll the clinic cards of patients attending skin clinic,\nSarawak General Hospital between 2000 and 2008\nwere searched. Of these, 87 patients were diagnosed\nto have cutaneous malignancy histopathologically.\nDemographic data and type of malignancy were\nrecorded. The data collected was subjected to\ndescriptive analysis. The analysis was done for the\npattern of the skin cancer seen and presented as the\npercentage of each type of cancer. Among each\ntype, demographic data regarding age, sex, race and\noccupation were described. The occupation\ndescribed in this study is divided into those who are\nfrequently sun exposed e.g. farmers and\nconstruction workers or those who are not sun\nexposed e.g. clerk, administrators and housewives.\nThis is to determine whether the cancer recorded\nhas any relevance to sun exposure.\n\n\n\nResults\nBetween 2000 and 2008, 87 patients were\ndiagnosed to have cutaneous malignancies. Of\nthese, 49.4% (n=43) had BCC, 26.4% (n=23) had\nSCC, 9.2% (n=8) had cutaneous lymphomas (CL),\n\n\n\n4.6% (n=4) had MM and 10.3% (n=9) had other\ncutaneous malignancies. For patients diagnosed\nwith CL, we observed that 50% (n=4) had mycosis\nfungoides, 25% (n=2) cutaneous B cell lymphoma,\n12.5% (n=1) cutaneous T cell lymphoma and 12.5%\n(n=1) anaplastic large cell lymphoma. For patients\ndiagnosed to have other cutaneous malignancies,\nwe noted that 66.7% (n=6) had metastases from\nother malignancy (1 acute myeloid leukemia, 1\nchronic myeloid leukemia, 1 lung carcinoma, 1\nbreast cancer, 1 nasopharyngeal cancer and 1\ncolonic cancer) and 33.3% (n=3) had\ndermatofibrosarcoma protuberans. Figure 1 shows\nthe type of malignancies diagnosed by year. It\nshows that cutaneous malignancies were steadily\nincreasing over the 8 year period. Most of the\nmalignancies especially BCC and SCC were\ndiagnosed from 2004 onwards.\n\n\n\nTable 1 Demographics of cutaneous malignancies in Sarawak General Hospital\n\n\n\nBCC (n=43)\n\n\n\n60.9\n\n\n\n22 (51.2%)\n\n\n\n15 (34.9%)\n\n\n\n19 (44.2%)\n\n\n\n14 (32.6%)\n\n\n\n6 (14.0%)\n\n\n\n3 (6.9%)\n\n\n\n1 (2.3%)\n\n\n\nSCC (n=23)\n\n\n\n62.7\n\n\n\n9 (39.1%)\n\n\n\n4 (17.4%)\n\n\n\n13 (56.5%)\n\n\n\n10 (43.5%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\nCL (n=8)\n\n\n\n54.3\n\n\n\n7 (87.5%)\n\n\n\n0\n\n\n\n3 (37.5%)\n\n\n\n1 (12.5%)\n\n\n\n1 (12.5%)\n\n\n\n3 (37.5%)\n\n\n\n0\n\n\n\nMM (n=4)\n\n\n\n59.0\n\n\n\n3 (75.0%)\n\n\n\n0\n\n\n\n3 (75.0%)\n\n\n\n1 (25.0%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\nOthers (n=9)\n\n\n\n40.6\n\n\n\n7 (77.8%)\n\n\n\n0\n\n\n\n6 (66.7%)\n\n\n\n0\n\n\n\n1 (11.1%)\n\n\n\n1 (11.1%)\n\n\n\n1 (11.1%)\n\n\n\nMean age (yrs)\n\n\n\nFemale sex\n\n\n\nOccupations with sun exposure\n\n\n\nRace\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nBidayuh\n\n\n\nIban\n\n\n\nOthers\n\n\n\nFigure 1 Cutaneous Malignancies in Sarawak General \nHospital (n-87)\n\n\n\n\n\n\n\n\n9MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 1 shows the demographic data of patients\nwith various cutaneous malignancies. We observed\na female predominance in all the malignancies\nexcept squamous cell carcinoma. Among patients\ndiagnosed with MM, CL and other malignancies,\nmore than 75% were female. The mean age of\npresentation was highest in patients suffering from\nSCC with 62.7 years (range, 33 to 85 years)\nfollowed by BCC with 60.9 years (range, 35 to 83\nyears); MM with 59 years (range, 40 to 75 years);\nCL with 54.3 years (range, 28 to 89 years) and other\nmalignancies with 40.6 years (range, 18 to 58\nyears). Occupation related to constant sun exposure\nwas observed in 34.9% with BCC and 17.4% with\nSCC. None of the patients with CL, MM and other\ncancers had occupation related to constant sun\nexposure. \n\n\n\nDiscussion\nIn Sarawak General Hospital, we noted that BCC is\nthe commonest skin cancer followed by SCC, CL\nand MM. In Singapore, Koh et al also noted that\nBCC was the commonest skin cancer in their study\nfollowed by SCC. However, they noted that MM\nwas ranked third4. The differences might be\nattributed to the ethnicity of the population. Seventy\nseven percent of Singaporeans are Chinese with\nFitzpatrick skin types III and IV, 14% Malays with\nskin type V and 8% Indians with having skin type\nVI4. In Sarawak, Ibans with skin type V make up\n30% of the total population, Chinese 26%, Malays\n21% and Bidayuhs with skin type VI and V 10%11.\nFairer skin Chinese are more prone to have MM\nthan darker skin Indians4. Moreover, Caucasians\nwith skin type I and II are 3 to 7 times more prone\nto develop MM than Hispanics with skin type II and\nIV. In turn, Hispanics are 1 to 4 times more prone\nthan blacks with skin type VI and Asians8,12. \n\n\n\nThus, by having a darker skin complexion,\npopulation of Sarawak are more protected from\ndeveloping MM. Another possibility is that MM is\nunder diagnosed in Sarawak as the acral lentiginous\ntype commonly seen here might be misdiagnosed as\nother diseases e.g. fungal infection, mole and\ntrauma and never referred to the skin clinic for\nproper assessment.\n\n\n\nThe finding of CL as the third commonest skin\nmalignancy in Sarawak is very interesting. The\nreason for the high incidence of CL of 9.2% and\nespecially in Ibans is unknown. Similarly, the high\n\n\n\nincidence of mycosis fungoides of 12.1% among\nblacks is also unknown7. Generally mycoses\nfungoides is seen twice as common in blacks\ncompared to whites13. A possible postulate is that\nthe darker skin type that protects against MM\nallows the expression of CL.\n\n\n\nThe pattern of primary CL seen in Sarawak\ncorresponds to the pattern seen in the United States.\nZackheim et al noted that mycosis fungoides\nconstituted 82.3% of total primary CL cases\nfollowed by lymphomatoid papulosis with 9.4%, B\ncell lymphoma 4.5%, primary T cell lymphoma\n2.9% and anaplastic large cell lymphoma 0.9%14. In\nour study, we found that mycosis fungoides was the\ncommonest primary CL seen followed by primary\nB cell CL, primary T cell CL and anaplastic large\ncell lymphoma. However, the proportion of patients\ndiagnosed with mycosis fungoides was lower, at\nonly 50%.\n\n\n\nIn Taiwan, 1.02% of the 12146 patients with\ninternal malignancies had metastasized to the skin15.\nThe highest rates of skin metastases were found to\noccur from carcinoma of the breast, followed by the\nlung, oral mucosa, colon and rectum, stomach, and\nesophagus. We also found skin metastases from\nbreast and colon. Interestingly, we also found a\npatient with skin metastases from nasopharyngeal\ncancer, one of the commonest cancers in Sarawak. \n\n\n\nBCC is commonly seen in males with a male to\nfemale ratio of 2: 116. In Australia, the incidence of\nBCC in those aged under 40 is higher in women\nthan men, after which rates in men exceed women17.\nHowever, our study showed the ratio of both sexes\nwas almost equal. In Singapore, Koh et al also\nnoted an almost equal incidence of BCC among the\npredominant Chinese and Malay population4. In\nSCC, the male to female ratio was between 1.5 and\n1.9 among the Singaporean Chinese4. Here, we\nnoted that the ratio was 1.6. CL is more common in\nmales with a ratio of 2:118. MM has almost equal\nsex distribution among Japanese but more common\nin males among Singaporean Chinese4,9. In\nSarawak, we noted that both these conditions were\nmore common in females. Nevertheless, the\nnumber of patients in this study is small and might\nnot be representative of the population in the whole\nstate.\n\n\n\n\n\n\n\n\n10 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nCutaneous malignancies are increased in\nindividuals with total, occupational, and\nrecreational sun exposure. Those with total and\noccupational sun exposure are at increase risk of\nhaving SCC while those with recreational exposure\nhave higher risk of MM and BCC19. The nature of\nultraviolet (UV) radiation exposure responsible for\nBCC is unclear16. However, it is noted that the risk\nof BCC is associated with ease of sun burning\nespecially during childhood16. High cumulative UV\nexposure is only related to SCC. It is expected that\nmost of the patients with SCC will be working and\nspending most of their time under the sun. However,\nwe only noted that 17.4% of our patients with SCC\nhad occupation related to constant sun exposure.\n\n\n\nThis might indicate that living in the tropics,\nwithout working constantly under the sun, increases\nthe individual risk to skin cancer. This study is\nlimited by its retrospective nature and the small\nnumber of patients. Analysis of CL, MM and other\nskin cancers were affected mainly by the small\nnumber of patients with these malignancies.\n\n\n\nIn conclusion, cutaneous malignancies in Sarawak\ndiffer from regional pattern in that CL is ranked as\nthe third commonest skin cancer. In addition,\nfemale predominance was seen in BCC, CL, MM\nand other skin cancers in Sarawak.\n\n\n\nReferences\n\n\n\n1. Gloster Jr HM, Neal K. Skin cancer in skin of color. J\nAm Acad Dermatol 2006; 55: 741-60\n\n\n\n2. Diepgen TL, Mahler V. The epidemiology of skin\ncancer. Br J Dermatol 2002; 146: 1-6\n\n\n\n3. LeBlanc WG, Vidal L, Kirsner RS, et al. Reported skin\ncancer screening of US adult workers. J Am Acad\nDermatol 2008;59: 55-63\n\n\n\n4. Koh D, Wang H, Lee J, et al. Basal cell carcinoma,\nsquamous cell carcinoma and melanoma of the skin:\nanalysis of the Singapore Cancer Registry Data 1968-\n1997. Br J Dermatol 2003; 148: 1161-1166\n\n\n\n5. Kikuchi A, Shimizu H, Nishikawa T. Clinical and\nhistopathological characteristics of basal cell\ncarcinoma in Japanese patients. Arch Dermatol 1996;\n132: 320-4\n\n\n\n6. Budhraja SN, Pillai VC, Periyanayagam WJ, et al.\nMalignant neoplasms of the skin in Pondicherry (a\nstudy of 102 cases). Indian J Cancer 1972; 9: 284-95\n\n\n\n7. Halder RM, Bang KM. Skin cancer in blacks in the\nUnited States. Dermatol Clin 1988; 6: 397-405\n\n\n\n8. Cress RD, Holly EA. Incidence of cutaneous melanoma\namong non-Hispanic whites, Hispanics, Asians, and\nblacks: an analysis of California Cancer Registry data,\n1988-1993. Cancer Causes Control 1997; 8: 246-52\n\n\n\n9. Ishihara K, Saida T, Yamamato A. Updated statistical\ndata for malignant melanoma in Japan. Int J Clin Oncol\n2001; 6: 109-16\n\n\n\n10. Isaacson C. Cancer of the skin in urban blacks of South\nAfrica. Br J Dermatol 1979; 100: 347-50\n\n\n\n11. www.sarawak.gov.my\n12. Bergfelt L, Newell GR, Sider JG, et al. Incidence and\n\n\n\nanatomic distribution of cutaneous melanoma among\nUnited States Hispanics. J Surg Oncol 1989; 40:222-6\n\n\n\n13. Weinstock MA, Horm JW. Mycosis fungoides in the\nUnited States. JAMA 1988; 260: 42-6\n\n\n\n14. Zackheim HS, Vonderheid EC, Ramsay DL, et al.\nRelative frequency of various forms of primary\ncutaneous lymphoma. J Am Acad Dermatol 2000; 43:\n793-6\n\n\n\n15. Hu SC, Chen GS, Wu CS, et al. Rates of cutaneous\nmetastases from different internal malignancies:\nexperience from a Taiwanese medical center. J Am\nAcad Dermatol 2009; 60: 379-87\n\n\n\n16. Tran H, Chen K, Shumack S. Epidemiology and\naetiology of basal cell carcinoma. Br J Dermatol 2003;\n149: 50-52\n\n\n\n17. Staples M, Marks R, Giles G. Trends in the incidence\nof nonmelanocytic skin cancer (NMSC) treated in\nAustralia 1985-95: Are primary prevention programs\nstarting to have an effect? Int J Cancer 1998; 78:144-8\n\n\n\n18. Panda S. Mycosis Fungoides: Current trend in\ndiagnosis and management. Indian J Dermatol 2007;\n52: 5-20\n\n\n\n19. Ridky TW. Nonmelanoma skin cancer. J Am Acad\nDermatol 2007; 57: 484-501\n\n\n\n\n\n\n\n\n11MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAUTOIMMUNE DISORDERS - Original Article\n\n\n\nHenoch - Sch\u00f6nlein Purpura: Relationship between \n\n\n\ncutaneous clinical manifestations with severity \n\n\n\noutcomes: A 5-year retrospective study\n\n\n\nTarita T, M Med, Lee CE, MBBS, Rohna R, MRCP\n\n\n\nAbstract\n\n\n\nBackground Hen\u00f6ch - Schonlein Purpura (HSP) is an Immunoglobulin A-mediated systemic small\nvessel vasculitis of childhood and adults. HSP usually presents with a classical tetrad of rash,\npolyarthralgia, abdominal pain, and renal disease. Complications may arise from vasculitis of\nsystemic organs.\n\n\n\nObjectives The  purpose of the study was to determine the clinical patterns of HSP and whether the\ncutaneous clinical manifestations of HSP can prognosticate the severity outcome of the disease.\n\n\n\nMethodology  We conducted a retrospective study of all patients diagnosed with HSP by\ndermatologists in Selayang Hospital between January 2003 and December 2007. The data were\nobtained from the case records and analyzed with regard to age, sex, race, associated triggering\nfactors, cutaneous clinical symptoms and signs, associated systemic clinical features and systemic\ncomplications.\n\n\n\nResults There was a total of 50 patients during this period. HSP was diagnosed more in adults than\nchildren. Fifty-four percent of patients were of Malay origin. The mean age at presentation for\nchildren was 6.6 years and 31 years for the adult group. There was an overall female preponderance\nin adults HSP. Majority (48%) of patients presented within 1 week of the onset of symptoms. The\npurpuric rashes were distributed on the trunk in 20% of cases, and on the upper limbs in 56% of\ncases. Vasculitic ulcer was part of the clinical features in 4% of cases while vasculitic blisters in 12%.\nThere was a significant association (Fisher Exact Test, p =0.02) and correlation (Pearson, p = 0.03)\nbetween the extent of skin involvement with gastrointestinal haemorrhage in the former and renal\ninvolvement in the latter. There was no significance association between vasculitic blisters or ulcer\nwith the disease severity outcomes. There was no significant difference of cutaneous presentation\nwith regards to the triggering factors of the disease.\n\n\n\nConclusion The results of our retrospective study demonstrated that the cutaneous clinical\npresentation is one of the predictive factors of renal and gastrointestinal outcomes in HSP. There was\na female preponderance among HSP in adults patients with a low occurrence of articular syndromes\n\n\n\nKeywords Henoch Sch\u00f6nlein Purpura, Leucocytoclastic Vasculitis\n\n\n\nCorrespondence\nDr Tarita Taib, M Med\nDepartment of Dermatology, Selayang Hospital\nLebuhraya Selayang-Kepong, 68100 Batu Caves, Selangor\nEmail : tarita@yahoo.com\nConflict of interest : Nil\n\n\n\nIntroduction\nHenoch - Schonlein Purpura (HSP) is an\nImmunoglobulin A- mediated systemic vasculitis of\n\n\n\nchildhood and adults. Complications arise from\nvasculitis of systemic organs. The long-term\nmorbidity of HSP is predominantly attributed to\nrenal involvement, while the short term morbidity is\nmainly attributed to gastrointestinal complication.\n\n\n\nThe rash, which occurs in all patients, is\ncharacterized clinically as palpable purpura. The\nlesions are typically nonblanching, as they\nrepresent extravasation of blood into the skin, and\nthey\n\n\n\n\n\n\n\n\n12 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nthey often occur in groups that can persist for 3 to\n10 days1. They can occur anywhere on the skin but\nare often concentrated on the lower legs and arms.\nThese vasculitic rashes may manifest with ulcer and\nvesico-bullous lesions. In children, local\nangioedema may precede the development of the\npurpura. Other cutaneous manifestations include\nskin oedema, urticaria and erythema multiforme.\n\n\n\nThe clinical manifestations of HSP are a\nconsequence of widespread leukocytoclastic\n\n\n\nvasculitis (LCV) with IgA deposition in vessel\nwalls. IgA deposition in the renal mesangium\ncauses nephritis in some patients. HSP is associated\nwith abnormalities involving IgA1 alone, but not\nIgA2. Pathogenesis may due to abnormalies in\nglycosylation of IgA1 and IgA1-receptor\ninteractions2. The histopathology reveals\nsubepidermal hemorrhages, necrotizing vasculitis\nof the small vessels of the dermis with IgA & C3\ndeposition.\n\n\n\nFigure 1 Flow-chart of the study work-process\n\n\n\n\n\n\n\n\n13MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAdult HSP is infrequently reported in adults over\nthe age of 20, is characterized by a lower frequency\nof abdominal pain and fever, and a higher frequency\nof joint symptoms, and renal involvement which\ntend be severe3,4,5,6. It has been reported that the\nspread of purpura to the trunk apart from other\nclinical factors; a recent infectious history, pyrexia,\nthe spread and biologic markers of inflammation,\nare predictive factors for renal involvement7. We\naim to study the clinical patterns of HSP referred to\nthe Dermatology Department, Selayang Hospital,\nMalaysia and to determine whether the cutaneous\nclinical signs could prognosticate the severity\noutcomes of the disease.\n\n\n\nMaterials and methods\nThis study was conducted in a retrospective - cohort\nmanner after research and ethical approval.\n\n\n\nIt included all patients with HSP who were\ndiagnosed by dermatologists in Selayang Hospital\nover a 5-year period, from January 2003 till\nDecember 2007. The diagnosis was established\nclinically in the presence of cutaneous syndrome\nwith symmetrical declivitous region non-\nthrombocytopenic purpura. The study group was\nselected by universal sampling, from the\ndepartment records which concluded the in-patient\nand out-patients census. Further data was abstracted\nfrom the Cerner system incorporated in Selayang\nHospital medical-services computers. A\nretrospective review of records had eliminated a\nfew patients diagnosed with vasculitis syndromes\nwhich mimicked HSP at initial presentations\n(Figure 1).\n\n\n\nDetails of information which was collected\nincluded the demographic data, associated\ntriggering factors, cutaneous clinical symptoms and\nsigns, associated systemic clinical features, related\nlaboratory investigations and systemic\ncomplications. The non - parametric variables\ngathered included the following; age, duration at\npresentation, haematuria, protenuria, 24 Hour-\nurinary protein, hemoglobin and anti-Streptolysin O\nTitre. Under categorical data were sex, race, stool\noccult blood, skin morphology, skin distribution\nand HSP trigger factors.\n\n\n\nThe data findings were analyzed using SPSS\n(version 14.0) statistical analysis software. The\nFisher's exact test was used for univariate analysis,\n\n\n\nand multiple logistic regression for multivariate\nanalysis. Bivariate linear correlations are used with\nnumerical data. The null hypothesis postulated were\nas following; 1) there is no relation between\ncutaneous manifestation of HSP and the severity of\nthe disease, 2) there is no relation between the\ndisease cutaneous manifestation and the various\nHSP triggering factors.\n\n\n\nAbbreviations\n\u2022 FBC full blood count\n\u2022 RP renal rofile \n\u2022 LFT liver function test \n\u2022 ESR erythrocyte sedimentation rate\n\u2022 ASOT anti-streptolysin O titre,\n\u2022 C3 complement factor 3,\n\u2022 C4 complement factor 4,\n\u2022 ANA antinuclear antibody,\n\u2022 UFEME urine full examination and\n\n\n\nmicroscopic examination,\n\u2022 GIT gastrointestinal\n\u2022 UFEME urine full examination and \n\n\n\nmicroscopic examination,\n\u2022 GIT gastrointestinal\n\n\n\nResults\nOver the 5-year period, a total 50 patients were\ndiagnosed with HSP of whom 27 (54%) were\nfemale and 23 (46%) male. The age at presentation\nranged between 4 to 65 yrs old (overall mean 31 +\n17). Among the children who comprised 10% of the\nstudy patients, the mean age at presentation was 6.2\nyears, whereas in adults it was 31 years old.\n\n\n\nOverall, 90% of patients were adults. There was\nmale preponderance in the children group with a\nmale to female ratio of 1.5:1 and a female\npreponderance in the adult group with a female to\nmale ration of 1.25: 1. Majority of patients (26%)\nseen were within the age category of 21 to 30 yrs\nold. The racial distribution for all cases of HSP was\nas follows: 54 % Malay, 28% Chinese, 12% Indian\nand 6% others (table 1).\n\n\n\nDigestive hemorrhage was found in 8 patients and\nrenal involvement of variable severity was found in\n38 patients. The age of patients who had digestive\nhaemorrhage is as following; 1 patient aged  6yrs\nold, 4 patients aged  between 20 to 24 yrs-old,  2\naged between 50 to 59 yrs old and 1 aged 64 yrs old.\nA 32 yr old Malay lady and a 20 yrs old Chinese\nman had urgent gastrointestinal endoscopy done\nwhich\n\n\n\n\n\n\n\n\n14 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nwhich demonstrated gut vasculitis. None of the\npatients reported gastrointestinal angiogram\nabnormality. 3 children (60% of total children) and\na similar percentage of adult patients had renal\ninvolvement. Chronic kidney desease secondary to\nIg A nehropathy was documented as early as 2\nmonths after disease onset in a 25 year old Indian\nlady and as late as 4 years in a 33 year old Malay\nlady. Thirty two percent of patients were\ndocumented as HSP post-Sreptococcus infection.\nHSP was associated with a Gullain Barre\nSyndrome, infective endocarditis in a case, varicella\nzoster infection, hepatocellular carcinoma in a case\nand metastatic mitotic lesions (died of myocardial\ninfarction) (Table 2). Several factors other than\nstreptococcal infection have been known to be\nassociated as triggers of HSP such as Helicobacter\npylori, various viral agents, foods, drugs, insect\nbites, vaccinations, exposure to cold and neoplastic\ndisorders.\n\n\n\nQuantitative data analysis revealed that there was a\nsignificant association (Fisher\u2019s Exact Test, p =\n0.02) between vasculitic rashes distribution on the\ntrunk and gastrointestinal haemorrhage. Correlation\nanalysis showed significant correlation (Pearson p =\n\n\n\n0.03) between distribution of vasculitic rash on\nhands with renal involvement and also significant\ncorrelation (Pearson, p = 0.03) between extent of\nvasculitic rash on the trunk and upper limbs with\nrenal involvement. Further analysis showed no\nsignificant association between cutaneous clinical\nmorphology and the severity outcomes of HSP.\nThere was also no significant difference between\nthe cutaneous clinical presentation of post-\nStreptococcus HSP and non post-Streptococcus\nHSP.\n\n\n\nThe result of fischer exact test is as follows:\n\n\n\nChi-Square Test\n\n\n\na. 1 cell (25.0%) have expected count less than 5. The minimum \nexpected count is 1.60.\n\n\n\nb. Computed only for a 2x2 table\n\n\n\nPearson Chi-Square\n\n\n\nContinuity Correctionb\n\n\n\nLikelihood Ratio\n\n\n\nFisher's Exact Test\n\n\n\nNumber of Valid Cases\n\n\n\nValue\n\n\n\n5.357a\n\n\n\n3.358\n\n\n\n4.500\n\n\n\n50\n\n\n\ndf\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\nAsymp. Sig.\n(2-sided)\n\n\n\n.021\n\n\n\n.067\n\n\n\n.034\n\n\n\nTable 1 Baseline demographic characteristics of study patients\n\n\n\nCharacteristics\n\n\n\nAge (mean) years\n\n\n\nAge (years)\n1 - 10\n11 - 20\n21 - 30\n31 - 40\n41 - 50\n51 - 60\n61 - 70\n\n\n\nSex\nMale\nFemale\nM: F ratio\n\n\n\nRace\nMalay\nChinese\nIndian\nOthers\n\n\n\nAdult (N = 45)\n\n\n\n31 (12 - 65)\n\n\n\n-\n10 (20%)\n13 (26%)\n9 (18%)\n3 (6%)\n7 (18%)\n3 (6%)\n\n\n\n20\n25\n0.8: 1\n\n\n\n24\n12\n6\n3\n\n\n\nChildren < 12yrs old (N = 5)\n\n\n\n6.2 (4 - 9) years\n\n\n\n5 (10%)\n\n\n\n3\n2\n1.5: 1\n\n\n\n3\n2\n0\n0\n\n\n\n\n\n\n\n\n15MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 2 Clinical manifestations of Hen\u00f6ch Schonlein Purpura\n\n\n\nClinical Presentation\n\n\n\nDuration at presentation:   \nLess than 1 week\n>/= 1 week to < 2 weeks\n>/= 2 weeks to < 1 month\n>/= 1 month\n\n\n\nCutaneous morphology:\nPalpable purpura\nVesico-bullous vasculitis\nVasculitic ulcer\n\n\n\nDistribution:\nUpper limbs\n\n\n\nHands\nForearms and arms\n\n\n\nTrunk\nLower Limbs\nGluteal  region\n\n\n\nArticular Syndrome\n\n\n\nDigestive Syndrome\n\n\n\nDigestive haemorrhage\n\n\n\nRenal involvement\n\n\n\nHSP post Streptococcus infection\n\n\n\nAssociated systemic Illness\nHepatocellular Ca\nMetastatic mitotic lesions of unknown primary\nGullain Barre Syndrome\nInfective endocarditis\nVaricella Zoster Infection\n\n\n\nNo of patients\n\n\n\n24\n7\n7\n\n\n\n12\n\n\n\n50\n6\n2\n\n\n\n28\n7\n\n\n\n25 \n\n\n\n10\n50\n21\n\n\n\n25\n\n\n\n30\n\n\n\n8\n\n\n\n38\n\n\n\n16\n\n\n\n1\n1\n1\n1\n1\n\n\n\nPercentage (%)\n\n\n\n48\n\n\n\n100\n12\n4\n\n\n\n56\n14\n50\n\n\n\n20\n100\n42\n\n\n\n50\n\n\n\n60\n\n\n\n16\n\n\n\n76\n\n\n\n32\n\n\n\nParametric correlation is used as both are categorical data\n\n\n\n* Correlation is significant at the 0.05 level (2-tailed)\n\n\n\nhand finger Pearson \nCorrelation\nSig. (2-tailed)\nN\n\n\n\nhaem + prot Pearson \nCorrelation\nSig. (2-tailed)\nN\n\n\n\nhand\nfinger\n\n\n\n1.000\n\n\n\n50.000\n\n\n\n.298*\n\n\n\n.036\n50\n\n\n\nhaem +\nprot\n\n\n\n.298*\n\n\n\n.036\n50\n\n\n\n1.000\n\n\n\n50.000\n\n\n\nCorrelation\n\n\n\n\n\n\n\n\n16 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nHenoch Schonlein Purpura was one of the\ncommonest causes of leucocytoclastic vasculitis\n(LCV) in our centre. Other common causes of LCV\ninclude drug induced, infection and connective\ntissue disease. There were 50 reported HSP cases in\nSelayang Hospital  between 2003 and 2007. \n\n\n\nThe racial predilection of HSP among the ethnic\nMalays probably reflects the pattern of racial\nattendance in the clinic. However, we believe that\nthis number was underestimated as smaller Malay\ncommunities still reside in rural areas and\nuncomplicated HSP especially among children\nwere under diagnosed. The palpable purpuric rash\nwas not the initial presenting sign in one-quarter of\npediatric case and in infants; they tend to be a\nmilder disease. Although the majority of cases were\nseen by dermatologist within 1 week of symptom,\nthere were still cases seen after months of symptom\nonset. This could be explained by the lack of\nurgency by primary care doctors in referring\npatients with suspected with HSP to the tertiary\nhospital centre.\n\n\n\nAlthough previous studies had showed male\npredominance (1.5:1)8,9, our study showed adult\nHSP had an overall female predominance (1.2:1).\nThe reason of this remains unclear. The children\ngroup however, showed male predominance.\n\n\n\nHSP is infrequent in adults over the age of 20. A\nstudy by Gedalia A et al10, showed that 75% of\npatients were between 2 to 11 years of age. Blanco\nR et al3 and Gedalia A et al found that 50% of their\nstudy population were aged l5 years or less. Adult\nHSP may manifest with blisters and necrosis\nalthough this is rare in children. None of the\nchildren in our study manifested with a vasulitic\nulcer. This is in contrast to a study by Blancho et al3\n\n\n\nwhere there was a significantly higher proportion of\ncutaneous ulcers in the adult population. Vesico-\nbullous vasculitis was found in 20% of the children\ngroup and 11% in adult group. It is worth\nmentioning that the cutaneous morphology of HSP\nin pediatric case has a tendency to become as severe\nas adult patient.\n\n\n\nOverall, our study also showed a lower incidence of\narticular syndromes. Symptoms of polyarthralgias\nwere reported to present in more than 80% of\npatients1. They most commonly affect the knees and\nankles and are often associated with edema.\n\n\n\nGastrointestinal manifestations are also common\nsymptoms in patients with HSP; including\nabdominal pain in 50%-75% of subjects, melena or\nguaiac-positive stools in 50%, haematemesis in\n30%, massive haemorrhage in 2%, and\nintussusception in 2%11,12,13. Our study showed 60%\nhad gastrointestinal involvement and 16%\ngastrointestinal haemorrhage as evidence by a\npositive of stool occult blood and decrease in\nhaemoglobin. None of our patients presented with\nmassive haemorrhage. Higher percentage (20%)\noccurrence of digestive haemorrhage was found\namong children compared to 16% in the adult\ngroup. Adult HSP is characterized by a lower\nfrequency of abdominal pain and fever, and a higher\nfrequency of joint symptoms and renal\ninvolvement3,4. These findings were challenged by a\nstudy by Blancho et al who found that adults had a\nsignificantly higher proportion of melena.\nHowever, the gastrointestinal manifestations were\nnoted to be more severe in the adult patients. Renal\ninvolvement was high in our study which reflected\nthe dominant adult patients in our study. Severity of\nhaematuria and protenuria had significant\npredictive factors for chronic kidney disease. The\nhigh number of adult HSP in our centre raised a\nconcern of long term sequelae of renal\ncomplications. Proper long term medical follow-up\nis required.\n\n\n\nA few studies have looked at the outcome and\nprognostic factors and also predictive factors of\nHSP associated with glomerulonephritis in adult\npatients5,6,7. However, as the researchers were mainly\nnephrologists, none observed the cutaneous\nmanifestation in detail. There was a significant\nassociation and correlation between extent of rash\ndistribution and severity of disease outcomes. This\nwas consistent with a study by Tancrede-Bohin E et\nal7 who showed that the spread of purpura to the\ntrunk was  one of the predictive factors of renal\ninvolvement. Our study found that there was no\nsignificant association between the severity of\ncutaneous morphology and severity disease\noutcomes. As the occurrence of these presentations\nis rare, a higher number of cases is probably\nrequired to contribute to statistical analysis\nconclusion. Lastly, the cutaneous clinical\npresentations didn\u2019t signify HSP trigger factor\nalthough isolated cases of HSP associated with\nmalignancy did demonstrate the severity in extent\nand morphology of cutaneous presentation.\n\n\n\n\n\n\n\n\n17MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAn epidemio-clinical study focusing on cutaneous\npresentation of HSP as one of the predictive factors\nof renal and gastrointestinal outcome in both adults\nand pediatric population is lacking in Malaysia.\nHence, identification of this prognostic factor may\npermit the design of future prospective studies.\n\n\n\nConclusion\nThe result of our retrospective study demonstrated\nthat the cutaneous clinical presentation is one of the\npredictive factors of renal and gastrointestinal\noutcomes in HSP. However, for more definitive\nconclusions, a prospective study would help in\nconfirming the results of our study.\n\n\n\nReferences\n\n\n\n1. Paul F.; Waller T A.; Brinker T M.; Riffe I Z et al.\nHenoch-Sch\u00f6nlein Purpura: A Review Article.\nSouthern Medical Journal 2007; 100(8) : 821-824\n\n\n\n2. Saulsbury FT. Clinical update: Henoch-Sch\u00f6nlein\npurpura. Lancet 2007; 369(9566): 976-8\n\n\n\n3. Blanco R, Martinez-Taboada VM, Rodriguez-Valverde\nV. Henoch- Sch\u00f6nlein purpura in adulthood and\nchildhood: two different expressions of the same\nsyndrome. Arthritis Rheum 1997; 40: 859-864  \n\n\n\n4. Roth R, Wilz DR, Theil GB. Sch\u00f6nlein-Henoch\nsyndrome in adults. Q J Med 1985; 55: 145-159\n\n\n\n5. Fogazzi G, Pasquali S, Moriggi M. Long-term\noutcome of Sch\u00f6nlein-Henoch nephritis in the adult.\nClin Nephrol 1989; 31(2): 60-66\n\n\n\n6. Pillebout E, Thervet E, Hill G. Henoch-Sch\u00f6nlein\npurpura in adults: outcome and prognostic factors. J\nAm Soc Nephrol 2002;13:1271-1278\n\n\n\n7. Tancrede - Bohin E. HSP in adult patients. Predictors\nfor IgA glomerulonephritis in a retrospective study of\n57 cases. Arch Dermatol 1997;133: 438-442\n\n\n\n8. Jennette JC, Falk RJ. Medical progress: small-vessel\nvasculitis. N Engl J Med 1997; 337: 1512-1523\n\n\n\n9. Piette WW. What is HSP and why should we care? Arch\nDermatol.1997; 133: 515-518\n\n\n\n10. Gedalia A. Henoch-Sch\u00f6nlein purpura. Curr\nRheumatol Rep 2004;6:195-202\n\n\n\n11. Abdel-Al YK, Hejazi Z, Majeed HA. Henoch-\nSchonlein Purpura in Arab children. Analysis of 52\ncases. Trop Geogr Med 1990; 42:52-57\n\n\n\n12. Hyams, Jeffrey S. Corticosteroids in the treatment of\ngastrointestinal disease. Curr Opin Paediatr 2000;\n12(5): 451-455\n\n\n\n13. Al-Sheyyab M, El-Shanti H, Ajlouni S. Henoch-\nSchonlein Purpura: Clinical experience and\ncontemplations on a streptococcal association. J Trop\nPaediatr 1996; 42:200-203\n\n\n\n14. Henoch-Sch\u00f6nlein purpura. Saulsbury, Frank T. MD.\nCurrent opinion in Rheumatol 2002; 13(1): 35-40\n\n\n\n15. Micki N, Thomas S B.  Henoch-Schonlein Purpura in\nan Adult. SKINmed 2003; 2(4):262-264 \n\n\n\n16. Wananukul S, Pongprasit P, Korkij W. Henoch-\nSchonlein purpura presenting as hemorrhagic vesicles\nand bullae: case report and literature review. Pediatr\nDermatol 1995; 12(4): 314-7 \n\n\n\n17. Crosby DL, Feldman SD. A pruritic vesicular eruption.\nHenoch-Schonlein purpura. Arch Dermatol 1990;\n126(11):1497-8, 1500 \n\n\n\n18. Robson WL, Leung AK. Henoch-Sch\u00f6nlein purpura.\nAdv Pediatr 1994; 41:163-194\n\n\n\n19. Mills JA, Michael BA et al. The ARA 1990 criteria for\nclassification of HSP. Athritis Rheum 1990; 33(8)\n1114-1121\n\n\n\n\n\n\n\n\n18 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nANNOUNCEMENT - Continuous Professional Development\n\n\n\n34th Annual General Meeting\n& Malaysian Dermatology\n\n\n\nCongress\n\n\n\nOrganizers\nDermatological Society of Malaysia\n\n\n\nTheme\nCutting Edge Dermatology\n\n\n\nVenue\nHotel Andaman, Langkawi\n\n\n\nDate\n10 - 13 December 2009\n\n\n\nProgram\nwebsite: www.dermatology.org.my\n\n\n\n19th Regional Congress\n\n\n\nof Dermatology\n(Asian - Australasian)\n\n\n\nOrganizers\nDermatological Society of Malaysia\n\n\n\nTheme\nDermatology without Borders\n\n\n\nVenue\nSutera Harbour Resort Hotel, Kota Kinabalu, Sabah (tentative)\n\n\n\nDate\n28th  - 31st  October 2010\n\n\n\nProgram\nIncorporation of the 2nd Meeting of the AADV\n\n\n\n\n\n\n\n\n19MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nKeywords acute cardiac failure, atopic, Churg-\nStrauss\n\n\n\nIntroduction\nChurg-Strauss syndrome is a granulomatous small-\nvessel vasculitis in which multiple organ systems\ncan be involved. It is often diagnosed late and\nphysicians need to be vigilant and keep this\nuncommon diagnosis in mind. The appearance of\nvisible cutaneous features is often the key to\ndiagnosis and skin biopsy is confirmatory. Early\nrecognition and aggressive therapy is required to\nprevent end-organ complications and mortality.\n\n\n\nCase report\nA 21 year old Chinese female event organiser\npresented with a one-month history of intermittent\nfever with myalgia, lethargy and loose stools. Her\ndiarrhoea had been persistent and she was admitted\nfor intravenous rehydration for a period of two days\nearlier in the month. Over a period of three days,\nshe developed bilateral lower limb swelling, a non-\nproductive cough with shortness of breath, and\nscattered non-painful hemorrhagic vesicles on the\nlower limbs and elbows. \n\n\n\nShe was a lifelong non-smoker and had a past\nhistory of asthma since childhood for which she has\nhad multiple admissions for exacerbations. She\nwas on inhaled beta-agonists and inhaled\ncorticosteroids. She had occasional short courses of\noral corticosteroids during flares, but had never\ntaken oral leukotriene antagonists before. She also\nhad allergic rhinitis and chronic sinusitis, for which\nshe underwent a frontal ethmoidectomy and\n\n\n\nAUTOIMMUNE DISORDERS - Case Report\n\n\n\nAcute cardiac failure in a young atopic patient\n\n\n\nPan JY1, MRCP, Yong WH2, FAMS, Audrey TWH1, FAMS\n\n\n\nfibreoptic endoscopic sinus surgery in November\n2007.\n\n\n\nOn examination, she was afebrile but tachypnoeic at\nrest. She had an elevated jugular venous pressure,\nbasal crepitations on auscultation of the lungs and\nbilateral pitting oedema of the lower limbs to the\nlevel of the knees. Her blood pressure and heart\nsounds were normal and she did not have any\nmurmurs on auscultation. Abdominal examination\nrevealed mild hepatomegaly but no splenomegaly\nand the kidneys were not ballotable. Multiple\nhemorrhagic vesicles and papules were noted on\nher feet, shins, ankles, knees and elbows (Figure 1).\nThere was no evidence of joint swelling or\nsynovitis.\n\n\n\nInvestigation\nInvestigations showed a haemoglobin value\nof  12.4 g/dL, a white blood cell count of 24.8 x\n109/L (with 15.8% eosinophils) and a platelet\ncount of 360 x 109/L. Urea, creatinine and\nelectrolytes were normal. Liver function\ntests revealed a raised alkaline phosphatase\n(139U/L) and gamma-glutamyltransferase (94U/L),\nwith hypoalbuminaemia (32g/L). Erythrocyte\nsedimentation rate (34 mg/L) and C-reactive protein\n(35.6mg/L) were both raised. Brain natriuretic\npeptide was raised (960 pg/mL). Creatinine kinase\nwas normal but Troponin I was mildly elevated\n(0.84 ug/L). Urine microscopy showed mild\nhaematuria and pyuria. \n\n\n\nThe chest X-ray showed bilateral basal pulmonary\ninfiltrates and widening of the cardiac silhouette.\nElectrocardiography revealed small voltages\ncompatible with a pericardial effusion. A skin\nbiopsy of the hemorrhagic blisters showed\nleucocytoclastic vasculitis with eosinophils in the\ndermis (Figure 2), and direct immunofluorescence\nrevealed deposits of IgM and C3 on the basement\nmembrane. The patient was negative for anti-\nnuclear antibodies and anti-neutrophil cytoplasmic\nantibodies. She had a rheumatoid factor titre of\n>200 RU/ml, and hepatitis B and C serologies were\nnegative.\n\n\n\nCorrespondence\nDr Pan Jiun Yit1, MRCP (UK)\n1National Skin Centre, Singapore\nE-mail : jypan@nsc.gov.sg\n\n\n\n2Department of Rheumatology\nAllergy and Immunology\nTan Tock Seng Hospital, Singapore\n\n\n\n\n\n\n\n\n20 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDifferential diagnosis\nGiven the presentation of hemorrhagic vesicles and\nblisters, breathlessness, pulmonary infilitrates and\npersistent gastroenteritis, the differential diagnosis\nof systemic vasculitis and hypereosinophilic\nsyndrome was considered.\n\n\n\nIn view of the long preceding history of asthma and\natopy, presence of eosinophila associated with\nevidence of a pericardial effusion and heart failure,\nraised cardiac troponins, a vasculitic lower limb\nrash and gastrointestinal symptoms, the diagnosis\nof Churg-Strauss syndrome was made.\n\n\n\nA high-resolution computerised tomography of the\nthorax revealed bilateral pulmonary infiltrates in\nthe lower lobes, and cardiomegaly with a prominent\npericardial effusion. Computerised tomography of\nthe abdomen showed multiple irregular hypodense\nlesions in the liver, spleen and kidneys suspicious of\nmicroinfarcts from small vessel vasculitis (Figure\n3). 2-dimensional echocardiography showed a\nreduced ejection fraction of 30%, with global\nhypokinesia and a moderate pericardial effusion.\n\n\n\nFigure 1 Hemorrhagic Blisters on the Feet\n\n\n\nFigure 2 Leukocytoclastic Vasculitis Figure 3 Vasculitic Infarcts in the Liver and Kidneys\n\n\n\n\n\n\n\n\n21MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nManagement and clinical course\nThe patient was initially treated with intravenous\nhydrocortisone at 100 mg 6 hourly for 2 days,\nfollowed by pulsed methylprednisolone at 500mg\ndaily for 3 days. She was also given an intravenous\ninfusion of cyclophosphamide at 700mg daily for 4\ndays.\n\n\n\nWith this treatment, the patient\u2019s symptoms\nrecovered significantly, with improvement of lower\nlimb swelling and resolution of the breathlessness\nand diarrhoea. The vasculitic lesions on her lower\nlimbs and elbows also started to resolve. She was\ndischarged on oral prednisolone 45 mg daily and\nenalapril 2.5mg twice a day. On follow-up, the\ncutaneous lesions were mostly healed with no\nscarring.\n\n\n\nDiscussion\nAllergic rhinitis, asthma, and prominent blood\neosinophilia are key features of Churg-Strauss\nsyndrome1. It is believed to be an autoimmune\nprocess due to prominent  allergic features, altered\nT-cell and humoral immunity, and vasculitis with\ncirculating IgE-containing immune complexes2.\nThe skin, lungs, gastrointestinal, kidneys,\ncardiovascular and nervous systems are often\ninvolved.\n\n\n\nAccurate diagnosis of Churg-Strauss syndrome is\ndifficult as individual features of the syndrome can\noccur in isolation, and there may be a large\ntemporal gap before additional features appear. For\nexample, in our patient, she had chronic relapsing\nasthma since childhood, together with chronic\nsinusitis which required surgery. As these\nconditions are common in our general population,\nthe attending physician may not be alerted to this\nunderlying condition until other symptoms occur.\n\n\n\nIn 1990, the American College of Rheumatology\n(ACR) developed the following criteria3 to\ncharacterize Churg-Strauss syndrome: (1) asthma,\n(2) blood eosinophilia > 10% (differential leukocyte\ncount), (3) mononeuropathy / polyneuropathy, (4)\nmigratory lung infiltrates, (5) paranasal sinus\nabnormalities, and (6) histology showing a blood\nvessel with extravascular granulomas. The finding\nof 4 of the 6 criteria has a sensitivity of 85% and a\nspecificity of 99.7% in the diagnosis of Churg-\nStrauss syndrome.\n\n\n\nThe clinical course occurs in 3 phases. The\nprodromal phase usually occurs when the patient is\nin his twenties or thirties, presenting with late-onset\nrespiratory atopy: (allergic rhinitis and asthma)\nwhich is often severe. However, our patient had\nasthma from a very young age (3 years old)\nrequiring multiple admissions, together with\nallergic rhinitis and sinusitis.\n\n\n\nAsthma severity and the number of exacerbations\nmay increase as the prodromal phase progresses.\nHowever, prolonged treatment of asthma may\npartially suppress the signs of untreated Churg-\nStrauss syndrome, and the disease may not be\nobvious until glucocorticoids are stopped, or\nsubstituted for a leukotriene receptor antagonist4.\nLeukotriene type I receptor antagonists like\nmontelukast block production of LTC4, LTD4, and\n\n\n\nLTE4 without affecting LTB4 receptors5. This results\n\n\n\nin unopposed LTB4 activity and chemoattraction for\n\n\n\neosinophils and neutrophils6. This mechanism has\nbeen postulated to be important in the pathogenesis\nof Churg-Strauss syndrome. Our patient did not\nhave any history of leukotriene antagonist usage,\nbut received about three short courses of oral\nprednisolone every year for the treatment of asthma\nexacerbations.\n\n\n\nThe second or eosinophilic phase is characterized\nby prominent blood eosinophilia. Multiple organs\nincluding the lung and gastrointestinal tract may be\ninfiltrated by eosinophils. The eosinophilia that was\ndetected on the full blood count examination of our\npatient during her previous admissions was\nattributed to her history of atopy and asthma, with\ncorticosteroid-induced reductions in eosinophil\ncounts.\n\n\n\nThe third phase or vasculitic phase usually occurs in\nthe mid-thirties to forties. Systemic vasculitis of the\nsmall and medium vessels may occur, leading to\ncutaneous, coronary and mesenteric vasculitis, lung\ninfiltrates, pericarditis, peripheral neuropathy, and\neosinophilic gastroenteritis. Our patient probably\nentered the vasculitic phase over a month\u2019s period,\nwhere she developed fever, breathlessness and\npersistent diarrhea due to eosinophilic\ngastroenteritis, culminating in the symptoms of\ncardiac failure and hemorrhagic papules and\nblisters on the legs over the duration of three days.\nThe cutaneous manifestations were instrumental in\nalerting the attending physician to the possibility of\nChurg\n\n\n\n\n\n\n\n\n22 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nChurg-Strauss Syndrome and the histological\nfindings of leucocytoclastic vasculitis were\nsupportive of this diagnosis.\n\n\n\nThe cutaneous manifestations of Churg-Strauss\nsyndrome are protean, ranging from erythema\nmultiforme-like lesions, to petechiae, purpura and\necchymosis, urticarial wheals, and tender\nsubcutaneous nodules7. Two-thirds of patients in the\nvasculitic phase of disease have cutaneous lesions.\nThe classic histologic findings are eosinophilic\ngranulomas surrounded by macrophages and giant\ncells. These granulomas are the reason for the\nclassical description of Churg-Strauss syndrome -\n`allergic granulomatous angiitis\u20198. A small vessel\nnecrotizing vasculitis may be also be commonly\nfound Cardiovascular disease is a frequent cause of\nmortality in Churg-Strauss syndrome9. Our patient\nhad evidence of pericarditis, pericardial effusion,\nmyocardial injury with elevated cardiac troponins\nand heart failure with a reduced ejection fraction.\nEarly corticosteroid and azathioprine therapy has\nbeen shown to halt worsening of biventricular\nfunction, leading to resolution of pericardial\neffusions10. Our patient responded well to the\nmethylprednisolone and cyclophosphamide regime\ndescribed above.\n\n\n\nAllergic rhinitis is extremely common8. Other\nforms of nasal and sinus involvement include\nrecurrent sinusitis and nasal polyposis.\nExophthalmos, deafmess, chronic otitis, and\neosinophilic granulomatous infiltration of the skull\nbase are rare late complications. Necrotizing\nlesions of the nasopharynx and upper airway are\nuncommon compared to Wegener Granulomatosis11.\n\n\n\nPeripheral neuropathy or mononeuritis multiplex\nmay occur in up to 75% of patients12, which may\nworsen to involve multiple nerves if untreated13.\nCerebral hemorrhage and infarction are important\ncauses of death. Joint and muscle involvement are\nrare.\n\n\n\nAbout 27% of patients have kidney involvement14.\nDisease severity ranges from proteinuria and\nmicroscopic hematuria to renal insufficiency.\nHowever, renal failure is uncommon and occurs in\nless than 10% of patients, unlike Wegener\u2019s\ngranulomatosis15. Renal infarction may result in\nsecondary hypertension. Our patient had mild\nhematuria on urine microscopy, but blood pressure\nwas normal. \n\n\n\nAn eosinophilic gastroenteritis may occur,\npresenting with abdominal pain, diarrhoea, or\ngastrointestinal bleeding. This may precede the\nvasculitic phase of Churg-Strauss syndrome. Our\npatient had diarrhoea of a month\u2019s duration\npreceding the onset of the vasculitic rash and was\ninitially thought to have an infective gastroenteritis.\n\n\n\nSystemic corticosteroids are the cornerstone of\ntherapy, usually at high doses of 0.5-1.5 mg/kg/day\nfor 6-12 weeks. Higher doses are needed for\npatients with neuropathy, cardiac or renal\nimpairment. Eosinophil count and erythrocyte\nsedimentation rate can be used to monitor response\nto treatment and to detect relapses. Late relapses\nafter a successful response to treatment are rare.\n\n\n\nCyclophosphamide, azathioprine and high dose\nintravenous immune globulin are useful in severe\ndisease, including fulminant glomerulonephritis not\nresponding to corticosteroids16. Glucocorticoids\ncombined with interferon-alpha have been reported\nto be beneficial17. Plasma exchange has not been\ndemonstrated to be useful18. Anti-IgE (omalizumab)\nwas reported to improve lung function and decrease\nabsolute eosinophil counts in a single patient19, but\nmore studies are required.\n\n\n\nMost deaths occur in the vasculitic phase of the\ndisease, and are most often due to heart failure or\nmyocardial infarction, cerebral bleeding, kidney\nfailure, gastrointestinal bleeding or status\nasthmaticus. The presence of significant cardiac or\ngastrointestinal disease is the strongest indicator of\npoor prognosis20, and both are present in our patient.\n\n\n\nConclusion\nChurg-Strauss syndrome is a multisystem disorder\nin which the diagnosis is easily missed in the early\nstages. Dermatologists should consider this\ndiagnosis in atopic patients with unexplained\npersistent eosinophilia who develop features of\ncutaneous vasculitis and other systemic symptoms.\nCutaneous manifestations of Churg-Strauss\nsyndrome, in combination with other symptoms of\nthe disease, were crucial in alerting the attending\nphysician to this important diagnosis. Our patient\nhas some indicators of poor prognosis and should\nbe followed up closely to monitor for relapses.\n\n\n\n\n\n\n\n\n23MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nReferences\n\n\n\n1. Churg J, Strauss L. Allergic granulomatosis, allergic\nangiitis, and periarteritis nodosa. Am J Pathol 1951;\n27:277-301\n\n\n\n2. Hellmich, B, Ehlers, S, Csernok, E, Gross, WL. Update\non the pathogenesis of Churg-Strauss syndrome. Clin\nExp Rheumatol 2003; 21:S69\n\n\n\n3. Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA,\nArend WP, et al. The American College of\nRheumatology 1990 criteria for the classification of\nChurg-Strauss syndrome (allergic granulomatosis and\nangiitis). Arthritis  Rheum. Aug 1990; 33(8):1094-100\n\n\n\n4. Wechsler, ME, Garpestad, E, Flier, SF, et al. Pulmonary\ninfiltrates, eosinophilia, and cardiomyopathy following\ncorticosteroid withdrawal in patients with asthma\nreceiving zafirlukast. JAMA 1998;279:455\n\n\n\n5. Drazen JM, Israel E, O\u2019Byrne PM. Treatment of\nasthma with drugs modifying the leukotriene pathway.\nN Engl J Med. 1999;340:197-203\n\n\n\n6. Crooks SW, Stockley RA. Leukotriene B4. Int J\nBiochem Cell Biol. 1998;30:173-178\n\n\n\n7. Schwartz, RA, Churg, J. Churg-Strauss syndrome. Br J\nDermatol 1992;127:199\n\n\n\n8. Chumbley LC, Harrison EG Jr, DeRemee RA: Allergic\ngranulomatosis and angiitis (Churg-Strauss syndrome):\nReport and analysis of 30 cases. Mayo Clin Proc\n52:477-484, 1977\n\n\n\n9. Hasley, PB, Follansbee, WP, Coulehan, JL. Cardiac\nmanifestations of Churg-Strauss syndrome: Report of a\ncase and review of the literature. Am Heart J 1990;\n120:996\n\n\n\n10. Uren NG, Hammond PJ. Myopericarditis in Churg-\nStrauss syndrome. Texas Heart Institute Journal\n1991;18:127-31\n\n\n\n11. Specks, U. Pulmonary vasculitis. In: Interstitial Lung\nDisease, 4th ed, King, TE Jr, Schwarz, MI (Eds), BC\nDecker, Hamilton, ON 2003. p. 615\n\n\n\n12. Guillevin, L, Cohen, P, Gayraud, M, et al. Churg-\nStrauss syndrome. Clinical study and long-term follow-\nup of 96 patients. Medicine (Baltimore) 1999;78:26\n\n\n\n13. Hattori, N, Ichimura, M, Nagamatsu, M, et al.\nClinicopathological features of Churg-Strauss\nsyndrome-associated neuropathy. Brain 1999; 122\n(Pt 3):427\n\n\n\n14. Sinico RA, Di Toma L, Maggiore U, et al. Renal\ninvolvement in Churg-Strauss syndrome. Am J Kidney\nDis 2006; 47:770-779\n\n\n\n15. Clutterbuck, EJ, Evans, DJ, Pusey, CD. Renal\ninvolvement in Churg-Strauss syndrome. Nephrol Dial\nTransplant 1990; 5:161\n\n\n\n16. Hellmich, B, Gross, WL. Recent progress in the\npharmacotherapy of Churg-Strauss syndrome. Expert\nOpin Pharmacother 2004;5:25\n\n\n\n17. Tatsis, E, Schnabel, A, Gross, WL. Interferon-alpha\ntreatment of four patients with the Churg-Strauss\nsyndrome. Ann Intern Med 1998;129:370\n\n\n\n18. Guillevin, L, Cevallos, R, Durand-Gasselin, B, et al.\nTreatment of glomerulonephritis in microscopic\npolyangiitis and Churg-Strauss syndrome. Indications\nof plasma exchanges, meta-analysis of 2 randomized\nstudies on 140 patients, 32 with glomerulonephritis.\nAnn Med Interne (Paris) 1997;148:198\n\n\n\n19. Giavina-Bianchi, P, Giavina-Bianchi, M, Agondi, R,\nKalil, J. Three months' administration of anti-IgE to a\npatient with Churg-Strauss syndrome. J Allergy Clin\nImmunol 2007;119:1279\n\n\n\n20. Guillevin, L, Cohen, P, Gayraud, M, et al. Churg-\nStrauss syndrome. Clinical study and long-term follow-\nup of 96 patients. Medicine (Baltimore) 1999;78:26\n\n\n\n\n\n\n\n\n24 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nANNOUNCEMENT - Administrative Update\n\n\n\nPain as a 5th vital sign\n\n\n\nMary SC, MMed (anaes)\n\n\n\nMinistry of Health Malaysia has introduced\npain as a 5th vital sign this year. It is\nparticularly relevant in Toxic Epidermal\nNecrolysis where uncontrolled pain may have\nsevere systemic consequences and increases\nmorbidity and mortality. \n\n\n\nRegular analgesia may be required for severe\npain, given 1/2 hr prior to dressing. DF118,\nTramadol morphine may be considered.\n\n\n\nSelf-administered analgesia i.e. PCA (patient\ncontrolled analgesia) with morphine may be\nindicated if patient is in severe pain.\n\n\n\nAfter administering analgesia, we need to re-\nassess the patient. Increasing the dose of\nanalgesia or changing to other analgesic may\nbe required if the patient continues to have\nsevere pain. Assess pain score on admission\nto assess the severity of pain (baseline score),\n1/2 an hour after analgesics given to assess\nanalgesic action and every time vital signs\ntaken (4 hourly) as the 5th vital sign.\n\n\n\nCorrespondence\nDr Mary Suma Cardosa \nDepartment of Anaesthesia\nSelayang Hospital, Selangor, Malaysia  \nEmail : mary.cardosa@gmail.com\n\n\n\n\n\n"
"\n\nDermatology\nMalaysian Journal of\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nVolume 29   \u2022  Dec 2012   \u2022   ISSN: 1511-5356\n\n\n\nwww.dermatology.org.myIndexed in: Western Pacific Research Index Medicus\n\n\n\nP E R S A T U A N  D E R M A T O L O G I  M A L A Y S I A   \u2022   D E R M A T O L O G I C A L  S O C I E T Y  O F  M A L A Y S I A\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ni \u2022   MJD 2012 Dec Vol 29\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the form of \noriginal articles, research papers, case reports and correspondence.  \nContributions are accepted for publication on condition that they \nare submitted exclusively to the Malaysian Journal of Dermatology. \nThe Publisher and Editors cannot be held responsible for errors or \nany consequences arising from the use of information contained in \nthis journal; the views and opinions expressed do not necessarily \nreflect those of the publisher and Editors, neither does the \npublication of advertisements constitute any endorsement by the \npublisher.\n\n\n\nManuscripts should be submitted via email:\nrohnaridzwan@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to me at: rohnaridzwan@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than three \nillustrations. This category offers a means for rapid communication \nabout a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation. This \ncategory provides rapid publications and is meant to be a succinct \npresentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and pathological \nphotographs in color. The diagnosis and legends for the \nphotographs should be listed after the references in the article. The \narticle should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article types \nmay include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an Introduction, \nMaterials and Methods, Results, Comment, and References. A \nStructured Abstract of not more than 240 words must be included. \nIt should consist of four paragraphs, labelled Background, \nMethods, Results, and Conclusions. It should describe the problem \nstudies, how the study was performed, the main results, and what \nthe author(s) concluded from the results. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and \nsummarizes the existing knowledge in a particular field. It should \nnot be an exhaustive review of the literature, and references should \nnot exceed 100 in number. Tables, diagrams, and selected figures \nare often helpful. The length is left to the judgment of the author, \nalthough it generally should not exceed 5000 words. Topics may \ninclude updates in clinically relevant basic science and cutaneous \nbiology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the \npaper, the author(s)\u2019 name(s), degrees, and affiliation(s), the \ncategory of the article, the number of figures and tables, and \nthree key words for indexing purposes. The name and full postal \naddress (including a street address), phone and fax numbers \nand an email address of the corresponding author who will be \nresponsible for reading the proofs must also be given on the title \npage. The author(s) must also declare any affiliation or significant \nfinancial involvement in any organizations or entity with a direct \nfinancial interest in the subject matter or materials discussed in the \nmanuscript on this page. \n\n\n\nAll measurements should be according to the metric system. If \nconfusion could result, please include other measurement systems \nin parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in the \nmanuscript. References from journals should include: (1) name(s) \nfollowed by the initials of the author(s), up to four authors: if more \nthan four authors, include the first three authors followed by et al.; \n(2) title of paper; (3) title of the journal as abbreviated in the Index \nMedicus; (4) year of publication; (5) volume number; (6) first and \nfinal page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A Hospital \nKuala Lumpur experience. M J Dermatol 2006;19:52-55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); (2) \nchapter (if any) book titles; (3) edition, volume, etc.; (4) place of \npublication; (5) publisher; (6) year; (7) page(s) referred to. \n\n\n\nFor example: \nFoong HBB. Transcontinental Dermatology: Virtual Grand \nRounds. In: Wootton R and Oakley A, editors. Teledermatology. \nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on separate \npages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of photomicrographs, \nthe stain type and original magnification should be stated. Each \nfigure should bear a reference number corresponding to a similar \nnumber in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for errors or \nany consequences arising from the use of information contained in \nthis journal; the views and opinions expressed do not necessarily \nreflect those of the publisher and Editors, neither does the \npublication of advertisements constitute any endorsement by the \npublisher and Editors of the products advertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\niiMJD 2012 Dec Vol 29   \u2022\n\n\n\nEditor-in-Chief     \nRohna Ridzwan, MRCP\nEmail: rohnaridzwan@yahoo.com\n\n\n\nEditorial Office \nMalaysian Dermatological Society \nRumah Dermatology\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur\nMalaysia\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP, Kuala Lumpur\nHenry Foong Boon Bee, FRCP, Ipoh Perak\nChan Lee Chin, MMed, Penang\nAgnes Heng Yoke Hui, MRCP, Ipoh Perak\n   \nFounding Editor\nSteven Chow Kim Wing, FRCPI\n\n\n\nDermatological Society of Malaysia / Persatuan Dermatologi Malaysia     \n\n\n\nExecutive Staff\nNajeeb Ahmad Safdar, MRCP  President \nKoh Chuan Keng, MRCP  Past President \nHenry Foong Boon Bee, FRCP  Vice President  \nAgnes Heng Yoke Hui, MRCP  Secretary\nNoor Zalmy Azizan, MRCP  Treasurer\nRohna Ridzwan, MRCP\nChan Lee Chin, MMed\nMd Noh Idris, MRCP\nKhaw Guat Ee, MRCP\n\n\n\nMalaysian Dermatological Society\nRumah Dermatolgy\n2-16, 16th floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur\nMalaysia\n\n\n\nIntroduction of internet world wide has \n\n\n\nincreased the patients\u2019 awareness of their own \n\n\n\nillness and this has led to an increase in their \n\n\n\ncuriosity in the way doctors manage them. \n\n\n\nProviding immediate therapy is insufficient to \n\n\n\nthe present patients who aspect their frontline \n\n\n\ndermatology care clinician to investigate and \n\n\n\nascertain the cause of their illness especially \n\n\n\nthose with eczema. In today\u2019s review article, \n\n\n\nwe have a Polish dermatologist Dr. Radoslaw \n\n\n\nSpiewak discussing on epidemiology of eczema. \n\n\n\nWe welcome you to share your views and \n\n\n\nfeedback on the articles in this journal. \n\n\n\neditorial\nDermatology Practice in the 21st Century\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009\n(July and December issues)\nPrinted by Percetakan Sri Jaya, No. 27, Jalan Emas SD 5/1A, Bandar Sri Damansara,\n52200 Kuala Lumpur\n\n\n\n\u00a9 2012 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nThe inclusion of an advertisement in MJD is not to be construed or publicized as an \nendorsement or approval by the Society of any product, service, or company; nor may the \nadvertiser represent that its advertising claims have been approved or endorsed by the Society.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\niii \u2022   MJD 2012 Dec Vol 29\n\n\n\nDermatologists and \nallergists may greatly \nbenefit from this \n\u201cepidemiological \napproach\u201d in case \nof diseases from the \nspectrum dermatitis \nand eczema, a \nheterogeneous group \nof diseases with similar \nclinical appearance.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1MJD 2012 Dec Vol 29   \u2022\n\n\n\nAgnieszka Dorynska1, MSc, MPH,\nRadoslaw Spiewak1,2, MD, PhD, Professor of Experimental Dermatology\n\n\n\nEpidemiology of Skin Diseases \nfrom the Spectrum of Dermatitis\nand Eczema\n\n\n\nAbstract\nParticular types of eczema may affect up to 29% individuals in certain populations \n\n\n\n(lifetime prevalence), thus placing the diseases among most frequent clinical problems. \n\n\n\nNevertheless, diseases from the spectrum of dermatitis and eczema are poorly defined \n\n\n\nand frequently misdiagnosed; they also frequently overlap, making the diagnostic \n\n\n\nprocess even more difficult. In doubtful cases, where no further means of clinical \n\n\n\nor laboratory differentiation are available, reliable epidemiological data may provide \n\n\n\nrelevant help in the diagnostic process, as the best candidate for a tentative diagnosis \n\n\n\nseems the most frequent among diseases in question, which can be verified later by \n\n\n\nthe effectiveness of respective treatment regimen. However, results of epidemiological \n\n\n\nstudies in the field of eczema and dermatitis may be strikingly contradictory, one \n\n\n\nof the possible reasons being definitions of various types of eczema/dermatitis \n\n\n\nthat leave too much space for individual decision and thus seem hardly suitable for \n\n\n\nepidemiological research. Better studies based on unequivocal definitions of various \n\n\n\ntypes of eczema are necessary to achieve the quality of epidemiological data that \n\n\n\nwould ensure the level of certainty expected from a diagnostic tool. The present \n\n\n\npaper collates results from available epidemiological data on various types of eczema: \n\n\n\natopic eczema, allergic and irritant contact dermatitis, protein contact dermatitis, \n\n\n\nseborrhoeic dermatitis, asteatotic dermatitis, stasis dermatitis, nummular eczema, \n\n\n\ndyshidrotic eczema (pompholyx), hand dermatitis and occupational dermatitis. \n\n\n\nProblems and possible sources of bias in available studies are addressed and discussed \n\n\n\nalong with the results from the studies.\n\n\n\nKeywords: epidemiology; atopic eczema; allergic and irritant contact dermatitis; protein \ncontact dermatitis; seborrhoeic dermatitis; asteatotic dermatitis; stasis dermatitis; \nnummular eczema; dyshidrotic eczema; pompholyx; hand dermatitis; occupational \ndermatitis\n\n\n\nCorrespondence\nRadoslaw Spiewak\n1 Institute of Dermatology, Krakow, Poland\n2 Department of Experimental Dermatology and Cosmetology, Faculty of Pharmacy\nJagiellonian University Medical College ul. Medyczna 9, 30-688 Krakow, Poland\nTel: +48 601 22 48 13   Fax: +48 12 416 62 62\nEmail: spiewak.eu@gmail.com\n\n\n\nREVIEW ARTICLE\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 \u2022   MJD 2012 Dec Vol 29\n\n\n\nIntroduction\nThe knowledge of the frequency of diseases is important \nfor policy makers, insurers, but it is also a very important \ndiagnostic tool in the hand of a clinician. In a considerable \ngroup of patients the clinical picture does not allow for \na clear-cut diagnosis, and after exhausting all available \npossibilities of differential diagnosis the clinician is stuck \nwith two or more possible diagnoses.\n\n\n\nIn such cases, the knowledge of epidemiology may be \nresorted to as the ultimate instance of clinical decision. \nKnowing the prevalence rates of otherwise equally possible \ndiseases that come in question, it seems rational to pick \nthe more prevalent disease as the tentative diagnosis, with \na possible revision if appropriate treatment turns out \nineffective.\n\n\n\nEczema \n(synonym: dermatitis) is noncontagious inflammation \nof the epidermis and dermis with characteristic clinical \nfeatures (itch, erythema, papule, seropapule, vesicle, \nscale, squame, crust or lichenification that emerge \nsimultaneously or evolve from one another) and distinct \nhistological picture (spongiosis, acanthosis, parakeratosis, \nlymphocytic and granulocytic infiltrates)1, 2. \n\n\n\nThe debate on the differences between the terms \u201ceczema\u201d \nand \u201cdermatitis\u201d has been ongoing for many decades, \nwith no definite conclusion3, 4. Therefore, in the present \narticle these terms will be considered as synonyms. The \nclinical spectrum of dermatitis/eczema diseases includes \nan array of diseases that sometimes are depicted as \nmutual opposites, however, their clinical features and \npathomechanisms overlap to an extent making any clear-\ncut differentiation virtually impossible.\n\n\n\nIn epidemiological studies of the various dermatitides, \nmost striking is the difficulty of drawing general \nconclusions, mainly due to imprecise definitions and \nincompatible outcome measures. This must be born in \nmind when looking at the epidemiological data discussed \nbelow. \n\n\n\nIn the analysis of diseases frequency, it is crucial \nto remember that different methods of collecting \nepidemiological data may give different outcomes. The \nmost popular method to obtain epidemiological data on \ndiseases is self-administered questionnaire. This method \nhas some advantages, which are very important when \nconducting an epidemiological research: it is inexpensive \nand easy to use, so it can be applied in large populations. \n\n\n\nDisadvantages of the questionnaire-based method \nare also very significant, especially the possibility of \nmisunderstanding the questions which may lead to the \nprobability of overestimation of the obtained results5.\n\n\n\nAnother method for assessing the frequency of diseases \nis medical examination. This method seems more \nobjective and thus more reliable because it allows for \nverification of symptoms by a specialist. In comparison \nto the questionnaire-based method, medical examination \nrequires much more costs and time for performing6. \nMoreover, when comparing these two methods of \ncollecting epidemiological data, it is important to \nremember that questionnaire-based method is more \nsuitable for collecting information about prevalence of \ndiseases over a period  of time (e.g., lifetime prevalence or \none-year prevalence), while medical examination is more \nappropriate for  assessing the presence of the disease at a \nparticular point in time (point prevalence)7. Thus these \nmethods should be regarded as complementary.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2012 Dec Vol 29   \u2022\n\n\n\nSome estimates about the frequency of diseases come from \nvarious registers, such as hospital records, national or \nlocal statistics (e.g. occupational diseases statistics). This \n\u201cecological\u201d (i.e. not consuming new resources) method \nhas its advantages, for example it allows for comparison \nof trends at different time points. However, discrepancies \nmay arise due to different classifications of diseases used \nin various data collecting systems, or in various periods of \ntime. \n\n\n\nA major possible disadvantage of using the \u201cepidemiological \napproach\u201d in clinical diagnosis is that of a \u201cself-fulfilling \nprophecy\u201d: With poor-quality epidemiological data at the \nstart, one may classify unclear cases of eczema for this \ntype that is believed to be most frequent, which may not \nnecessarily be the truth, however, by doing so the statistics \nare biased toward the tentative diagnosis, thus reinforcing \none\u2019s beliefs into seemingly \u201cscientific proof\u201d. It seems that \nthis is especially true for the diseases from the spectrum of \ndermatitis and eczema. \n\n\n\nTherefore, it is extremely important to be critical when \nlooking at the frequency rates of diseases from the spectrum \nof dermatitis and eczema. The differences in definitions of \nthe diseases in various studies or sometimes lack of any \ndefinitions, strongly supports this attitude. In this article, \nin order to be able to collate available epidemiological data, \nwe have adopted a simplistic attitude that the diagnosis \nof a given disease is defined by the authors\u2019 declaration \n(i.e. belief) that they studied this particular disease. The \nfollowing data, therefore, give us some idea about possible \nprevalence rates, however, due caution is recommended \nwhile using them for \u201cepidemiological\u201d diagnosis.\n\n\n\nAtopic eczema\n(AE, synonym: atopic dermatitis) is a chronic inflammatory \nskin disease that commonly begins in early infancy, runs a \ncourse of exacerbations and remissions, and is associated \nwith a characteristic distribution and morphology of skin \nlesions. Furthermore, pruritus and subsequent sleeplessness \nare hallmarks of this disease8. This \u201cminimalist\u201d definition \nseems most acceptable for the time being, as it puts \nforward the common clinical characteristics while avoiding \nreferences to pathomechanisms, which are still subject to \ncontroversy (see below). \n\n\n\nPrevalence of atopic dermatitis/eczema in children has been \nwidely assessed. The most known epidemiological study \non atopic eczema (AE) in children is the ISAAC Study9. \nThis questionnaire-based study allows estimating one-year \n\n\n\nand lifetime prevalence rates of AE among children. Table \n1 presents prevalence rates of atopic eczema according to \nstudies based on the ISAAC questionnaire. Both indices of \nthe disease frequency (one-year prevalence, and lifetime \nprevalence) showed great variability in the estimations \namong countries ranging from 4.5% to 20.2% (1-year \nprevalence) and from 2.4% to 28.7% (lifetime prevalence) \n10-12.\n\n\n\nHowever, there has been a heated discussion on how reliable \nis the ISAAC questionnaire in detecting AE13,14, with recent \ndata showing  that up to 50% of children with \u2018ISAAC \neczema\u2019 may in fact be ill with allergic contact dermatitis \n(ACD)15. Flexural eczema - almost a \u201cdiagnostic fetish\u201d \nin past epidemiological studies of AE has turned out less \nspecific to AE than previously believed16, not least so because \nthis clinical feature is also common in ACD17-21, and cases \nof ACD-related flexural eczema have been misdiagnosed as \nAE for decades22, 23. With this respect, ISAAC studies may \nbe looked at as an example of the \u201cself-fulfilling prophecy\u201d \nin the epidemiology of eczema in children. In order to \novercome these limitations, other methods were also used \nwhen assessing the frequency of AE. \n\n\n\nDetailed information on the prevalence of AE in children \naccording to studies not based on the ISAAC questionnaire \nis shown in Table 2. Less is known on the prevalence of \nAE in adults - available data are collated in Table 3. The \nmajor problem with the epidemiological data of AE is that \n\u201catopic eczema\u201d seems in fact to be a heterogeneous group \nof diseases with similar clinical appearance, rather than a \nsingle disease. \n\n\n\nThe spectrum of involved pathologies range from type I \nand IV allergy (possibly also types II and III), to barrier \ndysfunction, abnormalities of the innate immune response \nand autoimmunity, while it remains unclear, which of those \nare actual causes and which secondary phenomena24-27. For \nexample, the causal role of IgE-mediated food allergy in AE \nseems overrated28, 29 and the development of food-specific \nIgE may, in fact, be secondary to eczema30.\n\n\n\nThe name \u201catopic dermatitis\u201d itself was already criticized by \nRajka in 1975 as an \u201cunfortunate choice of term\u201d31, which is \nsupported by the fact that a majority of AE patients show \nno evidence of atopy32. Perhaps \u201cHanifin-Rajka Syndrome\u201d \nwould be a more appropriate name for this entity, avoiding \nthe reference to questionable aetiology and focusing \ninstead on the common clinical picture first compiled by \nthe authors.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 \u2022   MJD 2012 Dec Vol 29\n\n\n\n* prevalence rates were estimated using questions about presence of an itchy rash in the past 12 months and lifetime symptoms of an itchy rash\n** prevalence rates were estimated using questions about presence of dry itchy skin spots in the last 12 months and at any time\n^ calculated based on the figures provided by the authors\n\n\n\nTable 1  Prevalence rates of atopic dermatitis in children according to studies based on the ISAAC questionnaire.\n\n\n\nCountry\n\n\n\nAustria33*\n\n\n\nBrazil34\n\n\n\nChina35\n\n\n\nChina36^\n\n\n\nCroatia37\n\n\n\nGermany38\n\n\n\nGhana39^\n\n\n\nIran40\n\n\n\nItaly41\n\n\n\nKorea42\n\n\n\nMalta43\n\n\n\nMexico44**\n\n\n\nMontenegro45\n\n\n\nPoland46\n\n\n\nSerbia45 \n\n\n\nSpain47\n\n\n\nSpain48\n\n\n\nSweden49\n\n\n\nUnited Kingdom50\n\n\n\nGender of\nchildren\n\n\n\nBoys\nGirls\nBoys\nGirls\nBoys and girls\nBoys and girls\nBoys and girls\nBoys and girls\nBoys\nGirls\nBoys\nGirls\nBoys\nGirls\nBoys\nGirls\nBoys\nGirls\nBoys and girls\nBoys\nGirls\nBoys\nGirls\nBoys\nGirls\nBoys\nGirls\nBoys and girls\nBoys and girls\nBoys and girls\n\n\n\nBoys and girls\n\n\n\nBoys and girls\n\n\n\nBoys and girls\n\n\n\nBoys and girls\n\n\n\nBoys and girls\nBoys and girls\n\n\n\nBoys and girls\n\n\n\nBoys and girls\n\n\n\nBoys\nGirls\n\n\n\nAge of\nchildren\n\n\n\n6-9 (1995-97)\n\n\n\n6-9 (2001-03)\n\n\n\n13-14\n6-13\n0-14\n12-14\n6-7\n\n\n\n13-14\n\n\n\n6-7\n\n\n\n13-14\n\n\n\n4-16\n\n\n\n13-14\n2\n\n\n\n3\n\n\n\n4\n\n\n\n8-11\n\n\n\n13-15 (1995)\n13-15 (2000)\n6-8\n11-14\n6-8\n11-14\n6-7\n13-14\n7\n16\n6-7\n13-14\n6-7\n10-11\n1-2\n2-3\n3-4\n6-7\n7-8\n8-9\n6-7\n\n\n\nOne-year\nprevalence\n\n\n\n5.0%\n7.0%\n5.9%\n7.6%\n-\n5.5%\n-\n5.3%\n7.3%\n6.7%\n5.0%\n9.4%\n6.6%\n9.8%\n4.5%\n11.1%\n-\n\n\n\n10.1%\n16.8%\n18.7%\n16.2%\n20.2%\n19.1%\n17.2%\n12.7%\n14.5%\n12.8%\n10.1%\n10.1%\n10.5%\n5.8%\n5.4%\n9.5%\n9.1%\n-\n-\n11.2-17.2%\n8.2-16.2%\n-\n-\n15.0%\n20.2%\n20.7%\n17.8%\n16.6%\n20.7%\n-\n-\n\n\n\nLifetime\nprevalence\n\n\n\n8.2%\n10.2%\n10.2%\n11.8%\n16.2%\n-\n14.5%\n7.0%\n14.3%\n14.6%\n8.2%\n12.3%\n13.6%\n16.9%\n10.9%\n17.4%\n4.0%\n\n\n\n-\n-\n-\n-\n-\n-\n-\n26.8%\n28.7%\n11.2%\n8.5%\n15.0%\n17.0%\n7.3%\n7.0%\n-\n-\n9.4%\n3.4%\n-\n-\n5.9%\n11.4%\n16.2%\n23.7%\n25.8%\n22.5%\n21.2%\n26.1%\n27.8%\n27.0%\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2012 Dec Vol 29   \u2022\n\n\n\nTable 2  Prevalence of atopic eczema in children in various studies based on different methods.\n\n\n\nCountry\n\n\n\nDenmark51\n\n\n\nDenmark52 \n\n\n\nGabon39 \n\n\n\nGermany53\n\n\n\nGermany54\n\n\n\nGermany52\n\n\n\nGermany55\n\n\n\nGhana39^\n\n\n\nRwanda39 \n\n\n\nSpain48\n\n\n\nSweden52\n\n\n\nTurkey56\n\n\n\nUnited Kingdom57\n\n\n\nUnited States58\n\n\n\nMethod of\nassessment\n\n\n\nQ\n\n\n\nME\n\n\n\nQ\n\n\n\nME\n\n\n\nME\n\n\n\nQ\n\n\n\nQ\n\n\n\nQ\n\n\n\nME\n\n\n\nME\n\n\n\nME\n\n\n\nQ\n\n\n\nHR\n\n\n\nQ\n\n\n\nQ\n\n\n\nAge of\nchildren\n\n\n\n12-16\n\n\n\n7\n\n\n\n4-16\n\n\n\n5-7\n\n\n\n0-4\n\n\n\n7 \n\n\n\n< 10\n\n\n\n4-16\n\n\n\n4-16\n\n\n\n10-11\n\n\n\n7 \n\n\n\n0-16\n\n\n\n1-5\n\n\n\n5-9 \n\n\n\nResults\n\n\n\nlifetime prevalence: 21.3%\n(17.0% boys; 25.7% girls)\none-year prevalence: 6.7%\n(5.6% boys; 7.7% girls)\npoint prevalence: 3.6%\n(3.8% boys; 3.4% girls)\n\n\n\nlifetime prevalence: 22.9%\n\n\n\npoint prevalence: 4.0%\n\n\n\npoint prevalence: 12.9%\n\n\n\nlifetime prevalence: 21.4%\n\n\n\nlifetime prevalence: 13.1%\n\n\n\nlifetime prevalence: 13.0% (Leipzig),\n13.9% (Munich)\n\n\n\npoint prevalence: 1.6%\n\n\n\npoint prevalence:: 0.8%\n\n\n\npoint prevalence: 1.9%\n\n\n\nlifetime prevalence: 15.5%\n\n\n\nlifetime prevalence: 11.8%\n\n\n\none-year prevalence: 16.5%\n(22% in 1-2 y.o.; 19% in 2-3 y.o.;\n13% in 3-4 y.o.; 15% in 4-5 y.o.)\n\n\n\n17.2% (standard scoring criteria)\n6.8% (highly stringent criteria)\n\n\n\nQ - questionnaire; ME - medical examination; HR - hospital record         ^ own calculations based on the figures provided by the authors\n\n\n\nContact dermatitis\n(Synonym: contact eczema) is a collective term for three \ndermatitides with various aetiologies, whose common \nfeature is the development of skin inflammation in \nresponse to a direct contact with the provoking agent: 1) \nirritant contact dermatitis, 2) allergic contact dermatitis \nand 3) protein contact dermatitis66. \n\n\n\nAllergic contact dermatitis \n(Synonym: allergic contact eczema) is inflammatory skin \ndisease initiated by specific immune reaction to a hapten. \nIt occurs in individuals with previously acquired contact \nallergy following re-exposure to the sensitizing hapten67. \nIn contrast to ICD, only a minority of people exposed to \na particular hapten will respond with dermatitis. When \nlooking at epidemiological data, one must remember that \nACD is not the same as contact allergy (CA). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 \u2022   MJD 2012 Dec Vol 29\n\n\n\nThe term \u201ccontact allergy\u201d refers to a state of altered response \nof the immune system to a specific substance, which is not \nsynonymous with disease. Certain proportion of people \nwith CA will never develop clinical symptoms. Among \nthose symptomatic, vast majority will develop ACD, which \nis an inflammatory disease of the skin provoked by a hapten \n(a low molecular sensitizer), following the exposure to this \nhapten of a sensitized person68. Confusing contact allergy \nwith allergic contact dermatitis seems a frequent mistake \nof doctors and authors of clinical and epidemiological \nstudies.\n\n\n\nChildren \nA very comprehensive method of establishing the prevalence \nof ACD in children was used in the study conducted in \nDenmark. ACD in the group of 12-16 years old children was \ndefined by the co-existence of the three criteria: 1) contact \nallergy diagnosed by a positive patch test 2) exposure history \nand 3) history or present dermatitis pattern. Lifetime \nprevalence of ACD was 7.2%, and point prevalence 0.7% \n\n\n\n(calculated on the basis of data provided in the article)51. \nA Polish study showed that among 7-year old children \nthe lifetime prevalence of symptoms of ACD was slightly \nhigher than among 16-year olds (7.2% versus 6.1%)46. This \nis also reflected in higher contact hypersensitivity rates \namong children (67.0%) than adolescents (58.1%) seen in a \nsimilar cohort of Polish children69, which may be explained \nby changing exposure patterns in the rapidly westernising \ncountry70.\n\n\n\nAdults\nIn the United States, in a study of university students, ACD \nwas the cause of 3.1% of first-time visits to dermatologists, \nand 2.4% of total visits to dermatologists71. In Poland, \nprevalence of ACD was assessed among students of \nvocational agricultural schools. History and symptoms-\nbased physician diagnosis estimated the frequency of ACD \nas: 2.0% (point prevalence), 9.3% (one-year prevalence), \nand 17.5% (lifetime prevalence)65. \n\n\n\nTable 3  Prevalence rates of atopic eczema in adults.\n\n\n\nCountry\n\n\n\nAustralia59 \n\n\n\nDenmark60 \n\n\n\nGermany61 \n\n\n\nJapan62 \n\n\n\nNorway63 \n\n\n\nNorway64 \n\n\n\nPoland65\n\n\n\nRussia63\n\n\n\nMethod of\nassessment\n\n\n\nME\n\n\n\nQ\n\n\n\nQ\nME\n\n\n\nME\n\n\n\nQ\n\n\n\nQ\n\n\n\nQ\n\n\n\nME\n\n\n\nQ\n\n\n\nAge of\nchildren\n\n\n\n20+\n\n\n\n18-69\n\n\n\n0-99\n\n\n\n20+\n\n\n\n18-69\n\n\n\nborn in \n1970, 1960, \n1955, 1940-\n1941 and \n1924-1925\n\n\n\n18-19\n\n\n\n18-69\n\n\n\nResults\n\n\n\npoint prevalence: 5.7% in men, 8.1% in \nwomen\n\n\n\nlifetime prevalence: 10.0%\n\n\n\nlifetime prevalence: 23.5%\npoint prevalence: 16.0%\n\n\n\npoint prevalence: 6.9% (participants in \ntheir 20s: 9.8%; 30s: 8.7%; 40s: 4.4%; \n50/60s: 2.6%)\n\n\n\nlifetime prevalence: 13.8% in men,\n19.0% in women\n\n\n\nlifetime prevalence: 8.8%\n\n\n\nlifetime prevalence: 5.0%\none-year prevalence: 3.9%\npoint prevalence: 2.5%\n\n\n\nlifetime prevalence: 10.4% in men,\n12.0% in women\n\n\n\nQ - questionnaire; ME - medical examination\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2012 Dec Vol 29   \u2022\n\n\n\nIrritant contact dermatitis \n(ICD) is acquired inflammatory skin disease caused by \nchemical or physical insults leading to direct cellular injury. \nMost of ICD cases are associated with detergents, solvents, \nacids or alkali. Acute ICD (toxic dermatitis) develops rapidly \n(minutes to hours) after exposure to potent irritants, while \nchronic, cumulative variants of ICD develop gradually in \nresponse to repeated contacts with milder irritants72. ICD \nis essentially an injury, therefore, everyone will develop \nthis disease after an individual threshold of resistance to \nirritants is exceeded73. \n\n\n\nThe prevalence of irritant contact dermatitis (ICD) in \ngeneral population is hard to determine, especially among \nchildren. Study conducted on a group of university students \nin the United States, showed that ICD was the cause of \n2.3% of first-time visits to dermatologists, and 1.6% of \ntotal visits to dermatologists71. In Poland, estimations from \nthe study conducted among students of a vocational school \nwere: 0.5% (point prevalence), 4.3% (one-year prevalence), \nand 12.7% (lifetime prevalence)65.  \n\n\n\nProtein contact dermatitis \n(PCD) is acquired inflammatory skin disease initiated \nby specific immune reactions to allergens - proteins with \nmolecular weight exceeding 10000 Daltons, usually of animal \nor plant origin74, 75. There is lack of data on the frequency \nof protein contact dermatitis among children. Estimates \nfor adults are available only for work-related settings. In \nFinland, protein contact dermatitis (together with contact \nurticaria) accounted for 11.1% of all allergic occupational \ndiseases reported in 199176. Protein contact dermatitis was \nfound in 22% of a group of 144 slaughterhouse workers in \nDenmark77. \n\n\n\nSeborrhoeic dermatitis\nSeborrhoeic dermatitis is an inflammatory skin disease \nof the dermatitis/eczema spectrum, with a characteristic \nrestriction to \u201cseborrhoeic areas\u201d, i.e. areas with a high \ndensity of sebaceous glands (face, sternum, interscapular \narea). The aetiology remains unclear, one possibility being \nthe excessive development of lipophilic Malassezia yeasts \non the seborrheic skin with secondary development of \ninflammation in response to signalling molecules such as \nmalassezin78. \n\n\n\nLittle is known on the prevalence of seborrhoeic dermatitis. \nIn a Turkish study of paediatric patients (0-16 years old) \nin a hospital registry, 4.3% children were diagnosed with \nseborrhoeic dermatitis56. The prevalence of seborrhoeic \ndermatitis in adults was established in an Australian study \nbased on medical examination, was 12.3% in men, and \n7.3% in women59. Among university students in the USA, \n\n\n\nseborrhoeic dermatitis was the cause of 3.1% of first-time \nvisits, and of 2.4% of all dermatologist consultations71.\n\n\n\nIn a prospective, skin examination-based study of renal \ntransplant recipients in the UK, seborrhoeic dermatitis \nwas found in 9.5% of the participants79. The prevalence \nof  seborrhoeic dermatitis of the face and scalp diagnosed \namong mountain guides was 16.3%, which might hint on a \nrole of UV irradiation in these cases80. \n\n\n\nAsteatotic dermatitis\nAsteatotic dermatitis (dry skin dermatitis, winter itch) \nis an entity of unknown aetiology, characterised by the \npresence of dry, scaly, fissuring skin accompanied with \npruritus, typically localised on the calves, with a possibility \nof spreading. Among exacerbating/causative factors, skin \nageing with atrophy and xerosis, low humidity of ambient \nair, as well as frequent bathing and excessive detergent use \nare mentioned. Among Australian adults the prevalence of \ndoctor-diagnosed asteatotic dermatitis was 6.6% in men, \nand 10.4% in women59. \n\n\n\nStasis dermatitis\nStasis dermatitis is a skin manifestation of venous \ninsufficiency and frequently is accompanied by other \nsymptoms like the presence of varicous veins, leg \noedema and ulcers, hemosiderin deposits in the skin and \nliposclerosis of the skin. The typical localization is calves. \nIn the above-mentioned Australian study, the frequency of \nstasis dermatitis was assessed at 2.1% in men, and 1.5% in \nwomen59.\n\n\n\nNummular eczema\nNummular eczema (nummular dermatitis, discoid \ndermatitis) is characterized by solitary or multiple, well-\ndemarcated, round or oval-shaped itchy lesions. The typical \ncourse of the disease is chronic recurrent. The identity of \nthis disease is built based upon the characteristic clinical \nappearance; however, the aetiology remains unknown. One \nof the more popular hypotheses considers immunological \nresponse (allergic reaction type II or IV) to circulating \nantigens of bacteria, fungi or parasites. On the other hand, \nit seems that may various types of eczema may take this \nclinical appearance, e.g. atopic eczema, allergic contact \ndermatitis (to nickel, neomycin, etc.), along with asteatotic \nand stasis dermatitis. In a Turkish study utilizing data of \nhospitalised paediatric patients, 0.4% children (0-16 years \nold) were diagnosed with nummular dermatitis56.\n\n\n\nDyshidrotic eczema\nDyshidrotic eczema (pompholyx) is a non-infectious \ninflammation of the skin characterized by the appearance \nof pruritic vesicles on the palms and soles. The course of\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 \u2022   MJD 2012 Dec Vol 29\n\n\n\nTable 4  Prevalence rates of hand dermatitis/eczema.\n\n\n\nCHILDREN\n\n\n\nADULTS\n\n\n\nCountry\n\n\n\nDenmark51\n\n\n\nNorway84\n\n\n\nCountry\n\n\n\nDenmark60*\n\n\n\nNorway64\n\n\n\nPoland85\n\n\n\nSweden86\n\n\n\nSweden87\n\n\n\nSweden88*\n\n\n\nMethod of\nassessment\n\n\n\nQ\n\n\n\nME\n\n\n\nQ\nME\n\n\n\nMethod of\nassessment\n\n\n\nQ\n\n\n\nQ\n\n\n\nQ\n\n\n\nQ\nME\n\n\n\nQ\n\n\n\nQ\n\n\n\nAge of\nchildren\n\n\n\n12-16\n\n\n\n7-12\n\n\n\nAge of\nchildren\n\n\n\n18-69\n\n\n\nborn in \n1970, 1960, \n1955, 1940-\n1941 and \n1924-1925\n\n\n\n20-73\n\n\n\n20-65\n\n\n\n20-65\n\n\n\n20-77\n\n\n\nResults\n\n\n\nlifetime prevalence: 9.2%\n(6.3% boys, 12.2% girls)\none-year prevalence: 7.3%\n(4.6% boys, 10.1% girls)\npoint prevalence: 3.2%\n(2.2% boys, 4.2% girls)\n\n\n\none-year prevalence: 6.5%\npoint prevalence: 3.5%\n\n\n\nResults\n\n\n\nlifetime prevalence: 21.8%\n(17.0% men, 25.7% women)\none-year prevalence: 11.7%\n(8.9% men, 14.0% women)\n\n\n\nlifetime prevalence: 8.2%\n\n\n\nlifetime prevalence: 17.3% \none-year prevalence: 10.1% \npoint prevalence: 1.9%\n\n\n\none-year prevalence: 11.0%\npoint prevalence: 5.4%\n\n\n\none-year prevalence: 11.8% (1983) and \n9.7% (1996)\n\n\n\nlifetime prevalence: 11.0%\n(6.8% men, 14.0% women)\none-year prevalence: 6.5%\n(4.5% men, 8.1% women)\n\n\n\nQ - questionnaire; ME - medical examination         * calculated based on the figures provided by the authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9MJD 2012 Dec Vol 29   \u2022\n\n\n\nthe disease may be acute, recurrent, or chronic. The \nskin lesions frequently are restricted to areas with high \ndensity of sweat glands and frequently accompanied by \nhyperhidrosis81. However, it appears that the lesions are not \nconnected with the glands. \n\n\n\nIn the above-mentioned Turkish study, dyshidrotic eczema \nwas diagnosed in 1.0% of paediatric hospital patients (0-16 \nyears old)56. In an epidemiological study of adult Dutch \nmetalworkers, symptoms of dyshidrotic eczema were found \nin 7.3% of a group of metalworkers82. \n\n\n\nHand dermatitis\nHand dermatitis is a very special nosological entity that \nrefers to the clinical picture (dermatitis localized on the \nhands) rather, than to the cause. Hand dermatitis/eczema \nmay be a manifestation of ACD, ICD, atopic dermatitis, \nor other inflammatory diseases, which in this location are \nvery difficult to differentiate based on the clinical picture or \nmedical tests (including histopathology). A co-existence of \nmore than one causes of hand dermatitis (e.g. ACD + ICD \n+ atopic hand dermatitis) is relatively common, hence it \nseems practical to view hand dermatitis as a distinct clinical \nentity83. Prevalence rates of hand dermatitis/eczema in \nchildren and adults are shown in Table 4.\n\n\n\nOccupational dermatitis\nOccupational contact dermatitis is neither clinical nor \npathological entity; however, due to specific circumstances \nof appearance and special legal status in many countries, \ncases of such diseases are closely followed. OCD occurs \nmostly on hands (80% cases) and face (10% cases)89. The \nfrequency of occupational contact dermatitis (OCD) in the \nUnited Kingdom is estimated  as 12.9 cases per 10 thousand \nfull-time workers each year90. One-year prevalence of \noccupational hand dermatitis, depending on the method \n\n\n\nof estimation, varies from 0.5-6.7% (medical examination) \nto 8.2-10.6% (questionnaire) in different populations91. \n\n\n\nIn a study based on medical examination, 4.1% Polish \nfarmers were diagnosed with occupational hand eczema92. \nOne in three of those who stated to have hand dermatitis \never, and one in five with wrist and forearm dermatitis \nreported on exacerbations of dermatitis due to substances \npresent at workplace85. Irritant contact dermatitis (ICD) \nand allergic contact dermatitis (ACD) contribute to most \ncases of OCD. Different proportions of ICD and ACD are \nreported in studied populations - frequency of ICD varies \nfrom 32% (USA) to 71% (Australia)89. The differences \nmight reflect the diagnostic routines (most importantly the \nuse and extensiveness of patch tests).\n\n\n\nFinal remarks\nThe major disadvantage of available epidemiological studies \nof diseases from eczema and dermatitis spectrum is that \nthey depend on clinical symptoms, which are frequently \ndifficult to properly classify even by an experienced \nclinician, as clinical features and pathomechanisms of \nvarious types of eczema overlap to an extent making clear-\ncut differentiations virtually impossible. Studies based on \nself-administered questionnaires, are even more susceptible \nto bias as conclusions are built based upon patient\u2019s own \nopinions and interpretations. Furthermore, various types \nof eczema may co-exist, while most researchers and \ndoctors rest satisfied with a first diagnosis established. \nTo acquire reliable data on the epidemiology of various \ntypes of dermatitides, better studies are needed in the \nfuture based on well-defined criteria that would enable \naccurate differentiation between analysed diseases. Specific \nrequirements for such studies have been recently discussed \nelsewhere93.\n\n\n\nReference\nWeidinger S, Ring J. Diagnosis of atopic eczema. In: Ring J, 1. \nPrzybilla B, Ruzicka T, editors. Handbook of Atopic Eczema. \nSecond Edition. Berlin: Springer; 2006:84-99.\nDarsow U, Wollenberg A, Simon D, et al. ETFAD/EADV eczema 2. \ntask force 2009 position paper on diagnosis and treatment of \natopic dermatitis. J Eur Acad Dermatol Venereol 2009;24:317-\n328.\nAckerman AB, Ragaz A. A plea to expunge the word \u201ceczema\u201d 3. \nfrom the lexicon of dermatology and dermatopathology. 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Malassezia, dandruff and seborrhoeic dermatitis: an 78. \noverview. Br J Dermatol 2011;165 (Suppl 2): 2-8.\nLally A, Casabonne D, Newton R, Wojnarowska F. Seborrheic 79. \ndermatitis among Oxford renal transplant recipients. J Eur \nAcad Dermatol Venereol 2010;24:561-4.\nMoehrle M, Dennenmoser B, Schlagenhauff B, et al. High 80. \nprevalence of seborrhoeic dermatitis on the face and scalp in \nmountain guides. Dermatology 2000;201:146-7.\nWollina U. Pompholyx: a review of clinical features, differential 81. \ndiagnosis, and management. Am J Clin Dermatol 2010;11:305-\n14.\nde Boer EM, Bruynzeel DP, van Ketel WG. Dyshidrotic eczema 82. \nas an occupational dermatitis in metal workers. Contact \nDermatitis 1988;19:184-8.\nCoenraads PJ. Hand eczema is common and multifactorial. J 83. \nInvest Dermatol 2007;127:1568-70.\nDotterud LK, Falk ES. 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Curr 93. \nOpin Allergy Clin Immunol 2012 (in press).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 \u2022   MJD 2012 Dec Vol 29\n\n\n\nYin YL1, Adv M Derm,\nChew KL2, Adv M Derm\n\n\n\nA 10-Year Retrospective Review \nof Non-Scarring Alopecia in a \nTertiary Hospital in Malaysia\n\n\n\nGENERAL DERMATOLOGY - ORIGINAL ARTICLE\n\n\n\nAbstract\nBackground  Non-scarring alopecia is a common hair disorder with paucity of \n\n\n\nclinical reviews. \n\n\n\nObjectives  We aim to study the spectrum of non-scarring alopecia, its\u2019 demographic, \n\n\n\nclinical and treatment pattern among patients at University Malaya Medical Centre.\n\n\n\nMethodology We have retrospectively reviewed the demography, clinical   \n\n\n\ncharacteristics and treatment of non-scarring alopecia at University Malaya Medical \n\n\n\nCentre (UMMC). A total of 154 records were reviewed.\n\n\n\nResults A majority of patients had alopecia areata (28.6%), followed by               \n\n\n\nandrogenetic alopecia (12.3%), telogen effluvium (3.2%), tineacapitis (2.6%) and \n\n\n\nunspecified hair loss (53.2). Treatment for alopecia areata included topical steroids \n\n\n\n(53.3%), intralesional steroids (26.7%), topical minoxidil (17.8%), oral steroids \n\n\n\n(11.1%), oral finasteride (2.2%) and oral azathiopine (2.2%). Prescribed treatment \n\n\n\nfor androgenetic alopecia comprised of topical minoxidil (68.1%) or oral finasteride \n\n\n\n(10.5%).\n\n\n\nConclusion We concluded that alopecia areata was the most common cause of non-\n\n\n\nscarring alopecia diagnosed at UMMC and deduced that the high number of patients \n\n\n\ndiagnosed with unspecified hair loss was attributed to the lack of confidence amongst \n\n\n\nout-patient physicians in diagnosing the cause of alopecia.\n\n\n\nKeywords: alopecia areata, androgenetic alopecia, telogen effluvium, anagen effluvium \nand alopecia mucinosa\n\n\n\nCorrespondence\nYin Yin Lee MRCP, MMed, Adv M Derm                \n1 Sunway Medical Centre. No 5, Jalan Lagoon Selatan, Bandar Sunway\n46150, Petaling Jaya, Selangor, Malaysia\nEmail: leeyiy@sunway.com.my\n2 School of Anti-aging, Aesthetic and Regenerative Medicine, UCSI University, Malaysia;\nUniversity of Malaya\n\n\n\n\n\n\n\n\nIntroduction\nThere is a current paucity of information in non-scarring \nalopecia, especially in South-east Asia. Non-scarring \nalopecia is more common than scarring alopecia and \nincludes alopecia areata (AA), androgenetic alopecia \n(AGA), telogen effluvium, trichotillomania, tinea capitis \nand non-specific alopecia. \n\n\n\nAlopecia areata (AA)\nAA is relatively common in childhood1, 2, with a prevalence \nof 3.8% in Singapore2. It is linked to autoimmune \nendocrinopathies (e.g. type I diabetes mellitus, thyroid \ndiseases, Addison\u2019s diseases), pernicious anemia and \nvitiligo3, 4.\n\n\n\nStress is a known factor in onset and aggravation5. AA \nalso has a genetic component, with up to 20% of patients \nhaving a family history6. Onset of AA is also early, \noccurring before adulthood in 44% of patients7. \n\n\n\nAndrogenetic alopecia (AGA)\n A common cause of alopecia in adults1, AGA has a higher \nfrequency in Caucasians (approximately 50%)8 than in \nAsians9. In Korea, a prevalence of approximately 14.1% \n(Norwood types \u2265III) was observed in men and 5.6% \nin women (Ludwig scale)10. In China, this was 21.3% \nin men and 6.0% in women11, and a much higher 63% \nin Singaporean men12. The severity of AGA increases \nwith age10 and presence of family history13, which is also \npredictive of early-onset13. Smoking13 and metabolic \nsyndrome14 have been found to play a role in the \ndevelopment of AGA.\n\n\n\nWith different prevalence data in Asians compared to \nCaucasians, a better understanding of the aetiology and \ncurrent management of non-scarring alopecia in the \nregion is needed. Hence, we aim to study the spectrum \nof non-scarring alopecia, its\u2019 demographic, clinical and \ntreatment pattern among patients in University Malaya \nMedical Centre. A long-term retrospective study may \ntherefore impact the treatment and diagnosis of this \nspectrum of conditions.\n\n\n\nMethods\nThis was a retrospective review of patients diagnosed with \nnon-scarring alopecia from January 2000 to December \n2009 in a tertiary hospital in Malaysia. Patients classified \nas having the following conditions under the ICD-10 \n(International Classification of Diseases) were recalled \nfrom the dermatology and general out-patient database: \n\n\n\nalopecia areata (L63), androgenic alopecia (L64) and \nother non scarring hair loss (L65). This included male-\npattern baldness, telogen effluvium, anagen effluvium \nand alopecia mucinosa but excluded trichotillomania \n(F63.3).\n\n\n\nA total of 154 patients were included in the analysis. Data \non demography, clinical characteristics and treatment of \nthese patients were computed into a standard case report \nform in Microsoft Infopath 2007. These data were then \nexported to Microsoft Excel 2007 before being converted \ninto SPSS 17.0 files. The continuous data were analyzed \nvia means and standard deviations.\n\n\n\nResults\nA total of 154 medical records were reviewed. The mean \nage of patients at presentation was 24.6 \u00b1 11.8 years (range \n3-62 years). Of these, the majority were adults (70.1%), \nwith 29.9% under the age of 16. There were slightly more \nfemales, with a male to female ratio of 1:1.03.  The main \nethnic groups were well-represented, with 31.8% Malays, \n33.1% Indians, 27.3% Chinese and 7.8% classified as \n\u2018others\u2019. More than a quarter of patients were diagnosed \nwith AA (44, 28.6%), followed by AGA (19, 12.3%), \ntelogen effluvium (5, 3.2%), tinea capitis (4, 2.6%) and \nunspecified hair loss (82, 53.2%). (Table I) \n\n\n\nThe co-morbidities present were anaemia (9, 5.8%), \nthyroid disorders (4, 2.6%), atopy (3, 1.9%) and type 2 \ndiabetes mellitus (3, 1.9%). Stress was identified in 9 \npatients (5.8%) and 8 patients (5.1%) had family history \nof alopecia. Fourteen percent of patients received prior \ntreatment, either from other doctors, traditional healers or \nover-the-counter purchase. More than a third of patients \nwere lost to follow-up after first consultation (40.3%).\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2012 Dec Vol 29   \u2022\n\n\n\nWorkflow of retrospective review:\n\n\n\n1.\n\n\n\n2.\n\n\n\n3.\n\n\n\nRetrieval of patient cases from database \n(n=306)\n\n\n\nExclusion of inconsistent diagnoses; Final \npatient cohort (n=154)\n\n\n\nPatients divided into subgroups for further \nanalysis \nAA (n=44)\nAGA (n=19)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 \u2022   MJD 2012 Dec Vol 29\n\n\n\nAlopecia Areata (n=44)\nThe mean age of patients with AA was 24.7 \u00b111.6 years \n(range 5-62 years) with a mean age of onset at 24.2 \u00b1 11.9 \nyears (range 4-62 years). Nine (20.5%) were less than 16 \nyears old. A majority of patients were Malays (34.1%), \nfollowed by Indians (31.8%), Chinese (22.7%) and \u2018others\u2019 \n(11.4%). We had three patients with type 2 diabetes, \nanaemia and thalassemia traits respectively. None of the \npatients were found to have a positive family history of \nalopecia, thyroid disorder, vitiligo, atopic dermatitis \nand connective tissue disease. Stress was identified in 3 \npatients (6.7%). More than half received topical steroids \n(53.3%). This was followed by intralesional steroids \n(26.7%), topical minoxidil (17.8%), oral steroids (11.1%), \noral finasteride (2.2%) and azathiopine used concurrently \nwith oral steroids (2.2%).\n\n\n\nAndrogenetic Alopecia (n=19)\nThe mean age of patients with AGA was 25.4 \u00b1 2.2 years \n(range 17-55 years) and the mean age of onset was 23.3 \u00b1 \n9.6 years (range 16-55 years). Unsurprisingly, the ethnic \ncomposition of these patients was Malays (42.1%), Indians \n(26.3%), Chinese (26.3%) and others (5.3%). Five (26.3%) \nhad a positive family history of alopecia. Recommended \ntreatment was predominantly topical minoxidil (68.1%), \nfollowed by oral finasteride (10.5%).\n\n\n\nDiscussion\nThe prevalence of AA and AGA was similar to other studies \nconducted in the region10-12. The most common confirmed \ncause of non-scarring alopecia was AA. However, the \nsignificant proportion of unspecified alopecia (51.9%) \nreflects inexperience and lack of confidence in primary \nphysicians. This inability to provide a specific diagnosis \nmay hamper management of non-scarring alopecia, thus \nnecessitating in-depth understanding among physicians \non common causes and clinical presentations.\n\n\n\nAge groups affected by non-scarring alopecia\nNon-scarring alopecia affects adults mainly in their 3rd \ndecade of life but also affects patients below 16 years old. \nAA patients were found to be younger in our review, \nwith our paediatric patients almost double that of those \nreported in China15. AGA patients were also younger \ncompared to a Singaporean review reporting the highest \nage distribution at 37-46 years old12.The mean duration \nto presentation was longer by about 18 months for AGA \ncompared to AA. We postulate that this could be due to \nslower and more subtle presentation of AGA. Moreover, \npatients might have perceived AGA as part of natural \naging and not a medical condition.\n\n\n\nAutoimmune association \nAutoimmune association is well recognized with AA, \nwith a varying degree of association with vitiligo (0.4%-\n4.1%)15, 16. None of our patients had vitiligo, but this could \nbe attributed to the small sample size.\n\n\n\nGenetic correlation \nGenetic inheritance is the only significant factor leading to \nAGA and AA. Nevertheless, the low incidence of patients \nwith family history (5.5%) in our data could be due to \nunder-reporting. \n\n\n\nStress correlation \nSimilarly, we also had fewer patients identifying stress \npreceding the onset of hair loss, as opposed to figures \nranging from 9.5%-68.9% in other reviews17. The high \nnumber of patients lost to follow-up may be due to certain \nfactors such as lack of efficacy of prescribed treatment or \nlimited treatment options. Other factors include the self-\nlimiting nature of AA and the ambiguity of the diagnoses \ngiven. Studies showed that more than 70% of AGA patients \nseek non-medical sources of treatment12. Therefore, these \npatients may have sought alternative treatment after the \ninitial counselling and management at the hospital.\n\n\n\nTable 1  Ethnic composition of AA and AGA.\n\n\n\nEthnic group\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nTotal\n\n\n\nNumber of patients \n(AA, AGA, etc)\n\n\n\n42 (27.3%)\n\n\n\n49 (31.8%)\n\n\n\n51 (33.1%)\n\n\n\n12 (7.8%)\n\n\n\n154\n\n\n\nNumber with AA \n(28.2% of total patients)\n\n\n\n5 (26.3%)\n\n\n\n8 (42.1%)\n\n\n\n5 (26.3%)\n\n\n\n1 (5.3%)\n\n\n\n19\n\n\n\nNumber with AGA (12.2% of \ntotal patients) \n\n\n\n10 (22.7%) \n\n\n\n15 (34.1%)\n\n\n\n14 (31.8%) \n \n5 (11.4%)\n\n\n\n44\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2012 Dec Vol 29   \u2022\n\n\n\nLimitations\nThe low number of patients involved in the study may \naffect the statistical power of this review. However, the \nmain limitation of our study is the retrospective design, \nthus, the possibility of under-documentation. Having \ndifferent doctors involved in diagnosis could result in a \nnon-standardize assessment. Patients could also under-\nreport family history or wrongly describe their symptoms \nif a doctor-patient language barrier exists, given the three \ndifferent predominant ethnic groups. A standardized \npictorial description of alopecia eradicating the issue \n\n\n\nof comprehension or extensive interviewing of family \nmembers could address this, but may not be a viable \noption. \n\n\n\nConclusion\nOur review showed the most commonly diagnosed non-\nscarring alopecia was AA followed by AGA. Nevertheless, \nthe relatively high numbers of unspecified hair loss cases \nindicate a need for physician education to enable accurate \ndiagnosis and optimal management of various causes of \nnon-scarring alopecia.\n\n\n\nTosti A, Lorizzo M, Piraccini BM. Androgenetic Alopecia in 1. \nChildren: Report of 20 Cases. British J Dermatol 2005; 152: \n556-9.\nTan E, Tay YK, Goh CL, Chin Giam Y.The pattern and profile 2. \nof alopecia areata in Singapore--a study of 219 Asians. Int J \nDermatol2002 Nov;41 (11):748-53.\nPuavilai S, et al. Prevalence of thyroid diseases in patients with 3. \nalopecia areata. Int J Dermatol1994; 33: 632-3.\nKoev DG. Diabetes mellitus. Diabetes mellitus type LADA. In: 4. \nLosanov BS, ed. Endocrinology. Sofia: Academic Press Marin \nDrinov, 2000: 838.\nLiana M, Vasile B. Stress in Patients with Alopecia Areata and 5. \nVitiligo. JEADV 2007; 21: 921-8.\nMcDonaugh AJG, Messenger AG. The Pathogenesis of Alopecia 6. \nAreata.Dermatol.Clin1996; 14: 661-70.\nBolduc C, Elston DM, et al. Alopecia Areata \u2013 Medscape 7. \nReference.http://emedicine.medscape.com/article/1069931-\noverview. Accessed 7 July 2011.\nTsuboi R, Tanaka T, Nishikawa T, Ueki R, Yamada H, Katsuoka 8. \nK, et al. A randomized, placebo-controlled trial of 1% topical \nminoxidil solution in the treatment of androgenetic alopecia in \nJapanese women. Eur J Dermatol2007 Jan-Feb; 17(1):37-44.\nFeinstein RP, Elston DM, et al. Androgenetic Alopecia - 9. \nMedscape Reference. http://emedicine.medscape.com/article/ \n1070167-overview. Accessed 7 July 2011.\n\n\n\nPaik JH, Yoon JB, Sim WY, Kim BS, Kim NI. The prevalence 10. \nand types of androgenetic alopecia in Korean men and women.\nBr J Dermatol2001 Jul;145 (1):95-9.\nWang TL, Zhou C, Shen YW, Wang XY, Ding XL, Tian S, et al. 11. \nPrevalence of androgenetic alopecia in China: a community-\nbased study in six cities. Br J Dermatol2010 Apr; 162 \n(4):843-7.\nTang PH, Chia HP, Cheong LL. A Community Study of Male 12. \nAndrogenetic Alopecia in Bishan, Singapore. Singapore Med J \n2000; 41(5): 202-5.\nSu LH, Chen TH. Association of androgenetic alopecia with 13. \nsmoking and its prevalence among Asian men: a community-\nbased survey.  Arch Dermatol 2007 Nov; 143 (11):1401-6.\nSu LH, Chen TH. Association of androgenetic alopecia with 14. \nmetabolic syndrome in men: a community-based survey. Br J \nDermatol2010 Aug; 163 (2):371-7.\nXiao FL, Yang S, Liu JB, He PP, Yang J, Chui Y. The Epidemiology 15. \nof Childhood Alopecia Areata in China: A Study of 226 Patients. \nPaeds Dermatol 2006; 23:13-18.\nTan E, Tay YK, Goh CL, Giam YC. The Pattern and Profile of 16. \nAlopecia Areata in Singapore - a Study of 219 Asians. Int. J of \nDermatol 2002; 41:748-53.\nKakourou T, Karachristou K, Chrousos G. A Case Series of 17. \nAlopecia Areata in Children: Impact of Personal and Family \nHistory of Stress and Autoimmunity. JEADV 2007; 21:356-59.\n\n\n\nReference\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16 \u2022   MJD 2012 Dec Vol 29\n\n\n\nCh\u2019ng CC1, Wong SM1,\nLee YY1, Rokiah I1, Jayalaskmi Pailoor2\n\n\n\nA 7-Year Retrospective Review\nof Skin Cancer at University \nMalaya Medical Centre:\nA Tertiary Centre Experience \n\n\n\nGENERAL DERMATOLOGY - ORIGINAL ARTICLE\n\n\n\nAbstract\nIntroduction  Skin cancer is ranked the ninth commonest cancer among males and \n\n\n\ntenth among females in Malaysia. \n\n\n\nObjectives  To review the pattern of skin cancers at University Malaya Medical Centre \n\n\n\n(UMMC).\n\n\n\nMethods  This is a retrospective review of all histo-pathological confirmed skin \n\n\n\ncancers at UMMC from 2004 till 2010.\n\n\n\nResults Among the 155 patients reviewed, basal cell carcinoma (BCC) was the \n\n\n\ncommonest skin cancer (44.5%), followed by squamous cell carcinoma (SCC) (27.1%) \n\n\n\nand malignant melanoma (MM) (11.6%). The nodulo-ulcerative subtype made up \n\n\n\n46% of all BCC while 50% of MM was of acral lentiginous subtype. Patients with \n\n\n\nBCC were significantly older (>60 years old), (p=0.003). A majority of skin cancers \n\n\n\nwere found on the head and neck.\n\n\n\nConclusion BCC was the commonest skin cancer, with significantly older patients \n\n\n\nand located mainly on head and neck. MM was the least common skin cancer but \n\n\n\nassociated with the highest mortality.\n\n\n\nKeywords: basal cell carcinoma, squamous cell carcinoma, malignant melanoma, \nMalaysia\n\n\n\nCorrespondence\nCh\u2019ng Chin Chwen MRCP\n1 Dermatology Unit, Department of Medicine, Faculty of Medicine, Universiti Malaya\nEmail: chinchwen@gmail.com\n2 Dermatology Unit, Department of Pathology, Faculty of Medicine, Universiti Malaya\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2012 Dec Vol 29   \u2022\n\n\n\nIntroduction\nSkin cancer is the commonest malignancy among the \nCaucasians. Since the 1960s, the incidence of skin cancer \namong predominantly white populations has increased \nbetween 5% and 8% annually1. Skin cancer represents 20-\n30% of all neoplasms among Caucasians, but is only seen \nin 2-4% of Asians, and 1-2% of blacks and Asian Indians1. \nIt appears that darker skin has relative protection against \nskin cancers.\n\n\n\nThe three main types of skin cancers are basal cell \ncarcinoma (BCC), squamous cell carcinoma (SCC) and \nmalignant melanoma (MM), each named after the cells \nfrom which it arises.\n\n\n\nBCC is the commonest malignancy in Caucasians as well as \nAsians. In the United States, non-melanoma skin cancers \nconstitute more than one third of all cancers with 75% \nmade up of  BCC2. MM, though not as common, accounts \nfor 75% of deaths due to skin cancers2. A Japanese survey \nof skin cancers in 101 institutes from 1987 to1996 showed \nthat 47% were BCC, 30% were SCC and 19% were MM3. \n\n\n\nA review of skin cancers by our neighbouring country \nSingapore from 2003 till 2007 showed similar results where \nBCC accounted for 54.5% of all skin cancers whilst SCC \nand MM accounted for 25.3% and 5.8% respectively4-5.\n\n\n\nMalaysia is a multiracial country, at latitude 2\u00b0 30\u2019 North \nof the equator, with a population of 28.31 million people, \ncomprising Malays (51%), Chinese (23%), natives \n(11%), Indians (7%) and others (1%)6. A majority of \nthis population have Fitzpatrick skin phototype III to V7. \nIn 2003, the Malaysian National Cancer Registry (NCR) \nranked skin cancer as the 9th commonest cancer among \nmales and 10th among females8. However, to date, data on \nthe demography and clinical characteristics of skin cancer \nis still lacking.\n\n\n\nAim\nTo analyse the demography and spectrum of histo-\npathologically confirmed skin cancers at University \nMalaya Medical Centre (UMMC) from January 2004 to \nDecember 2010.\n\n\n\nTable 1  Type and Subtypes of Skin Cancer.\n\n\n\nNodular/noduloulcerative\n\n\n\nSuperficial\n\n\n\nCystic\n\n\n\nUnspecified\n\n\n\nDermatofibrosarcoma protuberans\n\n\n\nExtramammary Paget Disease\n\n\n\nKaposi Sarcoma\n\n\n\nVerrucous Carcinoma\n\n\n\nMalignant cutaneous adnexal tumor\n\n\n\nMalignant eccrine cylindroma\n\n\n\nSebaceous carcinoma\n\n\n\nCutaneous lymphoma\n\n\n\nBC\n\n\n\nSMC\n\n\n\nMM\n\n\n\nOthers\n\n\n\nNumber\n\n\n\n54\n\n\n\n2\n\n\n\n5\n\n\n\n8\n\n\n\n42\n\n\n\n18\n\n\n\n8\n\n\n\n5\n\n\n\n4\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n8\n\n\n\nTypes of skin cancers Total \n\n\n\n69* (44.5%)\n\n\n\n42* (27.1%)\n\n\n\n18* (11.6%)\n\n\n\n30 (19.4%)\n\n\n\n* Three patients had multiple skin cancers and one patient had concurrent pigmented and nodulo-ulcerative BCC.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 \u2022   MJD 2012 Dec Vol 29\n\n\n\nFig 1  Skin Cancer, Distribution According to Age Group\n\n\n\nFig 2  Skin Cancer, Gender Distribution.\n\n\n\n60\n\n\n\n50\n\n\n\n40\n\n\n\n30\n\n\n\n20\n\n\n\n10\n\n\n\n0\n\n\n\nAge Group of Skin Cancer Patients\n\n\n\nBCC SCC MM\n\n\n\n0 - 29\n\n\n\n30 - 59\n\n\n\n60 and above\n\n\n\n40\n\n\n\n35\n\n\n\n30\n\n\n\n25\n\n\n\n20\n\n\n\n15\n\n\n\n10\n\n\n\n5\n\n\n\n0\n\n\n\nMALE\n\n\n\nFEMALE\n\n\n\nBCC SCC MM\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2012 Dec Vol 29   \u2022\n\n\n\nMethodology\nThis is a retrospective study conducted at the Dermatology \nUnit, Department of Medicine and the Pathology \nDepartment at UMMC. Skin cancers were identified \nfrom the skin biopsy histopathology recording book and \nmedical files were retrieved from our hospital medical \nrecords. All patients diagnosed with skin cancers from \n1st January 2004 to 31st December 2010 were included. \nPatients were excluded if there was no confirmatory skin \nbiopsy performed or there were missing or incomplete \ndata.\n\n\n\nDemographic data and clinical characteristics of \npatients were collected. These data were analysed using \nStatistical Package for Social Sciences (SPSS) version 18.0. \nContinuous variables were expressed as mean \u00b1 standard \ndeviation (SD) and analysed using 2 sample independent \nt-tests. Categorical variables were described as frequencies \nand were analysed using Chi-Square test. Analysis was done \nfor comparison of clinical characteristics based on regions \nof involvement and gender. The level of significance was \nset at p-value less than 0.05.\n\n\n\nResults\nA total of 172 histo-pathologically confirmed skin cancers \nwere recorded between 2004 and 2010. Due to missing \nand incomplete medical records, only 155 patients were \nanalysed. There were 80 males and 75 females. The mean \nage of lesion onset and diagnosis were 59.1\u00b1 16.7 years \nand 63.4 \u00b1 15.3 years, respectively. The mean duration \nfrom onset of lesions until definite diagnosis was 3.5 \u00b1 \n5.9 years.\n\n\n\nBCC, SCC and MM were the three major skin cancers \nin our cohort followed by other rarer skin malignancies \n(Table 1). The mean age at diagnosis was the highest for \nBCC (68.0 \u00b1 11.0 years), followed by MM (65.1 \u00b1 11.1 \nyears) and SCC (63.4 \u00b1 15.9 years). Patients with BCC \nwere significantly older (p=0.003) but this was not seen in \npatients with SCC (p=0.63) and MM (p=0.506) (Fig. 1). \n\n\n\nMale to female ratio was 0.86:1 for BCC, 3:1 for SCC and \n0.64:1 for MM (Fig. 2). There were significantly more \nmale patients suffering from SCC (p=0.006).  However, \nthere was no significant gender preponderance among \npatients with BCC and MM (p=0.261, p=0.318).\n\n\n\nChinese patients made up the highest ethnic group for \nall types of skin cancers (Table 2). This was a significant \nfinding as a review into UMMC 2004-2007 outpatient \ncensus revealed that Malay (44%) was the major ethnic \ngroup that frequents our outpatient clinic, followed by \nChinese (31%), Indian (24%) and others (2%).\n\n\n\nBCC was significantly more common on the head and \nneck (p<0.001) compared to other skin cancers, whilst \nMM was significantly commoner in the lower limbs \n(p<0.001). (Fig. 3) \n\n\n\nA large proportion of patients with BCC had the nodulo-\nulcerative variant (n=54, 78%) while the superficial \nvariant made up the smallest proportion (n=2, 3%) (Fig. \n4). In addition, a majority of the nodulo-ulcerative variant \nwere pigmented (21/53, 38%). \n\n\n\nFifty percent (nine out of eighteen) of our cohort with \na malignant melanoma had the acral lentiginous (ALM) \ntype, although the number of patients with ALM was \ntoo small for statistical analysis. (Fig. 5) There were only \ntwo Indians in our study with malignant melanoma and \nboth had the ALM subtypes. Among the five Malays with \nmalignant melanoma, four had the ALM subtype. This \ntrend was not seen among the Chinese, as only two out \nof ten patients had the ALM subtypes, seven had nodular \nmelanoma and one had superficial spreading melanoma. \n\n\n\nAn analysis of the follow-up rate after skin biopsy showed \na remarkably high defaulter rate of 25.8% in our cohort \nof patients.  \n\n\n\nTable 2  Racial distribution of Skin Cancer Patients.\n\n\n\nEthnicity\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nBCC\n\n\n\n13 (18.8%)\n\n\n\n51 (73.9%)\n\n\n\n  2 (2.9%)\n\n\n\n  3 (4.4%)\n\n\n\nSCC\n\n\n\n8 (19.0%)\n\n\n\n25 (59.5%)\n\n\n\n  7 (16.7%)\n\n\n\n  2 (4.8%)\n\n\n\nMM \n\n\n\n5 (27.8%)\n\n\n\n10 (55.6%)\n\n\n\n  2 (11.1%)\n\n\n\n1 (5.6%)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 \u2022   MJD 2012 Dec Vol 29\n\n\n\nFig 3  Site of Skin Cancers.\n\n\n\nFig 4 Basal Cell Carcinoma, Clinical Subtypes. Fig 5 Malignant Melanoma, Subtypes.\n\n\n\n70\n\n\n\n60\n\n\n\n50\n\n\n\n40\n\n\n\n30\n\n\n\n20\n\n\n\n10\n\n\n\n0\n\n\n\nHead & Neck\n\n\n\nUpper Limbs\n\n\n\nLower Limbs\n\n\n\nTrunk\n\n\n\nGeneralised\n\n\n\nBCC SCC MM\n\n\n\n8,12%\n\n\n\n5,7%\n\n\n\n2,3%\n\n\n\n54,78%\n\n\n\nNodular/noduloulcerative\n\n\n\nSuperficial\n\n\n\nALM\n\n\n\nNM\n\n\n\nSuperficial spreadingCystic\n\n\n\nUnspecified\n\n\n\n9,50%\n\n\n\n1,6%\n\n\n\n8,44%\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2012 Dec Vol 29   \u2022\n\n\n\nDiscussion\nThis study aims at gaining an insight into the pattern of \nskin cancers in our local population. BCC is the most \ncommon skin cancer, followed by SCC and melanoma. \nThis is consistent with other studies in European and \nAsian populations3-6, 9-17. However, in comparison with a \nprevious local study conducted in Sarawak, we had more \ncases of melanomas and less cutaneous lymphomas16. In \naddition, the patients with BCC in our cohort were from \nan older age group and were significantly older compared \nto other skin cancers. This is not surprising as BCC is \nwell known for affecting the older population, whereas \nSCC and malignant melanoma are generally seen in the \nyounger and middle-age groups.\n\n\n\nIn general, BCC has a male preponderance in the Caucasian \npopulation. Male to female ratio for BCC ranges from \n1.4-1.9:1 in United States18,19,20, 1.3-1.7:1 in Australia12,21,22, \nand 1.1-1.4:1 in Europe11,23,24. Our study showed a slightly \nhigher female preponderance with a male to female ratio \nof 0.86:1. This also corresponds with other Asian countries \nsuch as Singapore (male:female ratio 0.81:1)3, Hong Kong \n(1:1.32-1.46)25, 26 and Korea (0.9:1)15. Asian females are at \nleast as likely as males to develop BCC despite the general \ngreater awareness of sun protection. We postulate that \nthis higher number of female patients may be because of \nhigher detection rate due to a heightened tendency to seek \nmedical treatment especially when most BCCs are found \non the head and neck and pigmented lesions are more \ncommon in the Asian population.\n\n\n\nOur study showed a male preponderance with a \nmale:female ratio of 3:1 for SCC. This data is similar with \nother Asian and Western studies (Australia 3:112, US \n2.4:1.017 and Singapore 1.29 to 2.4:13,10).\n\n\n\nFor MM, gender preponderance seems to vary with \ndifferent geographical locations. An Australian study \nreported a male preponderance with a male to female \nratio of 1.3:1.012, in the US, the ratio was 1:117, while \nin Europe, a slight female preponderance was reported4. \nCloser to our country, the male:female ratio was 0.93:1 in \nJapan5 and 0.81:1 in Singapore3. Our study with a ratio of \n0.64:1 concurred with our neighbouring countries which \ncould indicate that Asian females may be more susceptible \nto malignant melanoma. \n\n\n\nThe Chinese ethnicity made up the highest number of \npatients for all types of skin cancers. This was significant \nas a review of our outpatient census from 2004-2007 \n\n\n\nrevealed that the Malays were the major ethnic group \nthat frequented our outpatient clinic (44%), followed by \nChinese (31%), Indians (24%) and others (2%). These \nfindings are not surprising as most Chinese have a lower \nFitzpatrick skin phototype compared to the Malays and \nIndians, leading to lower protection from photodamage \nand subsequently, a higher risk of skin cancer.\n\n\n\nIn our study, most of the skin cancers were found on head \nand neck except for MM which is consistent with other \nstudies16-17. The head and neck regions are sun-exposed \nareas and are more susceptible to skin cancers. Not \nsurprisingly, the majority of BCC were of noduloulcerative \nsubtype. But there is a difference as compared with \nCaucasian population9-12 where a large portion of our \ncohort had the pigmented variant, perhaps related to \nincreased epidermal melanin. Pigmented BCC can be \neasily confused with other benign pigmented lesions \nsuch as seborrhoeic keratosis, dermatosis papulosa nigra, \ndermatofibroma or nevus. Hence, it is important for \nclinician to have a high index of suspicion. On the other \nhand, the high frequency of acral lentiginous melanoma \namong patients with darker Fitzpatrick skin type, \nwarrants further study to gain insight into the aetiology \nof malignant melanoma in Asian.\n\n\n\nIt is alarming that the defaulter rate for follow-up in our \ncohort of patients was as high as 25.8%. A third of patients \nwith potentially fatal SCC did not return for follow-up. \nThe lack of symptoms or knowledge about the disease \nmay contribute to this high defaulter rate. Although skin \ncancers in the Asian population is generally lower than \nin the West, perhaps we should be spending more time \neducating our patients and increasing public awareness of \nskin cancers among the general population.\n\n\n\nConclusion\nBCC was the commonest skin cancer in our cohort and \nfound mainly on the head and neck regions. Patients with \nBCC were also older and mainly of Chinese ethnicity with \na slight female preponderance. A majority of malignant \nmelanomas in our centre were of the acral lentiginous \nmelanoma subtype. Defaulter rate of skin cancer was high \nin our centre which demands urgent attention. There is a \nneed for public education to increase awareness of skin \ncancer in our country. Health campaigns to educate the \npublic on self skin examination and the importance of \nphotoprotection may be beneficial especially in high risk \nindividuals.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 \u2022   MJD 2012 Dec Vol 29\n\n\n\n1. Gloster H, Neal K. Skin cancer in skin of color. J Am Acad 1. \nDermatol. 2006;55:741\u201360.\n2. Gloster HM, Brodland DG. The epidemiology of skin 2. \ncancer. Dermatol Surg 1996: 22: 217-26.\n3. Ishihara K, Saida T, Yamamato A. Updated statistical 3. \ndata for malignant melanoma in Japan. Int J Clin Oncol 2001; \n6: 109\u201316.\n4. Koh D, Wang H, Lee J, et al. Basal cell carcinoma, 4. \nsquamous cell carcinoma and melanoma of the skin: analysis \nof Singapore Cancer Registry data 1968\u201397. British Association \nof Dermatologists. 2003;148:1161\u201366.\n5. Lee HP, Ang PT, Chow KY et al. Cancer Incidence in 5. \nSingapore 1968-2007. Singapore Cancer Registry Report No 7, \n2000.\n6. Department of Statistics. Yearbook of Statistics, Malaysia 6. \n2009. March 2010: 2-33\n7. Fitzpatrick TB. The validity and practicality of sun reactive 7. \nskin types I through VI. Arch Dermatol 1988;124: 869\u201371\n8. Gerard Lim Chin Chye, Halimah Yahay. Second Report of 8. \nNational Cancer Registry. Malaysia Cancer Registry. 2003.\n9. Halder RM, Bridgeman-Shah S. Skin cancer in African 9. \nAmericans. Cancer 1995;75:667-73.\n10. S L brown CJ Thirlaway, CM Lawrence. A 6 months 10. \nprospective study of the incidence and management of \ndermatological malignancies in an NHS teaching hospital. Br J \nDermatol 2005;153:74\n11. Holme SA, Malinovszky K, Roberts DL. Changing trends 11. \nin non-melanoma skin cancer in South Wales 1988-98. Br J \nDermatol 2000: 143: 1224-9\n12. Green A, Battistutta D, Hart V, et al. Skin cancer in 12. \na subtropical Australian population: incidence and lack of \nassociation with occupation. The Nambour Study Group. Am J \nEpidemiol. Dec 1 1996;144(11):1034-40\n13. Nakjang Y, Kullavanija P. Basal cell carcinoma: seven 13. \nyears\u2019 experience at the Institute of Dermatology in Bangkok. \nJ Dermatol 1994; 21: 660\u201363\n14. Diepgen TL, Mahler V. The epidemiology of skin cancer. 14. \nBr J Dermatol. Apr 2002;146 Suppl 61:1-6\n\n\n\n15. Cho S, Kim MH, Whang KK, Hahm JH. Clinical and 15. \nhistopathological characteristics of basal cell carcinoma in \nKorean patients. J Dermatol 1999; 26: 494\u2013501.\n16. Yap FB. Clinical characteristics of basal cell carcinoma in 16. \na tertiary hospital in Sarawak, Malaysia. Int J Dermatol. 2010 \nFeb;49(2):176-9.\n17. Raasch BA, Buettner PG, Garbe C. Basal cell carcinoma: 17. \nhistological classification and body site distribution. Br J \nDermatol. 2006;155(2):401-7.\n18. Miller DL, Weinstock MA. Nonmelanoma skin cancer in 18. \nthe United States: Incidence. J Am Acad Dermatol 1994; 30: \n774\u20138.\n19. Serrano H, Scotto J, Shornick G et al. Incidence of 19. \nnonmelanoma skin cancer in New Hampshire and Vermont. J \nAm Acad Dermatol 1991; 24: 574\u20139.\n20. Gray DT, Suman VJ, Su WPD et al. Trends in the 20. \npopulation-based incidence of squamous cell carcinoma of the \nskin first diagnosed between 1984 and 1992. Arch Dermatol \n1997; 133: 735\u201340.\n21. Buettner PG, Raasch BA. Incidence rates of skin Cancer in 21. \nTownsville, Australia. Int J Cancer 1998; 78: 587\u201393.\n22. Kaldor J, Shugg D, Young B et al. Non-melanoma skin 22. \ncancer: ten years of cancer-registry-based surveillance. Int J \nCancer 1993; 53: 886\u201391.\n23. Ko CB, Walton S, Keczkes HPR et al. The emerging 23. \nepidemic of skin cancer. Br J Dermatol 1994; 130: 269\u201372.\n24. Scottish Cancer Intelligence Unit ISD, National Health 24. \nService in Scotland. Cancer Registration Statistics Scotland \n1990\u201395. Edinburgh: National Health Service, 1998.\n25. Cheng SY, Luk NM, Chong LY. Special features of non-25. \nmelanoma skin cancer in Hong Kong Chinese patients: 10-year \nretrospective study. Hong Kong Medical Journal 2001;7: 22-28.\n26. Cheng SY. Non-melanoma skin cancer: A five-year 26. \nretrospective study in Social Hygiene Service of Hong Kong. \nHong Kong Journal of Dermatology and Vereneology. 1999; 7: \n162-69. \n\n\n\nReference\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23MJD 2012 Dec Vol 29   \u2022\n\n\n\nYin YL1, Adv M Derm, Chew KL2, Adv M Derm,\nKoh CK3, MRCP, Jayalakshmi P, FRCPath\n\n\n\nSquamous Cell Carcinoma\nArising from Linear Porokeratosis \nin a Young Chinese Man\n\n\n\nKeywords: skin cancer, extensive plaques, autosomal dominant\n\n\n\nBackground\nPorokeratosis is a specific disorder of epidermal keratinization, characterised \n\n\n\nhistologically by the presence of cornoid lamella1. Linear is a distinct, mosaic variant \n\n\n\nof this autosomal dominant condition. There is a well recognized association between \n\n\n\nporokeratosis and malignancy, especially the linear variant which has the highest \n\n\n\nmalignant potential2, 3.\n\n\n\nCase Report\nA 25-year old gentleman presented to our dermatology clinic in 2004 with non-\n\n\n\nhealing erosions within a pre-existing plaque on his left calf of one-year duration. \n\n\n\nThe erosions were not preceded by any trauma. On further questioning, he claimed to \n\n\n\nhave multiple asymptomatic cutaneous plaques over his face, trunk, upper and lower \n\n\n\nextremities since he was 3-months old. \n\n\n\nThe first lesion as noted by his mother was over his left calf, which subsequently \n\n\n\nincreased in size and number and spreading in a linear pattern. \n\n\n\nApart from cosmetic disfigurement, he developed multiple nodular lesions on \n\n\n\nhis left calf and thigh.These were not painful, itchy, did not ulcerate and were not \n\n\n\nassociated with discharge. There was no family history of similar skin lesions or skin \n\n\n\nmalignancy.\n\n\n\nCorrespondence\nYin Yin Lee MRCP, MMed, Adv M Derm                \n1 Sunway Medical Centre. No 5, Jalan Lagoon Selatan, Bandar Sunway, 46150, Petaling Jaya, \nSelangor, Malaysia.\nEmail: leeyiy@sunway.com.my\n2 School of Anti-aging, Aesthetic and Regenerative Medicine, UCSI University, Malaysia;\nUniversity of Malaya.\n3 Koh Skin Specialist Clinic; Department of Medicine, University of Malaya.\n4 Department of Pathology, University of Malaya. \n\n\n\nGENERAL DERMATOLOGY - CASE REPORT\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24 \u2022   MJD 2012 Dec Vol 29\n\n\n\nClinically, there were multiple hyperpigmented scaly \nplaques arranged in linear fashion along the Blaschko \ndistribution. The plaques were atrophied with raised, well-\ndefined, irregular margins and appeared more pigmented \nat the periphery than centrally. Over the medial aspect \nof his left calf and thigh, there were also several plaques, \nwhich are thicker and more hyperkeratotic (Figure 1 & \n2).\n\n\n\nSkin biopsies were taken from the margin of one lesion \nand another at a hyperkeratotic plaque over his left calf. \nThe margin of the lesion showed features of porokeratosis \n\n\n\nsuch as focal areas of acanthosis, parakeratosis and foci \nof cornoid lamella. The hyperkeratotic plaque showed \nmoderate to severe dysplasia. \n\n\n\nThe thickened plaques were treated with multiple \nsessions of cryotherapy. Concurrently, oral acitretin \nwas commenced. Unfortunately, he did not notice any \nimprovement despite taking acitretin. Hence, he defaulted \non his follow-up and treatment after a year of acitretin.\n\n\n\nFig 1\nLinear cutaneous plaques on \nthe anterior trunk, both upper \nand lower extremities in a \nBlaskho\u2019s distribution.\n\n\n\nFig 2  Excised nodule on his left calf leaving a crusted plaque.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25MJD 2012 Dec Vol 29   \u2022\n\n\n\nWe recently saw him, after a 4-year hiatus, with history \nof painful, gradually enlarging left calf nodule of 2-year \nduration. There was no associated discharge or bleeding. \nClinically, there was a 0.5 - 2.0 cm diameter flesh-coloured \nfirm nodule with superficial erosion seen. There was no \nregional lymphadenopathy. Incisional skin biopsy well \ndifferentiated squamous cell carcinoma with keratin pearls \nand intercellular bridging (Figure 3). He was subsequently \nreferred to a plastic surgeon for total excision and skin \ngrafting.\n\n\n\nIt typically presents as sharply demarcated hyperkeratotic \nplaques (annular, central atrophy, linear, punctate) \nsurrounded by a thread-like elevated border that expands \ncentrifugally. \n\n\n\nThere are a few clinical variants of porokeratosis, \ne.g.  porokeratosis of Mibelli, disseminated superficial \nporokeratosis (DSP), disseminated superficial actinic \nporokeratosis (DSAP), porokeratosis palmaris et plantaris \ndisseminata (PPPD), linear porokeratosis and punctate \nporokeratosis. \n\n\n\nOur patient was diagnosed with disseminated linear \nporokeratosis, a rare autosomal dominant keratinization \ndisorder that frequently presents unilaterally in a linear \npattern and bears a close resemblance to linear verrucous \nepidermal neavus. However, our patient has a far more \nextensive presentation with the involvement of his trunk, \nupper and lower extremities in a Blashko distribution \nbilaterally as opposed to the commonly described \nunilateral distribution. \n\n\n\nFig 3  Hematoxylin-eosin stain. Original magnification X100. Dense inflammatory infiltrate with squamous cells arranged \nin discrete nests, cords and trabeculae extending into the underlying dermis and subcutis. Presence of mature and well \ndeveloped keratin pearl.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26 \u2022   MJD 2012 Dec Vol 29\n\n\n\nThe pathogenesis of this condition is attributed to clones \nof abnormal epithelial cells, resulting in keratotic lesions \nthat can progress to cutaneous neoplasia. The high rate \nof abnormal DNA and malignant features, e.g. p53 over-\nexpression suggest an increased proliferative potential \nin affected keratinocytes4. The incidence of malignant \ndegeneration in porokeratosis can be as high as 10%4. \n\n\n\nOtsuka et al had reported malignant degeneration and \nmetastasis in this condition, which can be either be a \nbasal cell carcinoma, Bowen\u2019s disease or squamous cell \ncarcinoma, and most likely to occur in older adults5. \nA genetic mechanism of allelic loss may also be a \nrepresentation in the initial step leading towards the \ndevelopment of cancer3.\n\n\n\nThe chronicity of the plague and extensive involvement \npredisposes our patient to malignant transformation \neven though he did not have other frequently reported \npredisposition such as previous treatment with \nradiotherapy6,7. Being immunocompetent with no co-\nmorbidities, the squamous cell carcinoma was found at \nthe calf, a non-traumatic site consistent with the finding \nof Girla and Bhattacharya8. Other reported risk factors for \nthe development of  squamous cell carcinoma includes \npatients on immunosuppressive therapy, recipients of \norgan transplant, trauma sites, burn sites, Crohn\u2019s disease \nand end-stage liver disease9, 10.\n\n\n\nThe currently available topical treatments for porokeratosis \ninclude 5-fluorouracil, imiquimod, and retinoids, as \nwell as more destructive modalities such as cryotherapy, \nCO2 laser, curettage, excision, and dermabrasion. Oral \nacitretin has also been found to be useful in reducing the \nmagnitude of disease, but there is usually recurrence of \nlesions upon its discontinuation11. Our patient showed no \nresponse to oral acitretin. Nevertheless, cryotherapy with \nliquid nitrogen appeared to reduce the thickness of the \nhyperkeratotic plaques. \n\n\n\nDue to the localized nature of the squamous cell carcinoma, \nit was excised locally with a wide margin of clearance. We \nare monitoring for any possible transformation at the same \nsite, or other new areas. It is prudent for dermatologists \nmanaging patients with linear porokeratosis to follow \nup with the patient over a period of time, and perform \nbiopsies in the event of any cutaneous changes due to its \npreponderance for malignant degeneration, especially at \nthe distal extremities. \n\n\n\nConclusion\nDermatologists managing patients with porokeratosis \nshould follow them up closely and practice a low threshold \nfor biopsies of any suspicious lesions to detect early \ndysplasia or malignancy.\n\n\n\nI.M. Friedberg, A.Z. Eisen, K. Wolff, Editors, Fitzpatrick\u2019s 1. \ndermatology in general medicine (6th ed.), McGraw-Hill, New \nYork (2003).\nOtsuka F, Iwata M, Watanabe R, Chi HI, Ishibashi Y. 2. \nPorokeratosis: clinical and cellular characterization of its \ncancer-prone nature. J Dermatol 1992; 19:702-706.\nHapple R. Cancer proneness of linear porokeratosis may be 3. \nexplained by allelic loss. Dermatology 1997; 195:20-25. \nRongioletti F, Rebora A. Disseminated porokeratosis with fatal 4. \nmetastatic squamous cell carcinoma, an additional case of \n\u2018malignant disseminated porokeratosis.\u2019 Am J Dermatopathol \n2002; 24:144-8.\nOtsuka F, Someya T, Ishibashi Y. Porokeratosis and malignant 5. \nskin tumours. J cancer Res Clin Oncol 1991; 117:55-60.\n\n\n\nSasson M, Krain AD. Porokeratosis and cutaneous malignancy: 6. \na review. Dermatol Surg 1996; 22: 339\u2013342.\nCort DF, Abdel-Aziz AM. Epithelioma arising in porokeratosis 7. \nof Mibelli. Br J Plast Surg 1972; 25:318-328. \nGirla VS and Bhattacharya SK: Clinical study of Porokeratosis. 8. \nReport of 10 cases. Interna J Dermatol 1976; 15:43-51.\nShane G. Silver, Richard I. Crawford. Fatal squamous cell 9. \ncarcinoma arising from transplant-associated porokeratosis. J \nAm Acad Dermatol 2003 Nov; 49(5):931-3.\nMorton CA, et al. Porokeratosis and Crohn\u2019s disease. J Am Acad 10. \nDermatol 1995; 32:894.\nGoldman, GD, Milstone LM. Generalized linear porokeratosis 11. \ntreated with etretinate. Arch Dermatol 1995; 131:496\n\n\n\nReference\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27MJD 2012 Dec Vol 29   \u2022\n\n\n\nKar, Atul Mohankar, Ajay Krishnan, Nitin Gangane\n\n\n\nPseudocyst of Ear \n\n\n\nKeywords: intracartilagenous swelling, auricle\n\n\n\nIntroduction\nPseudocyst of the auricle is a rare, asymptomatic, cystic, swelling of the upper portion \n\n\n\nof the auricle. It results from spontaneous collection of an oily, serous fluid within an \n\n\n\nunlined intracartilaginous cavity1. The aetiology and pathogenesis of this condition \n\n\n\nis not known. Although various medical and surgical therapeutic approaches have \n\n\n\nbeen described, the treatment of pseudocyst of auricle is difficult and recurrences are \n\n\n\nfrequent2.\n\n\n\nCase report\nAn 18 year old young boy presented with asymptomatic swellings in both the pinna \n\n\n\nof the ear since 15 years. There was no preceding history of trauma to the ear and \n\n\n\nhis general condition was fair. On examination, there were 2 cystic, non-tender 1.5 x \n\n\n\n2cm sized swellings over each of the ear lobule. A clinical diagnosis of pseudocyst of \n\n\n\nthe auricle was made. The cyst was excised under all aseptic precautions and sent for \n\n\n\nhistopathological examination which confirmed a keratin inclusion cyst.\n\n\n\nDiscussion\nPseudocyst of the auricle is characterized by a unilateral, asymptomatic, cystic swelling \n\n\n\nof the helix or the antihelix, most often located in the scaphoid fossa. Engel in 1966 \n\n\n\nfirst reported the pseudocyst of auricle in the Chinese3. This rare disorder results from \n\n\n\nspontaneous accumulation of a sterile, oily yellowish fluid, resembling olive oil. It is \n\n\n\nmostly observed in young adult males and presents clinically as a solitary, fluctuant, \n\n\n\nnon-inflammatory swelling of the upper portion of the auricle with normal overlying \n\n\n\nskin.\n\n\n\nCorrespondence\nDr Sumit Kar\nDepartment of Dermatology, Venereology and Leprosy, MGIMS, Sewagram, Wardha,\nMaharashtra - 442102             \nEmail: karmgims@gmail.com\n\n\n\nGENERAL DERMATOLOGY - SHORT CASE\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28 \u2022   MJD 2012 Dec Vol 29\n\n\n\nFig 1  cyst in left ear lobule.\n\n\n\nFig 3  removal of cyst.\n\n\n\nFig 2  cyst in right ear lobule.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29MJD 2012 Dec Vol 29   \u2022\n\n\n\nHistopathology reveals an intracartilaginous accumulation \nof fluid without an epithelial lining. The lack of epithelial \nlining led to the term \u2018pseudocyst\u2019.  In early lesions, the cystic \nspace is surrounded by fibrosed cartilage while in some \nareas necrosis and total dissolution of the cartilage may be \npresent. In later stages, intracavity foci of granulation tissue \nand more extensive intracartilaginous fibrosis is present4.  \nThe aim of treatment is to ensure successful resolution of \nthe pseudocyst without damage to the healthy cartilage and \nto prevent its recurrences. Various treatments reported in \nliterature include simple aspiration, intralesional injection \nof corticosteroids, and aspiration in combination with \nbolstered pressure sutures or plaster of Paris cast. More \ninvasive techniques like incision and drainage of the \ncavity followed by its obliteration by curettage, sclerosing \nagent and pressure dressing; open deroofing that involves \n\n\n\nremoval of the anterior cartilaginous leaflet of pseudocyst \nwith repositioning of the overlying flap of skin have also \nbeen recommended. However, the invasive treatment \nmodalities carry the risk of perichondritis complicated by \nformation of floppy ear or cauliflower deformity and may \nbe followed by recurrences5.\n\n\n\nIn our case, we removed the cyst by simple excision \nunder local anaesthesia as an outpatient procedure. The \npatient has been followed up for next 6 months with no \nrecurrence.\n\n\n\nConclusions\nWe report this case due to its rare site, and bilateral \npresentation.\n\n\n\nCohen PR, Grossman ME. Pseudocyst of the auricle:case report 1. \nand world literature reviwe. Arch Otolaryngol Head Neck Surg \n1990; 116:1202-1204. \nHarder M, Zachary C. Pseudocyst of the ear: Surgical treatment. 2. \nJ Dermatol Surg Oncol 1993; 19:585-588.\nEngel D. Pseudocyst of the auricle in the Chinese. Arch 3. \nOtolaryngol 1966; 83;197-202.  \n\n\n\nHeffner DK, Hyamo VJ. Cystic chondromalacia (endochondral 4. \npseudocyst) of the auricle. Arch Pathol Lab Med 1986; 110:740-\n743.\nSchulte KW, Neumann NJ, Ruzicka T. Surgical pearl: The close 5. \nfitting ear cover cast-a noninvasive treatment for pseudocyst of \nthe ear. J Am Acad Dermatol 2001; 44:285-287\n\n\n\nReference\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30 \u2022   MJD 2012 Dec Vol 29\n\n\n\nDr Ng Su Yuen, MRCPch,\nSabeera BKI, MPaeds\n\n\n\nA Case of Cutaneous and \nParavertebral Infantile \nHaemangioma \n\n\n\nKeywords: mediastinal mass, vascular tumour, seizures\n\n\n\nIntroduction\nHaemangiomas are common during infancy, affecting as many as 10% of infants. \n\n\n\nHowever their occurrence in the mediastinum is rare with an incidence of less than \n\n\n\n0.5% of all mediastinal masses1. We present a case of mediastinal haemangioma with \n\n\n\nparavertebral extension complicated by neurological sequelae.\n\n\n\nCase report\nA 7 month-old infant presented with seizures and fever of one week duration and \n\n\n\nmild left hemiparesis. She was ventilated for status epilepticus and was treated with \n\n\n\nanticonvulsants and antibiotics for presumed meningitis. She was noted to have a \n\n\n\nmixed haemangioma measuring 7 by 4 cm over the back which appeared soon after \n\n\n\nbirth and rapidly increased in size (Figure 1 and 2 ) There are areas of healed ulceration. \n\n\n\nThere was another deep haemangioma over the upper right shoulder measuring 3 \n\n\n\nby 2 cm. Blood investigations showed no evidence of consumptive coagulopathy. \n\n\n\nTreatment with prednisolone 3 mg/kg/day, intravenous(IV) methylprednisolone, 8 \n\n\n\ncourses of IV Vincristine 0.05mg/kg and propranolol 2 mg/kg/day was instituted as \n\n\n\nhigh output cardiac failure complicated her condition.\n\n\n\nMagnetic resonance imaging (MRI) of the spine done at 8 and a half months of life \n\n\n\nshowed an extensive vascular tumour from the level of skull base extending down to \n\n\n\nthe cervical space and further down to bilateral retroperitoneal paravertebral spaces.\n\n\n\nCo-existence right subcutaneous posterior trunk mass is present communicating with \n\n\n\nintrathoracic mass and overall appearances are typical for haemangioma. (Figure 1 \n\n\n\nand 2)\n\n\n\nCorrespondence\nDr Ng Su Yuen MRCPch\nInstitute of Paediatrics, 50586 Hospital Kuala Lumpur, Malaysia\nEmail: ngsy2002@yahoo.com\n\n\n\nPAEDIATRIC DERMATOLOGY - SHORT CASE\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31MJD 2012 Dec Vol 29   \u2022\n\n\n\nFig 1  Right subcutaneous posterior trunk mass\n\n\n\nFig 3  The prominent cerebral vascularization and pacchymeningeal \nenhancement is likely attributable to hyperdynamic circulation. \n\n\n\nFig 2  Close-up view of right subcutaneous posterior \ntrunk mass.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32 \u2022   MJD 2012 Dec Vol 29\n\n\n\nMRI brain shows right subdural collection with \ncortical laminar infraction in both parietal lobes. The \nprominent cerebral vascularization and pacchymeningeal \nenhancement is likely attributable to hyperdynamic \ncirculation. (Figure 3) \n\n\n\nAfter a prolonged stay in the ward for 3 months, she was \ndischarged well. Unfortunately she was admitted a week \nlater with seizures and complete right hemiparesis. Repeat \nCT brain showed massive left cerebral infarction at middle \ncerebral artery territory. Conservative management was \nopted after discussion with parents and she succumbed to \nher illness soon after.\n\n\n\nDiscussion\nHaemangiomas are the most common tumours of \nchildhood with most lesions (>60%) found in the head \nand neck2. The diagnosis of haemangioma was made \nclinically in our patient based on physical examination, \nabsence of consumptive coagulopathy and supported by \nMRI findings. It is usually not present at birth as in our \npatient in contrast to vascular malformations.\n\n\n\nMediastinal extension of haemangiomas and paravertebral \nand intraspinal involvement are exceptional but potentially \nharmful because of the risk of neurological impairment3. \nChiller et al demonstrated that in a series of 327 patients, \nisolated cutaneous infantile hemangioma associated with \nhemangioma of the mediastinum were found in only 3 \npatients (<1%)4.\n\n\n\nOur patient presented with neurological impairment \ndue to rapid proliferation of her haemangioma which \n\n\n\nextended from the level of skull base down to bilateral \nretroperitoneal paravertebral spaces, also extending into \nthe anterior mediastinum. She was treated aggressively \nwith prednisolone, methylprednisolone, vincristine \nand propranolol but unfortunately did not respond to \ntreatment. She developed multiple episodes of ischaemic \nstroke possibly due to steal phenomenon, compression \neffect or cerebrovasculature anomalies. It is unfortunate \nthat we could not do a magnetic resonance angiogram \n(MRA) to delineate the cerebral vessels clearly as patient \nhad already succumbed to her illness. Neurological \ncomplications are rare in true infantile haemangiomas \nunlike PHACES syndrome5. In PHACES syndrome \nneurologic complications arise mainly due to abnormality \nof cerebral vessels like progressive stenosis and occlusion \nof principal cerebral arteries. Our patient did not \nfulfill criteria for PHACES as she did not have a large \ncervicofacial haemangioma. However the presence of \npossible abnormal vessels between anterior and posterior \ncerebral vessels as seen in the MRI brain of the patient \nindicate that patient may have a variant of PHACES.\n\n\n\nConclusions\nCutaneous haemangiomas over the spine should be \nstudied with ultrasound then MRI with gadolinium (if \nabnormalities are present on ultrasound) as they can \nbe associated with intraspinal extension and dysraphic \nlesions6. Paravertebral extension of haemangioma and \nmediastinal haemangioma are rare but associated with \nrisk of neurological complications. Our case highlights \nthis potential complication and acts as reminder to \nphysicians that imaging is essential in certain cases of \ninfantile haemangioma.\n\n\n\nSabharwal GK, Strouse PJ. Posterior mediastinal hemangioma. 1. \nPediatr Radiol 2005;35:1263-1266.\nMetry D. Update on hemangiomas of infancy. Curr Opin 2. \nPediatr 2004;16:373-377.\nHerna\u00b4ndez-Martin A, Torrelo A. Cutaneous and Paravertebral 3. \nInfantile Hemangioma: Report of Two Cases. Pediatric \nDermatology 2008;25:193-195.\nChiller KG, Passaro D, Frieden IJ. Hemangiomas of Infancy. 4. \nClinical Characteristics, Morphologic Subtypes, and Their \nRelationship to Race, Ethnicity, and Sex. Arch Dermatol \n2002;138:1567-1576. \n\n\n\nHeyer GL, Millar WS, Ghatan S, Garzon MC. The Neurologic 5. \nAspects of PHACE: Case Report and Review of the Literature. \nPediatric Neurology 2006;35:419-424.\nFrieden IJ, Haggstrom AN, Drolet BA et al. Infantile 6. \nHemangiomas \u2013 Current Knowledge, Future Directions. \nPediatric  Dermatology 2005;22:383-406.\n\n\n\nReference\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33MJD 2012 Dec Vol 29   \u2022\n\n\n\nSatya Wydya Yenny,\nYuanita, Rina Gustia\n\n\n\nA Rare Case of Suspected \nDystrophic Epidermolysis\nBullosa Pruriginosa \n\n\n\nKeywords: : congenital skin anomaly, skin ulceration, skin atrophy\n\n\n\nIntroduction\nInherited epidermolysis bullosa (EB) encompasses over 30 phenotypes or genotypes. \nA characteristic feature of all types of EB is the presence of recurrent blistering or \nerosions, the result of even minor traction to this tissues.1, 2\n\n\n\nThere are four major types of inherited EB: EB simplex (EBS), junctional EB (JEB), \ndystrophic EB (DEB), and Kindler syndrome. These differ not only phenotypically \nand genotypically but more importantly by the site of ultrastructural disruption or \ncleavage.1, 2 \n \nDystrophic epidermolysis bullosa (DEB) is a rare mechanobullous genodermatosis \ninherited either with autosomal dominant or recessive pattern and characterized by \nfragility, blistering and scarring of the skin and mucous membranes. Blistering is due \nto abnormalities in anchoring fibrils (AF), microstructures mainly composed of type \nVII collagen (COLLVII), which contributes to the maintaining of dermal-epidermal \nadhesion.3\n\n\n\nMost cases are sporadic, but a few show autosomal dominant or autosomal recessive \npattern of inheritance. Microscopic studies of EB pruriginosa show typical findings \nof dystrophic EB, and it has been postulated that itching lesions of EB pruriginosa \ncould represent an abnormal dermal reactivity of some subjects to their inherited \nbullous disorder.\n\n\n\nThe study of the molecular basis of dominant dystrophic EB (classical) and EB \npruriginosa shows that both diseases are caused by a missense glycine substitution \nmutation by different amino acids in the same codon of COL 7A (G2028R and \nG2028A).4\n\n\n\nCorrespondence\nYuanita Aznil\nDr. M. Djamil Hospital / Department of Dermato-Venereology\nFaculty of Medicine, Andalas University, Padang, West Sumatra, Indonesia\nEmail: yuanitaz78@gmail.com\n\n\n\nPAEDIATRIC DERMATOLOGY - SHORT CASE\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34 \u2022   MJD 2012 Dec Vol 29\n\n\n\nDystrophic epidermolysis bullosa puriginosa (DEB-Pr) is \na distinctive clinical subtype of dystrophic EB. In DEB-\nPr patients, autosomal dominant and autosomal recessive \ninheritance and sporadic inheritance patterns have been \nrecognized. DEB-Pr presents either at birth with mild acral \nblistering and erosions, or during infancy or childhood. It \nis clinically characterized by pruritus lichenified plaques \nor nodular prurigo-like lesions, violaceous linear scarring, \noccasional trauma induced blistering, excoriations, milia, \nnail dystrophy and, in some cases, albopapuloid lesions \non the trunk. The scarring is most evident on the limbs, \nparticularly on the shins, with relative sparing elsewhere. \nIntact blisters are rarely seen. The diagnosis of EB in these \npatients may therefore be difficult, particularly as the \ncondition may only manifest itself some years after birth. \nScars frequently have a lichenoid appearance which may \ncause confusion with non-EB dermatoses, particularly \nhypertrophic lichen planus, lichen simplex, cutaneous \namyloidosis and Nekam\u2019s disease.5\n\n\n\nCase report\nA 23-year-old unmarried woman, student, Batak \nethnic, referred from dermato-venereologist, came to \nthe Dermato-Venereology Policlinic of Dr. M.D Jamil \n\n\n\nHospital Padang complaining of itchy reddish patches \nwith blackish crusts and small blisters containing clear \nfluid  in most part of the body of one year duration.\n\n\n\nAbout 10 years ago, she complained of itchy reddish patches \non the folds of the breast and the abdomen followed by \nthe appearance of tiny blisters containing clear fluid that \nbroke easily and leaved black crusts which felt sore.  Those \nreddish patches persisted and never healed completely as \nwhitish papules and plaques.\n\n\n\nFor the past year, itchy reddish patches gradually \nappeared on her trunk and lower extremities followed by \nthe appearance of small blisters containing clear liquid \nthat broke easily and leaved blisters and reddish- black \ncrusts. There was no history of reddish patches or blisters \ntriggered by consumption of wheat-made foods (bread, \nbiscuits, noodles or cakes). There was no history of \ndiarrhoea after consumption of wheat-made foods. There \nwas no history of hair loss, brittle or discoloured nails. She \nlost 8 kg over the past one year. There was no history of \nherbal medicine and long-term medication. There was no \nhistory of having blisters before 10 years of age.\n\n\n\nFamily Pedigree :\n\n\n\nFEMALE\n\n\n\nMALE\n\n\n\nAFFECTED\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35MJD 2012 Dec Vol 29   \u2022\n\n\n\nFig 1 Image of patient.\n\n\n\nFig 2 Image of patient.\n\n\n\nFig 3 Image of patient.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36 \u2022   MJD 2012 Dec Vol 29\n\n\n\nShe is the fourth child in her family. Her younger brother, \nwho is a 19 year-old Batak student, had similar itchy \nreddish patches with black crusts in his left neck, and \nboth lower limbs for the past year. There was no history of \natopy in her family.\n\n\n\nClinically patient was underweight with a BMI of 14.45 \nand anaemic. Other examinations were in normal limits. \nThere was no hair loss. On extremities there was no \noedema.\n\n\n\nThere were erythematous plaques, black-reddish crusts, \nvesicles, reddish papules, hyperpigmented plaques, \nexcoriations, hypertrophic scars, atrophic scars, whitish/ \nalbupapuloid papules on most of her body. The size \nof the blisters ranges from pin-point to large plaques. \nKoebner\u2019s phenomenon was positive. Nikolsky sign was \nnegative. Tzanck test was negative. Mucous membranes \nwere normal. Hair and nails were normal. There were no \nenlargements of regional lymph nodes.\n\n\n\nThe provisional diagnosis was linear IgA dermatoses \nwith differential diagnosis of dermatitis herpetiformis, \nepidermolysis bullous acquisita and dystrophic \nepidermolysis bullous pruriginosa, \n \nFrom laboratory findings we found anemia and \nhypereosinophilia. Result of histopathology examination \nrevealed mild acanthosis in epidermis, there were debris \nwith fibrocollagen tissue with perivascular lymphocyte \nand eosinophils infiltrate noted in dermis. These feature \nsupported diagnosis of non-specific chronic dermatitis. \nResult of direct immunofluorescence from skin biopsy did \nnot show deposits of immunoglobulins (IgG, IgA, IgM), \nC3 and fibrinogen and from indirect immunofluorescence \nantibody against epidermal\u2019s component was negative, this \nresult indicate this case was not caused by immunological \nfactor, thus supporting the diagnosis of dystrophic \nepidermolysis bullosa.\n\n\n\nOur provisional diagnosis was dystrophic epidermolysis \nbullosa pruriginosa (DEB-Pr) with a differential diagnosis \nof generalized dystrophic epidermolysis bullosa. We \nsuggest the patient to do transmission electron microscope \nexamination, salt split technique and gene mutation \nanalysis examination to find mutation in COL7A1 gene \nencoding type VII collagen, but these examinations could \nnot be done in Indonesia.\n\n\n\nPatient was treated with oral methylprednisolone 20 mg \nand loratadine 10 mg daily. She was also prescribed with \ntopical desoximetasone 0.25% ointment twice daily for \nthe red patches.\n\n\n\nDiscussion\nDystrophic epidermolysis bullosa pruriginosa (DEB-\nPr ) was first described by McGrath et al. in 1994. It is a \nrare clinical variant of DEB,3, 7 characterized by marked \npruritus, trauma-induced blistering, especially on the \nextensor aspect of the leg, nail dystrophy, prurigo-like \nlesions and multiple milia. \n\n\n\nDEB is caused by mutations in the COL7A1 gene encoding \ntype VII collagen, resulting in a reduced number or \ndisorganization of anchoring fibrils. In DEB-Pr, mainly \nglycine substitutions have been reported. The onset of \nclinical symptoms of DEB-Pr is typically during the first \ndecade or even in infancy; however, in some cases clinical \nonset may be delayed until later in life.7\n\n\n\nPruritus is a well-known accompanying symptom in many \nepidermolysis bullosa (EB) subtypes but also in a number \nof other dermatological conditions and systemic diseases \nsuch an atopic eczema, chronic renal failure, cholestasis, \niron deficiency and thyroid malfunction. The itch may \nbe induced by a specific cause or occur spontaneously. \nRepeated scratching can eventually lead to a prurigo-like \nclinical picture, similar to the skin manifestations in DEB-\nPr.8 Our patient complaint of pruritus which accompanies \nthe skin disorders without any history of atopy from \npatient and family.\n\n\n\nThe aims of treatment for DEB-Pr are to ease the pruritus \nand to suppress the scratching activity that leads to the \nformation of blisters and or prurigo-like lesions; however, \nno universally successful treatment has been established. \n\n\n\nRecent studies have described the efficacy of topical \ntacrolimus, systemic cyclosporine and thalidomide.6,10,11 \nBanky et al. advocate use of topical tacrolimus6 and  \nHayashi found that a higher dose of prednisolone (10-30 \nmg/day) as potentially useful treatment options for DEB-\nPr.7 \n\n\n\nMeymandi SS et al. (Iran, 2010) reported a case of \nepidermolysis bullosa pruriginosa in a 15-year-old \nIranian girl who improve after four months therapy with \ntopical clobetasol propionate 0.05% ointment twice daily \nwith oral vitamin E 400 u/daily and oral antihistamine \n(loratadine 10 mg/daily).11 \n\n\n\nWe treated the patient with methylprednisolone 20 mg, \nloratadine 10 mg, and dexamethasone 0.25% ointment \ntwice daily. We gave the treatment for two weeks which \nresulted in decrease in pruritus and absence of new \nlesion.\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n37MJD 2012 Dec Vol 29   \u2022\n\n\n\nFine JD. Inherited epidermolysis bullosa. Fine Orphanet 1. \nJournal of Rare Diseases 2010, 5:12\nMarinkovich MP, Bauer EA. Inherited epidermolysis bullosa. 2. \nIn: Freedberg IM, Eisen AZ, Wolff AK, Austen KF, Goldsmith \nLA, Katz SI, Fitzpatrick TB, editors. Dermatology in general \nmedicine. 7th Edition. New York: Mc.Graw-Hill; 2008:505-15\nDrera B, Castiglia D, Zoppi N, Gardella R, Tadini G, Floriddia 3. \nG, De Luca N, Pedicelli C, Barlati S, Zambruno G, Colombi M. \nDystrophic epidermolysis bullosa pruriginosa in Italy: clinical \nand molecular characterization. Clin Genet 2006;70: 339\u201347.\nDas JK, Sengupta S, Gangopadhyay AK. Epidermolysis bullosa 4. \npruriginosa \u2013 Report of three cases. Indian J DermatolnVenereol \nLeprol 2005;71:109-11.\nMeymandi SS, Dabiri S, Shafiei H. Epidermolysis Bullosa 5. \nPuriginosa: report of a case. Iranian Journal of Dermatology \n2010;13:20-3.\nBanky JP, Sheridan AT, Storer AL, Marshman G. Successful 6. \nTreatment of Epidermolysis Bullosa Pruriginosa With Topical \nTacrolimus. Arch dermatol 2004;140:794-6\n\n\n\nHayashi M, Kawaguchi M, Hozumi Y, Nakano H, Sawamura 7. \nD, Suzuki T. Dystrophic epidermolysis bullosa pruriginosa of \nelderly onset. Journal of Dermatology 2011;38: 173\u20138\nSchumann H, Has C, Kohlhase J, Bruckner-Tuderman L. 8. \nDystrophic epidermolysis bullosa pruriginosa is not associated \nwith frequent FLG gene mutations. British Journal of \nDermatology 2008,159:464\u20139\namasaki H, Tada J, Yoshioka T, Arata J. Epidermolysis bullosa 9. \npruriginosa successfully controlled by oral cyclosporin. Br J \nDermatol 1997;137: 308\u201310.\nOzanic Bulic S, Fassihi H, Mellerio JE, McGrath JA, Atherton 10. \nDJ. Thalidomide in the management of epidermolysis bullosa \npruriginosa. Br J Dermatol 2005; 152: 1332\u20134.\nMeymandi SS, Dabiri S, Shafiei H. Epidermolysis bullosa 11. \npruriginosa: report of a case. Iran J Dermatol 2010;13:20-23 .\n\n\n\nReference\n\n\n\n\n\n\n\n\n\n"
"\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2014 Jul Vol 32\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:  rohnaridzwan@\nyahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology can \nbe sent to me at:\nrohnaridzwan@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. 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Topics may include updates in clinically relevant \nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author who \nwill be responsible for reading the proofs must also be given on \nthe title page. The author(s) must also declare any affiliation or \nsignificant financial involvement in any organizations or entity \nwith a direct financial interest in the subject matter or materials \ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in \nthe manuscript. 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Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on \nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\nNotice to Authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2014 Jul Vol 32\n\n\n\nEDITORIAL\n\n\n\n2 Malaysian Clinical Practice Guidelines for \n the Management of Psoriasis Vulgaris \n 2013: Summary of recommendations\n Choon SE, Adawiyah  J, Chan LC, Chong HC, \n Dawn A, Hazreen AM, Koh CH, Loh YL, \n Mohd Aminuddin MY, Sin LT, Suganthi T, \n Tang JJ, Wong SM, Yunus S\n\n\n\nGENERAL DERMATOLOGY \n\n\n\n ORIGINAL ARTICLE\n13 Pattern of metal allergy in Selayang \n Hospital, Malaysia\n Norazura M, Rohna R, Kasmawati T et al\n\n\n\n CASE REPORT\n20 Dyskeratosis Congenita: A case report and \n review of literature \n Norashikin S\n\n\n\n23 Generalised Sweet Syndrome lesions \n associated with Behcet\u2019s disease \n Ling HN, Julian MT, Pubalan M\n\n\n\n26 Nodular melanoma presenting with \n paraplegia \n Nur Ashikin A, Nor Salmah B, Tarita T, Yap SH\n\n\n\nDERMATOLOGY INFECTION\n\n\n\n ORIGINAL ARTICLE\n31 A Retrospective Review of Tinea Capitis \n Infection \n Tan SS, Chan LC\n  \n CASE REPORT\n35 Varicella Zoster-associated Vasculitis in\n an Immunocompetent Host\n Evelyn YT, Sai YC, Joyce Siong SL,  Jiun YP \n\n\n\nABSTRACTS OF MASTERS IN ADVANCE \nDERMATOLOGY (UKM) DISSERTATION\n\n\n\n ACNE\n39 Acne vulgaris: Quality of life and cost of illness\n in government dermatology clinics in Sarawak\n Felix Yap Boon Bin\n\n\n\n40 Antibiotic sensitivity of propionibacterium acnes \n isolated from patients with acne vulgaris in\n Kuala Lumpur Hospital, Malaysia\n Tang Jyh Jong\n\n\n\n ADVERSE DRUG REACTIONS\n41 Human leukocyte antigen (HLA) in toxic epidermal \n necrolysis (TEN) and Stevens Johnson Syndrome\n Chang Choong Chor \n\n\n\n DERMATITIS\n42 Fingerprint biometrics changes in hand dermatitis\n Lee Chew Kek\n\n\n\n43 Prevalence of positive patch test among healthcare \n workers to rubber additives, natural rubber latex and \n synthetic rubber gloves and risk factors associated \n with positive patch test\n Peter Ch\u2019ng Wee Beng\n\n\n\n44 Efficacy and safety of sodium hypochlorite (bleach) \n baths in patients with moderate to severe atopic \n dermatitis\n Wong Su-Ming\n\n\n\n45 The efficacy and safety of tacrolimus ointment in \n patients with moderate to severe atopic eczema\n Ng Ting Guan\n\n\n\n ERYTHRODERMA\n46 Comparison of transepidermal water loss (TEWL) \n between normal and erythrodermic patients of various \n aetiology\n Noorlaily Mohd Noor\n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2014 Jul Vol 32\n\n\n\n PEMPHIGUS\n47 Impact of systemic glucocorticoids on bone \n mineral density in patients with \n pemphigus\n Mazlin Baseri\n\n\n\n PHOTOBIOLOGY\n48 Narrowband UVB phototherapy: \n Comparison of two starting doses using \n 50%MED and skin phototype\n Kartini Farah Abd. Rahim\n\n\n\n PSORIASIS\n49 Cardiac abnormalities in Psoriasis\n Priya Gill\n\n\n\n50 The effect of smoking cessation on severity \n of psoriasis\n Adawiyah Jamil\n\n\n\n51 Development of a computerized objective \n assessment of area and erythema for PASI \n scoring of severity of psoriasis and \n comparing with the conventional visual \n assessment of PASI by dermatologist\n Azura Afandi\n\n\n\n52 Quality of life and cost of illness in patients \n with psoriasis in Malaysia: A multicentre \n study\n Tang Min Moon\n\n\n\n53 Comparison of two dosing regimens for \n administering oral methotraxate in \n patients with moderate to severe plaque \n psoriasis (the Co-tromp study)\n Chong Yew Thong\n\n\n\n SCABIES\n54 Comparative study of the efficacy of benzyl \n benzoate and permethrin in the treatment \n of scabies\n Penny Lim Poh Lu\n\n\n\n Vitiligo\n55 Efficacy and safety of tacrolimus ointment in vitiligo \n using both an objective and subjective method for \n the evaluation of repigmentation progression\n Norashikin Shamsudin\n\n\n\nANOUNCEMENT\n\n\n\n CPD\n56 39th Annual General Meeting and Dermatology \n Conference 2014\n\n\n\n57 73RD American Academy of Dermatology Annual \n Meeting San Francisco 2015\n\n\n\n58 23RD World Congress of Dermatology Vancouver 2015\n\n\n\nContents\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1MJD 2014 Jul Vol 32\n\n\n\nEditor-in-Chief \nRohna Ridzwan, MRCP\nrohnaridzwan@yahoo.com\n\n\n\nFounding Editor\nSteven Chow Kim Wing, FRCPI\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP \nghbelani@hotmail.com\n\n\n\nChang Chong Chor, MAdvDerm\nccchor@gmail.com\n\n\n\nTan Min Moon, MAdvDerm\nminmoon2005@yahoo.com\n\n\n\nHenry Foong Boon Bee, FRCP\nbbfoong@pc.jaring.my\n\n\n\nChan Lee Chin, MMed \nlccjess@yahoo.com\n\n\n\nAgnes Heng Yoke Hui, MRCP\nagnesheng2002@yahoo.com\n\n\n\nFelix Yap Boon Bin, MAdvDerm \nwoodzlamp@yahoo.com\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nExecutive Staff\nNajeeb Ahmad Safdar, MRCP - President \nKoh Chuan Keng, MRCP - Past President \nHenry Foong Boon Bee, FRCP - Vice President  \nAgnes Heng Yoke Hui, MRCP - Secretary\nNoor Zalmy Azizan, MAdvDerm - Treasurer\nMd Noh Idris, FRCP, FRCPI\nChan Lee Chin, MMed\nKhor Guat Ee, MRCP\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2014 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 MJD 2014 Jul Vol 32\n\n\n\neditorial\nMalaysian Clinical Practice Guidelines for \nthe Management of Psoriasis Vulgaris 2013:\nSummary of recommendations\nChoon Siew Eng FRCP,\non behalf of the Guideline Development group\n\n\n\nMalaysia Health Technology Assessment Section,\nMedical Development Division, Ministry of Health Malaysia\n\n\n\nMembers of Development group: Choon Siew En (chairman), Adawiyah  Jamil, Chan Lee Chin, Chong Hwee \nCheng, Dawn Ambrose, Hazreen Abdul Majid, Koh Chang Heng, Loh Yet Lin,\nMohd Aminuddin Mohd Yusof, Sin Lian Thye, Suganthi Thevarajah, Suriati Hashim, Tang Jyh Jong, Wong Su \nMing, Yunus Shariff\n\n\n\nIntroduction\nPsoriasis is a genetically determined, systemic \nimmune-mediated chronic inflammatory disease \nthat affects primarily the skin and joints. It has \nbeen estimated to affect 1 - 3% of the general \npopulation worldwide. There is no population-\nbased prevalence study on psoriasis in Malaysia. \nHowever, new cases of psoriasis accounted for 2 \nto 6% of all new dermatology clinic attendees in \nMalaysia1,2. There are several distinctive clinical \nsub-types of psoriasis. Psoriasis vulgaris (Figure \n1), the most common type, is seen in 85% of \nthe 4,445 patients registered in the Malaysian \nPsoriasis Registry3.Psoriatic arthritis (PsA) is \npresent in 16%.\n\n\n\nPsoriasis can be as physically and mentally \ndisabling  as other major medical diseases such \nas cancer, heart disease, diabetes, hypertension, \narthritis and depression4,5. Patients not only have \nto deal with their highly visible skin disease, they \nalso endure physical discomfort such as skin \ntightness, pain, bleeding and itch. When tested \nwith SF36, patients with psoriasis only score \nbetter than patients with congestive heart failure \nin terms of physical health and they are only better \noff than patients with depression and chronic \nlung disease in terms of mental health5. Psoriasis \nis a systemic chronic inflammatory disease \nwith significant increased risk of cardiovascular \nmorbidity and mortality. Numerous studies \ndemonstrated that patients with psoriasis are \n\n\n\nFigure 1  Well demarcated erythematous plaques with \nsilvery scales.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2014 Jul Vol 32\n\n\n\nmore prone to metabolic syndrome or the \nindividual component of metabolic syndromes \nnamely obesity, diabetes mellitus, dyslipidemia, \nand hypertension6-10. Co-morbidities are also \ncommon in Malaysian patients with psoriasis. \nAmong 4445 Malaysians with psoriasis, 36.8% \nwere overweight, 34.2% obese, 24.6% had \nhypertension, 17.4% had diabetes mellitus, \n15.9% had dyslipidemia, and 5.6% had ischaemic \nheart disease. Young adults with severe psoriasis \nhave a 3-fold increased risk of developing MI and \na reduction of 3 - 4 years in life expectancy7.8.11. \nThere is also increasing evidence that controlling \nchronic inflammation of psoriasis with systemic \nagents or biologics reduces cardiovascular co-\nmorbidity8,11-14.\n\n\n\nEffective treatments are available. Unfortunately, \nsurveys showed that patients frequently received \nsuboptimal care or were on ineffective treatment \nfor longer than neccessary15-16. To improve care \nof patients living with psoriasis, the Malaysia \nHealth and Technology Assessment Section \nof the Ministry of Health (MaHTAS) recently \npublished a clinical practice guidelines(CPG) for \nthe Management of Psoriasis Vulgaris in adults17. \nThis article summarises recommendations from \nthis evidence-based CPG. Evidence levels for the \nrecommendations are indicated in brackets.\n\n\n\nRecommendations\nMaHTAS recommendations are based on \nsystematic reviews of the best available evidence. \nWhen evidence is insufficient, recommendations \nare based on the Guideline Development Group\u2019s \nexperience and opinion of what constitutes good \npractice in Malaysia. The evidence used in these \nguidelines were graded using the US/Canadian \nPreventive Services Task Force Level of Evidence \n(2001), while the grading of recommendation \nwas modified from grades of recommendation of \nthe Scottish Intercollegiate Guidelines Network \n\n\n\n(Table 1). These clinical practice guidelines \n(CPG) are meant to be guides for clinical practice, \nbased on the best available evidence at the time \nof development. Adherence to these guidelines \nmay not necessarily guarantee the best outcome \nin every case. Every healthcare provider is \nresponsible for the management of his/her unique \npatient based on the clinical picture presented by \nthe patient and the management options available \nlocally.\n\n\n\nPrinciples of care\n\u2022\t Management\tshould\tstart\twith\tpatient\t\n education.\n\u2022\t Treatment\tof\tpsoriasis\tshould\tbe\ta\tcombined\t\n decision between patients and their healthcare \n providers. \n\u2022\t Treatment\tgoal\tand\tminimal\ttarget\tset\t\n should be based on disease severity and \n patient preferences.\n\u2022\t Treatment\tgoals\tachieved\tshould\tbe\t\n monitored regularly to detect loss of response \n which may necessitate modification of therapy \n (Table 2)\n\n\n\nAssessment of disease severity\n(Grade C)\n\u2022\t Assess\tseverity\tand\timpact\tof\tpsoriasis\ton\t\n patient\u2019s quality of life\n - At first presentation\n - Before referral for dermatologist advice \n  and at each referral point in the treatment \n  pathway (Algorithm 1)\n - To evaluate effectiveness of interventions at \n  specific time points (Table 2)\n\u2022\t Use\tpercentage\tof\tbody\tsurface\tarea\tinvolved\t\n (BSA) or psoriasis area and severity Index \n (PASI) score to measure physical severity of \n psoriasis\n\u2022\t Use\tDLQI\tto\tmeasure\timpact\tof\tpsoriasis\ton\t\n patient\u2019s quality of life\n\u2022\t Classify\tseverity\tinto\tmild,\tmoderate\tor\tsevere\t\n psoriasis (Algorithm 1 & 2)\n\n\n\nA At least one meta-analysis, systematic review, or RCT, or evidence rated as good \n and directly applicable to the target population \n\n\n\nB Evidence from well conducted clinical trials, directly applicable to the target \n population, and demonstrating overall consistency of results; or evidence \n extrapolated from meta analysis, systematic review, or RCT \n\n\n\nC Evidence from expert committee reports, or opinions and /or clinical \n experiences of respected authorities; indicates absence of directly applicable \n clinical studies of good quality\n\n\n\nTable 1  Grades of recommendations.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 MJD 2014 Jul Vol 32\n\n\n\nIdentification of PsA and other \ncomorbidities (Grade C)\n\u2022\t Assess\tjoint\tinvolvement\tat\tfirst\tpresentation\t\n and then regularly (at least annually) by \n looking for relevant signs and symptoms  \n - Joint swelling \n - Dactylitis\n - Significant early morning stiffness >1/2 \n  hour\n\u2022\t Assessment\tof\tpatient\twith\tpsoriasis\tshould\t\n include psychosocial measure and patients \n should be referred to mental health services if \n necessary.  \n\u2022\t Psoriasis\tpatients\tshould\tbe\tregularly\tscreened\t\n for metabolic syndrome and risk factors of \n artherosclerosis-related diseases \n\u2022\t Patient\twith\tpsoriasis\tor\tPsA\tshould\tbe\t\n\n\n\neditorial Malaysian Clinical Practice Guidelines for the Management of Psoriasis Vulgaris 2013: \n                Summary of recommendations\n\n\n\nTreatment\n\n\n\nTopical agents\n\n\n\nPhototherapy\n\n\n\nMethotrexate\n\n\n\nCyclosporin\n\n\n\nAcitretin\n\n\n\nInfliximab\n\n\n\nAdalimumab\n\n\n\nUstekinumab\n\n\n\nEtanercept\n\n\n\nTime to evaluate \ninitial response\n\n\n\n(weeks)\n\n\n\n 6\n\n\n\n 6\n\n\n\n 16\n\n\n\n 16\n\n\n\n 12\n\n\n\n 10\n\n\n\n 16\n\n\n\n 16\n\n\n\n 24\n\n\n\nMinimal targets\n\n\n\n$ BSA  \u2265 50% or PASI  \u2265 50 or \n\n\n\nDLQI \u2264 5\n\n\n\n$ BSA \u2265 75% or \n\n\n\nPASI  \u2265 75 or \n\n\n\nDLQI \u2264 5\n\n\n\nPASI  \u2265 75 or \n\n\n\nPASI 50 to < 75 plus DLQI \u2264 5\n\n\n\nTime to evaluate maintenance \nof response (months)\n\n\n\n 6-12\n\n\n\n 6\n\n\n\n 6\n\n\n\nTable 2  Treatment goals and time for evaluation of the effectiveness of therapeutic interventions.\n\n\n\nFigure 2  Erythrodermic psoriasis : \ngeneralised redness with thick scales on back.\n\n\n\nFigure 3  Generalised pustular psoriasis showing \nsuperficial pustules and lakes of pus.\n\n\n\n$ BSA \u2265 50% - at least a 50% reduction in body surface area involved (BSA) \nPASI \u2265 50 - at least a 50% reduction psoriasis area and severity index (PASI) score\nDLQI \u2013 Dermatology Life Quality Index; DLQI \u2264 5 means disease has little or no effect on patient\u2019s quality of life\n\n\n\n encouraged to adopt a healthy lifestyle \n - Regular exercise\n - Maintain healthy body weight (Body Mass \n  Index 18.5 - 24.9)\n - Stop smoking \n - Avoid alcohol or drink in moderation\n\n\n\nIndications for referral\n\u2022\t Dermatology\treferral\n - Diagnostic uncertainty.\n - Erythrodermic (Figure 2) or generalised \n  pustular psoriasis (Figure 3)should be \n  referred urgently for specialist assessment \n  and treatment.\n - Patients who have failed adequate trial of \n  topical therapy for 6 -12 weeks.\n - Psoriasis that requires phototherapy or \n  systemic therapy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2014 Jul Vol 32\n\n\n\n\u2022\t Rheumatology\treferral\n - Diagnostic evaluation of patients with \n  suspected arthritis.\n - Formulate management plan for PsA.\n\n\n\nTopical therapy\n\u2022\t Patients\twith\tmild\tor\tmoderate\tpsoriasis\twith\t\n minimal impairment in quality of life \n (DLQI\u2264 5) should be treated with topical \n agents. (Grade C)\n\u2022\t Emollient\tshould\tbe\tused\tregularly.\n (Grade C)\n\u2022\t Tar-based\tpreparations\tmay\tbe\tused\tas\ta\t\n first-line topical therapy. (Grade A)\n\u2022\t Short-term\tuse\tof\tpotent\tand\tvery\tpotent\t\n topical corticosteroid may be used to clear \n limited plaques. (Grade A)\n - Avoid use on the face, genitalia and body \n  folds. (Grade C)\n - Limit use of super potent corticosteroid to \n  less than 30gm/week. (Grade C)\n - Limit use of potent corticosteroid to less \n  than 60gm/week. (Grade C)\n - Continuous use of potent corticosteroid \n  should not exceed four weeks. (Grade C)\n - Continuous use of super potent \n  corticosteroid should not exceed two \n  weeks. (Grade C)\n\u2022\t Mild\tpotency\tcorticosteroid\tmay\tbe\tused\tfor\t\n face, genitalia and body folds. (Grade C)\n\u2022\t Vitamin\tD\tanalogue\tmay\tbe\tused\tmay\tbe\tused\t\n for short-term treatment. (Grade A)\n - Limit use to less than 100g/week\n\u2022\t Fixed\tdose\tcombination\tof\tvitamin\tD\t\n analogue and corticosteroid may be used for \n short-term treatment. (Grade A)\n\u2022\t Review\tpatient\t6\tweeks\tafter\tstarting\ta\tnew\t\n topical agent\n - Evaluate tolerability and initial response to \n  treatment.\n - Reinforce the importance of adherence \n  when appropriate.\n - Reinforce the importance of a not using  \n  potent or very potent corticosteroids long \n  term.\n - If there is little or no improvement at this \n  review.\n\u2022\t Discuss\tnext\ttreatment\toptions\t(refer\t\n dermatologist or change to another topical \n agents).\n\n\n\nPhototherapy \n\u2022\t Phototherapy\tshould\tbe\toffered\tto\tpatients\t\n who failed topical therapy before starting \n them on systemic agents. (Grade C)\n\n\n\n\u2022\t Phototherapy\t2-3\tsessions\tper\tweek\tmay\tbe\t\n offered to patients with moderate to severe \n psoriasis. (Grade A)\n\u2022\t Life\ttime\texposure\tto\tPUVA\tand\tUVB\tshould\t\n not exceed 200 and 350 sessions respectively. \n (Grade C)\n\u2022\t Review\tpatient\t6\tweeks\tafter\tstarting\t\n phototherapy\n - Evaluate tolerability and initial response to \n  treatment.\n - Reinforce the importance of adherence \n  when appropriate.\n - If there is little or no improvement at this \n  review, consider conventional systemic \n  therapy.\n\n\n\nConventional systemic therapy\n\u2022\t Conventional\tsystemic\ttherapy\tshould\tbe\t\n offered to patients with moderate to severe \n psoriasis who failed or have contraindications  \n to phototherapy or when phototherapy is not \n available. (Grade C)\n\u2022\t Pre-treatment\tassessment\t(Box\t1)\tand\tregular\t\n monitoring for toxicity should be done. \n (Grade C)\n\u2022\t Offer\tmethotrexate\tas\tthe\tfirst\tchoice\tof\t\n systemic agent except when contraindicated \n because of safety concerns. (Box 2)\n (Grade A)\n - Neutropenia and hepatotoxicity should \n  be closely monitored. (Box 3 &\n  Algorithm 3) (Grade C)\n\u2022\t Cyclosporine\tmay\tbe\toffered\tas\tshort-term\t\n treatment for rapid disease clearance in \n moderate to severe psoriasis. (Grade A)\n\u2022\t Cyclosporine\tmay\tbe\toffered\tas\tsecond-\n line systemic agent to patients who failed, \n are intolerant or have contraindications to \n methotrexate. (Grade A)\n - Cyclosporine should NOT be used for more \n  than 2 years. (Grade B)\n - Cyclosporine should be avoided in patient \n  with previous PUVA exposure. (Grade B)\n - Blood pressure, renal function, lipid profile \n  should be monitored closely in psoriasis \n  patient on cyclosporine (Box 4). (Grade C) \n\u2022\t Acitretin\tmay\tbe\toffered\tfor\tthe\ttreatment\tof\t\n moderate to severe plaque psoriasis. (Grade A)\n - Acitretin should be avoided in women of \n  childbearing age without reliable \n  contraception and in those who are \n  planning pregnancy. (Grade C)\n - However; it is safe for men who are \n  planning to have a child. (Grade C)\n - Lipid profile and LFT should be monitored \n  regularly (Box 5). (Grade C)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 MJD 2014 Jul Vol 32\n\n\n\nBiologics\n\u2022\t Biologic\tshould\tbe\toffered\tby\ta\tdermatologist\t\n to patients with moderate to severe plaque \n psoriasis who failed, have intolerance or \n contraindications to conventional systemic \n treatment and phototherapy. (Grade A)\n\u2022\t Careful\tevaluation\tfor\tcontraindication\tshould\t\n be done prior to initiation of biologics for \n psoriasis patients (Box 6). (Grade A)\n\n\n\n\u2022\t Safety\tissues\tshould\tbe\tmonitored\tduring\tand\t\n after treatment of biologics (Box 7).\n (Grade A)\n\u2022\t All\tpatients\ton\tbiologics\tshould\tbe\tregistered\t\n in National Psoriasis Registry. (Grade C)\n\u2022\t Psoriasis patients with latent tuberculosis \n should be referred to respiratory physician for \n treatment before biologics initiation. (Grade A)\n\n\n\neditorial Malaysian Clinical Practice Guidelines for the Management of Psoriasis Vulgaris 2013: \n                Summary of recommendations\n\n\n\nBox 1: Baseline assessment before \nstarting conventional systemic/\nbiologics therapy.\n\n\n\nHistory and examination to exclude the \nfollowing: \n\u2022\t Current\tand\tprevious\thistory\tof\tTB\tinfection\t\n\u2022\t Current\tand\tprevious\thistory\tof\tmalignancy\t\n\u2022\t Active\tinfection\t\n\u2022\t HIV\tinfection\t\n\u2022\t Hepatitis\tB/C\t\n\u2022\t Congestive\theart\tfailure\t\n\u2022\t Demyelinating\tdisease\t\n\u2022\t Pregnancy\t\t\n\u2022\t Intention\tto\tget\tpregnant\t\n\u2022\t Breast-feeding\t\n\n\n\nInvestigations \n\u2022\t FBC\t(\tFull\tblood\tcount)\n\u2022\t ESR\t(Erythrocyte\tsedimentation\trate)\n\u2022\t CRP\t(C-reactive\tprotein)\n\u2022\t UFEME\t(\tUrine\tanalysis)\n\u2022\t LFT\t(Liver\tfunction\ttest)\n\u2022\t FLP\t(Fasting\tlipid\tprofile)\n\u2022\t FBS\t(Fasting\tblood\tsugar)\n\u2022\t RP\t(Renal\tprofile)\n\u2022\t HBsAg\t-\tIf\tpositive\trefer\tGastroenterologist/\n General Physician \n\u2022\t Hepatitis\tB\t\tcore\tantigen\t-\tIf\tpositive\trefer\t\n Gastroenterologist/General Physician \n\u2022\t HCV\tAb\t-\tIf\tpositive\trefer\t\n Gastroenterologist/General Physician \n\u2022\t HIV\t\n\u2022\t ANA\t-\tIf\tpositive\tto\trefer\tRheumatologist/\n General Physician \n\u2022\t CXR\t\n\u2022\t Mantoux\ttest\t\n\u2022\t Interferon\tgamma\trelease\tassay\tif\tindicated\t\n (extra pulmonary tuberculosis)\n\u2022\t Urine\tpregnancy\ttest\t(UPT)\n\n\n\nBox 2: Risk factors for methotrexate \ntoxicity.\n\n\n\nRisk factors for methotrexate induced \nhematologic toxicity \n\u2022\t Renal\tinsufficiency\n\u2022\t Advanced\tage\n\u2022\t Lack\tof\tfolate\tsupplementation\n\u2022\t Medication\terrors\n\u2022\t Drug\tinteractions\n\u2022\t Hypoalbuminemia\n\u2022\t Excess\talcohol\tintake\n\u2022\t Multiple\tconcurrent\tmedications\n\n\n\nRisk factors for methotrexate induced \nhepatotoxicity\n\u2022\t Diabetes\tmellitus\n\u2022\t Obesity\n\u2022\t History\tof\tor\tcurrent\talcohol\tconsumption\n\u2022\t Persistent\tabnormal\tliver\tchemistry\tstudies\n\u2022\t History\tof\tliver\tdisease,\tincluding\tchronic\t\n hepatitis B or C\n\u2022\t Family\thistory\tof\tinheritable\tliver\tdisease\n\u2022\t History\tof\tsignificant\texposure\tto\t\n hepatotoxic drugs or chemicals\n\u2022\t Lack\tof\tfolate\tsupplementation\n\u2022\t Hyperlipidemia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2014 Jul Vol 32\n\n\n\nBox 3: Treatment regime and \nmonitoring of methotrexate in patients \nwith psoriasis.\n\n\n\nBefore initiation of therapy\n\u2022\t Ensure\tnormal\tbaseline\tassessment.\t(Box\t1)\n\u2022\t Discuss\tbenefit\tand\trisk\tof\ttreatment\twith\t\n patients.\n\n\n\nInitial therapy\n\u2022\t Start\twith\toral\ttest\tdose\tof\t5.0\t-\t7.5\tmg\t/\n week.\n\u2022\t Supplement\twith\tFolic\tacid\t5mg\tod\t(except\t\n the day of methotrexate) or 5mg once a week \n (the day after methotrexate).\n\u2022\t Repeat\tFull\tBlood\tCount\t(FBC),\tLiver\t\n Function Test (LFT) and Renal Profile (RP) \n within 2 weeks.\n\n\n\nMaintenance therapy\n\u2022\t Escalate\tdose\tfrom\t7.5\tmg/week\ttill\tclinical\t\n response (maximum  20 mg/week) \n [administered as  a single dose or divided \n into 3 doses and administered at 12-h \n intervals over 2 consecutive days].\n\u2022\t Monitor\tFBC/LFT/RP\tmonthly\tfor\tthe\tfirst\t3\t\n months and then after every 1 to 3 monthly.\n\u2022\t More\tfrequent\tmonitoring\tis\tneeded\twith\t\n dose  escalation.\n\u2022\t Do\tblood\ttest\t5\t-\t7\tdays\tafter\tlast\tdose\tof\t\t\n methotrexate.\n\u2022\t Monitor\ttotal\tcumulative\tdose\tof\t\n methotrexate\n - Consider Procollagen III aminopeptide/ \n  Fibroscan/Fibrotest or Liver biopsy \n  when total cumulative dose reach 3.5 \n  to 4.0g in patients without risk factors for \n  hepatotoxicity or 1.0 to 1.5g  for those \n  with risk factors for hepatotoxicit.\n\n\n\nBox 4: Treatment regime and \nmonitoring of cyclosporine in patients \nwith psoriasis.\n\n\n\nBefore initiation of therapy\n\u2022\t Ensure\tnormal\tbaseline\tassessment\t(Box\t1).\n\u2022\t Discuss\tbenefit\tand\trisk\tof\ttreatment\twith\t\n patients.\n\n\n\nInitial therapy\n\u2022\t Start\twith\t2.5\tmg/kg\tbody\tweight/day,\t\n divided in 2 doses.\n\u2022\t Escalate\tdose\tevery\t4\tto\t6\tweeks\ttill\tclinical\t\n response ( maximum 5 mg/kg /day).\n\n\n\nMaintenance  therapy\n\u2022\t Treatment\tfor\tmore\tthan\t2\tyears\tis\tnot\t\n recommended.\n\u2022\t Monitoring\twhile\ton\ttherapy:\n - Blood pressure, renal function, uric \n  acid, potassium, lipids, liver enzymes, \n  serum bilirubin,and magnesium should be \n  monitored monthly.\n\n\n\nBox 5: Treatment regime and \nmonitoring of acitretin in patients with \npsoriasis.\n\n\n\nBefore initiation of therapy\n\u2022\t Ensure\tnormal\tbaseline\tassessment\t(Box\t1).\n\u2022\t Discuss\tbenefit\tand\trisk\tof\ttreatment\twith\t\n patients.\n\n\n\nInitial therapy\n\u2022\t Start\twith\tdose\tof\t\t0.5\t-\t1\tmg/kg/day\tfor\t2\t-\t\n 4 weeks.\n\n\n\nMaintenance therapy\n\u2022\t Adjust\taccording\tto\tresponse,\tusually\twithin\t\n range of 25 - 50 mg daily (max 75 mg daily).\n\u2022\t Repeat\tlipid\tprofile\tand\tLFTs\tevery\t4\t-\t8\t\n weeks until stable, then every 6-12 weeks.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 MJD 2014 Jul Vol 32\n\n\n\nBox 6: Indications and contra-\nindications for initiation of biologics \ntherapy.\n\n\n\nIndications\nPatients with psoriasis vulgaris may be \nconsidered for biologics intervention if they have \nsevere disease as defined in Criteria A and fulfill \nat least one of the clinical categories in Criteria \nB. \n\n\n\nCriteria A\nSevere Disease\n1. PASI  \u226520 OR\n2. BSA   \u226530 OR\n3. DLQI  \u226520\n\n\n\nAND\n\n\n\nCriteria B\nClinical Categories\n1. Contraindications to phototherapy and \n standard systemic therapies AND/OR\n2.  Intolerance/inaccessibility to phototherapy \n and standard systemic therapies\n AND/OR\n3. Failed phototherapy and standard systemic \n therapies.\n\n\n\nAbsolute contraindications\n\u2022\t Active\tinfection\tincluding\tcurrent\t\n tuberculosis.\n\u2022\t Current\thistory\tof\tmalignancy.\n\u2022\t Congestive\tcardiac\tfailure\tclass\t3\tor\t4.\n\u2022\t Demyelinating\tdiseases.\n\n\n\nRelative contraindications\n\u2022\t Previous\thistory\tof\ttuberculosis\n\u2022\t HIV\tinfection\n\u2022\t Hepatitis\tB/C\n\u2022\t Current\tand/or\tprevious\thistory\tof\t\n malignancy\n\u2022\t Congestive\tcardiac\tfailure\n\u2022\t Pregnancy\tor\tbreast-feeding\n\u2022\t Intention\tto\tget\tpregnant\n\u2022\t Patient\twho\thave\thad\tprior\tPUVA\n (>200 sessions) and UVB (>350 sessions) \n\n\n\nBox 7: Treatment regime and \nmonitoring of biologics therapy in \npatients with psoriasis vulgaris.\n\n\n\nBefore initiation of therapy\n\u2022\t Ensure\tnormal\tbaseline\tassessment\t(Box\t1).\n\u2022\t Discuss\tbenefit\tand\trisk\tof\ttreatment\twith\t\n patients.\n\n\n\nDosing regime\n\u2022\t Infliximab\n - Intravenous, 5mg/kg bodyweight at week \n  0, 2, 6 and then 8 weekly.\n\n\n\n\u2022\t Ustekinumab\n - Subcutaneous, 45mg (90mg for \n  bodyweight >100kg) at week 0, 4 and \n  then 12 weekly.\n\n\n\n\u2022\t Adalimumab\n - Subcutaneous, 80mg at week 0 and then \n  every other week.\n\n\n\n\u2022\t Etanercept\n - Subcutaneous 25mg biweekly or 50mg \n  weekly or 50mg biweekly.\n\n\n\nMonitor for adverse events\n\u2022\t 6\tmonthly\tFBC,\tESR,\tCRP,\tLFT,\tRP,\tHbsAg,\t\n HCV Ab, HIV, ANA.\n\u2022\t Repeat\tlipid\tprofile\tand\tLFT\u2019s\tevery\t4\t-\t8\t\n weeks until stable, then every 6-12 weeks.\n\u2022\t Yearly\tscreening\tfor\tlatent\ttuberculosis\n\t (CXR,\tMantoux\ttest).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9MJD 2014 Jul Vol 32\n\n\n\nALGORITHM 1:\nMANAGEMENT OF PSORIASIS VULGARIS IN PRIMARY CARE\n\n\n\nPSORIASIS PATIENT \nPRESENTING TO\nPRIMARY CARE\n\n\n\nSEVERITY\n\n\n\nAssess\nDLQI\n\n\n\nAssess\nDLQI\n\n\n\n1. Assess\n \u2022 Severity \u2022 Arthritis (PsA)\n \u2022 co-morbidities\n\n\n\n2. Educate patient\n\n\n\nPresence of co-morbidities \nsuch as obesity, hypertension, \n\n\n\ndiabetes, depression etc.\n\n\n\nArticular symptoms /signs \nsuggestive of PsA\n\u2022 Joint swelling\n\u2022 Dactylitis\n\u2022 Signi\u00a0cant early morning \n stiffness > 1/2hour\n\n\n\nRegular follow-up as indicated \nAnnual assessment:-\n\u2022 Document severity\n\u2022 Assess co-morbidities and \n articular symptoms\n\u2022 Optimise topical treatment\n\n\n\nBSA - Body Surface Area\nPASI - Psoriasis area and severity index\nDLQI - Dermatology Life Quality Index\nResponder - BSA \u226550% reduction or PASI \u226550 achieved\n\n\n\nYES\nYES\n\n\n\nRefer to Rheumatologist\n\n\n\nMild\n(BSA \u226410% or PASI\u2264 10)\n\n\n\nTopical Therapy REFER DERMATOLOGIST\n\n\n\nRe-assess in 6 weeks Optimise topical therapy\n\n\n\nModerate\n(BSA >10% to 30% or PASI 10 to 20)\n\n\n\nSevere\n(BSA >30% or PASI >20)\n\n\n\nErythrodermic or generalised pustular \npsoriasis: urgent referral is indicated)\n\n\n\nMANAGE / REFER TO\nRELEVANT SPECIALITY \n\n\n\nRESPONDER\nNO\n\n\n\nYES\n\n\n\nDLQI >5\n\n\n\nDLQ \u2264I10 DLQ >I10\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10 MJD 2014 Jul Vol 32\n\n\n\nALGORITHM 2:\nTREATMENT OF PSORIASIS VULGARIS\n\n\n\nPSORIASIS\nVULGARIS\n\n\n\nMild\nBSA \u226410%\n\n\n\nor\nPASI\u226410\n\n\n\nTopical Therapy\n\n\n\nTar\n(Preferred therapy suitable \n\n\n\nfor extensive disease)\n\n\n\nDithranol\n(Large plaque)\n\n\n\nCorticosteroids\n(Short-term therapy)\n\n\n\nVitamin D analogues \n<100g/week\n\n\n\nCalcineurin inhibitors\n(Face & Flexures)\n\n\n\nModerate\n(BSA >10% to 30%\n\n\n\nor\nPASI >10 to 20)\n\n\n\nSevere\n(BSA >30%\n\n\n\nor\nPASI >20)\n\n\n\nPhototherapy\n\n\n\nSystemic Therapy\n\n\n\nAcitretin\n\n\n\nBiologics\n\n\n\nCyclosporine\n(short- term therapy)\n\n\n\nMothotrexate\n(\ufffdrst-line)\n\n\n\nAssess\nDLQI\n\n\n\nUstekinumab Adalimumab Etanercept In\ufffdiximab\n\n\n\nDLQI \u226410 DLQI>10\n\n\n\nFail / contraindicated / not available\n\n\n\nFail / contraindication / intolerance with BSA >30\nor PASI >20 or DLQI >20 or DLQI >20\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11MJD 2014 Jul Vol 32\n\n\n\nALGORITHM 3:\nMONITORING HEMATOTOXICITY AND HEPATOTOXICITY OF METHOTREXATE\n\n\n\nInitiation of Methotrexate by Dermatologist\n\n\n\n\u2022 Ensure normal baseline screening (refer appendix 7) prior to \n Methotrexate (MTX)\n\u2022 Assess risk factor for hematotoxicity & hepatotoxicity\n\u2022 Discuss bene\ufffdt & risk of MTX with patient\n (provide Patient Information Lea\ufffdet)\n\n\n\nNeutropenia / \nThrombocytopenia / \n\n\n\nAnaemia\n\n\n\nRaised liver enzymes\n\n\n\nAssess other risk factors \nfor hepatotoxicity\n\n\n\nStop M TX and change\nto other treatment\n\n\n\nElevation of ALT / AST \n(>3 fold upper limit)\n\n\n\nStop MTX and change to \nalternative drug\n\n\n\nModerate elevation of ALT / AST \n(>2 but <3 fold upper limit)\n\n\n\nReview ALT / AST in 2 to 4 weeks \nDecrease dose as needed\n\n\n\nPersistent elevation in\n5 out of 9 ALT / AST in a year\n\n\n\nRefer\ngastroenterologist / \n\n\n\nhepatologist\n\n\n\nPersistent elevation of ALT / AST\n(> 2 fold for 2 to 3 months)\n\n\n\nConsider:\n\u2022 Procollagen III aminopeptide / Fibroscan /\n Fibrotest / Liver biopsy\n\u2022 Consider alternative drug  \n\n\n\nRepeat Hep B / C\nscreening\n\n\n\nPresence of\nrisk factors\n\n\n\nYES\n\n\n\nPositive\n\n\n\nNegative\n\n\n\nNO\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 MJD 2014 Jul Vol 32\n\n\n\nReferences\n \n1. Siow KY, Safdar NA, Chong KH et al. A clinical appraisal \n\n\n\nof patients with psoriasis treated in Seremban General \nHospital, Malaysia. MJM 2004, 59(3):330 \u2013 334.\n\n\n\n2. Choon SE, Lai ML, Norshaleyna et al. Clinical profile, \nmorbidity and outcome of adult-onset Generalised \nPustular Psoriasis: Analysis of 102 cases seen in a tertiary \nhospital in Johor, Malaysia. International J Dermatol DOI \n: 10.1111/ijd.12070.\n\n\n\n3. Chang  CC, Noor Addillah S, Asmah J et al. Annual Report \nof the Malaysian Psoriasis Registry 2007-2009, National \nDermatology Registry (DermReg), Malaysia, and Clinical \nResearch Centre, Ministry of Health. Available from:http:// \nwww.acrm.org.my/dermreg.\n\n\n\n4. Weiss SC, Kimball AB, Liewehr DJ et al. Quantifying the \nharmful effect of psoriasis on health-related quality of life. \nJ Am Acad Dermatol 2002, 47:512-518.\n\n\n\n5. Rapp SR, Feldman SR, Exum L et al. Psoriasis causes as \nmuch disability as other major medical diseases. J Am \nAcad Dermatol 1999; 41:401-407.\n\n\n\n6. Mehta NN, Yu Y, Pinnelas R et al. Attributable risk estimate \nof severe psoriasis on major cardiovascular events. Am J \nMed 2011; 124(8775):e1-6.\n\n\n\n7. Mehta NN, Azfar RS, Shin DB et al. Patients with severe \npsoriasis are at increased risk of cardiovascular mortality: \ncohort study using the General Practice Research Database. \nEur Heart J 2010; 31(8):1000-1006.\n\n\n\n8. Prodanovich S, Kirsner RS, Kravetz JD et al. Association \nof Psoriasis With Coronary Artery, Cerebrovascular, and \nPeripheral Vascular Diseases and Mortality. Arch Dermatol \n2009; 145(6):700-703.\n\n\n\n9.\t Neimann\t AL,\t Shin\t DB,\t Wang\t X\t et\t al.\t Prevalence\t of\t\ncardiovascular risk factors in patients with psoriasis. J Am \nAcad Dermatol 2006; 55 (5):829-835.\n\n\n\n10. Gelfand JM, Neimann AL, Shin DB, et al. Risk of \nmyocardial infarction in patients with psoriasis. JAMA \n2006; 296:1735-1741.\n\n\n\n11. Prodanovich S, Ma F, Taylor JR et al. Methotrexate reduces \nincidence of vascular diseases in veterans with psoriasis or \nrheumatoid arthritis. J Am Acad Dermatol 2005; 52:262-\n267.\n\n\n\n12. Wu Y, Mills D, Bala M. Psoriasis: cardiovascular risk \nfactors and other disease comorbidities. J Drugs Dermatol \n2008;7(4):373-377.\n\n\n\n13. Wu JJ, Poon KT, Channual JC et al. Association Between \nTumor Necrosis Factor Inhibitor Therapy and Myocardial \nInfarction Risk in Patients With Psoriasis Arch Dermatol. \n2012;148(11):1244-1250.\n\n\n\n14. Ahlehoff O, Skov L, Gislason G et al. Cardiovascular \ndisease event rates in patients with severe psoriasis treated \nwith systemic anti-inflammatory drugs: a Danish real-\nworld cohort study. J Intern Med 2013; 273:197-204.\n\n\n\n15. Horn EJ, Fox KM, Patel V et al. Are patients with psoriasis \nundertreated? Results of National Psoriasis Foundation \nsurvey. J Am Acad Dermatol 2007;57:957-962.\n\n\n\n16. Nast A, Erdmann R, Hofelich V et al. Do guidelines change \nthe way we treat? Studying prescription behaviour among \nprivate practitioners before and after the publication of the \nGerman Psoriasis Guidelines. Arch Dermatol Res 2009; \n301:553-559.\n\n\n\n17. Malaysia Health and Technology Assessment Section \nof the Ministry of Health (MaHTAS); Clinical Practice \nGuidelines: Management of Psoriasis Vulgaris 2013. \nAvailable at www.moh.gov.my, www.acadmed.org.my, \nwww.dermatology.org.my\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2014 Jul Vol 32\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nPATTERN OF METAL ALLERGY IN SELAYANG HOSPITAL, \nMALAYSIA\n\n\n\nNorazura M, MMED (USM), Rohna R, MRCP, Kasmawati T, BcN, Norhasmie R, BcN, Nor Hayati AJ\n\n\n\nAbstract\n\n\n\nBackground: The standard allergen series used in patch testing contains only the top three metals \ncausing allergic contact dermatitis.\n\n\n\nAim: To study the pattern of metal allergy among patients who underwent patch test in Selayang \nHospital from March 2012 until March 2013.\n\n\n\nMethods: This is a retrospective prevalence study of all patients who underwent patch test in Selayang \nHospital from March 2012 to March 2013. Only patients suspected to have metal allergy were tested \nwith European Baseline Series plus additional metal series. Patch test readings were recorded according \nto the International Contact Dermatitis Research Group recommendation. The data of all patients with \nmetal allergy detected were analysed using SPSS Version 12.0.\n\n\n\nResults: 254 (1.94%) of new patients (13,081) were patch tested. 18 patients were suspected to have \nmetal allergy. Of 212 (83.4%) patients who had positive patch test, 136 patients were tested positive to \nmetal (64.1%). 15 patients (7.1%) were suspected to have metal allergy. Among the 15 patients who \nwere suspected to have metal allergy, 3 patients (20%) were tested positive to both standard and metal \nseries, 11 patients (73%) were positive to metal series but negative to standard series and one patient \n(7%) were positive to standard series but negative to metal series. The top metal allergens were nickel \nsulphate (77.7%), cobalt chloride (34.7%), potassium dichromate (17.4%), copper oxide (4.4%), gold \nsodium thiosulphate (3.7%) and palladium chloride (2.9%). The clinical distribution of the dermatitis \nwere upper limb only (31.6 %), face (19.9%), lower limbs only (19.1 %), all limbs (15.4%), trunk \n(5.9%), lips (4.4%) and whole body (3.7%).\n\n\n\nConclusion: This study highlighted metal allergies that would have been missed without patch testing \nfor additional metal series sensitizers. Under-diagnosis of metal allergy can be overcome by learning \nto recognise clinical signs of metal allergy and by including metal series sensitizers for patch testing.\n\n\n\nKeywords: nickel, cobalt, potassium dichromate, copper oxide, gold, palladium, dermatitis\n\n\n\nCorrespondence\nNorazura Mohamad, MRCP\nDepartment of Dermatology, \nSelayang Hospital\nEmail: azura1511@yahoo.com\n\n\n\nworldwide contains only the three most common \nmetals causing allergic contact dermatitis, namely \nnickel chromium and cobalt.\n\n\n\nThere has been documentation of patients developing \nallergic reactions to other metals like aluminum, \nberyllium, copper, gold and palladium. Palladium is \none of the noble metals that are chemically similar \nto platinum and it is used in jewellery, dental fillings \nand in the electronics industry.\n\n\n\nIntroduction\nMetal and metal salts are among the most common \nagents causing allergic contact dermatitis. The \nstandard allergen series used in patch testing \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 MJD 2014 Jul Vol 32\n\n\n\nAim\nThis study analysed the pattern of the various metal \nallergies in patients with positive patch test to metal \nseries in Selayang Hospital. \n\n\n\nMaterial and methods\nThis is a retrospective analysis of all patients \nwho underwent patch test in Selayang Hospital \nfrom 1st March 2012 until 31st March 2013. All \npatients who underwent patch testing for suggested \nallergic contact dermatitis from the time period \nwere identified from medical records. Consent was \nobtained from patients prior to the patch test being \ndone.  Patch test was conducted using allergens \nfrom the European Baseline Series (SE) and those \nwho were suspected of having metal allergy were \npatch tested with an additional metal series (MS) \nfrom Chemotechnique Diagnostics. \n\n\n\nThe allergens were prepared by using the IQ \nChambers and occluded at the back for 2 days. \nReadings were done on day 3 and day 5 in accordance \nto recommendation of the International Contact \nDermatitis Research Group. The medical records of \nthe patients patch tested to metal sensitizers were \nanalyzed. Site of dermatitis were grouped as lip, \nface, upper limbs, lower limbs, all limbs, trunk and \nwhole body. Patients were grouped into 2 groups; \nless than 35 years old and equal or more than 35 \nyears old.\n\n\n\nData obtained were analyzed using SPSS Version \n21. Association between categorical variables \nwas analyzed using the chi square test. Statistical \nsignificance was set at p<0.05.\n\n\n\nResults\nA total of 254 (1.94%) new patients (13,081) who \nattended dermatology clinic during this study period \nwere patch tested. Of these, 212 (83.4%) patients had \npositive patch test. Among those tested positive, 136 \n(64.1%) patients were positive to metal sensitizers. \nOf these, only 15 patients (7.1%) were suspected to \nhave metal allergy according to the medical records. \nThe majority were only diagnosed of metal allergy \nfrom the positive patch test to metal sensitizers. \n\n\n\nSuspected Metal Allergy\n\n\n\nPositive MS, positive SE\n\n\n\nPositive MS, negative SE\n\n\n\nNegative MS, positive SE\n\n\n\nN=15\n\n\n\n 3\n\n\n\n 11\n\n\n\n 1\n\n\n\nPercentage \n(%)\n\n\n\n 20.0\n\n\n\n 73.3\n\n\n\n 6.7\n\n\n\nTable 1  Frequency of positive patch test to metal \nsensitizers in patients with suspected metal allergy.\n\n\n\nGender\n   Male\n   Female\n\n\n\nRace\n   Malay\n   Chinese\n   India\n   Others\n\n\n\nAge\n    <35 years \n    >35 years & above \n \nAtopy \n\n\n\nSites\n   Lips\n   Face\n   Upper limbs\n   Lower limbs\n   All limbs\n   Trunk\n   Whole body\n\n\n\nMetal allergy suspected\nN=15\n\n\n\n \n 11\n 4\n\n\n\n 7\n 5\n 3\n 0\n\n\n\n 8\n 7\n\n\n\n 2\n\n\n\n 0\n 2\n 7\n 3\n 3\n 0\n 0\n\n\n\nPercentage\n(%)\n\n\n\n \n 35.3%\n 64.7%\n\n\n\n 54.4%\n 36.0%\n 8.1%\n 1.5%\n\n\n\n\n\n\n\n 28.7%\n\n\n\n 4.4%\n 19.9%\n 31.6%\n 19.1%\n 15.4%\n 5.9%\n 3.7%\n\n\n\nMetal allergy not suspected\nN=121\n\n\n\n \n 37\n 84\n\n\n\n 67\n 44\n 9\n 1\n\n\n\n 69\n 52\n\n\n\n 37\n\n\n\n 6\n 25\n 36\n 23\n 18\n 8\n 5\n\n\n\nTable 2  Demographic characteristic of the patients with metal allergy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2014 Jul Vol 32\n\n\n\nNICKEL SULPHATE\n  Gender\n       Male                                     \n       Female\n  Race\n      Malay\n      Non Malay\n  Age   \n      <35 years \n      >35 years & above\n   Sites\n      Lips                                        \n      Face\n      Upper limb\n      Lower limb\n      All limbs\n      Trunk\n      Whole body\n\n\n\nCOBALT CHLORIDE\n Gender\n       Male                                     \n       Female\n  Race\n      Malay\n      Non Malay\n  Age   \n      <35 years \n      >35 years & above\n  Sites\n      Lips                                        \n      Face\n      Upper limb\n      Lower limb\n      All limbs\n      Trunk\n      Whole body\n\n\n\nPOTASSIUM CHROMATE\n  Gender\n       Male                                     \n       Female\n  Race\n      Malay\n      Non Malay\n  Age   \n      <35 years \n      >35 years & above\n   Sites\n      Lips                                        \n      Face\n      Upper limb\n      Lower limb\n      All limbs\n      Trunk\n      Whole body\n\n\n\nPositive\nPatch test\n\n\n\n 15\n 50\n\n\n\n 37\n 28\n\n\n\n 37\n 28\n\n\n\n 5\n 16\n 19\n 10\n 7\n 5\n 1  \n\n\n\n\n\n\n\n 7\n 6\n\n\n\n 6\n 7\n\n\n\n 7\n 6   \n\n\n\n 0\n 2\n 6\n 1\n 1\n 2\n 1                    \n\n\n\n 7 \n 6\n\n\n\n 8                                    \n 5\n\n\n\n 7\n 6\n\n\n\n 0\n 0\n 3\n 3\n 6\n 0\n 1\n\n\n\nP value\n\n\n\n 0.004 \n \n\n\n\n 0.574\n\n\n\n 0.945\n\n\n\n 0.172\n 0.183\n 0.567\n 0.388\n 0.149\n 0.622\n 0.676\n\n\n\n 0.243\n\n\n\n 0.530\n\n\n\n 0.832\n\n\n\n 0.917\n 0.953\n 0.383\n 0.503\n 0.682\n 0.362\n 0.839\n\n\n\n 0.243\n\n\n\n 0.587\n\n\n\n 0.832\n\n\n\n 0.917\n 0.128\n 0.702\n 0.934\n 0.005\n 0.743\n 0.839\n\n\n\nNegative\nPatch test\n\n\n\n 33\n 38\n\n\n\n 37\n 34\n\n\n\n             40\n             31\n\n\n\n 1\n 11\n 24\n 15\n 14\n 3\n 3                                  \n\n\n\n 41\n 82\n\n\n\n 68\n 55\n\n\n\n 70\n 53\n\n\n\n 6\n 25\n 37\n 24\n 20\n 6\n 3\n\n\n\n 41\n 82\n\n\n\n 66\n 57\n\n\n\n 70\n 53\n\n\n\n 6\n 27\n 40\n 22\n 15\n 8\n 3\n\n\n\nTable 3  Clinical and demographic characteristics related to positive patch test to the top 4 metal allergens.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16 MJD 2014 Jul Vol 32\n\n\n\nGOLD SODIUM THIOSULPHATE\n  Gender\n       Male                                     \n       Female\n  Race\n      Malay\n      Non Malay\n  Age   \n      <35 years \n      >35 years & above\n   Sites\n      Lips                                        \n      Face\n      Upper limb\n      Lower limb\n      All limbs\n      Trunk\n      Whole body\n\n\n\nOffice workers\n\n\n\nStudent\n\n\n\nMetal and mechanical workers\n\n\n\nCashier\n\n\n\nHousewife\n\n\n\nRetired\n\n\n\nPositive\nPatch test\n\n\n\n 4 \n 1\n\n\n\n 2                                    \n 3\n\n\n\n 2\n 3\n\n\n\n 0\n 0\n 2\n 1\n 2\n 0\n 0\n\n\n\nNickel sulphate \n         N=65\n\n\n\n 24\n\n\n\n 20\n\n\n\n 3\n\n\n\n 3\n\n\n\n 12\n\n\n\n 3 \n\n\n\nP value\n\n\n\n 0.098\n\n\n\n 0.840\n\n\n\n 0.761\n\n\n\n 0.100\n 0.574\n 0.100\n 0.100\n 0.359\n 0.100\n 0.100\n\n\n\nCobalt chloride\nN=13\n\n\n\n 6\n\n\n\n 3\n\n\n\n 1\n\n\n\n 0\n\n\n\n 2\n\n\n\n 1\n\n\n\nNegative\nPatch test\n\n\n\n 44\n 87\n\n\n\n 72\n 59\n\n\n\n 75\n 56\n              \n 6\n 27\n 41\n 24\n 19\n 8\n 4\n\n\n\nPotassium dichromate \nN=13\n\n\n\n 4\n\n\n\n 3\n\n\n\n 1\n\n\n\n 2\n\n\n\n 2\n\n\n\n 0\n\n\n\nTable 4  Relationship between occupation and common metal allergens.\n\n\n\nDiscussion\nAllergic contact dermatitis (ACD) to metals is \nexpressed in a wide range of cutaneous reactions \nfollowing dermal and systemic exposure to products \nsuch as cosmetics, tattoos, detergents, jewellery \nand piercing, leather tanning, articular prostheses \nand dental implants. Apart from the well known \nsignificance of nickel in causing ACD, other metals \nsuch as aluminium, beryllium, chromium, cobalt, \ncopper, gold, iridium, mercury, palladium, platinum, \nrhodium and titanium represented emerging causes \nof skin hypersensitivity.\n\n\n\nAllergy patch-test reactions to metals may be \nmore prevalent than previously suspected. The less \ncommon sensitizing metals are not included in the \n\n\n\nstandard series. Metal series is a useful adjunct \nto the standard allergen series for the detection \nof metal allergies. The metal series has evolved \nover time to include multiple metals in different \nsalts and concentrations. Patients may react to \none concentration of a metal and not to another; \nsimilarly patients may react to one preparation of a \nmetal and not to another.\n\n\n\nAs only selected patients were patch tested \nwith metal series, the frequency of sensitization \nof different metal sensitizers are not directly \ncomparable. In Standard European series, there \nare only 3 metal allergens tested: nickel sulphate, \npotassium dichromate and cobalt chloride. The \nresults of our study showed that nickel sulphate is \nthe most frequently positive metal allergen and its \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2014 Jul Vol 32\n\n\n\nallergy is significantly more common in women. \nThis concurs with findings in other studies where \nwoman is 10 times at risk compared to men. Other \nstudies also associated nickel allergy with upper and \nlower limb dermatitis. Sources of nickel sensitization \ninclude jewellery, belt buckles, metal fasteners, \nspectacles frames and ear rings2. The epidemiology \nof metal allergy has recently changed in Europe as \nthe prevalence of nickel allergy among ear-pierced \nDanish women has decreased following regulatory \nintervention on nickel release from consumer \nproducts. In the United States, the prevalence of \nnickel allergy is still increasing, which may be \nexplained by the absence of regulation7.\n\n\n\nAlthough nickel sensitivity is more common than \ncobalt sensitivity, the two are frequently linked. \nRystedt and Fischer reported that a quarter of \nnickel-sensitive patients developed a cobalt allergy \nand patients with simultaneous nickel and cobalt \nallergies have more severe dyshidrotic eczema. \n\n\n\nCobalt is a metal found naturally in soil, dust and \nseawater and it is usually found in association with \nnickel allergy. In this study, cobalt sensitization \nis the second most common metal allergy among \nour study population. There is increased in cobalt \nsensitization with upper limb dermatitis in younger \nmales (\u2264 35 years old) as compared with previous \nstudy. Thyssen et al. in a retrospective study of \n10,335 Danish women between 1985 and 2007 \nnoted that nickel allergy diminished in younger \nwomen and increased in older ones, whereas cobalt \nsensitization remained relatively unchanged9.\n\n\n\nPotassium dichromate is a chromium salt and it is a \ncommon metal making up a significant part of the \nearth\u2019s crust. Chromium allergic contact dermatitis \nmainly affects male patients and often results from \noccupational skin contact with hexavalent chromium \nin cement. Most people relate chrome to the bright, \nshiny and durable finish of some metal products. \nHowever, contact with chrome plated objects is       \n\n\n\nFigure 1  Clinical presentations in relation to the common metal allergens.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 MJD 2014 Jul Vol 32\n\n\n\nan unlikely cause for chromium allergy. Exposure \nto this sensitizer is at workplace where chromium \nsalts are used as an ingredient in the manufacture \nof products such as cement, mortar, leather and \npaints. In this study, chrome allergy is significantly \nassociated with limb  dermatitis. The prevalence of \nchromium allergy is increasing in the United States, \nSingapore, and Denmark among dermatitis patients. \nThis increase is significantly associated with leather \nexposure in Denmark2.\n\n\n\nThe other common metal allergens are copper oxide, \ngold sodium thiosulphate and palladium chloride. \nThere is an increase in prevalence of contact \nallergy to gold and palladium recently. Gold causes \ndermatitis mainly on the face and eyelids9. Bjorkner \net al reported that among their patients, gold was the \nsecond most common allergen following nickel10. In \nour study, gold allergy is commoner in men with \nlimbs dermatitis. However there is no statistical \nsignificance difference in both sexes and sites of \nallergy.\n\n\n\nThe role of nickel as an occupational allergen is still \nunclear12. According to some authors, up to 12% \nof the total estimated cases of occupational contact \ndermatitis are thought to be due, at least partially, to \nnickel13. In this study, nickel sensitization was found \nto be more common in office workers and students. \nCobalt sensitization is believed to be involved in \nthe onset of allergic contact dermatitis in several \noccupations: hairdressing, building, hygiene and \ncleaning works14. Francesca et al found that in the \nfemale group, nickel sensitization was significantly \nassociated with metal and mechanical work, \nchromate sensitization was significantly associated \nwith construction work in both sexes and cobalt \nsensitization was significantly associated with \ntextile and leather work11.\n\n\n\nManagement of patient with metal allergy includes \navoidance of the allergen, no-touch technique at any \npossible time and avoiding foods containing nickel. \nPatients are advice to avoid or minimize contact with \nsilver coins, keys, artificial jewellery (necklaces, \n\n\n\nearrings, bracelets, rings, and watchbands), buckles, \nzippers, buttons, bra hooks, suspender clips, pens, \nhair clasps, electrical shavers, paperclips, and power \ntools that contain metal. Patients can purchase \nalternative products that are not made of metal. For \ninstance, patients can safely use coloured paper \nclips that are coated with plastic. Patients can wear \nhypoallergenic, stainless steel, solid gold, sterling \nsilver, or plastic jewellery. Patients should look \nfor clothing with plastic-coated or painted metal \nzippers, buttons, or clasps.\n\n\n\nMetal allergy has also been associated with device \nfailures following the insertion of intracoronary \nstents, hip and knee prostheses, and other implants. \nGao et al reported a case of contact dermatitis most \nlikely caused by exposure to chromium after a total \nknee arthroplasty, although this complication is \nvery rare15. The majority of total joint prostheses \nare now made of cobalt-chromium alloys with a \nnickel content of less than 1%16. The occurrence of \nACD is particularly uncommon following total knee \narthroplasty because there is a polyethylene insert \nbetween the femoral and tibial components and no \nmetal-on-metal contact exists.\n\n\n\nThis study also showed that 73% of patients who \nwere suspected to have metal allergy would have \nbeen missed if they were not tested with additional \nmetal series. In addition, 57% of patients suspected \nof contact dermatitis were not suspected to have \nmetal allergy.\n\n\n\nFrom our study, we find that under-diagnosis of \nmetal allergy can be overcome if clinicians are able \nto recognize signs of metal allergy clinically and \nadd metal series sensitizers beside standard baseline \nseries in patch test. A more extensive multicentre \nstudy is required to substantiate the findings of this \nstudy\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n \n1. Uter W, Hegewald J, Aberer W et al. The European standard \n\n\n\nseries in 9 European countries, 2002/2003 \u2013 first results \nof the European surveillance system on contact allergies. \nContact Dermatitis 2005; 53:136\u2013145.\n\n\n\n2. Fowler JF. Allergic Contact Dermatitis to metals. Am J \nContact Dermatitis 1990; 1:212.\n\n\n\n3. Scheman A, Jacob S, Zirwas M et al. Contact allergy: \nalternatives for the 2007 North American Contact \nDermatitis Group (NACDG) Standard Screening Tray. Dis \nMon 2008; 54:7\u2013156.\n\n\n\n4. Marino R, Capaccio P, Pignataro L, Spadari F. Burning \nmouth syndrome: the role of contact hypersensitivity. Oral \nDis 2009; 15:255\u2013258.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2014 Jul Vol 32\n\n\n\n5. Pantuzo MCG, Zenobio EG, de Andrade MH, Zenobio \nMAF. Hypersensitivity to conventional and to nickel-free \northodontic brackets. Braz Oral Res 2007; 21:298\u2013302.\n\n\n\n6. Bercovitch L, Luo J. Cellphone contact dermatitis with \nnickel allergy. CMAJ 2008; 178:23\u201324.\n\n\n\n7. Thyssen J P, Menn\u00b4e T, Lid\u00b4en C et al. Cobalt release from \nimplants and consumer items and characteristics of cobalt \nsensitized patients with dermatitis. Contact Dermatitis \n2012; 66: 113\u2013122.\n\n\n\n8. Athavale P, Shum KW, Chen Y et al. Occupational \ndermatitis related to chromium and cobalt: experience of \ndermatologists (EPIDERM) and occupational physicians \n(OPRA) in the UK over an 11-year period (1993\u20132004). \nBrJ Dermatol 2007; 157: 518\u2013522.\n\n\n\n9. Thyssen JP, Jensen P, Lid\u00b4en C et al. Assessment of nickel \nand cobalt release from 200 unused hand-held work tools \nfor sale in Denmark \u2013 sources of occupational metal contact \ndermatitis? Sci Total Environ 2011; 409: 4663\u20134666.\n\n\n\n10. Bruze M, Edman B, Bjorkner B et al. Clinical relevance \nof contact allergy to gold sodium thiosulfate. J Am Acad \nDer-matol 31: 579-583, 1994.\n\n\n\n11. Francesca R, Massimo B, Andrea P et al. Nickel, cobalt and \nchromate sensitization and occupation. Contact Dermatitis \n2010; 62: 225\u2013231.\n\n\n\n12. Tanko Z, Diepgen TL, Weisshaar E. Is nickel allergy an \noccupational disease? Discussions of the occupational \nrelevance of a type IV allergy to nickel (II) sulfate using \ncase reports. J Dtsch Dermatol Ges 2008; 6: 346\u2013349.\n\n\n\n13. Shum KW, Meyer JD, Chen Y et al. Occupational \ncontact dermatitis to nickel: experience of the British \ndermatologists (EPIDERM) and occupational physicians \n(OPRA) surveillance schemes. Occup Environ Med 2003; \n60: 954\u2013957.\n\n\n\n14. Athavale P, Shum KW, Chen Y et al. Occupational \ndermatitis related to chromium and cobalt: experience of \ndermatologists (EPIDERM) and occupational physicians \n(OPRA) in the U.K. over an 11-year period (1993\u20132004). \nBr J Dermatol 2007; 157:518\u2013522. \n\n\n\n15.\t Gao\tX,\tHe\tRX\tYan\tSG\tet\tal.\tDermatitis\tAssociated\tWith\t\nChromium Following Total Knee Arthroplasty, Journal of \nArthroplasty, 2011; 26(4) : 665, e13\u2013665, e16.\n\n\n\n16. A. Afolaranmi, J. Tettey, R.M. Meek, et al.\u201cRelease of \nchromium from orthopaedic arthroplasties,\u201d The Open \nOrthopaedics Journal, 2008; 2 :10\u201318.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 MJD 2014 Jul Vol 32\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nDYSKERATOSIS CONGENITA: A CASE REPORT AND\nREVIEW OF LITERATURE \n\n\n\nNorashikin Shamsudin1, AdvMDerm (UKM), Sabeera BKI2, MPaeds (UM)\n\n\n\nKeywords: genodermatosis, poikiloderma, leukoplakia\n\n\n\nIntroduction\nDyskeratosis congenita (DC) is classically \ncharacterised by a mucocutaneous triad of \nreticulated poikiloderma, nail dystrophy and \nmucosal leukoplakia together with bone marrow \nfailure and increased risk of malignancy1- 4. Due to \nits rarity and clinical heterogeneity it is not easily \nrecognised and patients are often treated for other \nentities. We report a case of dyskeratosis congenita \nwho presented to us with the classical triad in his \nlate twenties after years of being treated as lichen \nplanus. \n\n\n\nCase report\nA 29 year-old Malay man presented with 20-nail \ndystrophy, reticulate pigmentation on the sun-\nexposed areas of the skin and whitish adherent \nplaques on his tongue. He also suffered from \npainless, reddish watery eyes. The changes had been \ngradually appearing starting with the nail since aged \n13, followed by the other features two years later \nwhich were progressive in nature.  \n\n\n\nBorn of consanguineous parents who were first \ncousins, all five of his siblings except one had \nshort stature. None of them shared his physical \nabnormalities. Earlier in 1998 in another hospital, \nhe had oral biopsies in which the buccal mucosa \nshowed mild epithelial dysplasia while the tongue \n\n\n\nCorrespondence\nNorashikin Shamsudin, MAdvDerm (UKM)\nDermatology Unit, Department of Medicine,                           \nFaculty of Medicine and Health Sciences,                             \nUniversiti Putra Malaysia 43400 Serdang,                            \nSelangor Darul Ehsan, Malaysia. \nEmail: aliffarhan@yahoo.com\n\n\n\n2Dermatology Unit, Institute of Paediatrics,                    \nHospital Kuala Lumpur, Jalan Pahang,                                \nKuala Lumpur, Malaysia.\n\n\n\nrevealed atrophic glossitis. An ophthalmologist \ndiagnosed bilateral lacrimal duct stenosis causing \nepiphora and corrective surgery was advised, \nwhich he declined. No skin biopsy was performed \nand he was treated as lichen planus with topical \ncorticosteroids, with very little effect. \n\n\n\nPhysical examination revealed multisystem \nabnormalities. He had diffuse, poikilodermatous \nskin over photo distributed areas (Figure 1). Nail \nexamination revealed pterygium with total nail loss \nin all 20 digits (Figure 2). All fingers showed shiny, \ntight skin with loss of dermal ridges at the fingertips \nand there was palmar hyperhidrosis. Leukoplakia \nwas present on the tongue (Figure 3). \n\n\n\nDental caries were most severe on the lower molars. \nA triangular patch of leukotrichia was present in the \nfrontal hairline. His eyes were reddish and congested. \nApart from small build and short stature (height \n144 cm, weight 45 kg), other systems including the \ngenitals and secondary sexual characteristics were \nunremarkable.\n\n\n\nSkin biopsy from the forearm showed epidermal \natrophy with focal basal cell vacuolation, pigmentary \nincontinence as well as sparse lymphoplasmacytic \ninfiltrates in the dermis, consistent with \npoikiloderma. The direct immunoflourescence \nstudy was negative.  His full blood counts and \nperipheral blood film were normal and antinuclear \nantibody (ANA) was non-reactive.  Serum IgM was \nlow (0.28 g/L). Mutational analysis study by direct \nDNA sequence analysis and restriction enzyme \ndigestion (Centre for Paediatrics, Institute of Cell \nand Molecular Science, Barts and the London \nSchool of Medicine and Dentistry) demonstrated \nthat the patient was hemizygous for DKC1 mutation \n(Ala353Val), the commonest missense mutation in \nclassical\tX-linked\tDC.\t\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2014 Jul Vol 32\n\n\n\nFigure 1  Shows diffuse, reticulated hyperpigmentation on the nape of the neck.\n\n\n\nFigure 2  Shows eschewed and almost absent nails in all fingers.\n\n\n\nFigure 3  Shows extensive white adherent plaques \non the tongue.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 MJD 2014 Jul Vol 32\n\n\n\nDiscussion\nFirst described by Zinsser in 1910, DC is now \nrecognized with three patterns of inheritance: \nX-linked\t recessive,\t autosomal\t dominant\t and\t\nautosomal recessive1-4,5. In the last 15 years, eight DC \ngenes (DKC1, TERC, TERT, NOP10, NHP2, TIN2, \nC16orf57, and TCAB1) have been characterized. \nSeven of these are involved in telomere function, \nmutations of which lead to stem cell depletion \nand premature aging3-6. DKC1 gene mutation in \nX-linked\t DC\t is\t the\t commonest,\t which\t encodes\t\ndyskerin, an essential component of small nucleolar \nRNAs involved in ribosomal RNA processing and \nthe telomerase complex2,4. DC is therefore viewed \nas a disease of defective telomere maintenance, and \nhas been linked to several other \u2018telomereopathies\u2019 \nsuch as the severe multisystem disorders Hoyeraal-\nHreidarsson and Revesz syndromes2-5.\n\n\n\nIn classic DC, the mucocutaneous features usually \nappear first, below the age of 10 years1-4. Bone \nmarrow failure develops later with up to 80% of \npatients showing signs of bone marrow failure \nby the third decade1- 4,7. In addition to reticulated \nhyperpigmentation, other skin changes include \natrophy, hyperhidrosis of palms and soles, \ntelangiectasia and loss of dermal ridges7. There \nis a predisposition to hematological malignancy \nand carcinomas1,2,7. Bone marrow dysfunction \nresults in peripheral cytopaenias and biopsy \nshows hypocellular marrow with predisposition \nto myelodysplastic syndrome and acute myeloid \nleukaemia2,4. The main causes of mortality are \nbone marrow failure/immunodeficiency(60-70%), \npulmonary complications (10-15%) and \n\n\n\nmalignancy3,5,8 (10%). A wide spectrum of \nabnormalities have been described involving the \neye, neurological, pulmonary, skeletal, dental and \ngastrointestinal systems, hair loss or graying and the \ngenitourinary tract1-5,7. \n\n\n\nThe diagnosis of DC is often challenging due to \nheterogeneous clinical presentations which have \nvariable age of onset and degree of severity. Diagnosis \nis often made later, when the findings become more \nobvious with age1-3,7,8. It is also not uncommon for \nbone marrow failure or an abnormality in another \nsystem to precede the more classical features1,3,8. \nEven when the classical features are present, the \nrarity of this disorder may not alert the physician to \nthe diagnosis. \n\n\n\nSkin biopsy is not diagnostic as the histological \ndifferential diagnosis could include burnt out lichen \nplanus, drug eruption, lupus and graft-versus-host \ndisease (GVHD). The minimal clinical criteria for \ndiagnosis of DC include the presence of at least 2 of \nthe 4 major features (abnormal skin pigmentation, \nnail dystrophy, leukoplakia, and BM failure) and \n2 or more of the other somatic features known to \noccur in DC. Genetic studies are often necessary to \nconfirm the diagnosis; however in 50% of patients \nthe genetic mutation has not been identified8.\n\n\n\nSummary\nA diagnosis of DC should be suspected when  \na patient present with the classical features or \nsymptoms and signs of bone marrow failure. \nMissing the diagnosis could have fatal implications \nas majority of patients tend to develop bone marrow \nfailure. \n\n\n\nReferences\n \n1. Dokal I. Dyskeratosis Congenita: an inherited bone \n\n\n\nmarrow failure syndrome. Br J Haematol 1996; 92: 775-9.\n2. Dokal I. Dyskeratosis Congenita in all its forms. Br J \n\n\n\nHaematol 2000; 110: 768-779.\n3. Dokal I. Dyskeratosis Congenita. Hematology Am Soc \n\n\n\nHematol Educ Program 2011; 480-6. \n4. Kirwan M, Dokal I. Dyskeratosis congenita: a genetic \n\n\n\ndisorder of many faces. Clin Genet 2008; 73: 103-112.\n\n\n\n5. Vulliamy TJ, I Dokal I. Dyskeratosis congenita: the \ndiverse clinical presentation of mutations in the telomerase \ncomplex.  Biochimie 2008; 90: 122-130.\n\n\n\n6. Kirwan M, Dokal I. Dyskeratosis congenita, stem cells and \ntelomeres. Biochimica et Biophysica Acta 2009; 371\u20139.\n\n\n\n7. Handley TPB, McCaul JA, Ogden GR. Dyskeratosis \ncongenita. Oral Oncology 2006; 42: 331\u20136.\n\n\n\n8. Walne AJ, Dokal I. Advances in the understanding of \ndyskeratosis congenita. Br J Haematol 2009; 145: 164\u2013\n172.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23MJD 2014 Jul Vol 32\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nGENERALISED SWEET SYNDROME LESIONS ASSOCIATED \nWITH BEHCET\u2019S DISEASE \n\n\n\nLing Hee Ninh1, Julian Matius Tagal2, Pubalan  Muniandy1\n\n\n\nKeywords: plaques, oral genital ulceration, arthritis, lacunar infarct\n\n\n\nIntroduction\nSweet\u2019s syndrome (SS) or acute febrile neutrophilic \ndermatosis is characterized by painful erythematous \npapules, nodules and plaques in which mature \nneutrophilic infiltration of the upper dermis is \nseen histo-pathologically. SS can be divided into \n5 subtypes based on aetiology, namely Classical \n(Idiopathic), Paraneoplastic, Drug-induced, \nPregnancy related & associated with inflammatory \nand autoimmune disorders.\n\n\n\nCorrespondence\nLing Hee Ninh\nDepartment of Dermatology,\nSarawak General Hospital, Kuching, Malaysia\nEmail: heeninh@yahoo.com.sg\n\n\n\nBehcet\u2019s disease is a clinical diagnosis and the \nInternational Study Group (ISG) for Behcet\u2019s \nDisease is the best accepted criteria for diagnosis. \nGeneralized Sweet syndrome lesions are typically \nassociated with malignancies. SS lesions if present \nin patients with Behcet\u2019s disease are usually few \nin number. Herein, we describe a rare case of \ngeneralized Sweet syndrome lesions associated \nwith Behcet\u2019s disease.\n\n\n\nCase report\nA 44 year-old woman presented with sudden \neruption of painful, raised erythematous plaques \nwith fever, spreading from face, arms to her whole \nbody over 3 days. She had recurrent painful oral \nulcers and arthritis in the preceding 2 months. Old \nrecords (7 years earlier), showed she previously \nhad recurrent painful oral and genital ulceration, \nbouts of cellulitis (left leg, both hands) and multiple \nlacunar infarcts. Her symptoms responded well \nto Prednisolone 30mg daily. Unfortunately she \ndefaulted treatment then. \n\n\n\nFigure 1  Juicy Erythematous Plaques.\n\n\n\nFigure 2  Multiple oral aphthous ulcerations.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24 MJD 2014 Jul Vol 32\n\n\n\nFigure 3  Diffuse dermal neutrophilic infiltrates 4x H&E.\n\n\n\nFigure 4  Dermal spongiosis & diffuse dermal neutrophilic infiltrates 20x.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25MJD 2014 Jul Vol 32\n\n\n\nInvestigations showed elevated inflammatory \nmarkers with ESR of 101mm/hour, CRP of 96mg/L \nwith leukocytosis 11,900cells/mm3 & Neutrophilia \n(73%). Pathergy test was positive. Renal and \nliver function tests were normal. The hepatitis B \nsurface antigen, anti hepatitis C antibody, HIV, \nand antinuclear antibody were negative. Eye \nexamination was unremarkable. Malignancy screen \nuncovered a solitary right thyroid nodule that proved \nto be benign post hemi-thyroidectomy.\n\n\n\nHistopathological examination of an excised \nerythematous nodule showed marked edema \nof papillary dermis and diffuse infiltrate of \ninflammatory cells, predominantly neutrophils with \nsome eosinophils. No subepidermal bullae. Skin \nappendages were surrounded by inflammatory cells \n(lymphocytes, polymorphs and some eosinophils). \nAdjacent dermis showed a perivascular infiltrate of \nsimilar cells.\n\n\n\nThus, a diagnosis of Sweet syndrome with \nunderlying Behcet\u2019s disease was made. Both skin \nlesions and the mucosal ulcers resolved rapidly \nwith steroids. Frequent recurrences of ulcers, both \ncutaneous and mucosal were observed on tapering \nthe oral steroids. She was then commenced on \nazathioprine and colchicine in addition to oral \nsteroids. She is currently being closely monitored \nfor possible underlying malignancy & complications \nof immunosuppresion.\n\n\n\nDiscussion\nThis patient has longstanding BD that was poorly \ncontrolled and presented with SS lesions 7 years \nlater. Differentiation between SS associated with \nBD versus SS lesions seen in BD is difficult.\n\n\n\nOne of the main distinguishing features is that HLA \nB51 is more common in BD, whereas HLA B54 is \npredominantly positive in SS. We were unable to \nperform HLA typing. Another feature for differential \ndiagnosis is the lack of fibrinoid necrosis on vessel \nwalls in SS2. In the histopathologic examination of \nthis patient\u2019s skin biopsy, no fibrinoid necrosis was \nobserved. The pathogenesis of both SS and BD \nis unknown. It has been proposed that HSV may \nhave triggered an immune-regulatory defect in a \ngenetically predisposed patient and thus caused SS \nand BD to occur simultaneously3.\n\n\n\nConclusion\nMore studies are needed to establish whether a \ncommon etiology (immunology, environmental or \ngenetic) exists between BD and SS.\n\n\n\nAcknowledgement           \nThe authors would like to thank the Director General \nof Health Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Mizoguchi M, Chikakane K, Goh K et al. Acute febrile \nneutrophilic dermatosis (Sweet\u2019s syndrome) in Behcet\u2019s \ndisease. Br J Dermatol 1987; 116 : 727-34.\n\n\n\n2. International Study Group of Behcet\u2019s disease. Criteria for \ndiagnosis of Behcet\u2019s disease. Lancet 1990; 335 : 1078-80. \n\n\n\n3. Lee M-S, Barnetson St C. Sweet\u2019s syndrome associated \nwith Behcet\u2019s disease. Australasian J of Dermatol 1996; \n37: 99-101.\n\n\n\n\n\n\n\n\n\n"
"\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatologyMalaysian Journal of\n\n\n\nNotice to Authors\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more than \n2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Comment \nand References. A Structured Abstract of not more than 240 \nwords must be included. It should consist of five paragraphs, \nlabelled Background, Methods, Results, Discussion and \nConclusion. It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nORIGINAL ARTICLE\n\n\n\n2 Pattern of Sexually Transmitted Infections among \nFemales Attending Genitourinary Medicine Clinic, \nHospital Kuala Lumpur between 2013 and 2017\n\n\n\n V Krishnasamy, Tang MM, S Thevarajah\n\n\n\n8 Prevalence of Sexually Transmitted Infections in \nGenito-Urinary Medicine Clinic, Hospital Kuala \nLumpur between 2015 - 2016\n\n\n\n HR Hariyadurai, SR Syed Nong Chek, A Johar\n\n\n\n14  Leprosy and Tuberculosis Co-infection: A Review \nof Cases in Dermatology Clinics in Malaysia\n\n\n\n Tang MM, Tan SN, Tey KE, Lim YT, Tan WC, Chan \nLC, Ong CK, Voo MSY, S Thevarajah\n\n\n\n20  Perception and Psychosocial Impact of Acne \nVulgaris Among Secondary School Adolescents in \nIpoh, Malaysia\n\n\n\n Kwan JW, Lee HL, Low DE, Tang JJ\n\n\n\n25  No Evidence for Increased Risk of Breast Cancer \nin Patients with Axillary Osmidrosis: The First \nPopulation-based Cohort Study in Taiwan \n\n\n\n Ho WT, Chang YY, Lee LJH\n\n\n\n\n\n\n\nCASE REPORT \n\n\n\n33 The Clinical Spectrum of Cutaneous \nPhaeohyphomycosis in Three Immunocompetent \nPatients and a Review of Literature\n\n\n\n R Ramalingam\n\n\n\n39  An Infant with a Peculiar Rash \u2013 Getting Reacquainted \nwith an Ancient but Forgotten Disease\n\n\n\n R Ramalingam\n\n\n\n44  Successful Treatment of Familial Benign Chronic \nPemphigus with Oral Doxycycline\n\n\n\n Siew KSW, Toh YF, Kwan ZL\n\n\n\n47  The Use of a Limberg Flap for Closure of Defects \nLocated at the Interdigital Webs\n\n\n\n Kwan ZL, Yong SS, JR Willis\n\n\n\n49  Angiolipomatosis and Hepatitis C Infection \u2013 \nAssociation or Coincidence?\n\n\n\n R Ramalingam, NH M Salleh\n\n\n\nCORRESPONDENCE  \n\n\n\n52 Bowel Ischaemia in Henoch-Sch\u00f6nlein Purpura \u2013 \nUncommon or Under-reported?\n\n\n\n Low DW, ZF Baharom, Tang MM\n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n1\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, M Adv Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nExecutive Committee\nChan Lee Chin, MMed - President\nNoor Zalmy Azizan, Adv M Derm - Vice President\nSabeera Begum, MMed - Secretary\nTan Wooi Chiang, Adv M Derm - Treasurer\nAgnes Heng Yoke Hui, MRCP - Past President\nDr Tang Jyh Jong, Adv M Derm -            \nCommittee Member\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2019 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDr Teoh Tze Yuen, Adv M Derm -           \nCommittee Member\nDr. Sharifah Rosniza Syed Nong Chek,       \nAdv M Derm - Committee Member\n\n\n\nDermatological Society of Malaysia \n(Rumah Dermatology)\nG1, Medical Academics of Malaysia, 210, \nJalan Tun Razak, 50400 Kuala Lumpur, \nMalaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv \nM Derm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm\nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2\n\n\n\nORIGINAL ARTICLE\n\n\n\nPattern of Sexually Transmitted Infections among Females attending \nGenitourinary Medicine Clinic, Hospital Kuala Lumpur between 2013 \nand 2017          \nVijayaletchumi Krishnasamy, Dip. STD/AIDS, Min Moon Tang, AdvMDerm, Suganthi Thevarajah, MMed  \n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract \nIntroduction: \nSexually transmitted infections (STIs) have a profound impact on sexual and reproductive health \nworldwide. If left untreated, STIs may lead to long term sequelae including pelvic inflammatory \ndisease, infertility, chronic pelvic pain, adverse birth outcomes and cervical cancer in affected females. \nHere, we aim to determine the demography and pattern of STIs among females attending Genito-\nUrinary Medicine (GUM) Clinic, Hospital Kuala Lumpur (HKL).\n\n\n\nMethods: \nThis is a retrospective study on all females attending GUM clinic between 2013 and 2017. The case \nnotes were retrieved and reviewed. Data was obtained from case notes and further analysed.\n\n\n\nResults: \nA total of 831 females attended GUM clinic between 2013 and 2017. The mean age was 31.2 years \n(range 13-86). The majority (91.6%) were Malaysian. Among which about three-quarter (76.4%) were \nMalays, followed by Indians (15.2%) and Chinese (7.7%). Nearly a quarter (23.5%) were housewives \nand 9.6% were students. The majority (63.9%) were married and 12.4% were pregnant at presentation. \nEleven females were infected with the human immunodeficiency virus (HIV). One hundred and \neleven (13.5%) females were screened as contacts of sexual partners with STIs and 56% of them were \nasymptomatic. The most common presenting symptoms were growth at the genitalia (35.3%), followed \nby pain (16.7%), vaginal discharge (12.1%) and genital ulcer (4.5%). About 72% had confirmed STIs. \nThe most common STIs were genital wart (45.6%), followed by genital herpes (31.5%), syphilis \n(18.2%), Chlamydia infection (5.4%), gonorrhoea (3.9%), and trichomoniasis (0.2%). \n\n\n\nConclusion: \nThe three most common STIs among female attending GUM HKL were genital wart, genital herpes \nand syphilis.\n\n\n\nKey words: Sexually transmitted infections, Female, Genital warts, Genital herpes, Syphilis\n\n\n\nIntroduction \nBased on the latest available data by WHO, the \nglobal burden of sexually transmitted infections \n(STIs) remains high.1 It was estimated that 1 million \nnew cases of these four curable STIs namely \nchlamydia, gonorrhea, syphilis and trichomoniasis \nwere diagnosed per day worldwide in 2012.2 It was \nalso estimated that 267 million women aged 15-49 \nyears lived with the incurable STI i.e. herpes simplex \n\n\n\nCorresponding Author\nDr Vijayaletchumi Krishnasamy \nDepartment of Dermatology,\nHospital Kuala Lumpur, Jalan Pahang,\n50586 Kuala Lumpur, Malaysia\nEmail: vkrishnasamy44@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n3\n\n\n\nvirus-2 infection globally in 2012.3 Anogenital \nwarts are common worldwide but the data is much \nlimited as mandatory notification is not required. \nHowever, the median incidence rate among female \nwas estimated to be 120.5 per 100,000 per annum \nworldwide.4 \n\n\n\nSTIs cause consequences beyond the immediate \nmorbidity of the infection itself. STIs have a \nprofound impact on sexual and reproductive health \nworldwide. If left untreated, STIs may lead to \nlong term sequelae including pelvic inflammatory \ndisease, infertility, chronic pelvic pain, adverse \nbirth outcomes and cervical cancer in affected \nfemales. Mother-to-child transmission of STIs \ncan result in stillbirth, neonatal death, low-birth-\nweight and prematurity, sepsis, pneumonia, \nneonatal conjunctivitis and congenital deformities. \nOver 900,000 pregnant women were infected with \nsyphilis resulting in approximately 350,000 adverse \nbirth outcomes including stillbirth in 2012.2 Human \npapillomavirus (HPV) infection was estimated to \ncause 570,000 cases of cervical cancer and 311,000 \ncervical cancer deaths in 2018.5 Furthermore, \nherpes simplex virus (HSV) type 2 and syphilis are \nassociated with three-fold or more increased risk of \nHIV acquisition.6 \n\n\n\nIn this study we aimed to describe the pattern and \nthe clinical characteristics of sexually transmitted \ninfection in females who attended genitourinary \nclinic between 2013 and 2017.\n\n\n\nMaterials and Methods\nThis is a retrospective review of women who \nattended the Genitourinary Medicine clinic Hospital \nKuala Lumpur between 2013 and 2017. Data was \nobtained from case notes.\n\n\n\nResults \nA total of 831 females attended GUM clinic between \n2013 and 2017. The demographic data is shown in \nTable 1. The mean age was 31.2 years old (range \n13-86). Fifty seven (6.8%) females were below 20 \nyears of age. Three quarters of the patients were \nbetween 20 to 39 years old. The majority (93.3%) \nwere Malaysians. Of these 75% were Malays, \nfollowed by Indians (15%) and Chinese (7.7%).  \n\n\n\nAbout 23.5% were housewives and 9.6% were \nstudents. Majority (63.9%) were married and 12.4% \nwere pregnant at presentation. One hundred and \ntwelve (13.5%) females were screened as contacts \nof sexual partners with STIs and of these 56% were \n\n\n\nasymptomatic.  Eleven females were infected with \nhuman immunodeficiency virus (HIV). Eleven \npatients had a history of substance abuse.\n\n\n\nTable 1. Demographic data and sexual behaviour of 831 \nfemales attending GUM clinic Hospital Kuala Lumpur between \n2013 and 2017\n\n\n\nThe most common presenting symptoms were \ngrowth at genitalia (35.3%), followed by genital \npain (16.7%), vaginal discharge (12.1%) and \ngenital ulcer (4.5%). A total of 603 female (72.6%) \nhad confirmed STIs. The most common STIs were \nanogenital wart (43.2%), followed by genital herpes \n(30.2%), syphilis (17.7%), Chlamydia infection \n(5.1%), gonorrhoea (3.6%), and trichomoniasis \n(0.2%) as shown in Table 2.\n\n\n\nCharacteristics N=831\nMean age in years (range) 31.1 (13-86)\nAge group in years, n (%) <20 57 (6.7)\n\n\n\n20-29 388 (46.6)\n30-39 247 (30.0)\n40-49 83 (10.0)  \n50-59 31 (3.7)\n>60 25 (3.0)\n\n\n\nEthnicity among Malaysians Malay 581 (75.0)\nChinese 60 (7.7)\nIndians 117 (15.0)\nOthers 17 (2.2)\n\n\n\nForeign born, n (%) 56 (6.7)\nEmployment history, n (%) Employed 454 (54.6)\n\n\n\nUnemployed 69 (11.5)\nSelf employed 30 (3.6)\nHousewife 196 (23.5)\nStudent 79 (9.5)\nRetiree 3 (0.4)\n\n\n\nMarital status, n (%) Married 531 (63.8)\nSingle 254 (30.5)\nDivorcee 24 (2.8)\nWidow 21 (2.5)\nMissing data 1 (0.1)\n\n\n\nType of sexual partner, n (%) Spouse 560 (67.4)\nRegular 223 (26.8)\nCasual 18 (2.2)\nNo Partner 22 (2.6)\nMissing data 8 (1.0)\n\n\n\nNumber of sexual partner in \nthe last 6 months, n (%)\n\n\n\n1 669 (80.5)\n>2 136 (16.3)\nMissing data 26 (3.1)\n\n\n\nNumbers with documented substance abuse, n (%) 11 (1.3)\nCondom usage, n (%) Never 792 (95.3)\n\n\n\nOccasional 24 (2.8)\nAlways 4 (0.5)\nMissing data 11 (1.3)\n\n\n\nFinal diagnosis, n (%) STI 603 (72.6)\nNon STI 225 (27.1)\nRefuse test 3 (0.3)\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4\n\n\n\nTable 2. Pattern of Sexually Transmitted Infections in 603 females  \n\n\n\nThe non-STI diagnosis identified in 225 (27.1%) \nfemales included genital candidiasis, tinea \ncruris, bacterial vaginosis, cervicitis, molluscum \ncontagiosum, acrochordon, physiological \nleucorrhoea, pruritus vulvae, false positive venereal \ndisease research laboratory (VDRL) test and healthy \ncontact tracing.\n\n\n\nDiscussion \nIt is believed that monogamy prevents the spread \nof STIs.7,8 Nevertheless, studies have shown that \nthose who were in monogamous relationships did \nnot report fewer STIs than those in consensually \nnon-monogamous relationships.9 In this study, the \nmajority of our female patients who acquired STIs \nwere reported to be in monogamous relationship \nwith a single partner or spouse. There have been \nother studies which have reported similar results.10,11 \nOne explanation is that their partners or spouses \ncould have multiple sexual partners or engaged in \nhigh-risk behaviour. In addition, our female patients \nprobably underreport their sexual behaviour in \nterms of number of sexual partners, extramarital \nsexual exposure and premarital sexual exposure \ndue to embarrassment as well as our social cultural \nmilieu. Besides, the low condom usage as reflected \nin our cohort would have further added on to the \ngravity of the STIs among females.\n \nAdolescents, defined as individuals in the 10-19 \nyears age group by WHO, comprised about 6.8% in \nour cohort with the youngest female acquired an STI \nat the age of 13. This showed that our adolescent girls \nengaged in sexual activities at a younger age. This is \nnot rare and has been reported in other local studies. \nIn a survey done in Malaysia approximately 13% \nof 468 adolescents in Klang Valley were reported \nto have experienced premarital sexual intercourse.12 \nIn another study, 3.2% of rural female adolescents \nwere reported to engage in sexual intercourse.13 \nThe majority of them did not use any contraception \nat first intercourse.12,13 Another larger scale study \ninvolving 4500 secondary school students in Negeri \n\n\n\nAge group Anogenital \nwarts\n\n\n\nHerpes \ngenitalis\n\n\n\nSyphilis Chlamydia \ninfection\n\n\n\nGonorrhoea TV Total\n\n\n\n<20 19 16 3 1 3 0 42 (6.6%)\n20-29 148 86 38 24 13 0 309 (48.9%)\n30-39 73 61 41 5 6 0 186 (29.4%)\n40-49 23 18 15 2 1 0 59 (9.3%)\n50-59 6 7 9 0 0 1 23 (3.6%)\n>60 4 3 6 0 0 0 13 (2.1%)\nTotal 273 (43.2%) 191 (30.2%) 112 (17.7%) 32 (5.1%) 23 (3.6%) 1 (0.2%) 632 (100)\n\n\n\nTV: Trichomonas vaginalis \n\n\n\nSembilan reported that 5.4% of students had had \nsexual intercourse.14   Teenage pregnancy and \nSTIs among the adolescents in Malaysia are well \ndescribed.13-17 Female adolescents are particularly \nvulnerable to STI due to lack of social power and \nskill to refuse sexual activity. Greater efforts in \neffective sex education as well as better access \nto contraception services are paramount for the \nadolescents in our society. \n\n\n\nOur study revealed that the two most common STIs \nencountered among our cohort were anogenital \nwarts and herpes genitalis. Notification of these two \nSTIs is not mandatory by law. Viral STIs such as \nHPV and HSV infections are common worldwide \nbut the magnitude of the conditions is probably \nunderestimated in Malaysia. As shown in Table \n3, human papilloma virus infection which causes \nanogenital warts is the leading STI among the \nfemales observed in the United States,18 Brazil19 \nand in our cohort, with proportion ranging between \n40-70%. Interestingly, anogenital warts and herpes \ngenitalis were not reported in a study done among \nfemale inmates of a rehabilitation centre in Malaysia \nabout 25 years ago.20 In that study conducted by \ncommunity medicine physicians, syphilis and \ntrichomoniasis were the two most common STIs \nencountered.20 A plausible explanation for the high \nnumber of females with anogenital warts observed \nin our GUM clinic is that treatment services for \ngenital warts in this country are mainly offered by \ndermatologists. \n\n\n\nAccording to WHO, the global estimates of \ntrichomoniasis, chlamydia, gonorrhoea and \nsyphilis were 142.6 million, 130.9 million, 78.3 \nmillion and 5.6 million respectively in 2012.1 \nInterestingly, the number of gonorrhoea, chlamydia \nand trichomoniasis cases confirmed in our female \ncohort were much lower than syphilis. As infections \nwith Neiserria gonorrhoea, Chlamydia trachomatis \nand Trichomonas vaginalis in females are mostly \nasymptomatic or present as co-infection with other \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n5\n\n\n\nsymptomatic STIs, diagnosis and treatment of \nthese infections in females are imperative to reduce \nmorbidity and further transmission. The low number \nof gonorrhoea, chlamydia and trichomoniasis cases \nin our cohort could be due to the less sensitive \nmethods of testing used. In our satellite laboratory, \nswab samples collected from female patients are \nsmeared on 3 separate glass slides for examination \nunder light microscopy. Gram staining is done on \nthe swab sample collected from the endocervix to \ndetect intracellular diplococci, polymorphs, clue \ncells and other pathogens.  A wet mount is prepared \non the swab sample collected from posterior \nfornix to isolate Trichomonas vaginalis. Potassium \nhydroxide 10% is applied to sample collected \nfrom the vagina to detect fungal bodies or pseudo \nhyphae. Another swab specimen from endocervix \nis also cultured on modified Thayer-Martin agar \nor chocolate agar (depending on availability at the \ncentral laboratory) for Neisseria gonorrhoea. In \naddition, to detect Chlamydia sp the sample from \nendocervix is smeared on a MicroTrak\u00ae glass slide \nfor direct fluorescent-antibody (DFA) tests.\n\n\n\nThe sensitivity of gram stain in detecting gonorrhoea \nfrom endocervix in female is much lower (23-\n55%) as compared to men (more than 95%), in \nwhom the sample is obtained from the urethra.21-23 \nThe sensitivity of antigen tests including enzyme \nimmunoassay (EIA), direct fluorescent-antibody \n(DFA) and immune chromatographic rapid \ndiagnostic test (RDTs) in detecting Chlamydia sp \nfrom endocervical smears is generally low.23-27 \nAlthough the RDTs kits are widely available and \naffordable, their sensitivity is less than 45%.23-25 Wet \nmount microscopy for Trichomonas vaginalis has a \nsensitivity of 38-58%.23 Hence, Centers for Disease \nControl and Prevention (CDC) has recommended \nnucleic acid amplification tests (NAATs) as \ndiagnostic tools for Neiserria gonorrhoea, \nChlamydia trachomatis and Trichomonas \nvaginalis.28 NAATs give higher sensitivity and \nspecificity when compared to the other methods. \nFurthermore, NAATs can also be used to detect \nextra-genital STIs from a wide variety of clinical \nspecimens like urine, anorectal, conjunctival and \npharyngeal samples.23,24 NAATs should be made \navailable in all the GUM clinics in Malaysia public \nhospitals as a vital step in the management of STIs.\n\n\n\nWorldwide estimated adjusted prevalence of cervical \nHPV infection in women with normal cytological \nfindings was 11.7%.29 Nearly 90% of genital warts \nwere attributed to HPV6 and HPV11.30 The most \n\n\n\ncommon oncogenic HPV detected among women \nwith normal cytological findings globally were \nHPV types 16, 18, 31, 39, 51, 52, 56 and 58.29,30 \n\n\n\nHPV cause nearly 30% of infection-related cancer \nworldwide31 in which cervical cancer accounts for \n83% of cases in women.32 Other anogenital cancers \nincluding vulva, vagina, anus, penis and oropharynx \nare also HPV attributable cancers.32 In Malaysia \nstudies have consistently shown that HPV 16, 18, \n33, 52 and 58 were prevalent among female with \nboth normal and abnormal cytological findings \nfrom the cervical samples.33-35 \n\n\n\nSince June 2006, the prophylactic HPV vaccines \navailable commercially contain synthetically \nmanufactured oncogenic and verrucous protein \nsubunit components in the L1 epitope of virus \nlike particles.36 These include Cervarix\u00ae (HPV 16, \n18),  Gardasil\u00ae (HPV 6, 11, 16, 18), and Gardasil\u00ae9 \n(HPV 6, 11, 16, 18, 31, 33, 45, 52, 58). Current \nevidence suggests that these vaccines are efficacious \nfor the prevention of cervical cancer in which \nboth Cervarix\u00ae and Gardasil\u00ae9 prevent cervical \nintraepithelial neoplasia 2 or worse (by any HPV  \ntype) by about 62%.36 Based on intention to treat \nanalysis, quadrivalent HPV vaccine reduces the risk \nof anogenital wart by 62%.37 In the global health \nsector strategy on sexually transmitted infections \n2016-2021 endorsed by WHO, prophylactic HPV \nvaccination is advised in order to eliminate cervical \ncancer and genital warts.38 HPV vaccination has \nbeen incorporated in our national immunization \nprogram in 2010 for all female students who are 13 \nyears of age at government schools, with the aim of \nthree doses completion rate of 95%.  \n\n\n\nConclusion\nThe three most common STIs among female \nattending GUM Hospital Kuala Lumpur were \ngenital warts, genital herpes and syphilis. The \nlocal prevalence of chlamydia, gonorrhoea and \ntrichomoniasis among females is probably under-\nreported in government centres as the tests available \nhave unsatisfactory sensitivity. Nucleic acid \namplification tests (NAATs) as diagnostic tools for \nvarious STIs should be made available as soon as \npossible. The human papilloma virus vaccination \nin our national immunization program for female \nstudents should be continued in this country to \nreduce HPV-related cervical cancer. It should also \nbe promoted to male students to reduce genital \nwarts.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6\n\n\n\nTable 3. Comparisons of STIs among females of different countries\n\n\n\nAuthor, year Countries Age (years.) Sexual behaviour Prevalence of STI\nNordin et al.20 2001 Malaysia 20-29 group \u2013 47.7% \n\n\n\n30-39 group \u2013 40.0%\nSex worker 77.7% Syphilis 50.8% \n\n\n\nTV 19.2% \nGonorrhoea 8.5% \n\u2265 2 STI 57.7%\n\n\n\nYongjun et al.39 2009 China Mean age 34.3 I partner 92.4% \n2 partners 7.0% \n3 partners 0.7%\n\n\n\nChlamydia 6.4% \nNG 1.7% \nHPV 0.6% \nSyphilis 0.5%\n\n\n\nSetterwhite et al.18 2013 USA All ages NA HPV 67%\nHSV 2 27%\nTrichomoniasis 3.9%\nChlamydia 1.5%\nHIV 0.36%\nGonorrhoea 0.27%\n\n\n\nAraujo et al.19 2013 Brazil Mean age 20\u00b13 NA HPV 44% \nChlamydia 2% \nHPV & Chlamydia 2%\n\n\n\nNaidoo et al.40 2014 South Africa Mean age 28.6 NA Prevalence of STIs (CT,\nNG, TV or syphilis) 13%\n\n\n\nKrishnasamy et al. 2018    \n(present study)\n\n\n\nMalaysia Mean age 31.1 1 partner 80.5% Anogenital wart 43.2% \nHerpes genitalis 30.2% \nSyphilis 17.7% \nChlamydia 5.1% \nGonorrhoea 3.6% \nTrichomoniasis 0.2%   \n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director of \nHealth Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. WHO. Report on global sexually transmitted infection \nsurveillance 2015. Geneva: World Health Organization \n\n\n\nTV: Trichomonas vaginalis; NG: Neiserria gonorrhoea; CT: Chlamydia trachomatis; HPV: Human Papilloma Virus; HSV: Herpes \nSimplex Virus; HIV: Human Immunodeficiency Virus \n\n\n\n2016 (https://apps.who.int/iris/bitstream/handle/10665/\n249553/9789241565301-eng.pdf; jsessionid=1ABD\n35D8A272903BBEA3A7E5B13EFAF5?sequence=1, \naccessed 22 February 2019).\n\n\n\n6. Tobian AA, Quinn TC. Herpes simplex virus type 2 \nand syphilis infections with HIV: an evolving synergy \nin transmission and prevention. Curr Opin HIV AIDS \n2009;4:294-9.\n\n\n\n7. Centers for Disease Control and Prevention (2012) New \nHIV infections in the United States (fact sheet). Available \nat: http:// www.cdc.gov/nchhstp/newsroom/docs/2012/\nhiv-infections2007-2010.pdf (accessed 26th February, \n2019).\n\n\n\n8. Conley TD, Moors AC, Matsick JL, Ziegler A. The fewer \nthe merrier?: Assessing stigma surrounding non-normative \nromantic relationships. Anal Soc Issues Public Policy \n2013;13:1-30.\n\n\n\n9. Lehmiller JJ. A Comparison of Sexual Health History \nand Practices among Monogamous and Consensually \nNonmonogamous Sexual Partners. J Sex Med \n2015;12:2022-8.\n\n\n\n10. Ujevi\u0107 B, Habek JC, Habek D. Prevalence of infection \nwith Neisseria gonorrhoeae or Chlamydia trachomatis \nin acute mucopurulent cervicitis. Arh Hig Rada Toksikol \n2009;60:197-203.\n\n\n\n11. Gyawalee M, Pokhrel DB. Pattern of Sexually Transmitted \nInfection and Sexual Behaviour in Patients with Genital \nSymptoms. NJDVL 2014;12:20-7. \n\n\n\n12. Zulkifli SN, Low WY.  Sexual practices in Malaysia: \ndeterminants of sexual intercourse among unmarried \nyouths. J Adolesc Health 2000;27:276-80. \n\n\n\n13. Ahmadian M, Hamsan HH, Abdullah H, Samah AA, \nNoor AM. Risky sexual behavior among rural female \nadolescents in Malaysia: a limited role of protective \nfactors. Glob J Health Sci 2014;6:165-74.\n\n\n\n14. Lee LK, Chen PC, Lee KK, Kaur J. Premarital sexual \nintercourse among adolescents in Malaysia: a cross-\nsectional Malaysian school survey. Singapore Med J \n2006;47:476-81.\n\n\n\n15. Mohd Azri MS, Adibah HI, Haliza G. A review of \nteenage pregnancy research in Malaysia. Med J Malaysia \n2015;70:214-9.\n\n\n\n2. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, \nUnemo M, Low N et al. Global Estimates of Prevalence \nand Incidence of four Curable Sexually    Transmitted \nInfections in 2012 based on Systematic Review and Global \nReporting. PLoS One 2015;10:e0143304. \n\n\n\n3. Looker KJ, Magaret AS, Turner KM, Vickerman P, \nGottlieb SL, Newman LM. Global Estimates of Prevalent \nand Incident Herpes Simplex Virus Type 2 infections in \n2012. PLoS One 2015;10:e0140765. \n\n\n\n4. Patel H, Wagner M, Singhal P, Kothari S. Systematic \nreview of the incidence and prevalence of genital warts. \nBMC Infect Dis 2013;13:39. \n\n\n\n5. Ferlay J, Colombet M, Soerjomataram I, Mathers C, \nParkin DM, Pineros M et al. Estimating the global cancer \nincidence and mortality in 2018: GLOBOCAN sources \nand methods. Int J Cancer 2019;144:1941-53.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n7\n\n\n\n16. Anwar M, Sulaiman SA, Ahmadi K, Khan TM. Awareness \nof school students on sexually transmitted infections \n(STIs) and their sexual behaviour: a cross-sectional study \nconducted in Pulau Pinang, Malaysia. BMC Public Health \n2010;10:47. \n\n\n\n17. Tan P, Tohid H, Su X, Tan K, Azimah M, Khairani O. A \nstudy on pregnant adolescents residing in a government \nhome: common characteristics and their views on the \npregnancy. Malays Fam Physician 2012;7:11-5.\n\n\n\n18. Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan \nR, Ocfemia MC et al. Sexually transmitted infections \namong US women and men: prevalence and incidence \nestimates, 2008. Sex Transm Dis 2013;40:187-83.\n\n\n\n19. Araujo MP, Kleine HT, Parmigiano TR, Gomes NT, \nCaparroz GP, Silva ID et al. Prevalence of sexually \ntransmitted diseases in female athletes in S\u00e3o Paulo, \nBrazil. Einstein (Sao Paulo) 2014;12:31-5.\n\n\n\n20. Nordin RB, Rahman Bin Isa A, Rusli Bin Abdullah M. \nPrevalence of sexually transmitted diseases among new \nfemale drug abusers in a rehabilitation centre. Malays J \nMed Sci 2001;8:9-13. \n\n\n\n21. Bartelsman M, Straetemans M, Vaughan K, Alba S, van \nRooijen MS, Faber WR et al. Comparison of two Gram \nstain point-of-care systems for urogenital gonorrhoea \namong high-risk patients: diagnostic accuracy and cost-\neffectiveness before and after changing the screening \nalgorithm at an STI clinic in Amsterdam. Sex Transm \nInfect 2014;90:358-62.\n\n\n\n22. Jephcott AE. Microbiological diagnosis of gonorrhoea. \nGenitourin Med 1997;73:245-52.\n\n\n\n23. Herbst de Cortina S, Bristow CC, Joseph Davey D, \nKlausner JD. A Systematic Review of Point of Care \nTesting for Chlamydia trachomatis, Neisseria gonorrhoeae, \nand Trichomonas vaginalis. Infect Dis Obstet Gynecol \n2016:4386127.\n\n\n\n24. Meyer T Diagnostic Procedures to Detect Chlamydia \ntrachomatis Infections. Microorganisms 2016;4.pii: E25.\n\n\n\n25. Brook G. The performance of non-NAAT point-of-\ncare (POC) tests and rapid NAAT tests for chlamydia \nand gonorrhoea infections. An assessment of currently \navailable assays. Sex Transm Infect 2015;91:539-44.\n\n\n\n26. Tilton RC, Judson FN, Barnes RC, Gruninger RP, Ryan \nRW, Steingrimsson O. Multicenter comparative evaluation \nof two rapid microscopic methods and culture for detection \nof Chlamydia trachomatis in patient specimens. J Clin \nMicrobiol 1988;26:167-70.\n\n\n\n27. Lefebvre J, Laperriere H, Rousseau H, Masse R. \nComparison of three techniques for detection of Chlamydia \ntrachomatis in endocervical specimens from asymptomatic \nwomen. J Clin Microbiol 1988;26:726-31.\n\n\n\n28. Workowski KA, Bolan GA; Centre for disease Control \nand Prevention. Sexually transmitted diseases treatment \nguidelines, 2015. MMWR Recomm Rep 2015;64:1-137. \n\n\n\n29. Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de \nSanjose S. Cervical human papillomavirus prevalence in 5 \ncontinents: meta-analysis of 1 million women with normal \ncytological findings. J Infect Dis 2010;202:1789-99.\n\n\n\n30. Serrano B, Brotons M, Bosch FX, Bruni L. Epidemiology \nand burden of HPV-related disease. Best Pract Res Clin \nObstet Gynaecol 2018;47:14-26.\n\n\n\n31. Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, \nFranceschi S. Global burden of cancers attributable to \ninfections in 2012: a synthetic analysis. Lancet Glob \nHealth 2016;4:e609-16.\n\n\n\n32. De Martel C, Plummer M, Vignat J, Franceschi S. \n\n\n\nWorldwide burden of cancer attributable to HPV by site, \ncountry and HPV type. Int J Cancer 2017;141:664-70.\n\n\n\n33. Chong PP, Asyikin N, Rusinahayati M, Halimatun S Rozita \nR, Ng CK et al. High prevalence of human papillomavirus \nDNA detected in cervical swabs from women in \nsouthern Selangor, Malaysia. Asian Pac J Cancer Prev \n2010;11:1645-51.\n\n\n\n34. Khoo SP, Bhoo-Pathy N, Yap SH, Anwar Shafil MK, \nHairizan Nasir N, Belinson J et al. Prevalence and \nsociodemographic correlates of cervicovaginal human \npapillomavirus (HPV) carriage in a cross-sectional, \nmultiethnic, community-based female Asian population. \nSex Transm Infect 2018;94:277-83.\n\n\n\n35. Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R. \nPrevalence and type distribution of human papillomavirus \n(HPV) in Malaysian women with and without cervical \ncancer: an updated estimate. Biosci Rep 2018;38.pii: \nBSR20171268.\n\n\n\n36. Harper DM, DeMars LR. HPV vaccines - A review of the \nfirst decade .Gynaecol Oncol 2017;146:196-204. \n\n\n\n37. Tejada RA, Vargas KG, Benites-Azpata V, Mezones-\nHolguin E, Bolanos-Diaz R, Hernandez AV. Human \npapillomavirus vaccine efficacy in the prevention of \nanogenital warts: systematic review and meta-analysis. \nSalud Publica Mex 2017;59:84-94.\n\n\n\n38. WHO. Global Health Sector Strategy on Sexually \nTransmitted Infections 2016-2021 Towards Ending \nSTIs. Geneva: World Health Organization 2016;WHO/\nRHR/16.09. \n\n\n\n39. Yongjun T, Samuelson J, Qingsheng D, Ali MM, Li X, \nYanjian M et al. The Prevalence of Sexually Transmitted \nand other Lower Reproductive Tract Infections among \nrural women in Sichuan province, China. Southeast Asian \nJ Trop Med Public Health 2009;40:1038-47.\n\n\n\n40. Naidoo S, Wand H, Abbai NS, Ramjee G. High prevalence \nand incidence of sexually transmitted infections among \nwomen living in Kwazulu-Natal, South Africa.  AIDS Res \nTher 2014;11:31.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8\n\n\n\nORIGINAL ARTICLE\n\n\n\nPrevalence of Sexually Transmitted Infections in Genito-Urinary \nMedicine Clinic, Hospital Kuala Lumpur between 2015 - 2016         \nHare Randall Hariyadurai, MRCP, Sharifah Rosniza Binti Syed Nong Chek, AdvMDerm, Asmah Johar, MMed\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nBased on the data from the Department of Statistic of Malaysia, the incidences of notified gonorrhoea \nand syphilis are on a rising trend. We aim to determine the prevalence of sexually transmitted infections \n(STI) presented to the Genito-Urinary Medicine (GUM) Clinic Hospital Kuala Lumpur. \n\n\n\nMethods:\nThis is a retrospective study of all patients presented to the GUM clinic between January 2015 till \nDecember 2016. Data was obtained by reviewing patients\u2019 case notes and these were further analysed.\n\n\n\nResults:\nA total of 1,361 patients had attended the GUM clinic with a male to female ratio of 2.2:1. The mean \nage of the cohort was 32 years (range 12-85). The majority of patients (55.3%) were in the age group \nbetween 20-29 years. The ethnicity distribution of patients presented to GUM clinic was comparable to \nthe distribution in general skin clinic attendance. About 77.8% of the patients were heterosexual, 18% \nhomosexual and 4.2% bisexual. Majority of the patients (71.1%) were symptomatic. Asymptomatic \npatients were those with positive serological test for syphilis (12.9%), contact screening of partners \n(8.6%), voluntary STI screening (7.2%) and others. There were 1,296 (95.2%) patients confirmed \nto have STIs with a total of 1470 STI diagnosis. The most common STI presented were genital \nwarts (26.7%) followed by syphilis (19.3%), gonorrhoea (12.2%), genital herpes (11.8%), non-\nspecific urethritis (7.0%) and others. Latent syphilis was the commonest subtype (71.6%) of syphilis \nencountered. About 8.8% of the patients with STI were confirmed to have HIV infection.\n\n\n\nConclusion:\nThe three commonest STIs presented to GUM clinic were genital wart, syphilis and gonorrhoea.  \n\n\n\nKey words: Sexually transmitted infections (STI), Genito-Urinary Medicine Clinic (GUM), Malaysia\n\n\n\nCorresponding Author\nDr Sharifah Rosniza Binti Syed Nong Chek\nDepartment of Dermatology,\nHospital Kuala Lumpur, Jalan Pahang, \n50586 Kuala Lumpur, Malaysia \nEmail: srsyed@doctors.net.uk\n\n\n\nIntroduction\nSTIs consist of bacterial, viral and parasitic diseases \nthat are transmitted not only through sexual \ncontact but also through skin to skin contact and \nmixture of body fluids.  This further complicates \nthe management of sexually transmitted diseases.1 \n\n\n\nHowever, due to the HIV/AIDS epidemic, there \nhave been notable advances in the field of sexually \ntransmitted infections (STI). This is evident by \nimproved recognition of the range, severity and \nsequelae of the diseases and the development of \nnew approaches in case management.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n9\n\n\n\nSTIs display a higher incidence and prevalence, an \nalarming rate of antimicrobial resistance, a higher \nrate of serious complications and interaction with \nHIV infection in developing countries.2 Untreated; it \nhas deleterious effects during pregnancy and to the \nnewborn. Other complications especially in women, \nsuch as pelvic inflammatory disease, ectopic \npregnancy, infertility and cervical cancer, are large \nhealth and social problems. In most developing \ncountries, the incidence and prevalence of STI \nmay be 20 times higher than those in developed \ncountries.3\n\n\n\nSubstantial human movement and migration, gender \ninequalities and incipient medical and legal systems \nin many states stymie effective STI control in Asia. \nThe technological age has led to the ease of looking \nfor sexual partners, increasing use of erectile \ndysfunction agents, party drugs and sex toys, and \npossibly expanding the role of oral sex. There is \nalso a growing lack of fear of HIV because of the \nincreased manageability of the infection. In many \nparts of the world, self-treatment of undiagnosed STI \nis less expensive and more accessible than orthodox \nmedical care, particularly where antibiotics are \navailable without prescription.4\n\n\n\nThe Genitourinary Medicine Clinic in Hospital \nKuala Lumpur began in the year 1989. It was not \nuntil October 1995 that the clinic was incorporated \ninto the Department of Dermatology at Hospital \nKuala Lumpur.  An experienced senior medical \nofficer under the supervision of dermatologists \nmanages the clinic and relevant investigations can \nbe done in the same place.  The government hospital \nis centrally located in a densely populated Kuala \nLumpur.  Generally, the prevalence of STI tends to be \nhigher in urban areas, especially among unmarried \nyoung individuals. In addition, the increasing \nnumber of men who have sex with men (MSM) and \nalternative sexual preferences has altered the STI \nlandscape in recent times. Therefore, a study of this \nnature was undertaken to determine the pattern of \nSTI and act as a yardstick for evaluation of future \nSTI prevention programs.\n\n\n\nMaterials and Methods\nThis is a retrospective study of patients aged more \nthan 10 years attending the GUM Clinic, HKL \nbetween January 2015 till December 2016. Data was \nobtained from reviews of patients\u2019 case notes under \nstrict confidentiality. Each case note comes with a \nstandard clerking sheet provided by the clinic. Case \nnotes were classified using serial numbers. This was \n\n\n\nfurther computed into an Excel Format and analysed \nusing SPSS version 18.0.\n\n\n\nResults\nA total of 1361 patients had attended the clinic, of \nwhich 978 (71.9%) were males and 383 (28.1%) \nwere females. There were 1296 STDS diagnoses \nmade during this period. Patients\u2019 age ranged from \n12-85 with a mean of 32.09+/-12.08. The most \ncommon age group attending the clinic is between \n20-29 (48.1%), consisting of 472 (48.3%) males \nand 182 (47.5%) females. This was followed by \nthose aged 30-39 (26.9%), 40-49 (8.7%), 50-59 \n(6.2%), less than 20 (5.7%), 60-69 (2.9%) and \nmore than 70 (1.5%). Ethnicity wise, Malays were \nthe highest attendees with 801 (58.9%) patients. \nThis is subsequently, followed by Chinese, 234 \n(17.2%), Indians, 216 (15.9%), others, 82 (6.0%) \nand foreigners, 28 (2.1%). Most patients were \nheterosexuals consisting of 1059 (77.8%) patients \nwhile the rest were bisexuals, 245 (18.0%) and \nhomosexuals, 57 (4.2%). Majority of referrals \ncame from government hospitals, 586 (43.1%). \nApproximately, 311 (22.9%) referrals were from \ngovernment clinics, 209 (15.4%) were self referred, \n116 (8.5%) were from general practitioners. Pusat \nDarah Negara referred 83 (6.1%) cases while \nthe rest were from the emergency department, 39 \n(2.9%) and others, 17 (1.2%), consisting of non-\ngovernmental organizations and private hospitals. \nAmong the reasons patients visited the clinic include \nhaving STI symptoms, 968 (71.1%), positive \nVDRL results, 176 (12.9%), being a referred sexual \ncontact, 117 (8.6%), STI check up, 98 (7.2%), and \nothers. Of the 1296 diagnoses made, the commonest \nSTI was genital wart, which was found in 389 \n(30.2%) patients, followed by syphilis (21.7%), \ngonorrhea (13.8%), primary herpes (11.4%), \nand non specific urethritis (7.9%).  Collectively, \ndiagnoses that come under others include bacterial \nvaginosis, human immunodeficiency virus (HIV), \ncandidiasis, hepatitis C & B, chlamydia, and \nchancroid. Interestingly, the commonest STI \naffecting heterosexuals, homosexuals and bisexuals \nwere anogenital warts, syphilis and HIV.\n\n\n\nDiscussion \nYoung adults between ages 20-29 remain the \nmajority of those that present with sexually \ntransmitted diseases, representing almost 50% of \nnewly diagnosed cases. Most are unmarried and live \nin urban areas. As a result, this leads to a health and \neconomic burden to the society as patients remain \naway from work or school with some requiring \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10\n\n\n\nFigure 1. Sexually transmitted infections according to age group\n\n\n\nTable 1. Demographic characteristics of GUM clinic attendees.\n\n\n\nCharacteristics n=1361 %\n\n\n\nGender Male 978 71.9\n\n\n\nFemale 383 28.1\n\n\n\nMean age in years (range) Mean \u00b1 SD (Range) 32.09 \u00b1 12.080 (12,85)\n\n\n\nAge group in years (%)\n \n \n\n\n\n<20 78 5.7\n\n\n\n20-29 654 48.1\n\n\n\n30-39 366 26.9\n\n\n\n40-49 118 8.7\n\n\n\n50-59 84 6.2\n\n\n\n60-69 40 2.9\n\n\n\n>70 21 1.5\n\n\n\nEthnicity\n\n\n\nMalay 801 58.9\n\n\n\nChinese 234 17.2\n\n\n\nIndian 216 15.9\n\n\n\nOthers 82 6.0\n\n\n\nForeigner 28 2.1\n\n\n\nSexual orientation\n\n\n\nHeterosexual 1059 77.8\n\n\n\nBisexual 245 18.0\n\n\n\nHomosexual 57 4.2\n\n\n\nSource of referrals\n \n \n\n\n\nGovernment Hospital 586 43.1\n\n\n\nGovernment Clinic 311 22.9\n\n\n\nSelf referred 209 15.4\n\n\n\nGeneral Practitioner 116 8.5\n\n\n\nPusat Darah Negara 83 6.1\n\n\n\nEmergency Department 39 2.9\n\n\n\nOthers 17 1.2\n\n\n\nReason for visits\n \n\n\n\nSymptomatic 968 71.1\n\n\n\nPositive VDRL 176 12.9\n\n\n\nContact 117 8.6\n\n\n\nSTI Check Up 98 7.2\n\n\n\nNegative VDRL 1 0.1\n\n\n\nOthers 1 0.1\n\n\n\nDiagnosis\nSexually Transmitted Infections (STIs) 1296 95.2\n\n\n\nNon STI 65 4.8\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n11\n\n\n\nFigure 2. The types of Sexually Tranmitted Infections in GUM \nClinic Hospital Kuala Lumpur.\n\n\n\ninfections may also be missed from our statistics if \nthey are not referred to our GUM clinic. \n\n\n\nWHO in 2008 estimated that trichomoniasis, non \ngonococcal urethritis, gonorrhea and syphilis remain \nmajor contributors to the STI numbers.8 Evidence \nbased on trends in reported cases globally suggests \nthat public health programs have been successful \nin reducing the incidence of STI. Nevertheless, \nsuch trends need to be interpreted with caution, as \ndifferences data collection technique and access to \ncare may alter results. Despite such a caveat, the \ndata suggests optimism. For example, in Norway, \nthe number of reported cases of gonorrhea fell from \nmore than 10,000 in 1981 to less than 300 in 199313. \nIn Costa Rica, Chile, Zimbabwe, Thailand, and \nthe Western Pacific regions, steady and sustained \ndeclines in reported STI cases have been documented \nfollowing action prevention programs.14-17\n\n\n\nWithin the regions of South East Asia, gonorrhea, \nchancroid, non-gonococcal urethritis, syphilis, \ngenital herpes and genital warts are the major STIs \nwhich corresponds well to our study findings.5, 6,7 \n\n\n\nGenital warts are a common cause for attendance at \nSTD clinics and are a concern for cervical cancer.  On \nthe other hand, neonates risk developing respiratory \npapillomatosis during delivery if their mothers have \nnot been treated for genital warts.17 Though data on \nanogenital cancers other than cancer of the cervix \nare limited, there is an increasing body of evidence \nlinking HPV with cancers of the anus, vulva, vagina \nand penis. This makes them potentially preventable \nby using similar primary prevention strategies as \nthose of cervical cancer. These include education on \nsafe sexual practices, promotion and provision of \ncondoms, screening pap smears, male circumcision \nand HPV vaccination. \n\n\n\nThe HPV vaccination program in Malaysia was first \nintroduced in the year 2010 and targets children \naged 13-year olds. Nevertheless, certain bodies \nsuch as the National Population and Family Board \n(LPPKN) and private healthcare facilities are also \n\n\n\nhospital admission.10 The higher prevalence reflects \nmultiple barriers to accessing STI prevention \nprograms.11 These include quality sexual education, \nconcerns about confidentiality, embarrassment \nattached to STI and socio-cultural stigma attached \nto it.12 Reaching out to them requires innovative \napproaches along the entire continuum of prevention, \ntesting, treatment and care. Peer led interventions \nand the creation of safe spaces where young adults \nincluding adolescents can access information \nand services without fear of discrimination and \njudgmental societal perceptions will go a long way \nin addressing STIs in this vulnerable age group.  For \ninstance, our health clinics are able to cater STIs \nservices without the embarrassment associated with \nattending for such diseases.12\n\n\n\nAmong the top five STIs commonly seen within \nour clinical setting include anogenital warts, latent \nsyphilis, gonorrhea, genital herpes and non-specific \nurethritis, which is in line with those seen in other \nregions of the world (Table 2).  However, our data \nmay be underestimated as gonorrhea and chlamydia \nmay only present as oropharyngeal and rectal \ninfections, which may not be captured in our clinic. \nPatients with rectal infections may have presented \nto gastrointestinal or surgical clinics whereas \nthose with oropharyngeal infections may go to the \notorhinolaryngology clinics. Furthermore, these \npatients may have STI co-infections and these co-\n\n\n\nNSU: non specific urethritis; WHO: World Health Organization \n\n\n\nTable 2. Literature review\n\n\n\nRegion Country Author/Year Number (subjects) Top 5 STIs\nAsia Thailand Rugpao et al, 1997 195 Chlamydia, gonorrhea, warts, molluscum contagiosum, \n\n\n\ntrichomoniasis\nMalaysia Rohani et al, 2002 435 Gonorrhea, syphilis, NSU, other STDs, herpes genitalis\nIndonesia Hamzah et al, 2009 278 NSU, gonorrhea, warts, vulvovaginal candidiasis, bartholinitis\nMalaysia Hariyadurai et al, 2019 1361 Warts, latent syphilis, gonorrhea, primary herpes, NSU\n\n\n\nNorth America US Satterwhite et al, 2013 19.7 million Warts, chlamydia, trichomoniasis, gonorrhea, herpes genitalis\nWHO World WHO 1990 - Trichomoniasis, chlamydia, gonorrhea, herpes genitalis, syphilis\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12\n\n\n\nproviding them for a charge and they target women \nbetween ages 22-27. Early reports from Australia \nwho were the first to have introduced a national \nHPV vaccination program have shown a reduction \nin the prevalence of vaccine type HPV infections by \n86% in 18 to 24 year olds who had received three \nvaccine doses and 76% for those who had received \none or two doses.18 Further study involving our local \npopulation would be needed to determine if similar \ntrend is seen in our country after the introduction of \nthe HPV vaccination program.\n\n\n\nOur network of referrals remains our support system \nin providing us with a pool of patients from various \nsocioeconomic backgrounds thus allowing a wider \npool of patient capture within the Klang Valley. The \nclinic also functions as a one stop centre for patients \nwith sexually transmitted diseases as appointments \nare fast tracked, diagnosis made quickly, \ninvestigations taken and treatment administered on \nthe same day. Nevertheless, our primary care clinics \nin Klang Valley still cater to managing certain \npatients with STI via syndromic approach. However, \nthere is a loss of microbiological approach towards \ntreating these patients.\n\n\n\nThe STI seen in the clinic reflects the national \nhealth indicator that gonorrhea and syphilis remain \nat the forefront of commonest STI.  These notifiable \ndiseases continue to see an increasing incidence.19 \n\n\n\nViral warts on the other hand, remain a non notifiable \nSTD. HPV is so prevalent that it is estimated that \napproximately 75% to 80% of sexually active \nindividuals will become infected in their lifetime.20 \nIt can only be prevented with complete abstinence \nfrom all forms of sexual activity because condoms \ndo not offer complete protection from HPV and \nsome individuals infected with HPV may be \nasymptomatic but can still transmit the infection to \ntheir sexual partner.20 The high number of patients \nwith viral warts presenting to our clinic may also \nbe due to the availability of various modalities of \ntreatment available in our clinic which is rarely \navailable elsewhere within Kuala Lumpur. These \ninclude100% trichloroacetic acid solution, 20% \npodophyllin solution and cryotherapy.\n\n\n\nNevertheless, more initiative is needed to accurately \nmap the national and South East Asia regional \nvariations in STI rates, as well as the risk factors \nunderpinning STI spread. This can be achieved \nfrom more accurate population-based STI incidence \nand prevalence data. Important contextual data such \nas gender, socioeconomic variables, and ethnicity, \n\n\n\nand sexual behavior form a framework which will \nalso enrich the understanding of the spread of STI.21\n\n\n\nConclusion\nThe three commonest STIs presented to GUM clinic \nwere genital warts, syphilis and gonorrhoea.  Safe \nsex education should be considered in adolescent \nand those in their 20s as a measure to reduce future \noccurrences of STIs.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Gerbase AC, Rowley JT, Mertens TE. Global epidemiology \nof sexually transmitted diseases. Lancet 1998;351:2-4. \n\n\n\n2. Johnson LF, Lewis DA. The Effect of genital tract infections \non HIV-1 shedding in the genital tract: a systematic review \nand meta-analysis. Sex Transm Dis 2008;35:946-59. \n\n\n\n3. Adler MW. Sexually transmitted diseases: control in \ndeveloping countries. Genitourin Med 1996;72:83-8.\n\n\n\n4. Guan J, Wu Z, Li L, Lin C, Rotheram-Borus MJ, Detels R \net al. Self-reported sexually transmitted disease symptoms \nand treatment-seeking behaviors in China. AIDS Patient \nCare STDS 2009;23:443-8.\n\n\n\n5. Rugpao S, Wanapirak C, Sirichotiyakul S, Yutabootr Y, \nPrasertwitayakij W, Suwankiti S et al. Sexually transmitted \ndisease prevalence in brothel-based commercial sex \nworkers in Chiang Mai, Thailand: impact of the condom \nuse campaign. J Med Assoc Thai 1997;80:426-30.\n\n\n\n6. A Rohani, AA Nasir. Sexually Transmitted Infections \n(including HIV infection) Care Management Using the \n\u201cModified Syndromic Approach\u201d in Malaysia. MJPHM \n2002;2:52-7.\n\n\n\n7. Hamzah MS, Effendi A. Pattern of Sexually Transmitted \nInfection in Dr.H.Abdul Moeloek Hospital Lampung \n(2008-2009). 16th International Union Against Sexually \nTransmitted Infections 2010:PP-01. https://www.iusti.org/\nregions/asia-pacific/IUSTI_AP_Bali_papers_part2.pdf.\n\n\n\n8. World Health Organization WHO Office of information. \nSexually transmitted infections increasing--250 million \nnew infections annually. WHO Feature 1990;152:1-6.\n\n\n\n9. Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan \nR, Ocfemia MC et al. Sexually transmitted infections \namong US women and men: prevalence and incidence \nestimates, 2008. Sex Transm Dis 2013;40:187-93.\n\n\n\n10. Protocol for Management of Sexually Transmitted \nDiseases (STD) for Paramedical Staff, STD Series 2, \nMinistry of Health Malaysia.\n\n\n\n11. Anwar M, Syed Azhar SS, Keivan A, Tahir MK. Awareness \nof school students on sexually transmitted infections \n(STIs) and their sexual behavior: a cross-sectional study \nconducted in Pulau Pinang, Malaysia. BMC Public Health. \n2010;10:47. \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n13\n\n\n\n12. EC Tilson, V Sanchez, CL Ford, M Smurzynski, PA \nLeone, KK Fox et al. Barriers to asymptomatic screening \nand other STD services for adolescents and young adults: \nfocus group discussions. BMC Public Health. 2004;4:21.\n\n\n\n13. National Institute of Public Health (Norway). MSIS report. \nOslo: NIPH, 1993\n\n\n\n14. PAHO/WHO.AIDS, HIV & STD annual surveillance \nreport for the Americas, 1992\n\n\n\n15. Ministry of Health and Child Welfare (Zimbabwe). \nNational AIDS Coordination Programmed Annual Report. \nHarare: MHCW;1995.\n\n\n\n16. Hanenberg RS, Rojanapithayakorn W, Kunasol P, Sokal \nDC. Impact of Thailand\u2019s HIV Control Program as \nindicated by the decline in sexually transmitted diseases. \nLancet 1994;344:243-5.\n\n\n\n17. Thirumoorthy T. The epidemiology of sexually transmitted \ndiseases in Southeast Asia and Western Pacific. Semin \nDermatol 1990;9:102-4.\n\n\n\n18. Garland SM. The Australian Experience with the human \npapilloma vaccine. Clin Ther 2014;36:17-23. \n\n\n\n19. KKM Health Facts 2012-2016. Ministry of Health \nMalaysia. Planning Division. Health Informatics Centre. \nMOH/S/RAN/17.16(AR)\n\n\n\n20. Chesson HW, Dunne EF, Hariri S, Markowitz LE. \nThe estimated lifetime probability of acquiring human \npapillomavirus in the United States. Sex Transm \nDis. 2014;41:660-4.\n\n\n\n21. Aral SO, Lipshutz J, Blanchard J. Drivers of STD/HIV \nepidemiology and the timing and targets of STD/HIV \nprevention. Sex Transm Infect 2007;83:i1-4.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14\n\n\n\nORIGINAL ARTICLE\n\n\n\nLeprosy and Tuberculosis Co-infection: A Review of Cases in \nDermatology Clinics in Malaysia         \nMin Moon Tang1, AdvMDerm, Shir Nee Tan1, MD, Kwee Eng Tey2, MRCP, Yee Ting Lim2, MRCP, Wooi Chiang \nTan3, AdvMDerm, Lee Chin Chan4, MMed, Choo Khoon Ong5, MRCP, Michelle Sook Yee Voo6, AdvMDerm, Suganthi \nThevarajah1, MMed\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n2Department of Dermatology, Hospital Sultanah Aminah, Johor, Malaysia\n3Department of Dermatology, Hospital Sultanah Bahiyah, Kedah, Malaysia\n4Department of Dermatology, Hospital Pulau Pinang, Pulau Pinang, Malaysia\n5Department of Respiratory, Hospital Pulau Pinang, Pulau Pinang, Malaysia \n6Department of Dermatology, Hospital Queen Elizabeth, Sabah, Malaysia\n\n\n\nAbstract\nIntroduction: \nLeprosy and tuberculosis are both chronic granulomatous infections caused by Mycobacterium \nspecies with predominant neuro-dermatological and respiratory symptoms respectively. Co-infection \nof Mycobacterium leprae and Mycobacterium tuberculosis was observed in a handful of cases. We aim \nto describe the clinical features and the challenges in the management of both diseases that manifested \nat the same time.\n\n\n\nMethods: \nThis is a retrospective study on all patients with leprosy and tuberculosis co-infection managed in the \ndermatology clinics in Hospital Kuala Lumpur, Hospital Sultanah Aminah, Hospital Pulau Pinang, \nHospital Sultanah Bahiyah and Hospital Queen Elizabeth between 1999 and 2017. Data was obtained \nby reviewing patients\u2019 medical records. \n\n\n\nResults:\nA total of 22 patients were diagnosed to have leprosy and tuberculosis co-infection with a mean \nage of 43.6 years (range: 19-80) when the leprosy was diagnosed. Twelve (54.5%) were foreigners. \nMajority (72.7%) had lepromatous leprosy. The median bacteriological index and morphological index \nwere 3.2 and 1.3 respectively when leprosy was diagnosed. Twenty patients (80.1%) had pulmonary \ntuberculosis, one had tuberculous lymphadenopathy and another had scrofuloderma. One half of the \npatients (50%) had the tuberculosis diagnosed concurrently; 4 (18.2%) before and 7(31.8%) after \nleprosy was diagnosed. Thirteen patients (59.1%) developed erythema nodosum leprosum, 2 (9.1%) \nreversal reactions and 1 (4.5%) Lucio\u2019s phenomenon. Fifteen patients (68.2%) were treated with \nSungai Buloh Augmented Regime for the leprosy. Sixteen patients (68.2%) received prednisolone \nfor the leprae reactions. All had tuberculosis treatment with 16 (72.7%) who completed for at least 6 \nmonths (6-15 months). The documented adverse events that were directly related to the concurrent \nantileprosy and anti-tuberculosis drugs were hepatitis (1); lethargy (1) and transient maculopapular \neruption (1). Most tolerated both treatments well. Seven patients had completed both treatments and \npresently under surveillance. Four patients were transferred to another center and one defaulted both \ntreatments.\n\n\n\nConclusion: \nMajority of patients concurrently infected with leprosy and tuberculosis had lepromatous leprosy with \npulmonary tuberculosis. Nearly three-quarter developed leprae reactions. Most patients tolerated both \nanti-leprosy and anti-tuberculosis drugs well.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n15\n\n\n\nCorresponding Author\nDr Tang Min Moon\nDepartment of Dermatology,\nHospital Kuala Lumpur, Jalan Pahang, \n50586 Kuala Lumpur, Malaysia \nEmail: minmoon2005@yahoo.com \n\n\n\nIntroduction\nLeprosy and tuberculosis are both chronic \ngranulomatous diseases caused by Mycobacterium \nleprae (M. leprae) and Mycobacterium tuberculosis \n(M tuberculosis) respectively. Leprosy typically \naffects the skin and peripheral nerves while \ntuberculosis classically affects the lungs and rarely, \nother internal organs. The topographic variations \nof these two mycobacterial is mainly explained \nby their genomic features. M leprae has a smaller \ngenome size (3,268,203 bp vs. 4,411,532bp) and \nproportion of protein-coding genes (49% vs 90%) \ncompared to that of M tuberculosis.1 Furthermore, \nthe guanine and cytosine percentage (G+C%) of \nDNA in M tuberculosis is higher than M leprae.1 \nDNA with high G+C% are more thermostable but \nundergo autolysis which reduce the longevity of the \ncells. Hence, M. leprae tends to reside at cooler area \nof the body i.e. the skin and peripheral nerves and \nhas a much longer incubation period.  \n\n\n\nCo-infection of leprosy and tuberculosis has been \nwidely reported in the 1950\u2019s to 1990\u2019s.2-9 Gray \net al observed that about 16.9-26.4% of deaths in \na leprosarium in the United States between 1922 \nand 1950 were due to tuberculosis.3 In about 28% \nof autopsies performed on 35 patients with leprosy \nin Malaysia, pulmonary tuberculosis was detected.7 \nNevertheless, less cases were reported after 1990\u2019s.9 \nThis has invoked an interesting hypothesis that co-\ninfection of these two mycobacterium may result in \ncross-immunity and contribute to the reduction of \nleprosy.  \n\n\n\nHere we aim to describe the clinical characteristics \nand the management of patients who had leprosy \nand tuberculosis co-infection in Malaysia.\n\n\n\nMaterials And Methods\nThis is a retrospective study on all patients with \nleprosy and tuberculosis co-infection managed in \n5 dermatology clinics in Malaysia i.e. dermatology \nclinics in Hospital Kuala Lumpur, Hospital Sultanah \nAminah, Hospital Pulau Pinang, Hospital Sultanah \nBahiyah and Hospital Queen Elizabeth between \n1999 and 2017. Data was obtained by reviewing \npatients\u2019 medical records.\n\n\n\nResults\nA total of 22 patients were diagnosed with leprosy \nand tuberculosis coinfection (Table 1&2). The mean \n\n\n\nKey words: Leprosy, Tuberculosis, Mycobacterium leprae, Mycobacterium tuberculosis\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16\n\n\n\nage of patients when leprosy was diagnosed was \n43.6 (SD=16.3) years. Majority were male and more \nthan half were foreign-born patients. Of these, 75% \nwere Indonesian. More than 70% of the patients \nhad lepromatous leprosy. Sungai Buloh Augmented \nRegime10 (Table 3) was the most frequently \nprescribed treatment regime. About 40% received \nofloxacin as second line agent for leprosy treatment. \nErythema nosodum leprosum was the most frequent \nreaction (59.1%) experienced by the cohort. About a \nquarter of the patients did not develop any reaction \nwhile receiving treatment for leprosy.\n\n\n\nPulmonary tuberculosis was the most common \ntype of tuberculosis in our cohort. Half of the \npatients had symptoms of leprosy and tuberculosis \nconcurrently. About a third developed tuberculosis \nwhile receiving treatment for leprosy. Acid fast \nbacilli was detected in the sputum of nearly 60% of \nour patients. All patients received anti-tuberculosis \ntreatment. Sixteen patients (72.7%) completed at \n\n\n\nleast 6 months duration. The majority of patients \ncompleted anti-tuberculosis treatment. About 14% \nwere lost to follow up prior to treatment completion.\n\n\n\nThe average reduction of bacteriological index (BI) \nat 6 and 12 months were 0.6 (n=12; range -1.9 to \n+0.2) and 0.76 (n=11; range -2.3 to 0) respectively. \nThis was among those who completed at least \n6 months of anti-tuberculosis in addition to the \nleprosy treatment. The documented adverse events \nthat were directly related to the concurrent leprosy \nand tuberculosis treatments included hepatitis \n(1 patient); lethargy (1 patient) and transient \nmaculopapular eruption (1 patient). Most patients \ntolerated both treatments well. The only mortality \nrecorded in our cohort was due to pulmonary \nmetastasis of unknown primary. This patient had \ncompleted both leprosy and tuberculosis treatment \nand died while he was under post-leprosy treatment \nsurveillance. \n\n\n\nDemographic characteristics n=22\nMean age in years (range) 43.6 (19-80)\nGender, n (%) Male 19 (86.4)\n\n\n\nFemale 3 (13.6)\nNationality, n (%) Malaysian 10 (45.5)\n\n\n\nForeign born 12 (54.5)\nEthnicity among Malaysian, n (%) Malay 5 (50)\n\n\n\nChinese 2 (20)\nIndian 1 (10)\nOrang asli 2 (20)\n\n\n\nCountry of origin of foreign-born, n (%) Indonesia 9 (75)\nMyanmar 3 (25)\n\n\n\nLeprosy characteristics n=22\nType of cases, n (%) New case 20 (90.9)\n\n\n\nRelapse case 2 (9.1)\nDisease classification by Ridley & Jopling, n (%) Tuberculoid 1 (4.5)\n\n\n\nBorderline tuberculoid 1 (4.5)\nBorderline borderline 2 (9.1)\nBorderline lepromatous 2 (9.1)\nLepromatous leprosy 16 (72.7)\n\n\n\nMedian baseline slit skin smear (range) Bacteriological index (BI) 3.2 (0-5)\nMorphological index (MI) 1.3 (0-8)\n\n\n\nType of treatment prescribed, n (%) Sungai Buloh Augmented Regime  (multibacillary)- at least 36 months 14 (63.6)\n\n\n\nWHO regime \u2013 6 months 1 (4.5)\nWHO regime \u2013 12 months 2 (9.1)\nWHO regime \u2013 18 months 1 (4.5)\nWHO regime \u2013 24 months 3 (13.6)\n\n\n\nSecond line agent used, n (%) Ofloxacin 9 (40.9)\nMinocycline 2 (9.1)\n\n\n\nType of reactions, n (%) Reversal 2 (9.1)\nErythema nodosum leprosum 13 (59.1)\nLucio\u2019s phenomenon 1 (4.5)\nNo reactions 6 (27.3)\n\n\n\nTable 1. The demography and characteristics of leprosy in 22 patients.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n17\n\n\n\nTable 2. The characteristics of tuberculosis, investigations, management & outcome in 22 patients.\n\n\n\nPCR: polymerase chain reaction\n\n\n\nDiscussion\nBoth leprosy and tuberculosis are the oldest diseases \nof mankind. Humans had typical tuberculosis \nlesions about 9000 years ago11, and the analysis of \npathological conditions in skeletons showed that \nlepromatous leprosy was present much earlier in \nIndia in 2000 BC.12 Donoghue et al who examined \nselected archaeological samples from Roman period \nto the thirteenth century, discovered that leprosy and \ntuberculosis co-existed in the past.2 Co-infection \ndoes occur and has been reported from time to time. \nWhile some experts feel that concomitant infections \nare merely co-incidental, many were convinced \nthat interactions do occur between these two \nmycobacterial infections. Irrespective of relative or \nabsolute immunity, co-infection with leprosy and \ntuberculosis has been a topic of interest in the past, \nwith the aim to explore the degree of antagonism \nof both diseases. Indeed, ever since 1939, Bacillus \nCalmette-Gu\u00e9rin (BCG) vaccination was reported \nto confer some protective effect against leprosy \nbetween 20-80%.13-20 \n\n\n\nInterestingly, between 1930s and 1950s, Fernandez \nobserved more subjects with tuberculin-negative \n\n\n\nacquired leprosy, with the majority at the \nlepromatous pole.21 Conversely more than 95% \ntuberculin-positive patients who acquired leprosy \nhad tuberculoid leprosy, which was considered \n\u201cbenign\u201d.21 Furthermore, the prevalence of leprosy \nwas noted to be lower in a population with a high \nprevalence of tuberculosis.21 Subsequently, Lietman \net al attempted to assess the epidemiological \nconsequences of cross-immunity using a \nmathematical model of the transmission dynamics \nof tuberculosis and leprosy.22 It was suggested that \ntuberculosis could have contributed to the decline \nof leprosy if the basic reproductive rate of leprosy \nwas low. \n\n\n\nNevertheless, Donoghue et al believed that the \nhypothesis of cross-immunity was less likely to \nexplain the epidemiological decline of leprosy.2 \nThis was supported by another mathematical \nmodeling performed by Hohmann et al. It was \nthe co-infection hypothesis rather than the cross-\nimmunity hypothesis that resulted in the eventual \ndisappearance of leprosy.23 Cross-immunity \ndevelops after one is pre-immunized with \ntuberculosis infection or vaccination. On the other \nhand, pre-infection with leprosy is steering the \n\n\n\nTuberculosis (TB) characteristics n=22\nType of TB, n (%) Pulmonary tuberculosis 20 (90.9)\n\n\n\nTuberculosis lymphadenopathy 1 (4.5)\nScrofuloderma 1 (4.5)\n\n\n\nTiming of TB in relation to leprosy, n (%) Before leprosy 4 (18.2)\nConcurrently 11 (50.0)\nAfter leprosy 7 (31.8)\n\n\n\nMedian duration between the diagnosis of leprosy and TB in months (range) 6 (-46 to 11)\nInvestigation evidence of TB infection, n (%) Opacities in chest radiograph 11 (50)\n\n\n\nPositive sputum for acid fast bacilli 13 (59.1)\nPositive tuberculosis PCR 2 (9.1)\nPositive tuberculosis culture 8 (36.4)\nPositive GeneXpert\u00ae rapid TB test 1 (4.5)\n\n\n\nTreatment of TB, n (%) Intensive phase Rifampicin 21 (95.5)\nIsoniazid 21 (95.5)\nPyrazinamide 21 (95.5)\nEthambutol 16 (95.5)\nStreptomycin 2 (9.1)\nAkurit 4 1 (4.5)\n\n\n\nMaintenance phase Rifampicin 14 (63.6)\nIsoniazid 14 (63.6)\n\n\n\nMedian duration of TB treatment received in months at last follow up (range) 6 (1-15)\nStatus at last follow up, n (%) Completed both TB and Leprosy treatment and under surveillance 6 (27.3)\n\n\n\nCompleted both TB and Leprosy treatment & released from surveillance 1 (4.5)\nCompleted TB treatment but still on leprosy treatment 2 (9.1)\nTransfer care to other center 4 (18.2)\nCompleted TB treatment but lost to follow up 5 (22.7)\nLost to follow up before completed TB treatment 3 (13.6)\nCompleted both TB and Leprosy treatment but died during surveillance 1 (4.5)\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18\n\n\n\nprocess of co-infection hypothesis.23 Generally, \nleprosy itself has a low mortality. Co-infection with \ntuberculosis which has a much higher mortality \nmay result in eventual eradication of leprosy by \ntuberculosis, albeit a long process.23\n\n\n\nThe estimated incidence of tuberculosis in \nMalaysia has increased from 75/100,000 in 2000 \nto 89/100,000 in 2015, and further increased to \n93/100,000 in 2017.24-26 The incidence of leprosy \nin Malaysia was 0.7 per 100,000 in 2015.27 Based \non the probability calculator, it is estimated that \nthere are 0.0006 cases of tuberculosis and leprosy \nco-infection per 100,000 population in Malaysia. \nWith a population of nearly 32 million in Malaysia, \nthe prediction is that we will encounter a case of \nco-infection every 5 years. However, in this 18-\nyear audit, we have more cases of co-infection than \npredicted. Under-diagnosis, under-reporting and \nundertreatment of both tuberculosis and leprosy \ncases in this country could be the reasons. This \nis reflected from the failure to achieve the WHO \nindicators in the strategy to end the tuberculosis \nepidemic. The tuberculosis treatment coverage rate \nand the treatment success rate in Malaysia for 2017 \nwere 87% and 80% respectively which were below \nthe targets set by WHO at \u226590% for both.25 More \nthan half of our cohort in this audit were foreign-\nborn which included Indonesian and Myanmar. \nBoth Indonesia and Myanmar are high tuberculosis \nand leprosy burden countries listed by WHO. Hence \nour achievement in tuberculosis and leprosy control \n\n\n\nwas likely hampered by the immigrants.     \n\n\n\nRifampicin is the key agent in the treatment of \nleprosy and tuberculosis. Ofloxacin is a second line \nanti-tuberculosis treatment and Clofazimine is used \nto treat rifampicin resistant or multidrug resistant \ntuberculosis.28,29 In those who had the slit skin smear \n(SSS) monitored while receiving treatment for both \nleprosy and tuberculosis, concurrent treatment \ndid not seem to reduce the BI at a greater rate. It \nis a reflection of debilitated cell-mediated immune \nresponse among these patients especially those \nassociated with lepromatous leprosy. The reduction \nof cell-mediated immune response not only leads \nto activation of an underlying latent tuberculosis \nor superinfection with M tuberculosis, but results \nin sluggish response to intensive treatment as well. \nMoreover, in 7 patients who had tuberculosis after \nleprosy, the leprosy treatment did not seem to \nprotect them from developing tuberculosis. Five \nreceived long term prednisolone to treat their leprae \nreactions; which may be a risk factor for acquiring \ntuberculosis in these patients.   \n\n\n\nFuture research is needed to study the immuno-\ngenetic host factors which predispose to TB \nand leprosy co-infection and the antimicrobial \nresistance pattern in all concomitant infections. \nFurther epidemiology studies should be done to \nassess the interaction of tuberculosis and leprosy in \nthis country.  \n\n\n\nPaucibacillary leprosy Multibacillary leprosy\nAgents Duration Agents Duration\n\n\n\nIntensive daily Rifampicin 600mg\nClofazimine 100mg\n\n\n\nDapsone 100mg\n\n\n\n1 month or till morphological \nindex =0\n\n\n\nSupervised monthly Rifampicin 600mg\nClofazimine 300mg\n\n\n\n1 year Rifampicin 600mg\nClofazimine 300mg\n\n\n\n3 years or till smear negative\n\n\n\nDaily Clofazimine 100mg\nDapsone 100mg\n\n\n\n1 year Clofazimine 100mg\nDapsone 100mg\n\n\n\n3 years or till smear negative\n\n\n\nPost treatment\nsurveillance\n\n\n\n5 years 10 years\n\n\n\nTable 3. Sungai Buloh Augmented Regime of Multidrug therapy for leprosy\n\n\n\nConclusion\nMajority of patients who were concurrently infected \nwith leprosy and tuberculosis had lepromatous \nleprosy with pulmonary tuberculosis. Nearly \nthree-quarters developed leprae reactions with \nthe majority having erythema nodosum leprosum. \nMost patients tolerated concurrent leprosy and \ntuberculosis treatment well.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for the permission to \npublish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n19\n\n\n\nReferences\n\n\n\n1. Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson \nNR, Wheeler PR et al. Massive gene decay in the leprosy \nbacillus. Nature 2001;409:1007-11.\n\n\n\n2. Donoghue HD, Marcsik A, Matheson C, Vernon K, \nNuorala E, Molto JE et al. Co-infection of Mycobacterium \ntuberculosis and Mycobacterium leprae in human \narchaeological samples: a possible explanation for the \nhistorical decline of leprosy. Proc Biol Sci 2005;272:389-\n94.\n\n\n\n3. Rawson TM, Anjum V, Hodgson J, Rao AK, Murthy \nK, Rao PS et al. Leprosy and tuberculosis concomitant \ninfection: a poorly understood, age-old relationship. Lepr \nRev 2014;85:288-95.\n\n\n\n4. Gray HH, Bancroft H. Tuberculosis at the United States \nPublic Health Service Hospital, Carville, Louisiana, \n1922-1950. Int J Lepr 1952;20:467-78.\n\n\n\n5. Premanath M, Ramu G. The association of leprosy and \ntuberculosis. J Indian Med Assoc 1976;67:143-5.\n\n\n\n6. Glaziou P, Cartel JL, Moulia-Pelat JP, Ngoc LN, Chanteau \nS, Plichart R et al. Tuberculosis in leprosy patients \ndetected between 1902 and 1991 in French Polynesia. Int \nJ Lepr Other Mycobact Dis 1993;61:199-204.\n\n\n\n7. Jayalakshmi P, Looi LM, Lim KJ, Rajogopalan K. \nAutopsy Findings in 35 Cases of Leprosy in Malaysia. Int \nJ Lepr Other Mycobact Dis 1987;55:510- 4. \n\n\n\n8. Nigam P, Dubey AL, Dayal SG, Goyal BM, Saxena HN, \nSamuel KC. The association of leprosy and pulmonary \ntuberculosis. Lepr India 1979;51:65-73.\n\n\n\n9. Rajagopala S, Devaraj U, D\u2019Souza G, V Aithal V. Co-\nInfection with M. tuberculosis and M. leprae-Case Report \nand Systematic Review. J Mycobac Dis 2012;2:118. \ndoi:10.4172/2161-1068.1000118.\n\n\n\n10. Kementerian Kesihatan Malaysia. Manual Pengurusan \nProgram Kawalan Kusta Edisi Pertama. Bahagian \nKawalan Penyakit Unit Kawalan Tibi/Kusta 1997. \n\n\n\n11. Hershkovitz I, Donoghue HD, Minnikin DE, Besra GS, \nLee OY, Gernaey AM et al. Detection and Molecular \nCharacterization of 9000-Year-Old Mycobacterium \ntuberculosis from a Neolithic Settlement in the Eastern \nMediterranean. PLoS One 2008;3:e3426. doi:10.1371/\njournal.pone.0003426.\n\n\n\n12. Robbins G, Tripathy VM, Misra VN, Mohanty RK, \nShinde VS, Gray KM et al. Ancient skeletal evidence for \nleprosy in India (2000 B.C.) PLoS One 2009;4:e5669. \ndoi: 10.1371/journal.pone.0005669.\n\n\n\n13. Fernandez JMM. Estudio comparativo de la reacci\u00f3n de \nMitsuda con las reacciones tuberculiniccas. Rev Argent \nDermalosif 1939;23:425-53. \n\n\n\n14. Stanley SJ, Howland C, Stone MM, Sutherland I. BCG \nvaccination of children against leprosy in Uganda: final \nresults. J Hyg (Lond) 1981;87:233-48.\n\n\n\n15. Bechelli LM, Lwin K, Gallego Garbajosa P, Mg-Mg-\nGyi, Uemura K Sundaresan T et al. BCG vaccination \nof children against leprosy: nine-year findings of the \ncontrolled WHO trial in Burma. Bull World Health Organ \n1974;51:93-9.\n\n\n\n16. Scott GC, Russell DA, Boughton CR, Vincin DR. \nUntreated leprosy. Probability of shifts in Ridley-Jopling \nclassification. Development of \u201cflares\u201d, or disappearance \nof clinically apparent disease. Int J Lepr Other Mycobact \nDis 1976;44:110-22.\n\n\n\n17. Tripathy SP. The case for B.C.G. Ann Natl Acad Med Sci \n1983;19:11-21.\n\n\n\n18. D\u00fcppre NC, Camacho LA, da Cunha SS, Struchiner \nCJ, Sales AM, Nery JA et al. Effectiveness of BCG \nvaccination among leprosy contacts: a cohort study. Trans \nR Soc Trop Med Hyg 2008,102:631\u20138.\n\n\n\n19. Setia MS, Steinmaus C, Ho CS, Rutherford GW.1 The \nrole of BCG in prevention of leprosy: a meta-analysis. \nLancet Infect Dis 2006,6:162\u201370.\n\n\n\n20. Merle CS, Cunha SS, Rodrigues LC. BCG vaccination \nand leprosy protection: review of current evidence and \nstatus of BCG in leprosy control. Expert Rev Vaccines \n2010;9:209-22.\n\n\n\n21. Fernandez JM. Leprosy and tuberculosis; antagonistic \ndiseases. AMA Arch Derm 1957;75:101-6.\n\n\n\n22. Lietman T, Porco T, Blower S. Leprosy and tuberculosis: \nthe epidemiological consequences of cross-immunity. Am \nJ Public Health 1997;87:1923-7.\n\n\n\n23. Hohmann N, Voss-Bohme A. The epidemiological \nconsequences of leprosy-tuberculosis co-infection. Math \nBiosci 2013;241:225-37.\n\n\n\n24. Global tuberculosis report 2016. Geneva: World Health \nOrganization; 2016. \n\n\n\n25. Global tuberculosis report 2018. Geneva: World Health \nOrganization; 2018.\n\n\n\n26. WHO. Tuberculosis profile: Malaysia 2017 available \nfrom https://extranet.who.int/sree/Reports?op=Replet&\n\n\n\n name=%2FWHO_HQ_Reports% 2FG2%2FPROD%\n 2FEXT%2FTBCountryProfile&ISO2=MY&LAN=\n EN&outtype=html [Accessed on 10th April 2019].\n27. WHO. Global leprosy update, 2015: time for action, \n\n\n\naccountability and inclusion. WER 2016;91:405-20.\n28. WHO Treatment of tuberculosis guideline 4th Edition \n\n\n\n2010.\n29. WHO. WHO Treatment guidelines for drug-resistant \n\n\n\ntuberculosis 2016 Update.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20\n\n\n\nORIGINAL ARTICLE\n\n\n\nPerception and Psychosocial Impact of Acne Vulgaris Among \nSecondary School Adolescents in Ipoh, Malaysia         \nJing Wern Kwan, MRCP, Hock Leng Lee, AdvMDerm, Dyoi-E Low, AdvMDerm, Jyh Jong Tang, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia \n\n\n\nAbstract\nBackground: \nAcne is one of the most common skin diseases among adolescents. It has significant negative impact \non self-image and quality of life. Poor understanding and misperception of this condition can lead to \ndelayed in seeking treatment. The study aimed to evaluate the perception and understanding of acne \nvulgaris among adolescents as well as the psychosocial impact of acne vulgaris. \n\n\n\nMethods: \nA cross sectional study was conducted in conjunction with Project on Adolescents Skin Health (PASH) \nby Persatuan Dermatologi Malaysia (PDM) in 12 secondary schools in Ipoh, Perak, Malaysia from \nSeptember to November 2017. A self-administered questionnaire was distributed to students to assess \ntheir perception of acne vulgaris and psychosocial impact of acne vulgaris among the sufferers.\n\n\n\nResults: \nA total of 2105 students were recruited into this study, consist of 1673 (79.5%) female students and \n432 (20.5%) male students. More than half of them believed acne was related to food, stress, personal \nhygiene and hormonal imbalance. There was a total of 1363 (64.7%) students suffering from acne \nvulgaris. Acne was more common among boys than girls (72.0% vs 62.9%). Majority had mild acne \n(54%) followed by moderate acne (40.5%) and severe acne (5.5%). Forty percent of them were \nconcerned, felt miserable and depressed about their appearance. Only 11% of them sought treatment \nfrom doctors while majority (75%) bought medication from pharmacy and 14% were treated by \nbeautician.\n \nConclusion: \nAcne vulgaris is common and has significant psychosocial impact among our secondary school \nadolescents in Ipoh. Unfortunately, there is still misperception about this condition among our \nadolescent and majority choose to self-medicate from pharmacy. Hence, education is important to \nimprove the understanding of acne vulgaris and to encourage early treatment from qualified health \ncare providers.\n\n\n\nKey words: Acne vulgaris, Adolescents, Cardiff Acne Disability Index, CADI, Quality of life, Perception, Psychosocial impact\n\n\n\nCorresponding Author\nDr Kwan Jing Wern\nDepartment of Dermatology\nHospital Raja Permaisuri Bainun, \nJalan Raja Ashman Shah,\n30450 Ipoh, Perak\nEmail: kwanjingwern@gmail.com\n\n\n\nIntroduction \nAcne vulgaris is the most common dermatological \ncomplaints among adolescents. It affects almost \n85% of individuals ranges from 12-24 years of \nage.1 Acne vulgaris can affects one\u2019s body image \nperception. Individuals who are suffering from acne \nvulgaris may developed significant depression, \nanxiety, psychosomatic symptoms, and social \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n21\n\n\n\nand psychosocial impact of acne vulgaris among \nthe sufferers. The following data were collected: \ndemography, knowledge and perception of acne \nvulgaris, self-rated disease severity and assessment \nof psychosocial impact of acne vulgaris by using \nCardiff Acne Disability Index (CADI) score. \nAssessment of perception of acne vulgaris was \nbased on their knowledge regarding the causes and \nthe aggravating factors of acne vulgaris. CADI \nis a well validated self-reported questionnaires \nconsisting of 5 questions with a Likert scale, \nfour response categories (0-3)4. The scores range \nfrom 0-15. These 5 questions relate to feeling of \naggression, frustration, interference with social \nlife, avoidance of public changing facilities and \nappearance of the skin. CADI scores were graded \nas low (0-4), medium (5-9), and high (10-15). The \nhigher accumulative score indicating a higher level \nof disability. Statistical analysis was performed \nusing SPSS version 22 post data collection. \n\n\n\nResults\nDemographics data\nA total of 2105 students filled out the questionnaires \nvoluntarily with 79.5% female and 20.5% male. \nThe mean age was 14.6 years with a range of 13 \nto 18 years. The major ethnic group was Chinese \n(45%), followed by Malays (29%), Indians (25%) \nand others (1%) (Table 1).\n\n\n\nPrevalence and self-rated severity of acne \nAmong 2105 subjects, 64.7% of them suffered from \nacne vulgaris. According to gender breakdown, \n62.9% of female and 72% of male suffers from \nacne problem. Based on self-rated severity of acne \nvulgaris, majority has mild acne (53.7%), followed \nby moderate acne (40.4%) and severe acne (5.9%). \n\n\n\nKnowledge and perception on acne vulgaris\nMore than half of our subjects believed the following \nsix aggravating factors as the most common causes \nof acne vulgaris which include poor personal \nhygiene (77.8%), fried food (68.8%), hormonal \ndisturbances (68.1%), stress (66%), peanuts (57%), \ngerms (52%) and spicy food (51%) (Figure 1). Only \n37.5% of them believed that genetic and positive \nfamily history increase the risk of acne vulgaris. \nHowever, by looking at the established aggravating \nfactors, only hormonal, stress and germs were \nperceived as the aggravating factors in more than \n50% of the students.\n\n\n\nSource of acne treatment \nMajority of them (75%) purchased facial products \n\n\n\ndisinhibition.2 The psychosocial impact of acne is \noften underrated. It was found that even mild acne \ncan pose a significant psychological impact and \ncauses social dysfunction.\n \nDespite the high impact on the quality of life by \nits effect on the physical appearance, adolescents \noften have a tendency not to seek medical care but \ndepend on local remedies or commercially available \nproducts. Moreover, with the current digital \ntechnology, most of adolescents would choose to \nget health related information from the internet \nwhich could be inaccurate and misleading. These \nmisconceptions and myth often delay their treatment \nand adversely affect the treatment outcome.3 Our \nstudy aimed to evaluate the knowledge, perception \nand psychosocial impact of acne vulgaris among \nsecondary school adolescents in Ipoh, Perak. \n\n\n\nMaterials And Methods\nThis study was conducted in conjunction with \nProject on Adolescents Skin Health (PASH) by \nPersatuan Dermatologi Malaysia (PDM). This \nwas the first corporate social responsibility (CSR) \nproject by PDM. The aim of PASH was to provide \nskin health education among adolescents in order \nto increase their knowledge on the understanding \nof physiologic skin changes and common skin \ndiseases. The first phase of PASH was carried out \nin Ipoh, Perak, in collaboration with Department \nof Dermatology, Hospital Raja Permaisuri Bainun. \nThe target group was school going adolescents in \n12 secondary schools in Ipoh, Perak. Five teams, \neach comprising a dermatologist (headed by Dato\u2019 \nDr Sushil Kumar Ratti, Dr Agnes Heng, Dr Henry \nFoong, Dr Tang Jyh Jong and Dr Lee Hock Leng), \ntwo medical officers and two nurses, were assigned \nto 3 schools each to provide skin health education to \nthe students.  The first part of the project focused on \nacne vulgaris and a power point presentation on \u201cTen \ncommon questions on acne vulgaris\u201d was prepared \nby the PASH committee. The dermatologist in each \nteam used this power point presentation to educate \nthe students on acne and proper skin care. This was \nthen followed by question and answer session with \nsome students sharing their personal experience \nand battle against acne. PASH was successfully \nconducted from 21st September 2017 to 23rd \nNovember 2017.\n  \nA simple survey was also done during these \nsessions in which students were given a self-\nadministered questionnaire before the lecture. This \nwas to assess their perception on acne vulgaris \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22\n\n\n\nover the counters. 14% of them sought treatment \nfrom beautician, only 11% of them sought medical \ntreatment.\n\n\n\nPsychosocial impact of acne\nThe mean CADI score was 3.5 \u00b1 2.5. Majority of \nthem had mild CADI score (score 0 to 4) which was \nseen in 77.9% while 20.4% had medium CADI score \n(score 5 to 9) and the remaining 1.6% had high CADI \n(score 10 to 15). (Refer Table 2) Further analysis \nwas done on the individual CADI domain with \nscore \u2265 1 taken as minimal impact on the particular \ndomain. There was 69.4% of them who some degree \nof feeling aggressive, frustrated and embarrassed as \na result of acne vulgaris while 42.2% of them had \nsocial life and social relationship interference. Up \nto 79.5% perceived acne as a problem and 76.4% of \nthem were concerned, depressed and felt miserable \nto a certain extend. However, only 24.5% of them \navoiding public changing facilities or wearing \nswimming costumes because of acne. (Refer Table \n3)\n\n\n\nDiscussion\nOur study showed that acne vulgaris is common, \naffecting 64.7% of our secondary school adolescents. \nIt is more common among male students (72%) than \nfemale students (62.9%).  Hanisah et al conducted a \nsimilar prevalence study on 409 students (Form 1 to \nForm 5) in two secondary schools in Muar.1 It was \nshown that the prevalence of facial acne was 67.5% \namong adolescents and more male students (71.1%) \nwere affected than female students (64.6%).1  \nSimilar result was seen in an online survey of 2,284 \nhigh school and college students from central China \nshowed that the prevalence of acne was 50.6% with \nmore males than female students being affected by \nacne vulgaris (male 58.04% vs female 41.96%).5 \nHowever, a cross-sectional study involving 692 \nelementary school children aged 7\u201312 years in \nSeoul, Korea revealed that the prevalence rate of \nacne was 36.2% which was lower than our study.2  \nThis could be related to younger age group in the \nKorean study as acne vulgaris is generally less \ncommon among children less than 12 years old. \nStudies in Muar, China and Korea showed that \nmajority of adolescents have mild acne (90.2%, \n47.75% and 94.4% respectively) and this was \ncomparative to our study which showed 53.7% had \nmild acne.1,2,5\n\n\n\nTable 1. Demographic data of secondary school adolescents \ninvolved in PASH Ipoh  \n\n\n\nCharacteristics n (%)\nGender Girl 1673 (79.5)\n\n\n\nBoy 432 (20.5)\nEthnic Malay 610 (29.0)\n\n\n\nChinese 947 (45.0)\nIndian 528 (25.0)\nOthers 20 (1.0)\n\n\n\nMean age 14.6 years old\n(Range 13 to 18 years)\n\n\n\nAcne vulgaris Yes 1363 (64.7)\nNo 742 (35.3)\n\n\n\nCADI SCORE Percentage\n0-5 Mild 77.9%\n5-10 Moderate 20.4%\n11-15 Severe 1.6%\n\n\n\nPercentage of student with score \u2265 1 \n(at least mild impact) for each domain in CADI\n\n\n\nPercentage \n(%)\n\n\n\n1. Feeling aggressive, frustrated and \nembarrassed\n\n\n\n69.4%\n\n\n\n2. Social interference 42.2%\n3. Avoidance of public changing 24.5%\n4. Patient psychological state (concerned or \n\n\n\nfeeling depressed)\n76.4%\n\n\n\n5. Subjective assessment of acne severity \n(Perceive as problem)\n\n\n\n79.5%\n\n\n\nFigure 1. Knowledge and perception of acne vulgaris on \naggravating factors of acne vulgaris\n\n\n\nTable 2. Percentage of psychosocial severity based on CADI \nscore\n\n\n\nTable 3. Percentage of student with score \u2265 1 for each \ncomponent in CADI\n\n\n\nIn terms of knowledge and perception of acne \nvulgaris, there are misconceptions and beliefs \namong our adolescents with regards to the causes of \nacne. The established factors influencing acne were \nsignificant positive family history, high glycaemic \nload diet, dairy products, stress and hormones5-7. In \nour survey, students listed stress, hygiene, hormones, \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n23\n\n\n\nin seeking medical treatment. In Asian countries \ntreatment is greatly influenced by the wide \navailability of over-the-counter pharmaceutical \nproducts and facial treatments. There was only \n10.7% of our students who sought medical treatment \nfor their acne vulgaris. Up to 75% purchased over-\nthe-counter acne care products from pharmacy. Peiqi \net al also showed that only 18.8% of their patients \nhad medical treatment while Nobulazu et al in Japan \nrevealed 27% of the patients sought treatment from \nhealthcare providers.8,9 \n\n\n\nConclusion\nIn conclusion, acne vulgaris is very common, \naffecting up to 65% of secondary school adolescents \nin Ipoh especially among male students. Acne is \nperceived as a problem and can cause significant \npsychosocial impact on their quality of life. There are \nmisperceptions and poor knowledge on acne leading \nto delay in seeking appropriate treatment from \nhealthcare providers. Thus, more effort is needed \nto improve the understanding of acne vulgaris and \nto create awareness among our secondary school \nadolescents through health education. PASH, an \nadolescent educational skin health project, can serve \nas a platform in providing accurate information and \nstrengthening the relationship between adolescents \nand health care professionals. It is essential to work \nclosely with local education authority to incorporate \nskin health element into our education system.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare\n\n\n\nAcknowledgement\nWe would like to thank PASH (Project on \nadolescent skin health) committee members (Figure \n2), Persatuan Dermatologi Malaysia, all the staffs \nfrom Department of Dermatology, Hospital Raja \nPermaisuri Bainun Ipoh and dermatologists from \nIpoh, Dr Agnes Heng, Dato\u2019 Dr Sushil Kumar Ratti, \nDr Henry Foong, Dr Tang Jyh Jong and Dr Lee \nHock Leng for making this project a great success.\n\n\n\nReferences\n\n\n\n1. Hanisah A, Omar K, Shah SA. Prevalence of acne and its \nimpact on the quality of life in school-aged adolescents in \nMalaysia. J Prim Health Care 2009;1:20-5.\n\n\n\n2. Park SY, Kwon HH, Min S, Yoon JY, Suh DH. \nEpidemiology and risk factors of childhood acne in \nKorea: a cross-sectional communitybased study. Clin Exp \nDermatol 2015;40:844-50.\n\n\n\n3. Rigopoulos D, Gregoriou S, Ifandi A, Efstathiou G, \nGeorgala S, Chalkias J et al. Coping with acne: beliefs \n\n\n\nfried food and peanuts as the top 5 causes of acne.  \nA similar study in Singapore by Peiqi et al shared \nsimilar beliefs and conception, students listed stress \n(86.5%), poor hygiene (65%), hormones (59.7%), \nmenstruation (48.7%) and genes (43.6%) as \ncommon factors to cause acne.9 The impact of diet \non acne has been studied extensively and literature \nreviewed that milk consumption and high glycemic \nindex foods were associated with acne. Postulation \nthat stress induced or worsened acne could be \ndue to increase in secretion of adrenal androgens \nat the time of stress. This results in sebaceous \nhyperactivity.7,8 Poor hygiene was thought to be \nrelated to acne in 77.8% of our participants. It \nappears to be a common Asian misconception that \nacne is caused by insufficient cleansing of the face. \n\n\n\nSeverity of acne is highly related to psychosocial \nimpact. It has been shown that acne vulgaris \nmay lead to depression, embarrassment, lack of \nenjoyment and participation in social life activities. \n1,5,8,9 CADI is a simple questionnaire which is \nvalidated to assess quality of life among patients \nwith acne vulgaris.4 Our study showed that the mean \nCADI score was 3.5 \u00b1 2.5. with majority having \nmild CADI score (77.9%). Hanisah et al also found \nsimilar mean CADI score of 4 and CADI score \ncorrelated significantly with severity of facial acne.1 \n\n\n\nThere are 5 domains being assessed in CADI \nwhich include feeling of aggression, frustration, \ninterference with social life, avoidance of public \nchanging facilities and appearance of the skin.4 \nMajority of our students perceived acne as a problem \n(79.5%) while 76.4% of them were concerned, \ndepressed and felt miserable with acne vulgaris. \nThis was quite similar with Hanisah et al study \nwhich showed 90.9% perceived acne as a problem \nand 81.9% of them were concerned, depressed and \nfelt miserable with their appearance.1 Avoidance \nof public changing facilities was the domain being \nleast affected and was seen in 24.5% of our students. \nSimilarly, avoidance of public changing was only \nseen in 17.8% of students in Hanisah et al study.1 \nThere was 69.4% of our students experienced \nfeeling aggressive, frustrated and embarrassed as \nresult of acne vulgaris while 42.2% of them had \nsocial life and social relationship interference. This \nwas again consistent with Hanisah et al findings in \nwhich 71.1% of them felt aggressive, frustrated and \nembarrassed, while 58.7% had social interference.1\n\n\n\nMost teenagers believe that acne would clear \nspontaneously in adulthood leading to neglection \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24\n\n\n\nand perceptions in a sample of secondary school Greek \npupils. J Eur Acad Dermatol Venereol 2007;21:806-10.\n\n\n\n4. Motley RJ, Finlay AY. Practical use of a disability index \nin the routine management of acne. Clin Exp Dermatol \n1992;17:1\u20133\n\n\n\n5. Wen L, Jiang G, Zhang X, Lai R, Wen X. Relationship \nbetween acne and psychological burden evaluated by \nASLEC and HADS surveys in high school and college \nstudents from central China. Cell Biochem Biophys \n2015;71:1083-8.\n\n\n\n6. Tsai MC, Chen W, Cheng YW, Wang CY, Chen GY, Hsu \nTJ. Higher body mass index is a significant risk factor \nfor acne formationin schoolchildren. Eur J Dermatol. \n2006;16:251-3.\n\n\n\n7. Ismail NH, Manaf ZA, Azizan NZ. High glycemic load \ndiet, milk and ice cream consumption are related to acne \nvulgaris in Malaysian young adults: a case control study. \nBMC Dermatol 2012;12:13.\n\n\n\n8. Yosipovitch G, Tang M, Dawn AG, Chen M, Goh CL, \nHuak Y et al. Study of psychological stress, sebum \nproduction and acne vulgaris in adolescents. Acta Derm \nVenereol 2007;87:135-9.\n\n\n\n9. Su P, Chen Wee Aw D, Lee SH, Han Sim Toh MP. Beliefs, \nperceptions and psychosocial impact of acne amongst \nSingaporean students in tertiary institutions. J Dtsch \nDermatol Ges 2015;13:227-33.\n\n\n\n10. Hayashi N, Miyachi Y, Kawashima M. Prevalence of \nscars and \u201cmini-scars\u201d, and their impact on quality of life \nin Japanese patients with acne. J Dermatol 2015;42:690-\n6.\n\n\n\nConvent on 7th November 2017\n\n\n\nFigure 2. PASH team (headed by Dr Agnes Heng) with teachers \nand students from Sekolah Menengah Kebangsaan Ave Maria\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n25\n\n\n\nORIGINAL ARTICLE\n\n\n\nNo Evidence for Increased Risk of Breast Cancer in Patients with \nAxillary osmidrosis: The First Population-based Cohort Study in \nTaiwan         \nWen-Tsao Ho1, Yu-Yin Chang2, Lukas Jyuhn-Hsiarn Lee2-4\n\n\n\n1Ho Wen Tsao Skin Clinic, Linkou, New Taipei City, Taiwan\n2National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan\n3Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, \nTaiwan\n4PhD Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan\n\n\n\nAbstract\nIntroduction: \nGenetic polymorphism with the phenotype of wet earwax and axillary osmidrosis (AO) was associated \nwith an increased risk of breast cancer in Japanese women, but not in Caucasians or Koreans. We \naimed to investigate the risk of breast cancer in AO patients compared to those with contact dermatitis.\n\n\n\nMethods: \nWe conducted a retrospective population-based cohort study based on claims data from the Taiwan \nNational Health Insurance (NHI) linked with the Taiwan Cancer Registry through 2011. The AO cohort \nwas composed of female patients aged \u226530 years who were diagnosed using ICD-9-CM code 705.89 \nfrom the outpatient claims from 1998 to 2011, excluding prior cancer or catastrophic illness. The \ncomparison cohort was constructed with female patients with contact dermatitis using a 1:4 frequency \nmatched with age and year of diagnosis. The cohorts were followed-up until cancer diagnosis, death, \nwithdrawal, or the end of 2011. We used multivariate Cox proportional hazards models to estimate the \nhazard ratios (HRs) adjusted for age and diabetes mellitus. \n\n\n\nResults: \n3267 AO patients and 13068 comparison subjects were included. Twenty-six cases of breast cancer \nwith a mean age at diagnosis of 47.8\u00b110.6 years were in the AO cohort, and 137 cases were in the \ncomparison cohort. The adjusted HR of AO for breast cancer was 1.087 (95% confidence interval = \n0.713-1.659). \n\n\n\nConclusion: \nNo significant association between AO and breast cancer was found in this cohort study with 13 years \nof follow up. Further epidemiological studies to investigate the possible association in different ethnic \ngroups are warranted.\n\n\n\nKey words: Axillary osmidrosis, Breast cancer, National Health Insurance\n\n\n\nCorresponding Author\nDr Lukas Jyuhn-Hsiarn Lee\n35, Keyan Road, \nZhunan Town, Miaoli County, \n35053, Taiwan \nE-mail: lukaslee@gmail.com\n\n\n\nIntroduction\nBreast cancer is the leading cancer in women, \nthe most common cause of female cancer deaths \nworldwide,1 and among the most prevalent cancers \nin Taiwan.2 The overall global burden of breast \ncancer is already large and still increasing3. The \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26\n\n\n\npotential genetic susceptibility to breast cancer \nmay be associated with the phenotypes of apocrine \nglands. Petrakis (1971) first reported an association \nbetween international breast cancer mortality and \nthe frequency of the allele for wet-type earwax \n(cerumen).4 The phenotype of more breast fluid \nsecretors was associated with the wet cerumen \nphenotype.5 A similar relationship was reported \nbetween cerumen type and the amount of axillary \napocrine sweat. Women with the dominant wet-type \ncerumen were reported to have greater quantities \nof axillary apocrine secretion than those with the \nhomozygous recessive dry-type cerumen.6 Cerumen \ntype may play a role in the axillary odour and is \npossibly associated with breast cancer risk, although \nsuch an association remains controversial.7 Such \nfindings supported the hypothesis that the genetic \nvariation in the apocrine system may influence the \nsusceptibility to breast cancer.\n\n\n\nYoshiura et al. (2006) identified a single-nucleotide \npolymorphism (SNP), 538G>A (rs17822931), in \nthe ABCC11 gene as the determinant of human \ncerumen type. The A/A genotype corresponds to dry \ncerumen, and the G/G and G/A genotypes correspond \nto the wet cerumen8. Wide ethnic differences exist in \nthe frequencies of those alleles. The wet cerumen \nis very common in populations with European and \nAfrican ancestry (~95% and ~100%, respectively). \nIn contrast, the wet type is seen less frequently in \nEastern Asian populations, with the prevalence of \n~15% in Japan, ~5% in Korea and ~10% among \nthe Han Chinese.9 Nakano et al. (2009) reported \nexamining the SNP rs17822931 of the ABCC11 gene \nin Japanese individuals as a useful diagnostic marker \nfor axillary osmidrosis (AO).9 Approximately 99% \n(78/79) of AO patients had either the G/G or G/A \ngenotype, while these genotypes were observed \nin 35% (57/161) of the subjects from the general \npopulation. Toyoda et al. (2009) elucidated the \nmolecular mechanism that determines the cerumen \ntype and the possible connection between AO, \nwet cerumen and the risk of breast cancer.10 The \nSNP 538G>A variant of human ABCC11 lacks \nN-linked glycosylation and is recognised as a \nmisfolded protein in the endoplasmic reticulum that \nreadily undergoes ubiquitination and proteasomal \ndegradation, which determines the dry phenotype of \ncerumen. On the other hand, the wild-type (Gly180) \nis associated with the wet type of cerumen, AO, \ncolostrum secretion from the mammary gland,11 \nand a potentially increased susceptibility to breast \ncancer. Because ceruminous, mammary and certain \naxillary sweat glands histologically belong to the \n\n\n\napocrine type of glands,12 an association between \nwet cerumen type, AO, and breast cancer risk seems \ntheoretically plausible.\n\n\n\nOta et al. (2010) reported a positive association \nbetween ABCC11 genotyping and the risk of breast \ncancer in Japan.13 It was a relatively small-scale \ncase-control study involving 270 cases of breast \ncancer and 273 control volunteers. The odds ratio \nfor the genotypes G/G and G/A developing breast \ncancer was estimated to be 1.63 (p-value=0.026). \nThe G allele appears to be positively related to breast \ncancer frequency in Japanese women. However, \nno statistically significant difference was found \nbetween the wet earwax genotypes (G/G and G/A) \nand the dry earwax genotype (A/A) with respect \nto the clinicopathological features (ER, PR, Her2, \ntriple negatives and clinical stages) investigated in \nthe study. Yamada et al. showed that the expression \nof ABCC11 in females with breast cancer was \nassociated with aggressive phenotypes and poor \ndisease-free survival.14 These outcomes drew a great \ndeal of attention from investigators worldwide. \nHowever, there are some conflicting results in \ndifferent ethnic groups. Beesley et al. (2011) found \nno evidence for an association between ABCC11 \nand  breast cancer risk based on an analysis of the \nfrequency of the functional SNP in 1342 cases and \n2256 controls from two breast cancer studies in \nCaucasian women.15 Lang et al. (2011) conducted a \ncase\u2013control study comprising 1021 cases and 1015 \nage-matched controls in Germany that showed no \nevidence for an association between this SNP and \nthe risk of breast cancer.16 Na et al. (2016) obtained \ngenomic DNA samples from Koreans, with 170 \nbreast cancer cases and 100 controls, and the result \nshowed no association between the SNP rs17822931 \nand the risk of breast cancer.17 In summary, the \nliterature shows a potential link between breast \ncancer susceptibility and ABCC11 genotypes, which \nhas so far only been found in Japanese women, but \nnot in Caucasian or Korean women. Currently, it is \nstill uncertain whether the G allele of ABCC11 gene \ninfluences breast cancer risk.\n\n\n\nAO is  known as  a chronic skin condition  \ncharacterised by strong body odour and profuse \nsweating from the armpits that results from an \nexcessive secretion of the body\u2019s metabolites from \nwell-developed apocrine glands in the axillae.18 It is \nrecognised as a disease entity covered by the National \nHealth Insurance (NHI) system in Taiwan. AO is \nthe visible genetic trait of the functional ABCC11 \nprotein,18,19 and the phenotype is genetically linked \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n27\n\n\n\nwith the SNP rs17822931,20,21 and the genotypes \nG/G and G/A result in AO in the Chinese Han \npopulation.22-24 To the best of our knowledge, there \nhave been no longitudinal cohort studies to test the \nhypothesis that there is an association between AO \nand breast cancer. In the present study, we aimed to \ninvestigate the risk of breast cancer associated with \nAO through a retrospective nationwide population-\nbased cohort study using the Taiwan National Health \nInsurance (NHI) databases that are linked with the \nTaiwan Cancer Registry.\n\n\n\nMaterials and Methods\n\n\n\nData Source\nWe conducted a retrospective population-based \ncohort study based on data obtained from the \nNational Health Insurance (NHI) databases, which \nis a nationwide, electronic database containing \nthe longitudinal medical records of beneficiaries \nenrolled in the NHI programme in Taiwan. This NHI \nprogramme, a mandatory single-payer social health \ninsurance launched on March 1, 1995, provides \nuniversal health care coverage to more than 99% \nof the population in Taiwan (approximately 23 \nmillion people).17 The NHI includes the Registry of \nCatastrophic Illness Patients to protect vulnerable \nbeneficiaries by exempting these patients from co-\npayments for the corresponding medical services. \nThe Taiwan Government created a list of the \ncatastrophic illnesses, including all cancer, and \nend-stage renal disease, among others. To protect \nprivacy, the patients\u2019 personal information has \nbeen encrypted, and the NHI databases provide \nresearchers with anonymous identification numbers \nassociated with relevant claims information, \nincluding sex, date of birth, medical services \nreceived, and prescriptions. Patients\u2019 privacy was \nwell protected under the regulations of the Health \nand Welfare Data Science Center of the Ministry \nof Health and Welfare.25 The study was approved \nby the Institutional Review Board of the National \nHealth Research Institutes (EC1040418-E).\n\n\n\nStudy Population\nWe included female patients 30 years and older who \nwere diagnosed with axillary osmidrosis (AO) using \nthe International Classification of Diseases, Ninth \nRevision, Clinical Modification (ICD-9-CM) code \n705.89 and who had been followed up 3 times or \nmore in outpatient departments between 1 January \n1998 and 31 December 2011 as the AO cohort. \nPatients with a history of cancer or catastrophic \nillnesses diagnosed before the index date of their \n\n\n\nAO diagnosis or any cancer (recorded either in \nthe Registry of Catastrophic Illness Patients or the \nTaiwan Cancer Registry) within one month of the \nindex date of their AO diagnosis were excluded. \nThe comparison subjects were selected from the \nfemale patients diagnosed with contact dermatitis \n(ICD-9-CM code 692) who were followed up at \nleast 3 times in outpatient departments by board-\ncertified dermatologists and who did not have a \nhistory of AO. The reason we selected the patients \nwith contact dermatitis as the comparison group was \nthat the literature has revealed no evidence of any \nsignificant association between allergic status or the \ndiagnoses of eczema or atopic dermatitis and the risk \nof breast cancer.26-28 For each patient with AO, four \ncorresponding patients with contact dermatitis and \nwithout AO were selected (1:4 ratio) by randomised \nfrequency sampling matched by age and year \nof diagnosis. Using the same exclusion criteria, \npatients with a history of cancer or catastrophic \nillnesses that were diagnosed before the index date \nof their contact dermatitis diagnosis or any cancer \nwithin one month of the index date of their contact \ndermatitis diagnosis were excluded. In addition, \nbecause diabetes mellitus may significantly increase \nthe risk of breast cancer,29,30 baseline information \nconcerning the comorbidity of diabetes mellitus \n(ICD-9-CM 250) from hospital admissions among \nthe patients in the AO and the comparison cohorts \nwere also collected from the inpatient database of \nthe NHI. The study cohorts were followed-up until \ncancer diagnosis, death, withdrawal from the NHI \nprogramme, loss to follow-up, or the end of this \nstudy on December 31, 2011 (Figure 1). \n\n\n\nOutcome variables\nThe major study outcome of interest was a diagnosis \nof cancer after the index date of AO or contact \ndermatitis diagnosis through December 31, 2011. \nCancer events were identified from the Taiwan \nCancer Registry and the Registry of Catastrophic \nIllness Patients for any of the following ICD-9 \nCM codes 140-208 and divided into the following \ngroups: lip, oral cavity, and pharynx (ICD-9-CM \n140\u2013149), including nasopharynx (ICD-9-CM \n147); digestive organs and peritoneum (ICD-9-CM \n150\u2013159), including stomach (ICD-9-CM 151), \ncolon and rectum (ICD-9-CM 153, 154), and liver \nand biliary tract (ICD-9-CM 155, 156); respiratory \norgans (ICD-9-CM 160-165), including lung (ICD-\n9-CM 162); bone and soft tissue (ICD-9-CM 170-\n171); breast (ICD-9-CM 174); genitourinary system \n(ICD-9-CM 179\u2013189), including cervix (ICD-9-\nCM 180), ovary (ICD-9-CM 183), and bladder \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28\n\n\n\n(ICD-9-CM 188); thyroid (ICD-9-CM 193); and \nhaematological cancer (ICD-9-CM 200\u2013208).\n\n\n\nStatistical Analysis\nDescriptive data were presented as the mean \u00b1 \nstandard deviation (SD) for continuous variables \nand as frequency and percentage for categorical \nvariables. Student\u2019s t-test was applied to continuous \nvariables and the Chi-square test was used for \ncomparisons of percentages of two groups.\n\n\n\nCancer cases in both study cohorts were recorded \nas the number of patients with cancer diagnosed \nafter the diagnosis of AO or contact dermatitis. The \nrisk of cancer incidence for patients with AO was \ncompared with that of contact dermatitis without \nAO to estimate the crude hazard ratios (HRs) and \n95% confidence intervals (CIs) by use of univariate \nCox proportional hazards models; adjusted HRs and \n95% CIs were obtained by using Cox proportional \nhazards models adjusted for age and the comorbidity \nof diabetes mellitus. All statistical analyses were \ndone with SAS software version 9.4 (SAS Institute, \nCary, NC). A 2-sided P < 0.05 was considered \nstatistically significant.\n\n\n\nResults\nIn total, 3267 female patients with newly diagnosed \n\n\n\nAO with a mean age of 41.9\u00b110.2 years were \nidentified as the AO cohort, and 13068 female \npatients with contact dermatitis were included in the \ncomparison cohort. Table 1 shows the demographic \ncharacteristics of the study population. The \nproportions with the comorbidity of diabetes mellitus \nat the baseline were 1.07% and 1.35% in the AO \ncohort and the comparison cohort, respectively. The \nmean follow-up period from the index date of AO \nor contact dermatitis diagnosis to the date of cancer \ndiagnosis, loss to follow-up, or the end of study was \n7.5 years. During the follow-up period from 1998 to \n2011, a total of 101 cases of cancer were identified in \nthe AO cohort, and 452 cancer cases were identified \nin the comparison cohort. The mean age at cancer \ndiagnosis was 50.9\u00b111.5 and 50.8\u00b111.4 for the AO \ncohort and the comparison cohort, respectively. \nThe average latency period from the index date of \ndisease (AO or contact dermatitis) diagnosis to the \ndate of cancer diagnosis was approximately 5 years. \nIn total, 26 cases of breast cancer, with a mean age at \ndiagnosis of 47.8\u00b110.6 years, were identified in the \nAO cohort and 137 cases in the comparison cohort. \nThere were no differences in the age at diagnosis \nof disease (AO or contact dermatitis) or cancer, nor \nwere there differences in any of the demographic \ncharacteristics between the two study cohorts.\n\n\n\nAxillary osmidrosis (AO)\n(ICD-9-CM 705.89)\n\n\n\nContact dermatitis (CD)\n(ICD-9-CM 692.X)\n\n\n\nP value\n\n\n\nN 3267 13068\nAge (mean\u00b1SD), year\nmedian (range)\n\n\n\n41.9\u00b110.2\n40 (30-85)\n\n\n\n41.9\u00b110.2\n40 (30-85)\n\n\n\n1.0000\n\n\n\nBaseline comorbidity of diabetes mellitus (%) 1.07 1.35 0.2102\nFollow-up period, year (mean\u00b1SD) 7.5\u00b13.6 7.5\u00b13.7 0.8476\nCancer diagnosis during follow-up\nOverall cancer \n(ICD-9-CM 140~208) \n\n\n\n101 452\n\n\n\nDisease age, year\n(mean\u00b1SD)\n\n\n\n45.4\u00b111.7 45.5\u00b111 0.9239\n\n\n\nCancer age, year\n(mean\u00b1SD)\n\n\n\n50.9\u00b111.5 50.8\u00b111.4 0.8875\n\n\n\nLatency period, year (mean\u00b1SD) from index disease \nonset to cancer \n\n\n\n5.6\u00b13.3 5.3\u00b13.3 0.4562\n\n\n\nBreast cancer \n(ICD-9-CM 174), N\n\n\n\n26 137\n\n\n\nDisease age, year\n(mean\u00b1SD)\n\n\n\n42.6\u00b110.0 44\u00b19.3 0.5017\n\n\n\nCancer age, year\n(mean\u00b1SD)\n\n\n\n47.8\u00b110.6 49.2\u00b19.4 0.5127\n\n\n\nLatency period, year (mean\u00b1SD) from index disease \nonset to cancer\n\n\n\n5.3\u00b13.1 5.3\u00b13.3 0.9791\n\n\n\nTable 1. Demographic Characteristics of the Patients in the Axillary Osmidrosis (AO) Cohort and the Comparison Cohort with Contact \nDermatitis\n\n\n\nSD: standard deviation\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n29\n\n\n\nCancer site ICD-9-CM codes Model 1 Model 2 Model 3 \nCrude HR (95%CI) Adjusted HR (95%CI) Adjusted HR (95%CI)\n\n\n\nAll cancers 140-208 0.971(0.782-1.205) 0.984(0.792-1.222) 0.996(0.802-1.237)\nLip, Oral cavity, Pharynx 140-149 0.511(0.152-1.718) 0.203(0.043-0.952) 0.203(0.043-0.952)\n\n\n\n  Nasopharynx 147 0.757(0.166-3.455) 0.422(0.053-3.365) 0.422(0.053-3.365)\nDigestive organs, peritoneum 150-159 0.911(0.54-1.536) 1.097(0.64-1.882) 1.111(0.647-1.907)\n\n\n\n  Stomach 151 0.697(0.146-3.34) 0.899(0.171-4.718) 0.899(0.171-4.718)\n  Colon and rectum 153, 154 0.812(0.341-1.933) 0.820(0.344-1.954) 0.820(0.344-1.954)\n\n\n\n  Liver and biliary tract 155, 156 1.303(0.448-3.79) 2.723(0.862-8.599) 2.864(0.891-9.203)\nRespiratory organs 160-165 0.951(0.51-1.77) 0.945(0.507-1.76) 0.989(0.527-1.856)\n\n\n\n  Lung 162 0.993(0.523-1.883) 1.009(0.531-1.917) 1.039(0.543-1.988)\nBone, Soft tissue 170, 171 2.449(0.151-39.723)\n\n\n\nBreast 174 1.074(0.705-1.638) 1.078(0.707-1.644) 1.087(0.713-1.659)\nGenitourinary system 179-189 0.736(0.478-1.133) 0.738(0.479-1.137) 0.743(0.482-1.145)\n\n\n\n  Cervix 180 0.866(0.498-1.507) 0.849(0.481-1.498) 0.848(0.48-1.5)\n  Ovary 183 0.452(0.145-1.408) 0.436(0.127-1.501) 0.436(0.127-1.501)\n\n\n\n  Bladder 188 1.618(0.143-18.312) 1.283(0.092-17.995) 1.283(0.092-17.995)\nThyroid 193 3.148(1.033-9.592) 2.415(0.705-8.275) 2.415(0.705-8.275)\n\n\n\nTable 2 shows that there was no significant difference \nin overall cancer risk between the AO cohort and \nthe comparison cohort (crude hazard ratio (HR)= \n0.971 [95% CI 0.782-1.205]). The breast cancer risk \nwas not significantly increased in the AO cohort in \ncomparison with the contact dermatitis cohort in \nthe univariate analysis (crude HR= 1.074 [95% \nCI 0.705-1.638]; model 1 in Table 2). The breast \ncancer risk was similar even after adjustment for age \n\n\n\nModel 1: univariate analysis\nModel 2: multivariate analysis, adjusting for age at diagnosis \nModel 3: multivariate analysis, adjusting for age at diagnosis and diabetes mellitus\n\n\n\nFigure 1.  Flowchart Presenting Study Subjects Selection\n\n\n\n(model 2), as well as after adjustment for age and \ncomorbidity of diabetes mellitus (HR=1.087 [95% \nCI 0.713-1.659], model 3). An approximately three-\nfold elevated risk of thyroid cancer was observed \nin women with AO in the univariate analysis, but it \nwas not significant in the multivariate analyses after \nadjustment for age, or after adjustment for age and \ncomorbidity of diabetes mellitus.\n\n\n\nTable 2. Hazard Ratios (HRs) for Various Types of Female Cancer in the Axillary Osmidrosis (AO) Cohort in Comparison with the \nContact Dermatitis Cohort Using Cox Proportional Hazards Models\n\n\n\nA nationwide population-based cohort study from people\nenrolled in the National Health Insurance program\n\n\n\n(N=23.5 million)\n\n\n\nFemale patients diagnosed with axillary\nosmidrosis (ICD-9-CM 705.89) with \nat least 3 follow-up visits in outpatient\n\n\n\ndepartments during 1998 and 2011,\naged 30 years and older.\n\n\n\nFemale patients diagnosed with contact dermatitis \n(ICD-9-CM 692.X) with at least 3 follow-up visits in outpatient\n\n\n\ndepartments by board-certified dermatologists and\nwithout a history of axillary osmidrosis during 1998 and 2011,\n\n\n\naged 30 years and older.\n\n\n\nExcluding patients with a\nhistory of cancer or\n\n\n\ncatastrophic illnesses\ndiagnosed before index date\n\n\n\nor any cancer within one\nmonth of index date.\n\n\n\nExcluding patients with a\nhistory of cancer or\n\n\n\ncatastrophic illnesses\ndiagnosed before index date\n\n\n\nor any cancer within one\nmonth of index date.\n\n\n\nContact dermatitis cohort,\nfemale (n=13068)\n\n\n\nAxillary osmidrosis (AO) cohort,\nfemale (n=3267)\n\n\n\nFollow-up until cancer diagnosis (linked with the Taiwan Cancer Registry and the\nRegistry of Catastrophic Illness Patients), dealth, withdrawal from the National\n\n\n\nHealth Insurance program, or the end of 2011\n\n\n\n1:4 Frequency matched by\nage and year of diagnosis\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30\n\n\n\nDiscussion\nTo the best of our knowledge, this study represents \nthe first attempt to use a population-based cohort \nstudy to investigate the cancer risk of AO, adjusting \nfor potential confounders, including age and \ncomorbidity of diabetes mellitus. Our study showed \nthere was no significant association between AO \nand the risk of breast cancer, which corroborated \nnegative findings in the studies for Caucasian15,16 \nand Korean17 populations. A positive association \nbetween AO-related genotyping (SNP rs17822931) \nand the risk of breast cancer has only been reported \nin the Japanese population.13 All these were case-\ncontrol studies based on the analysis of SNP \ngenotyping profiles in blood samples collected from \npopulations of different ethnicities. The positive \nassociation in the Japanese population, which was \nbased on a relatively small number of patients, \nneeds further study, with a larger sample size or a \nprospective cohort study design for refutation or \ncorroboration. Because AO is genetically strongly \nassociated with this SNP, we tested the hypothesis \nby applying a retrospective nationwide population-\nbased cohort study using NHI databases linked with \nthe national cancer registry to take advantage of a \nrelatively large sample size of AO patients, and the \noutcome of interest included various sites of cancer. \nOur study indicated that AO patients seemed to have \nno increased risk of overall cancer compared to \npatients with contact dermatitis. The risk for thyroid \ncancer in the AO cohort was elevated only in the \nunivariate analysis, but it was not significant after \nadjustment for age or age and diabetes mellitus. A \nrecent meta-analysis of cohort studies indicated that \npatients with diabetes mellitus have significantly \nincreased risk of thyroid cancer and that such a \npositive association was prominent in women.31 \nThe lack of significance of an increased risk of \nthyroid cancer after adjustment for age and diabetes \nmellitus may imply that AO is not recognised as \na risk factor for thyroid cancer, as documented in \na recent review;32 age and diabetes mellitus were \npotential confounders that caused a statistical \nsignificant increased risk of thyroid cancer until the \nmodel was adjusted. \n\n\n\nContact dermatitis diagnosed in the outpatient \nclinics with at least three instances of coding by \ndermatologists was selected as the comparison \ndisease in this study to enhance the accuracy of disease \ndiagnosis. The reason why we selected the diagnosis \nof contact dermatitis instead of atopic dermatitis \nis to avoid the interference of cancer risk from \nmajor medical treatments associated with the latter. \n\n\n\nIncreased risk of lymphoma following treatment \nwith topical calcineurin inhibitors and systemic \nsteroids in atopic dermatitis had been identified.33,34 \nSome patients with severe atopic dermatitis \neven receive systemic immunosuppressants such \ncyclosporine, which is considered carcinogenic, \nto control the disease.35-37 In contrast, patients \nwith contact dermatitis were believed to have less \nmedical interference than atopic dermatitis, with \nsome immunosuppressive treatments and narrow-\nband ultraviolet phototherapy.38 If some patients \nwith atopic dermatitis were misclassified and \nerroneously included in our study as the comparison \ncohort, it might underestimate the true breast cancer \nrisk associated with the AO cohort because no \nsignificant association between atopic dermatitis and \nbreast cancer was found in the literature.26,27 Hwang \net al. (2011) used the 1 million dataset of the Taiwan \nNational Health Insurance Research Database to \nreveal no significant difference of overall cancer \nrisk in atopic dermatitis, and highest cancer risk in \nthe 20\u201339-year age group.27 They found that only \nbrain cancer was found to have increased risk, but \nthe difference was not statistically significant when \nstratified by gender. The standardised incidence \nratio of breast cancer in female patients with atopic \ndermatitis was 1.20 (95% CI 0.87\u20131.62), which \nwas not significantly elevated in comparison with \nthe general population. If contact dermatitis is a \nrisk factor for breast cancer, this bias may have \nmildly increased the incidence rate of breast cancer \nin the comparison cohort, and then the risk of AO \nfor breast cancer may be relatively underestimated. \nTo avoid the possible bias of the under-estimation \nof the cancer risk, we included patients with AO \nor matched subjects with contact dermatitis aged \n\u226530 years in this cohort study who were followed \nfrom 1998 to 2011 (mean follow-up 7.5\u00b13.6 years, \nmaximum of 13 years) with the consideration of \nallowing a mean latency period of 5 years for cancer \noccurrence (Table 1). The mean age at breast cancer \ndiagnosis in the AO cohort was 47.8 years, and it \nmay mainly indicate the risk for premenopausal \nwomen. Further studies are needed to evaluate if the \nbreast cancer risk among postmenopausal women \nis associated with AO by prolonging the follow-up \nperiod using a prospective cohort design.39\n\n\n\nA particular strength of the present study was the \nuse of population-based databases, which enabled \nus to identify all cases of AO, contact dermatitis, \nand cancer during a relatively long study period of \n13 years (1998-2011). Moreover, the large sample \nsize afforded considerable statistical power for \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n31\n\n\n\ndetecting real differences between the 2 cohorts.\n \nAnother strength of this study is the simultaneous \nuse of the Taiwan Cancer Registry and the Registry \nof Catastrophic Illness Patients to comprehensively \ninclude the cases of cancer because histopathological \ndata are mandatory before being recorded in the \ndatabase of the Taiwan Cancer Registry, and co-\npayments of cancer patients in the Taiwan NHI \nprogramme are waived, which will increase medical \naccessibility for cancer patients.\n\n\n\nThis study had several limitations that should be \nconsidered in interpreting study findings. First, \nthe patients with AO or contact dermatitis were \nidentified using ICD-9-CM codes in the claims-\nbased NHI databases. The original purpose of using \nICD-9-CM codes was for reimbursement in the NHI \nprogramme, not for research. Therefore, the ICD-\n9-CM codes used in our study may not have the \nsame quality of operative definitions as those of a \nwell-designed prospective clinical study. However, \nall insurance claims in the NHI programme \nwere scrutinised by medical doctors in clinical \npractice and then peer-reviewed by board-specific \nspecialists according to the standard diagnosing \ncriteria, which could improve the quality control of \nthe disease diagnosis. Second, the NHI databases \ndid not provide variables regarding disease severity \nor laboratory data for the ascertainment of definite \ndisease diagnoses. Consequentially, it was not \npossible to correlate the severity of AO with the \nfuture risk of cancer in a dose-response manner. \nThird, residual confounding variables, including \nsmoking, alcohol use, dietary habits, occupations, \nsocioeconomic status, and family history of cancer, \nare associated with the risk of cancer but were not \navailable in our databases. The association between \nAO and these factors is also unknown. Further study \nis suggested to clarify this issue. Finally, the study \npopulation mainly consisted of Taiwanese Chinese; \ntherefore, the results may not be applicable to other \nethnic groups.\n\n\n\nLimitation \nOur limitation was short follow up period. In the \n13-year retrospective cohort study (1998-2011), \nthe mean age of breast cancer in the AO cohort was \n47.8 (SD 10.6) with a mean latency of 5.3 (SD 3.1).  \nTherefore, the follow-up period was too short to \ndetect any increase of breast cancer risk. Also in this \nretrospective study design of Taiwan NHI system, \nthe treatment modalities of AO were not reimbursed \nand therefore the variables of treatment of AO were \n\n\n\nnot available in the NHI reimbursement databases. \nThe diagnosis of contact dermatitis was based on \nclinical presentation. Because of the high cost of \npatch testing in Taiwan, seldom patients underwent \nthis examination. \n\n\n\nConclusion \nIn conclusion, we found that the risk of breast \ncancer was not higher among patients with AO than \nin the comparison cohort of patients with contact \ndermatitis over a 13-year follow-up period. Our \nstudy is among the first to provide evidence in a \nnationwide population-based cohort study that AO, \nwhich is genetically linked with the wet cerumen \ntype caused by the SNP rs17822931, may not be \nassociated with breast cancer. Further studies should \nbe conducted to determine whether our findings can \nbe generalised to other ethnic populations.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgements\nThis study was supported in part by grants from \nthe National Health Research Institutes, Taiwan \n(intramural projects EM-106-PP-04, EM-107-\nPP-04). This study was based on data provided \nby the Health and Welfare Data Science Center \n(HWDC) of the Ministry of Health and Welfare, \nExecutive Yuan, Taiwan. The interpretation and \nconclusions contained herein do not represent those \nof the Ministry of Health and Welfare or National \nHealth Research Institutes.\n\n\n\nReferences\n\n\n\n1. Stewart BW, Wild C. International Agency for Research \non Cancer, World Health Organization. World cancer \nreport 2014.\n\n\n\n2. Liu FC, Lin HT, Kuo CF, See LC, Chiou MJ, Yu HP. \nEpidemiology and survival outcome of breast cancer in a \nnationwide study. Oncotarget 2017;8:16939-50.\n\n\n\n3. Global Burden of Disease Cancer Collaboration, \nFitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta \nZA et al. Global, Regional, and National Cancer Incidence, \nMortality, Years of Life Lost, Years Lived With Disability, \nand Disability-Adjusted Life-years for 32 Cancer Groups, \n1990 to 2015: A Systematic Analysis for the Global Burden \nof Disease Study. JAMA Oncol 2017;3:524-48.\n\n\n\n4. Petrakis NL. Cerumen genetics and human breast cancer. \nScience 1971;173:347-9.\n\n\n\n5. Petrakis NL, Ernster VL, Sacks ST, King EB, Schweitzer \nRJ, Hunt TK et al. Epidemiology of breast fluid secretion: \nassociation with breast cancer risk factors and cerumen \ntype. J Natl Cancer Inst 1981;67:277-84.\n\n\n\n6. Yamashita S. On the offensive odor of the armpit and the \nsoft earwax among Formosans in Canton. Jpn J Anthropol \n1939;54:444-6.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32\n\n\n\n7. Ing R, Petrakis L, Ho HC. Evidence against association \nbetween wet cerumen and breast cancer. Lancet 1973;1:41.\n\n\n\n8. Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa \nT, Kaname T et al.  A SNP in the ABCC11 gene is \nthe determinant of human earwax type. Nat Genet \n2006;38:324-30.\n\n\n\n9. Nakano M, Miwa N, Hirano A, Yoshiura K, Niikawa N. \nA strong association of axillary osmidrosis with the wet \nearwax type determined by genotyping of the ABCC11 \ngene. BMC Genet 2009;10:42.\n\n\n\n10. Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura \nK, Nakagawa H et al. Earwax, osmidrosis, and breast \ncancer: why does one SNP (538G>A) in the human ABC \ntransporter ABCC11 gene determine earwax type? FASEB \nJ 2009;23:2001-13.\n\n\n\n11. Miura K, Yoshiura K, Miura S, Shimada T, Yamasaki \nK, Yoshida A et al. A strong association between human \nearwax-type and apocrine colostrum secretion from the \nmammary gland. Hum Genet 2007;121:631-3.\n\n\n\n12. Gesase AP, Satoh Y. Apocrine secretory mechanism: recent \nfindings and unresolved problems. Histol Histopathol \n2003;18:597-608.\n\n\n\n13. Ota I, Sakurai A, Toyoda Y, Morita S, Sasaki T, Chishima \nT et al. Association between breast cancer risk and the \nwild-type allele of human ABC transporter ABCC11. \nAnticancer Res 2010;30:5189-94.\n\n\n\n14. Yamada A, Ishikawa T, Ota I, Kimura M, Shimizu D, \nTanabe M et al. High expression of ATP-binding cassette \ntransporter ABCC11 in breast tumors is associated with \naggressive subtypes and low disease-free survival. Breast \nCancer Res Treat 2013;137:773-82.\n\n\n\n15. Beesley J, Johnatty SE, Chen X, Spurdle AB, Peterlongo P, \nBarile M et al. No evidence for an association between the \nearwax-associated polymorphism in ABCC11 and breast \ncancer risk in Caucasian women. Breast Cancer Res Treat \n2011;126:235-9.\n\n\n\n16. Lang T, Justenhoven C, Winter S, Baisch C, Hamann \nU, Harth V et al. The earwax-associated SNP c.538G>A \n(G180R) in ABCC11 is not associated with breast cancer \nrisk in Europeans. Breast Cancer Res Treat 2011;129:993-\n9.\n\n\n\n17. Na AY, Heo JC, Sung JY, Lee JH, Kim YN, Kim DK. No \nAssociation of the rs17822931 Polymorphism in ABCC11 \nwith Breast Cancer Risk in Koreans. Asian Pac J Cancer \nPrev 2016;17:2625-8.\n\n\n\n18. Toyoda Y, Gomi T, Nakagawa H, Nagakura M, Ishikawa T. \nDiagnosis of Human Axillary Osmidrosis by Genotyping \nof the Human ABCC11 Gene: Clinical Practice and Basic \nScientific Evidence. Biomed Res Int 2016;2016:7670483.\n\n\n\n19. Martin A, Saathoff M, Kuhn F, Max H, Terstegen L, \nNatsch A. A functional ABCC11 allele is essential in the \nbiochemical formation of human axillary odor. J Invest \nDermatol 2010;130:529-40.\n\n\n\n20. Inoue Y, Mori T, Toyoda Y, Sakurai A, Ishikawa T, Mitani \nY et al. Correlation of axillary osmidrosis to a SNP in the \nABCC11 gene determined by the Smart Amplification \nProcess (SmartAmp) method. J Plast Reconstr Aesthet \nSurg 2010;63:1369-74.\n\n\n\n21. Toyoda Y, Takada T, Gomi T, Nakagawa H, Ishikawa T, \nSuzuki H. Clinical and Molecular Evidence of ABCC11 \nProtein Expression in Axillary Apocrine Glands of Patients \nwith Axillary Osmidrosis. Int J Mol Sci 2017;18.pii: E417. \ndoi: 10.3390/ijms18020417.\n\n\n\n22. Sun Y, Long J, Wang Y. [Correlation between ABCC11 \ngene single nucleotide polymorphism and the incidence \nof axillary osmidrosis in Chinese Han population]. Zhong \nNan Da Xue Xue Bao Yi Xue Ban 2013;38:1141-5.\n\n\n\n23. Zhu Z, Zhang H, Luo G, Xu N, Pan Z. Association between \nthe ABCC11 gene polymorphism and the expression \nof apolipoprotein D by the apocrine glands in axillary \nosmidrosis. Mol Med Rep 2015;11:4463-7.\n\n\n\n24. Ren Y, Liu W, Chen J, Wang J, Wang K, Zhou J et al. A \nmissense variant of the ABCC11 gene is associated with \nAxillary Osmidrosis susceptibility and clinical phenotypes \nin the Chinese Han Population. Sci Rep 2017;7:46335.\n\n\n\n25. Tomasek L, Darby SC. Recent results from the study of \nWest Bohemian uranium miners exposed to radon and its \nprogeny. Environ Health Perspect 1995;103 Suppl 2:55-7.\n\n\n\n26. Wedgeworth E, Powell AM, Flohr C. Eczema and cancer \nrisk: a critical appraisal and review of the literature. Br J \nDermatol 2011;165:457-62.\n\n\n\n27. Hwang CY, Chen YJ, Lin MW, Chen TJ, Chu SY, Chen \nCC et al. Cancer risk in patients with allergic rhinitis, \nasthma and atopic dermatitis: a nationwide cohort study in \nTaiwan. Int J Cancer 2012;130:1160-7.\n\n\n\n28. Turner MC, Chen Y, Krewski D, Ghadirian P. An overview \nof the association between allergy and cancer. Int J Cancer \n2006;118:3124-32.\n\n\n\n29. Chen HF, Liu MD, Chen P, Chen LH, Chang YH, Wen PC \net al. Risks of Breast and Endometrial Cancer in Women \nwith Diabetes: A Population-Based Cohort Study. PLoS \nOne 2013;8:e67420.\n\n\n\n30. Zhou Y, Zhang X, Gu C, Xia J. Diabetes mellitus is \nassociated with breast cancer: systematic review, meta-\nanalysis, and in silico reproduction. Panminerva Med \n2015;57:101-8.\n\n\n\n31. Li H, Qian J. Association of diabetes mellitus with thyroid \ncancer risk: A meta-analysis of cohort studies. Medicine \n(Baltimore) 2017;96:e8230.\n\n\n\n32. Liu Y, Su L, Xiao H. Review of Factors Related \nto the Thyroid Cancer Epidemic. Int J Endocrinol \n2017;2017:5308635.\n\n\n\n33. Arellano FM, Wentworth CE, Arana A, Fernandez C, Paul \nCF. Risk of lymphoma following exposure to calcineurin \ninhibitors and topical steroids in patients with atopic \ndermatitis. J Invest Dermatol 2007;127:808-16.\n\n\n\n34. Tennis P, Gelfand JM, Rothman KJ. Evaluation of \ncancer risk related to atopic dermatitis and use of topical \ncalcineurin inhibitors. Br J Dermatol 2011;165:465-73.\n\n\n\n35. Hern\u00e1ndez-Mart\u00edn A, Noguera-Morel L, Bernardino-\nCuesta B, Torrelo A, P\u00e9rez-Martin MA, Aparicio-L\u00f3pez \nC et al. Cyclosporine A for severe atopic dermatitis in \nchildren. efficacy and safety in a retrospective study of 63 \npatients. J Eur Acad Dermatol Venereol 2017;31:837-42.\n\n\n\n36. Totri CR, Eichenfield LF, Logan K, Proudfoot L, Schmitt \nJ, Lara-Corrales I et al. Prescribing practices for systemic \nagents in the treatment of severe pediatric atopic dermatitis \nin the US and Canada: The PeDRA TREAT survey. J Am \nAcad Dermatol 2017;76:281-5.\n\n\n\n37. Arellano FM, Arana A, Wentworth CE, Fernandez-\nVidaurre C, Schlienger RG, Conde E. Lymphoma among \npatients with atopic dermatitis and/or treated with topical \nimmunosuppressants in the United Kingdom. J Allergy \nClin Immunol 2009;123:1111-6.\n\n\n\n38. Simpson EL, Bruin-Weller M, Flohr C, Ardern-Jones MR, \nBarbarot S, Deleuran M et al. When does atopic dermatitis \nwarrant systemic therapy? Recommendations from an \nexpert panel of the International Eczema Council. J Am \nAcad Dermatol 2017;77:623-33.\n\n\n\n39. Fraser A, Macdonald-Wallis C, Tilling K, Boyd A, \nGolding J, Davey Smith G et al. Cohort Profile: the Avon \nLongitudinal Study of Parents and Children: ALSPAC \nmothers cohort. Int J Epidemiol 2013;42:97-110.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n33\n\n\n\nCASE REPORT\n\n\n\nThe Clinical Spectrum of Cutaneous Phaeohyphomycosis in Three \nImmunocompetent Patients and a Review of Literature         \nRajalingam Ramalingam, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nPhaeohyphomycosis is a heterogenous group of mycotic infections caused by dematiaceous fungi with \na wide spectrum of presentation, oftentimes leading to misdiagnosis and delayed treatment. Herein, \nwe report three cases of cutaneous phaeohyphomycosis in immunocompetent individuals with varying \nfeatures, with the hope of increasing awareness among clinicians in order to avoid delayed diagnosis \nand to institute prompt treatment.\n\n\n\nKey words: Phaeohyphomycosis, Exophiala, Phialophora, Dematiaceous fungi, Cutaneous mycosis, Mycology, Malaysia\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology,\nHospital Tengku Ampuan Afzan,\nJalan Tanah Putih,\n25100 Kuantan, Pahang, Malaysia\nEmail: raj.blueheart@gmail.com \n\n\n\nIntroduction\nPhaeohyphomycosis refers to a heterogenous group \nof fungal infections that are caused by dematiaceous \nfungi in tissue.1 It has a wide variety of clinical \npresentation, including superficial, subcutaneous, \ncerebral and systemic phaeohyphomycosis.1,2 It \nis an opportunistic infection caused by various \nspecies of fungi, including Exophiala, Phialophora, \nAlternaria and Cladosporium, among others. Most \nlocalized cases are due to traumatic implantation \ninjury, while systemic infection commonly occurs \nin immunocompromised individuals. However, \nthere are increasing numbers of reports describing \ncutaneous as well as systemic phaeohyphomycosis \nin immunocompetent individuals. We present here \nthree cases of cutaneous phaeohyphomycosis in \nimmunocompetent individuals along with a review \nof literature.\n\n\n\nCase 1\nMB, a 66-year-old laborer, presented with non-\npruritic, slowly enlarging, scaly erythematous \nlesions over the dorsal surface of his left forearm \nfor the past one year. He did not notice any prior \ntraumatic injury and there were no constitutional \nsymptoms.\n\n\n\nExamination revealed three well-demarcated, \nscaly, erythematous plaques ranging from two to \nfive centimeters in diameter (Figure 1: a & b). No \nerosion, ulceration, purulent or granular discharge \nwas noted. There was no lymphadenopathy and \nexamination of other systems was unremarkable. \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34\n\n\n\nOur differential diagnoses included fixed cutaneous \nsporotrichosis, chromomycosis, tuberculosis \nverrucosa cutis and non-tuberculous mycobacterial \ninfection.\n\n\n\nFigure 1. (a & b) Clinical presentation of the patient showing \ndistinct, well-demarcated, scaly, erythematous plaques on the \ndorsal surface of the left forearm, and (c) after two months on \nsystemic antifungal treatment.\n                              \n\n\n\nresolved after four months. \n\n\n\nCase 2\nNA, a 24-year-old housewife, presented with slowly \nenlarging lesions over her lower lip and chin for the \npast two months. She too, did not notice any prior \ntraumatic injury and was otherwise well. \n\n\n\nExamination revealed two erythematous nodules \nwith a verrucous surface, one over the left lower \nlip and one over the right submandibular region \n(Figure 2: a-b). No ulceration, purulent or granular \ndischarge, or lymphadenopathy was noted, and \nexamination of other systems was unremarkable. \nOur differential diagnoses included fixed cutaneous \nsporotrichosis, tuberculosis verrucosa cutis and \nnon-tuberculous mycobacterial infection.\n\n\n\nFigure 2. (a & b) Clinical presentation of the patient showing \nnon-scaly erythematous nodules over the left lower lip and right \nsubmandibular region.\n\n\n\na\n\n\n\na\n\n\n\nb\n\n\n\nb\n\n\n\nc\n\n\n\nSkin scraping did not reveal any hyphae or spores \nunder direct microscopy. Blood investigations were \nnormal. Skin biopsy showed a heavily infiltrated \ndermis by lymphocytes and neutrophils, with \nseveral non-caseating epithelioid granulomas and \nmultinucleated Langhans-type giant cells. Ziehl \nNeelsen, periodic acid Schiff (PAS) and Grocott\u2019s \nmethenamine silver (GMS) stains did not reveal any \nmicroorganisms. Tissue culture, however, isolated \nExophiala species.\n\n\n\nA diagnosis of subcutaneous phaeohyphomycosis \ncaused by Exophiala species was made and he \nwas commenced on oral itraconazole. His lesions \n\n\n\nBlood investigations were normal. Skin biopsy \nshowed epidermal hyperplasia, moderate \nlymphoplasmacytic cellular infiltration of the \nupper and deep dermis, epithelioid cell granulomas \nwith non-caseating necrosis and Langhans-type \nmultinucleated giant cells (Figure 3: a & b). One \nmultinucleated giant cell showed the presence \nof fungal bodies (Figure 3c). ZN and PAS stains \ndid not reveal any microorganisms, but culture \nisolated Phialophora species, and a diagnosis \nof subcutaneous phaeohyphomycosis caused by \nPhialophora species was made. Unfortunately, she \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n35\n\n\n\nlost to follow-up before treatment could be initiated.\n\n\n\nFigure 3. (a & b) Histology of the skin biopsy revealed \nepidermal hyperplasia, moderate cellular infiltration of the \ndermis and epithelioid cell granulomas with non-caseating \nnecrosis; and (c) a multinucleated giant cell with a probable \nfungal body within (red arrow).\n\n\n\ntraumatic injury. \n\n\n\nPhysical examination showed an erythematous \nannular plaque with an elevated scaly border over \nthe right cheek (Figure 4). No ulceration, discharge, \nhypoesthesia or lymphadenopathy were noted, and \nexamination of other systems was unremarkable. \nOur differential diagnoses included leprosy, \nchromomycosis, tuberculosis verrucosa cutis and \nnon-tuberculous mycobacterial infection.\n\n\n\nFigure 4. (a) Clinical presentation of the patient showing an \nerythematous annular patch with an elevated scaly margin over \nthe right cheek, and (b) after four months on systemic antifungal \ntreatment.\n\n\n\na: H&E x40\n\n\n\nb: H&E x200\n\n\n\nc: H&E x400\n\n\n\nCase 3\nHA, a 66-year-old housewife presented with a \nsolitary, progressively enlarging erythematous \nplaque over her right cheek for the past eight \nmonths. Similarly, she did not recall any prior \n\n\n\na\n\n\n\nb\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36\n\n\n\nNo hyphae or spores were appreciated with \nskin scraping and direct microscopy, and blood \ninvestigations were normal. Histopathological \nexamination showed an acanthotic epidermis \nand a dermis containing numerous non-caseating \nepithelioid cell granulomas and Langhans-type \nmultinucleated giant cells. ZN and PAS stains did \nnot reveal any microorganisms, but culture isolated \nExophiala species.\n\n\n\nA diagnosis of cutaneous and corneal \nphaeohyphomycosis caused by Exophiala species \nwas made and she was treated with oral itraconazole \nfor four months with complete clinical clearance. \n\n\n\nDiscussion \nPhaeohyphomycosis collectively refers to a \nheterogenous group of mycotic infections caused by \ndematiaceous yeast-like cells, pseudohyphae-like \nelements, hyphae, or any combination of these forms \nin tissue. It is categorized into superficial \u2013 which \nincludes cutaneous (tinea nigra palmaris), otitic \n(otomycosis) and ophthalmic (mycotic keratitis), \nsubcutaneous \u2013 including cystic (phaeohyphomycotic \ncyst) and nodular disseminated, cerebral, and \ndisseminated or systemic phaeohyphomycosis.1,2 \nPhaeohyphomycosis is an opportunistic infection \nthat has been reported worldwide. Many species \nof fungi cause phaeohyphomycosis, including \nExophiala, Phialophora, Alternaria, Cladosporium, \nScytalidium, Drechslera, Curvularia and Wangiella \nspecies, the most common reportedly being E. \njeanselmei.1 \n\n\n\nMost cases have been associated with rural \noccupations related to manual labor and agriculture \nthat pose a significant risk of traumatic implantation \ninjury. Indeed, Wangiella dermatitidis and \nExophiala jeanselmei have been recovered from \nplant materials, wood and soil. Lesions commonly \noccur on exposed limbs prone to trauma such as the \nfeet, legs, hands and arms, although involvement of \nother sites is not uncommon.3-8 While the majority \nof cases are due to traumatic inoculation, cases \nhave also been reported to occur without prior \nrecollection of traumatic injury,9-11 as in our cases \nabove. Typically, most cases of phaeohyphomycosis, \nespecially the disseminated types, have been \nassociated with immunocompromised states such \nas acquired immunodeficiency syndrome (AIDS),12 \nmalignancies,13 post-organ transplant,14-16 systemic \nlupus,17 vasculitis,4,18  primary immunodeficiency \nsyndromes,19 and heart failure20 among others.21 \nHowever, occurrences in immunocompetent \n\n\n\nindividuals, involving both limited and disseminated \ndiseases, have also been reported to be on the rise,5,8-\n\n\n\n10,22-28 as illustrated in our patients. The infection \nin immunocompetent hosts is thought to be due \nto the melanin pigment contained within these \ndematiaceous fungi acting as a virulence factor \nby scavenging free radicals and hypochlorites \nproduced by phagocytic cells, in addition to binding \nto hydrolytic enzymes.23,24,29 \n\n\n\nA longer duration of trauma history and screening for \nimmunosuppression is vital in making a diagnosis, \nespecially given its myriad clinical presentations. \nPhaeohyphomycosis should be distinguished \nfrom chromomycosis and eumycetoma which are \nalso caused by dematiaceous fungi. The presence \nof sclerotic bodies on histopathology supports \nchromomycosis, while the presence of draining \nsinuses, granules and tumefaction is indicative of \neumycetoma.29 \n\n\n\nThere are no standardized treatment regimens \ngiven the relative paucity of cases. Surgery is \npreferred for well-circumscribed lesions, although \nconcomitant medical treatment is favored to \navoid local spread as well as to treat subclinical \nlesions.16,27,29,30 Itraconazole was the antifungal \nmedication used in most reported cases and was \nassociated with high cure rates, especially against \nExophiala species.16,31,32 Except for Mrs NA, our \nother two patients showed dramatic response to \nitraconazole. Nevertheless, when considering \nsystemic azole antifungal, it is prudent to consider \nall possible drug-drug interactions. Other systemic \nagents used successfully include amphotericin B, \nflucytosine, voriconazole and posaconazole.9,19,20,28,33 \nFluconazole, ketoconazole and terbinafine were \nreported to be less effective, especially in serious \nsystemic infections.33,35 \n\n\n\nConclusion\nIn conclusion, there is a wide spectrum of \npresentation for cutaneous phaeohyphomycosis, \nsome of which were illustrated above. We hope to \nincrease the clinician\u2019s awareness with our report, \nso as to avoid delayed and unnecessary treatment.\n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of \nthe departments of Dermatology and Pathology of \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n37\n\n\n\nHospital Tengku Ampuan Afzan, Kuantan, Pahang, \nMalaysia for their hard work in assisting in this \nendeavor. We would also like to thank the Director-\nGeneral of Health, Malaysia, for his permission to \npublish this article.\n\n\n\nReferences\n\n\n\n1. McGinnis MR. Chromoblastomycosis and \nphaeohyphomycosis: New concepts, diagnosis, and \nmycology. J Am Acad Dermatol 1983;8:1-16. \n\n\n\n2. Perusqu\u00eda-Ortiz AM V\u00e1zquez-Gonz\u00e1lez D, \nBonifaz A. Opportunistic filamentous mycoses: \naspergillosis, mucormycosis, phaeohyphomycosis and \nhyalohyphomycosis. J Dtsch Dermatol Ges 2012;10:611-\n21.\n\n\n\n3. Tokuhisa Y, Hagiya Y, Hiruma M, Nishimura K. \nPhaeohyphomycosis of the face caused by Exophiala \noligosperma. Mycoses 2010;54:e240-3.\n\n\n\n4. Kan T, Takahagi S, Kamegashira A, Ooiwa H, Yaguchi T, \nHide M. Disseminated Subcutaneous Phaeohyphomycosis \ncaused by Exophiala oligosperma in a patient with \nWegener\u2019s Granulomatosis. Acta Derm Venereol \n2013;93:356-7.\n\n\n\n5. Chang CL, Kim DS, Park DJ, Kim HJ, Lee CH, Shin JH. \nAcute Cerebral Phaeohyphomycosis due to Wangiella \ndermatitidis accompanied by Cerebrospinal Fluid \nEosinophilia. J Clin Microbiol 2000;38:1965-6.\n\n\n\n6. Maudgil A, Johnson Z, Rogers N, Mudhar HS. Unusual \nOcular Presentations of Ocular Phaeohyphomycosis. \nEye(Lond) 2016;30:1517-9.\n\n\n\n7. Barenfanger J, Ramirez F, Tewari RP, Eagleton L. \nPulmonary Phaeohyphomycosis in a Patient with \nHemoptysis. Chest 1989;95:1158-60.\n\n\n\n8. Flynn BJ, Bourbeau PP, Cera PJ, Scicchitano LM, Jordan \nRL, Yap WT. Phaeohyphomycosis of the Epididymis \ncaused by Exophiala jeanselmei. J Urol 1999;162: 492-3.\n\n\n\n9. Ge H, Pan M, Chen G, Liu X, Shi T, Zhang F. The First \nCase of Cutaneous Phaeohyphomycosis caused by \nBipolaris spicifera in Northern China: A Case Report. Exp \nTher Med 2017;14:1875-8.\n\n\n\n10. Toluhisa Y, Hagiya Y, Hiruma M, Nishimura k. \nPhaeohyphomycosis of the face caused by Exophiala \noligosperma. Mycoses 2011;54:e240-3.\n\n\n\n11. Kang RB, Simonson DC, SToner SE, Hughes SR, \nAgger WA. The Clinical Presentation of Subcutaneous \nPhaeohyphomycosis: A Case Series from Yetebon, \nEthiopia. Clin Med Res 2017;15:88-92.\n\n\n\n12. Duvic M, Lowe L, Rios A, MacDonald E, Vance P. \nSuperficial Phaeohyphomycosis of the Scrotum in a \nPatient with the Acquired Immunodeficiency Syndrome. \nArch Dermatol 1987;123:1597-9.\n\n\n\n13. Ikai K, Tomono H, Watanabe S. Phaeohyphomycosis \ncaused by Phialophora richardsiae. J Am Acad Dermatol \n1988;19:478-81.\n\n\n\n14. Halaby T, Boots H, Vermeulen A, Van Der Ven A, Beguin \nH, Van Hooff H et al. Phaeohyphomycosis Caused by \nAlternaria infectoria in a Renal Transplant Recipient. J \nClin Microbiol 2001;39:1952-5.\n\n\n\n15. Aranegui B, Feal C, Garcia CP, Batalla A, Abalde T, Alvarez-\nMartinez M et al. Subcutaneous phaeohyphomycosis \ncaused by Exophiala jeanselmei treated with wide surgical \nexcision and posaconazole: case report. Int J Dermatol \n2013;52:255-6. \n\n\n\n16. Tirico M, Neto CF, Cruz LL, Mendes-Sousa AF, Valkinir \nD, Spina R et al. Clinical spectrum of phaeohyphomycosis \nin solid organ transplant recipients. JAAD Case Rep \n2016;2:465-9.\n\n\n\n17. Hussey SM, Gander R, Southern P, Hoang MP. \nSubcutaneous Phaeohyphomycosis Caused by \nCladophialophora bantiana. Arch Pathol Lab Med \n2005;129:794-7.\n\n\n\n18. Sato T, Yaguchi T. A case of phaeohyphomycosis \nof the face caused by Exophiala oligosperma in an \nimmunocompromised host. J Dtsch Dermatol Ges \n2013;11:1087-9.\n\n\n\n19. Zhang Y, Wang X, Li R, Kang Y, Shi X, Hagen F et al. Facial \nsubcutaneous phaeohyphomycosis caused by Phialophora \nverrucosa: successful treatment with itraconazole and \nlocal resection. JMM Case Reports 2015;e1-6.\n\n\n\n20. Xie Z, Wu W, Meng D, Zhang Q, Ma Y, Liu W et al. A case \nof Phaeohyphomycosis caused by Corynespora cassiicola \ninfection. BMC Infect Dis 2018;18:444.\n\n\n\n21. Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi \nMG. Disseminated Phaeohyphomycosis: Review of an \nEmerging Mycosis. Clin Infectious Dis 2002;34:467-76.\n\n\n\n22. Kimura M, Goto A, Furuta T, Satou T, Hashimoto \nS, Nishimura K. Multifocal Subcutaneous \nPhaeohyphomycosis Caused by Phialophora verrucose. \nArch Pathol Lab Med 2003;127:91-3.\n\n\n\n23. Mishra D, Singal M, Rodha MS, Subramanian A. \nSubcutaneous Phaeohyphomycosis of Foot in an \nImmunocompetent Host. J Lab Physicians 2011;3:122-4.\n\n\n\n24. Parente JN, Talhari C, Ginter-Hanselmayer G, Schettini \nAP, Eiras Jda C, de Souza JV et al. et al. Subcutaneous \nphaeohyphomycosis in immunocompetent patients: \ntwo new cases caused by Exophiala jeanselmei and \nCladophialophora carrionii. Mycoses 2009;54:265-9.\n\n\n\n25. Bonifaz A, Davoudi MM de Hoog GS, Padilla-\nDesgarennes C, Va\u00b4zquez-Gonza\u00b4lez D, Navarrete G \net al. Severe Disseminated Phaeohyphomycosis in an \nImmunocompetent Patient Caused by Veronaea botryosa. \nMycopathologia 2013;175:497-503.\n\n\n\n26. Chen YC, Su YC, Tsai CC, Lai NS, Fan KS, Liu KC. \nSubcutaneous phaeohyphomycosis caused by Exophiala \njeanselmei. J Microbiol Immunol Infect 2014;47:546-9.\n\n\n\n27. Shivamurthy A, Bhat ST, Jaiprakash P. Subcutaneous \nPhaeomycotic Cyst: A Case Report. Our Dermatol Online \n2014;5:273-5.\n\n\n\n28. Shruti S, Singh A, Ramesh V, Siraj F. Phaeohyphomycosis \nof the Face Masquerading as Basal Cell Carcinoma in \nan Immunocompetent Patient. Indian Dermatol Online J \n2017;8:271-3.\n\n\n\n29. Revankar SG. Phaeohyphomycosis. Infect Dis Clin North \nAm 2006;20:609-20.\n\n\n\n30. Manoharan M, Shanmugam N, Veeriyan S. A Rare Case of \na Subcutaneous Phaeomycotic Cyst with a Brief Review of \nLiterature. Malays J Med Sci 2011;18:78-81.\n\n\n\n31. McCown HF, Sahn EE. Subcutaneous phaeohyphomycosis \nand nocardiosis in a kidney transplant patient. J Am Acad \nDermatol 1997;36:863-6.\n\n\n\n32. Gold WL, Vellend H, Salit IE, Campbell I, Summerbell \nR, Rinaldi M et al. Successful treatment of systemic and \nlocal infection due to Exophiala species. Clin Infect Dis \n1994: 339-41.\n\n\n\n33. Isa-Isa R, Garc\u00eda C, Isa M, Arenas R. Subcutaneous \nphaeohyphomycosis (mycotic cyst). Clin Dermatol \n2012;30:425-31.\n\n\n\n34. Venkatesan P, Perfect JR, Myers SA. Evaluation and \nmanagement of fungal infections in immunocompromised \npatients. Dermatol Ther 2005;18:44-57.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38\n\n\n\n35. Rallis E, Frangoulis E. Successful treatment of subcutaneous \nphaeohyphomycosis owing to Exophiala jeanselmei with \noral tebinafine. Int J Dermatol 2006;45:1369-70.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n39\n\n\n\nCASE REPORT\n\n\n\nAn Infant with a Peculiar Rash \u2013 Getting Reacquainted with an Ancient \nbut Forgotten Disease       \nRajalingam Ramalingam, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nCongenital syphilis continues to be a public health concern worldwide despite comprehensive antenatal \nscreening programs. It leads to significant morbidity and mortality in both the mother and her child. \nThe diagnosis of congenital syphilis may not be straightforward given the atypical and nonspecific \nclinical features that mimic a wide variety of diseases. Herein, we report a case of an infant with \ncongenital syphilis with an unusual presenting rash mimicking pustular psoriasis.\n\n\n\nKey words: Congenital syphilis, Syphilis, Malaysia, Sexually transmitted infection, Venereal disease\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology,\nHospial Tengku Ampuan Afzan,\nJalan Tanah Putih,\n25100 Kuantan, Pahang, Malaysia\nEmail: raj.blueheart@gmail.com  \n\n\n\nIntroduction\nCongenital syphilis, caused by the transplacental \ntransmission of Treponema pallidum, continues to \nbe a global public health concern. Late diagnosis \nand delayed treatment lead to a higher risk of \nperinatal morbidity and mortality, despite the fact \nthat syphilis is entirely preventable and treatable. \nAlthough comprehensive antenatal screening and \ntreatment is well established in many countries, \nincluding Malaysia, the occurrence of sporadic \ncases indicates gaps in the system that require re-\nevaluation if we are to eradicate the mother-to-child \ntransmission altogether. Diagnosing congenital \nsyphilis can be challenging because the majority of \naffected infants are asymptomatic at birth, or have \nnonspecific signs. Hence, it is vital that physicians \nbe well aware of the various clinical features of \ncongenital syphilis to ensure early diagnosis and \nprompt treatment. \n\n\n\nCase Report\nA two-month-old girl was referred to the dermatology \nclinic for \u201cpustular psoriasis\u201d. The infant\u2019s \nbiological mother had an uneventful pregnancy \nand uncomplicated term vaginal delivery. The baby \npresented at two weeks of age with multiple annular \nerythematous patches over the limbs, associated \nwith low-grade fever, irritability, poor feeding \nand post-feeding vomiting. Subsequently, these \nannular patches increased in number and became \nscaly plaques with pustules over the upper back. \nThere was also scaling of the palms and soles, and \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40\n\n\n\nsuperficial erosions over the genitalia, buttocks, \nperianal and perioral regions. There was no history \nof any recent illness in the family and neither was \nthere any contact with sick children. The mother is \na clerk and the husband a long-distance truck driver. \nAntenatal infective screening of the mother was \nnegative in the first trimester.\n\n\n\nPhysical examination revealed an irritable and \nfebrile infant with multiple erythematous, annular, \nscaly patches and plaques over both upper and \nlower limbs, upper back and buttocks (Figure 1, \na-c). There were also nonfollicular pustules noted \nover the upper back and nape of the neck. Closer \n\n\n\ninspection of individual plaques showed collarette \nscaling with a rim of papules and pustules (Figure \n2). Desquamation of the palms and soles were \nprominent (Figure 3). In addition, superficial moist \nerosions were found over the perianal and perioral \nregions as well as the buttocks and genitalia (Figure \n4, a-b). No lymphadenopathy or organomegaly \nwas noted, and examination of other systems was \nunremarkable. A few differential diagnoses were \nentertained, including pustular psoriasis, inverse \npityriasis rosea, acrodermatitis enteropathica, \nneonatal lupus erythematosus and congenital \nsyphilis.\n\n\n\nFigure 1. (a) \u2013 (c) Clinical presentation of the patient showing multiple erythematous, annular, scaly patches and plaques over both upper \nand lower limbs, upper back and buttocks. Nonfollicular pustules were also seen over the upper back and nape of the neck       \n\n\n\na b c\n\n\n\nFigure 2. Closer inspection of plaques showing collarette \nscaling with a rim of papules and pustules\n\n\n\n Figure 3. Clinical presentation showing typical \u201cwasherwoman\u2019s \nfeet\u201d\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n41\n\n\n\nFigure 4. (a) \u2013 (b) Clinical presentation of the patient showing superficial erosions over the buttocks and genitalia\n\n\n\ntwo-thirds of affected infants are asymptomatic at \nbirth, while those who are symptomatic have non-\nspecific or subtle signs.14 This is further complicated \nby misinterpreted serological tests, given the \npassive transfer of maternal immunoglobulin G to \nthe fetus, and the fact that less than 30% of infants \nhave the required four-fold greater titers than their \nmothers17-19 to make a convincing diagnosis.\n\n\n\nThe cutaneous lesions of congenital syphilis are \noverwhelmingly numerous and generic, and most \noften seen in early congenital syphilis (below \ntwo years of age). Among those described in the \nliterature include erythema and desquamation of \nthe palms and soles (\u201cwasherwoman\u2019s hands and \nfeet\u201d),14,20,21 diffuse erythematous keratoderma of the \nhands and feet,14 onychauxis of the fingernails and \ntoenails,14 symmetrical copper-red maculopapular \nrash,14,15,22,23 acral vesiculobullae (pemphigus \nsyphiliticus),1,24,25,31 papules,6,26 vesicles,27 pustules,26 \ncollarette scales (Biett\u2019s collarette),26,30 perioral and \nperianal fissures (rhagades),6,13,14,28,38 moth-eaten \nalopecia,28,29 condylomata lata,6,28 mucous patches of \nthe mouth and genitalia,28 ulcerative plaques,1 loss \nof eyebrows,32 and erythema multiforme-like target \nlesions.24,26 To the best of the authors\u2019 knowledge, \nthere had been no prior report of non-ulcerative \nplaques bordered by a rim of pustules mimicking \npustular psoriasis.\n\n\n\nExtracutaneous manifestation of congenital syphilis \nis equally highly variable and non-specific. Early \ncongenital syphilis (between 0 to 2 years of age) \nincludes generalized edema,21,28,33,35 nephrotic \nsyndrome,1,33,35,38,40 bilaterally symmetrical with \nmetaphysitis, osteitis and periostitis of the long \nbones commonly involving the upper medial \n\n\n\nBlood investigations revealed hypochromic \nmicrocytic anemia (hemoglobin 7.7 g/dL) and \nleukocytosis (total white cell count 30.58 x109/L). \nHepatic and renal functions were normal. Blood \nculture was negative for growth. Venereal disease \nresearch laboratory (VDRL) was reactive with \na titer above 1:16 and the treponema pallidum \nhemagglutination assay (TPHA) was reactive. \nChest and long bone radiography were normal. \nCerebrospinal fluid examination was declined by \nthe parents. \n\n\n\nA diagnosis of congenital syphilis was made and \nthe infant was started on intravenous penicillin. \nScreening of both parents revealed that the mother \nhad reactive VDRL (titer above 1:16) and TPHA, \nwhile the father had non-reactive results.\n\n\n\nDiscussion\nCongenital syphilis is caused by the transplacental \ntransmission of Treponema pallidum, and rarely, \nvia contact with a syphilitic chancre in the birth \ncanal during parturition,1 or through nonsexual \ntransmission (syphilis brephotrophica) such as \nkissing and breastfeeding.2-4 It continues to be a \nglobal public health concern, in both developing5-7 \n\n\n\nand developed8-12 nations. Late diagnosis and \ndelayed treatment lead to a higher risk of perinatal \nmorbidity and mortality, including early fetal loss, \nhydrops fetalis, stillbirth, prematurity, low birth \nweight, neonatal and infant death, and congenital \nanomalies,13 despite the fact that syphilis is entirely \npreventable and treatable. \n\n\n\nThe diagnosis of congenital syphilis can be difficult \ngiven the relative paucity of cases in the post-\npenicillin era as well as the fact that more than \n\n\n\na b\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42\n\n\n\nmetaphysis of the tibiae (Wimberger sign),6,15,21,28 or \ncausing frontal bossing, saber shin and deformity of \nsternoclavicular joint (Higoum\u00e9nakis sign),6,21,28,34,38 \nhepatosplenomegaly,6,20,21,29,33,35,42 dactylitis,20 \nhemolytic anemia,6,20,26,29 pseudoparalysis due to \nchondroepiphysitis and pain (pseudoparalysis \nof Parrot),15,20,38,39 lymphadenopathy, especially \nlarge epitrochlear nodes,6,28,29,38 buphthalmos,29 \nglaucoma, chorioretinitis and uveitis,29,45 \njaundice,28,35 hepatitis,6,28,35,37 fibrosing pneumonitis \n(pneumonia alba) and pulmonary abscess,1,28,36,39,42 \nthrombocytopenia,6,26,28 high-output cardiac \nfailure,28 rhinitis (syphilitic snuffles)28,29,38 and \ncongenital neurosyphilis.28,38,42,43 Features of \nlate congenital syphilis (after 2 years of age) \ninclude nasal cartilage destruction and saddle-\nnose deformity,28,38 perforation of the hard \npalate,13,28,38 interstitial keratitis,6,38 peg-shaped, \nnotched central incisors (Hutchinson\u2019s teeth) and \nmulticuspid first molars (mulberry molars),38 eighth \ncranial nerve deafness,38,43 joint swelling,15,39,40 \ncleft lip,41 serosanguinous discharge from tear \nducts when crying,44 cerebral calcifications,31 \nventriculomegaly,31 myocarditis,45 pancreatitis,45 \nhypopituitarism causing diabetes insipidus,45 and \nhypoglycemia.45 \n\n\n\nThe prevention of transmission and the treatment \nof a seropositive mother is the most effective \nway to curb the scourge of congenital syphilis. \nAlthough comprehensive antenatal screening and \ntreatment is well established in many countries, the \ncontinued occurrence of sporadic cases indicates \ngaps in the system. Routine antenatal screening \nwith nontreponemal tests (VDRL or Rapid Plasma \nReagin) is recommended for pregnant women in the \nfirst trimester of pregnancy and again at 28 weeks of \ngestation by the World Health Organization (WHO),46 \nCenters for Disease Control and Prevention (CDC)47 \nas well as in Malaysia,48 especially for those women \nin areas with a high prevalence of syphilis. This is \nespecially crucial for those women who contract \nsyphilis late in their pregnancy. However, not all are \nsuccessfully screened, such as the case highlighted \nhere. Therefore, it is vital to identify shortfalls in \nlocal antenatal screening programs to further prevent \ncongenital syphilis and other vertically-transmitted \ninfections in the country. \n\n\n\nConclusion\nIn conclusion, the clinical features of congenital \nsyphilis are highly variable, non-specific and \nmisleading. It would be wise to suspect congenital \nsyphilis in an infant with a rash that looks like \n\n\n\npustular psoriasis, as this report illustrates.\n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of \nthe departments of Dermatology and Pediatrics of \nHospital Tengku Ampuan Afzan, Kuantan, Pahang, \nMalaysia for their hard work in assisting in this \nendeavor. We would also like to thank the Director-\nGeneral of Health, Malaysia, for his permission to \npublish this article.\n\n\n\nReferences\n\n\n\n1. Shim SH, Kim JY, Lee EK, Bang K, Cho KS, Lee J et \nal. Congenital Syphilis: An Uncommon Cause of Gross \nHematuria, Skin Rash, and Pneumonia. Korean J Pediatr \nInfect Dis 2014;21:65-70.\n\n\n\n2. Hofmann B, Schuppe HC, Ruzicka T, Kuhn A, Lehmann \nP. Acquired syphilis II in early childhood: Reappearance \nof syphilis brephotrophica. J Am Acad Dermatol \n1998;38:638-9.\n\n\n\n3. Echols SK, Shupp DL, Schroeter AL. Acquired secondary \nsyphilis in a child. J Am Acad Dermatol 1990;22:313-4.\n\n\n\n4. Menni S. Acquired Primary Syphilis on a Child\u2019s Lip. Acta \nDerm Venereol 2007;87:284.\n\n\n\n5. Walker GJ, Walker DG. Congenital syphilis: a continuing \nbut neglected problem. Semin Fetal Neonatal Med \n2007;12:198-206.\n\n\n\n6. Lugo A, Sanchez S, Sanchez JL. Congenital syphilis. \nPediatr Dermatol 2006;23:121-3.\n\n\n\n7. Mungrue K, Edwards J, Fyzul A, Boodhai B, Narinesingh \nA, Nanlal S. Towards the Elimination of Syphilis in a Small \nDeveloping Country. J Sex Transm Dis 2005;2015:801437.\n\n\n\n8. The Lancet. Congenital syphilis in the USA. Lancet \n2018;392:1168.\n\n\n\n9. Park HJ. Clinical observation and statistical consideration \nof syphilis (2000-2007). Korean J Dermatol 2008;46:1344-\n52.\n\n\n\n10. Tikhonova L, Salakhov E, Southwick K, Shakarishvili \nA, Ryan C, Hillis S. Congenital syphilis in the Russian \nFederation: magnitude, determinants, and consequences. \nSex Transm Infect 2003;79:106-10.\n\n\n\n11. Reyna-Figueroa J, Esparza-Aguilar M, Hern\u00e1ndez-\nHern\u00e1ndez Ldel C, Fern\u00e1ndez-Canton S, Richardson-\nLopez Collada VL. Congenital Syphilis, a Reemergent \nDisease in Mexico: Its Epidemiology During the Last 2 \nDecades. Sex Transmitted Dis 2011;38:798-801.\n\n\n\n12. Ortiz-Lopez N, Diez M, Diaz O, Simon F, Diaz A. \nEpidemiological Surveillance of Congenital Syphilis in \nSpain, 2000\u20132010. Ped Infectious Dis J 2012;31:988-90.\n\n\n\n13. Ingall D, S\u00b4anchez PJ. \u201cSyphilis,\u201d in Infectious Diseases \nof the Fetus and Newborn Infant, 5th edition; Remington \nJS, Klein JO, editors; Saunders, Philadelphia, USA; 2001. \n\n\n\n14. Leung AKC, Leong KF, Lam JM. A Case of Congenital \nSyphilis Presenting with Unusual Skin Eruptions. Case \nRep Pediatr 2018;2018:1761454 2018:e1-4.\n\n\n\n15. Agrawal PG, Joshi R, Kharkar VD, Bhaskar MV. \nCongenital syphilis: The continuing scourge. Indian J Sex \nTransm Dis 2014;35:143-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n43\n\n\n\n16. Fan P, Fu M, Liao W, Luan Q, Hu X, Gao T et al. Early \ncongenital syphilis presented with exclusive bending pain \nof extremity: case report. J Dermatol 2007;34:214-6.\n\n\n\n17. Peeling RW, Ye H. Diagnostic Tools for Preventing \nand Managing Maternal and Congenital Syphilis: An \nOverview. Bull World Health Organ 2004;82:439-46.\n\n\n\n18. Hollier LM, , Harstad TW, Sanchez PJ, Twickler DM, \nWendel GD Jr. Fetal Syphilis: Clinical and Laboratory \nCharacteristics. Obstet Gynecol 2001;97:947-53.\n\n\n\n19. Stoll BJ, Lee FK, Larsen S, Hale E, Schwartz D, Rice RJ \net al. Clinical and Serologic Evaluation of Neonates for \nCongenital Syphilis: A Continuing Diagnostic Dilemma. J \nInfect Dis 1993;167:1093-9.\n\n\n\n20. Koh MT, Lim CT. Early Congenital Syphilis: Experience \nwith 13 Consecutive Cases seen at the University Hospital, \nKuala Lumpur. Singapore Med J 1991;32:230-2.\n\n\n\n21. Lim CT, Koh MT, Sivanesaratnam V. Early Congenital \nSyphilis -- A Continuing Problem in Malaysia. Med J \nMalaysia 1995;50:131-5.\n\n\n\n22. Patel NU, Oussedik E, Landis ET, Strowd LC. Early \ncongenital syphilis: recognising symptoms of an \nincreasingly prevalent disease. J Cutan Med Surg \n2018;22:97-9.\n\n\n\n23. Basu S, Kumar A. Varied presentations of early congenital \nsyphilis. J Trop Pediatr 2013;59:250-4. \n\n\n\n24. Wang EA, Chambers CJ, Silverstein M. A rare presentation \nof congenital syphilis: Pemphigus syphiliticus in a newborn \ninfant with extensive desquamation of the extremities. \nPediatr Dermatol 2018;35:e110-3.\n\n\n\n25. Lago EG, Vaccari A, Fiori RM. Clinical Features and \nFollow-up of Congenital Syphilis. Sex Transm Dis \n2013;40:85-94.\n\n\n\n26. Kim HY, Kim BJ, Kim JH, Yoo BH. Early congenital \nsyphilis presenting with skin eruption alone: a case report. \nKorean J Pediatr 2011;54:512-4.\n\n\n\n27. Woznicov\u00e1 V, Smajs D, Wechsler D, Mat\u0115jkov\u00e1 P, \nFlasarov\u00e1 M. Detection of Treponema pallidum subsp. \npallidum from Skin Lesions, Serum, and Cerebrospinal \nFluid in an Infant with Congenital Syphilis after \nClindamycin Treatment of the Mother during Pregnancy. \nJ Clin Microbiol 2007;45:659-61.\n\n\n\n28. Woods CR. Syphilis in Children: Congenital and Acquired. \nSemin Pediatr Infect Dis 2005;16:245-57.\n\n\n\n29. Banapurmath CR1, Narasareddy B, Banapurmath SC, \nMuganagowda, Kesaree N. Unusual Presentation in Early \nCongenital Syphilis. Indian Pediatr 1994;31:843-6.\n\n\n\n30. Wu I, Rivitti-Machado MC, Orlandi R, Filho AM, Nico \nMM. Congenital Syphilis: A case report. J Am Acad \nDermatol 2017;76:AB83.\n\n\n\n31. Loaiza SC, Cruz AR, Vargas-Navia N, Salazar JC. \nCongenital syphilis: A menace that will not go away. J Am \nAcad Dermatol 2017;76:AB83.\n\n\n\n32. Simms I, Goh BT, French P, Wallace LA, Irvine N, Thomas \nDR et al. A brief recent history of the epidemiology of \ncongenital syphilis in the United Kingdom. Int J STD \nAIDS 2018:29:1110-9.\n\n\n\n33. Pollner P. Nephrotic Syndrome Associated with Congenital \nSyphilis. J Am Med Assoc 1966;198:263-6.\n\n\n\n34. Dzebolo NN. Congenital Syphilis: An Unusual \nPresentation. Radiology 1980;136:372.\n\n\n\n35. Simmank KC, Pettifor JM. Unusual presentation of \ncongenital syphilis. Ann Trop Paediatr 2000;20:105-7.\n\n\n\n36. Bell C, Taxy J. Pulmonary Abscesses in Congenital \nSyphilis. Arch Pathol Lab Med 2002;126:484-6.\n\n\n\n37. Kim SJ, Lee SW, Rhim JW, Youn YS, Lee JS, Lee KY et \nal. A case of congenital syphilis mistaken for possible child \nabuse. Korean J Pediatr 2009;52:710-2.\n\n\n\n38. De Santis M, De Luca C, Mappa I, Spagnuolo T, Licameli \nA, Straface G et al. Syphilis Infection during Pregnancy: \nFetal Risks and Clinical Management. Infect Dis Obs \nGynecol 2012:2012:430585.\n\n\n\n39. Murali MV, Nirmala C, Rao JV. Symptomatic Early \nCongenital Syphilis: A Common but Forgotten Disease. \nCase Rep Pediatr 2012;2012:934634.\n\n\n\n40. Quaresma L, Gon\u00e7alves J, Estanqueiro P, Salgado M. \nRecurrent fever, arthralgia and asymmetric genu varum \nof unexpected etiology. Pediatr Rheumatol Online J \n2014;12:229.\n\n\n\n41. Gupta R, Chotaliya K, Marfatia YS. Cleft lip as a \npresentation of congenital syphilis. Indian J Sex Transm \nDis AIDS 2012;33:58-9.\n\n\n\n42. Akahira-Azuma M, Kubota M, Hosokawa S, Kaneshige \nM, Yasuda N, Sato N et al. Republication: Two Premature \nNeonates of Congenital Syphilis with Severe Clinical \nManifestations. Trop Med Health 2015;43:165-70.\n\n\n\n43. Simms I, Tookey PA, Goh BT, Lyall H, Evans B, \nTownsend CL et al. The incidence of congenital syphilis \nin the United Kingdom: February 2010 to January 2015. \nBJOG 2017;124:72-7.\n\n\n\n44. Bembry W, Anderson M, Nelson S. Congenital Syphilis: \nThe Great Pretender Strikes Back. A Case Report. Clin \nPediatr (Phila). 2017;57:992-6.\n\n\n\n45. Cooper JM, S\u00e1nchez PJ. Congenital Syphilis. Semin \nPerinatol 2018;42:176-84.\n\n\n\n46. World Health Organization (WHO) Guideline on Syphilis \nScreening and Treatment for Pregnant Women 2017.\n\n\n\n47. Centers for Disease Control and Prevention (CDC) \nSexually Transmitted Diseases Treatment Guidelines \n2015.\n\n\n\n48. Malaysian Guidelines in the Treatment of Sexually \nTransmitted Infections, Fourth Edition, 2015.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44\n\n\n\nCASE REPORT\n\n\n\nSuccessful Treatment of Familial Benign Chronic Pemphigus with \nOral Doxycycline        \nKelvin Shenq Woei Siew1, MBBS, Yen Fa Toh2, MPath, Zhenli Kwan1, AdvMDerm\n\n\n\n1Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, \nMalaysia\n2Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n\n\n\nSummary\nFamilial benign chronic pemphigus is a rare autosomal dominant genodermatosis that frequently \ninvolves the flexures. The disease often runs a recurrent course with limited treatment options. We \nreport the case of a 65-year-old male patient who successfully achieved disease remission with a \nsingle course of oral doxycycline.\n\n\n\nKey words: Familial benign pemphigus, Hailey-Hailey diseases, Doxycycline\n\n\n\nCorresponding Author\nDr Kelvin Shenq Woei Siew\nDivision of Dermatology,\nDepartment of Medicine, \nFaculty of Medicine,\nUniversity of Malaya,\n50603 Kuala Lumpur, Malaysia.\nE-mail: ksiewsw@gmail.com \n\n\n\nIntroduction \nFamilial benign chronic pemphigus, also known \nas Hailey-Hailey disease (HDD), is an autosomal \ndominant disorder caused by a mutation in \nATP2C1gene.1,2 Disruption to intracellular \ncalcium signalling subsequently affects epidermal \ndesmosomal adhesion.3 This disease is characterised \nby recurrent vesicles, painful erosions and fissures \ninvolving the flexures. Superimposed microbial \ncolonisation in areas with excess moisture such as \nthe flexures may be a disease-modifying factor. \n\n\n\nSome of the current available treatment options \ninclude topical or systemic steroids, botulinum \ntoxin injection, oral retinoids, laser therapy and \nsurgical therapies such as dermabrasion and \nexcision with split thickness skin grafting.4 We \nreport the case of a gentleman with familial benign \nchronic pemphigus who responded to a course \nof oral doxycycline and we review the available \nliterature regarding the treatment response of the \ndisease to oral doxycycline \n\n\n\nCase Report \nA 65-year-old ethnic Chinese gentleman presented \nwith pruritic papules over his limb flexures and \nplaques over his scrotum (Figure 1a) which had \nbeen worsening for two weeks. He had a history \nof intermittent rashes on these areas for the past 34 \nyears with episodes of weeping and crusting, which \nwere treated as infected eczema. The episodes were \naggravated by increased perspiration and emotional \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n45\n\n\n\nstress. He had a prior skin biopsy of the scrotum \nin 1983 but he was unsure of the report. He had a \nsignificant medical history of diabetes mellitus, \nhypertension, dyslipidaemia, gout, renal calculi \nand carcinoma of the sigmoid colon. A sigmoid \ncolectomy was performed in 2000. His father also \nhad a history of similar lesions at the scrotum.\n\n\n\nA repeated skin biopsy revealed the presence of \nfocal full-thickness acantholysis in the epidermis, \nresembling a \u201cdilapidated brick wall\u201d appearance \n\n\n\nDiscussion \nA review of literature found 9 reported cases that \nsuccessfully achieved disease control with oral \ndoxycycline (Table 1). Postulated mechanisms \nof action for doxycycline were anti-collagenase \nactivity and the suppression of the nuclear factor \nkappa light-chain of activated B cells (NF-kB) \ninflammatory pathway.5 Flores et al. recommended \na dosing of oral doxycycline 100 mg daily for a \nvariable duration followed by maintenance therapy \nof oral doxycycline 50 mg daily for 16 months.6 \nNonetheless our patient reported satisfactory \ndisease control without a maintenance regimen. \nTherefore, we propose that the use of maintenance \ntherapy with oral doxycycline may be considered in \npatients with recurrent or severe disease while some \npatients may exhibit good and sustained response \nwith a single course of doxycycline.\n\n\n\nconsistent with a diagnosis of familial benign \nchronic pemphigus (Figure 1b).\n\n\n\nHe was commenced on oral doxycycline 100 mg \ntwice daily for 5 weeks with the concurrent use \nof topical clobetasone butyrate 0.05% ointment, \nemulsifying ointment and oral antihistamines \nfor itch. His condition improved with complete \nresolution of scrotal plaques and minimal residual \npapules over his cubital fossae.\n\n\n\nConclusion \nOral doxycycline may be considered as an option \nfor the first line therapy of familial benign chronic \npemphigus given the safety of doxycycline, efficacy \nand low cost of treatment. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nFigure 1. (a) Plaque over the scrotal region (b) Histopathological examination revealed focal full-thickness acantholysis with a \n\u201cdilapidated brick wall\u201d appearance.\n\n\n\na b\n\n\n\nReferences\n\n\n\n1. Chiaravalloti A, Payette M. Hailey-Hailey disease and \nreview of management. J Drugs Dermatol 2014;13:1254-\n7.\n\n\n\n2. Michel B. \u201cFamilial benign chronic pemphigus\u201d by \nHailey and Hailey, April 1939. Commentary: Hailey-\nHailey disease, familial benign chronic pemphigus. Arch \nDermatol 1982;118:774-83.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46\n\n\n\n3. Btadini W, Abou Hassan OK, Saadeh D, Abbas O, Ballout \nF, Kibbi AG et al. Identification of several mutations in \nATP2C1 in Lebanese families: insight into the pathogenesis \nof Hailey-Hailey disease. PLoS One 2015;10:e0115530.\n\n\n\n4. Arora H, Bray FN, Cervantes J, Falto Aizpurua LA. \nManagement of familial benign chronic pemphigus. Clin \nCosmet Investig Dermatol 2016;9:281-90.\n\n\n\n5. Henehan M, Montuno M, De Benedetto A. Doxycycline as \nan anti-inflammatory agent: updates in dermatology. J Eur \nAcad Dermatol Venereol 2017;31:1800-8.\n\n\n\n6. Flores-Terry MA, Cortina-de la Calle MP, Lopez-Nieto M, \nCruz-Conde de Boom R. Good Response to Doxycycline \nin Hailey-Hailey Disease. Actas Dermosifiliogr \n2016;107:537-9.\n\n\n\n7. Elfatoifi FZ, Fanian F, Chiheb S, Humbert P. [Hailey-\nHailey disease: Efficiency of combined doxycycline and \nvitamin PP]. Ann Dermatol Venereol 2017;144:216-7.\n\n\n\n8. Le Sache-de Peufeilhoux L, Raynaud E, Bouchardeau A, \nFraitag S, Bodemer C. Familial benign chronic pemphigus \nand doxycycline: a review of 6 cases. J Eur Acad Dermatol \nVenereol 2014;28:370-3.\n\n\n\n9. Warycha M, Patel R, Meehan S, Merola JF. Familial benign \nchronic pemphigus (Hailey-Hailey disease). Dermatol \nOnline J 2009;15:15.\n\n\n\nReference Patient Characteristics Management\nAge/\nGender\n\n\n\nDistribution Initial treatment Maintenance treatment Concurrent treatment \n\n\n\nOur patient 65/M Scrotum, cubital fossae, \npopliteal fossae\n\n\n\nDoxycycline 200mg/day for \n5 weeks \n\n\n\nNo Topical clobetasone \nbutyrate 0.05% ointment\n\n\n\nElfatoifi et al 2017 7 65/ F Axilla, inframammary, inguinal Doxycycline 200 mg/day \nfor more than 3 months until \nremission\n\n\n\nNo Nicotinamide 500 mg/\nday\n\n\n\nFlores et al 2016 6 60/M Axillary, inguinal, cubital fossa, \nneck and perineum. \n\n\n\nDoxycycline 100mg/day \nduring summer\n\n\n\nDoxycycline 50 mg/day \nfor 16 months\n\n\n\nNo\n\n\n\nLe Sache et al \n2014 8\n\n\n\n33/M Axillary, cervical, nails Doxycycline 100mg/day \nfor 3-month courses when \ndisease flares\n\n\n\nDoxycycline 50 mg/day \ncontinuously for 4 years \n\n\n\nNo\n\n\n\n36/F Axillary, inguinal Doxycycline 100mg/day (2 \ncourses for 3 months and 1 \nmonth each)\n\n\n\nNo No\n\n\n\n42/M Axillary, inguinal, cervical Doxycycline 100mg/day \n(3-month courses for 5 times \nand 1-month courses for 2 \ntimes for mild recurrences)\n\n\n\nNo No\n\n\n\n65/F Axillary, inguinal, elbow and \ntrunk\n\n\n\nDoxycycline 100mg/day \n(unspecified duration)\n\n\n\nNo No\n\n\n\n70/F Axillary, inguinal and cervical Doxycycline 100mg/day \n(unspecified duration)\n\n\n\nDoxycycline 50 mg/ day \ncontinuously for 5 years \n\n\n\nNo \n\n\n\n77/F All intertriginous areas Doxycycline 100mg/day \n(unspecified duration)\n\n\n\nDoxycycline 100 mg/\nday continuously for 5 \nyears  \n\n\n\nNo \n\n\n\nWarycha et al \n2009 9\n\n\n\n57/F Back, hips, flanks, \ninframammary, axillary and \ninguinal  \n\n\n\nDoxycycline 200mg/day \n(unspecified duration)\n\n\n\nNot stated Intralesional \ntriamcinolone 10 mg/ml \n(total given 1.5 ml)\n\n\n\nTable 1. Reported cases of familial benign chronic pemphigus successfully treated with oral doxycycline. \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n47\n\n\n\nCASE REPORT\n\n\n\nThe Use of a Limberg Flap for Closure of Defects Located at the \nInterdigital Webs      \nZhenli Kwan1, AdvMDerm, Shin Shen Yong1, MRCPI, James Robert Willis2, FACMS\n\n\n\n1Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n2Department of Dermatology, Division of Mohs Micrographic Surgery, Geisinger Medical Center, Danville, PA, USA\n\n\n\nSummary\nThe Limberg flap is a versatile transposition flap which can be used in many situations. We report a \ncase of a dysplastic naevus located in the interdigital web in which the Limberg flap was used for the \nclosure of the resulting defect after excision.\n\n\n\nKey words: Dermatologic surgery, Naevus, Cutaneous surgery\n\n\n\nCorresponding Author\nDr Zhenli Kwan,\nDivision of Dermatology, \nDepartment of Medicine,\nFaculty of Medicine, \nUniversity of Malaya,\n50603 Kuala Lumpur, Malaysia.\nEmail: zhenli@ummc.edu.my  \n\n\n\nIntroduction\nThe Limberg (rhomboid) flap was originally \ndesigned by Professor Alexander A. Limberg \nfrom Leningrad.1-3 This transposition flap design \nconsists of a parallelogram of equal sides with two \nangles of 60 degrees and another two angles of \n120 degrees (Figure 1). It is a versatile workhorse \nfor reconstruction in various sites and indications \nincluding skin cancers, lupus, cystic acne, spina \nbifida and pilonidal sinus.1 We report the use of the \nLimberg flap in the reconstruction of an interdigital \nweb defect after excision of a dysplastic naevus.\n\n\n\nFigure 1. The Limberg flap is designed as a parallelogram of \nequal sides with two angles of 60 degrees and another two \nangles of 120 degrees.\n\n\n\nCase Report\nAn 86-year-old Chinese gentleman with a \nbackground history of hypertension, basal cell \ncarcinoma excised in 2017, and actinic keratoses \npresented for his follow-up appointment. He was \nincidentally found to have a slowly-enlarging mole \non his right sole located on the skin between the \nsecond and third toes (Figure 2a). \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48\n\n\n\nIn view of the need to exclude a diagnosis of acral \nlentiginous melanoma which is more frequently found \nin patients of Asian ethnic origin, we performed a 4 \nmm punch biopsy. Histopathological examination \nwas reported as dysplastic naevus. As the microscopic \nmargins of the original excision were 0.5 mm, we \ndecided to re-excise around the area of the scar with a \nfurther 1.5 mm margin.4\n\n\n\nThe surgery was performed under local anaesthesia. \nWe found that the resulting defect extended between \nthe toe webs (Figure 2b). Due to the unavailability \nof tissue reservoir available for primary closure, we \ndecided to perform a Limberg flap transposing the \n\n\n\nDiscussion\nThe Limberg flap is a commonly-used flap in \nreconstructive surgery. We report a case of a patient \nwith a wound located at the interdigital web, which was \neasily closed using an appropriately-sized Limberg flap \nwith resulting minimal tension on the wound edges and \nexcellent post-operative recovery. This flap design has \na good safety record with excellent resulting cosmesis \ndue to the use of adjacent skin with similar colour and \ntexture.5 \n\n\n\nDue to the elegant simplicity of its design, it can be \neasily mastered and used in a variety of locations. The \nuse of the Limberg (rhomboid) flap has been reported on \nthe face, lumbosacral region, dorsal and inguinoscrotal \nregions, arm, trunk, shoulder and supraclavicular \nregions. Only 8% of patients in one review reported \ncomplications including epidermolysis (6%) and \nsurgical site infection (2%). These patients recovered \nwith favourable outcomes after further conservative \ntreatment.2\n\n\n\nConclusion\nAppropriately-sized Limberg (rhomboid) flaps can \n\n\n\nskin from the sole of the right foot to close the defect \nlocated at the toeweb area (Figure 2c). The defect was \nmeasured and the flap was drawn on the sole. The flap \nwas excised and elevated at the subcutaneous layer. \nThe secondary defect was closed with 3-0 dermal \nVicryl\u00ae sutures and the flap was transposed to cover \nthe defect located at the toe web region. Subsequently \nthe tip of the flap was tacked to the superior part of the \ndefect with absorbable 3-0 dermal Vicryl\u00ae sutures. \nThe periphery of the flap was secured to the wound \nedges using 3-0 dermal Vicryl\u00ae sutures and 4-0 nylon \nepidermal sutures. Antibiotic ointment and a paraffin \ngauze dressing were applied over the wound.\n\n\n\nbe used in various locations, including defects at the \ninterdigital webs which are not amenable to primary \nclosure.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare. \n \nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Chasmar LR. The versatile rhomboid (Limberg) flap. Can J \nPlast Surg 2007;15:67-71.\n\n\n\n2. Alvarez GS, Laitano FF, Siqueira EJ, De Oliveira MP, Martins \nPDE. Use of the rhomboid flap for the repair of cutaneous \ndefects. Rev Bras Cir Plast 2012;27:102-7.\n\n\n\n3. Mathew J, Varghese S, Jagadeesh S. The Limberg flap for \ncutaneous defects - a two year experience. Indian J Surg \n2007;69:184-6.\n\n\n\n4. Duffy K, Grossman D. The dysplastic nevus: from historical \nperspective to management in the modern era: part II. \nMolecular aspects and clinical management. J Am Acad \nDermatol 2012;67:19 e1-12.\n\n\n\n5. Aydin OE, Tan O, Algan S, Kuduban SD, Cinal H, Barin EZ. \nVersatile use of rhomboid flaps for closure of skin defects. \nEurasian J Med 2011;43:1-8.\n\n\n\nFigure 2. (a) A dysplastic naevus on the right sole; (b) After excision, the defect extended between the toewebs; (c) The use of the Limberg \nflap for closure of the defect on the sole extending between the toe webs.  \n\n\n\na b\n\n\n\nAlthough the patient developed post-operative surgical site infection, he recovered with local wound care and oral \nantibiotics. Subsequently the wound healed well with an excellent post-operative outcome after 2 months. \n \n\n\n\nc\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n49\n\n\n\nCASE REPORT\n\n\n\nAngiolipomatosis and Hepatitis C Infection \u2013 Association or \nCoincidence?      \nRajalingam Ramalingam1, AdvMDerm, Nor Hafliza M. Salleh2, MPath\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n2Department of Pathology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nAngiolipomas are benign mesenchymal neoplasms composed of adipose tissue and blood vessels.  \nThey typically present as multiple, painful subcutaneous nodules, more commonly seen in men. The \nupper limbs are most frequently affected. Herein we report a case of angiolipomatosis with hepatitis C \ninfection as a possible association, with a review of current literature. \n\n\n\nKey words: Angiolipoma, Adipocytic tumors, Hepatitis C, Malaysia\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology,\nHospial Tengku Ampuan Afzan,\nJalan Tanah Putih,\n25100 Kuantan, Pahang, Malaysia\nEmail: raj.blueheart@gmail.com\n\n\n\nIntroduction\nAngiolipomatosis usually presents as multiple, \npainful subcutaneous nodules. They most commonly \naffect men with a peak incidence between the \nsecond and the third decades of life, and most \nfrequently affect the upper limbs. Angiolipoma \nis distinguished from lipoma by an increase in \nthe vascular component of the connective tissue \nsepta of the tumor with fibrin thrombi seen within \nthe vessels. They typically occur sporadically, \nalthough familial types have been documented. \nWhile both lipomatosis and angiolipomatosis have \nbeen associated with various medications, only \nadiposis dolorosa (Dercum\u2019s disease) has been \nassociated with chronic hepatitis C infection. To our \nlimited knowledge, we are not aware of any cases \nof angiolipomatosis associated with hepatitis C \ninfection, and thus we hope that our report might be \nthe first of many to establish a relationship between \nthe two.\n\n\n\nCase Report\nA 38-year-old man, a former intravenous drug \nabuser undergoing rehabilitation, presented to us \ncomplaining of multiple, painful lumps over his \nanterior trunk, both forearms and thighs for the past \none month. The lumps were gradually increasing in \nnumber and size. There was no fever, weight loss \nor anorexia. He denied taking any over-the-counter \nor traditional and complimentary medicines. There \nwas no similar history in his family and systematic \nreview was unremarkable.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50\n\n\n\nExamination of the skin revealed multiple soft-to-\nfirm, tender, subcutaneous nodules of varying sizes \nbetween 1-3 centimeters over the anterior trunk, \nforearms and thighs. These nodules were discreet and \nhighly mobile (Figure 1, a-c). No lymphadenopathy \nor organomegaly was noted, and examination of \nother systems was unremarkable. Our differential \ndiagnoses included Dercum\u2019s disease (adiposis \ndolorosa), angiolipomatosis, myxolipomatosis, \nneurofibromatosis and panniculitis.\n\n\n\nFigure 1. (a) - (c) Clinical presentation of the patient showed \nmutiple skin-colored subcutaneous nodules of varying sizes \nover bilateral forearms.\n\n\n\nBlood investigations revealed normal blood counts \nand renal profile. However, liver transaminases \nwere elevated (alanine aminotransferase: 99 U/L; \naspartate aminotransferase: 61 U/L). Anti-hepatitis \nC was found to be reactive. Chest radiography \nand abdominal ultrasonography were normal. \nHistopathology of a subcutaneous nodule showed \nthinly encapsulated lobules of mature benign \nadipose tissue with vascular proliferation mainly at \nthe periphery (Figure 2, a-b). Fibrin thrombi were \nappreciated in some vessels. No atypical stromal \ncells or lipoblasts were seen. The overlying dermis \nand epidermis were unremarkable. These findings \nwere in keeping with angiolipoma. \n\n\n\nFigure 2. (a) - (b) Histology of the skin biopsy revealed \nencapsulated lobules of mature adipose tissue with vascular \nproliferation containing fibrin thrombi.\n\n\n\na\n\n\n\nb\n\n\n\nc\n\n\n\na: H&E x10\n\n\n\nb: H&E x200\n\n\n\nHe was prescribed analgesics for pain and \nreferred to the surgeon for excision of the larger, \nmore painful nodules. He was also referred to \nthe gastroenterologist for further management of \nhepatitis C.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n51\n\n\n\nDiscussion\nAngiolipomas are benign mesenchymal neoplasms \ncomposed of adipose tissue and blood vessels, \naccounting for approximately 17% of all fatty \ntumors. They typically present as multiple, painful \nsubcutaneous nodules, more commonly seen in \nmen, and with a peak incidence between the second \nand the third decades of life. The upper limbs are \nmost frequently affected (approximately two-thirds \noccurring in the forearm), followed by the trunk and \nthe lower limbs.1 Rarely, they have been reported to \noccur in the spinal region.2 Individual nodules may \nrange in size from 1-4 centimeters. \n\n\n\nAngiolipoma is distinguished from lipoma if the \nvascular component of the connective tissue septa \nof the tumor constitutes 15-50%3, and that the \ncapillaries contain fibrin thrombi.4 Angiolipoma \nis further subdivided into infiltrating and non-\ninfiltrating types, with the non-infiltrating type \nbeing the commonest.5,6 Although most cases of \nangiolipomatosis occur sporadically, a familial \nform has also been described, with both autosomal-\nrecessive7 and -dominant8 inheritance pattern, the \nformer being more prevalent. \n\n\n\nLipomatosis has been associated with drugs such as \nsystemic steroids9-11 and cytotoxic chemotherapeutic \nagents,12 while adiposis dolorosa (Dercum\u2019s \ndisease) has been reported in association with \nchronic hepatitis C infection.13 Angiolipomatosis on \nthe other hand, has been associated with protease \ninhibitors, particularly indinavir, as part of the fat \nredistribution syndrome.14 \n\n\n\nExcision is the preferred first-line treatment for \nsymptomatic angiolipomas. The prognosis for \nangiolipomas is excellent, with very low local \nrecurrence rates for the non-infiltrating subtype15. \nMain indications for resection are increasing size, \npain, cosmesis, neurological deficit, abnormal \naspiration cytology and subfascial location16. \n\n\n\nConclusion\nTo the best of our knowledge, there has been no \nreported case of angiolipomatosis associated with \nhepatitis C infection. This may be a coincidence in \nour patient, but considering how chronic hepatitis \nC infection is a systemic disease affecting many \norgans and how it has also been associated with \nDercum\u2019s disease, this may indeed represent a \nrelevant association. Future case reports will greatly \nadd value to the relationship.\n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of \nthe departments of Dermatology and Pathology of \nHospital Tengku Ampuan Afzan, Kuantan, Pahang, \nMalaysia for their hard work in assisting in this \nendeavor. We would also like to thank the Director-\nGeneral of Health, Malaysia, for his permission to \npublish this article.\n\n\n\nReferences\n\n\n\n1. Dei Tos AP. Chapter 4: Adipocytic Tumors; in Bone and \nSoft Tissue Pathology, first edition; Folpe AL, Inwards CY, \neditors; Saunders, USA;2010:P100-1.\n\n\n\n2. Konya D, Ozgen S, Kurtkaya O, Pamir NM. Lumbar \nspinal angiolipoma: a case report and review of literature. \nEur Spine J 2006;15:1025-8.\n\n\n\n3. Rasanen O, Nohteri H, Dammert K. Angiolipoma and \nlipoma. Acta Chir Scand 1967;133:461-5.\n\n\n\n4. Howard WR, Helwig EB. Angiolipoma. Arch Dermatol \n1960;82:924-31.\n\n\n\n5. Lin JJ, Lin F. Two entities in angiolipoma \u2013 a study of 459 \ncases of lipoma with review of literature on infiltrating \nangiolipoma. Cancer 1974;34:720-7.\n\n\n\n6. Stimpson N. Infiltrating angiolipomata of skeletal muscle. \nBr J Surg 1971;58:464-6.\n\n\n\n7. Cina SJ, Radentz SS, Smialek JE. A case of familial \nangiolipomatosis with Lisch nodules. Arch Pathol Lab \nMed 1999;123:946-8.\n\n\n\n8. Garib G, Siegal GP, Andea AA. Autosomal-dominant \nfamilial angiolipomatosis. Cutis 2015;95:e26-9.\n\n\n\n9. Siskind BN, Weiner FR, Frank M, Weiner SN, Bernstein \nRG, Luftschein S. Steroid-induced mesenteric lipomatosis. \nComput Radiol 1984;8:175-7.\n\n\n\n10. Tsai TF, Ko WC, Chen YF. Corticosteroid-induced \nDercum\u2019s disease. Dermatologica Sinica 2011;29:142-3.\n\n\n\n11. M\u00f6ller JC, Cron RQ, Young DW, Girschick HJ, Levy DM, \nSherry DD et al. Corticosteroid-induced spinal epidural \nlipomatosis in the pediatric age group: report of a new case \nand updated analysis of the literature. Pediatr Rheumatol \nOnline J 2011;9:1-6. \n\n\n\n12. Cronin PA, Myers E, Redmond HP, O\u2019Reilly S, Kirwan \nWO. Lipomatosis: An Unusual Side-effect of Cytotoxic \nChemotherapy? Acta Derm Venereol 2010;90:303-4.\n\n\n\n13. Gonciarz Z, Mazur W, Hartleb J, Machniak M, Bednarek \nI, Maznrek U et al. Interferon alfa-2b induced long-term \nrelief of pain in two patients with adiposis dolorosa and \nchronic hepatitis C. J Hepatol 1997;27:1141.\n\n\n\n14. Dank JP, Colven R. Protease inhibitor-associated \nangiolipomatosis. J Am Acad Dermatol 2000;42:129-31.\n\n\n\n15. Grivas TB, Savvidou OD, Psarakis SA, Liapi G, \nTriantafyllopoulos G, Kovanis I et al. Forefoot plantar \nmultilobular noninfiltrating angiolipoma: a case report and \nreview of the literature. World J Surg Oncol 2008;6:11.\n\n\n\n16. Papakonstantinou PE, Korkolopoulou P, Lassithiotakis \nD, Lolis ED. Giant angiolipoma of the arm in an elderly \npatient. Ann R Coll Surg Engl 2016; 98: e100\u20132.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52\n\n\n\nCORRESPONDENCE\n\n\n\nBowel Ischaemia in Henoch-Sch\u00f6nlein Purpura \u2013 Uncommon or \nUnder-reported?       \nDy-Win Low1, MRCP, Zuliatul Faizah Baharom2, MPath, Min Moon Tang1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Department of Pathology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nHere, we report a patient with Henoch-Sch\u00f6nlein purpura complicated with bowel ischamia. \nSurgical resection of the ischemic small intestines was performed. Histopathology of both skin and \nbowels revealed leucocytoclastic vasculitis. HSP associated gastrointestinal manifestations are not \nuncommon. High clinical suspicion and early intervention are utmost important to prevent potential \nsevere gastrointestinal tract complications. \n\n\n\nKey words: Henoch-Sch\u00f6nlein purpura, Gastrointestinal manifestations, Bowel ischaemia\n\n\n\nCorresponding Author\nDr Low Dy-Win\nDepartment of Dermatology, \nHospital Kuala Lumpur, \n50586 Jalan Pahang,\nKuala Lumpur, Malaysia \nE-mail: dywinlow@gmail.com  \n\n\n\nDear editor,\nHenoch-Sch\u00f6nlein purpura (HSP), a systemic immune-\nmediated vasculitis involving the small vessels, is \ncharacterized by perivascular deposition of immunoglobulin \nA (IgA)-immune complex in the skin, joints, gastrointestinal \ntract and kidney.1 While it is mostly self-limiting, its short-\nterm prognosis relies on the severity of gastrointestinal \ninvolvement and its long-term prognosis depends on the \nadvancement of renal involvement.2 Although classically \ndescribed as a disease of childhood (\u226420 years),3-5 there \nhave been a significant number  of reports describing HSP \nin adults.6-10 There are a few sets of diagnostic criteria \navailable for HSP which include the American College of \nRheumatology (ACR) criteria (1990)3, the Michel\u2019s criteria \n(1992)11, Chapel Hill Consensus Conference (CHCC) \n(1994),12 Helander\u2019s criteria (1995)13 and the European \nLeague Against Rheumatism/Paediatric Rheumatology \nInternational Trials Organization/Paediatric Rheumatology \nEuropean Society (EULAR/PRINTO/PRES) criteria \n(2010).14 To date the EULAR/PRINTO/PRES criteria yields \nthe highest sensitivity and specificity for both children \n(100% and 87% respectively)14 and adult (99.2% and 86% \nrespectively).15\n\n\n\nHere we described a patient who presented to us with HSP \ncomplicated by severe gastrointestinal involvement.  A \n20-year-old Malay male was referred to our dermatology \nclinic with fever and progressive purpuric macules over the \nfeet, legs, thighs, buttocks, palms and forearms for 2 weeks \nduration. Prior to the rash, he had intermittent periumbilical \ncolicky abdominal pain after meal for at least a week and \nhe was diagnosed as having acute gastroenteritis by his \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n53\n\n\n\nprimary care doctor. Apart from these, both his \nankle and wrist joints became swollen and painful \naggravated by movement for two days. He had mild \nblood-stained stool on the day of presentation to us. \n\n\n\nHe was not pale on examination. His temperature \nrecorded was 37.4oC, not tachycardic and other \nvital signs were normal. There was mild pharyngeal \nerythema. Non-tender, non-blanchable palpable \npurpuric macules involving both upper, lower \nextremities as well as his buttocks were noted as \nshown in Figure 1a & b. He was admitted to medical \nward for further evaluation and management.\n\n\n\nLaboratory work-up revealed leukocytosis with \nneutrophilia and positive antistreptolysin titer \n(ASOT) (400iU/L). His platelet counts were within \nnormal range. His serum albumin was 36g/L, other \nparameters of liver function test, renal function \ntest and the complement levels were normal. His \nantinuclear antibodies and ANCA antibodies were \nunremarkable. Serial urinary analyses did not show \nany proteinuria, hematuria or red cell casts. His \nhepatitis B, hepatitis C, HIV serology were negative. \nImmunoglobulin levels were within normal range. \nSkin biopsy showed small vessel vasculitis (Figure \n1c) and direct immunofluorescence was however \nnegative. His clinical pictures fulfilled the EULAR/\nPRINTO/PRES (2010) criteria of HSP (Table 1) \nalthough direct immunofluorescence did not show \nperivascular IgA deposits.\n \nIntravenous hydrocortisone 100mg 8hourly and \noral amoxicillin clavulanate 625mg 8 hourly \nwere initiated. His purpuric macules improved \nsignificantly and his arthritis resolved. However, on \nday 3 of admission, he developed severe, constant \nand diffuse abdominal pain worsened after meals.  \nHe also complained of massive altered bloody stool. \nClinically his abdomen was guarded and tender on \npalpation. Apart from persistent tachycardia, his \nblood pressure and temperature were normal. His \nhaemoglobin dropped from 13.3g/dl on admission \nto 8.6g/dl with a slightly prolonged INR of 1.51. \nA diagnosis of acute abdomen complicated by \nmassive gastrointestinal bleeding was made. Fluid \nresuscitation was immediately initiated. He was \ntransfused 2 units of whole blood and was brought \nto operation theatre for an emergency laparotomy. \nAntibiotics were changed to cefoperazone and \nmetronidazole. Intravenous pantoprazole was also \nadded. \n\n\n\nIntraoperatively, two area of ischemia were found \nat jejunum and terminal ileum. There was no bowel \n\n\n\nperforation. The ischaemic jejunum was resected \nand primary anastomoses was performed. In \naddition, a right hemicolectomy with double barrels \nileostomy was done for the ischaemic terminal \nileum. Resected bowel specimen showed presence \nof vasculitis of submucosal vessels (Figure 1d&e).  \nOther histopathology findings included vascular \ncongestion, hemorrhage and mucosal ulceration, \nwhich were the consequences of vasculitis induced \nmucosal ischemia. Immunofluroscence examination \nwas however not done for his bowel specimen. \n\n\n\nHe recovered post-operatively with no further active \nvasculitis. His renal profile and urinalysis remained \nnormal. He was continued with oral prednisolone at \n50mg/day (1mg/kg/day) and was tapered off slowly \nover a period of 8 months. He was also advised for \nileostomy reversal 6 months post laparotomy. He \nhas however not yet decided on the date for stoma \nreversal.\n\n\n\nGastrointestinal involvement has been reported to \noccur in up to 98% of patients with HSP as shown \nin Table 2. The rate of gastrointestinal involvement \nappeared to be higher in children with HSP as \ncompared to adults.8 The gastrointestinal symptoms \nreported include colicky periumbilical abdominal \npain typically worsened after meals, nausea, \nvomiting, haematemesis, melaena and/or bloody \nstool.1,16,17 In up to 40% of patients with HSP, \nabdominal symptoms preceded the onset of purpuric \neruption in the skin.16-17 As illustrated in our current \ncase report, he developed central abdominal pain a \nweek prior to the purpuric eruptions of the lower \nlimbs and was managed as acute gastroenteritis by \nprimary care doctor. In this scenario, the abdominal \npain was part of the clinical manifestations of HSP \nand likely not a triggering factor of HSP. \n\n\n\nThe gastrointestinal manifestations of HSP are \ndue to the vasculitis of the mesenteric vasculature. \nHence any part of the gastrointestinal system could \nbe involved although the small intestine is affected \npredominantly. While in majority of the cases \nthe gastrointestinal symptoms are mild and self-\nlimiting, up to 70% reported some form of bleeding \nin the gastrointestinal tract (Table 2). Severe \nlife-threatening complications such as massive \ngastrointestinal haemorrhage, intussusception, \nperforation, paralytic ileus and bowel ischaemia \nmay occur.16 Intussusception and bowel perforation \nwas reported to occur in up to 5% and 0.38% \nrespectively (Table 2). Rarely acute pancreatitis, \nnecrotizing vasculitis of the gall bladder and late ileal \nstrictures have been reported.16 Reports of mortality \n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54\n\n\n\ndirectly resulted from severe gastrointestinal \ncomplications have been described and was quoted \n2.8% in a series6. Interestingly two local case series \non cutaneous vasculitis reported by 2 dermatology \nclinics did not appear to observe any gastrointestinal \ncomplications in HSP.19,20 In addition, there was \nlack of local data on HSP in children. Although \nHSP with acute abdomen is rare and patients could \nbe managed by the surgical team, it is likely under-\nreported in this country. Henceforward, future \naudit should be collaborated among pediatricians, \ndermatologists, gastroenterologists, surgeons \nand nephrologists in order to describe the actual \nprevalence and complications of HSP. \n\n\n\nSpecific distribution of cutaneous purpuric eruption, \nwhether lesions occur above the waist or lesions \non upper and lower extremities, does not help the \nclinicians to predict the severity of gastrointestinal \ninvolvement in HSP.10 Hypoalbuminemia in the \n\n\n\nabsence of proteinuria may indicate protein loss in \nthe gastrointestinal tract.21 Hence close monitoring \nof serum albumin is warranted. Interestingly, \npatients with severe abdominal involvement were \nfound to have a rapid decline of factor XIII.22-24 \nAlthough the specificity of a decline in factor XIII \nas a prognostic biomarker is yet to be determined, \nreports of factor XIII replacement have been shown \nto treat severe abdominal symptoms in HSP.24 In \naddition, a study done in Spain showed that patients \nwith HSP who were not carrying the codon 469 \nK/E genotype were at decreased risk of developing \nsevere gastrointestinal complications.25\n\n\n\nThe use of corticosteroids in HSP with  \ngastrointestinal manifestation remains \ncontroversial.1 Our patient received intravenous \nhydrocortisone at a dose equivalent to 1.5mg/kg/\nday of prednisolone did not halt the progression of \nvasculitis of the gastrointestinal system. Studies have \n\n\n\nFigure 1 (a & b): Palpable purpura observed over extensor surface of the lower limbs predominantly and upper limbs and; (c) \nHistopathological examination of skin (H&E x 40) showed superficial perivascular infiltrate with neutrophils, swollen endothelial cells, \nextravasation of red blood cells (RBC), nuclear dusts and fibrinoid necrosis; (d & e) Histopathological examination of the resected \nischaemic jejunum showed ulcerated mucosal epithelium and submucosal perivascular infiltrate with neutrophils, swollen endothelial \ncells, extravasation of RBC and fibrinoid necrosis. \n\n\n\na b\n\n\n\nc d\n\n\n\ne\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n55\n\n\n\nshown that systemic corticosteroids may reduce the \nseverity and the duration of abdominal pain.21,26,27 \nNevertheless, the use of corticosteroids did not \nresult in a reduction in abdominal complications \nsuch as intussusception or surgery.21 Recurrence \nof vasculitis in the gastrointestinal system after \ntreatment has been reported to occur in up to 16% \nof children with HSP.28 Recurrence usually occurs \nwithin a month after the initial onset of HSP with \nabdominal pain as the most frequent complained \nsymptoms. \n\n\n\nIn conclusion, we reported a case of bowel \nischemia as a severe complication of HSP. The \ngastrointestinal manifestations in HSP especially \ndiffuse central abdominal pain worsened after meal \nare common although severe complications such as \nintussusception, perforation and bowel ischaemia \nare rare. These clinical features in HSP are likely \nunder-reported in our population. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Hetland LE, Susrud KS, Lindahl KH, Bygum A. Henoch-\nSch\u00f6nlein Purpura: A Literature Review. Acta Derm \nVenereol 2017;97:1160-6.\n\n\n\n2. Pillebout E, Verine J. [Henoch-Sch\u00f6nlein purpura in the \nadult]. Rev Med Interne 2014;35:372-81.\n\n\n\n3. Mills JA, Michel BA, Bloch DA, Calabrese LH, \nHunder GG, Arend WP et al. The American college of \nrheumatology criteria for the classification of Henoch-\nSchonlein purpura. Arthritis Rheum 1990;33:1114-21\n\n\n\n4. Gardner-Medwin JM, Dolezalova P, Cummins C, \nSouthwood TR. Incidence of Henoch\u2013Sch\u00f6nlein purpura, \nKawasaki disease, and rare vasculitides in children of \ndifferent ethnic origins. Lancet 2002;360:1197-202.\n\n\n\n5. Arkachaisri T, Tang SP, Daengsuwan T, Phogsamart G, \nVilaiyuk S, Charuvanij S et al. Paediatric rheumatology \nclinic population in Southeast Asia: are we different? \nRheumatology 2016;56:390-8.\n\n\n\n6. Gardner-Medwin JM, Dolezalova P, Cummins C, \nSouthwood TR. Incidence of Henoch-Sch\u00f6nlein purpura, \nKawasaki disease, and rare vasculitides in children of \ndifferent ethnic origins. Lancet 2002;360:1197-202.\n\n\n\n7. Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, \nNochy D. Henoch-Sch\u00f6nlein Purpura in adults: outcome \nand prognostic factors. J Am Soc Nephrol 2002;13:1271-\n8.\n\n\n\n8. Yong AM, Lee SX, Tay YK. The profile of adult onset \nHenoch\u2013Sch\u00f6nlein purpura in an Asian population. Int J \nDermatol 2015;54:1236-41.\n\n\n\n9. Lu S, Liu D, Xiao J, Yuan W, Wang X, Zhang X et \nal. Comparison between adults and children with \nHenoch\u2013Sch\u00f6nlein purpura nephritis. Pediatr Nephrol \n2015;30:791-6.\n\n\n\n10. Audemard-Verger A, Terrier B, Dechartres A, Chanal \nJ, Amoura Z, Le Gouellec N et al. Characteristics and \nManagement of IgA Vasculitis (Henoch-Sch\u00f6nlein) in \nAdults: Data From 260 Patients Included in a French \nMulticenter Retrospective Survey. Arthritis Rheumatol \n2017;69:1862-70.\n\n\n\n11. St John J, Vedak P, Garza-Mayers AC, Hoang MP, \nNigwekar SU, Kroshinsky D. Location of skin lesions \nin Henoch-Sch\u00f6nlein purpura and its association with \nsignificant renal involvement. J Am Acad Dermatol \n2018;78:115-20.\n\n\n\n12. Michel BA, Hunder GG, Bloch DA, Calabrese LH. \nHypersensitivity vasculitis and Henoch\u2013Sch\u00f6nlein \npurpura: a comparison between the 2 disorders. J \nRheumatol 1992;19:721-8.\n\n\n\nTable 1. The EULAR/PRINTO/PRES HSP criteria and classification definition14\n\n\n\nCriterion Glossary\nPurpura (mandatory criterion) Purpura (commonly palpable and in crops) or petechiae with lower limbs predominance*, not related to \n\n\n\nthrombocytopenia\nAbdominal pain Diffuse abdominal colicky pain with acute onset assessed by history and physical examination. May include \n\n\n\nintussusception and gastrointestinal bleeding\nHistopathology Typical leucocytoclastic vasculitis with predominant IgA deposit or proliferative glomerulonephritis with \n\n\n\npredominant IgA deposit\nArthritis or arthralgias Arthritis of acute onset defined as joint swelling or joint pain with limitation on motion. \n\n\n\nArthralgia of acute onset defined as joint pain without joint swelling or limitation on motion\nRenal involvement Proteinuria >0.3g/24 hour or >30mmol/mg of urine albumin/creatinine ratio on a spot morning sample.\n\n\n\nHaematuria or red blood cell casts: >5 red blood cells/high power field or red blood cells casts in the urinary \nsediment or \u22652+ on dipstick\n\n\n\nHSP EULAR/PRINTO/PRES classification definition\nPurpura or petechiae (mandatory) with lower limb predominance* and at least one of the\nfour following criteria:\n\n\n\n\u2022\t Abdominal pain\n\u2022\t Histopathology\n\u2022\t Arthritis or arthralgia\n\u2022\t Renal involvement\n\n\n\n* For purpura with atypical distribution a demonstration of an IgA deposit in a biopsy is required.\n\n\n\nEULAR - European League Against Rheumatism; HSP - Henoch\u2013Sch\u00f6nlein purpura; PRES - Paediatric Rheumatology European \nSociety, PRINTO - Paediatric Rheumatology International Trials Organisation.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56\n\n\n\nTa\nbl\n\n\n\ne \n2.\n\n\n\n L\nite\n\n\n\nra\ntu\n\n\n\nre\n re\n\n\n\nvi\new\n\n\n\n o\nf g\n\n\n\nas\ntro\n\n\n\nin\nte\n\n\n\nst\nin\n\n\n\nal\n in\n\n\n\nvo\nlv\n\n\n\nem\nen\n\n\n\nt i\nn \n\n\n\nH\nSP\n\n\n\n.\n\n\n\nA\nut\n\n\n\nho\nr, \n\n\n\nye\nar\n\n\n\n, c\nou\n\n\n\nnt\nry\n\n\n\nSp\nec\n\n\n\nia\nlty\n\n\n\nSt\nud\n\n\n\ny \npe\n\n\n\nri\nod\n\n\n\nn\nSt\n\n\n\nud\ny \n\n\n\npo\npu\n\n\n\nla\ntio\n\n\n\nn\nM\n\n\n\nea\nn \n\n\n\nag\ne \n\n\n\n(r\nan\n\n\n\nge\n)\n\n\n\nin\n y\n\n\n\nea\nrs\n\n\n\n%\n o\n\n\n\nf G\nas\n\n\n\ntr\noi\n\n\n\nnt\nes\n\n\n\ntin\nal\n\n\n\n in\nvo\n\n\n\nlv\nem\n\n\n\nen\nt\n\n\n\nA\nbd\n\n\n\nom\nin\n\n\n\nal\n p\n\n\n\nai\nn\n\n\n\nG\nI b\n\n\n\nle\ned\n\n\n\nIn\ntu\n\n\n\nss\nus\n\n\n\nce\npt\n\n\n\nio\nn\n\n\n\nPe\nrf\n\n\n\nor\nat\n\n\n\nio\nn\n\n\n\nD\nea\n\n\n\nth\nM\n\n\n\nill\ns e\n\n\n\nt a\nl3 , \n\n\n\n19\n90\n\n\n\n, U\nSA\n\n\n\nR\nhe\n\n\n\num\nat\n\n\n\nol\nog\n\n\n\nis\nts\n\n\n\nN\nA\n\n\n\n85\nH\n\n\n\nSP\n17\n\n\n\n.4\n (\u2264\n\n\n\n20\n)\n\n\n\n97\n.6\n\n\n\n71\n.8\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nSa\nul\n\n\n\nsb\nur\n\n\n\ny \net\n\n\n\n a\nl29\n\n\n\n, 1\n99\n\n\n\n9,\n U\n\n\n\nSA\nPe\n\n\n\ndi\nat\n\n\n\nric\nia\n\n\n\nns\n19\n\n\n\n79\n-1\n\n\n\n99\n9\n\n\n\n10\n0\n\n\n\nH\nSP\n\n\n\n*\n5.\n\n\n\n9 \n(1\n\n\n\n-1\n5)\n\n\n\n63\n33\n\n\n\n0\nN\n\n\n\nA\nN\n\n\n\nA\n\n\n\nC\nal\n\n\n\nvi\nno\n\n\n\n e\nt a\n\n\n\nl30\n, 2\n\n\n\n00\n1,\n\n\n\n S\npa\n\n\n\nin\nPe\n\n\n\ndi\nat\n\n\n\nric\nia\n\n\n\nns\n19\n\n\n\n80\n-1\n\n\n\n99\n9\n\n\n\n78\nH\n\n\n\nSP\n\u00a7\n\n\n\n5.\n5 \n\n\n\n(1\n-1\n\n\n\n3)\n73\n\n\n\n.1\n30\n\n\n\n.8\n1.\n\n\n\n28\nN\n\n\n\nA\nN\n\n\n\nA\n\n\n\nPi\nlle\n\n\n\nbo\nut\n\n\n\n e\nt a\n\n\n\nl,6  2\n00\n\n\n\n2,\n F\n\n\n\nra\nnc\n\n\n\ne\nIn\n\n\n\nte\nrn\n\n\n\nal\n M\n\n\n\ned\nic\n\n\n\nin\ne\n\n\n\n19\n83\n\n\n\n-2\n00\n\n\n\n0\n25\n\n\n\n0\nH\n\n\n\nSP\n w\n\n\n\nith\n \n\n\n\nne\nph\n\n\n\nrit\nis\n\n\n\n50\n\u00b6  \n\n\n\n(1\n5-\n\n\n\n86\n)\n\n\n\n48\n24\n\n\n\n.4\nN\n\n\n\nA\nN\n\n\n\nA\n2.\n\n\n\n8\n\n\n\nC\nha\n\n\n\nng\n e\n\n\n\nt a\nl31\n\n\n\n, 2\n00\n\n\n\n4,\n T\n\n\n\nai\nw\n\n\n\nan\nPe\n\n\n\ndi\nat\n\n\n\nric\nia\n\n\n\nns\n19\n\n\n\n91\n-2\n\n\n\n00\n1\n\n\n\n26\n1\n\n\n\nH\nSP\n\n\n\n*\n6.\n\n\n\n9 \n(1\n\n\n\n-2\n0)\n\n\n\n58\n17\n\n\n\n.6\n0.\n\n\n\n38\n0.\n\n\n\n38\nN\n\n\n\nA\n\n\n\nC\nhe\n\n\n\nn \net\n\n\n\n a\nl18\n\n\n\n, 2\n00\n\n\n\n4,\n T\n\n\n\nai\nw\n\n\n\nan\nPa\n\n\n\ned\nia\n\n\n\ntri\nc \n\n\n\nG\nas\n\n\n\ntro\nen\n\n\n\nte\nro\n\n\n\nlo\ngi\n\n\n\nst\ns\n\n\n\n19\n95\n\n\n\n-2\n00\n\n\n\n0\n20\n\n\n\n8\nH\n\n\n\nSP\n6.\n\n\n\n4 \n(9\n\n\n\nm\no \n\n\n\n\u2013 \n15\n\n\n\n)\n76\n\n\n\n.4\n16\n\n\n\n.8\n0.\n\n\n\n5\n0\n\n\n\n0\n\n\n\nTr\nap\n\n\n\nan\ni e\n\n\n\nt a\nl32\n\n\n\n, 2\n00\n\n\n\n5,\n It\n\n\n\nal\ny\n\n\n\nPe\ndi\n\n\n\nat\nric\n\n\n\nia\nns\n\n\n\n19\n98\n\n\n\n-2\n00\n\n\n\n2\n15\n\n\n\n0\nH\n\n\n\nSP\n*\n\n\n\n6.\n1 \n\n\n\n(1\n-1\n\n\n\n5)\n51\n\n\n\n18\n0.\n\n\n\n6\nN\n\n\n\nA\nN\n\n\n\nA\n\n\n\nA\nal\n\n\n\nbe\nrs\n\n\n\ne \net\n\n\n\n a\nl33\n\n\n\n, 2\n00\n\n\n\n7,\n \n\n\n\nN\net\n\n\n\nhe\nrla\n\n\n\nnd\nPe\n\n\n\ndi\nat\n\n\n\nric\nia\n\n\n\nns\n20\n\n\n\n04\n17\n\n\n\n9\nH\n\n\n\nSP\n6 \n\n\n\n(0\n-1\n\n\n\n8)\n31\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nYo\nng\n\n\n\n e\nt a\n\n\n\nl7 , \n20\n\n\n\n15\n, S\n\n\n\nin\nga\n\n\n\npo\nre\n\n\n\nD\ner\n\n\n\nm\nat\n\n\n\nol\nog\n\n\n\nis\nts\n\n\n\n20\n00\n\n\n\n-2\n01\n\n\n\n1\n48\n\n\n\nH\nSP\n\n\n\n#\n32\n\n\n\n.5\n \n\n\n\n(1\n8-\n\n\n\n66\n)\n\n\n\n31\n4\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nC\nhe\n\n\n\nn \net\n\n\n\n a\nl34\n\n\n\n, 2\n01\n\n\n\n3,\n C\n\n\n\nhi\nna\n\n\n\nPe\ndi\n\n\n\nat\nric\n\n\n\nia\nns\n\n\n\n20\n07\n\n\n\n-2\n01\n\n\n\n0\n12\n\n\n\n0\nH\n\n\n\nSP\n*\n\n\n\n6.\n6 \n\n\n\n(1\n-1\n\n\n\n2)\n56\n\n\n\n.7\n9.\n\n\n\n2\n0.\n\n\n\n8\nN\n\n\n\nA\nN\n\n\n\nA\n\n\n\nC\nal\n\n\n\nvo\n-R\n\n\n\nio\n e\n\n\n\nt a\nl35\n\n\n\n, 2\n01\n\n\n\n4,\n S\n\n\n\npa\nin\n\n\n\nR\nhe\n\n\n\num\nat\n\n\n\nol\nog\n\n\n\nis\nts\n\n\n\n19\n75\n\n\n\n-2\n01\n\n\n\n2\n41\n\n\n\n7\nH\n\n\n\nSP\n\u00a7\n\n\n\n7.\n5\u00b6  \n\n\n\n(8\nm\n\n\n\no \n-8\n\n\n\n7)\n64\n\n\n\n.5\n12\n\n\n\n.9\nN\n\n\n\nA\nN\n\n\n\nA\nN\n\n\n\nA\n\n\n\nLu\n e\n\n\n\nt a\nl8 , \n\n\n\n20\n15\n\n\n\n, C\nhi\n\n\n\nna\nN\n\n\n\nep\nhr\n\n\n\nol\nog\n\n\n\nis\nt\n\n\n\n20\n12\n\n\n\n-2\n01\n\n\n\n3\n20\n\n\n\n8\nH\n\n\n\nSP\n n\n\n\n\nep\nhr\n\n\n\niti\ns\n\n\n\n9.\n8 \n\n\n\n(3\n-2\n\n\n\n0)\n\u00ac5\n\n\n\n0\n\u00ac1\n\n\n\n2\n\u00ac2\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\n75\n40\n\n\n\n.1\n \n\n\n\n(2\n1-\n\n\n\n75\n)\n\n\n\n\u00ac2\n5\n\n\n\n\u00ac8\n\u00ac5\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nA\nud\n\n\n\nem\nar\n\n\n\nd-\nVe\n\n\n\nrg\ner\n\n\n\n e\nt a\n\n\n\nl9  2\n01\n\n\n\n7,\n \n\n\n\nFr\nan\n\n\n\nce\nIn\n\n\n\nte\nrn\n\n\n\nal\n M\n\n\n\ned\nic\n\n\n\nin\ne\n\n\n\n19\n90\n\n\n\n-2\n01\n\n\n\n5\n26\n\n\n\n0\nH\n\n\n\nSP\n50\n\n\n\n.1\n (>\n\n\n\n18\n)\n\n\n\n51\n.9\n\n\n\n16\n.5\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nSt\n Jo\n\n\n\nhn\n e\n\n\n\nt a\nl10\n\n\n\n, 2\n01\n\n\n\n8,\n U\n\n\n\nSA\nD\n\n\n\ner\nm\n\n\n\nat\nol\n\n\n\nog\nis\n\n\n\nts\n20\n\n\n\n00\n-2\n\n\n\n01\n4\n\n\n\n10\n2\n\n\n\nH\nSP\n\n\n\n#\n54\n\n\n\n.7\n \n\n\n\n(1\n8-\n\n\n\n90\n)\n\n\n\n24\n.5\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nN\nA\n\n\n\nH\nSP\n\n\n\n - \nH\n\n\n\nen\noc\n\n\n\nh-\nSc\n\n\n\nh\u00f6\nnl\n\n\n\nei\nn \n\n\n\npu\nrp\n\n\n\nur\na;\n\n\n\n U\nS-\n\n\n\n U\nni\n\n\n\nte\nd \n\n\n\nSt\nat\n\n\n\ne \nof\n\n\n\n A\nm\n\n\n\ner\nic\n\n\n\na;\n G\n\n\n\nI-\n g\n\n\n\nas\ntro\n\n\n\nin\nte\n\n\n\nst\nin\n\n\n\nal\n; N\n\n\n\nA \n\u2013 \n\n\n\nno\nt a\n\n\n\nva\nila\n\n\n\nbl\ne;\n\n\n\n m\no \n\n\n\n- m\non\n\n\n\nth\n\u00b6-\n\n\n\n m\ned\n\n\n\nia\nn;\n\n\n\n *\n - \n\n\n\nAm\ner\n\n\n\nic\nan\n\n\n\n C\nol\n\n\n\nle\nge\n\n\n\n o\nf R\n\n\n\nhe\num\n\n\n\nat\nol\n\n\n\nog\ny \n\n\n\ncr\nite\n\n\n\nri\na;\n\n\n\n \u00a7\n - \n\n\n\nM\nic\n\n\n\nhe\nl e\n\n\n\nt a\nl c\n\n\n\nri\nte\n\n\n\nri\na;\n\n\n\n #\n - \n\n\n\nEu\nro\n\n\n\npe\nan\n\n\n\n L\nea\n\n\n\ngu\ne \n\n\n\nAg\nai\n\n\n\nns\nt R\n\n\n\nhe\num\n\n\n\nat\nis\n\n\n\nm\n/P\n\n\n\nae\ndi\n\n\n\nat\nri\n\n\n\nc \nRh\n\n\n\neu\nm\n\n\n\nat\nol\n\n\n\nog\ny \n\n\n\nIn\nte\n\n\n\nrn\nat\n\n\n\nio\nna\n\n\n\nl T\nri\n\n\n\nal\ns O\n\n\n\nrg\nan\n\n\n\niz\nat\n\n\n\nio\nn/\n\n\n\nPa\ned\n\n\n\nia\ntr\n\n\n\nic\n \n\n\n\nRh\neu\n\n\n\nm\nat\n\n\n\nol\nog\n\n\n\ny \nEu\n\n\n\nro\npe\n\n\n\nan\n S\n\n\n\noc\nie\n\n\n\nty\n (E\n\n\n\nU\nLA\n\n\n\nR/\nPR\n\n\n\nIN\nTO\n\n\n\n/P\nRE\n\n\n\nS)\n c\n\n\n\nri\nte\n\n\n\nri\na\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 June Vol 42\n\n\n\nDermatology\n\n\n\n57\n\n\n\n13. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, \nGross WL et al. Nomenclature of systemic vasculitides. \nProposal of an international consensus conference. \nArthritis Rheum 1994;37:187-92.\n\n\n\n14. Helander SD, De Castro FR, Gibson LE. Henoch\u2013\nSch\u00f6nlein purpura: clinicopathologic correlation of \ncutaneous vascular IgA deposits and the relationship \nto leukocytoclastic vasculitis. Acta Derm Venereol \n1995;75:125-9.\n\n\n\n15. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin \nT, Brik R et al. EULAR/PRINTO/PRES criteria for \nHenoch\u2013Sch\u00f6nlein purpura, childhood polyarteritis \nnodosa, childhood Wegener granulomatosis and \nchildhood Takayasu arteritis: Ankara 2008. Part II: final \nclassification criteria. Ann Rheum Dis 2010;69:798-806.\n\n\n\n16. Ho\u010devar A, Rotar Z, Jur\u010di\u0107 V, Pi\u017eem J, \u010cu\u010dnik S, Vizjak \nA et al. IgA vasculitis in adults: the performance of the \nEULAR/PRINTO/PRES classification criteria in adults. \nArthritis Res Ther 2016;18:58.\n\n\n\n17. Choong CK, Beasley SW. Intra-abdominal manifestations \nof Henoch-Sch\u00f6nlein purpura. J Paediatri Child Health \n1998;34:405-9.\n\n\n\n18. Ellen CE. Gastrointestinal manifestations of Henoch-\nSch\u00f6nlein purpura. Dig Dis Sci 2008;53:2011-9.\n\n\n\n19. Chen SY, Kong MS. Gastrointestinal manifestations and \ncomplications of Henoch-Sch\u00f6nlein purpura. Chang \nGung Med J 2004;27:175-81.\n\n\n\n20. Leelavathi M, Aziz SA, Gangaram HB, Hussein SH. \nCutaneous vasculitis: a review of aetiology and clinical \nmanifestations in 85 patients in Malaysia. Med J Malaysia \n2009;64:210-2.\n\n\n\n21. Latha S, Choon SE, Tey KE, Chee YN. Clinical features \nand prognostic factors of cutaneous vasculitis among \ndermatology patients in Johor Bahru, Malaysia. Med J \nMalaysia 2017;72:345-9.\n\n\n\n22. Jauhola O, Ronkainen J, Koskimies O, Ala-Houhala M, \nArikoski P, H\u00f6ltt\u00e4 T et al. Clinical course of extrarenal \nsymptoms in Henoch-Sch\u00f6nlein purpura: a 6-month \nprospective study. Arch Dis Child 2010;95:871-6. \n\n\n\n23. Gunasekaran TS, Berman J, Gonzalez M. Duodenojejunitis: \nis it idiopathic or is it Henoch- Sch\u00f6nlein purpura without \nthe purpura? J Pediatr Gastroenterol Nutr 2000;30:22-28.\n\n\n\n24. Kamitsuji H, Tani K, Yasui M, Taniguchi A, Taira K, \nTsukada Set al. Activity of blood coagulation factor \nXIII as a prognostic indicator in patients with Henoch-\nSch\u00f6nlein purpura. Efficacy of factor XIII substitution. \nEur J Pediatr 1987;146:519-23.\n\n\n\n25. Kawasaki K, Komura H, Nakahara Y, Shiraishi M, \nHigashida M, Ouchi K. Factor XIII in Henoch-Sch\u00f6nlein \npurpura with isolated gastrointestinal symptoms. Pediatr \nInt 2006;48:413-5.\n\n\n\n26. Amoli MM, Mattey DL, Calvino MC, Garcia-Porrua C, \nThomson W, Hajeer AH et al. Polymorphism at codon \n469 of the intercellular adhesion molecule-1 locus is \nassociated with protection against severe gastrointestinal \ncomplications in Henoch-Sch\u00f6nlein purpura. J Rheumatol \n2001;28:1014-8.\n\n\n\n27. Ronkainen J, Koskimies O, Ala-Houhala M, Antikainen \nM, Merenmies J, Rajantie J et al. Early prednisone therapy \nin Henoch-Sch\u00f6nlein purpura: a randomized, double \nblind, placebo-controlled trial. J Pediatr 2006;149:241-7.\n\n\n\n28. Weiss PF, Feinstein JA, Luan X, Burnham JM, Feudtner \nC. Effects of corticosteroid on Henoch-Sch\u00f6nlein purpura: \na systematic review. Pediatrics 2007;120:1079-87\n\n\n\n29. Wang YJ, Chi CS, Shian WJ. Clinical studies of Henoch- \nSch\u00f6nlein purpura in Chinese Children. Chin Med J \n(Taipei) 1993;51:345-9.\n\n\n\n30. Saulsbury FT. Henoch-Sch\u00f6nlein purpura in children. \nReport of 100 patients and review of the literature. \nMedicine (Baltimore) 1999;78:395-409.\n\n\n\n31. Calvino MC, Llorca J, Garcia-Porrua C, Fernandez-\nIglesias JL, Rodriguez-Ledo P, Gonzalez-Gay MA. \nHenoch-Sch\u00f6nlein purpura in children from northwestern \nSpain: a 20-year epidemiologic and clinical study. \nMedicine (Baltimore) 2001;80:279-90.\n\n\n\n32. Chang WL, Yang YH, Lin YT, Chiang BL. Gastrointestinal \nmanifestations in Henoch- Sch\u00f6nlein purpura: a review of \n261 patients. Acta Paediatr 2004;93:1427-31.\n\n\n\n33. Trapani S, Micheli A, Grisolia F, Resti M, Chiappini E, \nFalcini F et al. Henoch-Sch\u00f6nlein purpura in childhood: \nEpidemiological and clinical analysis of 150 cases over a \n5-year Period and Review of Literature. Semin Arthritis \nRheum 2005;35:143-53.\n\n\n\n34. Aalberse J, Dolman K, Ramnath G, Pereira RR, \nDavin JC. Henoch\u2013Sch\u00f6nlein purpura in children: an \nepidemiological study among Dutch paediatricians \non incidence and diagnostic criteria. Ann Rheum Dis \n2007;66:1648-50.\n\n\n\n35. Chen O, Zhu XB, Ren P, Wang YB, Sun RP, Wei DE. \nHenoch-Sch\u00f6nlein Purpura in children: clinical analysis \nof 120 cases. Afr Health Sci 2013;13:94-9.\n\n\n\n36. Calvo-Rio V, Loricera J, Mata C, Martin L, Ortiz-Sanjuan \nF, Alvarez L et al. Henoch-Sch\u00f6nlein Purpura in Northern \nSpain: clinical spectrum of the disease in 417 patients \nfrom a single center. Medicine (Baltimore) 2014;93:106-\n13.\n\n\n\n\n\n\n\n\nMJD 2019 June Vol 42\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58\n\n\n\nACKNOWLEDGEMENT\nJune Issue 2019\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Dr Azura Mohd Affandi\n4. Dr Ch\u2019ng Chin Chwen\n5. Dr Chan Lee Chin\n6. Dr Chang Choong Chor\n7. Dr Chong Yew Thong\n8. Dr Dawn Ambrose\n9. Assoc Professor Dr Felix Yap Boon Bin\n10. Dr Henry Foong Boon Bee\n11. Dr Khor Yek Huan\n12. Dr Kwan Zhenli\n13. Dr Lo Kang Shang Chit\n14. Dr Ng Su Yuen\n15. Dr Ng Ting Guan\n16. Dato\u2019 Dr Noor Zalmy Azizan\n17. Dr Oh Hoey Hoey\n18. Dr Rajalingam Ramalingam\n19. Dr Sabeera Begum\n20. Dr Tang Jyh Jong\n21. Dr Tarita Taib\n\n\n\n\n\n"
"\n\n\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine \nand surgery in the form of original articles, research \npapers, case reports and correspondence. Contributions \nare accepted for publication on condition that they are \nsubmitted exclusively to the Malaysian Journal of \nDermatology. The Publisher and Editors cannot be held \nresponsible for errors or any consequences arising from \nthe use of information contained in this journal; the views \nand opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication \nof advertisements constitute any endorsement by the \npublisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of \nDermatology can be sent to:\ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more \nthan 2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, \nan Introduction, Materials and Methods, Results, \nDiscussion, Conclusion and References. A Structured \nAbstract of not more than 250 words must be included. It \nshould consist of four paragraphs, labelled Background, \nMethods, Results and Conclusion. It should describe \nthe problem studies, how the study was performed, the \nmain results, and what the author(s) concluded from the \nresults.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the \nliterature, and references should not exceed 100 in \nnumber. Tables, diagrams, and selected figures are often \nhelpful. The length is left to the judgment of the author, \nalthough it generally should not exceed 5000 words. \nTopics may include updates in clinically relevant basic \nscience and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the \ntitle of the paper, the author(s)\u2019 name(s), degrees, and \naffiliation(s), the category of the article, the number of \nfigures and tables, and three key words for indexing \npurposes. The name and full postal address (including \na street address), phone and fax numbers and an email \naddress of the corresponding author who will be \nresponsible for reading the proofs must also be given \non the title page. The author(s) must also declare any \naffiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in \nthe subject matter or materials discussed in the manuscript \non this page.\n\n\n\nAll measurements should be according to the metric \nsystem. If confusion could result, please include other \nmeasurement systems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they \nappear in the manuscript. References from journals \nshould include: (1) name(s) followed by the initials of \nthe author(s), up to six authors: if more than six authors, \ninclude the first six authors followed by et al.; (2) title of \npaper; (3) title of the journal as abbreviated in the Index \nMedicus; (4) year of publication; (5) volume number; (6) \nfirst and final page numbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: \nA Hospital Kuala Lumpur experience. Malaysian J \nDermatol 2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and \ncompleteness of all references; incomplete references \nmay result in a delay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include \nessential information. Drawings, graphs, and formulas \nshould be submitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case \nof photomicrographs, the stain type and original \nmagnification should be stated. Each figure should bear \na reference number corresponding to a similar number \nin the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and \nopinions expressed do not necessarily reflect those of \nthe publisher and Editors, neither does the publication \nof advertisements constitute any endorsement by the \npublisher and Editors of the products advertised.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\nREVIEW ARTICLE CASE REPORT\n\n\n\nPsoriasis Patients with Human Immunodeficiency \nVirus Infection: Data from the Malaysian Psoriasis \nRegistry\nTeh YC, Robinson S, Tan WC, Kwan ZL, Tang MM\n\n\n\nPrevalence and Types of Mucocutaneous Disorders, \nTheir Correlation to CD4 Count and Their Impact \non Quality of Life in Adults with HIV Infection\nLim YT, Tey KE, Choon SE\n\n\n\nPrevalence of Atopic Dermatitis Among Primary \nSchool Children and Its Impact on Quality of Life \nin Kuching, Sarawak\nLee SE, Foo SY, Badaruddin NSF, Bujang MA, \nMuniandy P\n\n\n\nThe Association of Skin and Nasal Colonisations \nof Staphylococcus aureus in Children with Atopic \nDermatitis with Disease Severity and Its Impact on \nQuality of Life\nLim JH, Mohamad AR, Tey KE\n\n\n\nA 5-years Retrospective Study on Narrowband \nUltraviolet B (NBUVB) Phototherapy Utilisation \nExperience in A Tertiary Hospital in East Malaysia\nTeo HG, Kiing JW, Muniandy P\n\n\n\n2\n\n\n\n11\n\n\n\n21\n\n\n\n31\n\n\n\n38\n\n\n\nDermoscopy of Dilated Pore of Winer\nBasavapura Madegowda S, Somaiah A Savitha\n\n\n\nCalcinosis Cutis Secondary to Trauma in a Patient \nwith Systemic Lupus Erythematosus and Ovarian \nCancer\nMashor M, Azizan NZ, Lee BR\n\n\n\nQuinacrine: An Effective Addition to the Treatment \nof Refractory Cutaneous Lupus Erythematosus\nDing HJ, Ong SG\n\n\n\nCutaneous Serratia Marcescens Infection - A Rare \nCase Report\nYew KM, Ong SSS, Ismail M, Tang JJ\n\n\n\nSymmetrical Flexural and Intertriginous \nExanthema: A Rare Manifestation Associated with \nCOVID-19 Infection\nGoh JY, Chin HH, Chin PW, Zaid M\n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n43\n\n\n\n46\n\n\n\n49\n\n\n\n52\n\n\n\n55\n\n\n\n\n\n\n\n\nMalaysian Journal of DermatologyMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n1\n\n\n\nEditor-in-Chief\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, M Adv Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2020 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm\nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nExecutive Committee \nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPresident\nDr Sabeera Begum, MMed - Vice President\nDr Tan Wooi Chiang, Adv M Derm - Secretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDr Chan Lee Chin, MMed - Past President\nDr Tang Jyh Jong, Adv M Derm -\nCommittee Member\n\n\n\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\nDr Teoh Tze Yuen, Adv M Derm - \nCommittee Member\nDr Nazirin Ariffin - Committee Member\n\n\n\nDermatological Society of Malaysia\nMedical Academics of Malaysia, Unit 1.6, Level \n1, Enterprise 3B, Technology Park Malaysia, \nJalan Innovasi 1, Lebuhraya Puchong-Sg Besi, \nBukit Jalil, 57000 Kuala Lumpur, Malaysia\n\n\n\n1\n\n\n\nEditor-in-Chief\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor\nDr Tang Min Moon\nMRCP, Adv M Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm     \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur\n\n\n\nExecutive Committee\nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPresident\nDr Sabeera Begum, MMed - Vice President\nDr Tan Wooi Chiang, Adv M Derm - Secretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDr Chan Lee Chin, MMed - Past President \nDr Tang Jyh Jong, Adv M Derm - Committee \nMember\n\n\n\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\nDr Teoh Tze Yuen, Adv M Derm - Committee \nMember\nDr Nazirin Ariffin - Committee Member\n\n\n\nDermatological Society of Malaysia\nMedical Academics of Malaysia, Unit 1.6, Level\n1, Enterprise 3B, Technology Park Malaysia,\nJalan Innovasi 1, Lebuhraya Puchong-Sg Besi,\nBukit Jalil, 57000 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2021 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nORIGINAL ARTICLE\n\n\n\nPsoriasis Patients with Human Immunodeficiency Virus Infection: \nData from the Malaysian Psoriasis Registry\nYeon Chiat Teh1, MRCP, Suganthy Robinson1, AdvMDerm, Wooi Chiang Tan2, AdvMDerm, Zhenli Kwan3, AdvMDerm, \nMin Moon Tang1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia  \n2Department of Dermatology, Hospital Pulau Pinang, Penang, Malaysia\n3Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n\n\n\nAbstract \nBackground\nPsoriasis can be a presenting feature of human immunodeficiency virus (HIV) infection. Our objective \nwas to determine the frequency of HIV infection among patients with psoriasis and to describe the \nclinical features, treatment and quality of life in this population.\n\n\n\nMethods\nThis is a multi-centre retrospective cross-sectional study of psoriasis patients who were registered to \nthe Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018.\n\n\n\nResults\nOf a total of 21,735 patients registered, 105 (0.5%) had HIV infection. Among these patients, 90 \n(85.0%) were male, mean age was 40.90 \u00b1 10.85 years, and plaque psoriasis was the most frequently \nencountered presentation (85.7%). Significantly more patients with HIV had severe psoriasis (61.3% \nvs 49.9%, p=0.043), face and neck (62.7% vs 51.4%, p=0.022) involvement, and nail disease (69.9% vs \n56.2%, p=0.005) compared to those without HIV. Only n patients (8.7%) had psoriatic arthropathy, and \nonly 9 (8.8%) received systemic therapy, namely acitretin and methotrexate. None received a biologic, \nand only one patient was treated with narrowband ultraviolet-B therapy. The mean Dermatology Life \nQuality Index (DLQI) score at enrolment was 10.98 \u00b1 7.07 for the HIV cohort compared to 8.68 \u00b1 \n6.60 for the non-HIV cohort (t=2.190, p=0.029). More patients with HIV reported a DLQI score >10 \ncompared to those without HIV (51.5% vs 40.2%, p=0.021).\n\n\n\nConclusion\nThe frequency of HIV infection among patients with psoriasis in the MPR was 0.5%. Patients with \nHIV had more severe disease, more nail, face and neck involvement, and greater impairment of quality \nof life. Treatment of HIV patients with psoriasis remains conservative in Malaysia.\n\n\n\nKey words: Psoriasis, Human immunodeficiency virus, Acquired immunodeficiency syndrome\n\n\n\nIntroduction\nPsoriasis is a chronic, immune-mediated, \ninflammatory skin disease, in which the \naetiopathogenesis is unclear.1,2 It can be a presenting \nfeature of human immunodeficiency virus (HIV) \ninfection and disease severity may reflect the state \nof immune dysfunction.3 Psoriasis in HIV patients \nis often more severe and refractory to treatment.4\n\n\n\nCorresponding Author\nDr Teh Yeon Chiat\nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur, Malaysia.\nEmail: tehyeonchiat@yahoo.com\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 462\n\n\n\n\n\n\n\n\nPrevalence of psoriasis among HIV patients ranges \nfrom 2-3% in the western cohort,2,5 similar to the \nprevalence in the general population.4,6 Although \nthere are many epidemiological studies on psoriasis, \ndata on HIV-infected psoriasis patients are lacking. \nThe aim of this study was to determine the prevalence \nof HIV infection among patients with psoriasis \nin Malaysia, and to describe the clinical features, \ntreatment and quality of life in this population.\n\n\n\nMaterials and Methods\nThis was a multicentre retrospective cross-sectional \nstudy of psoriasis patients who were entered into \nto the Malaysian Psoriasis Registry (MPR) from \nJanuary 2007 to December 2018. Psoriasis patients \nhad to have two positive HIV antibody tests to be \ndiagnosed as having HIV infection. The MPR is a \nprospective systematic collection of data of psoriasis \npatients in Malaysia from 32 public hospitals and 2 \nprivate hospitals. All psoriasis patients were enrolled \nat their first visit and those on systemic treatment or \nphototherapy were seen every 6 months thereafter f. \nThis study was approved by the Malaysian Medical \nResearch and Ethics Committee (MREC) number \nNMRR-20-802-53706.\n\n\n\nBody surface area (BSA) involvement was used to \nassess disease severity, whereas the Dermatology \nLife Quality Index (DLQI) was used to assess \nthe impact of psoriasis on quality of life.7 Severe \nimpact of psoriasis on health-related quality of life \n(HRQoL) is defined as a DLQI score of more than \n10.8 Body surface area (BSA) involvement of more \nthan 10% with or without a DLQI score of more \nthan 10 is also considered severe psoriasis.8\n\n\n\nDescriptive analyses were performed for \ncharacterizing sociodemographic characteristics, \nclinical pattern, and treatment modalities of the \npatients. Data were tabulated and analysed using \nIBM\u00ae Statistical Package for the Social Sciences \n(SPSS) Statistics for Windows, Version 24.0. \nArmonk, NY: IBM Corp. Descriptive data were \npresented as numbers and percentages for categorical \nvariables. Mean with standard deviation (SD) \nwas used for continuous data. Pearson Chi-square \ntest and Fisher\u2019s exact test were used to analyse \ncategorical data where applicable. Comparison of \nmeans was performed using independent sample \nT-test. A p value of <0.05 was considered as \nstatistically significant. \n\n\n\nResults \nThere were 105 patients (0.5%) reported to be \ninfected with HIV among a total 21,735 psoriasis \npatients registered in the MPR between January \n2007 and December 2018. Sociodemographic \ncharacteristics are presented in Table 1. There was a \nsignificantly higher proportion of males in the HIV \ngroup compared to those not infected with HIV \n(86.7% vs 55.3%, p<0.001). The mean age for HIV-\ninfected patients was 40.95 \u00b1 10.93 years. Overall, \n11.4% of HIV-infected patients had a positive family \nhistory of psoriasis, compared to 22.4% in the \nnon-HIV infected group (p=0.004). About twenty \npercent of the HIV-infected psoriasis patients were \nobese, with a body mass index (BMI) \u2265 25mg/kg2 \n\n\n\n(Table 2). Other comorbidities associated with the \nHIV-infected cohort were dyslipidaemia (13.1%), \nhypertension (7.8%), diabetes mellitus (4.9%) and \nischemic heart disease (2.0%). Six patients had co-\ninfection with either hepatitis B or hepatitis C.\n\n\n\nTable 1. Demographic characteristics of study population\n\n\n\nDemographic Characteristic HIV\nn=105 \n(%)\n\n\n\nNon-\nHIV\n\n\n\nn=21630\n\n\n\np-value\n\n\n\nAge (years) Mean (SD) 40.95 \n(10.93)\n\n\n\n41.80 \n(17.48)\n\n\n\np=0.621\n\n\n\nMin, Max 19, 82 1, 92\n\n\n\nGender Male 91 \n(86.7)\n\n\n\n11967 \n(55.3)\n\n\n\np<0.001\n\n\n\nFemale 14 \n(13.3)\n\n\n\n9663 \n(44.7)\n\n\n\n*Ethnicity Malay 39 \n(37.5)\n\n\n\n11762 \n(54.4)\n\n\n\np<0.001\n\n\n\nChinese 42 \n(40.4)\n\n\n\n4112 \n(19.0)\n\n\n\np<0.001\n\n\n\nIndian 13 \n(12.5)\n\n\n\n3537 \n(16.4)\n\n\n\np=0.288\n\n\n\nOthers 10 \n(9.6)\n\n\n\n2210 \n(10.2)\n\n\n\np=0.840\n\n\n\nFamily history of psoriasis 12 \n(11.4)\n\n\n\n4841 \n(22.4)\n\n\n\np=0.004\n\n\n\nComorbidities Dyslipidaemia 13 \n(13.1)\n\n\n\n3401 \n(15.7)\n\n\n\np=0.584\n\n\n\nHypertension 8 (7.8) 4979 \n(23.0)\n\n\n\np<0.05\n\n\n\nDiabetes mellitus 5 (4.9) 3323 \n(16.4)\n\n\n\np<0.05\n\n\n\nIschemic heart \ndisease\n\n\n\n2 (2.0) 1015 \n(4.7)\n\n\n\np=0.345\n\n\n\nCerebrovascular \ndisease\n\n\n\n0 (0 ) 311(1.4) p=0.401\n\n\n\nHIV, human immunodeficiency virus; SD, standard deviation; *HIV \nn=104, Non-HIV n=21621\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nTable 2. Clinical characteristics of study population\n\n\n\nClinical Characteristic HIV\nn=98 \n(%)\n\n\n\nNon-\nHIV\n\n\n\nn=20355 \n(%)\n\n\n\np-value\n\n\n\nType of \npsoriasis\n\n\n\nPlaque 84 \n(85.7)\n\n\n\n18905 \n(92.9)\n\n\n\np=0.002\n\n\n\nGuttate 9 (9.2) 729 (3.5) p=0.003\n\n\n\nErythrodermic 4 (4.1) 384 (1.9) p=0.116\n\n\n\nPalmoplantar \nnon-pustular\n\n\n\n1 (1.0) 85 (0.4) p=0.339\n\n\n\nInverse 0 (0) 104 (0.5) p=1.000\n\n\n\nGeneralised \npustular\n\n\n\n0 (0) 92 (0.5) p=1.000\n\n\n\nLocalised \npustular\n\n\n\n0 (0) 56 (0.3) p=1.000\n\n\n\n#Body mass \nindex (BMI) \n(kg/m2)\n\n\n\n<18.5 21 \n(22.1)\n\n\n\n1358 \n(7.2)\n\n\n\np<0.001\n\n\n\n18.5-22.9 38 \n(40.0)\n\n\n\n4129 \n(21.9)\n\n\n\np<0.001\n\n\n\n23-24.9 17 \n(17.9)\n\n\n\n2730 \n(14.5)\n\n\n\np=0.348\n\n\n\n>25 19 \n(20.0)\n\n\n\n10616 \n(56.4)\n\n\n\np<0.001\n\n\n\nbBody surface \narea (BSA) \n(%)\n\n\n\n<5 30 \n(36.6)\n\n\n\n7392 \n(44.8)\n\n\n\np=0.134\n\n\n\n5-10 19 \n(23.2)\n\n\n\n5173 \n(31.4)\n\n\n\np=0.110\n\n\n\n11-90 28 \n(34.1)\n\n\n\n3498 \n(21.2)\n\n\n\np=0.004\n\n\n\n>90 5 (6.1) 422 (2.6) p=0.044\ncFace and neck involvement 64 \n\n\n\n(62.7)\n10439 \n(51.4)\n\n\n\np=0.022\n\n\n\ndNail disease 72 \n(69.9)\n\n\n\n11797 \n(56.2)\n\n\n\np=0.005\n\n\n\neScalp 87 \n(85.3)\n\n\n\n16674 \n(81.2)\n\n\n\np=0.293\n\n\n\nfPsoriatic arthropathy 9 (8.7) 2747 \n(13.1)\n\n\n\np=0.180\n\n\n\ngDLQI >10 53 \n(51.5)\n\n\n\n7909 \n(40.2)\n\n\n\np=0.021\n\n\n\nhSevere psoriasis (BSA >10 and/\nor DLQI >10)\n\n\n\n49 \n(61.3)\n\n\n\n7553 \n(49.9)\n\n\n\np=0.043\n\n\n\nHIV, human immunodeficiency virus; BMI, body mass index; BSA, \nbody surface area; DLQI, dermatology life quality index; #HIV n=95, \nnon-HIV n=18833; bHIV n=82, non-HIV n=16485; cHIV n=102, non-\nHIV n=20301; dHIV n=103, non-HIV n=20988; eHIV n=102, non-HIV \nn=20529; fHIV n=104, non-HIV n=20973; gHIV n=103, non-HIV \nn=19651; hHIV n=80, non-HIV n=15128\n\n\n\nThe most common type of psoriasis in our HIV \ncohort was plaque psoriasis (85.7%), followed by \nguttate psoriasis (9.2%), erythrodermic psoriasis \n(4.1%) and non-pustular palmoplantar psoriasis \n(1.0%), as shown in Table 2. Non-plaque forms \nof psoriasis were significantly more frequently \nencountered in HIV-infected psoriasis patients \n(p=0.002), with guttate and erythrodermic psoriasis \n\n\n\nreported at a higher rate among those with HIV \ninfection. Scalp involvement in the HIV cohort \n(85.3%) was slightly higher compared to the non-\nHIV group (81.2%). HIV-infected psoriasis patients \nreported a higher rate of face and neck involvement \n(62.7% vs 51.4%) (p=0.022) and nail disease \n(69.9% vs 56.2%) (p=0.005) compared to non-\nHIV psoriasis patients. Psoriatic arthropathy was \nobserved in 8.7% of the HIV cohort, less frequently \nthan in the non-HIV-infected group (13.1%). Oligo-\nmono-arthropathy was the most common type of \npsoriatic arthropathy in both groups, followed by \ndistal hand joint involvement and symmetrical \nrheumatoid-like polyarthropathy.\n\n\n\nIn terms of disease severity, 40.2% of HIV-infected \npsoriasis patients had severe disease with a BSA \nof >10%, compared to 23.8% in the non-HIV \ninfected group (p=0.004). The rate of erythroderma \nwas observed to be significantly higher in the HIV \ncohort (6.1% vs 2.6%, p=0.044).\n\n\n\nFifty-three (51.5%) of the HIV-infected psoriasis \npatients had a DLQI score of more than 10 at \nenrolment versus 40.2% in the non-HIV group. The \nmean DLQI score for the HIV cohort was 11.58 \u00b1 \n7.02, which was significantly higher compared to \nthe non-HIV psoriasis group (9.61 \u00b1 6.75 p=0.003). \nThe domains that displayed a significant difference \nbetween the two groups were personal relationship \n(70.0% vs 56.4%, p=0.022) and work and school \n(65.8% vs 46.1%, p<0.001) (Table 3). In aggregate, \n61.3% of HIV-infected psoriasis patients had severe \npsoriasis defined by a BSA of more than 10% and/\nor a DLQI of more than 10, compared to 49.9% in \nthe non-HIV infected cohort (p=0.043).\n\n\n\nSimilar to the non-HIV cohort, the majority of the \nHIV patients were prescribed topical treatment \nwith topical corticosteroids and emollients as the \nmainstays of treatment (Table 4).\n\n\n\nOnly 9 patients (8.8%) in the HIV-infected \ncategory received systemic therapy (7 (6.9%) were \nprescribed acitretin and 2 (2%) were prescribed \nmethotrexate), compared to 14.3% of the non-HIV-\ninfected psoriasis patients. Only one HIV-infected \npsoriasis patient underwent narrow band ultra-\nviolet B (NBUVB) phototherapy treatment. None \nof the HIV-infected patients received a biologic \ntreatment, whereas 0.4% of non-HIV patients were \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 464\n\n\n\n\n\n\n\n\ntreated with a biologic agent.\n\n\n\nTable 3. Comparison of Dermatology Life Quality \nIndex (DLQI) scores between patients with human \nimmunodeficiency virus infection and those without\n\n\n\nDomain HIV (%) Non-HIV (%) p-value\ntPhysical symptoms and \nfeeling\n\n\n\n96.1 94.8 p=0.324\n\n\n\nvDaily activities 83.3 76.0 p=0.402\nwLeisure 83.3 75.2 p=0.318\nxWork and school 65.8 46.1 p<0.001\nyPersonal relationship 70.0 56.4 p=0.022\nzTreatment 70.7 60.8 p=0.149\n\n\n\nHIV, human immunodeficiency virus; DLQI, dermatology life quality \nindex; tHIV n=102, non-HIV n=19583; vHIV n=96, non-HIV n=18725; \nwHIV n=90, non-HIV n=17122; xHIV n=73, non-HIV n=12879; yHIV \nn=70, non-HIV n=14580, zHIV n=92, non-HIV n=18590\n\n\n\nTable 4. Types of treatment for psoriasis in study \npopulation\n\n\n\nTreatment Option HIV\nn=104 \n(%)\n\n\n\nNon-HIV\nn=20792 \n\n\n\n(%)\n\n\n\np-value\n\n\n\nTreatment Topical 96 (92.3) 19733 (94.9) p=0.23\n\u03b1Phototherapy 1 (1.0) 550 (2.7) p=0.282\n\u03b2Systemic \ntherapy\n\n\n\n9 (8.8) 2949 (14.3) p=0.116\n\n\n\nAcitretin 7 (6.9) 574 (2.8) p=0.013\n\n\n\nMethotrexate 2 (2.0) 2289 (11.1) p=0.003\n\n\n\nSystemic \ncorticosteroids\n\n\n\n0 179 (0.9) p=0.345\n\n\n\nCyclosporin 0 144 (0.7) p=0.398\n\n\n\nBiologics 0 78 (0.4) p=0.534\n\n\n\nHydroxyurea 0  23(0.1) p=0.736\n\n\n\nHIV, human immunodeficiency virus; \u03b1HIV n=103, non-HIV n=20461; \n\u03b2HIV n=102, non-HIV n=20461\n\n\n\nDiscussion\nThe reported prevalence of psoriasis varies in \ndifferent regions of the world based on different \nepidemiological studies.4,6,9,10 In Western countries, \nit is estimated to affect 2-4% of the general \npopulation1,11 and the prevalence of psoriasis among \nHIV patients ranges from 2-3%.2,5,12 A literature \nsearch revealed limited studies on the prevalence \nof HIV in psoriasis patients. It had reported that \n1.8% of psoriasis patients in Thailand were infected \nwith HIV,13 which is slightly higher than the 1.1% \nprevalence of HIV in the general population there.14 \n\n\n\nIt was estimated that there were 87,041 people \nliving with HIV in Malaysia with a prevalence of \n0.4%.14 The frequency of HIV infection among \nindividuals with psoriasis in our cohort (0.5%) \n\n\n\nwas comparable to the prevalence of HIV in the \ngeneral population of Malaysia.14 The lower rate \nof HIV infection among psoriasis patients in the \nMPR (0.5%) compared to Thailand was possibly be \ndue to voluntary notification, non-mandatory HIV \ntesting among psoriasis patients or management of \nHIV patients with mild psoriasis by primary care \ndoctors who are not registered with the registry. A \nFrench survey study revealed that currently health \npractitioners only screen psoriasis patients for HIV \nbased on risk factors such as high-risk behaviour, \nclinical severity and assessment prior to systemic \nand biologic therapy.15 An updated guideline on \nthe timing to screen for HIV in psoriasis patients is \nneeded to ensure HIV infection is detected early and \nmanaged accordingly.\n\n\n\nThe clinical manifestations of psoriasis observed in \nHIV-infected patients appear to be similar to those \nin non-HIV-infected persons in our cohort. Plaque \npsoriasis is the most common presentation in the \nHIV psoriasis population in Western countries.16 \n\n\n\nHowever, psoriasis patients with HIV can present \nwith multiple subtypes concurrently.3,4,17 Several \nstudies from the United States of America, the \nUnited Kingdom and South Africa reported that \nguttate, inverse and erythrodermic psoriasis occur \nwith higher frequency in HIV-infected psoriasis \npatients.3,4,16 Similar findings were also evident in \nour cohort, with the  exception of inverse psoriasis \nas none was reported. \n\n\n\nInterestingly, we observed a greater number in the \nHIV cohort having face and neck involvement. The \nliterature revealed that sebo-psoriasis is a psoriasis \nvariant associated with increased incidence in \nHIV infection.17,18 Sebo-psoriasis represents a \nclinical overlap between seborrheic dermatitis and \nplaque psoriasis, affecting the flexural areas, scalp \nand retro- auricular region.17,18 Lesions tend to \nbe more greasy and less scaly compared to scalp \npsoriasis.17 The MPR, however, does not capture \nthis phenotypic variant of psoriasis. Hence, sebo-\npsoriasis may be labelled as flexural psoriasis or as \npsoriasis involving the face and neck. It is important \nto recognise sebo-psoriasis as a separate entity as it \ncan occur in HIV patients with a normal CD4 count \nand/or those with a suppressed viral load. A high \nindex of suspicion among patients presenting with \nprominent sebo-psoriasis is therefore paramount as \nit may act as an indicator of early HIV infection.18 \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nAs sebo-psoriasis is reported to respond well to \ntopical or systemic antifungal treatment18, could be \noverlooked easily.\n\n\n\nUp to 50% of psoriasis patient have nail \ninvolvement13,19 and lifetime incidence is up to \n90%.20  Common manifestations  include onycholysis \n(69.6%) and pitting of the nails (62.6%).13 It has \nbeen reported that 32% of HIV-infected psoriasis \npatients, have nail involvement21, which may \npresent in a similar manner to nail psoriasis in non-\nHIV infected patients  (i.e. superficial pitting, distal \nand lateral onycholysis, subungual hyperkeratosis \nand onychodystrophy).3,22 Interestingly, in our \nstudy, nail disease in the HIV cohort was found \nto be significantly more prevalent than in the non-\nHIV infected cohort. Nail changes in psoriasis \nare strongly associated with arthropathy, which \naffects 23-50% of HIV-positive psoriasis patients \nworldwide.22,23 The prevalence of arthropathy is \nhigher among HIV-infected patients, compared to \nthe general psoriasis population(5.8% to 19%),2,24,25 \n\n\n\nand  it is associated with more severe types of \njoint disease.2,23,25,26 Symmetrical polyarthropathy, \nenthesopathy and dactylitis represent the most \nfrequently observed types of psoriatic arthropathy \nin HIV patients.2,27,28 In contrast, our study revealed \na significantly lower rate of arthropathy among \npatients in the HIV-infected group. The most \ncommon type of arthropathy described in our HIV \ncohort was oligo-arthritis. \n\n\n\nInterestingly we did not observe any cases of either \nlocalized or generalized pustular psoriasis in our \ncohort. Pustular psoriasis may be associated with \nspecific variants of the  IL36RN, AP1S3 and CARD14 \ngenes, resulting in different clinical manifestations \nand treatment response.29 IL36, which is implicated \nin the pathogenesis of pustular psoriasis, has not \nbeen described in HIV infection.30,33 Morar et al. \nobserved a reactive arthritis-like syndrome in HIV-\ninfected patients; these patients presented with \nkeratoderma blenorrhagica with palmoplantar \npsoriasiform plaque.3 Histology of  skin lesions from \nthese patients is identical to that seen in pustular \npsoriasis.3  Mikhail et al reported successful use of \netanercept to treat a case of von Zumbusch pustular \npsoriasis in a  HIV patient on antiretroviral therapy \n(ART) with a CD4 count of 435/\u00b5L.31\n\n\n\nPsoriasis has a detrimental effect on a person\u2019s \n\n\n\nquality of life comparable to other chronic illnesses.32 \nTo our knowledge, there are no other published \ndata assessing DLQI among psoriasis patients with \nHIV. In our study, more than one third of patients \nat enrolment had a DLQI score of more than 10, \nwhich indicates severe impairment in quality of \nlife. The higher mean DLQI among HIV-infected \npatients could be attributed to their manifesting \nmore severe disease compared to non-HIV infected \npatients.4 The DLQI domain most affected was \nphysical symptoms and feelings among both HIV- \nand non-HIV-infected psoriasis patients. In our \nstudy, work and school, and personal relationship \nwere significantly more impaired in the HIV group \ncompared to the non-HIV group. These items could \nbe influenced by other co-morbidities related to \nHIV infection that could cause disturbances in daily \nactivities as well as social interaction with others. \n\n\n\nManagement of psoriasis in HIV patients is \nchallenging due to the abnormal immune status of \npatients at various phases of their disease course.30,33 \nImbalance in the CD8+ to CD4+ ratio in HIV has \nbeen associated with the pathogenesis of psoriasis, \nwhich is CD8+ T-cell mediated.  A low CD4+ T-cell \ncount relative to CD8+ T-cells in the setting of HIV, \nmay lead to a propensity to develop more severe \npsoriasis.34,35 \n\n\n\nSome reports showed that psoriasis may improve \nafter treatment with ART.36-39 Case reports from \nItaly and Chile have reported improvement of \nerythrodermic psoriasis in HIV patients after ART \nwas initiated.36,37 ART as a first line therapy has been \nshown to control the progression of HIV and also \neffectively treat HIV-associated psoriasis, which \ncommonly occurs when CD4+ T-cell counts fall \nbelow 350cells/mm3.4,40 Zidovudine, a thymidine \nanalogue and a nucleoside reverse transcriptase \ninhibitor (NRTI) has also been reported to \nbe beneficial in improving psoriasis in HIV \npatients.16,41 Likewise, antiretroviral combinations \nof protease inhibitors and a non-nucleoside reverse \ntranscriptase inhibitor (NRTI), or two NRTIs plus \nan entry inhibitor, have demonstrated efficacy in \ntreating HIV-associated psoriasis.39 However, data \non neither CD4+ T-cell counts nor the use of ART \nwas available from our registry. \n\n\n\nOn the contrary, there have been reports of \nexacerbation of psoriasis as a manifestation of \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 466\n\n\n\n\n\n\n\n\nimmune reconstitution inflammatory syndrome \n(IRIS) upon commencement of antiretroviral therapy \nin HIV-infected psoriasis patients.35 Flare of plaque \npsoriasis has been reported after commencement \nof ART.35,42 Tripathi et al. reported a HIV-infected \npatient who had IRIS with worsening of the pre-\nexisting psoriasis plaques and acral involvement \nafter switching to new ART (elvitegravir, tenofovir, \ncobicistat and emtricitabine). The patient\u2019s \ncondition improved after ART was reintroduced \nwith concurrent phototherapy using psoralen \nand ultraviolet A therapy together with topical \nclobetasol.42 Another case report from Lebanon \ndescribed the occurrence of psoriasis for the \nfirst time in 2 patients after ART was introduced, \nmanifesting as IRIS.35 However, both patients were \nnot compliant with their ART leading to altered \nCD4+/CD8+ T-cell ratios, which further contributed \nto their psoriasis flare.35 These two scenarios reveal \nthat worsening of psoriasis in the context of IRIS \nmay occur at commencement or interruption of \nART.35\n\n\n\nHIV-infected patients who have mild psoriasis \nwere generally prescribed topical medications, \nsuch as topical corticosteroids, calcipotriene, tar \npreparations and emollients.33 Phototherapy with \nultraviolet (UV) radiation in combination with \nantiretroviral therapy is recommended as a first-\nline treatment for moderate-to-severe psoriasis in \npatients with HIV.4 Phototherapy does not induce \nimmunosuppression and low dose ultraviolet light \nhas been shown to be beneficial in HIV-infected \npatients with skin disease.43,44 However, it was not \nprescribed as a preferred modality in our cohort.  \nReasons for low usage of phototherapy in the HIV-\ninfected cohort could be adherence issues for these \npatients and the lack of access to phototherapy. Of \nnote, the use of phototherapy in HIV patients with \nKaposi\u2019s sarcoma is prohibited as it may lead to \nworsening of Kaposi\u2019s sarcoma.41,45,46 \n\n\n\nA majority of dermatologists were most \ncomfortable with prescribing acitretin, followed \nby phototherapy, for the treatment of psoriasis in \nHIV-infected patients based on a survey in France.15 \n\n\n\nOur data showed that only 10% of HIV-infected \npatients received systemic therapy despite having \nmore severe disease than patients in the non-HIV \ncohort. This showed that our dermatologist was \ncautious in prescribing these agents for fear of \n\n\n\nthe compounded immunosuppressive effect in the \nHIV cohort or hesitancy of HIV patients on ART \nto be on numerous medications. Further studies \nto assess factors contributing to the lack of use of \nsystemic therapy or phototherapy for treating HIV-\ninfected psoriasis patients are needed. Acitretin, \nan oral retinoid, can improve psoriasis signs and \nsymptoms, and is a preferred systemic treatment \noption over methotrexate and cyclosporin by virtue \nof its non-immunosuppressive effect.4,21 Monitoring \nof fasting serum lipid levels is important as risk \nof hypertriglyceridemia and pancreatitis may be \nincreased when oral retinoids are used together with \nantiretroviral medications.4\n\n\n\nTreatment of HIV-infected patients with recalcitrant \npsoriasis who have failed or were unable to tolerate \nfirst line therapy is challenging. Use of methotrexate \nshould be avoided in HIV-infected psoriasis \npatients.51 A report from Duvic et al discouraged the \nuse of methotrexate due to the risk of opportunistic \ninfections.41 Another case series reported \nPneumocystis carinii infection in 2 of 4 patients \ntreated with methotrexate.47 On the other hand, \ntreatment with cyclosporin, a calcineurin inhibitor, \nhad limited reports, though it has been used safely \nand with good responses in HIV-infected psoriasis \npatients.48,49 Of note, monitoring cyclosporin \nlevels may be required as the bioavailability may \nbe increased by the concomitant use of protease \ninhibitors.50 Due to the risk of nephrotoxicity and \nhypertension, short-term use is recommended for up \nto 12 weeks.3 Systemic treatment for HIV-infected \npsoriasis patients should be individualised with \nclose monitoring of the CD4 count and viral load.51 \n\n\n\nAlthough unavailable in Malaysia, apremilast, a \nphosphodiesterase-4 inhibitor is approved for the \ntreatment of moderate to severe psoriasis.49 Data on \nthe usage of apremilast in HIV-infected psoriasis \npatients is scarce. There were a few reports of \nsuccessful treatment of plaque and palmoplantar \npsoriasis in HIV-infected psoriasis patients.53-55 \n\n\n\nSacchelli et al. had also noted improvement in \npsoriatic nail disease in their cohort of patients.56\n\n\n\nThere are no guidelines on the usage of biologics \nin psoriasis patients with HIV. Not with standing, \nbiologic agents are predicted to be safe  in HIV-\ninfected psoriasis patients especially for those \non ART.57 Biologic agents such as etanercept, \nadalimumab, infliximab and ustekinumab have \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nbeen used to treat HIV-infected psoriasis patients \nwith good clinical response, safety outcomes and \ntolerability.40,57,58 Clinical responses among HIV-\ninfected psoriasis patients treated with a biologic are \nreported to be comparable to those with non-HIV-\ninfected psoriasis.31,59,60 Bardazzi et al. suggested \nthat biologic agents may be considered in psoriasis \npatients with stable HIV infection, and with close \nmonitoring of CD4 counts and HIV viral load \nlevels.57 The use of biologic agents for the treatment \nof psoriasis in our cohort study was low among non-\nHIV-infected patients, and no patients in the HIV-\ninfected group were treated with a biologic. Many \nfactors such as budget constraints and policies may \nhave contributed to this. \n\n\n\nLimitations  \nThe registry database does not discern whether \nmore than one type of psoriasis occurred in the same \npatient, as only the predominant type is documented. \nData on antiretroviral therapy, CD4 counts and \nwhether a diagnosis of psoriasis preceded HIV \ninfection, or vice versa, are also not available. As \nwith all retrospective studies, missing data may not \nbe accounted for and causal relationships could not \nbe determined. \n\n\n\nRecommendations\nA prospective study focusing on the evolution of \npsoriasis throughout the different stages of HIV/\nAIDS would be valuable. Research assessing \nsystemic and biological treatments for psoriasis \npatients with HIV infection is needed. Registries \ndedicated to studying HIV-infected psoriasis \npatients should be established to allow for more \ncomprehensive data collection.\n\n\n\nConclusion\nThe prevalence of HIV infection among psoriasis \npatients in the MPR was 0.5%. Most of the HIV-\ninfected psoriasis patients in this cohort had plaque \npsoriasis. Higher proportion of HIV-infected \npatients had more nail, face and neck involvement, \nand more severe disease, which significantly \naffected quality of life. Treatment of psoriasis in \npatients with HIV infection was comparatively \nless aggressive compared to treatment of non-HIV-\ninfected psoriasis patients in the MPR cohort. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nWe would like to acknowledge all contributors for \nproviding MPR data and thank the Director General \nof Health Malaysia for permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. 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Alterations in HIV expression \nin AIDS patients with psoriasis or pruritus treated with \nphototherapy. J Am Acad Dermatol 1999;40:48-60. \n\n\n\n44. Arisi M, Gelmetti A, Foc\u00e0 E, Rossi MT, Rovati C, \nClazavara-Pinton P et al. UVA1 phototherapy as a treatment \noption for plaque psoriasis in HIV\u2010positive patients. \nPhotodermatol Photoimmunol Photomed 2020;36:478-80.\n\n\n\n45. Meola T, Soter NA, Ostreicher R, Sanchez M, Moy JA. \nThe safety of UVB phototherapy in patients with HIV \ninfection. J Am Acad Dermatol 1993;29:216-20. \n\n\n\n46. Gelfand JM, Rudkoff D, Lebwohl M, Klotman ME. Effect \nof UV-B Phototherapy on Plasma HIV Type 1 RNA \nlevel: A self-controlled prospective study. Arch Dermatol \n1998;134:940-5. \n\n\n\n47. Maurer TA, Zackheim HS, Tuffanelli L, Berger TG. The \nuse of methotrexate for treatment of psoriasis in patients \nwith HIV infection. J Am Acad Dermatol 1994;31:372-5.\n\n\n\n48. Allen BR. Use of cyclosporin for psoriasis in HIV-positive \npatient. 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Biologic Therapies in HIV-\ninfected Patients with Psoriasis: An Italian Experience. \nActa Derm Venerol 2017;97:989-90. \n\n\n\n58. Paparizos V, Rallis E, Kirsten L, Kyriakis K. Ustekinumab \nfor the treatment of HIV psoriasis. J Dermatolog Treat \n2012;23:398-9. \n\n\n\n59. Fink DL, Hedley L, Miller RF. Systematic review of the \nefficacy and safety of biological therapy for inflammatory \nconditions in HIV-infected individuals. Int J STD AIDS \n2017;28:110-9.\n\n\n\n60. Cepeda EJ, Williams FM, Ishimori ML, Weisman MH, \nReveille JD. The use of anti-tumour necrosis factor therapy \nin HIV-positive individuals with rheumatic disease. Ann \nRheum Dis 2008;67:710-2.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4610\n\n\n\n\n\n\n\n\nORIGINAL ARTICLE\n\n\n\nPrevalence and Types of Mucocutaneous Disorders, Their Correlation \nto CD4 Count and Their Impact on Quality of Life in Adults with HIV \nInfection\nYee Ting Lim1, MRCP, Kwee Eng Tey1, MRCP, Siew Eng Choon2, FRCP\n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\n2Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Healthy Sciences, Monash University Malaysia, \nJohor Bahru, Johor, Malaysia\n\n\n\nAbstract \nBackground\nData on prevalence and type of mucocutaneous diseases in HIV-positive patients and their impact on \nquality of life (QoL) are sparse. We aim to determine prevalence and type of mucocutaneous disorders, \ntheir correlation to CD4+ counts and impact on QoL for adults with HIV, using the Dermatology Life \nQuality Index (DLQI).\n\n\n\nMethods\nA cross-sectional study of HIV-infected adults seen in HIV and Dermatology Clinic.\n\n\n\nResults\nThe majority (90%) of 174 participants recruited was male. Median age at diagnosis of HIV infection \nwas 29 years (IQR 10). Mucocutaneous disorders were present in 90.2%, out of which 58.6% had \ntwo or more mucocutaneous disorders. Mean CD4+ count was significantly lower in patients with, \ncompared to those without mucocutaneous disorders (363 vs 548 cells/\u00b5L; p=0.030). Infections \naccounted for 67.2% of all mucocutaneous disorders seen, followed by inflammatory dermatoses \n(51.7%), cutaneous adverse drug reactions (17.8%) and neoplasm (2.3%). The five most frequent \nmanifestations were eczema (22.4%), anogenital warts (21.2%), candidiasis (16.7%), dermatophytosis \n(15.5%) and secondary syphilis (12.0%). Oral candidiasis, pruritic papular eruption, drug-induced \nmaculopapular eruption and drug rash with eosinophilia and systemic symptoms were significantly \nmore prevalent in patients with CD4+ counts <200 cells/\u00b5L but anogenital warts were more prevalent \nin patients with CD4+ counts \u2265200 cells/\u00b5L. The mean DLQI score was 8.39 (SD \u00b1 6.83). QoL was \nseverely impaired (DLQI >10) in 34.4%.\n\n\n\nConclusion\nMucocutaneous disorders were common in HIV patients causing significant impairment in quality \nof life. Prevalence co-related with low CD4+ counts. Adequate management of HIV may reduce the \nprevalence of mucocutaneous disorders and improve QoL.\n\n\n\nKey words: Mucocutaneous manifestations, Human immunodeficiency virus infection, CD4+ T-cell counts, Quality of life\n\n\n\nIntroduction\nHuman immunodeficiency virus (HIV) is a retrovirus \nthat cripples immunity by the destruction of CD4+ \n\n\n\nT-lymphocytes.1 The underlying immunodeficiency \npredisposes the HIV-infected patient to a variety \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nCorresponding Author\nDr Lim Yee Ting \nDepartment of Dermatology,\nHospital Sultanah Aminah,\nJalan Persiaran Abu Bakar Sultan,\n80100 Johor Bahru, Malaysia.\nEmail: yeeting8899@yahoo.com\n\n\n\nof mucocutaneous disorders.2,3 Furthermore, \nthe incidence and severity of these disorders \nincreases as the HIV infection worsens.2,3 Although \nmucocutaneous diseases are rarely life-threatening, \nthey can severely impair the patients\u2019 quality of \nlife.4 The use of combination antiretroviral therapy \n(ART) may prolong the patient\u2019s life but drug-\ninduced adverse reaction is a problem5 because they \nmay cause disfiguring facial lipoatrophy.5,6,7 \n\n\n\nInterestingly, skin diseases may be the first \nmanifestations of HIV infection.8 Hence, knowledge \nof the prevalence of these mucocutaneous disorders, \nthe types and their impact on the HIV-infected \npatients\u2019 life are important aspects for their optimal \nmanagement. We set out to study the prevalence of \nmucocutaneous manifestations in these patients, \ntheir types and their impact on patients\u2019 quality \nof life (QoL). We also explored the relationship \nbetween these disorders and CD4+ T-cell counts, a \nknown indicator of disease progression.\n\n\n\nMaterials and Methods\nThis was a cross-sectional study involving adults \n(18 years and above) who were diagnosed with HIV \ninfection based on ICD-10-CM code B20. Study \nsubjects were approached when they attended their \nscheduled HIV or Dermatology Clinic, Hospital \nSultanah Aminah Johor Bahru (HSAJB), a tertiary \nreferral centre in southern Malaysia. All confirmed \nHIV patients seen consecutively between 1st May \n2019 to 31st July 2019 were recruited into the study \nwhich was approved by the Malaysian Ministry \nof Health Institutional Review Board and Medical \nResearch Ethnics Committee (NMRR-19-92-\n46001). Written consents were given by all patients.\n\n\n\nStudy Procedures\nAfter consent, patients underwent a thorough \ninterview and full physical examination. CD4+ \nT-cell counts and other relevant blood tests and \nprocedures such as skin biopsies, skin scrapings and \ncultures were performed based on clinical findings. \nAll findings were recorded in a standard Case \nReport Form (CRF). \n\n\n\nPatients with mucocutaneous disorders were \nasked to fill up the DLQI questionnaire. DLQI is \na 10-item dermatology-specific questionnaire that \nassesses the impact of skin disease and its treatment \non the patient\u2019s life such as their symptoms of \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4612\n\n\n\n\n\n\n\n\nitch, embarrassment, interferences with their \ndaily activities, leisure, work and study, personal \nrelationships and problems in taking the treatment. \nEach question is scored from 0 to 3; 0 for not at all or \nnot relevant, 1 for a little, 2 for a lot, 3 for very much. \nQuestions 3 to 10 offered a \u201cnot relevant\u201d response \n(NRR) option that was scored as an item that had \nno impact on study participants\u2019 life. A composite \nscore is then calculated by summing the score of \neach question. It could range from a minimum of 0 \nto a maximum of 30. A DLQI score of 0 to 1 means \nthe skin disease has no effect on the patient\u2019s life; \n2-5 a small effect, 6-10 a moderate effect, 11-20 a \nvery large effect and 21-30 an extremely large effect \non patient\u2019s life.9 \n\n\n\nStatistical Analysis\nDescriptive statistics were presented as counts and \npercentages for categorical variables. Means and \nstandard deviation (SD) was used for normally \ndistributed data while median with an interquartile \nrange (IQR) was used for data which were not \nnormally distributed. Chi-square test, Fisher\u2019s exact \ntest or Kruskal-Wallis test are used for univariate \nanalysis depending on data distribution. Statistical \nsignificance was set at p <0.05. Statistical analysis \nwas carried out with the Statistical Package for the \nSocial Sciences (SPSS) (version 23; SPSS Inc., \nChicago, IL. USA).\n\n\n\nResults\n\n\n\nDemographic Characteristics\nA total of 174 HIV-infected individuals participated \nin this study. The male to female ratio was 11.4:1. \nThe median age at diagnosis was 29 (IQR: 10) \nyears. In the racial distribution, 48.3% were Malays, \n43.1% Chinese, 8.0% Indian and 0.6% others. \nAbout 88% of the study participants completed at \nleast secondary school education level. Most of the \nparticipants were currently single and employed \n(Table 1).\n\n\n\nRisk Profile, CD4+ T-cell Counts and Treatment \nStatus of 174 HIV-positive Patients\nThe main mode of HIV transmission was through \nsexual intercourse with 85% of participants having \nmultiple sexual partners. Forty-five percent of them \nwere homosexual. \n\n\n\nTwenty-seven participants (15.5%) were \n\n\n\nintravenous drug users, five of them being active \nusers and nineteen of them (70.4%) had multiple \nsexual partners. Twenty-two participants (12.6%) \nwere either using or had a history of using stimulants \neither in the form of inhalational drugs or pills \nduring engagement of sexual activities (Table 2). \n\n\n\nThe median duration of HIV infection was 172 \n(IQR:287) weeks. The median CD4+ T-cell \ncounts were 335 (IQR:508) cells/\u00b5L. Most of the \nstudy participants had already commenced on \nantiretroviral treatment.\n\n\n\nMucocutaneous Manifestations of the Study \nParticipants\nClose to 90% of the participants had at least \none mucocutaneous manifestation (Table 3). \nFurthermore, the CD4+ T-cell counts were \nsignificantly lower in patients with mucocutaneous \nmanifestations when compared to those without \n(363 \u00b1 338 cells/\u00b5L vs 548 \u00b1 229 cells/\u00b5L; p=0.030). \n\n\n\nCommon mucocutaneous disorders were infections \n(67.2%), followed by inflammatory dermatoses \n(51.7%), cutaneous Adverse Drug Reactions \n(cADR) (17.8%) and neoplasm (2.3%). Participants \nwith CD4+ T-cell counts <200 cells/\u00b5L were \nsignificantly more likely to develop cADR. Most of \nthe drug eruption in our study were secondary to \nsulfamethoxazole/trimethoprim (54.8%), followed \nby antiretroviral therapy (35.5%), anti-tuberculous \ndrugs (6.5%) and antibiotics (3.2%).\n\n\n\nRelationship between CD4+ T-cell Counts and \nMucocutaneous Manifestations\nFor study participants with CD4+ T-cell counts of \n<200 cells/\u00b5L, there were 38% of them who had \nmucocutaneous manifestations compared to only \n6% of them without any manifestations (p=0.008) \n(Table 4).\n\n\n\nSeveral dermatoses were noted to be significantly \nhigher among participants with CD4+ T-cell counts \n<200 cells/\u00b5L when compared to those higher than \n200 cells/\u00b5L (Table 5). These were candidiasis \n(p=0.001), pruritic papular eruption (p=0.037), \ndrug-induced maculopapular eruption (p=0.001) \nand drug rash with eosinophilia and systemic \nsymptoms (DRESS) (p=0.001). \n\n\n\nHowever, anogenital warts were noted to be \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nsignificantly higher in those with CD4+ T-cell counts \nof \u2265200 cells/\u00b5L (p=0.006). No differences in CD4+ \nT-cell counts was observed for other mucocutaneous \nmanifestations.\n\n\n\nEffect of Mucocutaneous Manifestations on \nParticipants\u2019 DLQI Scores\nThe mean (\u00b1 SD) of the total DLQI score was 8.39 \u00b1 \n6.83 (range:0-27) (Table 6). When further analysed, \nthe mean (\u00b1 SD) DLQI score for participants \nwho had \u22653 mucocutaneous disorders was not \nsignificantly higher, scoring 8.73 \u00b1 6.54 (p=0.858). \nIn all, 54 participants (34.4%) with mucocutaneous \nmanifestations experienced severely impaired \nquality of life, having DLQI score >10. Thirty-five \nparticipants (22.3%) had moderate effect while 42 \nparticipants (26.8%) had a small effect. No effect \nwas seen in 26 participants (16.6%) (Figure 1). \n\n\n\nIn the questionnaire, Questions 3 to 10 had a \u201cnot \nrelevant response\u201d (NRR) option. About two-thirds \nof participants chose this option at least once from \nquestions 3 to 10. A higher proportion was recorded \nfor questions on sexual difficulties (38.9%), sports \n(36.3%) and working or studying (22.9%).\n\n\n\nTable 1. Demographic characteristics of 174 study \nparticipants with HIV infection\n\n\n\nVariables n (%)\n\n\n\nAge category in years 18-30 \n31-40 \n41-50 \n51-60 \n61-70 \n\n\n\n94 (53.7)\n44 (25.1)\n26 (14.9)\n8 (4.6)\n2 (1.1)\n\n\n\nGender Male\nFemale\n\n\n\n160 (92.0)\n14 (8.0)\n\n\n\nEthnicity Malay\nChinese\nIndian\nOthers\n\n\n\n84 (48.3)\n75 (43.1)\n14 (8.0)\n1 (0.6)\n\n\n\nEducation level Primary\nSecondary\nTertiary\n\n\n\n21 (12.1)\n86 (49.4)\n67 (38.5)\n\n\n\nMarital status Single\nMarried\nDivorced\nWidow / Widower\n\n\n\n127 (73.0)\n21 (12.1)\n19 (10.9)\n7 (4.0)\n\n\n\nOccupation Self-employed\nEmployee\nUnemployed\n\n\n\n33 (19.0)\n90 (51.7)\n51 (29.3)\n\n\n\nTable 2. Risk profile, CD4+ T-cell counts and treatment \nstatus of 174 HIV-positive patients\n\n\n\nVariables n (%)\n\n\n\nSexual orientation Homosexual\nHeterosexual\nBisexual\n\n\n\n79 (45.4)\n61 (35.1)\n33 (19.5)\n\n\n\nNumber of sexual \npartners\n\n\n\nMultiple\nSingle\n\n\n\n147 (84.5)\n26 (14.9)\n\n\n\nRisk factors of HIV \ntransmission\n\n\n\nSexual transmission\nSexual transmission & \nIntravenous drug user\nIntravenous drug user\n\n\n\n147 (84.5%)\n26 (14.9%)\n\n\n\n1 (0.6%)\n\n\n\nCD4+ T-cell counts <200 cells/\u00b5L\n200-349 cells/\u00b5L\n350-499 cells/\u00b5L\n>500 cells/\u00b5L\n\n\n\n61 (35.1)\n30 (17.2)\n28 (16.1)\n55 (31.6)\n\n\n\nParticipants on \nantiretroviral treatment \n(ART)\n\n\n\nYes\nNo\n\n\n\n129 (74.1)\n45 (25.9)\n\n\n\nTable 3. Comparison of mean CD4+ T-cell counts in 174 \nHIV-positive patients with and without Mucocutaneous \nDisorders\n\n\n\nVariables n (%) Mean CD4+ T-cell \nCounts (cells/\u00b5L \u00b1 SD)\n\n\n\np-valuea\n\n\n\nPresence of \nDisorders \n(n=157)                    \n\n\n\nAbsence of \nDisorders \n\n\n\n(n=17)\n\n\n\nAll \nmucocutaneous \nmanifestations\n\n\n\n157 \n(90.2) 363 \u00b1 338 548 \u00b1 229 0.030\n\n\n\n1 Disorder\n\n\n\n2 Disorders \n\n\n\n\u22653 Disorders\n\n\n\n65 \n(37.3)\n\n\n\n43 \n(24.7)\n\n\n\n49 \n(28.2)\n\n\n\n378 \u00b1 280\n\n\n\n364 \u00b1 362\n\n\n\n342 \u00b1 388\n\n\n\nInfection* 117 \n(67.2) 381 \u00b1 360 381 \u00b1 270 0.991\n\n\n\nInflammatory \ndermatoses*\n\n\n\n90 \n(51.7) 361 \u00b1 329 403 \u00b1 337 0.406\n\n\n\nCutaneous \nadverse drug \nreactions \n(cADR)*\n\n\n\n31 \n(17.8) 194 \u00b1 249 422 \u00b1 335 <0.001\n\n\n\nNeoplasm* 4 \n(2.3) 404 \u00b1 323 381 \u00b1 334 0.891\n\n\n\nSD = Standard deviation; aindependent samples T-Test\n*One patient may have multiple mucocutaneous manifestations; the \npercentage reported is based on total patients in each group\n\n\n\nTable 4. The effect of CD4+ T-cell counts on \nMucocutaneous Manifestations\n\n\n\nCD4+ T-cell Counts Mucocutaneous \nManifestations\n\n\n\np-valueb\n\n\n\nYes (%) No (%)\n\n\n\n<200 cells/\u00b5L\n\u2265200 cells/\u00b5L\n\n\n\n60 (34.5)\n97 (55.7)\n\n\n\n1 (0.6)\n16 (9.2)\n\n\n\n0.008\n\n\n\nbChi-Square test\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4614\n\n\n\n\n\n\n\n\nTable 5. Relationship between type of Mucocutaneous Manifestations and CD4+ T-cell counts\n\n\n\nVariables n (%) Participants with CD4+ \nT-cell Counts (cells/\u00b5L) \n\n\n\n<200 {n=60 (%)}\n\n\n\nParticipants with CD4+ \nT-cell Counts (cells/\u00b5L) \n\n\n\n\u2265200 {n=97 (%)}\n\n\n\np-valueb\n\n\n\nAll mucocutaneous manifestations 157 (90.2) 0.248\n\n\n\n1 Disorder\n2 Disorders\n\u22653 Disorders\n\n\n\n65 (37.3)\n43 (24.7)\n49 (28.2)\n\n\n\n24 (40.0)\n13 (21.7)\n23 (38.3)\n\n\n\n41 (42.3)\n30 (30.9)\n26 (26.8)\n\n\n\nInfection*\n\n\n\nViral\n\n\n\nHuman \npapillomavirus\n\n\n\nAnogenital warts\nPalmoplantar warts\nHerpes simplex virus \nMolluscum contagiosum\nVaricella and Herpes zoster virus infection\nOral hairy leukoplakia\n\n\n\n37 (21.2)\n6 (3.4)\n10 (5.7)\n6 (3.4)\n5 (2.9)\n3 (1.7)\n\n\n\n7 (11.7)\n3 (5.0)\n6 (10.0)\n3 (5.0)\n3 (5.0)\n3 (5.0)\n\n\n\n30 (30.9)\n3 (3.1)\n4 (4.1)\n3 (3.1)\n2 (2.1)\n0 (0)\n\n\n\n0.006\n0.675c\n\n\n\n0.183c\n\n\n\n0.675c\n\n\n\n0.371c\n\n\n\n0.054c\n\n\n\nFungal Candidiasis\nDermatophytes\nDeep fungal infection\n\n\n\n29 (16.7)\n27 (15.5)\n3 (1.7)\n\n\n\n20 (33.3)\n9 (15.0)\n3 (5.0)\n\n\n\n9 (9.3)\n18 (18.6)\n\n\n\n0 (0)\n\n\n\n0.000\n0.566\n0.054c\n\n\n\nBacterial Syphilis\nCellulitis\nImpetigo\nAbscesses / Carbuncle\n\n\n\n21 (12.0)\n12 (6.9)\n5 (2.9)\n1 (0.6)\n\n\n\n7 (11.7)\n3 (5.0)\n0 (0)\n0 (0)\n\n\n\n14 (14.4)\n9 (9.3)\n5 (5.2)\n1 (1.0)\n\n\n\n0.621\n0.375c\n\n\n\n0.157c\n\n\n\n1.000c\n\n\n\nParasitic Scabies\nPediculosis capitis\n\n\n\n1 (0.6)\n1 (0.6)\n\n\n\n1 (1.7)\n0 (0)\n\n\n\n0 (0)\n1 (1.0)\n\n\n\n0.382c\n\n\n\n1.000c\n\n\n\nInflammatory \ndermatosis*\n\n\n\nEczema\nPruritic papular eruption\nAcne vulgaris\nPsoriasis\nPrurigo nodularis\nSeborrheic dermatitis\nUrticaria\nHidradenitis suppurativa\nIchthyosis\nXerosis\nCutaneous vasculitis\nPhotodermatitis\nOther inflammatory dermatosis\n\n\n\n39 (22.4)\n14 (8.0)\n11 (6.3)\n10 (5.7)\n8 (4.6)\n7 (4.0)\n5 (2.9)\n4 (2.3)\n3 (1.7)\n2 (1.1)\n1 (0.6)\n1 (0.6)\n5 (2.9)\n\n\n\n12 (20.0)\n9 (15.0)\n2 (3.3)\n2 (3.3)\n4 (6.7)\n3 (5.0)\n2 (3.3)\n1 (1.7)\n2 (3.3)\n2 (3.3)\n1 (1.7)\n0 (0)\n0 (0)\n\n\n\n27 (27.8)\n5 (5.2)\n9 (9.3)\n8 (8.2)\n4 (4.1)\n4 (4.1)\n3 (3.1)\n3 (3.1)\n1 (1.0)\n0 (0)\n0 (0)\n\n\n\n1 (1.0)\n5 (5.2)\n\n\n\n0.270\n0.035c\n\n\n\n0.207c\n\n\n\n0.320c\n\n\n\n0.482c\n\n\n\n1.000c\n\n\n\n1.000c\n\n\n\n1.000c\n\n\n\n0.558c\n\n\n\n0.145c\n\n\n\n0.382c\n\n\n\n1.000c\n\n\n\n0.157c\n\n\n\nCutaneous \nAdverse Drug \nReactions \n(cADR)*\n\n\n\nMaculopapular eruption\nDrug rash with Eosinophilia and Systemic \nsymptoms\nLipodystrophy\nToxic epidermal necrolysis\nErythema multiforme\nOther cADRs\n\n\n\n16 (9.2)\n8 (4.6)\n\n\n\n5 (2.9)\n2 (1.1)\n1 (0.6)\n2 (1.1)\n\n\n\n12 (20.0)\n8 (13.3)\n\n\n\n0 (0)\n2 (3.3)\n1 (1.7)\n1 (1.7)\n\n\n\n4 (4.1)\n0 (0)\n\n\n\n5 (5.2)\n0 (0)\n0 (0)\n\n\n\n1 (1.0)\n\n\n\n0.001\n0.000c\n\n\n\n0.157c\n\n\n\n0.145c\n\n\n\n0.382c\n\n\n\n1.000c\n\n\n\nNeoplasm* Cutaneous lymphoma\nKaposi\u2019s sarcoma\nBowen\u2019s disease\n\n\n\n2 (1.1)\n1 (0.6)\n1 (0.6)\n\n\n\n1 (1.7)\n0 (0)\n0 (0)\n\n\n\n1 (1.0)\n1 (1.0)\n1 (1.0)\n\n\n\n1.000c\n\n\n\n1.000c\n\n\n\n1.000c\n\n\n\nbChi-Square test; cFisher\u2019s exact test\n*One patient may have multiple mucocutaneous manifestations; the percentage reported is based on total patients in each group\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nTable 6. The effect of Mucocutaneous Manifestations on participants\u2019 mean DLQI scores\n\n\n\nVariables Mean DLQI Scores (SD) p-valuea\n\n\n\nGeneral effect of Mucocutaneous Manifestations Yes\nNo\n\n\n\n8.39 (6.83)\n\n\n\nInfection Yes\nNo\n\n\n\n8.65 (6.95)\n6.05 (6.10)\n\n\n\n0.017\n\n\n\nInflammatory dermatoses Yes\nNo\n\n\n\n7.87 (5.84)\n7.73 (7.69)\n\n\n\n0.892\n\n\n\nNeoplasm Yes\nNo\n\n\n\n6.25 (9.85)\n7.84 (6.73)\n\n\n\n0.645\n\n\n\nCutaneous adverse drug reactions (cADR) Yes\nNo\n\n\n\n8.71 (6.34)\n7.60 (6.87)\n\n\n\n0.411\n\n\n\nDLQI components\n\n\n\nSymptoms and Feeling Yes\nNo\n\n\n\n2.38 (1.81)\n0.82 (0.95)\n\n\n\n0.001\n\n\n\nDaily activities Yes\nNo\n\n\n\n1.50 (1.89)\n0.06 (0.24)\n\n\n\n0.002\n\n\n\nLeisure Yes\nNo\n\n\n\n1.24 (1.76)\n0.12 (0.49)\n\n\n\n0.009\n\n\n\nDaily activities Yes\nNo\n\n\n\n0.65 (1.15)\n0.12 (0.49)\n\n\n\n0.009\n\n\n\nDaily activities Yes\nNo\n\n\n\n0.65 (1.15)\n0.12 (0.49)\n\n\n\n0.009\n\n\n\nTreatment Yes\nNo\n\n\n\n0.65 (1.15)\n0.12 (0.49)\n\n\n\n0.009\n\n\n\naIndependent samples T-Test\n\n\n\nFigure 1. Effects of Mucocutaneous Manifestations on participants\u2019 DLQI\n\n\n\nDiscussion\nEver since its recognition in 1981, HIV has become \na major global public health issue. In 2019, there \nwere 1.7 million newly infected people of whom \n690,000 people died from its related causes.10   \n\n\n\nMalaysia is no different; by the end of 2018 it is \nestimated that 87,041 people would have lived with \nHIV in Malaysia and 55% of these will be receiving \nantiretroviral treatment (ART).11 Close to 80% of \nour study participants were below 40 years old of \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4616\n\n\n\n 8 \n\n\n\nSymptoms and Feeling \nYes \nNo \n\n\n\n \n2.38 (1.81) \n0.82 (0.95) \n\n\n\n \n0.001 \n\n\n\nDaily Activities \nYes \nNo \n\n\n\n \n1.50 (1.89) \n0.06 (0.24) \n\n\n\n \n0.002 \n\n\n\nLeisure \nYes \nNo \n\n\n\n \n1.24 (1.76) \n0.12 (0.49) \n\n\n\n \n0.009 \n\n\n\nWork or School \nYes \nNo \n\n\n\n \n0.65 (1.15) \n0.12 (0.49) \n\n\n\n \n0.062 \n\n\n\nPersonal Relationship \nYes \nNo \n\n\n\n \n1.62 (1.81) \n0.82 (1.55) \n\n\n\n \n0.082 \n\n\n\nTreatment \nYes \nNo \n\n\n\n \n1.00 (1.21) \n0.35 (0.70) \n\n\n\n \n0.032 \n\n\n\naIndependent Samples T-Test \n \n \nFigure 1. Effects of Mucocutaneous Manifestations on Participants' DLQI \n \n\n\n\n \n \n \nDiscussion \nEver since its recognition in 1981, HIV has become a major global public health issue. In 2019, \nthere were 1.7 million newly infected people of whom 690,000 people died from its related \ncauses.10   Malaysia is no different; by the end of 2018 it is estimated that 87,041 people would \nhave lived with HIV in Malaysia and 55% of these will be receiving antiretroviral treatment \n(ART).11 Close to 80% of our study participants were below 40 years old of which, 92% were \n\n\n\n26 (16.5%)\n\n\n\n42 (26.8%)\n\n\n\n35 (22.3%)\n\n\n\n54 (34.4%)\n\n\n\n0\n\n\n\n10\n\n\n\n20\n\n\n\n30\n\n\n\n40\n\n\n\n50\n\n\n\n60\n\n\n\nNo Effect Small Effects Moderate Effects Large & Extremely\nLarge Effects\n\n\n\nNu\nm\n\n\n\nbe\nr o\n\n\n\nf P\nar\n\n\n\ntic\nip\n\n\n\nan\nts\n\n\n\nEffects on Quality of Life\n\n\n\nEffects of Mucocutaneous Manifestations on Participants' DLQI\n60\n\n\n\n50\n\n\n\n40\n\n\n\n30\n26 (16.5%)\n\n\n\nNo Effect Small Effects Moderate Effects\n\n\n\nEffects on Quality of Life\n\n\n\nLarge & Extremely\nLarge Effects\n\n\n\n42 (26.8%)\n\n\n\n35 (22.3%)\n\n\n\n54 (34.4%)\n\n\n\n20N\num\n\n\n\nbe\nr o\n\n\n\nf P\nar\n\n\n\ntic\nip\n\n\n\nan\nts\n\n\n\n10\n\n\n\n0\n\n\n\n\n\n\n\n\nwhich, 92% were of males. These figures are similar \nto those reported by Wang Jing in 2000 in Malaysia \nwho showed that 75% of his study participants were \nless than 40 years old and with a male preponderance \nof 87%.12 \n\n\n\nHomosexual contact was the most common mode \nof transmission in our patients. However, two \nprevious studies from Singapore and Malaysia \nshowed that most of their study participants were \nheterosexuals.12,13 Furthermore, Kanter et al.14 in \n2011 screened 517 men who had sex with men in \nKuala Lumpur and found that 3.9% of them tested \npositive for HIV infection. This study shows a \nchange in risk factor for HIV transmission and \ntherefore, targeted interventions should be offered \nto prevent and control HIV transmission.15 \n\n\n\nMucocutaneous manifestations are common in \npatients of HIV. They may occur anytime during the \ncourse of the disease. Ninety percent of our patients \ndisplayed at least one type of dermatological \nmanifestation whereby more than half had 2 or more \nmucocutaneous disorders. This high prevalence is \nlikely attributed to recruitment of patients done in \na tertiary referral centre of HIV and Dermatology \nClinic. Consistent with observation documented \nby Li et al.16, our study showed that patients with \nmucocutaneous disorders had significantly lower \nCD4+ T-cell counts. However, no significant \ndifference in CD4+ T-cell counts was observed \nbetween patients with one and more than one \nmucocutaneous disorders. This contradicted findings \nby Li et al.16 who showed that significant reduction \nin CD4+ T-cell count occurred with increasing \nnumber of mucocutaneous manifestations. \n\n\n\nInfections\nHuman papillomavirus (HPV) infection in the form \nof anogenital warts was noted to occur frequently \namong our participants, especially those with \nCD4+ T-cell counts >200 cells/\u00b5L. In contrast \nto our findings, Chikandiwa et al.17 showed that \nanogenital warts were more prevalent among those \nwith lower CD4+ T-cell counts (<200 cells/\u00b5L). \nHIV infection may have altered the natural history \nof HPV infection and thus were more common \namong individuals with HIV infection, regardless \nof their CD4+ T-cell counts.19 Furthermore, our \nfindings might be related to the fact that 84.5% of \nour study participants had multiple sexual partners \n\n\n\nand 45.4% of them were homosexual. This finding \nis supported by other workers. Dareng et al.18 \n\n\n\nshowed that anogenital warts were more prevalent \namong his study participants who had multiple \nsexual partners. Similarly, Sonnenberg et al.19 found \nthat the diagnosis of anogenital warts were more \nfrequent in men who had sex with men. \n\n\n\nOn the other hand, candidiasis seemed to be \npredominant among our participants with CD4+ \n\n\n\nT-cell counts of less than 200 cells/\u00b5L. Altuntas \net al.20 and Kore et al.21 showed similar results. \nInterestingly, in our study, there was a significant \nlower prevalence of candidiasis in patients who \nwere on ART treatment. This is in line with the \nstudy by Hengge et al.22 in which they found a \ndecrease in the prevalence of oral candidiasis after \nART administration. This implies that candidiasis \ninfection is related to low immune function. \nCandidiasis may therefore be an important indicator \nof progression of the HIV infection and starting \nART could decline its prevalence.\n\n\n\nSecondary syphilis was present in 12% of \nstudy participants, it being the most common \nbacterial infection with 71.4% occurring among \nthe homosexuals. This finding is not surprising \nas syphilis is associated with high-risk sexual \nbehaviours and infection substantially increases in \nassociation with HIV transmission and acquisition.23 \n\n\n\nIn Canada, the incidence of syphilis was 300-fold \ngreater among male who had sex with male positive \nfor HIV than the reported case rate in the general \nmale population.24 \n\n\n\nInflammatory Dermatoses\nOf the inflammatory dermatoses, the most common \nmanifestations were eczema (22.4%), followed by \npruritic papular eruption (PPE) (8.0%), psoriasis \n(6.3%) and acne vulgaris (6.3%). However, of these \nonly pruritic papular eruption was significantly \nassociated with CD4+ T-cell counts of less than \n200 cells/\u00b5L. A similar observation was reported \nby Resnick et al.25 and Farsani et al.26 and they \npostulated that PPE reflects an altered and \nexaggerated immune response to arthropod antigens \namong HIV-infected individuals. \n\n\n\nEczema was present in 22.4% of our participants. \nSimilar percentage was reported in a group of \npatients from Thailand.27 It is known that both \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\neczema and HIV share a similar Th2 cytokine profile \ncharacterized by elevated IgE, eosinophils, IL-4 \nand IL-5 levels. This may explain the relationship \nbetween the two diseases.28, 29\n\n\n\nPsoriasis was seen in 6.3% of our patients, an \nincidence much higher than that reported (2.9%) by \nothers from Iran.30 We also found that in about 50% \nof our patients\u2019 psoriasis were aggravated soon after \nthe diagnosis of HIV infection. This may be related \nto the fact that the HIV, in attacking CD4+ T-cells \nincreases the proportion of CD8+ T-cells which in \nturn secrete IFN-\u03b3 and aggravates psoriasis.31  \n\n\n\nCutaneous Adverse Drug Reactions\nHIV-infected individuals have both an immunologic \ndysfunction and do take a diverse set of drugs. A \nhigher incidence of drug eruption among these \nindividuals may therefore be expected.32 Cutaneous \nAdverse Drug Reactions (cADR) affected 17.8% \nof the study participants and this was positively \ncorrelated with those patients with CD4+ T-cell \ncounts of less than 200 cells/\u00b5L, especially in those \nwith maculopapular eruption and drug rash with \neosinophilia and systemic symptoms (DRESS). \nThis shows that drug eruptions are strongly related \nto the patient\u2019s immune function.33 \n\n\n\nMost of the cADR were secondary to \nsulfamethoxazole/trimethoprim, followed by \nantiretroviral therapy, anti-tuberculous drugs \nand antibiotics, which was also portrayed in \nother studies.34,35 The frequent occurrence of \nopportunistic infections among HIV patients36 \noften leads to concurrent use of sulfamethoxazole/\ntrimethoprim for Pneumocystis jirovecii pneumonia \nprophylaxis and anti-tuberculous therapy, both of \nwhich are well-documented instigators of mild to \nsevere cADR. These reactions can seriously impede \neffective management of HIV and opportunistic \ninfections among HIV-infected individuals. \n\n\n\nDermatology Life Quality Index\nHIV patients with mucocutaneous manifestations \nhad a mean (\u00b1 SD) DLQI score of 8.39 \u00b1 6.83. \nMore than one-third of HIV-infected individuals \nfelt that having mucocutaneous manifestations \nseverely affected their quality of life. This finding \nwas similarly reported by Shittu et al.37 Severe \nimpairment of QoL (DLQI >10) was clearly \nshown affecting our patients presenting with \n\n\n\nmucocutaneous disorders regardless of the numbers \nof manifestations experienced by them. \n\n\n\nNot with standing, the mean DLQI scores in our \npatients may have been underestimated because, \nabout 67% of them chose the \u201cnot relevant \nresponse\u201d. These were in the areas of sexual \ndifficulties (38.9%), sports (36.3%) and working or \nstudying (22.9%). Abstaining from these activities \non account of their mucocutaneous diseases might \nhave been the reason for them choosing the NRR \noption. Rencz et al.38 noted similar findings whereby, \ntheir participants with psoriasis also picked NRR \noptions for sexual difficulties, sports and working \nor studying.\n\n\n\nThe presence of mucocutaneous manifestations also \ncaused significant discomfort in terms of itchiness, \npain and embarrassment in our participants. A \nsimilar finding was seen in newly diagnosed HIV/\nAIDS-infected patients in a study from Nigeria.37 \nDaily and leisure activities were also impaired in \nour patients with mucocutaneous manifestations as \nopposed to those with none. In addition, they found \nit burdensome to seek treatment on account of their \nmucocutaneous manifestations. \n\n\n\nLimitations\nThis study involved only single centre and had a \nrelatively short study duration of three months. In \nusing convenience sampling, the participants may \nnot have been representative of the target population. \n\n\n\nConclusion\nMucocutaneous disorders were common and diverse \namong patients with HIV infection. More than one-\nthird of patients with mucocutaneous manifestations \nhad severely impaired quality of life. Hence, early \nand adequate treatment of HIV patients may reduce \nthe prevalence of mucocutaneous disorders and \ntheir impact on patients\u2019 QoL. Cutaneous ADR \nincluding potentially life-threatening DRESS were \nsignificantly higher in patients with CD4+ T-cell \ncounts <200 cells/\u00b5L. This highlights the need for \ncaution in prescribing only absolutely necessary \nmedication for HIV patients with low CD4+ T-cell \ncounts.  \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4618\n\n\n\n\n\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \narticle. \n\n\n\nReferences\n\n\n\n1. de Goede AL, Vulto AG, Osterhaus AD, Gruters RA. \nUnderstanding HIV infection for the design of a therapeutic \nvaccine. Part I: Epidemiology and pathogenesis of HIV \ninfection. Ann Pharm Fr 2015;73:87-99. \n\n\n\n2. Chandrakala C, Parimalam K, Wahab AJ, Anand N. \nCorrelating CD4 count with mucocutaneous manifestations \nin HIV-positive patients: A prospective study. Indian J Sex \nTransm Dis AIDS 2017;38:128-35.\n\n\n\n3. Raju PV, Rao GR, Ramani TV, Vandana S. Skin \ndisease: clinical indicator of immune status in human \nimmunodeficiency virus (HIV) infection. Int J Dermatol \n2005;44:646-9.\n\n\n\n4. Kanmani CI, Udayashankar C, Nath AK. Dermatology life \nquality index in patients infected with HIV: A comparative \nstudy. Egypt Dermatol Online J 2013;9:3.\n\n\n\n5. Masuka JT, Chipangura P, Nyambayo PP, Stergachis A, \nKhoza S. A Comparison of Adverse Drug Reaction Profiles \nin Patients on Antiretroviral and Antitubercular Treatment \nin Zimbabwe. Clin Drug Investig 2018;38:9-17. \n\n\n\n6. Ward HA, Russo GG, Shrum J. Cutaneous manifestations of \nantiretroviral therapy. J Am Acad Dermatol 2002;46:284-\n93.\n\n\n\n7. Birbal S, Dheda M, Ojewole E, Oosthuizen F. Adverse \ndrug reactions associated with antiretroviral therapy in \nSouth Africa. Afr J AIDS Res 2016;15:243-8.\n\n\n\n8. Mirnezami M, Zarinfar N, Sofian M, Botlani Yadegar B, \nRahimi H. Mucocutaneous Manifestations in HIV-Infected \nPatients and Their Relationship to CD4 Lymphocyte \nCounts. Scientifica (Cairo) 2020;2020:7503756. \n\n\n\n9. Finlay AY, Khan G. Dermatology Life Quality Index \n(DLQI): a simple practical measure for routine clinical \nuse. Clin Exp Dermatol 1994;19:210-6. \n\n\n\n10. Joint United Nations Programme on HIV/AIDS (2020). \nGlobal HIV & AIDS statistics - 2019 fact sheet. Available \nonline:http://www.unaids.org/en/resources/fact-sheet. \nAssessed on 19 February 2021.\n\n\n\n11. Ministry of Health Malaysia. Country Progress Report \non HIV/AIDS 2019 Malaysia. Available online: http://\nwww.moh.gov.my \u203a Umum \u203a Report_GAM_2019_(Final). \nAssessed on 19 February 2021.\n\n\n\n12. Jing W. A Retrospective Survey of Mucocutaneous \nManifestations of HIV Infection in Malaysia: Analysis of \n182 Cases. J Dermatol 2000;27:225-32. \n\n\n\n13. Goh BK, Chan RKW, Sen P, Theng CTS, Tan HH, Wu YJ et \nal. Spectrum of skin disorders in human immunodeficiency \nvirus-infected patients in Singapore and the relationship to \nCD4 lymphocyte counts. Int J Dermatol 2007;46:695-9. \n\n\n\n14. Kanter J, Koh C, Razali K, Tai R, Izenberg J, Rajan L et al. \nRisk behaviour and HIV prevalence among men who have \nsex with men in a multiethnic society: a venue-based study \nin Kuala Lumpur, Malaysia. Int J STD AIDS 2011;22:30-\n7. \n\n\n\n15. Ramakrishnan L, Ramanathan S, Chakrapani V, Goswami \nP, Deshpande S, Yadav D et al. Comparison of Sexual Risk, \nHIV/STI Prevalence and Intervention Exposure Among \nMen Who Have Sex with Men and Women (MSMW) \nand Men Who Have Sex with Men Only (MSMO) in \n\n\n\nIndia: Implications for HIV Prevention. AIDS Behav \n2015;19:2255-69. \n\n\n\n16. Li YY, Yang SH, Wang RR, Tang JT, Wang HM, Kuang \nYQ. Effects of CD4 cell count and antiretroviral therapy \non mucocutaneous manifestations among HIV/AIDS \npatients in Yunnan China. Int J Dermatol 2020;59:308-13. \n\n\n\n17. Chikandiwa A, Kelly H, Sawadogo B, Ngou J, Pisa PT, \nGibson L et al. Prevalence, incidence and correlates of \nlow risk HPV infection and anogenital warts in a cohort of \nwomen living with HIV in Burkina Faso and South Africa. \nPLoS One 2018;13:e0196018. \n\n\n\n18. Dareng EO, Adebamowo SN, Famooto A, Olawande O, \nOdutola MK, Olaniyan Y et al. Prevalence and incidence of \ngenital warts and cervical Human Papillomavirus infections \nin Nigerian women. BMC Infect Dis 2019;19:27:1-10. \n\n\n\n19. Sonnenberg P, Tanton C, Mesher D, King E, Beddows S, \nField N et al. Epidemiology of genital warts in the British \npopulation: implications for HPV. Sex Transm Infect \n2019;95:386-90. \n\n\n\n20. Altuntas Aydin \u00d6, Kumbasar Karaosmanoglu H, Korkusuz \nR, \u00d6zeren M, \u00d6zcan N. Mucocutaneous manifestations \nand the relationship to CD4 lymphocyte counts among \nTurkish HIV/AIDS patients in Istanbul, Turkey. Turk J \nMed Sci 2015;45:89-92.\n\n\n\n21. Kore SD, Kanwar AJ, Vinay K, Wanchu A. Pattern \nof mucocutaneous manifestations in human \nimmunodeficiency virus-positive patients in North India. \nIndian J Sex Transm Dis AIDS 2013;34:19-24. \n\n\n\n22. Hengge UR, Franz B, Goos M. Decline of infectious skin \nmanifestations in the era of highly active antiretroviral \ntherapy. AIDS 2000;14:1069-70. \n\n\n\n23. Peeling RW, Mabey D, Kamb ML, Chen XS, Radolf JD, \nBenzaken AS. Syphilis. Nat Rev Dis Primers 2017;3:17073. \n\n\n\n24. Burchell AN, Allen VG, Gardner SL, Moravan V, Tan DH, \nGrewal R et al. High incidence of diagnosis with syphilis \nco-infection among men who have sex with men in an HIV \ncohort in Ontario, Canada. BMC Infect Dis 2015;15:356. \n\n\n\n25. Resneck JS Jr, Van Beek M, Furmanski L, Oyugi J, LeBoit \nPE, Katabira E et al. Etiology of pruritic papular eruption \nwith HIV infection in Uganda. JAMA 2004;292:2614-21. \n\n\n\n26. Farsani TT, Kore S, Nadol P, Ramam M, Thierman SJ, \nLeslie K et al. Aetiology and risk factors associated with \na pruritic papular eruption in people living with HIV in \nIndia. J Int AIDS Soc 2013;16:17325. \n\n\n\n27. Punyaratabandhu P, Prasithsirikul W, Jirachanakul P. Skin \nmanifestation of Thai HIV infected patients in HAART \nera. J Med Assoc Thai 2012;95:497-504. \n\n\n\n28. Rudikoff D. The relationship between HIV infection and \natopic dermatitis. Curr Allergy Asthma Rep 2002;2:275-\n81. \n\n\n\n29. Garg T, Sanke S. Inflammatory dermatoses in human \nimmunodeficiency virus. Indian J Sex Transm Dis AIDS \n2017;38:113-10. \n\n\n\n30. Davarpanah MA, Motazedian N, Jowkar F. Dermatological \nmanifestations of HIV/AIDS individuals in Shiraz, South \nof Iran. J Glob Infect Dis 2018;10:80-3.\n\n\n\n31. Patel RV, Weinberg JM. Psoriasis in the patient with human \nimmunodeficiency virus, part 1: review of pathogenesis. \nCutis 2008;82:117-22. \n\n\n\n32. Tzung TY, Yang CY, Chao SC, Lee YJ. Cutaneous \nManifestations of Human Immunodeficiency Virus \nInfection in Taiwan. Kaohsiung J Med Sci 2004;20:216-\n24.\n\n\n\n33. Huang XJ, Li HY, Chen DX, Wang XC, Li ZC, Wu YS et \nal. Clinical analysis of skin lesions in 796 Chinese HIV-\npositive patients. Acta Derm Venereol 2011;91:552-6. \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\n34. Hoosen K, Mosam A, Dlova NC, Grayson W. An Update \non Adverse Cutaneous Drug Reactions in HIV/AIDS. \nDermatopathology (Basel) 2019;6:111-25.\n\n\n\n35. Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous \ndisease and drug reactions in HIV infection. N Engl J Med \n1993;328:1670-4. \n\n\n\n36. Lee CY, Wu PH, Lu PL, Tsai HC. Changing Spectrum of \nOpportunistic Illnesses among HIV-Infected Taiwanese \nPatients in Response to a 10-Year National Anti-TB \nProgramme. J Clin Med 2019;8:163. \n\n\n\n37. Shittu RO, Odeigah LO, Mahmoud AO, Sani MA, \nBolarinwa OA. Dermatology Quality of Life Impairments \namong Newly Diagnosed HIV/AIDS-Infected Patients \nin the University of Ilorin Teaching Hospital (Uith), \nIlorin, Nigeria. J Int Assoc Provid AIDS Care 2013; doi: \n10.1177/2325957413488207.\n\n\n\n38. Rencz F, Po\u00f3r AK, P\u00e9ntek M, Holl\u00f3 P, K\u00e1rp\u00e1ti S, Gul\u00e1csi L \net al. A detailed analysis of \u201cnot relevant\u201d responses on the \nDLQI in psoriasis: potential biases in treatment decisions. \nJ Eur Acad Dermatol Venereol 2018;32:783-90.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4620\n\n\n\n\n\n\n\n\nORIGINAL ARTICLE\n\n\n\nPrevalence of Atopic Dermatitis Among Primary School Children and \nIts Impact on Quality of Life in Kuching, Sarawak\nSut Enn Lee1, MRCP, Sze Ying Foo1, MD, Nur Shairah Fatin Binti Badaruddin1, MD, Mohamad Adam Bujang2, BSc, \nPubalan Muniandy1, FRCP\n\n\n\n1Department of Dermatology, Sarawak General Hospital, Kuching, Sarawak, Malaysia\n2Clinical Research Centre, Sarawak General Hospital, Kuching, Sarawak, Malaysia\n\n\n\nAbstract \nBackground\nAtopic dermatitis (AD) is a common chronic inflammatory skin disorder that significantly burdens \nboth children and caregivers\u2019 quality of life. This study aimed to investigate the prevalence and socio-\ndemography of AD and determine its impact on the quality of life among AD children and their \nfamilies in Sarawak.\n\n\n\nMethods\nThis was a cross-sectional, observational population-based epidemiological study of primary school \nchildren in Kuching. The U.K. Working Party\u2019s Diagnostic (UKWPD) criteria was utilized to diagnose \natopic dermatitis. Disease impact on quality of life was assessed via standardized questionnaires. Skin \nexamination was performed.\n\n\n\nResults\nA total of 968 children aged 7 to 12 years were recruited. The prevalence of AD was 7.0%. Malays \nwere the commonest affected ethnic group. Most of the AD children had other associated atopies. \nMajority of children with AD had mild to moderate severity based on IGA with mean EASI score \n(standard deviation) of 1.50 (2.0). The mean Children\u2019s Dermatology Quality Life Index (CDQLI) and \nDermatitis Family Impact (DFI) were 7.26 (5.53) and 7.74 (6.12), respectively. \u201cSymptoms of itch, \nsore or pain\u201d was the most affected domain in children, whereas \u201cTreatment impact\u201d most affected \nin families. There was significant association between disease severity and children\u2019s quality of life.\n\n\n\nConclusion\nAtopic Dermatitis is common in Kuching school children. Children with AD and their families had a \nsignificant impact on quality of life, although most were mild diseases.\n\n\n\nKey words: Atopic dermatitis, Eczema, Epidemiology, Quality of life, School children\n\n\n\nIntroduction\nAtopic dermatitis (AD) is a complex, chronic, and \nrecurrent inflammatory itchy skin disorder that \noften develops in early childhood and may persist \ninto adulthood.1 It is characterized by poorly \ndemarcated erythema with oedema, vesicles, and \nweeping in the acute stage. Recurrent episodes \nof flares eventually lead to lichenification.2,3 To \ndate, AD remains a clinical diagnosis. Hanifin and \nRajka criteria, the first validated diagnostic tool for \n\n\n\nCorresponding Author\nDr Lee Sut Enn\nDepartment of Dermatology,\nHospital Umum Sarawak,\nJalan Hospital,\n93586 Kuching, Sarawak.\nEmail: sutenn0601@yahoo.com\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nAD comprised of 4 major and 23 minor features.4 \nThe United Kingdom Working Party (UKWPD) \nrefined and proposed new criteria in the \u201890s to \nimprove practical applicability.5 This has become \na major advantage as its simplicity is favoured \namong researchers, particularly in population-based \nepidemiology studies.5,6  \n\n\n\nThe prevalence of AD among children was reported \nbetween 5 to 25%. The International Study of Asthma \nand Allergies in Childhood (ISAAC) revealed that \nthe prevalence of AD among Malaysian children \nin 2003 was 9.9% to 12.6%.7 The impact on the \nquality of life among affected children and families \nwas significant with the increase in AD. While the \nexisting local literature on AD was West Malaysia \nbased,7-14 lesser was known about the disease \nburden and sociodemography in East Malaysia. The \nprevalence of AD in the East could differ from the \nWest Malaysia due to the distinctive racial diversity, \ncultural background and urbanisation. Our study \naimed to establish and analyze the epidemiological \nbackground, risk factors, and treatment modalities \nof AD and its impact on the quality of life among \nthe affected children and their families in Kuching, \nSarawak. \n\n\n\nMaterials and Methods\nThis was a cross-sectional and observational \npopulation-based study of primary school children \nin Kuching, the capital city of Sarawak. Four out \nof 61 public national primary schools were selected \nby simple random selection to fulfil the calculated \nsample size of 954 students at 95% confidence \ninterval. The 4 schools were SK Jalan Ong Tiang \nSwee, SK Batu Lintang, SK James Quop, and SK \nChung Hua Pangkalan Baru. All Malaysian children \nattending the selected schools, from standard one to \nsix, aged between 7 to 12 years were included. \n\n\n\nThe data collection commenced from January to \nDecember 2020 upon approval from the medical \nethics committee. Questionnaire was utilized as \nresearch investigation tool and printed in multi-\nlingual hard copy format (Bahasa, English and \nChinese). Written consent was obtained from \nparents. The respondents were the parents or \nguardians, and the children. \n\n\n\nClinical skin examination and collection of \nquestionnaires were then conducted at the school \n\n\n\npremises 2 weeks later. Questionnaires were checked \nto ensure completeness. Parents or guardians were \ncontacted for incomplete questionnaires. Students \nwho were absent or unconsented during the day \nwere given another date for examination. \n\n\n\nData analysis was done using IBM SPSS Statistics \nVersion 22.0. Descriptive statistics such as \nmean with standard deviation or frequency with \npercentage were used to determine the characteristic \nof the students and the prevalence of AD. Univariate \nanalysis Pearson\u2019s Chi-square test was applied to \ndetermine the association of the risk factors towards \nAD and the factors affecting AD children\u2019s quality \nof life. Logistic regression was used in multivariate \nanalysis. P \u22640.05 was considered significant.\n\n\n\nQuestionnaire\nThe questionnaire was composed of 3 sections \nand translated in 3 languages (English, Malay and \nChinese). The questionnaire was completed by the \nparents, or guardians together with their children \n(except question 6 of section 2 was filled by research \nteam). Section 1 assessed the basic socioeconomic \nbackground of the children and their families. Age, \nsex, ethnicity, number of siblings, order in family, \nanthropometric measurement, parents\u2019 education \nand occupation, family history of atopy (based on \ndoctor\u2019s diagnosis), aggravating factor, treatments \nused and choice of medical advice were collected. \n\n\n\nSection 2 was for the diagnosis of AD through a \nvalidated UKWPD criteria.5 (1) A child must have \nan itchy skin condition, plus 3 or more of:  (2) history \nof involvement of the skin creases such as folds of \nelbows, behind the knees, fronts of ankles or around \nthe neck; (3) onset under the age of 2 (4) a personal \nhistory of asthma or allergic rhinitis; (5) a history of \ngeneral dry skin in the last year; (6) visible flexural \neczema noted by the research team.\n\n\n\nSection 3 measured the quality of life in AD children \nand their family using validated questionnaires, \nChildren\u2019s Dermatology Quality Life Index \n(CDLQI) and Dermatitis Family Impact (DFI).15,16 \n\n\n\nCDLQI consisted of 10 subjects and 7 domains \nrelated to the week before assessment. The domains \nare Symptoms (Itchy, sore or pain); Emotion \n(Embarrassment, sadness, or self-conscious); \nLeisure (Clothing, going out and play, or hobbies, \nswimming or other sports); Personal relationships \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4622\n\n\n\n\n\n\n\n\n(Friendships, bully or teasing); School or holidays; \nSleep; and Treatment problem. DFI consisted of 10 \nsubjects to measure how much having a child with \nAD affected the quality of life of the other (adult) \nmembers of the family in a one week recall period. \nFor both questionnaires, each question is given \na score based on the choice of the respondent, 0 \npoints for \u201cnot at all\u201d, 1 point for \u201ca little\u201d, 2 points \nfor \u201ca lot\u201d and 3 points for \u201cvery much\u201d. The sum of \nall 10 questions gives a total score range of 0 to 30.\n\n\n\nClinical Examination \nAll the consented children were examined at the \nselected school by the clinical team, consisting of \nthe investigator, medical officers, medical assistant, \nand staff nurses from Sarawak General Hospital\u2019s \ndermatology clinic. Clinical features of AD and its \nseverity were determined during the examination. \nTwo standardised AD severity scores were used-\nEczema Area and Severity Index (EASI) and \nInvestigator Global Assessment (IGA) scale.17,18\n\n\n\nEASI score is a tool to measure the extent and \nseverity of AD. The assessment is based on 4 \nbody regions-head & neck, trunk, upper and lower \nextremities. Extent and severity of eczema signs \nare evaluated for each body region. The extent is \nbased on percentage of skin affected by eczema \nand charted on a score from 0 to 6. The severity of \neczema signs, including erythema, oedema or papu-\nlation, excoriation, and lichenification are charted \nas none (0 points), mild (1 point), moderate (2 \npoints) or severe (3 points). The final score is the \nsum of the 4 region scores, which ranges from 0 \nto 72.  A higher score denotes greater AD severity. \nThe 5-point IGA scale categorises the AD severity \nas clear, almost clear, mild, moderate and severe. \nThe gradings are based on inflammatory signs like \nthe degree of erythema, population or induration, \nlichenification, and oozing or crusting. \n\n\n\nResults\n\n\n\nPrimary School Children\u2019s Demography\nA total of 968 from 1133 school children were \nenrolled in the study, giving a response rate of \n85.4%. SK Jalan Ong Tiang Swee contributed \n491 students to the study (97.8% response rate). \nThis was followed by 194 students from SK Batu \nLintang (60.6%), 159 students from SK James \nQuop (88.8%), and 124 students from SK Chung \n\n\n\nHua Pangkalan Baru (93.9%). Of the 165 students \nwho were not included, they were either absent \nduring the clinical examination or given no consent. \nRefer to Table 1 for the overall school children\u2019s \nsociodemography.\n\n\n\nChildren with Atopic Dermatitis \nThe prevalence of atopic dermatitis in school \nchildren was 7.0%. There were 68 students with \natopic dermatitis, 38 were girls and 30 were boys, \ngiving a slight predilection for girls with a M:F ratio \nof 1:1.27. Most of the children with AD were 7 to 9 \nyears old (54.4%). \n\n\n\nIn this study, AD was more common among Malays \n(29.4%) and Chinese (25.0%) when compared to the \nDayaks [Bidayuh (17.6%) and Iban (20.6%)]. Other \nethnicities accounted for 7.3%. The finding was \nrelatively similar to Kuching\u2019s racial distribution. \nThe 10 Indians in this study had no atopic dermatitis. \nThe Malay children were mostly in the elder age \ngroup, especially 12 years old (35.0%). On the \nother hand, Dayak children with AD were younger, \nbetween 7 to 9 years (61.5%).\n\n\n\nChildren with AD also had concomitant bronchial \nasthma (36.8%) or allergic rhinitis (61.2%). One-\nquarter of the children had AD only (25.0%). \nSixteen children (23.5%) had all the 3 diseases. \nAsthma was more common among Ibans and \nBidayuh (56.0%), while more Malays and Chinese \n(51.4%) had allergic rhinitis. Around 80% of the \nchildren with AD had at least one first degree family \nmember with atopy. Those affected family members \nwere either one or both parents (50.0%), especially \nmother. The remaining half was a combination of \nsiblings and parents. Mother was the most common \nfamily member to have atopic dermatitis (46.3%), \nasthma (48.2%) and allergic rhinitis (72.4%). \nThere were 14 AD children with no family history \nof atopy. In contrast, family history of atopy was \nsignificantly less in children without AD, accounted \nfor 29.6%. Most of the children had less than 4 \nsiblings (73.5%). Thirty- seven were the firstborn \nin the family, either the only child (37.8%) or eldest \namong siblings (62.2%). \n\n\n\nThe two most common aggravating factors were dust \nand hot weather. Most seek professional medical \nhelp as their first choice (85.3%). Those parents who \nseek consultation from a doctor preferred private \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\npractitioners or dermatologists (71.8%) over public \npolyclinic practitioners (23.5%). Neither ethnicity \nnor the parents\u2019 education level had influenced the \nchoice of consultation. We found that 67.6% of AD \nchildren used moisturisers as part of the treatment. \nHalf of them took antihistamines and applied topical \ncorticosteroids (Table 2). \n\n\n\nAlthough Pearson Chi-Square showed seven \nvariables (only child, order in family, concurrent \natopy and family history of atopy) were associated \nwith AD (Table 1), a subsequent binary logistic \nregression revealed 4 variables remained statistically \nsignificant (p<0.05). Eldest in the family was 2.6 \ntimes (95% CI 1.4, 4.6) more likely to have AD \nthan non-firstborn. The risk of having AD tripled \nin children with existing allergic rhinitis (95% CI \n2.0, 6.9) and doubled in asthma (95% CI 1.3, 5.1). \nMeanwhile, children with family history of eczema \nwere 7 times (95% CI 3.9, 13.6) more likely to have \nAD than non-family history. Refer Table 3.\n\n\n\nUKWPD Criteria and Atopic Dermatitis  \nSeverity (EASI and IGA)\nPruritus is a mandatory feature for diagnosis of \nAD. Thirty-eight (55.9%) school children fulfilled \n4 criteria, 16 (23.5%) met 5 criteria, 7 (10.3%) met \n6 criteria, and 7 (10.3%) had all 7 criteria. Half of \nthem had dry skin (51.5%).  Majority of the parents \nreported that the disease affected skin creases \n(89.7%) in the past, and approximately 80% of the \nchildren with AD had visible flexural dermatitis \nduring clinical examination. For the AD children \nwith onset below the age of two, 52.9% had asthma, \n58.8% had allergic rhinitis and one third had all the \n3 atopic diseases. (Table 2).\n\n\n\nOverall, school children with AD were mild with \na mean EASI score (SD) of 1.50 (2.0). Majority of \nthe AD children (98.5%) had EASI score less than \n7. Scores were higher on limbs compared to head, \nneck and trunk. Similarly, IGA based assessment \nshowed that more than half (54.4%) of the school \nchildren had almost clear to clear disease, 35.3% \nhad mild disease, and 10.3% had moderate disease. \nNone of the children had severe or very severe \ndisease. Children with IGA-based moderate disease \nhad a mean EASI score (SD) of 5.1  (3.75); whereas \nmean EASI score (SD) for children with IGA-based \n\n\n\nmild disease was 1.5 (0.76) and IGA-based almost-\nclear to clear disease was 0.56 (0.61). (Table 4).\n\n\n\nCDQLI and DFI in Quality of Life\nIn our series, CDLQI revealed that 90% of school \nchildren\u2019s quality of life was affected by AD to \nvarying degrees; more than half (52.9%) experienced \nmoderate to large effect on daily living. We had 19 \n(27.9%) children whose AD significantly affected \ntheir quality of life with CDLQI score of more than \n10. Two out of them (2.9%) had scored the highest \n19 points. (Table 5) The most affected domain was \n\u201cSymptoms\u201d [1.35 (0.69)], followed by \u201cSchool \nor holiday\u201d [0.97 (1.41)], \u201cEmbarrassment\u201d [0.96 \n(0.89)], \u201cTreatment problem\u201d [0.76 (0.85)] and \u201cGo \nout & Play\u201d [0.75 (0.82)]. Girls were slightly more \naffected than boys in all the domains. Looking into \nthe those 19 children\u2019s family aspect, 13 families \nwere severely affected with DFI score more than 10 \n(68.4%). The families of two children who scored \nhighest in CLDQI also had higher DFI scores, 14 and \n29. The other 6 families (31.6%) were moderately \naffected, and the scores were in the range of 6 to 10. \nThe affected domains in DFI were treatment impact \n[0.97 (1.17)], household expenditures [0.87 (0.91)], \nand housework [0.74 (0.84)]. Parents had to take \nmore effort and time to prepare the children\u2019s meals \n[0.62 (0.79)]. (Table 6).\n\n\n\nWe used logistic regression to appraise the \nrelationship between severity of AD to children \nand family\u2019s quality of life. The univariate analysis \nshowed that both the IGA and EASI scores \nnegatively impacted children\u2019s quality of life. \nIGA severity was statistically significant to the \ndomains of CDQLI (p=0.002). This relationship \nremained significant (p=0.002) after controlled for \nselected covariates such as gender, ethnicity and \nBMI. Post-hoc analysis showed strong association \nbetween moderate disease vs clear (p=0.012), \nmoderate disease vs almost clear (p=0.004) and \nmoderate disease vs mild disease (p<0.001). \nLikewise, statistical significance was seen between \nEASI severity and CDQLI in one-way ANCOVA \n(p=0.025). Higher EASI scores were associated \nwith a greater impact on children\u2019s quality of life. \nUnivariate and multivariate analysis showed no \nstatistical significance between the severity scores \nand DFI. (Table 7).\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4624\n\n\n\n\n\n\n\n\nTable 1. Demography of primary school children in Kuching\n\n\n\nCategory AD No AD Total p-value\n\n\n\nn (%) n (%) n (%)\n\n\n\nSex Male 30 (44.1) 482 (53.6) 512 (52.9) 0.133\n\n\n\nFemale 38 (55.9) 418 (46.4) 456 (47.1)\n\n\n\nAge 7-8 23 (33.8) 307 (34.1) 330 (34.1) 0.863\n\n\n\n9-10 26 (38.2) 318 (35.3) 344 (35.5)\n\n\n\n11-12 19 (27.9) 275 (30.6) 294 (30.4)\n\n\n\nRace Iban 14 (20.6) 194 (21.6) 208 (21.5) 0.556\n\n\n\nMalay 20 (29.4) 223 (24.8) 243 (25.2)\n\n\n\nChinese 17 (25.0) 174 (19.4) 191 (19.8)\n\n\n\nBidayuh 12 (17.6) 214 (26.8) 253 (26.2)\n\n\n\nMelanau 2 (2.9) 18 (2.0) 20 (2.1)\n\n\n\nIndian 10 (1.1) 10 (1.0)\n\n\n\nOthers 3 (4.4) 38 (4.2) 41 (4.2)\n\n\n\nOrder in family Only child 14 (20.6) 91 (10.7) 105 (11.4) 0.014\n\n\n\nSiblings 54 (79.4) 759 (89.3) 813 (88.6)\n\n\n\nEldest 23 (42.6) 220 (29.1) 243 (30.0) 0.037\n\n\n\nNon-firstborn 31 (57.4) 536 (70.9) 567 (70.0)\n\n\n\nBMI Normal 40 (58.8) 592 (65.9) 632 (65.4) 0.295\n\n\n\nOverweight 9 (13.2) 127 (14.1) 136 (14.1)\n\n\n\nObese 19 (27.9) 180 (20.0) 199 (20.6)\n\n\n\nOther atopic diseases Asthma <0.05\n\n\n\nYes 25 (36.8) 67 (7.8) 92 (9.9)\n\n\n\nNo 43 (63.2) 791 (92.2) 834 (90.1)\n\n\n\nAllergic rhinitis <0.05\n\n\n\nYes 42 (61.8) 153 (17.8) 195 (21.1)\n\n\n\nNo 26 (38.2) 705 (82.2) 731 (78.9)\n\n\n\nFamily history Atopy <0.05\n\n\n\nYes 54 (79.4) 266 (29.6) 320 (33.1)\n\n\n\nNo 14 (20.6) 634 (71.4) 648 (66.9)\n\n\n\nAsthma <0.05\n\n\n\nYes 29 (42.6) 158 (17.6) 187 (19.3)\n\n\n\nNo 39 (57.4) 742 (82.4) 781 (80.7)\n\n\n\nAllergic rhinitis <0.05\n\n\n\nYes 29 (42.6) 124 (13.8) 153 (15.8)\n\n\n\nNo 39 (57.4) 776 (86.2) 815 (84.2)\n\n\n\nEczema <0.05\n\n\n\nYes 41 (60.3) 113 (12.6) 154 (15.9)\n\n\n\nNo 27 (39.7) 787 (87.4) 814 (84.1)\n\n\n\nParents education None 3 (2.2) 13 (0.8) 16 (0.9) 0.017\n\n\n\nPrimary 1 (0.8) 108 (6.9) 109 (6.4)\n\n\n\nSecondary 53 (40.2) 879 (56.4) 932 (55.1)\n\n\n\nUniversity / \nCollege\n\n\n\n75 (56.8) 558 (35.8) 633 (37.5)\n\n\n\nHousehold [mean (SD)] Size 4.63 (1.40) 4.91 (1.28) 4.89 (1.29)\n\n\n\nBirth order 1.76 (1.00) 2.14 (1.22) 2.11 (1.21)\n\n\n\nSiblings no. 2.75 (1.31) 3.00 (1.28) 2.90 (1.28)\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nTable 2. AD diagnosis, aggravating factors, choice of \nconsultation and treatment pattern\n\n\n\nParents / Guardian\u2019s \nResponse, n (%)\n\n\n\nYes No\n\n\n\nUKWPD Questions for AD diagnosis\n\n\n\nQ1 - Itchy 68 (100.0) 0\n\n\n\nQ2 - Age onset\n\n\n\nUnder 2 34 (50.0)\n\n\n\n2 to 5 15 (22.1)\n\n\n\n5 to 10 16 (23.5)\n\n\n\nOver 10 3 (4.4)\n\n\n\nQ3 - Skin creases 61 (89.7) 7 (10.3)\n\n\n\nQ4a - Asthma 25 (36.8) 43 (63.2)\n\n\n\nQ4b - Allergic rhinitis 42 (61.8) 26 (38.2)\n\n\n\nQ5 - Dry skin 35 (51.5) 33 (48.5)\n\n\n\nQ6 - Visible flexural dermatitis 55 (80.9) 13 (19.1)\n\n\n\nAggravating factors\n\n\n\nDust 50 (73.5) 18 (26.5)\n\n\n\nHot weather 47 (69.1) 21 (30.9)\n\n\n\nFood 28 (41.2) 40 (58.8)\n\n\n\nGrass intolerance 24 (35.3) 44 (64.7)\n\n\n\nFurry pets 23 (33.8) 45 (66.2)\n\n\n\nPhysical exercise 16 (23.5) 52 (67.5)\n\n\n\nSchool stress 7 (10.3) 61 (89.7)\n\n\n\nPreferred healthcare provider\n\n\n\nDoctor 58 (85.3) 10 (14.7)\n\n\n\nPrivate general practitioner 31 (36.5)\n\n\n\nDermatologist 30 (35.3)\n\n\n\nPublic polyclinic doctor 20 (23.5)\n\n\n\nEmergency department 4 (4.7)\n\n\n\nPharmacist 40 (58.8) 28 (41.2)\n\n\n\nFamily or friends 10 (14.7) 58 (85.3)\n\n\n\nTraditional healer / Alternative \nmedicine\n\n\n\n8 (11.8) 60 (88.2)\n\n\n\nTreatment modalities\n\n\n\nMoisturisers or Emollients 46 (67.6) 22 (32.4)\n\n\n\nAntihistamines 36 (52.9) 32 (47.1)\n\n\n\nSteroids\n\n\n\nOral 6 (8.8) 62 (91.2)\n\n\n\nTopical 34 (50.0) 34 (50.0)\n\n\n\nAntibiotics 19 (27.9) 49 (72.1)\n\n\n\nTraditional herbs 9 (13.2) 59 (86.8)\n\n\n\nTable 3. The risk factors of atopic dermatitis\n\n\n\nFactors OR 95% CI p-value\n\n\n\nEldest among siblings 2.57 1.43 4.62 0.002\n\n\n\nConcomitant asthma 2.54 1.28 5.06 0.008\n\n\n\nConcomitant allergic rhinitis 3.75 2.05 6.87 0.000\n\n\n\nFamily history of asthma 1.23 0.65 2.29 0.526\n\n\n\nFamily history of allergic rhinitis 1.24 0.64 2.41 0.528\n\n\n\nFamily history of atopic dermatitis 7.24 3.86 13.58 0.000\n\n\n\nTable 4. Severity of AD by EASI and IGA\n\n\n\nEASI (Total scores)# n (%) IGA n (%)\n\n\n\nClear (0) 10 (14.7) Clear 11 (16.2)\n\n\n\nAlmost clear (0.1-1.0) 28 (41.2) Almost clear 26 (38.2)\n\n\n\nMild (1.1-7.0) 28 (41.2) Mild disease 24 (35.3)\n\n\n\nModerate (7.1-21.0) 2 (2.9) Moderate \ndiseases\n\n\n\n7 (10.3)\n\n\n\nSevere (21.1-50.0) 0 Severe diseases 0\n\n\n\nVery severe (50.1-72.0) 0 Very severe \ndiseases\n\n\n\n0\n\n\n\n#Mean total EASI score (SD)=1.50 (2.0). Mean EASI score (SD) for \neach section-head & neck 0.03 (0.14); trunk 0.20 (0.44); upper limb \n0.44 (0.53); and lower limb 0.83 (1.11)\n\n\n\nTable 5. The scores for CDQLI and DFI\n\n\n\nn (%)\n\n\n\nScores* 0 to 1 2 to 5 6 to \n10\n\n\n\n11 to \n20\n\n\n\n21 to \n30\n\n\n\nCDLQI 10 \n(14.7)\n\n\n\n22 \n(32.4)\n\n\n\n17 \n(25.0)\n\n\n\n19 \n(27.9)\n\n\n\n0\n\n\n\nDFI 17 \n(25.0)\n\n\n\n25 \n(36.8)\n\n\n\n11 \n(16.2)\n\n\n\n14 \n(20.6)\n\n\n\n1 (1.5)\n\n\n\n*Scores interpretation: 0-1=no effect; 2-6=small effect; 7-12=moderate \neffect; 13-18=very large effect; 19-30=extremely large effect\n\n\n\nTable 6. Mean score and standard deviation of each \ndomains in CDLQI and DFI\n\n\n\nMean Score (SD)\n\n\n\nCDLQI (n=68) Total Boys Girls p-\nvalue\n\n\n\nQ1 - Itchy, Sore \nor Pain\nQ2 - Embarrassed\nQ3 - Friendship\nQ4 - Clothes\nQ5 - Go out & \nPlay\nQ6 - Swimming \nor Sports\nQ7 - School or \nHoliday\nQ8 - Bully\nQ9 - Sleep\nQ10 - Treatment \nproblem\n\n\n\n1.35 (0.69)\n\n\n\n0.96 (0.89)\n0.26 (0.61)\n0.65 (0.75)\n0.75 (0.82)\n\n\n\n0.63 (0.95)\n\n\n\n0.97 (1.41)\n\n\n\n0.29 (0.69)\n0.63 (0.85)\n0.76 (0.85)\n\n\n\n1.40 (0.81)\n\n\n\n0.90 (1.00)\n0.27 (0.69)\n0.83 (0.83)\n0.67 (0.84)\n\n\n\n0.57 (0.86)\n\n\n\n0.70 (1.29)\n\n\n\n0.30 (0.65)\n0.57 (0.86)\n0.70 (0.88)\n\n\n\n1.32 (0.57)\n\n\n\n1.00 (0.81)\n0.26 (0.55)\n0.50 (0.65)\n0.82 (0.80)\n\n\n\n0.68 (1.02)\n\n\n\n1.18 (1.49)\n\n\n\n0.29 (0.73)\n0.68 (0.84)\n0.82 (0.83)\n\n\n\n0.633\n\n\n\n0.156\n0.788\n0.350\n0.812\n\n\n\n0.270\n\n\n\n0.162\n\n\n\n0.950\n0.769\n0.589\n\n\n\nTotal score 7.26 (5.53) 6.90 (5.85) 7.55 (5.33) 0.931\n\n\n\nDFI (n=68)\n\n\n\nQ1 - Housework\nQ2 - Feeding\nQ3 - Sleep\nQ4 - Family \nactivity\nQ5 - Shopping\nQ6 - Expenditure\nQ7 - Tiredness\nQ8 - Emotion\nQ9 - Relationship\nQ10 - Treatment \nimpact\n\n\n\n0.74 (0.84)\n0.62 (0.79)\n0.56 (0.80)\n0.44 (0.70)\n\n\n\n0.34 (0.66)\n0.87 (0.91)\n0.47 (0.78)\n0.49 (0.74)\n0.25 (0.56)\n0.97 (1.17)\n\n\n\n0.60 (0.77)\n0.57 (0.82)\n0.50 (0.78)\n0.27 (0.52)\n\n\n\n0.23 (0.43)\n0.73 (0.91)\n0.47 (0.78)\n0.40 (0.56)\n0.20 (0.41)\n1.03 (1.27)\n\n\n\n0.84 (0.89)\n0.66 (0.78)\n0.61 (0.82)\n0.58 (0.79)\n\n\n\n0.42 (0.79)\n0.97 (0.92)\n0.47 (0.80)\n0.55 (0.86)\n0.29 \u00b1 0.65\n0.92 (1.10)\n\n\n\n0.791\n0.830\n0.728\n0.055\n\n\n\n0.218\n0.387\n0.785\n0.052\n0.146\n0.187\n\n\n\nTotal score 5.74 (6.12) 5.00 (5.32) 6.32 (6.70) 0.241\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4626\n\n\n\n\n\n\n\n\nTable 7. Relationship between AD severity (by IGA or \nEASI) and Quality of life (by CDQLI or DFI)\n\n\n\nUnivariate Multivariate\n\n\n\nFactors CDLQI DFI CDLQI DFI\n\n\n\nIGA 0.002a 0.242a 0.002+ nil\n\n\n\nEASI 0.023c 0.248c 0.025b nil\nThe p-value for multivariate analysis were derived after controlled for \ngender, ethnicity and BMI category. \nap-value was derived from one-way ANOVA; bp-value was derived from \nANCOVA; cp-value was derived from linear regression\n\n\n\nDiscussions \n\n\n\nPrevalence and Risk Factors\nAD is one of the most common skin disorders \naffecting up to 20% of children in some countries.7 \nApproximately 28% of the Malaysian population \nare children.19 The ISAAC study published our \nnational prevalence of AD as 11.0% (6-7 years \nold) and 9.3% (13-14 years old) in 2008, based \non population study in cities of West Malaysia \n(WM).7,20 The urbanization of Malaysia\u2019s cities over \nthe decades has led to the rise of AD prevalence by \nnearly 4 folds.7\n\n\n\nThis is the first population-based study of AD among \nschool children in Kuching, in the age group of 7 \nto 12. Based on the UKWPD criteria questionnaire \nand clinical examination, the overall prevalence of \nAD was 7% and girls (8.3%) were more prevalent \nthan boys (5.9%).  This was comparable to the 7.6% \nof AD prevalence among secondary school children \nin Kota Kinabalu, the capital city in another state in \nEast Malaysia, Sabah.21\n\n\n\nHowever, the age-specific prevalence of AD in our \nstudy was lower than that in WM. The discrepancy \nmight have been attributed to many studies done in \nWM that were either clinic or hospital-based.8,9,10,11 \nThere were two population-based studies from WM \nthat reported a higher prevalence, 13.7% (5 to 7 years \nold) and 13.5% (Preschool age, less than 6 years \nold).12-14 This could be due the difference in ethnic \nmix of children, age and environmental factors. It \nwas also well recognised that AD prevalence varied \nbetween rural and urban areas. WM developed at \na pace greater than EM due to geographical and \nlogistic differences. Several studies reported a higher \nprevalence in specific races.20,22,23 ISAAC study \nshowed a significant difference in the prevalence \nof both within countries and between geographical \nareas.5,20 Scandinavia, Western Europe, Australasia, \n\n\n\nand urban areas in Africa have a higher prevalence \nrate than China, the Middle East, Central Asia and \nEastern Europe.24 Children in our cohort were of \ndiversified racial background while other studies \nfrom WM were predominantly Malays (80-90%) \nand Chinese. The prevalence of AD in Iban (6.7%) \nand Bidayuh (4.7%) children were slightly lower \nwhen compared to Malays (8.2%) or Chinese \n(8.9%). Nonetheless, these data showed that AD is \ncommon among school children in Malaysia. \nThe prevalence of AD is known to decrease with \nage;25 however, we found no difference in the \nprevalence of AD between 7 to 12 years old. A \nstable trend was noticed at a range of 6.4% to 8.0%. \nPrevalence was highest in 12 years old (8.4%) and \nlowest in 11 years old (4.6%). \n\n\n\nAD is a known disease of infancy and childhood, \nin which more than 80% had onset before the age \nof 7 years.26 Half of children with AD in our series \nhad onset before the age of 2 years. Only 3 of the \nchildren had onset after the age of 10 (4.4%). The \nfinding corresponded to a study in preschool children \nin Kuala Lumpur, 70% of children had AD onset \nless than 2 years old.14 A population-based study in \nSingapore also recorded similar results.27 A clinic-\nbased study at the paediatric institute reported early \nonset of disease with a median age of diagnosis \nof 22 months.28 Late-onset of AD is otherwise not \nuncommon. A study from the National University \nof Malaysia showed that 22.6% of patients had late \nonset of AD between 11 to 30 years old.10 Another \ncohort also reported that 32.2% of children had \ndisease onset after the age of 7 years.29\n\n\n\nAD was more common in girls, despite there \nbeing more boys in this study. The M:F ratio was \nthe most apparent amongst 12-year-olds (1:2). \nOne population-based study in Australia also \nfound higher prevalence in girls, either by clinical \nexamination (17.7%) or UKWPD criteria (12.3%) \nthan boys, 14.8% and 9.2% respectively.30 The \nfemale preponderance is similar to the ISAAC \nstudy and another clinic-based local study.5,11 On the \nother hand, other local studies showed more males \naffected with M:F ratio of 1.7:1.10,14,28 A Korean \nreview article mentioned that boys were more likely \nto develop AD than girls during infancy, but there \nwas a girls predominance in adolescence.31\n\n\n\nFamily history of atopy was the single most \n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27MJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\ncritical risk factor for atopy among children.32 \n\n\n\nWe found similar association in our cohort with a \nsevenfold increase risk of getting AD. Children with \nconcomitant asthma or allergic rhinitis had doubled \nto a tripled risk of developing AD. Approximately \nthree-quarter of the school children in this series \nhad at least one concomitant atopic disease. A \nstudy in Taiwan also showed increased risk of AD \ndevelopment by two folds among atopy children.33 \n\n\n\nThe local study had shown significant association \nbetween AD and concomitant atopic diseases.14 \nOur study also showed that the eldest in the family \nhad tripled AD development risk. Studies on siblings \nsuggested a diminished risk of atopy in younger \nsiblings due to the protective effect of early-life \nviral infections.34\n\n\n\nQuality of Life among AD Children\nAD\u2019s chronic and recurrent nature incurred \nsignificant negative impact on both affected \nchildren and their families.35 In our study, AD had \ninfluenced the children\u2019s quality of life in various \naspects, even though most had mild course of \ndisease. This was also true in a factor analysis study \ndone in Hong Kong.36 The most affected domains \nwere \u201cSymptoms\u201d, \u201cEmotions\u201d and \u201cSchool or \nholiday\u201d. Literature had shown consistent results \nin many studies worldwide.28,36-41 Constant itch, \nsore or pain was the most significantly affected \npsychosocial domains among children with AD. \nThe biggest challenge in AD is the management of \nitch. Itch had disturbed half of the children\u2019s sleep \nand 50% of them responded \u201cvery much\u201d and \u201cquite \na lot\u201d. Sleep deprivation would affect a child\u2019s \nbehavioural development and school performance \nin longterm.35,42\n\n\n\nFeeling of embarrassment, self-conscious, upset \nand sad among the AD children, particularly girls, \nhad indirectly taken a toll on school work and \nholiday enjoyment. Children with AD often shy \naway from their peers due to chronic and visible \nskin lesions.43 It also affected the domain \u201cGo out & \nplay and swimming or sports\u201d. The stigmatization \nand negative changes of self-perception would \ngradually drain the children emotionally to mental \ndistress. Although the disease did not affect the \ndomain \u201cfriendship\u2019 and \u201cbully\u201d, careful attention \nmust be emphasized to keep the social stigma of \nAD at minimal level in schools. The social relations \nwith peers in this age group grow significantly.44\n\n\n\nAlmost a quarter of the AD children also felt \nthat \u201cTreatment\u201d had bothered them at certain \nextend. A Thai study reported that taking oral \nmedications, especially number of medications \ncould significantly affect quality of life of the \nchildren and caretakers.37 Parental admonitions may \nfurther stigmatize the AD children to additional \nisolation.43 In our study, children between 10 to 12 \nyears were more affected than juniors (7 to 9 years) \nin most domains, particularly physical symptoms, \nschool work or holiday enjoyment and emotions. \nPre-adolescent children are more self-aware and \nhave a better cognitive, psychosocial and emotional \ndevelopment.45 They are in transition between \nchildhood and adulthood to gain independence and \nestablish a secure identity. This group of children\u2019s \nself-expression and concern on AD, including \nemotion and treatment, must be addressed during \nclinic consultation.\n\n\n\nQuality of Life among Families of AD Children\nAD affects the social and emotional aspects of \nfamilies of AD children. A study showed that \nrestrictions of everyday family life and limitations \nwith stringent treatment regimes have led to \nparental exhaustion, hopelessness, guilt, anger and \ndepression.46 Caring for a child with AD requires \nadjustments to family lifestyles and incurs financial \ncosts.47 \n\n\n\nDomains that were affected were \u201cTreatment \nimpact\u201d, \u201cExpenditure\u201d, \u201cHousework\u201d, and \n\u201cFeeding\u201d. About a quarter of the family felt \u201cA \nlot\u201d and \u201cVery much\u201d affected by the \u201cTreatment \nimpact\u201d. The family of children with clear to mild \ndisease responded to \u201cTreatment impact\u201d with a \nmean score (SD) of 0.84 (1.07), compared to those \nwith a moderate disease which was significantly \nhigher, 2.57 (1.13). This was in accordance with \nother studies.28,37,48 Parents had spent more time \nand effort helping the children deal with the \ndisease and its treatment, in addition to the chores \nin the house, especially to keep the linens clean \nand environment dust-free. Some of the parents \nbelieved that certain foods could aggravate the \ndisease and were meticulous with meal preparation \nfor the family. Consequently, adaptations to family \nlifestyles have expectedly increased the overall \nhousehold expenses. The treatment of AD could be \ncostly if parents self-purchased medications, seek \nconsultation from private clinics and alternative \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4628\n\n\n\n\n\n\n\n\ntreatment practitioners.\n\n\n\nCo-sleeping is a common habit in Malaysia. The \nmean score (SD) of domain \u201cSleep\u201d in family \nmembers was 0.56 (0.80). There were 16% of them \nresponded to sleep disturbances as \u201cA lot\u201d and \u201cVery \nmuch\u201d, of which half of the children had mild to \nmoderate disease. This negative effect on parental \nsleep pattern was also reported in a Thai study.37\n\n\n\nIn our study, majority of the primary caregivers were \nworking parents. Twenty AD children\u2019s mothers \nwere housewives. Nevertheless, the domains like \n\u201cRelationship\u201d, \u201cEmotion\u201d and \u201cTiredness\u201d were \nless affected. Less than 10% of families regarded \nthose as \u201cvery much\u201d or \u201cA lot\u201d. This could be \nexplained by the fact that approximately one-third \nof mothers had atopy. Their personal experience \nhelped in coping and understanding the disease. \nMothers were able to cope with emotional distress \nand exhaustion despite feeling more occupied \nwith childcare. Our cohort of school children was \npredominantly mild in disease severity. Literature \nshowed that parents of children with more severe \nAD had more impact on emotional distress.48 \nWe found that those families that responded with \nprofound impact on \u201cRelationship\u201d, \u201cEmotion\u201d and \n\u201cTiredness\u201d were in the younger age group (7 to 9 \nyears), about 10% had moderate disease. More than \n90% had no family history of atopy.\n\n\n\nIntervention in AD School Children \nThe clinical assessment had given the study a great \nadvantage to understand the AD disease burden \namong school children. We noticed that 33% of \nchildren with AD were not using moisturizers, \nwhich is the main therapy that improves skin barrier \nand reduces pruritus.49 Emollient therapy has \nproven to enhance topical corticosteroids\u2019 efficacy, \nthus reducing its steroid usage and dependency.50 \n\n\n\nThe research findings enable our team to plan and \norganize educational programs for the children and \nparents, which encompasses disease knowledge, \nprevention of triggers, practical skincare, treatment \nand wholesome AD\u2019s management. School children \nwith moderate disease or frequent flares were given \nappointment to be managed and followed up at \nSarawak General Hospital\u2019s dermatology clinic.  \n\n\n\nConclusion\nAtopic dermatitis is common among school \nchildren in Kuching. This study gave insight into \n\n\n\nAD in school children and acknowledged that AD \nhad a significant physical, emotional and social \nimpact on the affected children and their families, \nalthough the majority were mild in severity. The \nassociation between AD and other atopic diseases \nvis-\u00e0-vis asthma, allergic rhinitis is demonstrated, \nas is the association with genetic tendencies of \nAD\u2019s development. Clinicians should incorporate \nmeasurement of quality of life to accurately assess \nAD severity to improve long term management of \nAD. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nWe would like to thank the Director General of \nHealth Malaysia for permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. Development group of Ministry of Health and Ministry \nof Education. Malaysia Clinical Practice Guidelines: \nManagement of atopic eczema, 1st ed. Putrajaya. \nMalaysian Health Technology Assessment Section \n(MaHTAS) 2008:1-2.\n\n\n\n2. Williams HC. Clinical practice. Atopic dermatitis. N Engl \nJ Med 2005;352:2314-24.\n\n\n\n3. Simpson EL, Leung DYM, Eichenfield LF, Boguniewicz \nM. Atopic dermatitis. In Fitzpatrick\u2019s dermatology \n(Volume 1) 9th Ed. New York. McGraw-Hill Education \n2019:363-456. \n\n\n\n4. Hanifin JM, Rajka G. Dianostic features of atopic dermatitis. \nActa Derm Venereol Suppl (Stockh) 1980;59:44-7. \n\n\n\n5. Williams HC, Burney PGJ, Pembroke AC, Hay RJ. The \nU.K. Working Party\u2019s Diagnostic Criteria for Atopic \nDermatitis. III. Independent hospital validation. Br J \nDermatol 1994;131:406-16.  \n\n\n\n6. Brenninkmeijer EE, Schram ME, Leeflang MM, Bos \nJD, Spuls PI. Diagnostic criteria for atopic dermatitis: a \nsystematic review. Br J Dermatol 2008;158:754-65.\n\n\n\n7. Asher MI, Montefort S, Bj\u00f6rkst\u00e9n B, Lai CK, Strachan DP, \nWeiland SK et al. 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Simpson E, Bissonnette R, Eichenfield LF, Guttman-\nYassky E, King B, Silverberg JI et al. The Validated \nInvestigator Global Assessment for Atopic Dermatitis \n(vIGA-AD): The development and reliability testing of \na novel clinical outcome measurement instrument for \nthe severity of atopic dermatitis. J Am Acad Dermatol \n2020;83:839-46.\n\n\n\n19. Department of Statistics Malaysia. Press release: Children \nstatistics, Malaysia, 2019. [Accessed in Nov 2019] Available \nfrom: https://www.dosm.gov.my/v1/index.php?r=column/\npdfPrev&id= c3I4eitkb1RZTlMvUjNLZVRBMExVQT09\n\n\n\n20. Williams H, Robertson C, Stewart A, A\u00eft-Khaled N, \nAnabwani G, Anderson R et al. Worldwide variations \nin the prevalence of symptoms of atopic eczema in the \ninternational study of asthma and allergies in childhood. J \nAllergy Clin Immunol 1999;103:125-38.\n\n\n\n21. Leung R, Ho P. Asthma, allergy, and atopy in three south-\neast Asian populations. Thorax 1994;49:1205-10.\n\n\n\n22. Janumpally SR, Feldman SR, Gupta AK. In the United \nStates, blacks and Asian/Pacific Islanders are more likely \nthan whites to seek medical care for atopic dermatitis. \nArch Dermatol 2002;138:634-7.\n\n\n\n23. Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema \nprevalence in the United States: data from the 2003 \nNational Survey of Children\u2019s Health. J Invest Dermatol \n2011;131:67-73.\n\n\n\n24. Yong AMY, Tay YK. Atopic dermatitis: Racial and ethnic \ndifferences. Dermatol Clin 2017;35:395-402.\n\n\n\n25. Chidwick K, Busingye D, Pollack A, Osman R, Yoo J, \nBlogg S et al. Prevalence, incidence and management \nof atopic dermatitis in Australian general practice using \nroutinely collected data from Medicine Insight. Australas J \nDermatol 2020;61:e319-27.\n\n\n\n26. Rajka G. Essential Aspects of Atopic Dermatitis, 1st ed. \nBerlin. Springer-verlag 1989:4-55. \n\n\n\n27. Tay YK, Kong KH, Khoo L, Goh CL, Giam YC. The \nprevalence and descriptive epidemiology of atopic \ndermatitis in Singapore school children. Br J Dermatol \n2002;146:101-6.\n\n\n\n28. Aziah MS, Rosnah T, Mardziah A, Norzila MZ. Childhood \natopic dermatitis: a measurement of quality of life and \nfamily impact. Med J Malaysia. 2002;57:329-39. \n\n\n\n29. Williams HC, Strachan DP. The natural history of \nchildhood eczema: observations from the British 1958 \nbirth cohort study. Br J Dermatol 1998;139:834-9.\n\n\n\n30. Marks R, Kilkenny M, Plunkett A, Merlin K. The \nprevalence of common skin conditions in Australian \n\n\n\nschool students: 2. Atopic dermatitis. Br J Dermatol \n1999;140:468-73.\n\n\n\n31. Pyun BY. Natural history and risk factors of atopic \ndermatitis in children. Allergy Asthma Immunol Res \n2015;7:101-5.\n\n\n\n32. Tariq SM, Matthews SM, Hakim EA, Stevens M, Arshad \nSH, Hide DW. The prevalence of and risk factors for atopy \nin early childhood: a whole population birth cohort study. \nJ Allergy Clin Immunol 1998;101:587-93.\n\n\n\n33. Ho CL, Chang LI, Wu WF. The prevalence and risk factors \nof atopic dermatitis in 6-8 year-old first graders in Taipei. \nPediatr Neonatol 2019;60:166-71.\n\n\n\n34. Von Mutius E, Martinez FD, Fritzsch C, Nicolai T, \nReitmeir P, Thiemann HH. Skin test reactivity and number \nof siblings. BMJ 1994;308:692-5.\n\n\n\n35. Ng MS, Tan S, Chan NH, Foong AY, Koh MJ. Effect of \natopic dermatitis on quality of life and its psychosocial \nimpact in Asian adolescents. Australas J Dermatol \n2018;59:e114-7. \n\n\n\n36. Hon KL, Leung TF, Wong KY, Chow CM, Chuh A, Ng \nPC. Does age or gender influence quality of life in children \nwith atopic dermatitis? Clin Exp Dermatol 2008;33:705-9.\n\n\n\n37. Wisuthsarewong W, Nitiyarom R, Boonpuen N. Childhood \natopic dermatitis: Impact on quality of life in Thai children \nand their families. Astrocyte 2017;4:144-8. \n\n\n\n38. Chamlin SL, Frieden IJ, Williams ML, Chren MM. Effects \nof atopic dermatitis on young American children and their \nfamilies. Pediatrics 2004;114:607-11.\n\n\n\n39. Finlay AY. Quality of life in atopic dermatitis. J Am Acad \nDermatol 2001;45:S64-6.\n\n\n\n40. Xu X, van Galen LS, Koh MJA, Bajpai R, Thng S, Yew \nYW et al. Factors influencing quality of life in children \nwith atopic dermatitis and their caregivers: a cross-\nsectional study. Sci Rep 2019;9:15990. \n\n\n\n41. Ra\u017enatovi\u0107 \u0110urovi\u0107 M, Jankovi\u0107 J, Tomi\u0107 Spiri\u0107 V, \nReli\u0107 M, Sojevi\u0107 Timotijevi\u0107 Z, \u0106irkovi\u0107 A et al. Does \nage influence the quality of life in children with atopic \ndermatitis? PLoS One 2019;14:e0224618. \n\n\n\n42. Fishbein AB, Vitaterna O, Haugh IM, Bavishi AA, Zee \nPC, Turek FW et al. Nocturnal eczema: Review of sleep \nand circadian rhythms in children with atopic dermatitis \nand future research directions. J Allergy Clin Immunol \n2015;136:1170-7. \n\n\n\n43. Chernyshov Stigmatization and self-perception in children \nwith atopic dermatitis. Clin Cosmet Investig Dermatol \n2016;9:159-66.\n\n\n\n44. Eccles JS. The development of children ages 6 to 14. \nFuture Child 1999;9:30-44.\n\n\n\n45. Sanders RA. Adolescent psychosocial, social, and \ncognitive development. Pediatr Rev 2013;34:354-8.\n\n\n\n46. Pusti\u0161ek N, Vurnek \u017divkovi\u0107 M, \u0160itum M. Quality of Life \nin Families with Children with Atopic Dermatitis. Pediatr \nDermatol 2016;33:28-32. \n\n\n\n47. Al Shobaili HA. The impact of childhood atopic dermatitis \non the patients\u2019 family. Pediatr Dermatol 2010;27:618-23.\n\n\n\n48. Monti F, Agostini F, Gobbi F, Neri E, Schianchi S, \nArcangeli F. Quality of life measures in Italian children \nwith atopic dermatitis and their families. Ital J Pediatr \n2011;37:59. \n\n\n\n49. Van Zuuren EJ, Fedorowicz Z, Christensen R, Lavrijsen \nA, Arents BWM. Emollients and moisturisers for eczema. \nCochrane Database Syst Rev 2017;2:CD012119. \n\n\n\n50. Grimalt R, Mengeaud V, Cambazard F; Study Investigators\u2019 \nGroup. The steroid-sparing effect of an emollient therapy \nin infants with atopic dermatitis: a randomized controlled \nstudy. Dermatology 2007;214:61-7.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4630\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31\n\n\n\nORIGINAL ARTICLE\n\n\n\nThe Association of Skin and Nasal Colonisations of Staphylococcus \naureus in Children with Atopic Dermatitis with Disease Severity and \nIts Impact on Quality of Life\nJin Huang Lim1, MRCP, Anis Roziana Mohamad2, MPath, Kwee Eng Tey1, MRCP\n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\n2Department of Microbiology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\n\n\n\nAbstract \nBackground\nAtopic dermatitis (AD) is a chronic, recurrent, pruritic inflammatory skin disease that causes significant \nburden to affected children. Staphylococcus aureus plays a vital role in AD, and its resistance to current \ntopical antibiotics is worrying. This study aims to determine the frequency of Staphylococcus aureus \ncolonisation and its resistance pattern. It further assesses the association between Staphylococcus \naureus colonisation and disease severity; as well as its impact on quality of life.\n\n\n\nMethods\nA cross-sectional study was conducted among 153 children with AD. Skin and nasal swabs were \ncollected. Antibiotic sensitivity to penicillin, cefoxitin, erythromycin, methicillin, clindamycin, \ngentamicin, trimethoprim/sulfamethoxazole, tetracycline, rifampicin, fusidic acid and linezolid were \ntested. Clinical evaluation was performed using the SCORing Atopic Dermatitis index (SCORAD). \nQuality of life was assessed with the Dermatological Life Quality Index (DLQI).\n\n\n\nResults\nTwenty-nine patients had positive skin swab results. One patient had methicillin-resistant \nStaphylococcus aureus isolated from nasal swab. Skin colonisation with Staphylococcus aureus \n(p=0.03) and DLQI (p<0.01) were significantly associated with disease severity. The resistant rate is \nhighest in penicillin, followed by fusidic acid, tetracycline, and erythromycin.\n\n\n\nConclusion\nSkin colonisation with Staphylococcus aureus is an indicator of disease severity in children with AD. \nPatients with severe disease have lower quality of life. Clinicians need to be aware of high resistance \nrates towards penicillin and fusidic acid and be prudent in the choice of antibiotics. Antiseptic wash \ncan be considered in patients with Staphylococcus aureus colonisation.\n\n\n\nKey words: Staphylococcus aureus, Atopic dermatitis, Dermatological life quality index\n\n\n\nIntroduction\nAtopic dermatitis (AD) is a chronic, recurrent, \npruritic inflammatory skin disease with estimated \nprevalence of 10-30% in children and up to 2-5% \nin adults.1,2 The incidence of AD appears to be \nincreasing. A systematic review of epidemiologic \nstudies performed between 1990 and 2010 in \nseveral regions found increasing trends in incidence \n\n\n\nCorresponding Author\nDr Lim Jin Huang\nDepartment of Dermatology,\nHospital Sultanah Aminah,\nJalan Persiaran Abu Bakar Sultan,\n80100 Johor Bahru, Johor, Malaysia.\nEmail: jesling2001@yahoo.com\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4632\n\n\n\nand prevalence of AD.2 In addition, AD is the most \nsignificant contributor to the global burden of \ndisease among skin diseases.3\n\n\n\nSevere AD causes significant distress to the affected \nchildren and their parents.4,5,6,7 Children with AD \noften have behavioural problems such as increased \ndependency, fearfulness, and sleep difficulties.8 A \nholistic approach to patient care can be developed \nafter recognising the impact of the disease. \nClinicians will be more confident in judging the \nbenefits of therapeutic interventions and ensuring \ncompliance with therapy.\n\n\n\nSkin is the biggest organ of the body and it \ninterfaces with the environment. It has a complex \necosystem colonised by many microorganisms \n(that are either pathogen or mutualist), coexisting \nin a balance. Atopic dermatitis is well known to be \nassociated with altered skin microbiota, with high \nprevalence of Staphylococcus aureus colonisation \nand superinfection. The AD skin has a favourable \nenvironment for colonisation and proliferation of \nStaphylococcus aureus. The bacteria is frequently \nfound on the skin of AD patients (carriage rates of \n30% to 100% depending on the study methodology), \nwhereas in healthy subjects, the prevalence is about \n10 to 20%.9 The prevalence of nasal colonisation by \nS. aureus varies between 10 and 30%.10,11\n\n\n\nStaphylococci can be mutualist or pathogen \ndepending on its species. The dominant group of \nskin colonists is the coagulase-negatives, the most \nprominent of which, is S. epidermidis. The bacteria \ncan be an opportunistic pathogen in the context of \nimmunosuppression; it functions predominantly as \na mutualist. \n\n\n\nSkin-resident Staphylococcus species engage in \nmicrobe-microbe interactions that are beneficial \nto the host.9,12 For example, S. epidermidis and S. \nhominis have been shown to secrete antimicrobial \npeptides that kill S. aureus, and transplantation \nof these species onto the skin of patients with \natopic dermatitis led to decreased colonisation \nby S. aureus.13 However, an association between \nS. aureus colonisation and AD severity is still \ninconclusive.14,15,16\n\n\n\nIt is not uncommon for children who present with \nAD to be treated with antibiotics and antiseptic, as \n\n\n\nthis could lead to increased antibiotic resistance.17 \n\n\n\nMany studies were done to establish the current \nantimicrobial resistances and susceptibilities to \nfirst-line antibiotic therapy.18,19,20 With the rapid \nemergence of resistant bacteria worldwide, rationale \nuse of antibiotics needs to be advocated.\n\n\n\nThe objectives of this study are to evaluate \nthe frequency of skin and nasal colonisation \nby Staphylococcus aureus in children with \natopic dermatitis. In addition, it aims to identify \nantimicrobial sensitivity, as well as establish the \nassociation between colonisation of S. aureus and \ndisease severity, and its impact on psychosocial \nwellbeing of the children.\n\n\n\nMaterials and Methods\nA cross-sectional study was conducted. A total \nnumber of 153 children (age below 18 years old) \nwith confirmed diagnosis of atopic dermatitis by \ndermatologists were recruited between January 2020 \nand April 2020 from the Dermatology outpatient \nclinic of Hospital Sultanah Aminah, Johor Bahru, a \ntertiary hospital in Malaysia. \n\n\n\nThe estimated sample size was based on a study \nby Rezaei M, et al.21 Sample size estimation \nwas calculated using two population proportion \nformulae.22 A minimum sample size of 153 samples \nper group is needed to reject the null hypothesis with \nprobability (power) 0.8. The Type I error probability \nassociated with this test of this null hypothesis is \n0.05. Pearson\u2019s Chi-square test for independence \nwill be used to evaluate this null hypothesis. \nExclusion criteria were patients who received oral \nor topical antibiotic four weeks before the study, \npatients who have coexisting inflammatory skin \ndiseases, clinical evidence of cutaneous bacterial, \nviral or fungal infection and upper respiratory \ninfection within four weeks.\n\n\n\nA predesigned clinical research form for recording \ndemographic data, medical history, clinical \nexamination, and disease severity using SCORing \nAtopic Dermatitis (SCORAD) index was completed \nduring the visit. By using the SCORAD index, the \nseverity of eczema was scored in each patient as \nmild (<25), moderate (25-50) or severe (>50).23,24 All \npatients and their parents were required to fill up a \nvalidated and licensed Dermatological Life Quality \nIndex (DLQI) form according to the children\u2019s age \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33\n\n\n\ngroup. The DLQI stratifies the quality of life into \nfive categories: no effect at all on patient\u2019s life (0-1), \na small effect on patient\u2019s life (2-5), moderate effect \non patient\u2019s life (6-10), very large effect on patient\u2019s \nlife (11-20) and extremely large effect on patient\u2019s \nlife (21-30).25,26\n\n\n\nSkin and nasal swabs were collected from subjects \nusing Micro Science Microbiology Transport Swab \nwith Medium Amies with Charcoal. The skin swab \nwas taken from an eczematous lesion. Levine \nmethod was used for obtaining the skin swab. Nasal \nswab was taken from both nostrils by using the same \nswab. Specimens were sent to the Department of \nMicrobiology of Hospital Sultanah Aminah within \n24 hours for processing.\n\n\n\nThe nasal sample was inoculated onto 10% \nsheep blood agar plates, whereas the skin sample \nwas inoculated onto 10% sheep blood agar and \nMacConkey\u2019s medium. After 24 hours inoculation \nat 37\u00b0C, the agars were reviewed. S. aureus isolates \nwere identified by a coagulase test (to differentiate \nS. aureus and Staph spp.) and catalase test (to \ndifferentiate Strep spp. and Staph spp.). S. aureus \ncolony was cultured on the Staphylococcus panel \nincluding Cefoxitin disk (FOX-disk) for another \n24 hours to test for methicillin resistance. The \nantibiotic sensitivity test is done according to the \nClinical and Laboratory Standards Institute (CLSI, \n2019). The tested antibiotics included penicillin, \ncefoxitin, erythromycin, methicillin, clindamycin, \ngentamicin, trimethoprim/sulfamethoxazole, \ntetracycline, rifampicin, fusidic acid and linezolid. \nThe interpretation of the susceptibility was given \nas sensitive (S), intermediate susceptible (IS), or \nresistant (R) following standard recommendation.\n\n\n\nThe data analysis was done using the Statistical \nPackage of the Social Science (SPSS) version 22 \n(IBM Corporation, CA). Descriptive analysis was \nperformed and was presented as frequency and \npercentage. Association was analysed using Chi-\nsquare or Fisher\u2019s exact test. A value of p<0.05 \nis considered statistically significant. A graphical \npresentation was used to illustrate the antibiotic \nsusceptibility. Ethics approval was obtained from \nthe National Medical Research Registry, Malaysia \n(NMRR-19-3254-53344).\n\n\n\nResults \nFrom January 2020 through April 2020, a total of \n153 patients with Atopic Dermatitis were screened \nand all were recruited. There were 111 preschool \nchildren (72.5%), 26 primary school children (17%) \nand 16 secondary school participants (10.5%). \nEighty two participants (53.6%) were male. A \nhundred and twenty participants (78.4%) were \nMalay, 25 participants (16.3%) were Chinese and \nseven participants (4.6%) were Indian. Ninety six \nparticipants (62.8%) had normal body mass index \n(BMI), 25 participants (16.3%) were underweight, \nnine participants (5.9%) were overweight and 23 \nparticipants (15%) were obese. A hundred and \nthirty eight participants (90%) had family history of \natopy. Seventy one participants (46%) had personal \nhistory of another atopy (Table 1). The SCORAD \nIndex showed 30.7% mild, 53.6% moderate and \n15.7% severe. For quality of life, six participants \n(3%) reported no effect at all, 40 participants \n(26.2%) reported a small effect, 51 participants \n(33%) reported moderate effect, 46 participants \n(30%) reported very large effect and ten participants \n(6%) reported extremely large effect (Table 2).\n\n\n\nOut of 153 patients, 29 of them had positive skin \nswab. All of those with positive yield cultured \nmethicillin susceptible Staphyloccocus aureus \n(MSSA). One patient had Streptococcus dysgalactiae \nin addition to MSSA. No patient had methicillin-\nresistant Staphyloccocus aureus (MRSA) from the \nskin swab. Only one patient was a MRSA carrier \nfrom the nasal swab. This patient\u2019s skin swab had \nno growth (Table 3).\n\n\n\nThere was a significant association between \npositive skin swab and disease severity (p=0.03) \n(Table 4). Out of the 29 patients with positive skin \nswab, 89.7% with positive skin swab had moderate \nto severe disease. Three participants (10.3%) had \nmild SCORAD index, 20 participants (69%) had \nmoderate SCORAD index and six participants \n(20.7%) had severe SCORAD index. Majority of \npatients with mild SCORAD index had negative \nskin swab. Of those with mild SCORAD index, \n44 patients had negative skin swab and only three \nhad positive skin swab. Of those with negative skin \nswab, 44 participants (35.5%) had mild SCORAD \nindex, 62 (50%) had moderate SCORAD index \nand 18 (14.5%) had severe SCORAD index. There \nis no significant association between nasal swab \n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4634\n\n\n\ncolonisation and disease severity. Only one patient \nwith moderate disease was an MRSA carrier. \n\n\n\nThere was a highly significant association between \ndisease severity and quality of life (p<0.001). \nAmong patients with DLQI score >20 (extremely \nlarge effect), six patients (60%) had severe disease, \nthree patients (30%) had moderate disease and only \none patient (10%) had mild disease. All patients \nwho reported no effect at all on DLQI assessment \nhad mild disease. The DLQI score for most of the \npatients with mild disease were in small effect \n(44.7%) and moderate effect (25.5%) categories. \nThe DLQI score for most of the patients with \nmoderate disease were in moderate effect (36.6%) \nand very large effect (36.6%) categories. The \nDLQI score for most of the patients with severe \ndisease were in moderate effect (37.5%) and very \n\n\n\nlarge effect (37.5%) categories. The mean DLQI \nscore for patients with had no effect at all was 2; \nfor patients with small effect was 13.3; for patients \nwith moderate effect was 17; for patients with very \nlarge effect was 15.3 and for patients with extremely \nlarge effect was 3.3. Majority of participants had \nmoderate disease (53.6%), resulting in higher mean \nDLQI score from small effect to very large effect \ncategories.\n\n\n\nPenicillin (86.2%) was found to have the highest \nresistant rate followed by fusidic acid (34.5%), \ntetracycline (17.2%), erythromycin (3.4%) and \ngentamycin (3.4%) (Figure 1). The most susceptible \nantibiotics (100% sensitivity) were cefoxitin, \nmethicillin, trimethoprim/sulfamethoxazole, and \nrifampicin.\n\n\n\nTable 1. Demographic characteristics\n\n\n\nDemographic n (%)\n\n\n\nAge (years) Preschool (less than 7)\nPrimary school (7 to 12)\nSecondary school (13 to 17)\n\n\n\n111 (72.5)\n 26 (17.0)\n 16 (10.5)\n\n\n\nGender Male\nFemale\n\n\n\n82 (53.6)\n71 (46.4)\n\n\n\nEthnicity Malay\nChinese\nIndian\nOthers\n\n\n\n120 (78.4)\n 25 (16.3)\n  7 ( 4.6)\n  1 ( 0.7)\n\n\n\nBMI Underweight (\u22645th percentile)\nNormal (5th to \u2264 85th percentile))\nOverweight (85th to \u226495th percentile)\nObese (\u226595th percentile)\n\n\n\n25 (16.3)\n96 (62.8)\n  9 (5.9)\n23 (15.0)\n\n\n\nAge at diagnosed Preschooler (less than 7)\nPrimary school (7 to 12)\nSecondary school (13 to 17)\n\n\n\n136 (88.9)\n15 (9.8)\n2 (1.3)\n\n\n\nFamily history of atopy Yes\nNo\n\n\n\n138 (90.2)\n15 (9.8)\n\n\n\nPersonal history of another atopy Yes\nNo\n\n\n\n71 (46.4)\n82 (53.6)\n\n\n\nBMI, Body mass index\n\n\n\nTable 2. DLQI and SCORAD index\n\n\n\nDLQI and SCORAD Index n (%)\n\n\n\nDLQI No effect\nSmall effect\nModerate effect\nVery large effect\nExtremely large effect\n\n\n\n6 (3.9)\n40 (26.2)\n51 (33.3)\n46 (30.1)\n10 (6.5)\n\n\n\nSCORAD index Mild\nModerate\nSevere\n\n\n\n47 (30.7)\n82 (53.6)\n24 (15.7)\n\n\n\nDLQI, Dermatological life quality index; SCORAD, SCORing Atopic \ndermatitis\n\n\n\nTable 3. Skin (lesional) and nasal (non-lesional) swab \nyields for Staphylococcus aureus\n\n\n\nSkin Swab Result n (%)\n\n\n\nNo growth\nMSSA\nMSSA + Streptococcus dysgalactiae\n\n\n\n124 (81)\n28 (18.3)\n1 (0.7)\n\n\n\nNasal Swab Result n (%)\n\n\n\nNo MRSA\nMRSA\n\n\n\n152 (99.3)\n1 (0.7)\n\n\n\nMSSA, methicillin susceptible Staphyloccocus aureus; MRSA, \nmethicillin-resistant Staphyloccocus aureus\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35MJD 2021 Jun Vol 46\n\n\n\nscore for most of the patients with severe disease were in moderate effect (37.5%) and very \nlarge effect (37.5%) categories. The mean DLQI score for patients with had no effect at all was \n2; for patients with small effect was 13.3; for patients with moderate effect was 17; for patients \nwith very large effect was 15.3 and for patients with extremely large effect was 3.3. Majority \nof participants had moderate disease (53.6%), resulting in higher mean DLQI score from small \neffect to very large effect categories.  \n \nTable 4. Association between disease severity (SCORAD) and growth (skin and nasal) and \nquality of life (DLQI) \n \n\n\n\n    SCORAD index n (%) p value \n    Mild Moderate Severe   \nSkin swab    0.030a \n  Growth 3(10.3) 20(69) 6(20.7)  \n  No growth 44(35.5) 62(50) 18(14.5)  \nNasal swab    1.000b \n  MRSA 0(0) 1(100) 0(0)  \n  No MRSA 47(30.9) 81(53.3) 24(15.8)  \nDLQI    <0.001b \n  No effect 6(100) 0(0) 0(0)  \n  Small effect 21(52.5) 19(47.5) 0(0)  \n  Moderate effect 12(23.5) 30(58.9) 9(17.6)  \n  Very large effect 7(15.2) 30(65.2) 9(19.6)  \n  Extremely large effect 1(10) 3(30) 6(60)  \n\n\n\naChi-square tests; bFisher's exact Tests; SCORAD, SCORing Atopic Dermatitis; MRSA, \nmethicillin-resistant Staphyloccocus aureus; DLQI, Dermatological Life Quality Index \n \nPenicillin (86.2%) was found to have the highest resistant rate followed by fusidic acid \n(34.5%), tetracycline (17.2%), erythromycin (3.4%) and gentamycin (3.4%) (Figure 1). The \nmost susceptible antibiotics (100% sensitivity) were cefoxitin, methicillin, \ntrimethoprim/sulfamethoxazole, and rifampicin. \n \nFigure 1. Antibiotic sensitivities of Staphylococcus aureus \n \n\n\n\n\n\n\n\n0%\n10%\n20%\n30%\n40%\n50%\n60%\n70%\n80%\n90%\n\n\n\n100%\n\n\n\nPe\nni\n\n\n\ncil\nin\n\n\n\nCe\nfo\n\n\n\nxit\nin\n\n\n\nM\net\n\n\n\nhi\ncil\n\n\n\nin\n\n\n\nEr\nyt\n\n\n\nhr\nom\n\n\n\nyc\nin\n\n\n\nGe\nnt\n\n\n\nam\nyc\n\n\n\nin\n\n\n\nTe\ntr\n\n\n\nac\nyc\n\n\n\nlin\ne\n\n\n\nFu\nsic\n\n\n\nid\nic \n\n\n\nac\nid\n\n\n\nCl\nin\n\n\n\nda\nm\n\n\n\nyc\nin\n\n\n\nLin\nez\n\n\n\noi\nd\n\n\n\nTr\nim\n\n\n\net\nho\n\n\n\npr\nim\n\n\n\n/s\nul\n\n\n\nfa\nm\n\n\n\n\u2026\n\n\n\nRi\nfa\n\n\n\nm\npi\n\n\n\ncin\nNot done\n\n\n\nResistant\n\n\n\nIntermediate\n\n\n\nSensitive\n\n\n\n100%\n\n\n\n90%\n\n\n\n80%\n\n\n\n70%\n\n\n\n60%\n\n\n\n50%\n\n\n\n40%\n\n\n\n30%\n\n\n\n20%\n\n\n\n10%\n\n\n\n0%\n\n\n\nTr\nim\n\n\n\net\nho\n\n\n\npr\nim\n\n\n\n/s\nul\n\n\n\nfa\nm\n\n\n\n...\n\n\n\nR\nifa\n\n\n\nm\npi\n\n\n\nci\nn\n\n\n\nLi\nne\n\n\n\nzo\nid\n\n\n\nC\nlin\n\n\n\nda\nm\n\n\n\nyc\nin\n\n\n\nFu\nsi\n\n\n\nci\ndi\n\n\n\nc \nac\n\n\n\nid\n\n\n\nTe\ntra\n\n\n\ncy\ncl\n\n\n\nin\ne\n\n\n\nG\nen\n\n\n\nta\nm\n\n\n\nyc\nin\n\n\n\nEr\nyt\n\n\n\nhr\nom\n\n\n\nyc\nin\n\n\n\nM\net\n\n\n\nhi\nci\n\n\n\nlin\n\n\n\nC\nef\n\n\n\nox\niti\n\n\n\nn\n\n\n\nPe\nni\n\n\n\nci\nlin\n\n\n\n0%\n\n\n\nNot done\n\n\n\nResistant\n\n\n\nIntermediate\n\n\n\nSensitive\n\n\n\nTable 4. Association between disease severity (SCORAD) and growth (skin and nasal) and quality of life (DLQI)\n\n\n\nSCORAD Index n (%) p-value\n\n\n\nMild Moderate Severe\n\n\n\nSkin swab 0.030a\n\n\n\nGrowth\nNo growth\n\n\n\n3 (10.3)\n44 (35.5)\n\n\n\n20 (69)\n62 (50)\n\n\n\n6 (20.7)\n18 (14.5)\n\n\n\nNasal swab 1.000b\n\n\n\nMRSA\nNo MRSA\n\n\n\n0 (0)\n47(30.9)\n\n\n\n1 (100)\n81 (53.3)\n\n\n\n0 (0)\n24 (15.8)\n\n\n\nDLQI <0.001b\n\n\n\nNo effect\nSmall effect\nModerate effect\nVery large effect\nExtremely large effect\n\n\n\n6 (100)\n21 (52.5)\n12 (23.5)\n7 (15.2)\n1 (10)\n\n\n\n0 (0)\n19 (47.5)\n30 (58.9)\n30 (65.2)\n\n\n\n3 (30)\n\n\n\n0 (0)\n0 (0)\n\n\n\n9 (17.6)\n9 (19.6)\n6 (60)\n\n\n\naChi-square tests; bFisher\u2019s exact tests; SCORAD, SCORing Atopic dermatitis; MRSA, methicillin-resistant Staphyloccocus aureus; DLQI, Dermatological \nlife quality index\n\n\n\nFigure 1. Antibiotic sensitivities of Staphylococcus aureus\n\n\n\nDiscussion \nThe sample in this study was mainly preschoolers, \nfollowed by primary school children and secondary \nschool children. Similar trends were observed for \nage when AD was first diagnosed. This was in line \nwith the natural course of childhood eczema which \nmostly manifests AD before the age of two.27 Most \nof the affected children have family history of atopy \nwhich indicates the genetic role in the pathogenesis \nof atopic dermatitis. However, it was observed \nthat less than half of the patients have other atopy \nhistories. This could be due to the initial stage of \natopic march which begins with atopic dermatitis, \nand followed by IgE-mediated food allergy, asthma, \n\n\n\nand allergic rhinitis.28\n\n\n\nIn this study, the percentage of skin (lesional) \ncolonisation by S. aureus was only 19%, whereas \nnasal (non-lesional) colonisation was 0.7%. This \nwas lower than other studies where skin carriage \nrates among AD patients were reported between \n30% and 100%, while the percentage of nasal \ncolonisation by S. aureus varies between 10 and \n30%.9,10,11 This discrepancy might be attributed \nto the significant variation in AD clinical severity \nin each study. Most of the patients were found to \nhave mild to moderate AD. Other possibilities for \nsuch variations are intermittent colonisation by S. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4636\n\n\n\naureus resulting in negative detection at the time of \nexamination, hygienic status of patients, sampling \ntechnique, and sampling area of skin lesion.9,29\n\n\n\nFrom our study, we found that severity of disease \nwas associated with quality of life (p<0.01). About \n70 % of the patients with mild disease reported small \nor moderate effect during the DLQI assessment. On \nthe other hand, 73.2% of patients with moderate \ndisease and 75% of patients with severe disease \nreported moderate to very large effect during the \nDLQI assessment. The result showed that higher \nSCORAD index seemed to be associated with \nworse DLQI. Although most skin diseases are not \nlife-threatening, it could still lead to a significant \ndisability burden. This result was consistent with \nthe study by Holm et al., where AD had a negative \nimpact on the QoL, and was proportional to the \ndisease severity.30 Children with AD often have \nbehavioural problems such as increased dependency, \nfearfulness and sleep difficulties.34 These findings \nshould draw our attention to the long-term effect on \nchildren\u2019s behaviour and development. \n\n\n\nThe resistance rate to fusidic acid in this population \nwas found to be higher compared with other studies. \nTang (2011) found that fusidic acid resistance was \nlower than penicillin, erythromycin, clindamycin, \ntetramycin and gentamycin.31 Likewise, Hoeger \n(2004) and Niebuhr (2008) also had lower fusidic \nacid resistance rate in their findings.32,20 However \nmore current studies by Jung (2015) and Lee (2016) \nfound that fusidic acid is the second highest resistant \nantibiotic after penicillin.11,33 Higher resistance rates \ntowards fusidic acid in recent studies could be due \nto increased use of topical fusidic acid in treating the \npatient with infective or inflammatory skin diseases \nin recent years. In view of this finding, the use of \nfusidic acid should not be advocated. Besides that, \nthe use of neomycin and bacitracin were not advised \nas they were nominated as an allergen in 2003 and \n2010, respectively.34 Moreover, the resistance rates \nto neomycin and bacitracin were high in Bessa et \nal.\u2019s report.35 Sulphur-based topical treatments \nhave a high risk of hypersensitivity, leading to \nphysicians\u2019 hesitancy to use these in the paediatric \ngroup. Therefore, mupirocin and retapamulin are \nthe choice of antibiotics if clinically indicated. With \nthe concern of developing resistance to the newer \nantibiotic, continuous surveillance of antibiotic \nsusceptibility patterns are important.\n\n\n\nFrom our study, we found that 26 patients (89.7%) \nwith Staphylococus aureus colonisation and 105 \npatients (69.1%) with negative skin swab had \nmoderate to severe disease. As patients with \nStaphylococcus aureus colonisation tends to have \nmore severe disease, decolonisation with antiseptic \nwash such as a diluted bleach bath should be \nconsidered. It helps in relieving symptoms of AD \nand it is better tolerated than topical antibiotics. \nThis approach could potentially reduce antibiotic \nresistance.36,37 Decolonisation of MSSA with a \ntopical antibiotic is not recommended as quick \nrecolonisation occurs after discontinuing the \nantibiotic.38,39 \n\n\n\nConclusion \nStaphylococcus aureus skin colonisation among \nAD patients is associated with increased disease \nseverity. The severity of the disease has an impact \non patient\u2019s quality of life. Antiseptic wash should \nbe considered instead of topical antibiotics for \nStaphylococcus aureus decolonisation. Antiseptic \nwash is better tolerated and can potentially reduce \nantibiotic resistance.\n\n\n\nConflict of Interest Declaration\nThe authors declare no conflict of interest.\n\n\n\nAcknowledgment \nWe would like to thank the Director-General of \nHealth Malaysia for his permission to publish this \nstudy. This study was funded with a research grant \nfrom the Dermatological Society of Malaysia.\n\n\n\nReferences\n\n\n\n1. Barbarot S, Auziere S, Gadkari A, Girolomoni G, Puig \nL, Simpson EL et al. Epidemiolofy of atopic dermatitis \nin adults: Results from an international survey. Allergy \n2018;73:1284-93. \n\n\n\n2. Deckers IAG, McLean S, Linssen S, Mommers M, van \nSchayck CP, Sheikh A. Investigating international time \ntrends in the incidence and prevalence of atopic eczema \n1990-2010: a systematic review of epidemiological \nstudies. PLoS One 2012;7:e39803. \n\n\n\n3. Karimkhani C, Dellavalle RP, Coffeng LE, Flohr C, Hay \nRJ, Lagan SM et al. 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Translating the science of quality of life into practice: \nWhat do dermatology life quality index scores mean? J \nInvest Dermatol 2005;125:659-64. \n\n\n\n27. Spergel JM. Epidemiology of atopic dermatitis and atopic \nmarch in children. Immunol Allergy Clin North Am \n2010;30:269-80.\n\n\n\n28. Hill DA, Spergel JM. The atopic march: Critical evidence \nand clinical relevance. Ann Allergy, Asthma Immunol \n2018;120:131-7.\n\n\n\n29. Alenizi DA. Prevalence of Staphylococcus aureus and \nantibiotic resistance in children with atopic dermatitis in \nArar, Saudi Arabia. J Dermatology Dermatologic Surg \n2014;18:22-6. \n\n\n\n30. Holm JG, Agner T, Clausen ML, Thomsen SF. Quality of \nlife and disease severity in patients with atopic dermatitis. \nJ Eur Acad Dermatol Venereol 2016;30:1760-7.\n\n\n\n31. Tang CS, Wang CC, Huang CF, Chen SJ, Tseng MH, Lo \nWT. Antimicrobial susceptibility of Staphylococcus aureus \nin children with atopic dermatitis. Pediatr Int 2011;53:363-\n7.\n\n\n\n32. Hoeger PH. Antimicrobial susceptibility of skin-colonizing \nS. aureus strains in children with atopic dermatitis. Pediatr \nAllergy Immunol 2004;15:474-7. \n\n\n\n33. Lee CK, Yusof MY, Lee YY, Tan ESS, Wong SM, Ch\u2019ng \nCC et al. Staphylococcus aureus antibiotic resistance in \nAtopic eczema. Malaysian J Dermatol 2016;36:5-10. \n\n\n\n34. Vazirnia A. Review ACDS\u2019 Allergen of the Year 2000-2015. \nThe Dermatologist. 22(II). http://www.the-dermatologist.\ncom/content/review-acds\u2019-allergen-of-year-2000-2015.\n\n\n\n35. Bessa GR, Quinto VP, Machado DC, Lipnharski C, Weber \nMB, Bonamigo RR et al. Staphylococcus aureus resistance \nto topical antimicrobials in atopic dermatitis. An Bras \nDermatol 2016;91:604-10. \n\n\n\n36. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller \nAS, Schwarzenberger K et al. Guidelines of care for the \nmanagement of atopic dermatitis: section 2. Management \nand treatment of atopic dermatitis with topical therapies. J \nAm Acad Dermatol 2014;71:116-32. \n\n\n\n37. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller \nAS. Treatment of Staphylococcus aureus colonization in \natopic dermatitis decreases disease severity. Pediatrics \n2009;123:e808-14. \n\n\n\n38. B\u0142a\u017cewicz I, Ja\u015bkiewicz M, Bauer M, Piechowics \nL, Nowicki RJ, Kamysz W et al. Decolonization of \nStaphylococcus aureus in patients with atopic dermatitis: \na reason for increasing resistance to antibiotics? Postepy \nDermatol Alergol 2017;34:553-60. \n\n\n\n39. Gilani, Gonzalez M, Hussain I, Finlay AY, Patel GK. \nStaphylococcus aureus re-colonization in atopic dermatitis: \nbeyond the skin. Clin Exp Dermatol 2005;30:10-3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4638\n\n\n\nORIGINAL ARTICLE\n\n\n\nA 5-years Retrospective Study on Narrowband Ultraviolet B (NBUVB) \nPhototherapy Utilisation Experience in A Tertiary Hospital in East \nMalaysia\nTeo Hock Gin, MRCP, Kiing Jiu Wen, AdvMDerm, Pubalan Muniandy, FRCP\n\n\n\nDepartment of Dermatology, Hospital Umum Sarawak, Kuching, Sarawak, Malaysia\n\n\n\nAbstract \nBackground\nPhototherapy had been a less favourable treatment in recent years. Our study aims to audit the usage \nof NB-UVB phototherapy service in a tertiary hospital in East Malaysia.\n\n\n\nMethods\nThis is a retrospective study. Phototherapy file of patients who underwent NB-UVB phototherapy \nbetween year 2016 and 8 March 2021 were reviewed. Demographic data, treatment history, and acute \nside effects were analysed.\n\n\n\nResults\nForty eight subjects were recruited in this study. The majority (33.3%) of the subjects were in 20-29 \nage group. There was an equal number of male and female subjects. About 66.7% of the subjects had \npsoriasis and 18.8% of them had vitiligo. Nearly 36.6% of the subjects had 26-50% body surface \narea involved at initial phototherapy. Almost 54.2% of the subjects had <50 sessions of NB-UVB \nphototherapy. About 52.1% of the subjects had a cumulative dose of NB-UVB <25 J/cm2 while 26.7% \nof subjects had a cumulative dose >200 J/cm2. Acute side effects including burning (17.8%), pruritus \n(4.4%) and flare of psoriasis (2.2%).\n\n\n\nDiscussion\nLow utilization rate of NB-UVB phototherapy was likely due to logistical and transportation factors. \nPsoriasis was the commonest indication for NB-UVB in our study followed by vitiligo. Annual skin \nmalignancy surveillance should be done especially on patients received NB-UVB >350 sessions even \nafter the discontinuation of treatment. Most patients tolerate NB-UVB phototherapy well with no \nmajor side effects. \n\n\n\nConclusion\nIn conclusion, NB-UVB phototherapy is a relatively safe yet underutilised treatment in our centre.\n\n\n\nKey words: Phototherapy, Narrowband ultraviolet B (nb-UVB), Ultraviolet A, Psoriasis, Vitiligo\n\n\n\nIntroduction\nPhototherapy is a type of light therapy which had \nbeen used in various dermatological diseases such \nas atopic eczema, psoriasis, vitiligo, morphea and so \non. In 1925, Goeckerman was the first person who \nbrought in the advancement in phototherapy as part \nof important treatment in psoriasis by combining \n\n\n\nCorresponding Author\nDr Teo Hock Gin\nDepartment of Dermatology,\nHospital Umum Sarawak,\nJalan Hospital,\n93586 Kuching, Sarawak, Malaysia.\nEmail: hgteo86@hotmail.com\n\n\n\n\n\n\n\n\nFor the indication of NB-UVB phototherapy, 66.7% \n(n=32) of the subjects were started on nb-UVB \nphototherapy for their underlying psoriasis in which \n2 (4.2%) of the subjects had erythrodermic psoriasis \nwhile the remaining of them had plaque psoriasis. \nThis was followed by vitiligo in 18.8% (n=9) of \nthe subjects, while eczema and prurigo nodularis \nwere diagnosed in 8.3% (n=4) and 4.2% (n=2) of \nthe study populations, respectively. One subject \n(2.1%) was started on NB-UVB phototherapy for \nboth psoriasis and vitiligo. (Figure 3)\n\n\n\nFigure 3. Diagnosis of subjects receiving nbUVB\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n39\n\n\n\nultraviolet B (UVB) and crude coal tar.1 Since then \nmany modern phototherapies had been developed \nranging from narrowband UVB (NB-UVB) in 1988, \npsoralen and UVA (PUVA) in 1974 to targeted \nphototherapy with excimer lamp in 1997.2,3 In the \nera of biology, however, with the development \nof systemic treatment including biology therapy \nsince 2000, phototherapy therapy becomes less \nfavourable. \n\n\n\nAccording to a 5 year report in 2002 from the \nUnited States, patients visit for phototherapy, in \ngeneral, was reduced by more than 90%.4 The \nobjective of this study is to audit the usage of NB-\nUVB phototherapy service in Sarawak General \nHospital (SGH) for the past five years including \nphototherapy usage trend, common indications of \nphototherapy, characteristics of the patients, and \nside effects of phototherapy. SGH located in East \nMalaysia. It is a tertiary hospital in the state of \nSarawak, Malaysia and it is the only hospital with \nresident dermatologists in this state. \n\n\n\nMaterials and Methods\nThis is a retrospective study carried out at the \nphototherapy unit Sarawak General Hospital. We \nrecruited patients who had received phototherapy \ntreatment at our phototherapy unit between 2016 \nand 8 March 2021. Our centre is currently using \na Daavlin cabin (UVB) and a hands and feet unit. \nNo UVA phototherapy available at our unit. We \nexcluded subjects on hands and feet phototherapy \nas data was not complete. Patients\u2019 phototherapy \nfolders were reviewed. Data such as demographics, \nindications, treatment sessions, cumulative dose \nof the phototherapy, and acute side effects were \nextracted and analysed by using SPSS.\n\n\n\nResults\nA total number of 48 subjects received NB-UVB \nphototherapy between 2016 and 8 March 2021. \nThe demography data of the subjects were shown \nin Figure 1 & 2. The majority of the patients were in \nthe 20-29 age group. The mean age was 38.7 years \nold and ranged from 13 to 77 years old. There was \nan equal number of male and female subjects in the \nstudy populations. More than half (n=26, 54.2%) \nof the subjects were Chinese, followed by Malay \n(n=12, 25%), Bidayuh (n=5, 10.4%), and Iban (n=3, \n6.3%).\n\n\n\nFigure 1. Age distribution at the time of first nbUVB \nPhototherapy\n\n\n\n\n\n\n\nFigure 1. Age distribution at the time of first nbUVB Phototherapy \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFor the indication of NB-UVB Phototherapy, 66.7% (n=32) of the subjects were started on \nnb-UVB phototherapy for their underlying psoriasis in which 2 (4.2%) of the subjects had \nerythrodermic psoriasis while the remaining of them had plaque psoriasis. This was \nfollowed by vitiligo in 18.8% (n=9) of the subjects, while eczema and prurigo nodularis \nwere diagnosed in 8.3% (n=4) and 4.2% (n=2) of the study populations, respectively. One \nsubject (2.1%) was started on NB-UVB phototherapy for both psoriasis and vitiligo. \n(Figure 3) \n \n \n \n\n\n\n2\n\n\n\n16\n11\n\n\n\n8\n4 3 4\n\n\n\n0\n5\n\n\n\n10\n15\n20\n\n\n\n10-19 20-29 30-39 40-49 50-59 60-69 70-79\n\n\n\nFr\neq\n\n\n\nue\nnc\n\n\n\ny\n\n\n\nAge-Group\n\n\n\nAge Distribution at the Time of First \nNB-UVB Phototherapy\n\n\n\n26\n\n\n\n12\n\n\n\n5 3 1 1\n0\n\n\n\n10\n\n\n\n20\n\n\n\n30\n\n\n\nChinese Malay Bidayuh Iban Indian Melanau\nFr\n\n\n\neq\nue\n\n\n\nnc\ny/\n\n\n\n(%\n)\n\n\n\nEthnic\n\n\n\nEthnic Groups of the NB-UVB \nPhototherapy Subjects\n\n\n\nFigure 3. Diagnosis of subjects receiving nbUVB \nPhototherapy \n\n\n\nDistribution at the Time of First NB-UVB Phototherapy \n\n\n\n\n\n\n\nFigure 2. Ethnic groups of the nbUVB phototherapy subjects \nDistribution at the Time of First NB-UVB Phototherapy \n\n\n\n \nFigure 2. Ethnic groups of the nbUVB Phototherapy \nsubjects\n\n\n\n\n\n\n\nFigure 1. Age distribution at the time of first nbUVB Phototherapy \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFor the indication of NB-UVB Phototherapy, 66.7% (n=32) of the subjects were started on \nnb-UVB phototherapy for their underlying psoriasis in which 2 (4.2%) of the subjects had \nerythrodermic psoriasis while the remaining of them had plaque psoriasis. This was \nfollowed by vitiligo in 18.8% (n=9) of the subjects, while eczema and prurigo nodularis \nwere diagnosed in 8.3% (n=4) and 4.2% (n=2) of the study populations, respectively. One \nsubject (2.1%) was started on NB-UVB phototherapy for both psoriasis and vitiligo. \n(Figure 3) \n \n \n \n\n\n\n2\n\n\n\n16\n11\n\n\n\n8\n4 3 4\n\n\n\n0\n5\n\n\n\n10\n15\n20\n\n\n\n10-19 20-29 30-39 40-49 50-59 60-69 70-79\n\n\n\nFr\neq\n\n\n\nue\nnc\n\n\n\ny\n\n\n\nAge-Group\n\n\n\nAge Distribution at the Time of First \nNB-UVB Phototherapy\n\n\n\n26\n\n\n\n12\n\n\n\n5 3 1 1\n0\n\n\n\n10\n\n\n\n20\n\n\n\n30\n\n\n\nChinese Malay Bidayuh Iban Indian Melanau\nFr\n\n\n\neq\nue\n\n\n\nnc\ny/\n\n\n\n(%\n)\n\n\n\nEthnic\n\n\n\nEthnic Groups of the NB-UVB \nPhototherapy Subjects\n\n\n\nFigure 3. Diagnosis of subjects receiving nbUVB \nPhototherapy \n\n\n\nDistribution at the Time of First NB-UVB Phototherapy \n\n\n\n\n\n\n\nFigure 2. Ethnic groups of the nbUVB phototherapy subjects \nDistribution at the Time of First NB-UVB Phototherapy \n\n\n\n\n\n\n\n \n \nBody surface area (BSA) involved, total number of phototherapy sessions, cumulative dose, \nand acute side effect were summarised in Table 1. Among the 41 subjects with complete \ndata on BSA involved, 36.6% (n=15) of them had BSA of 26-50%, followed by subjects \nwith 6-10% BSA (n= 8,19.5%) and 11-25% BSA involvement (n=5,12.2%). 3 (7.3%) of \nthem had BSA of > 95%, which included 2 erythrodermic psoriasis subjects and one patient \nwith erythroderma secondary to eczema.  \n\n\n\nTable 1. Baseline BSA and treatments and side effects of the study populations \n\n\n\n Frequency \n(n) \n\n\n\nPercentage (%) \n\n\n\nBody Surface \nArea/BSA \n(n=41) * \n\n\n\n1-5 2 4.9 \n6-10 8 19.5 \n11-25 5 12.2 \n26-50 15 36.6 \n51-75 4 9.8 \n76-95 4 9.8 \n>95 3 7.3 \nTotal 41 100.0 \n\n\n\nTotal NB-UVB \nSessions (n=48) \n\n\n\n0-50 26 54.2 \n51-100 11 22.9 \n101-150 1 2.1 \n151-200 1 2.1 \n201-250 2 4.2 \n251-300 2 4.2 \n\n\n\n32\n\n\n\n9\n\n\n\n4\n2 1\n\n\n\n0\n\n\n\n5\n\n\n\n10\n\n\n\n15\n\n\n\n20\n\n\n\n25\n\n\n\n30\n\n\n\n35\n\n\n\nFr\neq\n\n\n\nue\nnc\n\n\n\ny(\n%\n\n\n\n)\n\n\n\nDiagnosis\n\n\n\nDiagnosis of Subjects Receiving NB-UVB Phototherapy\n\n\n\nBody surface area (BSA) involved, total number \nof phototherapy sessions, cumulative dose, and \nacute side effect were summarised in Table 1. \n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4640\n\n\n\nAmong the 41 subjects with complete data on BSA \ninvolved, 36.6% (n=15) of them had BSA of 26-\n50%, followed by subjects with 6-10% BSA (n= \n8, 19.5%) and 11-25% BSA involvement (n=5, \n12.2%). 3 (7.3%) of them had BSA of >95%, which \nincluded 2 erythrodermic psoriasis subjects and one \npatient with erythroderma secondary to eczema.\n\n\n\nTable 1. Baseline BSA and treatments and side effects of \nthe study populations\n\n\n\nFrequency \n(n)\n\n\n\nPercentage \n(%)\n\n\n\nBody surface \narea/BSA \n(n=41) *\n\n\n\n1-5 2 4.9\n\n\n\n6-10 8 19.5\n\n\n\n11-25 5 12.2\n\n\n\n26-50 15 36.6\n\n\n\n51-75 4 9.8\n\n\n\n76-95 4 9.8\n\n\n\n>95 3 7.3\n\n\n\nTotal 41 100.0\n\n\n\nTotal \nNB-UVB \nsessions \n(n=48)\n\n\n\n0-50 26 54.2\n\n\n\n51-100 11 22.9\n\n\n\n101-150 1 2.1\n\n\n\n151-200 1 2.1\n\n\n\n201-250 2 4.2\n\n\n\n251-300 2 4.2\n\n\n\n>300 5 10.4\n\n\n\nTotal 48 100.0\n\n\n\nCumulative \ndose (J/cm 2) \n(n=48)\n\n\n\n1-25 25 52.1\n\n\n\n>25-50 4 8.3\n\n\n\n>50-75 8 16.7\n\n\n\n>100-125 1 2.1\n\n\n\n>125-150 1 2.1\n\n\n\n>150-175 1 2.1\n\n\n\n>200 8 16.7\n\n\n\nTotal 48 100.0\n\n\n\nAcute \nside effect \n(n=45) #\n\n\n\nNo side effects 34 75.6\n\n\n\nBurning 8 17.8\n\n\n\nItching 2 4.4\n\n\n\nFlare of disease 1 2.2\n\n\n\nTotal 45 100.0\n*7 vitiligo subjects were not documented regarding their BSA finding in \ntheir phototherapy folders\n#3 subjects had missing data regarding phototherapy side effects as they \ndefaulted our clinic follow up\n\n\n\nFifty-four percent (n=26) of the study populations \nhad less than 50 sessions of NB-UVB phototherapy. \nAround twenty three percent (n=11) of them had 51-\n100 sessions of the same phototherapy treatment. Of \nnote, there were 5 (10.4%) subjects who received \nmore than 300 sessions of NB-UVB phototherapy in \ntheir lifetime, with the highest record of 963 sessions \n\n\n\nin 1 subject. All the 5 subjects were diagnosed with \nvitiligo, and until the closure of the study, there was \nno evidence of skin malignancy in all the 5 subjects.\n\n\n\nThe study populations had a wide range of \ncumulative UVB exposure dosage, which range \nfrom 0.15 to 924 J/cm2 with a median dose of 21 J/\ncm2. 52.1% (n=25) of them had a cumulative dose \nof UVB of 1-25 J/cm2 followed by >50-75 J/cm2 \n\n\n\ngroup and >200 J/cm2 group, which consisted of \n16.7% (n=8) of the study population respectively. \n\n\n\nWith regards to acute side effects after the NB-UVB \nphototherapy, there were 3 subjects who defaulted \nthe phototherapy during the first few sessions, \nand no clinical records of acute side effects were \ndocumented. Among 45 of the remaining subjects, \n75.6% (n=34) of them tolerate NB-UVB without \nsignificant side effects, while 17.8% (n=8) and 4.4% \n(n=2) of them complained of burning sensation and \npruritus, respectively. 1 (2.2%) subject documented \nflare of underlying psoriasis. 3 (6.7%) of subjects \nstopped the NB-UVB phototherapy due to not \ntolerating acute side effects. \n\n\n\nDiscussion\nOur study showed that in the past 5 years, we \nhave only 48 subjects who received treatment of \nNB-UVB phototherapy for their underlying skin \ndiseases. There were a few possible reasons for \nthe low prescribing rate of NB-UVB in our centre. \nThe most important reason is the logistical and \ntransportation factors as many of our subjects stay \nfar from Kuching city and some even come from \ndifferent divisions. They have difficulties to go to \nhospital 2 to 3 times a week for the phototherapy \ntreatments. The COVID-19 pandemic has an impact \non this as well. Dermatologists try to minimise \npatients\u2019 visit to the hospital to reduce the risk of \nCOVID-19 transmission. Therefore, phototherapy \nwas avoided if alternative treatments were available.  \n\n\n\nMost of our subjects who received NB-UVB \nphototherapy were in the age group of 20-29, with a \nmean age of 38.7 years old. This finding was similar \nto another study done in Hospital Kuala Lumpur, \nMalaysia during 2011-2015 in which the mean age \nof the study was 38.8 years old.5 Another study by \nPark et al. in Korea showed a similar finding with \nthe majority of the subjects receiving UVA or UVB \nin their study were in the age of 20-29 years old.6\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n41\n\n\n\nTable 2. Indications for phototherapy in different studies\n\n\n\nStudy Country Treatment Diagnosis (%)\n\n\n\nPsoriasis Atopic Dermatitis Vitiligo CTCL Prurigo Nodularis Others\n\n\n\nPark et al, 1996 Korea UVB 94.8 2.4 - - 0.5 2.4\n\n\n\nVaani et al, 2018 Malaysia UVA 28.0 0.5 70.2 0.5 - 0.7\n\n\n\nOral PUVA 17.4 4.3 21.7 47.8 - 8.6\n\n\n\nTopical PUVA 2.8 1.4 85.1 0.7 -- 9.8\n\n\n\nnbUVB 57.2 11.4 15.4 3.2 - 12.8\n\n\n\nCurrent study Malaysia nbUVB 66.7 8.3 18.8 - 4.2 2.1\n\n\n\nIn term of indication for NB-UVB treatment, our \nstudy finding was consistent with other studies in \nKorea and Malaysia in which psoriasis was the \ncommonest indication for UVB/NBUVB (Table \n2).5,6 Duarte et al. reported, in their study on \nprescribing behaviour for 67 psoriasis subjects in \nSao Paolo, Brazil, that 76% of the subjects received \nNB-UVB phototherapy with only 34 % was given \nPUVA.7 However, in our study, vitiligo is the second \ncommonest indication for NB-UVB phototherapy. \nThis is in contrast with the above studies in which \nPark et al. and Vaani et al. reported atopic dermatitis \nas the second commonest indication for UVB/NB-\nUVB. In their study, UVA is the preferred mode of \nphototherapy for vitiligo. PUVA or topical UVA \nwas not available in our centre, and this can explain \nthe difference between the studies. Unlike the other \ncentre, we did not have subjects with cutaneous T \ncell lymphoma in our study.\n\n\n\nThe total number of NB-UVB sessions in our study \nranged from 1 to 963 sessions, while Vaani et al. \nreported that subjects who underwent NB-UVB \nphototherapy in their study ranged from 1-252 \nsessions. More than half of our subjects underwent \nNB-UVB phototherapy for less than 50 sessions. \nAnother 22.9% underwent 51-100 sessions of \nNB-UVB phototherapy. This finding is similar to \nthe study by Park et al. in Korea.6 However, from \nour study, there were 5 (10.4%) subjects who had \nNB-UVB phototherapy of more than 300 sessions \n(963,922,818,547,324 sessions respectively). All 5 \nsubjects had vitiligo. Although NB-UVB is effective \nin vitiligo from several studies done previously, our \nsubjects seem to require long-term phototherapy to \nmaintain their disease.8,9 \n\n\n\nAlthough they had undergone an extremely high \nnumber of phototherapy sessions, there was no skin \nmalignancies reported in our subjects. Although \nNB-UVB phototherapy increases lifetime exposure \n\n\n\nto UVB, there is no evidence of increased risk of \nskin malignancies from the previous studies.10 \n\n\n\nTherefore, based on currently available data, the \nnumber of allowable UVB treatments can\u2019t be \ndefined, although Malaysia Clinical Practical \nGuideline on the management of psoriasis Vulgaris \nrecommends UVB treatments of not more than \n350 sessions.11 Nevertheless, close monitoring of \nthe side effects and annual skin examinations is \nimportant to monitor any skin tumours even after \nthe discontinuation of phototherapy.12 Subjects who \nreceived >350 sessions should be reassessed on the \nrisk and benefit of continue phototherapy. \n\n\n\nIn our centre, all patients with different skin types \nwere initiated with a low dose NB-UVB of 150m \nJ/cm2. This was followed by a 20% increment \nduring subsequent treatments if subjects tolerate the \nprevious dose. Parlak et al. did a study on the different \nregimes of NB-UVB phototherapy treatments.13 \nGroup 1 subjects were started with 50% of the \nminimal erythema dose followed by 20% increment \nin the next sessions as practised in our center, while \ngroup 2 subjects were given the starting dose and \ndose increment based on the skin types and applied \nwith fixed doses. They concluded that there was no \nsignificant difference in terms of cumulative dose, \nside effect profiles, and improvement in PASI score \nbetween the 2 groups. \n\n\n\nAmong 45 of the subjects with complete data, 75.6% \nof them tolerate NB-UVB without significant side \neffects, while 17.8% of them experienced burning \nsensation after phototherapy, and 4.4% of them \ncomplained of pruritus. Most of the side effects \nresolved with time or after dosage adjustment. \nOne (2.2%) of the subjects documented flare of \nunderlying psoriasis and phototherapy. However, \nthe patient had only received 4 sessions of NB-\nUVB phototherapy with a cumulative dose of 896m \nJ/cm2, which is less likely the cause of flare in this \n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4642\n\n\n\ncase. Two (4.4%) of them stopped the NB-UVB \nphototherapy and opted for other systemic therapy \nas they couldn\u2019t tolerate the phototherapy due to the \nburning sensation. \n\n\n\nOur study revealed lower rate of side effects from \nNB-UVB phototherapy compared to Vaani et al., \nwho reported a 30% rate of adverse reactions. \nOn the other hand, their study reported that 17% \nand 14% of the subjects reported pruritus and \nerythema, respectively. In our study population, \ncommonest side effects reported were burning \nsensation (17.8%) followed by pruritus (4.4%). \nThese data may be underreported as there was no \nstandard protocol to report any adverse reaction to \nNB-UVB treatment and the data was taken from \ndocumentation in clinical record and phototherapy \nfolders and subjected to bias.   \n\n\n\nConclusion\nOur study concluded that NB-UVB phototherapy is \nunderutilised at least in our centre. Psoriasis subjects \nwith a moderate disease or failed topical treatments \nshould be offered phototherapy if transportation \nis not an issue before we add in other systemic \ntreatments which bring more side effects or biologic \ntreatments which are costly. Lastly, well-designed \nprospective studies in the future on the effectiveness \nof NB-UVB phototherapy and their common side \neffects will give a clearer picture of the NB-UVB \nphototherapy treatment in different cutaneous \ndiseases and to identify the factors affecting the \nutilisation of NB-UVB in our centre.   \n\n\n\nConflict of Interest Declaration \nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. Honigsmann H. History of phototherapy in dermatology. \nPhotochem Photoiol Sci 2013;12:16-21.\n\n\n\n2. Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. \nPhotochemotherapy of psoriasis with oral methoxsalen and \nlongwave ultraviolet light. N Eng J Med 1974;291:1207-\n11.\n\n\n\n3. Ly K, Smith MP, Thibodeaux QG, Beck KM, Liao W, \nBhutani T. Beyond the booth: excimer laser for cutaneous \nconditions. Dermatol Clin 2020;38:157-63.\n\n\n\n4. Torres AE, Lyons AB, Hamzavi IH, Lim HW. Role of \nphototherapy in the era of biologics. J Am Acad Dermatol \n2021;84:479-85.\n\n\n\n5. Park SH, Hann SK, Park YK. Ten-year experience of \nphototherapy in Yonsei Medical Center. Yonsei Med J \n1996;37:392-6.\n\n\n\n6. Vaani VV, Tang MM, Tan LL, Asmah J. The utilization \nof phototherapy in the department of dermatology, \nHospital Kuala Lumpur: A 5-year audit. Med J Malaysia \n2018;73:125-30. \n\n\n\n7. Duarte I, Cunha JA, Bedrikow RB, Lazzarini R. What is \nthe most common phototherapy prescription for psoriasis: \nNB-UVB or PUVA? Prescription behavior. An Bras \nDermatol 2009;84:244-8.\n\n\n\n8. Adawiyah J, Suraiya HH. A retrospective study of \nnarrowband-UVB phototherapy for treatment of vitiligo in \nMalaysian subjects. Med J Malaysia 2010;65:297-9.\n\n\n\n9. Chen GY, Hsu MM, Tai HK, Chou TC, Tseng CL, Chang \nHY. Narrow-band UVB treatment of vitiligo in Chinese. J \nDermatol 2005;32:793-800. \n\n\n\n10. Lee E, Koo J, Berger T. UVB phototherapy and skin cancer \nrisk: a review of the literature. Int J Dermatol 2005;44:355-\n60.\n\n\n\n11. Malaysia Clinical Practice Guideline on Management of \nPsoriasis Vulgaris. June 2013. \n\n\n\n12. Archier E, Devaux S, Castela E, Gallini A, Aubin F, Le \nMa\u00eetre M, et al. Carcinogenic risks of psoralen UV-A \ntherapy and narrowband UV-B therapy in chronic plaque \npsoriasis: a systematic literature review. J Eur Acad \nDermatol Venereol 2012;26:22-31. \n\n\n\n13. Parlak N, Kundakci N, Parlak A, Akay BN. Narrowband \nultraviolet B phototherapy starting and incremental dose \nin subjects with psoriasis: comparison of percentage dose \nand fixed dose protocols. Photodermatol Photoimmunol \nPhotomed 2015;31:90-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n43\n\n\n\nCASE REPORT\n\n\n\nDermoscopy of Dilated Pore of Winer\nShashikumar Basavapura Madegowda1, MD(DVL), Savitha Somiiah Allaranda2, MD(DVL)\n\n\n\n1Department of Dermatology, Sparsha Skin Care Clinic, Mandya, Karnataka, India\n2Department of Dermatology, Sapthagiri Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India\n\n\n\nSummary\nDilated pore of Winer is a benign adnexal tumour of follicular differentiation. It has typical clinical \nfeature of asymptomatic, solitary enlarged pore with a keratin plug. Dermoscopy offers further assistance \nin diagnosis. In this case on dermoscopy, well defined lamellated central blackish area arranged in \nconcentric circles, surrounded by a bluish grey halo was seen with a rim of hyperpigmentation.\n\n\n\nKey words: Dilated pore, Dermoscopy, Adnexal tumour\n\n\n\nIntroduction\nDilated pore of Winer was first described by Louis \nH Winer in 1954.1 Though it is commonly located \nover the head and neck areas, it is usually found on \nthe trunk also. This frequently occurs in middle aged \nand elderly individuals. It is an adnexal neoplasm of \nthe follicular infundibulum.2 The clinical features \nare characteristic with a solitary dilated pore filled \nwith a black keratin plug. The lesion is benign and \nasymptomatic and treatment is advised only for \ncosmetic purposes. Histopathologic examination is \nadvised in doubtful cases to confirm the diagnosis. \nDermoscopy can now be used as an additional tool \nto confirm the diagnosis and thus help to avoid \nbiopsy.\n\n\n\nCase Report\nA 38-year-old male presented with an asymptomatic \nslowly enlarging lesion over the trunk for 6 months. \nOn examination, an elevated lesion measuring \n5mm x 5mm with central black plug like open \ncomedone was noted (Figure 1a). The surrounding \nskin was normal. On dermoscopy lamellated central \nblack area in concentric circles, surrounded by a \nbluish grey zone was noted and peripheral rim of \nhyperpigmentation was also seen. Biopsy was not \nperformed as the features were classical of dilated \npore of Winer (Figure 1b).Corresponding Author\n\n\n\nDr Shashikumar BM\nSparsha Skin Care Clinic,\n#1301, 2nd Cross,\nNehru Nagar, Mandya,\n57140n1 Karnataka, India.\nEmail: shashikumarbm@gmail.com\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4644\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4644\n\n\n\nFigure 1. (a) Papule woth central keratin plug; (b) Concentric areas in the centre, with bluish grey margins and rim of \nhyperpigmentation on dermoscopy\n\n\n\nDiscussion\nDilated pore of Winer is a common benign \ncondition. Some reports have considered it to be \nepidermal inclusion cyst with reactive hyperplasia \nof its epithelial lining and others proposed it to be a \nvariant of nevus comedonicus.3 Now it is said to be \nan adnexal neoplasm of the follicular infundibulum. \nThe exact etiology and pathophysiology is \nunknown. It is commonly located over the head \nand neck areas, and also frequently found on the \ntrunk of middle age to elderly individuals. It usually \npresents as an asymptomatic solitary lesion without \nany perilesional inflammatory changes.4 \n\n\n\nBiopsy and histopathological examination is advised \nonly in uncertain cases. On histopathology, single or \nmultiple contiguous enormously dilated follicular \ninfundibula is seen extending deep into dermis. It \nis lined by an acanthotic infundibular epithelium \nprojecting several finger-like projections into the \nadjacent dermis. These finger-like projections do \nnot contain keratin cysts, ducts, or hair shafts.3 \nThe cavity is filled with lamellar keratin material. \nExcessive melanization of this epithelium and/or \nthe central keratin plug may also be observed.\n\n\n\nOn dermoscopy with Dermlite 4, lamellated central \nblack area with concentric circles, surrounded \nby a bluish grey zone and peripheral rim of \nhyperpigmentation was noted. Previous reports on \nDermoscopy of Dilated pore of Winer describes a \ncentral homogenous bluish black material.4 In this \ncase the central keratin was organised in concentric \n\n\n\nlayers. The greyish margins correspond to epidermal \nhyperplasia around the follicular infundibulum.4\n\n\n\nDifferential diagnoses are solitary lesion of nevus \nsebaceous, pilar sheath acanthoma, epidermal \ninclusion cyst with punctum and large pore Basal \ncell carcinoma.\n\n\n\nFor these lesions, prognosis is excellent as they \nare benign and do not involve further testing or \nwork-up. Treatment is advised only for cosmetic \npurposes and excision is the best choice. It is \npossible to simply remove the keratin content using \na comedone extractor. However soon there will be \nreaccumulation of keratin. Due to the deeply located \nbase of the invagination, destructive methods like \nelectrodesiccation, electrocautery, laser surgery, \ndermabrasion, and cryotherapy are less efficient.1 \n\n\n\nConclusion\nDilated pore of Winer is a benign adnexal tumour of \nfollicular differentiation. There are very few reports \non the Dermoscopy of dilated pore of Winer and \nprevious reports described a homogenous central \narea. Hence, we report this dermoscopic finding of \ncentral keratin arranged in concentric layers.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nNil.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n45MJD 2021 Jun Vol 46\n\n\n\nReferences\n\n\n\n1. Winer L H. The dilated pore, a tricho-epithelioma. J Invest \nDermatol 1954;23:181-8.\n\n\n\n2. Steffen C. Winer\u2019s dilated pore: the infundibuloma. Am J \nDermatopathol 2001;23:246-53.\n\n\n\n3. Tellechea O, Cardoso JC, Reis JP, Ramos L, Gameiro \nAR, Coutinho I et al. Benign follicular tumors. An Bras \nDermatol 2015;90:780-96.\n\n\n\n4. Adya KA, Inamadar AC, Palit A. Dermoscopic \ncharacterization of dilated pore of Winer: Report of two \ncases. Clin Dermatol Rev 2019;3:96-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4646\n\n\n\nCASE REPORT\n\n\n\nCalcinosis Cutis Secondary to Trauma in a Patient with Systemic \nLupus Erythematosus and Ovarian Cancer\nMazliha Mashor1, Adv M Derm, Noor Zalmy Azizan1, Adv M Derm, Bang Rom Lee2, MPath\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n2Pantai Premier Pathology, Gleneagles Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nCalcinosis cutis is characterized by the accumulation of insoluble calcium salts in the cutaneous \nand subcutaneous tissue. This condition is classified into four subtypes of calcification: dystrophic, \nmetastatic, idiopathic and iatrogenic. Here, we describe a case of calcinosis cutis in a patient with \nsystemic lupus erythematosus (SLE) who was recently diagnosed with ovarian cancer. Following total \nhysterectomy with bilateral salphingo-oophorectomy, she developed a painful erythematous plaque \nover the anterior aspect of the left forearm which turned into single thin yellowish plaque over the \nfollowing days. Multiple attempts of intravenous cannulation for intravenous fluids occurred at the \nsite. Skin biopsy revealed calcification in the dermis and subcutaneous fat associated with altered \ndermal collagen. Von Kossa stain demonstrated the presence of calcium deposition. She responded to \ntopical calcineurin inhibitor which resulted in a complete resolution of the skin lesion.\n\n\n\nKey words: Calcinosis cutis, Systemic lupus erythematosus, Ovarian cancer\n\n\n\nIntroduction\nCalcinosis cutis is characterized by the accumulation \nof insoluble calcium salts in the cutaneous and \nsubcutaneous tissue. This condition is classified \ninto four subtypes of calcification: dystrophic, \nmetastatic, idiopathic and iatrogenic.1-3 Dystrophic \ntype is closely linked to autoimmune connective \ntissue diseases. Here, we describe a case of \ncalcinosis cutis in a patient with systemic lupus \nerythematosus (SLE) who was recently diagnosed \nwith ovarian cancer.\n\n\n\nCase Report\nA 58-year-old lady presented with a 2-week history \nof a single plaque on her left forearm. This patient \nwas diagnosed with SLE since 2007 and is currently \nin remission. Her treatment included prednisolone \n5mg daily and hydroxychloroquine 200mg daily. \nShe was also taking calcium carbonate and vitamin \nD supplement for more than 10 years. Recently, she \nwas diagnosed with ovarian clear cell carcinoma \nand a total hysterectomy with bilateral salphingo-\noophorectomy was performed. Post-operatively, she \ndeveloped a painful erythematous plaque over the \nanterior aspect of the left forearm. This was the site \nwhere multiple attempts of intravenous cannulation \n\n\n\nCorresponding Author\nDr Mazliha Mashor\nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur, Malaysia.\nEmail: ammz83@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n47\n\n\n\nfor intravenous fluids occurred, however there was \nno drug administered intravenously. \n\n\n\nOver the following few days, a single thin yellowish \nplaque appeared at the same site with an ill-defined \nborder and surrounding erythema (Figure 1a). The \nplaque was tender and not associated with any \nblister, ulcer or discharge. Patient was otherwise \nwell with no similar lesion elsewhere on her body. \nPlane xanthoma and necrobiosis lipoidica were \nconsidered as differential diagnoses.\n\n\n\nHistopathological examination of the skin lesion \nrevealed calcification in the dermis and subcutaneous \nfat associated with altered dermal collagen (Figure \n1b). Von Kossa stain demonstrated the presence \nof calcium deposition. Hence, the diagnosis of \ncalcinosis cutis was made (Figure 1c). Serum \ncalcium, phosphate and lipid levels were within \nnormal limits. Our patient was prescribed topical \ncalcineurin inhibitor to reduce the inflammation. \nShe had completed systemic chemotherapy post \noperatively for her ovarian carcinoma. During her \nlast clinic visit, there was a complete resolution of \nthe skin lesion with no recurrence noted.\n\n\n\nDiscussion\nCalcinosis cutis is more frequently manifested as \nchalky white subcutaneous nodules. In this case \nthe clinical appearance of a yellowish plaque could \nbe misleading and may look similar to xanthoma, \nas previously reported by Ankad et al.4 Von kossa \nstain would be helpful to confirm the diagnosis of \ncalcinosis cutis. \n\n\n\nThe exact pathophysiology of calcinosis cutis is \n\n\n\nstill unclear. Some studies hypothesized that local \ninflammation following tissue injury might lead to \ntissue calcification.2,3 At the site of trauma, increased \ncell permeability and damaged proteins of necrotic \ncells may further attract calcium deposition.1,2 In \nour case, local skin microtrauma caused by repeated \ncannulation might promote the development of \ncalcinosis cutis as suggested in past studies.5-7\n\n\n\nSLE-associated calcinosis cutis is usually localised \nwith the tendency to develop over the limbs and \nbuttocks.1,8 Typically, calcinosis cutis presents in \npatients with a long history of established SLE.2,8 \nSimilarly, our patient had SLE for more than 10 \nyears before developing calcinosis cutis, despite her \nSLE currently being in remission. \n\n\n\nElevated level of calcium or phosphate metabolism \nis usually found in metastatic calcification and \ncalciphylaxis.1 Normal level of serum calcium and \nphosphate is observed in idiopathic and dystrophic \ncalcification (as reflected in our case). The patient \nis unlikely to have idiopathic calcification due to \nthe presence of tissue damage. Other type such as \niatrogenic calcification mostly occurs following \nan intravenous calcium treatment.1 Whether the \noral calcium and vitamin D supplement intake \ncontributed to cutaneous calcification in our patient \nis unproven.\n\n\n\nThe treatment of calcinosis cutis in SLE is variable \nwith no standardised algorithm.8,9 Several medical \ntreatments which are reported to be beneficial \ninclude diltiazem, colchicine, minocycline. Surgical \ntreatment is generally considered for large localised \nand symptomatic lesions.9\n\n\n\nFigure 1. (a) Single thin yellowish plaque over the left forearm; (b) Histopathology shows calcification in the dermis and \nsubcutaneous fat (H&E x 100); (c) Calsium deposits in the dermis using Von Kossa stain x 20)\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4648\n\n\n\nConclusion\nWhen encountering a patient with long-standing \nSLE, normal serum calcium and phosphate levels, \nand following trauma especially at intravenous \ncannulation sites, the presence of yellowish plaque \nshould prompt the clinician to consider dystrophic \ncalcinosis cutis as a differential diagnosis.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nWe would like to thank the Director General of \nHealth Malaysia for permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. Reiter N, El-Shabrawi L, Leinweber B, Berghold A, \nAberer E. Calcinosis cutis: Part I. Diagnostic pathway. J \nAm Acad Dermatol 2011;65:1-12. \n\n\n\n2. Kim MS, Choi KC, Kim HS, Song IG, Shin BS. Calcinosis \ncutis in systemic lupus erythematosus: A case report and \nreview of the published work. J Dermatol 2010;37:815-8. \n\n\n\n3. Ammouri W, Harmouche H, Ahrikat O, Maamar M, Tazi \nMZ, Adanaoui M. Extensive calcinosis cutis in a patient \nwith systemic lupus erythematosus: An exceptional \ncomplication. Press Med 2018;47:410-1. \n\n\n\n4. Ankad BS, Miskin AT, Math MK, Sakhare PS. Calcinosis \ncutis mimicking xanthoma: A case report. Our Dermatol \nOnline J 2018;9:95-6. \n\n\n\n5. Larralde M, Giachetti A, C\u00e1ceres MR, Rodr\u00edguez M, Casas \nJ. Calcinosis cutis following trauma. Pediatr Dermatol \n2005;22:227-9. \n\n\n\n6. Kanda A, Uchimiya H, Ohtake N, Setoyama M, Kanzaki \nT. Two Cases of Gigantic Dystrophic Calcinosis Cutis \nCaused by Subcutaneous and/or Intramuscular Injections. \nJ Dermatol 1999;26:371-4. \n\n\n\n7. Chung EH, Kim YH. Iatrogenic calcinosis cutis of the \nupper limb arising from the extravasation of intravenous \nanticancer drugs in a patient with acute Lymphoblastic \nleukemia. Arch Plast Surg 2016;43:214-6.\n\n\n\n8. Gutierrez Jr A, Wetter DA. Calcinosis cutis in autoimmune \nconnective tissue diseases. Dermatol Ther 2012;25:195-\n206. \n\n\n\n9. Balin SJ, Wetter DA, Andersen LK, Davis MDP. Calcinosis \ncutis occurring in association with autoimmune connective \ntissue disease: The Mayo Clinic experience with 78 \npatients, 1996-2009. Arch Dermatol 2012;148:455-62.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n49\n\n\n\nCASE REPORT\n\n\n\nQuinacrine: An Effective Addition to the Treatment of Refractory \nCutaneous Lupus Erythematosus\nHui Jen Ding, MRCP, Swee Gaik Ong, MRCP\n\n\n\nRheumatology Unit, Department of Medicine, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nTreatment of refractory cutaneous lupus is challenging. When conventional therapy, including \nhydroxychloroquine (HCQ), corticosteroids and immunosuppressants, has failed, the addition of \nquinacrine may be a promising option. We describe a case of refractory chronic cutaneous lupus \nerythematosus (CCLE) who responded well to quinacrine.\n\n\n\nKey words: Quinacrine, Refractory cutaneous lupus erythematosus, Hydroxychloroquine\n\n\n\nIntroduction\nQuinacrine, also known as mepacrine, is a \nsynthetic quinine derivative which has been \nshown to be efficacious in the treatment of discoid \nlupus erythematosus (DLE) as early as in the \n1940s.1-3 However, its use was superseded by \nhydroxychloroquine (HCQ) because of quinacrine\u2019s \npurported side effects. Nevertheless, the use of \nquinacrine has seen a resurgence of late. We \nreport a case of refractory chronic cutaneous lupus \nerythematosus (CCLE) who responded favourably \nto quinacrine.\n\n\n\nCase Report\nOur patient is a 49-year-old man who was diagnosed \nwith systemic lupus erythematosus 22 years ago \nbased on the American College of Rheumatology \n(ACR) 1997 revised classification criteria for SLE.4 \nHe is anti-nuclear antibody positive but anti-double-\nstranded DNA and extractable nuclear antigen \nnegative. His complement levels (C3/C4) were \nnever low. He had mild cytopenias (leukopenia \nand lymphopenia) in the past but no major organ \ninvolvement. His manifestations are predominantly \ncutaneous: he has disfiguring DLE rashes on the \nscalp, face and both upper arms and forearms.\n\n\n\nHis rashes (Figure 1a) are refractory to almost \nall immunosuppressants that he has tried: \nmultiple rounds of  intravenous immunoglobulin \nand IV methylprednisolone, cyclosporine, \nazathioprine, colchicine, dapsone, methotrexate \nand mycophenolate mofetil. These were all used \n\n\n\nCorresponding Author\nDr Ding Hui Jen\nRheumatology Unit, \nDepartment of Medicine,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur, Malaysia.\nEmail: hjding1@gmail.com\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nazathioprine, colchicine, dapsone, methotrexate and mycophenolate mofetil. These were all \nused on a background of HCQ and topical and systemic corticosteroids. He is steroid-\ndependent, often flaring when his prednisolone dose is reduced to less than 20mg daily. He is \non HCQ 400mg daily, the maximum recommended dose. He developed avascular necrosis of \nboth femoral heads and recurrent serious infections as a result of prolonged high-dose \ncorticosteroid use.  \n \nHe is an ex-smoker who stopped in 2018 because of the development of peripheral vascular \ndisease and ischemic heart disease. However, despite stopping smoking, his rashes remained \nactive. In late 2019, we applied for special permission to purchase and use quinacrine through \nthe Ministry of Health, as it is not licensed for use in Malaysia. Quinacrine 100mg daily was \nadded to HCQ and prednisolone. He reported progressive improvements in his rashes in the \nfirst 6 months. CLASI activity scoring improved from 15 to 2. His prednisolone dose was \nreduced gradually to 5mg daily. He has now been on quinacrine for 15 months: his lesions \nhave remained inactive and his prednisolone use has not required dose escalation. He has not \ndeveloped any untoward side effects to quinacrine. Figure 1b shows his cutaneous lesions 6 \nmonths after initiation of quinacrine.  \n \nFigure 1. Side profile of the patient\u2019s face showing DLE rashes; (a) Pre-treatment; (b) Post  \n\n\n\n \n \nDiscussion \nAntimalarials, together with non-pharmacological methods like smoking cessation and \nsunscreen usage, are recommended as first-line treatment for cutaneous lupus erythematosus \n(CLE). Quinacrine is added when there is poor response, where quinacrine has been shown to \nwork synergistically with HCQ or chloroquine.5 \n\n\n\n \nAntimalarials have been used to treat CLE for years but their mechanism of action is not \ncompletely understood. Recent studies have implicated toll-like receptors (TLRs) in the \npathogenesis of CLE in producing pro-inflammatory cytokines like interferon-\u03b1 (IFN-\u03b1).6-7 \nAntimalarials are able to inhibit TLRs, hence dampening production of IFN-\u03b1.8 Quinacrine \nand HCQ were shown in a study to decrease the production of IFN-\u03b1.9 Other postulated \n\n\n\na b \n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4650\n\n\n\non a background of HCQ and topical and systemic \ncorticosteroids. He is steroid-dependent, often \nflaring when his prednisolone dose is reduced to \nless than 20mg daily. He is on HCQ 400mg daily, \nthe maximum recommended dose. He developed \navascular necrosis of both femoral heads and \nrecurrent serious infections as a result of prolonged \nhigh-dose corticosteroid use. \n\n\n\nHe is an ex-smoker who stopped in 2018 because of \nthe development of peripheral vascular disease and \nischemic heart disease. However, despite stopping \nsmoking, his rashes remained active. In late 2019, \nwe applied for special permission to purchase and \nuse quinacrine through the Ministry of Health, as \nit is not licensed for use in Malaysia. Quinacrine \n100mg daily was added to HCQ and prednisolone. \nHe reported progressive improvements in his \nrashes in the first 6 months. CLASI activity scoring \nimproved from 15 to 2. His prednisolone dose was \nreduced gradually to 5mg daily. He has now been on \nquinacrine for 15 months: his lesions have remained \ninactive and his prednisolone use has not required \ndose escalation. He has not developed any untoward \nside effects to quinacrine. Figure 1b shows his \ncutaneous lesions 6 months after initiation of \nquinacrine.\n\n\n\nFigure 1. Side profile of the patient\u2019s face showing DLE \nrashes; (a) Pre-treatment; (b) Post\n\n\n\nazathioprine, colchicine, dapsone, methotrexate and mycophenolate mofetil. These were all \nused on a background of HCQ and topical and systemic corticosteroids. He is steroid-\ndependent, often flaring when his prednisolone dose is reduced to less than 20mg daily. He is \non HCQ 400mg daily, the maximum recommended dose. He developed avascular necrosis of \nboth femoral heads and recurrent serious infections as a result of prolonged high-dose \ncorticosteroid use.  \n \nHe is an ex-smoker who stopped in 2018 because of the development of peripheral vascular \ndisease and ischemic heart disease. However, despite stopping smoking, his rashes remained \nactive. In late 2019, we applied for special permission to purchase and use quinacrine through \nthe Ministry of Health, as it is not licensed for use in Malaysia. Quinacrine 100mg daily was \nadded to HCQ and prednisolone. He reported progressive improvements in his rashes in the \nfirst 6 months. CLASI activity scoring improved from 15 to 2. His prednisolone dose was \nreduced gradually to 5mg daily. He has now been on quinacrine for 15 months: his lesions \nhave remained inactive and his prednisolone use has not required dose escalation. He has not \ndeveloped any untoward side effects to quinacrine. Figure 1b shows his cutaneous lesions 6 \nmonths after initiation of quinacrine.  \n \nFigure 1. Side profile of the patient\u2019s face showing DLE rashes; (a) Pre-treatment; (b) Post  \n\n\n\n \n \nDiscussion \nAntimalarials, together with non-pharmacological methods like smoking cessation and \nsunscreen usage, are recommended as first-line treatment for cutaneous lupus erythematosus \n(CLE). Quinacrine is added when there is poor response, where quinacrine has been shown to \nwork synergistically with HCQ or chloroquine.5 \n\n\n\n \nAntimalarials have been used to treat CLE for years but their mechanism of action is not \ncompletely understood. Recent studies have implicated toll-like receptors (TLRs) in the \npathogenesis of CLE in producing pro-inflammatory cytokines like interferon-\u03b1 (IFN-\u03b1).6-7 \nAntimalarials are able to inhibit TLRs, hence dampening production of IFN-\u03b1.8 Quinacrine \nand HCQ were shown in a study to decrease the production of IFN-\u03b1.9 Other postulated \n\n\n\na b a\n\n\n\nDiscussion\nAntimalarials, together with non-pharmacological \nmethods like smoking cessation and sunscreen \nusage, are recommended as first-line treatment for \ncutaneous lupus erythematosus (CLE). Quinacrine \nis added when there is poor response, where \nquinacrine has been shown to work synergistically \nwith HCQ or chloroquine.5\n\n\n\nAntimalarials have been used to treat CLE for years \nbut their mechanism of action is not completely \nunderstood. Recent studies have implicated toll-\nlike receptors (TLRs) in the pathogenesis of CLE \nin producing pro-inflammatory cytokines like \ninterferon-\u03b1 (IFN-\u03b1).6-7 Antimalarials are able to \ninhibit TLRs, hence dampening production of \nIFN-\u03b1.8 Quinacrine and HCQ were shown in a \nstudy to decrease the production of IFN-\u03b1.9 Other \npostulated mechanisms of action of antimalarials \ninclude immunomodulatory, anti-proliferative, anti-\ninflammatory and photoprotective properties.10\n\n\n\nQuinacrine is a safe drug with relatively few side \neffects. Notably, it has no retinal toxicity11-12  and \ndoes not potentiate the side-effects of HCQ or \nCQ when used in combination.13 However, the \ncommonest side effect is a yellowish discolouration \nof the skin, which reverses upon cessation of the \ndrug. Other side effects which could occur include \nheadache and gastrointestinal symptoms.13 Rare \nside effects include aplastic anaemia14 and acute \nhepatitis,15 although these occurred in conjunction \nwith the use of other drugs and concomitant \nHepatitis C infection. \n\n\n\nQuinacrine appears to be more efficacious in \npatients with acute cutaneous lupus and discoid \nlupus, with response rates ranging from 55-80%.15-\n\n\n\n18 However, it is still not widely available in the \nUnited States of America, Europe or Asia.11,17,19 \n\n\n\nthus limiting its use. Nonetheless, we hope this \nexperience would encourage the use of quinacrine \nin refractory cutaneous lupus in Malaysia and help \nreduce the incidence of adverse effects with other \nimmunosuppressants. \n\n\n\nConclusion \nSeveral case series have supported quinacrine\u2019s \nefficacy and safety. It can be considered in patients \nwith DLE who do not show adequate response \ndespite maximal HCQ therapy and corticosteroid \ntherapy.  \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle.\n\n\n\nb\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n51\n\n\n\nReferences\n\n\n\n1. Wallace DJ. The use of quinacrine (Atabrine) in rheumatic \ndiseases: a reexamination. Semin Arthritis Rheum \n1989;18:282-96.\n\n\n\n2. Dubois EL. Antimalarials in the management of discoid \nand systemic lupus erythematosus. Semin Arthritis Rheum \n1978;8:33-51. \n\n\n\n3. Page F. Treatment of lupus erythematosus with mepacrine. \nLancet 1951;2:755-8. \n\n\n\n4. Hochberg MC. Updating the American College of \nRheumatology revised criteria for the classification \nof systemic lupus erythematosus. Arthritis Rheum \n1997;40:1725.\n\n\n\n5. Kuhn A, Aberer E, Bata-Cs\u00f6rg\u0151 Z, Caproni M, Dreher A, \nFrances C et al. S2k guideline for treatment of cutaneous \nlupus erythematosus - guided by the European Dermatology \nForum (EDF) in cooperation with the European Academy \nof Dermatology and Venereology (EADV). J Eur Acad \nDermatol Venereol 2017;31:389-404. \n\n\n\n6. Aringer M, G\u00fcnther C, Lee-Kirsch MA. Innate immune \nprocesses in lupus erythematosus. Clin Immunol \n2013;147:216-22.\n\n\n\n7. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu \nRev Immunol 2003;21:335-76.\n\n\n\n8. Willis R, Seif AM, McGwin G Jr, Martinez-Martinez LA, \nGonz\u00e1lez EB, Dang N et al. Effect of hydroxychloroquine \ntreatment on pro-inflammatory cytokines and disease \nactivity in SLE patients: data from LUMINA (LXXV), a \nmultiethnic US cohort. Lupus 2012;21:830-5.\n\n\n\n9. Alves P, Bashir MM, Wysocka M, Zeidi M, Feng R, \nWerth VP. Quinacrine Suppresses Tumor Necrosis \nFactor-\u03b1 and IFN-\u03b1 in Dermatomyositis and Cutaneous \nLupus Erythematosus. J Investig Dermatol Symp Proc \n2017;18:S57-63.\n\n\n\n10. Rodriguez-Caruncho C, Bielsa Marsol I. Antimalarials in \ndermatology: mechanism of action, indications, and side \neffects. Actas Dermosifiliogr 2014;105:243-52. \n\n\n\n11. McCune WJ, Gonzalez-Rivera T. Should very low doses \nof hydroxychloroquine and quinacrine be employed in \ncombination for long-term maintenance of remission in \nsystemic lupus to reduce the risk of ocular toxicity? Curr \nOpin Rheumatol 2015;27:213-5.\n\n\n\n12. Zuehlke RL, Lillis PJ, Tice A. Antimalarial therapy for \nlupus erythematosus: an apparent advantage of quinacrine. \nInt J Dermatol 1981;20:57-61.\n\n\n\n13. Mittal L, Zhang L, Feng R, Werth VP. Antimalarial \ndrug toxicities in patients with cutaneous lupus and \ndermatomyositis: A retrospective cohort study. J Am Acad \nDermatol 2018;78:100-6.e1.\n\n\n\n14. Wallace DJ. Antimalarial agents and lupus. Rheum Dis \nClin North Am 1994;20:243-63.\n\n\n\n15. Cavazzana I, Sala R, Bazzani C, Ceribelli A, Zane C, \nCattaneo R et al. Treatment of lupus skin involvement with \nquinacrine and hydroxychloroquine. Lupus 2009;18:735-\n9. \n\n\n\n16. Benoit S, Goebeler M. Mepacrine in Recalcitrant \nCutaneous Lupus Erythematosus: Old-fashioned or Still \nUseful? Acta Derm Venereol 2015;95:596-9. \n\n\n\n17. Chang AY, Piette EW, Foering KP, Tenhave TR, Okawa J, \nWerth VP. Response to antimalarial agents in cutaneous \nlupus erythematosus: a prospective analysis. Arch \nDermatol 2011;147:1261-7.\n\n\n\n18. Gonz\u00e1lez-Sixto B, Garc\u00eda-Doval I, Oliveira R, Posada \nC, Garc\u00eda-Cruz MA, Cruces M. Aspectos pr\u00e1cticos de \nla quinacrina como tratamiento del lupus eritematoso \n\n\n\ncut\u00e1neo: serie de casos [Quinacrine in the treatment of \ncutaneous lupus erythematosus: practical aspects and a \ncase series]. Actas Dermosifiliogr 2010;101:54-8. Spanish. \n\n\n\n19. Mittal L, Werth VP. The quinacrine experience in a \npopulation of patients with cutaneous lupus erythematosus \nand dermatomyositis. J Am Acad Dermatol 2017;77:374-\n7.\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4652\n\n\n\nCASE REPORT\n\n\n\nCutaneous Serratia Marcescens Infection - A Rare Case Report\nKwang Meng Yew1, MMed, Stephanie Sue San Ong1, MD, Mazita Ismail2, MPath, Jyh Jong Tang1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia\n2Department of Pathology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia\n\n\n\nSummary\nCutaneous serratia marcescens (S. marcescens) infection is very rare and most cases had history of \nskin trauma or cutaneous procedure done before. It presents in various forms like non-healing ulcers, \nabscess formation, nodules with an intermittent course or as granulomatous lesions, thus mimicking \nnon-infective lesions. Antibiotic choice is challenging due to multiple antibiotic resistant strains. We \nare reporting a case of cutaneous S. marcescens in a 70-year old lady with diabetes mellitus presented \nwith non-healing ulcers over the dorsum of left hand for 6 months.\n\n\n\nKey words: Cutaneous, Serratia marcescens, Community acquired\n\n\n\nIntroduction\nSerratia marcescens, an opportunistic, Gram-\nnegative, facultative anaerobe bacterium, is \ncommonly associated with nosocomial infection \nand rarely community acquired.1 Skin infections \nby S. marcescens are extremely rare and usually \noccur in patients with underlying disease or \nimmunocompromised and almost never in \nimmunocompetent patients.2,3 It can present \nin acute or chronic form, with sporotrichoid \nspread or chronic granulomatous infections, thus \nmimicking certain types of skin pathology such as \nsporothricosis, cutaneous tuberculosis, nocardiosis \nand histoplasmosis.2,3,7 Worldwide, only a few cases \nof community acquired infection had been reported \ninvolving healthy individuals with no co-morbids.2-6\n\n\n\nCase Report\nA 70-year old Chinese lady with underlying diabetes \nmellitus on a single oral hypoglycemic agent for \nmore than 10 years, presented with multiple non-\nhealing ulcers over the dorsum surface of left hand \npast 6 months. She had history of developing solitary, \nerythematous swelling with ulceration over the left \narm, right elbow and leg, which appeared one after \nanother past 1 year. A new swelling would appear \nafter the previous one was removed and resolved. \nShe went to orthopaedic surgeon a few times to have \nthe swellings excised. Tissue and blood cultures \ndone were normal. She was completely free from \nany swelling after that. She denied any history of \n\n\n\nCorresponding Author\nDr Yew Kwang Meng\nDepartment of Dermatology,\nHospital Raja Permaisuri Bainun,\nJalan Raja Ashman Shah,\n30450 Ipoh, Perak, Malaysia.\nEmail: eastdragonkm@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n53\n\n\n\nskin trauma or animal bite prior to onset of above \nlesion. There was no contact with tuberculosis (TB) \npatient.\n\n\n\n4 months ago, she developed another swelling \nwith ulceration over dorsum of left hand, which \nagain being excised by orthopaedic surgeon but \nthis time, the ulcer persisted and developed a few \nmore on the same site. She sought treatment from \nprivate dermatologist and skin biopsy done showed \nacute abscess with vague granuloma infective, \nsuppurative granulomatous lesion. Swab culture and \nsensitivity (C + S) grew S. Marcescens, sensitive \nto Ceftazidime, Ciprofloxacin, Gentamicin, \nCeftriaxone, Ertapenam, Levofloxacin and Co-\nTrimoxazole. She was empirically started on oral \nDoxycycline for 3 months but no improvement \nnoted.\n\n\n\nSubsequently she was referred to us and her wound \n\n\n\nhad multiple, sloughy ulcers with raised surrounding \nborder and erythematous surrounding. Incisional \nskin biopsy showed acute on chronic inflammation, \nno granuloma, fungal body or malignancy (Figure \n1). Bacterial C + S was repeated twice which \nshowed S. Marcescens, susceptible to Cefepime \nand Trimethoprim/Sulfamethoxazole. TB work ups \ncomprising chest x-ray, mantoux test, skin sample \nfor TB polymerase chain reaction and fungal culture \nwere negative.\n\n\n\nShe was treated with oral sulfamethoxazole and \ntrimethoprim 2 tablets BD for 2 weeks and potassium \npermanganat 1:10,000 plus bactigrass dressing \ndaily, which showed slight improvement, thus \nsulfamethoxazole and trimethoprim was increased \nto 3 tablets BD. After 2 weeks, the wounds improved \nsignificantly (Figure 3). Oral sulfamethoxazole and \ntrimethoprim was continued for another 2 months \nand her skin lesion resolved completely after that.\n\n\n\nFigure 1. The dermis show moderate to dense lymphoplasma cells and neutrophils infiltrate, vascular congestion and areas \nof hemorrhage. a. H&E at low power b. H&E at x40  \n\n\n\n\n\n\n\n\n\n\n\nFigure 2. Improvement of the wound over dorsum of left hand lesion with oral Bactrim \n\n\n\nb\n\n\n\n\n\n\n\n\n\n\n\nFigure 2. Improvement of the wound over dorsum of left hand lesion with oral Bactrim \n\n\n\na\n\n\n\nFigure 2. Improvement of the wound over dorsum of left hand lesion with oral Bactrim\n\n\n\n\n\n\n\n\n\n\n\nDiscussion \nCommunity acquired S. marcescens infections commonly occur in immunocompromised \nindividuals,8 in association with contaminated depot, parenteral solutions and illicit drug usage.9-\n\n\n\n12 Most skin infection occurred after sustaining trauma or undergoing cutaneous procedures.2,3,5,6 \n\n\n\nHowever, there are some reports where no portal of entry or immunosuppression were identified \nin infected individuals.4,13  \n\n\n\nCutaneous infection has various forms ranging from acute type like cellulitis, abscess, ulcers and \nnecrotizing fasciitis or chronic forms such as fluctuant nodules with an intermittent course or \ngranulomatous lesions.2,4 Our patient has multiple non-healing, with sloughy ulcers over the \ndorsum of left hand.  \n\n\n\nIt is crucial to rule out differential diagnosis such as chronic granulomatous infections and causes \nof non-healing ulcers such as subcutaneous fungal infection like sporotrichosis, Tuberculosis, \nAtypical mycobacterium (mycobacterium ulcerans), Nocardiosis and others; due to variability in \nthe clinical presentation.2,6,7,8 Skin biopsy is important to confirm the underlying cause of any \nnon-healing ulcers. Histopathologically, there will be presence of granulomatous reaction and \nspecial stain, example, Ziehl Nelson & Periodic Acid-Schiff (PAS) are important to rule out \nother differential diagnosis, example subcutaneous fungal and mycobacterium infection. Skin \nbiopsy for culture is still the gold standard to confirm the diagmosis of Serratia Marcenscen. It is \nthrough pus and tissue biopsy sample culture of the ulcer, that we managed to identify the \ninfective etiology in our patient.  \n\n\n\nS. marcescens has multiple antibiotic resistant strains, including those resistant towards broad \nspectrum antibiotics1. Therefore, antibiotic choice has to be guided by culture sensitivity test. \nAmong the antibiotics used successfully to treat S. marcescens are ciprofloxacin, Trimethoprim-\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4654\n\n\n\nDiscussion\nCommunity acquired S. marcescens infections \ncommonly occur in immunocompromised \nindividuals,8 in association with contaminated \ndepot, parenteral solutions and illicit drug usage.9-12 \nMost skin infection occurred after sustaining trauma \nor undergoing cutaneous procedures.2,3,5,6 However, \nthere are some reports where no portal of entry or \nimmunosuppression were identified in infected \nindividuals.4,13 \n\n\n\nCutaneous infection has various forms ranging \nfrom acute type like cellulitis, abscess, ulcers \nand necrotizing fasciitis or chronic forms such as \nfluctuant nodules with an intermittent course or \ngranulomatous lesions.2,4 Our patient has multiple \nnon-healing, with sloughy ulcers over the dorsum \nof left hand.\n\n\n\nIt is crucial to rule out differential diagnosis such \nas chronic granulomatous infections and causes of \nnon-healing ulcers such as subcutaneous fungal \ninfection like sporotrichosis, Tuberculosis, Non-\ntuberculous mycobacterium (Mycobacterium \nulcerans), Nocardiosis and others; due to variability \nin the clinical presentation.2,6,7,8 Skin biopsy is \nimportant to confirm the underlying cause of any \nnon-healing ulcers. Histopathologically, there will \nbe presence of granulomatous reaction and special \nstain, example, Ziehl Nelson & Periodic Acid-Schiff \n(PAS) are important to rule out other differential \ndiagnosis, example subcutaneous fungal and \nmycobacterium infection. Skin biopsy for culture \nis still the gold standard to confirm the diagnosis \nof Serratia marcenscen. It is through pus and tissue \nbiopsy sample culture of the ulcer, that we managed \nto identify the infective etiology in our patient.\n\n\n\nS. marcescens has multiple antibiotic resistant \nstrains, including those resistant towards broad \nspectrum antibiotics.1 Therefore, antibiotic \nchoice has to be guided by culture sensitivity test. \nAmong the antibiotics used successfully to treat S. \nmarcescens are ciprofloxacin, sulfamethoxazole and \ntrimethoprim and ertapenem.2,3,5,6 Our patient was \nstarted on oral sulfamethoxazole and trimethoprim \nand showed significant improvement clinically.\n\n\n\nConclusion\nS. marcescens infection should be taken into \nconsideration when a patient presented with non-\n\n\n\nhealing cutaneous lesion. Culture and antibiotic \nsensitivity test are crucial in identifying the organism \nand Trimethoprim-sulfamethoxazole is an effective \nchoice of treatment for S. marcescens but this has to \nbe guided by sensitivity pattern.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Herra C, Falkiner FR. Serratia marcescens. Antimicrobial \nTherapy and Vaccines. Vol. 1. New York: Apple Trees \nProduction; 2002.\n\n\n\n2. Gir\u00e1ldez P, Mayo E, Pav\u00f3n P, Losada A. Skin infection due \nto Serratia marcescens in an immunocompetent patient. \nActas Dermosifiliogr 2011;102:236-7.\n\n\n\n3. Diranzo Garc\u00eda J, Villodre Jim\u00e9nez J, Zarzuela S\u00e1nchez \nV, Castillo Ruiperez L, Bru Pomer A. Skin abscess due to \nSerratia marcescens in an immunocompetent patient after \nreceiving a tattoo. Case Rep Infect Dis 2015;2015:626917.\n\n\n\n4. Garc\u00eda FR, Paz RC, Gonz\u00e1lez RS, Ruiz ES, Mart\u00edn-Neda \nFG, Rodr\u00edguez MS et al. Cutaneous infection caused by \nSerratia marcescens in a child. J Am Acad Dermatol \n2006;55:357-8.\n\n\n\n5. Grim KD, Doherty C, Rosen T. Cutaneous Serratia \nmarcescens infection in an immunocompetent patient after \nfiller injection. Acta Derm Venereol 2013;93:191-2.\n\n\n\n6. Grim KD, Doherty C, Rosen T. Serratia marcescens \nbullous cellulitis after iguana bites. J Am Acad Dermatol \n2010;62:1075-6.\n\n\n\n7. Jo\u00e3o AM, Serrano PN, Cach\u00e3o MP, B\u00e1rtolo EA, Brand\u00e3o \nFM. Recurrent Serratia marcescens cutaneous infection \nmanifesting as painful nodules and ulcers. J Am Acad \nDermatol 2008;58:55-7.\n\n\n\n8. Zhu S, Anil S, Nina R, Stephen P, Neil H. Community \nAcquired Severe Soft Tissue Infection Due to Serratia \nmarcescens in an Immunocompetent Host. Chest \n2014;146:141A.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n55\n\n\n\nCASE REPORT\n\n\n\nSymmetrical Flexural and Intertriginous Exanthema: A Rare \nManifestation Associated with COVID-19 Infection\nJin Yi Goh1, MRCP, Huang Hin Chin2, MRCP, Pek Woon Chin2, MRCP, Masliza Zaid3, MMED\n\n\n\n1Department of Medicine, Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia\n2Department of Medicine, Hospital Enche\u2019 Besar Hajjah Khalsom, Kluang, Johor, Malaysia\n3Department of Medicine, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\n\n\n\nSummary\nCutaneous manifestations of Coronavirus disease (COVID-19) are variable. We present a case of non-\ndrug related symmetrical flexural and intertriginous exanthema in a patient with COVID-19 infection. A \n58-year-old Chinese male who was diagnosed to have COVID-19 infection, developed maculopapular \nerythematous rashes at bilateral axillary and inguinal folds on the fourth day of illness. He was treated \nsymptomatically with anti-histamine and topical corticosteroid. The skin condition improved and he \nwas discharged well on tenth day of illness. Although symmetrical flexural intertriginous exanthema \nis classically caused by drug reaction, this case demonstrated the possibility of the rash being directly \nassociated with COVID-19 infection. More cohorts should be evaluated to fully describe the full \nspectrum of dermatological manifestation in COVID-19.\n\n\n\nKey words: Cutaneous, Rashes, Exanthema, COVID-19\n\n\n\nIntroduction\nCoronavirus disease (COVID-19) infection, which \nis caused by severe acute respiratory syndrome \ncoronavirus 2 (SARS-CoV-2), has become a global \npandemic in 2020. It was first reported in December \n2019 in Wuhan, China.1 The typical symptoms of \nCOVID-19 infections are fever, dry cough, anosmia, \nfatigue, and dyspnea. Serious complications include \nacute respiratory distress syndrome, secondary \ninfection, thrombotic events, and multiorgan failure \nleading to death. Besides, cutaneous manifestations \nhave been increasingly reported in COVID-19 \npatients. \n\n\n\nA nationwide consensus study in Spain has classified \nthe cutaneous lesions into five clinical patterns, \nwhich are acral areas of erythema with vesicles or \npustules (19%), vesicular eruptions (9%), urticarial \nlesions (19%), maculopapular eruptions (47%) and \nlivedo or necrosis (6%).2 Wollina et al. have also \nsuggested other possible cutaneous findings such as \nsymmetrical flexural and intertriginous exanthema, \npurpuric rash, erythema multiforme-like rash, and \nKawasaki like disease/Multisystemic inflammatory \nsyndrome in children.3 \n\n\n\nCorresponding Author\nDr Goh Jin Yi\nDepartment of Medicine,\nHospital Sultanah Nora Ismail,\nJalan Korma, Taman Soga,\n83000 Batu Pahat, Johor.\nEmail: jinyigoh1988@yahoo.com\n\n\n\nMJD 2021 Jun Vol 46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4656\n\n\n\nCOVID-19 infection related skin manifestations \nwere more commonly reported in United State \nand Europe countries compared to Asian cohort.4 \nIndeed, a systemic review of total 1211 patients with \nCOVID-19 related skin manifestations, 39 (3.1%) \npatients were from Asian populations and 1172 \n(96.9%) patients were from Europe and the United \nStates.4 Here, we would like to present a case of non-\ndrug-related symmetrical flexural and intertriginous \nExanthema in a patient with COVID-19 infection.\n\n\n\nCase Report\nA 58-year-old Chinese male presented with fever \nand cough for the past three days, followed by an \nalleged fall at home which he sustained a small \nlaceration wound over the scalp. He attributed the \nfall to an alleged slippery floor with no obvious \nneurological deficits. He underwent wound suturing \nat a private hospital, uneventfully. Incidentally, pre-\nprocedure nasopharyngeal swab showed SARS-\nCoV RNA PCR detected. (Ct value; E gene = \n18.41, RdRp gene = 21.09). He was then transferred \nto a designated COVID 19 hospital for further \nmanagement while the local health authorities \nperformed contact tracing amongst his family \nmembers and friends. His fever and cough were \nresolved in the ward. \n\n\n\nHowever, on the fourth day of illness, he developed \nblanchable maculopapular erythematous rashes at \nbilateral axillary and inguinal folds. The distribution \nof rash rapidly involved nape of the neck, forearm, \nanterior thigh, lower abdomen, and buttock \nsymmetrically over the following days. (Figure \n1 (a-d)) These lesions were mildly pruritic with \nno obvious discharges, vesicles, plaques or bullae \nnoted. Notably, the face, trunk, palm, and sole were \nspared. He denied taking any medications before \nthe onset of the rash. There was no prior incident of \nfood allergies or documented family history of skin \ndiseases.\n\n\n\nHis chest radiograph on admission was normal. \nLaboratory examination showed haemoglobin 15.6 \ng/dL, white cell counts 6.5 x 103 /uL (neutrophil \n72.9%, lymphocyte 11.7%, absolute lymphocyte \ncounts 0.76 x 103 /uL, monocyte 12.9%, eosinophil \n2.0%, absolute eosinophil counts 0.13 x 103 /uL, \nbasophil 0.5%), platelet 197, 000. Renal profile \nand liver function test were normal. C-reactive \nprotein was 5.7 ng/L (<5.0). Dengue IgM/IgG \nwere negative. Skin biopsy was not performed due \nto patient\u2019s consent not granted. He was treated \nsymptomatically with Tablet Loratadine 10mg once \ndaily and topical 0.1% Betamethasone -17-valerate.  \n\n\n\nnecrosis (6%).2 Wollina et al. have also suggested other possible cutaneous findings such as \nsymmetrical flexural and intertriginous exanthema, purpuric rash, erythema multiforme-like \nrash, and Kawasaki like disease/Multisystemic inflammatory syndrome in children.3  \n \nCOVID-19 infection related skin manifestations were more commonly reported in United \nState and Europe countries compared to Asian cohort.4 Indeed, a systemic review of total \n1211 patients with COVID-19 related skin manifestations, 39 (3.1%) patients were from \nAsian populations and 1172 (96.9%) patients were from Europe and the United States.4 Here, \nwe would like to present a case of non-drug-related symmetrical flexural and intertriginous \nExanthema in a patient with COVID-19 infection. \n \nCase Report \nA 58-year-old Chinese male presented with fever and cough for the past three days, followed \nby an alleged fall at home which he sustained a small laceration wound over the scalp. He \nattributed the fall to an alleged slippery floor with no obvious neurological deficits.  He \nunderwent wound suturing at a private hospital, uneventfully. Incidentally, pre-procedure \nnasopharyngeal swab showed SARS-CoV RNA PCR detected. (Ct value; E gene = 18.41, \nRdRp gene = 21.09). He was then transferred to a designated COVID 19 hospital for further \nmanagement while the local health authorities performed contact tracing amongst his family \nmembers and friends. His fever and cough were resolved in the ward.  \n \nHowever, on the fourth day of illness, he developed blanchable maculopapular erythematous \nrashes at bilateral axillary and inguinal folds. The distribution of rash rapidly involved nape \nof the neck, forearm, anterior thigh, lower abdomen, and buttock symmetrically over the \nfollowing days. (Figure 1 (a-d)) These lesions were mildly pruritic with no obvious \ndischarges, vesicles, plaques or bullae noted. Notably, the face, trunk, palm, and sole were \nspared. He denied taking any medications before the onset of the rash. There was no prior \nincident of food allergies or documented family history of skin diseases.   \n \nFigure 1 (a-d). Maculopapular exanthema over the nape of the neck, axilla and inguinal \n\n\n\nregion \n    \n \n \n \n\n\n\na b \n\n\n\nnecrosis (6%).2 Wollina et al. have also suggested other possible cutaneous findings such as \nsymmetrical flexural and intertriginous exanthema, purpuric rash, erythema multiforme-like \nrash, and Kawasaki like disease/Multisystemic inflammatory syndrome in children.3  \n \nCOVID-19 infection related skin manifestations were more commonly reported in United \nState and Europe countries compared to Asian cohort.4 Indeed, a systemic review of total \n1211 patients with COVID-19 related skin manifestations, 39 (3.1%) patients were from \nAsian populations and 1172 (96.9%) patients were from Europe and the United States.4 Here, \nwe would like to present a case of non-drug-related symmetrical flexural and intertriginous \nExanthema in a patient with COVID-19 infection. \n \nCase Report \nA 58-year-old Chinese male presented with fever and cough for the past three days, followed \nby an alleged fall at home which he sustained a small laceration wound over the scalp. He \nattributed the fall to an alleged slippery floor with no obvious neurological deficits.  He \nunderwent wound suturing at a private hospital, uneventfully. Incidentally, pre-procedure \nnasopharyngeal swab showed SARS-CoV RNA PCR detected. (Ct value; E gene = 18.41, \nRdRp gene = 21.09). He was then transferred to a designated COVID 19 hospital for further \nmanagement while the local health authorities performed contact tracing amongst his family \nmembers and friends. His fever and cough were resolved in the ward.  \n \nHowever, on the fourth day of illness, he developed blanchable maculopapular erythematous \nrashes at bilateral axillary and inguinal folds. The distribution of rash rapidly involved nape \nof the neck, forearm, anterior thigh, lower abdomen, and buttock symmetrically over the \nfollowing days. (Figure 1 (a-d)) These lesions were mildly pruritic with no obvious \ndischarges, vesicles, plaques or bullae noted. Notably, the face, trunk, palm, and sole were \nspared. He denied taking any medications before the onset of the rash. There was no prior \nincident of food allergies or documented family history of skin diseases.   \n \nFigure 1 (a-d). Maculopapular exanthema over the nape of the neck, axilla and inguinal \n\n\n\nregion \n    \n \n \n \n\n\n\na b \n\n\n\n\n\n\n\n\n\n\n\nHis chest radiograph on admission was normal. Laboratory examination showed \nhaemoglobin 15.6 g/dL, white cell counts 6.5 x 103/uL (neutrophil 72.9%, lymphocyte \n11.7%, absolute lymphocyte counts 0.76 x 103/uL, monocyte 12.9%, eosinophil 2.0 %, \nabsolute eosinophil counts 0.13 x 103/uL, basophil 0.5%), platelet 197, 000. Renal profile and \nliver function test were normal. C-reactive protein was 5.7 ng/L (<5.0). Dengue IgM/IgG \nwere negative. Skin biopsy was not performed due to patient\u2019s consent not granted. He was \ntreated symptomatically with Tablet Loratadine 10mg once daily and topical 0.1% \nBetamethasone -17-valerate.  On the tenth day of his hospital stay, the skin lesions showed \nimprovement and he was subsequently discharged well.  \n\n\n\nC \n\n\n\nE\n  \n\n\n\n\n\n\n\n\n\n\n\nHis chest radiograph on admission was normal. Laboratory examination showed \nhaemoglobin 15.6 g/dL, white cell counts 6.5 x 103/uL (neutrophil 72.9%, lymphocyte \n11.7%, absolute lymphocyte counts 0.76 x 103/uL, monocyte 12.9%, eosinophil 2.0 %, \nabsolute eosinophil counts 0.13 x 103/uL, basophil 0.5%), platelet 197, 000. Renal profile and \nliver function test were normal. C-reactive protein was 5.7 ng/L (<5.0). Dengue IgM/IgG \nwere negative. Skin biopsy was not performed due to patient\u2019s consent not granted. He was \ntreated symptomatically with Tablet Loratadine 10mg once daily and topical 0.1% \nBetamethasone -17-valerate.  On the tenth day of his hospital stay, the skin lesions showed \nimprovement and he was subsequently discharged well.  \n\n\n\nC \n\n\n\nE\n  \n\n\n\n\n\n\n\n\n\n\n\nHis chest radiograph on admission was normal. Laboratory examination showed \nhaemoglobin 15.6 g/dL, white cell counts 6.5 x 103/uL (neutrophil 72.9%, lymphocyte \n11.7%, absolute lymphocyte counts 0.76 x 103/uL, monocyte 12.9%, eosinophil 2.0 %, \nabsolute eosinophil counts 0.13 x 103/uL, basophil 0.5%), platelet 197, 000. Renal profile and \nliver function test were normal. C-reactive protein was 5.7 ng/L (<5.0). Dengue IgM/IgG \nwere negative. Skin biopsy was not performed due to patient\u2019s consent not granted. He was \ntreated symptomatically with Tablet Loratadine 10mg once daily and topical 0.1% \nBetamethasone -17-valerate.  On the tenth day of his hospital stay, the skin lesions showed \nimprovement and he was subsequently discharged well.  \n\n\n\nC \n\n\n\nE\n  \n\n\n\n\n\n\n\n\n\n\n\nHis chest radiograph on admission was normal. Laboratory examination showed \nhaemoglobin 15.6 g/dL, white cell counts 6.5 x 103/uL (neutrophil 72.9%, lymphocyte \n11.7%, absolute lymphocyte counts 0.76 x 103/uL, monocyte 12.9%, eosinophil 2.0 %, \nabsolute eosinophil counts 0.13 x 103/uL, basophil 0.5%), platelet 197, 000. Renal profile and \nliver function test were normal. C-reactive protein was 5.7 ng/L (<5.0). Dengue IgM/IgG \nwere negative. Skin biopsy was not performed due to patient\u2019s consent not granted. He was \ntreated symptomatically with Tablet Loratadine 10mg once daily and topical 0.1% \nBetamethasone -17-valerate.  On the tenth day of his hospital stay, the skin lesions showed \nimprovement and he was subsequently discharged well.  \n\n\n\nC \n\n\n\nE\n  \n\n\n\na b c\n\n\n\nd e f\n\n\n\nFigure 1 (a-f). Maculopapular exanthema over the nape of the neck, axilla and inguinal region\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n57MJD 2021 Jun Vol 46\n\n\n\nOn the tenth day of his hospital stay, the skin lesions \nshowed improvement and he was subsequently \ndischarged well. \n \nDiscussion \nThis case described a patient who developed \nskin rashes in the early phase of COVID-19 \nillness. The differential diagnosis that needs to be \nconsidered includes viral exanthem, drug-related, \nand systemic infection. The distribution of rashes \nwas predominantly at the flexural region, which \nresembles symmetrical intertriginous and flexural \nexanthema, often due to exposure to the drug \nsuch as Beta-lactam antibiotic. However, in this \ncase, the patient did not receive any antibiotics or \nother medications before or during hospitalization. \nHe also denied having any history of atopy. The \nnormal eosinophil count indicates the rash is less \nlikely to be allergen related. In view that the skin \ncondition appeared on Day 4 of illness with no other \nattributable factors, we concluded that this rash was \ndue to post-viral infection, likely the COVID-19 \nvirus. \nGiven various cutaneous manifestations in adult \npatients with COVID-19, histopathological \nexamination via skin biopsy would provide \nadditional information. Ahouach et al reported \nthe presence of basal cell vacuolation and mild \nperivascular lymphocytic infiltrate in the skin biopsy \nobtained from a patient with similar skin condition.3 \nUnfortunately, skin biopsy was not performed as \ncondition was improved and patient\u2019s consent was \nnot granted.  \n \nConclusion\nIn conclusion, various morphologies of cutaneous \nmanifestations are associated with COVID-19. \nThis case demonstrated an association between \nsymmetrical flexural and intertriginous exanthema \nwith COVID-19 infection. More cohorts should \nbe evaluated to fully describe the full spectrum of \ndermatological manifestation in COVID-19.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nWe would like to thank the Director General of \nHealth Malaysia for permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J et al. \nA Novel Coronavirus from Patients with Pneumonia in \nChina, 2019. N Engl J Med 2020;382:727-33.\n\n\n\n2. Galv\u00e1n Casas C, Catal\u00e0 A, Carretero Hern\u00e1ndez G, \nRodr\u00edguez-Jim\u00e9nez P, Fern\u00e1ndez-Nieto D, Rodr\u00edguez-Villa \nLario A et al. Classification of the cutaneous manifestations \nof COVID-19: a rapid prospective nationwide consensus \nstudy in Spain with 375 cases. Br J Dermatol 2020;183:71-\n7. \n\n\n\n3. Ahouach B, Harent S, Ullmer A, Martres P, B\u00e9gon E, Blum \nL et al. Cutaneous lesions in a patient with COVID-19: are \nthey related? Br J Dermatol 2020;183:e31.\n\n\n\n4. Tan SW, Tam YC, Oh CC. Skin manifestations of \nCOVID-19: A worldwide review. J Am Acad Dermatol Int \n2021;2:119-33.\n\n\n\n5. Mawhirt SL, Frankel D, Diaz AM. Cutaneous \nManifestations in Adult Patients with COVID-19 and \nDermatologic Conditions Related to the COVID-19 \nPandemic in Health Care Workers. Curr Allergy Asthma \nRep 2020;20:75.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Jun Vol 4658\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Dr Ch\u2019ng Chin Chwen\n4. Dr Chan Lee Chin\n5. Dr Chang Choong Chor\n6. Dr Chong Yew Thong\n7. Dr Dawn Ambrose\n8. Assoc Professor Dr Felix Yap Boon Bin\n9. Dr Henry Foong Boon Bee\n10. Dr Khor Yek Huan\n11. Dr Kwan Zhenli\n12. Dr Lo Kang Shang Chit\n13. Dr Mazlin bt Mohd Baseri\n14. Dr Ng Ting Guan\n15. Dato\u2019 Dr Noor Zalmy Azizan\n16. Dr Norashikin Bt Shamsudin\n17. Dr Rajalingam Ramalingam\n18. Dr Tang Jyh Jong\n19. Dr Tang Min Moon\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\nACKNOWLEDGEMENT\nJun Issue 2021\n\n\n\n\n\n\n\n\n\n"
"\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more than \n2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Comment \nand References. A Structured Abstract of not more than 240 \nwords must be included. It should consist of five paragraphs, \nlabelled Background, Methods, Results, Discussion and \nConclusion. It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and \nfax numbers and an email address of the corresponding \nauthor who will be responsible for reading the proofs must \nalso be given on the title page. The author(s) must also \ndeclare any affiliation or significant financial involvement \nin any organizations or entity with a direct financial \ninterest in the subject matter or materials discussed in the \nmanuscript on this page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and \nopinions expressed do not necessarily reflect those of \nthe publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher \nand Editors of the products advertised.\n\n\n\n\n\n\n\n\n39\n\n\n\n42\n\n\n\n46\n\n\n\n49\n\n\n\n52\n\n\n\n55\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 1\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm \nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office \nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nExecutive Committee\nChan Lee Chin, MMed - President\nNoor Zalmy Azizan, Adv M Derm - Vice President\nSabeera Begum, MMed - Secretary\nTan Wooi Chiang, Adv M Derm - Treasurer\nAgnes Heng Yoke Hui, MRCP - Past President\nDr Tang Jyh Jong, Adv M Derm - \nCommittee Member\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - \nCommittee Member\nDr. Sharifah Rosniza Syed Nong Chek, \nAdv M Derm - Committee Member\n\n\n\nDermatological Society of Malaysia \n(Rumah Dermatology)\nUnit 1.6, Level 1, Enterprise 3B, \nTechnology Park Malaysia, Jalan Innovasi 1, \nLebuhraya Puchong-Sungei Besi, Bukit Jalil, \n57000 Kuala Lumpur, Wilayah Persekutuan\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang.\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2018 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, \nAdv M Derm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 412\n\n\n\nREVIEW\n\n\n\nSurgery of the Nail\nEckart Haneke, MD, PhD\n\n\n\nDept Dermatol, Inselspital, Univ Bern, Berne, Switzerland\nDermatol Practice Dermaticum, Freiburg, Germany\nCentro Dermatol Epidermis, Inst CUF, Senhora da Hora, Grande Porto, Portugal\nDept Dermatol, Univ Hosp Gent, Ghent, Belgium\n\n\n\nKey words: Nail anatomy, Nail surgery, Anesthesia, Atraumatic surgery, Nail tumors \n\n\n\nCorresponding Author\nProfessor Eckart Haneka\nSchlippehof 5, 79110 Freiburg, Germany\nEmail: haneke@gmx.net\n\n\n\nIntroduction\nNail surgery is often regarded difficult and therefore \na neglected part of dermatologic surgery.1 However, \nthe nails are cutaneous appendages with many \ndifferent diseases, the diagnosis of which is an \nintegral part of every dermatologist\u2019s daily routine. \nIt is not different from surgery of other skin areas \nand there should be no reason for the patient and \nthe dermatologist not to perform a surgical act on \nthe nail.\n\n\n\nAims of nail surgery\nNail surgery is performed to treat an ungual disease \nthat is otherwise not amenable to therapy. It is also \noften done to alleviate pain and to make, confirm or \nrule out a specific diagnosis. Finally, surgery may \nbe performed to restore a normal nail or improve \nits aesthetic appearance. However, surgery cannot \nimprove brittle nails and some other nail consistency \ndeficiencies.\n\n\n\nPrerequisites of nail surgery\nExact and in-depth knowledge of the macro- \nand micro-anatomy of the nail unit, which in \nfact comprises the entire distal phalanx with the \nunderlying bone, the soft tissue of the pulp, the distal \ninterphalangeal joint with its tendons, ligaments \nand synovial membrane as well as the many nerves, \nsensory end organs, blood and lymph vessels (Figure \n1), is a must before embarking on nail surgery.2,3 \nFurther, the growth characteristics of the nails of \nthe fingers and toes (Figure 2) and their ways to \nreact to physiological and pathological stimuli must \n\n\n\nbe known. The dermatologic surgeon has to be \nfamiliar with atraumatic surgery and postoperative \nwound care; however, special instruments are rarely \nneeded.4 A certain knowledge of nail pathology \nis advisable to be able to understand why, where \nand how nail lesions develop, how they have to be \ndiagnosed, biopsied and treated.5,6\n\n\n\nIt is self-evident that a thorough personal history \nincluding drug intake and particular familiar and \ngenetic diseases has to be taken. (Pre)existing \ndiseases should be treated if possible.\n\n\n\nPatient selection\nAs most nail surgeries are not elective interventions, \nbut medically indicated procedures the dermatologic \nsurgeon does not have the opportunity to make \na great choice whom to operate or not; however, \nthere are some contraindications that have to \nbe respected. Acute nail infections must only \nbe operated if necessary for the treatment of \nthe infection or if the infection is not amenable \nto conservative therapy. Patients with severe \nperipheral circulatory impairment should not \nundergo surgery if not absolutely necessary. \nDiabetes mellitus, immunosuppression and known \ndisorders interfering with wound healing are relative \ncontraindications. Coagulation disorders are usually \nno contraindication.\n\n\n\nPreoperative patient preparation\nThe patient has to be informed about the type of \nnail surgery, the necessary anesthesia, the possible \npostoperative pain intensity, whether or not peri- or \npostoperative antibiotic therapy might be advisable, \nthat a thick padded dressing will be applied after \nthe surgery, that driving is discouraged right after \nthe procedure, and about the period of potential \ninability to work. An informed consent should be \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 3\n\n\n\nFigure 1. Anatomy of the nail\n\n\n\na. Comparison of finger and toenail.\nb. The matrix and the different layers of the nail \n\n\n\nplate: The dorsal layer derives from the apical \nmatrix, the mid-layer from the mid- and distal \nmatrix and the very thin physiological subungual \nkeratin is produced by the nail bed.\n\n\n\nc. Sagittal section through the distal phalanx \nshowing the relation of the nail to the underlying \nstructures.\n\n\n\nd. The apical matrix is about one millimeter above \nthe insertion of the extensor digiti tendon. The \nhyponychium is firmly bound to the bone by the \nphalangeo-hyponychial ligament.\n\n\n\ne. Schematic illustration of the blood supply of the \nnail unit.\n\n\n\nf. Innervation of the finger nails; note that the \nindex, middle and ring finger nails are innervated \nby the volar proper digital nerves.\n\n\n\nA\n\n\n\nB\n\n\n\nC\n\n\n\nD\n\n\n\nE\n\n\n\nF\n\n\n\nFigure 2. Growth characteristics of a finger nail; the \ntoe nail grows only one third that rate\n\n\n\nsigned by the patient.\n\n\n\nBoth the evening before and in the morning, the \nhand or foot has to be washed with an antiseptic \nsoap and the digit to be operated brushed in order \nto remove all dirt and foreign bodies. Smoking is \nabsolutely forbidden before surgery.\n\n\n\nThe entire hand or foot is generously disinfected \nwith isopropyl alcohol plus betadine or another \ndisinfective agent.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 414\n\n\n\nD\nAnesthesia for nail surgery\nA good anesthesia is a must for nail surgery. There \nare different techniques reaching this goal. Several \nauthors prefer the so-called distal block, which is \nessentially a local anesthesia of the nail region. \nAlthough it is often claimed that one injection in the \nmidline of the proximal nail fold is sufficient this is \nvery rarely the case and almost all of those using this \ntechnique require a series of needle pricks to achieve \na good anesthesia. As there is very little soft tissue \nin the dorsal half of the distal phalanx the injection \nof a certain volume of an anesthetic solution is \nusually painful. The most versatile technique is the \nproximal digital block that numbs the dorsal and \nvolar proper digital nerves. For the anesthesia of two \nneighboring fingers, the metacarpal block may be \nused that allows the opposing sides of the fingers to \nbe numbed with one needle prick. As the distal half \nof the index, middle and ring fingers are innervated \nby the volar proper digital nerves, the injection of \nthe anesthetic solution into the flexor tendon sheath \nat the level of the metacarpo-phalangeal joint \nreliably anesthetizes these nerves without the risk \nof damaging the neurovascular bundle if the fingers \n(Figure 3).\n\n\n\nClinical experience has shown that 2% lidocaine \nor mepivacaine give an anesthesia long enough for \nalmost all nail procedures; however, it wanes off after \napproximately 30 minutes. Adrenaline 1:200,000 \nmay be added to prolong its action; contrary to \nthe product information for virtually all local \nanesthetics, this concentration is not contraindicated \nin digits of patients without vascular compromise. \nHowever, it is not necessary for surgeries performed \nwith a tourniquet. My preferred local anesthetic \nagent is ropivacaine that combines the rapid onset \nof anesthesia of lidocaine with the long action of \nbupivacaine. The recommended concentration is \n0.5%, but it may be used off-label as 1% ropivacaine. \nIt also has a slight intrinsic vasoconstrictor action. \nThe anesthesia with 1% ropivacaine lasts between \n12 \u2013 18 (24) hours, which is long enough for most \nnail surgeries. For children who are operated under \ngeneral anesthesia, an additional block with either \nropivacaine or bupivaine is performed that allows a \nlighter general anesthesia and works overnight.\n\n\n\nPostoperative care\nA padded dressing finalizes the nail surgery \nprocedure. We prefer sterile gauze for any complex \nnail surgery and apply plenty of a vaseline-based \n(antibiotic) ointment in order to prevent the dressing \nfrom sticking to the wound.\n\n\n\nPain after nail surgery is the rule and should be \ngiven due attention. The level of pain depends \non the type of surgery with those procedures also \ninvolving the bone being more painful.7 In most \ncases, paracetamol is sufficient to relieve the pain, \nbut metamizole or even an opioid may be necessary. \nThis should be discussed beforehand with the patient \nas the individual pain threshold varies enormously. \nDepending on the type of anesthesia the first \nanalgesic should be taken before the pain appears \nand it should be given generously for a short period. \nElevating the operated extremity is very important \nas the anesthesia will last longer, there is less \nswelling, less bleeding and better overall healing \n\n\n\nFigure 3. Anaesthesia for nail surgery\n\n\n\nA. Proximal finger block \nB. Metacarpal block for the anaesthesia of \n\n\n\nneighbouring fingers\nC. So-called distal wing block\nD. Transthecal block\n\n\n\na b\n\n\n\nC\n\n\n\nA B\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 5\n\n\n\nwith less pain. The patient should bring a large shoe \nin case of toenail surgery and may get a sling for the \narm for fingernail surgery.\n\n\n\nThe time of the first dressing change is adapted to \nthe kind of surgery done. We prefer to give a new \ndressing after 24 to maximally 48 hours. This has \nthe advantage that the blood-stained dressing is \nremoved before bacteria can grow in it and that the \nblood has not yet turned into a stone-hard mass. The \ndressing is usually removed in a luke-warm hand \nor foot bath allowing the gauze to float off without \ncausing pain. The wound is cleaned with 2% \nhydrogen peroxide, disinfected and dressed with \nsterile gauze without or with ointment.\n\n\n\nBasic nail surgery procedures\n\n\n\nNail clipping\nAlthough rarely seen as surgery nail clippings yield \nexcellent diagnostic specimens for the diagnosis of \nonychomycosis, often also for psoriasis and some \nother nail disorders. All diagnostic nail clipping \nbiopsies should contain as much of the subungual \nkeratotic material as possible. The material can be \nsent to the histopathology lab without fixation and \nin a paper envelope. The sections should always be \nstained with hematoxylin & eosin and PAS.\n\n\n\nNail avulsion\nRemoving the nail plate is for most surgeons the \nonly type of nail intervention they know. It is never \na treatment per se except in retronychia. There are \nmany techniques in the surgical literature of which \nthe \u201cclassical nail avulsion technique\u201d using  a \nsturdy hemostat clamp that is first run under the \nproximal nail fold, then under one side of the nail \nplate in order to be able to grasp the nail and tear it \nout by rotating the clamp is the most traumatizing \nmethod; it is obsolete and must not be performed \nas it causes a lot of damage. If a nail avulsion is \ndeemed necessary the use of a nail elevator or \nsimilar instrument is recommended. It is inserted \nunder the proximal nail fold with its curvature \npointing to the nail plate and by gentle forward and \nback movements the nail fold is separated from the \nunderlying nail plate. Then the elevator is inserted \nthrough the hyponychium into the nail bed again \nwith its curvature pointing to the nail plate and \nthis is detached from the bed by back-and-forth \nmovements from the hyponychium to the proximal \nend of the matrix. The nail can then be taken out with \na forceps. An even less traumatizing approach is the \nproximal nail avulsion. The first step is identical to \n\n\n\nthe distal avulsion technique with separation of the \nnail from the overlying proximal fold. Then the tip \nof the elevator is slipped under the proximal end of \nthe nail plate and, by moving the elevator from the \nmatrix toward the hyponychium from one side to \nthe other, the nail plate is completely freed and can \nbe taken out. This method is the least traumatizing. \nHowever, it must be stressed that any nail avulsion \nis the start of a nailbed or matrix treatment, not a \ntreatment of any nail disorder.\n\n\n\nNail biopsies \nHistopathology is the diagnostic gold standard. \nIt requires a good biopsy from the correct site. \nDifferent biopsy techniques are available meeting \nvirtually all challenges (Figure 4).\n\n\n\nNail bed biopsy\nA nail bed biopsy may be performed with a punch \nor scalpel. A punch biopsy may have a diameter \nof 4 mm or less and may be taken after (partial) \nremoval/avulsion of the overlying nail or through \nthe nail plate after softening it in a warm bath for \napproximately 10 minutes. No suture is necessary, \nbut a piece of collagen foam may be pressed into \nthe punch hole.\n\n\n\nA fusiform scalpel biopsy of 2 \u2013 3 mm width is \nan alternative. It must always be longitudinally \noriented. Again, the overlying nail is removed before \nbiopsy. The wound margins may be undermined \nsharply to facilitate closing the biopsy defect with \nstitches. If the overlying nail plate was normal it \nmay be replaced at the end of the procedure.\n\n\n\nMatrix biopsy\nAll nail lesion causing surface alterations or \nlongitudinal streaks originate in the matrix and \nrequire an adequate biopsy site. The more proximal \nwithin the matrix the biopsy is located the more \nlikely a post-biopsy defect is. A punch must not \nexceed 3 mm in diameter. It may contain the \noverlying nail plate. \n\n\n\nA fusiform matrix biopsy is always oriented \ntransversely in order to prevent a post-biopsy split \nnail. The spindle may be 2 \u2013 3 mm wide and is \nclosed with 6-0 absorbable stitches.\n\n\n\nFigure 4. Biopsy techniques for the nail apparatus\n\n\n\nA. Punch biopsy of the proximal nail plate \nfor the diagnosis of proximal subungual \nonychomycosis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 416\n\n\n\nHaneke\n\n\n\nRNP  reflected portion of nail plate\nRPNF  reflected proximal nail fold\n\n\n\nRNPRPNF\n\n\n\nB. Lateral longitudinal nail biopsy\nC. Fusiform biopsy of the nail bed; note that the \n\n\n\nmatrix biopsy is oriented transversely, the nail \nbed biopsy longitudinally.\n\n\n\nD. Fusiform biopsy of the matrix biopsy; note this \nis oriented transversely, the nail bed biopsy \nlongitudinally\n\n\n\nE. Tangential matrix biopsy for the diagnosis of \nsuperficial lesions of the matrix and nail bed. \n\n\n\nLateral\tlongitudinal\tnail\tbiopsy\nThis technique meets all diagnostic requirements \nas the biopsy contains all constituents of the nail \napparatus: proximal nail, matrix, nail bed and \nhyponychium; however, the lateral nail fold is not \nincluded. It not only has the advantage of allowing \nall nail diseases to be diagnosed but also the time \ncourse to be estimated as the nail is a slow growing \nappendage and it takes 6 months for a fingernail and \nup to 18 months for a toenail to grow out.3\n\n\n\nThe digit is anesthetized and the nail plate softened \nby immersing it into warm water for approximately \n10 minutes. After sterile prepping, a tourniquet is \napplied. The first incision starts at the distal dorsal \ncrease of the distal interphalangeal (DIP) joint about \n2 mm medial of the presumed lateral nail margin \nand is carried out through the proximal nail fold \nall along the nail to the hyponychium. The tissue \nis soft until the cuticle is reached, then the exposed \nportion of the nail plate is reached, which is still \nhard; here, stabbing motions are recommended to \n\n\n\nget the scalpel through the nail down to the bone. \nParticular attention has to be paid when arriving \nat the free margin of the nail as the scalpel may \n\u201cfall\u201d into the soft tissue and one may hurt oneself. \nIt is therefore advisable to stop the scalpel incision \nshort of the distal end of the plate and cut this with \nsharp scissors. The second incision starts again \nat the level of the distal dorsal crease of the DIP \njoint about 2 mm lateral from the first one and is \ncarried out distally in one line through the proximal \nnail fold and lateral nail sulcus to meet the first \none distal of the hyponychium. At the proximal \nend of the two incision lines they are connected \nby a slightly outward slanted curved incision; this \nis done to prevent leaving part of the lateral matrix \nhorn behind. Then the entire block is dissected from \nthe bone with sharp pointed curved iris scissors. \nThe narrow wound is closed with simple stitches \nthrough the proximal nail fold and hyponychium \nand back-stitches in the proximal part of the lateral \nnail fold.8 This yields a nail about 2 mm less wide \nthan before. The surgical specimen is marked for the \nhistopathology lab so that it is cut from the medial \ntowards the lateral side. H&E, PAS and if needed \nother special stains as well as immunohistochemistry \nare performed.\n\n\n\nTangential horizontal nail biopsy\nSeveral lesions of the nail matrix and bed are very \nsuperficial without considerably involving the \nmatrix and nailbed dermis. This is particularly true \nfor most benign melanocytic lesions of the matrix \ncausing longitudinal melanonychia. This prompted \nus to develop a superficial biopsy technique \nthat greatly avoided the risk of post-biopsy nail \ndystrophy, which is in fact a frequent reason not \nto perform a biopsy in melanonychia and a variety \nof other potentially serious nail conditions.9 From \nexperience with split matrix grafts it is known that \nthe donor site of a thin sheet of matrix heals without \nscarring. \n\n\n\nThe digit is prepared as usual. The proximal nail \nfold is separated from the underlying nail plate and \nis incised at both sides to allow it to be retracted. \nThe proximal third to half of the nail is detached \nfrom the matrix from one side and cut transversely \nuntil about 3 \u2013 5 mm beyond the other side of the \nlesion to be removed. Depending on the presumed \ndiagnosis a shallow incision is carried around the \nlesion and a #15 scalpel blade is laid on the nail bed \nor matrix adjacent to lesion, gently pressed down and \nwith sawing movements, the lesion is horizontally \nexcised. The nail plate is laid back and fixed with \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 7\n\n\n\na stitch, then the proximal nail fold is put back and \nsecured with stitches or suture strips (Steristrips\u00ae). \nThe tissue slice is thin enough that the scalpel \nblade shines through during the tangential excision. \nCommonly, this procedure results in a 0.8 mm thick \ntissue specimen, which is spread out on a piece of \nfilter paper to avoid that it rolls in. It is transferred \nto a jar containing 4% neutral formalin. Fixation of \nthe thin tissue slice is complete within a few hours.\nThis biopsy technique is therapeutic for most benign \nlesions but should be followed by adequate surgery \nin case of a malignant diagnosis (Figure 5).10\n\n\n\nwhich often appears enlarged is completely \nphenolized. The proximal nail avulsion is preferred \nbecause an elevator can usually not be run under the \nthick nail without exerting undue force and the nail \npocket is anyway very short so that this technique is \nvery easy to perform. \n\n\n\nTreatment of peri and subungual warts\nCommon warts are benign, contagious proliferations \ndue to human papillomaviruses of different types. \nIn. the nail region, they are mainly due to HPV \ntypes 1, 2, 4, and 7. On the proximal nail fold they \nare usually round papules with a rough keratotic \nsurface, on the lateral nail fold they are more oval, \noften coalesce and may become hypertrophic with \ndeep fissures. Subungual warts may lift the nail \nplate (Figure 6). It is said that viral warts have a \nnatural life span of about 2 (-5) years, but they often \npersist longer and may give rise to new \u201cdaughter\u201d \nwarts. They are embarrassing and sometimes \npainful. The diagnosis is easy, but treatment is often \nfrustrating. Aggressive surgery should never be \nperformed as this may lead to scarring and distortion \nof the nail. We prefer the application of saturated \nmonochloroacetic acid, covering this with a 50% \nsalicylic acid plaster and fixing it with normal tape \nfor one week. During this period, twice daily hot \nbaths of the wart-bearing digits help the keratolytic \nagents to penetrate. After another hot bath, the \ntape and salicylic acid plaster are removed and the \nwhite soft keratotic mass of the wart gently curetted \nwithout any bleeding. This procedure is repeated on \na weekly basis until the warts are completely gone. \nIf, after a while, the monochloroacetic acid causes \na dull pulsating burning pain, continuation of the \ntreatment with daily (!) imiquimod under occlusion \nor another topical immunotherapy is useful. It has to \nstressed that warts have to be completely removed; \nonly decreasing their size is a treatment failure. \nBleomycin is a cytostatic drug that was also used \nfor the treatment of ungual warts. It is diluted to \n1U/m or even less and either injected into the wart \nor applied by \u201cbleopuncture\u201d; although there are \nmany reports of good results11 the author has seen \ntwo young girls with permanent nail dystrophy after \nbleomycin treatment for warts of the nail apparatus.\n\n\n\nUngual\tfibrokeratoma\nFibrokeratomas of the tip of the digit are sausage-\nlike fibromas with a keratotic tip that often contains \nplasma and/or blood inclusions. The may originate \nfrom the depth of the nail pocket under the proximal \nnail fold and grow on the nail plate causing a \n\n\n\nFigure 5. Superficial tangential biopsy for a wide \nmelanonychia in a youngster\n\n\n\nA. Clinical finding.\nB. Elevation of the nail plate exhibits the\n\n\n\nmelanocytic lesion.\nC. Intraoperative dermatoscopy reveals a regular\n\n\n\npattern of brown lines.\nD. The tangential excision is being performed.\n\n\n\nA B\n\n\n\nC D\n\n\n\nOnychogryposis\nMassive thickening of the nail, usually toenails, \nis common in elderly and debilitated persons. The \nnail looks like a rams horn (Greek: grypos = horn, \ngryphos = a fairy animal with the body of a lion \nand the head of a prey bird), often turns upwards \nand may cause extreme pain, sometimes even a \npressure ulcer when it returns to the distal phalanx. \nHistopathology shows many layers of nail keratin \npiled up irregularly, there is virtually no nail bed \nleft.6 Although podiatric treatment with grinding \nthe onychogrypotic nail down is effective the nail \nregrows in the same manner and a definite nail \neradication is frequently requested. The nail is \navulsed by the proximal approach and the matrix, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 418\n\n\n\nFigure 6. Subungual wart of the big toe lifting the \nfree margin of the nail plate\n\n\n\nlongitudinal canaliform depression, derive from \nthe mid-matrix and grow for a certain distance in \nthe nail plate until the overlying nail lamella breaks \noff and leaves a longitudinal depression (Figure 7), \nor grow in the nail bed and remain under the nail \ncausing a rim. Independent from their localization \nrelative to the nail plate, their removal requires a \ncircumferential incision down to, and dissection \nfrom the bone using sharp curved pointed scissors. \nThe defect can be left for second intention healing \nas it is usually so small as to yield a normal nail \nagain.\n\n\n\nMultiple ungual fibrokeratomas are a hallmark of \nthe tuberous sclerosis complex. They should be \nremoved as soon as possible by cutting them at their \nbase. Although they will recur this allows usually \nto avoid gross nail dystrophy from the multiple \nKoenen tumors.\n\n\n\nnail plate after a penetrating trauma. Conservative \ntreatment with topical timolol may be tried. If this \nis not successful, it is cut at its base and the feeder \nartery gently electrocauterized. Cryosurgery is \nanother alternative.\n\n\n\nFigure 7.  Intraungual fibrokeratoma of the big toe\n\n\n\nGlomus tumor\nGlomus tumors are benign hamartomas deriving \nfrom glomus bodies that are particularly frequent \nin the hand, specifically in the nail region. Their \nfunction is thermoregulation. Glomus tumors \nare relatively infrequent, but due to their unique \nsymptomatology probably the best known nail \ntumors. Clinically, they appear as a violaceous spot \nin the matrix or nail bed from which a reddish streak \nextends distally (Figure 8). They are very tender on \npalpation and may cause excruciating pain radiating \nup to shoulder when exposed to cold. Probing \nusually permits exact localization within the nail, but \nmagnetic resonance imaging may also be performed. \nIf they are localized in the central aspect of the nail \nthe plate is gently detached exposing the lesion. \nA slightly curved transverse incision is performed \nover a matrix tumor, a longitudinal incision in the \nnail bed. The glomus tumor is seen as a greyish \nglassy tumor, in most cases the size of a peppercorn \nto a pea, rarely bigger. It is gently dissected from the \nconnective tissue using fine scissors; the overlying \nepithelium is not resected. Even large glomus \ntumors can be extirpated without postoperative nail \ndystrophy.14 Laterally located subungual glomus \ntumors may be resected from the side of the distal \nphalanx. An incision is made parallel to the lateral \nnail margin roughly in the level of the dorsal surface \nof the bone and the wound margins are spread with \nscissors until the glomus tumor appears a greyish \nround lesion under the white connective tissue of the \nmatrix or nail bed. It is then bluntly dissected. This \ntechnique is often claimed to be \u201csubperiosteal\u201d, \n\n\n\nCoccal nail fold angiomatosis\nThis peculiar lesion was first described about \n25 years ago. The history of the patients is \ncharacteristic. After a wrist fracture treated with a \ncast for two weeks or longer, erosive, easily bleeding \nsmall tumors emerge from under the proximal nail \nfold that resemble granulation tissue or pyogenic \ngranuloma.12 They are easily extirpated by cutting \nthem at their base.\n\n\n\nPyogenic granuloma\nPyogenic granuloma is in fact an eruptive lobular \nangioma; it must not be confused with granulation \ntissue, which is very often seen in patients receiving \naromatic retinoids, certain antiretroviral drugs, \nepidermal growth factor receptor inhibitors or in \ningrown nails.13 It may develop on the nail folds \nor sometimes in the matrix or nail bed piercing the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 9\n\n\n\nA\n\n\n\nC\n\n\n\nE\n\n\n\nB\n\n\n\nD\n\n\n\nwhich is not true15 as the glomus tumor is always \non the periosteum. It is also assumed to give better \npostoperative results as these authors do not dissect \nthe glomus out from the matrix dermis but cut it \nout with the overlying matrix. Recurrences are rare \nand may be due to incomplete removal or primary \nmultiple tumors.\n\n\n\nFigure\t8.  Giant glomus tumor of the middle finger \nof an elderly women\n\n\n\nOnychomatricoma\nOnychomatricoma is a recently identified benign \nfibroepithelial tumor of the matrix.16 The main \ntumor mass is formed by a characteristic connective \ntissue component with fine collagen fibers and many \nfibroblasts with a relatively abundant cytoplasm. \nIt forms filiform projections that are covered by \nnormal matrix epithelium, which often penetrates \ndeeply into the fibrous tumor. This neoplasm \nactively produces nail that contains the filiform \nprojections that leave long channels in the nail \nplate, which run to the free margin of the nail plate. \nAfter avulsion of the affected nail a worm-eaten \naspect is seen on the proximal end of the nail. The \ntumor with its projections is excised in a saucer-like \nfashion (Figure 9, 10). The superficial wound heals \nby second intention from the margins of the lesion \nand a normal nail forms again in most cases. In case \nof lateral localization, a segmental longitudinal nail \nexcision is adequate.\n\n\n\nFigure 9.  Onychomatricoma\n\n\n\nA. Dorsal view\nB. End-on view exhibiting the small holes in the \n\n\n\nfree margin of the nail.\nC. Gentle proximal avulsion shows the wood-\n\n\n\nworm like channels in the proximal nail.\nD. The onychomatricoma is seen as a small villous \n\n\n\nlesion in the depth of the nail pocket.\n\n\n\nE. This \u00f6photograph depicts the shallow surgical \ndefect, the surgical specimen and the proximal \nnail plate portion.\n\n\n\nOnychocytic matricoma\nThis peculiar lesion was also described under \nthe term of linear melanonychia with subungual \nkeratosis and ungual seborrheic keratosis and is now \ncalled longitudinal subungual matrix acanthoma.18 \nIt originates in the proximal and mid-matrix and is \nan actively nail-producing lesion that gives rise to a \nlongitudinal yellowish, brownish or whitish streak \nin the nail. It is best removed by tangential excision \nof the lesion in the matrix and proximal nail bed \nafter partial separation of the overlying nail plate.\n\n\n\nof the lesion in the matrix and proximal nail bed \nafter partial separation of the overlying nail plate.\n\n\n\nFigure 10. Onychomatricoma (Courtesy of Dr \nNilton Di Chiacchio, Sao Paulo, Brazil)\n\n\n\nA. Clinical view\nB. After nail avulsion, the tumor is seen with its \n\n\n\ncharacteristic filiform projections\nC. The avulsed nail seen from proximal\nD. The shallow surgical defect after saucer-shaped \n\n\n\nexcision\nE. MRI of the onychomatricoma.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4110\n\n\n\nFigure 11. Onychopapilloma of the big toenail\n\n\n\nA. Fronto-dorsal view.\nB. Frontal view shows a circumscribed thickening \n\n\n\nof the nail.\nC. Magnetic resonance imaging demonstrates \n\n\n\na circumscribed indentation of the nail bed \ncorresponding to the onychopapilloma that \npresses into the soft tissue; both the nail plate as \nwell as the onychopapilloma are not depicted in \nMRI pictures.\n\n\n\nA B\n\n\n\nC D\n\n\n\nE\n\n\n\nOnychopapilloma\nThis is another longitudinal lesion of the nail that \noriginates from the distal matrix and stretches out all \nalong the nail bed to the hyponychium (Figure 11).19 \nAs the tumor involves the distal matrix, nail bed and \nhyponychium it has to be excised all along the nail \nbed to the hyponychium. If the tumor is localized \nvery laterally a longitudinal excision including the \nnail plate is indicated. In a more central localization, \nit is tangentially removed either with the overlying \nnail plate after having cut it longitudinally on both \nsides or after careful nail plate removal. Although \nthe latter technique with partial nail detachment is \nless traumatic the specimen for histopathological \nexamination is difficult to evaluate as most of \nthe characteristic lesion remains attached to the \nnail plate. Further, the excision must not be too \nsuperficial in order to avoid a recurrence.\n\n\n\nOnycholemmal cysts\nThese lesions were also called subungual \nepidermoid inclusions but are now recognized as \nbeing of nail bed origin.6 In most cases, they do not \ncause any signs and symptoms and are therefore \nchance observations; however, occasionally, they \nmay cause some subungual hyperkeratosis and \ntenderness. They are microscopic lesions clinically \nthe size of a needle tip, rarely bigger.\n\n\n\nOnycholemmal horn\nThis is the first nail-specific tumor published in \n1983. It is a slow growing, painless, warty to \nhyperkeratotic lesion usually seen in the lateral nail \nsulcus. Its histopathology is strikingly similar to that \nof a trichilemmal horn giving strong evidence that \nthe nail bed is analogous to the outer root sheath \nof the hair follicle.12 The treatment of choice is \ncomplete surgical extirpation, which usually does \nnot pose any problem (Figure 12). When involving \nmore of the lateral nail bed a segmental longitudinal \nnail excision is performed.\n\n\n\nProliferating onycholemmal tumor\nThis rare tumor is a slow-growing mass, usually \non the lateral aspect of the nail bed. It is painless \nand thus clinically distinguishable from subungual \nkeratotic tumors of incontinentia pigmenti which is \nhistologically identical but fast growing and painful. \nIt is excised under digital block anesthesia.\n\n\n\nUngual\tcysts\nOther than those cysts already mentioned, epidermal, \nmatrix and mixed (hybrid) cysts may occur. They \nare usually post-traumatic or post-surgical. The \npatient history often, but not always gives valuable \ninformation. Epidermal cysts may grow very slowly \nand insidiously deform the nail or very fast and \ninterfere with nail growth.22 Surgery is by cautious \nincision of the overlying skin and peeling the cyst \nout. Matrix and hybrid cysts are mainly seen after \ningrown nail surgery when remnants of the lateral \nmatrix horn were left behind. They may contain \nall components of a normal nail. Often, they lie in \na fibrous scar tissue and difficult to dissect so that \nafter extirpation curettage of the wound cavity is \nuseful to prevent a recurrence. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 11\n\n\n\nA\n\n\n\nC\n\n\n\nB\n\n\n\nA\n\n\n\nC\n\n\n\nB\n\n\n\nFigure 12. Onycholemmal horn\n\n\n\nA. Verrucous lesion in the lateral nail bed and \nsulcus.\n\n\n\nB. Segmental resection of the nail unit.\nC. One year after surgery.\n\n\n\nSquamous cell carcinoma\nBowen\u2019s disease and squamous cell carcinoma \nare the most frequent malignancies of the nail \napparatus.23 They are more common in men than \nin women and occur over the age of 35 years. The \npreferred localizations are the thumb, index and \nmiddle fingers. Most cases of Bowen\u2019s disease are \nassociated with high-risk HPV, particularly types 16 \nand 18, but many more were also found.24 Pigmented \nBowen\u2019s disease appears to be more often linked \nwith HPV 56. A genito-digital transmission has \nrepeatedly been postulated.25 Clinically, a rough-\nsurfaced to verrucous, reddish to yellowish lesion \nis seen in the lateral nail spreading (from) under the \nnail and to the proximal fold. Subungual growth \nleads to onycholysis. Involvement of the matrix \ncauses leukonychia. Sometimes, a fibrokeratoma-\n\n\n\nlike aspect is seen.26 Ungual Bowen\u2019s disease is often \nmisdiagnosed as a wart for years and treated as such \nin vain. It is an in situ carcinoma that progresses to \ninvasive carcinoma after years of insidious growth. \nThis is often seen as the development of a nodule \nor ulcer (Figure 13). A second type of ungual \nsquamous cell carcinoma is histomorphologically \ndistinct and not linked to HPV.6 It is more similar \nto cutaneous keratinizing squamous cell carcinoma \nwith no cytopathic effects. \n\n\n\nThe treatment of choice is complete extirpation \n(Figure 14). As the borders are often indistinct \nMohs micrographic surgery is indicated to lower \nthe frequency of local recurrences. Segmental nail \nresection may be indicated for laterally located \nand fibrokeratoma-like Bowen\u2019s disease whereas \ncomplete resection of the entire nail unit may be \nnecessary for invasive cancer. The full-thickness \ndefect of the dorsal half of the distal phalanx is left \nfor guided wound healing until enough scar tissue \nhas formed to perform a free full-thickness skin \ngraft.\n\n\n\nFigure 13. Squamous cell carcinoma of the nail unit\n\n\n\nA. Before excision.\nB. Mohs surgery defect.\nC. Overlapping full-thickness skin graft.\nD. Approximately 8 weeks after operation, even a \n\n\n\nnew cuticle is being formed.\n\n\n\nFigure 14. Deeply invasive squamous cell \ncarcinoma\n\n\n\nA. Clinical finding.\nB. Excision specimen.\nC. Histopathology\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4112\n\n\n\nFigure 15. Subungual melanoma of the index finger \nin a 40-year-old female sports teacher\n\n\n\nA. Relatively inconspicuous longitudinal \nmelanonychia with a slight indentation of the \nfree nail margin indicating a melanoma.\n\n\n\nB. After partial proximal nail avulsion, a very \nasymmetrical pigment lesion is seen in the \nmatrix.\n\n\n\nUngual\tmelanoma\nMelanoma of the nail unit is certainly the most \nserious diagnosis of all nail tumors. It is a variant \nof acral lentiginous melanoma and has a relatively \npoor prognosis as the diagnosis is often delayed for \nyears or even decades. There are a number of myths \nand misconceptions concerning ungual melanomas:\n\n\n\n1. Ungual melanoma is not so rare as often \nclaimed: roughly 1.5 -2.5 % of all melanomas \nin light skinned Caucasians are subungual \nmelanomas. However, the combined surface \nof all nails is much less than 1% of the body \nsurface. Thus, the nail is overrepresented as \nthe site of melanomas. To be more precise, \napproximately 75 % of the nail melanomas are \npigmented; these mostly derive from the matrix. \nThis means, that about 2% of all melanomas in \nCaucasians originate in the nail matrix, which is \nonly about \u00bc to 1/3 of the nail field. The matrix \nis thus a hotspot for melanomas.\n\n\n\n2. Most nail melanomas are not difficult to \ndiagnose in light-skinned persons. Two thirds to \nthree quarters of the tumors are pigmented and \ngive rise to a longitudinal brown streak in the \nnail called melanonychia. Any melanonychia \ndeveloping in a previously normal nail of a \nperson over 30 years should raise suspicion and \nprompt adequate examinations concerning the \nnature of the pigment and the internal structure \nof the brown streak.\n\n\n\n3. It is assumed that children do not get a nail \nmelanoma. This is unfortunately true although \nthis is exceedingly rare.27\n\n\n\n4. The ABCDEF mnemonic on nail melanomas \nclaims that Asians, African-Americans, native \nAmericans are at particular risk to develop nail \nmelanomas.28 However, they have very few \ncutaneous melanomas and only the percentage \nof ungual melanomas is 20 \u2013 30%; thus, in \nabsolute numbers nail melanomas are not more \nfrequent.\n\n\n\n5. A breadth of 3 mm of a brown streak in the nail \nis not per se indicative of nail melanoma it is \nmore the percentage of the nail width that is \noccupied by the brown streak.\n\n\n\n6. The intensity of the color of a melanonychia \nis not diagnostic for a melanoma as virtually \nall nailbed melanomas are non-pigmented and \neven matrix melanomas may be only lightly \npigmented.\n\n\n\n7. It was claimed that nail melanomas are \nparticularly aggressive as compared to other \ncutaneous melanomas. This is not true as many \ncase reports show that a nail melanoma had a \nhistory of decades before being diagnosed and \ntreated. It is the late diagnosis that makes the \nprognosis so poor.\n\n\n\n8. Nail melanomas are still often treated by \namputation. This is frank overtreatment in many \ncases as in situ and early invasive tumors can be \ncured with wide local excision.29 This has first \nbeen shown 40 years ago!30  \n\n\n\nAs outlined, nail melanomas are often not diagnosed \nor only very late. There are indeed no laboratory \nor blood examinations for nail melanomas so it \nremains the awareness of the treating physician \nthat is decisive for the diagnosis and the fate of the \npatient.\n\n\n\nTreatment of choice is complete excision. In situ \nand early invasive melanomas can be operated by \nwide local excision (Figures 15, 16).30 Our approach \nis the extirpation of the nail apparatus with a safety \nmargin of 6 mm around its anatomical borders. \nIn case of a Hutchinson sign, the margin should \nbe 10 mm around it. Even a local recurrence of \nthe Hutchinson sign was shown not to worsen the \ndiagnosis of nail melanoma.29 Advanced ungual \nmelanomas are still treated by amputation; however, \nthere is no unanimity as to the amputation level as \nstudies have shown the same poor prognosis for \nproximal amputations as for distal ones.31\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 13\n\n\n\nFigure 16. Melanoma of the nail apparatus and \nthe forefoot of an octogenarian. Amputation would \nhave resulted in an insecure gait\n\n\n\nA. Clinical view from dorsal, presumed excision \nlines drawn.\n\n\n\nB. Plantar view.\nC. About 6 months after total extirpation and \n\n\n\ndefect repair with a full-tjhickness wrap-around \ngraft, dorsal view.\n\n\n\nD. Plantar view. This surgery resulted in full \nfunction of the forefoot.\n\n\n\nA B\n\n\n\nE\n\n\n\nC D\n\n\n\nDC\n\n\n\nBA\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe author has no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\nNil \n\n\n\nReferences\n\n\n\n1. Krull E, Baran R, Zook E, Haneke E.  Nail Surgery: A Text \nand Atlas. Lippincott Williams and Wilkins: New York; \n2001\n\n\n\n2. Haneke E. Surgical anatomy of the nail apparatus. Dermatol \nClin 2006;24:291-6\n\n\n\n3. Haneke E. Nail surgery. J Cutan Aesthet Surg 2011;4:163-4\n4. Haneke E. Anatomy of the nail unit and the nail biopsy. \n\n\n\nSemin Cutan Med Surg 2015;34:95-100\n5. Haneke E. Nail surgery. Clin Dermatol 2013;31:516-25\n6. Haneke E. Histopathology of the Nail \u2013 Onychopathology. \n\n\n\nCRC Press, Boca Raton FL, 2017\n7. Richert B, Di Chicacchio N, Haneke E. Nail Surgery. \n\n\n\nInforma healthcare, Informa healthcare, New York \u2013 \nLondon 2011\n\n\n\nC. After complete extirpation of the nail apparatus.\nD. Defect repair with a cross finger flap.\nE. The cross-finger finger flap is severed and the \n\n\n\ntip of the finger remodeled.\nF. Perfect result after 5 years.\n\n\n\nConclusion\nNail surgery is a part of dermatologic surgery \nand should be performed by dermatologists. No \nother specialty cares for nails and has sufficient \nknowledge on basics of nail biology and anatomy. \nMuch progress has been achieved in this field in the \nrecent 20 years.1,7 And so is nail pathology growing.6 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4114\n\n\n\n8. Haneke E. Reconstruction of the lateral nail fold after \nlateral longitudinal nail biopsy. In: Robins P (ed) Surgical \nGems in Dermatology. Journal Publ Group, New York NY, \n91-93, 1988\n\n\n\n9. Haneke E. Operative Therapie akraler und subungualer \nMelanome. In: Rompel R, Petres J, editors. Operative \nund onkologische Dermatologie, vol 15. Berlin: Springer; \n1999; 15: 210\u20134\n\n\n\n10. Haneke E. Melanonychia longitudinalis und andere \nbraune Nagelpigmentierungen. In: Koller J, Hinter H, \neditors. Fortschritte der operativen und onkologischen \nDermatologie, vol 16. Berlin, Wien: Blackwell \nWissenschaftsverlag; 2000: 19\u201326\n\n\n\n11. Herschthal J, McLeod MP, Zaiac M. Management of \nungual warts. Dermatol Ther 2012;25:545-50\n\n\n\n12. Davies MG. Coccal nail fold angiomatosis. Br J Dermatol. \n1995;132:162-3\n\n\n\n13. Baran R. Etretinate and the nails (study of 130 cases) \npossible mechanisms of some side-effects. Clin Exp \nDermatol 1986;11:148-52\n\n\n\n14. Duarte AF, Correia O, Barreiros H, Haneke E. Giant \nsubungual glomus tumor: clinical, dermoscopy, imagiologic \nand surgery details. Dermatol Online J 2016;22(10). pii: \n13030/qt66f7b8wt\n\n\n\n15. Muramatsu K, Ihara K, Hashimoto T, Tominaga Y, Taguchi \nT. Subungual glomus tumours: diagnosis and microsurgical \nexcision through a lateral subperiostealapproach. J Plast \nReconstr Aesthet Surg 2014;67:373-6\n\n\n\n16. Baran R, Kint A. Onychomatrixoma. Filamentous tufted \ntumour in the matrix of a funnel-shaped nail: a new entity \n(report of three cases). Br J Dermatol 1992;126:510-5\n\n\n\n17. Haneke E, Fr\u00e4nken J. Onychomatricoma. Dermatol Surg \n1995;21:984-7\n\n\n\n18.   Baran R, Moulonguet I, Goettmann-Bonvallot S, Encaoua \nR, Robert C. Longitudinal subungual acanthoma: one \ndenomination for various clinical presentations. J Eur Acad \nDermatol Venereol 2018;32:608-13\n\n\n\n19. Delvaux C, Richert B, Lecerf P, Andr\u00e9 J. Onychopapillomas: \na 68-case series to determine best surgical procedure \nand histologic sectioning. J Eur Acad Dermatol Venereol \n2018;32:in press\n\n\n\n20. Haneke E. Review of a recently delineated longitudinal \nlesion of the nail: onychopapilloma. J Eur Acad Dermatol \nVenereol 2018;32: in press\n\n\n\n21. Haneke E. \u2018Onycholemmal\u2019 horn. Dermatologica \n1983;167:155-8\n\n\n\n22. Chavaillaz O, Boeeadori L, Haneke E. Subungual \nepidermoid cyst: Report of a case with rapid growth and \nnail loss mimicking a malignant tumor. J Clin Dermatol \n2010;1(2):73-5\n\n\n\n23.  Lecerf P, Richert B, Theunis A, Andr\u00e9 J. A retrospective \nstudy of squamous cell carcinoma of the nail unit diagnosed \nin a Belgian general hospital over a 15-year period. J Am \nAcad Dermatol 2013;69:253-61\n\n\n\n24. Peruchoud DL, Varonier C, Haneke E, Hunger RE, \nBeltraminelli H, Borradori L, Ehnis P\u00e9rez A. Bowen \ndisease of the nail unit: a retrospective study of 12 cases \nand their association with human papillomaviruses. J Eur \nAcad Dermatol Venereol 2016;30:1503-6\n\n\n\n25. R\u00fcdlinger R, Grob R, Yu YX, Schnyder UW. Human \npapillomavirus-35-positive bowenoid papulosis of the \nanogenital area and concurrent human papillomavirus-35-\npositive verruca with bowenoid dysplasia of the periungual \narea. Arch Dermatol 1989;125:655-9\n\n\n\n26. Haneke E. Epidermoid carcinoma (Bowen\u2019s disease) of \nthe nail simulating acquired ungual fibrokeratoma. Skin \nCancer 1991;6: 217-21\n\n\n\n27. Tosti A, Piraccini BM, Cagalli A, Haneke E. In situ \nmelanoma of the nail unit in children. Report of two cases \nin fair-skinned Caucasian children. Pediatr Dermatol \n2012;29: 79-83\n\n\n\n28. Levit EK, Kagen MH, Scher RK, Grossman M, Altman \nE. The ABC rule for clinical detection of subungual \nmelanoma. J Am Acad Dermatol 2000;42:269-74\n\n\n\n29. Moehrle M, Metzger S, Schippert W, Garbe C, Rassner \nG, Breuninger H. \u201cFunctional\u201d surgery in subungual \nmelanoma. Dermatol Surg 2003;29:366-74\n\n\n\n30. Haneke E, Binder D: Subunguales Melanom mit streifiger \nNagelpigmentierung. Hautarzt 1978;29:389-91\n\n\n\n31. Haneke E. Ungual melanoma \u2013 controversies in diagnosis \nand treatment. Dermatol Ther 2012;25:510-24\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 15\n\n\n\nORIGINAL ARTICLE \n\n\n\nClinical Profile of 128 Patients with Lichen Planus seen in Hospital \nSultanah Aminah Johor Bahru, Johor\nSenhong Lee1,2, MBBS (Hons), Gemma Therese Wen Min Law3, MBBS (Hons), Nalini M Nanu1, MBBS, Kwee Eng Tey1, \nFRCP, Siew Eng Choon1, FRCP\n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\n2Skin and Cancer Foundation Inc, Victoria, Australia \n3Health Promotion Board, Ministry of Health, Singapore \n\n\n\nAbstract\nIntroduction: \nLimited information exists regarding lichen planus in Malaysia. This study is to determine the clinical \nprofile of Malaysians with lichen planus.\n\n\n\nMethods: \nA retrospective hospital note review of all patients with dermatologist-confirmed diagnosis of lichen \nplanus (LP).\n\n\n\nResults:\nIndian comprised 78.1% of 128 patients identified, followed by Malay (14.1%) and Chinese (4.7%). \nMale to female ratio was 1:1.3. The median age at disease onset was 44.0 years (IQR 26.3, 55.8). \nSeventeen (13.3%) patients developed LP before 18-year-old. Median onset-age for paediatric and \nadult LP were 12 (IQR 7, 15) and 47 (IQR 33, 57) years respectively. Indian predominance remained \nin both groups accounting for 70.6% and 79.3 % of paediatric and adult LP respectively. Female \npreponderance in adults (61.3%) contrasted with the male preponderance (70.6%) observed in children. \nPaediatric patients were significantly more likely to be male (OR=1.82, 95% CI 1.23, 2.68, p=0.013) \nbut female preponderance observed in adults was not statistically significant. Eighty-nine (69.5%) \npatients had cutaneous involvement only, 13 (10.2%) had mucosal involvement only and 26 (20.3%) \nhad both cutaneous and mucosal involvement. Mucosal lesions are less common in children (11.8%) \ncompared to adults (33.3%) but the difference observed was not statistically significant (p=0.072). \nCutaneous distribution of lesions was on lower limbs (84.3%), upper limbs (71.3%), trunk (35.7%), \nhead and neck (17.4%), genitals (6%) and nails (6%). Mucosal LP predominantly involved the buccal \nmucosa (92.3%), followed by gum (7.7%), lips (5.1%) and tongue (2.6%). Hypertension, diabetes and \ndyslipidaemia were documented respectively in 9%, 10.8% and 11.7% of adult patients. Hepatitis B \nand hepatitis C tested in 23 (18%) and 32 (25%) patients respectively were all non-reactive. Amongst \nthe 106 patients who had follow-up, 87 (82.1%) demonstrated remission of skin lesions with treatment.\n\n\n\nConclusion:\nLP mainly affects Indians in our multi-ethnic population. Paediatric LP is not rare and affects \npredominantly boys. The majority of patients only had cutaneous LP without mucosal lesions. Our \nstudy confirmed the benign nature of LP which generally heals within 18 months after onset albeit \nwith prolonged hyperpigmentation\n\n\n\nKey words: Lichen planus, Clinical profile, Malaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4116\n\n\n\nCorresponding Author\nDr Senhong Lee\nSkin and Cancer Foundation Inc.\nLevel 1, 80 Drummond Street, \n3053 Carlton, Victoria, Australia\nEmail: senhonglee@hotmail.com\n\n\n\nIntroduction\nLichen planus (LP) is a chronic inflammatory disease \nthat affects the skin and mucous membrane.1,2 LP can \nbe categorised into cutaneous LP and mucosal LP. \nCutaneous LP can be further stratified into various \nclinical subtypes depending on its morphology (e.g. \nclassic, hypertrophic and annular LP) or the sites \nof involvement (e.g. scalp and nail LP). Classic LP \ntypically presents as pruritic, violaceous papules/\nplaques covered by whitish reticular streaks, known \nas Wickham\u2019s striae.2 Mucosal LP most commonly \ninvolves the oral mucosa, although it can also affect \nthe vulvovaginal area, oesophagus, larynx and \nconjunctiva.1 \n\n\n\nThe estimated prevalence of LP ranges from \n0.22% to 5% globally.1 LP has no evident gender \npredilection although some studies suggested \na female predominance of up to two folds.3,4,5 \nAlthough this condition is generally considered an \nadult disease, 5 to 10% of cases reported, particularly \nfrom India, occurred in children.2,6,7 \n\n\n\nLP has been associated with multiple conditions, \nincluding hepatitis C virus (HCV) infection, \ndyslipidaemia, stress/anxiety and internal \nmalignancies.1 The reported prevalence of HCV \nseropositivity in LP ranges from 0 to >60% \nworldwide.8 Although a meta-analysis, performed \nin 2014, revealed that patients with LP are \napproximately 5 times more likely than controls to \nbe seropositive for HCV (OR=5.58, 95% CI; 3.72, \n8.23, p< 0.05), a recent Malaysian study showed \nno significant association between LP and HCV \nseropositivity.9 \n\n\n\nCutaneous LP generally runs a self-limiting course \nwhereas mucosal LP tends to be chronic.2,10 The goals \nof treatment include expediting time to resolution \nand relieving symptoms.2 Topical corticosteroids \nremain the  mainstay of treatment, followed by \nnarrow-band UVB.2 Other treatment options include \n\n\n\ntopical and systemic retinoids, systemic steroids, \ncyclosporine and mycophenolate mofetil.2 The \nunderstanding of LP among Malaysians is limited \nby the lack of local data.9,11 In this study, we aim to \ndetermine the demography, disease characteristics \nand outcome of patients with LP and to identify \nany difference in clinical profile between adult and \npaediatric LP .\n\n\n\nMaterials and Methods\n\n\n\nStudy Design and Population\nThis retrospective study was done by reviewing \nthe medical records of patients with electronically \ndocumented diagnosis of lichen planus from January \n2005 to December 2016, mapped to L43.9 code, \nICD10 CM (International Classification of Diseases, \n10th revision, Clinical Modification). Complete \nmedical records of these patients, including manual \nand biopsy records were analysed. Diagnosis \nof LP was validated by either a confirmatory \nhistology or documentation of diagnosis by at \nleast one dermatologist or subsequent confirmation \nof diagnosis by a dermatologist after reviewing \npatients\u2019 medical notes. \n\n\n\nAll patients with histologic confirmation of LP \nand those without skin biopsy done but had well-\ndocumented characteristic classic physical findings \nwere included. Data collected includes demographic \ncharacteristics (age, gender and ethnicity), clinical \nfeatures of LP, laboratory findings, biopsy results if \navailable, treatment and outcome of treatment. \n\n\n\nStatistical Analysis\nDescriptive statistics are presented as counts and \npercentages for categorical variables. Mean with \nstandard deviation (SD) was used for normally \ndistributed data while median with interquartile \nrange (IQR) was used for data which were not \nnormally distributed. Independent sample t-test \nor Mann-Whitney U-test was used for univariate \nanalysis depending on data distribution. Chi-square \nand Fisher\u2019s Exact test were used where appropriate \nto investigate the association between two \ncategorical variables. Statistical significance was \nset at p<0.05. SPSS version 17.0 was used for data \nanalysis. This study was approved by the Malaysian \nMinistry of Health Institutional Review Board and \nMedical Research Ethics Committee (NMRR-18-\n1122-41655).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 17\n\n\n\nResults\n\n\n\nDemographic Characteristics \nTable 1 summarises the demographic and clinical \ncharacteristics of 128 patients identified with LP. \nIndian comprised 78.1% (n=100) of patients, \nfollowed by Malay (14.1%, n=18), Chinese (4.7%, \nn=6) and other ethnicities (3.1%, n=4) namely \nNepali, Bangladesh and Nigerian. Male to female \nratio was 1: 1.3. The median age at disease onset \nwas 44.0 years (IQR 26.3, 55.3). Seventeen (13.3%) \npatients developed LP before 18-year-old. A \nsubgroup analysis of patients stratified according \n\n\n\nto gender, race and age group was also performed \n(Table 2). Median onset-age for paediatric and \nadult LP were 12 (IQR 7, 15) and 47 (IQR 33, 57) \nyears respectively. Indian predominance remained \nin both groups accounting for 70.6% and 79.3 % \nof paediatric and adult LP respectively. Female \npreponderance in adults (61.3%) contrasted with the \nmale preponderance (70.6%) observed in children. \nPaediatric patients were significantly more likely to \nbe male (OR=1.82, 95% CI 1.23, 2.68, p=0.013) but \nfemale preponderance observed in adults was not \nstatistically significant as the odds ratio crosses 1 \n(OR=2.08, 95%CI 0.98, 4.41).\n\n\n\nTable 1.  Clinical characteristics of patients with Lichen planus\n\n\n\nClinical Characteristics \nEighty-nine (69.5%) patients had cutaneous \ninvolvement only, 13 (10.2%) had mucosal \ninvolvement only and 26 (20.3%) had both cutaneous \nand mucosal involvement. Only mucosal LP \nwithout cutaneous involvement was not identified \nin any children. Mucosal lesions are less common \nin children (11.8%) compared to adults (33.3%) \nbut the difference observed was not statistically \nsignificant (p=0.072). The most common site for \ncutaneous LP was lower limbs (84.3%), followed by \nupper limbs (71.3%), trunk (35.7%), head and neck \n(17.4%), genitals (6%) and nails (6%). Mucosal \nLP predominantly involved the buccal mucosa \n(92.3%), followed by gum (7.7%), lips (5.1%) and \n\n\n\nChildren\n(n=17)\n\n\n\nAdults\n(n=111)\n\n\n\nAll patients\n(n=128)\n\n\n\nOnset-age\tin\tyears,\tmedian\t(IQR) 12 (7.0, 15.0) 47.0 (33.0, 57.0) 44.0 (26.3, 55.8)\nGender, n (%)\nMale 12 (70.6) 43 (38.7) 55 (43.0)\nFemale 5 (29.4) 68 (61.3) 73 (57.0)\nEthnicity, n (%)\nIndian 12 (70.6) 88 (79.3) 100 (78.1)\nMalay 4 (23.5) 14 (12.6) 18 (14.1)\nChinese 1 (5.9) 5 (4.5) 6 (4.7)\nOthers 0 4 (3.6) 4 (3.1)\nType\tof\tLP\tn\t(%)\nCutaneous\tLP\tonly 15 (88.2) 74 (66.7) 89 (69.5)\nMucosal\tLP\tonly 0 13 (11.7) 13 (10.2)\nCutaneous\tand\tmucosal\tLP 2 (11.8) 24 (21.6) 26 (20.3)\nTreatment n (%)\nTopical therapy 17 (100) 106 (95.5) 123 (96.1)\nAnti-histamine 11 (64.7) 75 (67.6) 86 (67.2)\nUVB\tPhototherapy 1 (5.9) 3 (2.7) 4 (3.1)\nSystemic therapy\nPrednisolone 6 (35.3) 29 (26.1) 35 (27.3)\nDapsone 1 (5.9) 5 (4.5) 6 (4.7)\nMedian\tfollow-up\ttime\tin\tmonths\t(IQR) 6.0 (0.5, 28.5) 9.0 (2.5, 34.0) 8.0 (2.0, 34.0)\nOutcome\t(%\tresponse\tat\tlast\tfollow-up) 84.6% of 13 on follow-up 81.7% of 93 on follow-up 82.1% of 106 on follow-up\n\n\n\ntongue (2.6%). \n\n\n\nThe majority of patients had classic LP (Figure 1a) \nwith less than 10% body surface area involved, \nfollowed by 4 hypertrophic LP (Figure 1b) 4 acute \ngeneralised LP, 2 annular (Figure 1c), 2 lichen \nplanus pigmentosus, 1 lichen planopilaris, one \nbullous LP. Sixteen patients with classic LP had \nhypertrophic LP on their legs. Oral mucosal lesions \nare classically reticular LP with characteristic lace-\nlike whitish plaques on both buccal mucosa (Figure \n1d). Erosive LP (Figure 1e) was histologically-\nconfirmed in two patients who had mucosal only LP \ninvolving oral and genital regions. All patients with \nLP variants were histologically confirmed. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4118\n\n\n\nFigure 1. (a) Classic LP involving both dorsal wrists and hands; (b) Hypertrophic LP involving bilateral lower legs; (c)  Annular LP; (d) \nBuccal mucosal LP with evident Wickham\u2019s striae; (e) Erosive LP involving the lip\n\n\n\nBiopsies performed in 52 patients showed \ncharacteristics features of lichen planus namely \nlymphocytic infiltration in the dermal-epidermal \njunction associated with basal vacuolar changes. \nHBs Ag (hepatitis B surface antigen) and HCV Ab \n(hepatitis C antibody) tested in 23 (18%) and 33 \n(25.8%) patients respectively, were all non-reactive. \nAmong the adult subgroup, 11 patients (9%) had \nhypertension, 12 (10.8%) had diabetes, 13 (11.7%) \nhad dyslipidaemia and one patient (0.8%) had a \nhistory of ischaemic heart disease.\n\n\n\nTreatment\tand\tFollow-up\t\nThe majority (96.1%) of patients received topical \ntherapy (Table 1). Topical steroids, salicylic acid \nointment and fusidic acid cream were used to \ntreat 119, 20 and 19 patients respectively. Only \nfour patients (3.1%) received and benefitted from \nphototherapy due to logistic reasons. Eighty-six \npatients received anti-histamine as adjuvant therapy \nto control pruritus.\n\n\n\nThe median follow-up duration of 106 patients \n(86.2%) with at least one follow-up appointment \nwas 8 months (Table 1). Improvement of \nskin lesions albeit with post-inflammatory \nhyperpigmentation was documented in 87 (82.1%) \nof the 106 patients reviewed on last follow-up. \nOnly 35 (27.3%) required systemic therapy namely \noral prednisolone to control LP. However, a short, \nsharp course of oral prednisolone dosed at 0.5mg \nper kg body weight for 3-6 months benefitted only \n\n\n\na\n\n\n\nd e\n\n\n\ncb\n\n\n\n18 out of 35 patients (51.4%) treated. Patients with \nassociated hypertrophic LP after initial remission \nwith prednisolone required repeated courses of oral \nprednisolone to prevent relapse after failing super-\npotent topical steroid and/or 20% salicylic acid \nointment. Dapsone given to 6 patients as steroid-\nsparing or alternative agent only benefitted one \npatient who had recurrent LP affecting only the oral \nmucosae. No systemic immunosuppressants were \nused. Thirty-four patients (26.6%) including 14 \nwith mucosal involvement still had active disease \nafter 2 years. However, no malignant transformation \nof LP was documented. \n\n\n\nDiscussion\nOur demographic findings were similar to the \nliterature. The median age of 44 year-old correlated \nwith the literature, in which patients with LP typically \npresent between the third and sixth decades of life.2 \nThe slight female preponderance with a M:F ratio of \n1:1.3 was also consistent with previous Malaysian \nstudies which demonstrated a similar ratio of \n1:1.2.9,11 Paediatric patients constituted 13.3% of \nour cohort, which was slightly higher than 5-10% \nin the literature.2 However, the onset-age was not \ninfluenced by ethnicity.\n\n\n\nIndians constituted 78.1% (n=100) of 128 patients \nidentified. Although certain subtypes of LP, such \nas actinic LP and lichen planus pigmentosus \n(LPP) are commoner in the Indian population, \nLP in general does not demonstrate a racial \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 19\n\n\n\npredilection.1,2 A clinicoepidemiological study from \nIndia demonstrated that LP constituted 0.38% of \ntheir total dermatology outpatients, similar to the \nestimated global prevalence of LP, which is 0.22% \nto 5%.1,12 However, the involvement of Indian \npatients in our cohort (78.1%) was significantly out \nof proportion to the Malaysian Indian population \nthat was 7% in 2017.13 Our findings suggest that LP \nhas a racial predilection for Indians. Similar results \nwere demonstrated in another Malaysian study.9 \n\n\n\nLarger studies are required to corroborate this.\n\n\n\nThe commonest area of distribution for cutaneous \nLP was lower limbs (84.3%), followed by upper \nlimbs (71.3%), trunk (35.7%) and head and neck \n\n\n\nregion (17.4%). These findings were consistent with \nthe literature.7 Nail involvement was observed in \n6% of our patients, which was also similar to the \ndocumented prevalence of 1-10% in the literature.1,2 \n\n\n\nOur patients with mucosal LP had predominant \ninvolvement of the oral mucosa, which corroborated \nthe literature findings.1 Mucosal lesions are \nless common in children (11.8%) compared to \nadults (33.3%) although statistically insignificant \n(p=0.072). The estimated prevalence of oral lichen \nplanus in general adult population is 0.5-2%, while \nthe prevalence of paediatric oral lichen planus \nwas 0.4% in an Iranian study.14 Our findings are \nconsistent with the literature.\n\n\n\nTable 2. Subgroup analysis of patients with lichen planus\n\n\n\nSubgroup analysis n (%) Median\tage\tat\tfirst\t\npresentation \n\n\n\nCutaneous involvement \nonly (%)\n\n\n\nMucosal involvement only \n\u2013\tn\t(%)\n\n\n\nBoth\n\n\n\nGender\n\u2022\t Male\n\u2022\t Female\n\n\n\n55 (43)\n73 (57)\n\n\n\n45\n41\n\n\n\n37 (67.3)\n52 (71.2)\n\n\n\n5 (9.1)\n8 (11.0)\n\n\n\n13 (23.6)\n13 (17.8)\n\n\n\nRace\n\u2022\t Indians\n\u2022\t Malays\n\u2022\t Chinese\n\u2022\t Others \n\n\n\n100 (78.1)\n18 (14)\n6 (4.6)\n4 (3.1)\n\n\n\n44.5\n41.5\n38.5\n23.5\n\n\n\n70 (70.0)\n13 (72.2)\n3 (50.0)\n3 (75.0)\n\n\n\n8 (8.0)\n3 (16.7)\n2 (33.3)\n0 (0.0)\n\n\n\n22 (22.0)\n2 (11.1)\n1 (16.7)\n1 (25.0)\n\n\n\nAge group\n\u2022\t Adult\t(\u226518)\n\u2022\t Paediatric\t(<18)\n\n\n\n111 (86.7)\n17 (13.3)\n\n\n\n47\n12\n\n\n\n74  (66.7)\n15 (88.2)\n\n\n\n13 (11.7)\n0 (0.0)\n\n\n\n24 (21.6)\n2 (11.8)\n\n\n\nThe prevalence of hypertension, diabetes and \ndyslipidaemia in our adult cohort is 9%, 10.8% \nand 11.7% respectively. This is lower than the \ngeneral Malaysian adult population prevalence \nof 30.3%, 17.5% and 47.7 % correspondingly.15 \nAlthough previous studies demonstrated that \npatients with lichen planus had a higher prevalence \nof dyslipidaemia through a proposed mechanism of \nchronic inflammation, this was not reproduced in \nour study.16 Larger studies are required to elucidate \nthe relationship between metabolic syndrome and \nLP.\n\n\n\nHBV and HCV were tested in 23 (18%) and 32 \n(25%) patients respectively, and they were all non-\nreactive. Given only a small portion of our patients \nwere tested for HCV, our study suggested but could \nnot confirm the lack of association between chronic \nhepatitis C and LP. It is noteworthy that a recent \nlocal study also did not demonstrate a significant \nassociation between chronic hepatitis C infection \nand LP.9 This could be explained by the differences \nin hepatitis C virus prevalence, viral characteristics \nand genetic susceptibility for individuals with \nhepatitis C infection to develop LP, across various \n\n\n\nregions.17 Larger studies are required to investigate \nthis association to clarify the need of HCV screening \namongst LP patients in Malaysia.\n\n\n\nIn our cohort, 106 patients (86.2%) had attended \nat least one follow-up appointment and the \nmedian follow-up period was 8 months. Amongst \nthe 106 patients who had follow-up, 87 (82.1%) \ndemonstrated improvement of skin lesions with \ntreatment. The majority of our patients only required \ntopical therapy and anti-histamine. None of the \npatients required immunosuppressive therapy. These \nfindings support the self-limiting nature of LP.\n\n\n\nThis study provides insight into the \nclinicoepidemiological profile of both cutaneous \nand mucosal lichen planus in Malaysia. However, \nthe availability and validity of certain findings \nmay be limited by the retrospective observational \nnature of this study. Another limitation was that \nnot all cases of LP that were included in the study \nhad histological confirmation. However, for cases \nwithout skin biopsy, we only included those with \nwell-documented characteristic classic physical \nfindings.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4120\n\n\n\nConclusion\nThe clinic-epidemiological profile of LP in the \nMalaysian cohort is generally similar with the \nliterature. LP mainly affects Indians in our multi-\nethnic population. Paediatric LP is not rare and \naffects predominantly boys. The majority of patients \nonly had cutaneous LP without mucosal lesions. \nIn our study, LP is not associated with metabolic \ncomplications and hepatitis C infection. Our study \nconfirmed the benign, self-limiting nature of LP. \n\n\n\nConflict\tof\tInterest\tDeclaration\nAll authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\t\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle. \n\n\n\nReferences\n\n\n\n1. Gohouri F, Davari P, Fazel N. Cutaneous and mucosal lichen \nplanus: a comprehensive review of clinical subtypes, risk \nfactors, diagnosis, and prognosis. ScientificWorldJournal \n2014;742826. doi: 10.1155/2014/742826. \n\n\n\n2. Weston G, Payette M. Update on lichen planus and its \nclinical variants. Int J Womens Dermatol 2015;1:140-9.\n\n\n\n3. Alrashdan MS, Cirillo N, McCullough M. Oral lichen \nplanus: a literature review and update. Arch Dermatol Res \n2016;308:539-51.\n\n\n\n4. Kyriakis KP, Terzoudi S, Palamaras I, Michaeilides C, \nEmmanuelides S, Pagana S. Sex and age distribution of \npatients with lichen planus. J Eur Acad Dermatol Venereol \n2006;20:625-6.\n\n\n\n5. Farhi D, Dupin N. Pathophysiology, etiologic factors and \nclinical management of oral lichen planus, part I: facts and \ncontroversies. Clin Dermatol. 2010;28:100-8.\n\n\n\n6. Al-Hashimi I, Schifter M, Lockhart PB, Wray D, Brennan \nM, Migliorati CA et al. Oral lichen planus and oral lichenoid \nlesions: diagnostic and therapeutic considerations. Oral \nSurg Oral Med Oral Pathol Oral Radiol Endod 2007;103 \nSuppl:S25.e1-12.\n\n\n\n7. Parihar A, Sharma S, Bhattacharya SN, Singh UR. A \nclinicopathological study of cutaneous lichen planus. \nJournal of Dermatology & Dermatologic Surgery \n2015;19:21-6.\n\n\n\n8. Lodi G, Guiliani M, Majorana A, Sardella A, Bez C, \nDemarosi F et al. Lichen planus and hepatitis C virus: \na multicenter study of patients with oral lesions and a \nsystematic review. Br J Dermatol 2004;151:1172-81.\n\n\n\n9. Norazirah MN, Mazlin MB, Adawiyah J, Asmah J. Lichen \nplanus and hepatitis C infection: exploring the association \namong Malaysian patients. Malaysian J Dermatol \n2013;31:8-12.\n\n\n\n10. D Eisen. The clinical features, malignant potential, and \nsystemic associations of oral lichen planus: a study of 723 \npatients. J Am Acad Dermatol 2002;46:207-14.\n\n\n\n11. Yaacob HB, Tan PL, Ngeow WC. Malignancy in oral lichen \nplanus: a review of a group from the Malaysian population. \nJ Oral Sci 2002;44:65-71.\n\n\n\n12. Bhattacharya M, Kaur I, Kumar B. Lichen planus: a clinical \nand epidemiological study. The J Dermatol 2000;27:576-\n82.\n\n\n\n13. Department of Statistics Malaysia, Official Portal. Current \npopulation estimates, Malaysia, 2016-2017. [Accessed \nin Jan 2018]. Available from: https://www.dosm.gov.my/\nv1/index.php?r=column/cthemeByCat&cat=155&bul_\nid=a1d1UTFZazd5ajJiRWFHNDduOXFFQT09&menu_\nid=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09.\n\n\n\n14. Bakhtiari S, Taheri JB, Toossi P, Azimi S, Nezhad SK. \nPrevalence of oral lichen planus in Iranian children and \nadolescents: a 12-year retrospective study. Eur Arch \nPaediatr Dent 2017;18:419-22.\n\n\n\n15. Institute for Public Health (IPH) 2015. National Health \nand Morbidity Survey 2015 (NHMS 2015). Vol. II: Non-\nCommunicable Diseases, Risk Factors & Other Health \nProblems; 2015. \n\n\n\n16. Arias-Santiago S, Buenda-Eisman A, Aneiros-Fernndez J, \nGiron-Prieto MS, Gutierrez-Salmeron MT, Mellado VG \net al. Cardiovascular risk factors in patients with lichen \nplanus. Am J Med 2011;124:543-8.\n\n\n\n17. Lodi G, Pellicano R, Carrozzo M. Hepatitis C virus \ninfection and lichen planus: a systematic review with meta-\nanalysis. Oral Dis 2010;16:601-12.\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 21\n\n\n\nORIGINAL ARTICLE\n\n\n\nThe Effect and Tolerability of a Low pH Skin Cleanser in Children \nwith Atopic Dermatitis\nChoon Sian Lee1, MRCP, Najeeb Ahmad B Mohd Safdar1, MRCP, Adawiyah Jamil2, AdvMDerm.\n\n\n\n1Department of Dermatology, Hospital Tuanku Ja\u2019afar, Seremban, Negeri Sembilan, Malaysia\n2Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Cheras, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nThe pH of normal skin is in the acidic range. Higher pH observed in atopic dermatitis (AD) contributes \nto the skin barrier defect. This study aimed to assess the effect and tolerability of low pH skin cleanser \nin children with AD.\n\n\n\nMethods:\nA prospective open label study was performed involving AD children aged 4 -12 years old. Patients \nwith stable disease using only topical treatment were included. Patients with cutaneous infection, \non antibiotic, systemic corticosteroid or immunosuppressant, and allergy to milk and methylparaben \nwere excluded. A commercial low pH skin cleanser was used twice daily for 6 weeks. Skin pH, \ntransepidermal water loss (TEWL), erythema, EASI score, body surface area (BSA) affected, pruritus, \nChildren\u2019s Dermatology Life Quality Index (cDLQI) and patients\u2019 own severity assessment were \ndocumented at baseline, week 2 and week 6.  \n\n\n\nResults:\nAA total of 24 children aged 7.29 \u00b1 2.60 years completed the study. There were 14 (58.3%) girls and 10 \n(41.7%) boys. Baseline EASI score was 8.88\u00b18.20. EASI score improved from 8.88\u00b18.20 at baseline to \n4.10\u00b13.26, p<0.001) at the end of study while BSA reduced from 13.13\u00b118.53 to 5.75\u00b15.78,p=0.024. \nPruritus score decreased from 5.88\u00b14.87 to 2.92\u00b11.67, p<0.001, cDLQI reduced from 5.58\u00b14.87 to \n2.29\u00b12.07, p<0.001. Patients\u2019 self-assessment of AD severity improved from 3.71\u00b12.87 at week 2 to \n5.17\u00b12.29, p<0.026 at week 6. Skin pH at lesional skin improved but increased at non-lesional areas \nwhile TEWL and erythema improved at all areas, however the differences were not significant. Lesion \nA skin pH, TEWL and erythema improved from 5.07\u00b10.72, 29.96\u00b114.96, 584.13\u00b120.20 to 5.05\u00b10.44, \n23.96\u00b16.96, 579.75\u00b119.85 respectively; whereas lesion B skin pH, TEWL and erythema improved \nfrom 5.24\u00b10.70, 32.18\u00b115.67, 583.08\u00b127.04  to 5.02\u00b10.56, 24.02\u00b17.95, 574.42\u00b122.78 respectively.  \nOne patient reported transient stinging pain.\n\n\n\nConclusion:\nShowering with a low pH cleanser improved AD severity clinically. However, we were unable to \ndemonstrate skin pH lowering as the cause of AD improvement. The low pH cleanser was well \ntolerated.\n\n\n\nKey words: Atopic dermatitis, Low pH cleanser, Skin pH, TEWL, Erythema\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4122\n\n\n\nIntroduction\nThe normal stratum corneum is inherently acidic \nin nature. Skin pH is one of the major factors that \nmaintain skin barrier integrity.1 It varies by age, \nanatomical site, skin type and is altered by sweat and \nuse of topical products. Newborn skin pH is neutral, \ntransiting into acidic skin during first year of life.2 \nThereafter, children pH values are similar to adults\u2019 \nwhich are between 4 to 6.3 Skin pH rises in elderly \ndue to physiological ceramide deficiency.4 Skin pH \nvaries at different sites. In infants, the cheek pH \nis higher corresponding to atopic dermatitis (AD) \nfavouring this site in infancy.5 Intertriginous pH is \nhigher in adults which explains the predilection of \natopic eczema at these sites after infancy.6 \n\n\n\nThe \u2018acid mantle\u2019 conceptualised by Schade \nand Marchionini in 1928 confers a physiologic \nprotective mechanism for the skin.7 Skin cleansers \ncould potentially disrupt this protective acidic layer. \nCleansers are broadly divided into soap-based and \nsoap-free formulations known as syndet. Syndets \nare neutral or acidic whereas soaps are alkaline \nin nature.8 Alkaline cleansers has significant \ncorrelation with development of skin irritation.9 \nRegular showers with a skin cleanser at least once or \ntwice a day is a lifestyle practice in our country with \nhot and humid weather all year. In atopic dermatitis \n(AD) with skin barrier defect and higher skin pH,10 \nregular frequent showers is a double edge sword as \nit could be beneficial or detrimental depending on \ntype of cleanser used. \n\n\n\nStudies on the effect of skin cleansers especially \nlower pH cleansers in AD are lacking. It is imperative \nto determine a simple and easy way that contributes \nto AD control by identifying cleansers that are \nbeneficial, or at least not deleterious to AD. This \nstudy aimed to evaluate the effect and tolerability of \na low pH cleanser in children with AD.\n\n\n\nCorresponding Author\nDr Adawiyah Jamil\nDepartment of Medicine,\nUniversity Kebangsaan Malaysia Medical Center,\nBandar Tun Razak, Cheras,\n56000 Kuala Lumpur, Malaysia \nEmail: adda_jamil@yahoo.com  \n\n\n\nMaterials and Methods\nThis was a 6 weeks prospective open label pilot \nstudy conducted from October 2017 till January \n2018. Patients were recruited from the Dermatology \nClinic of Tuanku Ja\u2019afar Hospital in Seremban, \nNegeri Sembilan, a tertiary care centre in Malaysia. \nPatients aged from 4 to 12 years old, diagnosed with \nAD based on the U.K. Working Party\u2019s Diagnostic \nCriteria for Atopic Dermatitis, on topical treatment \nonly and stable with no changes in their treatment \nregime for the past 3 months prior to study were \nincluded. Severity of AD was rated using Eczema \nArea and Severity Index (EASI). Patients with \ncutaneous infection, on antibiotic and on systemic \ncorticosteroid or immunosuppressant in last 6 \nmonths were excluded. Patients with recent (4 \nweeks) changes in their usual environment or daily \nactivities and known to be sensitive to study product \ningredients such as milk and methylparaben were \nexcluded as well. Consents were obtained from the \nchildren\u2019s parents or guardians.\n \nOn the first visit, baseline EASI score, body surface \narea (BSA) affected, skin pH, transepidermal water \nloss (TEWL), erythema, pruritus intensity and \nChildren Dermatology Life Quality Index (cDLQI) \nwere assessed. Skin pH, TEWL and erythema were \nperformed at 2 lesional sites (A & B), 2 non-lesional \nsites (C & D) and 1 control lesional site on the face.  \nObjective clinical measurements were obtained \nusing the HI 99181 skin pH meter by placing a \nprobe gently on the skin. Tewameter TM300 was \nused to assess TEWL. The tewameter measured \nthe density gradient of the water evaporation from \nthe skin in the unit of g/m2/h. Skin erythema was \nmeasured by Mexameter MX16. The probe placed \non skin to measure melanin and haemoglobin \n(erythema) which were responsible for skin colour. \nThe measurement was based on absorption and \nreflection on a broad scale value from 000 to 900 in \narbitrary units  for erythema and melanin. Intensity \nof pruritus was evaluated using a visual analog \nscale from 0 to 10. The validated, self-administered \ncDLQI questionnaire was used to evaluate the \ndisease impact on patient\u2019s quality of life with the \nscore of 0-30.11 The patients\u2019 parents assisted in \ncompleting the cDLQI. \n\n\n\nA commercial low pH liquid skin cleanser together \nwith a 5ml measuring cap were given to the patients \nfor regular twice a day shower at least 4 hours apart \nfor 6 weeks. Patients were instructed to measure \n5ml of  the cleanser, wet the body and limbs with \ntap water, apply the cleanser from the neck to the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 23\n\n\n\ntoes (sparing the face), wait for about 3 to 5 minutes \nand then rinse thoroughly with tap water. The face \nis avoided to serve as the control site. A diary was \ngiven for the patients to record the shower schedule \nand adverse events encountered. The commercial \nskin cleanser used in this study has a pH of 3.5. \nThe ingredients included lactoserum, lactic acid \nand sodium methylhydroxybenzoate. Patients were \nmaintained on their routine standard treatment \nregime of moisturisers, topical corticosteroids and \noral antihistamines. Standard topical treatment \nwas applied at interventional site (body and limbs) \nas well as control site (face). No new topical or \nsystemic treatment was allowed during the study \nperiod.\n\n\n\nAt week 2 and week 6, the same measurements \nand questionnaire were performed. In addition, \nassessments on compliance, patients\u2019 own \nassessment on the severity of their eczema and \nadverse effects of the cleanser were conducted. \nPatients\u2019 compliance was evaluated based on \nthe records in the diary. Patients\u2019 own severity \nassessment was graded using a visual analog scale \nfrom -1 to -10. Negative one denotes worsening, \n0 = status quo, 1 to 10 = degree of improvement \nwith 10 for maximum improvement. Side effects \nwere recorded based on the patients\u2019 report or the \ninvestigator observation on any unwanted symptoms \nor signs such as erythema, pain, stinging or burning \nsensation. \n\n\n\nStatistical analysis\nData was analysed using the Statistical Package \nfor Social Science version 16.0 (SPSS, Chicago, \nIL, USA). All statistical tests were two-sided, \nwith a significance level of p <0.05. Demographic \ninformation was summarised using descriptive \nstatistics. Paired Student\u2019s t-test was used to evaluate \nthe effects before and after intervention. Independent \nT test was used to identify the difference between \ninterventional and control sites. Ethical approval \nwas obtained from Medical Research and Ethnics \nCommittee with the research code of NMRR-17-\n1054-35621.\n\n\n\nResults\nA total of 25 patients were recruited, 24 patients \ncompleted the 6 weeks study and 1 dropped out at \nweek 2 due to logistic reasons. Demography and \nbaseline characteristics of the study population are \nshown in Table 1. The mean age was 7.29 \u00b1 2.60 \nyears. There were 14 (58.3%) girls and 10 (41.7%) \n\n\n\nboys. The mean age of AD onset was 3.03 \u00b1 2.10 \nyears. Mean EASI score was 8.88\u00b18.20 which \nfalls under moderately severe AD. The majority \nof patients (79.2%) had lesions which were \npredominantly at the flexurals, however at disease \nonset almost half (41.7%) had extensor surfaces \naffected mainly. About 58.3% patients used syndet \nwhile 41.7% used soap based skin cleanser prior \nto the study. All patients were on standard topical \ntreatment which included moderate potency \ncorticosteroid and emollients except one patient \nwith additional topical tacrolimus. \n\n\n\nAD severity improved significantly with EASI \nscore 8.88\u00b18.20 at baseline reduced to 4.10\u00b13.26, \np<0.001 at the end of the study (Figure 1). \nSignificant improvement was observed as early as \nweek 2. The improvement in AD severity was further \ndemonstrated by other parameters. BSA reduced \nfrom 13.13\u00b118.53 at baseline to 5.75\u00b15.78 at week \n6, p=0.024. Pruritus score reduced from 5.88\u00b14.87 \nto 2.92\u00b11.67, p<0.001 and DLQI reduced from \n5.58\u00b14.87 to 2.29\u00b12.07, p<0.001. Patients\u2019 own \nassessment of their disease severity improved from \nmean of 3.71\u00b12.87 at week 2 to 5.17\u00b12.29, p<0.026 \nat the end of study. The results are summarized in \nTable 2.\n\n\n\nAt lesional sites A and B, the values of skin pH, \nTEWL and erythema were reduced at the end of \nstudy, however the reduction was not statistically \nsignificant except for lesional site B where the TEWL \ndecreased significantly (p=0.01). In non-lesional \nsites C and D, the skin pH increased significantly \nwhile the TEWL values were not significantly \ndecreased. Erythema improved at both sites but is \nstatistically significant only at site D. (Figure 2).\n\n\n\nThe skin pH, TEWL and erythema improved at \nthe control lesional site on the face, however the \nchanges were not significant. The magnitudes of \nthe changes in the skin pH, TEWL and erythema \nform baseline to end of study were compared for \nlesional sites A & B and control lesional site (Figure \n3). There were no significant differences between \ninterventional sites and control site. \n\n\n\nIn terms of tolerability, one patient had stinging pain \nat lesional sites while using the low pH cleanser on \nday 1 to day 4. The symptom disappeared from day \n5 onwards till the end of the study. Compliance rate \nto the skin cleanser and shower schedule was 96.3%.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4124\n\n\n\nTable 1. Characteristics of the study population, N=24\n\n\n\nParameters Mean \u00b1 SD or n (%)\nAge, years 7.29 \u00b1 2.60\nGender\n\u2022\t Male\n\u2022\t Female\n\n\n\n10 (41.7)\n14 (58.3)\n\n\n\nEthnicity\n\u2022\t Malay\n\u2022\t Chinese\n\n\n\n17(70.8)\n7 (29.2)\n\n\n\nPersonal history of atopy other than AD 10 (41.7)\nFamily history of atopy 15 (62.5)\nAge of AD onset, years 3.03 \u00b1 2.10\nDistribution of AD lesions at onset\n\u2022\t Extensors\n\u2022\t Flexor\n\n\n\n10 (41.7)\n14 (58.3)\n\n\n\nCurrent distribution of AD\n\u2022\t Mainly extensors\n\u2022\t Mainly\tflexors\n\n\n\n5 (20.8)\n19 (79.2)\n\n\n\nEASI score 8.88\u00b18.20\nCurrent topical treatment\n\u2022\t Standard treatment\n\u2022\t Standard treatment with tacrolimus\n\n\n\n23 (95.8)\n1 (4.2)\n\n\n\nSkin\tcleanser\n\u2022\t Syndet \n\u2022\t Soap\n\n\n\n14 (58.3)\n10 (41.7)\n\n\n\nBaseline Week\t2 End of study\nEASI 8.88\u00b18.20 7.92\u00b17.57 4.10\u00b13.26b\n\n\n\nBSA (%) 13.13\u00b118.53 10.21\u00b113.37a 5.75\u00b15.78b\n\n\n\nPruritus score 5.88\u00b12.68 4.58\u00b12.45a 2.92\u00b11.67b\n\n\n\nDLQI 5.58\u00b14.87 4.38\u00b13.63a 2.29\u00b12.07b\n\n\n\nSubjective response 3.71\u00b12.87 5.17\u00b12.79c\n\n\n\nFigure 1. Atopic dermatitis severity measured by EASI at baseline, week 2 and week 6 (end of study)\n\n\n\na p<0.05 between baseline and week 2\nb p<0.05 between baseline and week 6\n\n\n\nTable 2. EASI, BSA, Pruritus Score, DLQI and patients\u2019 own severity assessment at baseline, week 2 and end of study\n\n\n\na p<0.05 between baseline and week 2\nb p<0.05 between baseline and week 6\nc p<0.05 between week 2 and week 6\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 25\n\n\n\nFigure 2. pH, TEWL and Erythema Trend\n\n\n\nb p<0.05 between baseline and week 6\n\n\n\nFigure 3.  Magnitude of pH, TEWL and erythema change in 6 weeks\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4126\n\n\n\nDiscussion\nThe integrity of the epidermis is formed by \nprotein-rich corneocytes and lipid-rich cementing \nsubstance constituting of 50% ceramide. Synthesis \nof ceramide involved \u03b2-glucocerebrosidase and \nsphingomyelinase which worked optimally at pH \nof 5.6 and 4.5 respectively.12 \u03b2 -glucocerebrosidase \nactivity is reduced in an alkaline environment at \nthe pH of 7.4 compared to pH of 5.5. In addition, \nhigher pH activates serine proteases which \ndegrade desmoglein 1 resulting in corneocytes \ndehiscence and desquamation contributing to \nfurther breaching of the epidermal integrity.13 A \nlow pH milieu of stratum corneum is desirable \nas it will enable ceramide production and reduce \nthe breakdown corneo desmosomes by inhibiting \nserine proteases activity, hence restoring skin \nbarrier integrity. Growth of Staphylococcus aureus \nis strongly suppressed at pH 4.7.14 Dermcidin, \nanionic antimicrobial peptide expressed in eccrine \nsweat glands permeabilized negatively charged \nbacterial membrane including Staphylococcus \naureus leading to bacterial death at lower pH of 5.4. \nThe permeability is absent at pH of 7.15,16 Patients \nwith AD who are susceptible to Staphylococcus \naureus colonization may improve with lowering of \ntheir skin pH as epidermal antimicrobial activity \nis optimized. However, the benefit of reducing the \nskin pH in AD to normal values and its subsequent \neffect on the disease severity pH is unclear. \n\n\n\nGalenic forms of skin cleansers which include \nsyndets and aqueous solutions are recommended \nfor bathing in patients with AD. Non-irritating, \nhypoallergenic, fragrance free and neutral to \nlow pH are listed as the properties for choosing a \ncleanser. A shorter bath duration lasting around 5 \nminutes and water temperature between 27 - 300 C \nare considered good bathing practices. However, \nthese recommendations are based on limited level \nIII evidence.17,18\n\n\n\nThe use of a pH 3.5 cleanser in our study initially \nresulted in a small reduction in skin pH which \nwas not sustained. The pH eventually became \neven higher at non lesional skin. The unexpected \nchanges in the pH values did not go hand in \nhand with the improvement observed in TEWL \nand erythema values, reduction in EASI, BSA, \nDLQI, pruritus score and overall improvement in \nAD based on the patients\u2019 own assessment. The \nlesional control site (face) skin pH, TEWL and \nerythema improved at the end of the study with \nthe use of standard AD treatment without low pH \n\n\n\ncleanser. These results imply that the improvement \nof disease activity could be due to the effect of \ntopical corticosteroids and emollients as patients \nwere more vigilant and adhered to treatment during \nthe study period. The Hawthorne effect may have \noccurred. In interventional AD studies19,20, placebo \nor vehicle arm compared with interventional arm in \naddition to standard topical treatment also showed \nimprovement in AD. The most likely reason we fail \nto demonstrate the expected reduction in pH is the \nfact that a skin cleanser is a rinse-off product which \ncould not sustain lower pH effect on the skin. \n\n\n\nCleansers has short term effect on skin pH lasting \nabout two hours after a washing.21 The use of a \nleave-on product like an emollient may show better \nresults and should be further evaluated. Acidifying \nthe skin in murine studies demonstrated promising \neffect in murine AD. Hatano et al22 showed \nthat maintenance of an acidic stratum corneum \nwith topical applications of lactobionic acid in \noxazolone-challenged mice prevented emergence of \noxazolone-induced AD. Lee NR et al23 applied acidic \ncream, vehicle and neutral cream on oxazolone-\ninduced AD mice. Mice applied with acidic cream \nhad fewer AD-like lesions, lower eczema score, \nlower TEWL. Lee et-al24 \u2018atopic march murine \nmodel\u2019 showed prevention of the occurrence of \nrespiratory allergy and skin inflammation using \nacidified Cetaphil\u00ae cream with pH 2.8. Peltonen et-\nal25 used 5% cis-urocanic acid cream with pH 6.5 \nin healthy adults and AD patients. TEWL values \nin both healthy subjects and AD patients were \nreduced. Concurrently, EASI and physician\u2019s global \nassessment improved. However, the changes in skin \npH was not documented in these studies.\n\n\n\nThere was no major intolerability or irritation with \nthe use of the low pH cleanser in this study. Only one \npatient reported initial stinging sensation. The low \npH cleanser was generally well tolerated. There were \nseveral limitations in this study. The EASI and BSA \nwere assessed by a single investigator which could \ncause bias in an outcome-based evaluation. More \nthan one assessor should be involved to calculate \nkappa value of inter-researcher agreement to \nenhance the reliability of the study. Furthermore, AD \nis a very dynamic disease affected by environmental \nchanges and daily activity causing difficulties in \nstandardization of possible confounding factors. \nIt would be best to perform a proper randomized \ncontrolled trial. Other topical AD treatments need \nto be discontinued in order to assess the sole effect \nfrom low pH cleanser. However, this would be \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 27\n\n\n\nunethical as there is a high risk of AD exacerbation \nfollowing removal of patients\u2019 standard treatment.\n\n\n\nConclusion\nRegular twice daily shower with a low pH cleanser \nimproved AD severity in terms of EASI, BSA, \nDLQI, pruritus and patients\u2019 own assessment. \nThere was a non significant improvement in skin \npH at lesional areas. At non lesional areas, pH \nsignificantly worsened. TEWL improved overall but \nonly significantly at some lesional areas. Erythema \nimproved overall but only significantly at some non \nlesional areas. The results failed to demonstrate skin \npH lowering as the cause of AD improvement. The \nlow pH cleanser was well tolerated.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowlegement\nThe authors would like to thank the Director \nGeneral of Health, Malaysia for the permission to \npublish this paper. The study received an research \ngrant from the Dermatological Society of Malaysia.\n\n\n\nReferrences\n\n\n\n1. Panther DJ, Jacob SE. The Importance of Acidification in \nAtopic Eczema: An Underexplored Avenue for Treatment. \nJ Clin Med 2015;4:970\u20138.\n\n\n\n2. Yosipovitch G, Maayan-Metzger A, Merlob P, Sirota \nL. Skin Barrier Properties in Different Body Areas in \nNeonates. Pediatrics 2000;106:105-8.\n\n\n\n3. Fluhr JW, Pfistere S, Gloor M. Direct comparison of skin \nphysiology in children and adults with bioengineering \nmethods. Pediatr Dermatol 2000;17:436\u20139.\n\n\n\n4. Jin K, Higaki Y, Takagi Y, Higuchi K, Yada Y, Kawashima M \net al. Analysis of beta-glucocerebrosidase and ceramidase \nactivities in atopic and aged dry skin. Acta Derm Venereol \n1994;74:337\u201340.\n\n\n\n5. Hoeger PH, Enzmann CC. Skin physiology of the neonate \nand young infant: A prospective study of functional \nskin parameters during early infancy. Pediatr Dermatol \n2002;19:256\u201362. \n\n\n\n6. Braun-Falco O, Korting HC. Normal pH value of human \nskin Hautarzt 1986;37:126\u20139.\n\n\n\n7. Schade H, Marchionini A. Der S\u00e4uremantel der Haut (nach \nGaskettenmessung). Klin Wochenschr 1928;7:12-4.\n\n\n\n8. Draelos ZD. The science behind skin care: Cleansers. J \nCosmet Dermatol 2018;17:8\u201314.\n\n\n\n9. Baranda L, Gonz\u00e1lez-Amaro R, Torres-Alvarez R, Alvarez \nC, Ram\u00edrez C. Correlation between pH and irritant \neffect of cleansers marketed for dry skin. Int J Dermatol \n2002:41:494\u20139.\n\n\n\n10. Knor T, Meholji\u0107-Fetahovi\u0107 A, Mehmedagi\u0107 A. Stratum \ncorneum hydration and skin surface pH in patients with \natopic dermatitis. Acta Dermatovenerol Croat 2011;19:242-\n7.\n\n\n\n11. Lewis-Jones MS, Finlay AY. The Children\u2019s Dermatology \nLife Quality Index (CDLQI): initial validation and practical \nuse. Br J Dermatol 1995;132:942-9.\n\n\n\n12. Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu \nof the horny layer: New findings on the physiology \nand pathophysiology of skin pH. Am J Clin Dermatol \n2002;3:261\u201372.\n\n\n\n13. Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown \nBE, Rogiers V et al. Sustained serine proteases activity \nby prolonged increase in pH leads to degradation of lipid \nprocessing enzymes and profound alterations of barrier \nfunction and stratum corneum integrity. J Invest Dermatol \n2005;125:510\u201320.\n\n\n\n14. Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural \nskin surface pH is on average below 5, which is beneficial \nfor its resident flora. Int J Cosmet Sci 2006;28:359\u201370.\n\n\n\n15. Burian M, Schittek B. The secrets of dermcidin action. Int \nJ Med Microbiol 2015;305:283-6.\n\n\n\n16. Becucci L, Valensin D, Innocenti M, Guidelli R. Dermcidin, \nan anionic antimicrobial peptide: influence of lipid \ncharge, pH and Zn2+ on its interaction with a biomimetic \nmembrane. Soft Matter 2014;10:616-26.\n\n\n\n17. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech \nS, Deleuran M, Fink-Wagner A et al. Consensus-based \nEuropean guidelines for treatment of atopic eczema (atopic \ndermatitis) in adults and children: Part I. J Eur Acad \nDermatol Venereol 2018;32:657-82. \n\n\n\n18. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller \nAS, Schwarzenberger K et al. Guidelines of care for the \nmanagement of atopic dermatitis: section 2. Management \nand treatment of atopic dermatitis with topical therapies. J \nAm Acad Dermatol 2014;71:116-32.\n\n\n\n19. Guttman-Yassky E, Brunner PM, Neumann AU, Khattri S, \nPavel AB, Malik K et al. Efficacy and safety of fezakinumab \n(an IL-22 monoclonal antibody) in adults with moderate-\nto-severe atopic dermatitis inadequately controlled by \nconventional treatments: A randomized, double-blind, \nphase 2a trial. J Am Acad Dermatol 2018;78:872\u201381.\n\n\n\n20. Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, \nTa\u00efeb A et al. Efficacy and safety of lebrikizumab (an anti-\nIL-13 monoclonal antibody) in adults with moderate-to-\nsevere atopic dermatitis inadequately controlled by topical \ncorticosteroids: A randomized, placebo-controlled phase II \ntrial (TREBLE). J Am Acad Dermatol 2018;78:863-71.\n\n\n\n21. Korting HC, Braun-Falco O. The effect of detergents on \nskin pH and its consequences. Clin Dermatol 1996;14:23\u2013\n7.\n\n\n\n22. Hatano Y, Man MQ, Uchida Y, Crumrine D, Scharschmidt \nTC, Kim EG et al. Maintenance of an Acidic Stratum \nCorneum Prevents Emergence of Murine Atopic Dermatitis. \nJournal of Investigative Dermatology 2009;129:1824\u201335.\n\n\n\n23. Lee NR, Lee HJ, Yoon NY, Kim D, Jung M, Choi EH. \nApplication of Topical Acids Improves Atopic Dermatitis \nin Murine Model by Enhancement of Skin Barrier \nFunctions Regardless of the Origin of Acids. Ann Dermatol \n2016;28:690-6.\n\n\n\n24. Lee HJ, Yoon NY, Lee NR, Jung M, Kim DH, Choi EH. \nTopical acidic cream prevents the development of atopic \ndermatitis- and asthma-like lesions in murine model. Exp. \nDermatol 2014;23:736\u201341.\n\n\n\n25. Peltonen JM, Pylkk\u00e4nen L, Jans\u00e9n CT, Volanen I, Lehtinen \nT, Laihia JK et al. Three randomised phase I/IIa trials of \n5% cis-urocanic acid emulsion cream in healthy adult \nsubjects and in patients with atopic dermatitis. Acta Derm \nVenereol 2014;94:415\u201320.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4128\n\n\n\nORIGINAL ARTICLE\n\n\n\nSevere Cutaneous Adverse Reactions: A 5-year Experience in a \nTertiary Referral Hospital in Malaysia\nRajalingam Ramalingam, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang\n\n\n\nAbstract\nIntroduction: \nSevere cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and \ntoxic epidermal necrolysis (TEN) carry significant morbidity and mortality. Awareness of local \nclinicoepidemiology of SCARs may play a vital role in future clinical management protocols. \n\n\n\nMethods: \nA retrospective review of all patients referred to the Department of Dermatology of Hospital Tengku \nAmpuan Afzan, Kuantan, Pahang, Malaysia with confirmed SCAR from 2013 to 2017 was carried out \nto determine the epidemiologic pattern of SCARs in the local population. \n\n\n\nResults: \nA total of 45 patients with 45 reactions were seen among 9,813 new patients, yielding an incident \nrate of 0.46% (yearly SCAR rate range: 0.38 \u2013 0.73%). SCARs accounted for 32.8% of all cutaneous \nadverse drug reactions. SJS (16 cases) was the most frequent SCAR, followed by drug reaction with \neosinophilia and systemic symptoms (DRESS) (12), TEN (8), acute generalized exanthematous \npustulosis (AGEP) (8) and acute erythroderma (1). A third of our patients were aged between 41 \nand 60 years, while the median age was 50 years (range: 4 \u2013 92). The male:female ratio was 1.04:1. \nAllopurinol was the commonest single culprit drug causing 50%, 25% and 16.7% of SJS, TEN and \nDRESS respectively. Antimicrobials as a group contributed to 44.4% of SCARs. Eight patients died, \nincluding 5 from DRESS, resulting in a mortality rate of 17.8%. \n\n\n\nConclusion: \nSJS was the commonest SCAR encountered in our center, while the commonest culprit drug was \nallopurinol. Antimicrobials as a group caused the most SCARs.\n\n\n\nKey words: Severe cutaneous adverse reaction (SCAR), Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), \nDrug reaction with eosinophilia and systemic symptoms (DRESS), Acute generalized exanthematous pustulosis (AGEP), \n\n\n\nIntroduction\nCutaneous adverse drug reactions (CADR) range \nwidely from pruritus, urticaria and maculopapular \nexanthem to potentially life-threatening severe \ncutaneous adverse reactions (SCARs) such as \nStevens-Johnson syndrome (SJS), toxic epidermal \nnecrolysis (TEN), drug reaction with eosinophilia \nand systemic symptoms (DRESS), acute generalized \nexanthematous pustulosis (AGEP), generalized \nbullous fixed drug eruptions and acute erythroderma \namong others. SCARs are associated with significant \n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology,\nHospial Tengku Ampuan Afzan, \nJalan Tanah Putih,\n25100 Kuantan, Pahang\nEmail: raj.blueheart@gmail.com \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 29\n\n\n\nmortality, ranging from 2.4 \u2013 8.2%1,2 in neighboring \nAsian countries to 6.1 \u2013 6.9%3,4 locally. This in turn \nleads to higher healthcare costs.5 Early recognition \nand prompt diagnosis of SCARs are fundamental in \nthe identification of culprit drugs, where rapid drug \nwithdrawal is essential in reducing mortality and \npreventing long-term sequelae such as disfiguring \ndystrophic scars and dyspigmentation, alopecia and \nnail loss, visual impairment and symblepharon, \nsialadenitis and dental loss, genital synechiae \nand never forgetting long-lasting psychological \ncomplications. \n\n\n\nDrugs implicated in SCARs vary according to region \nand local health care policies. The commonest \nculprit drugs worldwide have almost always been \nantibiotics, anti-epileptic drugs (AEDs), non-\nsteroidal anti-inflammatory drugs (NSAIDs) and \nallopurinol,1-4,6-9 although other newer drugs are \nnow increasingly being reported to cause SCARs, \nespecially chemotherapy drugs, monoclonal \nantibodies and targeted therapies.10-12 Unfortunately, \na lack of awareness of drug reactions both among \nhealth care providers as well as the general public, \nleads to under-reporting and subsequently, an \nincomplete picture of the true epidemiology and \nburden of SCARs in many countries, including \nMalaysia.\n\n\n\nThe state of Pahang is the largest in Peninsular \nMalaysia, with an approximate land area of \n35,840km2 and with a population of 1,670,000, \nwhich includes 1,304,300 (78.1%) Malays, 232,700 \n(13.9%) Chinese, 65,700 (3.9%) Indians and \n67,500 (4.0%) indigenous peoples.13,14 Pahang has \nthe largest population of indigenous peoples in \nPeninsular Malaysia. As different ethnic groups \nhave different risks for developing SCARs,15,16 \nwe sought to determine the local epidemiological \npattern, as such data is greatly limited.\n\n\n\nWe hope that awareness of the pattern of SCARs \nin Pahang, especially with regards to gender \nand ethnicity, will play a vital role in prescribing \npractices by health care providers.\n\n\n\nMaterials and Methods\nThis is a retrospective review of all patients with \nconfirmed SCAR referred to the Department of \nDermatology of Hospital Tengku Ampuan Afzan, \nPahang, the state hospital and the sole dermatology \nreferral center, from 2013 to 2017. Both outpatients \nand inpatients were included. As SCAR notification \nis required as part of the national dermatological \n\n\n\nservices key performance index (KPI) monitoring, \nthe list of patients referred to the Department of \nDermatology and subsequently notified, was readily \navailable in departmental data storage. \n\n\n\nThe respective case-notes were traced and reviewed \nbefore demographic data and other variables were \nrecorded. The diagnosis of SCARs was established \nbased on the RegiSCAR-Group diagnostic criteria, \nand includes SJS, TEN, DRESS and AGEP.17,18 The \nmost likely culprit drug was determined via the \nNaranjo Probability Scale.19 The data were then \nanalyzed using Microsoft Office Excel 2017. \n\n\n\nResults\nOut of 137 cases of CADR referred to our center \nover that period of time, 45 (32.8%) were SCARs. \nThey were among 9,813 new patients seen in the \ndepartment of dermatology during that five-year \nperiod, yielding an incidence rate of 0.46% (yearly \nSCAR rate range: 0.38 \u2013 0.73%). There were 23 \n(51.1%) men and 22 (48.8%) women with SCARs, \nwith a male:female ratio of 1.04:1. SCARs were \nfound in 32 (71.1%) Malay, 8 (17.8%) Chinese, 2 \n(4.4%) Indian and 3 (6.7%) indigenous patients, as \nillustrated in Table 1. Despite indigenous peoples \nhaving a noticeably higher SCAR rate compared to \nthe other ethnicities, this difference was statistically \nnot significant. However, this difference was \nsignificant when comparing the SCAR rate between \nindigenous and non-indigenous groups (p=0.02). \n\n\n\nFour (8.9%) patients were 20 years of age or below, \n10 (22.2%) were aged 21 \u2013 40, 15 (33.3%) were \naged 41 \u2013 60, 12 (26.7%) between 61 \u2013 80, while \n4 (8.9%) were above the age of 80. The median age \nwas 50 years (range: 4 \u2013 92 years).\n\n\n\nTable 1. Rates of SCAR among both genders and various ethnic \ngroups\n\n\n\nNo. of new \npatients\nN (%)\n\n\n\nNo. with \nSCAR\nN (%)\n\n\n\nSCAR \nrate\n(%)\n\n\n\np\n\n\n\nGender\nMale\nFemale\n\n\n\n4,738 (48.3)\n5,075 (51.7)\n\n\n\n23 (51.1)\n22 (48.9)\n\n\n\n0.48\n0.43\n\n\n\n0.704\n\n\n\nEthnicity\nMalay\nChinese\nIndian\nIndigenous\nForeigners\n\n\n\nIndigenous\nNon-indigenous\n\n\n\n7,714 (78.6)\n1,469 (15.0)\n\n\n\n424 (4.3)\n195 (2.0)\n11 (0.1)\n\n\n\n195 (2.0)\n9,618 (98.0)\n\n\n\n32 (71.1)\n8 (17.8)\n2 (4.4)\n3 (6.7)\n\n\n\n0\n\n\n\n3 (6.7)\n42 (93.3)\n\n\n\n0.41\n0.54\n0.47\n1.54\n\n\n\n0\n\n\n\n1.54\n0.44\n\n\n\n0.136\n\n\n\n0.024\n\n\n\nTotal 9,813 45 0.46\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4130\n\n\n\nThere were 16 cases (35.6%) of SJS, 12 (26.7%) \nDRESS, 8 (17.8%) TEN, 8 (17.8%) AGEP and one \n(2.2%) acute erythroderma. There were no cases \nof SJS/TEN overlap in our cohort. SJS was seen in \n12 (75.0%) Malay and 4 (25.0%) Chinese patients, \nDRESS in 7 (58.3%) Malay, 2 (16.7%) Chinese and \n3 (25.0%) indigenous patients, TEN in 4 (50.0%) \nMalay, 2 (25.0%) Chinese and 2 (25.0%) Indian \npatients, while AGEP was seen exclusively among \nMalay patients. The only SCAR seen among the \nindigenous peoples in our cohort was DRESS, all \nof them secondary to Dapsone as part of the World \nHealth Organization (WHO) multi-drug therapy \n(MDT) for leprosy. Twice as many women had \nSJS compared to men (68.8% versus 31.2%), while \ntwice as many men had DRESS compared to women \n\n\n\nSJS DRESS TEN AGEP Acute Erythroderma\nN 16 12 8 8 1\nMedian age (years) \n(range)\n\n\n\n51.1\n(4-92)\n\n\n\n49\n(19-71)\n\n\n\n55.1\n(34-74)\n\n\n\n47.9\n(14-87)\n\n\n\n38\n\n\n\nAge group (years) (%)\n\u226420\n21-40\n41-60\n61-80\n>80\n\n\n\n1 (6.2)\n4 (25.0)\n6 (37.5)\n2 (12.5)\n3 (18.8)\n\n\n\n1 (8.3)\n2 (16.7)\n6 (50.0)\n3 (25.0)\n\n\n\n0\n\n\n\n0\n1 (12.5)\n3 (37.5)\n4 (50.0)\n\n\n\n0\n\n\n\n2 (25.0)\n2 (25.0)\n\n\n\n0\n3 (37.5)\n1 (12.5)\n\n\n\n0\n1 (100.0)\n\n\n\n0\n0\n0\n\n\n\nEthnicity (%)\nMalay\nChinese\nIndian\nIndigenous\n\n\n\n12 (75.0)\n4 (25.0)\n\n\n\n0\n0\n\n\n\n7 (58.3)\n2 (16.7)\n\n\n\n0\n3 (25.0)\n\n\n\n4 (50.0)\n2 (25.0)\n2 (25.0)\n\n\n\n0\n\n\n\n8 (100.0)\n0\n0\n0\n\n\n\n1 (100.0)\n0\n0\n0\n\n\n\nGender (%)\nMale\nFemale\nMale:Female\n\n\n\n5 (31.2)\n11 (68.8)\n\n\n\n1:2.2\n\n\n\n8 (66.7)\n4 (33.3)\n\n\n\n2:1\n\n\n\n5 (62.5)\n3 (37.5)\n1.67:1\n\n\n\n4 (50.0)\n4 (50.0)\n\n\n\n1:1\n\n\n\n1 (100.0)\n0\n-\n\n\n\nMedian latency (days) 23 22.5 5 3 14\nCulprit individual drugs \n(%)\n\n\n\n1.   Allopurinol: 8 \n(50.0)\n\n\n\n2.   Erythromycin, \nAmoxycillin-\nClavulanate: 2 \neach (12.5)\n\n\n\n3.   Amoxycillin, \nCarbamazepine, \nAnti-TB: 1 each \n(6.25)\n\n\n\n1.  Dapsone: 3 (25.0)\n2.  Allopurinol: 2 \n\n\n\n(16.7)\n3.  Cefuroxime, \n\n\n\nPhenytoin, \nBenzylpenicillin, \nAnti-TB, \nCloxacillin, TCM, \nCephalexin: 1 each \n(8.3)\n\n\n\n1.   Allopurinol: 2 \n(25.0)\n\n\n\n2.   TCM, \nCefuroxime, \nPiperacillin-\nTazobactam, \nCotrimoxazole: 1 \neach (12.5)\n\n\n\n1.   Ampicillin-\nSulbactam: 3 \n(37.5)\n\n\n\n2.   TCM: 2 (25.0)\n3.   Clindamycin, \n\n\n\nParacetamol, \nErythromycin: 1 \neach (12.5)\n\n\n\n1.   TCM: 1 (100.0)\n\n\n\nCulprit group of drugs 1.   Allopurinol: 8 \n(50.0)\n\n\n\n2.   Antimicrobials: 6 \n(37.5)\n\n\n\n3.   AED: 1 (6.25)\n\n\n\n1.   Antimicrobials: 8 \n(66.7)\n\n\n\n2.   Allopurinol: 2 \n(16.7)\n\n\n\n3.   AED: 1 (8.3)\n\n\n\n1.   Antimicrobials: 3 \n(37.5)\n\n\n\n2.   Allopurinol: 2 \n(25.0)\n\n\n\n3.   TCM: 1 (12.5)\n\n\n\n1.   Antimicrobials: 5 \n(62.5)\n\n\n\n2.   TCM: 2 (25.0)\n3.   Analgesic: 1 \n\n\n\n(12.5)\n\n\n\n1.   TCM: 1 (100.0)\n\n\n\nOutcome (%)\nRecovered\nDeath\nNo data\n\n\n\n7 (43.8)\n1 (6.2)\n8 (50.0)\n\n\n\n6 (50.0)\n5 (41.7)\n1 (8.3)\n\n\n\n2 (25.0)\n2 (25.0)\n4 (50.0)\n\n\n\n8 (100.0)\n0\n0\n\n\n\n1 (100.0)\n0\n0\n\n\n\n(66.7% versus 33.3%). Eight patients died, 5 from \nDRESS, 2 from TEN and one from SJS, giving rise \nto an overall mortality rate of 17.8%. \n\n\n\nAllopurinol was the commonest individual culprit \ndrug causing 12 (26.7%) SCARs, namely 8 (50.0%) \nSJS, 2 (16.7%) DRESS and 2 (25.0%) TEN. This \nis followed by traditional and complimentary \nmedicine (TCM), causing 5 SCARs, namely 2 \n(25.0%) AGEP, one (8.3%) DRESS, one (12.5%) \nTEN and one (100.0%) acute erythroderma. As a \ngroup, antimicrobials were the predominant group \nwhich contributed to 22 (48.9%) SCARs, with \nDapsone, Ampicillin-Sulbactam and Erythromycin \ncausing 3 (6.7%) SCARs each. These results are \ndescribed in detail in Table 2 below. \n\n\n\nTable 2. Demographic Pattern, Culprit Drugs and Clinical Outcome for various SCARs\n\n\n\nSJS: Stevens-Johnson syndrome; DRESS: drug-related eosinophilia with systemic symptoms; TEN: toxic epidermal necrolysis; AGEP: \nacute generalized exanthematous pustulosis; anti-TB: antituberculous drugs; TCM: traditional and complimentary medicine; AED: \nantiepileptic drugs\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 31\n\n\n\nThe most common comorbid disease seen in our \ncohort was hypertension (16 patients), followed by \ntype 2 diabetes mellitus (13) and hyperlipidemia \n(9). Chronic kidney disease was seen in 5 patients, \ngout in 4, human immunodeficiency virus (HIV) \ninfection in 2 while 5 patients had concomitant \nsepsis. Nine individuals had no comorbid disease. \nSeven (15.6%) patients were current smokers \nwhile 12 (26.7%) had never smoked. Housewives \naccounted for 7 (15.6%) of SCARs, more than any \nother occupation. \n\n\n\nClose to half of our patients were taking 2 \u2013 4 drugs \nat the time they developed SCAR, while 8 (17.8%) \nwere only taking a single drug and another 8 (17.8%) \nwere taking 5 drugs or more.\n\n\n\nDiscussion\nSCARs accounted for 32.8% of reported CADR \nin the same time period in our center. This is \ncomparable to many local as well as international \nstudies,3,6,20-22 with prevalence rates ranging from \n10.8 \u2013 52.8%. It is not surprising considering all \nof these studies, including ours, involved tertiary \ndermatological referral centers. While we may \nsee many SCARs, the same cannot be said about \nCADR, whereby mild, transient exanthems might \ngo unnoticed or unrecognized as a CADR. This may \nin turn reflect the insufficient awareness of drug \nreactions both among health care providers as well \nas the general public. \n\n\n\nOverall, SCARs occurred with equal frequency \namong men and women in our cohort. Once again, \nsimilar findings were noted in other retrospective \nreviews,3,6,23,24 although there are others that found \nvarying results.2,4,25 SCAR rate was noticeably \nhigher among the indigenous peoples when \ncompared to the non-indigenous group. This is \nmost likely due to the higher prevalence of leprosy \namong the indigenous peoples referred to our center \ncompared to non-indigenous races, since all three \ncases of SCAR among the indigenous peoples in \nthis study were due to Dapsone-induced DRESS \nand all three had leprosy. Nevertheless, we are \nalso aware that there are specific genetic markers \nfor carbamazepine26-29 and phenytoin-induced30-33 \nSCARs, and that these alleleic markers occur with \nvarying frequency in different ethnic populations. \nWe also know that the HLA-B*13:01 allele is \nassociated with dapsone-induced hypersensitivity \nsyndrome (DHS),34-37 and that this allele is found \nin various ethnic populations worldwide with \nvarying frequency, including among the three \n\n\n\nmain indigenous groups in Peninsula Malaysia, \nnamely the Temuan, Jehai and Kensiu.38 In fact, two \nindigenous siblings with lepromatous leprosy being \ntreated with dapsone as part of the WHO MDT \nregime who developed dapsone-induced DRESS in \nour cohort were found to be heterozygous carriers \nof the HLA-B*13:01 allele.39 Clearly, future, more \ncomprehensive pharmacogenomic studies involving \nthe indigenous peoples of Pahang are required.\n\n\n\nSJS was the commonest SCAR observed in our \nstudy, and this is the same with the other Asian \ncountries as well as the other Malaysian centers, as \nillustrated in Table 3. However, SJS in our center \nonly made up approximately a third of all SCARs, \nwhereas in the other Malaysian hospitals, SJS made \nup more than half. Twice as many women had \nSJS compared to men, while twice as many men \nhad DRESS. Other studies also showed that more \nwomen had SJS compared to men5,40 while more \nmen had DRESS.7,41\n\n\n\nIndividually, allopurinol was the most frequent \nindividual cause of SCARs in many centers both in \nand outside of Malaysia.1-4,7,8,20,42 Nevertheless, as a \ngroup, antimicrobials were the predominant group \ncausing SCARs in most of the studies listed in Table \n3, including ours, ranging from 33.7 \u2013 58.0% of all \nSCARs.1,2,6,7 This is not surprising given the high \ninfectious diseases burden in tropical and subtropical \nAsia. Antimicrobials, antiepileptic drugs (AEDs) \nand allopurinol continue to be the major causes of \nSCARs in Malaysia for close to twenty years. It is \ninteresting to note that antimicrobials contributed \ntowards 66.7% of DRESS in our study. A review \nof literature revealed that the culprit drugs most \ncommonly causing DRESS were AEDs, allopurinol \nand sulfonamides.43-46 While other cohorts did \nrecord antimicrobials as the predominant cause of \nDRESS,47,48 the percentage was not nearly as high \nas ours, although ranging from 42.2 \u2013 51.0%.  This \nis probably due to a referral bias of DRESS patients \nwith severe infections by other departments within \nthe hospital or from district health care facilities.\n\n\n\nOur overall SCARs mortality rate of 17.8% was \nhigher than all the other centers listed in Table 3, \nand this was largely due to mortality from DRESS \n(41.7%). Several studies have reported overall in-\nhospital mortality of 22% in Europe for both SJS \nand TEN9,49 which is comparable to our cohort, and \n5-10% for DRESS.43,50,51 The high mortality in our \nstudy may be explained by the fact that as the only \ntertiary dermatology referral center in the entire \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4132\n\n\n\nstate, we tend to receive most, if not all, SCARs to \nour center. The long latency period of DRESS and \nits mimicry of common systemic infections also \ndelays prompt diagnosis, referral and treatment, thus \nfurther contributing to an overall increased mortality \nrate. Nevertheless, in light of the exceptionally high \nmortality rate of DRESS in our cohort, the cause \nof death, duration of systemic therapy, presence \nof systemic complications, reactivation of latent \nviruses and duration of post-discharge surveillance \nof these cases should be analyzed in greater detail. \n\n\n\nThe lower mortality rates in the other Malaysian \nhospitals listed in Table 3 below may be due to \n\n\n\nthe availability of many other health care facilities \nnearby providing tertiary dermatology consult and \ncare. Unfortunately, this is not the case in Pahang. \n\n\n\nLimitations\tof\tthe\tStudy\nNot all the case-notes had complete data entry. \nHence, the study is subjected to confounding, where \ncertain risk factors may be present but unfortunately \nwere not measured. Other variables associated with \nmortality, such as cause of death and organ-specific \ncomplications were not always recorded in the case-\nnotes either, making explanation of high mortality \nrates challenging.\n\n\n\nTable 3. Comparison of clinicoepidemiological studies on SCAR in Malaysia and various Asian countries\n\n\n\nLi\tLF,\t\net al6\n\n\n\n(1994\t\u2013\t2002)\nBeijing,\nChina\nN=50\n\n\n\nChoon SE, \net al3\n\n\n\n(2001\t\u2013\t2010)\nJohor Bahru, \n\n\n\nMalaysia\nN=144\n\n\n\nSu P, \net al1\n\n\n\n(2007\t\u2013\t2011)\nSingapore\n\n\n\nN=42\n\n\n\nTee SH, \net al4\n\n\n\n(2009\t\u2013\t2013)\nKlang,\n\n\n\nMalaysia\nN=33\n\n\n\nKlaewsongkram\t\nJ, et al2\n\n\n\n(2013\t\u2013\t2015)\nThailand\n\n\n\nN=97\n\n\n\nSharma R, \net al22\n\n\n\n(2015)\nJammu,\n\n\n\nIndia\nN=44\n\n\n\nLoo\tCH,\t\net al7\n\n\n\n(2006\t\u2013\t2015)\nPenang, \nMalaysia\nN=189\n\n\n\nOur Study\n(2013\t-\t2017)\n\n\n\nKuantan,\nMalaysia\n\n\n\nN=45\n\n\n\nMale:Female \nratio\n\n\n\n1:0.86 NA 1:1 1.36:1 1:2.03 1.59:1 1:1.20 1.04:1\n\n\n\nMean age \n(years)\n\n\n\n40.0 \u00b1 20.0 NA 51.8 42.8\t(7\t\u2013\t81) 52.7 (17 \u2013 97) (3 \u2013 65) 45\t(2\t\u2013\t87) 50.3\t(4\t\u2013\t92)\n\n\n\nMedian \nlatency \n(days)\n\n\n\n7.64 \u00b1 8.32 16\t\u2013\t28 10 (1 \u2013 36) 13.1 NA 3 \u2013 5 weeks 7 10.5\n\n\n\nIncidence/\nPrevalence \n(%)\n\n\n\nIncidence: 0.16\nPrevalence: 18.6\n\n\n\nIncidence: \n0.34\n\n\n\nPrevalence: \n43.6\n\n\n\nNA NA NA NA Incidence: \n0.42\n\n\n\nIncidence: \n0.46\n\n\n\nPrevalence: \n32.8\n\n\n\nCommonest \nSCAR (%)\n\n\n\n1. SJS (46.0)\n2. Erythroderma  \n    (32.0)\n3. DRESS \n    (20.0)\n4. TEN (12.0)\n\n\n\n1. SJS (61.1)\n2. DRESS \n    (23.6)\n3. TEN (14.6)\n4. AGEP \n    (10.4)\n\n\n\n1. SJS (54.8)\n2. AGEP \n    (23.8)\n3. TEN (11.9)\n4. DRESS \n    (4.8)\n\n\n\n1.\tSJS\t(75.8)\n2. DRESS \n    (15.1)\n3. TEN (9.1)\n\n\n\n1. SJS/TEN \n    (42.3)\n2. DRESS (40.2)\n3. AGEP (17.5)\n\n\n\n1. SJS (45.4)\n2. DRESS \n    (36.4)\n3. TEN (6.8)\n4. AGEP \n    (6.8)\n\n\n\n1. SJS (55.0)\n2.\tTEN\t(23.8)\n3. DRESS \n    (12.7)\n4.\tAGEP\t(4.8)\n\n\n\n1. SJS (35.6)\n2. DRESS \n    (26.7)\n3.\tTEN\t(17.8)\n4. AGEP \n\t\t\t\t(17.8)\n\n\n\nCommonest \nGroups \nof Culprit \nDrugs (%)\n\n\n\n1. AMs (58.0)\n2. AEDs (22.0)\n3. TCM (32.0)\n\n\n\n1. AEDs \n    (31.9)\n2. Allopurinol \n    (26.4)\n3. AMs (24.3)\n\n\n\n1. AMs (50.0)\n2. Allopurinol \n    (14.3)\n3. AEDs \n    (11.9)\n\n\n\n1. Allopurinol \n    (33.3)\n2. AMs (30.3)\n3. AEDs (12.1)\n\n\n\n1. AMs (24.7)\n2. Allopurinol \n    (21.6)\n3. AEDs (19.6)\n\n\n\n1. AEDs \n    (59.1)\n2. AMs \n    (18.2)\n3. NSAIDs \n    (11.4)\n\n\n\n1. AMs (33.7)\n2. Allopurinol \n\t\t\t\t(18.9)\n3. AEDs\n\t\t\t\t(18.4)\n\n\n\n1.\tAMs\t(48.9)\n2. Allopurinol \n    (26.7)\n3. TCM (11.1)\n\n\n\nMortality \nrate (%)\n\n\n\nNA 6.9 2.4 6.1 8.2 4.5 5.8 17.8\n\n\n\n*SJS: Stevens-Johnson syndrome; DRESS: drug-related eosinophilia with systemic symptoms; TEN: toxic epidermal necrolysis; \nAEDs: anti-epileptic drugs; TCM: traditional and complimentary medicine; NSAIDs: non-steroidal anti-inflammatory drugs; AMs: \nantimicrobials; NA: not available\n**Incidence: refers to confirmed SCAR among hospitalized patients; prevalence: refers to patients with drug hypersensitivity reactions\n\n\n\nConclusion\nSJS was the commonest SCAR encountered in our \ncenter, while DRESS had the highest mortality. \nThe commonest individual culprit drug was \nallopurinol while antimicrobials as a group caused \nthe most SCARs, reminding us of more judicious \n\n\n\nprescriptions of these agents by health care providers. \nIn addition, the indigenous peoples of Pahang may \nhave a genetic predisposition to developing SCARs, \nespecially to dapsone, but this requires future, large-\nscale, community-based pharmacogenomic studies. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 33\n\n\n\nDeclaration\tof\tConflict\tof\tInterest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of the \ndepartment of Dermatology of Hospital Tengku \nAmpuan Afzan, Kuantan, Pahang, Malaysia for \ntheir hard work in compiling the relevant records. \nWe would also like to thank the Director-General \nof Health, Malaysia, for his permission to publish \nthis article.\n\n\n\nReferences\n\n\n\n1. 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Common adverse \ncutaneous drug reaction patterns and the causative drugs in \nMalaysia. South African Family Practice 2015;57:227\u201330.\n\n\n\n22. Grando LR, Schmitt TA, Bakos RM. Severe cutaneous \nreactions to drugs in the setting of a general hospital. An \nBras Dermatol 2014;89:758-62.\n\n\n\n23. Garg HK, John LJ, Thomas IN, Muttappallymyalil J, \nKadhum W, Sreedharan J. Variety and incidence of \nCutaneous Adverse Drug Reactions in a UAE Hospital. Int \nJ Med Res Prof 2016;2:45-9.\n\n\n\n24. Hakkarainen KM, Gyllensten H, J\u00f6nsson AK, Sundell \nKA, Petzold M, H\u00e4gg S. Prevalence, nature and potential \npreventability of adverse drug events \u2013 a population-based \nmedical record study of 4970 adults. Br J Clin Pharmacol \n2013;78:170\u201383.\n\n\n\n25. Sharma R, Dogra N, Dogra D. A clinical study of \nSevere Cutaneous Adverse Drug Reactions and role of \ncorticosteroids in their Management. Indian J Drugs \nDermatol 2017;3:20-3.\n\n\n\n26. Lim KS, Kwan P, Tan CT. Association of HLA-B*1502 \nallele and carbamazepine-induced severe adverse \ncutaneous drug reaction among Asians: A review. Neurol \nAsia 2008;13:15-21.\n\n\n\n27. Chang CC, Too CL, Murad S, Hussein S. H. Association \nof HLA-B*15:02 allele with carbamazepine-induced toxic \nepidermal necrolysis and Stevens-Johnson syndrome in \nthe multi-ethnic Malaysian population. Int J Dermatol \n2011;50:221-4.\n\n\n\n28. Kulkantrakorn K, Tassaneeyakul W, Tiamkao S, \nJantararoungtong T, Prabmechai N, Vannaprasaht S et al. \nHLA-B*15:02 strongly predicts carbamazepine-induced \nStevens-Johnson syndrome and toxic epidermal necrolysis \nin Thai patients with neuropathic pain. Pain Pract \n2012;12:202-8.\n\n\n\n29. Wang Q, Zhou JQ, Zhou LM, Chen ZY, Fang ZY, Chen \nSD et al. Association between HLA-B*15:02 allele \nand carbamazepine-induced severe cutaneous adverse \nreactions in Han people of southern China mainland. \nSeizure 2011;20:446-8.\n\n\n\n30. Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung \nWH et al. Association of HLA-B*15:13 and HLA-B*15:02 \nwith phenytoin-induced severe cutaneous adverse reactions \nin a Malay population. Pharmacogenomics J 2017;17:170-\n3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4134\n\n\n\n31. Cheung YK, Cheng SH, Chan EJ, Lo SV, Ng MH, Kwan \nP. HLA-B alleles associated with severe cutaneous \nreactions to antiepileptic drugs in Han Chinese. Epilepsia \n2013;54:1307-14.\n\n\n\n32. Locharernkul C, Loplumlert J, Limotai C, Korkij W, \nDesudchit T, Tongkobpetch S et al. Carbamazepine \nand phenytoin induced Stevens-Johnson syndrome is \nassociated with HLA-B*15:02 allele in Thai population. \nEpilepsia 2008;49:2087-91.\n\n\n\n33. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui \nRC et al. Common risk allele in aromatic antiepileptic \ndrug-induced Stevens-Johnson syndrome and toxic \nepidermal necrolysis in Han Chinese. Pharmacogenomics \n2010;11:349-56.\n\n\n\n34. Wang N, Parimi L, Liu H, Zhang FA. Review on Dapsone \nHypersensitivity Syndrome among chinese patients with \nan emphasis on preventing Adverse Drug Reactions with \ngenetic testing. Am J Trop Med Hyg 2017;96:1014-8.\n\n\n\n35. Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ et \nal. HLA-B*13:01 and the Dapsone Hypersensitivity \nSyndrome. N Engl J Med 2013;369:1620-8.\n\n\n\n36. Tempark T, Satapornpong P, Rerknimitr P, Nakkam N, \nSaksit N, Wattanakrai P et al. Dapsone-induced severe \ncutaneous adverse drug reactions are strongly linked with \nHLA-B*13:01 allele in the Thai population. Pharmacogenet \nGenomics 2017;27:429-37.\n\n\n\n37. Chen WT, Wang CW, Lu CW, Chen CB, Lee HE, Hung \nSI et al. The Function of HLA-B*13:01 Involved in the \nPathomechanism of Dapsone-Induced Severe Cutaneous \nAdverse Reactions. J Invest Dermatol 2018;138:1546-54.\n\n\n\n38. Jinam TA, Saitou N, Edo J, Mahmood A, Phipps ME. \nMolecular analysis of HLA Class I and Class II genes in \nfour indigenous Malaysian populations. Tissue Antigens \n2010;75:151-8.\n\n\n\n39. Ramalingam R, Too CL, Tang MM. Dapsone \nHypersensitivity Syndrome and Dapsone-induced Liver \nInjury in Four Malaysian Indigenous Individuals with \nLeprosy. Malaysian J Dermatol 2018;40:73-9.\n\n\n\n40. Yamane Y, Aihara M, Ikezawa Z. Analysis of Stevens-\nJohnson Syndrome and Toxic Epidermal Necrolysis in \nJapan from 2000 to 2006. Allergol Int 2007;56:419-25.\n\n\n\n41. Correa-de-Castro B, Paniago AM, Takita LC, Murback \nNDN, Hans-Filho G. Drug reaction with eosinophilia and \nsystemic symptoms: a clinicopathological study of six \ncases at a teaching hospital in midwestern Brazil. Int J \nDermatol 2016;55:328\u201334.\n\n\n\n42. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bavinck \nJNB, Sidoroff A et al. Allopurinol is the most common \ncause of Stevens-Johnson syndrome and toxic epidermal \nnecrolysis in Europe and Israel. J Am Acad Dermatol \n2008;58:25-32.\n\n\n\n43. Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu \nCY, Creamer D et al. Drug reaction with eosinophilia and \nsystemic symptoms (DRESS): An original multisystem \nadverse drug reaction. Results from the prospective \nRegiSCAR study. Br J Dermatol 2013;169:1071-80.\n\n\n\n44. Chiou CC, Yang LC, Hung SI, Chang YC, Kuo TT, Ho HC \net al. Clinicopathological features and prognosis of drug \nrash with eosinophilia and systemic symptoms: a study \nof 30 cases in Taiwan. J Eur Acad Dermatol Venereol \n2008;22:1044\u20139.\n\n\n\n45. Shiohara T, Kano Y. Drug reaction with eosinophilia and \nsystemic symptoms (DRESS): incidence, pathogenesis and \nmanagement. Expert Opin Drug Saf 2017;16:139\u201347.\n\n\n\n46. Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, \nFinzi L et al. The DRESS syndrome: A literature review. \nAm J Med 2011;124:588-97.\n\n\n\n47. Skowron F, Bensaid B, Balme B, Depaepe L, Kanitakis \nJ, Nosbaum A et al. Drug reaction with eosinophilia and \nsystemic symptoms (DRESS): clinicopathological study \nof 45 cases. J Eur Acad Dermatol Venereol 2015;29:2199\u2013\n205.\n\n\n\n48. Nam YH, Park MR, Nam HJ, Lee SK, Kim KH, Roh \nMS et al. Drug reaction with eosinophilia and systemic \nsymptoms syndrome is not uncommon and shows better \nclinical outcome than generally recognized. Allergol \nImmunopathol (Madr) 2015;43:19\u201324.\n\n\n\n49. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, \nMockenhaupt M. Effects of treatments on the mortality \nof Stevens-Johnson syndrome and toxic epidermal \nnecrolysis: A retrospective study on patients included in \nthe prospective EuroSCAR Study. J Am Acad Dermatol \n2008;58:33-40.\n\n\n\n50. Bocquet H, Bagot M, Roujeau JC. Drug-induced \npseudolymphoma and drug hypersensitivity syndrome \n(Drug Rash with Eosinophilia and Systemic Symptoms: \nDRESS). Semin Cutan Med Surg 1996;15:250\u20137.\n\n\n\n51. Chen YC, Chiu HC, Chu CY. Drug reaction with \neosinophilia and systemic symptoms. Arch Dermatol \n2010;146:1373-9.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 35\n\n\n\nORIGINAL ARTICLE\n\n\n\nExtramammary Pagets Disease: 10-year Experience in a Tertiary \nDermatology Centre In Malaysia\nAnisha Bhullar1, AdvMDerm, Zhen Li Kwan2, AdvMDerm, Azura Mohd Affandi3, AdvMDerm\n\n\n\n1Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia\n2Dermatology Unit, Department of Medicine, Universiti Malaya Medical Centre, Kuala Lumpur, Malaysia\n3Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction: \nExtramammary Paget\u2019s disease (EMPD) is a rare neoplasm of apocrine gland-bearing skin. Common \nsites of occurrence include the vulva, perianal region, perineum and scrotum. Diagnosis is frequently \ndelayed, and it can also be associated with underlying genitourinary malignancies. This study is to \nevaluate the cases of EMPD and ascertain if there are higher rates of genitourinary malignancies.\n\n\n\nMethod: \nA retrospective review of all patients confirmed with EMPD histologically from Hospital Kuala \nLumpur over 10 years.\n\n\n\nResults: \nFourteen patients were identified and the median age of presentation was 64 years old. All patients \nwere of Chinese origin. None of the patients had a personal history of skin cancer. The scrotum was \nthe commonest site of presentation in males, while in women the vulva lesions predominate. The \nmedian duration of the lesions at presentation was 24 months. At the time of diagnosis, our screening \ninvestigations did not detect any visceral malignancy in the majority of the patients.\n\n\n\nConclusion: \nMajority of our patients presented late. Association with genitourinary malignancy was not established. \nOnly one patient had underlying adenocarcinoma of the vulva detected.\n\n\n\nKey words: Extramammary pagets disease, Apocrine gland, Genitourinary malignancies\n\n\n\nIntroduction\nExtramammary Paget\u2019s disease (EMPD) is a rare \nintraepidermal adenocarcinoma which commonly \npresents as erythematous eczematous plaques \naffecting skin with apocrine glands with the genitalia \nbeing the commonest site. There is an association \nwith apocrine carcinomas and internal malignancies \nparticularly affecting the gastrointestinal or \ngenitourinary tract.1\n\n\n\nThe characteristic histological finding is the \npresence of Paget cells, which are large round \ncells with abundant pale-staining cytoplasm and \na large vesicular nucleus. Immunohistochemical \nstains of primary intra-epithelial Paget\u2019s disease \n\n\n\nCorresponding Author\nDr Anisha Bhullar\nFaculty of Medicine and Health Sciences,\nUniversiti Putra Malaysia, \n43400 Serdang, Selangor, Malaysia\nEmail: anishabhullar@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4136\n\n\n\nare cytokeratin (CK) 7 positive, CK20 negative \nand gross cystic disease fluid protein (GCDFP-15) \npositive while Paget\u2019s disease spread from an \nassociated internal carcinoma are CK7 negative, \nCK20 positive and GCDFP-15 negative. Paget\u2019s \ncells also stain for periodic acid-Schiff (PAS) and \ncarcinoembryonic antigen (CEA).3  \n\n\n\nThe objective of this review was to identify the \ndemographic layout, risk factors and clinical \ncharacteristics of EMPD cases in a multiethnic \nMalaysian population.4 The current data available \nfrom the Dermatology Clinic, Hospital Kuala \nLumpur (2006-2014) showed that basal cell \ncarcinoma (BCC) is the commonest type of skin \ncancer seen in the clinic, accounting for 0.34% of \nall patient followed by squamous cell carcinoma is \n0.55%.5 At present , there are no published studies \nin Malaysia which have looked into these various \naspects of EMPD.\n\n\n\nMethodology\nWe conducted a review of all EMPD patients seen \nin the Department of Dermatology, Hospital Kuala \n\n\n\nLumpur from January 2006 to December 2015 \nof all EMPD patients. All patients with EMPD \nwere manually logged under the care of the onco-\ndermatologist. Case files were traced and data \ncollection consisting of demographics, lesion site and \nclinical morphology, investigations, management \nand follow up were documented in a data collection \nform. All cases were confirmed histologically \n(Hematoxylin and eosin stain) and CK7 positivity. \nData analysis was done using Excel.\n \nResults\nFourteen patients were identified, 9 men and 5 \nwomen. The ethnic backgrounds of all the patients \nwere Chinese with a median age of 64 years (range \n47 to 81).  The demographic and risk factors for the \n14 patients are summarized in Table 1.\n\n\n\nTwo of our patients were confirmed to be smokers \nand none worked outdoors. One patient had a history \nof skin cancer (BCC) and 1 had a past history of \nEMPD was which treated prior to the start date of \nour review. The median duration of lesions was 24 \nmonths before seeking treatment in our department.\n\n\n\nPatient/\nYear of \n\n\n\nDiagnosis\n\n\n\nAge\n(years) Sex Ethnicity Comorbidities Occupation Smoking Family History \n\n\n\nof\tSkin\tCancer\n\n\n\nHistory of \nPrevious \n\n\n\nMalignancy\n\n\n\nHistory of \nEMPD\n\n\n\n1/2006 79 F Chinese  NA NA NA NA - +\n2/2006 81 M Chinese NA Retired NA NA - -\n3/2007 56 F Chinese NA Housewife - NA - -\n4/2008 47 F Chinese - Travel Agent NA - - -\n5/2009 70 M Chinese Hypertension Restaurateur - - - -\n6/2009 67 M Chinese - NA + NA Colon cancer -\n7/2012 70 F Chinese - Housewife - - - -\n8/2013 67 M Chinese Hyperlipidemia Retired NA - - -\n9/2013 60 M Chinese - Factory worker NA NA - -\n10/2013 54 M Chinese Hypertension Mechanic - - - -\n11/2013 56 F Chinese Diabetes \n\n\n\nMellitus\nHousewife - - - -\n\n\n\n12/2014 63 M Chinese BPPV Technician + - - -\n13/2014 67 M Chinese - Retired (I) - - Prostate Cancer -\n14/2015 65 M Chinese Hypertension Retired(I) - - - -\n\n\n\nTable 1. Demographics and risk factors of patients with Extramammary Paget Disease\n\n\n\nThe clinical characteristics and further management \nare shown in Table 2. In our cohort, all EMPD \nlesions were situated in the genitalia region. Vulval \nwas the most common clinical site (90%) in women, \nout of which 2 cases had lesions extending to the \nperianal region. In addition, both patients with \nvulval-perianal disease had histological findings \nof EMPD with invasive adenocarcinoma of the \nvulva. A predominant localization of scrotal lesions \n\n\n\nwas seen in 8 males with 2 of these patients having \nlesions extending to the base of the penis and one had \nco-existing plaques on the inner thigh.\n\n\n\nScreening for associated neoplasms includes \ncolonoscopy, esophagastroduodenoscopy, \ncystoscopy and CT scan of the thorax, abdomen \nand pelvis. In the patients that had been screened, \none patient was found to have lung nodules detected \n\n\n\nNA - not available; BPPV - Benign paraxysmal positional vertigo\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 37\n\n\n\non CT scans and diagnosed with lung metastases. \nThis patient had a past history of prostate cancer 4 \nyears prior to developing EMPD, and his metastatic \ndisease was confirmed as recurrence of the prostate \nmalignancy.\n\n\n\nTwelve cases underwent surgical intervention.\nEight patients had wide local excision of the \ntumour followed by split skin graft. In the case of \nvulval adenocarcinoma, the patient had to undergo \na subsequent radical vulvectomy and lymph node \n\n\n\ndissection followed by localized radiotherapy daily \nfor 5 weeks and 2 sessions of brachytherapy a week \napart. Four patients had wide local excision without \ngrafting done. One patient opted for topical treatment \nconsisting of 5% imiquimod that was used for 2 \nmonths\u2019 duration with very minimal improvement. \nAnother patient underwent radiation therapy and \nwas in remission for a few months and subsequently \nrelapsed with local recurrence and developed distant \nmetastases to the bones and eventually passed away.\n\n\n\nTable 2: Clinical characteristics and management of Extramammary Paget Disease patients\n\n\n\nPatient Site Type of \nLesion\n\n\n\nLength\tof\t\nLesion\t(mm) Treatment\n\n\n\nInternal\tMalignancy\tWorkup Current \nStatus Last\tvisit\n\n\n\nOGDS Colonoscopy Cystoscopy CT Scan\n1 Perianal NA NA WLE ND ND ND ND X 2007\n2 Scrotum NA 84 WLE+SG ND ND ND ND X 2006\n3 Vulval NA 24 WLE+SG \u221a \u221a \u221a \u221a X 2007\n4 Vulval/perianal Patch 132 WLE+SG,RT \u221a \u221a \u221a \u221a Demised 2010\n5 Scrotum Plaque/\n\n\n\nerosions\n12 WLE \u221a \u221a \u221a \u221a Remission 2010\n\n\n\n6 Suprapubic Patch/\nPlaque\n\n\n\n24 WLE+SG ND \u221a ND ND X 2009\n\n\n\n7 Vulval/perianal Ulcer 10 RT \u221a \u221a ND \u221a Demised 2012\n8 Penoscrotal Plaque 48 WLE \u221a \u221a \u221a \u221a Remission 2013\n9 Scrotum Patch 12 WLE+SG \u221a \u221a \u221a \u221a Remission 2015\n10 Penoscrotal Patch/\n\n\n\nPlaque\n24 WLE \u221a \u221a ND \u221a Remission 2015\n\n\n\n11 Vulval Patch 144 WLE+SG ND ND ND \u221a X 2014\n12 Scrotum Ulcer 120 Topical \n\n\n\nimiquimod 5%\n\u221a \u221a \u221a \u221a X 2015\n\n\n\n13 Scrotum Patch 10 WLE+SG ND \u221a ND \u221a Stage 4 \nprostate \ncancer\n\n\n\n2016\n\n\n\n14 Scrotum/\nInner thigh\n\n\n\nPlaque 60 WLE+SG \u221a \u221a ND \u221a Remission 2016\n\n\n\nND- not done; \u221a- investigation carried out; WLE - wide local excision; SG- skin graft; RT- radiotherapy; X- loss to follow up\n\n\n\nDiscussion\nEMPD is a rare tumour that typically tends to occur \nat the genitalia. There are 2 postulated theories \nbehind the pathogenesis of this disease. First is \nthe development of malignancy de novo from \nwithin the epidermis and its subsequent spread to \ninvolve the adnexal structures while the second is \nthe initial proliferation of malignant cells from an \ninternal malignancy /adnexal structure followed by \ninfiltration into the epidermis.\n\n\n\nGiven the rarity of EMPD, precise risk factors have \nnot been defined. Our study shows very few smokers \nand no link to personal/family history of cancer \nin EMPD patients. Interestingly, only patients of \nChinese ethnicity have had EMPD despite Malaysia \nbeing a multi-ethnic population with a Malay \nmajority. In the Surveillance, Epidemiology and \nEnd Results (SEER) registry, the largest review till \n\n\n\ndate of EMPD cases with 1465 patients analyzed \nfound the disease to be mostly in white women but \nthe female to male ratio was only 2:1.6 In contrast \nto the female predominance among Caucasians, a \nmale predominance has been noted in studies done \nin Japan, Korea, China and Taiwan.7,8 There is no \nknown genetic basis although familial cases have \nbeen reported among Japanese and British patients.9 \nThis finding is consistent in our population where the \nmale to female ratio was found to be 1.6:1. However \nthe small sample size may not be reflective of the \nactual prevalence in an Asian setting.\n \nPruritus has been long associated as the main \ncomplaint in EMPD and Schuerch et al stated that \nmedian duration of pruritus was 2 years before \na diagnosis was made. Vulval lesions have been \nreported to occur in the highest frequencies.10 In men, \npenoscrotal lesions were predominantly seen.11 In \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4138\n\n\n\nkeeping with this study, in our patients, the median \nlength of the lesions was unusually long spanning \n8 months. As EMPD tends to share similar clinical \nappearance to other dermatoses such as eczema \n/ contact dermatitis, the initial diagnosis may be \nmissed. This may account for the delay in diagnosis \nin our center. Moreover, the small number of EMPD \ncases seen in a span of ten years may be misleading \nas some of these cases may have been directly \nreferred to the plastic surgery and/or obstetrics and \ngynaecology department.\n\n\n\nManagement is challenging due to the difficulties \nin diagnosis in view of the insidious onset and the \nsimilarity of the clinical presentation to other skin \nconditions.9 Surgical treatment, namely wide local \nexcision (WLE), has remained the mainstay of \ntreatment. In a retrospective study on Asian patients \nby Lee et al, MOHS micrographic surgery was found \nto be more effective with better long term outcomes \nas higher recurrences were found in patients who \nunderwent WLE.12\n\n\n\nRadiation therapy has demonstrated some success \nas the sole treatment modality in primary disease, \nalthough data is limited.13 Topical chemotherapy \nusing 5% topical imiquimod, has shown positive \noutcomes in the literature but it is difficult to assess \nits efficacy in our cohort as only one patient was \ntried on this treatment modality and that patient \nwas lost to follow-up.14 In one patient where local \nrecurrence occurred, we conclude the primary factor \nwas the patient\u2019s refusal to undergo surgery. This \nfemale patient had very extensive lesions that would \nhave needed radical surgery. Due to this she opted \nfor conservative treatment instead. Other treatment \noptions include photodynamic therapy (PDT), \ncarbon dioxide (CO2) laser for superficial lesions, \ntopical 5-fluorouracil and bleomycin, topical \nretionoids, systemic chemotherapy and combined \nmodality treatment.9 \n\n\n\nEMPD has long had an association with the \ndevelopment of secondary malignancies. Dorigo \net al. conducted a large review on 965 patients \nwith invasive EMPD and found an increased risk \nof colorectal and anal cancers.15 We examined \nthis in our patients and found concomitant vulval \nadenocarcinoma in 2 cases occurring at the same \nsite of the EMPD lesion detected during the initial \nskin biopsy.\n\n\n\nConclusion\nClinicians should have a high index of suspicion in \npatients presenting with eczematous/non-healing \nlesions in the genitalia. Early diagnosis with \nhistological confirmation will likely benefit the \npatients with a better prognosis, given the ability of \nthis malignancy to metastasize. Most of our patients \nhad been found to be in remission.  \n\n\n\nConflict\tof\tInterest\tDeclaration\nThere are no conflicts of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences \n\n\n\n1. Koo YT, Minn KW, Chang H. Penoscrotal extramammary\nPaget\u2019s disease with multiple lymph node metastasis. Arch\nPlast Surg 2013;40:650-2.\n\n\n\n2. Wilkinson EJ, Brown HM. Vulvar Paget disease of urothelial \norigin: a report of three cases and a proposed classification\nof vulvar Paget disease. Hum Pathol 2002;33:549-54.\n\n\n\n3. Shepherd V, Davidson EJ, Davies-Humphreys J.\nExtramammary Paget\u2019s disease. BJOG 2005;112:273-9.\n\n\n\n4. http://www.indexmundi.com/malaysia/demographics_\nprofile.html [Accessed in June 2018 December 2018]\n\n\n\n5. Heah SK, Md Noor N and Johar A. Prevalence of Skin\nDiseases in Dermatology Outpatient Clinic, Hospital Kuala\nLumpur. Malaysian J of Dermatol 2017;38:19-24.\n\n\n\n6. Karam A, Dorigo O. Treatment outcomes in a large cohort\nof patients with invasive Extramammary Paget\u2019s disease.\nGynecol Oncol 2012;125:346\u201351.\n\n\n\n7. Qi Y, Hu J, Sun C, Zhang J, Liu Q. Extramammary Paget\u2019s\ndisease: Analysis of 17 Chinese cases. Indian J of Dermatol\nVenerol Leprol 2014;80:129-33.\n\n\n\n8. Cheng PS, Lu CL, Cheng CL, Lai FJ. Significant\nmale predisposition in extramammary Paget disease: a\nnationwide population-based study in Taiwan. Br J Dermatol \n2014;171:191-3.\n\n\n\n9. Delport ES. Extramammary Paget\u2019s disease of the vulva:\nAn annotated review of the current literature. Australas J\nDermatol  2013;54:9-21.\n\n\n\n10. Fanning J, Lambert HC, Hale TM, Morris PC, Schuerch C.\nPaget\u2019s disease of the vulva: prevalence of associated vulvar \nadenocarcinoma, invasive Paget\u2019s disease, and recurrence\nafter surgical excision. Am J Obstet Gyneco 1999;180:24-7.\n\n\n\n11. Lam C, Funaro D. Extramammary Paget\u2019s disease: summary \nof current knowledge. Dermatol Clin 2010;28:807-26.\n\n\n\n12. Lee KY, Roh MR, Chung WG, Chung KY. Comparison\nof Mohs micrographic surgery and wide excision for\nextramammary Paget\u2019s disease: Korean experience.\nDermatol Surg 2009;35:34-40.\n\n\n\n13. Hata M, Omura M, Koike I, Wada H, Miyagi E, Tayama\nY et al. Role of radiotherapy as curative treatment of\nextramammary Paget\u2019s disease. Int J Radiat Oncol Biol\nPhys 2011;80:47-54.\n\n\n\n14. Ho SA, Aw DC. Extramammary Paget\u2019s disease treated with \ntopical imiquimod 5% cream. Dermatol Ther 2010;23:423-\n7.\n\n\n\n15. Karam A, Dorigo O. Increased risk and pattern of secondary \nmalignancies in patients with invasive extramammary Paget \ndisease. Br J Dermatol 2014;170:661-71.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 39\n\n\n\nCorresponding Author\nHow Kang Nien\nDermatology Unit,\nInternal Medicine Department,\nFaculty of Medicine and Health Sciences,\nUniversity Putra Malaysia,\n43400 Serdang, Selangor, Malaysia\nEmail: hkangnien@upm.edu.my\n\n\n\nCASE REPORT\n\n\n\nClear Cell Papulosis: A Rare Benign Entity with Possible Histogenetic \nRelation to Paget\u2019s Disease\nKang Nien How1, MRCP, Ikmal Hisyam Bakrin2, MPath, Norashikin Shamsudin1, FRCP\n\n\n\n1Dermatology Unit, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia\n2Pathology Department, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia\n\n\n\nSummary\nClear cell papulosis is a rare, benign disease observed in early childhood. Typically presented as white \npapules arise and cluster bilaterally along the mammary line, over the lower abdomen and pubis. The \nlesions usually spontaneously resolve with age. The significance of CCP is because of its potential \nhistogenetic relationship with Paget\u2019s disease. Herein we report the first case from Malaysia. \n\n\n\nKey words: Clear cell papulosis, Paget\u2019s disease, Extramammary paget\u2019s disease\n\n\n\nIntroduction\nClear cell papulosis is a rare, benign disease \nobserved in early childhood.1-10 There is only one \nadult reported case in the literature.4 Ever since \nclear cell papulosis (CCP) was reported in 1987 by \nKuok et al,1 there have been almost 36 other cases \nreported, mainly from Asia.1-10 It is postulated that \nhypopigmented lesions in CCP may have gone \nundetected in the white population. However, there \nare no reported cases in the dark-skinned African \ndescendent as well.11 The significance of CCP is \nbecause of its potential histogenetic relationship \nwith Paget\u2019s disease. Herein we report the first case \nfrom Malaysia. \n\n\n\nCase Report\nA 4 years old Chinese boy with glucose-6-phospate \ndehydrogenase (G6P) deficiency presented with \nmultiple asymptomatic hypopigmented tiny macules \nover the abdomen, pubic area and axillae from 3 \nmonths of age. The lesions were not hypoesthetic. \nThe skin lesions had been increasing in number for \nthe past 1 year. Treatment with topical antifungal by \na general practitioner showed no clinical response. \nThe lesions seemed to be appeared spontaneously, \nwith no history of preceding erythema on the skin. \nA skin biopsy was then obtained, revealing solitary \nlarge clear pagetoid cell scattered in basal layer \n(Fig. 1), which stained positive for CK-7, AE1/AE3 \nand periodic acid-Schiff. S-100 stain was negative \n(Fig. 2). A diagnosis of clear cell papulosis was \nthen made. Reassurance and follow up was given. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4140\n\n\n\nThroughout the 1 year follow-up, no new lesions had \ndeveloped although existing lesion did not regress. \nUnfortunately, he was lost to follow-up thereafter.\n\n\n\nFigure 1. Intraepidermal large oval to round cells displaying \ninconspicuous nucleoli with ample pale clear cytoplasm \narranged in singly and small nests (arrows), scattered in the \nbasal layer. Basal cells pigmentation is absent (Hematoxylin \nand eosin stain, original magnification x 100).\n\n\n\nFigure 2: The neoplastic cells are immunoreactive for, CK7 \n(Fig. 2a), CEA (Fig. 2b) and periodic acid-Schiff (PAS) \nfocally (Fig. 2c). They are immune-negative for Cd1a (Fig. \n2d) and S100 (Fig. 2e) (Immunohistochemical stain, original \nmagnification x400).\n\n\n\nDiscussions \nCCP affects young children with a female \npredominance. The skin lesions typically start \nbefore the age of two. The skin lesions are typically \ndescribed as asymptomatic hypopigmented macules \nor papules at the lower abdomen, pubic and anterior \ntrunk, which follows the milk line. The size ranges \n\n\n\nfrom one to 10mm of diameter, numbering from a few \nlesions to 100.6 During the first few months to years, \nlesions of CCP increase in number.11 The lesions can \neasily go unnoticed until they become numerous. \nThere is a possible genetic predisposition, inherited \nin an autosomal recessive pattern.11 However, our \npatient does not appear to have a family history of a \nsimilar skin condition. \n\n\n\nHistologically, clear cells arranging in single \nor clusters are seen at the basal or suprabasal \nkeratinocytes. These cells are larger than \nkeratinocytes, rounded, and contains abundant \neosinophilic to clear cytoplasm. Nuclei were round-\nto-oval without pleomorphism or mitosis. Melanin \npigmentation may be absent or reduced over the \nclear cell area. The dermis and subcutis level are not \ninvolved.  \n\n\n\nImmuno-histochemical features include strongly \npositive anti-cytokeratin antibody AE1/ AE3, and \nvariable carcinoembryonic antigen (CEA) and \nepithelial membrane antigen (EMA) staining and \nnegative for S-100 and CD1a, excluding them \nfrom melanocytes and Langerhans cells. Toker \ncells, Paget\u2019s disease and extramammary Paget\u2019s \ndisease demonstrates a similar staining pattern.8,11,12 \nPaget cells are stained by mucin stains, but not \ntoker cells. CCP have been reported to be variably \nstained positively by mucin stain. CCP is thought \nto be potentially preceding MPD/ EMPD in view \nof its clinical distribution, histology appearance and \nstaining properties.11 However, there are no cases of \nMPD/ EMPD reported till date.11  \n\n\n\nOnce the diagnosis is confirmed, reassurance is \nthe key. No effective therapeutic measures have \nbeen reported. In a median follow-up duration of \n11.5 years, regression was observed in 85.7% of \npatients.11 \n\n\n\nConclusion\nCCP is a disease of early childhood, demonstrating \na benign course. There is a female predominance \nand likely genetic tendency. Clinicopathological \ncorrelation is required for a diagnosis of CCP.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\t\nNil\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 41\n\n\n\nReferences\n\n\n\n1. Kuo TT, Chan HL, Hsueh S. Clear cell papulosis of the skin: \na new entity with histogenetic implications for cutaneous\nPaget\u2019s disease. Am J Surg Pathol 1987;11:827-34.\n\n\n\n2. Kumarasinghe SP, Chin GY, Kumarasinghe MP. Clear cell\npapulosis of the skin: a case report from Singapore. Arch\nPathol Lab Med 2004;128:e149-52.\n\n\n\n3. Kim YC, Bang D, Cinn YW. Clear cell papulosis: case\nreport and literature review. Pediatr Dermatol 1997;14:380-\n2.\n\n\n\n4. Mohanty SK, Arora R, Kakkar N, Kumar B. Clear cell\npapulosis of the skin. Ann Diagn Pathol 2002;6:385-8.\n\n\n\n5. Gianotti R, Cambiaghi S, Locatelli A, Gelmetti C. Clear\ncell papulosis (pagetoid papulosis) in a non-Asian patient.\nDermatology 2001;203:260-1.\n\n\n\n6. Lee JY, Chao Sc. Clear cell papulosis of the skin. Br J\nDermatol 1998;138:678-83.\n\n\n\n7. Kim SW, Roh J, Park CS. Clear cell papulosis: a case\nreport. J Pathol Transl Med 2016;50:401-3.\n\n\n\n8. Bisi Dos Santos JE, Ribeiro de Miranda MF. Clear Cell\nPapulosis: Report of a Case With Unique Clinical and\nHistologic Findings. Am J Dermatopathol 2016;38:924-6.\n\n\n\n9. Benouni S, Kos L, Ruggeri SY, North PE, Drolet BA.\nClear cell papulosis in Hispanic siblings. Arch Dermatol\n2007;143:358-60.\n\n\n\n10. Kuo TT, Huang CL, Chan HL, Yang LJ, Chen MJ. Clear\ncell papulosis: report of three cases of a newly recognized\ndisease. J Am Acad Dermatol 1995;33:230-3.\n\n\n\n11. Tseng FW, Kuo TT, Lu PH, Chan HL, Chan MJ, Hui RC.\nLong-term follow-up study of clear cell papulosis. J Am\nAcad Dermatol 2010;63:266-73.\n\n\n\n12. Yu Y, Sukhatme S, Loo DS. Clear cell papulosis: a\nconnection of clear cells to toker cells or paget disease.\nArch Dermatol 2009;145:1066-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4142\n\n\n\nCASE REPORT\n\n\n\nReactive Lymphoid Hyperplasia Occurring at both Tattoo and Non-\nTattoo Sites \nPeiqi Su, MRCP, Weiting Michelle Liang, MRCP\n\n\n\nNational Skin Centre, Singapore\n\n\n\nSummary\nCutaneous reactions to tattoos may manifest in several ways. Some of these reactions include \nsuperficial and deep local infections, systemic infections, allergic reactions, photosensitivity, \ngranulomatous reactions, lichenoid reactions and reactive lymphoid hyperplasia. Additionally, there \nare very rare reports of such complications occurring outside the tattoo site. Red tattoos are more \nfrequently associated with complications than other colours such as black, blue or green. We report an \nunusual case of reactive lymphoid hyperplasia to a black tattoo occurring at both tattoo and non-tattoo \nsites. \n\n\n\nKey words: Tattoo, Pseudolymphoma, Reactive lymphoid hyperplasia\n\n\n\nCorresponding Author \nDr Su Peiqi\nNational Skin Centre, \n1, Mandalay Road,\n308205 Singapore  \nEmail: supeiqi@nsc.com.sg\n\n\n\nIntroduction \nDecorative tattoos are a popular form of body \nart. Unfortunately, cutaneous reactions to tattoos \nmay occur in up to 30% of cases.1 These include \nsuperficial and deep local infections, systemic \ninfections, allergic reactions, photosensitivity, \ngranulomatous reactions, lichenoid reactions and \nreactive lymphoid hyperplasia. Most of these \nreactions occur at the tattoo site. Red tattoos are most \ncommonly implicated in allergic reactions but have \nalso been known to cause pseudo-lymphomatous \nreactions.2 We report an unusual case of reactive \nlymphoid hyperplasia occurring secondary to a \nblack tattoo at both the tattoo sites and over other \nparts of the body as well.\n\n\n\nCase Report \nA 42-year-old gentleman was referred to us for \nkeloids over his tattoos which were done 2 years \nago. He was treated for latent tuberculosis several \nyears ago but was otherwise healthy. He reported \nnew skin lumps over his tattoo for the past one \nmonth. There were no symptoms of pain, itch, fever \nor respiratory symptoms. On examination, he had \nblack tattoos over his right upper arm and upper \nback. Skin coloured dermal papules were palpable \nover his tattoos but other similar papules were also \nnoted medial to his right arm tattoo, left arm, left \nabdomen and right cheek (Figure 1). The initial \nclinical impression was sarcoidosis/ granulomatous \nreaction to tattoos.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 43\n\n\n\nA punch biopsy was performed over the nodule \nadjacent to the right upper arm tattoo. The \npatient declined a biopsy of the papules directly \nsuperimposed on his tattoo as he was reluctant to \nhave a scar over the tattoo.\n\n\n\nHistology showed an infiltrate consisting of \nsmall lymphocytes with no atypia. No lymphoid \nfollicles were present and there was no rimming of \nadipocytes (Figure 2). Immunostains showed that \nthe lymphocytes comprised of a mixture of CD3+ \nT cells and CD20+ B cells. The ratio of CD4+ cells \n\n\n\nto CD8+ was preserved (Figure 3). There were no \ngerminal centres seen with CD10 and no formed \nnetwork of follicular dendritic cells with CD21. \nKi67 index was about 60%.\n\n\n\nThe patient was treated with intralesional \ntriamcinolone injections to some of the larger \npapules over both arms and clobetasol propionate \ncream.  He showed a good clinical response with \nalmost complete resolution of the papules one \nmonth later (Figure 4).\n\n\n\nFigure 1. (a) Multiple papules over the right arm tattoo. Black arrow indicates biopsy site over the extra-tattoo papules. (b) Several \npapules occuring over the upper back tattoo. (c) and (d) Isolated palpable skin coloured papules over the left arm and abdomen\n\n\n\nba\n\n\n\nc d\n\n\n\nFigure 2. (a) A moderately superficial and deep perivascular and periadnexal infiltrate without any lymphoid follicles. (b) The infiltrate \nconsists mainly of lymphocytes that are small with no overt cellular atypia\n\n\n\nFig 2a Fig 2b\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4144\n\n\n\nFigure 4. Near complete resolution one month after treatment with intralesional triamcinolone and clobetasol propionate cream over \nboth arms (a)&(b) and upper back (c). Black arrows indicate previous biopsy site healed with a flat scar (a) and previous papules over \nleft arm (b)\n\n\n\nFigure 3. Immunostaining shows that the lymphocytes comprise of a mixture of CD3+ T cells (Fig 3a) and CD20+ B cells (Fig 3b). The \nratio of CD4+ (Fig 3c) to CD8+ (Fig 3d) was preserved\n\n\n\nFig 3a\n\n\n\nFig 3c\n\n\n\nFig 3b\n\n\n\nFig 3d\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 45\n\n\n\nDiscussion \nAdverse reactions to tattoos are relatively rare \nand generally unpredictable. They predominantly \ninclude immunologic (e.g. allergic dermatitis, type \nIV hypersensitivity reactions), skin infections, \nlocalised and systemic inflammatory skin reactions \n(e.g. lichen planus, granulomatous reactions, pseudo-\nlymphoma) and tumours.3 Reactive lymphoid \nproliferation, sometimes termed as cutaneous \npseudolymphoma, represents a variable group of \nbenign reactive T or B cell lymphoproliferative \nprocesses which simulate cutaneous lymphoma \nboth clinically and histologically. In such cases, \ntattoo pigments are thought to interact with the local \nimmune system to cause a chronic inflammation \nleading to a benign nonclonal proliferation of B and \nT cells. \n\n\n\nRed ink is associated more frequently with long-\nterm reactions, including granulomatous and \npseudo-lymphomatous phenomena or morphea-like \nlesions and vasculitis. Black ink is reportedly the \nsecond most common ink or pigment responsible \nfor delayed reactions although this is still rare.4,5 In a \nliterature review of 19 cases, the mean time of onset \nof cutaneous pseudolymphoma after tattooing was \n9 years.6 Red ink was the most common causative \nagent (79 %), but black, blue and green dyes also \nwere able to induce cutaneous pseudolymphoma.  In \nour case, the onset of reactive lymphoid hyperplasia \noccurred about 2 years after the tattooing with \nblack ink. Interestingly, this reaction also occurred \naway from the tattoo sites, which to the best of our \nknowledge, has not been reported before.\n\n\n\nNonallergic reactions prevalent in black tattoos may \nbe associated with carbon black. Carbon black \nnanoparticles agglomerate in the dermis over time \nforming foreign bodies that elicit reactions. Many \nblack tattoos even develop sarcoid granuloma, and \nthe \u2018papulonodular\u2019 pattern is strongly associated \nwith sarcoidosis affecting other organs.7 Similarly, \nin our case, the reactive lymphoid hyperplasia \naffected not just the tattoo site, but also other sites \nas well.\n\n\n\nPseudolymphomas may regress spontaneously, \nalthough treatment with corticosteroids, laser \ntherapy, or surgical excision may be helpful.6 In the \npresent case, the patient was treated successfully \nwith both topical and intralesional corticosteroids \nwith good response after a month. However, \ntransformation from an inflammatory response such \nas pseudolymphoma to lymphoma has been reported \n\n\n\nto occur.8 Thus, it is perhaps prudent to monitor such \npatients long term for any potential complications.\n\n\n\nConclusion\nOur report illustrates an unusual tattoo reaction of \nreactive lymphoid hyperplasia occurring over and \naway from a black tattoo which responded well \nto potent topical corticosteroids. Such patients, \nhowever, should be followed up to monitor for any \ntransformation to cutaneous lymphomas.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Kluger N. Cutaneous Complications Related to Tattoos: 31\nCases from Finland. Dermatology 2017;233:100-9.\n\n\n\n2. King BJ, Lehman JS, Macon WR, Sciallis GF. Red tattoo-\nrelated mycosis fungoides-like CD8+ pseudolymphoma. J\nCutan Pathol 2018;45:226-8.\n\n\n\n3. Islam PS, Chang C, Selmi C, Generali E, Huntley A,\nTeuber SS et al. Medical Complications of Tattoos: A\nComprehensive Review. Clin Rev Allergy Immunol\n2016;50:273-86.\n\n\n\n4. Brady BG, Gold H, Leger EA, Leger MC. Self-reported\nadverse tattoo reactions: a New York City Central Park\nstudy. Contact Dermatitis 2015;73:91-9.\n\n\n\n5. Campolmi P, Bassi A, Bonan P, Cannarozzo G, Gola M,\nRossi Degl\u2019Innocenti D et al. Cutaneous pseudolymphoma\nlocalised to black tattoo. J Am Acad Dermatol\n2011;65:e155-7.\n\n\n\n6. Marchesi A, Parodi PC, Brioschi M, Marchesi M,\nBruni B, Cangi MG et al. Tattoo ink-related cutaneous\npseudolymphoma: a rare but significant complication.\nCase report and review of the literature. Aesthetic Plast\nSurg 2014;38:471-8.\n\n\n\n7. Serup J. How to Diagnose and Classify\nTattoo Complications in the Clinic: A System of Distinctive \nPatterns. Curr Probl Dermatol 2017;52:58-73.\n\n\n\n8. Sangueza OP, Yadav S, White CR Jr, Braziel RM.\nEvolution of B-cell lymphoma from pseudolymphoma:\na multidisciplinary approach using histology,\nimmunochemistry and Southern blot analysis. Am J\nDermatopathol 1992;14:408-13.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4146\n\n\n\nCASE REPORT\n\n\n\nA Case of Beh\u00e7et\u2019s Disease with Erythema Annulare Centrifugum- \nLike Cutaneous Manifestation \nWen-Tsao Ho, MD\n\n\n\nDepartment of Dermatology, Ho Wen Tsao Skin Clinic, New Taipei City, Taiwan\n\n\n\nSummary\nBeh\u00e7et\u2019s disease is a multi-system vascular inflammatory disorder manifesting as recurrent episodes \nof oral and genital ulcers, uveitis, characteristic skin lesions, and involvement of other systems. \nDiagnosis based on clinical criteria such as the International Study Group diagnostic criteria. Two \nmain skin manifestations are papulopustular lesions and erythema nodosum-like lesions. We present \na rare case of Beh\u00e7et\u2019s disease presenting with erythema annulare centrifugum- like cutaneous lesion.\n\n\n\nKey words: Beh\u00e7et\u2019s disease, Erythema annulare centrifugum\n\n\n\nCorresponding Author \nDr Ho Wen-Tsao\nHo Wen Tsao Skin Clinic, \n179 , Sec 2, Wenhua 3rd Rd, \nLinkou District, New Taipei City, \nTaiwan, ROC\nEmail:  varec.clinic@gmail.com\n\n\n\nIntroduction \nBeh\u00e7et\u2019s disease (BD), a systemic inflammatory \ndisorder of unknown etiology, is characterized by \nrecurrent attacks of oral aphthous ulcers, genital \nulcers, skin lesions, uveitis or other manifestations \naffecting the blood vessels, gastrointestinal tract, \nand respiratory and central nervous systems. \n\n\n\nCase Report\nWe present a 34-year-old Chinese woman with \na 2-month history of a palm-sized arciform \nerythematous plaque with peripheral trailing scales \nand central clearing over left buttock (Figure 1a). \nThe annular erythema was associated with severe \nitching. This lesion had previously been treated \nwith topical antifungal agents and topical steroids \nbut it still progressively enlarged centrifugally. She \nthen came to our dermatology department for a \nsecondary opinion. \n\n\n\nPotassium hydroxide examination of the skin lesion \nyielded no hyphae or other microbes. Further blood \ntests including complete blood counts, HLA-B51 \nand antinuclear antibodies were negative. Erythema \nannulare centrifugum (EAC) was clinically \nimpressed. \n\n\n\nOn review, she recalled having had recurrent \nwell-circumscribed and painful aphthous ulcers \nand genital ulcers at least 3 times a year for two \nconsecutive years. She also complained of ocular \ndiscomfort for which the diagnosis of retinal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 47\n\n\n\nvasculopathy was subsequently designated by an \nophthalmologist who did not give any medication \nbecause of spontaneous resolution of vasculopathy \nduring follow-up. The s Pathergy test was negative \n\n\n\nby a small sterile needle penetrating the skin. The \nclinical presentations fulfilled the International \nStudy Group diagnostic criteria for incomplete \ntypes of Beh\u00e7et\u2019s disease.1 \n\n\n\nFurther incisional biopsy of the annular erythema \nwas performed and microscopically (Figure 1b); \nit presented as a neutrophilic dermatosis with \nvasculopathy. The epidermis revealed parakeratosis, \nmild acanthosis and neutrophil exocytosis. Marked \nperivascular and peri-appendageal neutrophils and \nlymphocytes infiltration were noted within the \npapillary and reticular dermis. Periodic-acid-Schiff \nstain and Acid-Fast stain were unremarkable. The \ndirect immunofluorescence study displayed no \nIgA, IgG, IgM, or C3 deposition. These findings \nwere consistent with the clinical impression of \nBD. Thereafter, the skin lesion was treated with \nsystemic corticosteroids and colchicine with rapid \nand dramatic resolution along with oral and genital \nulcers. She had no further relapse of skin lesions till \nthe time of writing, although there were recurrences \nof oral and genital ulcers.\n\n\n\nDiscussion \nBecause of the lack of a universally recognized \npathognomonic laboratory test, the diagnosis \nof BD is primarily based on clinical criteria as \nlisted in the International Study Group criteria.1 \nPathergy test is an additional but not specific exam \nand only small percent of BD patients present \npositive. Skin lesions occur in about 80% of \npatients and can be divided into two main types\u2014\npapulopustular lesions and erythema nodosum-like \nlesions.2 Papulopustular lesions represent the most \ncommon skin manifestations and consist of sterile \nfollicular lesions over an erythematous base. The \nerythema nodosum-like lesions, most commonly \n\n\n\na b\n\n\n\nseen on the legs, do not ulcerate and can resolve \nas hyperpigmented areas.3 Both of these classical \ncutaneous manifestations are included in current \nInternational Study Group criteria.\n\n\n\nInterestingly, other rare and diverse cutaneous \npresentations have been associated with BD; these \ninclude pernio-like,4 pyoderma gangrenosum-like,5 \nand Sweet\u2019s-like lesions,6 as well as verrucous \nand atrophic plaques with hemorrhagic crusts.7 In \nTaiwan, cutaneous lesions were observed in 88% \nof patients at the time of diagnosis, with pseudo-\nfolliculitis and erythema nodosum being the most \ncommon skin manifestations. Our case with an \nEAC-like skin manifestation was a distinctive \nclinical presentation of BD.8 Histologically Chen \net al. suggested that vascular inflammation is the \npathologic basis in BD and the histological spectrum \nranges from fully developed necrotizing vasculitis \nwith marked fibrinoid necrosis of vessel walls to \nperivascular inflammation with or without a marked \ninterstitial infiltrate.9 The patient\u2019s pathological \npictures corresponded to these findings in BD.\n\n\n\nThe preferred treatment modalities combine \ndifferent drugs, including topical therapies as \nwell as systemic steroids, NSAIDs, colchicine, \nand immunosuppressive and cytotoxic agents. In \nour case, the EAC-like lesion had poor response \nboth to topical antifungal and potent topical \ncorticosteroid agents but showed good response \nto oral prednisolone and colchicine. We presented \nthis unusual EAC-like manifestation over the left \n\n\n\nFigure 1. (a) An arciform erythematous plaque with peripheral trailing scales and central clearing over left buttock mimicking erythema \nannulare centrifugum; (b) Marked perivascular neutrophils and lymphocytes infiltration within the dermis. (H.E.x400)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4148\n\n\n\nbuttock in a BD patient. EAC-like annular erythema \nmay need to be considered as an atypical or rare \ncutaneous presentation of BD.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe author has no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. O\u2019Neill TW, Rigby AS, Silman AJ, Barnes C. Validation of\nthe International Study Group criteria for Beh\u00e7et\u2019s disease.\nBr J Rheumatol 1994;33:115-7.\n\n\n\n2. Balabanova M, Calamia KT, Perniciaro C, O\u2019Duffy JD. A \nstudy of the cutaneous manifestations of Beh\u00e7et\u2019s disease\nin patients from the United States. J Am Acad Dermatol\n1999;41:540-5.\n\n\n\n3. Chun SI, Su WP, Lee S, Rogers RS 3rd. Erythema nodosum-\nlike lesions in Beh\u00e7et\u2019s syndrome: a histopathologic study\nof 30 cases. J Cutan Pathol 1989;16:259-65.\n\n\n\n4. Cantini F, Salvarani C, Niccoli L, Senesi C, Truglia MC,\nPadula A et al. Beh\u00e7et\u2019s disease with unusual cutaneous\nlesions. J Rheumatol 1998;25:2469-72.\n\n\n\n5. Joshi A, Mamta. Beh\u00e7et\u2019s syndrome with pyoderma-\ngangrenosum-like lesions treated successfully with\ndapsone monotherapy. J Dermatol 2004;31:806-10.\n\n\n\n6. Cho KH, Shin KS, Sohn SJ, Choi SJ, Lee YS. Beh\u00e7et\u2019s\ndisease with Sweet\u2019s syndrome-like presentation - A report\nof six cases. Clin Exp Dermatol 1989;14:20-4.\n\n\n\n7. Aydin F, Senturk N, Yildiz L, Canturk MT, Turanli AY.\nBeh\u00e7et\u2019s disease with unusual cutaneous lesions. J Eur\nAcad Dermatol Venereol 2006;20:106-7.\n\n\n\n8. Kim DH, Lee JH, Lee JY, Park YM. Erythema annulare\ncentrifugum: analysis of associated diseases and clinical\noutcomes according to histopathologic classification. Ann\nDermatol 2016;28:257-9.\n\n\n\n9. Chen KR, Kawahara Y, Miyakawa S, Nishikawa T.\nCutaneous vasculitis in Beh\u00e7et\u2019s disease: a clinical and\nhistopathologic study of 20 patients. J Am Acad Dermatol\n1997;36:689-96.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 49\n\n\n\nCASE REPORT\n\n\n\nIntestinal Strongyloidiasis Presenting as Protein Losing Enteropathy \nin an Immunocompetent Psoriatic Child: A Case Report\nAi Leen Wee, MRCPCH \n\n\n\nPaediatric Department, Hospital Melaka, Melaka, Malaysia\n\n\n\nSummary\nIn a patient with psoriasis presenting with protein losing enteropathy, both inflammatory bowel disease \n(IBD) and parasitic infestations need to be excluded.  High index of suspicion is utmost important in \nview of the difficulty in ascertaining the diagnosis.\n\n\n\nKey words: Psoriasis, Intestinal strongyloidiasis, Protein losing enteropathy\n\n\n\nIntroduction\nChronic plaque psoriasis is the commonest type \nof psoriasis. The main differential diagnoses when \na psoriatic child presented with features of protein \nlosing enteropathy include parasitic infestations and \nIBD. Intestinal strongyloidiasis has been reported \nin a psoriatic patient following immunosuppressive \ntherapy.1 They are also more commonly seen in \nadults with chronic conditions.2 On the other hand, \nIBD and psoriasis have been shown to be related \ninflammatory diseases, probably sharing immune-\npathogenetic mechanisms.3 \n\n\n\nCase Report\nThe case illustrated here is a ten-year-old girl with \nchronic plaque psoriasis, on topical corticosteroids \nand regular phototherapy. She presented with \ngradual worsening of periorbital and pedal oedema \nfor 2 weeks. It was associated with intermittent \ncolicky epigastric pain, abdominal bloating, \nflatulence and altered bowel habit that has been \ngradually worsening past 3 months. There was \nmucus but no blood in her stool.  She experienced \nweight loss of 4 kilogrammes within a month but no \nother significant systemic symptoms. \n\n\n\nPhysical examinations revealed generalised, \nmultiple erythematous, well demarcated borders, \nscaly plaques with marked pedal oedema up to the \nshin and mild ascites. Vital signs were stable with \nno other remarkable systemic findings.  \n\n\n\nBlood investigations revealed severe \nhypoalbuminaemia of 13g/L, mildly elevated \n\n\n\nCorresponding Author \nDr Wee Ai Leen\nPaediatric Department, Hospital Melaka, \nJalan Mufti Hj Khalil, 75400 Melaka\nEmail address: weeaileen78@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4150\n\n\n\nliver enzymes (ALT 136U/L; AST 104U/L), \nhypokalaemia 2.2mmol/L, hypomagnesaemia \n0.44mmol/L and normal total white count with \neosinophilia. Inflammatory markers were within \nnormal limits and stool cultures were negative. \nOesophago-gastroduodenoscopy was normal \nwhile colonoscopy showed some non-specific \ninflammation. Biopsy results were insignificant. She \nwas transfused with albumin and started on regular \nhigh protein milk formula. Her condition improved \nand she was discharged home.  \n\n\n\nHowever, she again experienced gradual worsening \nof similar symptoms few days after discharged.  She \nwas still having intermittent colicky abdominal pain \nalthough diarrhoea was milder.  She was admitted \nwith severe anasarca.  Repeated stool culture was \nnegative but repeated biopsy via scope revealed \nlarge amount of strongyloides larvae. Strongyloides \nstercoralis was detected in stool helminth PCR. She \nwas treated with two courses of oral Albendazole \nand her condition gradually improved and resolved. \nCurrently she remained asymptomatic with \nsatisfactory growth velocity. Psoriasis improved \n(Figure 1) and phototherapy was ceased. \n\n\n\nFigure 1. Multiple erythematous, scaly, well defined borders \nplaques over bilateral legs\n\n\n\nin the stool, the possibility of IBD needed to be \nexcluded. Psoriasis and IBD are related inflammatory \ndiseases with well described epidemiologic and \ngenetic correlations.4 IBD has been increasingly \nreported in patients with psoriasis since the 1990s.4 \nIntestinal strongyloidiasis has been shown to \ninfrequently mimic IBD or to disseminate when a \npatient with IBD and unrecognised strongyloides is \ntreated with immunosuppression therapy.3\n\n\n\nStrongyloides stercoralis is an endemic intestinal \nnematode in tropical and temperate areas around \nthe world.3 It has a complicated life cycle and \ninfects humans percutaneously and has a direct, \nautoinfective and a nonparasitic free living \ndevelopmental cycle (Figure 2a).1,5 Several risk \nfactors have been associated with strongyloides \ninfestation including immunosuppressive therapy, \nhuman immunodeficiency virus infection, diabetes \nand chronic renal failure.1,2  Clinically, intestinal \nstrongyloidiasis can present as acute gastroenteritis \nbut when it becomes chronic; undiagnosed and \nuntreated, the clinical features mimics protein losing \nenteropathy.3,5 \n\n\n\nFigure 2. (a) Strongyloides stercoralis life cycle; (b) \nStrongyloides stercoralis larvae in stool\n\n\n\nDiscussion \nThe case illustrated here is a known case of chronic \nplaque psoriasis. When she presented with clinical \ncharacteristics of protein losing enteropathy \nassociated with significant weight loss and mucus \n\n\n\na\n\n\n\nb\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 51\n\n\n\nDiagnosis is not easy and straightforward. Gold \nstandard for diagnosis is serial stool examination \n(Figure 2b).5 However traditional stool \nexaminations are insensitive and require up to seven \nstool examinations to reach a sensitivity of 100%.5 \nAlthough serologic tests are quite sensitive, cross \nreactions with other filarial parasites, schistosomes, \nand Ascaris lumbricoides decreases the specificity \nof the tests.5 Duodenal biopsy is another useful \ntool, but it can be falsely negative in cases where \nnematode has not invaded the mucosa, or may \nbe misdiagnosed as eosinophilic duodenitis.3 As \nillustrated in this case, the stool examinations were \nnot sent repeatedly and the diagnosis was only \nclinched with the second duodenal biopsy. \n\n\n\nFigure 3. Strongyloides stercoralis larvae in stool\n\n\n\nOral Ivermectin is recommended as the first line \ntherapy for strongyloidiasis by the Centers for \nDisease Control and Prevention (CDC).5 Ivermectin \nwas not prescribed here as it is not licensed for \nhuman use in Malaysia. However, our patient \nresponded well to the Albendazole, CDC second \nline therapy.5\n\n\n\nConclusion\nIn this patient who is immunocompetent and not on \nimmunosuppressive therapy, it remained uncertain \nwhether there is a definite correlation of the intestinal \nstrongyloidiasis with chronic psoriasis or just a mere \ncoincident. Nonetheless, this case illustrated that \nparasitic infestation is still an important differential \nand high index of suspicion is essential.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Kumaraswamy PL, Chinnachamy R, Palanivel N,\nRajamani N. Intestinal strongyloidiasis in a psoriatic\npatient following immunosuppressive therapy: Seeing the\nunforeseen. J Sci Soc 2016;43:102-5.\n\n\n\n2. Cabral AC, Iniguez AM, Moreno T, Boia MN, Caralho-\nCosta FA. Clinical conditions associated with intestinal\nstrongyloidiasis in Rio de Janeiro, Brazil. Rev Soc Bras\nMed Trop 2015;48:321-5.\n\n\n\n3. Bosc\u00e1 Watts MM, Marco Marqu\u00e9s A, Savall-N\u00fa\u00f1ez E,\nArtero-Fullana A, Lanza Reynolds B, Andrade Gamarra\nV et al. IBD or Strongyloidiasis? Rev Esp Enferm Dig\n2016;108:516-20.\n\n\n\n4. Skroza N, Proietti I, Pampena R, La Viola G, Bernardini\nN, Nicolucci F et al. Correlations between psoriasis and\ninflammatory bowel disease. 2013;1-8.\n\n\n\n5. Parasites Strongyloides: Resources for Health\nProfessionals. Centres for Disease Control and Prevention.\nResources for Health Professional 2016.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4152\n\n\n\nCASE REPORT\n\n\n\nPeriorbital Lumps and Bumps \u2013 It\u2019s not always Xanthelasma\nRajalingam Ramalingam1, AdvMDerm, Arfahiza Selimin2, MPath\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n2Department of Pathology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nBenign fibrous histiocytoma (BFH) is a common soft tissue tumor that is commonly found in the \ndermis and subcutis. Although it can occur in any part of the body, facial involvement is rare. Herein \nwe report a rare case of periorbital BFH misdiagnosed as xanthelasma, in the hopes that increased \nawareness of this entity will lead to early intervention with improved outcomes.\n\n\n\nKey words: Benign fibrous histiocytoma, Periorbital, Fibrohistiocytic tumor, Histiocytes, Fibroblasts\n\n\n\nIntroduction\nFibrohistiocytic tumors are composed of fibroblasts, \nmyofibroblasts, neoplastic cells and multinucleated \ngiant cells of varying ratios demonstrating some \ndegree of phagocytic activity1. They include benign \nfibrous histiocytoma (BFH), a common soft tissue \ntumor commonly found in the dermis and subcutis. \nIt can occur in any part of the body, especially in \nthe extremities and rarely over the head and neck \nregion.  It is most often seen in women and can occur \nin all ages but is more common in the 20-50 age \ngroup. BFH frequently poses a diagnostic dilemma, \nfurther compounded by the variety of terms used \nfor this tumor. It is hoped that increased awareness \nof this entity may lead to early and appropriate \ninvestigation and intervention.\n\n\n\nCase Report\nA 50-year-old lady with hypercholesterolemia \npresented to our dermatology clinic complaining \nof multiple, slowly enlarging, painless lumps \nsurrounding both her eyes for the past ten years. \nThe lesions initially started as yellowish papules \nthat gradually increased in size and coalesced to \nform larger nodules. She had sought the opinion \nof many doctors and was reassured that it was due \nto her hypercholesterolemia, for which she was on \ntreatment. In the beginning, she did not pay much \nattention to the lesions as they were asymptomatic, \nbut is only now concerned because the lumps are \nbeginning to obscure her peripheral vision due to \ntheir increase in size.\n\n\n\nExamination of the skin revealed multiple firm, \n\n\n\nCorresponding Author \nDr Rajalingam Ramalingam\nDepartment of Dermatology,\nHospial Tengku Ampuan Afzan,\nJalan Tanah Putih,\n25100 Kuantan,\nPahang, Malaysia\nEmail: raj.blueheart@gmail.com \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 53\n\n\n\nnon-tender, skin-colored and yellowish papules, \nplaques and lobulated nodules of various sizes over \nbilateral periorbital regions (Figure 1, a-c). Some \nnodules and plaques were seen encroaching onto \nthe upper eyelids. There were also multiple small \nyellow papules and plaques over both medial canthi \n\n\n\nH&E x100\n\n\n\n(Figure 1, d). There were no other similar lesions \nelsewhere on her body. No lymphadenopathy or \norganomegaly was noted, and examination of \nother systems were unremarkable. Our differential \ndiagnoses included xanthelasma, plane xanthoma \nand xanthogranuloma.\n\n\n\nFigure 1. (a) \u2013 (d) Clinical presentation of the patient showed mutiple lobulated lumps, skin-colored and yellowish papules, nodules and \nplaques over bilateral periorbital regions including the eyelids and medial canthi.\n\n\n\nc dba\n\n\n\na\n\n\n\nBlood investigations revealed elevated serum \ncholesterol, LDL-cholesterol and triglycerides \n(6.79, 4.98 and 1.93 mmol/L respectively). All \nother investigations were normal. Histopathology \nof lesions over the left lower eyelid and medial \ncanthus showed diffuse infiltrates of plump spindle-\n\n\n\nAn ophthalmology consult excluded orbital \ninvolvement and she was promptly referred to the \nplastic surgeon for intervention.\n\n\n\nH&E x200\n\n\n\nFigure\t 2.\t (a)\t \u2013\t (b) Histology of the skin biopsy revealed diffuse infiltrates of plump spindle-shaped cells in a storiform pattern \ninterdigitating with deep dermal collagen.\n\n\n\nshaped cells in storiform and fasicular patterns \ninterdigitating with deep dermal collagen (Figure \n2, a-b). These cells were positive for CD68 but \nnegative for S100, CD34 and SMA. Xanthoma cells \nand multinucleated giant cells were not seen. These \nfindings were suggestive of BFH. \n\n\n\nb\n\n\n\nDiscussion \nBFH is a common quasi-neoplastic mesenchymal \nsoft tissue tumor that is commonly found in the \ndermis and subcutis.1,2 It can occur in any part of the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4154\n\n\n\nbody, especially in the extremities and rarely in the \nfacial tissues,3-6 although orbital involvement is said \nto be an exception.7,8 It has no racial predilection \nand is most often seen in women and in the 20-50 \nage group. Its histogenesis remains unclear, but is \nthought to arise from primitive mesenchymal stem \ncells following either a reactive process or a defect \nin cellular development.1\n\n\n\nThe lesions located solely to the periorbital region \nis peculiar, thus the misdiagnosis of xanthelasma \nwas not surprising. Xanthelasmas are typically \nsmall, soft, flat, yellowish plaques, although \nlarge and nodular varieties have been reported.9 \nHistology typically shows perivascular foamy \nhistiocytes within the upper dermis, with minimal \nor no fibrosis.10 Our patient however, had large, firm \nlumps with histiocytes seen infiltrating the deep \ndermis. A similar clinico-pathologic description was \nalso observed in Ronan\u2019s patient.2 Periorbital plane \nxanthomas are usually macular and demonstrate \nnumerous peri-appendageal foamy histiocytes in the \nwhole dermis.11 These were absent in our patient. \nWhile clinical presentation may be similar, adult-\nonset xanthogranulomatosis is usually associated \nwith hematologic disorders and has characteristic \nTouton giant cells in the upper and mid-reticular \ndermis,12,13 and these were not appreciated in our \npatient. \n\n\n\nThe treatment of choice is wide, local excision \nensuring clear margins.1 BFH rarely recurs (<5% \nof cases), usually following incomplete excision, \nalthough higher rates (up to 25%) have been \nreported with atypical variants.1,2 Occasionally, \nmetastasis has been documented, especially with \ndeep, penetrating types.14-16 \n\n\n\nConclusion \nIt is imperative to consider other differential \ndiagnoses of periorbital lesions other than \nxanthelasma, and not be misled by the presence of \nhypercholesterolemia. Ideally, BFH should also be \nconsidered.\n\n\n\nDeclaration\tof\tConflict\tof\tInterest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of \nthe departments of Dermatology and Pathology of \nHospital Tengku Ampuan Afzan, Kuantan, Pahang, \nMalaysia for their hard work in assisting in this \n\n\n\nendeavor. We would also like to thank the Director-\nGeneral of Health, Malaysia, for his permission to \npublish this article.\n\n\n\nReferences\n\n\n\n1. Guillou L, Folpe AL. Chapter 3: Fibroblastic and\nFibrohistiocytic Tumors; in Bone and Soft Tissue\nPathology, first edition; Folpe AL, Inwards CY, editors;\nSaunders, USA;2010:p71-5.\n\n\n\n2. Ronan SG, Tso MO. Multiple Periorbital Fibrous\nHistiocytomas \u2013 A light and Electron Microscopic Study.\nArch Dermatol 1978;114:1345-7.\n\n\n\n3. Femiano F, Scully C, Laino G, Battista G. Benign fibrous\nhistiocytoma (BHF) of the cheek: CD 68-KP1Positivity.\nOral Oncol 2001;37:673-5.\n\n\n\n4. Blitzer A, Lawson W, Biller HF. Malignant Fibrous\nHistiocytoma of the Head and Neck. Laryngoscope\n1977;87:1479-99.\n\n\n\n5. Mentzel T, Kutzner H, R\u00fctten A, H\u00fcgel H. Benign\nfibrous histiocytoma (dermatofibroma) of the face:\nclinicopathologic and immunohistochemical study of 34\ncases associated with an aggressive clinical course. Am J\nDermatopathol 2001;23:419-26.\n\n\n\n6. Honma M, Minami-Hori M, Komatsu S, Hashimoto\nM, Ishida-Yamamoto A. Subcutaneous benign Fibrous\nHistiocytoma of upper eyelid: A Review of the\nhistopathological Database at a Single Faculty in Japan. Int \nJ Clin Dermatol Res 2015;3:65-7.\n\n\n\n7. Font RL, Hidayat AA. Fibrous Histiocytoma of the Orbit\n\u2013 A Clinicopathologic Study of 150 Cases. Hum Pathol\n1982;13:199-209.\n\n\n\n8. Elbarbary HE, Idriss HF. A Case of Orbital Fibrous\nHistiocytoma: Case Report. J Clin Exp Opthamol\n2018;9:719.\n\n\n\n9. Wang P, Luo Q, Tang L. Bilateral extensive nodular\nxanthelasma palpebrarum: an infrequent case report. Int\nOphthalmol 2018;38:803-5.\n\n\n\n10. Kim J, Kim YJ, Lim H, Lee SI. Bilateral Circular\nXanthelasma Palpebrarum. Arch Plast Surg 2012;39:435-\n7.\n\n\n\n11. Lorenz S, Hohenleutner S, Hohenleutner U, Landthaler\nM. Treatment of Diffuse Plane Xanthoma of the Face with\nErbium:YAG Laser. Arch Dermatol 2001;137:1413-5.\n\n\n\n12. Ramalingam R, Johar A, Lee BR. Adult\nXanthogranulomatosis: A Case Report. Malaysian J \nDermatol 2015;35:10-2.\n\n\n\n13. Tan LC, Tan KB, Aw CW. Unusual Presentation of Adult\nXanthogranuloma. Singapore Med J 2014;55:e25-7.\n\n\n\n14. Doyle LA, Fletcher CD. Metastasizing \u201cbenign\u201d cutaneous \nfibrous histiocytoma: a clinicopathologic analysis of 16\ncases. Am J Surg Pathol 2013;37:484-95.\n\n\n\n15. Gleason BC, Fletcher CD. Deep \u201cBenign\u201d Fibrous\nHistiocytoma: Clinicopathologic Analysis of 69 Cases of\na Rare Tumor Indicating Occasional Metastatic Potential.\nAm J Surg Pathol 2008;32:354-62.\n\n\n\n16. Chung J, Namkoong S, Sim JH, Lee JS, Hong SP, Kim\nMH et al. Deep Penetrating Benign Fibrous Histiocytoma\nof the Foot associated with Throbbing Pain. Ann Dermatol\n2011;23:S239-42.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 55\n\n\n\nCORRESPONDENCE\n\n\n\nMicro-focused Ultrasound for the Treatment of Axillary Osmidrosis: \nA case report\nJiun-Yit Pan1, MRCP, Wen-Tsao Ho2, MD \n\n\n\n1National Skin Centre, Singapore  \n2Department of Dermatology, Ho Wen Tsao Skin Clinic, New Taipei City, Taiwan, ROC\n\n\n\nKey words: Micro-focused ultrasound, Axillary osmidrosis \n\n\n\nCorresponding Author\nDr Wen-Tsao Ho\nDepartment of Dermatology, \nHo Wen Tsao Skin Clinic, \n179, Sec 2, Wenhua 3rd Rd, \nLinkou District, New Taipei City, \nTaiwan, ROC \nE-mail: varec.clinic@gmail.com\n\n\n\nDear Sir,\nWe report a case of 40-year-old healthy male with \nboth hyperhidrosis and bromhidrosis who underwent \nmicro-focused ultrasound therapy. Micro-focused \nultrasound therapy is used for face lifting but also in \nliterature for axillary hyperhidrosis.1 We would like \nto extend its application on osmidrosis. \n\n\n\nWe treated the left side armpit with \u201cClassys\u201d \nUltraformer III Focused Ultrasound system. The \nhair-bearing area was treated with 400 lines of micro-\nfocused ultrasound (2MHZ 3.0mm cartridge). The \nenergy was set at 0.7 J, pitch 1.4mm and wavelength \n25mm. One month after treatment, we performed \na 3 mm punch biopsy on the both armpits for \nhistologic evaluation. A sweat collection was done \none month before and after treatment to assess the \nmolecular change of axillary secretions using liquid \nchromatography-mass spectrometry (LCMS).2 \n\n\n\nPatient tolerated the procedure well and felt \nimprovement on the malodour. A 50% reduction \nof odour after one moth follow-up was noted \nsubjectively. The apocrine glands in the high-\nintensity focused ultrasound (HIFU) treated \nspecimen demonstrated a tendency of cystic \ndilatation compared with the untreated control. \nThe glandular cells in those dilated glands are \nflat to cuboid in shape with decreased amounts of \neosinophilic cytoplasm (Fig. 1). The proportion of \ncystically dilated glands to those relatively normal \ncounterparts is about 1:1. The untreated control \nshowed normal variation from columnar glandular \ncells with abundant eosinophilic cytoplasm to cuboid \nglandular cells (Fig. 2). The peak height in LCMS \nof hydroxy-3-metyl-hexanoic acid (HMHA) was \n763082 cps (counts per second) before treatment to \n373817 cps 1 month after treatment. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 4156\n\n\n\nFigure 1. The glandular cells are flat to cuboid in shape with \ndecreased amounts of eosinophilic cytoplasm with cystic \ndilatation. (H&E stain at 40x magnification).\n\n\n\nFigure 2. As a control specimen, the apocrine glands demonstrate \nnormal variation from columnar glandular cells with abundant \neosinophilic cytoplasm (H&E stain at 40x magnification).\n\n\n\nThe axilla was suspected to show peculiarity in the \ndistribution of sweat glomeruli as there are both \napocrine and eccrine glands. The apocrine glomeruli \nwere present in the intermediate zone of the layers \nwhere the eccrine glomeruli are distributed.2 Cystic \ndilatation was present in the apocrine glands, and \nthe lining cells became flat to cuboid in shape \nhistologically. This might be because of degeneration \ncaused by heat energy delivered. HMHA in LCMS \ndropped nearly 51%. \n\n\n\nMicro-focused ultrasound may be an effective non-\ninvasive modality in the treatment of bromhidrosis. \nLarger scale studies will need to be done to assess \nits efficacy and safety.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReference\n\n\n\n1. Nestor MS, Park H. Safety and Efficacy of Micro-focused\nUltrasound Plus Visualization for the Treatment of Axillary \nHyperhidrosis. J Clin Aesthet Dermatol 2014;7:14-21.\n\n\n\n2. Ho WT, Lee LJ, Pan JY. Following Changes in the\nAxillary Secretions of Two Patients Before and After\nBromhidrosis Surgery Using Liquid Chromatography-\nMass Spectrometry. Dermatol Surg 2017;43:459-62.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 Dec Vol 41 57\n\n\n\nACKNOWLEDGEMENT\nDec\tIssue\t2018\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Adrian Yong Sze Wai\n3. Dr Agnes Heng Yoke Hui\n4. Dr Azura Mohd Affandi\n5. Dr Ch\u2019ng Chin Chwen\n6. Dr Chan Lee Chin\n7. Dr Chang Choong Chor\n8. Dr Chong Yew Thong\n9. Dr Dawn Ambrose\n10. Assoc Professor Dr Felix Yap Boon Bin\n11. Dr Henry Foong Boon Bee\n12. Dr Khor Yek Huan\n13. Dr Kwan Zhenli\n14. Dr Lee Bang Rom\n15. Dr Lo Kang Shang Chit\n16. Dr Michelle Voo Sook Yee\n17. Dr Ng Ting Guan\n18. Dato\u2019 Dr Noor Zalmy Azizan\n19. Assoc Professor Dr Norashikin bt Shamsudin\n20. Dr Norazirah Md Nor\n21. Dr Oh Hoey Hoey\n22. Dr Rajalingam Ramalingam\n23. Dr Sabeera Begum\n24. Dr Tang Jyh Jong\n25. Dr Tarita Taib\n\n\n\n\n\n"
"\n\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2014 Dec Vol 33\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:  rohnaridzwan@\nyahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology can \nbe sent to me at:\nrohnaridzwan@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation. \nThis category provides rapid publications and is meant to be a \nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in the \narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods , Results, Comment and \nReferences. A Structured Abstract of not more than 240 words \nmust be included. It should consist of four paragraphs, labelled \nBackground, Methods, Results, and Conclusions. It should \ndescribe the problem studies, how the study was performed, \nthe main results, and what the author(s) concluded from the \nresults. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and \nsummarizes the existing knowledge in a particular field. \nIt should not be an exhaustive review of the literature, and \nreferences should not exceed 100 in number. Tables, diagrams, \nand selected figures are often helpful. The length is left to the \njudgment of the author, although it generally should not exceed \n5000 words. Topics may include updates in clinically relevant \nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author who \nwill be responsible for reading the proofs must also be given on \nthe title page. The author(s) must also declare any affiliation or \nsignificant financial involvement in any organizations or entity \nwith a direct financial interest in the subject matter or materials \ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in \nthe manuscript. References from journals should include: (1) \nname(s) followed by the initials of the author(s), up to four \nauthors: if more than four authors, include the first three authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; (5) \nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A \nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) referred \nto. \n\n\n\nFor example: \nFoong HBB.  Transcontinental Dermatology: Virtual Grand \nRounds. In: Wootton R and Oakley A, editors. Teledermatology. \nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on \nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\nNotice to Authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY \n\n\n\n ORIGINAL ARTICLE\n2 Dermatomyositis: Clinical profile and \n association with malignancies in 43 \n patients\n Yap EWY, Lee BS, San VE, See CKL,\n Wong NKL, Choon SE\n\n\n\n9 A 5 year retrospective study on the clinical \n patterns and treatment outcomes of severe \n cutaneous adverse drug reactions (SCARs) \n in Hospital Tengku Ampuan Rahimah, \n Malaysia\n Tee SH, Ng TG\n\n\n\n18 Cost of medications in the treatment of \n moderate to severe acne vulgaris in \n Sarawak, Malaysia\n Yap FBB, Pubalan M\n\n\n\n23 Study of awareness and misconception \n regarding acne among non-medical college \n students\n Ti T, Oh YL, Romemacedonia JC, Wong HX, \n Mariette DS, Theingi MM\n\n\n\n QUIZ\n30 Multiple hypopigmented patches on the skin\n   Yap FBB\n\n\n\n CASE REPORT\n32 Pitfalls in the diagnosis and treatment of \n pemphigus foliaceus in a young boy\n         Ling HN,  Tagal JM,  Lee BR, Kho WM,  \n Leong KP, Pubalan M\n\n\n\n34 Perianal basal cell carcinoma: report of\n a case\n Ochi H, Pan JY\n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1MJD 2014 Dec Vol 33\n\n\n\nEditor-in-Chief \nAssociate Professor Dr Felix Yap Boon Bin \nMRCP Adv MDerm\nUniversiti Tunku Abdul Rahman\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCPI\nKuala Lumpur\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nDr Gangaram Hemandas FRCP\nKuala Lumpur\n\n\n\nDr Henry Foong Boon Bee FRCP\nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP\nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed, Penang\n\n\n\nDr Chang Choong Chor AdvMderm\nKuala Lumpur\n\n\n\nDr Ng Ting Guan MRCP AdvMDerm\nKlang, Selangor\n\n\n\nDr Tang Min Moon AdvMDerm\nKuala Lumpur\n\n\n\nDr Adawiyah Jamil MMed AdvMDerm\nKuala Lumpur\n\n\n\nDr Tang Jyh Jong MRCP AdvMDerm\nIpoh, Perak\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nExecutive Staff\nNajeeb Ahmad Safdar, MRCP - President \nKoh Chuan Keng, MRCP - Past President \nHenry Foong Boon Bee, FRCP - Vice President  \nAgnes Heng Yoke Hui, MRCP - Secretary\nNoor Zalmy Azizan, MAdvDerm - Treasurer\nMd Noh Idris, FRCP, FRCPI\nChan Lee Chin, MMed\nKhor Guat Ee, MRCP\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2014 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 MJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nDERMATOMYOSITIS: CLINICAL PROFILE AND ASSOCIATION \nWITH MALIGNANCIES IN 43 PATIENTS\n\n\n\nYap EWY1, Lee BS2, San VE2, See CKL2, Wong NKL2, Choon SE1\n\n\n\nAbstract\n\n\n\nIntroduction: Dermatomyositis is a rare idiopathic inflammatory myopathy with distinctive cutaneous \nmanifestations. This study aims to determine the demographic characteristics, clinical features and \nassociated malignancies in patients with dermatomyositis.\n\n\n\nMaterials & Methods: Dermatomyositis is a rare idiopathic inflammatory myopathy with distinctive \ncutaneous manifestations. This study aims to determine the demographic characteristics, clinical \nfeatures and associated malignancies in patients with dermatomyositis.  \n\n\n\nResults: Forty-three cases were identified, with female to male ratio of 1.26:1. Mean age of onset was \n47.8 +18.0 years. Malay and Chinese patients made up the bulk of the patients, contributing 53.5% and \n44.2% respectively. Photosensitive rash was the commonest clinical presentation, occurring in 55.8% \nof the patients, followed by Gottron\u2019s papules (46.5%), heliotrope rash (44.2%), alopecia (23.3%) \nand calcinosis (9.3%). Median Creatinine Kinase level was 293IU/L (interquartile range 89-1166), \nLactate Dehydrogenase 641IU/L (interquartile range 459-986) and Aspartate Transaminase 70.5IU/L \n(interquartile range 41.5-156.25). Concomitant malignancies occurred in 14 patients (32.5%), the \ncommonest being nasopharyngeal carcinoma (6 patients), followed by gastrointestinal tumours (3 \npatients), breast cancer (2 patients) and lymphoproliferative disorders (2 patients) and lung cancer \n(1 patient).  Of these 14 patients, malignancies were detected in 10 patients within the first year, and \n2 patients within the second year after diagnosis of DM. Two patients had malignancies diagnosed \nwithin 6 months prior to the diagnosis of DM. Malignancy accounts for 64.7% of the 17 mortalities \nrecorded. The proportion of Malay patients with paraneoplastic dermatomyositis with respect to the \ntotal number of Malay new clinic attendees over the past 13 years is 7 in 10,000 persons whereas in \nChinese patients, the proportion is 15 in 10,000 persons. \n\n\n\nConclusion: Malignancy is found in about a third of all patients, with Chinese predisposition seen. \nThis could explain why nasopharyngeal carcinoma is most prevalent in our centre.  \n\n\n\nKeywords: Dermatomyositis, paraneoplastic, malignancy\n\n\n\nCorresponding Author and Reprint Request \nEvelyn Yap, MRCP\nDepartment of Dermatology, Hospital Sultanah Aminah \nJohor Bahru, 80100 Johor Bahru,  Johor, Malaysia\nEmail: Chervil_82@hotmail.com\n\n\n\n1 Department of Dermatology, Hospital Sultanah \n Aminah Johor Bahru, Johor, Malaysia\n2 Jeffrey Cheah School of Medicine and Health \n Sciences, Monash University Malaysia\n\n\n\nIntroduction\nDermatomyositis (DM) is an idiopathic \ninflammatory myopathic condition with cutaneous \nfindings as  distinguishing feature. Classical skin \nmanifestations include Gottron\u2019s papules, heliotrope \nrash, photodermatitis, periungual telangiectasias \nand calcinosis. Amongst these, pruritus is the \ncommonest initial symptom. Muscle involvement \nis characterized by symmetrical proximal muscle \nweakness, with or without myalgia or tenderness. \nDistal muscle weakness may occur late in the course \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2014 Dec Vol 33\n\n\n\nof disease. In addition, patients may also present  \nwith systemic manifestations. It is estimated that \n35-40% of patients with DM suffers from interstitial \nlung disease.1, 2\n\n\n\nThe most commonly used criteria for the diagnosis of \nDM is the Bohan and Peters criteria, which consists \nof: (1) symmetrical proximal muscle weakness \n(2) elevated muscle enzymes such as creatinine \nkinase and aldolase (3) pathological features of \nmyositis on muscle biopsy (4) evidence of myositis \non electromyogram (EMG), e.g. polyphasic, short, \nsmall motor unit potentials, fibrillation, positive \nsharp waves, increased insertional irritability, and \nrepetitive high-frequency discharge (5) classical \ncutaneous features. Presence of cutaneous features \nis mandatory to diagnose DM. Along with \ncutaneous features, presence of 3 out of criteria 1-4 \nfulfilled will render the diagnosis of DM \u2018definite\u2019, \n\u2018probable\u2019 if 2 criteria are fulfilled and \u2018possible\u2019 if \nonly 1 criteria is fulfilled.3\n\n\n\nMany studies have highlighted the rarity of this \ndisease with incidences ranging from 7.1 to 9.63 \nper million populations.4, 5 Despite its rarity, DM \ncontinues to be a major concern due to it association \nwith a wide range of malignancies. The types \nof malignancies associated vary across different \npopulation, and include nasopharyngeal, ovarian, \nlung, gastric, colorectal, breast, pancreactic cancers \nand non-Hodgkin\u2019s lymphoma.1, 6\n\n\n\nThis study aims to look at the clinical profile of \npatients with DM in Dermatology Clinic, Hospital \nSultanah Aminah, Johor Bahru, which is a tertiary \nreferral centre for the state of Johor, Malaysia. \nOver the past 13 years, the Dermatology clinic \nhas total new patient load of 57,655 patients with \nMalay patients making up 34,491 (59.8%), 22.7% \nChinese patients 13,071 (22.7%), Indian patients \n8568 (14.9%) and 1525 (2.6%) in patients of other \nethnicities. The types of malignancies associated \nwill be studied as well.\n\n\n\nMaterials & Methods\nThis is a retrospective review of all patients with \nDM followed up in the Department of Dermatology \nHospital Sultanah Aminah, Johor Bahru from 1st \nFebruary 2000 to 31st October 2013. The diagnosis \nof DM was made using the Bohan and Peter \ncriteria, whereby patients have to fulfill at least 1 \nother criterion in addition to presence of cutaneous \nfeatures. Demographic information, clinico-\nlaboratory features, and outcome are collected and \n\n\n\nanalysed. Outcome is defined as either alive or \ndeceased. For patients who were lost to follow up, \na search was done at the Registry of Life and Death \nto verify their life/death status and identify the \ncauses of death for the deceased. All data collected \nwere tabulated using Microsoft Office Excel 2007 \nand then analysed using SPSS statistical software. \nStatistical significance is determined using T-test, \nPearson Chi-Square, Fischer\u2019s Exact Test and \nMann-Whitney U Test. Ethical clearance is obtained \nfrom Ethics Committee of the Ministry of Health \nMalaysia (NMRR-13-1451-17317).\n\n\n\nResults\nA total of 43 patients were identified. The \ndemographic characteristics and clinico-laboratory \nfeatures are summarized in Table 1. Figure \n1 illustrates some of the cutaneous features \ncommonly encountered in our centre. There is slight \npredisposition towards females. Mean age of onset \nwas 47.8 \u00b1 18.0 years. Malay and Chinese patients \nmade up the bulk of patients, contributing 53.5% \nand 44.2% respectively.\n\n\n\nDemographic \ncharacteristics\n\n\n\nAge* (years) \n\n\n\nSex (%)\n   Male\n   Female  \n\n\n\nEthnicity (%)\n   Malay\n   Chinese\n   Indian \n   Others\n\n\n\nClinical features (%)\n   Photosensitivity\n   Gottron papule\n   Heliotrope rash\n   Alopecia\n   Calcinosis\n\n\n\nMuscle enzymesb \n   Creatinine Kinase (CK)\n   Aspartate Transaminase        \n   (AST)\n   Lactate Dehydrogenase \n   (LDH)\n\n\n\nValues\n\n\n\n47.8 \u00b1 18.0\n\n\n\n44.2\n55.8\n\n\n\n53.5\n44.2\n0\n2.3\n\n\n\n55.8\n46.3\n44.2\n23.3\n9.3\n\n\n\n \n293 (89-1166)\n641 (459-986)\n\n\n\n70.5 (41.5-156.25)\n\n\n\nTable 1 Demographic and clinic-laboratory characteristics \n of DM patients (n=43)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 MJD 2014 Dec Vol 33\n\n\n\nConcomitant malignancies occurred in 14 \npatients (32.5%). Figure 2 illustrates the types of \nmalignancies encountered.\n\n\n\nThere were 17 mortalities recorded, and malignancy \naccounts for 64.7% of total mortalities (11 patients). \nOther causes of death include sepsis (3 patients), \nacute pulmonary edema (1 patient), dissecting aortic \naneurysm (1 patient) and interstitial lung disease (1 \npatient).\n\n\n\nOut of the 14 patients with paraneoplastic DM, \nmalignancies were detected in 10 patients within the \nfirst year, and 2 patients within the second year after \n\n\n\ndiagnosis of DM. Two patients had malignancies \ndiagnosed within 6 months prior to the diagnosis \nof DM. These findings are summarized in Table \n2. The proportion of Malay patients developing \nparaneoplastic dermatomyositis with regards to \nthe total Malay new clinic attendees is 7 in 10,000 \npersons. This finding is similar in patients of other \nethnicities, whereas Chinese patients report a higher \nproportion of 15 in 10,000 persons.\n\n\n\nTable 3 illustrates possible indicators of occurrence \nof malignancies. A statistical significant association \nwas found between raised C-reactive protein (CRP) \nand malignancy (p <0.05).\n\n\n\nFigure 1  Clinical features on presentation\n\n\n\nFigure 2  Proportion of patients with/without malignancies and the types of associated malignancies \n\n\n\n(a) Heliotrope rash (b) Gottron\u2019s papules\n\n\n\nPercentage of Dermatomyositis Patients with/without Malignancies\n(n=43)\n\n\n\nWith malignancy\n\n\n\nLung Cancer\n\n\n\nGastrointestinal Malignancy\n\n\n\nNasopharyngoal Carcinoma\n\n\n\nBreast Cancer\n\n\n\nHomatological/Lymphoproliforative Malignancy\n\n\n\n67.4%\n(39)\n\n\n\n32.6%\n(14)\n\n\n\n14.0%(6) 47%(2)\n\n\n\n7.0%(3)\n\n\n\n4.7%(2)2.3%(1)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2014 Dec Vol 33\n\n\n\nNo\n\n\n\nMalignancy detected within 6 months prior to diagnosis\n1.\n2.\n\n\n\nMalignancy detected within 1 year after diagnosis \n3.\n4.\n5.\n6.\n7.\n8.\n9.\n10.\n11.\n12.\n\n\n\nMalignancy detected within 2 years after diagnosis\n13.\n14.\n\n\n\nAge\n\n\n\n26\n49\n\n\n\n47\n47\n53\n57\n57\n59\n66\n67\n70\n74\n\n\n\n41\n57\n\n\n\nSex\u2020\n\n\n\nF\nM\n\n\n\nM\nF\nF\nF\nF\nM\nM\nM\nM\nM\n\n\n\nM\nM\n\n\n\nRace\u00a7\n\n\n\nViet\nMly\n\n\n\nChi\nMly\nMly\nChi\nMly\nMly\nMly\nChi\nChi\nMly\n\n\n\nMly\nChi\n\n\n\nMalignancy*\n\n\n\nBreast Ca\nLung Ca\n\n\n\nNPC\nGastric Ca\nThymoma\nBreast Ca\n\n\n\nGall bladder Ca\nNPC\nNPC\nNPC\nNPC\n\n\n\nGastric lymphoma\n\n\n\nPancreatic Ca\nNPC\n\n\n\nOutcome\n\n\n\n \nDied\nDied\n\n\n\nDied\nDied\nDied\nDied\nAlive\nDied\nDied\nDied\nDied \nDied\n\n\n\nAlive\nDied\n\n\n\nTable 2 Characteristics of patients with paraneoplastic dermatomyositis\n\n\n\nPossible\nindicators\n\n\n\nGender a (%)\n Male\n Female \n\n\n\nEthnicity b (%)\nMalay\nChinese\nOthers\n\n\n\nClinical Features (%)\nHeliotrope rasha  \nPhotosensitivitya \nGottron papulea \nAlopeciab \nCalcinosisb \n\n\n\nAge of diagnosisc (years)\n\n\n\nESR c  (mm/hr) \n\n\n\nCRP d (mg/L) \n\n\n\nMuscle enzymesd (U/L)\n     AST\n     LDH\n     CK \n\n\n\nWith\nmalignancy \n\n\n\n(n=14)\n\n\n\n64.3\n35.7\n\n\n\n57.1\n35.7\n7.2\n\n\n\n28.6\n78.6\n42.9\n7.1\n0.0\n\n\n\n51.1 \u00b1 7.3\n\n\n\n72.1 \u00b1 39.5\n\n\n\n122.90\n\n\n\n76.0\n565.0\n335.0\n\n\n\nWithout \nmalignancy \n\n\n\n(n=29)\n\n\n\n34.5\n65.5\n\n\n\n51.7\n48.3\n\n\n\n0\n\n\n\n51.8\n44.8\n48.3\n31.0\n13.8\n\n\n\n46.4 \u00b1 7.7\n\n\n\n70.2 \u00b1 29.4\n\n\n\n6.44\n\n\n\n61.0\n677.0\n143.0\n\n\n\np-value\n\n\n\n0.102\n\n\n\n0.369\n\n\n\n0.199\n0.052\n0.758\n0.128\n0.286\n\n\n\n0.432\n\n\n\n0.929\n\n\n\n0.016\n\n\n\n0.303\n0.377\n0.573\n\n\n\nTable 3 Possible indicators for development of malignancy\n\n\n\n\u2020 F = Female, M = Male \n\u00a7 Chi = Chinese, Mly = Malay, Viet = Vietnamese\n* Ca = Cancer, NPC = Nasopharyngeal carcinoma\n\n\n\na Variables were analysed using Pearson Chi-Square test, with values reported in percentages.\nb Variables were analysed using Fisher\u2019s Exact test, with values reported in percentages. \nc Variables were analysed using T-test, with values reported in mean \u00b1 standard error.\nd Variables were analysed using Mann-Whitney test, with values reported in median.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 MJD 2014 Dec Vol 33\n\n\n\nDiscussion\nDermatomyositis (DM) is an autoimmune condition, \nlikely due to a combination of environmental and \ngenetic susceptibility. It appears to be more prevalent \nin Asians as compared to the Western community, \nsignifying the role of ultraviolet radiation in their \npathogenesis, as previously described by Okada et \nal.7 Recent advances also revealed the role of HLA \ngene polymorphisms in the pathogenesis of DM. \nThis may be partly attributed to the influence of \nHLA molecules on T-cell receptor development, \nperipheral tolerance, and immune response to \nenvironmental agents. To support this, a recent \nstudy by Gao et al concluded that presence of HLA-\nDRB1*07, DQA1*01, DQB1*02, DRB1*07 and \nDQA1*0104 alleles increase risk of DM amongst \nHan Chinese population.8  \n\n\n\nSince the first case of paraneoplastic DM reported \nby Stertz in 1916, there has been a lot of attention \ndrawn to the relationship between DM and cancer. \nAlthough the association of malignancies in patients \nwith DM is well established, the exact mechanism \nremains elusive. Some parties believe environmental \ncarcinogens and bioactive mediators produced in \nparaneoplastic conditions are responsible for the \nimmune reactions against the muscle fibers and \nskin. Others believe that the immunocompromised \nstate triggers development of both malignancies and \nmyositis.9-11\n\n\n\nCancer diagnosis can precede, parallel, or follow \nDM diagnosis. The risk of malignancy in patients \nwith DM declines steadily with increasing years \nsince initial diagnosis of DM. The cancer risk \nis six fold during the first year, 2.5 fold during \nthe second year, with no significant increase \nin subsequent years of follow-up.12 The grave \noutcome in paraneoplastic DM patients emphasises \nthe importance of predicting those at risk of \ndeveloping cancer. Over the years, many attempts \nhave been made to identify these predictors. A \nmeta-analysis by Wang et al reported age, male sex, \ncutaneous necrosis and dysphagia as indicators of \nmalignancy. The same study also found arthritis \nand interstitial lung disease to be protective.13 In a \nseparate study by Trallero-Araguas involving 312 \npatients, the presence of anti-p155 autoantibody \nis linked with malignancies. Anti-p155/140 has \na high negative predictive value (89-100%) and \ntherefore, a negative result reasonably exclude the \npresence of occult malignancy (14). Other features \nidentified by smaller studies in the past as predictors \nof malignancies include necrotic skin ulcerations, \npruritus, elevated ESR and periungual erythema.15,16\n\n\n\nOur centre reports raised C-reactive protein (CRP) \nas a marker of cancer.  C-reactive protein (CRP) \nis a sensitive inflammatory biochemical marker, \nfrequently elevated in infections, inflammatory \ndiseases, traumas, myocardial infarctions, \nsurgeries, and cancers.17 Malignancies that have \nbeen implicated with raised CRP include lung, \ncolorectal, and pharyngolaryngeal carcinoma.18,19 \nThe biological reason between malignancies and \nelevated CRP is unclear. Two theories have been \npostulated. The first suggests that the growth of a \ntumour and its surrounding tissue inflammation \nis responsible. Tumour cells produce various \ncytokines and chemokines that attract leukocytes \nand secrete interleukin-6 and interleukin-8, which \nstimulate CRP production in the liver. The second \nhypothesis on the contrary, postulates that chronic \ninflammation, of which CRP is a marker, plays a \npivotal role in carcinogenesis by inducing DNA \ndamage and promoting angiogenesis, propagating \nneoplastic spread and further metastasis.\n\n\n\nThe range of malignancies seen in paraneoplastic \nDM is vast, and encompasses from nasopharyngeal \ncarcinoma, to gastrointestinal, gynaecological and \nbreast malignancies. Amongst Chinese patients, \nnasopharyngeal carcinoma is the leading associated \nmalignancy, with consistent reports seen in south \nChina, Hong Kong, Taiwan and Singapore.5,20-26 \n\n\n\nGastric cancer, on the other hand is most prevalent \namongst Japanese patients.27 In Europe, Hill et \nal reported ovarian, lung, pancreatic, gastric, \ncolorectal cancers and non-Hodgkin\u2019s lymphoma \nin Scandinavian patients with paraneoplastic DM. \nA previous study from Hospital Kuala Lumpur, \nMalaysia reported nasopharyngeal carcinoma as the \ncommonest malignancy, which is consistent with \nour results.28 These findings suggest that the type \nof malignancy associated parallels the expected \nprobability of that cancer within each ethnic or \nregional population. This should be taken into \nconsideration while screening for malignancy in \nDM patients.\n\n\n\nSeveral weaknesses were identified in this study. \nFirstly, as this is a retrospective review, data deficit \nwas encountered. The study sample size is small, \nand possibly underestimated as general physicians \nand rheumatologists also manage DM patients in \nour region. In addition, a large number of patients \nwere not screened for interstitial lung disease, either \nvia a lung function test or high resolution computed \ntopography (HRCT) of thorax due to resource \nlimitations. Despite these shortcomings, our results \nare in agreement with many of the earlier studies. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2014 Dec Vol 33\n\n\n\nMalignancy is seen in 32.6% of our patients. \nAlthough lower than the reported 47.4% from \nHospital Kuala Lumpur, Malaysia, this is in keeping \nwith the rates reported overseas, which range \nfrom 13-42%.28,29 Nasopharyngeal carcinoma is \nthe commonest malignancy seen, possibly due to \nChinese predisposition seen amongst our clinic new \nattendees.\n\n\n\nIn conclusion, the high mortality rates amongst \nparaneoplastic DM patients warrant thorough \nsearch for malignancy. Basic workout should \ninclude complete history taking and physical \nexamination together with inflammatory markers \nsuch as erythrocyte sedimentation rate (ESR) and \n\n\n\nC-reactive protein (CRP). In patients with high risk \nfeatures, more aggressive screening strategies, such \nas positron emission tomography (PET)/CT scan \nshould be considered.30 PET/CT scan had been \nproven to be comparable in sensitivity and specificity \nto thoracic / abdominal CT, mammography, \ngynecologic examination, ultrasonography, and \ntumor marker analysis.31 In addition, due to the \nhigh incidence of nasopharyngeal carcinoma in this \nregion, patients should also be referred to the ear, \nnose and throat surgeon for a complete ear, nose \nand throat (ENT) assessment, which include a blind \nbiopsy of the fossa of Rossenmuller even when \nthere\u2019s no apparent abnormality seen.\n\n\n\nReferences\n \n1. Dalakas MC, Hohlfeld R. Polymyositis and \n\n\n\ndermatomyositis. Lancet 2003; 362: 971-82. \n2. Yosipovitch G, Tan A, Lossico K, et al. A comparative \n\n\n\nstudy of clinical characteristics, work-up, treatment, and \nassociation to malignancy in dermatomyositis between \ntwo tertiary skin centers in the USA and Singapore. Int J \nDermatol 2012; 52: 813-9.\n\n\n\n3. Bohan A, Peter JB. Polymyositis and dermatomyositis \n(second of two parts). N Engl J Med. 1975; 292: 403-7.\n\n\n\n4. Reeder MJ, Wetter DA, Li X, et al. Incidence \nof dermatomyositis and clinically amyopathic \ndermatomyositis: A population-based study in Olmsted \nCounty, Minnesota. Arch Dermatol. 2010; 146: 26-30. \n\n\n\n5. Kuo CF, See LC, Yu KH, et al. Incidences, cancer risk and \nmortality of dermatomyositis and polymyositis in Taiwan: \na nationwide population study. Br J Dermatol. 2011; 165: \n1273-9. \n\n\n\n6. Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency of \nspecific cancer types in dermatomyositis and polymyositis: \na population-based study. Lancet 2001; 357: 96-100. \n\n\n\n7. Okada S, Weatherhead E, Targoff IN, et al, \u201cGlobal surface \nultraviolet radiation intensity may modulate the clinical \nand immunologic expression of autoimmune muscle \ndisease,\u201d Arthritis Rheum 2003, 48: 2285\u20132293.\n\n\n\n8. Gao X, Lei H, Yuan L. HLA class II alleles may influence \nsusceptibility to adult dermatomyositis and polymyositis in \na Han Chinese population. BMC Dermatol 201;,14: 9.\n\n\n\n9. Naschitz JE, Rosner I, Rozenbaum M, et al. Rheumatic \nsyndromes: clues to occult neoplasia. Semin Arthritis \nRheum 1999; 29: 43\u201355.\n\n\n\n10. Bonnetblanc JM, Bernard P, Fayol J. Dermatomyositis \nand malignancy. A multicenter cooperative study. \nDermatologica 1990; 180: 212-16.\n\n\n\n11. Airio A, Pukkala E, Isomaki H. Elevated cancer incidence \nin patients with dermatomyositis: a population based study. \nJ Rheumatol 1995; 22: 1300-3.\n\n\n\n12. Chow WH, Gridley G, Mellemkjaer L, et al. Cancer risk \nfollowing polymyositis and dermatomyositis: a nationwide \ncohort study in Denmark. Cancer Causes Control 1995; 6: \n9-13.\n\n\n\n13. Wang J, Guo G, Chen G et al. Meta-analysis of the \nassociation of dermatomyositis and polymyositis with \ncancer. Br J Dermatol 2013; 169, 838-847.\n\n\n\n14. Trallero-Araguas E, Rodrigo-Pendas J_A, Selva-\nO\u2019Callaghan A, et al. Usefulness of anti-p155 autoantibody \nfor diagnosing cancer-associated dermatomyositis: a \nsystematic review and meta-analysis. Arthritis Rheum \n2012; 64: 523=32.\n\n\n\n15. Gallais V, Crickx B, Belaich S. Prognostic factors and \npredictive signs of malignancy in adult dermatomyositis. \nAnn Dermatol Venereol 1996; 123: 722-6.\n\n\n\n16. Hidano A, Torikai S, Uemura T, et al. Malignancy \nand interstitial pneumonitis as fatal complications in \ndermatomyositis. J Dermatol 1992; 19: 153-60.\n\n\n\n17. Burtis CA, Ashwood ER, Bruns DE: Tietz Textbook of \nClinical Chemistry and Molecular Diagnostics (ed 4). St \nLouis, MO, Elsevier Saunders, 2006\n\n\n\n18. Allin KH, Bojesen SE, Nordestgaard BG. Baseline \nC-Reactive Protein Is Associated With Incident Cancer and \nSurvival in Patients With Cancer. J Clin Oncol 2009; 27: \n2217-2224.\n\n\n\n19. Chen HH, Wang HM, Fan KH, et al. Pre-Treatment \nLevels of C-Reactive Protein and Squamous Cell \nCarcinoma Antigen for Predicting the Aggressiveness \nof Pharyngolaryngeal Carcinoma. PLoS One 2013; 8: \ne55327.\n\n\n\n20. Ang P, Sugeng MW, Chua SH. Classical and amyopathic \ndermatomyositis seen at the National Skin Centre of \nSingapore: a 3-year retrospective review of their clinical \ncharacteristics and association with malignancy. Ann Acad \nMed Singapore 2000; 29: 219-223.\n\n\n\n21. Chan HL. Dermatomyositis and cancer in Singapore. Int J \nDermatol 1985; 24: 447-450.\n\n\n\n22. Goh CL, Rajan VS. Dermatomyositis in a skin clinic. Ann \nAcad Med Singapore 1983; 12: 6-12.\n\n\n\n23. Leow YH, Goh CL. Malignancy in adult dermatomyositis. \nInt J Dermatol 1997; 36: 904=907.\n\n\n\n24. Fung WK, Chan HL, Lam WM. Amyopathic \ndermatomyositis in Hong Kong - association with \nnasopharyngeal carcinoma. Int J Dermatol 1998; 37:659-\n663.\n\n\n\n25. Lam WW, Chan H, Chan YL, et al. MR imaging in \namyopathic dermatomyositis. Acta Radiol 1999; 40: 69-\n72.\n\n\n\n26. Zhang W, Jiang SP, Huang L. Dermatomyositis and \nmalignancy: a retrospective study of 115 cases. Eur Rev \nMed Pharmacol Sci 2009; 13: 77-80.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 MJD 2014 Dec Vol 33\n\n\n\n27. Azuma K, Yamada H, Yamasaki Y, et al. Incidence and \npredictive factors for malignancies in 136 Japanese \npatients with dermatomyositis, polymyositis and clinically \namyopathic dermatomyositis. Mod Rheumatol 2011; 21: \n178-183.\n\n\n\n28. Tang MM, Thevarajah S. Paraneoplastic Dermatomyositis: \nA 12-year Retrospective Review in the Department of \nDermatology Hospital Kuala Lumpur. Med J Malaysia. \n2010; 65: 138-142.\n\n\n\n29. Zampieri S, Valente M, Adami N, et al. Polymyositis, \ndermatomyositis and malignancy: a further intriguing link. \nAutoimmun Rev 2010; 9: 449-53.\n\n\n\n30. Zahr ZA, Baer AN. Malignancy in myositis. Curr \nRheumatol Rep. 2011; 13 :208-15.\n\n\n\n31. Selva-O\u2019Callaghan A, Grau-Junyent JM, Gamez-Cenzano \nC, et al. Conventional cancer screening versus PET/CT in \ndermatomyositis/polymyositis. Am J Med. 2010; 123: 558-\n62.\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Dermatomyositis has a typical dermatologic features e.g. heliotrope rash, Gottron\u2019s sign and papules, \nshawl sign, poikiloderma and musculoskeletal features e.g. proximal muscle weakness. Practising \nclinician must have a high index of suspicion when seeing patients with these features. Early diagnosis \nportends better clinical outcome.\n\n\n\n2. In this study, 32.5% of patients with dermatomyositis seen in Hospital Sultanah Aminah Johor Bahru \nwas diagnosed to have concomitant malignancies. The age range of these patients were between 26 and \n74 years with a mean of 55 years. Thus, it is imperative that all adult patients with dermatomyositis be \nscreened for underlying malignancies.\n\n\n\n3. The commonest malignancy detected was nasopharyngeal carcinoma. This has been shown in this \nstudy and another in Hospital Kuala Lumpur. Nasopharyngeal carcinoma is more commonly seen among \nthe Chinese and also the Bidayuhs of Sarawak. Hence, it is important that clinician refer all adult patients \nwith dermatomyositis for assessment of their fossa of Rosenmuller for the presence of nasopharyngeal \ncarcinoma. A blind biopsy of the area is advised to allow early diagnosis.\n\n\n\n4. In this study, malignancies were detected 6 months prior to and within 2 years of the diagnosis of \ndermatomyositis. Majority of malignancies were diagnosed with a year. Screening for underlying \nmaligancies should be done early in the diagnosis to allow early management and stratification of the \npatients.\n\n\n\n5. An interesting finding from this study is the association of paraneoplastic dermatomyositis with elevated \nC reactive protein (CRP). This finding might suggest the use of CRP as a risk predictor for underlying \nmalignancy. Those with increased CRP should be more aggressively screened especially for pharyngeal, \ncolonic and lung malignancies.\n\n\n\n6. Medical professionals from all disciplines must be educated on this association of dermatomyositis and \ncancer so as to allow better multidisciplinary collaboration in the management of the patients.\n\n\n\nYap FBB \nEditor-in-Chief, Malaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9MJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nA 5 YEAR RETROSPECTIVE STUDY ON THE CLINICAL \nPATTERNS AND TREATMENT OUTCOMES OF SEVERE \nCUTANEOUS ADVERSE DRUG REACTIONS (SCARS) IN \nHOSPITAL TENGKU AMPUAN RAHIMAH, MALAYSIA\n\n\n\nTee SH, Ng TG \n\n\n\nAbstract\n\n\n\nIntroduction: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) , and drug reaction \nwith eosinophilia and systemic symptoms (DRESS) are severe cutaneous adverse drug reactions \n(SCARs) related to a variety of medications.\n\n\n\nObjectives: We aim to document the epidemiological features, the causative drugs and clinical \noutcomes of patients with SCARs treated in Hospital Tengku Ampuan Rahimah (HTAR) between \nJanuary 2009 and December 2013.\n\n\n\nMaterials & Methods: A retrospective review of the data of all patients with SJS, TEN and DRESS \ntreated from January 2009 to December 2013 was retrieved and analyzed.  \n\n\n\nResults: A total of 33 SCARs patients were seen, which included SJS (25), TEN (3) and DRESS (5). \nThe mean age was 42.8 years. The male-to-female ratio was 1.36:1. Allopurinol (33.3%) was the \ncommonest offending drug, followed by antibiotics (30.3%), anticonvulsants (12.1%), non-steroidal \nanti-inflammatory drugs (12.1%) and traditional medications (6.1%). Eighty percent of SJS and all \nTEN and DRESS patients were given systemic corticosteroids. One patient with TEN (33.3%) was \nconcurrently given intravenous immunoglobulin. All SJS patients survived. Two patients with TEN \n(66.7%) and one patient with DRESS (20%) succumbed due to sepsis. \n\n\n\nConclusion: The commonest drugs implicated for SCARs in our study were allopurinol and antibiotics. \nInappropriate use of these drugs leads to increased risk of SCARs. Early recognition and prompt \ntreatment of patients with SCARs may improve their outcome.\n\n\n\nKeywords: Severe cutaneous adverse drug reactions (SCARs), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis \n\n\n\n(TEN), drug reaction with eosinophilia and systemic symptoms (DRESS).\n\n\n\nCorresponding Author and Reprint Request \nDr Tee Shwu Hoon, MRCP\nDepartment of Dermatology, Hospital Tengku Ampuan \nRahimah, Jalan Langat, 41200 Klang, Selangor DE.\nE-mail: shwuhoontee@hotmail.com\n\n\n\nmorbidity and mortality. TEN has an estimated \nincidence of 0.4 to 1.9 million people annually \nworldwide.1-3\n\n\n\nThe overall combined incidence of SJS, SJS/TEN \noverlap and TEN is estimated to be 2 to 7 per million \nper year.4-8 SJS has an annual incidence of 1.2 to 6 \nper million people,9 approximately outnumbering \nTEN by three folds. A prospective seven-year study \nin a West Indian general population estimated an \nannual incidence of DRESS to be 0.9 per 100,000.10\n\n\n\nIntroduction\nStevens-Johnson syndrome (SJS), toxic epidermal \nnecrolysis (TEN), and drug reaction with \neosinophilia and systemic symptoms (DRESS) are \nsevere cutaneous adverse drug reactions (SCARs) \nwhich are rare but associated with significant \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10 MJD 2014 Dec Vol 33\n\n\n\nThe overall mortality rate among patients with SJS \nand TEN is approximately 25 percent, ranging from \napproximately 10 percent for SJS to more than 30 \npercent for TEN.11,12 Retrospective studies have \nreported mortality rates for DRESS to be 5 to 10 \npercent.13,14\n\n\n\nClinically, SJS and TEN are characterized by \npolymorphic lesions characterized by erythematous \nmacules, papules, plaque, vesicles, and bullae. It \nusually affects the distal extremities with positive \nNikolsky\u2019s sign. Oral, genital, and conjunctival \nmucosae are often involved in the form of erosion \nor ulceration. The basic difference between SJS \nand TEN is the percentage of body surface area \n(BSA) involved: <10% in SJS; >30% in TEN and \n10 to 30% in SJS-TEN overlap. DRESS is a drug-\ninduced hypersensitivity reaction that includes skin \neruption, hematologic abnormalities (eosinophilia \nand atypical lymphocytosis), lymphadenopathy, and \ninternal organ involvement (liver, kidney and lungs). \nThere is no highly sensitive and specific in vivo or in \nvitro tests available for identifying offending agents \nin SJS and TEN.15\n\n\n\nFurthermore, a drug challenge in a case of SCARs is \nnot ethically justified as these are the life-threatening \nreactions. So, to identify the drugs associated with \nrisk of causing severe skin reactions, retrospective \nepidemiological data are required. \n \nThis study aims to determine the demography,  \ncausative drugs and clinical outcomes of patients \nwith SCARs in Hospital Tengku Ampuan Rahimah \n(HTAR), Selangor, Malaysia during a five-year \nperiod between 2009 and 2013.\n\n\n\nMaterials & Methods\nA retrospective review of all cases admitted to the \nward or seen in the dermatology clinic in HTAR \nwith a diagnosis of SJS, TEN and DRESS was done \nfor a period of 5 years between 1st January 2009 \nand 31st December 2013. Data were retrieved from \nclinical notes in the Medical Records Department. \nData studied included the age, gender, ethic group, \nmedical history, presenting complaints, causative \ndrugs, duration between the initial consumption of \nthe drug and the onset of symptoms, and score for \ntoxic epidermal epidermal necrolysis (SCORTEN). \nTreatment regimes, duration of hospitalization, \ncomplications and mortality were also recorded.\n\n\n\nThe diagnosis was made by clinicians or \ndermatologists based on clinical features. A \nclinical diagnosis of SJS and TEN was made based \n\n\n\non criteria proposed by Bastuji-Garin et al. The \ndiagnosis of DRESS was established according to \nRegiSCAR (European Registry of Severe Cutaneous \nAdverse Reaction) and J-SCAR (Japanese Research \nCommittee on Severe Cutaneous Adverse Reaction) \ncriteria.  SCARs in this study included only SJS/\nTEN spectrum of cutaneous adverse drug reaction \nand DRESS.\n\n\n\nSCORTEN is a score of 7 independent risk factors \nfor high mortality i.e. age, heart beat, serum blood \nurea nitrogen, percentage of detached body surface \narea, serum bicarbonate and serum glucose. The \nmortality rate is dependent on the number of risk \nfactors with 1 risk factor portending a risk of 3.2% \nand 5 or more risk factors giving a mortality rate of \n>90%.\n\n\n\nData collected were compiled on a Microsoft \nExcel\u00ae sheet and subjected to descriptive statistical \nanalysis.\n\n\n\nResults\nEpidemiology\nThere were 25 patients with SJS(75.8%), 3 with \nTEN (9.1%), 5 with DRESS (15.1%) (Figure 1). \nThis study showed a slight male preponderance \nwith a male-to-female ratio of 1.36:1. Mean age \nwas 42.8 years ranging between 7 and 81 years. The \nmajority of the patients were in the age group of 20-\n59 years. The gender, ethnic and age distribution of \nthe patients for each diagnosis are shown in Table 1.\n\n\n\nDrugs implicated for SCARs\nDrugs implicated in the various SCARs patterns are \nshown in Table 2. Allopurinol (33.3% ) was the most \ncommon implicated drug, followed by antibiotics \n(30.3%) and anti-convulsants (12.1%).\n\n\n\nCotrimoxazole (3 patients) was the commonest \ncausative drug among the antibiotics, followed by \nerythromycin and amoxicillin (2 patients each). \nAmong the anticonvulsants, carbamazepine (2 \npatients) was the commonest drug followed by \nlamotrigine and phenytoin (1 patient each).\n\n\n\nInterval between the drugs taken and onset\nof symptoms and duration of hospital stay\nThe mean incubation period i.e. the interval between \ncommencement of the drug  and onset of symptoms \nof SCARs were 10.7 days, 14 days and 14.7 days for \nSJS, TEN and DRESS respectively. The duration of \nhospital stay in patients with TEN was longer with \na mean of 11 days compared to only 8.8 days in \npatients with SJS (Table 3)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11MJD 2014 Dec Vol 33\n\n\n\nTreatment\nFor patients with SJS, 5 (20%) of them were treated \nwith supportive therapy only whereas 20 (80%) of \nthem were given systemic corticosteroids (either \nintravenous hydrocortisone 300 - 400mg/day or \noral prednisolone 0.5 \u2013 1mg/kg/day). Intravenous \n\n\n\nhydrocortisone was changed to oral prednisolone \nonce the patients were able to tolerate orally \nwell. All TEN and DRESS cases were treated \nwith corticosteroids. Out of 3 patients with TEN, \none patient was also treated with intravenous \nimmunoglobulins (IVIG).\n\n\n\nDemographics\n\n\n\nGender\n      Male\n      Female\n\n\n\nEthnicity\n      Malay\n      Chinese\n      Indian\n      Others\n\n\n\nAge Group \n(years)\n      <10\n      10 - 19\n      20 - 59\n      >60\n\n\n\nSJS\n(n=25)\nNo (%)\n\n\n\n15 (60)\n10 (40)\n\n\n\n18 (72)\n6 (24)\n\n\n\n0\n1 (4)\n\n\n\n1 (4)\n2 (8)\n\n\n\n17 (68)\n5 (20)\n\n\n\nTEN\n(n=3)\n\n\n\nNo (%)\n\n\n\n3 (100)\n0\n\n\n\n3 (100)\n0\n0\n0\n\n\n\n0\n0\n\n\n\n3 (100)\n0\n\n\n\nDRESS\n(n=5)\n\n\n\nNo (%)\n\n\n\n1 (20)\n4 (80)\n\n\n\n1 (20)\n2 (40)\n2 (40)\n\n\n\n0\n\n\n\n0\n0\n\n\n\n3 (60)\n2 (20)\n\n\n\nTotal\n(n=33)\nNo (%)\n\n\n\n19 (58)\n14 (42)\n\n\n\n22 (67)\n8 (24)\n2 (6)\n1 (3)\n\n\n\n1 (3)\n2 (6)\n\n\n\n23 (70)\n7 (21)\n\n\n\nTable 1 Demographics of patients with SCARs\n\n\n\nSJS\n\n\n\nTEN\n\n\n\nDRESS\n\n\n\n9.10%\n\n\n\n75.80%\n\n\n\n15.10%\n\n\n\nFigure 1  Distribution of SCARs\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 MJD 2014 Dec Vol 33\n\n\n\nDrugs\n\n\n\nAnti-gout (Allopurinol)\n\n\n\nAntibiotics\n      \nCo-trimoxazole\n      \nErythromycin\n      \nAmoxycillin\n      \nFansidar\n      \nCiprofloxacin\n\n\n\nCloxacillin\n\n\n\nAnticonvulsants\n\n\n\nCarbamazepine\n     \n Lamotrigine\n      \nPhenytoin\n\n\n\nNSAIDs\n\n\n\nTraditional medications\n\n\n\nOthers \n\n\n\nSJS\n(n=25)\nNo (%)\n\n\n\n8 (32.0)\n\n\n\n8 (32.0)\n\n\n\n3 (12.0)\n\n\n\n2 (8.0)\n\n\n\n2 (8.0)\n\n\n\n1 (4.0)\n\n\n\n0\n\n\n\n0\n\n\n\n3 (12.0)\n\n\n\n2 (8.0)\n\n\n\n1 (4.0)\n\n\n\n0\n\n\n\n3 (12.0)\n\n\n\n1 (4.0)\n\n\n\n2 (8.0)\n\n\n\nTEN (n=3)\nNo (%)\n\n\n\n1 (33.3)\n\n\n\n1 (33.3)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1 (33.3)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1 (33.3)\n\n\n\n0\n\n\n\nDRESS \n(n=5)\n\n\n\nNo (%)\n\n\n\n2 (60.0)\n\n\n\n1 (20.0)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1 (20.0)\n\n\n\n0\n\n\n\n1 (3.0)\n\n\n\n0\n\n\n\n0\n\n\n\n1 (3.0)\n\n\n\n0\n\n\n\n0\n\n\n\n1 (3.0)\n\n\n\nTotal \n(n=33)\nNo (%)\n\n\n\n11 (33.3)\n\n\n\n10 (30.3)\n\n\n\n3 (9.1)\n\n\n\n2 (6.1)\n\n\n\n2 (6.1)\n\n\n\n1 (3.0)\n\n\n\n1 (3.0)\n\n\n\n1 (3.0)\n\n\n\n4 (12.1)\n\n\n\n2 (6.1)\n\n\n\n1 (3.0)\n\n\n\n1 (3.0)\n\n\n\n3 (9.1)\n\n\n\n2 (6.1)\n\n\n\n3 (9.1)\n\n\n\nTable 2 Drug groups and individual drugs implicated for SCARs\n\n\n\nSCORTEN, morbidity and mortality\nScore for toxic epidermal necrolysis (SCORTEN) \nwas calculated in patients with SJS or TEN to \nevaluate patients\u2019 prognosis. Thirteen patients had \nSCORTEN of 0, 9 patients had SCORTEN of 1, 3 \npatients had SCORTEN of 2 and 3 respectively. Two \nout of three patients with SCORTEN of 3 succumbed \nto their illness. One of them was a 57-year-old \nMalay man who received cloxacillin for cellulitis. \nHe developed TEN which was then complicated \nby septicaemia secondary to pneumonia. He died \n13 days after onset the of TEN. Another patient \nwith SCORTEN of 3 was an Indonesian man who \ndeveloped TEN due to traditional medication, which \nwas taken to boost his energy. This patient also had \nconcomitant leptospirosis infection. He succumbed \n7 days after the onset of TEN due to septicaemia \nwith multiorgan failure.\n\n\n\nIncubation period (Days)\n      Mean \n      Range \n\n\n\nDuration of stay (Days)\n      Mean \n      Range\n\n\n\nSJS\n\n\n\n10.7\n1 - 35\n\n\n\n8.8\n0 - 21\n\n\n\nTEN\n\n\n\n10.3\n7 - 14\n\n\n\n11.0\n9 - 13\n\n\n\nDRESS\n\n\n\n14.7\n1 - 30\n\n\n\n9.3\n6 - 12\n\n\n\nTable 3 Incubation period and duration of hospital stay\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2014 Dec Vol 33\n\n\n\nDiscussion\nThis study showed an overall slight male \npreponderance with a male-to-female ratio of \n1.38 to 1 and a ratio of 1.4 to 1 for SJS and TEN \nonly. This finding is in contrast with earlier studies \nshowing females are affected twice as often as \nmales in SJS and TEN.16,17 A study conducted in \nDr. Hasan Sadikin General Hospital Bandung  also \nreported similar finding as our study with a slight \nmale preponderance (male-to-female ratio of 1.11 \nto 1)18, while a study conducted in Changi General \nHospital in Singapore showed equal numbers of \nmales and females affected with  SJS/TEN.19\n\n\n\nIn our series, we reported 25 cases of SJS (75.8%), \n3 TEN (9.1%) and 5 DRESS (15.1%) over a 5-year \nperiod between 1st January 2009 and 31 December \n2013. In our neighboring country, Indonesia, 39 \ncases of SJS, 7 cases of SJS-TEN overlap and 11 \ncases of TEN were reported in Dr. Hasan Sadikin \nGeneral Hospital Bandung during the same period \nof time.18 In Singapore, there were 18 cases of SJS, \n7 SJS/TEN and 3 TEN reported in Changi General \nHospital over a 7-year period between January 2004 \nand November 2010.19 Local data reported 88 cases \nof SJS, 21 cases of TEN and 34 cases of DRESS in \nHospital Sultan Aminah, a tertiary hospital in Johor, \nMalaysia over a 10-year period between January \n2001 and December 2010.20\n\n\n\nIn our study, the majority of the patients were aged \nbetween 20 and 59 years. The mean age of 42.8 years \nis similar to other Asian studies which reported \nyounger patients\u2019 cohort compared to studies from \nEurope and US.20 \n\n\n\nThe most common drug implicated in our hospital \nwas allopurinol, accounting for 32% of SJS and \nTEN patients; and 40% of DRESS patients. Several \nrecent reports suggested that allopurinol is the \ndrug most commonly responsible for SJS/TEN in \nEuropean and Asian countries.21,22 A study involving \n30 patients with DRESS in Taiwan also showed that \nallopurinol was the main culprit in DRESS.23\n\n\n\nSimilar to the findings in our study, a local study at \nHospital Sultan Aminah Johor Bahru reported that \nallopurinol, carbamazepine and cotrimoxazole were \nthe top three main culprit drugs for SCARs which \naccounts for 38 cases (26.3%), 25 cases (17.4%) \nand 17 cases (11.8%) respectively.20 A 4-year \n(January 2004 to December 2007) review of SJS and \nTEN in Sarawak reported that allopurinol was the \ncommonest drug implicated which accounts for 7 \n\n\n\ncases (36.8%); followed by carbamazepine (26.3%) \nand phenytoin (10.5%).24 Study in Changi Hospital \nSingapore showed that the commonest implicated \ndrugs for SJS and TEN were carbamazepine, \nfollowed by beta-lactam antibiotics and NSAIDS.19 \nIn Indonesia, paracetamol (16.56%), carbamazepine \n(7%), amoxicillin (5.73%) were the main causative \ndrugs in 57 cases of SJS/TEN reported in Dr Hasan \nSadikin General Hospital from 2009-2013.18\n\n\n\nThe commonest implicated drug for SCARs in our \nstudy which is allopurinol is similar to studies done \nlocally in Hospital Sultan Aminah and Sarawak \nGeneral Hospital as well as studies in European and \nAsian countries. All the patients with SCARs due \nto allopurinol in our study survived. The analysis \nof cutaneous adverse drug reactions (cADRs) in \nHospital Sultan Aminah Johor Bahru showed that \nthe majority of allopurinol-induced cADRs (78% of \n50 cases) were SCAR with 5 fatalities yielding a \nmortality rate of 10%.20\n\n\n\nRisk factors for SCARs attributed to allopurinal \nare presence of HLA-B*5801, older age, renal \nimpairment, concomitant use of diuretic and recent \ninitiation of the drug.25 High allopurinol dose, \npreviously suggested to be a risk factor, was not \nconfirmed as such in a recent systematic review of \nall published cases on allopurinol hypersensitivity.25\n\n\n\nIn Malaysia, the number of allopurinol-induced \nadverse drug reactions reported to our National \nPharmaceutical Control Bureau (NPCB), increased \nfrom 16 cases in 2001 to 80 cases in 2008. After \nan alert issued by our NPCB in 2008, the number \nof cases reported dropped to about 50 cases per \nyear. Allopurinol was prescribed for asymptomatic \nhyperuricemia in 34% of treated patients.26 A 10-\nyear observational survey in Italy on ADRs to \nallopurinol reported that 95% of allopurinol was \nprescribed for asymptomatic hyperuricemia and 12 \npatients were under allopurinol dosage adjustment \naccording to creatinine clearance.27 Other published \nstudies also revealed inappropriate indications \nfor allopurinol in up to 86% of patients.28,29 Our \nstudy showed that allopurinol was prescribed in \nasymptomatic hyperuricaemia in 36% of patients (4 \nout of 11 cases), which is consistent with our local \nreported data but lower that of the data reported \nin Italy, Australia and New Zealand. Despite \nthe availability of allopurinol usage guidelines \nin the Malaysian Clinical Practice Guideline in \nManagement of Gout  published in October 2008, it \nis evident from our data that a significant proportion \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 MJD 2014 Dec Vol 33\n\n\n\nof clinicians remain perplexed about the preferred \nmanagement of asymptomatic hyperuricaemia. It is \nof utmost importance that clinicians should justify \nthe use of allopurinol on the basis of a favorable \nbenefit/risk assessment for the patients. Therefore, \nwe recommend judicious prescription of allopurinol \nfor only accepted indications and the dose adjusted \nto patient\u2019s renal function. Our data indicate \nthe continuing need to disseminate information \nregarding the appropriate use of allopurinol in \ntreating patients to minimize the unnecessary \nmorbidity and mortality which may occur with  \nallopurinol-induced ADRs.\n\n\n\nOur study reported two cases (6%) of SCARs due to \ntraditional medicines. One patient took traditional \nmedicines for energy boosting developed TEN and \nsuccumbed due to sepsis with multiorgan failure. \nAnother patient was a 22-year-old Malay man \nwho developed SJS due to traditional medicine \nand had complete recovery. A retrospective study \ndone in Peking University Third Hospital, Beijing \non SCARs over a 8-year period (from January \n1994 to December 2002) reported that Chinese \ntraditional medicines were the third most common \noffending drugs for SCARs.30 The study included \ncases of exfoliative dermatitis on top of SJS/TEN \nand DRESS.29 In Singapore, 7.1 % of SJS and TEN \ncases treated in Changi General Hospital were \ndue to Chinese traditional medicines19 SCARs to \ntraditional medicines can be a reaction to naturally-\noccurring medicinal compounds, natural toxins, or \nto contaminants or adulterants in these medicines.  \nThe problem of SCARs to traditional medicines will \nbecome more significant as the use of traditional \nmedicine becomes more widespread and of \nincreasing healthcare and economic importance. \nAlready, in many parts of the world, expenditure \non traditional medicine is growing rapidly. \nTherefore, it is important that the public, traditional \npractitioners and qualified doctors be cognizant of \npotential adverse reactions of traditional medicines. \nAwareness will help in dispensing the appropriate \nadvice and therapy, which will in turn prevent \nunnecessary complications and fatalities. This may \nalso reduce unwanted readmissions, prolonged \nhospital stays or inappropriate labeling of drug \nallergy to other medicines.31\n\n\n\nCurrently, no treatment modality has been \nestablished as standard for patients with SJS \nand TEN. Out of 25 cases of SJS, 20 cases were \ntreated with corticosteroids, whereas 5 cases were \n\n\n\ngiven supportive therapy only. Out of these 5 \ncases, one patient had retroviral disease and sepsis \nsecondary to pneumonia while another patient had \nlate presentation to dermatology clinic. Out of 20 \npatients treated with systemic corticosteroids, one \npatient who had underlying bronchial asthma who \ndeveloped pneumonia during the hospitalization. \nAll patients with SJS treated with corticosteroids \nor supportive therapy survived. The controversy \nover whether systemic corticosteroids should be \nused to curtail progression remains unresolved. A \nlarge multicenter European study, suggested that a \nshort course of moderate to high dose of systemic \ncorticosteroids (e.g. prednisone 1 to 2 mg/kg per day \nfor three to five days) may not be harmful and may \nhave a beneficial effect if given early in the course \nof the disease (i.e. within 24 to 48 hours of symptom \nonset).32,33 However, an updated mortality analysis \nof the RegiSCAR cohort and a systematic review \nof case series did not confirm a survival benefit for \npatients treated with systemic corticosteroids.34,35 \nThe patient outcome in our study showed that it \nappears reasonable to initiate corticosteroids as \nearly as possible before significant tissue damage \noccurs. Nevertheless, patients should be monitored \nfor immunosuppression-related infections, and \nantimicrobial agents should be used accordingly if \nthere is evidence of infection.\n\n\n\nIVIG contains anti-Fas antibodies that can abrogate \nthe Fas-mediated keratinocyte apoptosis. A \nsystematic review and meta-analysis on the efficacy \nof IVIG for the treatment of TEN concluded that \nalthough high-dose IVIG exhibited a trend towards \nimproved mortality and children treated with IVIG \nhad a good prognosis, the evidence does not support \na clinical benefit of IVIG.36 Randomized controlled \ntrials are necessary.\n\n\n\nIn our series, one out of three cases with TEN was \ngiven IVIG. He was a 53 year-old Indonesian who \ndeveloped TEN secondary to traditional medicines. \nHe had concomitant leptospirosis which was \ncomplicated with multiorgan failure resulting in \nhis death 7 days after the onset of TEN. He was \nplanned for IVIG 0.4g/kg over 5days (2g/kg total \ndose). However, only 2 doses were given as he died \nbefore the administration of the third dose of IVIG. \nWe could not make any conclusion about the use of \nIVIG in treatment of SJS and TEN as it was used \nonly in one patient in our study. Two out of three \npatients with TEN succumbed due to sepsis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2014 Dec Vol 33\n\n\n\nFor all patients with DRESS, systemic corticosteroids \nwere given. Four patients (80%) with DRESS \nsurvived. One out of 5 patients died of multiple \ncomplications including sepsis, perforated gastric \nulcer, acute renal failure, atrial fibrillation 8 days \nafter the onset of DRESS. The early administration \nof systemic steroids is generally recommended for \nall cases of DRESS syndrome.37 Systemic steroid \ntherapy should be given with a minimum dose of \n1.0 mg/kg/day of prednisone or equivalent. Gradual \ntaper after clinical and laboratory stabilization \nis recommended to avoid relapse.38 There is \noften significant improvement of symptoms and \nlaboratory abnormalities within several days after \ninitiating steroid treatment.38,39,40 A consensus \ngroup of the French Society of Dermatology has \n\n\n\npublished recommendations for the management of \nDRESS syndrome which recommended the use of \ncorticosteroids equivalent to 1 mg / kg per day of \nprednisone on top of multidisciplinary evaluation \nin DRESS with the presence of signs of severity \n(transaminases > 5 times normal, renal involvement, \npneumonia, hemophagocytosis, cardiac, etc.).41\n\n\n\nConclusion\nIn conclusion, the commonest drugs implicated for \nSCARs in our study were allopurinol, antibiotics, \nNSAIDs, and anticonvulsants. Inappropriate use of \nthese drugs leads to increased risk of SCARs. 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J Eur \nAcad Dermatol Venereol 2008; 22: 1044- 9.\n\n\n\n24. Yap FBB, Wahiduzzaman M, Pubalan M. A 4-year \nretrospective study of Stevens-Johnson Syndrome and \ntoxic epidermal necrolysis . Malaysian J Dermatol 2008; \n21: 35-9.\n\n\n\n25. Ramasamy SN, Korb-Wells CS, Kannangara DR, et al.  \nAllopurinol hypersensitivity: a systematic review of all \npublished cases, 1950-2012. Drug Saf. 2013; 36: 953-80.\n\n\n\n26. Choon SE. Allopurinol Hypersensitivity in Malaysia. \nRegional Conference of Dermatology 2014;51\n\n\n\n27. Atzori L, Pinna AL, Mantovani L, et al. Cutaneous adverse \ndrug reactions to allopurinol: 10 year observational survey \nof the dermatology department--Cagliari University \n(Italy). J Eur Acad Dermatol Venereol. 2012; 26: 1424-30\n\n\n\n28. Bellamy N, Brooks PM, Emmerson BT, et al. A survey \nof current prescribing practices of anti-inflammatory and \nurate lowering drugs in gouty arthritis in New South Wales \nand Queensland. Med J Aust. 1989; 151: 531- 7.\n\n\n\n29. Stuart RA, Gow PJ, Bellamy N, et al. A survey of current \nprescribing practices of anti-inflammatory and urate-\nlowering drugs in gouty arthritis.  NZ Med J.1991; \n104:115-7.\n\n\n\n30. Li LF, Ma C. Epidemiological study of severe cutaneous \nadverse drug reactions in a city district of China. Clin Exp \nDermatol 2006; 31: 642\u2013647\n\n\n\n31. Lim Y L, Thirumoorthy T. Serious cutaneous adverse \nreactions to traditional Chinese medicines. Singapore Med \nJ. 2005; 46: 714-7.\n\n\n\n32. Schneck J, Fagot JP, Sekula P, et al. Effects of treatments \non the mortality of Stevens-Johnson syndrome and toxic \nepidermal necrolysis: A retrospective study on patients \nincluded in the prospective EuroSCAR Study. J Am Acad \nDermatol 2008; 58:33.\n\n\n\n33. Finkelstein Y, Soon GS, Acuna P, et al. Recurrence \nand outcomes of Stevens-Johnson syndrome and toxic \nepidermal necrolysis in children. Pediatrics 2011; 128:723.\n\n\n\n34. Sekula P, Dunant A, Mockenhaupt M, et al. Comprehensive \nsurvival analysis of a cohort of patients with Stevens-\nJohnson syndrome and toxic epidermal necrolysis. J Invest \nDermatol 2013; 133:1197.\n\n\n\n35. Roujeau JC, Bastuji-Garin S. Systematic review of \ntreatments for Stevens-Johnson syndrome and toxic \nepidermal necrolysis using the SCORTEN score as a tool \nfor evaluating mortality. Ther Adv Drug Saf 2011; 2:87.\n\n\n\n36. Huang YC, Li YC, Chen TJ. The efficacy of intravenous \nimmunoglobulin for the treatment of toxic epidermal \nnecrolysis: asystematic review and meta-analysis.Br J \nDermatol. 2012 Aug;167(2):424-32.\n\n\n\n37. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome. \nPart II. Management and therapeutics. J Am Acad \nDermatol 2013; 68: 709.\n\n\n\n38. Bocquet H, Bagot M, Roujeau JC. Drug-induced \npseudolymphoma and drug hypersensitivity syndrome \n(drug rash with eosinophilia and systemic symptoms: \nDRESS). Semin Cutan Med Surg 1996; 15: 250-7.\n\n\n\n39. Shiohara T, Inaoka M, Kano Y. Drug-induced \nhypersensitivity syndrome (DIHS): a reaction induced by a \ncomplex interplay among herpesviruses and antiviral and \nantidrug immune responses. Allergol Int 2006; 55: 1-8.\n\n\n\n40. Gentile I, Talamo M, Borgia G. Is the drug-induced \nhypersensitivity syndrome (DIHS) due to human \nherpesvirus 6 infection or to allergy-mediated viral \nreactivation? Report of a case and literature review. BMC \nInfect 2010; 10: 49.\n\n\n\n41. Descamps V, Ben Sa\u0131d B, Sassolas B, et al. Management \nof drug reaction with eosinophilia and systemic symptoms \n(DRESS). Ann Dermatol Venereol 2010; 137: 703-8. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2014 Dec Vol 33\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. SJS is the commonest SCARs seen in Tengku Ampuan Rahimah Hospital, Klang, Selangor. All \nclinicians should identify SCARs early and refer them to Dermatologist urgently to prevent associated \nmorbidity and mortality. \n\n\n\n2. Allopurinol is the commonest offending drug causing SCARs. Most cases are due to inappropriate \nuse of allopurinol to treat asympotomatic hyperuricaemia. Judicious use of allopurinol is of utmost \nimportance to prevent SCARs. Education of healthcare professionals about risks of allopurinol should \nbe done nationwide. Identification of HLA-B*5801 as shown by study by Chang et al in Hospital Kuala \nLumpur will help stratify patients who require antigout medications in the near future.\n\n\n\n3.Antinbiotics namely co-trimoxazole is also a common offending agent causing SCARs in Klang. \nThis antibiotic should be use appropriately for specific indications e.g. treatment and prophylaxis of \nPneumocystis jiroveci pneumonia. \n\n\n\n4. Anticonvulsants namely the aromatic anticonvulsants (carbamazepine, phenytoin and phenobarbitone) \nwere the third commonest cause of SCARs in Klang. It is essential that health care providers prescribe \nthese medications with caution. Proper justification of their use is very important. Their use in treatment \nof neuralgias should be replaced with newer and safer medications. Identification of HLA-B*1502 as \nshown by Chang et al in Hospital Kuala Lumpur will in the near future help clinicians decide on the use \nof carbamazepine in their potential patients. \n\n\n\n5. The high mortality rate of SCARs  in which 66.7% of TEN patients and 20% of SJS patients in Klang \nsuccumbed due to the drug related allergy should warrant proper education of the health care professionals \nand general public about proper prescription of oral and systemic medications. It is imperative that all \njunior healthcare professional namely medical, dental, pharmacy and paramedical students be exposed to \nthe dangers prescription medications early in their medical profession. \n\n\n\nYap FBB \nEditor-in Chief, Malaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 MJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nCOST OF MEDICATIONS IN THE TREATMENT OF MODERATE \nTO SEVERE ACNE IN SARAWAK, MALAYSIA\n\n\n\nYap FBB1, Pubalan M2\n\n\n\nAbstract\n\n\n\nIntroduction: Acne is a common problem causing impairment in quality of life requiring topical and \noral treatment. The objective of this study is to determine the cost of medications for the treatment \nof an episode of moderate to severe acne vulgaris in patients attending the dermatology clinics in \nSarawak.\n\n\n\nMaterials & Methods: This cross sectional study was conducted between June 2008 and January 2009 \nin all the 3 dermatology clinics in Sarawak. Data were collected from 165 patients with moderate to \nsevere acne  and analysed using SPSS ver 15. Statistical significance was set at p < 0.05. \n\n\n\nResults: The mean cost of medications to treat 1 episode of acne was RM 1170.48 per patient. The \ngovernment and patients spent an average of RM 519.41 and RM 651.07 respectively. The cost to \ntreat 1 episode of severe acne (mean RM1861.75) was significantly higher than to treat moderate acne \n(mean RM 470.79, p < 0.001). Working patients paid more for their acne medications (mean RM \n1624) compared to students (mean RM 732.21, p = 0.001). In patients with moderate acne, patients \nwith tertiary education spent more (mean RM 657.54) on their medications compared to those with \nprimary/secondary education (mean RM 338.50, p = 0.04) There was no association between the cost of \nmedications and the socio-demographic variables of gender, ethnic group and economic background.\n\n\n\nConclusion: Cost of treating moderate to severe acne in Sarawak is high and comparable to Western \nsocieties. This data might help in formulating and optimizing resource allocations for the treatment \nof acne.\n\n\n\nKeywords: Acne vulgaris, costing, medications\n\n\n\nCorresponding Author and Reprint Request \nDr Felix Yap Boon Bin\nFaculty of Medicine and Health Sciences, Universiti \nTunku Abdul Rahman, Sungai Long Campus, Sungai \nLong, 43000 Kajang, Selangor DE\nEmail: woodzlamp@yahoo.com\n\n\n\n2 Department of Dermatology, Sarawak General \n Hospital, Jalan Hospital, 93200 Kuching, Sarawak\n\n\n\ntreatment.2-5 Multiple anti-acne medications are \navailable for the treatment of acne. These consist \nof facial cleansers, topical agents and oral agents.  \nMoreover, there are also multiple types of cosmetic \nagents and traditional medications for the treatment \nof acne.\n\n\n\nThe cost of anti-acne medications vary widely. The \ncost of these medications are lower in the government \nclinics compared to the private institutions and local \npharmacies/chemists in Malaysia. The cost also \nvaries with the practice of the treating clinicians. \nThis costing is important for clinicians and health \ncare administrators for the optimal resource \nallocation and utilization.\n\n\n\nIntroduction\nAcne vulgaris is a common problem, affecting \nmore than 80% of the population in their lifetime.1 \nIt causes psycho-social disabilities and significant \nmorbidities among its sufferers, requiring optimal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2014 Dec Vol 33\n\n\n\nData on the cost of medications for the optimal \ntreatment of acne vulgaris is lacking. Health care \nproviders and administrators depended heavily on \nregional and international studies. Nevertheless, the \nrelevance of these data are frequently questioned \nbecause of the difference in the socio-cultural \nbackground of the population studied and the \npractice of the treating clinicians.\n\n\n\nThe objective of this study is to determine the cost \nof medications for the treatment of an episode \nof moderate to severe acne vulgaris in patients \nattending the dermatology clinics in Sarawak, \nMalaysia.\n\n\n\nMaterials and Methods\nThis cross sectional study was conducted between \nJune 2008 and January 2009 in all the 3 dermatology \nclinics in Sarawak (Sarawak General Hospital, Miri \nHospital and Sibu Hospital). All the patients with \nmoderate and severe acne on initial presentation to \nthe dermatology clinics were invited to participate in \nthe study. All the consecutive patients who consented \nwere included. Data on socio-demography, number \nand duration of each episode of acne vulgaris and the \nanti-acne treatment given were recorded in the case \nreport forms. The type, cost (Table 1) and duration \nof each anti-acne medication given in the clinics \nwere recorded. This constituted the government cost \nof the anti-acne medications. For patient cost of the \nanti-acne medications, the patients were required to \nrecall the type, duration and cost of all the anti-acne \nmedications used before attending the government \ndermatology clinics.\n\n\n\nData collected were analyzed with SPSS ver. 15 \n(SPSS Inc, Chicago, IL, USA). Continuous variables \nwere expressed as mean \u00b1 standard deviation (SD). \nCategorical data were expressed as frequencies \nand percentages. Analysis was done to determine \nthe relationship between cost of medications and \nsocio-demographic variables using student t test for \ncomparison of means.\n\n\n\nResults\nA total of 165 patients consented for the study. Of \nthese, 82 (49.7%) patients had moderate acne and \n83 (51.3%) patients had severe acne on presentation \nto the dermatology clinics. Females constituted \n61.8% (n= 102) of the patients. The mean age was \n23.1 \u00b1 6.72 years ranging between 10 and 46 years. \nChinese make up 41.8% (n = 69), Malays 39.4% (n \n= 65) and Sarawakian natives 18.7% (n = 31).\n\n\n\nThere were 159 (96.4%) patients who had 1 episode \nof acne, 5 (3.0%) patients had 2 episodes of acne \nand 1 (0.6%) patient had 3 episodes. Of the patients \nwith 1 episode of acne, 109 (68.6%) patients were \nsuccessfully treated with 1 complete course of oral \nanti-acne treatment and 50 (31.4%) patients required \n2 complete courses. Of the patients who had 1 \ncomplete course of anti-acne medications, 91.7% \nhad incomplete course of oral anti-acne antibiotics. \nThe mean duration of treatment per episode was 8.4 \nmonths ranging from 3 to 24 months.\n\n\n\nOral anti-acne agents were utilized in all the 165 \npatients. Isotretinoin was utilized in 89 episodes of \nacne, antibiotics in 128 episodes, oral contraceptive \nagents in 10 episodes (Table 2). Of the patients \nwho had 1 episode of acne successfully treated \nwith 1 course of oral anti-acne medications, 72 \n(66.0%) patients had doxycycline, 33 (30.3%) \npatients had isotretinoin and 4 (3.7%) patients had \noral contraceptive agents (1 had Diane-35, 2 had \nMarvelon and 1 had spironolactone). There were 8 \n\n\n\nAnti-acne medications  \n\n\n\nTopical medications\n2% Sulphur in calamine\n\n\n\nBenzoyl peroxide 5% gel \n\n\n\nBenzoyl peroxide 10% gel\n\n\n\nTretinoin 0.05% cream\n\n\n\nTretinoin 0.01% gel\n\n\n\nFacial cleansers\n 2% Cetrimide lotion\n\n\n\nOral medications\nSpironolactone 25 mg tablet \n\n\n\nDoxycycline 100 mg capsule\n\n\n\nErythromycin ethyl succinate\n400 mg tablet\n\n\n\nDesogestrol 150 mcg/ethinylestradiol\n30 mcg tablet (Marvelon)\n\n\n\nCyproterone acetate 2 mg/ethinylestradiol   \n0.035 mg tablet (Diane-35)\n\n\n\nIsotretinoin 10 mg capsule (Nimegen) \n\n\n\nCost (RM)\n\n\n\n3.63/100mL\n\n\n\n11.85/40gm\n\n\n\n13.90/40gm\n\n\n\n16.40/20gm\n\n\n\n19.20/15gm\n\n\n\n2.63/1L\n\n\n\n0.08/tablet\n\n\n\n0.08/capsule\n\n\n\n0.19/tablet\n\n\n\n0.45/tablet\n\n\n\n1.13/tablet\n\n\n\n1.58/capsule\n\n\n\nTable 1 Cost of anti-acne medications in the government \n dermatology clinics in Sarawak\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 MJD 2014 Dec Vol 33\n\n\n\npatients who used traditional Chinese medications \nfor the treatment of their condition before attending \nthe dermatology clinics.\n\n\n\nTopical agents and facial cleansers were used by \n150 (90.9%) and 160 (94.7%) patients respectively. \nThe most common topical agent used was \nbenzylperoxide (67.9%), tretinoin (45.4%) and \nclindamycin (18.8%). Multiple types of facial \ncleanser of various prices were used, mostly of \nmajor cosmetic brands.\n\n\n\nThe mean cost of medications in the treatment of \n1 episode of acne per patient was RM 1170.48 \u00b1 \n1654.69. The government and patients spent a mean \nof RM 519.41 \u00b1 650.44 and RM 651.07 \u00b1 1377.32 \nper patient per episode on the anti-acne medications \nrespectively. The mean cost of medications for the \ntreatment of 1 episode of severe acne was  RM \n1861.75 \u00b1 2023.13 per patient, significantly higher \nthan the mean cost of RM 470.79 \u00b1 644.02 per \npatient for the treatment of 1 episode of moderate \nacne (p<0.001). The mean government expenditure \nfor 1 patient with an episode of moderate acne was \nRM 204.15 \u00b1 330.51 and the patient expenditure \nwas RM 266.63 \u00b1 501.29. For severe acne, the mean \ncost was RM830.87 \u00b1 735.50 and RM 1030.88 \u00b1 \n1803.32 respectively.\n\n\n\nTable 3 shows the relationship between the cost of \nmedications and the socio-demographic variables. \nThe mean cost of medications for the treatment of \nacne in students was significantly less than working \npatients. The mean cost for working patient was \nRM 1624.99 \u00b1 2026.44 per patient per episode, \nsignificantly more than the mean of RM 732.21 \n\u00b1 1027.63 per patient per episode for students (p \n\n\n\n= 0.001). This trend was seen in both the patients \nwith moderate and severe acne. The breakdown of \nmedication costs showed that for working patients, \nthe government cost was RM 602.92 \u00b1 715.31 per \npatient per episode and the patient cost was RM \n1022.07 \u00b1 1756.05 per patient per episode. For \nstudents, the costs were RM 438.89 \u00b1 573.94 and \nRM 293.32 \u00b1 738.88 respectively. The patient cost \nfor working patients was significantly more than \nthat of students (p = 0.001) whereas the government \ncost was not different between the two groups of \npatients (p = 0.11).\n\n\n\nIn patients with moderate acne, patients with tertiary \neducation spent a mean of RM 657.54 \u00b1 811.11 per \npatient per episode. This was significantly more \nthan the mean of RM 338.50 \u00b1 458.01 for those \nwith primary or secondary education (p = 0.04). \nHowever, this trend was not noted in patients with \nsevere acne. There was no association between the \ncost of medications and the socio-demographic \nvariables of gender, ethnic group and economic \nbackground.\n\n\n\nDiscussion\nThere are very few studies examining the cost of \nmedications in the treatment of acne. Such studies \nare difficult to conduct because of the differences \nin practice among dermatologists. In Sarawak, the \naverage cost of treating one episode of acne was RM \n1170.48 (USD 374.55). In comparison, the mean \ncost was USD 463.61 per episode in the United \nStates and USD 99.75 per annum in South Africa.6,7 \nThis difference might be related to the anti-acne \npreferences of the dermatologists, patient factors \nand the socio-economic factors. \n\n\n\nIt is interesting to note that the cost of treating one \nepisode of acne in Sarawak is almost comparable \nto a developed nation of United States. This is \ndespite the differences in the per capita income \nof both nations. This might be attributed by the \nstudy being done in the tertiary dermatological \nclinics in Sarawak, where the treatment of acne \nis optimal compared to treatment in the primary \nhealth care settings where the number of topical \nagents is limited and isotretinoin is not available. \nAnother possible reason for the high cost of acne \ntreatment in this study is the estimation of cost for \npatients with only moderate and severe acne. These \npatients required the use of oral anti-acne especially \nisotretinoin, thus, escalating the medication cost.\n\n\n\nOral anti-acne\n\n\n\nIsotretinoin\n\n\n\nAntibiotics\n\n\n\n     Doxycycline\n\n\n\n     Erythromycin \n\n\n\nEthylsuccinate\n\n\n\nOral contraceptives\n\n\n\n     Diane-35\n\n\n\n     Marvelon\n\n\n\n     Spironolactone\n\n\n\nNumber of courses used\n\n\n\n89\n\n\n\n128\n\n\n\n127\n\n\n\n1\n\n\n\n10\n\n\n\n5\n\n\n\n3\n\n\n\n2\n\n\n\nTable 2 Oral anti-acne agents used\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2014 Dec Vol 33\n\n\n\nIt was interesting to note that only occupational \nstatus was associated with cost of medications. The \ncost was significantly higher in working patients \ncompared to students. The higher cost in working \npatients might be due to the fact that these patients \nare more willing to spend for their condition as they \nare more cosmetically concerned. It is surprising to \nnote that the cost was not associated with gender \nand socio-economic status. Male patients attending \ndermatology clinics are more cosmetically \nconcerned and more aware of their condition, thus \ndemanding optimal treatment. The treatment of acne \nis not dependent on the socio-economic status of the \npatients as all the patients are treated optimally in \nthe dermatology clinics in Sarawak.\n \n\n\n\nIn conclusion, cost of medications for the treatment \nof one episode of moderate and severe acne vulgaris \nin Sarawak is high, with patient cost higher than \nthe government cost. Working patients were more \nlikely to spend more on their condition compared \nto students. This finding is likely to help the health \nadministrators in Malaysia and other regional \ncountries in allocating the optimal resources and \nutilization for the treatment of acne vulgaris.\n\n\n\nSocio-demographic\nvariables\n\n\n\nGender\nMale\n\n\n\nFemale\n\n\n\nEthnic group\nChinese\n\n\n\nNatives\n\n\n\nEducation level\nPrimary/Secondary \n\n\n\nTertiary \n\n\n\nFamily income \n<RM3000 \n\n\n\n\u2265RM3000 \n\n\n\nOccupation status\nStudent\n\n\n\nWorking \n\n\n\nAll patients \n(n = 165)\n\n\n\nMean (SD)\n\n\n\n890.60  \n(1216.35)\n\n\n\n1343.3 \n(1859.73)\n\n\n\n1293.51  \n(1816.95)\n1082.06  \n\n\n\n(1531.25)\n\n\n\n952.51  \n(1518.86)\n1407.77  \n\n\n\n(1770.15)\n\n\n\n990.30  \n(1388.17)\n1421.18  \n\n\n\n(1949.79)\n\n\n\n732.21  \n(1027.63)\n1624.99  \n\n\n\n(2026.44)\n\n\n\nModerate acne\n(n = 82)\n\n\n\nMean(SD)\n\n\n\n347.69\n(448.03)\n545.61\n\n\n\n(732.37)\n\n\n\n556.95\n(677.43)\n409.75\n\n\n\n(619.21)\n\n\n\n338.50\n (458.01)\n657.54\n\n\n\n(811.11)\n\n\n\n395.74\n(499.66)\n576.73\n\n\n\n(801.70)\n\n\n\n302.67\n(473.23)\n696.54\n\n\n\n(770.45)\n\n\n\nSevere acne\n(n = 83)\n\n\n\nMean(SD)\n\n\n\n1416.55 \n(1478.00)\n2141.09 \n\n\n\n(2269.75)\n\n\n\n2009.02 \n(2255.59)\n1754.37 \n\n\n\n(1852.75)\n\n\n\n1728.11 \n(1981.50)\n1974.60 \n\n\n\n(2073.12)\n\n\n\n1584.85 \n(1709.77)\n2241.50 \n\n\n\n(2360.87)\n\n\n\n1277.85 \n(1265.57)\n2331.41 \n\n\n\n(2381.44)\n\n\n\np value\n\n\n\n0.06\n\n\n\n0.42\n\n\n\n0.08\n\n\n\n0.12\n\n\n\n0.001\n\n\n\np value\n\n\n\n0.18\n\n\n\n0.31\n\n\n\n0.04\n\n\n\n0.25\n\n\n\n0.01\n\n\n\np value\n\n\n\n0.11\n\n\n\n0.57\n\n\n\n0.58\n\n\n\n0.15\n\n\n\n0.01\n\n\n\nTable 3 Relationship between cost of medications and the sociodemographic variables\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 MJD 2014 Dec Vol 33\n\n\n\nReferences\n \n1. Purdy S, de Berker D. Acne. BMJ. 2006; 333: 949-53.\n2. Cunliffe WJ. Acne and unemployment. Br J Dermatol. \n\n\n\n1986; 115(3): 386\n3. Koo J. The psychosocial impact of acne: patients\u2019 \n\n\n\nperceptions. J Am Acad Dermatol. 1995; 32(5 Pt 3): \nS25-S30.\n\n\n\n4. Aktan S, Ozmen E & Sanli B.. Anxiety, depression, and \nnature of acne vulgaris in adolescents. Int J Dermatol. \n2000; 39(5): 354-7.\n\n\n\n5. Law PM, Chuh AAT & Lee A.. Acne: its psychological \nconsequences and management. Hong Kong Practitioner. \n2006; 28: 1\u20135.\n\n\n\n6. Balkrishnan R, Uhas A, Reese E, Feldman S. Overall \nmedication cost for the treatment of acne across different \nregions in the United States. J Am Acad Dermatol. 2009; \n60(3 Suppl 1): AB12.\n\n\n\n7. Wessels F, Anderson AN, Kropman K. The cost \neffectiveness of isotretinoin in the treatment of acne. Part \n2: A chronic medication plan profiling study. S Afr Med J \n1999.; 89(7 Pt 2): 785-90. \n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Acne is a common problem affecting not only adolescence but also adults. It causes significant impact \non the quality of life. Moderate to severe acne are commonly treated with combination of oral and topical \nmedications. This study have shown that these medications are not cheap and comparable with Western \nsocieties.\n\n\n\n2. The average cost of treating 1 episode of acne in the government service is RM 1170.48 per patient. \nThe government spend an average of RM 519.41 per patient. It has to be stressed that cost of medications \nin the government setting is many times cheaper than in the private setting. So, this cost is only relevant \nin the government setting.\n\n\n\n3. Patients with acne who are working are more conscious about their outer appearance and would spend \nmore on anti-acne products. Facial appearance is very important for the working class especially those \ninvolved in human relations. A better facial appearance translate to better self esteem and confidence.\n\n\n\n4. This study provide a baseline costing on treatment of acne. Hopefully, this data can be utilized by \nhospital administrators to optimize resource allocations for patients with acne in Malaysia. \n\n\n\nYap FBB \nEditor-in-Chief, Malaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23MJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nSTUDY OF AWARENESS AND MISCONCEPTIONS REGARDING \nACNE AMONG NON-MEDICAL COLLEGE STUDENTS\n\n\n\nTi T1, Romemacedonia JC1, Oh YL1, Wong HX1, Mariette DS1, Theingi MM1\n\n\n\nAbstract\n\n\n\nIntroduction: Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous apparatus. \nAlthough acne is a widely studied disease, the misconception and myths about acne are still prevalent \nin our population. This study aimed to evaluate the awareness and misconceptions of acne among non-\nmedical college students.\n\n\n\nObjectives: A cross-sectional study was conducted among the AIMST University Foundation students \nin March 2014.\n\n\n\nMaterials & Methods: A retrospective review of the data of all patients with SJS, TEN and DRESS \ntreated from January 2009 to December 2013 was retrieved and analyzed.  \n\n\n\nResults: 200 students ranging from 18 to 21 years participated in the study. The female to male \nratio was 2:1. 83.3% agreed that acne is curable. 48.5% understood that acne is not a serious health \nproblem. 51.8% believed that acne is not contagious. Regarding the risk factors, 59.3% attributed acne \nto genetics. Many agreed that acne affects adolescents (52.8%) and teenage boys have more severe \nacne (57.8%). 92% believed that dirt causes blackheads. Most students claimed that poor hygiene \n(58.3%), stress (94.9%), sleep (96.4%), diet (92%), shaving (74.4%) and sunlight (81.9%) cause acne \nformation. Greasy hair products (52.5%) and cosmetic products (85.9%) can aggravate acne. As to the \ntreatment, 52.6% suggested that acne should be treated. Popping/squeezing pimples with pus rapidly \nheals acne (53.6%). Those with history of acne agreed that acne could lead to scarring without picking \n(61.4%), and that acne scars is treatable (65.8%).\n\n\n\nConclusion: The misconceptions of acne are prevalent among the non-medical college students. This \nissue has to be addressed with the collective effort from all parties to dispel the misconceptions and \nmyths of acne.\n\n\n\nKeywords: acne vulgaris, misconception, myths\n\n\n\nCorresponding Author and Reprint Request \nDr Ti Tiana, MBBS (Hons)\n51-A Lintang Angsana,Bandar Baru Ayer Itam,\n11500 Pulau Pinang, Malaysia.\nE-mail: tiana_bunny@hotmail.com\n\n\n\n2 Unit of Dermatology, Faculty of Medicine,\n AIMST University\n3 Department of Population Medicine,\n Faculty of Medicine and Health Sciences,\n Universiti Tunku Abdul Rahman\n\n\n\nIntroduction\nAcne vulgaris is a chronic inflammatory disorder of \nthe pilosebaceous apparatus of certain body areas like \nface and trunk and is characterized by the formation \nof comedones (blackheads and whiteheads), \nerythematous papules, pustules, nodules and cysts. \nThis skin disorder is more common among the \nyoung people. Nonetheless, it occurs in everyone. \nThe age group affected by acne is 10 to 17 years old \nfor females and 14 to 19 years old for males.1 It is \nfound to be more severe in males (71.1%) compared \nto females (64.6%) in adolescents.2 It also affects 3% \nof male and 12% of female adults.3\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24 MJD 2014 Dec Vol 33\n\n\n\nAcne vulgaris is a multifactorial disease. The four \nmain factors in the ethiopathogenesis of acne are \nincreased sebum secretion, follicular plugging, \nbacterial colonization and inflammation. It is also \nnoted that majority of the individuals who suffer \nfrom acne have a positive family history.1\n\n\n\nThere have been extensive researches on the \nethiopathogenesis, treatment and psychosocial \nimpact of acne but there is a paucity of data \nregarding the beliefs and misconceptions about \nacne among the general public.4,5 A local study \ndone in UKM has shown that the prevalence of \nacne among medical students is high.6 Therefore, \na survey was conducted among the Foundation \nstudents of AIMST University to help us to have a \nbetter understanding of the misconceptions of acne \namong the non-medical college students.\n\n\n\nMaterials and methods\nThis was a cross-sectional study carried out at \nAIMST University in March 2014. The Foundation \nstudents from April, May and July batches were \nenrolled in the study. All students regardless of their \nsex, age and students with or without acne were \nincluded in the study. The exclusion criteria included \nstudents who voluntarily excluded themselves, those \nwho were ill on the day of the survey and refused to \nparticipate in the survey.\n\n\n\nA set of specially designed questionnaire (as \nattached in the Appendix) was formulated with \nreference to several creditable sources and validated \nby a dermatologist. Three choices were given for \neach question, namely \u2018agree\u2019, \u2018disagree\u2019 and \u2018not \nsure\u2019. The questionnaire addressed three main issues \non acne, namely the risk factors, causative factors \nand general measures to combat acne.4 A verbal \nconsent was obtained prior to the distribution of the \nquestionnaire. The questionnaire was distributed \nunannounced to the students and completed during \ntheir classes. Upon completion of the questionnaire, \npamphlets were disseminated to all the participants \nto enhance their understanding and correct their \nmisconceptions about acne. The identification \nof the students was kept confidential. The data \nobtained was interpreted and tabulated to evaluate \nthe participant\u2019s awareness of acne. The data was \ntabulated using Microsoft Excel while data analysis \nwas done by using Epi Info Version.3,5,4 Data was \nsubjected to descriptive analysis and presented as \nnumber (percentages).\n\n\n\nResults\nA total of 200 AIMST Foundation students, \nrandomly selected from April, May and July batches \nwere enrolled in this study. The students\u2019 age ranges \nfrom 18 to 21 years old. The ratio of female to male \nstudents is 2:1, as shown in Figure 1. The gender of \nthe remaining 14 students is not known.\n\n\n\nOf the total subjects, 83.2% of the students had \nprevious history of acne while 16.8% remained as \nnon-sufferers. According to the 83.2% of the acne \nsufferers, only 24.2% of them have sought treatment \nfor acne. 83.3% of the students were aware that acne \nis a curable disease. However, approximately half \nof the students (48.5%) agreed that acne is not a \nserious systemic health problem (Table 1).\n\n\n\nThe first part of the questionnaire intended to \nevaluate the awareness of the subjects regarding the \nrisk factors of acne (Table 1). Most of the students \n(59.3%) are not aware that acne is not purely \nattributable to genetic factor. 52.8% of the students \nalso thought that acne is only seen in adolescents. \n57.8% of the students either believed or are not sure \nthat acne is more severe in teenage boys than in \nteenage girls.\n\n\n\nThe second part of the questionnaire was about \nthe students\u2019 awareness and misconceptions on \nthe causes of acne (Figure 2). 92% of the students \nbelieved that blackheads are due to the accumulation \nof dirt. 58.3% of the students thought that acne is \npurely due to poor hygiene. 94.9%, 96.4%, 92% and \n74.4% of the students either believed or are not sure \nthat acne is contributed by stress, sleep, diet and \nshaving respectively. Only 18.1% of the students \nwere aware that sunlight does not worsen acne. Most \nstudents agreed that greasy hair products (52.5%) \nand cosmetic products (85.9%) can aggravate acne. \nAbout half of the students (51.8%) gave a negative \nresponse for the statement \u2018acne is contagious\u2019.\n\n\n\nFifty three point six percent of the students believed \nthat popping/squeezing pimples with pus allows \nacne to heal rapidly4. 52.6% agreed that acne should \nbe treated whereas 13.4% believed acne should run \nits course and that no treatment is required. 11.9% \ndid not know that treatment options are available \nfor acne scars. 61.4% of the students who have had \nacne before agreed that acne could lead to scarring \nwithout picking. 65.8% of the acne sufferers gave a \npositive response that acne scars are treatable.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25MJD 2014 Dec Vol 33\n\n\n\n33.3%\n\n\n\n66.7%\n\n\n\nMale\n\n\n\nFemale\n\n\n\nFigure 1  Gender distribution\n\n\n\nFigure 2  Perception on causes of acne\n\n\n\nImpression on acne (N = 198)\nCurable disease\nSerious systemic health problem\n\n\n\nRisk factors (N = 199)\nGenetic factor\nAdolescence age group\nSeverity in boys\n\n\n\nAgree\nNo (%)\n\n\n\n165 (83.3)\n55 (27.8)\n\n\n\n55 (27.6)\n67 (33.7)\n61 (30.7)\n\n\n\nDisagree\nNo (%)\n\n\n\n8 (4.0)\n90 (48.5)\n\n\n\n81 (40.7)\n94 (47.2)\n84 (42.2)\n\n\n\nNot sure\nNo (%)\n\n\n\n25 (12.6)\n47 (23.7)\n\n\n\n63 (31.7)\n38 (19.1)\n54 (27.1)\n\n\n\nTable 1 Impression on acne and risk factors for acne\n\n\n\n100.00%\n\n\n\n90.00%\n\n\n\n80.00%\n\n\n\n70.00%\n\n\n\n60.00%\n\n\n\n50.00%\n\n\n\n40.00%\n\n\n\n30.00%\n\n\n\n20.00%\n\n\n\n10.00%\n\n\n\n0.00%\n\n\n\nB\nla\n\n\n\nck\nh\n\n\n\nea\nd\n\n\n\ns\n\n\n\nH\nyg\n\n\n\nie\nn\n\n\n\ne\n\n\n\nS\ntr\n\n\n\nes\ns\n\n\n\nS\nle\n\n\n\nep\n\n\n\nD\nie\n\n\n\nt\n\n\n\nG\nre\n\n\n\nas\ny \n\n\n\nh\nai\n\n\n\nr\n\n\n\nS\nh\n\n\n\nav\nin\n\n\n\ng\n\n\n\nC\no\n\n\n\nsm\net\n\n\n\nic\n\n\n\nS\nu\n\n\n\nn\nlig\n\n\n\nh\nt\n\n\n\nC\no\n\n\n\nn\nta\n\n\n\ng\nio\n\n\n\nu\ns\n\n\n\nAgree\n\n\n\nDisagree\n\n\n\nNot sure\n\n\n\nStudents\u2019 Awareness on Causes of Acne\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26 MJD 2014 Dec Vol 33\n\n\n\nDiscussion\nNowadays, societal norms have placed perpetual \nemphasis on an individual\u2019s outer appearance \nand having clear, beautiful skin is a trait that is \nhighly esteemed in many cultures. Many have \nconsequently sought treatment for skin conditions \nsuch as acne. Acne vulgaris is one of the commonest \nskin disorders with profound psychosocial impact.4 \nFor many years, the understanding of society on \nacne has been guided mostly, if not entirely, by \nmisconceptions/myths which have been passed down \nfrom generation to generation, circulated among \npeers and published in the mass media. Therefore, it \nis of no surprise that the misconceptions about acne \nremain prevalent to this day. \n\n\n\nThis research aims to study the misconceptions of \nacne among the Foundation students in AIMST \nUniversity and at the same time, educating them \nabout the facts of acne as well as correcting their \nmisconceptions. The selection of sample was made \nto ensure adequate representation of different \ndemographic groups in Malaysia. Foundation \nstudents are selected for this study because they are \nmore representative of the general population as \nthey are not yet exposed to the medical education. \n\n\n\nOf the 200 respondents, 124 are females, 62 are \nmales and the remaining 14 did not specify their \ngender. Therefore, analysis of data cannot be \nperformed based on gender because it would be \nquestionable.\n\n\n\nWith reference to the results obtained from this study, \nit is confirmed that the misconceptions about acne \nremains prevalent among the Foundation students. \nThe 83.2% who reported having suffered from acne \nin this study supports the already known fact that \nacne is a common problem affecting adolescents. \nSome students still have the wrong belief about \nacne as evidenced by the fact that despite 83.3% \ncorrectly identified acne as a curable disease, less \nthan half of the students (48.5%) believed that acne \nis not a systemic health problem.  Similar results \nwere reported from a study from France where a \nmajority of the subjects did not perceive acne as a \ndisease, but a normal phase of adolescents.7 Besides \nthat, 59.3% students are not aware that acne is not a \ngenetically inherited disease.\n\n\n\nUnfortunately, a significant number of students \n(92%) thought that blackheads are caused by dirt \naccumulation and more than half of them (58.3%) \nattributed acne to poor hygiene alone. The findings \n\n\n\nthat majority of them did not truly understand \nthe fact that acne is not caused by stress (94.9%), \nsleep deprivation (96.4%), diet (92%) and shaving \n(74.4%) further reflects the poor awareness of the \nsubjects on the etiologies of acne. Furthermore, \nabout half of the students (48.2%) are not aware that \nacne is not a contagious disease. This shows that the \nmisconceptions of acne are highly prevalent among \nstudents despite the high availability of information. \n\n\n\nMost of the students (53.6%) failed to understand \nthat popping or squeezing pimples with pus will not \nhasten the recovery of this skin condition. 52.6% of \nthe students are aware that acne should be treated \nwhereas 13.4% believed acne should run its course \nand that no treatment is required. 11.9% are ignorant \nthat treatment options are available for acne scars. \nWe found that of the 83.2% acne sufferers in this \nstudy, only 24.2% of them have sought treatment \nfor acne. Majority of the students (61.4%) who \nhave suffered from acne agreed that acne could \nlead to scarring without picking. From the figures \nregarding the treatment of acne, we can deduce that \nthe treatment utilization for acne is still very low \nand the misconceptions about acne are prevalent \namong the AIMST Foundation students.\n\n\n\nThis study confirms that the prevalence of the \nmisconceptions of acne among the AIMST \nFoundation students is significantly high. The \nstudents\u2019 misconceptions towards acne could stem \nfrom their repetitive exposure to beauty magazines \nwritten by non-health experts that further strengthen \nthe already existing misconceptions they have. In \naddition, the existence of the already large group \nthat hold the misconceptions tend to enhance \nand promote the misconceptions through counter \nconfirmation of the same ideas from members of \nthe peers that hold the same misconceptions. The \nmisconceptions have also been passed down from \ngenerations to generations, and whatever that is \nheld over many generations is often difficult to be \ndispelled. \n\n\n\nThe booming beauty industries like beauty parlours, \ntogether with beauty and cosmetics magazines, \nskincare websites have indirectly encourage a \ngrowing trend of seeking advice and treatment of \nacne from non-health professionals, rather than \nconsulting a dermatologist. These non-health \nprofessionals have inadequate understanding about \nacne and have been offering advices that may further \npropagate the misconceptions about acne.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27MJD 2014 Dec Vol 33\n\n\n\nSuch misconceptions about acne can lead to \nimproper or under-treatment of acne, which could \nresult in poor response and complications such as \nacne scarring that can potentially affect the quality \nof life of the affected adolescents. Therefore, \ncorrective actions should be taken to address this \nissue. Further studies on different populations are \nnecessary to highlight this issue so that proper \nmeasures can be taken to correct the misconceptions \nof acne among students.\n\n\n\nIt is a common old wives saying: \u2018Acne is a sign \nof adolescence and will wear out with time.8\u2019 \nWhile it is true that acne usually occurs during the \nadolescence period, it may persist in some long \nafter teenage days are gone, creating a considerable \npsychological impact on the quality of life of the \nadolescents.2 Therefore, treatment of acne should \nalways take into consideration this important aspect \nof life caused by acne.9 \n\n\n\nEarly treatment should be instituted for acne because \na proactive approach towards acne can minimize the \nrisk of scarring.10 The widely held misconceptions \nabout acne among adolescents can be corrected \nthrough promotion of public education about the \nfacts of acne. It is time to look into these myths and \nscientifically remove the hurdle surrounding one of \nthe most treatable skin disorders.8 \n\n\n\nConclusion\nIn conclusion, the result of our study revealed \nthat acne and the misconceptions of acne among \nadolescents are both common. The findings from \nour study were consistent with other studies on \nsimilar populations elsewhere.11-14 The prevalence \nof misconceptions of acne among students remains \nhigh in spite of the availability of information about \nacne in the media. There is a need to understand the \nreason behind this so that appropriate and effective \nactions can be constructed to overcome this problem \neffectively.\n\n\n\nReferences\n \n1. Wolff K, Johnson RA. Section 1: Disorders of Sebaceous \n\n\n\nand Apocrine Glands: Acne vulgaris (common acne) and \ncystic acne. Fitzpatricks color atlas and synopsis of clinical \ndermatology. 6th edition. McGraw Hill Professional 2009. \np.2.\n\n\n\n2. Hanisah A, Omar K, Shah SA. Prevalence of acne and its \nimpact on the quality of life in school-aged adolescents in \nMalaysia. J Prim Health Care 2009; 1 : 20-5.\n\n\n\n3. Goulden J, Stables GI, Cunliffe WJ. Prevalence of facial \nacne in adults. J Am Acad Dermatol 1994; 41: 577-80.\n\n\n\n4. Farid R, Khan N, Nadeem A. Beliefs and perceptions about \nacne among undergraduate medical student. J Pak Assoc \nDermatol 2007; 17: 231-234. \n\n\n\n5. Tan JKL, Kirsten V, Fung KY. Beliefs and perceptions of \npatients with acne. J Am Acad Dermatol 2001; 44 : 439-\n45.\n\n\n\n6. Muthupalaniappen L, Tan HC, Puah JWD, et al. Acne \nprevalence, severity and risk factors among medical \nstudents in Malaysia. Clin Ter 2014; 165 : 187-92. \n\n\n\n7. Poli F, Auffret N, Beylot C, et al. Acne as seen by \nadolescents: results of questionnaire study in 852 French \nindividuals. Acta DermVenereol 2011; 91: 531-536.\n\n\n\n8. Zohra Z. Dispelling the myths and misconceptions of acne. \nJ Pak Assoc Dermatol 2009; 5: 264-265. \n\n\n\n9. Yap FB. Cardiff Acne Disability Index in Sarawak, \nMalaysia. Ann Dermatol 2012; 24: 158-61.\n\n\n\n10. Clearihan L. Acne. Myths and management issues. Aust \nFam Physician 2001; 30: 1039-44 in acne management: \ndiet, face-washing, and sunlight. Fam Pract 2004; 1: 62-70.\n\n\n\n11. Tan HH, Tan AW, Barkham T, et al. Community-based \nstudy of acne vulgaris in adolescents in Singapore. Br J \nDermatol 2007; 157: 547-51.\n\n\n\n12. Pearl A, Arroll B, Lello J, Birchall NM. The impact of \nacne: a study of adolescents\u2019 attitudes, perception and \nknowledge. N Z Med J 1998; 111: 269-71.\n\n\n\n13. Al-Hoqail IA. Knowledge, beliefs and perception of youth \ntoward acne vulgaris. Saudi Med J 2003; 24: 765-68.\n\n\n\n14. Smithard A, Glazebrook C, Williams HC. Acne prevalence, \nknowledge about acne and psychological morbidity in \nmid-adolescence: a community-based study. Br J Dermatol \n2001; 145: 274-79.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28 MJD 2014 Dec Vol 33\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Misconception of acne is common among the lay person. Many still believe the myths linked to acne.\n\n\n\n2. Acne is not only a disease of adolescence as perceived by 52.8% of respondents. It is also commonly \nseen in adults especially females. Knowledge that acne still persist in adults is important as it will allay \nanxiety about having other facial skin diseases and allow for proper treatment seeking behaviour.\n\n\n\n3. Only 24.2% of respondent in this study seek treatment for their acne and 52.6% think that acne should \nbe treated. This might be due to the perceived notion that acne will heal itself with time. Those with \nsevere acne who don\u2019t seek treatment will eventually end up having severe facial scarring.\n\n\n\n4. Many respondents perceived acne to be due to dirt and poor hygiene. This will lead to stigmatization \nof those with acne being dirty and unkempt.\n\n\n\n5. Proper education should be given to the general public about acne and its treatment to dispel all these \nmyths and wrong perception about this condition.\n\n\n\nYap FBB MD MRCP AdvMDerm\nEditor-in-Chief, Malaysian J Dermatol\n\n\n\nAppendix\n\n\n\nMisconception of Acne Questionnaires\nMainly modified from Journal of Pakistan \nAssociation of Dermatologists 2007; 17:232. \n\n\n\nPlease fill in your details and tick on the\nchoice you agree with.\nAge:\nSex:\n\n\n\nDid you experience acne before? \n[  ] Yes  [  ] No\n\n\n\nIf yes, please answer the next question.\nDid you seek medical attention for the acne \nbreakout? \n[  ] Yes  [  ] No \n \nPlease tick on the choice you agree with:\n1. Acne is a curable disease.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n2. Acne is a serious systemic health problem.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\nQuestions related to the risk factors of acne:\n3. Acne is purely attributable to genetic factor.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n4. Acne is seen only in adolescence.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n5. Acne is always more severe in teenage boys \n than in girls.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\nQuestions related to the causes of acne:\n6. Blackheads are formed by dirt.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n7. Acne is caused by poor hygiene alone.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29MJD 2014 Dec Vol 33\n\n\n\n8. Acne is caused by stress.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n9. Lack of sleep contributes to acne.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n10. Acne is caused by diet (chocolate, oily or\n fatty food, high sugar-content food).\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n11. Greasy hair products can aggravate acne.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n12. Shaving causes acne breakouts in men.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n13. Some cosmetic products can worsen acne.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n14. Sunlight worsens acne in all patients.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n15. Acne is contagious. (It can spread by contact \n from one person to the other or by sharing \n towels.)\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\nQuestions related to the treatment of acne:\n16. Squeezing/popping pimples with pus will\n help them go away faster.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n17. Topical steroid alone is a treatment option.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n18. One should allow acne to run its course \n without treatment.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n19. Severe acne can lead to scarring even\n without picking. \n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n20. There\u2019s no treatment for acne scars.\n a. [  ] Agree\n b. [  ] Disagree\n c. [  ] Not sure\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30 MJD 2014 Dec Vol 33\n\n\n\nQUIZ\n\n\n\nMULTIPLE HYPOPIGMENTED PATCHES ON THE SKIN\n\n\n\nCorresponding Author and Reprint Request \nYap FBB, MRCP AdvMDerm\nFaculty of Medicine and Health Sciences,\nUniversiti Tunku Abdul Rahman, Sungai Long Campus, \nJalan Sungai Long, 43000 Kajang, Selangor DE\nEmail: woodzlamp@yahoo.com\n\n\n\nQuestions\n\n\n\n1. What is the most likely diagnosis?\n a. Pityriasis alba\n b. Lichen planus\n c. Pityriasis versicolor\n d. Epidermodysplasia verruciformis (EV)\n\n\n\n2. What is the investigation of choice?\n a. Tape test\n b. Skin biopsy\n c. Skin scraping for fungal culture\n d. None\n\n\n\n3. What is the expected histological finding?\n a. Interface dermatitis\n b. Presence of spores and short \u2018cigar-butt\u2019 \n  hyphae in stratum corneum\n c. Large keratinocytes with perinuclear haloes \n  and blue-gray pallor\n d. Non specific finding\n\n\n\n4. What treatment can be prescribed for this \n patient?\n a. Acitretin\n b. Phototherapy\n c. Oral antifungal\n d. Topical steroids\n\n\n\nc.  Closed up view of the skin lesions\n\n\n\nb.  Multiple hypopigmented macules patches on the chest \n     and neck\n\n\n\na.  Multiple hypopigmented macules patches on the back\n\n\n\nA 35 year old Indian lady presented with multiple \nhypopigmented macules and patches on the whole \nbody concentrated mainly on the trunk and proximal \nlimbs. She started to notice the skin lesions since \nher teenage years. The skin lesions were neither \nitchy nor painful. She has seen many doctors over \nthe years without much improvement.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31MJD 2014 Dec Vol 33\n\n\n\nDiscussion\nEpidermodysplasia verruciformis (EV) is a rare \nautosomal recessively inherited disease. Patients \nwith EV are susceptible to infection by specific \ntypes of human papillomavirus (HPV).1 The disease \nwas first described by Lewandowsky and Lutz.2 \n\n\n\nThe increased susceptibility to certain HPV \ninfections is caused by a defective cell medicated \nimmunity. This in turn is due to mutation in the \nEVER1 and EVER2 genes located in the EV1 locus \non chromosome 17. Another EV susceptibility \nlocus is the EV2 locus on chromosome 2.1,3 The \nHPVs that are specific to EV are usually referred \nto as \u201cEV-HPVs\u201d. They are HPV 3, 5, 8, 9, 10, 12, \n14, 15, 17, 19 to 25, 28, 29, 36, 46, 47, 49 and 50.1 \n\n\n\nThere are 2 clinical forms of EV based on \npotential malignant transformation. The commoner \nbenign form presents with pityriasis versicolor \nlike hypopigmented flat wart-like macules and \npatches on the trunk and proximal limbs. It usually \nmanifests in infancy and early childhood. On the \nother hand, the potentially malignant form presents \nwith verrucous and seborrheic warts-like lesions. \nThe lesions are commonly seen on the sun exposed \nareas.1 The transformation to skin malignancy \nusually occurs in the forth to fifth decade. Malignant \ntransformation is seen in 30% to 60% of patients.5 \n\n\n\nInvasive squamous cell carcinoma is the commonest \nskin cancer detected. Other malignancies include \nBowen\u2019s disease and adnexal carcinomas. \n \nThe diagnosis of EV must be suspected in patients \nwith pityriasis versicolor-like lesions who failed \nto respond to treatment or patients with multiple \nverrucous skin lesions. The key to diagnosis is typical \nclinical features, histopathological examination and \nHPV typing (this is not widely available).1 \n\n\n\nThe histopathological examination of skin lesion in \nEV is mainly focused on the epidermis. Hematoxylin \nand eosin staining reveals moderate hyperkeratosis \nof the stratum corneum with presence of acanthosis \nand koilocytes (vacuolated keratinocytes) that have \nblue-gray pallor and perinuclear haloes.1 These \nare the typical features of planar warts. There is \nno definitive treatment for EV. Preventive measure \nnamely sun avoidance and protection is of utmost \nimportance. \n \nTreatment for warts are employed for each individual \nlesions and this include destructive treatment e.g. \ncryotherapy and immunomodulating treatment e.g. \nimiquimod. Treatment with retinoids e.g. acitretin \nare also useful. They are believed to down regulate \nHPV transcription and up regulate Langerhans \ncells.1 \n\n\n\nReferences\n \n1. Wolff K, Johnson RA. Section 1: Disorders of Sebaceous 1. \n\n\n\nSri JC, Dubina MI, Kao GF, et al. Generalized verrucosis: \nA review of the associated diseases , evaluation and \ntreatments. J Am Acad Dermatol 2012; 66: 292-311.\n\n\n\n2. Tanigaki T, Endo H. A case of epidermodysplasia \nverruciformis (Lewandowsky-Lutz, 1922) with skin \ncancer: histopathology of malignant cutaneous changes. \nDermatologica 1984; 169: 97-101.\n\n\n\n3. Majewski S, Jablonska S. Do epidermodysplasia \nverruciformis human papillomaviruses contribute to \nmalignant and benign epidermal proliferations? Arch \nDermatol 2002; 138: 649-54.\n\n\n\n4. de Oliveira WR, Festa Neto C, Rady PL, Tyring SK. \nClinical aspects of epidermodysplasia verruciformis. J Eur \nAcad Dermatol Venereol 2003; 17: 394-8.\n\n\n\n5. Jablonska S, Orth G. Epidermodysplasia verruciformis. \nClin Dermatol 1985;3:83-96\n\n\n\nAnswers: 1.d, 2.b, 3.c, 4.a\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32 MJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nPITFALLS IN DIAGNOSIS AND TREATMENT OF PEMPHIGUS \nFOLIACEUS IN A YOUNG BOY \n\n\n\nLing HN1,  Tagal JM2,  Lee BR3, Kho WM1,  Leong KP4, Pubalan M1\n\n\n\nIntroduction\nPemphigus foliaceus (PF) is due to loss of \nmalphigian cell coherence through binding of IgG \n+/\u2212 C3 antibody directed against a polypeptide \nantigen complex on the keratinocyte surface. \nChildhood PF typically causes erythema and scalp \nscaling that slowly progresses to involve the trunk \nand limbs. It is rare in children.1  \n\n\n\nHerein we report a case of a young boy with PF \ncomplicated with allergic contact dermatitis, sepsis \n& erythroderma.\n\n\n\nCorresponding Author and Reprint Request \nDr Ling Hee Ninh\nDepartment of Dermatology\nSarawak General Hospital, Jalan Hospital,\n93586 Kuching, Sarawak\nEmail: heeninh@yahoo.com.sg\n\n\n\n\u00b2 Opthalmology, Sarawak General Hospital,\n Jalan Hospital, 93586 Kuching, Sarawak\n\u00b3 Department of Pathology\n4 Paediatrics, Hospital Kuala Lumpur, Jalan Pahang,  \n 50586 Kuala Lumpur\n\n\n\nCase Report\nA 9 year old boy presented with scaly scalp lesions \nassociated with crusting & oozing (Figure 1). He \nwas initially treated as impetiginized scalp psoriasis. \nDifferentials were tinea capitis & seborrheic \ndermatitis. Mucosal surfaces, joints & nails were \nspared. No blisters were seen. Oral cephalexin, \nacitretin & topical steroids was initiated. His lesions \nprogressed unto his face despite those treatments. \nSpecimens taken were positive for Trichophyton & \nPseudomonas. He was treated with oral terbinafine \nfor 4 weeks. Acitretin was stopped due to intolerable \nitch.\n\n\n\nLesions progressed rapidly to erythroderma. Patient \ndeveloped MRSA sepsis after immunosuppression \nwith cyclosporin & prednisolone. First skin \nbiopsy (right arm) showed spongiotic dermatitis \nwith eosinophilia suggestive of allergic contact \ndermatitis. Papillary dermis had perivascular \ninflammation with prominent eosinophilic infiltrate. \nAdnexa & subcutis was unremarkable with no blister \nformation. PAS stain was negative. No immuno-\nflorescence was done at that time. Repeat open \n\n\n\nFigure 1B   Erythrodermic with generalized scales and \nunderlying erythema.\n\n\n\nFigure 1A   At initial presentation with dominant scalp \ninvolvement and few scattered lesions on the trunk.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33MJD 2014 Dec Vol 33\n\n\n\napplication test (ROAT) on a unilateral arm showed \npatient\u2019s skin lesions worsened on Aqueus cream & \nBetamethasone. The positive ROAT coupled with \nthe skin biopsy findings strongly suggested the  \npossibility of ongoing allergic contact dermatitis \nalthough a patch test could not be performed at that \npoint of time.\n\n\n\nDiscussion\nPF usually presents with erythematous scaly plaques \nand superficial erosions resembling an exfoliative \ndermatitis.2 If a child is seen in the early stage of \nthe disease with only scalp involvement, lesions can \nbe mistaken for the commoner causes of childhood \nscalp scaliness such as tinea capitis, seborrheic \ndermatitis or scalp psoriasis. Intact blisters may not \nbe seen as blisters are superficial with too thin a \nblister roof to allow fluid accumulation. \n\n\n\nAs lesions progress to the erythrodermic stage, \ndifferential diagnoses include severe or disseminated \nforms of impetigo, seborrheic dermatitis, psoriasis, \nand staphylococcal scalded skin syndrome. In an \nerythrodermic child, it is important to consider \nthe diagnosis of PF & biopsy lesions early before \ntreatment complicates the clinical picture.  Diagnosis \nis confirmed by histo-pathological findings, mainly \nthe presence of a sub corneal blister with positive \ndirect immunofluorescence for IgG and C3.3,4 PF in \nchildren is rare 4 with only 7 cases in the pediatrics \npopulation reported over a period of 12 years (1986-\n1997).5 Given its rarity, treatment guidelines for \njuvenile pemphigus foliaceus are lacking.6 \n\n\n\nSevere PF are usually treated with systemic steroids \n& immunosuppressants. Multiple studies have \nshown Dapsone to be effective in PF in children.1,2,6 \nThe potential toxicity (methaemoglobinaemia \n& hemolysis, life threatening neutropenia & \nagranulocytosis) of this well known product at this \nage calls for very close hematological monitoring. \n\n\n\nPF should be suspected in erythematous scalp \nlesions. Concomittant allergic contact dermatitis & \nsuperimposed fungal /bacterial infection can blur \nclinical picture & delay diagnosis. \n\n\n\nFigure 2C   Fishnet pattern of IgG (top) and C3 (bottom) \ndeposition on direct immunoflourescence\n\n\n\nFigure 2B   Subcorneal blister\n(Magnification X40, H & E stain)\n\n\n\nFigure 2A   Presence of subcorneal blisters\n(Magnification X 20, H & E stain)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34 MJD 2014 Dec Vol 33\n\n\n\nReferences\n\n\n\n1. Leibowitz MR, Voss SP. Juvenile Pemphigus Foliaceus: \nResponse to Dapsone [letter]. Arch Dermatol 1993; \n129:910.\n\n\n\n2. Garc\u00eda-Mel\u00e9ndez ME, Eichelmann K, Salas-Alan\u00eds JC et \nal. Pemphigus Foliaceus  in an 11 year old Mexican Girl \nWith Response to Oral Dapsone. Case Reports Pediatr \n2013; 291256.\n\n\n\n3. Kanwar AJ, Dhar S, Kaur S. Further Experience with \nPemphigus in Children. Pediatr Dermatol 1994; 11(2):107-\n111.\n\n\n\n4. Yorav S, Trau H, Schewach-Millet M. Pemphigus Foliaceus \nin an 8-Year-Old Girl. Int J Dermatol. 1989; 28(2):125-\n126.\n\n\n\n5. Galambrun C, Cambazard F, Clavel C et al. Pemphigus \nFoliaceus. Arch Dis Childhood 1997; 77:255\u2013257\n\n\n\n6. Mehravaran M, Morvay M, Moln\u00e1r K et al. Juvenile \npemphigus foliaceus. Br J Dermatol 1998; 139(3): 496-9.\n\n\n\nAcknowledgement:\nThe authors would like to thank the Director General of Health Malaysia for permission to publish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35MJD 2014 Dec Vol 33\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nPERIANAL BASAL CELL CARCINOMA: REPORT OF A CASE \n\n\n\nOchi H, Pan JY2\n\n\n\nIntroduction\nBasal cell carcinoma (BCC) is the most common \nhuman malignancy in the world. Ultraviolet light \nexposure is an established risk factor of BCC, which \nexplains its predilection for sun-exposed areas. \nBCCs occurring in sun-protected areas are rare and \nother etiologies must be considered.\n\n\n\nCase synopsis\nA 68-year-old Chinese male presented with a painful \nperianal nodule for more than 1 year. He had a past \nmedical history of hypertension with no prior note \nof basal cell carcinoma or immunosuppression. He \nalso denied any radiotherapy, chronic irritation or \ntrauma to the anus. Physical examination revealed \n\n\n\nCorresponding Author and Reprint Request\nDr Ochi Harumi\n26B, Jalan Haji Alias, Singapore 268528\nEmail: ochiharumi89@gmail.com\n\n\n\n2 National Skin Centre, 1 Mandalay Road,\n Singapore 308205\n\n\n\nan indurated area at the perineum measuring 1.8 \nby 0.9 cm. (Fig. 1). Incisional biopsy performed \nshowed nodular BCC. Magnetic resonance imaging \nof the pelvis showed no deep extension or lymph \nnode involvement. The patient underwent wide \nlocal excision (WLE) and reconstructive surgery. \nNo metastasis was observed in the 2-year follow-up \nperiod.\n\n\n\nDiscussion\nBasal cell carcinoma in non sun-exposed areas is \nrare. In the largest study of 18 943 cases of BCC, \nonly 15 perianal BCCs (0.08%) were reported. \nNodular BCC was the commonest histological \nsubtype.1\n\n\n\nFigure 1  The patient presented with an indurated area with \nirregular margins in the perianal region measuring 1.8 by \n0.9cm. There was no inguinal lymphadenopathy. \n\n\n\nFigure 2  Infiltrating basaloid tumour composed of nests, \ncords and islands with peripheral palisading. The tumour \ncells had oval hyper-chromatic nuclei with frequent mitotic \nactivity. There was invasion into the reticular dermis \nto a depth of 3 mm. (Haemotoxylin and Eosin stain, \nmagnification x20).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36 MJD 2014 Dec Vol 33\n\n\n\nFactors implicated in development of BCC include \nfamilial syndromes (nevoid basal cell carcinoma \nsyndrome), radiotherapy, immune deficiencies and \nchronic irritation. The human papilloma virus is not \na proven etiological factor in the pathogenesis of \nBCC in non sun-exposed areas. In situ hybridization \nfailed to detect the human papilloma virus in the \nspecimens from patients with perianal and genital \nBCC.2,3\n\n\n\nPerianal BCC accounts for only 0.2% of the anorectal \ntumors. Squamous cell carcinoma (SCC) is the most \ncommon tumour of the anal canal and the basaloid \nvariant is the most common phenotype.3 \n\n\n\nBCC and basaloid SCC show overlapping \nhistological features that pose diagnostic \nchallenges. Both comprise nests of oval cells with \nmoderate amount of eosinophilic to basophilic \ncytoplasm and peripheral nuclear palisading. The \nonly significant distinguishing factor is retraction \nartifacts suggestive of BCC. Immunohistochemistry \npatterns can aid in diagnosis. Diffuse Ber-EP4 and \nBCL2 expression are features of BCC. CDKN2A \nand SOX2 expression characterize basaloid SCC.3\n\n\n\nBCCs are locally invasive with little metastatic \npotential.  Lesions <2 cm can be treated by wide \nlocal excision with 1 cm margins.4  The recurrence \nrates after surgery vary. Paterson et al2 followed 19 \npatients treated with local excision (LE) (17/19), \nelectrocautery (1/19) and Moh\u2019s microsurgery \n(1/19). All patients were free of recurrence 72 months \nafter excision. Nielson had 34 cases of perianal \nBCC managed with LE (27/34), abdominoperineal \nresection (4/34) and radiotherapy (3/34).5 There \nwas a recurrence rate of 24 % following LE. They \nunderwent a repeated LE with no recurrence in 5 \nyears.\n\n\n\nBCCs in sun-protected areas present late. Gibson et \nal reported perianal BCC with an average size of \n1.95 cm and ulceration in 30% of cases.1 Paterson et \nal reported average perianal BCC size as < 2cm and \nulceration in 29% of cases.2 Although no correlation \nbetween tumour size and metastatic potential exists, \nlarger tumours require reconstructive surgery and \ncause greater morbidity. It is conceivable that the \npoor visualization of such areas by patients could \ncontribute to its late detection. It is thus imperative \nfor clinicians to increase surveillance in these areas.\n\n\n\nThis case illustrates that BCC can occur in sun-\nprotected areas and suspicious lesions should be \nbiopsied with immunohistochemistry analysis.\n\n\n\nReferences\n\n\n\n1. Gibson GE, Ahmed I. Perianal and genital basal cell \ncarcinoma: a clinicopathologic review of 51 cases. J Am \nAcad Dermatol. 2001; 45(1): 68-71.\n\n\n\n2. Paterson CA, Young-Fadok TM, Dozois RR. Basal cell \ncarcinoma of the perianal region: 20-year experience. Dis \nColon Rectum.1999; 42(9): 1200-2.\n\n\n\n3. Patil DT, Goldblum JR, Billings SD. Clinicopathological \nanalysis of basal cell carcinoma of the anal region and its \ndistinction from basaloidsquamous cell carcinoma. Mod \nPathol. 2013; 26: 1382-9.\n\n\n\n4. Wietfeldt ED, Thiele J. Anal Cancer and Retrorectal Tumor.  \nClin Colon Rectal Surg. 2009; 22: 127\u2013135.\n\n\n\n5. Nielsen OV, Jensen SL. Basal cell carcinoma of the anus-a \nclinical study of 34 cases. Br J Surg. 1981; 68: 856-7.\n\n\n\n\n\n"
"\n\nVolume 28   |  Jul 2012   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.my\n\n\n\nIndexed in: Western Pacific Research Index Medicus\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\nMJD 2012 July Vol 28\n\n\n\nSungai Buloh\nAugmented vs\nWorld Health\nOrganisation\nanti-Leprosy\nMutiple Drug\nTherapy\n\n\n\nIs contact\nscreening of\ninfant whose\nmum has leprosy\nadequate?\n\n\n\nAdvance Masters\nin Dermatology\n- Graduates &\nthesis\n\n\n\n9\n\n\n\n2 2\n\n\n\n4 5\n\n\n\nH i g h l i g h t s\n\n\n\n30 Be aware of persistent \nfacial rash in infant. \n\n\n\n18 Do you recognise this \nhistology in immunosuppressed \npatients?\n\n\n\nEditorial\nThe decision to reve rt back to World Health\nOrganisation (WHO) regime of multidrug therapy for\nHansen disease was based on the outcome study done\nby Felix Yap together with the group of dermatologists\nwhen they compared the outcome of patients who had\nWHO and the Sungai Buloh augmented leprosy multi-\ndrug therapy. Paucibacilliary leprosy will need only 6\nmonths anti-leprosy therapy while multibacilliary\nleprosy a year. There is a unanimous decision to\nprolong the Hansen therapy to 2 years instead of 1 for\npatients presenting with bacteriological index more\nthan 4. \n\n\n\nToday\u2019s challenge is how we attract medical officers\nto become dermatologists. This has become the main\nagenda for Malaysian Derm a t o l ogical Society\nmeeting - creating more dermatologists to meet the\nincrease in demand for this service. The attainment of\nSaint John\u2019s Diploma of Dermatology and in-house\ndermatology training was initially adequate to fulfil\none to be credentialed as a dermatologist. After 1986\na pass in post-graduate course in internal Medicine\nl o c a l ly, United Kingdom or from Australia is a\nprerequisite to a fellowship dermatology training.  In\n2004, the attainment of Masters in A d va n c e\nD e rm a t o l ogy following an exit examination and\nproduction of a thesis is the preferred criteria for\ncredentialing.\n\n\n\n\n\n\n\n\nMJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nEditor-in-Chief (Administrative)\nRohna Ridzwan, MRCP\nEmail : rohnaridzwan@yahoo.com\n\n\n\nEditorial Office\nMalaysian Dermatological Society\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nAdvertisement Committee\nIndependent team members\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP\nKuala Lumpur\n\n\n\nHenry Foong Boon Bee, FRCP\nIpoh, Perak\n\n\n\nChan Lee Chin, MMed\nPenang\n\n\n\nAgnes Heng Yoke Hui, MRCP\nIpoh, Perak\n\n\n\nFounding Editor\nSteven Chow Kim Wing FRCPI\n\n\n\nExecutive Staff\n\n\n\nKoh Chuan Keng, MRCP - President\nMardziah Alias, MMed - Past President\nNajeeb Ahmad Mohd Safdar, MRCP - Vice President\nHenry Foong Boon Bee, FRCP - Secretary\nAgnes Heng Yoke Hui, MRCP - Treasurer\nMd Noh Idris, MRCP\nChan Lee Chin, MMed\nNoor Zalmy Azizan, MRCP\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJalan 112, Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Cetak Sri Jaya, Jalan Ambong Kanan 3, Kepong Baru, 52100 Kuala Lumpur, Malaysia\n\n\n\n@2012 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board\n\n\n\nThe inclusion of an advertisement in MJD is not to be construed or publicized as an endorsement or\napproval by the Society of any product, service, or company; nor may the advertiser represent that its\nadvertising claims have been approved or endorsed by the Society.\n\n\n\ni\n\n\n\n\n\n\n\n\nMJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nNotice to Au t h o rs\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts\non all aspects of cutaneous medicine and surg e ry in the form of\noriginal articles, research papers, case reports and\nc o rrespondence.  Contributions are accepted for publication on\ncondition that they are submitted ex c l u s ive ly to the Malay s i a n\nJ o u rnal of Derm a t o l og y. The Publisher and Editors cannot be\nheld responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and\nopinions expressed do not necessarily reflect those of the\np u blisher and Editors, neither does the publication of\na d ve rtisements constitute any endorsement by the publ i s h e r.\n\n\n\nManuscripts should be submitted via email:\nro h n a r i d z wa n @ ya h o o . c o m\n\n\n\nQuestions regarding the Malaysian Journal of Derm a t o l og y\ncan be sent to me at:\nro h n a r i d z wa n @ ya h o o . c o m\n\n\n\nC o n t r i butions should be written for one of the follow i n g\nc a t egories: \n\n\n\nCase Report *\nA report of 400-600 words, illustrated by no more than three\nillustrations. 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Ta bles, diagr a m s ,\nand selected figures are often helpful. The length is left to the\njudgment of the author, although it generally should not ex c e e d\n5000 words. Topics may include updates in clinically releva n t\nbasic science and cutaneous biolog y. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the\np a p e r, the author(s)' name(s), degrees, and affiliation(s), the\nc a t eg o ry of the article, the number of figures and tables, and\nthree key words for indexing purposes. The name and full postal\naddress (including a street address), phone and fax numbers and\nan email address of the corresponding author who will be\nr e s p o n s i ble for reading the proofs must also be given on the title\npage. The author(s) must also declare any affiliation or\ns i g n i ficant financial invo l vement in any organizations or entity\nwith a direct financial interest in the subject matter or materials\ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. If\nconfusion could result, please include other measurement\nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should\nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in\nthe manuscript. References from journals should include: (1)\nname(s) followed by the initials of the author(s), up to four\nauthors: if more than four authors, include the first three authors\nf o l l owed by et al.; (2) title of paper; (3) title of the journal as\na b b r eviated in the Index Medicus; (4) year of publication; (5)\nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A\nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n5 5 .\n\n\n\nReferences to books should include: (1) author(s) or editor(s);\n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4)\nplace of publication; (5) publisher; (6) year; (7) page(s) referr e d\nto. \n\n\n\nFor example:\nFoong HBB.  Transcontinental Derm a t o l ogy: Vi rtual Grand\nRounds. In: Wootton R and Oakley A, editors. Te l e d e rm a t o l og y.\nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of\nall references; incomplete references may result in a delay to\np u blication. \n\n\n\nTa bles should be typed, double-spaced with a heading, each on\na separate sheet, and should only include essential inform a t i o n .\nD r awings, graphs, and formulas should be submitted on\nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of\np h o t o m i c r ographs, the stain type and original magnifi c a t i o n\nshould be stated. Each figure should bear a reference number\nc o rresponding to a similar number in the tex t .\n\n\n\nTo minimise the publication time of your manuscript it is\ni m p o rtant that all electronic art work is supplied to the Editorial\nO ffice in the correct format and resolution. \n\n\n\nD i s c l a i m e r\nThe Publisher and Editors cannot be held responsible for err o r s\nor any consequences arising from the use of inform a t i o n\ncontained in this journal; the views and opinions expressed do\nnot necessarily reflect those of the publisher and Editors, neither\ndoes the publication of adve rtisements constitute any\nendorsement by the publisher and Editors of the products\na d ve rt i s e d .\n\n\n\n\n\n\n\n\n1MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Original Art i c l e\n\n\n\nAntibiotic sensitivity of pro p i o n i b a c t e r i u m\nacnes isolated from patients with acne vulgaris\nin Hospital Kuala Lumpur, Malaysia\nTang JJ1, Heng A1, Chan LC2, Tang MM3, Roshidah B3\n\n\n\nAbstract\n\n\n\nBackground Antibiotic therapy directed against Propionibacterium acnes (P. acnes) has been a\nmainstay of treatment in acne vulgaris for more than 40 years. Prolonged antibiotic usage has been\nassociated with emergence of antibiotic-resistant P. acnes and is linked to treatment failure. Little\nwork has been done in Malaysia on drug resistance in P. acnes and there is no surveillance data on\nthis aspect to guide the clinical decision.\n\n\n\nObjective This study aims to evaluate antibiotic sensitivity of P. acnes isolated from patients with\nacne vulgaris in Kuala Lumpur Hospital, Malaysia.\n\n\n\nMethods This is a non interventional, single centered, cross-sectional hospital-based survey of\nantibiotic sensitivity of P. acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital\nfrom January 2010 to June 2010.\n\n\n\nResults A total of 100 patients were recruited in our study. P. acnes was isolated in 53% of patients\nand 11% had gram negative organism. Antibiotic resistant P. acnes was found in 15.1% of positive\nisolates. Clindamycin resistance was the highest (15.1%) followed by erythromycin (7.5%),\ndoxycycline (5.7%), tetracycline (1.9%) and minocycline (0%). Isolates of antibiotic resistant\nP. acnes was significantly higher in patients treated with antibiotics within the last 6 months (29%)\nas compared with non antibiotic treated patients (0%) (p<0.05).The mean duration of prior antibiotic\ntreatment was significantly longer in the group of antibiotic resistant P. acnes as compared with\nantibiotic sensitive P. acnes (17.13 weeks vs 5.74 weeks, p<0.05).\n\n\n\nConclusion Antibiotic resistant P. acnes is present locally with clindamycin and erythromycin\naccounting for the highest resistance. Longer duration of antibiotic treatment predisposes to\nantibiotic resistant P. acnes and may also induce emergence of gram negative organisms. Strategies\nto reduce antibiotic resistance should be emphasized when prescribing antibiotic for acne vulgaris\nin order to achieve optimal therapeutic results while reducing the potential for antibiotic resistance.\n\n\n\nKeywords Acne vulgaris, Antibiotic sensitivity, Antibiotic resistance, Propionibacterium acnes, Clindamycin, Erythromycin,\nDoxycycline, Tetracycline, Minocycline\n\n\n\nCorrespondence\nTang Jyh Jong \n1Department of Dermatology,\nHospital Raja Permaisuri Bainun, Ipoh \nEmail: tangjyhjong@yahoo.com\n\n\n\n2Department of Dermatology, Hospital Pulau Pinang\n3Department of Dermatology, Hospital Kuala Lumpur\n\n\n\nIntroduction\nAcne vulgaris is a disorder of the pilosebaceous\nfollicle characterized by non-inflammatory\n(comedones) and inflammatory lesions\n(papules, pustules, nodules and cy s t s ) .\nAlthough the pathogenesis of acne vulgaris is\nm u l t i factorial, a commensal skin bacteria,\nPropionibacterium acnes (P. acnes) plays a\nmajor role in the formation of inflammatory\nacne\n\n\n\n\n\n\n\n\n2 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nacne lesion and comedogenesis. A n t i b i o t i c\ntherapy directed against P. acnes has been a\nmainstay of acne treatment for more than 40\nyears. Howeve r, prolonged antibiotic usage\nwhether oral or topical has been associated with\nan increased risk of antibiotic-resistant P. acnes\nove rgr owth. There are evidences linking the\nc a rriage of antibiotic-resistant P. acnes t o\ntreatment failure.1 The first clinically relevant\ne ry t h r o mycin resistant P. acnes strains wa s\nreported in 1979 from a small group of patients in\nthe United States.2 Subsequently, more cases of\nantibiotic resistant P. acnes were reported from\nvarious countries3,4,5,6.\n\n\n\nAcne vulgaris is highly prevalent and is of\nconcern in our population. However, little work\nhas been done in Malaysia on antibiotic resistant\nP. acnes and there is no surveillance data to guide\nthe clinical decision. Hence, the aim of the study\nis to assess the antibiotic sensitivity pattern of P.\nacnes among patients with acne vulgaris. This\ninformation would be useful in the formulation of\nappropriate local prescription practices and\nincrease the awareness of judicious use of\nantibiotics in acne vulgaris among our doctors.\n\n\n\nMethodology\nThis is a non interventional, single centered,\ncross-sectional hospital-based survey of\nantibiotic sensitivity of P. acnes isolated from\npatients with acne vulgaris in Kuala Lumpur\nHospital, Malaysia. Both old and new cases of\nacne vulgaris were consecutively sampled over a\n6-month period from January 2010 till June 2010.\nThe patients with active acne vulga r i s\ncharacterised by both inflammatory (papules,\npustules, nodules or cysts) and non inflammatory\n(closed and open comedones) lesions and more\nthan 12 years old were recruited. Those with\ndisease in clinical remission were excluded from\nthe study.\n\n\n\nThe study consisted of three parts. The first part\nof the study involved interviewing patients with\nacne vulgaris by using a standard data collection\nsheet. Data collected included age, gender,\ne t h n i c i t y, fa m i ly history of acne vulga r i s ,\nduration of disease, previous and curr e n t\ntreatment taken within the last 6 months. This\nwas followed by assessment of acne severity\naccording to lesional count. Acne seve r i t y\nassessment was based on criteria defined by\n\n\n\nLehmann et al 2002 i.e. mild : < 20 comedones,\nor < 15 inflammatory lesions, or total lesion\ncount < 30; moderate: 20-100 comedones, or\n15\u201350 inflammatory lesions, or total lesion count\n30-125; severe : > 5 cysts, or total comedones\ncount > 100, or total inflammatory lesion count >\n50, or total lesion count > 1257.\n\n\n\nThe third part of study consisted of swa b\nsampling for P. acnes culture after informed\nconsent was obtained. The entire surface of the\nacne affected area (face and/or trunk) wa s\nswabbed with a sterile swab stick. The swab was\nimmediately inoculated onto sheep blood agar\nplate. It was then placed in an air tight anaerobic\nchamber and sent to microbiology laboratory,\nKuala Lumpur Hospital, for culture and\ns e n s i t iv i t y. The blood agar plate was then\nincubated in anaerobic conditions at 37\u00baC for 5\ndays. All agar plates were opened after 5 days of\nincubation. P. acnes colony was first identified\nfrom the appearance of the colony on the blood\nagar which typically has small, dome-shaped\ncolony with beige to pink colour. Gram stain,\nCatalase test and Indole test were done on all\nsuspected colonies. P. acnes is a Gram-positive,\nnon motile bacilli with short branching and\nc o ry n e f o rm appearance which shows positive\nCatalase and Indole production tests. T h e\nsuspected colonies were then analyzed by an\nautomated bacteriology system - VITEK 2\ncompact to confirm the species of the organism.\nAntibiotic sensitivity to the five common\nantibiotics include tetracycline, dox y cy c l i n e ,\nminocycline, erythromycin and clindamycin were\nthen determined for all positive cultures with P.\na c n e s. The Minimal inhibitory concentration\n(MIC) to the five antibiotics was measured by\nusing E tests. The MICs breakpoint by European\nCommittee on Antibiotic Susceptibility Testing\n(EUCAST2003) was used to define the resistance\nstrain. Documentation and analysis of the data\nwere carried out using the Statistical Product and\nS e rvices (SPSS version 14.0) software for\nWindows. Mann-Whitney U test was used to\nanalyze non-normally distributed variables and\nthe values were expressed as median. Non-\nparametric tests such as Fisher\u2018s exact test was\nused to examine the relationship between 2\ncategorical variables (with two levels). A 2-tailed\np value of <0.05 is considered as statistically\nsignificant.\n\n\n\n\n\n\n\n\n3MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nResults\nThe general characteristics of our patients as\nshown in Table 1. A total of 100 patients were\nrecruited with mean age of 22.8 \u00b1 5.6 years old.\nThe female to male ratio was comparabl e\n(1.04: 1). Majority of our patients were Malay\n(67%) followed by Chinese (15%) and Indian\n(14%). Up to 63% of our patients have an\nimmediate family history of acne vulgaris. The\nmean duration of disease was 61.5 \u00b1 50.3 months.\nMajority of our patients had moderate to severe\nacne vulgaris (78%). as the clinic is a tertiary\nreferral centre.\n\n\n\nMajority of our patients were prescribed both\ntopical benzoyl peroxide (96%) and a topical\ntretinoin (95%). Topical sulphur was used in 19%\nof our patients. Sixty one percent of our cohort\nhad used ove r-the-counter treatment from a\np h a rm a cy. Howeve r, majority of them we r e\n\n\n\nunsure of the content of their treatment. As\ntopical clindamycin and topical erythromycin are\nnot available in our centre, only 1% of our cohort\nwere on these topical antibiotics. This figure may\nnot reflect the real usage of topical clindamycin\nand topical erythromycin as these treatment are\neasily available over the counter in most of the\npharmacies. There were 80 patients (80%) on oral\nantibiotic with the remaining 20 patients (20%)\non topical treatment alone. Majority (68%) of our\npatients were given oral Doxycycline. This was\nf o l l owed by oral Ery t h r o mycin (21%) and\nTetracycline (18%). Only 9 patients (9%) were\nprescribed oral Isotretinoin. All of the patients\nwho were given oral Isotretinoin had been on oral\nantibiotic previously. There was only one patient\non oral Bactrim and oral contraceptive pill\n(Diane 35) respectively. None of our patients\nwere given oral Minocycline, Clindamycin or\nSpironolactone.\n\n\n\nCharacteristics\n\n\n\n1. Age (years)\n\n\n\n2. Gender\n\n\n\n3. Ethnic\n\n\n\n4. Immediate family history of acne vulgaris\n\n\n\n5. Duration of acne vulgaris (months)\n\n\n\n6. Severity of acne based on lesional count (Lehmann et al 2002)\n\n\n\nMean\nMedian\nRange\n\n\n\nMale\nFemale\n\n\n\nMalay\nChinese\nIndian\nOthers\n\n\n\nYes\nNo\n\n\n\nMean\nRange\n\n\n\nMild\nModerate\nSevere\n\n\n\nn=100 (%)\n\n\n\n22.78 \u00b1 5.62 \n23 \n12 to 44 \n\n\n\n49 (49%)\n51 (51%)\n\n\n\n67 (67%)\n15 (15%)\n14 (14%)\n4 (4%)\n\n\n\n63 (63%)\n37 (37%)\n\n\n\n61.50 \u00b1 50.29 \n2 to 252\n\n\n\n22 (22%)\n59 (59%)\n19 (19%)\n\n\n\nTable 1 Dermographic data\n\n\n\n\n\n\n\n\n4 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nFigure 1 summarizes the type of orga n i s m\ncultured from swab sampling. Positive cultures\nfor P. acnes was seen in 53 patients, giving an\nisolation rate of 53%. As for the remaining\n47 swabs: 24 gr ew Staphylococcus species;\n11 Klebsiella species; 10 C o r y n e b a c t e r i u m\nspecies; 1 P ropionibacterium granulosum and\nPropionibacterium propionicus respectively. It is\ninteresting to note that 11% of swab sampling\nactually grew gram negative organism (Klebsiella\nspecies) which is not a normal commensal on the\nskin. Antibiotic sensitivity to the five antibiotics\ninclude tetracycline, doxycycline, minocycline,\nerythromycin and clindamycin were determined\nfor all positive cultures with P. acnes. P. acnes\nstrain with resistance to at least one of the five\nantibiotics was found in 15.1% of positive\nisolates (8 out of 53 positive isolates).\n\n\n\nFigure 2 shows the sensitivity pattern of P. acnes\naccording to the types of antibiotic. Clindamycin\nresistance was the highest (15.1%) followed by\nerythromycin (7.5%), doxycycline (5.7%) and\nt e t r a cycline (1.9%). There was no resistance\nnoted to minocycline. Virtually all the isolates\nwith antibiotic-resistant P. acnes were resistant\nto clindamycin. All isolates resistant to\nerythromycin were also resistant to clindamycin.\nIsolates of antibiotic resistant P. acnes wa s\ns i g n i fi c a n t ly higher in patients treated with\nantibiotics within the last 6 months (29%) as\ncompared with non antibiotic treated patients\n(0%) (p<0.05).The mean duration of antibiotic\ngiven within the last 6 months was significantly\nlonger in the group of antibiotic resistant P. acnes\nas compared with antibiotic sensitive P. acnes\n(17.13 weeks vs 5.74 weeks, p< 0.05).\n\n\n\nFigure 1 Types of organism from swab sampling culture\n\n\n\nFigure 2 Antibiotic sensitivity pattern of P. acnes according to types of antibiotic\n\n\n\n\n\n\n\n\n5MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDiscussion\nOur study showed that 15.1% of P. acnes strain\nwas resistant to at least one of the five antibiotics\n( t e t r a cycline, dox y cycline, minocy c l i n e ,\ne ry t h r o mycin and clindamycin). When we\ncompared our study with other studies, we found\nthat our P. acnes resistance rate is lower than the\nstudies in Europe countries (ranged from 25% to\n94%) but comparable to our neighboring\ncountry, Singapore (14.9%). Table 2 shows the\ncomparison of antibiotic sensitivity of P. acnes in\nvarious studies. A 10-year study at the Leeds\nGeneral Infirmary in United Kingdom involving\n4274 patients reported that the incidence of\n\n\n\nantibiotic resistance of P. acnes increased from\n34.5% in 1991 to 55.5% in 2000, with a peak of\n64% in 1997.8 Ross et al conducted a multicentre\ntrial to determine the preva l e n c e\nof skin colonization by antibiotic-resistant\npropionibacteria in the United Kingdom, Spain,\nItaly, Greece, Sweden, and Hungary and showed\nthat the prevalence of carriage of isolates\nresistant to at least one antibiotic was lowest in\nHungary (51%) and highest in Spain (94%)5.\nSimilarly, a higher resistance rate was reported by\nD u m o n t - Wallon G et al from France wh i c h\nshowed that 75.1% of the patients were carriers of\nantibiotic resistant P. acnes strains9.\n\n\n\nStudy\n\n\n\nCurrent study 2010\nMalaysia\n\n\n\nTan HH 2007 9\n\n\n\nSingapore\n\n\n\nEl-Mahdy 2007 10\n\n\n\nEgypt\n\n\n\nKurokawa 1999 11\n\n\n\nJapan\n\n\n\nRoss JI 2003 5\n\n\n\nSpain \nGreece\nUK\nItaly\nHungary \nSweden\n\n\n\nCoates P 2002 7\n\n\n\nUK\n\n\n\nDumont-WG 2010 8\n\n\n\nFrance\n\n\n\n% of overall antibiotic\nresistance\n\n\n\n15.1%\n\n\n\n14.9%\n\n\n\n<27%\n\n\n\n<4%\n\n\n\n94%\n75%\n<56%\n<65%\n51%\n<55%\n\n\n\n1991 : 34.5%\n\n\n\n1997 : 64%\n\n\n\n2000 : 55.5%\n\n\n\n75.1%\n\n\n\nTop 2 antibiotic\nresistance\n\n\n\n\u2020 Clin 15%\n\u2021 Ery 7.5%\n\n\n\nEry 10.3%\nClin 7.5%\n\n\n\nClin 26.9%\nEry 13.5%\n\n\n\nClin & Ery 4%\n\n\n\nClin & Ery 91%\nClin & Ery <75%\nClin & Ery 55.5%\nClin & Ery <58%\nClin & Ery <45%\nClin & Ery <49%\n\n\n\n1991 : Ery 29% \nClin 20%\n\n\n\n1997 : Ery 57.6% \nClin 49%\n\n\n\n2000 : Ery 55%\nClin 45%\n\n\n\nEry  75.1%\n\n\n\nOther antibiotic\nresistance\n\n\n\n\u00b1 Doxy 5.6% \n+ Tetra 1.9%\n# Mino 0%\n\n\n\n* Co-T 5.7%\nDoxy 3.4% \nMino 1.7%\nTetra 1.7%\n\n\n\nTetra 3.8%\n\n\n\nTetra 2%\nDoxy 2%\n\n\n\nTetra <5%\nTetra <7%\nTetra 26.4%\nTetra 0%\nTetra 0%\nTetra <15%\n\n\n\n-\n\n\n\nTetra 9.5%\nDoxy 9.5%\n\n\n\nTable 2 Comparison of antibiotic sensitivity of P. acnes in various studies\n\n\n\n\u2020Clin=Clindamycin    \u2021Ery=Erythromycin    +Tetra=Tetracycline    \u00b1Doxy=Doxycycline    #Mino=Minocycline    *Co-T=Bactrim\n\n\n\n\n\n\n\n\n6 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nWe postulate a few explanations why our\nresistance rate is lower than the European\ncountries.  Firstly, majority of our patients (up to\n96%) were prescribed topical BPO and retinoid\nconcurrently for their acne. BPO is a powerful\nnon-antibiotic antimicrobial agent that has the\nability to suppress emergence and proliferation of\nantibiotic resistant P. acnes and topical retinoid\nhas a complementary mode of action as a\ncomedolytic agent. Hence, routine use of topical\nBPO and retinoid can actually help to control\nP. acnes resistance. Secondly, topical antibiotics\nsuch as erythromycin and clindamycin are not\navailable in our clinic and this helps to further\nreduce the risk of antibiotic resistance. Thirdly,\nthe low resistance may partly be due to low\nP. acnes isolation rate (53%) in our study.\n\n\n\nOur study showed that clindamycin resistance\nwas the most common (15.1%) followed by\nerythromycin (7.5%), doxycycline (5.7%) and\nt e t r a cycline (1.9%). There was no P. acnes\nisolates resistant to minocycline. Virtually all the\nisolates with antibiotic-resistant P. acnes were\nresistant to clindamycin. Even though\nclindamycin resistance was the highest in our\nstudy, there was in fact only 1 patient who was\nprescribed topical clindamycin in our cohort. We\nbelieve some of our patients may have purchased\ntopical clindamycin over the counter and used it\nprior to this study which led to higher resistance\nrate towards clindamycin. Our result is in keeping\nwith other studies worldwide which also found\nthe highest resistance rate to ery t h r o my c i n\nand clindamy c i n5 , 8 , 9 , 1 0 , 1 1 , 1 2. Neve rtheless our\nclindamycin and erythromycin resistance rate as a\nwhole, were still lower than that reported in\nEurope. In United Kingdom, Coates P et al\nr e p o rted highest resistance to ery t h r o my c i n\nwhich rose steadily from 29% in 1991 to 57.6%\nin 1997 and the rates of resistance to clindamycin\nmirrored those for erythromycin but were always\nslightly lower8.\n\n\n\nIt was also been shown by Ross et al that\ncombined resistance to ery t h r o mycin and\nclindamycin was more common in European\ncountries with highest prevalence in Spain (91%)\nand lowest in Hunga ry (45%)5. In Fr a n c e ,\nDumont-Wallon G et al also showed that 75.1%\nof P. acnes strains were resistant to\ne ry t h r o my c i n9. Our clindamycin and\n\n\n\nerythromycin resistance rate was comparable to\nS i n gapore which was 7.5% for clindamy c i n\nresistance and 10.3% for ery t h r o my c i n\nresistance10. Erythromycin-resistant P. acnes is\nassociated with 3 phenotypes of mutations at\n23S rRNA whereas tetracycline resistance is\nassociated with a single mutation at\n16S rRNA1,13. It has been well described that\ne ry t h r o mycin-resistant P. acnes m ay also be\ncross-resistant to clindamycin and it is common\nto have resistance to both ery t h r o mycin and\nclindamycin together8.\n\n\n\nThe resistance rate towards the tetracycline group\nin our patients was lower than erythromycin and\nc l i n d a mycin. Among the three drugs in the\ntetracycline group, doxycycline (5.7%) had the\nhighest resistance in our study, followed by\ntetracycline (1.9%) and minocycline (0%). This\nseems to mirror our prescription pattern where\ndoxycycline is the most commonly prescribed\noral antibiotic (68%) followed by  tetracycline\n(18%) and minocycline (0%). Most of other\nstudies also reported the lowest resistance rate for\nm i n o cycline. Results from other studies also\nshowed a lower resistance rate to the tetracycline\ngroup as compared to ery t h r o mycin and\nclindamycin. Study by Coates P et al in United\nKingdom showed that resistance to tetracycline\nincreased from 12.5% in 1991 to 25.6% in 1996,\nreaching a peak of 29.9% in 19988. Ross et al\nreported resistance to tetracyclines as the highest\nin United Kingdom (26.4%) but no isolates\nresistant to tetracycline were detected in Italy or\nHungary in a multicentre trial in Europe5. In\nFrance, Dumont-Wallon G et al also showed that\nresistance to tetracycline (9.5%) was lower than\nerythromycin (75.1%) and all strains resistant to\ntetracycline were also resistant to doxycycline9.\nTan HH et al from Singapore also reported a\nlower resistance rate to tetracycline group with\ndoxycycline resistance being the most commonly\ndetected, accounting for 3.4% of all isolates while\nresistance to tetracycline and minocycline were\nboth 1.7%10. In general, tetracycline has lower\nresistance rate because it exerts less selection\npressure on antibiotic resistant P. acnes a s\ncompared with ery t h r o my c i n / c l i n d a my c i n7.\nTe t r a cycline resistant isolates also displaye d\nva rying degrees of cross-resistance to\ndoxycycline and minocycline1,13.\n\n\n\n\n\n\n\n\n7MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAll of the antibiotic resistant P. acnes we r e\nisolated from patients who were prescribed\nantibiotic within the last 6 months and the mean\nduration of antibiotic given within the last 6\nmonths was significantly longer in the group of\nantibiotic resistant P. acnes as compared with\nantibiotic sensitive P. acne. This suggests that the\npatients who were given longer duration of\nantibiotic within the last 6 months were at higher\nrisk of developing antibiotic resistant P. acnes as\ncompared to those who were on shorter duration\nof antibiotic. In fact numerous studies have\naddressed the relationship between antibiotic\nresistant P. acnes and previous antibiotic\ntreatment. Oprica C et al from Sweden found that\nantibiotics resistant P. acnes isolates wa s\ns i g n i fi c a n t ly higher in the group of patients\ntreated with antibiotic (37%) as compared with\nnon-antibiotic group (13%) of patients (odds\nratio, 3.8; p = 0:01)14. In France, Dumont-Wallon\nG et al showed that P. acnes resistance to\nerythromycin was significantly higher in patients\nwho were prev i o u s ly treated with topical\nerythromycin (p = 0.03) and P. acnes resistance to\nt e t r a cycline was also signifi c a n t ly higher in\npatients who were prev i o u s ly given systemic\ncyclines (p= 0.002)9. In Singapore, Tan HH et al\nshowed that the isolates of antibiotic resistant\nP. acnes were higher in patients who had been on\nantibiotics for longer (>18 weeks) periods\n(21.6%) as compared with patients who had been\non short-term (between 6 to 18 weeks) antibiotics\n(6.25%) or patients who had never been on\nantibiotics (0%)6.\n\n\n\nIt is interesting to note in our study that 11% of\nswab sampling grew gram negative organism\n(Klebsiella species) which is not a norm a l\ncommensal on the skin. Further analysis showed\n81.8% (9 patients) of the patients had been given\nantibiotic within the last 6 months with a mean\nduration of 11.73 weeks. Long term antibiotic\nt h e r a py will change the normal follicular\nmicrobial population and predispose to gram\nn ega t ive bacteria1 6. Gram nega t ive folliculitis\nshould be suspected in patients with acne vulgaris\n\n\n\nwho have been long term antibiotic and present\nwith predominantly inflamed lesions e.g pustules,\nnodules or papules especially in the perinasal and\nchin area1 6 , 1 7. Our study suggests that long\nduration of antibiotic may also contribute to\nemergence of gram negative organism besides\nantibiotic resistant P. acnes. Howeve r, the\nsignificance of gram negative organism and its\nrelationship to duration of antibiotic therapy are\nstill beyond the scope of our study.\n\n\n\nThere are a few limitations in our study. We were\nnot able to look into the clinical outcome of\npatients with antibiotic resistant P. acnes in view\nof the small number of patients with antibiotic\nresistant P. acnes. It would be of clinical\nr e l evance to correlate clinical response with\nantibiotic sensitivity to establish the relevance of\ncolonization with antibiotic resistant P. acnes.\nOur study is a single centre, cross sectional study\nwhich does not reflect the overall antibiotic\nsensitivity pattern of P. acnes in Malaysia. Hence,\nwe strongly feel that a multicentre trial involving\nprimary care physicians may be able to address\nthis issue better.\n\n\n\nConclusion\nOur study showed that 15.1% of the patients\ncarry antibiotic resistant P. acnes. Resistance to\nc l i n d a mycin was the highest followed by\nerythromycin and doxycycline. Longer duration\nof antibiotic treatment within the last 6 months\npredispose to antibiotic resistant P. acnes. There\nis also evidence from our study to suggest\nemergence of gram negative organism as a result\nof long duration of antibiotic therapy. Strategies\nto reduce antibiotic resistance include limiting\nthe duration of therapy, using combination\ntherapy regimens with a rational topical program\n(Retinoid and BPO) and avoid using oral\nantibiotics as maintenance. By increasing our\nunderstanding of the multifaceted actions of\nantibiotics and the known clinical implications of\nantibiotic resistance, we can improve our decision\nmaking in prescribing these agents.\n\n\n\n\n\n\n\n\n8 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nReferences\n\n\n\n1. Eady EA, Cove JH, Layton AM. Is antibiotic resistance\nin cutaneous propionibacteria clinically releva n t ?\nImplications of resistance for acne patients and\nprescribers. Am J Clin Dermatol 2003;4:813-31.\n\n\n\n2. Leyden JJ. The evolving role of Propionibacterium\nacnes in acne. Semin Cutan Med Surg 2001;20(3):\n139-143. \n\n\n\n3. Kurokawa I, Nishijima S, Asada Y. The antibiotic\nsusceptibility of Propionibacterium acnes: a 15-year\nbacteriological study and retrospective evaluation. J\nDermatol 1988;15:149-54.\n\n\n\n4. Oakley A, Rademaker M, Duffill M, Leng R, Shewan J.\nPropionibacterium: resistance of acne to antibiotics. N\nZ Med J 1995;108:43-4.\n\n\n\n5. Ross JI, Snelling AM, Carnegie E, Coates P, Cunliffe\nWJ, Bettoli V,Tosti G, Katsambas A, Galvan JI, Pulgar\nP D, Rollman O, Torok L, Eady EA, Cove JH.\nAntibiotic-resistant acne: lessons from Europe. Br J\nDermatol 2003;148:467-78.\n\n\n\n6. Tan HH, Goh CL, Yeo MG, Tan ML. A n t i b i o t i c\nsensitivity of Propionibacterium acnes isolates from\npatients with acne vulgaris in a tertiary dermatological\nreferral centre in Singapore. Ann Acad Med Singapore\n2001;30(1):22-5.\n\n\n\n7. Lehmann HP, Robinson KA, Andrews JS, Holloway V,\nGoodman SN. Acne therapy: A methodologic review. J\nAm Acad Dermatol 2002;47:231-40.\n\n\n\n8. Coates P, Vyakrnam S, Eady EA, Jones CE, Cove JH,\nC u n l i ffe W J. Prevalence of antibiotic-resistant\npropionibacteria on the skin of acne patients: 10-year\nsurveillance data and snapshot distribution study. Br J\nDermatol 2002;146:840-8.\n\n\n\n9. Dumont-Wallon G, Moyse D, Blouin E, Dre\u00b4no B.\nBacterial resistance in French acne patients. Int J\nDermatol 2010;49:283-8.\n\n\n\n10. Tan HH, Tan AWH, Barkham T, Yan XY, Zhu M.\nCommunity-based study of acne vulgaris in\nadolescents in Singapore. Br J Derm a t o l\n2007;157:547-551.\n\n\n\n11. El Mahdy TSM, Abd-Elaziz MM, El-Sayed MH, Ross\nJI, Abd Allah S, Radwan H. Antibiotic resistance\namongst cutaneous propionibacteria from Egyptian\nacne patients. 17th ECCMID/25th ICC. 2007.\n\n\n\n12. Kurokawa I, Nishijima S, Kawabata S. Antimicrobial\nsusceptibility of Propionibacterium acnes isolated from\nacne vulgaris. Eur J Dermatol 1999;9:25-28.\n\n\n\n13. L eyden JJ, Del Rosso JQ, Webster GF. Clinical\nconsiderations in the treatment of acne vulgaris and\nother inflammatory skin disorders: a status report.\nDermatol Clin 2009;27:1-15.\n\n\n\n14. Oprica C, Emtestam L, Lapins J, Borglund E, Nyberg F,\nStenlund K, Lundeberg L, Sillerstrom E, Nord CE.\nAntibiotic-resistant Propionibacterium acnes on the\nskin of patients with moderate to severe acne in\nStockholm. Anaerobe 2004;10:155-164.\n\n\n\n15. Tan HH, Goh CL, Yeo MG, Tan ML. A n t i b i o t i c\nsensitivity of Propionibacterium acnes isolates from\npatients with acne vulgaris in a tertiary dermatological\nreferral centre in Singapore. Ann Acad Med Singapore\n2001;30(1):22-5.\n\n\n\n16. C u n l i ffe W J, Gollnick HPM. Acne Diagnosis and\nmanagement. London;Martin Dunitz 2001:1-46.\n\n\n\n17. Shalita AR. Acne: Clinical Presentations. Clinics in\nDermatology 2004;22:385-386.\n\n\n\n\n\n\n\n\n9MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Original Art i c l e\n\n\n\nComparison of the efficacy and safety of Sungai Buloh\nAugmented Multiple Drug Therapy (SBA-MDT) and the\nWorld Health Organisation Multiple Drug Therapy\n(WHO-MDT) in the Treatment of Leprosy in Malaysia\nFelix Boon Bin Yap, AdvMDerm, Chang Choong Chor, AdvMDerm, Asmah Johar, MMed, Roshidah Baba, FRCP\n\n\n\nAbstract\n\n\n\nBackground Multiple drug therapy for leprosy has been in use in Malaysia since 1985. The SBA-\nMDT is a modified WHO-MDT with an initial intensive phase and a longer duration of treatment.\n\n\n\nObjective The aim of the study is to compare the efficacy and safety of  SBA-MDT against WHO-\nMDT in the Treatment of Leprosy in Malaysia.\n\n\n\nMethodology A retrospective study was conducted between 1985 and 2009 in thirteen Malaysian\ndermatology centres. Data collected were analysed for comparison of relapse rates, compliance rates\nand adverse drug effects between the 2 regimes.\n\n\n\nResults A total of 1113 patients were included, of which 966 patients completed the SBA-MDT and\n147 patients completed the WHO-MDT. Both the MDT regimes had a treatment failure rate of less\nthan 2%. The relapse rate was 1.7% with SBA-MDT and 1.4% with WHO-MDT (p = 0.79). For\nmultibacillary leprosy, the relapse rates were 0.9% with the former and 0 with the latter (p = 0.32).\nFor paucibacillary leprosy, it was 3.1% and 5.0% respectively (p = 0.52). Patients on SBA-MDT had\nhigher type 1 (16.1% vs. 8.8%, p =  0.03) and type 2 lepra reactions (19.2% vs. 6.1%, p < 0.001).\nSimilarly, those on SBA-MDT also had higher rate of severe adverse drug reactions (11.1% vs.\n5.6%, p = 0.01).\n\n\n\nConclusion Both the SBA-MDT and the WHO-MDT regimes were effective in inducing clinical\nremission. Incidence of lepra reactions and severe adverse drug reactions were higher in patients\nwith SBA-MDT.\n\n\n\nKeywords Hansen\u2019s disease, Outcome study, relapse rate, multibacilliary leprosy, paucibacilliary leprosy\n\n\n\nCorrespondence\nFelix Boon-Bin Yap \nDepartment of Dermatology\nKuala Lumpur Hospital\nKuala Lumpur, Malaysia\nEmail: woodzlamp@yahoo.com\n\n\n\nIntroduction\nLeprosy is a chronic granulomatous infection\ncaused by Mycobacterium leprae aff e c t i n g\nmainly the skin and nerves. In Malaysia, leprosy\nhad been eliminated as a public health problem,\nwith prevalence of less than 1 per 10,000\npopulations since 19941. Neve rtheless, it\ncontinued to be seen especially among the native\npopulations in particular the Orang Asli and the\nPenans; and also the immigrant workers from\nIndonesia, the Phillipines, Myanmar and Nepal2.\n\n\n\n\n\n\n\n\n10 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDapsone was the first drug to be used in Malaysia\nfor the treatment of leprosy in 1948 by the\nNational Leprosy Control Centre in Sunga i\nBuloh3. However, in 1964, the first case of\ndapsone resistance was detected3. In 1982,\nthe World Health Organisation (WHO)\nrecommended the use of multiple drug therapy\n\n\n\n(MDT) consisting of rifamipicin, dapsone and\nclofazimine to prevent the development of drug\nr e s i s t a n c e4. In 1985, the WHO-MDT wa s\nmodified by the National Leprosy Control Centre\nfor use in Malaysia3. The differences between the\nSungai Buloh Augmented MDT (SBA-MDT), the\nWHO-MDT 1982 regime and the updated WHO-\nMDT 1997 regime is shown in Table 13,4,5.\n\n\n\nMDT\n\n\n\nSungai Buloh Augmented \n\n\n\nWHO (1982)\n\n\n\nWHO (1997)\n\n\n\nRegime\n\n\n\nPaucibacillary\nT Rifampicin 600 mg per month (supervised)\nT Clofazimine 300 mg per month (supervised)\nT Dapsone 100 mg per day\nT Clofazimine 100 mg per day\nDuration: 1 year\nSurveillance: 5 years\n\n\n\nMultibacillary\nIntensive phase\nT Rifampicin 600 mg per day (supervised)\nT Dapsone 100 mg per day (supervised)\nT Clofazimine 100 mg per day (supervised)\nDuration: Minimum 3 weeks or until MI = 0\nMaintenance phase\nT Rifampicin 600 mg per month (supervised)\nT Clofazimine 300 mg per month (supervised)\nT Dapsone 100 mg per day\nT Clofazimine 100 mg per day\nDuration: minimum 3 years or until MI = 0\nSurveillance: 10 years\n\n\n\nPaucibacillary\nT Rifampicin 600 mg per month (supervised)\nT Dapsone 100 mg daily\nDuration: 6 months\nSurveillance: 5 years\n\n\n\nMultibacillary\nT Rifampicin 600 mg per month (supervised)\nT Clofazimine 300 mg per month (supervised)\nT Dapsone 100 mg daily\nT Clofazimine 50 mg daily\nDuration: 2 years\nSurveillance: 10 years\n\n\n\nPaucibacillary\nT Rifampicin 600 mg per month (supervised)\nT Dapsone 100 mg daily\nDuration: 6 months\nSurveillance: 2 years\n\n\n\nMultibacillary\nT Rifampicin 600 mg per month (supervised)\nT Clofazimine 300 mg per month (supervised)\nT Dapsone 100 mg daily\nT Clofazimine 50 mg daily\nDuration: 1 years\nSurveillance: 5 years\n\n\n\nTable 1 SBA-MDT, WHO-MDT (1982) and WHO-MDT (1997)\n\n\n\n\n\n\n\n\n11MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThere were 2 reasons cited for the longer duration\nof treatment in the SBA-MDT compared to the\nWHO-MDT. Firstly, funding of longer duration\nof MDT was not a problem in Malaysia compared\nto other countries like India. Secondly,  most of\nthe patients seen in Malaysia had a high\nbacteriologic index (BI) and it was noted that\nthere was a high relapse rate associated with\ns h o rter duration of treatment, especially in\npatients with BI > 36,7,8.\n\n\n\nIn Malaysia, the SBA-MDT has been widely used\nin Peninsular Malaysia. Howeve r, in East\nM a l aysia, the WHO-MDT has been adopted\nsince 1993 because of the high number of\ni m m i grant wo r kers from Indonesia and the\nPhillipines having the disease. This is to allow\nstandardization of the MDT treatment when these\nworkers continue their treatment back in their\ncountry of origin.\n\n\n\nThus, we aim to determine the efficacy and safety\nof the SBA-MDT compared with the WHO-MDT\nused in Malaysia.\n\n\n\nMaterials and methods\nThis is a retrospective study to determine the\nefficacy and safety of the SBA-MDT regime and\nthe WHO-MDT in the treatment of leprosy in\nMalaysia between January 1985 and December\n2009. Thirteen dermatology centres in Malaysia\np a rticipated in this study i.e. Derm a t o l og y\nDepartments of Hospital Kuala Lumpur, Hospital\nMelaka, Hospital Selayang, Sarawak General\nHospital, Queen Elizabeth Hospital, Hospital\nPulau Pinang, Hospital Tengku A m p u a n\nRahimah, Hospital Sultanah Bahiyah, Hospital\nSultanah Aminah, Hospital Kota Bahru, Hospital\nSeremban, Hospital Tengku Ampuan Afzan,  and\nHospital Tuanku Fauziah.\n\n\n\nThe inclusion criteria for this study is all the\npatients with leprosy who successfully completed\neither the SBA-MDT or the WHO-MDT. The\nexclusion criteria are patients who failed to\ncomplete the MDT, patients given MDT other\nthan the SBA-MDT or the WHO-MDT regime,\nand patients who were on other antilepromatous\ntreatment before given the SBA-MDT or the\nWHO-MDT.\n\n\n\nData collection was done using the standardized\ncase report forms. These forms and the study\nprotocol were distributed to all the participating\ncentres. Completed case report forms we r e\nr e t u rned to the coordinating centre in the\nD e p a rtment of Derm a t o l og y, Hospital Ku a l a\nLumpur for data processing and analysis. The\ndata collected include sociodemogr a p h i c\ncharacteristics, clinical characteristics, MDT\nregimes used and outcomes including relapse,\ntreatment failure and side effects of treatment. \n\n\n\nIn this study, the clinical types of leprosy are\nd e fined according to the Ridley - J o p l i n g\nclassification9. In addition to the 5 types of\nleprosy in the Ridley-Jopling classification, we\nalso included indeterminate leprosy and neural\nleprosy. Neural leprosy is a subtype of leprosy\npresenting with only nerve involvement without\nskin manifestations. \n\n\n\nMDT treatment failure is defined as failure to\nrespond to the MDT regime in terms of clearance\nof skin lesion(s) or reduction in the bacteriologic\ni n d ex and morp h o l ogical index on slit skin\nsmears. Relapse of disease is defined as a patient\nwho successfully completed an adequate course\nof MDT regime but subsequently develops new\nsigns and symptoms of the disease either during\nthe surveillance period or thereafter10. In patients\nwith multibacillary leprosy, relapse is defined by\nWHO as the multiplication of Mycobacterium\nleprae, suspected by the marked increase (at least\n2+ over the previous value) in the BI at any single\nsite, usually with evidence of clinical\ndeterioration manifested as new skin lesions\nand/or new nerve damage. In paucibacillary\nleprosy, relapse is suspected by the evidence of\nclinical deterioration manifested by development\nof new skin lesions and/or new nerve damage.\n\n\n\nCompliance of treatment is divided into good,\nmoderate, poor and very poor compliance. Good\ncompliance is defined as patients who never or\nhardly missed their treatment i.e. not more than 1\nweek in the entire treatment period. Moderate\ncompliance denotes patients who did not take\ntheir medications for a period up to 1 month\nduring the entire treatment period. Po o r\ncompliance is patients who did not take their\nmedications\n\n\n\n\n\n\n\n\n12 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nSociodemographic\ncharacteristics\n\n\n\nGender\nMale\nFemale\n\n\n\nMean age (years)\n\n\n\nEthnicity [n(%)]\nMalay\nChinese\nIndian\nBumiputera Sabah\nBumiputera Sarawak\nOrang Asli\nIndonesian\nOthers\n\n\n\nNationality [n(%)]\nMalaysian \nOthers\n\n\n\nSBA-MDT\n(N=966)\n\n\n\n719 (74.4%)\n243 (25.6%)\n\n\n\n39.8 \u00b1 16.30\n\n\n\n400 (41.4%)\n233 (24.1%)\n72 (7.5%)\n\n\n\n5 (0.5%)\n2 (0.1%)\n\n\n\n20 (2.1%)\n198 (20.6%)\n36 (3.7%)\n\n\n\n781 (80.8%)\n185 (19.2%)\n\n\n\nSBA-MDT\n(N=966)\n\n\n\n106 (72.1%)\n41 (27.9%)\n\n\n\n39.7 \u00b1 17.88\n\n\n\n28 (19.0%)\n32 (21.7%)\n6 (4.0%)\n\n\n\n34 (23.0%)\n5 (4.0%)\n0 (0%)\n\n\n\n15 (10.1%)\n27 (18.2%)\n\n\n\n107 (72.8%)\n40 (27.2%)\n\n\n\np value\n\n\n\n0.51\n\n\n\n0.98\n\n\n\n<0.001\n\n\n\n0.02\n\n\n\nTable 2 Sociodemographic characteristics of the patients who completed the SBA-MDT and the WHO-MDT.\n\n\n\nClinical\ncharacteristics\n\n\n\nRidley-Jopling classification [n(%)]\nIndeterminate (Ind)\nTuberculoid (TT)\nBorderline Tuberculoid (BT)\nMid Borderline (BB)\nBorderline Lepromatous (BL)\nLepromatous (LL)\nNeural (Neu)\n\n\n\nMean Bacteriologic Index (BI)\nPre treatment\nPost Treatment\n\n\n\nMean Morphological Index (MI)\nPre treatment\nPost treatment\n\n\n\nSBA-MDT\n(N=966)\n\n\n\n37 (3.8%)\n175 (18.1%)\n138 (14.3%)\n\n\n\n61 (6.3%)\n167 (17.3%)\n375 (38.8%)\n\n\n\n13 (1.4%)\n\n\n\n2.5 \u00b1 1.66\n0 \u00b1 0.07\n\n\n\n2.3 \u00b1 4.01\n0 \u00b1 0.06\n\n\n\nWHO-MDT\n(N=147)\n\n\n\n9 (6.1%)\n31 (21.1%)\n16 (10.9%)\n7 (4.8%)\n\n\n\n20 (13.6%)\n64 (43.5%)\n0 (0%)\n\n\n\n2.6 \u00b1 1.82\n0.7 \u00b1 1.38\n\n\n\n9.4 \u00b1 15.13\n0.1 \u00b1 0.29\n\n\n\np value\n\n\n\n0.28\n\n\n\n0.58\n<0.001\n\n\n\n<0.001\n0.01\n\n\n\nTable 3 Clinical characteristics of patients who completed the SBA-MDT and the WHO-MDT.\n\n\n\n\n\n\n\n\n13MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nmedications for a period of between 1 to 3\nmonths during the entire treatment period. Very\npoor compliance is patients who did not take their\nmedications for a period of more than 3 months\nduring the entire treatment period. Severe adverse\ndrug reaction is defined as severe unwanted\nreaction caused by the MDT which might result\nin the cessation or alteration of the offending\ndrug(s).\n\n\n\nCollected data were analysed using SPSS (SPSS\nInc., Chicago, IL, USA). Continuous data were\ndescribed as means and standard dev i a t i o n s .\nCategorical data were expressed as frequencies\nand percentages. Statistical comparisons were\nconducted using Chi-square test or Fisher\u2019s exact\ntest for categorical data and t-test for continuous\ndata. The level of significance was set at p < 0.05.\n\n\n\nResults\nThere were 1531 patients with leprosy seen\nwithin the study period of which 1113 patients\nfulfilled the inclusion sand exclusion criteria.\nThere were 966 patients who successfully\ncompleted the SBA-MDT whereas 147 patients\ncompleted the WHO-MDT. Most of the patients\nwho completed the WHO-MDT were from the\nDermatology Departments of Sarawak General\nHospital and Queen Elizabeth Hospital, both in\nEast Malaysian Borneo.\n\n\n\nThere were more male patients receiving both\nMDTs (Table 2). The female to male ratio was\nhigher in patients who completed the SBA-MDT\n(1:3.0) compared to the WHO-MDT (1:2.6)\nalthough the difference was not statistically\ns i g n i ficant (p = 0.51). There were also no\nsignificant differences between these two MDTs\nin terms of age. Howeve r, there were more\nMalaysian receiving the SBA-MDT (80.8% vs.\n72.8%, p = 0.02). There were also racial\ndifferences in both the regimen (p < 0.001). \n\n\n\nThe clinical characteristics of patients on both the\nMDTs is shown in Ta ble 3. There were no\nd i fferences in the types of leprosy betwe e n\npatients receiving SBA-MDT and WHO-MDT\n(p = 0.28). The mean pre-treatment\nm o rp h o l ogical index (MI) was signifi c a n t ly\nhigher in patients who completed WHO-MDT\n(9.4 vs. 2.3, p < 0.001). Howeve r, the pre\ntreatment bacteriological index (BI) was not\nsignificantly different. In the SBA-MDT, all the\n\n\n\npatients except one were smear negative upon\ncompletion of treatment. On the other hand, only\n60.9% of patients on WHO-MDT were smear\nnegative after completing treatment.\n\n\n\nThe mean duration of treatment using the\nmultibacillary SBA-MDT was longer than the\nmultibacillary WHO-MDT (43.1 months vs. 32.1\nmonths, p < 0.001). Similarly, the mean duration\nusing the paucibacillary SBA-MDT was also\nlonger than the paucibacillary WHO-MDT (21.4\nmonths vs. 10.6 months, p < 0.001).\n\n\n\nThe mean duration of multibacillary WHO-MDT\nof 32.1 months was much longer than the\nstandard WHO-MDT protocol of 12 months. It\nwas also surprising to note that the mean duration\nof the paucibacillary WHO-MDT of 10.6 months\nwas longer than the 6 months recommendation.\nSimilarly, the mean duration of the paucibacillary\nSBA-MDT of 21.4 months was also longer than\nthe recommended 12 months.\n\n\n\nBoth the SBA-MDT and WHO-MDT had a\nfailure rate of l.4%. Surp r i s i n g ly, 43.5%\nof patients on SBA-MDT completed the\nsurveillance compared to only 38.1% on WHO-\nMDT (p<0.001) despite the longer surveillance\nperiod in the former (Table 4). Patients on WHO-\nMDT had better compliance to treatment\ncompare to SBA-MDT (p = 0.03).\n\n\n\nMore patients treated with SBA-MDT developed\nlepra reactions (Ta ble 4). In the SBA - M D T\ngroup, 16.1% and 19.2% developed type 1 and\ntype 2 lepra reactions respectively.\n\n\n\nIn comparison, in the WHO-MDT group, only\n8.8% (p = 0.03) and 6.1% (p < 0.001)\nrespectively developed type 1 and type 2 lepra\nreaction.\n\n\n\nThe relapse rate was 1.7% in patients wh o\ncompleted the SBA-MDT compared with only\n1.4% in patients who completed WHO-MDT\nalthough it was not statistically signifi c a n t\n(p = 0.79). The relapse rates were 3.1% and 0.9%\nwith paucibacillary and multibacillary leprosy\nrespectively in those who completed SBA-MDT\ncompared to 5.0% (p = 0.52) and 0% (p =0.32)\nrespectively in those who completed WHO-MDT\n(Table 5).\n\n\n\n\n\n\n\n\n14 MJD 2011 July Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nCharacteristics of patients with relapse are shown\nin Table 6.\n\n\n\nSevere adverse reactions to drugs to MDT were\nr e p o rted 11.1% of patients given SBA - M D T\ncompared to only 5.6% given W H O - M D T\n(p = 0.01). The most common severe adverse\nreactions were haemolytic anaemia and hepatitis. \n\n\n\nDiscussion \nIt was noted in this study that both the SBA-MDT\nand WHO-MDT effectively reduced the load of\nMycobacterium leprae in patients with leprosy.\n\n\n\nBoth regimes were equally effective where the\ntreatment failure rates were low (1.4%). However,\nwe found that the relapse rate was higher with\nS BA-MDT although it was not statistically\nsignificant. It is surprising as treatment with\nSBA-MDT required patients to be on treatment\nuntil BI = 0. In Sarawak, East Malaysian Borneo,\na similar comparison between SBA-MDT and\nWHO-MDT failed to detect any relapse in both\ntreatment regimens11.\n\n\n\nTreatment\ncharacteristics\n\n\n\nMean duration of treatment (months)\nMultibacillary\nPaucibacillary\n\n\n\nTreatment failure [n(%)]\n\n\n\nCompleted surveillance [n(%)]\n\n\n\nCompliance to treatment\nGood\nModerate\nPoor \nVery poor\n\n\n\nLeprosy Reactions [n(%)]\nType 1\nType 2\n\n\n\nSBA-MDT\nN=966\n\n\n\n43.1 \u00b1 18.03\n21.4 \u00b1 20.64\n\n\n\n14 (1.4%)\n\n\n\n420 (43.5%)\n\n\n\n704 (72.9%)\n69 (7.1%)\n59 (6.1%)\n\n\n\n134 (13.9%)\n\n\n\n156 (16.1%)\n185 (19.2%)\n\n\n\nWHO-MDT\nN=147\n\n\n\n32.1 \u00b1 20.89\n10.6 \u00b1 9.99\n\n\n\n2 (1.4%)\n\n\n\n56 (38.1%)\n\n\n\n120 (81.6%)\n11 (7.6%)\n\n\n\n8 (5.4%)\n8 (5.4%)\n\n\n\n13 (8.8%)\n9 (6.1%)\n\n\n\np value\n\n\n\n< 0.001\n<0.001\n\n\n\n0.85\n\n\n\n<0.001\n\n\n\n0.03\n\n\n\n0.03\n<0.001\n\n\n\nTable 4 Treatment characteristics of patient.\n\n\n\nRelapse\n\n\n\nNumber of patients [n(%)]\n\n\n\nTypes of leprosy\nPaucibacillary\nMultibacillary\n\n\n\nSBA-MDT\nN=966\n\n\n\n16 (1.7%)\n\n\n\n10 (3.1%)\n6 (0.9%)\n\n\n\nWHO-MDT\nN=147\n\n\n\n2 (1.4%)\n\n\n\n2 (5.0%)\n0 (0%)\n\n\n\np value\n\n\n\n0.79\n\n\n\n0.52\n0.32\n\n\n\nTable 5 Relapse in patients receiving SBA-MDT and WHO-MDT.\n\n\n\n\n\n\n\n\n15MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nrespectively in those who completed WHO-MDT\n(Table 5). Characteristics of patients with relapse\nare shown in Table 6.\n\n\n\nSevere adverse reactions to drugs to MDT were\nr e p o rted 11.1% of patients given SBA - M D T\ncompared to only 5.6% given W H O - M D T\n(p = 0.01). The most common severe adverse\nreactions were haemolytic anaemia and hepatitis. \n\n\n\nDiscussion \nIt was noted in this study that both the SBA-MDT\nand WHO-MDT effectively reduced the load of\nMycobacterium leprae in patients with leprosy.\n\n\n\nBoth regimes were equally effective where the\ntreatment failure rates were low (1.4%). However,\nwe found that the relapse rate was higher with\nS BA-MDT although it was not statistically\nsignificant. It is surprising as treatment with\nSBA-MDT required patients to be on treatment\nuntil BI = 0. In Sarawak, East Malaysian Borneo,\na similar comparison between SBA-MDT and\nWHO-MDT failed to detect any relapse in both\ntreatment regimens11.\n\n\n\nNone of our patients with multibacillary leprosy\ntreated with the WHO-MDT relapsed. This is\nsimilarly seen in the Sarawak study11. However,\nstudies from other countries showed a relapse rate\nof between 0.5% and 3% for patients with\nmultibacillary leprosy who had completed the\n1 year\n\n\n\nNo \n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\n11 \n\n\n\n12 \n\n\n\n13\n\n\n\n14 \n\n\n\n15\n\n\n\n16\n\n\n\n17\n\n\n\n18\n\n\n\nR-J type\n\n\n\nInd \n\n\n\nTT \n\n\n\nTT \n\n\n\nTT \n\n\n\nBT \n\n\n\nBT \n\n\n\nBT \n\n\n\nBT\n\n\n\nBT\n\n\n\nBT \n\n\n\nBB \n\n\n\nBL \n\n\n\nBL \n\n\n\nLL \n\n\n\nLL \n\n\n\nLL \n\n\n\nTT \n\n\n\nTT\n\n\n\nMDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT \n\n\n\nSBA-MDT \n\n\n\nSBA-MDT \n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nSBA-MDT\n\n\n\nWHO-MDT \n\n\n\nWHO-MDT\n\n\n\nType\n\n\n\nPB \n\n\n\nPB \n\n\n\nPB \n\n\n\nPB \n\n\n\nPB \n\n\n\nPB \n\n\n\nPB \n\n\n\nMB \n\n\n\nMB \n\n\n\nMB \n\n\n\nPB \n\n\n\nMB \n\n\n\nMB \n\n\n\nMB \n\n\n\nMB \n\n\n\nMB \n\n\n\nPB \n\n\n\nPB\n\n\n\nPreRx\nSSS *\n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0.1 / 0.1 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n1.0 / 2.0 \n\n\n\n0 / 0 \n\n\n\n3.2 / 4.9 \n\n\n\n3.1 / 0 \n\n\n\n2.3 / 1.6 \n\n\n\n3.4 / 4.2 \n\n\n\n2.1 / 2.7 \n\n\n\n0 / 0 \n\n\n\n0 / 0\n\n\n\nPostRx\nSSS *\n\n\n\n0 /0\n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n-\n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0\n\n\n\nRx\nDuration\n\n\n\n19 mth \n\n\n\n14 mth \n\n\n\n34 mth \n\n\n\n13 mth \n\n\n\n11 mth \n\n\n\n25 mth \n\n\n\n13 mth \n\n\n\n30 mth\n\n\n\n13 mth\n\n\n\n37 mth \n\n\n\n11 mth \n\n\n\n37 mth \n\n\n\n34 mth \n\n\n\n36 mth \n\n\n\n34 mth \n\n\n\n42 mth \n\n\n\n5 mth \n\n\n\n12 mth\n\n\n\nCompliance \n\n\n\nGood \n\n\n\nGood \n\n\n\nModerate \n\n\n\nGood \n\n\n\nGood \n\n\n\nGood \n\n\n\nGood \n\n\n\nModerate\n\n\n\nGood\n\n\n\nGood \n\n\n\nModerate \n\n\n\nGood \n\n\n\nGood \n\n\n\nGood \n\n\n\nVery poor \n\n\n\nModerate \n\n\n\nModerate \n\n\n\nPoor\n\n\n\nRelapse\nInterval  \n\n\n\n2yr 6mth \n\n\n\n6 mth \n\n\n\n4 mth \n\n\n\n3 mth \n\n\n\n5 mth \n\n\n\n1yr 9mth \n\n\n\n3 mth \n\n\n\n2 yr 1 mth\n\n\n\n2 yr 2 mth\n\n\n\n9 mth \n\n\n\n1yr 2mth \n\n\n\n1yr 7mth \n\n\n\n2yr 2mth \n\n\n\n2yr 2mth \n\n\n\n4yr 11mth \n\n\n\n3yr 5mth \n\n\n\n2yr 11mth \n\n\n\n24 mth\n\n\n\nSSS on\nrelapse* \n\n\n\n+ve\n\n\n\n0.5 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n2.0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0 \n\n\n\n0 / 0\n\n\n\nTable 6 Characteristics of patients who relapsed during the surveillance period.\n\n\n\nFootnote:\nRx = treatment\nSSS = slit skin smear\nyr = years, mth = months\nMB = multibacillary, PB = paucibacillary\nR-J = Ridley-Jopling, Ind = indeterminate, TT = tuberculoid, BT = borderline tuberculoid, BB = mid borderline,\nBL = borderline lepromatous, LL = lepromatous\n*  indicates BI / MI\n\n\n\n\n\n\n\n\n16 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nReference\n\n\n\nCurrent study\n\n\n\nCurrent study\n\n\n\nYap et al11\n\n\n\nKyaw et al12\n\n\n\nFajardo et al13\n\n\n\nHo & Lo14\n\n\n\nShen et al15\n\n\n\nDesikan et al16\n\n\n\nPoojabylaiah et al17\n\n\n\nBalagon et al18\n\n\n\nFajardo et al13\n\n\n\nMedeiros et al19\n\n\n\nFajardo et al13\n\n\n\nFajardo et al13\n\n\n\nCountry\n\n\n\nMalaysia\n\n\n\nMalaysia\n\n\n\nMalaysia\n\n\n\nMyanmar\n\n\n\nPhilippines\n\n\n\nHong Kong\n\n\n\nChina\n\n\n\nIndia\n\n\n\nIndia\n\n\n\nPhilippines\n\n\n\nPhilippines\n\n\n\nPortugal\n\n\n\nPhilippines\n\n\n\nPhilippines\n\n\n\nYear\n\n\n\n2010\n\n\n\n2010\n\n\n\n2008\n\n\n\n2008\n\n\n\n2009\n\n\n\n2006\n\n\n\n2006\n\n\n\n2008\n\n\n\n2008\n\n\n\n2009\n\n\n\n2009\n\n\n\n2009\n\n\n\n2009\n\n\n\n2009\n\n\n\nRelapse rate\n\n\n\n0.9%\n\n\n\n0%\n\n\n\n0%\n\n\n\n0.5%\n\n\n\n3%\n\n\n\n2.7%\n\n\n\n0.2%\n\n\n\n0.8%\n\n\n\n1.8%\n\n\n\n4.6%\n\n\n\n3%\n\n\n\n8.8%\n\n\n\n0%\n\n\n\n25%\n\n\n\nRegime\n\n\n\nSBA-MDT\n\n\n\nWHO-MDT (1 year)\n\n\n\nBoth SBA-MDT and WHO-MDT\n(1 and 2 years)\n\n\n\n1 year WHO-MDT\n\n\n\n1 year WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\n2 years WHO-MDT\n\n\n\nIntensive daily rifampicin and orfloxacin \nfor a month followed by 1 year\n\n\n\nWHO-MDT\n\n\n\nDaily rifampicin and orfloxacin for\na month\n\n\n\nTable 7 Comparison of the relapse rate among patients with multibacillary leprosy in the current study with\nother studies.\n\n\n\n1 year WHO MDT regime and between 0.2% and\n8.8% for those who had completed the 2 years\nWHO MDT regime (Ta ble 7). It is unsure\nwhether the relapse rate of 0% in our study was\nan underestimation. This might be due to failure\nto capture relapse because of the short\nsurveillance period of only 5 years for patients\nwith multibacillary leprosy who completed the\nM D T- W H O. Balagon et al found that most\npatients relapsed between 6 and 16 years after\ncompletion of treatment18.\n\n\n\nThe relapse rate of patients with multibacillary\nleprosy who had completed the SBA-MDT was\n0.9%. This figure was within the range of\nb e t ween 0.5% and 8.8% in those who had\ncompleted the 1 and 2 years W H O - M D T\nregimes. However, the relapse rate of this regime\nwas higher than the WHO-MDT although it\nrequired patients to be on longer treatment\nduration until BI = 0. A possible reason for the\nhigher relapse might be due to longer period of\ns u rveillance (10 years compared to 5 ye a r s )\nwhich allowed detection of the relapse. Moreover,\nhigher percentages of patients on SBA-MDT\ncompleted surveillance (43.5%) and thus allowed\ndetection of relapse compared to patients on\nWHO-MDT (38.1%).\n\n\n\nWe noted that the type 1 and type 2 lepra\nreactions were signifi c a n t ly higher among\npatients on Sungai Buloh Augmented MDT. This\nmight be due to the intensive phase of SBA-MDT\nwhich might have caused more intense release of\nmycobacterial antigens. The higher rate of type 1\nlepra reaction in patients on SBA-MDT might\nalso be related to the higher proportion of patients\n(37.9%) in the borderline spectrum of disease\n(comprising the borderline tuberculoid, mid\nborderline and borderline lepromatous)\ncompared to those on WHO-MDT (29.3%)20, 21.\n\n\n\nThe incidence of adverse drug reactions was\nhigher in patients on the SBA-MDT compared to\nW H O - M D T. This might be due the use of\nintensive phase, higher dosage of dapsone and\nlonger duration of treatment in the SBA-MDT.\nHowever, the rate of these reactions with SBA-\nMDT in our study of  11.1% was lower than the\nrate of 21.1% with similar MDT in Penang22. The\nhigher rate of dapsone induced hemolysis and\nhepatitis with SBA-MDT might be attributed by\nthe higher dosage of dapsone (100 mg daily with\nSBA-MDT vs. 50 mg daily with WHO-MDT)\nand the use of intensive phase of rifampicin 600\nmg daily for at least 3 weeks respectively.\n\n\n\n\n\n\n\n\n17MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThe limitations in this study are the retrospective\nnature of the study and the different socio-\ndemographic characteristics of patients receiving\nthe 2 different MDT regimes. The retrospective\nnature of this study placed a heavy emphasis on\nthe previous documentations in the medical\nrecords and also the variation in the interpretation\nof the data by the investigators from the different\nparticipating centres. The differences in clinical\ncharacteristics of patients and variable treatment\nduration in the two MDT regimes might also\ncontribute to the differences in the results.\n\n\n\nIn conclusion, both the SBA-MDT and the\nWHO-MDT regimes are effective in inducing\nclinical remission and reducing bacterial counts.\nThe SBA-MDT regime give a higher relapse rate\n\n\n\nalthough not statistically significant. It also\ncontributed to a higher rate of severe adverse\ndrug reactions and leprosy reactions. \n\n\n\nAcknowledgements\nWe would like to thank Datuk Dr Ong Cheng\nLeng, Dr Pubalan Muninady, Dr Choon Siew\nEng, Dr Tey Kwee Eng, Dr Rohna Ridzwan, Dr\nChan Lee Chin, Datin Dr Saraswa t hy a/p\nSubramaniam, Dr Zaigham Mahmood, Dr M\nBalakrishnan, Dr RG Muthulakshmi, Dr M Uma\nSelvam and all the doctors in the participating\ncentres for their help in data collection. We would\nalso like to thank Cik Noor Addillah binti Sheuff,\nthe research officer for the Malay s i a n\nDermatology Registry for her help in the data\nentry.\n\n\n\nReferences\n\n\n\n1. Fadillah K. Report on a workshop of leprosy\nelimination in the western Pacific region, Manila,\nPhilippines. 4-7 March 1996.\n\n\n\n2. Yap FB. Leprosy in Sarawak, East Malaysian Borneo.\nScand J Infect Dis. 2009; 41: 320.\n\n\n\n3. Jayalakshmi P. Leprosy in Malaysia. Malaysian J Pathol\n1994; 16(1): 7-9.\n\n\n\n4. WHO Study Group on Leprosy. Chemotherapy of\nleprosy control programmes. No. 675 of technical\nr e p o rt series. Geneva: World Health Orga n i z a t i o n ;\n1982. \n\n\n\n5. WHO Expert Committee on Leprosy. 7th report .\nNo.874 of technical report series. Geneva: Wo r l d\nHealth Organization; 1998. \n\n\n\n6. Ganesapillai T. The Augmented Sungei Buloh MDT\nregime. Guidelines for MDT 1991: 8-15.\n\n\n\n7. Ganesapillai T. The Short MDT Regime in Sabah.\nCutaneous Mycobacteria an update from Malay s i a\nLads- JRC Travelling Fellowship lecture 1996: 7 -11.\n\n\n\n8. Jamet P, Ji B, the Marchoux Chemotherapy Study\nGroup. Relapse after long term follow up of\nm u l t i b a c i l l a ry patients treated by WHO multidru g\nregimen. Int J Lepr 1994; 63: 195-201.\n\n\n\n9. Ridley DS, Jopling WH: Classification of leprosy\naccording to immunity. A five-group system.  Int J Lepr\nOther Mycobact Dis 1966; 34(3): 255-273.\n\n\n\n10. WHO. Guide to Leprosy Control 1988.\n11. Yap FBB, Awang T, Pubalan M. Comparison of\n\n\n\nmultiple drug therapy in leprosy. Malaysian J\nDermatol. 2008; 21: 47-51.\n\n\n\n12. Kyaw K, Tsoh TM, Swe SYY, Nagaoka Y, Takezaki S,\nSuzuki K, Ichii N. Clinical analysis of multibacillary\nleprosy patients after 1-year fi xed World Health\nO rganization recommended multidrug therapy at\nYangon General Hospital, Myanmar. J Dermatol. 2008;\n35: 264-9. \n\n\n\n13. Fajardo TT, Villahermosa L, Pardillo FEF, Abalos RM,\nBurgos J, dela Cruz E, Gerber RH. A comparative\nclinical trial in multibacillary leprosy with long-term\nrelapse rates of four different multidrug regimens. Am\nJ Trop Med Hyg. 2009; 81(2): 330-4.\n\n\n\n14. Lo CK, Ho KK. Epidemiology of leprosy and response\nto treatment in Hong Kong. Hong Kong Med J 2006;\n12: 174-9.\n\n\n\n15. Shen J, Liu M, Zhang J, Su W, Ding G. Relapsed in MB\nleprosy patients treated with 24 months of MDT in\nSouth West China: a short report. Lepr Rev 2006; 77:\n219-24.\n\n\n\n16. Desikan KV, Sundaresh P, Tulasidad I, Rao PVR. 1n\n8-12 year follow-up of highly bacillated Indian leprosy\npatients treated with the WHO multi-drug therapy. Lepr\nRev. 2008; 79: 303-10.\n\n\n\n17. Poojabylaiah M, Marne RB, Varikkodan R, Bala N,\nD a n d a keri S, Martis J. Relapses in multibacillary\nleprosy patients after multidrug therapy. Lepr Rev\n2008; 79: 320-4.\n\n\n\n18. Balagon MF, Cellona RV, dela Cruz E, Burgos JA,\nAbalos RM, Walsh GP, Saunderson PR, Walsh DS.\nLong-term relapse risk of multibacillary leprosy after\ncompletion of 2 years of multiple drug therapy (WHO-\nMDT) in Cebu, Philippines. Am J Trop Med Hyg.\n2009; 81(5): 895-9.\n\n\n\n19. Medeiros S, Cartorze MG, Vieira MR. Hansen\u2019s disease\nin Portugal: multibacillary patients treated between\n1988 and 2003. J Eur Acad Dermatol Venereol. 2009;\n23: 29-35.\n\n\n\n20. Yap FBB, Pubalan M. Risk factors for type 1 leprosy\nreaction in a tertiary clinic in Sarawak. Malaysian J\nDermatol 2009; 22: 29-32. \n\n\n\n21. Yap FBB. Clinical characteristics predicting erythema\nnodosum leprosum (ENL) among patients with\nmultibacillary leprosy (MBL) in Sarawak. Asian Pac J\nTrop Med. 1009; 2(5): 66-70.\n\n\n\n22. Tan WC, Lo Kang SC, Ong CK. Hansen\u2019s disease in\nPenang: a 10 year retrospective analysis. Malaysian J\nDermatol 2007; 19: 89-94.\n\n\n\n\n\n\n\n\n18 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Case Report\n\n\n\nDisseminated fusariosis in a patient with acute\nlymphoblastic leukaemia: A case re p o rt and literature\nre v i e w\nTang Jyh Jong\n\n\n\nCorrespondence\nTang Jyh Jong\nDepartment of Dermatology,\nHospital Kuala Lumpur\nEmail: tangjyhjong@yahoo.com\n\n\n\nIntroduction\nFusarium spp are molds found in the soil and\nm ay be saprophytic or fa c u l t a t ive plant\np a t h ogens. These are rare but import a n t\nopportunistic pathogens in immunocompromised\npatients especially those with hematolog i c\nmalignancies.  Fusarium spp usually cause local\ninfections such as onychomycosis and infections\nof surgical and bu rn wound. However more\nimportantly, these pathogens can lead to severe\ndisseminated infection with invo l vement of\nmultiple organs including skin. This disseminated\nform of fusariosis occurs exclusively in patients\nwith prolonged, severe neutropaenia especially in\npatients with acute leukaemia or those\nu n d e rgoing bone marr ow transplantation.\nPrognosis of disseminated fusariosis is usually\nguarded if not recognized early. We report a rare\ncase of disseminated fusariosis in a patient with\nacute lymphoblastic leukaemia.\n\n\n\nCase 1\nA 21 ye a r-old lady with refractory acute\nly m p h o blastic leukemia on salva g e\nc h e m o t h e r a py presented to us with multiple\npainful erythematous papules and nodules\ninvolving face, both upper limbs and lower limbs\nfor 10 days prior to admission. The lesions started\non both upper limbs and then spread to both\nlower limbs. These lesions subsequently ulcerated\nwith central necrosis.\n\n\n\nIt was associated with fever and lethargy. There\nwas no history of preceding trauma or animal\nbite.\n\n\n\nOn examination, she was febrile and ill looking.\nShe was pale but not jaundiced. Her\nhaemodynamic status was stable. There were\nmultiple erythematous macules as well as tender,\nindurated erythematous papules and nodules on\nher face, upper and lower limbs. Some of the\nlesions were ulcerated and covered with thick\nblack eschar (Figure 1.1, 1.2, 1.3). There were no\ndigital ulcers, paronychia or ony c h o my c o s i s .\nThere was presence of hepatosplenomegaly but\nno ly m p h a d e n o p a t hy. Examinations of other\nsystems include lung, cardiovascular were all\nunremarkable.\n\n\n\nOur initial differential diagnosis included\nL e u kemia cutis, nodular vasculitis, Swe e t \u2019s\nsyndrome and disseminated fungal infection.\nSkin biopsy for histopathological examination\ns h owed unremarkable epidermis and derm i s .\nThere were focal clusters as well as singly\nscattered fungal bodies and hyphae (Periodic\nAcid Schiff and Gomori-Grocott methenamine\nsilver were positive). The fungal bodies were\nsized 2-3 times larger than RBC and the hyphae\nwere septated, branching and broad (Figure 2.1,\n2.2, 2.3). These features were consistent with\ndeep fungal infection. Subsequent skin biopsy for\nfungal culture grew Fusarium spp (Figure 2.4). In\naddition to that, the blood culture also grew\nsimilar Fusarium spp. Hence, final diagnosis of\ndisseminated fusariosis was made.\n\n\n\nKeywords disseminated fusariosis, acute Lymphoblastic Leukaemia, fusarium spp, deep fungal infection\n\n\n\n\n\n\n\n\n19MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nhyperpigmentation. However this patient passed\naway few weeks later in the ward due to her\nnosocomial sepsis secondary to her underlying\nacute lymphoblastic leukaemia.\n\n\n\nIV Voriconazole was started subsequently and\nwas given for a total duration of one month. She\nresponded well to IV Voriconazole and all lesions\nhealed well with post inflammatory\n\n\n\nFigure 1.1  Numerous erythematous macules with tender erythematous papules and nodules, some \nwith necrotic centre on left forearm.\n\n\n\nFigure 1.2  Close view of a tender erythematous nodule on leg.\n\n\n\nFigure 1.3  Close view of a late stage nodule covered with thick black eschar with a rim of\nerythema on leg.\n\n\n\n\n\n\n\n\n20 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nFigure 2.1 Focal clusters as well as singly scattered \nfungal bodies and hyphae in subcutaneous tissue.\n(H&E x10)\n\n\n\nFigure 2.3  Gomori-Grocott methenamine silver stain \nhighlights fungal bodies and septated branching\nhyphae in the subcutaneous tissue.\n\n\n\nFigure 2.2 Fungal bodies sized 2-3 times larger than\nRBC with broad, branching and septated hyphae in\nsubcutaneous tissue. (H&E x40).\n\n\n\nFigure 2.4  Microscopy:  large sickle or banana\nshaped macroconidia (with 3 to 5 septa).\n\n\n\nwith indwelling catheters, wounds and burns1,2.\nInitial source of disseminated fusariosis is usually\nsinus or pulmonary infection but skin make up of\n33% of initial portal of entry and it is usually\nrelated to paronychia or trauma induced digital\nu l c e r3. The F u s a r i u m spp. most frequently\ni nvo l ved in human infections are F. Solani,\nF. O x y s p o r u m, F. Ve r t i c i l l o i d e s, and\nF. Moniliforme3.\n\n\n\nSkin lesions are seen in more than 70% of\ndisseminated fusariosis3. A variety of skin\nmanifestations are seen in disseminated\nfusariosis, however, the most prominent feature\nof the lesion is a red or gray macule with a central\nulceration or black eschar4. The central ulceration\nis due to dermal vessel thrombosis caused by\nhyphae elements. Other manifestation include\np u rpuric papules, pustules and subcutaneous\nnodules4\n\n\n\nDiscussion\nFusarium spp. is saprophytic mould that can be\nfound in the soil and plant1. The incidence of\ndisseminated fusariosis is increasing and had\nbeen reported in neutropenic patients with\nh e m a t o l ogical malignancies (especially acute\nleukaemia) and those who had bone marrow\ntransplant1. These fungi may cause a variety of\ncutaneous infection ranging from onychomycosis\nin healthy individual to widely disseminated\ninfection in immunocompromised patients\ne s p e c i a l ly those with haematolog i c a l\nmalignancy undergoing intensive antileukaemic\nchemotherapy or allogenic hematopoetic stem\ncell transplantation2.\n\n\n\nDisseminated fusariosis may infest via inhalation\nof airborne conidia or the inoculation of conidia\nthrough a breach in the skin, especially associated\n\n\n\n\n\n\n\n\n21MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nn o d u l e s4. Disseminated fusariosis should be\nsuspected in a febrile patient with neutropenia\nand hematological malignancy who have one or\nmore of the following: 1) a digital paronychia\nespecially with onychomycosis. 2) a digital ulcer\nor escar 3) suggestive disseminated skin lesions4.\nOur patient had classical presentation of\ndisseminated fusariosis with feve r, multiple\ntender erythematous papules and nodules which\nwere covered with black eschar.\n\n\n\nThe diagnosis of Fusarium is usually based on a\nhigh index of suspicion in immunocompromised\nhosts5. Investigations should include skin biopsy\nfor histolopathological examination, culture and\nimmediate fungal stains, blood cultures,\nradiological evaluation of the lungs and sinuses4,5.\nSkin lesions contribute to the diagnosis of\nfusariosis in about 60% of patients whereas blood\ncultures are positive in about 60% of cases5.\nF u s a r i u m species can gr ow rapidly on most\nc o nventional fungal medium, but gr owth is\nrestricted by cycloheximide1. The microscopic\nmorphology of Fusarium species is characterized\nby the presence of unbranched or branched\nconidiophores with phialides that produce\nmulti-septate, banana or sickle-shaped\nmacroconidia1.\n\n\n\nTreatment of fusariosis is especially difficult as\nF u s a r i u m spp is relative ly resistant to most\nantifungal medication5. IV Amphotericin B still\nremains the drug of choice but higher dose\nis required in treating fusariosis6. The new\ntriazole agents (voriconazole, posaconazole,\nravuconazole) has shown been to be effective in\n\n\n\nthe treatment of disseminated fusariosis5 , 6.\nCombination treatment with Amphotericin B and\nvoriconazole or posaconazole have been widely\nused too6. However Ketoconazole, miconazole,\nt e r b i n a fine, and echinocandins have\nlimited activity5. Fluconazole, itraconazole and\nflucytosine have no activity against Fusarium\ns p e c i e s5 , 6. A p a rt from antifungal therapy,\nstrategies to improve host immunity and surgical\nexcision of necrotic tissue may help to improve\nthe outcome of disseminated fusariosis6.\n\n\n\nDisseminated fusariosis carries a poor prognosis.\nMortality rate in disseminated fusariosis can be\nas high as 75% which is related to the\nangiotropism of Fusarium and its ability for\nadventitious sporulation in tissues6. Patients with\nu n d e r lying hematological disease, neutropenia\nand late diagnosis and treatment contribu t e\nfurther to the poor prognosis of this condition6.\nHence, it is important to have high index of\nsuspicion in this group of patients  so that early\nempirical intravenous antifungal can be given as\nearly as possible to improve the outcome of this\ndisease.\n\n\n\nConclusion\nIn conclusion, disseminated fusariosis is not\ncommon. The report of this case serves as a\nreminder of the ability of an innocuous,\ns a p r o p hytic, environmental mould namely\nFusarium spp to emerge as a clinically\ns i g n i ficant opportunistic pathogen in the\nimmunocompromised host especially those with\nh a e m a t o l ogical malignancy. Failure of early\nrecognition of the disease can be fatal.\n\n\n\nReferences\n\n\n\n1. Shelly A Gilroy, Jane Roller, Russell A Rawling et al.\nDisseminated Fusariosis: an Emerging Opportunistic\nInfection. Clinical Microbiology New s l e t t e r\n2006;28 (22):174-175.\n\n\n\n2. Groll A. H., Walsh T. J. Uncommon opportunistic\nfungi: new nosocomial threats. Clin Microbiol Infect\n2001;7 (2):8-24.\n\n\n\n3. Jos\u00e9-Manuel Vagace, Cesar Sanz-Rodriguez, Maria-\nSoledad Casado et al. Resolution of disseminated\nfusariosis in a child with acute leukemia treated with\ncombined antifungal therapy: a case report. BMC\nInfectious Diseases 2007;7:40.\n\n\n\nR\n\n\n\n4. Gerald P. Bodey, Maha Boktour, Steven Mays, Skin\nlesions associated with Fusarium infection. J Am Acad\nDermatol. 2002;47(5):659-666.\n\n\n\n5. M. Halpern, E. Balbi, L. Carius. Cellulitis and Nodular\nSkin Lesions Due to Fusarium spp in Liver Transplant:\nCase Report. Transplantation Proceedings 2010;\n42:599-600.\n\n\n\n6. Jossi M., Ambrosioni J., Macedo-Vinas M, Garbino J.\nInvasive Fusariosis With Prolonged Fungaemia in A\nPatient with Acute Lymphoblastic Leukaemia: Case\nReport And Review of the Literature. International\nJournal of Infectious Diseases. 2010;14:354-356.\n\n\n\n\n\n\n\n\n22 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPA E D I ATRIC DERMAT O L O G Y - Short Case\n\n\n\nAsymptomatic infant with high titre of immunoglobulin\nM Mycobacterium Leprae antibody whose mother has\nMorbus borderline lepromatous leprosy \nWahyu Lestari, Sri Lestari, Qaira Anum, Zainal H, Satya W\n\n\n\nCorrespondence\nWahyu Lestari \nDepartement of Dermato-Venereology\nof Dr. M. Djamil Hospital, Medical Faculty\nof Andalas University, Padang, Indonesia\nE-mail: Mulia_1@yahoo.com\n\n\n\nI n t ro d u c t i o n\nLeprosy is a chronic infectious disease with a\nlong incubation period caused by Mycobacterium\nl e p ra e. The average incubation period for\ntuberculoid and lepromatous cases are 2-5 years\nand 8-12 years respectively1,2. Risk factors for\nleprosy includes age, sex, household contact and\nBacilli Calmette-Guerin (BCG) vaccination3.\n\n\n\nWe present an asymptomatic 3 month-old\ni n fant with high immunog l o bulin M titre\nmycobacterium leprae antibody whose mother\nhas morbus borderline lepromatous leprosy.\n\n\n\nCase report\nA 3-month old baby girl whose mother has\nclinical signs of leprosy was referred to Dermato-\nVe n e r e o l ogy Department of Dr. M. Djamil\nHospital on December 15th 2011 to exclude\nleprosy. She was born per vagina weighing 3.4kg\nat birth. She had BCG vaccination at one month\nof age. There was no history of fever, respiratory\nsymptoms or skin signs suggestive of leprosy.\nShe is breast-fed since birth and only cared by her\nmother. She lives in a small house at Damasraya\nin a 8x6 m2 large house and sleeps in the same\nbed as her parents. Her father earns two million\nrupiahs per month.\n\n\n\nFigure A The patient with a body weight of 5.5kg and height of 68cm.\n\n\n\nA\n\n\n\n\n\n\n\n\n23MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nClinically patient appears well nourished with no\nsigns of cutaneous rash (Figure A). Whereas her\nmother has multiple facial plaques and nodules\non the face and ear lobes. Annular rashes with\ncentral hypoaesthesia were noted on the mother\u2019s\nchest, gluteus, abdomen, forearms, hands, legs\nand feet.\n\n\n\nG l ove and stocking hypoaesthesia were also\nnoted. Only bilateral ulnar nerves were thickened\nand tender. Xerosis cutis was noted on the lesions\nand the extremities. The slit skin smears on both\nearlobes, leg and gluteus showed acid fast bacilli\n\n\n\nbacteriology index of +3. No acid fast bacilli\nnoted in the breast milk. The skin biopsy\nh i s t o p a t h o l ogical finding showed features of\nVirchow\u2019s cells and epitheliod cells that was\nconsistent of Morbus borderline lepromatous\nleprosy.\n\n\n\nThe infant was diagnosed as having subclinical\nleprosy and her mother Morbus borderline\nlepromatous leprosy. Infa n t \u2019s IgM and IgG\nprotein were 174 (normal for her age: 25-100\nmg/dl) and 614  (normal for age : 200-700 mg/dl)\nrespectively.\n\n\n\nFigure B, C, D and E  The patient\u2019s mother.\n\n\n\nB\n\n\n\nC D E\n\n\n\n\n\n\n\n\n24 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDiscussion\nThis infant has subclinical leprosy. The 65 kd\nprotein is not specific for M. leprae and can be\ncause by other pathogenic mycobacteria, such as\nM. tuberculosis7. In this case there was no sign of\ntuberculosis in the infant nor history of\ntuberculosis in family members. Patient\u2019s  mother\nhas borderline lepromatous leprosy support\nsubclinicaql leprosy in this patient.\n\n\n\nThe main mode of transmission in leprosy is via\ndroplet spread. Droplet transmission may be from\nmother to child or from other family members\nsuch as parents, grandparents or siblings and even\nclose friends4. In young children, infection may\nbe acquired through placenta or breast milk.\n\n\n\n20% of children born to mothers with leprosy\nmay develop leprosy by puberty. Leprosy in\nyoung children may resolve spontaneously,\nGetting pregnant at a young age may trigger\nleprosy complicated with neuropathy. T h u s\npatient education and awareness of this\ncomplication during pregnancy is essential. Close\nmonitoring of pregnant ladies with leprosy to\nscreen for sign of nerve damage associated with\nMDT reaction5. Contact tracing of her children is\nrequired to screen for leprosy in her children.\n\n\n\nIn pregnant woman with active lepromatous\nleprosy, the placenta is exposed to a high bacteria\nload of M. leprae which can cross the placenta\nand infect the fetus. Mother\u2019s immunoglobulin G\ncan cross the placenta and can be detected in the\ncord blood. IgM do not cross the placenta. Thus\nan elevated level of this antibody in the cord may\nbe an indication of the fetal immune system\nstimulation by antigen transfer in utero.\n\n\n\nNormally, IgM in the infant is produced at 6\nmonths of age. Presence of IgM before 6 months\nof age indicates possibility of infection in the\ninfant6.\n\n\n\nAlthough leprosy is very rare in infant, 50% of\nbabies of lepromatous mothers have rising titers\nof IgM antibodies to M. leprae, showing that they\nhave been infected1. Transplacental transmission\nof M. leprae in mice is well established. Whereas\ninfection in human fetus is only proven recently4.\nIn a study for a period of up to two years after\nbirth, Duncan ME (UK,1984) noted acid-fast\nbacilli present in the cord blood of babies born to\n\n\n\nwomen with active lepromatous leprosy and\nsignificant increase of IgM antibody activity after\nbirth in babies of mothers with active leprosy\ncompared with the children of normal mothers7.\n\n\n\nAntibody tests can be used as diagnostic tools to\ndetect asymptomatic and subclinical leprosy\npatient. They have high titers of antibody such as\nphenolic glycolipid I and arabinomannan and\nM. leprae antigens may be detected in the sera1,5.\n\n\n\nDoughlas JT, et al. (Philippines, 2004) perform a\nc o h o rt study of contacts of multibacilliary\nleprosy patients in Philippines with a follow-up\ntime of 11 years. He noted seropositive contacts\nhad a seven times higher risk of developing\nleprosy and a 24 times higher risk of developing\nMB leprosy. Household contacts, neighbours,\nand social contacts have a higher chance of\ncontracting the disease. Whether this is mainly\nthe result of closer contacts to the index case of\nthe infection, similar genetic and immunological\nbackground, environmental, or a combination of\nall, is not yet resolved8.\n\n\n\nBakker MI, et al. (Indonesia, 2005) screened\nhousehold contacts and noted an  increasing IgM\nantibodies in 7 out of 122 patients age 0 to 5 years\nand in 211 out of 219 patients aged 6 to 20 years.\nHaving contact with an infectious patient is a risk\nfactor in harboring antibodies, but to develop MB\nleprosy genetic factors plays an important role. In\nIndonesia, people who are seropositive have a 3\u00b78\ntimes higher risk of developing leprosy than\nnegative people9.\n\n\n\nGindhar A, et al. (USA, 1998) reported two cases\nof leprosy in a 4 and 2 months female infants. On\nexamination there were two small lesions (about\n3 cm), ill - defined, hypopigmented patches over\nthe left back near the buttocks. The infant was\nsuspected of having indeterminate leprosy. Skin\nsmears from one ear and one lesion were both\nnegative for acid-fast bacilli (AFB). The serum\nshowed the presence of IgM antibodies, and PGL\nantibodies were also detected. It is also possible\nthat these infants acquired the infection at\npostnatal through household contact10. In our\npatient, subclinical leprosy was probably as a\nresult of transmission of bacilli via placenta from\nher mother who had active lepromatous leprosy\nduring pregnancy.\n\n\n\n\n\n\n\n\n25MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nIn a recent prospective study IgM anti M. leprae\nantibody activity was significantly increased in\none-third of babies of mothers with lepromatous\ntype taken 3-6 months after birth, but not in any\nof the sera from babies of mothers with\ntuberculoid leprosy10. Liu D, et al. (Wuhan, 2009)\nreported during a 5-year follow-up study of a\nhyperendemic community in Wuhan. T h e s e\nobservations suggest that subclinical infection\nwith Mycobacterium lepra e is common in\nendemic communities and that antibody\nseropositivity is a marker of subclinical infection.\nDetection of subclinical infection may confound\ncontrol strategies which use screening tests to\nidentify asymptomatic highly infectious cases for\nearlier therapy1 1. Thus the IgM antibodies\nM. leprae response signifies the presence of\na c t ive disease, part i c u l a r ly in multi-bacillary\ncases, and has the potential to be used not only to\nmonitor the response of these patients to therapy,\nbut also to detect subclinical leprosy in high-risk\ngroups such as the relatives of patients with\nlepromatous disease11,12.\n\n\n\nPatient and her mother could not be tested for anti\nPGL-1. Anti PGL-1 (phenolic gly c o l i p i d )\nantibodies is a specific test for Mycobacterium\nleprae which measured by ELISA in sera from\nn ew ly diagnosed and treated leprosy patient.\nBritton W J, et al. (Sydney, 1997) report e d\nantibodies to the species-specific phenolic\nglycolipid (PGL-1) of Mycobacterium leprae in\nsera from newly diagnosed and treated leprosy\n\n\n\npatients from Sydney and Nepal. IgM anti-PGL-\n1 antibodies were present in 88-90% of untreated\npatients at the lepromatous pole of the clinical\nspectrum and 35-55% of those at the tuberculoid\np o l e1 2. Thus the IgM anti-PGL-1 response\ns i g n i fies the presence of active disease,\nparticularly in multi-bacillary cases, and has the\npotential to be used not only to monitor the\nresponse of these patients to therapy, but also to\ndetect subclinical leprosy in high-risk groups\nsuch as the relatives of patients with lepromatous\ndisease13.\n\n\n\nIn this case, the prognosis for quo ad sanationam\nof this patient is dubia ad bonam, according the\nliterature most of the babies will probably control\ntheir subclinical leprosy infection without\ndeveloping clinical signs of leprosy. This will be\nin agreement with the demonstration of self\nhealing in 75% of early childhood1 0. IgM\nantibodies against M. leprae were present in all\nthe sera examined. A gain, the lepromatous\nleprosy groups had the highest concentration of\nantibodies. The median value was 140%, with a\nvariation between 10 and 350 % in active\nlepromatous leprosy14.\n\n\n\nConclusion\nInfant with subclinical leprosy should be examine\nregularly for sign of leprosy because the risk of\nsuffering from leprosy in childhood and also at\nthe puberty6. Contact tracing and screening of all\nfamily members for the possibility leprosy.\n\n\n\nReferences\n\n\n\n1. Bryceson A, Pfaltzgraff RE. Mycobacterium leprae. In:\nBryceson A, Pfaltzgraff RE Leprosy. 3th ed, London:\nChurchill Livingstone; 1990.\n\n\n\n2. Rea TH, Modin RL. Leprosy. In : Wolff K, Goldsmith\nLA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ eds.\nDermatology in general medicine, Fitzpatrick, 7th ed,\nvol 2, New York: Mc Graw Hill, Medical Publishing\nDivision, 2008: 1786-96.\n\n\n\n3. Lockwood DN. Leprosy. In: Burns T, Breatnach S, Cox\nN, Griffiths CH, editor. Rook\u2019s textbook of\ndermatology; 8th Ed. London: Blackwell publishing;\n2010: 32.1-20.\n\n\n\n4. Sylvia MR, Castro MCR. Mycobacterial infection. In :\nBolognia JL, Jorizzo JL, Rapini R, Horn TD, Mascaro\nJM editor. Dermatology. 1 th edition, vol 1, London,\nMosby, 2004: 1145-50.\n\n\n\n5. Duncan ME, Fox H, Harkness RA, Rees JW. The\nplacenta in leprosy. Placenta 1984;189-98.\n\n\n\n6. Duncan ME. An historical and clinical review of the\ninteraction of leprosy and pregnancy: a cycle to be\nbroken. Soc. Sci. Med; 1993:457-72.\n\n\n\n7. Ochoa MT, Teles R, Haas BE, Zaghi D. A role for\ninterleukin-5 in promoting increased immunoglobulin\nM at the site of disease in leprosy. Immunology Journal\n2010;131: 405-14.\n\n\n\n8. Bakker MI, May L, Hatta M, Kwenang A, Klatser.\nGenetic, household and spatial clustering of leprosy on\nan island in Indonesia: a population-based study. BMC\nMedical Genetics; 2005: 1-10.\n\n\n\n9. Douglas JT, Cellona RV, Fajardo TT et al. Prospective\nstudy of serological conversion as a risk factor for\ndevelopment of leprosy among household contacts.\nClin Diagn Lab Immunol, 2004; 11: 897-900.\n\n\n\n10. Girdhar A, Mishra B, Lavania RK, Ashok. Leprosy in\ninfants : report of two cases. International journal of\nleprosy 1998; 57:472-8.\n\n\n\n\n\n\n\n\n26 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\n11. Liu D, Li G, Huang W, Gao j.Analysis of newly\ndetected Leprosy cases and misdiagnosis in Wuhan\n(1990-2004). Lepr Rev 2009; 80: 410-5.\n\n\n\n12. Britton W J, Garsia RJ, Basten A. The serolog i c a l\nresponse to the phenolic glycolipid of Mycobacterium\nleprae in australian and nepali leprosy patients. Aust\nNZ J Med 1997:568-74. \n\n\n\n13. Melsom R, Harboe M, Duncan ME. IgM and IgG anti\nM. leprae antibodies in babies of leprosy mothers\nduring the first 2 years of life. Clin. Exp.Immunol\n1982: 532-42.\n\n\n\n14. Moet FJ, Meima A, Oskam L, Richardus JH. Risk\nfactors for the development of clinical leprosy among\ncontacts, and their relevance for targeted interventions.\nLepr Rev, 2004; 75: 310-326.\n\n\n\n\n\n\n\n\n27MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPA E D I ATRIC DERMAT O L O G Y - Short Case\n\n\n\nCutis marmorata telangiectatica congenita\nSabeera BKI, Mardziah Alias\n\n\n\nCorrespondence\nKI Sabeera, MBBS MPaeds\nInstitute of PaediaAtrics,\nHospital Kuala Lumpur, Malaysia\nEmail: dr_sabeera@yahoo.com\n\n\n\nIntroduction\nCutis marmorata telangiectatica congenita\n(CMTC) is a rare congenital disorder with\npersistent cutis marmorata, telengiectasia, and\nphlebectesia, which may be associated with\ncutaneaus atrophy and ulceration of the involved\nskin. We herewith report a three month old male\nbaby with CMTC at birth involving left side of\nthe face, upper limbs, both flanks, and left gluteal\nand left leg with ulceration over the extensor\naspects of the left knee joint. The baby had a\nreticulated bluish purple skin changes all over the\nbody including the face and limb. Although it\nresembled physiological cutis marmorata, it was\ns t r i k i n g ly pronounced and defi n i t e ly wa s\nunvarying and permanent. A variety of vascular\nmalformation has been described along with this\ndisorder. Etiology is not very clear. Prognoses in\nuncomplicated cases are good.\n\n\n\nCase report\nA three month old Chinese male infant presented\nwith ex t e n s ive cutis marmorata like lesion\ninvolving left side of the face, upper limbs, both\nflanks, and left gluteal and left leg since birth.\nThe affected left leg was noted to be smaller. The\nlesions are of the same colour, size and\ndistribution since birth. Some areas of the lesion\nwere ulcerated and healed spontaneously with\nskin atrophy.\n\n\n\nHe is otherwise well. His deve l o p m e n t a l\nmilestones are within normal limit. He is the third\nchild of a non consanguineous marriage. Other 2\n\n\n\ns i blings are well. Antenatal and postnatal\nhistories were normal. No similar skin problem\nnoted in the family.\n\n\n\nOn examination there were extensive purplish\nreticulated vascular network on the left side of\nbody involving the left leg, left flank, right arm,\nand back (Figure 1 and 2).\n\n\n\nThere were areas of subcutaneous atrophy and\nulceration noted along these vascular lesions. The\nleft lower limb was atrophic but there were no\nsignificant limb length discrepancy.\n\n\n\nNo dysmorphism was noted. His head\ncircumference was above the 90th percentile\ncompare to weight and height which was on the\n50th percentile. Other systemic ex a m i n a t i o n s\nincluding full neurological examination we r e\nnormal.\n\n\n\nBlood investigations including the autoimmune\nscreening were normal. MRI brain showe d\nnormal study. MRI of the left lower limbs showed\nsignificant thinning of overlying subcutaneous\ntissue.\n\n\n\nA diagnosis of cutis marmorata telangiectatica\ncongenital  was made from the clinical features\nand inve s t i gations. At 1 year follow up, he\nshowed no further clinical improvement of the\nskin lesions and he was neuro-developmentaly\nnormal. \n\n\n\nDiscussion\nOur patient demonstrates an unusual clinically\ndistinctive cutaneous vascular malformation with\ncutaneous atrophy and ulceration known as cutis\nmarmorata telangiectatic congenita.\n\n\n\nKeywords congenital skin anomaly, skin ulceration, skin atrophy\n\n\n\n\n\n\n\n\n28 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nCUTIS MARMORATA T E L A N G I E C TAT I C A\nCONGENITA (CMTC) was first described by\nthe Dutch peadiatrician van Lohuizen in 19221. It\nis defined as a localized or generalized\nreticulated, vascular, blue-violet network that is\nusually present at birth. This marbled pattern is\nalways visible, but may be enhanced by cold\ntemperatures or distress. The skin lesions show a\nmarked improvement over time, with the greatest\ni m p r ovement occurring during the first and\nsecond years of life2.\n\n\n\nThe pathogenesis of CMTC is unknown. A\nnumber of hypotheses have been proposed. These\ninclude environmental factors, autosomal\ndominant inheritance with low or va r i a bl e\npenetrance, a multifactorial cause, or a lethal\ngene surviving by mosaicism2.\n\n\n\nThe diagnosis is established on clinical grounds.\nH i s t o p a t h o l ogic examination of biopsy\nspecimens may show an increase in the number\nand the size of capillaries and veins but is usually\nnot necessary to confirm the diagnosis1,2.\n\n\n\nSome overlapping features and clinical\nsimilarities to the Klippel-Trenaunay-Weber and\nSturge-Weber syndromes have been observed. It\nhas been suggested that these 3 entities should be\nc l a s s i fied as a group of vascular diseases\nassociated with other developmental defects\nrepresenting defects of the mesodermal system\nduring embryonic life3.\n\n\n\nFigure 1  Reticulated, vascular, blue-violet network involving the whole length of right upper limb.\n\n\n\nFigure 2  Reticulated, vascular, blue-violet network involving the whole of left lower limb with \nsignificant epidermal atrophy over the extensor of the left knee and visible veins.\n\n\n\n\n\n\n\n\n29MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAdditional anomalies have been frequently\nreported in association with CMTC. The most\nc o m m o n ly associated findings include body\na s y m m e t ry (usually limb hy p e rplasia or\nhypoplasia), other vascular anomalies (mostly\ncapillary malformation), glaucoma, hypoplasias\nor aplasias (ranging from transverse limb defects\nto localized aplasia cutis congenita to a cleft\npalate), and, infrequently, psychomotor and/or\nmental retardation. Cutaneous atrophy and\nulcerations may also be observed. These are not\nalways regarded as associated anomalies, but are\nincluded in the specific skin findings in\nCMTC4,5,6.\n\n\n\nFor many patients, CMTC is a benign condition,\nbut a full physical examination by a paediatrician\nand a dermatologist should always be performed.\nChildren with clinically detectable abnormalities\nmust be referred to an appropriate specialist. In\nthe case of a periocular vascular lesion including\nCMTC, an ophthalmologic examination should\nbe performed to exclude glaucoma or other eye\nabnormalities. Follow-up for the skin lesions,\nassociated abnormalities and psychomotor\ndevelopment is advisable in patients with CMTC. \n\n\n\nFor parents, and in later life for the patient,\ngenetic counseling may be necessary. However,\nalmost all reported cases have been sporadic. The\nsegmental distribution, along with the preferred\none-sided body invo l vement, support the\nhypothesis that CMTC is a disorder to which the\nlethal gene theory of Happle could be applied, in\nwhich he suggests the concept of lethal genes\nsurviving by mosaicism. The mosaic may arise\neither in an early postzygotic mutation, or from a\nhalf chromatid mutation that has occurred before\nfertilization in one of the two gametes forming\nthe zygote7.\n\n\n\nThe differential diagnosis reveals seve r a l\nconditions such as capillary malformation,  KTW\nsyndrome, neonatal lupus erythematosus, nevus\nanemicus, and physiological cutis marmorata,\nl ivedo reticularis associated with collagen\nvascular disorder, nevus flammus, and diffuse\nphlebectasia.\n\n\n\nThe prognosis of CMTC is good. Devillers C. A\net al observed 35 patients with CMTC, who had\nrapid improvement of the skin lesions within 2\nyears either leading to a total disappearance of\nthe lesions or marke d ly improved residual\nlesions, a finding that agrees with those of other\nstudies6.\n\n\n\nIn conclusion, CMTC is a relative ly mild\ncondition. The prognosis is usually good, with\nminor associated anomalies and an improvement\nof the mottled, vascular pattern within 2 years. A\ncareful clinical examination of all patients to\nexclude possible associated anomalies is\nimportant.\n\n\n\nReferences\n\n\n\n1. Van Lohuizen CHJ. Uber eine seltene angeborene\nHautanomalie (Cutis marmorata telangiectatica\ncongenita). Acta Derm Venereol (Stockh). 1922;3:\n201-211. \n\n\n\n2. R ogers M, Poyzer KG. Cutis marm o r a t a\ntelangiectatica congenita. Arch Dermatol. 1982;\n118:895-899.  \n\n\n\n3. Kennedy C, Oranje AP, Keizer K, van den Heuvel MM,\nC a t s m a n - B e rr evoets CE. Cutis marm o r a t a\ntelangiectatica congenita. Int J Dermatol. 1992;31:\n249-252. \n\n\n\n4. Pehr K, Moroz B. Cutis marmorata telangiectatica\ncongenita: long-term follow-up, rev i ew of the\nliterature, and report of a case in conjunction with\ncongenital hy p o t hyroidism. Pediatr Derm a t o l .\n1993;10:6-11.\n\n\n\n5. Devillers, Arjan C. A, De Waard-van der Spek, Flora B,\nOranje, A rnold P. Cutis Marmorata Te l a n g i e c t a t i c a\nCongenita: Clinical Features in 35 Cases. Archives of\nDermatology; 1999 Volume 135(1):pp 34-38.\n\n\n\n6. Gerritsen MJP, Steijlen PM, Brunner HG Rieu P. Cutis\nm a rmorata telangiectatica congenita: report of 18\ncases. British Journal of Derm a t o l ogy 2000; 142:\n366\u00b1369.\n\n\n\n7. Happle R. Lethal genes surviving by mosaicism: a\np o s s i ble explanation for sporadic birth defects\ninvolving the skin. J Am Acad Dermatol. 1987;16:\n899-906.\n\n\n\n\n\n\n\n\n30 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPA E D I ATRIC DERMAT O L O G Y - Short Case\n\n\n\nNeonatal lupus erythematosus presenting as multiple\nphotosensitive annular plaques with skin atro p h y\nSabeera BKI. Mardziah A\n\n\n\nCorrespondence\nKI Sabeera, MBBS MPaeds\nInstitute of PaediaAtrics,\nHospital Kuala Lumpur, Malaysia\nEmail: dr_sabeera@yahoo.com\n\n\n\nIntroduction\nNeonatal lupus erythematosus (NLE) is an\nautoimmune disease affecting the fetus as a\nresult of transplacental transfer of anti-Ro\nautoantibodies. Typically, it presents in the first\nfew months of life with an annular form of\nsubacute cutaneous lupus erythematosus. We\nreport an infant of NLE presenting at birth with\nmultiple annular erythematous plaques with skin\natrophy involving the face, head, and upper trunk.\nHistopathology of skin biopsy was consistent\nwith subacute cutaneous lupus. The mother was\nclinically free of disease and had no family\nhistory of autoimmune disease. Serology (extra-\nnuclear antigens) was positive in both the baby\nand the mother. This is a rare presentation of a\nrare disease.\n\n\n\nCase report\nA four month old Chinese baby girl presented\nwith red annular lesions on the forehead, cheek,\nscalp and chest. These lesions were noted since\nbirth and were regarded as birthmarks. She was\ndescribed as a difficult baby since she was always\ncrying, irritable and had poor sleep pattern. She is\notherwise feeding and thriving well. T h e s e\nlesions appear to be exacerbated by exposure to\nsun light. Birth history was normal. Her mother is\na 28 year old Chinese lady with unremarkable\nantenatal history.\n\n\n\nOn examination the baby was haemodynamically\nstable with normal limit of heart rate and blood\npressure. She had annular erythematous plaques\nwith central violaceous hue over the forehead,\n\n\n\nperiorbital region, cheek, scalp and anterior\nchest. There were peeling of skin at peripheries\nand some lesions showed areas of skin atrophy\n(Figure I). Other systemic examinations were\nnormal including CVS and CNS examinations.\n\n\n\nHer blood inve s t i gation including full bl o o d\ncount, liver enzyme profile, basic chemistry\npanel, peripheral blood picture, VDRL and\nTORCH were normal. ESR = 21mm/hr, C3 & C4\nwere normal. Antinuclear antibody was reactive\nwith titer of 1:1280. Extractable nuclear antigen\nwere detected of which antibodies to Ro and La\nwere >240 units and >320 units respectively.\nAnti-smooth muscle antibody and Anti-U1RNP\nwere not detected. ECG showed sinus tachycardia\nwith no evidence of heart block and a normal\ne c h o c a r d i ogram study. Skin biopsy showe d :\ne p i d e rmal thining with basal cell va c u o l a r\ndegeneration, epidermal necrotic keratinocytes\nand dermal mononuclear infiltrate (Figure 2).\n\n\n\nAlthough the mother was asymptomatic, her\ninvestigation showed Antinuclear antibody titer\nof 1: 2560, with speckled pattern. Extractable\nnuclear antigen antibodies, both SSA &SSB were\ndetectable.\n\n\n\nA diagnosis of Neonatal lupus erythematosus\nwas made and the baby was closely monitored.\nShe was treated with topical hydrocortisone 1%\ncream to be applied on the facial rash and broad\nspectrum sunblock  to the whole face daily.\n\n\n\nOn follow up, the annular lesions resolve d\ns l ow ly with residual post inflammatory\nhy p e rpigmentation and some skin atrophy.\nRepeat antinuclear antibody at 10 months old\nwas non reactive. The mother was referred to\nphysician for further assessment and follow up.\n\n\n\nKeywords congenital skin anomaly, skin ulceration, skin atrophy\n\n\n\n\n\n\n\n\n31MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDiscussion\nNeonatal lupus erythematosus (NLE) results\nfrom the transfer of maternal autoantibodies\nusually anti-Ro, to the fetus between the 12th and\n16th week of gestation1. The most common\nsymptom is rash (90%), which can be distributed\nover the body and does not necessarily involve\nthe face, followed by congenital heart block\n(50%), which is the most serious complication\nand abnormalities in blood findings (10%)2.\nThese three symptoms affect children aged up to\n6 months, occurring in approximately 1 in 20,000\nn ew b o rns, and can affect all ethnic gr o u p s .\nFemales are more commonly affected by NLE\nwith a ratio of 2:1 for cutaneous lesions1.\n\n\n\nSkin findings occur in nearly half of NLE infants.\nThe eruption, which can occur at birth but more\ntypically within a few weeks after birth, is similar\nto the lesions of subcutaneous lupus\nerythematosus. Typically, erythematous scaling\nand annular plaques appear on sun-ex p o s e d\nareas. After several months, lesions resolve with\nresidual hypopigmentation, epidermal atrophy,\nand telangiectasia. Commonly, the lesions are in\na photodistribution, especially on the head and\nneck, and often in a malar distribution. Sun\nexposure is not a prerequisite for the eruption;\nhowever, sunlight may initiate or exacerbate the\neruption1. Rarely, discoid lesions may be seen3.\nAs\n\n\n\nFigure 1  Multiple annular erythematous plaques with central \nviolaceous hue over the forehead, periorbital region, cheek \nand erythema and crusting of the lips.\n\n\n\nFigure 2  Skin biopsy showed epidermal thining with basal cell \nvacuolar degeneration, epidermal necrotic keratinocytes and \ndermal mononuclear infiltrate.\n\n\n\n\n\n\n\n\n32 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAs in adults with SCLE, autoantibodies to\nRoSSA / La-B antigens correlate with skin\nlesions. In NLE, autoantibodies are maternal in\norigin and disappear by 6 months of age. The\ndisappearance of these antibodies parallels the\ndisappearance of the skin lesions. Children with\ncutaneous neonatal lupus erythematosus need to\nbe evaluated for haematological and hepatic as\nwell as cardiac involvement.\n\n\n\nExtra-cutaneous manifestations\nBy far, the most significant organ involvement in\nNLE patients is the heart. Irr eve r s i ble and\ncomplete heart block (CHB) occurs in half of the\naffected infants. It usually presents in utero and\nm ay be first detected around 18-24 we e k s\ngestation4. NLE appears to be the most common\ncause of CHB in all patients presenting with this\ndefect. Other conduction defects have been\nr e p o rt e d, as has congestive heart fa i l u r e .\nImmunodeposits of RoSS antibody may result in\nfibrosis and calcification in and around the\na t r i oventricular node and appears to be\nresponsible for the heart block1,2.\n\n\n\nCHB is associated with significant mortality (20-\n30%) and morbidity. Early recognition of infants\nat risk is important.\n\n\n\nWhile thrombocytopenia occurs in 10-20%\nof patients, it is transient in nature and usually\nnot problematic. Occasionally, ga s t r o i n t e s t i n a l\nhemorrhage may occur5.\n\n\n\nA p p r ox i m a t e ly 20-40% of patients will have\nhepatomegaly. This may occur as a result of\np a s s ive congestion in patients with heart\nfailure or it may be due to ex t r a m e d u l l a ry\nhematopoiesis. Histologic liver changes include\ncholestasis, fibrosis, and hepatitis6.\n\n\n\nOther extracutaneous findings have been\nreported in patients with NLE, but may not be\nsignificant and include neurologic abnormalities\nand anemia.\n\n\n\nPathogenesis\nAlthough the mechanisms responsible for NLE\nhave not been fully characterized, there is strong\nevidence to support the hypothesis that maternal\n\n\n\nanti-SSA/Ro and anti-SSB/La autoantibodies are\ninvolved in the pathogenesis7. How and why\nmaternal autoantibodies affect the target organs\nin such variable ways is unclear, although it is\napparent that the fetal heart is uniquely\nvulnerable. Boutjdir et al8 have demonstrated that\nmaternal autoantibodies can interfere with fetal\ncardiac calcium channels, thus contributing to\nconduction defects.\n\n\n\nManagement\nIdentification of fetuses at risk is paramount.\nMothers with a history of autoimmune diseases\nor with circulating anti-Ro or anti-La antibodies\nare at highest risk, as are women with a\npreviously affected child. As previously noted,\ndespite having positive anti-Ro antibodies, the\nrisk of developing NLE is low. Detection of\nmaternal Ro/La autoantibodies during pregnancy\nwarrants careful and close monitoring of the\nfetus.\n\n\n\nSkin lesions of affected infants should be treated\nconservatively with avoidance of sunlight and\njudicious use of topical corticosteroids. The long-\nterm prognosis of children with skin disease is\nexcellent.\n\n\n\nLong term outcome\nAlthough long-term follow-up studies have\no b s e rved several patients with subsequent\ndevelopment of autoimmune diseases, there does\nnot appear to be any significantly increased risk\nfor developing autoimmune disorders later in life. \n\n\n\nConclusions\nNLE is an acquired autoimmune disorder\naffecting infants of mothers with anti-RoSSA and\nanti-SSB/La autoantibodies. It represents a\nprototypical example of passive transfer of\nautoantibodies and the direct role of these\nautoantibodies in the development of lupus skin\nlesions. Babies with NLE have an excellent long-\nterm outcome when only skin lesions are present.\nChildren with CHB also have good long-term\noutcomes if the heart block is successfully\ntreated. Although uncommon, it is important to\nrecognize early in the gestation period those\ninfants at risk for developing NLE.\n\n\n\n\n\n\n\n\n33MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nReferences\n\n\n\n1. Boh EE. Neonatal lupus erythematosus. Clin Dermatol.\n2004;22:125-128.\n\n\n\n2. 2. Lee LA. Neonatal lupus erythematosus: clinical\nfindings and pathogenesis. J Investig Dermatol Symp\nProc. 2004;9:52-56.\n\n\n\n3. N. Lawrence, C. Bligard, J. Storer et al., Neonatal lupus\nin twins. South Med J 82 (1989), pp. 657-660.\n\n\n\n4. Lee LA, Weston WL. Special considerations\nconcerning the cutaneous manifestations of rheumatic\ndisease in children: Cutaneous manifestations of\nrheumatic diseases. Philadelphia: Williams & Wilkins,\n1996:323-42.\n\n\n\n5. R. Watson, J.E. Kang, M.May et al. Thrombocytopenia\nin the neonatal lupus syndrome. Arch Dermatol 1988;\n124: 560-563. \n\n\n\nR\n\n\n\n6. R.M. Laxer, E.A. Roberts, K.R. Gross et al., Liver\ndisease in neonatal lupus erythematosus. J Pediatr\n1990; 116: 238-242. \n\n\n\n7. Sontheimer RD, McCauliffe DP. Pathogenesis of anti-\nRo/SS-A autoantibody associated cutaneous lupus\nerythematosus. Dermatol Clin. 1990;8:751-758\n\n\n\n8. BoutjdirM, Chen L, Zhang ZH, et al. Arrthymogenicity\nof IgG and anti-52-kd SSA/Ro affi n i t y - p u r i fi e d\nantibodies from mothers of children with congenital\nheart block. Circ Res. 1997; 80:354-362.\n\n\n\n9. Multiple Annular Plaques in an Infant. Arch Dermatol\n2006;142:1351-1356.\n\n\n\n\n\n\n\n\n34 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nD E R M ATOLOGY THERAPEUTICS - Original Art i c l e\n\n\n\nE ffect of oral or pulse cyclosphosphamide in\nrecalcitrant pemphigus: an audit of eighteen patients\nf rom Hospital Kuala Lumpur\nTang MM, Priya G, Suganthi T\n\n\n\nAbstract\n\n\n\nBackground Autoimmune pemphigus is a potentially life threatening bullous disease. The\nc o rnerstone of treatment is systemic corticosteroids. Howeve r, adjuvant therapy with\nimmunosuppressant drugs is commonly used to improve disease control and alleviate the high\nmorbidity and mortality associated with the use of corticosteroids. Adjunctive treatment with pulse\ni n t r avenous cyclophosphamide may be more efficacious and less toxic than other\nimmunosuppressants.\n\n\n\nObjective To retrospectively review the clinical outcome of 18 patients with recalcitrant pemphigus\nwho were treated with cyclophosphamide over the past 10 years.\n\n\n\nMethodology A retrospective study was conducted between 1985 and 2009 in thirteen Malaysian\ndermatology centres. Data collected were analysed for comparison of relapse rates, compliance rates\nand adverse drug effects between the 2 regimes.\n\n\n\nResults Eighteen patients were included in this audit of which 12 patients had pemphigus vulgaris\nand 6 patients had pemphigus foliaceous. Prior to treatment with cyclophosphamide, fourteen\npatients were on azathioprine, three were given intravenous immunoglobulin, and two were\nprescribed dapsone; however all these patients were either unresponsive, intolerant or suffered\nserious side-effects with these drugs. Subsequently, 7 patients (median age: 31 years) received a\ncombination of pulse intravenous cyclophosphamide and either intravenous dexamethasone or\nm e t hylprednisolone. These seven patients received between 2 to 21 pulses of intrave n o u s\ncyclophosphamide and steroids at monthly intervals with oral prednisolone and cyclophosphamide\n(50-100mg) in between pulses. The remaining 11 patients (median age: 46 years) received oral\ncyclophosphamide and corticosteroids. Of the 18 patients in our cohort, 15 achieved control and\nconsolidation of disease activity at an average of 4 weeks and 10 weeks respectively. The remaining\nthree patients are yet to achieve disease control. The total duration of treatment with\ncyclophosphamide ranged from 2 to 62 months with a cumulative dose ranging from 2.95g to\n93.55g. Four patients achieved partial remission on minimal therapy and 3 achieved complete\nremission. None of patients experienced serious side effects.\n\n\n\nConclusion Cyclophosphamide may be an alternative treatment option in patients in patients with\npemphigus who fail to respond to standard therapy. Controlled trials are needed to further evaluate\nthe efficacy and safety of this therapy.\n\n\n\nKeywords Pemphigus vulgaris, pemphigus foliaceous, cyclophosphamide\n\n\n\nCorrespondence\nPriya Gill\nDepartment of Dermatology,\nHospital Kuala Lumpur\nEmail: drpriya74@yahoo.com\n\n\n\n\n\n\n\n\n35MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nIntroduction\nPemphigus encompasses a group of potentially\nlife-threatening autoimmune diseases with\nextensive blistering of the skin with or without\nmucous membrane invo l vement1. It is\ncharacterized by intraepidermal intercellular loss\nof adhesion caused by autoantibodies against\nd e s m oglein 1 and 3 between epiderm a l\nkeratinocytes.\n\n\n\nSystemic corticosteroids remain the forefront in\nthe management of pemphigus. A d j u va n t\nimmunosuppressive drugs such as azathioprine,\nmycophenolate mofetil, dapsone,\nmethotrexate, cyclophosphamide, cyclosporine,\ni n t r avenous immunog l o bulin, rituximab and\nimmunoadsorption have been used to minimize\nthe short- and long-term side effects of systemic\ncorticosteroids2,3. Current literature however is\ni n s u fficient to conclude which is the most\ne ff e c t ive and safest treatment reg i m e4. In\naddition, the response to treatment may vary\nb e t ween individuals. Cyclophosphamide wa s\nfound to be both efficacious & successful in\nmaintaining remission5. However, its potential\nserious side effect profile causes a lot of\nhesitancy among prescribing physicians.\n\n\n\nObjective\nThe objective of this review is to report our\nexperience in the use of oral and pulse\nintravenous cyclophosphamide in patients with\npemphigus vulgaris and pemphigus foliaceous.\n\n\n\nMaterials and Methods\nThis is a 10 year retrospective review. The case\nnotes of all patients with confirmed pemphigus\nvulgaris or pemphigus foliaceous who received\ncyclophosphamide were reviewed. The diagnosis\nof pemphigus was made according to the clinical\nfeatures together with histopathological and\ndirect immunofluorescence study. These patients\nr e c e ived either oral or pulse IV\ncyclophosphamide according to the extent of\nbody surface area involvement using the \u201crule of\nnine\u201d, oral cyclophosphamide for body surface\ni nvo l vement of less than 20% and pulse\ncyclophosphamide for body surface involvement\nof more than 20%.\n\n\n\nOral cyclophosphamide was prescribed at the\ndose of 0.5-1.5mg/kg/day (ranging from 50-\n150mg a day) for patients who were unresponsive\n\n\n\nor developed side effects to other steroid sparing\nagents. It was given in addition to oral\nprednisolone in all the cases studied.\n\n\n\nPulse intravenous cyclophosphamide was used in\npatients with severe rapidly progressive disease\nwhich could not be controlled with high doses of\nsystemic corticosteroids. There were 3 phases in\nthe pulse regime. In the first phase, intravenous\nd examethasone was given for 3 days with\nintravenous cyclophosphamide 500mg given on\nday 2. Oral cyclophosphamide at the dose of 0.5-\n1.5mg/kg/day and oral prednisolone were given\nin between. This was repeated every 3-4 weeks\nuntil the clinical remission was achieved. During\nphase II, the above pulse therapy was repeated for\nanother 6 cycles which was then followed by\nphase III in which the intravenous therapy was\ndiscontinued and patients were maintained on\noral cyclophosphamide with or without oral\nprednisolone for another 6-9 months. \n\n\n\nWe used the consensus guideline recommended\nby Murell et al6 for the definition of disease\nactivities (Appendix 1).\n\n\n\nResults\nThe patients\u2019 characteristics are shown in Table 1.\nA total of 18 patients received cyclophosphamide\nin the past 10 years; 11 were on oral treatment\nand 7 received pulse intrave n o u s\ncyclophosphamide. The mean disease duration\nwas about 15 months in both groups prior to the\ncommencement of cyclophosphamide. A l l\npatients had refractory disease and had\npreviously been on azathioprine, dapsone and\nintravenous immunoglobulin. \n\n\n\nTable 2 demonstrates the disease response to\ncyclophosphamide. Patients on oral\ncyclophosphamide had a median time to disease\ncontrol of 3 weeks. Disease control was achieved\nat 25 weeks in patients on pulse\ncyclophosphamide therapy.  In the oral\ncyclophosphamide group, partial remission was\nachieved within a median of 10 months, but it\ntook twice as long in the pulse cyclophosphamide\ngroup. No patient on pulse therapy achieved\ncomplete remission. 2 patients in each group\ndefaulted a number of monitoring visits but they\nwere recommenced on the treatment regimen on\nsubsequent attendance.\n\n\n\n\n\n\n\n\n36 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nMean age in years (range)\n\n\n\nMean duration of disease before cyclophosphamide in months \n\n\n\nMale : female\n\n\n\nType of pemphigus \n\n\n\nPrevious steroid sparing\nimmunosuppressive\nagents used\n\n\n\nOral\nCyclophosphamide\nn=11\n\n\n\n43.7 (35-53)\n\n\n\n16.0\n\n\n\n4:7\n\n\n\n8\n\n\n\n3\n\n\n\n9\n\n\n\n1\n\n\n\n0\n\n\n\nPulse Intravenous\nCyclophosphamide\nn=7\n\n\n\n35.3 (24-51)\n\n\n\n14.6\n\n\n\n4:3\n\n\n\n4\n\n\n\n3\n\n\n\n5\n\n\n\n1\n\n\n\n3\n\n\n\nTable 1 Characteristics of patients received cyclophosphamide.\n\n\n\nVulgaris \n\n\n\nFoliaceous\n\n\n\nAzathioprine \n\n\n\nDapsone\n\n\n\nIVIG \n\n\n\nMedian time to control in weeks (range)\n\n\n\nMedian time to disease consolidation in weeks (range)\n\n\n\nMedian time to partial remission on minimal therapy in\nmonths (range)\n\n\n\nMedian time to complete remission on minimal therapy in\nmonths (range)\n\n\n\nMedian time to complete remission off therapy in months\n(2 patients)\n\n\n\nMedian daily prednisolone dose pre Cyclophosphamide in\nmg (range)\n\n\n\nLast daily prednisolone dose in mg (range)\n\n\n\nMedian duration of cyclophosphamide in months (range)\n\n\n\nMedian total cumulative dose in g (range)\n\n\n\nControl of disease\n\n\n\nConsolidation\n\n\n\nPartial remission on minimal therapy\n\n\n\nComplete remission\n\n\n\nStill active\n\n\n\nLatest activity 0\n\n\n\n3\n\n\n\n3\n\n\n\n2 (off therapy)\n2 (on minimal therapy)\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n3\n\n\n\n0\n\n\n\n2\n\n\n\nOral\nCyclophosphamide\nn=11\n\n\n\n3 (1-8)\n\n\n\n9 (4-13)\n\n\n\n10 (7-26) *7 patients\n\n\n\n16.2 (11-28) *4 patients\n\n\n\n55 (49 & 61)\n\n\n\n60 (45-80) \n\n\n\n5 (0-50) \n\n\n\n30.0 (4.2-58.0) \n\n\n\n48.85 (7.85-90.50) \n\n\n\nPulse Intravenous\nCyclophosphamide\nn=7\n\n\n\n25 (4-27) *5 patients\n\n\n\n20.5 (6-29) *4 patientts\n\n\n\n20 (5-42)\n* 3 patients\n\n\n\n-\n\n\n\n-\n\n\n\n75 (60-80) \n\n\n\n15 (0-40) \n\n\n\n11 (3-42) \n\n\n\n32.55 (5.32-96.10)\n\n\n\nTable 2 Response to therapy.\n\n\n\nIVIG - Intravenous immunoglobulin\n\n\n\n\n\n\n\n\n37MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nSide effects\n\n\n\nTransient leucopenia \n\n\n\nMenstrual irregularity \n\n\n\nPruritus \n\n\n\nDiffuse hyperpigmentation \n\n\n\nHepatitis \n\n\n\nInfection \n\n\n\nOral Cyclophosphamide\nonly\nn=11\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n-\n\n\n\n1\n\n\n\n3\n\n\n\nPulse Intravenous\nCyclophosphamide\n\n\n\nn=7\n\n\n\n1\n\n\n\n2\n\n\n\n-\n\n\n\n1\n\n\n\n-\n\n\n\n7\n\n\n\nTable 3 The side effects experienced by patients.\n\n\n\nBefore cyclophosphamide was initiated, the 11\npatients on oral cyclophosphamide were on a\nmedian dose of 60mg /day of prednisolone; and\nthe group that received pulse cyclophosphamide\nt h e r a py was on a higher median dose of\n75mg/day of prednisolone. Assessment during\nthe last follow up visit at the end of the study\nrevealed a reduction in dose of prednisolone by\nabout 90% in the oral cyclophosphamide group\nand 50% in the pulse cyclophosphamide therapy\ngroup. The median cumulative dose of\ncyclophosphamide was notably higher in the  oral\ncyclophosphamide group. When this cohort of\npatients was last reviewed, 3 patients still had\nactive disease. Four patients who had received\noral cyclophosphamide were in complete\nremission. Of these 4 patients, 2 were completely\no ff treatment and on subsequent follow up,\nremained disease free for one and three years\nrespectively. The duration of follow-up for our\npatients ranged from two to nine years with a\nmedian of five years.\n\n\n\nThe side effect profile was similar in both groups.\nHowever, there was a slight increase in infection\nrate among patients on pulse cyclophosphamide\n( Ta ble 3). These infections included upper\nrespiratory infections, pneumonia, urinary tract\ninfections and cutaneous infections such as\nfolliculitis and furunculosis. One patient died of\nischaemic heart disease. He had prev i o u s ly\nreceived 30 months of oral cyclophosphamide\nwith cumulative dose of 44g, and was in\nremission on 2.5 mg of prednisolone at the time\nof his death. \n\n\n\nDiscussion\nCyclophosphamide is an alkylating agent\napproved by the Food and Drug Administration\n(FDA) in the treatment of acute and chronic\nleukaemia, advanced staged mycosis fungoides,\nmultiple myeloma, lymphoma, breast carcinoma,\novarian carcinoma and retinoblastoma7,8. Pulse\ntreatment in high doses has also been used in\nsystemic lymphoma and systemic lupus\ne rythematosus. It has both cy t o t oxic and\nimmunosuppressive activities. However, there are\nno standard practice guidelines to date on the\nusage of cyclophosphamide be it oral or pulse\nintravenous therapy.\n\n\n\nThe use of oral cyclophosphamide in the\ntreatment of pemphigus was first described in\n1969 by Ebringer et al9. Oral cyclophosphamide\nhas been used at a dosage of 1-2.5mg/kg/day to\na c h i eve optimum immunosuppression. T h e\npioneer of pulse cylophosphamide therapy in the\nmanagement of recalcitrant pemphigus wa s\nParischa et al10 who has used this regimen for\nmore than 30 years.\n\n\n\nParischa et al1 3 recommended the pulse\nintravenous cyclophosphamide administration for\nsevere pemphigus since 1984. There are 4 phases\nin this dexamethasone-cyclophosphamide pulse\ntherapy (DCP). In the first phase, intravenous\ndexamethasone 100mg in 5% glucose is given as\nslow infusion over a period of 1-2 hour for 3\nc o n s e c u t ive days, with co-administration of\ncyclophosphamide on the 1st day. Oral\ncyclophosphamide 50mg is given daily between\nthe pulse intravenous therapies. The DCP is\nrepeated eve ry 2-4 weeks depending on the\nclinical activity. Once the disease is controlled,\npatients\n\n\n\n\n\n\n\n\n38 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\npatients then enter the second phase in which\nDCP is repeated monthly for another 6 months.\nAfter that, the pulse therapy is stopped and oral\ncyclophosphamide was continued for a ye a r\n(phase III). Fi n a l ly in phase IV, oral\ncyclophosphamide is stopped altog e t h e r. T h e\ntotal duration of treatment is about 2 years.\n\n\n\nIn our department, all patients with pemphigus\nwere initially prescribed oral prednisolone with\nadjuvant drugs such as azathioprine, dapsone or\nintravenous immunoglobulin. The dose of oral\nprednisolone was initiated at 1mg/kg per day, but\nin severe cases the patients received up to 1.5\nm g / k g / d ay. Howeve r, some patients we r e\nu n r e s p o n s ive, intolerant, or developed side\neffects to conventional first line steroid sparing\nagents. These patients were continued on oral\nprednisolone, and prescribed either oral or pulse\nintravenous cyclophosphamide therapy. In our\ncase series, the cohort with less extensive disease\nresponded more rapidly and we were able to taper\ntheir oral prednisolone faster as compared to the\ngroup with more extensive body surface area\ninvolvement. However, this group also received a\nhigher cumulative dose of cyclophosphamide,\nalthough serious side effects was not seen during\nthe follow-up period. The overall response in our\n\n\n\npatients to oral cyclophosphamide wa s\ncomparable to studies done by Cummins et al10,\nMomeni et al11 & Olszewska et al5. We favoured\npulse cyclophosphamide for patients with rapidly\nprogressive disease. The regime described by\nParischa et al was modified. The initial part of the\nregimen with intravenous cyclophosphamide on\nday 2 was adhered to. However oral prednisolone\nwas not abruptly discontinued but was prescribed\nat a dose of 0.5-1 mg/kg/day along with oral\ncyclophosphamide (50-100mg daily) in between\npulses. We tapered the oral prednisolone when\nthe patients entered phase II.\n\n\n\nThis modality was used in 7 patients and our\nresults were comparable with other studies done\nin Europe and USA (Ta ble 4). Complete\nremission occurred in only a handful of patients.\nIn most other studies, about 50% of patients\nimproved. The exception to this is the cohort\nfrom India described by Parischa et al, where\ncomplete remission was reported in more than\n80% of their patients.\n\n\n\nAll the patients in our cohort had rapidly\nprogressive, extremely difficult to control and\nlife-threatening disease. Although some of them\nhad yet to complete their families, they were\noffered\n\n\n\nNumber of\npatients\n\n\n\nNo of pulses \n\n\n\nResults \n\n\n\nParischa et al\n1995\n\n\n\n(India)\n\n\n\n227\n\n\n\nNA\n\n\n\n84% CR.\n24pt CR\nstill on Rx\n13 still\nactive\n\n\n\nFleischli et al\n1999\n(US)\n\n\n\n9\n\n\n\n3-24\n\n\n\n6pts: ER, \n2pts: MinR \n\n\n\nRose et al\n2005\n\n\n\n(Germany)\n\n\n\n11\n\n\n\n6\n\n\n\n5pts: \nremission\n6pts: \nprogression\n(24 months \nafter \ntreatment \ninitiation) \n\n\n\nSaha et al\n2010\n(UK)\n\n\n\n21\n\n\n\n3-22\n\n\n\n4pts: CR \n7pts:  ER\n2pts: GR \n5pts: ModR \n6 pts: MinR  \n1 pt: NR \n\n\n\nZivanovic et\nal 2010\n(Serbia)\n\n\n\n72\n\n\n\n1-28\n\n\n\n59.7% CR\n18.1% NR\n\u2022 50% used \n\n\n\nas first \nline\n\n\n\n\u2022 10pts:\n2 courses\n\n\n\nTang et al\n2010\n\n\n\n(Malaysia)\n\n\n\n7\n\n\n\n3-21\n\n\n\n3 pt: PR \n1 pt: \nconsolidate \n1 pt: dis \ncontrol\n2 pts: active\n\n\n\nTable 4 Comparisons of treatment response of pulse intravenous cyclophosphamide.\n\n\n\nCR - complete remission; ER- Excellent response, GR - Good response; ModR - moderate response; MinR - Minimal response;\nNR - No response; pt - patient; Cycloph - cyclophosphamide; PR - partial remission, Rx - therapy, pts - patients, pt - patient\n\n\n\n\n\n\n\n\n39MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\no ffered cyclophosphamide. Prior to\nadministration, the patients were fully counseled\nabout the side effects; after which consent was\nobtained. None of patients experienced severe\nside effects while on cy c l o p h o s p h a m i d e .\nHaemorrhagic cystitis, which is reported to occur\nin up to 50% of patients on cyclophosphamide20,\nwas not observed in our patients. No patient\ndeveloped bladder carcinoma. This is probably\nbecause the follow up period was still short, and\nthe average time of development of bl a d d e r\ncarcinoma from the first exposure to\ncyclophosphamide is several years. Thus, long\nterm follow-up and close monitoring is extremely\ni m p o rtant for patients who have receive d\ncyclophosphamide in the past.\n\n\n\nSome of our patients relapsed while on therapy.\nIn most cases, this occurred as they defaulted.\nOur patients cite many reasons for their actions\n\n\n\nincluding long distances from hospital, the\ninconvenience of frequent hospital admissions\nand the perception of apparent disease\nimprovement causing them to discontinue their\nmedication prematurely. Many other authors\nreported similar experiences with their patients.\nParischa et al observed disease relapse of less\nthan 10% among those who strictly adhered to the\npulse intravenous cyclophosphamide.\n\n\n\nConclusion\nCyclophosphamide was beneficial in the\nmanagement of patients with recalcitrant\npemphigus. We were able to reduce the dose of\noral corticosteroids and achieve better disease\ncontrol. Having said that, our results were not as\ndramatic as other reports, this was probably\nbecause our cohort of patients had very stubborn\ndisease and their compliance to treatment left\nmuch to be desired.\n\n\n\nTerm \n\n\n\nDisease control\n\n\n\nEnd of the consolidation phase\n\n\n\nMinimal therapy\n\n\n\nMinimal adjuvant therapy\n\n\n\nPartial remission on minimal\ntherapy\n\n\n\nPartial remission  off therapy\n\n\n\nComplete remission off therapy\n\n\n\nComplete remission on therapy\n\n\n\nRelapse\n\n\n\nDefinitions \n\n\n\nThe time at which new lesions cease to form and established lesions begin\nto heal.\n\n\n\nThe time at which no new lesions have developed for a minimum of\n2 weeks, approximately 80% of lesions have healed  and when most\nclinicians start to taper steroids.\n\n\n\nPrednisolone at 10mg/d and/or minimal adjuvant therapy for at least\n2 months.\n\n\n\nHalf of the dose required to be defined as treatment failure.\n\n\n\nPresence of transient  new lesions that heal within 1 week while the patient\nis receiving minimal therapy including topical steroids.\n\n\n\nPresence of transient new lesions that heal within 1 week without\ntreatment & while the patient is off all systemic therapy for at least\n2 months.\n\n\n\nAbsence of new or established lesions while the patient is off all systemic\ntherapy for at least 2 months.\n\n\n\nThe absence of new or established lesions while the patient is receiving\nminimal therapy.\n\n\n\nAppearance of >3 new lesions/month that do not heal spontaneously\nwithin 1 week or by the extension of established lesions in a patient\nwho has achieved disease control.\n\n\n\nAppendix 1 Definitions of disease activity.\n\n\n\nAdapted from Murell et al6.\n\n\n\n\n\n\n\n\n40 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nReferences\n\n\n\n1. H e rtl M, Zillikens D. Clinical and Molecular\nCharacterization of Autoimmune Bullous Diseases. J\nInvest Dermatol 2008; 128:E19-E21.\n\n\n\n2. Meurer M. Immunosuppressive therapy for\nautoimmune bullous diseases. Clin Dermatol 2012;\n30:78-83.\n\n\n\n3. Kasperkiewicz M, Schmidt E, Zillikens D. Current\ntherapy of the pemphigus group. Clin Dermatol 2012;\n30:84-94.\n\n\n\n4. Martin LK, Agero AL, Werth V, Villanueva E, Segall J,\nMurrell DF. Interventions for pemphigus vulgaris and\npemphigus foliaceus. Cochrane Database of Systematic\nReviews 2009, Issue 1. Art. No.: CD006263. DOI:\n10.1002/14651858.CD006263.pub2.\n\n\n\n5. Olszewska M, Kolacinska-Strasz Z, Sulej J, Labecka H\net al. Effi c a cy and Safety of Cyclophosphamide,\nAzathioprine, and Cyclosporine (Ciclosporin) as\nAdjuvant Drugs in Pemphigus Vulgaris. Am J Clin\nDermatol 2007;8(2): 85-92.\n\n\n\n6. Murell DF, Dick S, Ahmed AR, Amagai M et al.\nConsensus statement on definitions of disease, end\npoints, and therapeutic response for pemphigus. J Am\nAcad Dermatol 2008;58:1043-6.\n\n\n\n7. Ahmad AR, Hombal SM. Cyclophosphamide\n(Cytoxan). A review on relevant pharmacology and\nclinical uses. J Am Acad Dermatol 1984; 11:\n1115-1126.\n\n\n\n8. Ghate J. Immunosuppressive therapies in Dermatology:\nCyclophosphamide. Curr Prob Dermatol 2000;\n12: 265-267.\n\n\n\n9. Ebringer A, Mackay IR. Pemphigus vulga r i s\nsuccessfully treated with cyclophosphamide. Ann Int\nMed 1969;71:125-127.\n\n\n\n10. Pasricha JS, Sood V D, Minocha Y. Treatment of\npemphigus with cyclophosphamide. Br J Dermatol\n1975; 93:573-576.\n\n\n\n11. Cummins DL, Mimouni D, Anhalt GJ, Nousari CH.\nOral Cyclophosphamide for the treatment of\npemphigus vulgaris and foliaceous. J Am A c a d\nDermatol 2003;49:276-80.\n\n\n\nR\n\n\n\n12. Momeni AZ, Iraji F, Aminjavaheri M, Emami MR et al.\nThe use of oral cyclophosphamide with dexamethasone\npulse therapy in the treatment of pemphigus vulgaris. J\nDermatolog Treat 2007;18: 275-278.\n\n\n\n13. Pasricha JS,Thanzama J, Khan UK. Intermittent high-\ndose dex a m e t h a s o n e - cyclophosphamide therapy for\npemphigus. Br J Dermatol 1988;119:73-77.\n\n\n\n14. Pasricha JS, Khaitan BK, Raman RS, Chandra M.\nDexamethasone-cyclophosphamide pulse therapy for\npemphigus. Int J Dermatol 1995; 34:875-82.\n\n\n\n15. Fleischli ME, Valek RH et al. Pulse intrave n o u s\ncyclophosphamide therapy in pemphigus. A r c h\nDermatol 1999;135:57-61.\n\n\n\n16. Rose E, Wever S, Zilikens D et al. Intrave n o u s\nd ex a m e t h a s o n e - cyclophosphamide pulse therapy in\ncomparison with oral methylprednisolone-azathioprine\nt h e r a py in patients with pemphigus: results of a\nmulticenter prospective ly randomized study. JDDG\n2005;3:200-206.\n\n\n\n17. Saha M, Powell AM, Bhogal B,Black MM, Groves RW.\nPulsed intravenous cyclophosphamide and\nmethylprednisolone therapy in refractory pemphigus.\nBr J Dermatol 2010:162;790-797.\n\n\n\n18. Zivanovic D, Medenica L, Tanasilovic S, Vesic S et al.\nDexamethasone-Cyclophosphamide Pulse Therapy in\nPemphigus. A Review of 72 cases.  Am J Clin Dermatol\n2010; 11(2): 123-129.\n\n\n\n19. Pandya AG, Sontheimer RD. Treatment of pemphigus\nv u l garis with pulse intravenous cy c l o p h o s p h a m i d e .\nArch Dermatol 1992; 128:1626-1630.\n\n\n\n20. Lawson M, Vasilaras A, De Vries A, Mactaggart P et al.\nU r o l ogical implications of cyclophosphamide and\nifosfamide. Scand J Urol Nephrol 2008; 42;309-317.\n\n\n\n\n\n\n\n\n\n"
"\n\nMalaysian Journal of Dermatology\n\n\n\n26 MJD 2014 Jul Vol 32\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nNODULAR MELANOMA PRESENTING WITH PARAPLEGIA:\nA CASE REPORT \n\n\n\nNur Ashikin Ahmad, MRCP, Nor Salmah Bakar, MPath(UKM), Tarita Taib, MAdvDerm, Yap Shean Huet, MMed (Rad)(UKM)\n\n\n\nKeywords: skin cancer, bone metastasis, spinal cord compression\n\n\n\nIntroduction\nNodular melanoma (NM) is clinically a distinct \nsubtype of melanoma. It is the predominant \ncontributor to melanoma-related deaths1. Clinically \nlesion of a NM is most often symmetric, elevated, \nuniform in colour, and non-pigmented in contrast \nto superficial spreading melanoma (SSM)2. It is an \naggressive form of skin cancer and it can metastasize \nquickly from the primary site to other sites in the \nbody3-4. Bone metastasis is very rare, affecting \nmainly the axial skeleton, represents the end stage \nof the disease and carries a poor prognosis5. We \nhere describe a young man with metastatic nodular \nmelanoma with features of spinal cord compression. \nTo date, there are very few reported cases of nodular \nmelanoma with bone metastasis presented in young \nage group4.\n\n\n\nCorrespondence\nNur Ashikin Ahmad, MRCP (UK)\nUniversiti Teknologi MARA, Selangor, Malaysia\nEmail: nurashikin_ahmad@yahoo.com\n\n\n\nCase report\nA 33-year-old Burmese man presented with sudden \nonset of paraplegia and altered bowel habit for 3 \ndays prior to presentation. He also had a 2-month \nhistory of constant back pain irrespective of type \nof activities. He also had multiple hyperpigmented \npainful nodules and papules for the past 2 months.  \nThe nodular lesions were predominantly located on \nthe left lower limb and were rapidly increasing in \nsize and numbers. He reported no recent trauma, \nfever, chills or difficulty with gait. He lost 10kg in \n2 months prior to presentation. There was no family \nhistory of malignant melanoma or congenital naevus \nand he was not immunosuppressed.\n\n\n\nFigure 1  Clinical image showed multiple hyper \npigmented dome-shaped nodules and papules over the left \nthigh. \n\n\n\nFigure 2  Close-up view of ulcerated nodule.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27MJD 2014 Jul Vol 32\n\n\n\nClinically on the left thigh there were multiple \nhyperpigmented, ulcerated small papules and \nnodules at the periphery of the large nodules. \nSome of the bigger nodules were ulcerated with \nhemorrhagic discharge (Figure 1 & 2). There were \nmultiple non-matted bilateral inguinal lymph nodes, \nwith largest nodes measured 2 x 2 cm.\n\n\n\nThe neurological examination of the lower limbs \nrevealed bilateral lower limb weakness with muscle \npower of 1/5 and sensory loss from L1 onwards.   \nHis blood investigations revealed a raised lactate \ndehydrogenase at 1138U/L. Other investigations \nincluding blood culture were normal. \n\n\n\nMRI of the spine revealed heterogeneous enhancing \nlesions involving bilateral pedicles and posterior \narch of T10 vertebra (with necrotic centre) and \nspinous process of T1. There was intraspinal \nextradural extension of the lesion from the level \nof T7 until T12 level with high T2 signal intensity, \nresulting in narrowing and compression of the spinal \ncord at the level T8 to T12. There was also extension \nof the lesion in the right T8, T12 neural foramen and \nbilateral T9-11 neural foramen, which encases the \nexiting nerve roots. Nodules were seen in the lung \nand liver base from ultrasound of the abdomen. \n\n\n\nThe patient underwent excisional biopsy of a small, \nhyperpigmented papule over the dorsal-medial \naspect of the left thigh. The histology revealed a \ndiffuse dermis infiltration by malignant cells which \nextends into the subcutaneous tissue. There were \noccasional abnormal mitotic figures. The cells \nhave mildly pleomorphic, hyperchromatic nuclei \nwith  ample clear to pale cytoplasm (Figure 3a-d). \nThe histology finding is consistent with nodular \nmelanoma. \n\n\n\nGiven the clinicopathologic characteristics and \ninvestigations, the patient was diagnosed to have \nnodular melanoma with multiple distant metastases \nof the skeletal system, lymph nodes, liver and \nlung. He was staged IV (N2b, M1c) according to \nthe American Joint Commission on Cancer6. Due \nto the extremely poor prognosis, he was managed \nconservatively by the palliative care team. The \npatient succumbed to his disease a month after the \ndiagnosis was made.\n\n\n\nDiscussion\nMalignant melanoma accounts for 1% to 3% of \nall cancers. The reported incidence and mortality \nof melanoma is rapidly rising and is second only \nto lung cancer7. Currently, melanoma comprises \n\n\n\n65% to 75% of all skin cancer deaths. Melanoma \nhas been classified based on histologic and clinical \nappearances, with superficial spreading melanoma \n(SSM) as  the most common  followed by nodular \nmelanoma (NM), and lentigo maligna melanoma \n(LMM)8. NM often presents with atypical clinical \nfeatures that mimic other benign and malignant \ntumours and some inflammatory lesions.\n\n\n\nNodular  melanomas are typically encountered in \nthe fourth through sixth decades of life8. However \nour patient is in the younger age group without pre-\nexisting pigmented macule. It has been suggested \nthat the incidence of melanoma in younger age \ngroup is also increasing but with more favourable \nprognosis9. \n\n\n\nNodular melanoma is an aggressive subtype of \ncutaneous melanoma with evidence of metastases \nupon presentation1,3. Initial metastases are most \ncommonly found in the skin, subcutaneous tissue, \nlymph nodes, and lungs Metastases to the bone \nis very rare and usually represents an end-stage \nsituation of the disease. The axial and peripheral  \nbones are effected and lesion is predominantly lytic \nlesion4,10-12. In our patient, metastatic lesions were \nfound in the spine, lung, lymph node and liver at the \ntime of diagnosis.\n\n\n\nOne of the malignancy that has similar clinical, \nhistopathological and immunochemistry \npresentation is clear cell sarcoma (CCS) or \nmelanoma of the soft part. It occurs more common \nin the young age group (30 - 40 year old)13,14. Clear \ncell sarcomas are rarely aggressive, soft tissue \ntumour which shared  similar  clinical, pathologic, \nand molecular properties with melanoma13,14. The \ntumours are located almost exclusively on the \nextremities; the foot and ankle are the most common \nlocations. Clear cell sarcoma is a slowly growing \ntumour, commonly presented with subcutaneous \nmass with associated tenderness13.\n\n\n\nIn the present case, the rapid progression and \nmetastases of the painless nodules within 2 months \nsupport nodular melanoma. In contrast to melanoma, \nCCS is characterized by a recurrent chromosomal \ntranslocation t (12; 22), which results in fusion of the \nEWS gene on 22q with the ATF1 gene on 12q. This \ngenomic abnormality may represent a good marker \nfor identifying these tumours14 . This differentiation \nis clinically important due to significant differences \nin patient management. However the molecular \ntest was not available to this patient at the time of \ndiagnosis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28 MJD 2014 Jul Vol 32\n\n\n\nFigure 3a  Low-power magnification showed diffuse \ninfiltration by malignant cells which extends up to the \nsubcutaneous fat. H&E x20.\n\n\n\nFigure 3c  This high-power image of malignant melanoma \ncells showed nuclear hyperchromatism and pleomorphism \nwith mitotic figure (arrow). H&Ex400.\n\n\n\nFigure 3b  Higher magnification of the deep portion \nlesion seen in image (a) illustrating the involvement of the \nsubcutaneous fat. H&E x40.\n\n\n\nFigure 3d  The cells were diffusely positive with HMB-45 \n(Human Melanoma Black). HMB45 x40.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29MJD 2014 Jul Vol 32\n\n\n\nReferences\n\n\n\n1.  Mar V, Roberts H, Wolfe R. Nodular melanoma: A distinct \nclinical entity and the largest contributor to melanoma \ndeaths in Victoria, Australia. J Am Dermatology. \n2012;68(4):568\u2013575. doi:10.1016/j.jaad.2012.09.047.\n\n\n\n2.  Greenwald HS, Friedman EB, Osman I. Superficial \nspreading and nodular melanoma are distinct biological \nentities. Melanoma Res. 2012;22:1\u20138. doi:10.1097/\nCMR.0b013e32834e6aa0.\n\n\n\n3.  Erkurt MA, Aydogdu I, Kuku I et al. Nodular melanoma \npresenting with rapid progression and widespread \nmetastases: a case report. J Med Case Rep. 2009;3:50.\n\n\n\n4.  Herrera-perez M, Ayala-rodrigo A, Sanchez-hernandez \nP. Foot and Ankle Surgery Pathologic fracture of the \ndistal tibia secondary to melanoma : A case report of a \nvery rare entity. Foot Ankle Surg. 2012;18(1):e18\u2013e20. \ndoi:10.1016/j.fas.2011.10.008.\n\n\n\n5.  Barth A, Wanek LA, Morton DL. Prognostic factors in \n1,521 melanoma patients with distant metastases. J Am \nColl Surg. 1995;181:193\u2013201.\n\n\n\n6.  Balch CM, Gershenwald JE, Soong S-J et al. Final version \nof 2009 AJCC melanoma staging and classification. \nJ Clin Oncol. 2009; 27:6199\u20136206. doi:10.1200/\nJCO.2009.23.4799.\n\n\n\n7.  Markovic SN, Erickson LA, Rao RD, et al. Malignant \nmelanoma in the 21st century, part 1: epidemiology, risk \nfactors, screening, prevention, and diagnosis. Mayo Clin \nProc. 2007;82:364\u2013380. doi:10.4065/82.3.364.\n\n\n\n8.  Avil\u00e9s-Izquierdo J a., L\u00e1zaro-Ochaita P, Su\u00e1rez-Fern\u00e1ndez \nR at el. Epidemiological changes in cutaneous melanoma: \nRetrospective study of 969 cases (1996\u20132010). Rev Cl\u00ednica \nEspa\u00f1ola (English Ed. 2013;213(2):81\u201387. doi:10.1016/j.\nrceng.2012.11.001.\n\n\n\n9.  Lasithiotakis K, Leiter U, Meier F et al. Age and gender are \nsignificant independent predictors of survival in primary \ncutaneous melanoma. Cancer. 2008;112:1795\u20131804. \ndoi:10.1002/cncr.23359.\n\n\n\n10.  Darko K, Branimir A, Ranka S et al. Low back pain as \nthe presenting sign in a patient with primary extradural \nmelanoma of the thoracic spine - A metastatic disease \n17 Years after complete surgical resection. World J Surg \nOncol. 2011;(9):150.\n\n\n\n11.  Shakur SF, Takagi I, Lukas R V, Chmura S, Gajewski TF, \nRoitberg BZ. Ocular melanoma metastasis to the cervical \nspine. J Clin Neurosci. 2012;19(4):610\u2013611. doi:10.1016/j.\njocn.2011.06.022.\n\n\n\n12.  M. Malonea, Al Gannassb, A. Binahmedc, F.L. Bowlingd \nAJB. An extensive primary nodular metastases: A case \nreport. TheFoot. 2012:235\u2013239. \n\n\n\n\n\n\n\nThe Breslow thickness is the most important \nprognostic marker in nodular melanoma1. The \nnumber and localization of metastases are useful \nfor assessing disease stage and the potential \nresponse to therapy15. Patients with cutaneous, \nnodal or gastrointestinal metastases have a median \nsurvival time of 12.5 months; those with pulmonary \nmetastases have a median survival time of 8.3 \nmonths; and in those with liver, brain, or bone \nmetastases, the median survival is 4.4 months15. In \nour patient, the number of metastases was more than \nthree sites and he died 3 months after the onset of \nhis illness. \n\n\n\nObservations by Egger et al16 on 736 patients \ndiagnosed with primary nodular melanomas, the \npresence of ulceration, with involvement of the \nsentinel lymph node (SLN) was an important \nprognostic factor. In his cohort of patients with \nnodular melanoma with a tumour positive SLN \nbiopsy had thicker lesions and were younger than \npatients with a tumour-negative SLN biopsy15. \n\n\n\nManagement of metastatic melanoma involves \neither a single-drug or multi-drug chemotherapeutic \nregimen. DTIC is considered the most active single \nagent. It gives a response rate of about 5.3-28 %16.  \n\n\n\nOther treatment options include alkylating agents, \nantineoplastic antibiotics (anthracyclines), platinum \nagents, vinca alkaloids, nitrosoureas, tamoxifen, \nbiological response modifiers and immunotherapies. \nSome have shown promising results, but it is unclear \nwhich treatments offer survival improvements.\n\n\n\nRadiation therapy is indicated for spinal cord \ncompression due to metastasis and for pain relief. \nPalliative radiotherapy using either conventional \nor hypofractionated regimens is effective in 71% \nof patients, with total doses in the range of 20-36 \nGy, with individual dose per fraction of 3-6Gy over \n2-3 weeks17. However due to the advance stage and \npoor health status of the patient, a conservative \nmanagement was opted for him.\n\n\n\nConclusion \nNodular melanomas with spine metastases \npresented in young age group is a rare presentation. \nTheir devastating effects require early diagnosis and \nprompt treatment given their poor prognosis.\n\n\n\nAcknowledgement\nThe authors would like to thank Department of \nPathology, Selayang Hospital, for the histopathology \nslides.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30 MJD 2014 Jul Vol 32\n\n\n\n13.  Mackey SL, Hebel J, Mar W. Melanoma of the soft parts \n( clear cell sarcoma ) : A case report and r eview of the \nliterature. J Am Dermatology. 1998;(38):815\u2013819.\n\n\n\n14.  Hocar O, Le Cesne a, Berissi S et al. Clear cell sarcoma \n(malignant melanoma) of soft parts: a clinicopathologic \nstudy of 52 cases. Dermatol Res Pract. 2012;2012:984096. \ndoi:10.1155/2012/984096.\n\n\n\n15.  Egger ME, Dunki-Jacobs EM, Callender GG et al. \nOutcomes and prognostic factors in nodular melanomas. \nSurgery. 2012;152(4):652\u20139; discussion 659\u201360. \ndoi:10.1016/j.surg.2012.07.006.\n\n\n\n16.  Lui P, Cashin R, Machado M et al. Treatments for metastatic \nmelanoma: synthesis of evidence from randomized trials. \nCancer Treat Rev. 2007;33(8):665\u201380. doi:10.1016/j.\nctrv.2007.06.004.\n\n\n\n17.  Forschner A, Heinrich V, Pflugfelder A et al. The role \nof radiotherapy in the overall treatment of melanoma. \nClin Dermatol. 2013;31(3):282\u20139. doi:10.1016/j.\nclindermatol.2012.08.009. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31MJD 2014 Jul Vol 32\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nA RETROSPECTIVE REVIEW OF TINEA CAPITIS INFECTION\n\n\n\nTan SS, MBBS, Chan LC, MMed\n\n\n\nAbstract\n\n\n\nBackground: Tinea capitis (TC), a fungal infection of the scalp, hair follicles and hair shafts, is \ncommon among the paediatric population especially under tropical conditions1. The etiological factors \nvary between different regions of the world. Clinical presentation of tinea capitis varies widely from \nnon-inflammatory to severe, painful inflammatory lesions.\n\n\n\nAim: To look into the clinical manifestations, causative agents and the treatment pattern for tinea \ncapitis in Penang Hospital.\n\n\n\nMethods: A retrospective study of all patients who were treated clinically for tinea capitis in Penang \nHospital from January 2011 to June 2013.\n\n\n\nResults: There were a total of thirty nine patients treated for tinea capitis during this period. Tinea \ncapitis was found to be most common in the 7-12 year age group (44%) with a male to female ratio \nof 2:1. Non-inflammatory type (54%) was more common then the inflammatory type. Twenty seven \nof them (69%) had positive fungal culture of their pluck hair roots. The most common dermatophyte \ndetected was Microsporum canis (92%) followed by Trichophyton rubrum (4%) and Trichophyton \nmetagraphyte (4%). Thirty-one (80%) of them were treated with griseofulvin at a dose of 10-15mg /\nkg /day. The rest were treated with itraconazole, terbinafine or fluconazole. All of them responded well \nto the treatment. In this cohort only one patient, has a second episode of infection a year later. He is a \nchild who was concomitantly undergoing chemotherapy for acute lymphoblastic leukaemia.\n\n\n\nConclusion: Tinea capitis is predominantly an infection of pre-adolescent children and M. canis was \nthe most common dermatophyte isolated.\n\n\n\nKeywords: Fungal infection, Microsporum canis, scalp lesion, Malaysia\n\n\n\nCorrespondence\nTan Sam Siew\nDepartment of Dermatology, Hospital Penang,\n10990, Georgetown, Penang, Malaysia                               \nEmail: tansamsiew@hotmail.com\n\n\n\nMicrosporum(M) canis is the commonest cause of \nzoophilic infections transmitted by cats and dogs2. \nInfection could be ectothrix (infection occurs outside \nhair shaft with cuticle destruction) or endothrix \n(infection occurs within hair shaft without cuticle \ndestruction). \n\n\n\nClinical presentation of TC varied widely from \nnon-inflammatory to severe, painful inflammatory \nlesions3. Non-inflammatory type includes \u201cblack \ndot\u201d or \u201cgray patch\u201d. Inflammatory lesions consist \nof kerion, flavus and arginate folliculitis4. \n\n\n\nIntroduction\nTinea capitis (TC), a fungal infection of the scalp, \nhair follicles and hair shafts, is common among \nthe paediatric population especially under tropical \nconditions1. The etiological factors vary between \ndifferent regions of the world. Infections can spread \nfrom child to child (anthropophilic) or from animals \nto children (zoophilic).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32 MJD 2014 Jul Vol 32\n\n\n\nAim\nThis study was performed to look into the clinical \nmanifestations, causative agents and the treatment \npattern of tinea capitis in our centre.\n\n\n\nMethods\nThis is a retrospective study carried out in the \nDermatology Department, Penang Hospital from \nJanuary 2011 to June 2013. Clinic notes of all the \npatients who were treated clinically for TC during \nthis period were reviewed. Patients were categorized \ninto pre-school (< 7year-old), school going (7 to \n<13 year-old) and adolescents and adults (\u226513 year-\nold).  All of them have their involved hair plucked \nand sent for fungal culture to identify the causative \ndermatophyte. The samples were then inoculated \non Sabouraud\u2032s Dextrose Agar (SDA) plate, \nSDA with chloramphenicol plate and SDA with \n\n\n\nchloramphenicol with cycloheximicle plate. The \ncultures were examined twice a week for up to three \nweeks. No growth after 21 days was considered as \nnegative culture.\n\n\n\nResults\nA total of 39 patients were treated for TC. The male \nto female ratio was 2:1. Majority of them were \nMalays (87%), Indians (8%) and Chinese (5%). TC \nwas found to be most common in the 7-12 year age \ngroup (44%) (Figure 1).\n\n\n\nNon-inflammatory type (54%) was more common \nthan the inflammatory type. Twenty seven of patients \n(69%) had positive fungal culture of their plucked \nhair roots. Wood\u2019s lamp examination was done in \n15 patients. Ten patients had positive bluish-green \nfluorescence of their hair shaft and in 9 of them, the \ncultures grew M. canis.\n\n\n\nFigure 1  Patients gender and age group distribution.\n\n\n\nn = 39\n\n\n\nFemale\n\n\n\nMale\n\n\n\nNumber\n\n\n\n< 7 7 to 12 > 13 Age Group (years)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33MJD 2014 Jul Vol 32\n\n\n\nFigure 2  Types of lesions.\n\n\n\nFigure 3  Types of dermatophyte isolated.\n\n\n\nThirty-one (80%) of them were treated with \ngriseofulvin at a dose of 10-15mg /kg /day for the \nduration of 3 to 12 weeks.  Majority of them (15, \n48%) were treated for 8 to 10 weeks. Only one patient \nrequired up to 12 weeks of therapy. The rest were \ntreated with itraconazole, terbinafine or fluconazole. \nAll of them responded well to the treatment. In this \ncohort only a child with an acute lymphoblastic \nleukaemia undergoing chemotherapy, had a second \nepisode of tinea capitis infection a year later.\n\n\n\nDiscussion\nIn our cohort, the rate of infection was significantly \nhigher among the Malay population as the racial \ndistribution of Penang state was 45.5% Chinese, \n43.7% Malay, 10.4% Indian and others 0.4% (base \non 2010 population census). TC was found to be \nmost common in the school going group. They were \nat a higher risk of transmission probably due to close \ncontact with each other. Beyond this age group, the \nincidence declines because of the onset of puberty \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34 MJD 2014 Jul Vol 32\n\n\n\nand seborrhoea. The infection was more common \nin boys. Similar finding was also reported by \nFriedlander et al5 and other studies done in West \nBengal6, Rajasthan7 and Kenya8. It may be due to \nshorter hair, allowing easy access for circulating \nspores5. However, two studies reported by Singal et \nal9 and Chander et al10 respectively from north India \nshowed no sex difference.\n\n\n\nClinical presentation of the patients to the clinic was \nalso consistent with other studies done in Rajasthan7, \nNorth India9,10, Eastern Nepal11, Lahore(Pakistan)12 \nand Tirupati13.\n\n\n\nThe most common dermatophyte detected was \nM. canis followed by Trichophyton rubrum and \nTrichophyton metagraphyte. This might due to the \nstray cats or dogs in the residential area or even \npets at home. None of the specimen here grew \nTrichophyton violaceum which is the most common \ndermatophyte reported in India7, Nepal11, Pakistan14, \nSouth Africa and the UK15.\n\n\n\nTreatment was not a challenge in this cohort. A \nmeta-analysis was done by Tey et al16 showed that \ngriseofulvin was more efficacious than terbinafine \nin treating TC caused by Microsporum species, \nwhereas terbinafine was more efficacious than \ngriseofulvin in treating TC caused by Trichophyton \nspecies. \n\n\n\nConclusion\n TC is predominantly an infection of pre-adolescent \nchildren and M. canis was the most common \ndermatophyte isolated. \n\n\n\nAcknowledgement\nThe authors would like to thank Miss Keah Kwee \nChu, microbiologist, for her help in providing the \nlaboratory support.  \n\n\n\nReferences\n\n\n\n1. Ghannoum M, Isham N, Hajjeh R et al. Tinea capitis in \nCleveland: Survey of elementary school students. J Am \nAcad Dermatol 2003;48:189-93.\n\n\n\n2. Roderick Hay, Sandra E. Bendeck, Suephy Chen et al. \nChapter 37, Skin Diseases: Disease Control Priorities in \nDeveloping Countries. 2nd edition.\n\n\n\n3. Hay RJ, Moore MK. Mycology. In: Burns. Rook\u2019s Textbook \nof Dermatology. 7th ed. Massachusetts: Blackwell \nPublishing;  2004; 31.1-31.101.\n\n\n\n4. Section 23, Cutaneous Fungal Infection, Fitzpatricks Color \nAtlas and Synopsis of Clinical Dermatology, 5th edition: \n707 - 712.\n\n\n\n5. Friedlander SF, Rueda M, Chen BK, Caceros-Rios HW. \nFungal, protozoal and helminthic infections. Pediatric \nDermatology. 3 rd ed. Mosby 2003; 1093-140.\n\n\n\n6. Kundu et al. Prevalence of Tinea capitis in school going \nchildren in Kolkata, West Bengal. J Nat SciBiol Med. 2012 \nJul-Dec; 3(2): 152\u2013155.\n\n\n\n7. Kalla G, Begra B, Solanki A, Goyal A, Batra \nA. Clinico-Mycological study of Tinea capitis \nin Desert district of Rajasthan. Indian J \nDermatolVenereolLeprol.1995;61:342\u20135.\n\n\n\n8. Ayaya SO, Kamar KK, Kakai R. Aetiology of Tinea capitis \nin school children. East Afr Med J. 2001; 78:531\u20135.\n\n\n\n9. Singal A, Rawat S, Bhattacharya S, Mohanty S, Baruah \nMC. Clinico- mycological profile of tinea capitis in North \nIndia and response to griseofulvin. J Dermatol 2001; \n28:22-6.\n\n\n\n10. Chander Grover, Pooja Arora, Vikas Manchanda. Tinea \ncapitis in the Pediatric Population: A Study In North \nIndia. Indian Journal of Dermatology, Venereology, and \nLeprology September-October, 2010;76:527-532.\n\n\n\n11. Jha BN, Garg VK, Agrawal S et al. Tinea capitis in Eastern \nNepal. Int J Dermatol 2006;45:100-2.\n\n\n\n12. Hussain I, Aman S, Haroon TS et al. Tinea capitis in \nLahore, Pakistan. Int J Dermatol 1994;33:255-7.\n\n\n\n13. Kumar AG, Lakshmi N. Tinea capitis in Tirupati. Ind J \nPathol Microbiol 1990;33:360-3.\n\n\n\n14. Jahangir M, Hussain I, Khurshid K, Haroon TS. A clinico-\netiologic correlation in Tinea capitis. Int J Dermatol \n1999;38:275-8.\n\n\n\n15. Mills CM, Philpot CM. Tinea capitis in south Wales-\nobservations in change of causative fungi. Clin Exp \nDermatol 1994;19:473-5.\n\n\n\n16. Hong Liang Tey, Andy Soon Leong Tan, Yuin Chew Chan. \nMeta-analysis of randomized, controlled trials comparing \ngriseofulvin and terbinafine in the treatment of tinea capitis \nJ Am Acad Dermatol 2011; 64:663-70).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35MJD 2014 Jul Vol 32\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nVARICELLA ZOSTER-ASSOCIATED VASCULITIS IN\nAN IMMUNOCOMPETENT HOST \n\n\n\nEvelyn Tay Yuxin, Chuah Sai Yee, Joyce Lee Siong See, Pan Jiun Yit \n\n\n\nKeywords: herpes virus, leukocytoclastic vasculitis, haemorrhagic vesicles\n\n\n\nIntroduction\nVaricella zoster virus (VZV) infection can present \nwith a myriad of cutaneous and extracutaneous \nsigns. It can cause vasculitis, most commonly \nvasculitis of the central nervous system where it \nspreads to the arteries via ganglionic afferent fibres1.  \nHowever, VZV can also affect renal, coronary, \nretinal, choriodal  and cutaneous arteries2-11. We \nreport an unusual case of varicella zoster-associated \nvasculitis occuring in an immunocompetent 83-year-\nold Chinese female. \n\n\n\nCase report\nAn 83-year-old Chinese female presented with a \none week history of left lower limb pruritic rash. \nThis was preceded by left knee and calf pain one \nday before onset of the rash. The rash then spread \nto involve her right lower limb and hip. She had a \npast medical history of ischaemic heart disease \nand Child\u2019s A cryptogenic liver cirrhosis. She was \notherwise well with no fever or prior injury, new \nmedications or contactants. \n\n\n\nOn examination, there were purpuric macules \nand papules, some with central haemorrhagic \nvesiculation more prominent on the left lower limbs.  \nThere were also some scattered purpuric macules \non the right shin and hip. Our initial differential \ndiagnoses were bullous vasculitis, vasculitis \nsecondary to infections. Routine blood tests \nincluding vasculitic screening and a skin biopsy \nfor histology and direct immunofluorescence (DIF) \nwere done.\n\n\n\nCorrespondence\nDr. Evelyn Yuxin Tay\nNational Skin Centre\n1 Mandalay Road, Singapore 308205\nEmail: evelynyxtay@gmail.com\n\n\n\nShe was treated with topical corticosteroids and oral \nanalgesia, pending the results of investigations. On \nreview two days later, her rash had progressed. There \nwere more clustered haemorrhagic vesicles and \nbullae along the L3 and L4 dermatomal distribution \nof the left lower limb (Figure 1). The diagnosis \nof varicella zoster-associated leukocytoclastic \nvasculitis was considered.\n\n\n\nThis was supported by the histology results \nshowing an intraepidermal blister with necrotic \nand acantholytic keratinocytes exhibiting steel-\ngray nuclear inclusions and chromatin margination. \nMultinucleated giant cells with moulded, steel-grey \nnuclei were present. In addition, there was fibrinoid \nnecrosis of the upper dermal blood vessels in \nassociation with red cell extravasation, neutrophils \nand nuclear dust. There was a superficial and \ndeep perivascular infiltrate of lymphocytes and \nneutrophils. This was consistent with herpes \ninfection and concomitant leukocytoclastic \nvasculitis (Figure 2). Direct immunofluorescence \nwas negative for any immunoreactants. \n\n\n\nHepatitis B and C serologies, anti-neutrophil \ncytoplasmic antibodies (ANCA), anti-streptolysin-O \ntitres (ASOT) were negative. Erythrocyte \nsedimentation rate was 12mm/hour (Normal range: \n0-10mm/hour).  Retroviral screen was negative. Of \nnote, antinuclear antibody (ANA) titres were high \nat 1:640 in a speckled pattern. However, the patient \ndid not have any systemic symptoms suggestive \nof an underlying connective tissue disease and her \nanti-double stranded DNA was also negative. \n\n\n\nThe patient was initiated on oral acyclovir 800mg \nfive times a day for 10 days with complete resolution \nof the rash. She experienced post herpetic neuralgia \nthat was controlled with oral analgesia and has not \nexperienced recurrence of vasculitic lesions one \nmonth after receiving treatment.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36 MJD 2014 Jul Vol 32\n\n\n\nFigure 1  A) Purpuric macules, some with central vesiculation, along the distribution of the L3 and L4 dermatome of the left \nlower limb. B) Posterior  and C) Anterior views of the left lower limb one week after completion of antiviral therapy showing \npost inflammatory hyperpigmentation in a dermatomal distribution.\n\n\n\nFigure 2  An intraepidermal blister containing acantholytic keratinocytes and multinucleated giant cells with steel-\ngray nuclear inclusions was seen. In addition, there was fibrinoid necrosis of the upper dermal blood vessels in \nassociation with red cell extravasation and nuclear dust (H&E, x 200). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n37MJD 2014 Jul Vol 32\n\n\n\nDiscussion\nThis case highlights an atypical presentation \nof VZV in the skin. VZV can be an infectious \ncomplication of primary vasculitis4. It can also \nbe responsible for a myriad of vascular disorders \nthat range from leukocytoclastic vasculitis5,6,7, \ngranulomatous vasculitis8 to obliterative \nangiitis9,10. The most widely reported is \ngranulomatous vasculitis, which is induced \nby the persistence of viral glycoproteins in \narterioles post-infection8. \n\n\n\nGiven that i) the rash was preceded by pain, ii) \nwas predominantly along the distribution of the \nL3 and L4 dermatome of the left lower limb and \niii) resolved completely with the administration \nof oral antivirals; we believe that this is a case of \nsegmental leukocytoclastic vasculitis induced \nby herpes zoster. On the other hand, VZV \nreactivation in a primary systemic vasculitis \ncannot be ruled out as this presentation was \npeculiar in that there were vasculitic lesions on \nthe right hip and right shin of the patient. \n\n\n\nWe postulate that there could be a low level of \nviremia with deposition of immune complexes \nin the blood vessels away from the site of \nzoster reactivation. Direct immunofluorescence \ncould have been negative due to the specimen \nbeing taken six days after the onset of the \nrash, and usually has a sensitivity of 60 to 80 \npercent for cutaneous vasculitis12. Notably, \nthe inflammatory markers were not raised and \nwork-up for an underlying cause for a systemic \nvasculitis was negative. \n\n\n\nImpairment of cell-mediated immunity is often \nassociated with unusual presentations of VZV \ninfection such as verrucous, hyperkeratotic, \n\n\n\npox-like or ecchymotic lesions9. Previous case \nreports of acute herpes-related vasculitis have \ncentred around individuals on methotrexate \nor combination chemotherapy for underlying \nmalignancies5,6,9 and  on corticosteroids for \npulmonary sarcoidosis and systemic lupus \nerythematosus7,11.\n\n\n\nWe also seek to highlight that unusual \nmanifestations of herpes zoster can occur in \nimmunocompetent hosts, especially in elderly \npatients like ours. In addition to our case \noccurring in an immunocompetent elderly \nfemale, there was another report of a healthy \n90-year-old patient who developed acute \nherpetic folliculitis and lymphocytic obliterative \narteritis of the face and neck10. \n\n\n\nOur patient responded to a 10-day course of \nacyclovir without the need for any systemic \nimmunosuppressants. This is similar to previous \nreports in the literature in which patients \nresponded to oral or acyclovir6,9, brivudine7 \nand valacyclovir10 without the need for any \nadditional immunosupression. \n\n\n\nSummary\nWe present an unusual case of leukocytoclastic \nvasculitis secondary to concomitant VZV \ninfection in an immunocompetent patient. \nClues to the diagnosis included significant pain \nprior to the onset of the rash and the dermatomal \ndistribution of the vesicles. When the diagnosis \nof VZV related vasculitis is suspected, a skin \nbiopsy is required to confirm the diagnosis and \ntests for underlying immunosuppression should \nbe performed. This entity is usually responsive \nto antivirals without the need for concomitant \nuse of immunosuppressants.\n\n\n\nReferences\n\n\n\n1. Nagel MA, Traktinskiy I, Azarkh Y et al.  Varicella zoster \nvirus vasculopathy. Neurology 2011; 77: 364-70.\n\n\n\n2. Lidar M, Lipschitz N, Langevitz P et al.  The infectious \netiology of vasculitis.  Autoimmunity 2009; 42: 432-8.\n\n\n\n3. Shimizu J, Inatsu A, Oshima S et al.  Unique angiopathy \nafter herpes virus infection.  J Rheumatol 2004; 31: 925-\n30.\n\n\n\n4. Moosig F, Holle JU, Gross WL. Value of anti-infective \nchemoprophylaxis in primary systemic vasculitis: what is \nthe evidence?  Arthritis Res Ther 2009; 11: 253.\n\n\n\n5. Cohen C, Trapuckd S. Leukocytoclastic vasculitis \nassociated with cutaneous infection by herpesvirus. Am J \nDermatopath 1984; 6: 561-5.\n\n\n\n6. Uhoda I, Pi\u00e9rard- Franchimont C, Pi\u00e9rard GE.  Varicella-\nZoster Virus Vasculitis: A Case of Recurrent Varicella \nwithout Epidermal Involvement.  Dermatology 2000; 200: \n173-5. \n\n\n\n7. Wollina U, Sch\u00f6nlebe J.  Segmental leukocytoclastic \nvasculitis in herpes zoster.  Int J Dermatol 2012; 51 :   \n1351-2.\n\n\n\n8. Carlson JA, Chen K-R.  Cutaneous Vasculitis Update: \nNeutrophilic Muscular Vessel and Eosinophilic, \nGranulomatous, Lymphocytic Vasculitis Syndromes.  Am \nJ Dermatopath; 29: 32-43.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38 MJD 2014 Jul Vol 32\n\n\n\n9. Erhard H, R\u00fcnger TM, Kreienkamp M et al. Atypical \nvaricella-zoster virus infection in an immunocompromised \npatient: Result of a virus-induced vasculitis.  J Am Acad \nDermatol 1995; 32: 908-11.\n\n\n\n10. Aram G, Rohwedder A, Nazeer T et al. Varicella-Zoster-\nVirus Folliculitis Promoted Cutaneous Lymphoid \nHyperplasia.  Am J Dermatopathol 2005; 27: 411-7.\n\n\n\n11. Chi Y-W, Osinbowale O.  Herpes vasculitis in systemic \nlupus erythematosus.  Vasc Med 2009; 14: 401.\n\n\n\n12. Boom BW, Mommaas AM, Vermeer BJ.  Presence and \ninterpretation of vascular immune deposits in human skin: \nThe value of direct immunofluorescence.  J Dermatol Sci \n1992; 3: 26-34.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n39MJD 2014 Jul Vol 32\n\n\n\nABSTRACTS OF MASTERS\nIN ADVANCE DERMATOLOGY (UKM) DISSERTATION\n\n\n\nACNE\nACNE VULGARIS: QUALITY OF LIFE AND COST OF ILLNESS\nIN GOVERNMENT DERMATOLOGY CLINICS IN SARAWAK \nFelix Yap Boon Bin \n\n\n\nBackground: Acne vulgaris is a common disorder of the pilosebaceous units with significant impact \non the quality of life. However, little is known about this impact and the cost of illness in Malaysia \nalbeit their importance in the optimal management of acne vulgaris.\n\n\n\nObjective: The aim of this study is to determine the quality of life impairment in patients with acne \nvulgaris attending government Dermatology Clinics in Sarawak and to estimate the cost of illness.\n\n\n\nMethod: This cross sectional study involved 200 patients with acne vulgaris attending the government \nDermatology Clinics in Sarawak. The severity of acne was assessed using subjective visual analog \nscale and objective facial lesional counting and Global Acne Grading System (GAGS). The quality of \nlife was measured using Dermatology Life Quality Index (DLQI), Children Dermatology Life Quality \nIndex (CDLQI) and Cardiff Acne Disability Index (CADI). The cost of illness involved estimates of \ndirect medical and direct non medical costs.\n\n\n\nResults: Majority of patients had mild to moderate quality of life impairment. The median DLQI, \nCDLQI and CADI scores were 3, 1 and 4 respectively. Symptoms and feelings was the main domain \naffected. The quality of life impairment was significantly more severe in patients with specialist care < \n6 months and family income < RM 3000 (p < 0.05). There were significant positive linear correlations \nbetween acne severity and quality of life impairment (p < 0.001). The correlation between GAGS \nand DLQI (Spearman\u2019s coefficient 0.268) and CADI (Spearman\u2019s coefficient 0.422) was low. The \ncorrelation between subjective patient\u2019s assessment and DLQ1 was low (Spearman\u2019s coefficient 0.425) \nand CADI was moderate (Spearman\u2019s coefficient 0.649). The median cost of illness was RM 957.87. \nThe cost of illness was higher in patients with tertiary education, working, > 18 years, specialist care \n< 6 months, severe acne using objective scoring and severe quality of life impairment using CADI (p \n< 0.05).\n\n\n\nConclusion: Acne vulgaris has considerable impact on the quality of life in Sarawak, with a low to \nmoderate correlation with the acne severity. The cost of treating patients with acne in government \nDermatology Clinics in Sarawak is high.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40 MJD 2014 Jul Vol 32\n\n\n\nACNE\nANTIBIOTIC SENSITIVITY OF PROPIONIBACTERIUM ACNES \nISOLATED FROM PATIENTS WITH ACNE VULGARIS IN\nKUALA LUMPUR HOSPITAL, MALAYSIA \nTang Jyh Jong\n\n\n\nBackground: Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of \ntreatment in acne vulgaris for more than 40 years. Prolonged antibiotic usage has been associated with \nemergence of antibiotic-resistant P. acnes and is linked to treatment failure. Little work has been done \nin Malaysia on drug resistance in P. acnes and there is no surveillance data on this aspect to guide the \nclinical decision.\n\n\n\nObjective: This study aims to evaluate antibiotic sensitivity of P. acnes isolated from patients with acne \nvulgaris in Kuala Lumpur Hospital, Malaysia.\n\n\n\nMethod: This is a non interventional, single centered, cross-sectional hospital-based survey of \nantibiotic sensitivity of P. acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital \nfrom January 2010 to June 2010.\n\n\n\nResults: A total of 100 patients were recruited in our study. P. acnes was isolated in 53% of patients \nand 11% had gram negative organism. Antibiotic resistant P. acnes was found in 15.1% of positive \nisolates. Clindamycin resistance was most common (15.1%) followed by erythromycin (7.5%), \ndoxycycline (5.7%), tetracycline (1.9%) and minocycline (0%). Isolates of antibiotic resistant P. acnes \nwas significantly higher in patients treated with antibiotics within the last 6 months (29%) as compared \nwith non antibiotic treated patients (0%) (p<0.05).The mean duration of prior antibiotic treatment was \nsignificantly longer in the group of antibiotic resistant P. acnes as compared with antibiotic sensitive P. \nacnes (17.13 weeks vs 5.74 weeks, p<0.05).\n\n\n\nConclusion: Antibiotic resistant P. acnes is present locally with clindamycin and erythromycin \nconferring the highest resistance. Longer duration of antibiotic treatment predisposes to antibiotic \nresistant P. acnes and may also induce emergence of gram negative organisms. Strategies to reduce \nantibiotic resistance should be emphasized when prescribing antibiotic for acne vulgaris in order to \nachieve optimal therapeutic results while reducing the potential for antibiotic resistance.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n41MJD 2014 Jul Vol 32\n\n\n\nADVERSE DRUG REACTIONS\nHUMAN LEUKOCYTE ANTIGEN (HLA) IN TOXIC EPIDERMAL \nNECROLYSIS (TEN) AND STEVENS JOHNSON SYNDROME \nChang Choong Chor  \n\n\n\nBackground: Severe adverse cutaneous drug reactions (ACDR) such as toxic epidermal necrolysis \n(TEN) and Stevens-Johnson syndrome (SJS) are potentially life-threatening hazards of health care that \nhave largely been unpredictable. Previous studies in other countries have identified a number of HLA \nassociations which may be exploited in the future development of a screening test for these reactions. \n\n\n\nObjectives: This study aims to investigate the association between HLA and TEN/SJS in general and \nthe association between HLA and TEN/SJS caused by specific drugs in a population consisting mainly \nof Malays, Chinese and Indians in Malaysia. \n\n\n\nMethod: 95 unrelated patients who had been diagnosed to have TEN or SJS caused by drugs, and race-\nmatched healthy controls (300 Malays, 300 Chinese, and 150 Indians) were recruited and genotyped \nfor HLA-A, B and DR with polymerase chain reaction (PCR) technique. Woolf and Haldane Odds \nratio (OR) and corrected P-value (P\u2032) obtained from two-tailed Fisher\u2019s exact test were used in the \nanalysis of the HLA associations. \n\n\n\nResults: The allele frequencies of HLA-B*1502 were significantly higher in Malay patients with \ncarbamazepine-induced TEN/SJS than in normal controls [Odds Ratio (OR)=16.15, Pc<0.0001]. \nWhereas frequencies of HLA-B58, A33 and DR17 were higher in allopurinol-induced TEN/SJS \nthan in normal controls in both Malays (OR=64.7, Pc<0.0001; OR=11.9, Pc=0.0054; and OR=23.0. \nPc=0.00025 respectively), and Chinese patients (OR=89.9, Pc<0.0001: OR=28.9. Pc=0.00025; and \nOR=49.1, Pc<0.0001 respectively). HLA-B*1513 was more frequently present in Malay patients with \nphenytoin-induced TEN/SJS compared to controls (0R=12.2, Pc=0.011). These HLA associations \nseemed to be specific to the drugs causing the reactions. Frequencies of the associated alleles were \ngenerally higher in Asian populations (Malaysia, Singapore, Thailand and Taiwan) than Caucasians in \nthe US and Ireland. \n\n\n\nConclusion: HLA-B*1502 for carbamazepine-induced TEN/SJS, and HLA-B58. A33 and DR17 \nfor allopurinol-induced TEN/SJS, and HLA-B*1513 for phenytoin-induced TEN/SJS are potentially \nuseful genetic markers for these ACDR. More studies with larger number of patients are required to \nelucidate the genetic susceptibility of TEN and SJS induced by other drugs and in other races.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42 MJD 2014 Jul Vol 32\n\n\n\nDERMATITIS\nFINGERPRINT BIOMETRICS CHANGES IN HAND DERMATITIS \nLee Chew Kek\n\n\n\nBackground: Hand dermatitis is common and causes fingerprint changes that interfere with fingerprint \nbiometric verification processes.\n\n\n\nObjectives: The objectives of the study were to determine the prevalence of fingerprint verification \nfailure, the effectiveness of betamethasone valerate in recovering verification with treatment and to \ndevelop fingerprint verification failure prediction model for patients with hand dermatitis.\n\n\n\nMethod: A case - control observational study involving one hundred patients and one hundred controls \nwas conducted. Data on demographics, history of a verification failure, disease severity and quality of \nlife impairment were collected. All recruits underwent fingerprint verification with My Kad. Patient \nwhich failed verification were treated with betamethasone valerate 0.1% ointment and followed up \nmonthly for 2 months.\n\n\n\nResults: Compared to the controls, hand eczema patients had higher prevalence of failed fingerprint \nverification history (36.0% vs 6.0%, p<0.001) and failed verification at enrolment (27.0% vs 2.0%, \np<0.001). The main fingerprint abnormalities were areas of dystrophy (42.0%) and abnormal white \nlines (79.5%). Risk factors of verification failure were disease severity, presence of \u226525.0% area of \nof dystrophy, abnormal long white lines and abnormal braod white lines. Fingerprint verification \nprediction model comprising of one major criterion (area of dystrophy \u226525%) and two minor criteria \n(long horizontal lines and long vertical lines) were validated. The positive predictive value with one \nmajor criterion were 77.6%, two minor criteria were 77.6% and 1 minor criterion were 20.0%. in \nthe absence of these criteria, the negative predictive value was 98.7%. Following treatment, 25.3% \nof patients had successful recovery from verification failure. Presence long fine horizontal lines was \nassociated with higher verification recovery (p=0.023).\n\n\n\nConclusion: Fingerprint verification failure is prevalent in hand dermatitis. The proposed verification \nfailure prediction model is highly predictive, specific and reliable. Betamethasone valerate 0.1% \nointment is effective in recovering fingerprint verification in some patients.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n43MJD 2014 Jul Vol 32\n\n\n\nDERMATITIS\nPREVALENCE OF POSITIVE PATCH TEST AMONG\nHEALTHCARE WORKERS TO RUBBER ADDITIVES, NATURAL \nRUBBER LATEX AND SYNTHETIC RUBBER GLOVES AND RISK \nFACTORS ASSOCIATED WITH POSITIVE PATCH TEST \nPeter Ch\u2019ng Wee Beng \n\n\n\nBackground: Occupational hand eczema is a major burden to healthcare workers. Rubber gloves and \ntheir contents are known to cause allergic contact hand eczema among healthcare workers. Malaysia \nis the world\u2019s leading producer and exporter of medical gloves in 2011. \n\n\n\nObjectives: The aim of this study is to determine the prevalence of positive patch test among healthcare \nworkers to rubber additives, natural rubber latex and synthetic rubber gloves and risk factors associated \nwith positive patch test. \n\n\n\nMethod: This is a cross-sectional study conducted in Selayang Hospital, Malaysia from 1st July to \n31st December 2011. An announcement and explanation about the study was communicated through \nthe hospital intranet to all doctors, assistant medical officer and nurses. All participants (symptomatic \nor asymptomatic) were patch tested to extended Chemotechnique rubber additive series including \nthiuram and mercapto mix and 6 types of rubber gloves. \n\n\n\nResults: Out of the 174 subjects who completed the patch test, 77 (44.3%) subjects were positive to \nat least 1 rubber additive or rubber glove. Seventy-five (43.1%) subjects were positive to at least 1 \nrubber additive while 18 (10.3%) subjects had positive patch test to at least 1 type of rubber glove. \nTwo (2.6%) subjects who had tested negative to rubber additives had a positive patch test to rubber \ngloves. Testing solely against the Chemotechnique European Standard Series and omitting the rubber \nadditive series and gloves, 64/174 (36.8%) subjects who were sensitized to rubber additive would have \nbeen missed. Seven subjects (4.0%) were clinically relevant while 28/174(16.1%) had past relevance. \nMales [OR (95%CI): 4.0 (1.601, 10.080); p-value = 0.003] and those who worked for more than 10 \nyears in healthcare service [OR (95%CI): 3.3 (1.514, 7.288); p-value = 0.003] were at higher risk of \ngetting positive results. \n\n\n\nConclusion: There is a high prevalence of sensitization to rubber gloves and its additives among \nhealthcare workers though they may be asymptomatic. Healthcare workers with glove related hand \neczema should undergo patch test to extended rubber additive series in addition to European Standard \nseries and suspected rubber gloves.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44 MJD 2014 Jul Vol 32\n\n\n\nDERMATITIS\nEFFICACY AND SAFETY OF SODIUM HYPOCHLORITE \n(BLEACH) BATHS IN PATIENTS WITH MODERATE TO SEVERE \nATOPIC DERMATITIS \nWong Su-Ming\n\n\n\nBackground: Atopic dermatitis (AD) is a pruritic, chronically relapsing inflammatory skin condition \ncharacterized by papules, excoriations and lichenification. It has been shown that individuals with AD \nhave an increased susceptibility to colonization with Staphylococcus aureus (S.aureus), contributing \nto the exacerbation of the disease. Sodium hypochlorite (bleach) has both in vitro and in vivo \nantimicrobial activity against S.aureus. We therefore sought to determine if the addition of sodium \nhypochlorite (bleach) baths as an adjunctive treatment could result in improvement of the clinical \nseverity of atopic dermatitis and a reduction of S.auretts density in patients with atopic dermatitis in \nour Malaysian population.\n\n\n\nObjectives: This study aims to evaluate the efficacy and safety of diluted sodium hypochlorite (bleach) \nbaths in patients with moderate to severe atopic dermatitis.\n\n\n\nMethod: This was a prospective randomized, investigator-blinded, placebo-controlled study. Patients \nwere randomly assigned to treatment (bleach baths) or placebo (distilled water baths). Patients were \ninstructed to soak in the baths neck down for 10 minutes, twice a week for 2 months. They were \nmaintained on a stable topical regimen throughout the study. The efficacy outcome measures were the \nEczema Area and Severity Index (EASI) score, percentage body surface area involved, quantitative \nS.aureus counts and patient\u2019s assessment of overall response (including itch scores). Safety outcomes \nwere also assessed.\n\n\n\nResults: A total of 36 patients completed the study. EASI scores showed significant improvement \nbetween treatment and placebo groups at 2 months (p=0.02). In the treatment group, there was also \nsignificant improvement at 1 month and 2 months (p < 0.001) from baseline. Body surface area also \nhad significant improvement at 2 months compared to placebo (p=0.002) and in the treatment group, \nthere was significant improvement of the itch scores at 2 months (p=0.02). At baseline, 88% of patients \nS.aureus from lesional skin. Although most cultures in the treatment group at 1 month and 2 months \ncontinued to yield S.aureus, there was a reduction in the density over time, although not statistically \nsignificant. Five patients reported burning/stinging and dry skin in the treatment arm which did not \ndiffer significantly compared to placebo. No patient in the treatment group withdrew from the study \nbecause of intolerance to the baths.\n\n\n\nConclusion: Diluted sodium hypochlorite baths as an adjunctive treatment decreased the clinical \nseverity of patients with moderate to severe atopic dermatitis and may reduce S.aureus density. This \ntreatment was well tolerated with minimal adverse effects.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n45MJD 2014 Jul Vol 32\n\n\n\nDERMATITIS\nTHE EFFICACY AND SAFETY OF TACROLIMUS OINTMENT IN \nPATIENTS WITH MODERATE TO SEVERE ATOPIC ECZEMA \nNg Ting Guan \n\n\n\nBackground: Atopic dermatitis is an intensely pruritic, chronic relapsing, inflammatory, \nimmunologically mediated skin disease which can significantly impact the physical and psychosocial \nhealth of a patient. Topical immunomodulator like tacrolimus ointment and pimecrolimus cream has \nrecently been found to be effective in the treatment of atopic dermatitis. This study represents the first \nclinical experience in the use of topical tacrolimus with atopic dermatitis in Hospital Kuala Lumpur. \n\n\n\nObjective: To evaluate the safety and efficacy of tacrolimus ointment 0.1% in adults and 0.03% in \npaediatric patients with moderate to severe atopic dermatitis. \n\n\n\nMethod: This is an open-label, single arm study with topical tacrolimus ointment twice daily for four \nweeks. Patients enrolled were divided into 2 groups of the paediatric (2 -15 years old) and the adult \n(16 years and older).11 adult patients and 10 paediatric patients were enrolled with statistical analysis \nperformed separately. \n\n\n\nResults: Based on a primary efficacy endpoint, the Physician\u2019s Global Evaluation of Clinical \nResponse, 80% and 100% of paediatric and adult patients had moderate improvement respectively. \nThe improvement in secondary endpoints: Patient\u2019s Assessment of Overall Response, Eczema Area \nand Severity Index (EASI), percentage of body surface area ( BSA) involved, and patients\u2019s assessment \nof pruritus were significant (p< 0.003).Safety profile was based on adverse events reported by patients \nor observed by the physician. 60% paediatric and 100% adult patients reported adverse events. The \nmost common adverse events reported were transient skin burning and/or pruritus at the application \nsite. One patient discontinued therapy because of the adverse event. \n\n\n\nConclusion: Tacrolimus ointment is effective and safe for treatment of moderate to severe atopic \ndermatitis in both the paediatric and adult patients.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46 MJD 2014 Jul Vol 32\n\n\n\nERYTHRODERMA\nCOMPARISON OF TRANSEPIDERMAL WATER LOSS (TEWL)\nBETWEEN NORMAL AND ERYTHRODERMIC PATIENTS OF \nVARIOUS AETIOLOGY \nNoorlaily Mohd Noor\n\n\n\nBackground: Barrier to water loss at the stratum corneum is one of the critical skin barrier functions. \nThe passive movement of water through the stratum corneum into the atmosphere is known as \ntransepidermal water loss (TEWL) and is used as a measure of skin barrier function. Erythroderma is a \ncondition associated with a significant breakdown of skin functions due to extensive skin involvement, \nresulting in skin failure and its complications. Knowing the TEWL in these patient will enable us to be \nmore precise in fluid managment and skin directed therapy of this potential dermatological emergency.\n\n\n\nObjectives: This study aims to compare TEWL between the skin of healthy subjects and erythrodermic \npatients of various aetiologies and at different anatomical sites. TEWL between patients with acute \nand chronic erythroderma were also compared.\n\n\n\nMethod: 25 erythrodermic  patients of various causes and 26 age, race and sex-matched healthy controls \nwere recruites. TEWL measurements were  perfomed on each patient and control at 5 sites, namely the \nright cheek, left volar forearm, abdomen, upper back and right calf according to the guidelines of the \nStandardization Group of the European Society of Contact Dermatitis using Tawameter TM 210 under \na controlled room temperature of 20-22\u2032C and humidity of 50%.\n\n\n\nResults: The mean TEWL (in g/m\u00b2h) in erythrodermic patients were: right cheek 34.01\u00b117.59, \nleft volar forearm 31.68\u00b111.26, abdomen 38.77\u00b113.23, upper back 29.36\u00b112.85 and right calf \n31.60\u00b112.11; whereas TEWL in the control group were: right cheek 15.13\u00b14.17, left volar forearm \n6.28\u00b11.21, abdomen 7.92\u00b11.90, upper back 7.53\u00b11.49 and right and right calf 6.12\u00b11.04. TEWL \nvalues in erythrodermic patients were significantly higher compared to healthy individuals at all \nthe five sites (p<0.001). There were significant differences  in TEWL between different anatomical \nsites in the controls groups were that of the abdomen (38.77\u00b113.23 g/m \u00b2h) and the right cheek  \n(15.13\u00b14.17 g/m \u00b2h) respectively. The mean TEWL in patients with acute arythroderma were: right \ncheek 41.37\u00b122.41, left volar forearm 32.07\u00b110.46, abdomen 36.15\u00b111.20, upper back 31.58\u00b18.01 \nand right calf 35.88\u00b111.65; whereas TEWL in patients with chronic erythroderma were: right cheek \n29.87\u00b113.28, left volar  forearm 31.46\u00b112.01, abdomen 40.25\u00b114.38,upper back 28.11\u00b115.01 and \nright calf 29.20\u00b112.04. Acute erythrodermic patients (n=9) seemed to have a higher TEWL than \nchronic erythrodermic patients (n=16) although the difference were not statistically significant. There \nwas no significant different aetiologies and between acute and chronic erythroderma were difficult to \nachieve, even if larger number of patients have been recruited.\n\n\n\nConclusion: Erythrodermic skin regardless of aetiology has much higher TEWL compared to normal \nskin. Difference in TEWL among various anatomical sites observed in normal skin were not abserved in \nerythroderma. TEWL measurements performed in a larger number of patients under local temperature \nand humadity may be more reflective of the actual clinical condition.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n47MJD 2014 Jul Vol 32\n\n\n\nPEMPHIGUS\nIMPACT OF SYSTEMIC GLUCOCORTICOIDS ON BONE\nMINERAL DENSITY IN PATIENTS WITH PEMPHIGUS \nMazlin Baseri \n\n\n\nBackground: Glucocorticoid-induced osteoporosis (GIOP) is a well-known complication of prolonged \nsystemic glucocorticoid (GC) therapy. GC is the cornerstone of treatment for pemphigus but data on \nits impact on bone mineral density (BMD) in patients with pemphigus is scarce. \n\n\n\nObjectives: To describe the changes of BMD over time in patients with pemphigus, with reference \nto\tDEXA\tscan\tresults\tavailable\tin\tthe\tmedical\trecords\tand\tto\tcompare\tour\tresults\twith\tthe\tnormal\t\npopulation data. \n\n\n\nMethod: This cross sectional study was conducted at the Department of Dermatology Hospital Kuala \nLumpur\tfrom\tJanuary\tuntil\tJune\t2011.\tDemographic\tdata,\tGC\tdoses\tand\tduration\tand\tDEXA\tscan\t\nresults were obtained from medical notes. Patients were interviewed about level of daily activity, \nmenopausal\tstatus,\tsmoking\thabits\tand\talcohol\tintake.\tA\tsecond\tDEXA\tscan\twas\tperformed\tfor\tthose\t\nwho have not had a scan at least a year apart.\n\n\n\nResults: 29 patients with pemphigus were recruited. Twelve patients were males and 17 were females \nwith a mean age of 52.2 \u00b1 12.04 years. 20 patients had pemphigus vulgaris and 9 had pemphigus \nfoliaceous.\tAll\tpatients\treceived\telemental\tcalcium\tand\tvitamin\tD\tsupplementation.\tOn\tinitial\tDEXA\t\nscan, 3 (10.3%) patients were osteoporotic and 11 (37.9%) were osteopenic. Reduction in BMD was \nseen in 20 (69%) patients; increase BMD in 8 (27.6%) and BMD remained stable in 1 (3.4%) patient. \nCumulative GC dose was 24980 mg (8457- 99735 mg) and median daily dose of GC was 23.42 \n\u00b1 17.61 mg/day (4.98-75.96) over 41 months. Among the patients with reduced BMD, the rate of \nreduction in BMD was 0.02 \u00b1 0.02 g/cm2/year in the lumbar spine and 0.01% \u00b1 0.03 g/cm2/year in \nthe left hip. Percentage reduction of BMD was 4.22% \u00b1 3.08 and 2.44% \u00b1 6.44 in the lumbar spine and \nleft hip respectively. Our patients\u2019 BMD was lower than the normal population across all age groups. \n\n\n\nConclusion: There appears to be a varied BMD response to GC but the BMD of our patients are generally \nlower than normal population. Elemental calcium and activated vitamin D started concurrently with \nGC appear to be adequate in preventing GIOP in some but not all patients. Bisphosphonates should be \nconsidered early in high risk patients.\n\n\n\n\n\n\n\n\nPHOTOBIOLOGY\nNARROWBAND UVB PHOTOTHERAPY: COMPARISON OF TWO \nSTARTING DOSES USING 50%MED AND SKIN PHOTOTYPE \nKartini Farah Abd. Rahim\n\n\n\nBackground: Narrow-band Ultraviolet B (NB-UVB) phototherapy is an established treatment option \nfor psoriasis. There are two methods of starting the treatment, either based on Fitzpatrick skin phototype \n(SPT) or minimal erythema dose (MED). The SPT classification, initially proposed for Caucasian skin, \nhad failed in predicting cutaneous response to UV radiation in Asian population. Objective method by \ndetermining individual MED using phototest might be a better alternative. To date, there is still debate \non the best method in determining the starting dose of NB-UVB in Asians. \n\n\n\nObjectives: This study aims to determine the optimal NB-UVB starting dose for the treatment of \npsoriasis, by comparing 50% MED and SPT based regimen. Our primary objective is to look at the \nnumber of treatments to 50%, 75% and 90% reduction in PASI score. Our secondary objective is to \nstudy the MED of these patients from multi-ethnic population and to correlate it with SPT classification. \n\n\n\nMethod: This was a randomized, double-blind, controlled study comparing two different starting doses \nin patients referred to the phototherapy unit of Hospital Kuala Lumpur for chronic plaque psoriasis. \nAssessment of SPT and MED were performed prior to treatment. Treatment was given three times \nweekly as per protocol. Clinical efficacy using Psoriasis Area and Severity Index (PASI) scoring \nwas evaluated in a blinded manner at baseline, every 6th treatment and clearance. Dermatology Life \nQuality Index (DLQI) was used to measure disease-related quality of life. \n\n\n\nResults: There were 37 patients, of which 65% were males and 35% were females. They were made up \nof Malays, 62%, followed by Indians, 22% and Chinese 16%. The mean age was 38.7, ranging from 13 \nto 64 years. SPT ranged from SPT III, 48.6% to SPT IV, 48.6% and SPT V, 2.8%.Majority of Malays \nhad SPT III and IV. All Chinese had SPT III. Most Indians had SPT IV and one had SPT V. There was \nsignificant overlap of MEDs for all the different skin phototypes. Mean MED for SPT HI was 714.7 \u00b1 \n283.26 mJ/cm2 and SPT IV was 952.9 \u00b1 285.30 mJ/cm2.\n\n\n\nThe number of visits to reach PASI 50 was lower in the 50% MED arm. The median number of visits \nwere 10 in the 50% MED arm compared to 16.5 in the SPT arm (p = 0.03). There were no significant \ndifferences in reaching PAST 75 and PAST 90 in both arms. Despite higher doses used in 50% MED \narm, there were no increase in adverse effects and protocol adjustments compared to SPT arm. \n\n\n\nConclusion: Starting NB-UVB treatment with 50% MED resulted in clearance of psoriatic lesions \nfaster than using SPT regime. Thus, MED should form the basis of starting NB-UVB phototherapy in \nour multi-ethnic patients.\n\n\n\n48 MJD 2014 Jul Vol 32\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n49MJD 2014 Jul Vol 32\n\n\n\nPSORIASIS\nCARDIAC ABNORMALITIES IN PSORIASIS \nPriya Gill \n\n\n\nBackground: Psoriasis is considered as an independent cardiovascular risk factor due to its chronic \nsystemic inflammatory nature. It is also associated with other cardiac abnormalities like abnormal \ncardiac conduction, valvular heart disease, pulmonary hypertension and myocardial disease. \n\n\n\nObjectives: This study aims to determine and describe the cardiac abnormalities using echocardiography \nand electrocardiography in patients with plaque psoriasis compared to healthy controls. \n\n\n\nMethod: This is a case control study of psoriasis patients with no previous history of cardiac disease. \nOne hundred and thirty five consecutive patients with chronic plaque psoriasis attending Dermatology \nClinic, Hospital Kuala Lumpur were recruited. A full history, physical examination, echocardiogram \nand electrocardiogram were done. The controls group were 135 age and sex matched healthy individuals. \n\n\n\nResults: The psoriasis group had a significantly higher body mass index and blood pressure. The \nechocardiogram results showed that the mean left ventricular wall diastolic thickness, aortic annulus \ndiameter and the isovolumetric relaxation time of the left ventricle was significantly prolonged in \nthe psoriasis group. The prevalence of tricuspid regurgitation was higher in the psoriasis group. On \nthe electrocardiogram, more psoriasis patients had left ventricular hypertrophy, ischaemia and right \nbundle branch block. The QRS interval was significantly shorter in the psoriasis group. The tricuspid \nvalve E/A ratio was significantly lower in patients with arthropathy. The mitral valve early filling \nvelocity deceleration time, tricuspid valve E/A ratio and QRS interval were significantly higher among \npatients who had never received systemic therapy. The mean mitral valve and tricuspid valve E/A ratio \nwere significantly lower in patients with disease duration of more than 10 years. This group also had a \nsignificantly larger mean ascending aorta diameter. \n\n\n\nConclusion:  Psoriasis may be associated with an increased risk of cardiac abnormalities suggesting \ndiastolic dysfunction, pulmonary hypertension and conduction disturbances; demonstrated on the \nechocardiogram and electrocardiogram. These abnormalities appear to be related to disease duration.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50 MJD 2014 Jul Vol 32\n\n\n\nPSORIASIS\nTHE EFFECT OF SMOKING CESSATION ON SEVERITY\nOF PSORIASIS \nAdawiyah Jamil\n\n\n\nBackground: Smoking is a risk factor in the onset and exacerbations of psoriasis. Smoking in psoriasis \npatients is important due to the association of psoriasis with cardiovascular disease. It may be an \nessential modifiable aspect in psoriasis management. \n\n\n\nObjectives: We investigated the association between smoking and psoriasis severity, and concomitant \ncardiovascular risk factors in our psoriasis patients.\n\n\n\nMethod: This was a case control study involving patients with chronic plaque psoriasis. Smokers were \nidentified, and age, gender and ethnic matched non-smokers were recruited. Psoriasis severity was \nevaluated using Psoriasis Severity Index (PASI) and body surface area (BSA) affected by psoriasis. \n\n\n\nResults: A total of 89 patients were screened. 24 were active smokers, 55 non smokers and 10 ex-\nsmokers. 24 smokers and 24 matched non-smokers were included in the study. There were no significant \ndifferences in the presence of medical co-morbidities, blood pressure, body mass index (BMI), age \nof psoriasis onset and duration of disease in both groups. The mean age patients started smoking was \n20.2\u00b15.6 years. The mean duration of smoking was 16.3\u00b111.1 years, the number of cigarette per day \n11.9\u00b16.1 sticks and the number of cigarette pack per year was 10.7\u00b19.2. BSA affected by psoriasis \nand PASI scores were significantly higher in the subjects who smoked compared to the non smokers. \n\n\n\nConclusion: Smoking is associated with more severe psoriasis. Psoriasis patients (smokers and non-\nsmokers) with multiple cardiovascular risk factors require intervention in risk reduction. Cessation of \nsmoking is relevant as psoriasis is increasingly recognized as an independent cardiovascular risk.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n51MJD 2014 Jul Vol 32\n\n\n\nPSORIASIS\nDEVELOPMENT OF A COMPUTERIZED OBJECTIVE ASSESSMENT \nOF AREA AND ERYTHEMA FOR PASI SCORING OF SEVERITY OF \nPSORIASIS AND COMPARING WITH THE CONVENTIONAL VISUAL \nASSESSMENT OF PASI BY DERMATOLOGIST \nAzura Afandi\n\n\n\nBackground: Psoriasis Area and Severity Index (PASI) is the gold standard method used in clinical \ntrials for evaluating the severity of psoriasis. However, PASI is not frequently used in daily practice, \ndue to the complexity of the assessments and calculations. Furthermore, it is subjective, and has \nmarked inter-individual variations. Therefore, an objective method is needed, which is reliable, valid \nand consistent from investigator to investigator. \n\n\n\nObjectives: The aim of this study is to develop an objective and computerized image analysis system \nto assess the surface area and erythema of psoriasis for use in PASI scoring. We also want to compare \nthe scores from the computerized image analysis with the conventional visual assessment of PASI by \ndermatologists. \n\n\n\nMethod: 41 patients with plaque psoriasis participated in this study. Photographs of the patients \n(head, upper limbs, trunk and lower limbs) were taken using a digital camera and Konica Minolta \nNon Contact 3D Digitizer VIVID-910. The colour of the normal skin and representative plaques were \nassessed using Konica Minolta Chroma Meter CR-400. Two dermatologists evaluated independently \nthe surface area and erythema for PASI score by visual inspection. \n\n\n\nResults: There were moderate agreements in PASI score for area in the head region between \nDermatologists 1 and Computerized Image Analysis (Kappa 0.54) and Dermatologist 2 and \nComputerized Image Analysis (Kappa 0.69). For the upper limb, trunk and lower limb, there were no \nagreement in the surface area scores given between Dermatologist 1 & 2 and Computerized Image \nAnalysis. There were moderate agreements in PASI scores between Dermatologist 1 and Computerized \nImage Analysis for the assessment of erythema in both the head and trunk regions (Kappa 0.56 and 0.53 \nrespectively). However, there were minimal agreements in the erythema scores between Dermatologist \n1 and Computerized Image Analysis in the upper and lower limbs regions. There was substantial \nagreement in PASI scores for erythema between Dermatologist 2 and Computerized Image Analysis \nin the head region (Kappa 0.79). For the upper limb, trunk and lower limbs, there was no agreement \nin the erythema scores between Dermatologist 2 and Computerized Image Analysis. There were \nmore agreements between the two dermatologists in the assessments of surface area. For erythema \nassessment, apart from the head and lower limb regions, there were minimal agreements between the \ntwo dermatologists. \n\n\n\nConclusion: In this study, we have developed an objective assessment of the surface area and erythema \nof psoriasis using a computerized image analysis system. There were marked variations in the PASI \narea and erythema scores obtained using the newly developed computerized  method, compared to \nthe conventional visual assessment of PASI by dermatologists. There was more inter-rater variability \nnoted between the two dermatologists in the assessment of erythema, compared to area of psoriasis \ninvolvement. Work is currently in progress to evaluate the thickness and scaliness scores objectively.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52 MJD 2014 Jul Vol 32\n\n\n\nPSORIASIS\nQUALITY OF LIFE AND COST OF ILLNESS IN PATIENTS WITH \nPSORIASIS IN MALAYSIA: A MULTICENTRE STUDY \nTang Min Moon\n\n\n\nBackground: Psoriasis is an immune mediated chronic inflammatory skin disease which affects \napproximately 2% of the world\u2019s population. It has a major impact on patients\u2019 quality of life, influencing \ntheir career, social activities, family and all other aspects of life. Many studies have described the \nvarious ways in which psoriasis can affects patients\u2019 life. Very little is known however about the impact \nof psoriasis on the quality of life of patients treated in Malaysia and the cost of illness in this region. \n\n\n\nObjectives: This study aims to describe the extent of psoriasis affecting the quality of life of patients \ntreated in the government dermatology clinics in Malaysia and to estimate the cost of illness.  \n\n\n\nMethod:  A total of two hundred and fifty patients with psoriasis treated at 8 dermatology clinics in the \ngovernment hospitals Malaysia were studied. The severity of psoriasis was assessed by dermatologists. \nQuality of life was evaluated using the Dermatology Life Quality Index (DLQI) and the second version \nof 12-Item Short Form Health Survey (SF12v2). The SF12v2 of healthy subjects and patients with other \nmedical conditions such as depression, diabetes mellitus, hypertension and ischaemic heart disease \nwere also assessed for comparison. The costs of dermatology outpatient consultant fees, medications, \ninvestigations, procedures, transportation fees, over-the-counter medications and hospitalizations \nwere retrospectively estimated using questionnaires. \n\n\n\nResults: The studied cohort had median PASI of 9.9 and a median DLQI of 10.0. The average SF12v2 \nwere 43.68 (SD 9.23) and 42.25 (SD 10.7) for physical health summary and mental health summary \nrespectively. The impact of disease on the quality of life is greater in those with more extensive \npsoriatic lesion involvement, in younger patients and in those with psoriatic arthropathy. Psoriasis \naffects the quality of life in both genders equally. Body mass index has no effect on the severity of \npsoriasis and the quality of life. Patients with psoriasis had a significantly lower SF12v2 score than \nhealthy subjects. The comparison with other chronic medical conditions demonstrated that psoriasis \nimparts a negative health related quality of life similar to the impact of other chronic conditions. \nThe estimated cost of illness for psoriasis in the current cohort was RM1,307.47 per person per year \nexcluding hospitalization. Patients were noted to spend a large amount of money on over-the counter \nproducts without doctors\u2019 prescriptions. \n\n\n\nConclusion: The quality of life of patients with psoriasis was significantly impaired compared to \nhealthy subjects and was comparable to patients with other chronic medical illnesses. The estimated \ncost of illness for psoriasis in the current study was lower than other countries mainly because the \npublic hospitals healthcare cost was heavily subsidized by government and also low usage of newer \nbut more expensive treatment options.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n53MJD 2014 Jul Vol 32\n\n\n\nPSORIASIS\nCOMPARISON OF TWO DOSING REGIMENS FOR \nADMINISTERING ORAL METHOTRAXATE IN PATIENTS WITH \nMODERATE TO SEVERE PLAQUE PSORIASIS\n(THE CO-TROMP STUDY) \nChong Yew Thong\n\n\n\nBackground: Methotrexate has been widely used as an effective systemic therapy for psoriasis for \nmore than 50 years. Quality data on its efficacy and side effects is sparse. Retrospective data showed \nan efficacy rate of 70-80% but recent RCTs using PASI 75 as primary endpoint showed wide variations \nin efficacy. Different dosing regimens for methotrexate may explain this variation \n\n\n\nObjective: The aim of this study was to compare the efficacy and tolerability of two different dosing \nrigimes (\u2018step-up dose\u2019 regime or \u2018step-down dose\u2019 regime) of administering oral methotrexate in the \ntreatment of patients with moderate to severe plaque psoriasis. \n\n\n\nMethod: A prospective, multicentre, randomized, comparative study was conducted from October \n2009 to June 2010 at three dermatology clinics in Malaysia. Patients with moderate-to-severe plaque \npsoriasis were randomized to receive either a \u2018step-up dose\u2019 regime (started at 7.5mg) or a \u2018step-down \ndose\u2019 regime (started at 20mg) of oral methotrexate for 16 weeks. The primary efficacy endpoint was \nat least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16 and analysis \nwas by intent-to-treat. The secondary endpoints were Dermatology Life Quality Index (DLQI) and \nphysician global assessment (PGA). Tolerability and safety were assessed at all visits. \n\n\n\nResults: Forty patients received oral methotrexate treatment with equal numbers in each arm. Two \npatients from \u2018step-down dose\u2019 group discontinued study prematurely; one due to adverse effect (raised \nliver enzyme) and one withdrew due to earlier response achieved. After 16- week treatment with oral \nmethotrexate, 55% (11) of patients in \u2018step-up dose\u2019 group and 65% (13) of patients in \u2018step-down \ndose\u2019 group achieved PASI 75 (p > 0.05). A significantly higher number of patients in \u2018step-down \ndose\u2019 group achieved PASI 75 at week 4 and week 8 (p < 0.05) compared to the `step-up dose\u2019 group. \nThere was no significant difference in efficacy between the two groups from week 12 onwards. The \nphysician\u2019s global assessment (PGA) and dermatology life quality index (DLQI) were also similar in \nthe two groups at week 16. The rate of adverse events was similar in both groups. Elevation of liver \nenzymes more than 1.5 times upper normal limit was noted in 4 patients in \u2018step-down dose\u2019 group \nwhile none was noted in step-up dose\u2019 group (p > 0.05). \n\n\n\nConclusion: There was no significant difference in efficacy between both regimes at the end of 16 \nweeks study but significant efficacy was observed in patients on \u2018step-down dose\u2019 regime as early as \nweek 4. The side effect profile and tolerability were similar in both groups.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54 MJD 2014 Jul Vol 32\n\n\n\nSCABIES\nCOMPARATIVE STUDY OF THE EFFICACY OF BENZYL \nBENZOATE AND PERMETHRIN IN THE TREATMENT OF \nSCABIES \nPenny Lim Poh Lu\n\n\n\nBackground: Scabies is highly contagious ectoparasitic infestation caused by sarcoptes scabiei var \nhominis mite. In Malaysia, it is commonly found in crowded dwellings such as orphanages, boarding \nschools, dormitories, nursing homes and council flats. It causes intense pruritus especially at night \nleading to impairment in the quality of life. Mass treatment of patients and contacts is vital in a \noutbreak. The treatment should be effective, safe, well-tolerated, and preferably requiring a single \ntopical application to encourage compliance. Many available treatments are often irritating to skin, \nhave an odour and are cumbersome to use.\n\n\n\nObjective: To compare the therapeutic efficacy and to determine the safety and tolerability between \ngeneric topical permetherin (A-scab\u00ae, HOE pharmaceuticals) and topical benzyl benzoate (BB) \nlotion in the treatment of scabies.\n\n\n\nMethod: A randomized, prospective, investigator-blinded, comparative study was conducted at \nDermatology Clinic, Kuala Lumpur Hospital from June 2007 till December 2008. A total of 62 \npatients with clinically diagnosed scabies were randomized to receive either topical permetherin 5% \nlotion (A-scabs\u00ae) single application or topical benzyl benzoate lotion( 25% for adults and 12.5% for \nchildren) daily for three consecutive days. Primary end points were clinical cure and pruritus reduction. \nSecondary endpoint were clinical evolution of skin lesions and adverse effects. Study outcomes were \nassessed at baseline and then at 2 and 4 weeks after treatment.\n\n\n\nResults: 62 patients (31permetherin, A-scabs\u00ae, 31 benzyl benzoate) completed the study. At 2 weeks \npost treatment, clinical cure rate were 81.5% and 71.4% for the permethrin and benzyl benzoate \ngroups respectively (p=0.4982). Those who did not respond were treated with a repeat dose of the \nsame drug. At 4 weeks post-treatment, the cure rate remained the same in permethrin (A-scabs\u00ae) \ngroup and increased to 84.2% in the benzyl benzoate groups (p=1.0000). 5 patients in the permethrin \n(A-scabs\u00ae) group and three patients in the benzyl benzoate group had reinfestation. Burning were \nexperienced by 14 out of 27 (51.9%) in the benzyl benzoate group and only one (1.4%) patient in the \npermethrin (A-scabs\u00ae) group (p=0.001).\n\n\n\nConclusion: Permethrin (A-scabs\u00ae) was as effective in treating with single dose compared with \nsingle dose compared with three 24-hour consentive applications of benzyl benzoate in the treatment \nof scabies, and better tolerated with less adverse effects\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n55MJD 2014 Jul Vol 32\n\n\n\nVITILIGO\nEFFICACY AND SAFETY OF TACROLIMUS OINTMENT IN \nVITILIGO USING BOTH AN OBJECTIVE AND SUBJECTIVE \nMETHOD FOR THE EVALUATION OF REPIGMENTATION \nPROGRESSION\nNorashikin Shamsudin\n\n\n\nBackground: Vitiligo is an acquired pigmentary disorder characterized by depigmented patches due to \nloss of epidermal melanocytes. Tacrolimus ointment is a topical calcineurin inhibitor which has recently \nshown encouraging efficacy and safety profile in treating vitiligo. In this study, we collaborated with \nresearchers from the Universiti Teknologi Petronas to develop a computerized digital imaging analysis \ntechnique that could measure changes in lesional vitiligo skin surface area in response to treatment.  \n\n\n\nObjectives: This study aimed to evaluate the efficacy and safety of tacrolimus ointment in vitiligo \npatients objectively by using a computerized method and subjectively with the Physician\u2019s Global \nAssessment. The efficacy results from the two methods were compared.\n\n\n\nMethods: This was a prospective, open-labelled study involving 60 adult (>15 years) and 17 paediatric \n(2-15 years) patients. Upon ethical approval from the National Institute of Health, Ministry of Health \nMalaysia, tacrolimus ointment 0.1% in adult patients and 0.03% in paediatric patients were applied \non identified areas for 24 weeks and patients were followed-up thereafter for 12 weeks. Patients were \nseen once every six weeks for efficacy and safety assessment.\n\n\n\nPhotographs were taken at each visit for repigmentation analysis with the digital imaging analysis \ntechnique. The primary efficacy endpoint was the mean percentage of repigmentation as assessed \nby the computerized method (MPR-Digital) and by the Physician\u2019s Global Assessment (MPR-PGA).  \nResponse was graded from none (0%) to mild (1-25%), moderate (26-50%), good (51-75%) and \nexcellent to complete (76-100%). Safety was based on adverse events reported by the patient or \nobserved by the physician. \n\n\n\nAll statistical tests were two-sided, with the significance level of alpha = 0.05 and 95% confidence \ninterval.\n\n\n\nResults: A total of 71 patients were eligible for analysis (56 adults, 15 children). MPR-Digital: the \nmean percentage of repigmentation for adults were 18.5%\u00b1 18.8% (95% CI: 13.5-23.5%) and for \nchildren, 23.6% \u00b1 38.6% (95% CI: 2.2-45%). 44 (79%) adult and 9(60%) paediatric patients showed \nsome repigmentation to tacrolimus ointment. 3(20%) children had excellent repigmentation (76-\n100%)  and 1 (2%) adult showed good (50-75%) response.\n\n\n\nMPR-PGA: 39 (70%) adults and 10(67%) paediatric patients responded to tacrolimus ointment. 2(4%) \nadults and 2 (14%) children achieved > 50% repigmentation.\n\n\n\nLesions on the head and neck responded the best as assessed by both the computerized method (adult, \np<0.0001; paediatric, p=0.028) and the physician. The efficacy results of the computerized method \ndid not correspond well to that of the Physician\u2019s Global Assessment particularly in adults. (children, \n\u2032= 0.64; adults, \u2032=0.18). The most common side-effects were transient burning and pruritus which \nsubsided with continued use. No serious adverse effects were reported.  \n\n\n\nConclusion: Tacrolimus ointment demonstrated some efficacy and was safe in the treatment of vitiligo. \nThe computerized method did not produce comparable results with the Physician\u2019s Global Assessment. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56 MJD 2014 Jul Vol 32\n\n\n\n39th Annual\nGeneral Meeting &\nMalaysian Dermatology\nCongress\n\n\n\nOrganizers\nDermatological Society of Malaysia\n\n\n\nTheme\nChallenges in Skin, Hair & Nail Diseases\n\n\n\nVenue\nG Hotel Penang\n\n\n\nDate\n15-18 September 2014\n\n\n\nAbstract Deadline\nJuly 31st, 2014\n\n\n\nRegistration\nWebsite: www.dermatology.org.my\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n57MJD 2014 Jul Vol 32\n\n\n\nAbstract Deadline\nAugust 29th, 2014\n\n\n\nRegistration\nWebsite: www.aad.org/meetings\n\n\n\nPARTICIPATE IN THE WORLD\u2019S LARGEST\nDERMATOLOGY MEETING\n\n\n\nThe 73rd Annual Meeting\nin San Francisco\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58 MJD 2014 Jul Vol 32\n\n\n\nWelcome to the\n23rd WORLD CONGRESS\n\n\n\nOF DERMATOLOGY\n\n\n\nIMPORTANT DATES\n\n\n\nAbstract Deadline\nSeptember 2014\n\n\n\nRegistration\nWebsite: http://derm2015.org\n\n\n\n\n\n\n\n\n\n"
"\n\n27MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nKeywords cetirizine, fixed drug eruptions\n\n\n\nIntroduction\nA fixed drug eruption (FDE) is a distinct drug\ninduced reaction pattern that characteristically\nrecurs at the same site on the skin or mucosa. We\nreport a case of bullous FDE following ingestion of\ncetirizine, a common treatment for allergic\ndisorders but a rare causative agent for cutaneous\nadverse drug reaction.\n\n\n\nCase report\nA 30 year old lady presented with multiple painful\nblisters in the oral cavity and over the right wrist\nand left breast for 4 days duration. The lesions\ndeveloped within 3-4 hours after taken a single\ntablet of Cetirizine Hydrochloride which was\nprescribed for her allergic rhinitis. This was the 2nd\nepisode. She had a similar problem about 1 month\nago. She took Cetirizine for allergic rhinitis. The\nsimilar blistering lesions occurred in the oral cavity\nand over the right wrist which resolved after 1 week\nwith minimal residual hyperpigmentation. She did\nnot seek medical attention during the first episode.\nIn the past she had taken multiple courses of\n\u201cclarinase\u201d and \u201cclarityn\u201d without any complaint.\n\n\n\nOn examination, she was afebrile and well. There\nwere multiple tense bullae at the buccal mucosa and\nright wrist of various sizes ranging from 4mm -\n10mm (Figure 1 & 2). A hyperpigmented patch was\nnoted over the left breast. The blisters were\nsurrounded by an erythematous rim. There was no\nlesions elsewhere. No target lesion were seen and\nno eye and genital involvement were detected. Skin\nbiopsy, patch test and oral provocation test were not\ndone in this patient because of the clear drug history\nand the patient did not consent for the tests.\n\n\n\nADVERSE DRUG REACTIONS - Case Report\n\n\n\nCetirizine induced bullous fixed drug eruptions\n\n\n\nTan WC, MRCP, Chan LC, MMed\n\n\n\nThe patient was counselled on medication\navoidance and possible cross-reactions of similar\nmedications such as cetirizine, hydroxyzine,\nlevocetirizine and ethylenediamine. She was given a\nshort course of oral prednisolone, in a tapering\ndose, for 2 weeks. The lesions improved and healed\nwith residual hyperpigmentation.\n\n\n\nCorrespondence\nTan Wooi Chiang, MRCP\nDepartment of Dermatology, Penang Hospital\nJalan Residensi, 10990 Penang\nE-mail : tanwooichiang@yahoo.com\n\n\n\nFigure 1 Tense bullae with erythematous \nrim over the right wrist\n\n\n\nFigure 2 Circular hyperpigmented lesions \nover the lip with superficial \nerosions\n\n\n\n\n\n\n\n\n28 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nBrocq first introduced the term \u201cfixed drug\neruption\u201d in 18941. The term FDE describes the\ndevelopment of one or more annular or oval\nerythematous patches as a result of systemic\nexposure to a drug. These reactions normally\nresolve with hyperpigmentation and may recur at\nthe same site with re-exposure to the drug2.\nRepeated exposure to the offending drug may cause\nnew lesions to develop in addition to \u201clighting up\u201d\nthe older hyperpigmented lesions.\n\n\n\nThe pathogenesis of FDE is still enigmatic. The\nmost commonly accepted hypothesis is the\npersistence of memory T cell in the affected skin3.\nCD8+ cells phenotypically resembling effector\nmemory T cells have been shown to be greatly\nenhanced in the lesions of FDE. \n\n\n\nThe skin lesion of FDE usually starts as an\nerythematous macule then subsequently evolves\ninto a plaque. Vesicles and bullae develop at a later\nstage. The lesions can occur on any part of the skin\nand mucous membranes. The sites of predilection\nare the genitalia, limbs, sacral region, palmar and\nplantar area. The oral mucosa may be involved in\nassociation with skin lesions or in isolation. \n\n\n\nMore than 100 drugs have been implicated in FDE\nbut the causative drugs that are commonly\nassociated with FDE include co-trimoxazole,\ntetracycline, non-steroidal anti inflammatory drugs\n(NSAIDs), phenytoin, griseofulvin, salicylates,\npenicillin and phenolphthalein4. It has also been\ndescribed as a side-effect of some anti-H1-\nantihistamine drugs, such as cyclizine lactate,\ndiphenhydramine hydrochloride, phenothiazines,\nhydroxyzine5 and loratadine6. To the best of our\nknowledge, there were only a few cases of FDE\nsecondary to cetirizine being reported7-8. \n\n\n\nCetirizine is a specific histamine H1-receptor\nantagonist and a second-generation antihistamine\nand generates the lowest rate of cutaneous\nreactions. Cetirizine is used worldwide in the\ntreatment of allergic disorders and is generally well\ntolerated without much problem. Although topical\nantihistamines commonly leads to sensitization and\ncan cause contact and photo-contact dermatitis9,\nskin reactions provoked by their systemic use is\nrare10-11.  \n\n\n\nCross-reactions among ethylenediamine, cetirizine\nand hydroxyzine had been reported by Bark-Lin\nLew et al12. Cutaneous reactivity to the H1-\nantihistamines is caused by the fact that they share\nthe same chemical piperazine structure and similar\npharmacologic profiles12-13. In vivo, 45% of\nhydroxyzine is transformed into cetirizine and\nlevocetirizine is the active (R)-enantiomer of\ncetirizine5.\n\n\n\nOral challenge can be used to confirm the etiology\nof FDE14. But there are risks involved in this\napproach, mainly anaphylactic reactions or intense\nlesional reactivation with a significant increase in\nthe number of lesions.\n\n\n\nPatch testing is not regularly performed.\nReappearance of skin lesions with re-challenge\nidentifies offending agent. Furthermore, reactivity\nof patch tests in FDE is variable. Some study\nshowed patch testing at the site of a previous lesion\nyields a positive response in up to 43% of cases15,\nbut the reactivity depends on the drug and the\nvehicle. Reactivity is usually seen before 24 hours\nand is observed exclusively on the lesional skin.\nPatch testing is safer than oral provocation tests. It\nalso allows the study of several drugs at the same\ntime. \n\n\n\nPhysicians should watch carefully for eruptions\nfrom antihistamines and not to misinterpret them as\nunresponsiveness to the medications. Because oral\nantihistamines are one of the most common\nmedications used to treat itchy dermatoses, it is\nprudent to listen to patients when they indicate that\nthese medications seem to worsen their condition.\n\n\n\nThis report highlights an uncommon causative\nagent of FDE.\n\n\n\nReferences\n\n\n\n1. Brocq I. Eruption erythemato-pigmentee fixe due al\u2019\nantipyrine. Ann Dermatol Venereol. 1894; 5: 308-13.\nQuoted from: Shiohara T, Nickoloff BJ, Sagawa Y,\nGomi T et al. Fixed drug eruption. Expression of\nepidermal keratinocyte intercellular adhesion\nmolecule-1 (ICAM-1). Arch Dermatol 1989; 25:\n1371-6\n\n\n\n2. Lee AY. Fixed Drug Eruptions: Incidence, recognition,\nand avoidance. Am J Clin Dermatol 2000; 1(5):277-85\n\n\n\n\n\n\n\n\n29MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3. Shiohara T, Nickoloff BJ, Sagawa Y, Gomi T et al. Fixed\ndrug eruption. Expression of epidermal keratinocyte\nintercellular adhesion molecule-1 (ICAM-1). Arch\nDermatol 1989; 25: 1371-6\n\n\n\n4. Magee P. Drug-induced skin disorders. In: Walker R,\nEdwards C \u2018editors\u2019. Clinical Pharmacy and\nTherapeutics. 3rd edition. Phildelphia: Churchill\nLivingstone 2003; 843-52\n\n\n\n5. Mahajan VK, Sharma NL, Sharma VC. Fixed drug\neruption: a novel side-effect of levocetirizine. Int J\nDermatol 2005; 44: 796-798\n\n\n\n6. Pionetti CH, Kien MC, Alonso A. Fixed drug eruption\ndue to loratadine. Allergol Immunopathol (Madr) 2003;\n31: 291-293\n\n\n\n7. Inamadar AC, Palit A, Athanikar SB, Sampagavi VV,\nDeshmukh NS. Multiple fixed drug eruptions due to\ncetirizine. Br J Dermatol 2002; 147: 1025-6\n\n\n\n8. Kranke B, Kern T. Multilocalized fixed drug eruption\nto the antihistamine cetirizine. J Allergy Clin Immunol\n2000; 106: 988\n\n\n\n9. Kulthanan K, Tiprungkorn P, Linpiyawan R. Cutaneous\nreaction to oral antihistamine. Clin Exp Dermatol\n2003; 28: 229-30\n\n\n\n10. Spencer CM, Faulds D, Peters DH. Cetirizine: a\nreappraisal of its pharmacological properties and\ntherapeutic use in selected allergic disorders. Drugs\n1993; 46: 1055-80\n\n\n\n11. Campoli-Richards DM, Buckley MMT, Fitton A.\nCetirizine: a review of its pharmacological properties\nand clinical potential in allergic rhinitis, pollen-induced\nasthma, and chronic urticaria. Drugs 1990; 40: 762-81\n\n\n\n12. Lew BL, Haw CR, Lee MH. Cutaneous drug eruption\nfrom cetirizine and hydroxyzine. J Am Acad Dermatol.\n2004; 50(6): 953-6\n\n\n\n13. Assouere MN, Mazereeuw-Hautier J, Bonafe JL.\nCutaneous drug eruption with two antihistaminic drugs\nof the same chemical family: cetirizine and\nhydroxyzine. Ann Dermatol Venereol 2002; 129:\n1295-1298\n\n\n\n14. Kauppinen K, Stubb S. Fixed eruptions: causative\ndrugs and challenge tests. Br J Dermatol 1985; 112:\n575-578.\n\n\n\n15. Barbaud A, Reichert-Penetrat S, Trechot P, et al. The\nuse of skin testing in the investigation of cutaneous\nadverse drug reactions. Br J Dermatol 1998; 139: 49-\n58.\n\n\n\n\n\n\n\n\n30 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nVitamin K injection is a common treatment for the\nprevention of bleeding. It acts by promoting the\nformation of liver coagulation factor II, VII, IX and\nX. Anaphylactic reaction with the use of this\nproduct is rare and suspected to be caused by its\nnon-ionic solubilizing and emulsifying agent;\nCremophor EL formulated in Vitamin K Injection\n(KISAN\u00ae 10mg/ml)1,2. The main component of\nCremophor EL is glycerol-polyethylene glycol\nricinoleate. It is widely used as a formulation\nvehicle for various poorly-water soluble drugs\nincluding the lipid soluble vitamin A, D, E and K.\nExtra precautions should be taken when\nadministering pharmaceutical products containing\n\n\n\nADVERSE DRUG REACTIONS - Update\n\n\n\nIntravenous Vitamin K Administration\n\n\n\nNorkasihan Ibrahim, Fadilah Othman, Norliza Mat Ariffin, Zainon Abudin\n\n\n\nCremophor EL. This agent has been found to cause\nsevere anaphylactoid-like reaction especially when\nhigh doses are administered via bolus infusion1,2. It\nis recommended to dilute Vitamin K Injection\n(KISAN\u00ae 10mg/ml) in normal saline, dextrose 5%\nor dextrose saline to a concentration not exceeding\n1mg/ml. The diluted product should be infused for\nnot less than 30 minutes1,2.\n\n\n\nReferences\n\n\n\n1. KISAN\u00ae Injection 10mg/ml Product Information\nLeaflet\n\n\n\n2. Cremophor EL the drawbacks and advantages of\nvehicle selection for drug formulation.\n\n\n\nCorrespondence\nNorkasihan Ibrahim \nDepartment of Pharmacy, Selayang Hospital Selangor\nE-mail : NrKasihan@selayanghospital.gov.my\n\n\n\n\n\n\n\n\n31MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDear Editor,\nWe have encountered a 42 year old Malay lady with\nantiphospholipid syndrome for the past 3 years\npresented with red cutaneous swelling at both\ndeltoid regions a week after given intramuscular\nVitamin K injection. She was referred to us 6 weeks\nfollowing the Vitamin K injection. Psoriasiform\nplaques with perilesional warm erythematous skin\nwere noted over both deltoid regions (Figure 1). A\nskin biopsy (Figure 2a & 2b) showed subepidermal\nvesicular change with formation of bullae including\n\n\n\nADVERSE DRUG REACTIONS - Short Communication\n\n\n\nHypersensitivity reaction to intramuscular Vitamin K \n\n\n\nRaoul RS1, MBBS, Rohna R, MRCP, Shalini Kumar2, MPath\n\n\n\nbasal cell vacuolation and necrotic keratinocytes.\nThe upper dermis was infiltrated with mononuclear\ninflammatory cells. The features are in keeping\nwith a hypersensitivity reaction.\n\n\n\nA diagnosis of hypersensitivity reaction to Injection\nVitamin K was made based on the history and skin\nbiopsy. The skin lesions flattened and became\nhyperpigmented after two weeks application of\npotent topical steroid and oral antihistamine.\n\n\n\nCorrespondence\nRaoul Roger Sibert, MBBS \n1Department of Dermatology\nSelayang Hospital, Selangor\nE-mail : raoul@selayanghosp.gov.my\n\n\n\n2Department of Pathology, Selayang Hospital\n\n\n\nFigure 1 Lesion at right deltoid Figure 2A HPE of skin biopsy at 4X magnification  \n\n\n\nFigure 2B HPE of skin biopsy at 40X magnification \n\n\n\n\n\n\n\n\n32 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nVitamin K1 (Phytomenadione) is a fat soluble,\nnaturally occurring vitamin used to treat certain\ncoagulation disorders1. Injectable vitamin K can\ncause skin reactions whatever the dose and mode of\ninjection2. The first few cases of hypersensitivity to\nvitamin K were reported in patients with liver\ndisease. The pathophysiological mechanism of the\nacute form would involves type IV allergy to\nPhytomenadione3. There are three distinct types of\ncutaneous reactions to vitamin K1: localized\neczematous, localized morphea-form4-5, and, very\nrarely, diffuse maculopapular eruption2. The\neczematous type appears at the site of injection.\n\n\n\nThe morphea-form type is a localized morphea-\nform patch that appears at the site of injection. The\ndiagnosis of an adverse cutaneous reaction to\nvitamin K can be made if the possibility is\nconsidered. Many of these reactions are very slow\nto clear up and some may persist as a chronic\nsclerodermoid change4-5. Managing may be\nfrustrating for both the patient and the clinician. \n\n\n\nIn our patient, the localized psoriasiform dermatitis\nwith perilesional erythema and oedema was treated\nwith topical steroids and resolved with post-\ninflammatory hyperpigmentation.\n\n\n\nReferences\n\n\n\n1. Gimenez-Arnau, A.M., A. Toll, and R.M. Pujol,\nImmediate cutaneous hypersensitivity response to\nphytomenadione induced by vitamin K in skin\ndiagnostic procedure. Contact Dermatitis 2005; 52(5):\n284-5\n\n\n\n2. Moreau-Cabarrot, A., F. Giordano-Labadie, and J.\nBazex, [Cutaneous hypersensitivity at the site of\ninjection of vitamin K1]. Ann Dermatol Venereol,\n1996; 123(3): 177-9\n\n\n\n3. Bruynzeel, I., et al., Cutaneous hypersensitivity\nreactions to vitamin K: 2 case reports and a review of\nthe literature. Contact Dermatitis 1995; 32(2):78-82.\n\n\n\n4. Finkelstein, H., M.C. Champion, and J.E. Adam,\nCutaneous hypersensitivity to vitamin K1 injection. J\nAm Acad Dermatol, 1987; 16(3 Pt 1): 540-5.\n\n\n\n5. BK Pang, V Munro, S Kossard. Pseudoscleroderma\nsecondary to phytomenadione (vitamin K1) injections:\nTexier's disease. Australasian Journal of Dermatology,\n1996 - interscience.wiley.com\n\n\n\n\n\n\n\n\n33MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nKeywords autoimmune bullous disease,\npemphigus, thymoma, paraneoplastic\n\n\n\nIntroduction\nPemphigus foliaceous (PF) is an autoimmune\nblistering disease resulting from acquired\nimmunoglobulin G autoantibodies against\ndesmoglein 1 of the skin, which is one of the\nadhesion molecules of keratinocytes. Clinically\npatients with PF develop crusted and scaly erosions\nmainly over the seborrhoeic distribution i.e. the\nface, scalp and upper trunk. Mild cases of PF may\nbe localized but in some cases it may progress to\nerythrodermic exfoliative dermatitis. There is\nhowever no mucosal involvement in PF in contrast\nto pemphigus vulgaris and paraneoplastic\npemphigus. Light microscopy of lesional biopsy\nshows subcorneal acantholysis. Direct\nimmunofluorescence study of perilesional skin\nreveals presence of intraepithelial intercellular\ndeposit of IgG and C3. We describe 2 cases of PF in\nthe presence of thymoma, a relatively rare\nassociation, which could further support the fact of\nthymoma associated autoimmune disease.\n\n\n\nCase report 1\nA 35-year-old Malay painter, presented to us in\nAugust 2008 with a month history of flaccid blisters\nstarting over the anterior chest, progressively\ninvolving the face, arms, abdomen, legs and then\nbecame generalized. There was no oral or genital\ninvolvement. The lesions were not aggravated by\nsun exposure. There was no significant drug\nhistory. There were no other constitutional\nsymptoms. On further questioning, the patient was\ndiagnosed to have a thymoma after being\n\n\n\nAUTOIMMUNE DISORDERS - Case Report\n\n\n\nPemphigus foliaceous and thymoma: a report of 2 cases\n\n\n\nTang MM1, AdMDerm, Lee YY2, AdMDerm, Suganthi T1, MMed (UKM)\n\n\n\ninvestigated for difficulty in swallowing and\nchanges of voice in 2006. He was advised for\nsurgical resection of the mediastinal mass by\ncardiothoracic surgeon. He however declined any\nform of surgery and defaulted subsequent follow\nup.\n\n\n\nOn examination, the patient was afebrile. His blood\npressure was normal but has tachycardia. He was\nerythrodermic with erosions and crusts over the\nface, scalp, chest, back, arms and thighs sparing the\noral mucosal and genitalia. Examination of other\nsystems revealed no abnormality.\n\n\n\nSkin biopsy of lesion demonstrated subcorneal\nbullae with acantholytic cells (Figure 1). The direct\nimmunofluorescence study showed strong\nintraepidermal IgG deposits (Figure 2).\n\n\n\nThese confirmed the clinical diagnosis\nof pemphigus foliaceous. His indirect\nimmunofluorescence study showed a titre of 1:320.\nHis blood counts were normal with ESR of\n35mm/hr. Full blood picture showed leucocytosis\nwith predominant neutrophils, toxic granulation\nwere seen but immature cell were absent. His\nalanine aminotransferase was 283U/l (normal 0-41\nU/l) Serology tests for HepBsAg, Anti Hep C\nantibody, anti-HIV-1&2, anti-smooth muscle\nantibody were negative. Ultrasound of abdomen\nshowed normal liver echogenicity and echotexture\nwith no other abnormality. His chest radiograph\nrevealed a mass at the right mid zone, obliterating\nthe right heart border (Figure 3).\n\n\n\nDue to the severity of his skin lesions, the patient\nwas admitted and initially given intravenous\nhydrocortisone 100mg 8hrly. Multiple courses of\nintravenous antibiotic were given for the\nsuperimposed bacterial infection of the eroded skin.\nThe skin lesions progressed further despite with\nabove treatment and aggressive skin nursing care.\nSteroid sparing immunosuppresants such as\nazathioprine, mycophenolate mofetil and\nmethotrexate were not considered due to hepatitis.\nDue to the poor response after 3 weeks of\nintravenous hydrocortisone, we initiated pulse\ndexamethasone \n\n\n\nCorrespondence\nTang MM, AdMDerm\n1Department of Dermatology, Hospital Kuala Lumpur\nE-mail : minmoon2005@yahoo.com\n\n\n\n2Department of Dermatology\nUniversity Malaya Medical Centre\n\n\n\n\n\n\n\n\n34 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 1 The skin biopsy showed superficial subcorneal \nbulla with collection of neutrophils. Haematoxylin \nand Eosin stain x400\n\n\n\nFigure 3 Presence of a mass at the right mid zone on \nthe chest radiograph\n\n\n\nFigure 4 Computed tomography of thorax showed a heterogeneously enhancing anterior mediastinal mass measuring \n5.5x5.6cm on the right mid thoracic level\n\n\n\nFigure 2 Positive deposition of Ig G of the intraepithelial and \nintercellular spaces. (Direct immunofluorescence \nstain IgG x200) \n\n\n\n\n\n\n\n\n35MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ndexamethasone-cyclophosphamide (DCP) regime\nafter obtained consent from the patient. This regime\nwas modified to include oral prednisolone at\n0.5mg/kg/day, after the first 2 pulses, the skin\nlesions stopped progressing and healed gradually.\nFurther investigation included a CT thorax which\nshowed a heterogeneously enhancing anterior\nmediastinal mass measuring 5.5 x 5.6cm on the\nright mid thoracic level. There was calcification\nwithin the mass. There was clear demarcation with\nthe adjacent vessels. The mediastinal lymph nodes\nwere not enlarged and there were no lung nodules or\npleural effusion (Figure 4). Fatty liver was also\nnoted in the CT scan. His carcinoembryonic antigen\n(CEA) was 11.1U/l Units (twice above the upper\nnormal limit) Other tumour markers included\nlactate dehydrogenase and alpha fetoprotein were\nnot elevated. Computed tomography guided biopsy\nconfirmed a type A thymoma.\n\n\n\nThe patient was repeatedly counseled on the need\nfor surgical excision of the thymoma as the\npemphigus foliaceous which could be a\nparaneoplastic manifestation may probably resolve\npost-thymectomy. However the patient adamantly\nrefused surgical intervention. He subsequently\nunderwent 11 pulses of DCP and he has been lesion\nfree for the past 4 months.\n\n\n\nCase report 2\nA 43-year-old Chinese lady presented to us in\nMarch year 2004 with 2-week history of erosions\nstarted over the neck which became generalized.\nThere were however no oral or genital ulcers. She\nwas diagnosed to have malignant thymoma in 1997\nand had thymectomy done in the same year. She\nwas also suffering from end stage renal failure due\nto chronic glomerulonephritis in 1999 and had a\ncadaveric renal transplant done in China in 2001.\nAfter the renal transplant, she was prescribed a few\nimmunosuppressants which included oral\nprednisolone, high dose of oral cyclosporine and\noral mycophenolate mofetil. She had recurrence of\nthymoma in 2002 and was re-operated followed by\n30 fractions of radiotherapy. Unfortunately she\ndeveloped another recurrence of the thymoma at the\nend of 2003 and the tumour was deemed\ninoperable. She was referred to Oncology team and\nwas offered chemotherapy. However she declined.\nThe dosage of cyclosporine was reduced and\nmycophenolate mofetil was stopped.\n\n\n\nClinically she was anemic. She was not jaundiced.\nThere were no lymph nodes palpable. She had\n\n\n\nerosions with crust over the face, chest, back,\nabdomen and limbs. There was crust over the\nlower lip but there were no oral or genital ulcers.\nThere was also no hepatosplenomegaly or\nlymphadenopathy.\n\n\n\nSkin biopsy demonstrated subcorneal blister with\npresence of intraepithelial intercellular deposits of\nimmunoglobulin G and C3 and these confirmed the\ndiagnosis of pemphigus foliaceous. Her\nhaemoglobin was 6.7g/dl with reticulocyte count of\n6.8%. Her direct Coomb\u2019s test was positive but the\nserum bilirubin was not raised. Her full blood\npicture revealed normocromic normocytic anaemia\nwith features of combined iron and folate\ndeficiency, and there was no active haemolysis\nnoted. Her upper endoscopy and colonoscopy\nshowed normal findings. She had a positive\nhomogenous antinuclear antibody test but her\nextractable nuclear antibody and anti ds-DNA\nantibody were non reactive. Her renal profile and\nliver function tests were also normal. Computed\ntomography of the thorax showed a solid mass at\nanterior lower mediastinum with multiple right\nparacardiac lymph nodes.\n\n\n\nPrednisolone at the dose of 1mg/kg/day was started\ninitially and new erosions ceased to form and pre-\nexisting lesion healed slowly. There were no other\nsteroid sparing agents added while the cyclosporine\nwas maintained at 25mg bd. Nevertheless she\ndeveloped new lesions each time when the\nprednisolone was tapered below 20mg/day. She was\nat the same time co-managed by oncology team and\nnephrology team. The malignant thymoma had\nincreased in size in 2007 and she had right pleural\neffusion, enlarged mediastinal lymph nodes and\nliver metastasis. She was given 6 cycles of palliative\nchemotherapy consisting of Doxorubicin, Cisplatin\nand Cyclophosphamide every 3 weeks. At the end\nof the chemotherapy, the thymoma shrank, the liver\nmetastasis resolved and the right lower thorax\npleural effusion was slightly improved. The skin\ncondition was well controlled at that point of time\nwith oral prednisolone 15-20mg a day.\n\n\n\nUnfortunately she deteriorated rapidly in\nSeptember 2008 when she developed ascites, ankle\noedema and right pleural effusion. She was\ndependant on continuous nasal oxygen therapy and\nher symptoms were only slightly controlled with\nsymptomatic treatment and oral dexamethasone.\nShe was then finally succumbed to the disease at\nhome in October 2008.\n\n\n\n\n\n\n\n\n36 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nThymoma is the commonest primary mediastinal\ntumour in the adult population with those\nassociated with paraneoplastic syndromes, tend to\noccur at younger age group1. It has been associated\nwith many paraneoplastic syndromes such as the\nneuromuscular syndrome with Myasthenia Gravis\nbeing the most common (30-45%); hematologic\nsyndromes; collagen and autoimmune disorders;\nimmune deficiency syndromes; dermatologic\ndisorders; endocrine disorders; gastrointestinal\ndisorders and renal disease2. Pemphigus, alopecia,\nchronic candidiasis. have rarely been reported to\nsporadically occur in the presence of thymoma.\n\n\n\nBoth our patients presented with history of\nthymoma a few years prior to the onset of cutaneous\nmanifestations. They developed superficial erosions\nwithout any mucous membrane involvement. There\nwas no history to suggest myasthenia gravis. The\nhistopathologic and direct immunofluorescence\nfeatures confirmed pemphigus foliaceus. The\nclinical manifestations were not suggestive of a\ntypical natural history paraneoplastic pemphigus\n(PNP). There was no intractable stomatitis which is\nthe most constant feature of PNP3. Besides, the\ncutaneous lesions in PNP are usually polymorphic\nincluding macules, tense blisters, erosions, EM-\nlike, lichenoid and GVHD-like3. In both our cases,\nthere were only erosions with no other form of\nlesions. In addition, the histopathology of PNP is\nalso variable including a combination of PV-like,\nEM-like, LP like histological features i.e.\nintraepidermal suprabasal acantholytic blister;\ninterface dermatitis with vacuolar degeneration of\nbasement membrane zone, necrotic keratinocytes,\nsuperficial perivascular lymphocytic infiltrates and\nlichenoid dermatitis3. Direct immunofluorescence\nshows IgG and complement on intercellular spaces\nof keratinocytes and basement membrane\nzone. These were not present in our patients.\nPositive staining of rat urothelium on indirect\nimmunofluorescence is another diagnostic criteria\nfor PNP but this test is not available in this country.\n\n\n\nThe coexistence of thymoma and pemphigus was\nfirst reported in 1964 by Kough & Barners and\nsince then case reports have appeared sporadically\nin the literature. The subtypes of pemphigus that\nwere indentified to be associated with thymoma in\nthe literature include pemhigus vulgaris, pemphigus\nfoliaceous and pemphigus erythematosus. The\n\n\n\ntypes of thymoma reported ranged from benign to\nmalignant. It is still not understood exactly how\nthymic neoplasms are associated with pemphigus.\nThe thymus gland is important in the\nimmunological make-up of an individual. It is\npostulated that the altered constituents of the\nthymus may act as antigens which may mimic\nepidermal intercellular adhesion molecules in\npemphigus, which induce autoantibodies that react\nagainst the epidermal intercellular adhesion\nmolecules. This is supported by the development of\nantibodies against intercellular adhesion molecules\nin 3 patients with thymomas without clinically\napparent pemphigus reported by Imamura et al4.\nTakeshita K et al in 2000 also reported a case of\nthymoma associated with pemphigus foliaceous\nwho had underwent total thymectomy which\nresulted in the resolution of cutaneous lesions and\nreduction of serum anti-Dsg 1 antibody5.\n\n\n\nIn our first patient, his skin lesions were not well\ncontrolled with high dose of systemic steroid. Pulse\ndexamethasone-cyclophosphamide (DCP) was used\nnot only because of the severity of the skin\ncondition but also because other agents such as\nazathioprine and MMF were contraindicated in the\nface of hepatitis. The skin lesions resolved on the\nDCP regime with oral prednisolone and oral\ncyclophosphamide in between pulses. The patient\nrefuses surgical intervention despite extensive\ncounseling. We are currently exploring other\nmodality of treatment such as chemotherapy or\nradiotherapy for the thymoma. Interestingly,\nLoehrer PJ et al reported a 50% response rate in\npatients with unresectable / advance thymoma\ntreated with the PAC regime (combination of\ncisplatin, doxorubicin and cylcophosphamide)6.\nThis paper made us wonder if the\ncyclophosphamide, which is a known agent in the\ntreatment of thymoma administered in our patient,\nhalted the progression of his thymoma through its\nantimitotic property.\n\n\n\nOur second patient had a rather complex\ncombination of malignant thymoma, chronic\nglomerulonephritis leading to end stage renal\nfailure with renal transplant and pemphigus\nfoliaceus. It is unclear whether the chronic\nglomerulonephritis could be part of the disorders\nassociated to epithelial thymic tumour. Besides, her\ntreatment with immunosuppressive agents such as\nhigh dose cyclosporine, mycophenolate mofetil and\n\n\n\n\n\n\n\n\n37MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nprednisolone post renal transplant might play a role\nin escalating her tumour progression as she\nexperienced the first relapse of thymoma a year\nafter the renal transplant. Studies have shown that\norgan-transplant recipients have an increased\nincidence of cancer as compared with an age-\nmatched healthy population or with patients\nundergoing dialysis. London NJ et al found that\nafter 20 years of immunosuppressive therapy, 40\npercent of recipients had cancer7. Sasaki et al\nreported immune suppression may have been a\ncontributing factor in the induction of thymoma8. In\nour patient, the dose of cyclosporine was reduced\nand the MMF was taken off successfully without\ncompromising the renal graft function. However the\nthymoma progressed for the next 4 years since the\ndiagnosis of pemphigus folicaceous and she\nsuccumbed to her malignancy with metastases. The\naggressive nature of her malignant thymoma was\nthe main contributing factor to the mortality. Her\nskin lesions were well controlled few months before\nshe passed away, probably because she received a\ncycle of palliative chemotherapy consisting of\nDoxorubicin, Carboplatin and Cyclophosphamide\nand also dexamethasone in her palliative care\nperiod.\n\n\n\nIn conclusion, we reported 2 cases of pemphigus\nfoliaceous associated with thymic neoplasms which\ncould be the manifestations of immune system\ninstability. Based on our experience managing these\n2 patients, it is pertinent for us to seriously consider\nthe possibility of thymoma if there is abnormal\n\n\n\nmediastinal widening or mass in the chest\nradiograph of patients presenting with pemphigus\nfoliaceous. Further studies are needed to analyze\nthe pathogenesis of the natural course of pemphigus\nfoliaceous co-existing with, or after discovery of\nthymoma and also the role of thymectomy in\nrelation to the natural course of the cutaneous\nmanifestations.\n\n\n\nReferences\n\n\n\n1. Detterbeck FC, Parsons AM. Thymic tumors. Ann\nThorac Surg 2004;77: 1860-9\n\n\n\n2. Venuta F, Anile M, Diso Daniele et al. Thymoma and\nthymic carcinoma. Eur J Cardiothorac Surg (2009),\ndoi:10.1016/ j.ejcts.2009.05.038\n\n\n\n3. Camisa C, Helm TN. Paraneoplastic pemphigus is a\ndistinct neoplasia-induced autoimmune disease. Arch\nDermatol 1993;129:883-6\n\n\n\n4. Imamura S, Takigawa M, Ikai K, Yoshinaga H, Yamada\nM. Pemphigus foliaceus, myasthenia gravis, thymoma\nand red cell aplasia. Clin Exp Dermatol 1978; 3: 285-\n291\n\n\n\n5. Takeshita K, Amana M, Shimizu T et al. Thymoma with\npemhigus foliaceous. Int Med 2000; 39:742-747\n\n\n\n6. Loehrer Sr PJ, Chen M, Kim K et al. Cisplatin,\ndoxorubicin and cyclophosphamide plus thoracic\nradiation therapy for limited stage unresectable\nthymoma: and intergroup trial. J Clin Oncol 1997;\n15:3093-9\n\n\n\n7. London NJ, Farmery SM, Will EJ, Davison AM, Lodge\nJP. Risk of neoplasia in renal transplant patients. Lancet\n1995;346:403-6\n\n\n\n8. Sasaki J, Saito A, Hoshino M, Yanagawa S, Mizoguchi\nM, Takahashi H. A case of pemphigus vulgaris with\nmediastinal tumor, a case report and literature review.\nHifukano Rinsho (Rincho Derma) 31: 479-483, 1989\n\n\n\n\n\n\n\n\n38 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nIntroduction\nPemphigus erythematosus (PE) is an autoimmune\nbullous disease where the antibody is directed at\ndesmoglein 1, a desmosomal protein important in\nkeratinocyte adhesion, resulting in intraepidermal\nbullae. Pemphigus erythematosus also known\nas Senear-Usher syndrome, is a variant of\nsuperficial pemphigus with features of both\nlupus erythematosus and pemphigus. The skin\nbiopsy exhibits histopathological and direct\nimmunofluoresence features of both lupus\neythematosus and pemphigus i.e. granular IgG and\nC3 at the basement membrane zone and\nintercellular IgG and C3 on the cell surface of\nkeratinocytes with circulating antinuclear\nantibodies in the blood. We describe an interesting\ncase of a Myanmar refugee with pemphigus\nerythematosus presenting with cutaneous features\nresembling lupus erythematosus.\n\n\n\nAUTOIMMUNE DISORDERS - Case Report\n\n\n\nMimicry of the great mimicker\n\n\n\nLee YY, AdMDerm, Priya GP, MRCP, Suganthi T, MMed\n\n\n\nCase report\nA 26-year-old Myanmar refugee presented in April\n2009 with four months history of erythematous\npapules, pustules and blisters over both her cheeks\n(Figure 1). The lesions progressed to involve her\nwhole face, anterior chest wall, arms and trunk with\nno oral or genital involvement. There was no\nprevious similar skin rash. The lesions were pruritic\nbut not painful.\n\n\n\nThe erythema was aggravated by sun exposure.\nHowever, she was systemically well. There were no\nsymptoms suggesting an underlying connective\ntissue disease, such as joint pain, hair loss, oral\nulcers or muscle weakness. She denied recent\nintake of new medicines, traditional medications, or\nsupplements.\n\n\n\nCorrespondence\nPriya Gill, MRCP (UK)\nDepartment of Dermatology, Hospital Kuala Lumpur\nWilayah Persekutuan, Malaysia\nE-mail : drpriya74@yahoo.com\n\n\n\nFigure 1 Extensive, erythematous papules \nand pustules involving the malar \nregions bilaterally\n\n\n\nFigure 2 Pemphigus Erythematosus\nHistopathology: A subcorneal blister is filled with \nacantholytic keratinocytes and numerous \nneutrophils.  The granular layer is diminished but \ndyskeratotic acantholytic granular cells are not seen \nin this case. (H&E 200X)\n\n\n\n\n\n\n\n\n39MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nClinically, there were extensive erosions with\nerythematous crusts and scales involving the malar\nregion, anterior trunk and entire back. There were\nalso a few intact flaccid bullae on the upper limbs\nand back. However, there was no Raynaud\u2019s\nphenomenon or cutaneous vasculitic changes.\nExamination of other systems was normal.\nThe provisional diagnosis was pemphigus\nerythematosus with a differential of pemphigus\nfoliaceus and acute cutaneous lupus erythematosus. \n\n\n\nSkin biopsies were performed from 2 sites; an\nerythematous, scaly patch from the left cheek and a\nflaccid bulla from the right forearm. The first\nbiopsy showed follicular plugging, mild oedema\nof the upper dermis with perivascular\nand periappendegeal infiltration by chronic\ninflammatory cells plus focal basal cell\nvacuolation. The second biopsy demonstrated\nsubcorneal bullae containing few neutrophils\nand acantholytic cells (Figure 2). Direct\nimmunofluorescence showed moderately strong\nintraepidermal and dermo-epidermal junction IgG\ndeposits. These confirmed the clinical diagnosis of\npemphigus erythematosus.\n\n\n\nThe full blood counts, renal profile, liver function\nand serum complements were normal. Anti nuclear\nantibody and extractable nuclear antibody were non\nreactive. There was microscopic hematuria which\ncould be attributed to a Klebsiella urinary tract\ninfection. \n\n\n\nThe patient was admitted to the dermatology ward\nand subjected to intensive skin nursing. She was\nprescribed intravenous hydrocortisone 100mg 8\nhourly and oral Cefuroxime Axetil (for urinary tract\ninfection) and  improved dramatically over the next\n5 days. The patient requested an early discharge and\nwas discharged on Prednisolone 45mg daily,\ncalcium carbonate 600mg twice daily, _-calcidiol\n0.5mg daily, titanium dioxide as a sun block and\ntopical betamethasone valerate 0.025% twice daily.\nWe planned to add on oral Azathioprine 100mg\ndaily as a steroid sparing agent on follow up.\n\n\n\nUnfortunately, she defaulted her follow up and was\nnot contactable thereafter. \n\n\n\nDiscussion\nPemphigus erythematosus (PE), also known as\nSenear-Usher syndrome is an antibody-mediated\nautoimmune bullous disease with combined\n\n\n\nfeatures of pemphigus foliaceous and\nlupus erythematosus. The term \u2018pemphigus\nerythematosus\u2019 was initially coined to describe\npatients with immunological features of both lupus\nerythematosus and pemphigus foliaceous. PE\nrepresents approximately 8% of all cases of\npemphigus. In pemphigus foliaceous, antibodies\nwere directed at desmoglein 1, a desmosomal\nprotein important in keratinocyte adhesion.\n\n\n\nHistopathology and direct immunofluorescence\nexamination of PE elucidate features of both lupus\nerythematosus and pemphigus, i.e. granular IgG\nand C3 at the basement membrane zone and\nintercellular IgG and C3 on the cell surface of\nkeratinocytes in a fishnet appearance 1.\n\n\n\nPE affects mainly middle-aged adults and manifests\nitself on sun-exposed areas as flaccid bullae with\nscales and crusts. The main areas of distribution\ninclude the scalp, face, upper chest and back. Facial\nmanifestations are localized to the typical butterfly\ndistribution as seen in lupus erythematosus (LE)2,3.\nPemphigus and LE have been reported to coexist in\nthe same patient. However, the incidence of the co-\nexistence is low. Most of these patients are non-\nCaucasian females in their reproductive age groups,\nwhich is similar to LE. In a review conducted by\nMohsin Malik et al, majority of these patients had\npemphigus vulgaris (PV) and less commonly the\nother variants of pemphigus4.\n\n\n\nOur patient, presented with a history and clinical\nexamination suggestive of LE such as\nphotosensitivity and malar rash. The bullae also led\nus to think of bullous lupus erythematosus.\nHowever, the connective tissue screening was\nunremarkable with a negative anti nuclear factor\n(ANA) and extractable nuclear antibody (ENA).\nThe confirmatory diagnosis of PE was only\nelucidated from the skin histopathological and\ndirect immunofluorescence examination whereby\nthere were features of both pemphigus foliaceous\nand lupus erythematosus.\n\n\n\nThe natural course of PE is relatively milder, more\nsteroid sensitive and carries a better prognosis5.\nTreatment for PE has relied heavily on the use\nof systemic steroids, with adjuvant steroid\nsparing drugs such as dapsone, azathioprine,\ncyclophosphamide and methotrexate. In our\npatients, oral prednisolone at 0.5mg/kg/day was\nsuccessful \n\n\n\n\n\n\n\n\n40 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nsuccessful in controlling the initial eruption.\nUnfortunately, we are unable to monitor her long\nterm disease progress. This patient is an excellent\nexample of how the great mimicker (LE) is\nmimicked (PE).\n\n\n\nReferences\n\n\n\n1. Amagai M. Pemphigus. In: Dermatology (Bolognia JL,\nJorizzo J, Rapini RP, eds). London: Mosby, 2003; 449-\n62\n\n\n\n2. Senear FE, Usher B. An unusual type of pemphigus:\ncoming features of lupus erythematosus. Arch\nDermatol Syphilol 1926; 13: 761\n\n\n\n3. Chorzelski J, Jacblonska S, Blaszczyk M.\nImmunopathological investigations in the Senear-Usher\nsyndrome (coexistence of pemphigus and lupus\nerythematosus). Br J Dermatol 1968; 80: 211)\n\n\n\n4. Mohsin Malik, A. Razzaque Ahmed. Concurrence of\nSystemic Lupus Erythematosus and Pemphigus:\nCoincidence or Correlation? Dermatology 214:231-\n239, 2007\n\n\n\n5. Ahmed AR, Salm M. Juvenile pemphigus. J Am Acad\nDermatol 1983; 8: 799-807\n\n\n\n\n\n\n\n\n41MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nCONTACT DERMATITIS & OCCUPATIONAL DERMATOSES - Original Article\n\n\n\nClinical pattern and causative allergens of hand and / or\n\n\n\nfeet eczema identified from patch test - a retrospective\n\n\n\n5 year study                                                               \n\n\n\nPriya G, MRCP, Asmah J, MMED, Gangaram HB, FRCP, Suraiya HH, FRCP\n\n\n\nAbstract\n\n\n\nBackground Hand and/or feet eczema may be due to contact dermatitis, either irritant or allergic in\nnature. Difficulties often arise in distinguishing purely endogenous eczema from the possibility of\ncontact dermatitis clinically. Patch test is carried out to detect the presence of allergic contact\ndermatitis. This is important for optimum patient care and to obtain a favourable outcome.\n\n\n\nObjectives To identify the demography, clinical characteristics and causative allergens of hand\nand/or feet eczema among patients from the patch test clinic.\n\n\n\nMethods Patients who attended the patch test clinic in the Department of Dermatology, Hospital\nKuala Lumpur from 2003 to 2007 were evaluated retrospectively. All of them were having hand\nand/or feet eczema. Data were collected for their demography, sites affected and patch test findings.\n\n\n\nResults 379 patients were included in the study. The age of patients ranged from 6 years to 78 years\nwith an average of 36.7 years. Their occupations ranged from blue collar (20.3%) and white collar\n(38.3%) workers, housewives (9.5%), pensioners (7.1%) and students (20.3%). Clinical\npresentations included isolated hand eczema (34.6%), isolated feet eczema (21.9%), hand and feet\neczema (19.0%), and hand and/or feet with eczema with involvement of other parts of the body\n(24.5%).The mean duration of eczema was 3.8 years. The rate of positive patch test was 58.0 %( n\n= 220/379).Clinically relevant allergens were identified in 123 (32.5%) patients only. Fifty two\npercent of the clinically relevant allergens were identified from the European Standard Series patch\ntest, 9.0% from the Specific Series patch test and 39.0 % from the patients\u2019 own personal products\nthat were tested. The most common source was metal items containing nickel (33.3%), followed by\ntoiletries (14.6%) and detergents (10.6%). Other sources include fragrance, cosmetics, rubber,\nmedicaments and hair dye. In 256 (67.5%) patients, there were no underlying causes detected, and\nthey were managed as endogenous hand and feet eczema. There is a possibility that the causative\nallergen was not suspected/tested and hence not detected.\n\n\n\nConclusion Hand and/or feet eczema can affect any age group and patch testing forms a very\nimportant diagnostic tool in the management.\n\n\n\nKeywords Clinical pattern, allergens, hand and/or feet eczema, patch test\n\n\n\nCorrespondence\nPriya Gill, MRCP (UK)\nDepartment of Dermatology, Hospital Kuala Lumpur\nWilayah Persekutuan, Malaysia\nE-mail : drpriya74@yahoo.com\n\n\n\nIntroduction\nThe hand and feet are often exposed to various\npotential allergens and irritants. Exclusive hand\neczema affects 9.1% of patients and another 9.0%\n\n\n\nhave exclusive feet eczema. Difficulties often arise\nin distinguishing endogenous eczema from the\nprobability of contact dermatitis clinically and\npatch testing is of much help in these situations1,2.\n\n\n\nThe aim of this study is to determine the\ndemography, clinical pattern and causative\nallergens identified from patch test in hand and / or\nfeet eczema.\n\n\n\n\n\n\n\n\n42 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMaterials and methods\nThis is a retrospective study on patients from the\nPatch Test clinic in the Department of Dermatology,\nHospital Kuala Lumpur. All patients with hand\nand/or feet eczema who underwent Patch Test from\nJanuary 2003 to December 2007 were included.\nPatch Test was carried out according to the\nrecommendations made by the International\nContact Dermatitis Research Group using Trolab\u00ae\n\n\n\nallergens. All patients were patch tested against the\nEuropean Standard Series allergens and if\nnecessary, with an additional specific series e.g.\nhairdressing chemicals, shoe allergens, rubber\nchemicals etc and their own products. The readings\nwere done on day 3 and day 5.\n\n\n\nData was analyzed using SPSS. The patients were\nassessed in terms of demographic data, clinical\npresentations, patch test results, clinically relevant\npatch test results and source of allergens.\n\n\n\nResults\nA total of 379 patients were included in this review\n(259 female,120 male). Two hundred and twenty\npatients had a positive patch test (164 female, 56\nmale). The racial distribution of patients in each\ncategory mimicked the racial attendance of the\nOutpatient specialist clinic, Department of\nDermatology, Hospital Kuala Lumpur in 2007 with\n58.6% Malays, 21.9% Chinese, 17.4% Indian and\n2.1% of patients belonging to other races. They\n\n\n\nwere categorized into patients with only hand\neczema or only feet eczema, hand and feet eczema\nand hand and / or feet eczema with generalization.\nThe demography of patients is shown in Table 1.\nThere is a female preponderance and the mean age\ngroups were in their thirties for all categories. The\nage distribution is shown in Figure 1.\n\n\n\nTable 2 details the patients\u2019 occupations. They were\nclassified into white collar workers (e.g.\nsupervisors, clerks, nurses, professionals, teachers,\nsecretaries, executives, film producers etc), blue\ncollar workers (soldiers, labourers, machine\noperators, welders, attendants, taxi drivers, baby\nsitters, cleaners etc), housewives, pensioners and\nstudents.The white collar patient subgroup\npresented mainly with hand and feet eczema while\nthose who held blue collar jobs had mainly feet\neczema. Interestingly, the many of the students had\nfeet eczema.\n\n\n\nThe working diagnosis for all the patients is shown\nin Table 3. Patch Test was undertaken only when a\ncontact element was suspected.\n\n\n\nTwo hundred and twenty patients had a positive\nPatch Test (58%). The positive Patch Test was\nclinically relevant in only 123 patients (32.5 %)\n(Table 4). Fifty two percent of the relevant allergens\nwere identified from the European Standard Series,\n39% from the patients\u2019 personal products and 9%\nfrom the Specific Series.\n\n\n\nTable 1 Patient demographics\n\n\n\nType\n\n\n\nNumber\n\n\n\nMale: Female ratio\n\n\n\nAge (years)\n\n\n\nRange\n\n\n\nMean\n\n\n\nHand Eczema\n\n\n\n131\n\n\n\n(34.6%)\n\n\n\n1: 2.4\n\n\n\n(38 male, 93 female)\n\n\n\n7 - 72\n\n\n\n34.4\n\n\n\nFeet Eczema\n\n\n\n83\n\n\n\n(21.9%)\n\n\n\n1:1.4\n\n\n\n(35 male, 48 female)\n\n\n\n6 - 72\n\n\n\n34.4\n\n\n\nHand & Feet Eczema\n\n\n\n72\n\n\n\n(19.0%)\n\n\n\n1:2.0\n\n\n\n(24 male, 48 female)\n\n\n\n7 - 66\n\n\n\n36.0\n\n\n\nHand and/or Feet Eczema\n\n\n\nwith generalization\n\n\n\n93\n\n\n\n(24.5%)\n\n\n\n1:3.0\n\n\n\n(23 male, 70 female)\n\n\n\n7 -78\n\n\n\n38.0\n\n\n\n\n\n\n\n\n43MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe top 10 allergens detected from the European\nStandard Series were nickel, fragrance mix, balsam\nof Peru, paraben, chromium, neomycin, colophony,\ncobalt, thiuram mix and formaldehyde which were\nclinically relevant in 41.3%, 31.0%, 42.9%, 35.0%,\n41.2%, 31.3%, 33.3%, 28.6%, 50.0% and 42.9%\nrespectively. (Table 5). Only the top 20 allergens\nidentified from the European Standard Series and\ntheir clinical relevance are shown in Table 5.\n\n\n\nFifty four patients were tested with rubber\nchemicals; clinically relevant in 4 patients (9%)\n(Table 6). A total of 26 patients were tested with\nshoe allergens; clinically relevant in 2 patients [n =\n2/26, (8%)]. Twenty nine patients were tested with\nthe textile and leather dyes allergens; relevant in\nonly 1 patient [n = 1/29, (3%)]. Only 4 patients were\ntested with hairdressing allergens and two of them\nwere clinically relevant. [n= 2/4, (50%)].\n\n\n\nFigure 1 Age distribution\n\n\n\nTable 2 Occupation\n\n\n\nOccupational field\n\n\n\nWhite Collar\n\n\n\nBlue Collar\n\n\n\nHousewife\n\n\n\nPensioner\n\n\n\nStudent\n\n\n\nNot available\n\n\n\n145 (38.3%)\n\n\n\n77 (20.3%)\n\n\n\n36 (9.5%)\n\n\n\n27 (7.1%)\n\n\n\n77 (20.3%)\n\n\n\n17 (4.5%)\n\n\n\n57 (43.5%)\n\n\n\n27 (20.6%)\n\n\n\n9 (6.9%)\n\n\n\n13 (9.9%)\n\n\n\n16 (12.2%)\n\n\n\n9 (6.9%)\n\n\n\n18 (21.7%)\n\n\n\n21 (25.3%)\n\n\n\n7 (8.4%)\n\n\n\n5 (6.0%)\n\n\n\n29 (35.0%)\n\n\n\n3 (3.6%)\n\n\n\n32 (44.4%)\n\n\n\n9 (12.5%)\n\n\n\n8 (11.1%)\n\n\n\n5 (7.0%)\n\n\n\n17 (23.6%)\n\n\n\n1 (1.4%)\n\n\n\n38 (40.9%)\n\n\n\n20 (21.5%)\n\n\n\n12 (12.9%)\n\n\n\n4 (4.3%)\n\n\n\n15 (16.1%)\n\n\n\n4 (4.3%)\n\n\n\nN=379 Hand Eczema\n\n\n\nN = 131\n\n\n\nFeet Eczema\n\n\n\nN=83\n\n\n\nHand & Feet Eczema\n\n\n\nN = 72\n\n\n\nHand & / or Feet Eczema \n\n\n\nwith eczema elsewhere\n\n\n\nN=93\n\n\n\n7\n\n\n\n50\n\n\n\n90\n\n\n\n60\n\n\n\n80\n\n\n\n61\n\n\n\n28\n\n\n\n3\n\n\n\n\n\n\n\n\n44 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 3 Working diagnosis and Patch test results\n\n\n\n72 (58.6%)\n\n\n\n16 (13.0%)\n\n\n\n13 (10.6%)\n\n\n\n18 (14.6%)\n\n\n\n0 (0%)\n\n\n\n2 (1.6%)\n\n\n\n2 (1.6%)\n\n\n\n0 (0%)\n\n\n\nRelevant Allergen identified\n\n\n\nN=123\n\n\n\n163 (43.0%)\n\n\n\n75 (19.8%)\n\n\n\n62 (16.3%)\n\n\n\n59 (15.6%)\n\n\n\n6 (1.6%)\n\n\n\n8 (2.1%)\n\n\n\n5 (1.3%)\n\n\n\n1 (0.3%)\n\n\n\nAll patients\n\n\n\nN=379\n\n\n\nDiagnosis\n\n\n\nContact Dermatitis\n\n\n\nHand Eczema\n\n\n\nFeet Eczema\n\n\n\nHand & Feet Eczema\n\n\n\nDiscoid Eczema\n\n\n\nAtopic Eczema\n\n\n\nPhotodermatitis\n\n\n\nJuvenile Plantar Dermatitis\n\n\n\nTable 4 The top 20 allergens from the European Standard Series\n\n\n\nAllergens \n\n\n\nNickel\n\n\n\nFragrance mix\n\n\n\nBalsam of Peru\n\n\n\nParaben\n\n\n\nChromium\n\n\n\nNeomycin\n\n\n\nColophony\n\n\n\nCobalt\n\n\n\nThiuram Mix\n\n\n\nFormaldehyde\n\n\n\nIsothiazolin\n\n\n\nFlavin\n\n\n\nWool Alcohol\n\n\n\nMercaptobenzothiazole\n\n\n\nMercapto  Mix\n\n\n\nSesquiterpene Lactone Mix\n\n\n\nParatertiary Phenol Formaldehyde Resin ( PPFR)\n\n\n\nN-Isopropyl-N2-phenyl paraphenylenediamine ( PPD)\n\n\n\nHydroxymethylpentylhexenecarboxyaldehyde\n\n\n\nBenzocaine\n\n\n\n104 (47.3)\n\n\n\n42 (19.1)\n\n\n\n21 (9.5)\n\n\n\n20 (9.1)\n\n\n\n17 (7.7)\n\n\n\n16 (7.3)\n\n\n\n15 (6.8)\n\n\n\n14 (6.4)\n\n\n\n14 (6.4)\n\n\n\n14 (6.4)\n\n\n\n10 (4.5)\n\n\n\n8 (3.6)\n\n\n\n7 (3.2)\n\n\n\n5 (2.3)\n\n\n\n4 (1.8)\n\n\n\n3 (1.4)\n\n\n\n1 (0.5)\n\n\n\n1 (0.5)\n\n\n\n2 (0.9)\n\n\n\n3 (1.4)\n\n\n\n43 (41.3)\n\n\n\n13 (31.0)\n\n\n\n9 (42.9) \n\n\n\n7 (35.0)\n\n\n\n7 (41.2) \n\n\n\n5 (31.3)\n\n\n\n5 (33.3)\n\n\n\n4 (28.6)\n\n\n\n7 (50.0)\n\n\n\n6 (42.9)\n\n\n\n3 (30.0)\n\n\n\n1 (12.5)\n\n\n\n4 (57.1)\n\n\n\n3 (60.0)\n\n\n\n4 (100.0)\n\n\n\n3 (100.0)\n\n\n\n1 (100.0)\n\n\n\n1 (100.0)\n\n\n\n0\n\n\n\n0\n\n\n\n+ve PT (%) Clinically\n\n\n\n(%)\n\n\n\nRelevant\n\n\n\n\n\n\n\n\n45MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 5 Patch Test result for rubber allergens\n\n\n\nFrequency\n\n\n\n1\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n2\n\n\n\n1\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n%\n\n\n\n25\n\n\n\n50\n\n\n\n50\n\n\n\n25\n\n\n\n25\n\n\n\n50\n\n\n\n25\n\n\n\n50\n\n\n\n25\n\n\n\n25\n\n\n\nAllergens\n\n\n\nHexamethylenetetramine\n\n\n\nDiphenylthiourea\n\n\n\nDibutylthiourea\n\n\n\n1, 3 - Diphenylguanidine\n\n\n\nBis (diethyldithiocarbamato) Zinc\n\n\n\nN, N - Diphenyl Paraphenylenediamine\n\n\n\nBis (dibuhyldithiocarbamato)Zinc\n\n\n\nCyclohexyl Thiophtalimide\n\n\n\n4, 4\u2019- Dihydroxybiphenly\n\n\n\nZinc dibenzyldithiocarbamate\n\n\n\nRubber Chemicals, n = 54, clinically relevant in 4 patients\n\n\n\nTable 6 Patch Test result for Hand eczema\n\n\n\nAllergens \n\n\n\nNickel\n\n\n\nFragrance mix\n\n\n\nBalsam of Peru\n\n\n\nParaben\n\n\n\nThiuram Mix\n\n\n\nCobalt\n\n\n\nColophony\n\n\n\nFormaldehyde\n\n\n\nIsothiazolin\n\n\n\nNeomycin\n\n\n\nChromium\n\n\n\nWool Alcohol\n\n\n\nBenzocaine\n\n\n\nFlavin\n\n\n\nSesquiterpene Lactone Mix\n\n\n\nSpecial Series: Rubber Chemicals\n\n\n\nSpecial Series : Hairdressing\n\n\n\n32 (39.0)\n\n\n\n20 (24.4)\n\n\n\n9 (11.0)\n\n\n\n8 (9.8)\n\n\n\n7 (8.5)\n\n\n\n7 (8.5)\n\n\n\n6 (7.3)\n\n\n\n6 (7.3)\n\n\n\n6 (7.3)\n\n\n\n4 (4.9)\n\n\n\n4 (4.9)\n\n\n\n4 (4.9)\n\n\n\n3 (3.7)\n\n\n\n3 (3.7)\n\n\n\n2 (2.4)\n\n\n\n4 (4.9)\n\n\n\n2 (2.4)\n\n\n\n10 (31.3)\n\n\n\n4 (20.0)\n\n\n\n2 (22.2)\n\n\n\n2 (25.0)\n\n\n\n3 (42.9)\n\n\n\n0\n\n\n\n1 (16.7)\n\n\n\n2 (33.3)\n\n\n\n2 (33.3)\n\n\n\n2 (50.0)\n\n\n\n0\n\n\n\n3 (75.0)\n\n\n\n0\n\n\n\n0\n\n\n\n1 (50.0)\n\n\n\n3 (75.0)\n\n\n\n2 (100)\n\n\n\n+ve          PT\n(%) ( N = 82)\n\n\n\nClinically \nrelevant (%)\n\n\n\nSource\n\n\n\nCoins, Costume jewellery, Watch Strap,\nBelt buckle, pins etc\n\n\n\nPerfume & After shave\nPerfume & After shave / Cosmetics\n\n\n\nCosmetics\n\n\n\nRubber Gloves\n\n\n\n-\n\n\n\nMedicament\n\n\n\nCosmetics\n\n\n\nCosmetics /Detergents\n\n\n\nMedicament\n\n\n\n-\n\n\n\nCosmetics\n\n\n\n-\n\n\n\n-\n\n\n\nCosmetics\n\n\n\nRubber Gloves\n\n\n\nHair Dye\n\n\n\n\n\n\n\n\n46 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 7 Patch Test result for Feet eczema\n\n\n\nAllergens \n\n\n\nNickel\n\n\n\nNeomycin\n\n\n\nColophony\n\n\n\nThiuram Mix\n\n\n\nParaben\n\n\n\nChromium\n\n\n\nIsothiazolin\n\n\n\nFragrance mix\n\n\n\nBalsam of Peru\n\n\n\nCobalt\n\n\n\nFlavin\n\n\n\nN-Isopropyl-N2-phenyl\nparaphenylenediamine (PPD)\n\n\n\nParatertiary Phenol Formaldehyde\nResin ( PPFR)\n\n\n\nWool Alcohol\n\n\n\nSpecial Series: Textile and Leather\nDyes\n\n\n\nSpecial Series: Shoe Allergens\n\n\n\n18 (46.1)\n\n\n\n3 ( 7.7)\n\n\n\n3 (7.7)\n\n\n\n3 (7.7)\n\n\n\n2 (5.1)\n\n\n\n2 (5.1)\n\n\n\n2 (5.1)\n\n\n\n2 (5.1)\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n2 (5.1)\n\n\n\n2 (5.1)\n\n\n\n+ve          PT\n( N = 39) (%)\n\n\n\n8 (44.4)\n\n\n\n1 (33.3)\n\n\n\n1 (33.3)\n\n\n\n1 (33.3)\n\n\n\n1 (50.0)\n\n\n\n2 (100)\n\n\n\n1 (50)\n\n\n\n1 (50)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n2 (100)\n\n\n\n2 (100)\n\n\n\nClinically \nrelevant (%)\n\n\n\nSource\n\n\n\nCostume jewellery, Shoe buckle,\nFootwear\n\n\n\nMedicaments\n\n\n\nFootwear\n\n\n\nFootwear\n\n\n\nCosmetics\n\n\n\nFootwear\n\n\n\nCosmetics\n\n\n\nPerfume & AfterShave\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nFootwear\n\n\n\nFootwear\n\n\n\nOn further analysis looking at the source of\nclinically relevant allergens, the most common\nsource of nickel were coins, costume jewellery,\nwatch straps, belt buckles, pins, zippers and shoe\nbuckles. Balsam of Peru and fragrance mix were\nmainly found in perfumes, after shave lotions and\ncosmetics. (Tables 7, 8, 9, 10)\n\n\n\nIn this study, nickel was the main source of\nallergens (33%), followed by toiletries (15%),\ndetergents (11%), rubber (8%), 6% each from\ncosmetics, fragrance and hair dye and finally 5%\neach from medicaments, footwear and\nmiscellaneous. (Figure 2)\n\n\n\nDiscussion\nIn centres with patch test clinics the overall rate of\npositive patch tests was 40-50%3. These were\nclinically relevant in 16 - 40 % of total patch tests\ndone. Forty to eighty five percent of those with\npositive patch tests were clinically relevant. This\nstudy has similar results with a positive patch test\nrate of 58% (n = 220 / 379).The clinical relevance\nwas found in 56% of patients and 32.5% of all patch\ntests carried out.\n\n\n\n\n\n\n\n\n47MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 8 Patch Test result for Hand & Feet eczema\n\n\n\nAllergens \n\n\n\nNickel\n\n\n\nFragrance mix\n\n\n\nBalsam of Peru\n\n\n\nParaben\n\n\n\nChromium\n\n\n\nIsothiazolin\n\n\n\nFormaldehyde\n\n\n\nCobalt\n\n\n\nMercaptobenzothiazole\n\n\n\nMercapto  Mix\n\n\n\nFlavin\n\n\n\nColophony\n\n\n\nWool Alcohol\n\n\n\nNeomycin\n\n\n\nBenzocaine\n\n\n\nSpecial series: Rubber Chemicals\n\n\n\nSpecial Series: Shoe Allergens\n\n\n\n17 (42.5)\n\n\n\n8 (20.0)\n\n\n\n6 (15.0)\n\n\n\n6 (15.0)\n\n\n\n5 (12.5)\n\n\n\n2 (5.0)\n\n\n\n2 (5.0)\n\n\n\n2 (5.0)\n\n\n\n2 (5.0)\n\n\n\n2 (5.0)\n\n\n\n2 (5.0)\n\n\n\n2 (5.0)\n\n\n\n1 (2.5)\n\n\n\n1 (2.5)\n\n\n\n1 (2.5)\n\n\n\n1 (2.5)\n\n\n\n1 (2.5)\n\n\n\n6 (35.3)\n\n\n\n2 (25.0)\n\n\n\n4 (66.7)\n\n\n\n4 (66.7)\n\n\n\n2 (40.0)\n\n\n\n1 (50.0)\n\n\n\n2 (100)\n\n\n\n2 (100)\n\n\n\n2 (100)\n\n\n\n2 (100)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1 (100)\n\n\n\n1 (100)\n\n\n\n+ve          PT\n(%)  ( N = 40)\n\n\n\nClinically \nrelevant (%)\n\n\n\nSource\n\n\n\nCoins, Costume jewellery, Zipper,\nWatch Strap, Belt & shoe buckle etc\n\n\n\nFragrance/Cosmetics\n\n\n\nToiletries/Cosmetics/\nPerfume & After shave\n\n\n\nCosmetics\n\n\n\nCement/Industrial oils\n\n\n\nCosmetics\n\n\n\nCosmetics\n\n\n\nPersonal Items/Industrial oils\n\n\n\nRubber Gloves\n\n\n\nRubber Gloves\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nRubber Gloves\n\n\n\nFootwear\n\n\n\nFigure 2 Sources of clinically relevant positive Patch test in Hand & / or Feet Eczema\n\n\n\nMedicaments 5%\n\n\n\nHair Dye 6%\n\n\n\nFragrance 6%\n\n\n\nCosmetics 6%\n\n\n\nRubber 8%\n\n\n\nDetergent 10%\n\n\n\nToileteries 15%\n\n\n\nNickel 34%\n\n\n\nFootware 5%\nMiscellanous 5%\n\n\n\n\n\n\n\n\n48 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 9 Patch Test result for Hand & / or Feet Eczema with generalization\n\n\n\nAllergens \n\n\n\nNickel\n\n\n\nFragrance mix\n\n\n\nNeomycin\n\n\n\nChromium\n\n\n\nFormaldehyde\n\n\n\nParaben\n\n\n\nColophony\n\n\n\nBalsam of Peru\n\n\n\nThiuram Mix\n\n\n\nMercaptobenzothiazole\n\n\n\nCobalt\n\n\n\nHydroxymethylpentylhexenecarbox\nyal-dehyde\n\n\n\nMercapto  Mix\n\n\n\nSesquiterpene Lactone Mix\n\n\n\nFlavin\n\n\n\nWool Alcohol\n\n\n\nSpecial Series: Metal Compounds\n\n\n\n37 (51.4)\n\n\n\n12 (20.3)\n\n\n\n8 (13.6)\n\n\n\n7 (11.9)\n\n\n\n6 (10.2)\n\n\n\n4 (6.8)\n\n\n\n4 (6.8)\n\n\n\n4 (6.8)\n\n\n\n4 (6.8)\n\n\n\n3 (5.1)\n\n\n\n3 (5.1)\n\n\n\n2 (3.4)\n\n\n\n2 (3.4)\n\n\n\n1 (1.7)\n\n\n\n1 (1.7)\n\n\n\n1 (1.7)\n\n\n\n1 (1.7)\n\n\n\n19 (51.4)\n\n\n\n1 (8.3)\n\n\n\n3 (38.0)\n\n\n\n2 (28.6)\n\n\n\n0\n\n\n\n2 (50.0)\n\n\n\n0\n\n\n\n0\n\n\n\n2 (50.0)\n\n\n\n1 (33.3)\n\n\n\n0\n\n\n\n1 (50.0)\n\n\n\n1 (50.0)\n\n\n\n1 (100)\n\n\n\n0\n\n\n\n0\n\n\n\n1 (100)\n\n\n\n+ve          PT\n(%)  ( N = 59)\n\n\n\nClinically \nrelevant (%)\n\n\n\nSource\n\n\n\nCoins, Costume jewellery, Zipper,\nWatch Strap, Belt & shoe buckle etc\n\n\n\nPerfume & After shave\n\n\n\nMedicaments\n\n\n\nDental Material/ Leather Strap\n\n\n\n-\n\n\n\nMedicaments\n\n\n\n-\n\n\n\n-\n\n\n\nGloves\n\n\n\nLeather Strap\n\n\n\nDental Material\n\n\n\nPerfume & After shave\n\n\n\nLeather Strap\n\n\n\nFlower\n\n\n\n-\n\n\n\n-\n\n\n\nFactory machinery\n\n\n\nThe predominance of young women corresponds to\nthe cohort of Meding et al6. In the South India study\nlooking at lower leg and feet eczema, the average\npatient age was 40.49 years with a female to male\nratio of 1.6:14. However there are studies that with a\nmale preponderance. Smith et al reported a male to\nfemale ratio of 1.25:1 in their study on descriptive\nepidemiology of hand eczema7. Goh CL from\nSingapore observed a male preponderance as well\nin the prevalence of hand eczema in his cohort of\npatients. (Male 56.0%, Female 44.0%)8. The\ndifference between studies could be explained by\ndifferent jobs being carried out by men and women\nand their tolerance to develop hand and / or feet\nirritant contact dermatitis with different types of\nexposure to allergens / irritants.\n\n\n\nThe working diagnosis for our patients was contact\ndermatitis (43.0%), hand eczema (19.8%), feet\neczema (16.3%), hand and feet eczema (15.6%)\nwith about 5% of patients having a diagnosis of\ndiscoid eczema/ atopic eczema/photodermatitis/\njuvenile dermatitis. As these patients were\nidentified from patch test, those with one type of\nendogenous eczema do not have to undergo this\nprocedure unless suspected to have contact\ndermatitis. Therefore, those with hand and feet\neczema are more likely to undergo patch test.\n\n\n\n\n\n\n\n\n49MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nChougule et al reported that among patients with\nlower leg and foot eczema in South India, the most\ncommon working diagnosis was lichen simplex\nchronicus (36%), followed by discoid eczema\n(18.5%), stasis eczema (7.5%), juvenile plantar\ndermatoses (5%), hyperkeratotic eczema (3%) and\nunclassified endogenous eczema (3%)4. The North\nAmerican Contact Dermatitis Group (NACDG)\nlooked at 6953 patients with hand eczema only\n(1994-2004) and their common working diagnosis\nwere allergic contact dermatitis (27.8%), irritant\ncontact dermatitis (19.7%), psoriasis (3.3%), atopic\neczema (2.5%), pompholyx (1.7%) and other\ndermatitis/dermatoses (8.9%)5. In this paper,\nhowever, the authors were not specifically looking\nfor contact dermatitis but rather at the range of\nconditions that presented with hand eczema.\nDifferent centres will have different working\ndiagnosis prevalence as a lot of factors will\ninfluence their decision to carry out patch test.\n\n\n\nMajority of patients were in the white collar group\n(38.3%), followed by the blue collar group and\nstudents (20.3% each), housewives (9.5%) and\nfinally pensioners (7.1%). Our results are different\ncompared to studies by Cherry et al and Smith et al.\nCherry concluded that contact dermatitis is by far\nthe most commonly reported occupational skin\ndisease, especially in the blue collar group. Their\nstudy showed that women were most likely to have\ndermatitis attributed to wet work, and men to oils\nand related substances. In Smith\u2019s paper, the most\nfrequent types of employment associated with\noccupational hand eczema were caterers, metal\nworkers, mechanics, builders and printers (blue\ncollar workers)7,9. Unfortunately, as this is a\nretrospective review, we are unable to ascertain for\nsure the relationship of eczema in our group of\npatients to the occupation. The majority of patients\nin our review were from white collar occupations.\nThis can be attributed to our patient population that\nunderwent patch testing in general being from the\nwhite collar group as this department is located in\nthe heart of Kuala Lumpur, the biggest city in\nMalaysia. Smith et al also suggested that low office\nhumidity as an irritant factor and the\nrecommendation of office work as a \u201cclean, safe\njob\u201d might need to be reviewed7.\n\n\n\nThe most common presentation for white collar\nworkers, blue collar workers and pensioners was\nhand eczema. Feet eczema was the most common\nsubtype among students and not surprisingly,\n\n\n\nhousewives presented most commonly with hand\nand/ or feet eczema with eczema elsewhere. This\ncould be due to the possible contact to various\npotential irritants in everyday household chores like\nwashing clothes and utensils with detergents and\nwater. Many housewives as well squat on the\nground while doing their chores; and their feet are\ncontinuously exposed to detergents and water while\nother areas are affected by splashing of the water.\n\n\n\nThe highest proportion of  clinically relevant\nallergens were identified in patients who were being\nmanaged as contact dermatitis (44.2%), compared\nto hand eczema (21.3%), feet eczema (21.0%),\nhand & feet eczema (30.5%) and atopic dermatitis\n(25.0%).This could be due to a lower index of\nsuspicion for a contact element in those diagnosed\nto have endogenous eczema. However, studies have\nshown that endogenous eczema is commonly\ncomplicated by a contact element and eliminating\nthe causative factor will greatly facilitate the\nmanagement10,11.\n\n\n\nThe most common positive patch test allergens in\nthis study were nickel (47.3%), fragrance mix\n(19.1%) and balsam of Peru (7.9%). However, for\nthose with feet eczema, the most common allergens\nwere nickel, chromium, shoe allergens and textile\nand leather dyes. The results in our centre differed\nslightly compared to Osmania General Hospital,\nHyderabad, India where a similar study was done\nusing the Indian Standard Series Patch test\nallergens. Their most common allergens were nickel\nand chromium (25% each), followed by fragrance\nmix (21.4%) and wool alcohol (14.3%).These\nresults were probably due to  the different series\nbeing used for Patch test and the different patient\nfactors, commercial products and environmental\nfactors the two populations are exposed to2.\n\n\n\nThe most common sources of allergens were\npersonal items containing nickel (33%), toiletries\n(15%) and detergents (15%). Our findings are\nsimiliar that of the North American Contact\nDermatitis Group. They found the most common\nsources to be soaps, cleaners, detergents, solvents,\noil and lubricants5. These are common everyday\nitems individuals are exposed to.\n\n\n\nThere are several limitations to this study. The data\nis retrospective with some even incomplete\ninformation; therefore a more definite causal\nrelationship cannot be determined. The study\nsample\n\n\n\n\n\n\n\n\n50 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nsample was drawn only from patients with hand\nand/or feet eczema who were patch tested; as such,\nthey are not representative of the general population\nor the general dermatology population. More\nresearch in a clinical setting is needed to address\nsome of the issues raised in our review, especially\nprospective research.\n\n\n\nConclusions\nHand and/ or feet eczema affects all ages and\ndifferent types of occupations. This disease can\ncause significant disability and economic loss to\nboth individuals and society. Patch testing is a very\nimportant diagnostic tool to exclude allergic contact\ndermatitis in those suspected as having endogenous\neczema or other types of dermatoses. The specific\nseries patch test allergens and the patient\u2019s own\nproducts are of added benefit if clinically indicated.\nContact avoidance remains the most important\nmeasure in the prevention and management of\nallergic and irritant contact dermatitis. Therefore,\neducation about avoidance of, or protection from,\nthe most common antigens is critical, especially in\nhigh risk occupations\n\n\n\nReferences\n\n\n\n1. Ng SK, Goh CL, M Shahidullah. Clinical patterns  of\nFeet Eczema in Singapore. Bulletin for medical\npractitioners 1998; 9 (1)\n\n\n\n2. G Vani , Rao GA, V Gowri TSS Lakshmi. Allergic\ncontact dermatitis of the hands and/or feet - common\nsensitizers. Contact Dermatitis 2005; 52 (1):50-52\n\n\n\n3. Ormond P, Hazelwood E et al. The importance of a\ndedicated patch test clinic.  Br J Derm 2002; 146: 304-\n307\n\n\n\n4. Chougule A, Thappa DM. Patterns of lower leg and foot\neczema in south India. Indian J Dermatol Venereol\nLeprol 2008; 74:458-61\n\n\n\n5. Warshaw ME, Ahmed AL, Belsito DV et al. Contact\ndermatitis of the hands: Cross-sectional analyses of\nNorth American Contact  Dermatitis Group Data,1994-\n2004; J Am Acad Dermatol 2007; 57; 301-14)\n\n\n\n6. Veien NK, Hattel T, Laurberg G.  Hand eczema: causes,\ncourse, and prognosis I. Contact   Dermatitis 2008; 58;\n330-334\n\n\n\n7. Smith HR, Armstrong DKB, WakelinSH et\nal. Descriptive epidemiology of hand dermatitis at the\nSt John\u2019s contact dermatitis clinic. Br J Dermatol 2000;\n142: 284-287\n\n\n\n8. Goh CL. An epidemiological comparison between\noccupational and non-occupational hand eczema. Br J\nDermatol 1989; 120: 77-82\n\n\n\n9. Cherry N, Meyer JD, Adidesh A et al. Surveillance of\noccupational skin disease: EPIDERM and OPRA. Br J\nDerm 2000; 142:1128-1134\n\n\n\n10. Shackelford KE, Belsito DV. The etiology of allergic-\nappearing foot dermatitis: a 5-year retrospective study.\nJ Am Acad Dermatol 2002; 47 (5): 715-721\n\n\n\n11. Fowler JF, Ghosh A, Sung J et al. Impact of chronic\nhand dermatitis on quality of life, work productivity,\nactivity impairment and medical costs. J Am Acad\nDermatol 2006; 54 (30): 448-457\n\n\n\n\n\n\n\n\n51MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nKeywords Uveitis, lymphadenopathy, leprosy,\nsarcoidosis\n\n\n\nIntroduction\nSarcoidosis is a chronic systemic disorder\nof unknown etiology, characterized\nhistopathatologically by non-caseating, epithelioid\ngranulomatous infiltration in various organs.1,2\n\n\n\nCutaneous sarcoidosis is also known as a\ndermatologic masquerader because the lesions can\nexhibit many different morphologies.3 We report a\npatient who was initially diagnosed as having\ntuberculoid leprosy based on histological findings.\nHe was treated with multi-drug therapy for 18\nmonths without clinical improvement. In addition,\nhe had left panuveitis and mediastinal\nlymphadenopathy.\n\n\n\nCase report\nA 28 year old gentleman with no previous medical\nillness first presented to the ophthalmologist with\ncomplaint of acute onset of left eye redness and\npain. He was diagnosed and treated for left\npanuveitis. He was referred to us two months later\nfor further management of non-pruritic\nerythematous skin rashes of 1 year duration. At the\nsame time, he was referred to the respiratory team\nfor further work up of possible tuberculosis.\n\n\n\nThe skin eruption first started over the upper limbs\nand subsequently involved the trunk, sparing the\nface, palm and soles. There was no associated limb\nnumbness or weakness and no fever, cough or\nshortness of breath. His appetite was normal and\nthere was no significant weight loss. Review of\nother systems was unremarkable.\n\n\n\nClinically, he was pink and not jaundiced. His\nheight was 108 cm and weight 102 kg. There were\nmultiple well-defined erythematous papules and\n\n\n\nGRANULOMATOUS DISEASE - Case Report\n\n\n\nCutaneous Sarcoidosis Mimicing Tuberculoid Leprosy\n\n\n\nChong YT, MRCP, Tey KE, MRCP, Choon SE, FRCP\n\n\n\nplaques distributed symmetrically over the trunk\nand upper limbs. Sensation was normal and there\nwas no peripheral nerve thickening. Lymph nodes\nwere not palpable. Examinations of the cardio-\nrespiratory system and abdomen did not review any\nabnormalities.\n\n\n\nBlood investigations revealed hypochromic\nmicrocytic anaemia with a hemoglobin of\n13.1gm/dl and eosinophilia. His erythrocyte\nsedimentation rate (ESR) was 30mm per hour. He\nhas hyperglobulinaemia (51 g/L) and slightly raised\nalanine aminotransferase (40 IU/L). The renal\nprofile, serum calcium and fasting blood glucose\nwere normal. Serological screen for viral hepatitis,\nrapid reagent test for syphilis (RPR) and anti-HIV\nwere negative. Mantoux test was negative (2mm).\nThe slit skin smear was negative for acid fast\nbacilli. \n\n\n\nThe skin biopsy was reported as tuberculoid leprosy\nwhich showed numerous epitheliod granuloma\naround neurovascular bundles with occasional\nLangerhan\u2019s giant cells, many epitheliod cells and\nlymphocytes. There was no caseation necrosis and\nthe Fite stain was negative for acid fact bacilli.\nTissue culture for mycobacteria and fungus was\nalso negative.\n\n\n\nBased on the histology report, multi-drug therapy\n(MDT) for paucibacillary leprosy (rifampicin,\nclofazimine and dapsone) was commenced. At the\nsame time, he was treated with prednisolone for\npanuveitis by the ophthalmologist. His skin lesions\nimproved initially. However, two months into\ntreatment, he developed raised liver enzymes.\nUltrasound of the liver showed fatty changes. The\nMDT was withheld for one month and later\nrestarted with minocycline and dapsone. After one\nyear of treatment, his skin lesions did not show\nmuch improvement despite the initial response. A\nrepeat skin biopsy showed similar findings as the\ninitial one.\n\n\n\nFurther investigations with CT scan and endoscopic\nultrasound showed multiple small mediastinal\nlymph nodes. Fine-needle aspiration cytology of the\nsub-carinal lymph node was reported as a\ngranulomatous lesion. PCR test from a repeat skin\nbiopsy was negative for Mycobacteria DNA. \n\n\n\nCorrespondence\nChong Yew Thong \nDepartment of Dermatology\nHospital Sultanah Aminah\n80100 Johor Bahru, Johor\nE-mail : cytusm@yahoo.com\n\n\n\n\n\n\n\n\n52 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nHe was diagnosed as having cutaneous sarcoidosis\nand referred back to the respiratory physician for\nfurther management. He was treated empirically\nwith anti-tuberculous drugs (ethambuthol,\nisoniazid, rifampicin and pyrazinamide) for another\ntwo months with no response. At the same time,\nhigh dose prednisolone was restarted by the\nophthalmologist for a flare-up of his left panuveitis.\nHis skin lesions resolved after one month of\ntreatment.\n\n\n\nDiscussion\nThis gentleman presented with a diagnostic\nchallenge. He had erythematous papules and\nplaques over the upper limbs and trunk of one year\nduration. The cutaneous eruption preceded the\ndevelopment of uveitis. Based on cutaneous\n\n\n\nfindings, various differential diagnosis were\nentertained including cutaneous atypical\nmycobacteria infection, fungal infection, leprosy\nand  cutaneous lymphoma. \n\n\n\nHe was treated for tuberculoid leprosy based on\nhistological findings. The initial response was most\nlikely due to the steroids prescribed for uveitis.\nHowever, the skin lesions relapsed when the steroid\nwas tapered and was subsequently stopped.\n\n\n\nSarcoidosis is a chronic systemic disorder\nof unknown etiology, characterized\nhistopathatologically by non-caseating, epithelioid\ngranulomatous formation.1,2 It can affect various\norgans, with lungs, lymph nodes, skin and eyes\nbeing  more commonly affected.4\n\n\n\nFigure 1-4 Multiple symmetrical erythematous papules \nand plaques seen on the upper limbs and trunk \nbefore treatment with steroid (Figure 1 & 2) and \nafter treatment with steroid (Figure 3 & 4)\n\n\n\nFigure 5&6 Multiple well-formed non-caseating \ngranulomas seen in the dermis (Figure 5) which \nconsist of numerous epitheliod cells and \nlymphocytes around neurovascular bundles \nwith occasional Langerhan\u2019s giant cells\n(Figure 6)\n\n\n\n\n\n\n\n\n53MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSarcoidosis affects all races, both sexes and all\nages. Incidence reported ranged from 64/100, 000\nin Sweden to 1.4/100, 000 in Japan.1\n\n\n\nCutaneous involvement occurs in 20 to 35 percent\nof patients with systemic sarcoidosis but it may\noccur without systemic involvement.3 It is most\ncommonly  seen at the onset of the disease process.1\n\n\n\nVarious morphologies have been described,\nincluding papules, follicular papules, plaques,\nnodules, ulcerative lesions and alopecia.1\n\n\n\nThe eye and adnexa are involved in 25 to 80% of\npatients with sarcoidosis and anterior uveitis is the\nmost common manifestation, occurring up to 65%\nof patients with ophthalmologic involvement. In\nabout 10 to 15%, both the anterior and posterior\n(panuveitis) segments may be involved.11\n\n\n\nIn developed countries, sarcoidosis was reported to\nbe the second most common non-infectious cause\nof uveitis, after sero-negative spondyloarthropathy,\nespecially in US, Netherland and Japan.10\n\n\n\nThere is no single test to confirm the diagnosis of\nsarcoidosis.3 Sarcoidal granulomas have no unique\nhistologic features to differentiate them from other\ngranulomas. Patients are diagnosed with\nsarcoidosis on the basis of compatible clinical,\nradiologic findings, supported by histologic\nevidence of non-caseating granulomas, and when\nother potential causes, such as infections, are\nexcluded.11\n\n\n\nCutaneous sarcoidosis has quite often been\nmisdiagnosed as leprosy because of near similar\nskin lesions and histologic findings of non-\ncaseating granuloma. Diagnosis of sarcoidosis was\nsuspected when  the patient did not respond to a\ncourse of anti-leprosy drugs.6,7,8,9\n\n\n\nCutaneous sarcoidosis is rare in South-East Asia,\nincluding Malaysia. Liam et al 12 reported 14 cases\nof sarcoidosis from a single centre in eighteen years\n(1972 to 1990), out of which, twelve patients had\npulmonary involvement and five developed\nerythema nodosum. A case series of 25 patients\nwith cutaneous sarcoidosis in twenty three years\n(1980 to 2003) was also reported in Singapore by\nChong et al.5 10 out of 25 patients had extra\ncutaneous manifestation. \n\n\n\nAs this condition is rare, the clinical diagnosis of\ncutaneous sarcoidosis is often not suspected and is\nmade on subsequent biopsy excluding other causes,\nin particular tuberculoid leprosy and other\nmycobacterial infections which are more prevalent.5\n\n\n\nIn summary, our patient presented with\nerythematous skin eruption associated with uveitis\nand bilateral hilar lymphadenopathy. His skin\nbiopsy revealed a non-caseating granulomatous\nreaction. He was treated with anti-leprosy and anti-\ntuberculous drugs without clinical improvement.\nThus, he was diagnosed as having sarcoidosis after\nthe infectious causes were ruled out. Cutaneous\nsarcoidosis is rare and a high index of suspicion\nwith clinical correlation of various features is\nimportant to make a correct diagnosis.\n\n\n\nReferences\n\n\n\n1. English III JC, Patel PJ, Greer KE. Sarcoidosis. J Am\nAcad Dermatol 2001; 44:725-743\n\n\n\n2. Young RJ III, Gilson RT, Yanase D, Elston DM.\nCutaneous sarcoidosis. Int J Dermatol 2001; 40:249-\n253\n\n\n\n3. Katta, R. Cutaenous sarcoidosis: A dermatologic\nmasquerader. Am Fam Physician 2002; 65:1581-1584\n\n\n\n4. Mahajan VK, Sharma NL, Sharma RC, Sharma VC.\nCutaneous sarcoidosis: Clinical profile of 23 Indian\npatients. Indian J Dermatol Venereol Leprol 2007;\n73:16-21\n\n\n\n5. Chong WS, Tan HH, Tan SH. Cutaneous sarcoidosis in\nAsians: a report of 25 patients from Singapore. Clin\nExp Dermatol 2005; 30:120-124\n\n\n\n6. Singh K, Raina V, Narulla AK, Singh R. Sarcoidosis\nmasquerading as leprosy, pulmonary tuberculosis and\nurolothiasis. J Assoc Physicians India 1990; 38(9):657-\n9 [Abstract]\n\n\n\n7. Ramanujam K. Tuberculoid leprosy or sarcoidosis? A\ndiagnostic dilemma. Lepr India 1982; 54(2):318-23\n[Abstract]\n\n\n\n8. Kaur S, Dhar S, Bambery P, Kanwar AJ, Khajuria A.\nCutaneous sarcoidosis masquerading as relapsed\nborderline tuberculoid leprosy? Int J Lepr Mycobact\nDis 1993; 61(3):455-458 [Abstract]\n\n\n\n9. Thaipisuttikul Y, Kateruttanakul, P. Sarcoidosis mimics\nlepromatous leprosy: a case report. J Med Assoc Thai\n2007; 90:171-174\n\n\n\n10. Rathinam SR, Namperumalsamy P. Global variation\nand pattern changes in epidemiology of uveitis. Indian\nJ Ophthalmol 2007; 55:173-183\n\n\n\n11. Lannuzi, MC, Rybicki, BA, Teirstein AS. Sarcoidosis.\nN Engl J Med 2007; 357(21):2153-2165\n\n\n\n12. Liam CK, Menon A. Sarcoidosis: A review of cases\nseen at the University Hospital, Kuala Lumpur. Sing\nMed J 1993; 34:153-156\n\n\n\n\n\n\n\n\n54 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAssessment of doctors\u2019 performance is an integral\npart of quality improvement in health care.\nTraditionally, evaluation of competency in\nperforming procedures involves informal peer\nreview and formal credentialing. However, these\nmethods are often subjective and are without\nexplicit reference to universally accepted standards\nof practice1,2. Recently, statistical process control\ntechniques which have long been used in\nmanufacturing industry, have gained popularity in\nquality improvement in health care3. One of the\ntechniques used in the objective monitoring of\ndoctors\u2019 performance is the Cumulative Sum\n(CUSUM) method. First described by E.S. Page in\n1954, CUSUM is based on sequential monitoring of\na cumulative performance measure over time2. A\ngraphical representation of CUSUM in a line chart\nis designed to detect any early change in\nperformance associated with an unacceptable rate\nof adverse outcome2. Early warning of poor\nperformance ensures patient safety with minimum\nmorbidity, and timely corrective actions can be\ntaken to improve the doctor\u2019s performance.\n\n\n\nSkin biopsy is an important diagnostic and\ntherapeutic procedure in dermatology. Although it\nis a minor surgical procedure, its outcome depends\ngreatly on the surgeon\u2019s skill and competency. A\ngood outcome of a skin biopsy can be defined by\nthe absence of post-biopsy wound infection,\npresence of cosmetically acceptable scar, and the\ntissue sample collected being representative as well\nas adequate for histopathological interpretation. A\nSkin Biopsy Registry has been established by a\ngroup of dermatologists and it has the following\nobjectives:\n1) To monitor the performance and competency \n\n\n\nof doctors in performing skin biopsies\n2) To determine factors affecting the outcome of \n\n\n\nskin biopsies\n\n\n\nANNOUNCEMENT - Administrative Update\n\n\n\nMonitoring doctors\u2019 performance in skin biopsy using\n\n\n\nCUSUM technique\n\n\n\nChang CC, AdvMDerm (UKM), Azizan NZ, AdvMDerm (UKM), Roshidah B, FRCP\n\n\n\n3) To assess the concordance rates between pre-\nbiopsy clinical diagnosis and \nhistopathological diagnosis from skin biopsy\n\n\n\nIndividual doctors are required to collect data on the\nskin biopsies he or she performs. Data on each\nbiopsy is collected prospectively at three separate\noccasions.\n\n\n\nFirstly, patient demographic and clinical data as\nwell as details of biopsy and post-biopsy care are\ndocumented immediately after biopsy. Next, during\npost-biopsy review when patient returns for suture\nremoval, any complications such as wound\ndehiscence or infection are recorded.\n\n\n\nLastly, during histopathological review, the biopsy\ntissue sample is evaluated by the pathologist\nwhether it is adequate and representative for\nhistopathological interpretation.\n\n\n\nFor the purpose of CUSUM charting, two outcome\nparameters of skin biopsy are measured:\n\n\n\n1) Wound infection rate within 14 days post-\nbiopsy\n\n\n\n2) Rate of biopsy tissue sample being \nrepresentative of skin lesion and adequate for \nhistopathological interpretation\n\n\n\nAs there are no universally accepted standards for\nthese outcome measures in the published literature,\nthe acceptable and unacceptable failure rates can be\ndetermined by performing a retrospective audit of\navailable data or a consensus decision of\ndermatologists4. Following implementation of\nCUSUM charting, these rates may be revised and\nadjusted based on the average performance of the\ntrainees and dermatologists.\n\n\n\nThe CUSUM chart is a plot of a cumulative score\nversus the index number of a series of consecutive\nprocedures. The CUSUM score is determined by\nthe following formula when the outcome of each\nconsecutive procedure is known2:\n\n\n\nCn = max ( 0, Cn-1 + Xn - k )\n\n\n\nCorrespondence\nDr Chang Choong Chor, AdvMDerm\nDepartment of Dermatology, Hospital Kuala Lumpur\nJalan Pahang, 50586 Kuala Lumpur, Malaysia\nE-mail : ccchor@gmail.com\n\n\n\n\n\n\n\n\n55MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nXn is the outcome measure for the nth procedure.\n\n\n\nXn is 0 for success and 1 for failure.\n\n\n\nk is the reference value determined by pre-defined\nstandards of performance in terms of acceptable\nand unacceptable failure rates.\n\n\n\nAt the start, CUSUM C0 = 0.\n\n\n\nWhen an individual performs at an acceptable level\nof performance, the CUSUM curve runs at a\nhorizontal trend. However, when the failure rates\nreach an unacceptable level, the curve slopes\nupward and crosses a horizontal line called decision\ninterval, h, signaling unacceptable performance.\nWhen this occurs, the individual is required to\ndetermine and correct the cause of poor\nperformance.\n\n\n\nFigure 1 shows an example of typical CUSUM\ncurves of a trainee learning to perform a procedure\nand a consultant who is an expert on the procedure.\nThe consultant\u2019s CUSUM curve is flat, indicating\nthat he has been performing within the specified\nstandards. In contrast, the trainee\u2019s CUSUM curve\nrises initially crossing two horizontal lines (decision\nintervals). This indicates poor performance\nrequiring close supervision and re-training.\nNevertheless, this trainee seems to have acquired\nthe competence after a certain period, as shown by\nhis CUSUM curve which later plateaus to a\nhorizontal trend.\n\n\n\nWith the financial and technical support received\nfrom the Ministry of Health through the Clinical\n\n\n\nResearch Centre, the Skin Biopsy Registry is\ncurrently being developed with an online electronic\ndatabase. This is then linked to the eCUSUM web\napplication (http://app.acrm.org.my/eCUSUM)\nwhich will obviate complex manual calculations\nand tedious charting on paper graphs. Individual\ndoctor can evaluate his or her own performance by\nlogging in to the eCUSUM application to view the\nCUSUM charts. Supervisors can have access to\ntheir trainees\u2019 CUSUM charts for periodic\nmonitoring.\n\n\n\nA 3-month pilot study is currently being conducted\nin the Department of Dermatology, Hospital Kuala\nLumpur. CUSUM for skin biopsy will be used in\nthe public hospitals in the very near future. It is our\nfervent hope that CUSUM will encompass other\ndiagnostic and therapeutic procedures in\ndermatology and will interest dermatologists in\nprivate practice as well.\n\n\n\nReferences\n\n\n\n1. Williams SM, Parry BR, Schlup MMT. Quality control:\nan application of the CUSUM. Br Med J 1992; 304:\n1359-1361\n\n\n\n2. Lim TO, Soraya A, Ding LM, Morad Z.  Assessing\ndoctors\u2019 competence: application of CUSUM technique\nin monitoring doctors\u2019 performance. Int J Quality\nHealth Care 2002; 14(3):251-258\n\n\n\n3. Lim TO. Statistical process control tools for monitoring\nclinical performance. Int J Quality Health Care 2002;\n15(1):1-2\n\n\n\n4. Kestin IG. A statistical approach to measuring the\ncompetence of anaesthetic trainees at practical\nprocedures. Br J Anaesth 1995; 75:805-809\n\n\n\nFigure 1 CUSUM chart for a procedure performed by a trainee and a consultant\n\n\n\n\n\n\n\n\n56 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nANNOUNCEMENT\nContinuous Professional Development\n\n\n\n22nd World Congress of Dermatology\n\n\n\nOrganizers : International Leagues of Dermatological Societies \n(ILDS) with the support of the Korean Dermatological \nAssociation (KDA)\n\n\n\nTheme : Connecting the World Through Innovative Dermatology \n\n\n\nVenue : Seoul, Korea \n\n\n\nDate : 24 - 29 May 2011\n\n\n\nProgram : website: www.wcd2011.org \n\n\n\nAbstract submission deadlines for Free papers: 31 October 2010\n\n\n\n\n\n\n\n\n57MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswer is given on page 60\n\n\n\nQuiz\n\n\n\nDermatology Care Plan Quiz for nurses\n\n\n\nState the nursing care plan required by each patient.\n\n\n\ne.g.\nNursing problem Nursing intervention Expected Outcome Comment\nWeeping lesion Wet wrap with astringent Dry scaly lesion Stop using astringent \n\n\n\nsolution regularly when lesions are dry\n\n\n\nSlide A Patient is admitted for management of \nerysipelas at his left leg\n\n\n\nSlide B Patient has fixed drug eruptions on his\ngenital\n\n\n\n\n\n\n\n\n58 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswers to Clinical Diagnositic Skill Test\n\n\n\nSlide A ADR\ntumour\nappendageal disorders\nbacterial infection\nautoimmune disorders\npsedolymphoma\nlupus ertyhematosus\nlymphoma\nleprosy\nrosacea\n\n\n\nSlide B ADR\ntumour\nappendageal disorders\nbacterial infection\nautoimmune disorders\npsedolymphoma\nlupus ertyhematosus\nlymphoma\nleprosy\nrosacea\n\n\n\nSlide C psoriasis\nkeratoderma\nacanthosis\nerythroderma\nscabies\nlichen planus\ncontact dermatitis\nfungal infection\nsecondary syphilis\nkeratoderma blenorrhagica\n\n\n\nSlide D pomphylx\nkeratoderma\nacanthosis\nerythroderma\nscabies\nlichen planus\ncontact dermatitis\nvasculitis\nbullous disease\nscalding\n\n\n\nThis autoimmune bullous disease is easily\nmistaken for common chronic inflammatory\ndisease. The round erosions and crusting on these\nerosions should prompt the diagnosis of bullous\ndisease.\n\n\n\nOpaque scaling at finger webs that may extend to\npalms is a sign of Norwegian scabies. If mistaken\nfor dermatitis, psoriasis or fungal infection will\nresult in prolonged morbidity and spread of\nscabies to others including healthcare providers.\n\n\n\nDifferential diagnosis of facial plaques include\nleprosy, lupus erythematosus, granuloma fasciale,\npolymorphic light reaction, benigh lymphocytoma\ncutis, lymphoma. By suspecting this condition will\npatient be investigated fully with regular follow-\nup.\n\n\n\nThis patient has roasacea as evidence by the\nacneiform-like papules in the absence of\ncomedone and the slightly large and reddish nose\nwhich can result in rhinophyma. It is important to\nrecognise this condition because of the risk of\nassociate keratitis. Rosacea patient may respond to\nantbiotic, topical metronidazole gel or retin A\ncream.\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n2\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n2\n-3\n\n\n\n-2\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\n-2\n\n\n\n-2\n\n\n\n0\n-2\n\n\n\n-3\n\n\n\n-3\n\n\n\n-3\n\n\n\n-3\n\n\n\n-3\n\n\n\n-3\n\n\n\n-3\n\n\n\n-3\n\n\n\n2\n-3\n\n\n\n\n\n\n\n\n59MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSlide E ADR\nnon-infective inflammation\nfungal infection\ntumour\ndermatitis\npost-inflammatory \nhyperpigmentation\ncongenital naevus\nacnathosis\narsenic poisoning\nmycosis fungoides\n\n\n\nSlide F dermatitis\nnon-infective inflammation\nfungal infection\nviral infection\nappendageal disorders\npityriasis versicolor\npsoriasis\nherpes viral infection\ndiscoid dermatitis\npityriasis rosacea\n\n\n\nPityriasis versicolor can appear as hyperpigmented\nmacules in fair skin patient whereas in dark skin\npatient they appear as hypopigmented macules.\nThe round and wrinkled macules which can\nbecome confluent but still retain the curved edge\nprompt the diagnosis of Pityriasis versicolor.\n\n\n\nThe skin lesions on patient\u2019s back resemble water\ndroplets on a dirty windscreen. This should\nprompt the diagnosis of arsenic poisoning. The\ndyspigmentation represent sun damage skin with\nformation of pigmented macules and actinic\nkeratoses.\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n2\n0\n\n\n\n-1\n\n\n\n-1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\n-1\n\n\n\n0\n\n\n\n-1\n-1\n\n\n\nHow did you performed? You should aim for correct diagnosis and minimize delayed diagnosis.\n\n\n\nSum up the number of score 2, 1, 0, -1, -2 and -3 that you have collected.\n\n\n\nSCORE\n\n\n\n-3\n\n\n\n-2\n\n\n\n-1\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\nTOTAL NUMBER COLLECTED IMPLICATION\n\n\n\nDelayed diagnosis may result in irreversible outcome / deformity\n\n\n\nDelayed diagnosis may result in prolonged morbidity\n\n\n\nTherapy for wrong diagnosis may worsen the primary skin lesion\n\n\n\nNo effect on outcome of primary skin lesion but cost wastage of \nmedication, investigation kit and money\n\n\n\nTherapy for this diagnosis can have good outcome\n\n\n\nCorrect diagnosis enables appropriate investigations, thearpy and even \nlong term follow-up\n\n\n\n\n\n\n\n\n60 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswers to Dermatology Care Plan Quiz\n\n\n\nSlide A Erysipelas\n\n\n\nNursing problem\n\n\n\nPain in the leg\n\n\n\nSwollen leg \n\n\n\nBlistering & \nweeping lesions          \n\n\n\nDry scaly skin\n\n\n\nNursing intervention\n\n\n\nanalgesics\n\n\n\nRest & elevate leg           \n\n\n\nWrap lesion with diluted \nKMNO4 solutions Wet \n\n\n\nUse moisturising soap\n\n\n\nExpected Outcome\n\n\n\nImprove  pain score\n\n\n\nReduced calf circumference\n\n\n\nDry wrinkled scaly skin \n\n\n\nMoist non-scaly skin\n\n\n\nComment\n\n\n\nStop analgesic when  pain has \nsubside\n\n\n\nDo not elevate the leg. \n\n\n\nStop wet wraps once swelling\nand blisters have resolved\n\n\n\nStop moisturizing soap when\nskin normalise\n\n\n\nSlide B Fixed drug eruptions on the genitals\n\n\n\nNursing problem\n\n\n\nWeeping lesion\n\n\n\nAdverse drug \neruptions (ADR)\n\n\n\nNursing intervention\n\n\n\nWash genitals with                   \nastringent solution             \n(normal saline or diluted \nKMNO4 solutions)\n\n\n\nEducate patient to avoid drug \nby giving allergy card\n\n\n\nExpected Outcome\n\n\n\nDry scaly skin\n\n\n\nPrevent recurrent ADR\n\n\n\nComment\n\n\n\nStop astringent solution once \nskin dries up\n\n\n\nInform patient the possibility of \ncross reactions with sulphur\ndrugs and black dye if  patient\nhas ADR to bactrim\n\n\n\n\n\n"
"\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more than \n2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Comment \nand References. A Structured Abstract of not more than 240 \nwords must be included. It should consist of five paragraphs, \nlabelled Background, Methods, Results, Discussion and \nConclusion. It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nORIGINAL ARTICLE\n\n\n\n2 Validation of the Malay version of Autoimmune \nBullous Disease Quality of Life (ABQOL) \nquestionnaire\n\n\n\n Yap EWY, Tey KE, Subramaniam P, Murrell DF, \nChoon SE\n\n\n\n14\t Efficacy\tand\tSafety\tof\tLong\tPulsed\tNd:Yag\tLaser\t\nIn The Management of Hypertrophic Scars and \nKeloids\n\n\n\n Rajegowda HM, Gopal G, Madegowda SB, Kalegowda \nD\n\n\n\n19 A Randomized Single Blinded Study Comparing \nthe\t Efficacy\t of\t Bilastine\t Versus\t Cetirizine\t In\t\nAutoimmune Urticaria\n\n\n\n Raja T, Md Shah MN, Ng TG\n\n\n\n30 Basal Cell Carcinoma in The Department of \nDermatology, Hospital Kuala Lumpur, Malaysia\n\n\n\n\t Shahajan\tR,\tGoh\tSW,\tA\tMohd\tAffandi\n\n\n\n\n\n\n\nCASE REPORT \n\n\n\n38\t Jessner\u2019s\tLymphocytic\tInfiltration\tof\tthe\tSkin:\tA\tCase\t\nReport and Discussion of Current Literature\n\n\n\n Lim HB, Lee BR, Lim SW\n\n\n\n41 Adult onset Still\u2019s Disease: a case report in Hospital \nKuala Lumpur\n\n\n\n Lee CS, Tay LL, Chan GP, Baharom ZF, Lee BR, \nThevarajah S, Tang MM\n\n\n\n50\t A\t Curious\t Case\t of\t Diffuse\t Systemic\t Sclerosis\t with\t\nDiscoid\tLupus\tErythematosus-Like\tLesions:\tEnigma\t\nof An Overlap\n\n\n\n Abhijit BV, Brahmadeo CR, Sanjay DN, Vijay R, Kopal A.\n\n\n\n54 Benign cephalic histiocytosis: A Rare Dermatological \nEntity\tin\tthe\tPaediatric\tPopulation\n\n\n\n Ab Halim SA, Oh HH, Mohamad Taib F, Wan Ahmad \nKammal WSE\n\n\n\n57\t Post\t Surgical\t Cutaneous\t Nocardiosis\t Mimicking\t\nHypertrophic Scar: A Case Report\n\n\n\n Shashikumar BM, Savitha AS, Katwe K.\n\n\n\n60 Alleviating diagnostic dilemma of Maduramycosis: A \nCase Series\n\n\n\n Date P, Kar S, Gangane N, Deshmukh A, Pratiksha \nSonkusale P, Patrik S, Sawant A, Manwa P\n\n\n\n65 Online, Game-based Learning (GBL) On Melanoma: \nThe Learning Experiences Of A Medical Student\n\n\n\n Lim TLC\n\n\n\nCLINICAL IMAGE  \n\n\n\n69\t Quackery\tand\tsuperstitions:\tThe\tSkin\tdoctor\u2019s\tbane\n Date P, Kar S, Patrik S, Sawant A\n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n1\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, M Adv Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2019 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv \nM Derm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm\nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nExecutive Committee \nChan Lee Chin, MMed - President\nNoor Zalmy Azizan, Adv M Derm - Vice President\nSabeera Begum, MMed - Secretary\nTan Wooi Chiang, Adv M Derm - Treasurer\nAgnes Heng Yoke Hui, MRCP - Past President\nDr Tang Jyh Jong, Adv M Derm - \nCommittee Member\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - \nCommittee Member\nDr. Sharifah Rosniza Syed Nong Chek, \nAdv M Derm - Committee Member\n\n\n\nDermatological Society of Malaysia \n(Rumah Dermatology)\nG1, Medical Academics of Malaysia, 210, \nJalan Tun Razak, 50400 Kuala Lumpur, \nMalaysia\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2\n\n\n\nORIGINAL ARTICLE\n\n\n\nValidation of the Malay version of Autoimmune Bullous Disease \nQuality of Life (ABQOL) questionnaire          \nEvelyn Wen Yee Yap1, AdvMDerm, Kwee Eng Tey1, MRCP, Premaa Supramaniam2, BSc, Dedee Murrell3, FRCP, Siew \nEng Choon1, FRCP  \n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia\n2Clinical Research Centre, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia\n3St. George Hospital, University of New South Wales, Sydney, Australia\n\n\n\nAbstract\nIntroduction\nAutoimmune blistering diseases (AIBD) represent a group of rare and chronic disorders with significant \nimpact on quality of life (QoL). The aim of this study was to assess the validity and reliability of the \nMalay translation of the autoimmune bullous disease quality of life (ABQOL) questionnaire.\n\n\n\nMethods\nThis was a cross-sectional, questionnaire based study involving 75 patients with AIBD. The Malay \nversion of ABQOL was produced by forward-backward translation of the original ABQOL. This was \nthen administered to patients with pemphigus vulgaris, pemphigus foliaceous and bullous pemphigoid \nalong with validated Malay versions of Dermatology Life Quality Index (DLQI) and Short Form \nHealth Survey (SF-36) questionnaires. Validity was evaluated across a range of indices and reliability \nwas assessed using internal consistency and test-retest methods. \n\n\n\nResults\nInternal consistency and test-retest reliability were high (Cronbach alpha= 0.940, r= 0.89). The \nMalay ABQOL had high correlation with the DLQI (r=0.73. p<0.001) and moderate correlation with \nthe SF-36 (r=0.50, p<0.001). It also correlated moderately with PDAI and BPDAI disease severity \nscores (r=0.47, p<0.001, and r=0.60, p= 0.002). There was no significant difference in proportion of \ninsensitive items between the ABQOL versus DLQI, and ABQOL versus SF-36.\n\n\n\nConclusion\nThe Malay ABQOL is a valid and reliable tool for assessing QoL in AIBD patients.\n\n\n\nKey words: Autoimmune blistering disease, quality of life, Malay, pemphigus, pemphigoid\n\n\n\nCorresponding Author\nEvelyn Yap Wen Yee\nDepartment of Dermatology, Hospital Sultanah Aminah \nJohor Bahru, Jalan Persiaran Abu Bakar Sultan, 80100 \nJohor Bahru, Johor, Malaysia\nEmail: Chervil_82@hotmail.com\n\n\n\nIntroduction\nAutoimmune blistering diseases (AIBD) represent \na group of rare and chronic condition which causes \nsignificant distress to those suffering from it. Clinical \nsubtypes are dependent on the protein sites within \nthe keratinocyte membrane and dermo-epidermal \njunction to which pathogenic auto-antibodies target. \nRegardless of subtype, AIBD cause enormous \nphysical and psychological burden.1 Painful and \nitchy blisters and erosions are particularly disabling \nif the mucous membranes are involved. As the skin \nis also an integral part of the image we project to the \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n3\n\n\n\noutside world, disfigurement from blisters, erosions, \ncrusting or post inflammatory hyperpigmentation \ncan lead to low self-esteem and depression. \n\n\n\nQuality of life (QoL) assessment tools take into \nconsideration patients\u2019 perspectives of their disease \nand treatment, their perceived need for health care, \nand their preferences for treatment and outcomes.2 \nBeing patient centred, aspects of patients\u2019 health \nstatus that are significant for the patient, but may \nnot correlate with clinical severity can be better \nidentified with the use of QoL assessment tools. In the \npast, QoL issues amongst patients have frequently \nbeen overlooked by clinicians due to various \nreasons, amongst which include time constrains and \ndifficulty in interpreting as compared to laboratory \nparameters. However, this had begun to change as \ndoctors and researchers started recognizing QoL as \noutcome measures in clinical trials.3 Over the past \ntwo decades, multiple attempts of evaluating AIBD\u2019s \nimpact on quality of life (QoL) have been conducted \nin various parts of the world, mostly using generic \nand skin specific QoL questionnaires. Some of these \ninclude The Medical Outcome Study 36-item Short-\nform Survey (SF-36), Dermatology Life Quality \nIndex (DLQI), Skindex and 12-item General Health \nQuestionnaire (GHQ-12). Although all of these \nstudies consistently reported negative QoL impact, \nthe generic nature of these questionnaires may have \nlimitations in capturing small changes affecting \nAIBD patients.4-7 This had led to the formulation of \nthe Autoimmune Bullous Disease Quality of Life \n(ABQOL) questionnaire by the Australian panel of \nbullous experts, which is a 17-item questionnaire \nlooking at impact of autoimmune bullous disease \non QoL.8 \n\n\n\nThere is paucity of Malaysian data regarding AIBD \nimpact on QoL which was partly contributed by the \nlack of validated AIBD-specific QoL instruments, \nparticularly in the Malay language. Malaysia is \na country of multiethnicity, comprising of 60% \nMalays, 23% Chinese, 7% Indians and 10% others.9 \nProficiency in the Malay language is not only seen \nin the native Malays, which comprise the majority \nof Malaysians, but also Malaysians of other races.  \nThis is because the Malay language is the main \nmedium of education throughout the entire period \n(11 years) of primary and secondary education in \nthe country since 1969.10 As clinical trials of new \ntherapies in AIBDs are occurring and using patient \nreported outcomes such as DLQI and ABQOL as \noutcome measures, there is a need for the ABQOL \nto be validated in Malay to enable Malaysia to be \n\n\n\nincluded in these studies. Thus, the purpose of \nthis study was to translate and adapt the ABQOL \nquestionnaire into Malay and evaluate its validity \nand reliability in the Malaysian context. \n\n\n\nMaterials and Methods\n\n\n\nPatients\tSelection\nThis cross-sectional, questionnaire based study \nwas carried out after approval from the Malaysian \nResearch Ethics Committee (NMRR-14-574-\n20838) was obtained. The inclusion criteria were: \npatients with histologically confirmed diagnosis \nof AIBD with self-professed proficiency in Malay \nlanguage who are at least 18 years old and able \nto give informed consent. Proficiency in Malay \nlanguage was confirmed via conversation with a \nMalay nurse, followed by reading and filling up of \nthe consent form, which was in Malay.\n\n\n\nTranslation of questionnaire\nPermission to translate and use this questionnaire \nwas obtained from the author who developed it \n(DFM).8 This questionnaire was forward translated \nto Malay by a certified translation agency in \nMalaysia. The Malay questionnaire was then \nreviewed by a group of doctors who are proficient in \nthe language to ensure cultural relevance. Following \nthat, the forward translated questionnaire was given \nto a different translation agency which had no access \nto the original ABQOL to be back-translated. The \nback-translated version was then reviewed against \nthe original by the original developer of the ABQOL \n(DFM). Discrepancies found between the forward \nand backward translations were resolved between \nthe developer of the original ABQOL (DFM), \nprincipal investigator (EY), forward translation and \nback translation agencies. \n\n\n\nStudy procedures\nMedical Information\nMedical records of recruited patients were \nreviewed by two Dermatology consultants (SEC \nand KET) and one Dermatology trainee (EY) to \nverify diagnosis of AIBD, duration of disease and \ntreatment regimens. This was then followed by a \ncomplete physical examination evaluating severity \nand stage of AIBD. Severity of AIBD was scored \nusing either the Pemphigus Disease Activity Index \n(PDAI) or Bullous Pemphigoid Disease Activity \nIndex (BPDAI).11-12 Disease stage was determined \naccording to the \u2018Consensus statement on definitions \nof disease, end points and therapeutic response for \npemphigus\u2019 and \u2018Definitions and outcome measures \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4\n\n\n\nfor bullous pemphigoid\u2019.13-14 \n\n\n\nQuestionnaires\nPatients recruited were asked to complete 3 patient-\nadministered questionnaires. The questionnaires \ninvolved are the validated Malay versions of:\n \na. Dermatology Life Quality Index (DLQI)15\n\n\n\nb. The Medical Outcome Study 36-item Short-\nform Survey (SF-36)16\n\n\n\nc.  Autoimmune Bullous Disease Quality of Life \n(ABQOL)9\n\n\n\nTwenty-one out of the 75 patients recruited were \nrequired to return to the clinic 10-14 days after \ncompletion of the questionnaires for a repeat \nABQOL questionnaire. \n\n\n\nReliability\nInternal consistency along with construct validity \nwas determined using Cronbach\u2019s alpha coefficient. \nTest-retest reliability evaluated reproducibility of the \nABQOL results at different times. This is determined \nusing the intra-class correlation coefficient (ICC), \ngenerated by comparing the ABQOL scores at Day \n0 and Day 10-14. An interval of 10-14 days was \nobserved before administering the repeat ABQOL \nto eliminate risk of recall bias.\n\n\n\nValidity \nValidation of the Malay translation of ABQOL \nincluded the assessment of face, content, construct, \nconvergent, and discriminant validity. Face and \ncontent validity were established by forward-\nbackward translation of the ABQOL. Convergent \nvalidity was determined by comparing the ABQOL \nscores with the DLQI or SF-36 scores. Discriminant \nvalidity was evaluated by comparing the proportions \nof insensitive items in the ABQOL and DLQI or \nABQOL and SF-36. The definition of insensitive \nitems were items with more than 50% of patients \nresponding with an extreme value (ie, a response of \nnever or always), which was an accepted threshold \nin the literature.17 \n\n\n\nFactor analysis\nThe dimensionality of the questions in the Malay \ntranslation of ABQOL was assessed using \nexploratory principal components analysis followed \nby Oblimin rotation.18 Significance was defined as a \nloading of more than 0.4. Item complexity occurred \nif an item loaded less than 0.4 or loaded more than \n0.4 on more than 1 factor.8 In the event where an \nitem loaded significantly on more than 1 factor, \n\n\n\nthe item will be assigned to the factor which best \nrepresents it.\n\n\n\nStatistical analysis \nAll statistical analyses were performed using SPSS \nv19.0 (SPSS, Inc., Chicago, IL) by a biostatistician \n(PS) and the principal investigator (EY). A p-value \nof <0.05 was considered statistically significant. \n\n\n\nRESULTS\nSeventy-five patients with AIBD were recruited \nfrom May 2014 to January 2015. Demographic \nand clinical characteristics of our patients were \nsummarised in Table 2. Figure 1 summarised the \nresponses of AIBD patients to the questions in \nthe Malay ABQOL questionnaire. There was a \nsignificant difference between the median ABQOL \nscores in patients with disease duration less than 6 \nmonths and those with disease duration more than \n6 months (21.0 versus 10.5, p=0.012). A significant \ndifference was also found in the median ABQOL \nscores between patients aged less than 55 and \npatients aged 55 years old and above (18.0 versus \n9.0, p<0.001). Patients of the pemphigus spectrum \nscored worse than pemphigoid patients (15.5 versus \n7.0, p=0.001). Chinese patients reported a better QoL \ncompared to Malay and Indian patients. (Chinese \nversus Malay: 7.5 versus 18.5, p<0.001, Chinese \nversus Indian: 7.5 versus 17.0 p=0.025). There was \nno significant difference in ABQOL scores amongst \ndifferent genders. (Table 3)\n\n\n\nReliability and validity\nThere was high level of internal consistency and \nconstruct validity of the Malay translation of ABQOL \n(Cronbach alpha = 0.940). Test-retest reliability \nshowed high level of intraclass correlation (ICC) \n(r=0.89). The Malay ABQOL had high correlation \nwith the DLQI (r=0.73. p<0.001) and moderate \ncorrelation with the SF-36 (r=0.50, p<0.001). \nSpearman\u2019s correlation revealed the Malay \ntranslation of ABQOL correlated moderately with \nthe PDAI (r=0.47, p<0.001) and BPDAI (r=0.60, \np=0.002) scores. With regards to discriminant \nvalidity, insensitive items were found in 10 out of \n17 ABQOL, 8 out of 10 DLQI and 17 out of 36 \nSF-36 items. There were no significant difference \nin the proportion of these insensitive items between \nthe ABQOL versus DLQI, and ABQOL versus SF-\n36. Table 3 summarised measures of validity and \nreliability of the Malay translation of ABQOL.\n \nFactor analysis\nThe Kaiser-Meyer-Olkin measure of sampling \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n5\n\n\n\nVariables Frequency (%)\nAge (years) (mean, S.D) 54.7 (+15.6)\nGender\nMale\nFemale\n\n\n\n24 (32.0)\n51 (68.0)\n\n\n\nRace\nMalay\nChinese\nIndian\nOthers\n\n\n\n30 (40.0)\n30 (40.0)\n14 (18.7)\n1 (1.3)\n\n\n\nAutoimmune bullous disease (AIBD)\nPemphigus vulgaris\nPemphigus foliaceous\nBullous pemphigoid\n\n\n\n35 (46.7)\n17 (22.7)\n23 (30.7)\n\n\n\nDisease severity\nPemphigus vulgaris (PDAI score: median, IQR)\nPemphigus foliaceous (PDAI score: median, IQR)\nBullous pemphigoid (BPDAI score: median, IQR)\n\n\n\n17.0 (18.0)\n15.0 (24.5)\n 2.0 (17.0)\n\n\n\nDistribution of patients in different disease stages with regards to disease duration\n7 (41.2)\n4 (23.5)\n2 (11.8)\n1 (5.9)\n0 (0)\n0 (0)\n\n\n\n3 (17.6)\n0 (0)\n0 (0)\n\n\n\nLess than 6 months\n(n=17)\n\n\n\nBaseline\nControl of disease activity\nTime to disease control\nEnd of consolidation phase\nPartial remission on therapy\nPartial remission off therapy\nFlare\nComplete remission on therapy\nComplete remission off therapy\n\n\n\nMore than 6 months\n(n=58)\n\n\n\nBaseline\nControl of disease activity\nTime to disease control\nEnd of consolidation phase\nPartial remission on therapy\nPartial remission off therapy\nFlare\nComplete remission on therapy\nComplete remission off therapy\n\n\n\n0 (0)\n1 (1.7)\n1 (1.7)\n\n\n\n38 (65.5)\n3 (5.2)\n0 (0)\n\n\n\n3 (5.2)\n11 (19.0)\n\n\n\n1(1.7)\n\n\n\nTable 1. Demographic and clinical characteristics of autoimmune bullous disease patients recruited (n=75)\n\n\n\nFigure 1. Responses of patients (in percentage) to questions in the Malay ABQOL (n=75)\n\n\n\nResponses of patients (%) to questions in the Malay ABQOL (n=75)%\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6\n\n\n\nTable 2. Effects of gender, age group, disease duration, \nautoimmune bullous disease (AIBD) subtypes and treatment \ngrade on ABQOL scores\n\n\n\nTable 3. Validity and reliability of the Malay translation of \nABQOL\n\n\n\nFigure 2. Test-retest reliability of the ABQOL (n=21)\n\n\n\np-values generated using Mann-Whitney test\n\n\n\nABQOL scores (IQR) p-value\nGender Male 12.5 (22.0) 0.941\n\n\n\nFemale 11.0 (15.0)\nAge <55 18.0 (17.0) p<0.001\n\n\n\n>55 9.0 (14.0)\nDisease \nDuration\n\n\n\n<6 months 21.0 (26.0) p=0.012\n>6 months 10.5 (14.0)\n\n\n\nAIBD subtype Pemphigus 15.5 (16.0) p=0.001\nPemphigoid 7.0 (8.0)\n\n\n\nEthnic group Malay 18.5 (15.0) p<0.001\nChinese 7.5 (10.0)\nMalay 18.5 (15.0) p=0.562\nIndian 17.0 (28.0)\nChinese 7.5 (10.0) p=0.025\nIndian 17.0 (15.0)\n\n\n\nMethods Results\nFace and \ncontent validity\n\n\n\nForward-backward translation, \nresolution of discrepancies by \nauthor and owner of the original \nquestionnaire\n\n\n\nAcceptable\n\n\n\nConvergent \nvalidity\n\n\n\nCorrelation with PDAI\nCorrelation with BPDAI\nCorrelation with DLQI\nCorrelation with SF-36\n\n\n\nr= 0.47, \np<0.001\nr= 0.60, \np=0.002\nr= 0.73, \np<0.001\nr= -0.50, \np<0.001\n\n\n\nDiscriminant \nvalidity\n(Fisher exact test)\n\n\n\nDLQI\nSF-36\n\n\n\np= 0.758\np= 0.803\n\n\n\nInternal \nconsistency\n\n\n\nCronbach\u2019s alpha \u03b1= 0.940, \np<0.001\n\n\n\nTest-retest \nreliability\n\n\n\nICC r=0.89\n\n\n\nAB\nQ\n\n\n\nO\nL \n\n\n\nSc\nor\n\n\n\nes\n: D\n\n\n\nay\n 1\n\n\n\n0 \nto\n\n\n\n 1\n4\n\n\n\nABQOL Scores: Day 0\n\n\n\nadequacy (0.840) and the Bartlett test of sphericity \n(p < 0.001) suggested that factor analysis of the data \nwas appropriate. Scree plot generated suggested that \nthree factors (symptom, mucosal, and psychosocial) \nshould be retained, representing 57.47% of the \ncumulative variance. The rotation matrix obtained \nby the exploratory principal components analysis \nfollowed by Direct Oblimin rotation indicated that \n11 items loaded on symptom subscale (questions 1, \n2, 3, 5, 9, 10, 12, 14, 15, 16 and 17); four items \nloaded on mucosal subscale (questions 6, 7, 8 and \n11); and two items loaded on psychosocial subscale \n(questions 4 and 13). Of these 17 questions, question \n9 (embarrassment) exhibited complexity (symptoms \nfactor loading 0.598 and psychosocial factor loading \n0.420). This was eventually assigned to psychosocial \nfactor as we felt it represented embarrassment \nmore accurately. The three dimensions and their \nrepresenting items were summarised in Table 4.\n\n\n\nDiscussion\nOur study confirmed the Malay translation of the \nABQOL questionnaire was a valid and reliable tool \nin capturing the impact of autoimmune bullous \ndisease (AIBD) on quality of life. In the Malaysian \ncontext, a very high level of internal consistency was \nfound (Cronbach\u2019s alpha 0.94). This is in keeping \nwith the results of the original authors in Australia \n(Cronbach\u2019s alpha 0.84) and other similar studies in \nvarious parts of the world such as the North America \n(Cronbach\u2019s alpha 0.90), China (Cronbach\u2019s alpha \n0.88) and Poland (Cronbach\u2019s alpha 0.95).8,19-21 There \nwas high level of reproducibility of questionnaire \nresults under similar conditions, as evidenced by \nintraclass coefficient (ICC) of 0.89. Again, this is \nconsistent with studies mentioned earlier.8,19-21 Like \nthe Chinese group, we found the ABQOL correlated \nhighly with the DLQI but moderately with the SF-\n36.20 Studies done in Australia, North America and \nPoland showed the English and Polish ABQOL \nhad a moderate correlation with the DLQI and SF-\n36.8,19,21 The Greek ABQOL had good correlation \nwith the DLQI, but no comparison was made with \nthe SF-36.22 \n\n\n\nAll of our subjects were patients of pemphigus \nvulgaris, pemphigus foliaceous and bullous \npemphigoid. This reflected the majority of AIBDs \nseen in our practice. In both the pemphigus \nand pemphigoid group of patients, the ABQOL \ncorrelated moderately with disease severity (PDAI, \nr=0.47, p<0.001, BPDAI, r=0.60, p<0.002). This \nphenomenon is also seen amongst the Greek (PDAI, \nr= 0.56, BPDAI, r= 0.55) and Australian (PDAI, \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n7\n\n\n\nTable 4. Principal components and factor analysis of Malay \ntranslation of ABQOL\n\n\n\naBold items load on assigned factor. Extraction method was \nprincipal components analysis; rotation method was Oblimin \nwith Kaiser normalization.\nbIndicates\tfinding\tof\titem\tcomplexity.\n\n\n\nNo. Items Component\nSymptoms Mucosal Psychosocial\n\n\n\n1. Pain .734 .081 -.010\n2. Itch .428 .352 -.031\n3. Healing .619 .143 -.150\n4. Clothing changes .013 .198 .716\n5. Bathing/Showering .794 -.247 .068\n6. Pain (mouth) .096 .733 .192\n7. Gingival bleeding -.108 .847 .055\n8. Food avoidance .261 .565 .078\n9. Embarrassmentb .598 -.168 .420\n10. Depression .693 .217 -.003\n11. Anxiety .346 .454 .323\n12. Family/friends .558 .137 .239\n13. Sexual activity -.007 .083 .800\n14. Relationships .665 .209 -.266\n15. Social life .761 -.241 .109\n16. Work & Study .689 .201 .012\n17. Discrimination .585 -.035 .227\n\n\n\nr= 0.42, ABSIS, r= 0.48) patients.7,22 The Polish \ngroup however, found poor correlation between \nthe ABQOL with the PDAI (r= 0.38) and BPDAI \nscores (r=0.40).21 All of these results suggested \nthat the degree to which patient\u2019s QoL was affected \nmay not be dependent on clinical severity alone. \nOther factors contribute as well, including patient \ndemographic characteristics, the natural history and \nsite of skin disorders, and time to diagnosis.5 \n\n\n\nOur study showed that disease duration of less \nthan 6 months had a significantly higher impact on \npatients\u2019 ABQOL scores. This could be accounted \nby the fact that more than half (58.8%) of patients \nwith disease duration less than 6 months had clinical \nstages of baseline and flare, where clinical states \nwere expected to be most severe. In comparison, \namongst patients with disease duration more \nthan 6 months, only 5.2% were of these stages. \nAnother explanation is that patients may not have a \nsufficient understanding of the clinical implications \nof the AIBDs when they were first diagnosed \nwith the conditions, leading to poorer coping and \nadaptation abilities to their condition.5 Patients of \nthe pemphigus spectrum were also found to have \npoorer health status compared to the pemphigoid \ngroup. This could be because bullous pemphigoid is \ngenerally considered a less severe disease compared \nto pemphigus vulgaris. Moreover, pemphigus \ntends to affect a younger group of patients who \nare employed and more socially active.23 Heelan et \n\n\n\nal proved that AIBDs affected work performance, \nespecially in patients with severe disease. This \nwas evidenced by the high Work Productivity and \nActivity Impairment Questionnaire-Specific Health \nProblems (WPAIQ-SHP) scores, which took into \nconsideration work missed, impairment while \nworking, total work productivity impairment, and \ntotal activity impairment. The same study also \nreported that patients with worse DLQI scores \nhad higher overall work impairment and activity \nimpairment, reiterating the fact that disturbance in \nwork performance negatively affects QoL.24 Even \nthough there was no significant difference in disease \nseverity amongst the three main races, Chinese \npatients scored significantly lower compared to \nMalay and Indian patients. The Chinese culture \npromotes endurance, acceptance and adaptation to \none\u2019s fate, including presence of illnesses. Hence, \nthe lower life expectations may have contributed \nto the Chinese rating their health status more \nfavourably.25\n\n\n\nThe Australian group who developed the original \nABQOL questionnaire found it to be more sensitive \nthan the DLQI and SF-36 in capturing the effects on \nQoL caused by changes in the clinical status.8 Our \ndata however showed that all 3 tools are good in \nmeasuring changes in QoL with disease stage. We \nfound 10 insensitive items in the Malay version of \nABQOL, which was 3 items more compared to the \noriginal version of ABQOL. Of all the insensitive \nitems on the Malay ABQOL, questions pertaining \nto sexual activity, interpersonal relationships and \nworkplace or school discrimination had the highest \npercentage of respondents with scores of zero \n(73.3%, 81.3% and 81.3% respectively). We felt \nthe Asian culture may have played a role here. Sex \nand sexuality is not comfortably discussed amongst \nmany Asians. This was confirmed by a study \nconducted across China, Taiwan, South Korea, \nJapan, Thailand, Singapore, Malaysia, Indonesia \nand the Philippines looking at sexual behaviour, \ndysfunction and help-seeking patterns amongst an \nurban Asian population.26 Besides, many Asians \nemphasises the importance of family harmony and \ninterpersonal relationships, and the high value of \neducation and hard work. Saving face \u2013 the ability \nto preserve the public appearance of the patient \nand family for the sake of community propriety is \nextremely important to most Asian groups.27 This \nmay have accounted for the low scores of these \nquestions.\n\n\n\nOur study was limited by overrepresentation of \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8\n\n\n\nAIBD by pemphigus vulgaris, pemphigus foliaceous \nand bullous pemphigoid patients. Hence suitability \nof this questionnaire for patients of other AIBDs \nsuch as epidermolysis bullosa acquisita (EBA), \nparaneoplastic pemphigus, cicatricial pemphigoid, \ndermatitis herpetiformis (DH) and linear IgA \nbullous dermatoses (LABD) is unknown. \n\n\n\nConclusion\nThe Malay version of ABQOL was a valid and \nreliable tool that will enable clinicians gain better \ninsight into our Malaysian patients\u2019 experience \nin AIBD. In addition, this could serve as a tool \nfor disease monitoring. The applicability of this \nquestionnaire may also be extended to the Malay-\nspeaking patients within the region, such as in \nSingapore, Brunei and Indonesia. We believe a better \nunderstanding of the impact of AIBD on patients\u2019 \nQoL will enhance patients\u2019 care and satisfaction.\n\n\n\nDeclaration\tof\tConflict\tof\tInterest\nThe authors have no conflict of interest to declare.\n\n\n\nFootnote\nThe Malay version of the ABQOL is included at \nthe end of this article (Appendix 1). The license \nfor this Malay ABQOL belongs to the Australasian \nBlistering Diseases Foundation.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper. The authors also would like to thank the \nMalaysian Society of Dermatology for a grant in \nconducting this research.\n\n\n\nReferences\n\n\n\n1. Sebaratnam DF, McMillan JR, Werth VP, Murrell DF. \nQuality of life in patients with bullous dermatoses. Clin \nDermatol. 2012;30:103-7.\n\n\n\n2. Carr AJ, Higginson IJ. Are quality of life measures patient \ncentred? BMJ 2001; 322:1357-60.\n\n\n\n3. 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Quality of life and psychological \nstatus of patients with pemphigus vulgaris using \nDermatology Life Quality Index and General Health \nQuestionnaires. J Dermatol 2012;39:141-4.\n\n\n\n8. Sebaratnam DF, Hanna AM, Chee SN, Frew JW, \nVenugopal SS, Daniel BS et al. Development of a quality-\nof-life instrument for autoimmune bullous disease: \nThe Autoimmune Bullous Disease Quality of Life \nquestionnaire. JAMA Dermatol 2013;149:1186-91.\n\n\n\n9. Chung CM, Lu MZ, Wong CY, Goh SG, Azhar MI, Lim \nYM et al. The SAD\u2013MEN questionnaire: a new and \nreliable questionnaire for assessing sexual dysfunction in \nAsians with diabetes. Diabet Med 2016;33:674-80.\n\n\n\n10. Thirusanku J, Yunus MM. Status of English in Malaysia. \nAsian Social Science 2014;10:254-60.\n\n\n\n11. Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, \nFakharzadeh S et al. Reliability and convergent validity \nof two outcome instruments for pemphigus. J Invest \nDermatol 2009;129:2404-10.\n\n\n\n12. Wijayanti A, Zhao CY, Boettiger D, Chiang YZ, Ishii \nN, Hashimoto T et al. The reliability, validity and \nresponsiveness of two disease scores (BPDAI and ABSIS) \nfor bullous pemphigoid: Which one to use? Acta Derm \nVenereol 2017;97:24-31.\n\n\n\n13. Murrell DF, Dick S, Ahmed AR, Amagai M, Barnadas \nMA, Borradori L et al. Consensus statement on definitions \nof disease, end points, and therapeutic response for \npemphigus. J Am Acad Dermatol 2008;58:1043-6.\n\n\n\n14. Murrell DF, Daniel BS, Joly P, Borradori L, Amagai M, \nHashimoto T et al. Definitions and outcome measures for \nbullous pemphigoid: recommendations by an international \npanel of experts. J Am Acad Dermatol 2012;66:479-85.\n\n\n\n15. Finlay A, Khan G. Dermatology Life Quality Index \n(DLQI) - a simple practical measure for routine clinical \nuse. Clin Exp Dermatol 1994;19:210-6.\n\n\n\n16. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form \nhealth survey (SF-36). I. Conceptual framework and item \nselection. Med Care. 1992;30:473-83.\n\n\n\n17. Chen SC, Yeung J, Chren MM. Scalpdex: a quality-\nof-life instrument for scalp dermatitis. Arch Dermatol \n2002;138:803-7.\n\n\n\n18. Costello AB, Osborne J. Best practices in exploratory \nfactor analysis: four recommendations for getting the most \nfrom your analysis. Practical Assessment, Research and \nEvaluation 2005;10:1-7\n\n\n\n19. Sebaratnam DF, Okawa J, Payne A, Murrell DF, Werth VP. \nReliability of the autoimmune bullous disease quality of \nlife (ABQOL) questionnaire in the USA. Qual Life Res \n2015;24:2257-60.\n\n\n\n20. Yang B, Chen G, Yang Q, Yan X, Zhang Z, Murrell DF \net al.  Reliability and validity of the Chinese version of \nthe autoimmune bullous disease quality of life (ABQOL) \nquestionnaire. Health Qual Life Outcomes. 2017;15:31.\n\n\n\n21. Kalinska-Bienias A, Jakubowska B, Kowalewski C, \nMurrell DF, Wozniak K. Measuring of quality of life in \nautoimmune blistering disorders in Poland. Validation of \ndisease\u2013specific Autoimmune Bullous Disease Quality of \nLife (ABQOL) and the Treatment Autoimmune Bullous \nDisease Quality of Life (TABQOL) questionnaires. Adv in \nMedical Sciences 2017;62:92-6.\n\n\n\n22. Patsatsi A, Kokolios M, Kyriakou A, Lamprou F, \nStylianidou D, Tsapas A et al. Quality of Life in Greek \nPatients with Autoimmune Bullous Diseases Assessed \nwith ABQOL and TABQOL Indexes. Acta Derm Venereol \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n9\n\n\n\n2017;97:1145-7.\n23. Sav A, Whitty JA, McMillan SS, Kendall E, Kelly F, King \n\n\n\nMA et al. Treatment burden and chronic illness: who is at \nmost risk. Patient 2016;9:559-69.\n\n\n\n24. Heelan K, Hitzig SL, Knowles S, Drucker AM, Mittmann \nN, Walsh S et al. Loss of work productivity and quality \nof life in patients with autoimmune bullous dermatoses. J \nCutan Med Surg 2015;19:546-54.\n\n\n\n25. Lam CL, Lauder IJ. The impact of chronic diseases on the \nhealth-related quality of life (HRQOL) of Chinese patients \nin primary care. Fam Pract. 2000;17:159-66.\n\n\n\n26. Nicolosi A, Moreira ED, Villa M, Glasser DB. A population \nstudy of the association between sexual function, sexual \nsatisfaction and depressive symptoms in men. J Affect \nDisord 2004;82:235-43.\n\n\n\n27. Kramer EJ, Kwong K, Lee E, Chung H. Cultural factors \ninfluencing the mental health of Asian Americans. West J \nMed 2002;176:227-31.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10\n\n\n\nAppendix 1: Malay ABQOL Questionnaire\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n11\n\n\n\n\n\n\n\n \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12\n\n\n\n\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n13\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFootnote: The license for this Malay ABQOL belongs to the Australasian Blistering Diseases Foundation.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14\n\n\n\nORIGINAL ARTICLE\n\n\n\nEfficacy and Safety of Long Pulsed Nd:YAG Laser in the Management \nof Hypertrophic Scars and Keloids         \nHarish Muddenahalli Rajegowda, MD; Gagana Gopal, MBBS; Shashikumar Basavapura Madegowda, MD; Deepadarshan \nKalegowda, MD\n\n\n\nDepartment of Dermatology, Venereology and Leprosy, Mandya Institute of Medical Sciences, Mandya, Karnataka, India\n\n\n\nAbstract\nIntroduction\nKeloid scars have always been a therapeutic challenge. Lasers due to their versatile action are being \ntried in the management of hypertrophic scars and keloid. Use of Nd:YAG laser especially in dark skin \ntypes is justifiable but sufficient data is not available. \n\n\n\nMethods\n30 clinically diagnosed cases of keloids and hypertrophic scars were enrolled and treated by 1064nm \nlong pulsed Nd:YAG laser for 3 sessions at 4 weekly interval. Therapeutic effectiveness was evaluated \nat baseline, during each visit and one month after the last session using Vancouver Scar Scale (VSS). \nPhotographs were taken during each visit.\n\n\n\nResults\nA total of 26 patients with keloid and four patients with hypertrophic scar were included in the study. Common \nage group encountered was 21 \u2013 30 years with M:F ratio of 2:1. Chest was the commonest site involved as \nnoticed in 13 (43.3%) patients. Altogether, 15.7% improvement was evidenced in the VSS from baseline to \npost-treatment with response being documented in 13 (43.3%) of the 30 patients. Clinical response was seen \nin 13 patients of whom 5 patients showed < 25% improvement and the remaining 8 patients showed 25 \u2013 75% \nimprovement. Statistically significant improvement was recorded in pliability (p= 0.00) parameter of the VSS. \nSide effects were minimal like pruritis and pain seen in 30% patients.\n\n\n\nConclusion\n1064nm long pulsed Nd:YAG laser has limited efficacy as monotherapy in the treatment of keloid and \nhypertrophic scar. Nevertheless, it is a safe and well-tolerated procedure.  \n\n\n\nKey words: 1064nm Nd:YAG laser, keloid, hypertrophic scar\n\n\n\nCorresponding Author\nDr Shashikumar Basavapura Madegowda\nDepartment of Dermatology, Venereology and \nLeprosy, Mandya Institute of Medical Sciences MIMS, \nMandya-571401 Karnataka, India\nEmail: shashikumarbm@gmail.com\n\n\n\nIntroduction\nKeloid and hypertrophic scar represent an inadvertent \naftermath of the normal wound healing process \ncharacterized by overgrowth of fibrotic tissue. The \ntrending therapeutic modalities in the management \nof these scars involve intralesional corticosteroids, \nsilicone gel sheets, mechanical pressure dressings, \n5-fluorouracil, bleomycin, verapamil and laser \ntherapy.1 Despite extensive research, no treatment \nmodality has proved effective in the permanent \nremoval of keloid.\n\n\n\nCurrently, the focus is on techniques that are \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n15\n\n\n\nminimally invasive, which calls for laser based \ntreatment. Apfelberg et al first reported the use of \nlasers on keloid by irradiation with CO2 and argon \nlasers.2\n\n\n\nLong-pulse Nd:YAG laser has caught the attention \nin the management of scars due to its multi-\npotential action on dermal vasculature and matrix \nmetalloproteinase (MMP).3 The mechanism of \naction is based on the principle of heat generation \nleading to an increase in vascular permeability, \nincreased MMP production and decomposition \nof collagen fibers.4 Nd:YAG laser is capable of \ngenerating changes in the collagen bearing tissue at \ndepths of 500 to 1000\u03bc.5 The heat attained reaches \na depth of mid-dermis which correlates well with \nthe level from where keloids generate. Furthermore, \nthe energy is only weakly absorbed by melanin and \nbetter absorbed by blood vessels making it safer for \nthe Indian skin.3\n\n\n\nMaterials and Methods\nThe study was carried out in a tertiary care hospital, \nMandya. Study protocol was approved from the \ninstitutional ethics committee. A detailed history \nof each patient was obtained and a thorough \ncutaneous examination was done with additional \nfocus on patient\u2019s skin type. Clinically diagnosed \ncases of keloids and hypertrophic scars fulfilling the \ninclusion and exclusion criteria were enrolled for \nthe study. Written informed consent was procured \nfrom the participants.\n\n\n\nInclusion criteria \nPatients with clinical diagnosis of hypertrophic scar \nand keloid.\n\n\n\nExclusion criteria\n1. Scar on the face\n2. Size of the scar > 5cm at presentation\n3. Age < 12 years\n4. Pregnant and lactating females\n5. Active infections in the area to be treated\n6. History of any topical or intralesional treatment \n\n\n\nfor the scar 4 weeks prior to the initiation of \ntherapy\n\n\n\n7. History of malignancy or radiation therapy\n8. Patients with unrealistic expectations\n\n\n\nProcedure\nEach of the participants were treated by 1064 nm \nlong pulse Nd:YAG laser. The area to be treated \nwas cooled with ice packs and protective eyewear \nwas provided to the patient as well as the treating \n\n\n\ndoctor. Topical anesthetic cream was avoided. \nNd:YAG laser (Celphia, Dermaindia) was delivered \nat a fluence of 25 J/cm2 with a spot size 7 mm. After \nthe procedure, the treated area was again cooled. A \ntotal of 3 sessions were given for each patient at 4 \nweekly intervals.\n\n\n\nTherapeutic effectiveness was evaluated at baseline, \nduring each visit and one month after the last session \nusing Vancouver Scar Scale (VSS). Photographs \nwere taken during each visit to monitor the clinical \nimprovement.\n\n\n\nVancouver Scar Scale\n\n\n\nStatistical Analysis \nData was analyzed with the help of the One-way \nANNOVA and other relevant tests using SPSS \nversion 20 software.\n\n\n\nRESULTS\nThe basic demographic characteristics of the study \nparticipants are tabulated in Table 1. The most \ncommon age group affected was 21 to 30 years \n(n=15, 50) and the M:F ratio = 2:1. Of the 30 study \nsubjects, 26 (86.7%) were found to have keloid and \n4 (13.3%) had hypertrophic scar.\n\n\n\nTable 1: Demographic characteristics of 30 study subjects\n\n\n\nUpon probing the history of inciting event, 15 \n(50%) patients gave history of trauma, surgical scar \nor pre-existing lesions like pyoderma, acne, burns or \nvaricella, while 11 (36.7%) patients claimed to have \ndeveloped keloid spontaneously. All the 4 cases of \nhypertrophic scar gave history of trauma or surgery.\n\n\n\nPIGMENTATION: \n0 - Normal colour\n1 - Hypopigmented\n2 - Hyperpigmented\n\n\n\nVASCULARITY:\n0 - Normal\n1 - Pink\n2 - Red\n3 - Purple\n\n\n\nPLIABILITY:\n0 - Normal\n1 - Supple (flexible with minimum resistance)\n2 - Yielding (giving way to pressure)\n3 - Firm (solid/inflexible, not easily moved)\n4 - Banding (rope like)\n5 - Contracture present\n\n\n\nHEIGHT: \n0 - Normal (flat)\n1 - <2mm\n2 - >2mm and <5mm\n3 - >5mm\n\n\n\nCharacteristics\n\n\n\nMean age (years) 29.87 years\n\n\n\nSex Male 20 (66.7%)\n\n\n\nFemale 10 (33.3%)\n\n\n\nFitzpatrick skin type Type IV 20 (66.7%)\n\n\n\nType V 10 (33.3%)\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16\n\n\n\nOut of a total of 30 study subjects, 6 patients (20%) \nwere asymptomatic and 24 patients had associated \nsymptoms. Pruritis was the most common symptom \nseen in 20 patients (66.7%) followed by pain seen in \n8 patients (26.7%). \n\n\n\nThe duration of onset ranged from 2 to 12 months \nfor hypertrophic scar and 1 - 16 years for keloid. \nThe duration was arbitrarily divided into early onset \nand late onset; lesions less than or equal to 1 year \nold were classified as early and lesions older than \n1 year were classified as late [Table 2]. However, \nduration had no statistically significant bearing on \nthe outcome of the laser treatment (p= 0.765).\n\n\n\nTable 2. Comparison of duration of the scar with response to \ntreatment\n\n\n\nChest was the most common site involved, recorded \nin 13 patients (43.3%). There was no statistically \nsignificant correlation (p=0.40) between site \ninvolved and response to treatment [Table 3].\n\n\n\nTable 3. Comparison of site of the lesions with response to \ntreatment\n\n\n\nOut of the 30 cases, response to treatment as \nassessed by VSS was seen in only 13 (43.3%) while \nthe remaining 17 (56.7%) cases did not show any \nresponse [Table 4]. The overall improvement in \nVSS from baseline to post-treatment session was \n15.7%.\n\n\n\nAt the end of study, response with respect to various \ncomponents of the VSS was analysed. Maximal \nresponse was seen in pliability where 10 (33.3%) \npatients showed improvement compared to baseline \nscore. Response pertaining to pigmentation, \nvascularity and height were documented in 5 \n(16.7%), 6 (20%) and 3 (10%) patients respectively \n\n\n\n[Graph 1]. On comparing the means of individual \nparameters with the mean improvement in VSS, \nstatistically significant improvement was recorded \nin pliability (p= 0.00) parameters.\n\n\n\nGraph 1. Response seen in individual parameters of the \nVancouver Scar Scale at the end of study\n\n\n\nPatients included in the study experienced negligible \nside effects, none of them severe enough to warrant \ndiscontinuation of treatment. Of the 30, only 9 \npatients complained of pruritis and pain in the \nlesions post treatment and it was more commonly \nencountered in the first session.\n\n\n\nDiscussion\nWith a growing knowledge regarding the basic \nanatomy and physiology of wound healing, \ntremendous advances have been made in the \nmanagement of keloid and hypertrophic scar. The \nhigh recurrence rate has always been and still \ncontinues to be the major limiting factor and so far, \nthere is no one gold standard treatment available for \npermanent keloid removal.3 \n\n\n\nIn the last two decades, pulsed dye laser (PDL) and \nCO2 laser have been given more emphasis in the \nmanagement of keloid. Keeping in view of the depth \nof keloid scars, we can expect better penetration \nand action with lasers of longer wavelength like \nNd:YAG (1064nm) than PDL (585nm) . The ample \nstudies available on the use of long-pulsed Nd:YAG \nlasers as monotherapy for keloid treatment on Indian \nskin is the basis for undertaking this study.\n\n\n\nDURATION n=30\nRESPONSE TO TREATMENT\n\n\n\nAbsent\nn=18\n\n\n\nPresent\nn=12\n\n\n\nEarly 14 8 6\n\n\n\nLate 16 10 6\n\n\n\nSITE n=30\nRESPONSE TO TREATMENT\n\n\n\nAbsent\nn=18\n\n\n\nPresent\nn=12\n\n\n\nAbdomen 2 0 2\n\n\n\nBack 3 2 1\n\n\n\nChest 13 7 6\n\n\n\nUpper limbs 9 7 2\n\n\n\nLower limbs 2 2 1\n\n\n\nTable 4. The analysis of response before and after treatment \nbased on total Vancouver Scar Scale\n\n\n\nRESPONSE n=30 Percent (%) \n\n\n\n0 17 56.7\n\n\n\n< 25% 5 16.7\n\n\n\n25 \u2013 50 % 4 13.3\n\n\n\n50 \u2013 75% 4 13.3\n\n\n\n75 \u2013 100% 0 0\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n17\n\n\n\nIn the present study, response was seen in only \n43.3% while the remaining 56.7% cases did not \nshow any response with an overall improvement \nof 15.7% in the VSS analysed one month after \nthe treatment session [Figure 1-3]. On the other \nhand, study conducted by Venkataram Mysore et al \nshowed total improvement of 29.6% in the VSS at \nthe end of their study.3 Another study conducted by \nShady Mahmoud Ibrahim et al reported a significant \nimprovement of 65.44% (p < 0.001) in the final \nVSS.6 In a study done by Kumar et al, of the 17 \nkeloids treated with Nd:YAG laser, 10 lesions \n(58.8%) completely resolved and 7 lesions (41.2%) \nshowed only partial resolution.7 The low response \nrate documented in our study may be due to the use \nof lower fluence and lesser sessions compared to the \naforementioned studies.\n\n\n\nFigure 1. Female patient with keloid over the chest before \ntreatment (A) and one month after treatment (B) showing \nresponse with respect to pigmentation, vascularity and height.\n\n\n\nFigure 2. Male patient with hypertrophic scar over his right \nknee before treatment (A) and after treatment (B) showing \nimprovement in pliability of the scar\n\n\n\nFigure 3. Male patient with keloid over his upper chest before \ntreatment (A) and after treatment (B) showing response \npertaining to pigmentation and pliability.\n\n\n\nIn our study, 17 patients did not show any \nimprovement, 5 patients showed less than 25% \nimprovement, 25 \u2013 50% and 50 \u2013 75% improvement \nwere seen in 4 patients each. These findings are, \nto some degree, comparable with the study done \nby Ashwini Annabathula et al who combined \npatients fractional CO2 laser, PDL and long pulse \nNd:YAG laser. Of the 11 patients enrolled in their \nstudy, 1 patient had excellent improvement, 1 \nhad good improvement, 4 patients had moderate \nimprovement, 2 patients had mild improvement and \n3 had no improvement.8\n\n\n\nAssessing the improvement in the individual \nparameters of the VSS, our study revealed \nstatistically significant response with respect to \npliability. This is consistent with the study done by \nShady Mahmoud Ibrahim et al who also reported \na significant reduction in the pliability of the scar.6 \n\n\n\nVenkataram Mysore et al reported that lesions of \nless than 6 months duration showed statistically \nsignificant improvement in terms of vascularity, \npliability, height and total VSS; on the other hand, \nkeloids of more than 6 months duration showed \nstatistically significant improvement in terms \nof vascularity, pliability and total score.3 On the \ncontrary, no statistically significant correlation was \nseen with treatment response and duration of the \nlesion in the current study. Neither did we document \nany correlation with the treatment response and site \nof the lesions.\n\n\n\nFurthermore, patients experienced negligible \nside effects like pain and pruritis reported in 30% \npatients, none of them severe enough to warrant \n\n\n\nA\n\n\n\nA B\n\n\n\nB\n\n\n\nA\nB\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18\n\n\n\ndiscontinuation of treatment. This finding was \nconsistent with other studies who also reported \nminimal adverse effects.6,7,8 Lower incidence of \nadverse effects can be attributed to the use of lower \nfluence in our study as a precaution to the high \nmelanin content of the patients\u2019 skin type.\n\n\n\nLimitation\nThe small sample size, short duration of the study \nand lack of adequate follow-up period are the \nlimitations of this study. For further research on this \ntopic, large scale studies combining other modalities \nwith laser therapy may be required.\n\n\n\nConclusion\nTo conclude, 1064nm long pulsed ND:YAG laser \nis safe but less effective as monotherapy in the \nmanagement of keloid and hypertrophic scar. On \nthe other hand, considering the simplicity, non-\ninvasiveness and safety profile, it may be explored \nas an adjuvant to other modalities which can be \ndirected at different components of the keloid. \nHowever, it must be borne in mind that laser therapy \ncan be time-consuming and most definitely bears a \nfinancial burden on the patient.\n\n\n\nConflict\tof\tInterest\tDeclaration \nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\t\nNil\n\n\n\nReferences\n\n\n\n1. Kelly AP. Medical and surgical therapies for keloids. \nDermatol Ther 2004;17:212-8.\n\n\n\n2. Apfelberg DB, Maser MR, Lash H, White D, Weston \nJ. Preliminary results of argon and carbon dioxide laser \ntreatment of keloid scars. Lasers Surg Med 1984;4:283-90.\n\n\n\n3. Alster TS, Handrick C. Laser treatment of hypertrophic \nscars, keloids and striae. Semin Cutan Med Surg \n2000;19:287-92.\n\n\n\n4. Akaishi S, Koike S, Dohi T, Kobe K, Hyakusoku H, Ogawa \nR. Nd:YAG laser treatment of keloids and hypertrophic \nscars. Eplasty 2012;12:e1.\n\n\n\n5. Mysore V, Mhatre M. Safety and Efficacy of Long-\npulsed Nd:YAG Laser for the Treatment of Keloids \u2013 A \nProspective Study of 39 Keloids. J LAHA 2015;1:1-6.\n\n\n\n6. Al-Mohamady Ael-S, Ibrahim SM, Muhammad MM. \nPulsed dye laser versus long-pulsed Nd:YAG laser in the \ntreatment of hypertrophic scars and keloid: A comparative \nrandomized split-scar trial. J Cosmet Laser Ther \n2016;18:208-12.\n\n\n\n7. Kumar K, Kapoor BS, Rai P, Shukla HS. In-situ irradiation \nof keloid scars with Nd:YAG laser. J Wound Care \n2000;9:213-5.\n\n\n\n8. Annabathula A, Sekar CS, Srinivas CR. Fractional carbon \ndioxide, long pulse Nd:YAG and pulsed dye laser in the \nmanagement of keloids. J Cutan Aesthet Surg 2017;10:76-\n80.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n19\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Randomized Single Blinded Study Comparing the Efficacy of \nBilastine Versus Cetirizine in Autoimmune Urticaria         \nTeeba Raja1, MRCP, Mohamad Nazri Md Shah2, MBBS, Ting Guan Ng1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia\n2Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction\nAutoimmune chronic spontaneous urticaria (aiCSU) is characterized by the presence of anti-FceR1 \nand anti-IgE autoantibodies. In this study we aimed to compare the efficacy and safety of bilastine \nversus cetirizine in aiCSU.\n\n\n\nMethods \nIn a single blinded study, thirty-six patients with chronic spontaneous urticaria with positive autologous \nserum skin test (ASST) were randomly assigned to receive bilastine (20mg to 80 mg per day) or \ncetirizine (10mg to 40 mg per day) for 12 weeks. The disease activity score (UAS7) was documented \nat baseline, week 1, 2, 4, 8 and 12. The ASST and chronic urticaria quality of life scores (CUQ2oL) \nwere evaluated before and after treatment. Safety was assessed according to adverse events reported \nby patients during treatment period.\n\n\n\nResults\nA total of 14 male (38.9%) and 22 female (61.1%) patients aged between 21 to 70 years old (40.92 \n\u00b1 13.59) were randomly assigned to receive bilastine (n=18) and cetirizine (n=18). Baseline UAS \n7 scores improved significantly in both treatment groups; in the bilastine group from 20.50 \u00b1 11.00 \nto 2.50 \u00b1 5.00 (p<0.01) and in the cetirizine group from 16.50 \u00b1 18.00 to 2.00 \u00b1 4.00 (p<0.01). The \nevaluation of CUQ2oL score revealed significant reduction in both groups; in the bilastine group from \n43.50 \u00b1 22.00 to 1.00 \u00b1 2.00 (p<0.01) and in the cetirizine group from 41.00 \u00b1 19.00 to 3.00 \u00b1 11.00 \n(p<0.01). \n\n\n\nConclusion\nBilastine and cetirizine were similarly effective during a 12-week treatment period in patients with \naiCSU.\n\n\n\nKey words: Autoimmune chronic spontaneous urticaria, autologous serum skin testing, bilastine, cetirizine\n\n\n\nIntroduction\nUrticaria is primarily a mast cell driven, \nheterogeneous group of disease characterized \nby sudden development of transient episodes of \nwheals, angioedema or both.1 Urticaria can be \nclassified based on its duration; acute if less than \n6 weeks or chronic if more than 6 weeks.1 Chronic \nurticaria (CU) is classified into two types based \non the presence or absence of inducing factor; \nchronic spontaneous urticaria and chronic inducible \nurticaria. \n\n\n\nCorresponding Author\nDr Teeba Raja\nDepartment of Dermatology, Hospital Tengku Ampuan \nRahimah, Jalan Langat, Klang, Selangor, Malaysia\nEmail: teebaraja@gmail.com\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20\n\n\n\nChronic spontaneous urticaria (CSU) is defined \nas spontaneous occurrence of wheals and/or \nangioedema; occurring daily and persisting for more \nthan 6 weeks without an obvious stimulus. CU is a \nhighly prevalent disease with a point prevalence of \n0.5 \u2013 1.0 %.2 Data on the current burden of urticaria \nin the Asia- Pacific region have yet to be reported, \nhowever it is suggested that the lifetime prevalence \nmay be as high as 23%.3\n\n\n\n \nThe prevalence of urticaria among clinic attendees \nin a tertiary center in Malaysia is 4.13%.4 Several \nfactors could possibly contribute to underlying \npathogenesis of CSU which includes autoimmunity, \npseudo-allergy to food or drugs and infections.1 In \n30-50% of cases autoimmunity has been reported \nto be the causative factor.5 Autoimmune chronic \nspontaneous urticaria (aiCSU) is defined by the \npresence of IgG autoantibodies to IgE or its high \naffinity receptor FceR1.6 Two types of autoimmunity \nhas been proposed; Type 1 autoimmunity (also \nknown as autoallergy) is the presence of IgE against \nauto-allergens and Type IIb autoimmunity refers to \npresence of IgG  autoantibodies against IgE or its \nreceptor.7 \n\n\n\nThe proposed diagnostic criteria for aiCSU is a \npositive in vivo autoreactivity (a positive Autologous \nserum skin test [ASST]), a positive in vitro basophil \nreactivity [a positive basophil histamine release \nassay(BHRA) or basophil activation test(BAT)]  and \na positive immunoassay for specific identification \nof IgG autoantibodies against FceR1 and/or anti-\nIge (western blot or ELISA).6 The PURIST study \nreported only 8% of its patients met the combined \ncriteria for aiCSU. This study also suggested that \na positive in vitro basophil reactivity has high \npredictive value for aiCSU.8 However, Basophil \nreactivity test is not practical in clinical use as it \nis time consuming and difficult to standardize. \nTherefore, ASST is still used widely as a screening \nmethod to assess for autoreactivity as it is a simple \nclinical test that has a sensitivity of 70% and \nspecificity of 80%.6 A systematic review comparing \nASST responses in patients with CSU suggests that \npatients with positive ASST responses had higher \nUAS and higher levels of serum total IgE than those \nof patients with negative ASST responses.9 \n\n\n\nThe recent position paper on management of chronic \nurticaria recommended non-medical management \nsuch avoidance of allergic stimuli if known.1 It also \nproposed the use of non-sedating second generation \nH1 antihistamines at conventional dose as the first-\n\n\n\nline management and increasing up to four-fold the \nrecommended dose as second line management.1 \nSubsequently, for the non-responders, the use of \nomalizumab or ciclosporin can be added as third \nline therapy.1 \n\n\n\nThere are many second generation anti-histamine \ndrugs available for the treatment of urticaria. \nHowever, only seven (cetirizine, loratadine, \ndesloratadine, fexofenadine, levocetrizin     \nrupatadine and bilastine) have been studied in detail \nfor urticaria.1 Bilastine is a non-sedating second \ngeneration H1-receptor inverse agonist, approved in \nmany countries throughout the world and Malaysia \nfor the treatment of allergic rhino-conjunctivitis \nand urticaria in adults and children over 12 years \nof age.10-11 \n\n\n\nBilastine has a rapid onset of action within 60 mins \nand it is sustained up to 24 hours. It undergoes \nminimal hepatic metabolism and is largely eliminated \nunchanged in both feces and urine. Studies in healthy \nvolunteers and patients have shown that bilastine \ndoes not affect cardiac conduction, vigilance or \ndriving ability, is free from antimuscarinic effects, \nand does not promote significant changes in \nlaboratory tests, electrocardiograms or vital signs.12 \n\n\n\nThe most commonly reported side effects of bilastine \nare headache, somnolence and fatigue.10 Cetirizine \nis a highly selective second generation H1-receptor \nantagonist and an active metabolite of hydroxyzine \nthat is directly absorbed and not metabolized by the \ncytochrome P-450 enzyme system. The peak plasma \nconcentration occurs approximately one hour after \nintake. It is mainly excreted in urine. Commonly \nreported side effects are headache, dry mouth, \ndrowsiness and fatigue.13 Cetirizine is widely used \nin our local setting for the treatment of urticaria due \nto its availability and cost. \n\n\n\nIn general, aiCSU is a disease which runs a \nprolonged and severe course that is difficult to \ncontrol with conventional antihistamine and often \nthird line of management is preferred. Many \nstudies have been conducted looking into the \neffectiveness of various anti-inflammatory drugs, \nanti-leukotrienes, immunomodulators and biologics \nin aiCSU patients who failed second line treatment \nwith antihistamines.16-19 In this study we aim to look \ninto the effectiveness and safety profile of bilastine \nversus cetirizine in aiCSU. \n\n\n\nMaterials and Methods\nThis was a randomised, single blinded study \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n21\n\n\n\ncomparing the efficacy of bilastine versus cetirizine \nin aiCSU. The study was conducted at the \ndermatology clinic in Hospital Tengku Ampuan \nRahimah, Malaysia from April 2018 to December \n2018. \n\n\n\nStudy Drugs\nBilastine (trade name Bilaxten) is a second \ngeneration anti-histamine. It was developed in \nSpain by FAES Farma and have been approved \nby European Union for the symptomatic treatment \nof allergic rhino-conjunctivitis and urticaria. \nBilastine is recommended as one of the first-line \nantihistamines in the treatment of urticaria by \nthe European Academy of Allergy and Clinical \nImmunology (EAACI)/WAO/EDF guideline and \nMalaysian guideline MARTEG.1,11 \n\n\n\nCetirizine (brand name Zyrtec) is a second \ngeneration anti-histamine and has been approved by \nFDA US for the treatment of hay fever, allergies, \nangioedema and urticaria. Zyrtec was developed in \nBrussels by the company, UCB Pharmaceutical.\nThe study drugs were dispensed in its original \npackaging.\n\n\n\nDisease severity assessment\n\n\n\nUAS 7\nUAS7 is a validated, unified and simple scoring \nsystem that is proposed for the assessment of disease \nactivity in CSU by international guidelines.1,24 The \nsigns and symptoms are evaluated by the patient \nthemselves. The subjects were taught on how to \nperform UAS 7 scoring. UAS was done every day \nonce in the evening for 7 days prior to each clinic \nreview.  This tool assesses two items: daily intensity \nof pruritus and number of hives ratings (0: none to \n3: severe). Assessment is done for seven days prior \nto appointment in order to build the UAS7 score \n(range 0-42). The UAS 7 scores are categorized \ninto five categories to facilitate in disease severity \nmonitoring. The five categories of disease state \nare; absent \u2013 0, well-controlled \u2013 1-6, mild \u2013 7-15, \nmoderate \u2013 16-27, and severe \u2013 28-42.\n\n\n\nChronic Urticaria Quality of Life Questionnaire \n(CUQ2oL)\nCUQ2oL is a quality of life questionnaire specifically \ndeveloped for CSU.1 It is a validated questionnaire \nthat assesses the physical, emotional, social and \npractical aspects characteristic of this condition. \nIt is a self-administered 23-item questionnaire, \nwhere patients have to indicate, on a Likert scale \n\n\n\nwith multiple options; (1: not at all, 2: a little, 3: \nsomewhat; 4: a lot, 5: very much) how much they \nhave been troubled by each problem, with higher \nscores indicating worse quality of life (range of \nthe score from 23-115). There are six factors in \nthe questionnaire; pruritus, swelling, impact of life \nactivities, sleep problems, limitation, and looks. \n\n\n\nAutologous\tserum\tskin\ttesting\t(ASST)\nASST was performed following the recommendation \nby EAACI/GA2LEN task force consensus report.14 \nBriefly; 0.05 mL of autologous serum, 0.05 mL \nof normal saline 0.9% (as a negative control) and \n0.05 mL of histamine diphosphonate (as a positive \ncontrol) were injected intradermally. The wheal \nresponses were measured at 30 mins. ASST is \nconsidered positive when autologous serum induced \nwheal was at least 1.5 mm greater than the negative \ncontrol.14\n\n\n\nStudy population\nMale and female patients aged 18 and above who \nare able to give consent with a clinical diagnosis \nof CSU were recruited. Eligible patients were \nadditionally required to have a positive ASST. A \ntotal of 69 patients underwent ASST. Thirty-six \nCSU patients with positive ASST were diagnosed \nwith aiCSU and were included in this study. \n\n\n\nThe exclusion criteria included pregnant or \nbreast-feeding mothers; those who had severe \nangioedema; those with a history of hypersensitivity \nto antihistamine; those with urticarial vasculitis, \nchronic inducible urticaria, hereditary angioedema, \nor ACE-inhibitor induced angioedema or other \ndermatological disorder that could interfere in \nthe evaluation of disease activity scoring (eg. \npsoriasis, endogenous or exogenous eczema); those \nwho have hepatic, renal, cardiac, neurological, \nhaematological, autoimmune, malignant diseases \nor any severe and uncontrolled disease; those who \nhad received phototherapy, any systemic steroids/\nsystemic immunomodulatory medications, or on \ntopical steroid within the last 4 weeks; those who \nhad received drugs that are P-glycoprotein inhibitors \n(eg. amiodarone, ketoconazole/itraconazole, \nerythromycin/clarithromycin, verapamil, quinidine, \nprotease inhibitors, tacrolimus) or P- glycoprotein \ninducers (eg. rifampicin, carmabazepine and \nphenytoin) in the last 30 days and patients who are \ninvolved in other on-going studies.\n\n\n\nRandomization and blinding\nRandomization codes were generated using the \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22\n\n\n\n\u2018Research Randomizer\u2019 program. Two sets of 18 \nunique numbers per set were generated. Designated \nuninvolved staff were in-charge of maintaining \nthe randomization code and dispensing the study \ndrugs to study subjects during each clinic visit. \nClinical outcome measurements were assessed by \nthe clinical investigators who were blinded. The \nunblinding was carried out in the event of serious \nadverse event or pregnancy. \n\n\n\nStudy design\nThis was a randomized, investigator blinded study \ncomparing efficacy of bilastine versus cetirizine in \naiCSU. The study was conducted at the dermatology \nclinic in Hospital Tengku Ampuan Rahimah, \nMalaysia from April 2018 to December 2018. \nSubjects who were clinically diagnosed with CSU \nwere approached and detailed information regarding \nthe study was given by the clinical investigator. \nEach subject was then reviewed two weeks later. \nSubjects who provided informed consent for the \nstudy underwent physical examination and basic \nblood investigations (full blood count, renal profile \nand liver function test) to assess their eligibility \nto participate in the study. Those who met the \ninclusion/exclusion criteria underwent ASST. \nSubjects were required to withhold their anti-\nhistamines 3 days prior to ASST. Subjects with \npositive ASST were included in the study and \nbaseline UAS7 and CUQ2oL scores were recorded. \nSubsequently, subjects were randomized to either \nthe bilastine group or cetirizine group. Subjects \nwere evaluated weekly for 2 weeks after initiation \nof treatment. Thereafter, the subjects were reviewed \nat week 4, 8 and 12. Subjects were provided with \na diary to record UAS7 scores, adverse events and \nmissed pills.  Compliance to treatment was assessed \n\n\n\nby pill counting and direct questioning of subjects \nduring follow-up visit. The dose of anti-histamine \nwas increased based on the subjects UAS7 scores \nduring each review. For subjects with absent or well-\ncontrolled symptoms, dose was maintained and for \nsubjects with mild, moderate and severe symptoms, \nthe anti-histamine dose were increased accordingly. \nThe CUQ2oL scores and ASST were repeated at \nthe end of the study. The study end points are the \nobjective changes in disease activity, quality of life \nscoring and ASST responses (Figure 1).\n\n\n\nEfficacy\tmeasures\nThe study end points are the objective changes in \nclinical scorings (UAS7 and CUQ2oL) and change \nin the diameter of serum induced wheal (ASST).\n\n\n\nUAS7 \nThe efficacy assessment was the change from \nbaseline in the subjects\u2019 UAS7 score over the 12-\nweek period. UAS7 was documented at baseline, \nweek 1, 2, 4, 8 and 12. Subjects with UAS7 \u2264 6 \nwas classified as responders and UAS7 > 7 was \nclassified as non-responders.\n\n\n\nChronic urticaria quality of life score (CUQ2oL) \nThe efficacy assessment was the change from \nbaseline in the subjects CUQ2oL score over the \n12-week period. The validated English CUQ2oL \nquestionnaire was used. It was a self-administered \nquestionnaire. CUQ2oL was documented at baseline \nand week 12. The total score of CUQ2oL (0-100) \nwas calculated based on the sum of all completed \nitems/total possible score of all completed items X \n100.15 Higher scores indicate greater impairment in \nthe quality of life of the subjects.\n\n\n\n69 clinically diagnosed CSU patients at Dermatology \nClinic HTAR, who were eligible underwent Autologous \n\n\n\nserum skin testing (ASST) \n\n\n\n\u2022 36 patients with +ve ASST included in the study \n\u2022 Urticaria Activity Score 7 (UAS 7) \n\u2022 Chronic Urticaria Quality of Life Questionnaire \n\n\n\n(CUQ2oL) n=2 withdrawn \n- Pregnant \n- Lost to follow up  \n\n\n\nExcluded 33 \npatients with \u2013\n\n\n\nve ASST \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nBilastine (n=18) \n20 mg \u2013 80 mg/day \n\n\n\nCetirizine (n=18) \n10 mg \u2013 40 mg/day \n\n\n\nUAS 7 \nAssessed for adverse effect \nAntihistamine dose adjusted \n\n\n\nUAS 7, CUQ2oL \nAssessed for adverse effect \n\n\n\nASST \nWeek 12 \n\n\n\nWeek 2,4 & 8 \n\n\n\nFigure 1. Study flowchart \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n23\n\n\n\nAutologous serum skin test (ASST) \nASST was done at baseline and repeated upon \ncompletion of study. The differences between the \nserum induced wheals and negative control were \nmeasured in millimeter. If the difference between \nserum induced wheal and negative control is more \nthan 1.5mm, it was considered positive and less \nthan 1.5mm was considered negative.\n\n\n\nSafety assessment\nThe number and severity of adverse events were \nassessed at each visit (weeks 1, 2, 4, 8 and 12) by \nthe investigators. Subjects had patient\u2019s diary to \ndocument events and the investigator\u2019s emergency \ncontact number. All adverse events were judged \nclinically, and subjects were dropped out from the \nstudy if deemed necessary. \n\n\n\nStatistical analysis\nData were compiled, entered into a dataset and \nanalysed using Statistical Package for Social \nSciences version 20.0 (SPSS). Descriptive analysis \nincluded using frequencies, means (standard \ndeviations) and medians (interquartile range) for \ndependent variables i.e. UAS7 at baseline, week 1, \n2, 4, 8 and 12 and CUQ2oL and ASST at baseline \nand at week 12. Mean and standard deviation were \nused for normally distributed data whereas median \nand interquartile range were used when data was not \nnormally distributed. \n\n\n\nThe significant differences within bilastine and \ncetirizine groups (at week 0, 1, 2, 4, 8 and 12) and \nbetween bilastine and cetirizine groups (at week 0, 2 \nand 4) were tested using Wilcoxon signed rank test \nand Mann Whitney Test respectively with p-value \nof less than 0.05 used as the levels of significance. \n\n\n\nEthical approval was obtained from the Medical \nResearch and Ethics Committee with research code \nof NMRR-18-414-39554.\n\n\n\nRESULTS\n\n\n\nDemographics\nA total of 69 clinically diagnosed CSU subjects \nwho were eligible underwent ASST. 36 subjects \nwith positive ASST were randomized to bilastine \nand cetirizine group, 18 subjects in each group. \nOne subject was withdrawn from study at week \n9 because of pregnancy and another subject was \nlost to follow up at week 10. However, all of the \nsubjects were included in the intention to treat \npopulation. The demographic and baseline clinical \ncharacteristics are as shown in table 1. Mean age \nof subjects were 40.92 years \u00b1 13.59. There were \n61.1% females in total. The male to female ratio is \n1:1.6 in both groups. The mean duration of disease \nfor the entire study population is 29.33 months \n\u00b1 27.82.  The mean disease duration is 24.17 \u00b1 \n23.87 in the bilastine group and 34.50 \u00b1 31.10 in \n\n\n\nCharacteristics Bilastine\n(n = 18)\n\n\n\nCetrizine\n(n = 18)\n\n\n\nTotal\n(n = 36) p-value\n\n\n\nMean age in years (mean\u00b1SD)\nAge range\n\n\n\n39.67 \u00b1 14.33\n21 \u2013 71\n\n\n\n42.17 \u00b1 13.09\n25 \u2013 63\n\n\n\n40.92 \u00b1 13.59\n21-71\n\n\n\na0.606\n\n\n\nGender, n (%)\n\n\n\nMale 7 (38.9) 7 (38.9) 14 (38.9) b0.633\n\n\n\nFemale 11 (61.1) 11 (61.1) 22 (61.1)\n\n\n\nRace, n (%)\n\n\n\nMalay 7 (38.9) 9 (50.0) 16 (44.4) b0.723\n\n\n\nChinese 6 (33.3) 4 (22.2) 10 (27.8)\n\n\n\nIndian 5 (27.8) 5 (27.8) 10 (27.8)\n\n\n\nMonths since diagnosis (mean\u00b1SD)\nDisease duration (range in months)\n\n\n\n24.17 \u00b1 23.87\n5 \u2013 84\n\n\n\n34.50 \u00b1 31.10\n3 \u2013 120\n\n\n\n29.33 \u00b1 27.82\n3 \u2013 120\n\n\n\na0.719\n\n\n\nUAS 7 score (95% CI) at baseline\n\n\n\nPruritus 11.44 (9.23-13.66) 10.00 (7.32-12.68) 10.72 (9.06-12.39) a0.521\n\n\n\nWheals 10.11 (7.90-12.32) 7.83 (5.24-10.43) 8.97 (7.31-10.63) a0.143\n\n\n\nTotal 21.56 (17.62-25.49) 17.83 (13.22-22.45) 19.69 (16.75-22.64) a0.279\n\n\n\nCUQoL scores, mean (SD) 47.64 \u00b1 17.29 45.52 \u00b1 20.57 42.86\u00b116.96 a0.542\n\n\n\nPre study ASST in mm, mean (SD) 5.89 \u00b1 2.54 5.26 \u00b1 1.71 5.58\u00b12.16 a0.563\naMann Whitney test\nbFisher\u2019s Exact test\n\n\n\nTable 1. Demographic data and clinical characteristics\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24\n\n\n\nthe cetirizine group. The mean total UAS7 score \nat baseline was 21.56 \u00b1 7.91 in the bilastine group \nand 17.83 \u00b1 9.28 in the cetirizine group. At baseline \n66.7% of the total subjects had moderate to severe \ndisease activity. The mean CUQ2oL score is 47.64 \n\u00b1 17.29 for the bilastine group and 45.52 \u00b1 20.57 \nfor the cetirizine group. The mean baseline ASST \nis 5.89 \u00b1 2.54 in the bilastine group and 5.26 \u00b1 1.71 \nin the cetirizine group. Both groups were similar \nwith respect to demographics and baseline clinical \ncharacteristic, there were no significant differences \nnoted between the groups (p>0.05) (Table 1).\n\n\n\nEfficacy\nThe disease severity score improved significantly \nin both groups with reduction of total UAS7 score \n(median \u00b1 IQR) from 20.50 \u00b1 11.00 at baseline to \n2.50 \u00b1 5.00 (p<0.01) in the bilastine group and from \n16.50 \u00b1 18.00 at baseline to 2.00 \u00b1 4.00 (p<0.01) \nin the cetirizine group.  Significant improvement \nwas observed as early as week 1, with a trend of \nrapid improvement seen in the bilastine group \nwhen compared to the cetirizine group. However, \nthese differences were not statistically significant \n(p=0.293).  Similar significant reduction was also \nnoticed in both pruritus and wheal components of \nUAS 7 score. Pruritus score reduced from 11.00 \u00b1 \n6.00 to 1.50 \u00b1 2.00 (p<0.01) in bilastine group and \n\n\n\nTable 2. Pre-treatment and post-treatment scores for bilastine and cetirizine at week 12.\n\n\n\na ASST, the difference between serum induced wheal \u2013 saline induced wheal\n*Wilcoxon Signed rank test.\n\n\n\nFigure 2. Total reduction in mean scores of UAS 7 & CUQ2oL for  Bilastine & Cetirizine group from  baseline to week 12\n\n\n\n9.00 \u00b1 10.00 to 1.00 \u00b1 2.00 (p<0.01) in the cetirizine \ngroup. The wheal score improved from 10.50 \u00b1 7.00 \nat baseline to 1.00 \u00b1 3.00 (p<0.01) in the bilastine \ngroup and 7.50 \u00b1 9.00 at baseline to 0.50 \u00b1 2.00 \n(p<0.01) in the cetirizine group. Both groups showed \na statistically significant improvement in quality of \nlife with reduction of scores from 43.50 \u00b1 22.00 \nat baseline to 1.00 \u00b1 2.00 (p<0.01) in the bilastine \ngroup and from 41.00 \u00b1 19.00 at baseline to 3.00 \u00b1 \n11.00 (p<0.01) in the cetirizine group. There was \nno significant inter-group difference in the UAS7 \nand CU2QoL (p=0.211 and p=0.273 respectively) \nbetween the bilastine and cetirizine groups at the \nend of treatment (Table 2, Figure 2 & 3).\n\n\n\nIn the bilastine group 8 subjects had responded with \nstandard dose of 20 mg per day, 8 subjects responded \nwhile on 40mg per day and 1 subject was on 60mg \nper day. 1 subject remained having mild disease \nactivity (UAS7 =15) despite being on bilastine 80 \nmg per day. Meanwhile in the cetirizine group, 7 \nsubjects responded with standard dose of 10 mg per \nday throughout the study, 5 subjects responded at \n20 mg per day and 4 subjects responded at 30 mg \nper day. 2 subjects were on maximum dose of 40 \nmg per day. One of the 2 subjects who required 40 \nmg of cetirizine per day remained having moderate \ndisease activity.\n\n\n\nTotal scores\nBilastine (n=18) Cetrizine (n=18)\n\n\n\nPre-treatment Post-\ttreatment *p-value Pre-\ttreatment Post-\ttreatment *p-value\nTotal\nMedian\u00b1IQR\nRange\n\n\n\n20.50\u00b111.0\n27\n\n\n\n2.50\u00b15.00\n15\n\n\n\n<0.01 16.50\u00b118.00\n28\n\n\n\n2.00\u00b14.00\n16\n\n\n\n<0.01\n\n\n\nCUQ2oL\nMedian\u00b1IQR\nRange\n\n\n\n43.50\u00b122.00\n57\n\n\n\n1.00\u00b12.00\n28\n\n\n\n<0.01 41.00\u00b119.00\n73\n\n\n\n3.00\u00b111.00\n17\n\n\n\n<0.01\n\n\n\naASST \nMean\u00b1SD 5.89 \u00b1 2.54 6.14 \u00b1 2.05 0.566 5.26 \u00b1 1.71 5.34 \u00b1 2.58 0.756\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n25\n\n\n\nFigure 3. Trend of improvement of  (a) total UAS 7, (b) pruritus and (c) wheals scores in the Bilastine & Cetirizine groups from baseline \nto week 12.\n\n\n\na)\n\n\n\nb)\n\n\n\nc)\n\n\n\nTrend of improvement of total UAS7 from baseline to week 12\n\n\n\nTrend of improvement of pruritus score from baseline to week 12\n\n\n\nTrend of improvement of wheals score from baseline to week 12\n\n\n\nPe\nrc\n\n\n\nen\nta\n\n\n\nge\n o\n\n\n\nf i\nm\n\n\n\npr\nov\n\n\n\nem\nen\n\n\n\nt\nPe\n\n\n\nrc\nen\n\n\n\nta\nge\n\n\n\n o\nf i\n\n\n\nm\npr\n\n\n\nov\nem\n\n\n\nen\nt\n\n\n\nPe\nrc\n\n\n\nen\nta\n\n\n\nge\n o\n\n\n\nf i\nm\n\n\n\npr\nov\n\n\n\nem\nen\n\n\n\nt\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26\n\n\n\nThere was no significant change in the ASST \nresponses before and after treatment in both the \nbilastine and cetirizine groups. Although not \nstatistically significant, there was a slight increase \nin the mean diameter of serum induced wheal at the \nend of treatment; in the bilastine group it increased \nfrom 5.89 \u00b1 2.54 to 6.14 \u00b1 2.05 (p = 0.556) and in \nthe cetirizine group from 5.26 \u00b1 1.71 to 5.34 \u00b1 2.58 \n(p= 0.756). One subject from the cetirizine group \nshowed negative ASST response at the end of the \nstudy.\n\n\n\nTolerability\nBoth the study drugs were safe and well tolerated \nby all the subjects of this study. Table 4 lists the \nadverse events reported by subjects. Sleepiness was \nreported in both groups however it was significantly \nlesser in bilastine group when compared to cetirizine \ngroup, with 11.1 % in bilastine group and 38.9% in \nthe cetirizine group. Only one subject experienced \nheadache in the bilastine group as compared to \n4 subjects in the cetirizine group. Incidences \nof giddiness were reported by 2 subjects in the \ncetirizine group and none in the bilastine group. \nOther adverse events reported were lethargy (11.1% \nin the bilastine group and 5.6% in the cetirizine \ngroup) and dryness of mouth/eyes (5.6% in the \nbilastine group and 22.2% in the cetirizine group). \n(Table 3)\n\n\n\nTable 3. Adverse events reported by subjects\n\n\n\nDiscussion\nThere is general understanding that aiCSU presents \nwith severe symptoms and a long disease duration \nwhich often requires a third line of management \nwith immunomodulatory or anti-inflammatory \ndrugs for control of symptoms. Previous studies on \naiCSU had looked into the effectiveness of various \nimmunomodulatory and anti-inflammatory drugs \nsuch as omalizumab16, cyclosporin17, dapsone18 and \nprednisolone19 in subjects who had failed to respond \nto anti-histamines. A meta-analysis had proven \nthe efficacy of standard and higher doses of anti-\nhistamine in CSU, however there was no mention \n\n\n\nSide\teffects Bilastine\nn (%)\n\n\n\nCetirizine\nn (%)\n\n\n\nap value\n\n\n\nSleepiness 2 (11.1) 7 (38.9) 0.054\n\n\n\nHeadache 1 (5.6) 4 (22.2) 0.148\n\n\n\nLethargy 2 (11.1) 1 (5.6) 0.546\n\n\n\nDryness 1 (5.6) 4 (22.2) 0.148\n\n\n\nGiddiness 0 (0) 2 (11.1) 0.146\naMann Whitney test\n\n\n\nof the effectiveness of these anti-histamines in \nthe subgroup of aiCSU.20 This study was done to \ncompare the effectiveness of bilastine and cetirizine \nin aiCSU patients.\n\n\n\naiCSU is more prevalent among females around the \nworld as reported by many studies in Western and \nAsian countries19,21-22. Similar female predominance \nis seen in our cohort with a ratio of 1:1.6, however \nthe distribution was not as remarkable as shown in \nother studies.19,21-22 The mean age at diagnosis in \nour study was 40.92 years, which was comparable \nto studies done in Thailand and Korea which \nreported a mean age of 37.21-22 The prevalence of \npositive ASST varies between 35%-58% in patients \nwith chronic urticaria.14,23,25 In our study the ASST \nprevalence was high at 52.2% of the CSU patients \nstudied. This is likely because our center is a tertiary \ncenter where the more severe and persistent CSU \npatients are given follow ups. \n\n\n\nIn our study we found that both bilastine and \ncetirizine were equally effective in controlling \nthe symptoms and improving the quality of life \nin patients with aiCSU. There was significant \nreduction in disease activity scores (p<0.01) and \nchronic urticaria quality of life scores (p<0.01) \nfrom baseline to week 12 in both the bilastine \nand cetirizine group. There were no significant \ndifferences in the disease activity scores & chronic \nurticaria quality of life scores reduction over the \n12 weeks when both the groups were compared \n(p-values were 0.211 & 0.27 respectively). In a \nstudy comparing efficacy and safety of bilastine \nversus levocetirizine in the treatment of CSU, it was \nshown that bilastine is equivalent to levocetirizine \nin relieving symptoms and improving quality of life \nin CSU patients.26 A one-year study done in Japan, \nevaluating safety and efficacy of bilastine in the \ntreatment of CSU revealed that bilastine improved \ndisease symptoms of CSU early in the treatment and \nefficacy was maintained throughout the treatment.27 \nRecent studies have proven bilastine to be effective \nin treating pruritus and difficult to treat CSU that did \nnot respond to other antithistamines.28-29\n\n\n\nAlthough the mean total UAS7 score was higher in \nthe bilastine group (21.56 \u00b1 7.91) when compared \nto the cetirizine group (17.83 \u00b1 9.28) at baseline, the \nrate of improvement was more rapid in the bilastine \ngroup and it was sustained till the end of the study \n(Figure 3a). In a randomized double-blinded study \nin 21 healthy volunteers evaluating the effect of \n2 different bilastine doses (20 and 50mg) versus \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n27\n\n\n\ncetirizine 10mg on histamine-induced wheal/flare \nover a period of 24 hours, Chruch MK et al. found that \nthere was no significant difference between overall \ninhibitions of wheal/flare by 20 mg bilastine & 10 \nmg cetirizine.30 However, bilastine had more rapid \nonset of action when compared to cetirizine.30 It was \nalso proven in previous studies that bilastine had a \nrapid onset of action in reducing histamine induced \nwheals and controlling pruritis in comparison to \ncetirizine, desloratadine or rupatadine.30-31 A meta-\nanalysis reported that up-dosing of anti-histamines \ndid not significantly improve response control or \nreduce number of wheals. However, up-dosing did \nshow significant improvement in pruritus control.20 \nThe current study shows that there is a significant \nimprovement in both pruritus and number of wheals \nin both cetirizine (change in mean of pruritus; 8.19 \n\u00b1 5.49 and number of wheals; 6.13 \u00b1 5.19, p<0.05) \nand bilastine (change in mean of pruritus ; 9.72 \u00b1 \n4.11 and number of wheals; 8.61 \u00b1 4.54, p<0.05) \ngroups (Figure 3b,c).\n\n\n\nThe same meta-analysis reported that the response \nrate to standard doses of antihistamine in CSU \npatients was 38.6%.20 Among the antihistamines, \ncetirizine had a lower proportion of responders, at \n41.98%.20 The response rate to up-dosing in CSU \npatients who were non-responders to standard doses \nwas 63.2%.20 In our study, the response rate to \nstandard dose of bilastine was 44.4% and standard \ndose of cetirizine was 38.8%. In both groups, 94.4% \nresponded to up-dosing. However, direct comparison \ncannot be made between current study and previous \nstudies because the definition of responder differs; \none study defined responders as UAS7 less than 329 \n\n\n\nand another defines as more than 30% improvement \nin symptoms28.  One patient in the bilastine group \nand two patients in the cetirizine group required a \nfourfold increase in the dose of antihistamine. \n\n\n\nBoth bilastine and cetirizine were generally well \ntolerated in our study. All reported adverse events \nwere mild. More subjects in the cetirizine group \ncomplained of sleepiness. Among these 7 subjects \nwho reported sleepiness, 5 of them were on higher \nthan standard dose of cetirizine, at a dose of 20-\n30mg per day. This finding confirms the findings \nof previous studies that reported bilastine to be \nnon-sedative as it does not cross the blood brain \nbarrier.32-33 \n\n\n\nA research testing the effect of bilastine on the \nability to perform tasks related to flying found \nthat bilastine did not cause sleepiness or impaired \n\n\n\nperformance on tasks related to flying.34 Second \ngeneration anti- histamines (SGAH) ,which are \nhighly selective for H1 receptor, have limited blood \nbrain barrier penetration as their translocation across \nthe central nervous system are under the control of \nactive transporter proteins (ATP-dependent efflux \npump, Pgp).35 Pgp is essentially a cell detoxification \nmechanism where it helps to clear SGAH from the \nbody.35 \n\n\n\nAs such, the SGAH is minimally sedating or non-\nsedating with almost no adverse effect. Bilastine \nshows negligible H1 receptor occupancy in the brain, \nhence they do not have CNS effects even at higher \ndoses.35 However, single oral doses of 10 and 20 mg \nof cetirizine caused 12.5 and 25.2% occupancy of \nH1 receptors in prefrontal and cingulate cortices and \nsubsequently causing drowsiness.35 This explains \nthe higher incidence of sleepiness experienced by \nsubjects in the cetirizine group who were on higher \ndoses.\n\n\n\nASST indicates the presence of functional circulating \nautoantibodies to FceR1 and/or to IgE and a positive \nASST only suggest \u2018autoreactivity\u2019. However, \ncombining a positive ASST with characteristic \nclinical features (severe symptoms and anti-thyroid \nantibodies) may increase the sensitivity (94%) \nand specificity (86%) of this test.36 In Malaysia, \nsophisticated tests like basophil histamine release \nassay(BHRA) or basophil activation test(BAT)  \nand  immunoassay for specific identification of \nIgG autoantibodies against FceR1 and/or anti-Ige \n(western blot or ELISA) are not available, hence \nour diagnosis of aiCSU mainly relies on a positive \nASST and established clinical characteristics. In \nour cohort, only 1 subject had a negative ASST \nat week 12 and was completely symptom free at \nthe end of the study. Keeping in mind the natural \nprogression of the disease, this could possibly be \ndue to spontaneous remission of disease activity. \nThe remaining 33 subjects had positive ASST at the \nend of the study. A negative ASST serves as a good \npredictor for achieving urticaria remission within \n2 years.9 Positive ASST at week 12 in most of our \npatients suggests they have not achieved remission.\n\n\n\nThere were two drop outs in this study and both \nwere in the cetirizine group. One subject was lost \nto follow up at week 8 and the other subject was \nwithdrawn from study due to pregnancy. The subject \ninformed of her pregnancy (6 weeks of amenorrhea) \nat week 10 of the study. She was taking 40mg of \ncetirizine per day when she was withdrawn and \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28\n\n\n\nreferred to the obstetric team for further care. We are \nhappy to report that she had an uneventful antenatal \nfollow up and delivered a healthy full-term baby. \nContrary to our concerns, an observational cohort \nstudy and a meta-analysis concluded that cetirizine \nwas not associated with an increased risk of major \nmalformations or other adverse fetal outcomes.37\n\n\n\nIn the era of biologics, with the availability \nof effective anti-IgE monoclonal antibodies \nlike omalizumab and upcoming novel anti-IgE \nmonoclonal antibodies like Ligelizumab and UB-\n22138, it is important to have a clearer idea on the \nefficacy of antihistamine in aiCSU management. \nThis study concludes that both bilastine and \ncetirizine at standard or higher dosing are equally \neffective and safe in controlling the symptoms of \nautoimmune urticaria, although bilastine has proven \nto have lesser side effects. Since cetirizine of more \nthan 10mg causes drowsiness in more than one \nthird of our patients, we need to be cautious when \nprescribing to a patient especially higher dosage \neg 20 to 40mg to patients who will drive or handle \nmachinery at work.\n\n\n\nWe feel that this study was limited as it only involved \na small cohort of patients. It was also a single \nblinded study where the investigator was blinded \nbut the subjects were aware of the drugs consumed. \nThis could have let to response biasness, whereby \nsubjects are aware of the expected findings and adapt \ntheir responses to suit. The diagnosis of autoimmune \nurticaria was based on positive ASST alone as other \ntests were not available in Malaysia. Nevertheless, \nthere was careful selection of the patients before \nenrolment into this study. The patients were followed \nup closely only by the primary investigator and the \nprimary outcome measures were patient-reported. \nFuture studies should be multicenter, double-blind \nplacebo-controlled and designed with a larger \nnumber of patients. \n\n\n\nConclusion\nAutoimmune chronic spontaneous urticaria is more \nprevalent among female patients with a prolonged \ncourse of disease and severe symptoms which \nsignificantly affect patients\u2019 quality of life.  Both \nbilastine and cetirizine at standard or higher dosing \nare equally effective and safe in controlling the \nsymptoms of autoimmune chronic spontaneous \nurticaria.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowlegdement\t\nWe would like to thank Persatuan Dermatology \nof Malaysia for funding this study. We also would \nlike to express my profound gratitude to Dr. \nMuralitharan a/l Perumal and Dr. Shubashini, from \nCRC Department, HTAR for their guidance and \nsupport in conducting this study. We would like to \nthank the Director General of Health Malaysia for \nhis permission to publish this article.\n\n\n\nReferences\n\n\n\n1. Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker \nD, Ballmer\u2010Weber B et al. The EAACI/GA\u00b2LEN/EDF/\nWAO guideline for the definition, classification, diagnosis \nand management of urticaria. Allergy 2018;73:1393-414. \n\n\n\n2. Maurer M, Weller K, Bindslev\u2010Jensen C, Gim\u00e9nez\u2010Arnau \nA, Bousquet PJ, Bousquet J et al. Unmet clinical needs \nin chronic spontaneous urticaria. A GA2LEN task force \nreport. Allergy 2011;66:317-30.\n\n\n\n3. Pawankar R, Canonica GW, Holgate ST, Lockey RF, \nBlaiss MS. Introduction and executive summary: Allergic \ndiseases as global public health issues. WAO white book \non allergy: update 2013. 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Allergy 2018;73:2073-5.\n\n\n\n30. Church MK. Comparative inhibition by bilastine and \ncetirizine of histamine-induced wheal and flare responses \nin humans. Inflamm Res 2011;60:1107-12.\n\n\n\n31. Antonijoan R, Coimbra J, Garc\u00eda-Gea C, Puntes M, \nGich I, Campo C et al. Comparative efficacy of bilastine, \ndesloratadine and rupatadine in the suppression of wheal \nand flare response induced by intradermal histamine in \nhealthy volunteers. Curr Med Res Opin 2017;33:129-36.\n\n\n\n32. Sadaba B, Azanza JR, Gomez-Guiu A, Rodil R. Critical \nappraisal of bilastine for the treatment of allergic \nrhinoconjunctivitis and urticaria. Ther Clin Risk Manag \n2013;9:197-205.\n\n\n\n33. Scaglione F. Safety profile of bilastine: 2nd generation \nH1-antihistamines. Eur Rev Med Pharmacol Sci \n2012;16:1999-2005.\n\n\n\n34. Valk PJ, Simons R, Jetten AM, Valiente R, Labeaga L. \nCognitive performance effects of bilastine 20 mg during 6 \nhours at 8000 ft cabin altitude. Aerosp Med Hum Perform \n2016;87:622-7.\n\n\n\n35. S\u00e1nchez-Borges M, Ansotegui IJ. Second generation \nantihistamines: an update. Curr Opin Allergy Clin \nImmunol. 2019;19:358-364.\n\n\n\n36. Hajdu K, Irinyi B, Gyimesi E, Kapit\u00e1ny A, Dajnoki Z, \nBata-Cs\u00f6rg\u0151 Z et al. A simple, combined test can improve \nthe diagnosis of autoimmune urticaria. Br J Dermatol \n2017;177:864-6.\n\n\n\n37. Etwel F, Djokanovic N, Moretti ME, Boskovic R, \nMartinovic J, Koren G. The fetal safety of cetirizine: an \nobservational cohort study and meta-analysis. J Obstet \nGynaecol 2014;34:392-9.\n\n\n\n38. Kolkhir P, Altrichter S, Munoz M, Hawro T, Maurer M. \nNew treatments for chronic urticaria. Ann Allergy Asthma \nImmunol 2020;124:2-12.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30\n\n\n\nORIGINAL ARTICLE\n\n\n\nBasal Cell Carcinoma in the Department of Dermatology, Hospital \nKuala Lumpur         \nRafiq Shajahan, MBBS, Siew Wen Goh, MRCP, Azura Mohd Affandi, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.\n\n\n\nAbstract\nIntroduction\nBasal cell carcinoma (BCC) is the commonest skin cancer seen worldwide. This study aims to determine the \nclinical pattern of BCC in the Department of Dermatology, Hospital Kuala Lumpur, Malaysia\n\n\n\nMethods\nA retrospective review of 142 cases of BCC between January 2005 and December 2018 in the Department of \nDermatology, Hospital Kuala Lumpur.\n\n\n\nResults\nMean age at presentation was 66.0\u00b111.7 years. There were 71 male and female patients. Chinese accounted \nfor 49.3% of patients, followed by Malay (32.4%), Indian (5.6%) and other ethnic groups (12.7%). Our study \nfound that 32.6% of the patients presented within 1 year after the lesion appeared, 43.9% between 1-5 years, \nand 23.5% of patients presented after 5 years. Most patients (81.6%) had BCC over the head and neck region, \nfollowed by trunk (14.9%), lower limbs (8.5%) and upper limbs (5.7%). Most patients required simple surgical \nexcision (82.4%) while 7.0% of patients had more extensive excisions. Radiotherapy was given to 3% of \npatients. Staging was available for 75 of the patients, and majority (78.7%) were in Stage 1. Patient\u2019s outcome \nwas available for 67 patients and 82.1% were in complete remission.  \n\n\n\nConclusion\n\n\n\nOur data showed that BCC tend to occur in older age groups (above 60) and in Chinese patients. \nMajority of the lesions occurred in the head and neck region. Simple surgical excision was the \ncommonest treatment method, with very good outcome as evidenced by high percentage of complete \nremission.  \n\n\n\nKey words: Basal cell carcinoma, non-melanoma skin cancer, national cancer resgistry\n\n\n\nCorresponding Author\nDr Goh Siew Wen\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang 50586 Kuala Lumpur, Malaysia\nEmail: gohsiewwen@gmail.com\n\n\n\nIntroduction\nThe World Health Organization (WHO) states \nthat the global incidence of skin cancers has been \nsteadily increasing since the past decade. It is now \nestimated that around 2-3 million non-melanoma \nskin cancers and 132,000 melanoma skin cancers \noccur globally each year.1 Basal cell carcinoma \n(BCC) specifically, is estimated to affect 1-3% of \nthe world\u2019s population.2\n\n\n\nMalaysia, a country prominently known for its \nethnic plurality, is a country located near the \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n31\n\n\n\nequator and is home to approximately 32.6 million \npeople as of 2018. Its main ethnic constituents are \nMalay (54.7%), Chinese (24.3%), Indian (7.3%) \nand multiple other denominations (13.7%) and \nethnicities. Malaysia, therefore, represents a study \npopulation that is unique in its heterogeneity of its \npeople.3 The latest available national data on skin \ncancer was taken from the Malaysian National \nCancer Registry (MNCR) (2007-2011). It was \nreported that skin cancer is ranked 12th among the \nmost common cancers in the Malaysian population, \n10th most common cancer in males and 14th amongst \nfemales.4 According to the registry, BCC alone \naccounted for 51.9% of all skin cancers in Malaysia \nfrom years 2007 to 2011, the highest amongst the \ndifferent types of skin cancers.4\n\n\n\nOnce a disease occurring exclusively in the elderly, \nBCC are increasingly diagnosed in individuals \nunder the age of 50, due to frequent exposure of \nknown risk factors in susceptible patients and \nimprovement in diagnostic modalities.5,6 Classical \nrisk factors include prolonged UV light exposure, \nfamily history of skin cancers and fairer Fitzpatrick \nskin subtypes.7,8 Contrastingly, BCC can also \nappear on areas that are relatively sun protected as \nwell such as the inner canthus of the eyes and the \nposterior aspect of the ears as it is estimated that a \nfifth of all BCC may occur on areas that are void of \nsun exposure.9 \n\n\n\nThese statistics lead us to the overarching \nobservation that both sun exposure and degree of \nskin pigmentation are notable risk factors in the \ndevelopment of skin cancers but skin cancer can \nstill occur in patients who are seen as low risk as \nwell. Hence, we are analyzing our BCC patients to \nidentify clinical patterns and treatment outcomes \nto describe risk factors of acquiring BCC in our \npopulation of patients.\n\n\n\nMaterials and Methods\nThis was a 14-year retrospective review conducted \nat the Department of Dermatology, Hospital Kuala \nLumpur (HKL), Malaysia. HKL serves as a tertiary \nreferral center for various dermatological illnesses, \nincluding BCC. The data used for this study was \nretrieved from the Department of Dermatology \nSkin Cancer Registry. The source document for this \nregistry was obtained from patient notes whom have \nclinically and histologically proven BCC. For the \npurpose of this study, we collected information from \npatients presenting to our department from January \n2005 to December 2018.\n\n\n\nRaw data regarding patient demographics, clinical \nattributes, symptoms, treatment modalities, \noutcomes and other clinical characteristics were \namong the information collected. The following data \nwere then processed through Statistical Package for \nSocial Sciences (SPSS) Version 20.0. Continuous \nvariables were expressed as mean +/- standard \ndeviation (SD), and categorical variables were \ndescribed as frequencies/percentages. We excluded \npatients of whom clinical data was insufficient.\n\n\n\nRESULTS\nA total of 142 patients were diagnosed with BCC in \nour department over the span of 14 years from year \n2005 to year 2018. The mean age of diagnosis was \n66.0 \u00b1 11.7 years old. There were equal numbers \nof male and female patients at 71 patients each \n(Table 1). In terms of frequency of BCC amongst \nthe Malaysian ethnicities, 70 patients (49.3%) were \nChinese, 46 patients (32.4%) were Malay, 8 patients \n(5.6%) were Indian, and 18 patients (12.7%) were \nof other ethnicity. Regarding ethnicity and gender, \nour study showed that the incidence of BCC was \nslightly lower in Chinese females compared to \nChinese males, with a male to female ratio of 1.15. \nWithin the Malay community, the ratio of male to \nfemale was 0.57, whilst in the Indians the ratio was \n0.33 (Table 2). Forty-six patients (32.6%) presented \nwithin 1 year of symptoms, while 95 patients \n(67.4%) presented 1 year after the manifestation \nof skin lesions. The vast majority of patients (118, \n83.1%) had no history of previous malignancies. \nIt was observed that 20 patients (14.1%) had prior \nhistory of skin malignancy and only 2 patients \n(1.4%) had a history solid organ malignancy. \n\n\n\nUpon analyzing the location of BCC lesions, we \nfound that 115 patients (81.6%) had BCC on the head \nand neck region. This was followed by trunk, seen \nin 21 patients (14.9%), lower limbs in 12 patients \n(8.5%), and upper limbs in 8 patients (5.7%). Three \npatients were found to have multiple BCC over \ndifferent areas. The first patient was a 49-year-\nold Malay lady who was found to have lesions on \nher abdomen and feet. Following investigations, \nshe was diagnosed with Gorlin Syndrome, also \nknown as nevoid basal cell carcinoma syndrome, \na hereditary condition that increases one\u2019s risk of \ndeveloping multiple BCC. She still developed \nmultiple, recurrence BCC to date. The second \npatient is a 43-year-old Iban male with underlying \noculocutaneous albinism with a personal history of \na previous BCC. He had multiple ulcerated plaques \non his back and neck which required excision with \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32\n\n\n\nSites of BCC\nMalay\n\n\n\n(no. of patients)\nChinese\n\n\n\n(no. of patients)\nIndian\n\n\n\n(no. of patients)\nOthers ethnicity\n(no. of patients) Sites Total \n\n\n\n(% of sites)\nMale Female Male Female Male Female Male Female\n\n\n\nHead\tand\tNeck 11 23 32 28 2 5 8 6 115 (81.6)\n\n\n\nUpper Limb 1 - 4 1 - - 1 1 8 (5.7)\n\n\n\nLower Limb - 3 5 - - - 2 2 12 (8.5)\n\n\n\nTrunk 5 4 5 1 - 1 3 2 21 (14.9)\n\n\n\nTotal BCC lesions 17 30 46 30 2 6 14 11 156 (100)\n\n\n\nCharacteristics n (%) or mean \u00b1 SD\n\n\n\nAge, years 66.0 \u00b1 11.7\n\n\n\nGender\n     Male\n     Female\n\n\n\n \n71 (50%)\n71 (50%)\n\n\n\nEthnicity\n     Malay\n     Chinese\n     Indian\n     Others\n\n\n\n \n46 (32.4%)\n70 (49.3%)\n8 (5.6%)\n\n\n\n18 (12.7%)\n\n\n\nDuration of lesion prior to presentation\n     < 1year\n     1-5 years\n     >5 years\n\n\n\n \n46 (32.6%)\n62 (43.9%)\n33 (23.5%)\n\n\n\nPrevious\tHistory\tof\tMalignancy\n      None\n\t\t\t\t\t\tSkin\tmalignancy\n      Solid organ malignancy\n      Not recorded\n\n\n\n \n118 (83.1%)\n20 (14.1%)\n2 (1.4 %)\n2 (1.4 %)\n\n\n\nStaging\n      Stage 1\n      Stage 2 \n      Stage 3\n      Stage 4\n      Staging not available\n\n\n\n \n59 (41.5%)\n13 (9.2%)\n2 (1.4%)\n1 (0.7%)\n\n\n\n67 (47.2%)\n\n\n\nMode of treatment\n    Simple excision\n\t\t\t\tExcision+\tgraft/flap\n    Radiotherapy    \n\n\n\n \n117 (82.4%)\n\n\n\n10 (7%)\n3 (2.1%)\n\n\n\nTable 1. Demography, Clinical Features, Staging and Mode of Treatments\n\n\n\nTable 2. Total number and sites of BCCs according to Gender and Ethnicities\n\n\n\na graft for skin reconstruction. The third patient was \nan 83-year-old Chinese male with an underlying \nhistory of Bowen\u2019s disease, presented with lesions \nover his shoulders, trunk and calves. He was treated \nwith a mixture of excision and cryotherapy which \nlead to only partial remission, and he later defaulted.  \n\n\n\nData on staging was available for 75 out of 142 \npatients (52.8%). It revealed that a majority of \n59 (41.5%) patients were diagnosed at Stage 1, \n13 patients (9.2%) Stage 2, two patients (1.4%) \nStage 3 and 1 patient (0.7%) Stage 4. A Majority \nof patients of 117 (82.4%) required simple excision \nof BCC as the treatment of choice. Ten patients \n(7%) had wide excisions with graft or flap closure \nand 3 patients (2.1%) received radiotherapy. \n\n\n\nUnfortunately, outcome data was available for only \n67 out of 142 patients. On analyzing the outcomes \nto the previously mentioned treatments, 55 patients \n(38.7%) achieved complete remission. Asides from \nthat, 6 patients (4.2%) had stable disease, another 6 \npatients (4.2%) had a relapse in condition. Our study \nalso found that 64 patients (45.1%) was transferred \nto other departments (namely Plastic Surgery) for \nfurther follow up and management and 10 patients \n(7%) were lost to follow up (Figure 1). \n\n\n\nDiscussion\n\n\n\nAge and Sex\nThis study serves to provide better insight into \nthe pattern of occurrence of BCC in Malaysia in \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n33\n\n\n\narguably the largest tertiary center for Dermatology \nin the country. Firstly, our study identified that there \nwas a predilection for the malignancy to occur in the \nelderly population with no gender predominance. \nThe average age of our population for BCC was 65 \nyears in males and 66 years in female. Similarly, \nother studies confirmed this finding, as evidenced by \nCh\u2019ng et al in another study conducted in University \nMalaya, who found that the average age for BCC \nwas 68 years of age.10  A retrospective study done in \n2006 in our neighbouring country Singapore by Sng \net al looked into various skin cancers from years \n1968 to 2006.11 The study found that BCC had a \nparticularly alarming incidence in those aged 60 and \nabove, with an average of 4.5/100,000 person years \nin 2003-2006.11 Globally, this range of age group \nis fairly consistent with studies carried out in other \ncountries such as Poland and Turkey.12,13 \n\n\n\nHowever, when age and gender were taken into \naccount, the data in many other studies around \nthe world is conflicted. While many studies found \nthat men were more likely to develop BCC in \ntheir lifetime, women were seemingly diagnosed \nat younger ages comparatively.5,14,15 Studies from \ncountries such as Taiwan, Turkey and Poland \ndemonstrated that women with BCC presented at \na slightly younger age compared to men.12,13,15 The \nstudy done in Taiwan specifically, showed that \nmedian age in years for BCC was 67 in females \nand 71 in males, a noticeably older overall cohort \nas well.15 This could be due to the fact that women \nare often more concerned by their appearance and \nsought treatment earlier compared men who may not \nseek treatment until the lesion worsens. However, \na large study carried out in Strasbourg, France in \n2002 revealed a slightly higher female ratio to male \nratio instead (52% vs 48%).14 This study which \n\n\n\nincluded 10,245 patients with histologically proven \nBCC identified that women with BCC presented at \nan older age and that older female preponderance \ncould be in part due to women living to an older \nage in regions of the world where mortality to \ncardiovascular diseases and internal cancers were \nhigher in the male population.14\n\n\n\nEthnicity\nEthnicity is a major determinant of one\u2019s risk of \ndeveloping BCC. Malaysia is a multiracial country \nwith different Fitzpatrick skin phototypes. It is \npurported that the Malaysian population has a wide \nrange of skin phototype from III to V.15 Our study \nshowed that the ethnicity associated with the lowest \nFitzpatrick skin tone, Chinese ethnicity, were \ndiagnosed with more BCC, followed by Malay and \nthe Indian ethnicity. We also found that females \nin both Malay and Indian races outnumbered their \nmale counterparts, differing from the Chinese race \nwhich showed male to be more affected than female. \nOur findings of a majority Chinese ethnicity were \nconsistent with a study by Yap FBB in Sarawak with \nthe Chinese population representing 44% of the 43 \nBCC patients.17 A Singaporean study published in \n1995 investigated skin cancers in 2 tertiary referral \nskin hospitals in Singapore, namely the Middle \nRoad Hospital and National Skin Centre. In 190 \nbiopsy proven BCC patients, 68.9% were Chinese, \n22.6% were Caucasians with Malay and Indians \nforming a small minority.18 Even when expanding \nthese observations to include other skin cancers \nsuch as Bowen\u2019s disease or SCC, Chinese ethnicity \nwas still heavily afflicted at rates of 90.8% and \n83.5% respectively.18 In many western reviews, \nBCC occurs more frequently in individuals with fair \nskin, red haired and those with light eye colors.16,19 \nConversely, dark skinned individuals are estimated \n\n\n\nFigure 1. Outcomes of patients with BCC\n\n\n\nnumber of patients\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34\n\n\n\nto be 19 times less at risk of developing BCC due to \nthe protective role of skin pigmentations against the \nmutagenic nature of UV light.9,19\n\n\n\nLate\tPresentation\nWe recorded that only 32.6% of our histologically \nconfirmed BCC patients presented to our department \nwithin 1 year of skin lesion onset while an alarming \n67.4% presented after 1 year. These findings may \nreflect the indolent but insidious nature of BCCs, \ncausing almost no symptoms that would trigger \na visit to a doctor for many years until its later \nstages.6,14 This effect is further compounded by the \nfact that Malaysian elderly may not seek medical \nconsultation if they deem the skin lesion to be of \na \u201ccosmetic issue\u201d. In addition, many benign skin \nlesions that are related to photo-ageing such as \nsolar lentigo can be difficult to distinguish between \nthe more malignant BCC in its early stages.6,14 \nMabula et al conducted a retrospective study in \n2012 among 64 Albinos in Northwestern Tanzania \nand found that most of their patients presented late \nwith a median presentation time of 24 months.20 \nMany of these skin cancers were SCC, BCC and \nmalignant melanoma that were already ulcerating \nor fungating upon presentation. Furthermore, 42% \nof their patients had defaulted treatment after initial \nexcision or during courses of radiotherapy. The \nauthors reported that due to inadequate facilities, \npatients often needed to spend heavily on time and \nresources to travel far for radiotherapy.20 Delays in \ndiagnosis, and therefore treatment, will lend itself \nto the rapid emergence of locally invasive tumours \nand metastatic BCC. 21 However the healthcare in \nMalaysia is of a single-payer system that is heavily \nsubsidized and most defaulter rates can be attributed \ninadequate education or access to healthcare in \nsome rural areas.\n\n\n\nLocation of Lesions\nThis study found that the vast majority of BCCs \nhave a site specific occurrence. This study was able \nto reproduce similar findings to other studies. In this \nstudy, most BCC occur on areas of the head and \nneck (81.6%) followed by trunk (14.9%), lower limb \n(8.5%) and upper limb (5.7%). Rates of BCC on the \nhead and neck have been similarly high in many \nplaces of the world.7,8,10,13,17,18,22,24 The head and neck \nare areas typically exposed to sunlight over the years. \nProlonged sunlight exposure causes photo-damaged \nskin which increases the likelihood of accruing not \njust BCC but other skin cancers as well.2,25 In recent \nyears, artificial UV radiation has been designated \nas a human carcinogen. The International Agency \n\n\n\nfor Research on Cancer, an affiliate of the WHO \nhas included UV tanning devices in the same group \nas smoking, plutonium and solar UV radiation as \ncancer causing to humans.26 The literature is clear; \nskin cancers such as BCC have become increasingly \nmore common in women under 40 primary due to \nincreased exposure to UV radiation either from the \nsun or artificial sources. It is reported that having 5 \nor more sunburns doubles risk for skin cancers such \nas BCC and melanoma while any history of indoor \ntanning increases the risk of developing BCC before \nthe age of 40 by 69%.15, 25, 27, 28   \n\n\n\nMultiple BCC\nWhile many BCCs occur solitarily in each patient, \nmultiple lesions can occur in the same patient. \nIn our three patients with multiple BCC, many \nof these lesions occured over the abdomen, feet, \nshoulders, and back. Interestingly, these areas \nare not commonly associated with chronic UV \nlight exposure. In an Iranian study published \nin 2013 by Zargaran et al, the authors found that \nthey had identified 804 BCC in 746 patients.22 \nSimilar findings were found from various studies. \nHakverdi et al study in Turkey identified 197 BCC \nin 181 patients with 12 patients having 2 or more \ntumours.12 A UK case control study in 1997 of 827 \nhistologically proven BCC found 278 patients with \nmultiple BCC. That study in particular found that \npatients with multiple lesions were more likely to \nhave truncal tumour at first presentation (p=0.002, \nOR 4.03, 95% CI 1.64 - 9.89).23 Conferring from \nthe breadth of information regarding multiple BCC \nin a single patient, it was found that those with BCC \nof the trunk, impaired immune responses, previous \narsenic treatment in psoriatic patients, possessing \nhigh risk immunogenentics (i.e. HLA-DR4), \nhistory of radiation exposure, and the  presence of \nthe CYP2D6 genetic polymorphism were known \nrisk factors of having multiple or recurrence \nBCC.2,5,19,22,25,29\n\n\n\nModes of Treatment\nMost of our patients underwent simple excisions \n(82.4%), followed by excision and skin graft/\nflap and radiotherapy. This is in keeping with the \nvast majority of our patients who presented earlier \nat Stage 1 and Stage 2, allowing for relatively \nlocalized therapy. Our study identified a relatively \nlow relapse rate of 0.04% (only 6 patients) in \nwhich further therapy was mandated.  Most simple \nexcisions carried out in our center included a margin \nof clinically normal skin. Evidence from a large \nretrospective study of 3957 patients in 2014 by \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n35\n\n\n\nCodazzi et al support the notion of having negative \nmargins during excision of BCC. The  paper \nfound that recurrent rates following histologically \npositive margins was 26.8% compared to 5.9% in \nhistologically negative margins.30 Indeed, other \nstudies support that an excision of non-aggressive \nsubtypes of BCC with 3-4mm margins in low risk \nanatomic regions translated to a 2-4% recurrence \nrate after a 3-5 year period.21  However, apart \nfrom good margin clearance, subtype of BCC \nand anatomical sites are the predictor factors for \nrecurrence rate, in which our study did not collect \nthe data. Hakverdi et al found that the most common \nsite for margin positivity included the eyes (34.4%), \nnose (25%) and ears (15.6%).13 These tumors are \ndifficult to treat due to the potential unwanted facial \ndisfigurement hence are liable to recurrence.21,25 \n\n\n\nTumours in areas that are difficult to treat such as \nthe ears and periocular regions are routinely referred \n\n\n\nsubclinical extensions during MMS and found that \nbeing male, Fitzpatrick skin type 1 and having prior \nhistory of BCC were predictors of requiring more \nextensive tissue removal.33 \n\n\n\nLimitations of study\nThis study is limited by its retrospective nature \nand small number of cases. This study collected \ndata from a single tertiary center, the Dermatology \nDepartment of Hospital Kuala Lumpur. As a result, \nthis number of cases only allowed us to perform a \nunivariate analysis in this study as we did not have the \nrequired sample size to proceed with a multivariate \nanalysis.  We had selected proven BCC patients to \nlook for clinical parameters to tie correlations to the \ndevelopment of BCC, possibly opening our study \n\n\n\nto the plastic surgeons in our institution for optimal \nmultidisciplinary care as surgical defects in these \nareas require their expertise for reconstruction.  \nInfiltrative BCC tumours, are believed to have \nan aggressive nature and also relate to a high \nhistopathological positivity after excision.31 Mohs \nMicrographic surgery (MMS) has been touted as a \nmethod to remove difficult or recurrent cutaneous \ntumours since its inception in the 1940s. A RCT \ncomparing Surgical Excision (SE) and MMS with \n10 year follow up had shown that for primary facial \nBCC, the cumulative risk for recurrence was 4.4% \nin the MMS group compared to 12.2% in the SE \ngroup.32 Furthermore, the 10 year probability for \nrecurrence in patients treated for recurrent BCC \nwere 3.9% in MMS but 13.5% in SE group thus \nconfirming the clinical superiority of MMS over \nSE in cutaneous tumours arising in inconvenient \nareas.32 A study by Greywal et al in 2019 looked \ninto factors that would lead to BCC requiring large \n\n\n\nto selection bias. We did not include categories into \nthe different subtypes of BCC as some other studies \ncited may have as this was not collected in the 14 \nyears\u2019 time frame chosen for the study. Studies that \nsampled patients in multiple centers and prospective \nstudy designs may resolve some of the limitations \npertaining to this study.\n\n\n\nConclusion\nOur study confirmed the long held beliefs that BCC \nis commonly found in older age groups (above 60), \nChinese patients, over the head & neck area and \nmostly have good prognosis if managed early. The \nresults of our study concur with other studies in the \nSouth East Asian region that the Chinese ethnicity \nwas the most implicated ethnic group, followed by \n\n\n\nClinical features Current study\n2005-2018\n\n\n\nYap\tBB\tet\tal3\n2000-2008 \n\n\n\nYeh\tYW\tet\tal4\n1985- 2011\n\n\n\nHakverdi\tS\tet\tal5\n2005-2010\n\n\n\nCi\u0105\u017cy\u0144ska\tM\tet\tal6\n1999-2015\n\n\n\nPopulation HKL, Malaysia \n(n=142)\n\n\n\nSarawak GH \n(n=43)\n\n\n\nTaiwan \n(n=103)\n\n\n\nTurkey \n(n=181)\n\n\n\nPoland \n(n=890)\n\n\n\nMean age (years)\n   Male\n   Female\n\n\n\n65\n66\n\n\n\n62\n60\n\n\n\n71\n67\n\n\n\n64\n59\n\n\n\n66\n66\n\n\n\nGender\n   Male\n   Female\n\n\n\n71(50%)\n71(50%)\n\n\n\n22 (52%)\n21 (48%)\n\n\n\n59 (57%)\n44 (43%)\n\n\n\n101 (56%)\n80 (44%)\n\n\n\n386 (43%)\n504 (57%)\n\n\n\nEthnicities Chinese : 49%\nMalay: 32% \nIndians : 5%\nOthers : 12%\n\n\n\nChinese : 44%\nMalay: 32% \n\n\n\nBidayuh : 14%\nIban : 7%\n\n\n\nTaiwanese Fair Turkish Polish\n\n\n\nCommonest site of \nBCC\n\n\n\nHead & neck - 115 \n(81%)\n\n\n\nHead & neck - 36 \n(83%)\n\n\n\nHead & neck - 91 \n(83%)\n\n\n\nHead & neck - 166 \n(92%)\n\n\n\nHead & neck - 409 \n(46%) \n\n\n\nTable 3. Comparison of our study with other published studies\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36\n\n\n\nMalay and Indian. Simple surgical excision was \nthe commonest treatment method and deemed to \nbe adequately effective. This study is limited by its \nretrospective nature, single-centre data, and lack \nof histology analysis on the types of BCC. These \nfindings may serve as a useful guide in screening \npatients at primary care in early detection of BCC. \nPublic awareness on risk exposure are crucial to \nreduce morbidity of BCC by early presentation to a \ncertified Dermatologist.\n\n\n\nConflict\tof\tInterest\tDeclaration \nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\t\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Department of Public Health. Skin cancers: World Health \nOrganisation. https://www.who.int/uv/faq/skincancer/en/\nindex1.html.\n\n\n\n2. Foundation SC. Skin Cancer Facts & Statistics. https://\nwww.skincancer.org/skin-cancer-information/skin-cancer-\nfacts/.\n\n\n\n3. Current Population Estimates, Malaysia, 2018-\n2019. Department of Statistics Malaysia Official \nPortal. https://www.dosm.gov.my/v1/index.\np h p ? r = c o l u m n / c t h e m e B y C a t & c a t = 1 5 5 & b u l _\nid=aWJZRkJ4UEdKcUZpT2tVT090Snpydz09&menu_\nid=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09. \nAccessed on 31th May 2020.\n\n\n\n4. Azizah AM, Nor Saleha I, Noor Hashimah A, Asmah Z, \nMastulu W. Malaysian National Cancer registry Report \n2007-2011. Malaysia Cancer Statsitics, Data And Figure. \nPutrajaya: National Cancer Institute, Ministry of Health. \n2016.\n\n\n\n5. Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N \nEngl J Med 2005;353:2262-9.\n\n\n\n6. Chinem VP, Miot HA. Epidemiology of basal cell \ncarcinoma. An Bras Dermatol 2011;86:292-305.\n\n\n\n7. Affandi AM. Skin Cancer: 13-Year Experience at the \nDepartment of Dermatology, Hospital Kuala Lumpur, \nMalaysia. JGO 2018;4:79s-79s.\n\n\n\n8. Gallagher RP, Ma B, McLean DI, Yang CP, Ho V, \nCarruthers JA et al. Trends in basal cell carcinoma, \nsquamous cell carcinoma, and melanoma of the skin from \n1973 through 1987. J Am Acad Dermatol 1990;23:413-21.\n\n\n\n9. Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am \nAcad Dermatol 2006;55:741-60.\n\n\n\n10. Ch\u2019ng C, Wong S, Lee Y, Rokiah I, Jayalakshmi P. A \n7-Year Retrospective Review of Skin Cancer at University \nMalaya Medical Centre: A Tertiary Centre Experience. \nMalaysian J Dermatol 2012;29:16-29.\n\n\n\n11. Sng J, Koh D, Siong WC, Choo TB. Skin cancer trends \namong Asians living in Singapore from 1968 to 2006. J \nAm Acad Dermatol 2009;61:426-32.\n\n\n\n12. Hakverdi S, Balci DD, Dogramaci CA, Toprak S, Yaldiz \nM. Retrospective analysis of basal cell carcinoma. Indian J \n\n\n\nDermatol Venereol Leprol 2011;77:251.\n13. Ci\u0105\u017cy\u0144ska M, Narbutt J, Wo\u017aniacka A, Lesiak A. Trends \n\n\n\nin basal cell carcinoma incidence rates: a 16-year \nretrospective study of a population in central Poland. \nPostepy Dermatol Alergol. 2018;35:47-52.\n\n\n\n14. Scrivener Y, Grosshans E, Cribier B. Variations of basal \ncell carcinomas according to gender, age, location and \nhistopathological subtype. Br J Dermatol 2002;147:41-7.\n\n\n\n15. Wong LC, Jamil A, Md Nor N. The effect of pre\u2010phototest \nsun exposure on minimal erythema dose and minimal \nmelanogenic dose among skin phototypes III, IV and V. \nPhotodermatol Photoimmunol Photomed 2018;34:400-4.\n\n\n\n16. Yeh YW, Chen SY, Wu BY, Gao HW, Liu CY, Chien WC \net al. Epidemiologic and pathologic characteristics of basal \ncell carcinoma in northern Taiwan: Experience from a \nmedical center. J Med Sci 2014;34:98-103.\n\n\n\n17. Yap FBB. Clinical characteristics of basal cell carcinoma \nin a tertiary hospital in Sarawak, Malaysia. Int J Dermatol \n2010;49:176-9.\n\n\n\n18. Tan SH, Tham SN, Goh CL. Skin cancers at tertiary referral \nskin hospital in Singapore. Int J Dermatol 1995;34:770-6.\n\n\n\n19. Roewert\u2010Huber J, Lange\u2010Asschenfeldt B, Stockfleth \nE, Kerl H. Epidemiology and aetiology of basal cell \ncarcinoma. Br J Dermatol 157 Suppl 2:47-51.\n\n\n\n20. Mabula JB, Chalya PL, Mchembe MD, Jaka H, Giiti G, \nRambau P et al. Skin cancers among Albinos at a University \nteaching hospital in Northwestern Tanzania: a retrospective \nreview of 64 cases. BMC Dermatol 2012;12:5.\n\n\n\n21. Work Group; Invited Reviewers, Kim JYS, Kozlow JH, \nMittal B, Moyer J.\n\n\n\n22. Zargaran M, Moghimbeigi A, Monsef A, Teimourian \nH, Shojaei S. A clinicopathological survey of basal cell \ncarcinoma in an Iranian population. J Dent (Shiraz) \n2013;14:170.\n\n\n\n23. Lear JT, Tan BB, Smith AG, Bowers W, Jones PW, \nHeagerty AH et al. Risk factors for basal cell carcinoma in \nthe UK: case-control study in 806 patients. J R Soc Med \n1997;90:371-4.\n\n\n\n24. Kricker A, English DR, Randell PL, Heenan PJ, Clay \nCD, Delaney TA et al. Skin cancer in Geraldton, Western \nAustralia: a survey of incidence and prevalence. Med J \nAust 1990;152:399-407.\n\n\n\n25. Wong C, Strange R, Lear J. Basal cell carcinoma. BMJ \n2003;327:794-8.\n\n\n\n26. El Ghissassi F, Baan R, Straif K, Grosse Y, Secretan B, \nBouvard V et al on behalf of the WHO International \nAgency for Research on Cancer Monograph Working \nGroup. A review of human carcinogens-Part D: radiation. \nLancet Oncol 2009;10:751-2.\n\n\n\n27. Ferrucci LM, Cartmel B, Molinaro AM, Leffell DJ, Bale \nAE, Mayne ST. Indoor tanning and risk of early-onset \nbasal cell carcinoma. J Am Acad Dermatol 2012;67:552-\n62.\n\n\n\n28. Pfahlberg A, K\u00f6lmel KF, Gefeller O; Febim Study Group. \nTiming of excessive ultraviolet radiation and melanoma: \nepidemiology does not support the existence of a critical \nperiod of high susceptibility to solar ultraviolet radiation\u2010\ninduced melanoma. Br J Dermatol 2001;144:471-5.\n\n\n\n29. Samarasinghe V, Madan V, Lear JT. Focus on basal cell \ncarcinoma. J Skin Cancer 2011;2011:328615.\n\n\n\n30. Codazzi D, Van Der Velden J, Carminati M, Bruschi S, \nBocchiotti M, Di Serio C et al. Positive compared with \nnegative margins in a single-centre retrospective study \non 3957 consecutive excisions of basal cell carcinomas. \nAssociated risk factors and preferred surgical management. \nJ Plast Surg Hand Surg 2014;48:38-43.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n37\n\n\n\n31. Rippey J. Why classify basal cell carcinomas? \nHistopathology 1998;32:393-8.\n\n\n\n32. van Loo E, Mosterd K, Krekels GA, Roozeboom MH, \nOstertag JU, Dirksen CD et al. Surgical excision versus \nMohs\u2019 micrographic surgery for basal cell carcinoma of \nthe face: a randomised clinical trial with 10 year follow-\nup. Eur J Cancer 2014;50:3011-20.\n\n\n\n33. Greywal T, Goldenberg A, Eimpunth S, Jiang S. Key \ncharacteristics of basal cell carcinoma with large \nsubclinical extension. J Eur Acad Dermatol Venereol \n2020;34:485-90.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38\n\n\n\nCASE REPORT\n\n\n\nJessner\u2019s Lymphocytic Infiltration of the Skin \u2013 A Case Report and \nDiscussion of Current Literature         \nHuat Bee Lim1, AM (Derm), Bang Rom Lee2, MPath, Shueh Wei Lim1, FACD \n\n\n\n1Lim Skin Specialist Clinic, Penang, Malaysia\n2Department of Pathology, Gleneagles TM Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nJessner\u2019s lymphocytic infiltration of skin is an uncommon disorder characterised by benign \naccumulations of lymph cells in the skin.  It is of unknown aetiology and presents as erythematous \npapules and plaques on the face, neck and/or back, with possible itching of the skin surrounding \nthe lesions.  The lesions may remain unchanged for many years and then spontaneously disappear, \nwithout residual scarring.  Current literature on this topic are limited and numerous treatments have \nbeen tried with limited success.  We report a recent case of Jessner\u2019s lymphocytic infiltration seen in \nour practice and discuss the histology and our approach to management.\n\n\n\nKey words: Jessner\u2019s lymphocytic infiltration\n\n\n\nCorresponding Author\nDr Shueh Wei Lim\nLim Skin Specialist Clinic, 14-A, Lorong Abu Siti, \n10400, Penang, Malaysia\nEmail: lim.wei@yahoo.com \n\n\n\nCase Report\nA 41-year-old woman presented to our clinic in \nDecember 2016 with three years of erythematous \npapules and plaques on her face.  She denied \nany itching but was bothered by her cosmetic \nappearance. She also did not experience any \nphotosensitivity. She had a past history of Sjogren\u2019s \ndisease with minimal joint symptoms and was anti \nRo positive. This was previously treated with oral \nsteroids, doxycycline and at presentation was on a \nmaintenance dose of hydroxychloroquine at 200mg \nper day for the previous 1 year. \n\n\n\nClinical examination showed multiple erythematous \ninfiltrated papules and plaques with no epidermal \nchanges, predominantly distributed on her chin \nbilateral cheeks and temporal regions (Figure 1).  \nThere was no other lesion on the body and the rest \nof her physical examination was normal.  \n\n\n\nHer ANA was negative but her ENA showed Anti \nRo positive. All her other blood tests including \nfurther connective tissue disease screening (ESR, \nCRP, C3, C4, CK, Rh factor, anti-dsDNA, lupus \nanti-coagulant, anti-cardiolipin antibodies) blood \nfilm and urinalysis were unremarkable. Phototesting \nwas not performed due to patient preference. \n\n\n\nHistopathology of the skin biopsy showed \nmild superficial perivascular and peri-adnexal \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n39\n\n\n\nlymphoplasmacytic cells infiltration with absence \nof lichenoid reaction (Figure 2-3).  Alcian Blue \nPAS stain showed superficial perivascular and \nperifollicular mucin deposit.  Giemsa stain was \nnegative for mast cells.  Jessner\u2019s lymphocytic \ninfiltration was the most likely diagnosis given the \nsuperficial changes. Immunofluorescence studies \nwere not performed. The histological features \nof Jessner\u2019s lymphocytic infiltration is difficult \nto distinguish from tumid lupus erythematosus. \nHowever tumid lupus erythematosus shows \nabundant and denser mucin deposition which is not \ndemonstrated in this case.\n\n\n\nShe was treated initially with an increased dose of \nhydroxychloroquine (400 mg daily) and Cutivate\u00ae \ncream (fluticasone propionate 0.05%) topically \ntwice a day. Intralesional steroids were not used due \nto concern about possible atrophy. No new lesion \ndeveloped but there was only mild improvement \nafter 2 months. Hence oral Methotrexate was started \nat 15mg/week with folic acid supplementation. She \nremained stable with overall limited improvement \nat the time of this publication.\n\n\n\nFigure 1. Clinical photo of patient\u2019s left cheek\n\n\n\nFigure 3. ABPAS stain highlighted the mucin deposit. \n\n\n\nDiscussion\nJessner\u2019s lymphocytic infiltration of the skin is an \nuncommon disorder.  It is a benign chronic T-cell \ninfiltrative disease, first described in 1953 by Jessner \nand Kanof1.  The condition may remain unchanged \nfor several years and then disappear spontaneously \nwithout residual scarring.   \n\n\n\nThis condition often presents as rosy-red papules, \nplaques and less commonly nodules mostly on the \nupper face, cheeks, neck and back.  The lesions are \nnon-scaly in nature and may last for several months.  \nThey often expand from the perimeter to form well \ndefined, smooth, red plaques.  Central clearing may \noccur.  The skin surrounding the lesions may be \nreddened or itchy.  Sensitivity to sunlight may occur \nbut is unusual.  Generally the symptoms disappear \nafter several years but they may recur later.1, 2\n\n\n\nThe exact cause of Jessner\u2019s lymphocytic infiltration \nis not known. It has been found that abnormal \nnumbers of lymphocytes accumulate in the skin.2  \nThere is doubt whether this is a disorder distinct \nfrom other benign lymphocytic infiltration of the \nskin.3  Some believe that Jessner\u2019s lymphocytic \ninfiltration may be a type of lupus erythematosus \ntumidus (LET) or discoid lupus erythematous \n(DLE)3-6.  Symptoms of other disorders can be \nsimilar to Jessner\u2019s lymphocytic infiltration of \nthe skin and these include lupus erythematosus \ntumidus, polymorphous light eruption, certain \npseudolymphomas, lymphocytoma cutis, mycosis \nfungoides, leprosy.2, 3 Evolution to cutaneous or \nextracutaneous lymphoma is not common although \nsome can progress to discoid lupus erythematosus \nor are related to lupus erythematosus.4\n\n\n\nFigure 2. HEx400: Moderate perivascular and periadnexal \nlymphoplasmacytic cells infiltration in the superficial dermis. \nLichenoid reaction at the epidermal basal layer was not seen. \n(Hematoxylin-eosin stain; original magnification: x400.)\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40\n\n\n\nSkin biopsy of a recently formed lesion is very \nhelpful for excluding these other possible conditions.  \nHistopathologically, Jessner\u2019s lymphocytic \ninfiltration is characterised by a superficial and deep \nprimarily perivascular, sleeve-like lymphocytic \ndermal infiltrate with a predominance of small \nmature polyclonal lymphocytes without epidermal \nor basal membrane involvement.4  Jessner\u2019s \nlymphocytic infiltration is sometimes difficult to \ndistinguish histologically from polymorphic light \neruption or chronic cutaneous lupus erythematosus. \nChronic cutaneous lupus erythematosus can be \ndifferentiated by the presence of lichenoid reaction \nand its involvement of the dermoepidermal \njunction. Epidermal atrophy and focal thickening \nof the dermoepidermal junction were found more \ncommon in chronic cutaneous lupus erythematosus3. \nDeposits of mucin in the reticular dermis have been \ndescribed.3\n\n\n\nPrognosis is good because lymphocytic infiltration \nof the skin may resolve spontaneously.2 A period \nof observation may be reasonable as the lesions \nmay clear spontaneously.  However, many patients \nelect to start treatment early because the lesions are \ncosmetically unacceptable.\n\n\n\nNumerous treatments have been tried with variable \nsuccess.  These include cosmetic camouflage, topical \nor intralesional steroids, oral hydrochloroquine, \nsystemic steroids, cryotherapy, methotrexate, \ndapsone, thalidomide, auranofin, phototherapy and \npulsed dye laser.1, 7, 8, 9, 10, 11. Treatment with anti-\nmalarials is usually effective especially in cases \nwith photo-sensitivity7.\n\n\n\nConflict\tof\tInterest\tDeclaration\t\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\t\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Calnan CD. Lymphocytic infiltration of the skin (Jessner). \nBr J Dermatol 1957;69:169-73.\n\n\n\n2. Bolognia JL, Jorizzo JL, Rapini PR. Dermatology, 2nd ed. \nSpain. Elsevier Limited. 2008; p121:1887-8\n\n\n\n3. Remy-Leroux V, Leonard F, Lambert D, Wechsler J, \nCribier B, Thomas P et al. Comparison of histopathologic-\nclinical characteristics of Jessner\u2019s lymphocytic infiltration \nof the skin and lupus erythematosus tumidus: Multicenter \nstudy of 46 cases. J Am Acad Dermatol 2008;58:217-23.\n\n\n\n4. Lipsker D, Mitschler A, Grosshans E, Cribier B. Could \nJessner\u2019s lymphocytic infiltrate of the skin be a dermal \nvariant of lupus erythematosus? An analysis of 210 cases. \nDermatology 2006;213:15-22.\n\n\n\n5. Teixeira M, Ferreira M, Alves R, Selores M. Lupus \nerythematosus tumidus: an underestimated entity. Lupus \n2006;15:296-300.\n\n\n\n6. Toonstra J, Wildschut A, Boer J, Smeenk G, Willemze R, \nvan der Putte SC et al. Jessner\u2019s lymphocytic infiltration of \nthe skin. A clinical study of 100 patients. Arch Dermatol \n1989;125:1525-30.\n\n\n\n7. Adamski H, Labrousse AL, Sparsa A, Leonard F, Le Gall F, \nLabrousse F et al. [Positive photobiological investigation \nin Jessner\u2019s lymphocytic infiltration of the skin]. Ann \nDermatol Venereol 2002;129:1370-3.\n\n\n\n8. Laurinaviciene R, Clemmensen O, Bygum A. Successful \ntreatment of Jessner\u2019s lymphocytic infiltration of the skin \nwith methotrexate. Acta Derm Venereol 2009;89:542-3.\n\n\n\n9. Guillaume JC, Moulin G, Dieng MT, Poli F, Morel P, \nSouteyrand P et. al. Cross over study of thalidomide vs \nplacebo in Jessner\u2019s lymphocytic infiltration of the skin. \nArch Dermatol 1995;131:1032-5\n\n\n\n10. Green CM. Successful Treatment of Jessner\u2019s lymphocytic \ninfiltrate with auranofin. Clin Exp Dermatology \n2008;33:108-9.\n\n\n\n11. Borges da Costa J, Boixeda P, Moreno C. Pulse-dye laser \ntreatment of Jessner lymphocytic infiltration of the skin. J \nEur Acad Dermatol Venereol 2009;23:595-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n41\n\n\n\nCASE REPORT\n\n\n\nAdult Onset Still\u2019s Disease: A Case Report in Hospital Kuala Lumpur         \nChoon Sian Lee1, AdvMDerm, Li Lian Tay2, MRCP, Gin Peng Chan1, MRCP, Zuliatul Faizah Baharom3, MPath, Bang \nRom Lee4, MPath, Suganthi Thevarajah1, MMed, Min Moon Tang1, AdvMDerm\n\n\n\n1 Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2 Department of Medicine, Hospital Kuala Lumpur, Malaysia\n3 Department of Pathology, Hospital Kuala Lumpur, Malaysia\n4 Department of Pathology, Gleneagles TM Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nAdult onset Still\u2019s disease (AOSD) is a rare systemic autoinflammatory disorder of unknown etiology \ncharacterized by a clinical triads of daily spiking high fever, evanescent rash and arthritis; with \nlaboratory findings of hyperferritinemia, neutrophilic leucocytosis and negative autoantibodies of \nrheumatoid factor and antinuclear antibody. Diagnosis is made after exclusion of infections, autoimmune \ndiseases and malignancy. Here we illustrate a case of AOSD with prolonged high fever, evanescent \nrash presenting as scattered erythematous patches, polyarthritis, lymphadenopathy, serositis, anemia, \nleukocytosis, hyperferritinemia and hepatitis. It was complicated by crico-arytenoid arthritis, acute \ninterstitial nephritis with nephrogenic diabetes insipidus. Skin biopsy showed distinctive dyskeratotic \nkeratinocytes at the upper epidermis. Diagnosis of AOSD was made at 6 weeks from the onset of \nfever. She responded partially to high dose of systemic corticosteroids, intravenous immunoglobulin, \nmethotrexate and anakinra.\n\n\n\nKey words: Adult\tonset\tStill\u2019s\tdisease,\tautoinflammatory\tdisorder,\tdyskeratotic\tkeratinocytes\n\n\n\nCorresponding Author\nDr Choon Sian Lee\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586 Kuala Lumpur\nMalaysia\nEmail: lchoonsian@gmail.com \n\n\n\nIntroduction\nAdult onset Still\u2019s disease (AOSD) is a sporadic \ncomplex autoinflammatory syndrome first described \nin 1971.1 It is characterised by high spiking fever, \npolyarthritis, sore throat, lymphadenopathy, \nhepatosplenomegaly, serositis, and evanescent skin \neruptions.1,2 It is associated with life-threatening \ncomplications too. Diagnosis of AOSD is laborious \nas it requires extensive investigations to exclude \ninfections, autoimmune diseases and malignancy. \nHere we illustrate a young female who exhibited a \nturbulent presentation of ASOD.  \n\n\n\nCase Report\nA 30-year-old Chinese female presented with 2 \nweeks of fever, chills, rigors, sore throat, and dry \ncough associated with polyarthalgia at proximal \ninterphalangeal joints, wrists, elbows, shoulders, \nankles and knees. There were no oral ulcers, \nphotosensitivity, alopecia, weight loss, abdominal \npain, diarrhea, heat intolerance and palpitation. \nThere was also no prior new medication or history \nof travelling. She did not respond to antibiotics and \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42\n\n\n\nparacetamol given at a private health care facility. \nShe was then hospitalized in Hospital Kuala Lumpur \nin September of 2018 after 3 weeks of prolonged \nand persistent high fever. \n\n\n\nShe was pale, blood pressure was low to normal and \ntachycardic. Her weight on admission was 42kg. \nHer fever was spiking at 40\u00b0C every night. This was \nassociated with evanescent erythematous patches \nover the knuckles which resolved when fever \nsubsided. She also had pruritic erythematous patches \nat the upper anterior chest as shown in Figure 1(a). \nHer condition deteriorated with dyspnoea requiring \nnon-invasive ventilation at high dependency unit. \n\n\n\nLaboratory tests revealed normocytic normochromic \nanemia (Hb 7.5g/dL) and leucocytosis (highest \nwhite blood cells count 44.4 x 109/L, 88-93% \nneutrophils). The acute phase reactants were \nelevated with erythrocyte sedimentation rate \n(ESR): 65 mm/hr; highest C-reactive protein \n(CRP): 288 mg/L; and highest ferritin: 36,737\u03bcg/L. \nShe had mild transaminitis (highest aspartate \ntransaminase: 90U/L; highest alanine transaminase: \n848U/L; and alkaline phosphatase: 204U/L) and \nhypoalbuminemia (lowest albumin 14g/L). Viral \nscreening including HIV and Hepatitis A IgM, \nanti Hep BsAg antibody, anti HepB core antibody \nand anti Hep C virus antibody were negative. \nVDRL titre was 1:4 and TPHA was negative.  \nHer Mantoux test was 0mm, and the Quanteron \ngold (performed twice with 2 weeks apart) were \nindeterminate. Leptospira serology, mycoplasma \nserology, melioidosis serology, blood films for \nmalaria parasites, Widal Weil Felix (WWF) test, \nsputum acid fast bacilli (AFB) were all non-\nreactive. Anti-nuclear antibody (ANA), rheumatoid \nfactor (RF), anti-cyclic citrullinated peptide (Anti-\nCCP), anti-smooth muscle antibodies (ASMA), \nanti-mitochondrial antibodies (AMA) antibody and \nAnti-Liver Kidney Microsomal (LKM) antibodies \nwere negative. Complement level C3, C4, were \nwithin normal range. Chest radiography showed \nbilateral pleural effusion. \n\n\n\nThere was pericardial effusion on her \nechocardiogram with free wall of the right atrium \nand posterior left ventricle which ranged between \n1.4-1.6cm. Apart from mild mitral and tricuspid \nregurgitation, her ejection fraction was between \n58-60% without any thrombus and vegetations. \nComputed tomography (CT) of her brain was \nnormal. Her CT thorax, abdomen and pelvis \nrevealed bilateral hilar mediastinal lymph node \n\n\n\nenlargement and hepatomegaly. No paraprotein \nwas detected from serum and urine electrophoresis. \nApart from increased granulocytic series especially \nthe granulocyte precursor, her bone marrow \naspiration and trephine biopsy did not detect any \nhemophagocytic lymphohistiocytosis (HLH), acute \nleukemia or lymphoma. Cultures (bacterial fungal \nand mycobacterium) from the bone marrow biopsy \nwere negative.\n\n\n\nTen days into hospitalization, a referral was made \nto the Department of Dermatology for her rash. She \nwas tachypnoeic, hypotensive and febrile. There \nwere persistent erythematous patches noted at the \nneck (Figure 1a), erythematous patches over the \nknuckles of fingers with tender swollen proximal \ninterphalangeal joints bilaterally. There were \nbilateral pedal edema. Breath sound was reduced \nat the base of the lungs. There were however \nno murmur, lymphadenopathy, hepatomegaly, \nsplenomegaly or ascites.\n\n\n\nSkin biopsy at the erythematous patch of the \nanterior chest showed spongiotic epidermis with \npresence of dyskeratotic keratinocytes at the stratum \ngranulosum. The upper dermis showed perivascular \neosinophils and neutrophils infiltration. (Figure \n2a, H&E, x200). There were no interface changes, \nvasculitis or mucin deposition. Clinical pathological \ncorrelation with the skin histological findings were \nconsistent with Still\u2019s Disease. \n\n\n\nThe diagnosis of Adult Onset Still\u2019s Disease (AOSD) \nwas finally made nearly 6 weeks after the onset of \nfever.  She was started on IV Hydrocortisone 100mg \n8 hourly. During the same admission, she received \nintravenous ceftriazone (2 days), intravenous \ntazobactam + piperacillin (2 courses at different \noccasions, total 12 days), intravenous meropenem \n(2 courses at different occasion, total 3 weeks), oral \ndoxycycline (1 week), intravenous augmentin (7 \ndays) and oral cloxacillin (7 days). The antibiotics \nwere given for presumed sepsis initially and \nsubsequently positive blood and urine cultures of \nAcinetobacter baumanii and Enterococcus species \nrespectively. Despite the concomitant systemic \ncorticosteroids and antibiotics, her fever did not \nresolve.\n\n\n\nThree weeks after intravenous hydrocortisone \nwas initiated, she developed scattered vesicular \neruptions involving the right temple, oral cavity, \nupper limbs and trunk. A repeated skin biopsy \nshowed intraepidermal blister containing numerous \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n43\n\n\n\nviral cytopathic effect cells exhibiting very large \nnuclei with multiple inclusions and nuclear clearing \n(Figure 2b, H&E, x100). This was suggestive of \nherpes infection. Herpes simplex virus 1 & 2 DNA \nPCR were not detected probably due to a late \nsampling from the lesions. However, herpes simplex \nvirus 1 & 2 IgM was detected. Other human herpes \nvirus screenings (CMV and EBV) were negative. \nA diagnosis of disseminated herpes infection was \nmade. She was treated with IV Acyclovir 500md \n8-hourly for a week. \n\n\n\nSubsequently, she developed dysphagia and \nphonatory gap with vocal cords paralysis. \nExtensive investigations including abnormal \nflexible endoscopic examinations of swallowing, \na non-reactive anti\u2013acetylcholine receptor (AChR) \nantibody and a normal Magnetic Resonance Imaging \n(MRI) with angiography of the brain had concluded \nthat these were the complications of ASOD due to the \narthritis of the crico-arytenoid joints. Her symptoms \nresponded to IV methylprednisolone 500mg od for \n3 days. Apart from that, she received 2 units of \npacked cell transfusion. She improved finally and \nthen was discharged with oral prednisolone 30mg \ndaily, oral pantoprazole, cholecalciferol, calcium \nsupplements, ferrous fumarate and vitamins after 3 \nmonths of hospital stay. \n\n\n\nUnfortunately, she was readmitted to the hospital \ntwice in January 2019 for severe hepatitis (highest \nlevel of ALT=1,372U/L and AST=1,351U/L) with \npersistent high fever. Her serum ferritin peaked at \n64,114ug/L. Her serum fibrinogen was normal and \nD-dimer was slightly raised at 7.2ug/ml (<0.5). \nRepeated bone marrow aspiration in February \n2019 showed no evidence of acute leukaemia nor \nhaemophagocytosis. Liver biopsy showed mild to \nmoderate interface hepatitis with inflammatory \ninfiltrates consisted of lymphocytes, plasma cells and \nneutrophils. Mild focal hepatocellular cholestasis, \nmild cytoplasmic vacuolation of some bile duct \nlining and lymphocytic lobular inflammation was \nobserved. There was no intraepithelial fibrosis \nand granuloma. She was given intravenous \nimmunoglobulin 2g/kg twice (3 weeks apart) and \na course of intravenous methylprednisolone 500mg \ndaily for 3 days. Her hepatitis improved and she was \ndischarged with oral prednisolone 40mg daily with \nvitamins, cholecalciferol and calcium supplements. \n\n\n\nSubcutaneous Anakinra 90mg daily was initiated \nend of February 2019 while the dose of oral \nprednisolone was taper down slowly. Two weeks \n\n\n\nafter the initiation of anakinra, she was readmitted \nwith high fever and cough. She was diagnosed \nwith hospital acquired pneumonia based on the \nappearance of infective changes at the right middle \nlobe on her chest radiograph. Her liver enzymes \nwere almost normalized with serum ferritin of \n6,891\u03bcg/L. Anankira was withheld, intravenous \ntazocin was initiated and oral prednisolone was \nmaintained at 15mg daily. Cloxacillin was added \non day 6 of tazocin for five days for cellulitis of \nher right hand. She then developed new cutaneous \nreactions. Firstly, she presented with persistent \nperiorbital swelling followed with Stevens Johnson \nSyndrome (SJS) like lesions. She had severe oral \nand genitalia erosions, conjunctivitis and blanchable \nmaculopapular eruptions on her face, body and limbs \nwith less than 10% body surface area of detached \nskin. Based on the algorithm of drug causality for \nepidermal necolysis (ALDEN)3, both tazocin and \ncloxacillin scored 3 out of 10, which means they \nwere only \u201cpossible\u201d culprits, neither \u201cprobably\u201d \nnor \u201cvery probable\u201d. This is mainly because they \nwere given in her previous admission (twice for \ntazocin and once for cloxacillin) without any \nreactions documented.  Both tazocin and cloxacillin \nwere withheld. Her skin lesions gradually resolved \nin 2 weeks with supportive skin care treatment and \nintravenous hydrocortisone 50mg 8hourly. \n\n\n\nUnfortunately, she had hospital acquired infections \nwith right mid lobar pneumonia (broncho-\nalveolar lavage culture grew methicillin-resistant \nStaphylococcus aureus [MRSA]), urine culture grew \nMRSA and Escherichia coli, blood culture grew \ncoagulase-negative Staphylococci). She was then \ngiven intravenous meropenem (total 10 days) and \nvancomycin (total 14 days). While receiving these \nantibiotics and systemic corticosteroids (equivalent \nof prednisolone dose 15mg to 50mg daily) she \ndeveloped periorbital swelling with heliotrope \nlike rash, mildly scaly malar erythema sparing \nthe infraorbital and nasolabial fold, mildly scaly \nscalp together with non-pruritic purpuric to brown \nmacules over trunk, upper and lower limbs including \nthe palms without any mucosal erosions (Figure \n1b-e). Her high fever persisted despite antibiotics. \nShe had thrombocytopenia (lowest platelet count of \n67x109), low fibrinogen, raised D-dimer and mildly \nprolonged prothrombin time. Her ferritin was again \nraised at 12,444 \u03bcg/L, liver enzymes raised at ALT: \n570U/L, AST:1773U/L signifying the active AOSD.  \nSkin biopsy was also performed on a lesion on her \npalm and showed singly apoptotic keratinocytes at \nthe upper epidermis, similar to the findings of the \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44\n\n\n\nFigure 1. a. Persistent pruritic erythematous patches at the upper anterior chest and neck in September 2018, b-e. Periorbital swelling \nwith heliotrope-like rash, mildly scaly malar erythema sparing the infraorbital and nasolabial fold, non-pruritic purpuric macules on the \npalms, brown macules over trunk, and dorsum of feet in April 2019. \n\n\n\nFigure 2. a. Skin biopsy on the erythematous patch of the anterior chest in September 2018 showed spongiotic epidermis with presence \nof dyskeratotic keratinocytes (arrow) at the stratum granulosum. The upper dermis showed perivascular eosinophils and neutrophils \ninfiltration. (H&E, x200); b. A repeated skin biopsy in October 2018 done on a vesicle showed intraepidermal blister containing \nnumerous viral cytopathic effect cells exhibiting very large nuclei with multiple inclusions and nuclear clearing (H&E, x100); c. Another \nskin biopsy on her left palm showed singly apoptotic keratinocytes (arrow) at the upper epidermis (H&E, x200)\n\n\n\na cb\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n45\n\n\n\nfirst skin biopsy, which was suggestive of AOSD \n(Figure 2c, H&E, x200), rather than cutaneous \nadverse drug reactions. She also developed polyuria \nas a sign of nephrogenic diabetes insipidus resulted \nfrom acute interstitial nephritis. Her antibiotics was \nchanged to intravenous colistin for 7 days. A course \nof oral oseltamivir was also prescribed. Intravenous \nimmunoglobulin (IVIg) 0.4g/kg/ day for 5 days \nwas administered and subcutaneous anakinra \n90mg was resumed. Her diabetes insipidus was \ncontrolled by desmopressin and later replaced with \nfludrocortisone treatment. She improved clinically \nand was finally discharged with oral prednisolone \n10mg daily, subcutaneous anakinra 90mg daily, \nfluodrocortisone 0.1mg daily, cholecalciferol, \ncalcium supplements and vitamins.\n\n\n\nHer subsequent outpatient follow-ups with \nrheumatologist showed that her disease activity was \nsub-optimally controlled. She was still experiencing \nfever almost every day. Apart from that she had \ngeneralized lymphadenopathy (size ranged from \nsubcentimeter to 2.4cm) demonstrated on repeated \nCT scan. Her latest ferritin level was 1820 \u03bcg/L \nwith normalized liver enzymes. Lymph node biopsy \nshowed reactive hyperplasia and had excluded \nlymphoma. Her latest medications included \nsubcutaneous anakinra 200mg daily and oral \nmethotrexate 20mg weekly together with calcium \nsupplements and vitamins. \n\n\n\nDiscussion\nASOD is phenotypically likened to childhood-onset \nStill\u2019s disease, which is now known as systemic \njuvenile idiopathic arthritis (sJIA). sJIA occurs \nin children less than 16 years-old. sJIA is more \ncommon in children with the worldwide incidence \nranges between 0.4 to 0.8 per 100,000 children.4 \nBoth male and female children are affected equally.4 \nsJIA is reported to affect children of all ethnic \nbackgrounds.4 The incidence of ASOD worldwide \nis much lower incidence as compared to sJIA i.e. \n0.16 to 0.4 per 100,000 adults.4 Like sJIA, ASOD \nhas equal gender distribution2,6-7 in most reports but \nthere is a female preponderance in the Japanese, \nKorean and Chinese studies.6 Although ASOD may \npresent for the first time in adults above 65 years \nold8,9 (reported to be between 5-23%), it usually \naffects younger people, with bimodal peak at 15-25 \nyears and 36-46 years.2,6-7 \n\n\n\nBeing a multigenic autoinflammatory disease \ninvolving mainly the innate immune system, AOSD \nis believed to be triggered by some factors (viral or \n\n\n\nbacterial infections, malignancies and possibly other \nenvironmental elements) in a genetically susceptible \nindividual.5-7 No definite trigger has been identified. \nAOSD has been associated with HLA-B17, -B18, \n-B35, -DR2 and -DR4, DRB1*12, DRB1*15, Bw35 \nand DRB1*14.  HLA-BRB1*1501 (DR2) and \nDRB1*1201 (DR5) were associated with chronic \ndisease course of AOSD and HLA-DQB1*0602 \n(DQ1) was associated with chronic and systemic \ndisease.6,10 Polymorphisms in both interleukin (IL)-\n18 gene and macrophage migration inhibitory factor \n(MIF) gene were associated with AOSD. In addition, \ngain-of-function mutation of the MEFV, a hereditary \nperiodic fever syndrome gene was identified with \nsevere form of AOSD.6,10 Dramatic activation of \nthe inflammatory cells of the innate immunity is \nthe hallmark of AOSD. Toll-like receptor (TLR) \n7 ligation is up-regulated in the dendritic cells.6,10 \nRecruitment of neutrophils and macrophages are \nheightened, resulting in pro-inflammatory responses \nand cytokine \u201cstorm\u201d. Amplified production of \nIL-1\u03b2, IL-6 and IL-18 was studied extensively in \nAOSD.6,10 Anti-IL-1 treatment has been shown \nto be useful in treating AOSD. Interestingly, the \ncytotoxic functions of NK cells were impaired in \nAOSD. Besides, the circulating CD4+CD25high Treg \ncells, serum transforming growth factor \u03b2 (TGF- \u03b2) \nand IL-10 were found to be low in severe AOSD \nwhich allow unhindered inflammation in AOSD.5,9 \nOther cytokines including IL-17, IL-23, TNF, \nCXCL9,10,11, and 13 were also found to be raised \nin AOSD, albeit undetermined significance.10\n\n\n\nAOSD typically present with a clinical triad of high \nspiking fever of at least 39oC, joint involvement \nand typical evanescent erythema.5-7 The fever is \nabrupt, once or twice a day, highest in the evening \nand lasts less than 4 hours. The joint involvement is \nusually symmetrical polyarthritis, mainly affecting \nthe wrists, knees and ankles.5-7 In about a third of \narthritis, joint becomes erosive where patients may \ndevelop isolated bilateral carpal ankylosis.5-7 \n\n\n\nCutaneous manifestation is one of the major \ndiagnostic criteria for AOSD. It is described in \n58-87% of patients with ASOD.5 Our patient has \ndemonstrated a few types of cutaneous manifestations \nwith different morphology at different stages of \ndisease activity. She had the classical evanescent \nerythematous patches over her knuckles during \nher febrile attack before the diagnosis of AOSD.  \nClassical evanescent rash has been described in the \nliterature as salmon-pink, maculopapular eruption \naccompanied by fever, predominantly found on \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46\n\n\n\nTable 1. Yamaguchi et al20 and Fautrel et al21 Classification criteria for adult onset Still\u2019s Disease\n\n\n\nCriteria Yamaguchi\tet\tal20, 1992 Fautrel et al21, 2002\n\n\n\nMajor criteria \u2022 Fever =39 \u00b0C lasting 1 week or more\n\u2022 Arthralgia lasting 2 weeks or more\n\u2022 Typical skin rash: maculopapular, nonpruritic, salmon-\n\n\n\npink rash with concomitant fever \n\u2022 Leukocytosis =10,000/mm3 with neutrophil \n\n\n\npolymorphonuclear proportion =80%\n\n\n\n\u2022 Spiking fever =39 \u00b0C\n\u2022 Arthralgia\n\u2022 Transient erythema\n\u2022 Pharyngitis\n\u2022 Neutrophil polymorphonuclear proportion =80%\n\u2022 GF proportion =20%\n\n\n\nMinor criteria \u2022 Pharyngitis or sore throat\n\u2022 Lymphadenopathy and/or splenomegaly\n\u2022 Liver enzyme abnormalities (aminotransferases)\n\u2022 Negative for rheumatoid factor or antinuclear \n\n\n\nantibodies\n\n\n\n\u2022 Typical rash\n\u2022 Leukocytosis =10,000/mm3\n\n\n\nExclusion criteria \u2022 Absence of infection, especially sepsis and Epstein\u2013\nBarr viral infection\n\n\n\n\u2022 Absence of malignant diseases, especiallylymphomas\n\u2022 Absence of inflammatory disease, especially \n\n\n\npolyarteritis nodosa\n\n\n\nNone\n\n\n\nRequirement At least five criteria, including two major criteria and no \nexclusion criteria\n\n\n\nFour major criteria or three major criteria and two minor \ncriteria\n\n\n\nthe extremities and trunk.11-14 Histological findings \nof these lesions usually show a normal epidermis \nwith mild perivascular lymphocytes and neutrophils \ninfiltration at superficial dermis.11-14\n\n\n\nOur patient also presented atypical eruption of \nAOSD which was the persistent mildly pruritic \nerythematous patch on her neck and anterior chest. \nThe presence of the unique histology of the skin \nlesion i.e. distinctive distribution of dyskeratotic \nkeratinocytes at the upper epidermis as well as \ncornified layers11-14 expedited the diagnosis of \nAOSD in our patient. Interestingly our patient \nhad presented with SJS-like eruption preceded by \npersistent periorbital swellings. SJS and/or toxic \nepidermal necrolysis-like eruption, apart from \ndrug induced, has been associated with infections \n(especially herpes simplex and mycoplasma \ninfection), systemic lupus erythematosus, graft-\nversus-host disease (GVHD) and pseudoporphyria \nin haemodialysis patients.15 Although antibiotics \ncould possibly be implicated in our patient, the \nlikelihood was perhaps low based on low ALDEN \nscores. Regrettably, a skin biopsy was not performed \nwhile she had the SJS-like eruption. The incidence \nof drug eruption has been reported is significant \namong AOSD patients ranging from 8-92% and \nmostly described as urticaria and maculopapular \neruptions.12 \n\n\n\nThe true incidence of cutaneous adverse drug \nreactions is probably questionable as they could be \nthe atypical eruption of AOSD. AOSD presenting \nas SJS-like eruption has not been described before. \nHowever GVHD-like skin reaction has been \ndescribed in a patient with AOSD presenting as \n\n\n\nimmune reconstitution inflammatory syndrome \n(IRIS) during steroid tapering.16 Our patient was \nonly given minimal immunosuppressants (low dose \nof oral prednisolone 15mg daily and anakinra was \nwithheld) for her AOSD while she developed SJS-\nlike eruption. Hence, the SJS-like eruption that she \nexperienced may not be drug related but could be \nthe presenting feature of GVHD like reaction as part \nof her AOSD. The skin lesions improved when her \ncorticosteroids increased to a higher dose.\n\n\n\nFurthermore, our patient also presented with \ndermatomyositis-like persistent eruptions together \nwith purpuric and brown macules over her \ntrunk, hands, palms and feet after resolution of \nthe SJS-like eruption. A repeated biopsy again \ndemonstrated the unique features of AOSD. The \nmanifestations of atypical or persistent AOSD-\nrelated cutaneous eruptions include persistent \nurticaria, persistent pruritic papules and plaques, \nerythematous to violaceous or pigmented lichenoid \npapules, dermatomyositis-like, cutaneous GVHD, \nlichen amyloidosis, prurigo pigmentosa like, \nmaculopapular or lichenoid eruptions, peau d\u2019orange \nlike, vesiculo-pustular eruptions of the limbs and \nlichen simplex chronicus.11-14 The presentation may \nappear as the earlier presentation of AOSD or as a \ncutaneous marker of disease activity. Hence a high \nindex of clinical suspicious is needed in order to \navoid delay in diagnosis or introducing aggressive \ntreatment.  \n\n\n\nOther clinical manifestations such as odynophagia \nand pharyngitis, generalized lymphadenopathy, \npericarditis (pericardial effusion), hepatomegaly, \ninterstitial nephritis (diabetes insipidus), pleuritis \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n47\n\n\n\n(pleural effusion) were all present in our patients. \nOther clinical involvement such as subacute \nglomerulitis, collapsing gloerulopathy, pancreatitis, \nmeningitis, cranial nerves paralysis and seizures \nwhich have been reported in AOSD,5-7 were, \nfortunately not present in our patient.\n\n\n\nA significant leucocytosis (>10x109/L) with \nneurophilia (>80%) is another hallmark of AOSD. \nThe highest documented leucocyte count in our \npatient was 44.4x109/L with 88-93% neutrophils.5-7 \nNeutropenia, in the presence of anemia and/\nor thrombocytopenia may indicate reactive \nhemophagocytic syndrome.5-7 Raised liver enzymes \nare very common and it was observed in our \npatient.5-7 Being an autoinflammatory disease, all \nthe auto-antibodies especially rheumatic factor and \nantinuclear antibodies are typically non-reactive.5-7 \nNot surprisingly, acute phase reactants such as ESR \nand CRP are substantially increase in AOSD.5-7\n\n\n\nSerum ferritin, an indicator of macrophage activation, \nis raised in many inflammatory conditions including \nAOSD.10 Several cytokines mentioned earlier such \nas IL-1\u03b2, IL-6, IL-18 and TNF\u03b1 appeared to drive \nthe production of ferritin.10  It is observed that the \nserum ferritin levels in AOSD were much higher \nthan many other autoimmune, inflammatory, \ninfectious and neoplastic diseases, usually >1000ng/\nml (normal between 40-200).10,17,18 This was seen \nin our patient with the highest ferritin level above \n64,000). The specificity of serum ferritin level alone \nin the diagnosis of AOSD was however reported to \nbe low, between 41 and 46%.10,17,18 Glycosylated \nfraction of ferritin (GF) has been described as a \nmore specific diagnostic marker for AOSD, where \nthe GF is typically <20% (50-80% of ferritin in \nhealthy subjects is glycosylated).10,17,18 The AOSD \ndiagnostic sensitivity and specificity improved \nto 70.5% and 92.9% respectively when there is \nat-least five-fold rise in serum ferritin combined \nwith GF\u226420%. Nevertheless, total serum ferritin \nappears to be a more useful marker in terms of \ndisease activity monitoring.10,17,18 It often normalises \nwhen the disease goes into remission. GF however \nremained low despite disease remission, and hence \ncannot be used to monitor disease activity of \nresponse to treatment.19 Other potential markers \nsuch as procalcitonin, calpotectin, serum IL-1, \nIL-6, IL-18, CD163, CXCL 10, CXCL13, MIF \nare again not specific to AOSD and have not been \nrecommended for routine investigation for AOSD.10\n\n\n\nDiagnosing AOSD is extremely challenging as \n\n\n\nillustrated in our patient. The lack of diagnostic \nbiomarkers and non-specific clinical presentations \noften result in a significant delay in the diagnosis and \ntreatment in this rare condition. A few classification \ncriteria have been developed but the Yamaguchi \ndiagnostic criteria20 (1992, Table 1) for AOSD is \nthe most widely used. It however requires exclusion \nof infections, malignancies and other autoimmune \ndiseases. The Fautrel criteria21 (2002, Table 1) on \nthe other hand, included ferritin and GF levels \nas diagnostic biomarkers. The latest validation \nstudy showed that both sets of criteria yield high \nsensitivity and specificity.22 Although we could not \ndetermine the GF in our patient, she fulfilled both \ndiagnostic criteria for AOSD.\n\n\n\nThe course of AOSD is unpredictable. Our patient \nwas probably has a chronic and progressive course. \nSince the onset of symptoms, she appeared to \nhave regular systemic flares of AOSD for at least \n18 months despite on various immune-modulatory \nagents. A monocyclic course is described to be \nself-limited disease or being able to achieve drug-\nfree remission without relapses.5-7 A recurrent or \npolycyclic course is featured by AOSD relapses \nafter a period (months or years) of disease control \nwith or without immune-modulatory agents.5-7\n\n\n\nManagement of AOSD is extremely challenging too. \nNon-steroidal anti-inflammatory drugs (NSAIDs), \nsystemic corticosteroids, immunosuppressive \nagents such as methotrexate, leflunomide, gold, \nazathioprine, ciclosporin A, hydroxychloroquin \nand cyclophosphamide as well as intravenous \nimmunoglobulin have been described as helpful.5-7,23 \nThe use of NSAIDs and sulfasalazine have been \nassociated with macrophage activation syndrome \n(MAS).24 Biologic agents such as IL-1 inhibitors \n(anakinra and canakinumab),  IL-6 inhibitors \n(tocilizumab), TNF-inhibitors (infliximab, \netanercept and adalimumab) are indicated for \nsevere form of AOSD.5-7 Anti-TNF-\u03b1 appeared to be \nuseful in controlling the joint symptoms of AOSD, \nbut less effective on other systemic symptoms.5-7 An \nagent under development includes IL-18 inhibitor \n(Tadekinig alpha).5-7 \n\n\n\nThe objective of aggressive treatment of AOSD \naims to induce remission of disease and also prevent \ncomplications and end-organ damage. The well-\nknown serious complications of AOSD include \nreactive hemophagocytic lymphohistiocytosis \n(HLH), coagulation disorders (disseminated \nintravascular coagulation ad thrombotic \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48\n\n\n\nmicroangiopathy), fulminant hepatitis, pericarditis, \ncardiac tamponade, myocarditis, endocarditis, \npulmonary arterial hypertension, pleuritis, \ninterstitial lung disease, aseptic empyema, diffuse \nalveolar haemorrhage and amyloid A amyloidosis.24 \nHLH, also known as macrophage activation \nsyndrome is the most feared deadly complications \nof AOSD with a reported mortality rate of \nbetween 10-20%.24 It is characterized by persistent \nhigh fever, hepatosplenomegaly and cytopenia \nwith the presence of activated macrophages in \nhematopoeietic organs.24 It has been considered in \nour patient and repeated bone marrow aspiration \nhad excluded HLH. In addition, patients may suffer \nfrom complications from the treatment of AOSD \nsuch as bacterial and viral infections. This happened \nin our patient. She developed herpes simplex \nviral infection and pneumonia while receiving \nsystemic corticosteroids. Furthermore, delayed \nassociation with malignancy has been described \nin AOSD including lymphoma, myelodysplastic \nsyndrome, leukemia, breast cancer, thyroid cancer, \nlung cancer, esophageal cancer, rectal cancer, \ncholangiocarcinoma and etc.25 Hence, long term \nfollow up of patients with AOSD is mandatory.\n\n\n\nConclusion\nWe described a young female with AOSD with \nseveral severe complications. She presented \nwith both classical and non-classical cutaneous \nmanifestations.  Her skin biopsy on the persistent \nerythematous patch demonstrated distinctive \nfeatures of AOSD which had enabled the clinician \nto achieve the diagnosis. Unfortunately, she had a \nchronic and progressive disease and more aggressive \ntreatment options may need to be considered for her.\n\n\n\nConflict\tof\tInterest\tDeclaration\nAll authors have no financial/conflict of interest to \ndisclose. \n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. Bywaters EG. Still\u2019s disease in the adult. Ann Rheum Dis \n1971;302:121-33.\n\n\n\n2. Pouchot J, Sampalis JS, Beaudet F, Carette S, D\u00e9cary \nF, Salusinsky-Sternbach M et al. Adult Still\u2019s disease: \nmanifestations, disease course, and outcome in 62 patients. \n\n\n\nMedicine (Baltimore). 1991;70:118-36.\n3. Sassolas B, Haddad C, Mockenhaupt M, Dunant A, Liss \n\n\n\nY, Bork K et al. ALDEN, an algorithm for assessment of \ndrug causality in Stevens-Johnson Syndrome and toxic \nepidermal necrolysis: comparison with case-control \nanalysis. Clin Pharmacol Ther 2010;88:60-8.\n\n\n\n4. Lee JJY, Schneider R. Systemic Juvenile Idiopathic \nArthritis. Pediatr Clin North Am 2018;65:691-709.\n\n\n\n5. Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive \nreview on adult-onset Still\u2019s disease. J Autoimmun \n2018;93:24-36. \n\n\n\n6. Gerfaud-Valentin M, Jamilloux Y, Iwaz J, S\u00e8ve P. Adult-\nonset Still\u2019s disease. Autoimmun Rev 2014;13:708-22.\n\n\n\n7. Kadavath S, Efthimiou P. Adult-onset Still\u2019s disease-\npathogenesis, clinical manifestations, and new treatment \noptions. Ann Med. 2015;47:6-14.\n\n\n\n8. Sakata N, Shimizu S, Hirano F, Fushimi K. Epidemiological \nstudy of adult-onset Still\u2019s disease using a Japanese \nadministrative database. Rheumatol Int 2016;36:1399-\n405.\n\n\n\n9. Wouters JM, van Rijswijk MH, van de Putte LB. Adult \nonset Still\u2019s disease the elderly: a report of two cases, J. \nRheumatol. 1985;12:791-3\n\n\n\n10. Feist E, Mitrovic S, Fautrel B. Mechanisms, biomarkers \nand targets for adult-onset Still\u2019s disease. Nat Rev \nRheumatol 2018;14:603-18.\n\n\n\n11. Yamamoto T. Cutaneous manifestations associated with \nadult-onset Still\u2019s disease: important diagnostic values. \nRheumatol Int 2012;32:2233\u20137.\n\n\n\n12. Lee JY, Hsu CK, Liu MF, Chao CS. Evanescent and \npersistent pruritic eruptions of adult-onset Still disease: \na clinical and pathologic study of 36 patients. Semin \nArthritis Rheum 2012;42:317\u201326.\n\n\n\n13. Narv\u00e1ez Garcia FJ, Pascual M, L\u00f3pez de Recalde M, \nJuarez P, Morales-Ivorra I, Notario J et al. Adult-onset \nStill\u2019s disease with atypical cutaneous manifestations. \nMedicine (Baltimore). 2017;96:e6318.\n\n\n\n14. Damevska K, Fran\u00e7a K, Nikolovska S, Gucev F. Adult-\nonset Still\u2019s disease as a cutaneous marker of systemic \ndisease. Clin Dermatol 2019;37:668-74.\n\n\n\n15. Yildirim Cetin G, Sayar H, Ozkan F, Kurtulus S, Kesici F, \nSayarlioglu M. A case of toxic epidermal necrolysis-like \nskin lesions with systemic lupus erythematosus and review \nof the literature. Lupus 2013;22:839-46.\n\n\n\n16. Yamaga K, Hanafusa T, Azukizawa H, Tanemura A, Nii \nT, Nishide M et al. Immune reconstitution inflammatory \nsyndrome in a patient with adult-onset Still\u2019s disease: graft-\nversus-host-like skin reaction with possible asymptomatic \nhuman herpes virus reactivation during steroid tapering. \nEur J Dermatol. 2014;24:101-3.\n\n\n\n17. Fautrel B, Le Mo\u00ebl G, Saint-Marcoux B, Taupin P, \nVignes S, Rozenberg S et al. Diagnostic value of ferritin \nand glycosylated ferritin in adult onset Still\u2019s disease. J \nRheumatol. 2001;28:322-9.\n\n\n\n18. Van Reeth C, Le Mo\u00ebl G, Lasne Y, Revenant MC, Agneray \nJ, Kahn MF et al. Serum ferritin and isoferritins are tools \nfor diagnosis of active adult Still\u2019s disease. J Rheumatol. \n1994;21:890-5.\n\n\n\n19. Vignes S, Le Mo\u00ebl G, Fautrel B, Wechsler B, Godeau \nP, Piette JC. Percentage of glycosylated serum ferritin \nremains low throughout the course of adult onset Still\u2019s \ndisease. Ann Rheum Dis 2000;59:347-50.\n\n\n\n20. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, \nMizushima Y, Kashiwagi H et al. Preliminary criteria \nfor classification of adult Still\u2019s disease. J Rheumatol \n1992;19:424-30.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n49\n\n\n\n21. Fautrel B, Zing E, Golmard JL, Le Moel G, Bissery A, \nRioux C et al. Proposal for a new set of classification \ncriteria for adult-onset Still disease. Medicine (Baltimore) \n2002;81:194-200.\n\n\n\n22. Lebrun D, Mestrallet S, Dehoux M Golmard JL, Granger \nB, Georgin-Lavialle S et al. Validation of the Fautrel \nclassification criteria for adult-onset Still\u2019s disease. Semin. \nArthritis Rheum. 2018;47:578-85.\n\n\n\n23. Kalyoncu U, Solmaz D, Emmungil H, Yazici A, Kasifoglu \nT, Kimyon G et al. Response rate of initial conventional \ntreatments, disease course, and related factors of patients \nwith adult-onset Still\u2019s disease: Data from a large \nmulticenter cohort. J Autoimmun 2016;69:59-63.\n\n\n\n24. Mitrovic S, Fautrel B. Complications of adult-onset Still\u2019s \ndisease and their management. Expert Rev Clin Immunol \n2018;14:351-65.\n\n\n\n25. Sun NZ, Brezinski EA, Berliner J, Haemel A, Connoly \nMK, Gensier L et al. Updates in adult-onset Still disease: \nAtypical cutaneous manifestations and associations with \ndelayed malignancy. J Am Acad Dermatol 2015;73:294-\n303.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50\n\n\n\nCASE REPORT\n\n\n\nA Curious Case of Diffuse Systemic Sclerosis with Discoid Lupus \nErythematosus-Like Lesions: Enigma of an Overlap          \nBelgaumkar Vasudha Abhijit, MD, Chavan Ravindranath Brahmadeo, MD, Deshmukh Nitika Sanjay, MD, Raut Vijay, \nMBBS, Agrawal Kopal, MBBS\n\n\n\nDepartment of Skin and Venereal Diseases, Byramjee Jeejeebhoy Government Medical College (BJGMC) and Sassoon \nGeneral Hospital, Pune, Maharashtra, India.\n\n\n\nSummary\nOverlap syndrome is a term used to describe a condition wherein a patient has features of more \nthan one classic inflammatory rheumatic disease like systemic lupus erythematosus, polymyositis, \nscleroderma and rheumatoid arthritis. Individuals with an overlap syndrome may, but need not meet, \ncomplete diagnostic criteria for one or more than one classic rheumatic disease. Mixed connective \ntissue disease is a specific subset of overlap syndrome wherein patients have antibodies to the U1 \nsmall nuclear ribonuclear protein (anti- U1RNP) and clinical features like hand edema, synovitis, \nRaynaud phenomenon, acrosclerosis and biologically or histologically proven myositis. We came \nacross an interesting case showing clinical features of both Systemic Sclerosis and Discoid Lupus \nerythematosus (DLE). On complete evaluation, a final diagnosis of Diffuse Systemic Sclerosis - DLE \noverlap was made on the basis of histopathopathological and serological findings. Patient was started \naccordingly on systemic and topical medications and responded well.\n\n\n\nKey words: Systemic sclerosis, discoid lupus rrythematosus, antinuclear antibodies\n\n\n\nCorresponding Author\nDr Chavan RB\nDepartment of Skin and Venereal Diseases, Sassoon \nGeneral Hospital and B.J.G.M.C, Pune 411001, India\nEmail: drravindranathchavan@gmail.com  \n\n\n\nIntroduction\nOverlap syndrome describes the clinical situation \nwherein symptoms of various connective tissue \ndiseases co-exist. It is more common in females \n(female to male ratio of 3.3:1). Systemic sclerosis \noverlaps with other autoimmune disorders in about \n10-20% cases. Here we highlight a patient with \nclinical, serological and histopathologic findings \nconsistent with diffuse systemic sclerosis (dSSc) \nand discoid lupus erythematosus overlap.\n\n\n\nCase Report\nA 36-year-old married multipara Hindu female \nfarmer presented with itchy lesions over back, \nhands and legs since 2 months, with intermittent \nfever, breathlessness, brownish skin discoloration, \npatchy hair loss, skin tightness and photosensitivity. \nPatient denied history of difficulty in swallowing, \nsquatting or combing hair, bowel disturbances, \njoint pain, oral lesions, Raynaud\u2019s phenomenon, \ndyspnea, abdominal pain or burning micturition. \nShe was not on any treatment. Dermatological \nexamination showed taut shiny skin on face \nand scarring alopecia over scalp. Face showed \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n51\n\n\n\nerythematous - hyperpigmented non-confluent \nmalar rash. Erythematous scaly plaques with \ncentral depigmentation and atrophy [DLE- like] \nwere present on scalp, upper and lower back and \nupper arms (photo-exposed areas). Salt and pepper \npigmentation were seen over neck, trunk, upper and \nlower limbs. Tightness of skin was noted on digits \nof hands and feet extending beyond metacarpo and \nmetatarso-phalyngeal joints upto mid-forearm and \nmid-shin respectively and over face, neck, chest and \nupper back. Oral, genital and ocular mucosae were \nnormal. Clinical differential diagnosis considered \nwas dSSc-DLE overlap syndrome and mixed \nconnective tissue disease (MCTD). \n\n\n\nHemogram and renal function tests were \nnormal. Aspartate aminotransferase, Alanine \naminotransferase levels and Erythrocyte \nsedimentation rate were raised. C-reactive Protein, \nRheumatoid factor, HIV- Elisa and HBsAg were \nnegative. Creatinine Kinase (MB), 24-hour urine \nprotein were normal. Serum ANA was positive \n(2.92). ANA blot indicated high levels of anti \nRo/ SSA (17AU) and anti Scl-70 (60KD) with \nnormal anti ds DNA and anti-Smith antibodies. \n\n\n\nUltrasonography (Abdomen and pelvis) showed \nno abnormality except right ectopic kidney. Chest \nX-ray (PA view) showed few homogenous opacities \nin bilateral middle lobes. HRCT chest confirmed \ninterstitial lung disease (ILD).  Pulmonary function \ntests showed restrictive pattern. Barium swallow \nand nail fold capillaroscopy were unremarkable.   \nHistopathology of DLE-like lesion (over neck) \nshowed focal basal vacuolar degeneration and \nincreased dermal collagen with periadnexal \nmononuclear infiltrate. \n\n\n\nBiopsy from hidebound skin over left thumb \ndemonstrated increased dermal fibrocollagenous \ntissue. Direct Immunofluorescence could not be \ndone due to non-availability. Final diagnosis of \ndiffuse Systemic sclerosis-DLE overlap was made. \n\n\n\nPatient was started Tab Methotrexate 7.5mg \nweekly, Tab Hydroxychloroquine 200 mg bd and \nTab Prednisolone (1mg/kg/day) in slow tapering \ndoses along with topical corticosteroids and \nsunscreen. Currently, patient is under follow up \nwith improvement in skin lesions and respiratory \ncomplaints.\n\n\n\nFigure 1. (a) Hyperpigmented malar rash, (b) scarring alopecia, (c) DLE-like lesions over photo exposed parts. (d) Histopathology (DLE- \nlike lesion) showing combination of DLE (hyperkeratosis with atrophy and flattening of rete ridges, focal basal vacuolar degeneration, \nperi-adnexal chronic mononuclear inflammatory infiltrate) and scleroderma (increased collagen in papillary and reticular dermis)\n\n\n\na\n\n\n\nc d\n\n\n\nb\n\n\n\nH&E\nstain, 10x\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52\n\n\n\nFigure 2. (a & b) Poikiloderma over extremities. (c) Biopsy (from hide-bound skin over left thumb) consistent with scleroderma \n{hyperkeratosis and acanthosis with focal elongation of rete ridges, increased fibro- collagenous tissue in dermis}\n\n\n\na b cH&E\nstain, 40x\n\n\n\nDiscussion\nPatients with one classic autoimmune connective \ntissue disease (CTD) are likely to possess multiple \nautoantibodies with a small proportion developing \nsymptoms and/or signs of another CTD (overlap \nsyndrome).1 The commonest systemic sclerosis \noverlap is seen with Myositis (34.2%) and \ninfrequently, Systemic lupus erythematosus (SLE) \n(8.4%).2 Scleroderma- Lupus Erythematosus \noverlap can occur either in a setting of systemic \ndisease or with isolated cutaneous involvement. \nMost previous cases have been examples of Type \n1 (Table 1)1 though few have been Type 2, with \nlocalized scleroderma coexisting with SLE or vice \nversa (like ours).1,3  In our case, histopathology from \nDLE-like lesions showed a combination of interface \nchanges with peri-adnexal inflammation (typical \n\n\n\nConclusion\nOverlap syndromes pose diagnostic difficulty \nand impact management strategies. Meticulous \ninterpretation of clinical, histopathological and \nserological clues is warranted in such scenarios. \n\n\n\nConflict\tof\tInterest\nThe authors have no conflict of interest to declare.\n\n\n\nTable 1. Dermatologic classification of overlap syndromes in connective tissue diseases\n\n\n\nof DLE) and dermal sclerosis (characteristic of \nscleroderma) which supported the diagnosis of \nOverlap syndrome. Anti-Ro antibodies can be \ndetected in SS (70-100%), SLE (40-90%), SS/SLE \noverlap, subacute cutaneous lupus erythematosus \nand neonatal lupus erythematosus.4 They are also \nstrongly associated with photosensitivity (present \nin our patient). Although anti-Scl 70 antibodies are \nconsidered to be more prevalent in SSc with ILD (as \nin our case) indicating poorer prognosis, they may \noccur in up to 25% of SLE5 carrying higher risk of \npulmonary hypertension and renal involvement.6 \nInterestingly, Raynaud\u2019s phenomenon was absent \nin our patient. MCTD was ruled out due to lack \nof sufficient criteria.7 In view of photosensitivity \nand Anti-Ro antibodies, she will require stringent \nmonitoring for early detection of SLE.  \n\n\n\nAcknowledgement\nDr Vasudha Belgaumkar is supported by the Fogarty \nInternational Centre of the US National Institutes \nof Health (grant # D43TW00957). The content is \nsolely the responsibility of the authors and does not \nrepresent the official views of the National Institutes \nof Health. Authors would like to thank Department \nof Pathology, B. J. Govt. Medical College, Pune for \ntheir valuable support.\n\n\n\nDermatologic\tclassification\tof\toverlap\tsyndromes\tin\tconnective\ttissue\tdiseases\n\n\n\nType 1 Systemic disease overlapping with systemic disease\n\n\n\nType 2 Cutaneous disease (e.g. localized scleroderma, cutaneous LE) overlapping with systemic disease (e.g. systemic LE)\n\n\n\nType 3 Cutaneous disease (e.g. localized scleroderma) overlapping with cutaneous disease (e.g. cutaneous LE); overlap may occur \nwith distinctive lesions developing at separate sites or clinical and/or histological features of both diseases within the same site \n(coincident overlap)\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n53\n\n\n\nReferences\n\n\n\n1. Iaccarino L, Gatto M, Bettio S, Caso F, Rampudda M, \nZen M et al. Overlap connective tissue disease syndromes. \nAutoimmun Rev 2013;12:363-73.\n\n\n\n2. Cooper GS, Stroehla BC. The Epidemiology of \nautoimmune diseases. Autoimmune Rev 2003:2;119-25.\n\n\n\n3. Balbir-Gurman A, Braun-Moscovici Y. Scleroderma \noverlap syndrome. Isr Med Assoc J 2011;13:14-20.\n\n\n\n4. Yoshimi R, Ueda A, Ozato K, Ishigatsubo Y. Clinical and \npathological roles of Ro/SSA autoantibody system. Clin \nDev Immunol. 2012;2012:606195.\n\n\n\n5. Mahler M, Silverman ED, Schulte-Pelkum J, Fritzler MJ. \nAnti-Scl-70 (topo-I) antibodies in SLE: myth or reality? \nAutoimmun Rev 2010;9:756-60.\n\n\n\n6. Gussin HA, Ignat GP, Varga J, Teodorescu M. Anti-\ntopoisomerase I (anti-Scl-70) antibodies in patients \nwith systemic lupus erythematosus. Arthritis Rheum \n2001;44:376-83.\n\n\n\n7. Alarcon-Segovia D, Villareal M. Classification and \ndiagnostic criteria for mixed connective tissue disease. \nKasukawa R, Sharp GC, eds. Mixed Connective Tissue \nDisease and Anti-Nuclear Antibodies. Amsterdam: \nExcerpta Medica;1987. pg33-40.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54\n\n\n\nCASE REPORT\n\n\n\nBenign Cephalic Histiocytosis: A Rare Dermatological Entity in the \nPaediatric Population          \nSiti Atiqah Ab Halim,1,2MBChB, Oh Hoey Hoey,3 MRCPCh, Faridah Mohamad Taib,4  MPath, Wan Syahira Ellani Wan \nAhmad Kammal,2 MPath.\n\n\n\n1Department of Pathology, Hospital Pulau Pinang, Pulau Pinang, Malaysia\n2Department of Pathology, The National University of Malaysia, Kuala Lumpur, Malaysia, 3Department of Paediatric, \nHospital Pulau Pinang, Pulau Pinang, Malaysia, \n4Department of Pathology, Hospital Seberang Jaya, Pulau Pinang, Malaysia.\n\n\n\nSummary\nHistiocytic proliferation of the skin can be categorised into Langerhan and non-Langerhan types. \nBenign cephalic histiocytosis (BCH) is a rare cutaneous non-Langerhan histiocytosis typically \naffecting infants and young children. We report a case of benign cephalic histiocytosis in a boy who, at \nseven months of age, presented with multiple yellowish papular eruptions on his face. Over the course \nof 18 months, the lesion spread to his trunk and upper extremities, sparing the mucous membranes, \npalms and soles. There was no systemic involvement identified. A histopathologic examination of \nthe skin lesion showed diffuse infiltration of histiocytes within the superficial dermis intermingled \nwith scattered eosinophils and small lymphocytes. Immunohistochemical studies showed that the \nhistiocytes were diffusely positive for CD68. Langerhan markers CD1a and S100 were negative. The \ncorrect distinction between BCH and other histiocytic proliferations of the skin is important because \nBCH has a self-limiting clinical course with a tendency of spontaneous remission.\n\n\n\nKey words: Benign cephalic histiocytosis (BCH), histiocytic proliferation, cutaneous histiocytosis\n\n\n\nCorresponding Author\nDr Siti Atiqah binti Ab Halim\nJabatan Patologi, Hospital Pulau Pinang, Jalan Residensi \n10990 Georgetown, Pulau Pinang\nEmail: sitiatiqahabhalim@gmail.com\n\n\n\nIntroduction\nCutaneous histiocytic proliferation is typically \ncategorised into Langerhan and non-Langerhan \ntypes. Benign cephalic histiocytosis (BCH) are rare, \nnon-Langerhan, self-limiting cutaneous lesions in \nchildren. Sixty cases of BCH have been reported in \nEnglish literatures. 1 To the best of our knowledge, \nthis study is the first published occurrence of BCH \nin Malaysia.\n \nCase Report\nA two-year-old boy exhibited multiple skin \nrashes, appearing on his face at seven months \nold.  Gradually, over 18 months, the rash spread \nto his trunk and bilateral upper limbs.  There was \nno history of bone pain, increased urination or \nconstitutional symptoms. \n \nA clinical examination showed multiple papular \nlesions of varying sizes, measuring up to 5 mm in \ndiameter (Figure 1). These papules ranged from \nyellow-orange to brown, predominantly on the \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n55\n\n\n\nhead, neck, trunk and proximal upper extremities \n(Figure 1). There was an absence of organomegaly \nand lymphadenopathy, and the serum lipid profile \nand full blood count were normal. Previous clinical \n\n\n\nHistopathological examination of the skin biopsy \n(Figure 2: a & b) revealed diffuse infiltrate of \nhistiocytes within the superficial epidermis, with \nscattered, small lymphocytes and rare eosinophils. \nNuclear atypia was minimal, with no mitotic \nactivity. There were no cytoplasmic lipids or Touton \ncells, which supported the diagnosis of BCH instead \n\n\n\nFigure 1. (a) \u2013 (b) Multiple yellow-orange to brownish papules predominantly over the face, extending to trunks\n\n\n\nFigure 2. (a) Diffuse histiocytic infiltrate at the upper dermis. (b) The histiocytes displayed oval kidney-shaped nuclei and ill-defined \npale cytoplasm. (c) The histiocytes strongly expressed CD68 and (d & e) were negative for Langerhan markers CD1a and S100 protein.\n\n\n\ndifferential diagnoses included benign cephalic \nhistiocytosis (BCH), juvenile xanthogranuloma \n(JXG), and generalized eruptive histiocytosis \n(GEH).\n\n\n\nof JXG. The histiocytic expression of CD68 and \nthe absence of Langerhan marker CD1a and S100 \nprotein were also in keeping with BCH (Figure 2: \nc-e).\n\n\n\nA diagnosis of BCH was made based on clinical \nhistory, morphology and immunohistochemistry. \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56\n\n\n\nThe parents were informed of the benign condition, \nrequiring no active treatment. At a six-month follow \nup, signs of spontaneous regression were noted over \nthe face and trunk.\n\n\n\nDiscussion\nBCH is characterised by eruptions of asymptomatic, \nred-brown, maculopapular lesions measuring from \n2 mm to 8 mm in diameter2. In more than 90% of \ncases, the initial eruption appears on the face and \nspreads to other body parts with predilection to the \nhead, neck and upper extremities.2,3 BCH is strictly \nlimited to the skin3, with no effect on mucocutaneous \nsites or deep organs.2\n\n\n\nThe age of onset ranges from two to 66 months \n(average 15 months).3 With a natural self-healing \ncourse, spontaneous regression begins as early as \neight months from the onset but may take up to \n48 months to disappear3. Complete regression has \nbeen noted at an average of 50 months.3 Signs of \nspontaneous regression observed in our patient \nfurther confirmed the diagnosis of BCH.\n\n\n\nTwo important differential diagnoses of dermal \nnon-Langerhan histiocytosis are juvenile \nxanthogranuloma (JXG) and generalized eruptive \nhistiocytosis (GEH).1,2 JXG typically affects \nyoung children and exhibits similar papular \nlesions affecting the head and neck region, but it \nmay occur on extremities and trunk.4 JXG is also \nassociated with rare extracutaneous involvement, \nparticularly in the eye, which may lead to secondary \nglaucoma and blindness.4 Internal organs may also \nbe affected.4 GEH is more common among adults \nand has a more widespread and symmetrical skin \ndistribution with occasional mucosal involvement.5 \nThere were overlapping clinical features of JXG and \nBCH observed in our patient, but extracutaneous \ninvolvement was absent. Lesions were not only \nconfined to the head and neck but also spread to \nthe trunk and upper extremities. Histopathological \nexamination confirmed the diagnosis of BCH. \n\n\n\nBCH, JXG and GEH at early nonxanthomatous \nstages cannot be differentiated based on histology or \nimmunohistochemistry alone.2 All three conditions \nshow dense dermal infiltrations of histiocytes, \nwhich are negative for Langerhan cell markers.2,3 \nMorphological features favouring JXG are the \npresence of foamy macrophages and Touton giant \ncells.2 The absence of Touton giant cells and foamy \nhistiocytes are essential in excluding JXG in this \ncase, as the other morphological features can be \n\n\n\nsimilar to BCH.\n\n\n\nA diagnosis of BCH implicates a benign, self-\nlimiting condition, requiring no treatment2. \nHowever, an association with diabetes insipidus has \nbeen reported in one child,6 and there have also been \nreports of possible progression to JXG.7,8\n\n\n\nConclusion\nThis case illustrates classic clinical and \nhistopathological presentations of BCH. Proper \nattention to history, examination of findings, \nhistological examination, immunohistochemistry \nand follow up are important for a correct diagnosis.\n\n\n\nDeclaration\tof\tConflict\tof\tInterest\t\nNone declared\n\n\n\nAcknowledgement\nWe would like to thank the Director-General of \nHealth Malaysia for his permission to publish this \nstudy. This research was approved by the Medical \nResearch and Ethics Committee, Ministry of Health \nMalaysia (NMRR-19-7-45787).\n\n\n\nReferences\n\n\n\n1. Hattori-Murakami M, Tanaka R, Yamamoto T, Hayashi H, \nNishimura H, Fujimoto W. Benign cephalic histiocytosis: \nA case with infiltration of CD1a-positive langerin-negative \ncells. J Dermatol 2018;45:e181\u20132.\n\n\n\n2. Polat Ekinci A, Buyukbabani N, Baykal C. Novel clinical \nobservations on benign cephalic histiocytosis in a large \nseries. Pediatr Dermatol 2017;34:392\u20137.\n\n\n\n3. Koca R, Bekta\u015f S, Altinyazar HC, Sezer T. Benign cephalic \nhistiocytosis: A case report. Ann Dermatol 2011;23:508\u2013\n11. \n\n\n\n4. Pajaziti L, Hap\u00e7iu SR, Pajaziti A. Juvenile \nxanthogranuloma: a case report and review of the literature. \nBMC Res Notes 2014;7:174. \n\n\n\n5. Jih DM, Salcedo SL, Jaworsky C. Benign cephalic \nhistiocytosis: A case report and review. J Am Acad \nDermatol 2002;47:908-13. \n\n\n\n6. Weston WL, Travers SH, Mierau GW, Heasley D, \nFitzpatrick J. Benign cephalic histiocytosis with diabetes \ninsipidus. Pediatr Dermatol 2000;17:296-8.  \n\n\n\n7. Rodriguez-Jurado R, Duran-McKinster C, Ruiz-\nMaldonado R. Benign cephalic histiocytosis progressing \ninto juvenile xanthogranuloma: a non-Langerhans cell \nhistiocytosis transforming under the influence of a virus? \nAm J Dermatopathol 2000;22:70\u20134. \n\n\n\n8. Zelger BG, Zelger B, Steiner H, Mikuz G. Solitary giant \nxanthogranuloma and benign cephalic histiocytosis--\nvariants of juvenile xanthogranuloma. Br J Dermatol \n1995;133:598-604. \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n57\n\n\n\nCASE REPORT\n\n\n\nPost Surgical Cutaneous Nocardiosis Mimicking Hypertrophic Scar: \nA Case Report          \nShashikumar Basavapura Madegowda1, MD, Savitha AS2, MD, Kirti Katwe3, MD\n\n\n\n1Sparsha Skin Care Clinic, Mandya, India\n2Sapthagiri Medical College and Research Centre, Bangalore, India\n3Karnataka Institute of Medical Sciences (KIMS), Hubli, India\n\n\n\nSummary\nNocardia species are gram-positive, aerobic, acid-fast bacteria which exist as saprophytes in nature. \nInvasive disseminated infections are particularly common in immunocompromised or debilitated \nhosts. Superficial infections with Nocardia species occur as a result of local trauma and contamination \nof the wound. Clinically, it may manifest as an acute infection (abscesses or cellulitis), mycetoma, \nor sporotrichoid infection. Herein we report a rare case of cutaneous nocardiosis following surgery \nmimicking a hypertrophic scar.\n\n\n\nKey words: Nocardiosis, hypertrophic scar, post surgical\n\n\n\nCorresponding Author\nDr Shashikumar BM\nDepartment of Dermatology, Venereology and Leprosy, \nMandya Institute of medical Sciences, Mandya, 571401 \nKarnataka, India\nEmail: shashikumarbm@gmail.com  \n\n\n\nIntroduction\nThe genus Nocardia comprises gram-positive, \naerobic, acid-fast, filamentous bacteria with a \ntendency to fragment into bacillary and coccoid \nforms. Nocardia asteroides complex, N. brasiliensis, \nN. farcinica, and N. nova are commonly implicated \nfor infection in humans.1 Cutaneous disease \nmay manifest clinically as acute superficial skin \ninfection with abscesses or cellulitis, mycetoma, \nlymphocutaneous (sporotrichoid) infection, or \ndisseminated infection with skin involvement.1,2\n\n\n\nTraumatic inoculation into the skin is the typical mode \nfor acquisition of infection in immunocompetent \nhosts, resulting in an acute inflammatory response \nwith subsequent necrosis and abscess formation; \ngranuloma formation is uncommon. Here, we report \na rare accidental inoculation of nocardia following \nsurgery mimicking as hypertrophic scar.\n\n\n\nCase Report\nA 16-year-old Indian female patient presented \nwith an asymptomatic erythematous linear plaque \nover the right nasal bridge following a surgery \non the nose of 6 months duration for melanocytic \nnevi. No discharge or ulceration was reported. On \nexamination, a club shaped plaque was present over \na linear scar measuring 3\u00d71 cm, on the right lateral \naspect of nose (Figure 1). Differential diagnoses \nof hypertrophic scar, keloid, sarcoidosis were \nconsidered clinically.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58\n\n\n\nSkin biopsy showed dense and diffuse suppurative \ngranulomatous infiltrate on a background of \ngranulation tissue. Within the suppurative center \nnumerous dark blue stained grains in various shapes \nand size were seen, surrounded by scant Splendore \nHoeppli material, which is suggestive of nocardial \nmycetoma (Figure 2).  Aspirate from the lesion \nshowed Gram positive and acid fast, thin, beaded, \nbranching filaments. Fungal cluture from the tissue \ndid not demonstrate any growth.\n\n\n\nCotrimoxazole in double strength was (trimethoprim/\nsulfamethoxazole-160mg/800mg) was given for 4 \nweeks which cleared the lesions with residual scar \nwithout any recurrence (Figure 3). \n\n\n\nFigure 1. Linear erythematous swelling over the lateral side of \nnose\n\n\n\nFigure 2. (a) 10 X magnification; (b) on higher power dark blue \ngranules with Splendore Hoeppli phenomenon\n\n\n\nDiscussion\nThe genus Nocardia belongs to the order \nActinomycetales, a group of aerobic, Gram \npositive, filamentous bacteria. The organism is \n\n\n\nmainly geophilic, occurring in soil and decaying \nplant parts. This group of organisms can cause \nserious human and animal infections.3 The exact \nincidence of primary cutaneous nocardiosis is not \nclear. According to Palmar et al, the incidence of \nprimary cutaneous nocardiosis reported in the \nEnglish literature between 1961 and 1971 was 5%.4 \n\n\n\nSuperficial cutaneous nocardiosis is the least serious \nof the cutaneous infections. This form of nocardiosis \nusually occurs in an immunocompetent individual \n1 to 3 weeks following some type of local trauma \nwith subsequent environmental contamination of \nthe wound. Cellulitis is usually subacute with pain, \nswelling, erythema, and warmth at the affected site. \nIt is prevalent among the rural population where \nagriculture is the main way of livelihood.  \n\n\n\nA history of thorn prick or splinter injury is common \nin patients with superficial cutaneous infection. \nUnusual modes of inoculation like animal scratch, \nburn injury and insect bite have been described.3 \nPrimary cutaneous nocardiosis over a surgical scar \nhas not been reported before.\n\n\n\nMycetoma is the commonest clinical pattern of \nprimary cutaneous nocardiosis. Nocardia species \nare frequently isolated as the causative agents for \nmycetoma.5 The lymphocutaneous pattern of the \ndisease is the rarest type and commonly occurs \nin otherwise healthy individuals.6 Clinically, it \nsimulates sporotrichosis but differs from this fungal \ninfection by its acute onset, erythema of the overlying \n\n\n\na b\n\n\n\nFigure 3. Significant reduction in lesion after 4 weeks \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n59\n\n\n\nskin, tenderness and a highly inflammatory course. \nRarely, granules may be observed in the discharge \nfrom noduloulcerative lesions.7\n\n\n\nThe initial clinical diagnosis may be difficult due \nto the non-specific clinical picture. Demonstration \nof the organism from clinical specimens like \ngranules, pus or aspirated fluid from an unruptured \nnodule by Gram stain and modified Kinyoun stain \nis the mainstay of diagnosis. Gram positive and \nacid fast, thin, beaded, branching filaments are \nthe characteristic appearance of the organism. \nIdentification of the Nocardia species by culture is \na tedious process. 8\n\n\n\nCotrimoxazole (trimethoprim/sulfamethoxazole) \nis the therapy of choice for proven or presumed \nnocardiosis. Drug therapy should be continued \nfor 6 to 18 months, depending on the extent of the \ndisease, because of the high incidence of relapse \nand metastatic abscesses with shorter duration of \ntherapy. 9 \n\n\n\nThe present case presented as cutaneous nocardial \nmycetoma which mimicked a hypertrophic scar.  \nIn conclusion, primary cutaneous nocardiosis is \nchallenging to diagnose due to varied clinical \npresentations. A high degree of clinical suspicion \nis required along with stringent efforts of the \nmicrobiologist to isolate the organism.  \n\n\n\nConflict\tof\tInterest\tDeclaration\t\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\t\nNil\n\n\n\nReferences\n\n\n\n1. Maraki S, Chochlidakis S, Nioti E, Tselentis Y. Primary \nlymphocutaneous nocardiosis in an immunocompetent \npatient. Ann Clin Microbiol Antimicrobiol 2004;3:24.\n\n\n\n2. Saubolle MA, Sussland D. Nocardiosis: Review of clinical \nand laboratory experience. J Clin Microbiol 2003;41:4497-\n501.      \n\n\n\n3. McNeil MM, Brown JM. The medically important aerobic \nactinomycetes: Epidemiology and microbiology. Clin \nMicrobiol Rev 1994;7:357-417.\n\n\n\n4. Palmar DL, Harvey RL, Wheeler JK. Diagnosis and \ntherapeutic considerations in Nocardia asteroides infection. \nMedicine (Baltimore). 1974;53:391-401. \n\n\n\n5. Vyas MCR, Arora HL, Joshi KR. Histopathological \nidentification of various causal species of mycetoma \nprevalent in North-West Rajasthan (Bikaner region). \nIndian J Dermatol Venereol Leprol 1985;51:76-9.\n\n\n\n6. Tsuboi R, Takamori K, Ogawa H, Mikami Y, Arai T. \nLymphocutaneous nocardiosis caused by Nocardia \n\n\n\nasteroides. Arch Dermatol 1986;122:1183-5.\n7. Dufresne RG Jr, Latour DL, Fields JP. Sulfur granules \n\n\n\nin lymphocutaneous nocardiosis. J Am Acad Dermatol. \n1986;14:847. \n\n\n\n8. Garcia-Benitez V, Garcia-Hidalgo L, Archer-Dubon C, \nOrozco-Topete R. Acute primary superficial cutaneous \nnocardiosis due to Nocardia brasiliensis : A case report in \nan immunocompromized patient. Int J Dermatol 2002;41: \n713-4.\n\n\n\n9. Welsh O, Sauceda E, Gonzalez J, Ocampo J. Amikacin alone \nand in combination with trimethoprim-sulfamethoxazole \nin the treatment of actinomycotic mycetoma. J Am Acad \nDermatol 1987;17:443-8.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n60\n\n\n\nCASE REPORT\n\n\n\nAlleviating Diagnostic Dilemma of Maduramycosis: A Case Series          \nPriyanka Date1, MD, Sumit Kar1, MD, Nitin Gangane2, MD (Pathology), Abhay Deshmukh2, MD (Pathology), Pratiksha \nSonkusale1, MD, Safa Patrik1, MBBS, Ajinkya Sawant1, MBBS, Pooja Manwar1, MBBS\n\n\n\n1Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, \nWardha, Maharashtra, India.\n2Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra, India.\n\n\n\nSummary\nMaduramycosis1 is chronic infection of cutaneous and subcutaneous tissue caused by bacteria and \nfungi. It involves skin, subcutaneous tissue and bones.2 Here we report a case series of 14 patients of \nmycetoma describing their epidemio-clinical features and laboratory investigations. The most common \nclinical presentation in the patients were infiltrated subcutaneous swelling with multiple discharging \nsinus tracts (fistulas). Lesions were located on the foot in all the cases.\n\n\n\nKey words: Mycetoma, actinomycetoma, deep fungal infections,diagnosis, management\n\n\n\nCorresponding Author\nDr Sumit Kar\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences, \nSewagram, Maharashtra, 442102, India \nEmail: karmgims@gmail.com\n\n\n\nIntroduction\nMaduramycosis1 also called as mycetoma is chronic \ngranulomatous suppurative mycosis.2 It is caused \nby traumatic implantation of causative organism \non exposed area of the body most commonly lower \nextremity.3 Broadly, mycetoma is etiologically \nclassified as eumycetoma and actinomycetoma \nas caused by filamentous fungi or aerobic \nactinomycetes respectively.2,3,4\n\n\n\nCase Series\nWe present our experience of management of \nfourteen cases of leg mycetoma who presented to \nus in our OPD section in the preceding two years \n(Table 1). Presenting complaints of the patients \nwere swelling with or without erosions, discharge \nor ulcer for duration ranging from 3 months to 10 \nyears. All the cases gave prior history of trauma \nwith a wooden splinter while doing outdoor work. \nThe incubation period for developing clinical signs \nand symptoms ranged from three months to six \nyears. \n\n\n\nSamples from all the patients presenting with \nclinical features of mycetoma were sent for Fine \nNeedle Aspiration Cytology (FNAC), biopsy and \ntissue culture & sensitivity. FNAC samples were \nstained with Giemsa stain and for histopathological \nexamination H & E staining method is used. As we \nwere not having facility for PCR-RFLP analysis \nwas not done.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n61\n\n\n\nOut of the fourteen cases, 8 cases were of \nactinomycotic mycetoma and 6 were eumycotic \nmycetoma (Figure 1). Histology of biopsied tissue \n(Figure 2) and FNAC from discharging sinuses were \nperformed and was confirmatory in them. However; \nthe culture studies did not yield growth of causative \norganisms in all the cases as were cultured for 7 \ndays only.\n\n\n\nOne of our patients required debulking of the \ngrowth along with concomitant antimycotic therapy \nand all of them responded well to treatment. Simple \ntreatment by 160 mg trimethoprim and 800 mg \nsulfamethoxazole till lesions heal and minor surgical \ninterventions were sufficient on treatment part.\nAfter relief from the symptom, patients were lost to \nfollow up.\n\n\n\nFigure 1. Swelling with multiple discharging sinuses. Grains \nare seen on the surface of the discharging sinuses.\n\n\n\nFigure 2. H&E stained histopathology slide of Eumycetoma \nshowing thin layer of neutrophils adherent to outer surface of \ngrain.\n\n\n\nFigure 3. Giemsa stained FNAC slide of Actinomycetoma \nshowing Grains with homogenously blue centre and radiating \nfilaments at the periphery. Grains are surrounded by neutrophils, \nmacrophages, and lymphocytes.\n\n\n\nDiscussion \nMaduramycosis or mycetoma is chronic \ngranulomatous suppurative1,2 mycosis caused \nby traumatic implantation of soil organisms on \nsubcutaneous tissue.3 It characteristically presents \nwith triad of painless8 localized tumor-like swelling, \nunderlying sinus tract and presence of grains.2,3 \nMainly located over extremities.5 More than 75% \ncases involve leg and lower extremity.3\n\n\n\nThe oldest description about mycetoma is found \nin Atharva Veda as \u201cpadavalmikam\u201d, meaning \n\u201cAnthill Foot\u201d. In 1842, Gill recognized a disease \nentity prevalent in Madura from where name \n\u201cMadura Foot\u201d came. Later, Carter proposed a term \nMycetoma meaning \u201cFungal tumor\u201d1,2\n\n\n\nCarter also classified Mycetoma on the basis of \ncolour of grains. Later a formal classification \nbased on causative organism was put forward by \nChalmers and Archibald, they grouped mycetoma \nas Group 1-maduramycosis caused by fungi, Group \n2- actinomycosis caused by actinomycetes (Higher \nbacteria).2\n\n\n\nMadura foot is classical example of neglected \ndisease which primarily affects the poor and rural \npopulation of Tropic and Sub-tropic climate. These \nregions are located between latitudes 15 degrees \nto 30 degrees and defined as \u201cMycetoma belt\u201d. \nIt includes countries with highest occurrence of \nmycetoma, India is one of those. Mycetoma belt is \ncharacterized by low humidity and low rainfall with \nwell-defined alternating rainy and dry seasons3,but \ndisease can occur sporadically in any part of the \nworld.6\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n62\n\n\n\nSN\nA\n\n\n\nge\n \n\n\n\n(y\nea\n\n\n\nrs\n) /\n\n\n\nSe\nx\n\n\n\nM\nor\n\n\n\nph\nol\n\n\n\nog\ny\n\n\n\nAv\ner\n\n\n\nag\ne\n\n\n\ndu\nra\n\n\n\ntio\nn \n\n\n\nH\nis\n\n\n\nto\npa\n\n\n\nth\nol\n\n\n\nog\ny \n\n\n\nE\nxa\n\n\n\nm\nin\n\n\n\nat\nio\n\n\n\nn\nFN\n\n\n\nA\nC\n\n\n\nC\nU\n\n\n\nLT\nU\n\n\n\nR\nE\n\n\n\n\n\n\n\n1.\n78\n\n\n\n/M\nal\n\n\n\ne\nM\n\n\n\nul\ntip\n\n\n\nle\n sw\n\n\n\nel\nlin\n\n\n\ngs\n w\n\n\n\nith\n d\n\n\n\nis\nch\n\n\n\nar\ngi\n\n\n\nng\n \n\n\n\nsi\nnu\n\n\n\nse\ns o\n\n\n\nve\nr l\n\n\n\nef\nt f\n\n\n\noo\nt. \n\n\n\n6 \nm\n\n\n\non\nth\n\n\n\ns\nFr\n\n\n\nag\nm\n\n\n\nen\nts\n\n\n\n o\nf t\n\n\n\nhe\n d\n\n\n\nes\ntro\n\n\n\nye\nd \n\n\n\ngr\nai\n\n\n\nns\n a\n\n\n\nre\n \n\n\n\nw\nith\n\n\n\nin\n m\n\n\n\nul\ntin\n\n\n\nuc\nle\n\n\n\nat\ned\n\n\n\n g\nia\n\n\n\nnt\n c\n\n\n\nel\nls\n\n\n\n. F\new\n\n\n\n \nne\n\n\n\nut\nro\n\n\n\nph\nils\n\n\n\n p\nre\n\n\n\nse\nnt\n\n\n\n\n\n\n\nO\nn \n\n\n\nG\nie\n\n\n\nm\nsa\n\n\n\n st\nai\n\n\n\nni\nng\n\n\n\n g\nra\n\n\n\nin\ns a\n\n\n\npp\nea\n\n\n\nr h\nom\n\n\n\nog\nen\n\n\n\neo\nus\n\n\n\n b\nlu\n\n\n\ne \nin\n\n\n\n c\nen\n\n\n\ntre\n, a\n\n\n\nt \npe\n\n\n\nrip\nhe\n\n\n\nry\n fi\n\n\n\nne\n g\n\n\n\nra\nnu\n\n\n\nle\ns w\n\n\n\nith\n p\n\n\n\nin\nk \n\n\n\nra\ndi\n\n\n\nat\nin\n\n\n\ng \nfil\n\n\n\nam\nen\n\n\n\nts\n se\n\n\n\nen\n \n\n\n\nN\no \n\n\n\ngr\now\n\n\n\nth\n se\n\n\n\nen\n \n\n\n\n2.\n56\n\n\n\n/M\nal\n\n\n\ne\nM\n\n\n\nul\ntip\n\n\n\nle\n d\n\n\n\nis\nch\n\n\n\nar\ngi\n\n\n\nng\n si\n\n\n\nnu\nse\n\n\n\ns o\nve\n\n\n\nr \nle\n\n\n\nft \nso\n\n\n\nle\n. \n\n\n\n2 \nye\n\n\n\nar\ns\n\n\n\nFr\nag\n\n\n\nm\nen\n\n\n\nts\n o\n\n\n\nf t\nhe\n\n\n\n d\nes\n\n\n\ntro\nye\n\n\n\nd \ngr\n\n\n\nai\nns\n\n\n\n a\nre\n\n\n\n \nw\n\n\n\nith\nin\n\n\n\n m\nul\n\n\n\ntin\nuc\n\n\n\nle\nat\n\n\n\ned\n g\n\n\n\nia\nnt\n\n\n\n c\nel\n\n\n\nls\nIn\n\n\n\nfla\nm\n\n\n\nm\nat\n\n\n\nor\ny \n\n\n\nG\nra\n\n\n\nnu\nlo\n\n\n\nm\na \n\n\n\nw\nith\n\n\n\n m\nul\n\n\n\ntin\nuc\n\n\n\nle\nat\n\n\n\ned\n g\n\n\n\nia\nnt\n\n\n\n c\nel\n\n\n\nls\n, l\n\n\n\nym\nph\n\n\n\noc\nyt\n\n\n\nes\n \n\n\n\neo\nsi\n\n\n\nno\nph\n\n\n\nils\n a\n\n\n\nnd\n fi\n\n\n\nbr\nos\n\n\n\nis\n su\n\n\n\nrr\nou\n\n\n\nnd\nin\n\n\n\ng \nth\n\n\n\ne \ngr\n\n\n\nai\nns\n\n\n\n is\n se\n\n\n\nen\nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\n3.\n27\n\n\n\n/M\nal\n\n\n\ne\nSw\n\n\n\nel\nlin\n\n\n\ng \nw\n\n\n\nith\n m\n\n\n\nul\ntip\n\n\n\nle\n sm\n\n\n\nal\nl e\n\n\n\nro\nsi\n\n\n\non\ns \n\n\n\nov\ner\n\n\n\n ri\ngh\n\n\n\nt s\nol\n\n\n\ne.\n9 \n\n\n\nm\non\n\n\n\nth\ns\n\n\n\nG\nra\n\n\n\nin\ns s\n\n\n\nur\nro\n\n\n\nun\nde\n\n\n\nd \nby\n\n\n\n n\neu\n\n\n\ntro\nph\n\n\n\nils\n a\n\n\n\nnd\n \n\n\n\nla\nye\n\n\n\nr o\nf fi\n\n\n\nbr\nou\n\n\n\ns t\nis\n\n\n\nsu\ne \n\n\n\nis\n se\n\n\n\nen\n  \n\n\n\nO\nva\n\n\n\nl g\nra\n\n\n\nin\n su\n\n\n\nrr\nou\n\n\n\nnd\ned\n\n\n\n b\ny \n\n\n\nne\nut\n\n\n\nro\nph\n\n\n\nils\n is\n\n\n\n se\nen\n\n\n\n.\nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\n4.\n38\n\n\n\n/M\nal\n\n\n\ne\nM\n\n\n\nul\ntip\n\n\n\nle\n n\n\n\n\nod\nul\n\n\n\nes\n w\n\n\n\nith\n d\n\n\n\nis\nch\n\n\n\nar\ngi\n\n\n\nng\n \n\n\n\nsi\nnu\n\n\n\nse\ns o\n\n\n\nve\nr l\n\n\n\nef\nt f\n\n\n\noo\nt. \n\n\n\n1 \nye\n\n\n\nar\nG\n\n\n\nra\nin\n\n\n\ns s\nur\n\n\n\nro\nun\n\n\n\nde\nd \n\n\n\nby\n n\n\n\n\neu\ntro\n\n\n\nph\nils\n\n\n\n a\nnd\n\n\n\n \nla\n\n\n\nye\nr o\n\n\n\nf p\nla\n\n\n\nsm\na \n\n\n\nce\nlls\n\n\n\n, m\nac\n\n\n\nro\nph\n\n\n\nag\nes\n\n\n\n, \ngr\n\n\n\nan\nul\n\n\n\nat\nio\n\n\n\nn \ntis\n\n\n\nsu\ne \n\n\n\n&\n fi\n\n\n\nbr\nou\n\n\n\ns t\nis\n\n\n\nsu\ne \n\n\n\nis\n se\n\n\n\nen\n.\n\n\n\nO\nva\n\n\n\nl g\nra\n\n\n\nin\ns s\n\n\n\nur\nro\n\n\n\nun\nde\n\n\n\nd \nby\n\n\n\n n\neu\n\n\n\ntro\nph\n\n\n\nils\n is\n\n\n\n se\nen\n\n\n\n \nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\n5.\n41\n\n\n\n/M\nal\n\n\n\ne\nSw\n\n\n\nel\nlin\n\n\n\ng \nov\n\n\n\ner\n le\n\n\n\nft \nan\n\n\n\nkl\ne \n\n\n\nw\nith\n\n\n\n m\nul\n\n\n\ntip\nle\n\n\n\n \ndi\n\n\n\nsc\nha\n\n\n\nrg\nin\n\n\n\ng \npo\n\n\n\nin\nts\n\n\n\n. \n5 \n\n\n\nye\nar\n\n\n\ns\nFr\n\n\n\nag\nm\n\n\n\nen\nts\n\n\n\n o\nf t\n\n\n\nhe\n d\n\n\n\nes\ntro\n\n\n\nye\nd \n\n\n\ngr\nai\n\n\n\nns\n a\n\n\n\nre\n \n\n\n\nw\nith\n\n\n\nin\n m\n\n\n\nul\ntin\n\n\n\nuc\nle\n\n\n\nat\ned\n\n\n\n g\nia\n\n\n\nnt\n c\n\n\n\nel\nls\n\n\n\n se\nen\n\n\n\n \nde\n\n\n\nep\n g\n\n\n\nra\nnu\n\n\n\nlo\nm\n\n\n\nat\nou\n\n\n\ns i\nnfl\n\n\n\nam\nm\n\n\n\nat\nio\n\n\n\nn \nco\n\n\n\nns\nis\n\n\n\ntin\ng \n\n\n\nof\n m\n\n\n\nul\ntin\n\n\n\nuc\nle\n\n\n\nat\ned\n\n\n\n g\nia\n\n\n\nnt\n c\n\n\n\nel\nls\n\n\n\n, \nly\n\n\n\nm\nph\n\n\n\noc\nyt\n\n\n\nes\n a\n\n\n\nnd\n p\n\n\n\nla\nsm\n\n\n\na \nce\n\n\n\nlls\n su\n\n\n\nrr\nou\n\n\n\nnd\ned\n\n\n\n b\ny \n\n\n\nfib\nro\n\n\n\nus\n ti\n\n\n\nss\nue\n\n\n\n is\n se\n\n\n\nen\n \n\n\n\n6.\n52\n\n\n\n/F\nem\n\n\n\nal\ne\n\n\n\nM\nul\n\n\n\ntip\nle\n\n\n\n sw\nel\n\n\n\nlin\ngs\n\n\n\n o\nve\n\n\n\nr a\nnk\n\n\n\nle\n. \n\n\n\n6 \nye\n\n\n\nar\ns\n\n\n\nW\nel\n\n\n\nl o\nrg\n\n\n\nan\nis\n\n\n\ned\n in\n\n\n\nfla\nm\n\n\n\nm\nat\n\n\n\nor\ny \n\n\n\ngr\nan\n\n\n\nul\nom\n\n\n\na \nw\n\n\n\nith\n L\n\n\n\nan\nge\n\n\n\nrh\nan\n\n\n\ns g\nia\n\n\n\nnt\n c\n\n\n\nel\nls\n\n\n\n w\nith\n\n\n\nou\nt g\n\n\n\nra\nin\n\n\n\ns \nis\n\n\n\n se\nen\n\n\n\n\n\n\n\nG\nra\n\n\n\nin\ns w\n\n\n\nith\n h\n\n\n\nom\nog\n\n\n\nen\nou\n\n\n\ns b\nlu\n\n\n\ne \nce\n\n\n\nnt\nre\n\n\n\n a\nnd\n\n\n\n p\ner\n\n\n\nip\nhe\n\n\n\nra\nl p\n\n\n\nin\nk \n\n\n\nfil\nam\n\n\n\nen\nts\n\n\n\n se\nen\n\n\n\n \nw\n\n\n\nith\n m\n\n\n\nul\nti-\n\n\n\nnu\ncl\n\n\n\nea\nte\n\n\n\nd \ngi\n\n\n\nan\nt c\n\n\n\nel\nls\n\n\n\n, l\nym\n\n\n\nph\noc\n\n\n\nyt\nes\n\n\n\n a\nnd\n\n\n\n fe\nw\n\n\n\n n\neu\n\n\n\ntro\nph\n\n\n\nils\n in\n\n\n\n th\ne \n\n\n\nba\nck\n\n\n\ngr\nou\n\n\n\nnd\n.\n\n\n\nN\no \n\n\n\ngr\now\n\n\n\nth\n se\n\n\n\nen\n\n\n\n7.\n24\n\n\n\n/M\nal\n\n\n\ne\nSw\n\n\n\nel\nlin\n\n\n\ng \nw\n\n\n\nith\n si\n\n\n\nnu\nse\n\n\n\ns w\nith\n\n\n\n sm\nal\n\n\n\nl u\nlc\n\n\n\ner\n \n\n\n\nov\ner\n\n\n\n ri\ngh\n\n\n\nt a\nnk\n\n\n\nle\n. \n\n\n\n1y\nea\n\n\n\nr\nG\n\n\n\nra\nin\n\n\n\ns s\nur\n\n\n\nro\nun\n\n\n\nde\nd \n\n\n\nby\n n\n\n\n\neu\ntro\n\n\n\nph\nils\n\n\n\n a\nnd\n\n\n\n \nla\n\n\n\nye\nr o\n\n\n\nf fi\nbr\n\n\n\nou\ns t\n\n\n\nis\nsu\n\n\n\ne \nis\n\n\n\n se\nen\n\n\n\n  \nG\n\n\n\nra\nin\n\n\n\ns w\nith\n\n\n\n h\nom\n\n\n\nog\nen\n\n\n\nou\ns b\n\n\n\nlu\ne \n\n\n\nce\nnt\n\n\n\nre\n a\n\n\n\nnd\n p\n\n\n\ner\nip\n\n\n\nhe\nra\n\n\n\nl p\nin\n\n\n\nk \nfil\n\n\n\nam\nen\n\n\n\nts\n w\n\n\n\nith\n \n\n\n\npr\ned\n\n\n\nom\nin\n\n\n\nan\ntly\n\n\n\n p\nol\n\n\n\nym\nor\n\n\n\nph\non\n\n\n\nuc\nle\n\n\n\nar\n c\n\n\n\nel\nls\n\n\n\n su\nrr\n\n\n\nou\nnd\n\n\n\nin\ng \n\n\n\nth\ne \n\n\n\ngr\nai\n\n\n\nns\n. \n\n\n\nN\no \n\n\n\ngr\now\n\n\n\nth\n se\n\n\n\nen\n\n\n\n8.\n42\n\n\n\n/M\nal\n\n\n\ne\nSw\n\n\n\nel\nlin\n\n\n\ng \nw\n\n\n\nith\n m\n\n\n\nul\ntip\n\n\n\nle\n d\n\n\n\nis\nch\n\n\n\nar\ngi\n\n\n\nng\n \n\n\n\nsi\nnu\n\n\n\nse\ns o\n\n\n\nve\nr l\n\n\n\nef\nt s\n\n\n\nol\ne.\n\n\n\n \n2 \n\n\n\nye\nar\n\n\n\ns\nFr\n\n\n\nag\nm\n\n\n\nen\nts\n\n\n\n o\nf t\n\n\n\nhe\n d\n\n\n\nes\ntro\n\n\n\nye\nd \n\n\n\ngr\nai\n\n\n\nns\n a\n\n\n\nre\n \n\n\n\nw\nith\n\n\n\nin\n m\n\n\n\nul\ntin\n\n\n\nuc\nle\n\n\n\nat\ned\n\n\n\n g\nia\n\n\n\nnt\n c\n\n\n\nel\nls\n\n\n\n fe\nw\n\n\n\n d\nes\n\n\n\ntro\nye\n\n\n\nd \nbl\n\n\n\nui\nsh\n\n\n\n g\nra\n\n\n\nin\ns w\n\n\n\nith\n p\n\n\n\noo\nrly\n\n\n\n a\npp\n\n\n\nre\nci\n\n\n\nat\ned\n\n\n\n p\ner\n\n\n\nip\nhe\n\n\n\nra\nl p\n\n\n\nin\nki\n\n\n\nsh\n \n\n\n\nfil\nam\n\n\n\nen\nts\n\n\n\n se\nen\n\n\n\n \nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\n9.\n68\n\n\n\n/M\nal\n\n\n\ne\nM\n\n\n\nul\ntip\n\n\n\nle\n d\n\n\n\nis\nch\n\n\n\nar\ngi\n\n\n\nng\n si\n\n\n\nnu\nse\n\n\n\ns o\nve\n\n\n\nr \nle\n\n\n\nft \nle\n\n\n\ng.\n \n\n\n\n5 \nye\n\n\n\nar\ns\n\n\n\nFr\nag\n\n\n\nm\nen\n\n\n\nts\n o\n\n\n\nf t\nhe\n\n\n\n d\nes\n\n\n\ntro\nye\n\n\n\nd \ngr\n\n\n\nai\nns\n\n\n\n a\nre\n\n\n\n \nw\n\n\n\nith\nin\n\n\n\n m\nul\n\n\n\ntin\nuc\n\n\n\nle\nat\n\n\n\ned\n g\n\n\n\nia\nnt\n\n\n\n c\nel\n\n\n\nls\nW\n\n\n\nel\nl d\n\n\n\niff\ner\n\n\n\nen\ntia\n\n\n\nte\nd \n\n\n\ngr\nan\n\n\n\nul\nom\n\n\n\na \nw\n\n\n\nith\n p\n\n\n\nre\ndo\n\n\n\nm\nin\n\n\n\nan\ntly\n\n\n\n m\nul\n\n\n\ntin\nuc\n\n\n\nle\nat\n\n\n\ned\n g\n\n\n\nia\nnt\n\n\n\n \nce\n\n\n\nlls\n, a\n\n\n\nnd\n ly\n\n\n\nm\nph\n\n\n\noc\nyt\n\n\n\nes\n su\n\n\n\nrr\nou\n\n\n\nnd\ned\n\n\n\n b\ny \n\n\n\nfib\nro\n\n\n\nsi\ns i\n\n\n\ns s\nee\n\n\n\nn \nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\n10\n.\n\n\n\n32\n/M\n\n\n\nal\ne\n\n\n\nSw\nel\n\n\n\nlin\ng \n\n\n\nov\ner\n\n\n\n le\nft \n\n\n\nan\nkl\n\n\n\ne \nw\n\n\n\nith\n \n\n\n\ndi\nsc\n\n\n\nha\nrg\n\n\n\nin\ng \n\n\n\nsi\nnu\n\n\n\nse\ns a\n\n\n\nnd\n sm\n\n\n\nal\nl u\n\n\n\nlc\ner\n\n\n\n. \n3 \n\n\n\nye\nar\n\n\n\ns\nFr\n\n\n\nag\nm\n\n\n\nen\nts\n\n\n\n o\nf t\n\n\n\nhe\n d\n\n\n\nes\ntro\n\n\n\nye\nd \n\n\n\ngr\nai\n\n\n\nns\n a\n\n\n\nre\n \n\n\n\nw\nith\n\n\n\nin\n m\n\n\n\nul\ntin\n\n\n\nuc\nle\n\n\n\nat\ned\n\n\n\n g\nia\n\n\n\nnt\n c\n\n\n\nel\nls\n\n\n\nW\nel\n\n\n\nl d\niff\n\n\n\ner\nen\n\n\n\ntia\nte\n\n\n\nd \ngr\n\n\n\nan\nul\n\n\n\nom\na \n\n\n\nw\nith\n\n\n\n p\nre\n\n\n\ndo\nm\n\n\n\nin\nan\n\n\n\ntly\n m\n\n\n\nul\ntin\n\n\n\nuc\nle\n\n\n\nat\ned\n\n\n\n g\nia\n\n\n\nnt\n \n\n\n\nce\nlls\n\n\n\n, a\nnd\n\n\n\n ly\nm\n\n\n\nph\noc\n\n\n\nyt\nes\n\n\n\n su\nrr\n\n\n\nou\nnd\n\n\n\ned\n b\n\n\n\ny \nfib\n\n\n\nro\nsi\n\n\n\ns i\ns s\n\n\n\nee\nn \n\n\n\nN\no \n\n\n\ngr\now\n\n\n\nth\n se\n\n\n\nen\n\n\n\n11\n.\n\n\n\n44\n/M\n\n\n\nal\ne\n\n\n\nSw\nel\n\n\n\nlin\ng \n\n\n\nw\nith\n\n\n\n m\nul\n\n\n\ntip\nle\n\n\n\n d\nis\n\n\n\nch\nar\n\n\n\ngi\nng\n\n\n\n \nsi\n\n\n\nnu\nse\n\n\n\ns o\nve\n\n\n\nr l\nef\n\n\n\nt f\noo\n\n\n\nt. \n5 \n\n\n\nye\nar\n\n\n\ns\nW\n\n\n\nel\nl o\n\n\n\nrg\nan\n\n\n\nis\ned\n\n\n\n in\nfla\n\n\n\nm\nm\n\n\n\nat\nor\n\n\n\ny \ngr\n\n\n\nan\nul\n\n\n\nom\na \n\n\n\nw\nith\n\n\n\n p\nre\n\n\n\ndo\nm\n\n\n\nin\nan\n\n\n\nt L\nan\n\n\n\nge\nrh\n\n\n\nan\ns g\n\n\n\nia\nnt\n\n\n\n c\nel\n\n\n\nls\n \n\n\n\nis\n se\n\n\n\ne\n\n\n\nfe\nw\n\n\n\n d\nes\n\n\n\ntro\nye\n\n\n\nd \nbl\n\n\n\nui\nsh\n\n\n\n g\nra\n\n\n\nin\ns w\n\n\n\nith\n p\n\n\n\noo\nrly\n\n\n\n a\npp\n\n\n\nre\nci\n\n\n\nat\ned\n\n\n\n p\ner\n\n\n\nip\nhe\n\n\n\nra\nl p\n\n\n\nin\nki\n\n\n\nsh\n \n\n\n\nfil\nam\n\n\n\nen\nts\n\n\n\n se\nen\n\n\n\nN\no \n\n\n\ngr\now\n\n\n\nth\n se\n\n\n\nen\n\n\n\n12\n.\n\n\n\n26\n/M\n\n\n\nal\ne\n\n\n\nSw\nel\n\n\n\nlin\ng \n\n\n\nw\nith\n\n\n\n m\nul\n\n\n\ntip\nle\n\n\n\n d\nis\n\n\n\nch\nar\n\n\n\ngi\nng\n\n\n\n \nsi\n\n\n\nnu\nse\n\n\n\ns o\nve\n\n\n\nr l\nef\n\n\n\nt f\noo\n\n\n\nt. \n5 \n\n\n\nm\non\n\n\n\nth\ns\n\n\n\nG\nra\n\n\n\nin\ns s\n\n\n\nur\nro\n\n\n\nun\nde\n\n\n\nd \nby\n\n\n\n n\neu\n\n\n\ntro\nph\n\n\n\nils\n a\n\n\n\nnd\n \n\n\n\nm\nac\n\n\n\nro\nph\n\n\n\nag\nes\n\n\n\n se\nen\n\n\n\nIn\nfla\n\n\n\nm\nm\n\n\n\nat\nor\n\n\n\ny \ngr\n\n\n\nan\nul\n\n\n\nom\na \n\n\n\nw\nith\n\n\n\n b\nla\n\n\n\nck\n g\n\n\n\nra\nin\n\n\n\n a\nt t\n\n\n\nhe\n c\n\n\n\nen\ntre\n\n\n\n su\nrr\n\n\n\nou\nnd\n\n\n\ned\n b\n\n\n\ny \nne\n\n\n\nut\nro\n\n\n\nph\nils\n\n\n\n, f\new\n\n\n\n m\nac\n\n\n\nro\nph\n\n\n\nag\nes\n\n\n\n, p\nla\n\n\n\nsm\na \n\n\n\nce\nlls\n\n\n\n a\nnd\n\n\n\n g\nra\n\n\n\nnu\nla\n\n\n\ntio\nn \n\n\n\ntis\nsu\n\n\n\ne \nar\n\n\n\ne \nse\n\n\n\nen\nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\n13\n. \n\n\n\n36\n/M\n\n\n\nal\ne\n\n\n\nSw\nel\n\n\n\nlin\ng \n\n\n\nw\nith\n\n\n\n m\nul\n\n\n\ntip\nle\n\n\n\n d\nis\n\n\n\nch\nar\n\n\n\ngi\nng\n\n\n\n \nsi\n\n\n\nnu\nse\n\n\n\ns w\nith\n\n\n\n b\nla\n\n\n\nck\n g\n\n\n\nra\nin\n\n\n\ns o\nve\n\n\n\nr r\nig\n\n\n\nht\n \n\n\n\nfo\not\n\n\n\n.\n\n\n\n18\n m\n\n\n\non\nth\n\n\n\ns\nG\n\n\n\nra\nin\n\n\n\ns s\nur\n\n\n\nro\nun\n\n\n\nde\nd \n\n\n\nby\n n\n\n\n\neu\ntro\n\n\n\nph\nils\n\n\n\n is\n \n\n\n\npr\nes\n\n\n\nen\nt. \n\n\n\nPl\nas\n\n\n\nm\na \n\n\n\nce\nlls\n\n\n\n a\nnd\n\n\n\n fi\nbr\n\n\n\nou\ns t\n\n\n\nis\nsu\n\n\n\ne \nsu\n\n\n\nrr\nou\n\n\n\nnd\n th\n\n\n\nis\n la\n\n\n\nye\nr.\n\n\n\nSu\npp\n\n\n\nur\nat\n\n\n\niv\ne \n\n\n\ngr\nan\n\n\n\nul\nom\n\n\n\na \nco\n\n\n\nns\nis\n\n\n\ntin\ng \n\n\n\nof\n n\n\n\n\neu\ntro\n\n\n\nph\nils\n\n\n\n, m\nac\n\n\n\nro\nph\n\n\n\nag\nes\n\n\n\n, f\new\n\n\n\n g\nia\n\n\n\nnt\n \n\n\n\nce\nlls\n\n\n\n a\nre\n\n\n\n se\nen\n\n\n\nN\no \n\n\n\ngr\now\n\n\n\nth\n se\n\n\n\nen\n\n\n\n14\n.\n\n\n\n28\n/F\n\n\n\nem\nal\n\n\n\ne\nSw\n\n\n\nel\nlin\n\n\n\ng \nw\n\n\n\nith\n m\n\n\n\nul\ntip\n\n\n\nle\n d\n\n\n\nis\nch\n\n\n\nar\ngi\n\n\n\nng\n \n\n\n\nsi\nnu\n\n\n\nse\ns o\n\n\n\nve\nr l\n\n\n\nef\nt f\n\n\n\noo\nt. \n\n\n\n10\n y\n\n\n\nea\nrs\n\n\n\nFr\nag\n\n\n\nm\nen\n\n\n\nts\n o\n\n\n\nf d\nes\n\n\n\ntro\nye\n\n\n\nd \ngr\n\n\n\nai\nns\n\n\n\n w\nith\n\n\n\nin\n \n\n\n\nm\nul\n\n\n\ntin\nuc\n\n\n\nle\nat\n\n\n\ned\n g\n\n\n\nia\nnt\n\n\n\n c\nel\n\n\n\nls\n se\n\n\n\nen\nG\n\n\n\nra\nin\n\n\n\ns h\nom\n\n\n\nog\nen\n\n\n\nou\nsl\n\n\n\ny \nbl\n\n\n\nue\n a\n\n\n\nt t\nhe\n\n\n\n c\nen\n\n\n\ntre\n a\n\n\n\nnd\n ra\n\n\n\ndi\nat\n\n\n\nin\ng \n\n\n\npi\nnk\n\n\n\n fi\nla\n\n\n\nm\nen\n\n\n\nts\n a\n\n\n\nt t\nhe\n\n\n\n \npe\n\n\n\nrip\nhe\n\n\n\nry\n a\n\n\n\nre\n se\n\n\n\nen\nN\n\n\n\no \ngr\n\n\n\now\nth\n\n\n\n se\nen\n\n\n\nTa\nbl\n\n\n\ne \n1:\n\n\n\n T\nhe\n\n\n\n c\nlin\n\n\n\nic\nal\n\n\n\n a\nnd\n\n\n\n la\nbo\n\n\n\nra\nto\n\n\n\nry\n d\n\n\n\nat\na \n\n\n\nof\n o\n\n\n\nur\n p\n\n\n\nat\nie\n\n\n\nnt\ns.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n63\n\n\n\nThis deforming granulomatous disease is common \nin poor rural workers and homemakers who work \noutdoors without protective garments and shoes.3 \n\n\n\nHost factors such as immune status, adaptive \nhumoral response and nature of occupation  as well \nas organism related factors such as virulence and \nsize of inoculum are related to the development of \ndisease.2,3,6 Male to female ratio is 3-4:1.3 The age \ngroup most commonly affected is 20-40 years.6 \n\n\n\nAlthough various studies have been done for \nestimation of burden of disease, the estimated \nprevalence does not reflect the actual magnitude of \ndisease. The gap lies in the fact that the studies done \nwere single center studies.5\n\n\n\nThe three subtypes based on etiology are (1) \nActinomycotic mycetoma \u2013 caused by filamentous \naerobic and anaerobic organisms, e.g. Nocardia \nbrasiliensis, Actinomadura madurae; (2) \nEumycotic mycetoma \u2013 caused by true fungi; and \n(3) Botryomycosis \u2013 caused by true bacteria, e.g. \nStaphylococcus aureus, Pseudomonas spp.\n\n\n\nMycetoma is differentiated from other mycoses \nby its characteristic draining sinuses containing \ngrains (sclerotia, sulfur granules).1 Grains contain \norganism both inside and outside the grains.7 Various \nquestions remained unanswered till date regarding \nroute of transmission. These questions include \u2013 \nWhere the causative organism resides? What is its \nnatural habitat? Soil and dung are most probable \nhabitat but there can be other possible habitat). How \nthe organism introduced in subcutaneous tissue \n(thorn prick is estimated but intermediate hosts \ncan be involved). Will the organism always cause \nmycetoma? Does co- infection play role?5 What is \nincubation period?3\n\n\n\nIn host, T- cell mediated immune responses play \nimportant role.2 Three types of responses to \ngrains of mycetoma have been described which \ninclude: Type-1: Degranulation and adherence of \nneutrophils to the outer grain surface leading to \ngradual destruction of grains. Outside this layer \nof neutrophils macrophages, lymphocytes, plasma \ncells and a granulation tissue present enclosed in a \nfine layer of fibrous tissue. Type-2: Disappearance \nof neutrophils and predominant presence of \nmacrophages for clearance of grains and neutrophils \ndebris owing to presence of disintegrated grains \ninside the multinucleated giant cells. Type-3-\ndevelopment of epithelioid cell granulomas and \nwith few or no remnants of grains and presence of a \n\n\n\nfibrous tissue in abundance.2,8\n\n\n\nAs it is a painless condition it usually presents in \nadvanced stage.8 Diagnosis of the disease is \nessential as left untreated can invite superimposed \ninfection sometimes leading to septicemia and can \ncause fatal outcome.2 Also disfigurement of the limb \nis an important concern. \n\n\n\nAnother need for diagnosing the disease is that, \nmycetoma is caused by taxonomically different \norganism i.e fungi, bacteria which require different \napproaches for the treatment.5 Diagnosis is made \nby classical triad, histopathology, FNAC, culture \nstudies, ultrasonography, Magnetic resonance \nimaging, skin testing, serology etc7.\n\n\n\nAs of today, no protective vaccine is available \nagainst any of the causative agents of mycetoma.9 \n\n\n\nOne of our patient required debulking of the growth \nalong with concomitant antimycotic therapy and \nall of them responded well to treatment. Wearing \nof protective shoes and clothing prevent against \ntrauma from thorn pricks and its importance should \nbe emphasised.  Knowledge and early identification \nby examination and minimum investigation of the \ncondition leads to alleviating the poor farmer\u2019s \nanguish. Moreover we found simple treatment by \n160 mg trimethoprim and 800 mg sulfamethoxazole \ntill lesions heal and minor surgical interventions \nprevent patients from the debilitating disease.\n\n\n\nDifferential diagnosis included infectious-\nsuch as cutaneous tuberculosis, nontuberculous \nmycobacterial infections of skin, osteomyelitis, \nchromomycosis, sporotrichosis, blastomycosis, \ndermatophyte pseudomycetoma etc. Non- infectious \nsuch as mossy foot or podoconiosis, malignant \ntumors (sarcoma of skin and soft tissue or bones and \nKaposis\u2019s sarcoma).2\n\n\n\nConclusion \nWhen left untreated, disease continues to progress, \nand bacterial superinfection can lead to increased \nmorbidity from local abscess formation, cellulitis, \nbacterial osteomyelitis and, rarely, septic death. It \nenjoys little attention by health and social sectors \nacross the world, as it is a non-glorious (and, \nindeed, low-priority) disease. There is no consensus \non treatment that is often prolonged with numerous \nrelapses. Also, to combat the globally prevalent \ndisease condition, actual prevalence of the disease \nshould be known for this integrated approach with \nuse of standardised forms and establishment of \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n64\n\n\n\nnational reference centres is expected.\n\n\n\nConflict\tof\tInterest\tDeclaration\t\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\t\nNil\n\n\n\nReferences \n                                                                                               \n1. J Bolognia, J Schaffer, L Cerroni. Infections, Infestations, \n\n\n\nand Bites: Fungal Diseases; 4th Edition, Volume 2, 2018; \np.1348-9.  \n\n\n\n2. Relhan V, Mahajan K, Agarwal P, Garg VK. Mycetoma: \nAn update. Indian J Dermatol 2017;62:332-40.  \n\n\n\n3. Bonifaz A, Tirado-S\u00e1nchez A, Calder\u00f3n L, Sa\u00fal A, \nAraiza J, Hern\u00e1ndez M et al. Mycetoma: Experience \nof 482 Cases in a Single Center in Mexico. PLoS Negl \nTrop Dis 2014;8:e3102. https://doi.org/10.1371/journal.\npntd.0003102.  \n\n\n\n4. Ahmed A, Adelmann D, Fahal A, Verbrugh H, \nBelkum AV, Hoog SD. Environmental Occurrence of \nMadurella mycetomatis, the Major Agent of Human \nEumycetoma in Sudan. J Clin Microbiol 2002;40:1031-\n6.                                                                                                                                                      \n\n\n\n5. van de Sande WWJ, Maghoub ES, Fahal AH, Goodfellow \nM, Welsh O, Zijlstra E. The Mycetoma Knowledge Gap: \nIdentification of Research Priorities. PLoS Negl Trop Dis \n2014;8:e2667. https://doi.org/10.1371/journal.pntd.00026\n67.                                                                                                          \n\n\n\n6. Loulergue P, Hot A, Dannaoui E, Dallot A, Poir\u00e9e S, \nDupont B et al. Short report. Successful treatment of \nblack-grain mycetoma with voriconazole. Am J Trop Med \nHyg 2006;75:1106-7.\n\n\n\n7. van de Sande WWJ, Fahal AH, Goodfellow M, Mahgoub \nES, Welsh O, Zijlstra EE.  Merits and Pitfalls of Currently \nUsed Diagnostic Tools in Mycetoma. PLoS Negl Trop \nDis 2014;8:e2918. https://doi.org/10.1371/journal.\npntd.0002918.\n\n\n\n8. Ahmed AA, van de Sande W, Fahal AH. Mycetoma \nlaboratory diagnosis: Review article. PLoS Negl Trop \nDis 2017;11:e0005638. https://doi.org/10.1371/journal.\npntd.0005638.\n\n\n\n9. Porte L, Khatibi S, El Hajj L, Cassaing S, Berry A, Massip \nP et al. Scedosporium apiospermum mycetoma with bone \ninvolvement successfully treated with voriconazole. \nTransactions of Royal Society of Tropical Medicine and \nHygiene 2006;100:891-4.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n65\n\n\n\nCASE REPORT\n\n\n\nOnline, Game-Based Learning (GBL) on Melanoma: The Learning \nExperiences of a Medical Student          \nTessa Li Chyin Lim\n\n\n\nJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia Campus, Johor Bahru, Johor, \nMalaysia\n\n\n\nSummary\nThe use of GBL in dermatology education is not uncommon. GBL provides education to audiences \naround the world, wherever their learning environment allows them. The paper serves to present the \nexperience of a medical student who developed a GBL program for malignant melanoma (MM) without \nprior skills in the development of GBL software or computer programming. The commercial GBL \nsoftware used is \u2018Chat Mapper\u2019. The program can be published in HTML and embedded in Moodle. \nIt allows the creation of non-linear branching dialogue trees. The users will interact with a virtual \nphysician which discusses the clinical features, risk factors, management, staging and prognosis of \nMM. A 6-minute GBL program was practical to have a basic coverage of MM. To limit learner fatigue, \nthe program is completed with audio, graphics and dialogue menus. It tailors to English-speaking \nusers with visual and auditory learning styles. A straightforward navigating system can accommodate \nusers at all levels of computer literacy. The program is compatible with laptop, desktop but not all \nphones. A period of one week was used to master the software, resolve any technical issues and to \ndevelop this program. Users who completed the program will be able to know more about MM. The \nprogram can be viewed at: https://tlderm.webnode.com/. Physicians may consider integrating GBL \nprograms into routine practice. The development, however, might be hampered by the time factor, cost \nfactor and the need for technical experts. \n\n\n\nKey words: Melanoma; educational gaming; game-based learning\n\n\n\nCorresponding Author\nMs Tessa Li Chyin Lim\nFaculty of Medicine, Nursing and Health Sciences, \nMonash University Malaysia Campus, \n80100 Johor Bahru, Johor, Malaysia\nEmail: tessalim15@gmail.com\n\n\n\nIntroduction\nThe use of game-based learning (GBL) programs \nin education is not uncommon and is increasing \nthroughout the years. GBL provides education to \naudiences around the world, wherever their learning \nenvironment allows them. Not only does it provide \nopportunities for patient and interdisciplinary \neducation, it also works as a medium for promoting \nhealth professions.1 Therefore, it is essential to have \ncritical effective online education interventions with \nthe increasing use of Internet for health information. \nGBL programs can used for dermatology patient \neducation, for example, education on malignant \nmelanoma (MM).1,2\n\n\n\nAccording to Centers for Disease Control and \nPrevention (CDC), MM is the sixth most common \ncancer among males and females in the United \nStates in 2016, which is the latest year for which \nstatistics are available. The state with the highest \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n66\n\n\n\nincidence is Utah and the lowest incidence is Texas. \nIn general, for every 100,000 people, there were 22 \nreported cases of new MM cases and 2 deaths due to \nMM.3 Thus, there is a need to create content which \ncan help to raise and spread awareness about MM \nto the public. A research which was carried out by \nNishita (2018) highlighted that it is imperative to \nimprove MM patient education materials through \nGBL programs as well as written materials.1 \n\n\n\nThis paper serves to present the experience of a \nmedical student who developed a GBL program for \nMM without prior skills in the development of GBL \nsoftware or computer programming.\n \nMaterials and Methods\nThe commercial GBL software used was \u2018Chat \nMapper\u2019. It is a full featured visual editor for \nmanaging storylines for games. It allows the creation \nof non-linear branching dialogue trees which imitate \nthe normal interaction in real life. The core is a lean, \nefficient conversation system.4 Numerous branching \nconversations which were created enabled the users \nto interact and have a medical interview with a virtual \nphysician who will then discuss with them the basic \nclinical features, risk factors, management, staging \nand prognosis of MM. All the information regarding \nMM would be discussed in layman\u2019s terms to make \nthe contents straightforward, concise and simple to \nunderstand. The information used to create the GBL \nprogram were obtained from DermNet NZ. Under \nthe clinical features, the users would be exposed to \nthe \u2018A-B-C-D-E\u2019 rule for detecting MM.5,6\n\n\n\nAfter designing the conversations, a conversation \nsimulator was used to present all the dialogue trees \nas a game. This ensured that the game would work \nas intended in the final product.4 Our GBL program \nwould start off with a short question as illustrated \nin Figure 1. The user would then have to respond \naccordingly as shown in Figure 2. Users are free to \nchoose any action decisions. Selecting a different \naction decision will lead to a different response and \nthis conversation will continue.\n\n\n\nAll these conversations were designed with the \nhelp of on-screen buttons, menu options, right-click \ncontext menus, as well as shortcut keys. The layout \nwas also fully configurable with interface elements \nand tabs. To automise workflow to the maximum, \nthe command line tools of \u2018Chat Mapper\u2019 was used \nto automate the publishing and exporting process. \nThis project was published in the form of HTML5 \nplayer.4 A website was created under \u2018Webnode\u2019 \n\n\n\nwhich can remain free for unlimited time. The GBL \nprogram was then embedded into the website for \neasy viewing by the users. \n\n\n\nFigure 1. The introduction part of the GBL program\n\n\n\nFigure 2. The response options following introduction\n\n\n\nThe GBL program can be viewed at: https://tlderm.\nwebnode.com/. Users who completed the whole \nprogram will be able to know more about MM. \n\n\n\nDiscussion\nThe aim of our GBL project is to improve the \nconfidence of users towards skin cancer detection \nand identification, in particular MM. It also aims to \nincrease the level of preparedness of users to make \nappropriate dermatology referrals when suspicious \nlesions appear and when they have risk factor(s) of \nMM.\n\n\n\nAccording to an article by BMC Medical \nEducation, there are several elements which are \nimportant in the architecture of gamification. It \nstarts with goal setting, followed by the capacity to \novercome challenges, the provision of feedback on \ngame performance, reinforcement of information, \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n67\n\n\n\ncomparison of progress, social connectivity, and \nlastly fun and playfulness.7 In short, when GBL \nprograms are effective, they play a tremendous \npart to improve knowledge and skills acquisition \nand can provide repetitive learning experience and \nuseful feedback.1,7\n\n\n\n\u2018Chat Mapper\u2019 software is a novel approach \nto facilitating dermatology education, be it for \npatients, medical students or any audience. The \ntotal duration of our GBL project is approximately \n6 minutes. A time period of 6 minutes is practical. \nThe range and depth of the knowledge in our GBL \nproject is enough to have a basic coverage and help \nusers learn quickly. This is because many people, \nespecially those who are working nowadays might \nface time constraints and can lose motivation and \ninterest if the program is taking too long.7\n\n\n\nOur GBL project is not a one-time game. It can be \nplayed as many times as the users want, depending \non their level of personal motivation. Therefore, \nonly users who play the game more than once can \nhave a repetitive learning experience which will \nreinforce their knowledge and learning objectives. \nNo feedback is provided for our GBL project. There \nis also no context for recall. These could potentially \nbe a few areas to look at when developing GBL \nprograms.\n\n\n\nFurthermore, for our GBL project, users can always \nclarify any misconceptions with the instructors. This \nwill in turn improve instructor-user relationship, \nor even doctor-patient relationship if this GBL \nprogram is carried out in a hospital or clinic setting. \nTherefore, in general, GBL programs should be \ncarried out in a safe environment, provide user \nautonomy and independence, and if possible, put a \npositive impact on assessment.1,7\n\n\n\n\u2018Chat Mapper\u2019 was chosen as it is user-friendly and \nstylish. The building blocks are also easy to learn \nas no scripting is required. This saves time and \nis suitable for people who wish to develop GBL \ndermatology programs without prior experience \nin computer programming. A large collection of \nincluded, optional add-ons make it quick and easy \nto drop conversations into the project through a \nvisual node-based editor. As \u2018Chat Mapper\u2019 can \ncombine HTML5 Text to Speech with the web \nplayer to create realistic conversations, this program \nhelps to save a lot of money and time on real voice \nactors.1,4 This shows that the success of the creation \nof any GBL program depends a lot on money and \n\n\n\ntime factor.\n\n\n\n\u2018Chat Mapper\u2019 software also has a straightforward \nnavigating system which can accommodate users at \nall levels of computer literacy. The HTML5 player \nworks out well on modern Internet browsers, for \nexample, Internet Explorer, Google Chrome and \nSafari. The project can also be exported into game \nengines or e-learning systems. Common formats \nare XML, JSON, RTF, PDF, JPEG, EXCEL and \nZip packages. If there is a need for more formats, \ncustom exporter creation services are available. \nFor e-learning integration, it can be embedded in \nMoodle, SCORM, Adobe Captivate, Articulate \nStoryline and Lectora. After publishing the project \nonline, it can be shared with anyone for feedback \nand testing.4 Thus, it is preferable to select GBL \nsoftwares which are user-friendly, compatible \nwith most of the common Internet browsers, have \ne-learning integration, as well as exporters for \ncommon formats.\n\n\n\nThis GBL project also tailors to users who have \na good proficiency in English. However, multiple \nlanguages can be defined for the dialogue trees. Thus, \n\u2018Chat Mapper\u2019 can be used to create dermatology \ncontents in other languages which suit other users. \nIn the creation of GBL programs, it is worth taking \nnote of the languages most well understood by the \naudience they want to reach for maximum learning \nbenefits. \n\n\n\nSome of the GBL programs engagement factors \ninclude safe learning environment, prize, surprise, \nexcitement, fun and pride in achievement or \naccomplishment.1 In this GBL project, some of \nthe engagement factors are lacking, for example, \nsurprise and prize (reward). It can be useful \nto implement surprise and prize into the GBL \nprograms. However, this ultimately depends on the \ntype of software and content which the developers \nchoose to deliver. Other than that, this GBL project \nis also suitable for users with visual and auditory \nlearning styles. However, this can be a barrier if \nthere is a mismatch of learning styles of some users. \nThus, to enhance the motivation and interest of the \nusers, the key is to provide a learning variety which \nis also learner oriented. It can attract more users if \nthe GBL program is appealing to users with diverse \nlearning styles aligned with their preferred learning \nstyles. If possible, these programs can even be \nmade to involve all the senses of the users including \ntheir eyes, ears, touch and mind. This can be in the \nform of music and colorful illustrations which can \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n68\n\n\n\ngenerate excitement and spark the imagination of \nthe users at the same time. \n\n\n\nThe disadvantages of GBL programs are only \nmentioned in one citation. However, it is due to the \ncompetitive nature of the game which intimidates \nthe users and this element is not present in our GBL \nproject.7 One drawback is the pricing of $45 billed \nevery month for its commercial license but can \nbe unsubscribed anytime. A commercial package \ncomes as a single license, but a team package \nconsists of 3 licenses. When no license is being \npurchased, an evaluation trial can be opted for, but it \ndoes not allow exportation, thus the game cannot be \npublished online.4,8 This GBL project is compatible \nwith laptop, desktop but not all phones. A period of \none week was taken to master the software, resolve \nany technical issues and to develop this program. \nIdeally, a GBL program should have good functions \nwith low price, and is compatible with as many \nsmartphones, tablets and computers as possible for \nbetter accessibility. It is also essential to consider \nthe type of subscription for the software which the \nproducers want and need. The time taken to develop \nany project will depend on the amount and type of \ncontent covered.\n\n\n\nIt is established that lack of enthusiasm from the \nparticipants, an organization\u2019s culture, time factor, \ncost factor, and a combination of all these can \nbecome barriers to prevent the implementation of \nGBL program whereas engagement factors can be \nlearner-dependent. Some of the engagement factors \ninclude cognitive skills such as problem-solving, \ndecision-making, active or deep learning, mental \nchallenge and knowledge reinforcement. Other \nengagement factors will depend on interaction \nskills, for example, collaborative, cooperative and \ninteractive learning, competition with peers, and \npeer learning.1 All these are factors to consider \nwhen creating a GBL program.\n\n\n\nMoreover, it is also imperative to look at some \npotential barriers. Lack of cooperation of the users \ncan lead to game failure and insufficient information \nlearned during the game.1,7,9 Since our GBL project \nis straightforward and short, there is significantly \nless chance of game failure. It is important to \nnote that there can also be users do not want to be \ninvolved in the program because of anxiety and fear \nof embarrassment or rebuke if they do not complete \nthe game. Users can also potentially be bored of the \nGBL program leading to demotivation and quitting. \nWhen the contents are too wordy and serious, it can \n\n\n\neventually lead to loss of gaming characteristics and \nconsequent loss of enjoyment. The overall game \ndesign is another factor to look at.1,7,9\n\n\n\nConclusion\nPhysicians may consider integrating GBL programs \ninto routine practice so that patients can better \nunderstand their own diseases or even common \ndiseases like MM. The development, however, \nmight be hampered by some factors, for instance, \ntime factor, cost factor and the need for technical \nexperts. To better understand how GBL programs \ncould be used in dermatology education, further \nresearch should be carried out to investigate the \nmost motivating and engaging factors, and the type \nof content best-suited to be delivered to the targeted \naudience. In reporting the rationale, the author seeks \nto help other healthcare professionals to employ the \nadvantages that GBL programs has to offer.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe author has no conflict of interest to disclose.\n\n\n\nAcknowledgements\nNil\n\n\n\nReferences\n\n\n\n1. Bigdeli S, Kaufman D. Digital games in health professions \neducation: Advantages, disadvantages, and game \nengagement factors. Med J Islam Repub Iran. 2017;31:117.\n\n\n\n2. Maganty N, Ilyas M, Zhang N, Sharma A. Online, game-\nbased education for melanoma recognition: A pilot study. \nPatient Educ Couns 2018;101:738-42.\n\n\n\n3. American Cancer Society. Leading Cancer Cases and \nDeaths, Male and Female, Georgia, 2016. [Accessed in Jan \n2020]. Available from: https://www.cancer.org/research/\ncancer-facts-statistics/all-cancer-facts-figures/cancer-\nfacts-figures-2020.html\n\n\n\n4. LearnBrite. What is ChatMapper? Arizona, 2019. \n[Accessed in Jan 2020]. Available from: https://www.\nchatmapper.com/\n\n\n\n5. DermNet NZ. Skin Cancer, New Zealand, 2019. [Accessed \nin Jan 2020]. Available from: https://dermnetnz.org/topics/\nskin-cancer/\n\n\n\n6. DermNet NZ. Melanoma, New Zealand, 2019. [Accessed \nin Jan 2020]. Available from: https://dermnetnz.org/topics/\nmelanoma/\n\n\n\n7. Jiang AJ, Eide MJ, Alexander GL, Altschuler A, Asgari \nMM, Geller AC et al. Providers\u2019 experiences with a \nmelanoma web-course: a discussion on barriers and \nintentions. J Cancer Educ 2017;32:272-9.\n\n\n\n8. ChatMapper. Downloads and Pricing, Arizona, 2019. \n[Accessed in Jan 2020]. Available from: https://www.\nchatmapper.com/pricing/\n\n\n\n9. Ismail MA, Ahmad A, Mohammad JA, Fakri NMRM, Nor \nMZM, Pa MNM. Using Kahoot! as a formative assessment \ntool in medical education: a phenomenological study. \nBMC Med Educ 2019;19:230.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n69\n\n\n\nCLINICAL IMAGE\n\n\n\nQuackery and Superstitions: The Skin Doctor\u2019s Bane          \nPriyanka Date, MD, Sumit Kar, MD, Safa Patrik, MD, Ajinkya Sawant, MD\n\n\n\nDepartment of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, \nWardha, Maharashtra.\n\n\n\nSummary\nCamphor, a waxy white sublimable chemical, widely used worldwide by various communities for \nmany religious purposes. Here we report a clinical image of self-inflicted injury from burning camphor \non the palm resulting in burns. It also highlights the sociocultural pattern of this injury and need of \npsychopathic and therapeutic help of the patients.\n\n\n\nKey words: Quackery, camphor, innocence\n\n\n\nCorresponding Author\nDr Sumit Kar\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences. \nSewagram, Maharashtra, 442102.\nEmail: karmgims@gmail.com\n\n\n\nCase Report\nA 26 years old male presented to dermatology OPD \nwith an ulcer over his right palm. On enquiring he \ngave history of burn injury by camphor 15 days ago. \nPatient had allowed the entire block of camphor \nto burn on his hand, even though it was associated \nwith pain and burning sensations. He himself took \nphotographs immediately after the event and after \n24 hours and brought those photos to show us. \n(Figure 1) shows central pallor with 2 blisters of \nsize 0.5 x 1 cm surrounded by well defined zone of \nerythema. (Figure 2) shows well defined erosion of \nsize 2 x 2cm with granulation tissue at periphery. \nHe didn\u2019t seek any medical care. On enquiring he \nadmitted, that he has done it to prove his innocence \nto the lord.  He reported on 15th day with (Figure \n3) full thickness burn of size 2 x 2 cm with exposed \ntendons, he applied turmeric for wound healing. \nThese events though uncommon but are commonly \nevident in rural settings.\n\n\n\nMultidisciplinary approach was taken for this \npatient. A course of oral antibiotics for 1 week and \nalternate day dressings for 1 month were prescribed, \nalso psychiatrist counselling was done. We wanted \nto plan for plastic surgery but patient didn\u2019t follow \nup. Though plastic surgery couldn\u2019t be performed \nprobably due to monetary issues we could see the \nchange in his behaviour after counselling. It was \nthough a small but important step we could take to \nchange his beliefs.\n\n\n\nDiscussion\nCamphor is used for medicinal purposes in Ayurveda. \nIt is an organic, transparent, waxy flammable solid \n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n70\n\n\n\nwith a strong odour. Camphor has soothing and \nslightly local anaesthetic effect. It is antimicrobial \nin nature also used as a cough suppressant and a \nnasal decongestant.1\n\n\n\nCamphor is burn at the end of Aarti in temples and \nhousehold prayers. Devotees takes the flame from \ndistant with both hands cupped and touches their \neyes and face. It denotes purity of vision, thought \nand soul. The camphor is sublimable, doesn\u2019t leave \nany residue and produce pleasant fragrance in the \nair which is analogous to human ego. It conveys \ndissolve your ego like camphor and join superior \nconsciousness.2\n\n\n\nThe palmar skin is a specialized structure. It is \nthick, glabrous, hairless and tightly adherent to its \nunderlying structures. A burn occurs when people \nare misguided to place an ignited camphor directly \non their palm. Sometimes, this is done to prove an \nindividual\u2019s innocence in a crime.3\n\n\n\nIt is often related to psychologically sick behaviour \nto commit non suicidal self-inflicted injury. Many \ntimes, an individual is asked to prove their innocence \nby placing an ignited camphor on the palm. Similar \nthing is happened in our case It is believed that \nthe power of God does no harm to a person who is \nInnocent.3\n\n\n\nFigure 1. Blisters with central pallor with well-defined ring of \nerythema\n\n\n\nFigure 3. Full thickness burn with exposed tendon with \noverlying turmeric\n\n\n\nFigure 2. Healing of palm with granulation tissue\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 June Vol 44\n\n\n\nDermatology\n\n\n\n71\n\n\n\nConclusion\nDue to high rate of illiteracy, poverty, unapproachable \nmedical facilities in rural setting and mental \nincapacity patient may not seek immediate medical \ncare and land up with complications. Because of \npoverty and lack of education in rural areas, these \ninjuries go unreported. It\u2019s a tiny modest effort to \nbring this unnoticed reality into picture.\n\n\n\nConflict\tof\tInterest\tDeclaration\t\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\t\nNil\n\n\n\nReferences\n\n\n\n1. Elsa, W. Poisons Information Monograph: Camphor (PIM \n095). 1989. Available online: http//www.inchem.org/\ndocuments/pims/pharm/campor.htm [Last accessed on \n2017 Dec 20].\n\n\n\n2. Bahadur OL. The Book of Hindu Festivals and \nCeremonies. 3rd ed. New Delhi: UBS Publishers; 1994. \np. 177.\n\n\n\n3. Chittoria RK, Mohapatra DP, Friji MT, Kumar SD, Asokan \nA, Pandey S. Camphor burns of the palm and non-suicidal \nself-injury: An uncommonly reported, but socially relevant \nissue. Indian J Plast Surg 2014;47:252-5.\n\n\n\n\n\n\n\n\nMJD 2020 June Vol 44\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n72\n\n\n\nACKNOWLEDGEMENT\nJune Issue 2020\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Adrian Yong Sze Wai\n3. Dr Agnes Heng Yoke Hui\n4. Datin Dr Asmah Johar\n5. Dr Ch\u2019ng Chin Chwen\n6. Dr Chan Lee Chin\n7. Dr Chang Choong Chor\n8. Dr Chong Yew Thong\n9. Dr Dawn Ambrose\n10. Assoc Professor Dr Felix Yap Boon Bin\n11. Dr Henry Foong Boon Bee\n12. Dr. Irene Lee Chew Kek\n13. Dr Kwan Zhenli\n14. Dr Leong Kin Fon\n15. Dr Ng Ting Guan\n16. Dato\u2019 Dr Noor Zalmy Azizan\n17. Associate Professor Dr Norashikin Bt Shamsudin\n18. Dr Rajalingam Ramalingam\n19. Dr Tang Jyh Jong\n20. Dr Tang Min Moon\n\n\n\n\n\n"
"\n\n57\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nUse of cyclosporine in the treatment of psoriasis\n\n\n\nMM Tang MD MRCP, LC Chan MD MMed and A Heng MBBS MRCP\n\n\n\nDepartment of Dermatology Ipoh Hospital\n\n\n\nCorrespondence\n\n\n\nTang Min Moon MRCP (UK)\n\n\n\nDepartment of Dermatology\nIpoh Hospital, 30990 Ipoh\nPerak, Malaysia\nEmail: minmoon2005@yahoo.com\n\n\n\nAbstract\n\n\n\nIntroduction The efficacy of cyclosporine in the treatment of\n\n\n\npsoriasis is well established. However widespread use of it has been\n\n\n\nlimited by concerns over adverse effects such as hypertension, renal\n\n\n\nimpairment and the potential risk of malignancy. The aim of this study\n\n\n\nis to determine the profile of our local psoriasis patients treated with\n\n\n\ncyclosporine, their response to treatment, their tolerability and the\n\n\n\nside-effects experienced.\n\n\n\nMaterials and Methods This is a retrospective study of all psoriasis\n\n\n\npatients treated with cyclosporine for more than one month from\n\n\n\nJanuary 1996 to June 2007 at the Department of Dermatology Ipoh\n\n\n\nHospital.\n\n\n\nResults There were a total 21 patients, 8 males and 13 females. Their\n\n\n\nmean age was 40 years. There were 7 Malays, 10 Chinese and 4\n\n\n\nIndians. Cyclosporine was given as the second or third line of\n\n\n\ntreatment. The average starting dose was 2.76mg/kg and maximum\n\n\n\ndose was 3.89mg/kg. Best response was noted after 3 months of\n\n\n\ntreatment. Thirteen (61.9%) patients had excellent response, 4(19%)\n\n\n\nhad good response, 3 (14.3%) had moderate response and 1(4.8%) had\n\n\n\npoor response. Thirteen (61.9%) patients developed raised serum\n\n\n\ncreatinine level exceeding 30% of the baseline while on treatment but\n\n\n\nall of them improved when the dosages of cyclosporine were reduced.\n\n\n\nNone of them developed renal failure. There were 5 patients who had\n\n\n\nhypertension while on cyclosporine therapy, 2 of them required\n\n\n\nantihypertensive agents while for the remaining 3, blood pressure\n\n\n\nnormalized after dosage reduction. Other side effects reported include\n\n\n\ngastrointestinal upset, gum hypertrophy and hypertrichosis.\n\n\n\nConclusion Cyclosporine is effective in the treatment of psoriasis but\n\n\n\nclose monitoring of serum creatinine and blood pressure is needed.\n\n\n\nKeywords Cyclosporine, psoriasis, continuous therapy\n\n\n\nIntroduction\nCyclosporine (CyA) is an immunomodulator which is now\nincreasingly being used in certain conditions in dermatology\nsuch as severe psoriasis, severe atopic eczema and\nrecalcitrant pyoderma gangrenosum. In moderate to severe\npsoriasis, it can produce marked improvement at dosage\nbetween 2.5-5mg/kg/day. However the widespread use of\nCyA is limited by the well known adverse effects such as\nhypertension, renal impairment and the potential risk of\nmalignancy.\n\n\n\nThe objective of this study is to determine the profile of\nlocal psoriasis patients treated with CyA at the Department\nof Dermatology Ipoh Hospital. The clinical response to\nCyA, tolerability, duration of treatment and side effects\nexperienced were also evaluated.\n\n\n\nMaterials and Methods\nThis is a retrospective study of all patients who had\ncompleted more than a month of cyclosporine for the\ntreatment of psoriasis from January 1996 to June 2007 at\nthe department of Dermatology Ipoh Hospital. Diagnosis\nof psoriasis was made clinically by the attending doctors.\nStudy parameters include the patients\u2019 biodata, dosage and\nduration of CyA treatment, baseline & highest blood\npressure and serum creatinine during treatment, extent of\ndisease pre-and post-treatment (body surface area).\n\n\n\nResponse of treatment was assessed by the doctor treating\nthe patients according to the reduction of body surface area\ninvolvement. \u201cExcellent\u201d response was defined as more than\n75% improvement; \u201cGood\u201d response as improvement of\nbetween 50-75%; \u201cModerate\u201d response as improvement of\nbetween 25-50% while \u201cPoor\u201d response as less than 25%\nimprovement or worsening of psoriasis. The data were\nanalyzed using SPSS statistical analysis for Windows 10.\n\n\n\n\n\n\n\n\n58\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nResults\nThere were a total of 21 patients (8 males and 13 females)\ngiven Cyclosporine for more than a month in the treatment\nof psoriasis during the study period. Most of them had long\nhistory of psoriasis with a mean duration of disease of about\n12 years. All patients had plaque psoriasis at the outset and\n9 went on to develop exfoliative dermatitis/erythroderma.\nThirteen patients had associated arthropathy. The\ndemographic data and baseline characteristics of the\npatients were demonstrated in Table 1.\n\n\n\nCyclosporine was prescribed as the second or third line\nsystemic treatment in all patients. They were all previously\nusing topical treatments. All patients were treated with\nmethotrexate previously. Fourteen patients (66.7%) had\nphototherapy in the past either with narrowband UVB or\nPUVA. Eleven patients (52.4%) were given acitretin\n(Neotigason) and 7 patients (33.3%) were given\nsulfasalazine before cyclosporine was started.\n\n\n\nWhile the patients were taking CyA, their topical\nmedications were continued. In 13 patients (61.9%) CyA\nwas used alone as systemic treatment. Acitretin was added\nin 6 cases and isotretinoin was added in 1 case when the\nCyA dosages were tapered down. In another patient who\nalso had psoriatic arthritis, sulfasalazine was added as CyA\nalone did not help in controlling the joint pain.\n\n\n\nThe mean starting dose and maximum dose of CyA was\n2.76mg/kg/day (2.11-3.5mg/kg/d) and 3.89mg/kg/day\n(2.91-5.3mg/kg/day) respectively. The mean total duration\nof treatment was 16.6 months (3.75-28 months). The\nmaximum clinical improvement was noted after a mean of\n3.11 months (0.5-8.5 months). Thirteen patients (61.9%)\nand 4 patients (19%) achieved excellent and good response\nrespectively at the point of maximum clinical improvement.\nOn the other hand, 3 patients (14.3%) and one patient\n(4.8%) experienced moderate and poor response\nrespectively. The comparison between the body surface area\ninvolvement before and during the maximum clinical\nresponse was shown in Figure 1.\n\n\n\nOur series of patients experienced raised serum creatinine,\nnew onset hypertension, gastrointestinal upset, gum\nhypertrophy and hypertrichosis and the frequency of each\nside effect was shown in Table 2. There were 13 patients\nwho developed elevation of serum creatinine more than\n30% from baseline at a mean of 7.4 months (1.25-20\nmonths) after initiation of cyclosporine. The average\nhighest cyclosporine dose used was 3.8mg/kg/day (2.9-\n5.3mg/kg) and the mean elevation of serum creatinine was\n45.2% (30-71.4%) from baseline. All the 13 patients had\ntheir serum creatinine level normalized after reducting the\ndose of CyA.ion.\n\n\n\nThere were 5 patients who had underlying well-controlled\nhypertension before cyclosporine was started. Two of them\nhad worsening of control of hypertension requiring\nadjustment of anti-hypertensive agents. Newly onset\nhypertension (elevation of blood pressure reading of more\nthan 90mmHg diastolic or more than 140mmHg systolic\nblood pressure) was experienced by 5 patients (23.8%).\nBlood pressure readings were normalized after reduction of\ndosage of cyclosporine in 3 patients while the other 2\npatients required anti-hypertensive agent to control their\nblood pressure. Amlodipine was used in both cases.\n\n\n\nAt the point of the study in July 2007, cyclosporine\ntreatment was taken off in 15 patients, in which 11 of them\nhad underwent at least 12 months of treatment (13-28\nmonths). Out of the 11 patients, 8 patients had achieved the\nmaximum recommended duration of treatment of 2 years.\nIn the other 3 patients, 1 had achieved remission; while 2\npatients had to stop the treatment because the dose of CyA\nwas unable to increase further to achieve better clinical\nresponse due to side effects. Out of the 4 patients who took\nCyA less than a year, one achieved remission; one patient\nwas found to have carcinoma of breast 2 months after\ninitiation of CyA and defaulted follow up in dermatology\nclinic; one had intolerable hypertrichosis; and another one\nstopped because her arthritis was not improved with CyA.\nAfter cessation of CyA, 6 patients developed a relapse,\nwhich is defined as a flare of lesions more than 50% from\nthe time when CyA was ceased. The mean duration of\nrelapse was 1.8 months (range 2 weeks to 5 months).\n\n\n\nDiscussion\nCyA has been proven to be a very effective systemic agent\nin treating severe plaque psoriasis: 80-90% had rapid and\nmarked improvement or complete clearance of disease when\nCyA given at the dose of 2.5-5.0mg/kg/d for 12-16 wks1.\nHowever, its well known side effects namely, renal\nimpairment and hypertension require extreme care during\ntreatment and is not advisable for long term use. Thus,\nCyA can only be used as second or third line treatment\nmodality in severe form of psoriasis when other systemic\ntreatments such as phototherapy (NBUVB & PUVA),\nmethotrexate or acitretin are not feasible.\n\n\n\nThe present study demonstrated that long term continuous\ncyclosporine is effective in treating psoriasis with 81% of\npatients achieved good and excellent improvement. The\neffect of CyA could be seen as soon as 2 weeks with the best\nresponse noted at about 3 months after initiation of CyA.\nThe side effects experienced in our series of patients were\nno different from those reported elsewhere. Nonetheless, it\nis worth mentioning that the rate of raised serum creatinine\nlevel of more than 30% from baseline in the present study\nwas higher than reported in similar studies done in other\ncountries\n\n\n\n\n\n\n\n\n59\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.    Patient demographics and baseline clinical \ncharacteristics\n\n\n\nFigure 1.    Comparison between the Body Surface Area involved with psoriasis \nbefore and during the maximum effect of Cyclosporine therapy \n\n\n\nCharacteristic\n\n\n\nMean age in years (range)\n\n\n\nMalay\n\n\n\nEthnic Chinese\n\n\n\nIndian\n\n\n\nM:F ratio\n\n\n\nDuration of Psoriasis (years)\n\n\n\nSeverity of Disease (mean BSA)\n\n\n\nPsoriatic arthropathy\n\n\n\nN=21\n\n\n\n40.1 (20-62)\n\n\n\n7 (33.3%)\n\n\n\n10 (47.6%)\n\n\n\n4 (19.0%)\n\n\n\n1:1.63\n\n\n\n12.1 (3-30)\n\n\n\n68.1 (3-100)\n\n\n\n13 (61.9%)\n\n\n\n\n\n\n\n\n60\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 2.    Side effects experienced by patients\n\n\n\nSide effects\n\n\n\nRaised serum creatinine >30% from baseline\n\n\n\nNew onset hypertension\n\n\n\nGastrointestinal upset\n\n\n\nGum hypertrophy\n\n\n\nHypertrichosis\n\n\n\nN (%)\n\n\n\n13 (61.9)\n\n\n\n5 (23.8)\n\n\n\n2 (9.5)\n\n\n\n3 (14.3)\n\n\n\n1 (4.8)\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\nTable 3.    Comparison of the use of Cyclosporine in Psoriasis between Skin clinic Hospital Ipoh Malaysia and\nother centers\n\n\n\nNumber of patients studied\n\n\n\nStudy period\n\n\n\nMean age (years)\n\n\n\nMean starting dose (mg/kg/d)\n\n\n\nMaximum dose (mg/kg/d)\n\n\n\nMaximal clinical response (month)\n\n\n\nTotal duration of treatment (month)\n\n\n\nNumber & percentage achieved improvement >50%\n\n\n\nNumber & percentage developed elevated serum\ncreatinine >30% from baseline\n\n\n\nNumber & percentage developed hypertension\n\n\n\nSpain\n2004\n\n\n\n53\n\n\n\n1992-1999\n\n\n\n44.49 (18-65)\n\n\n\n-\n\n\n\n3.0 (1-5)\n\n\n\n-\n\n\n\n31.4 (4-95)\n\n\n\n-\n\n\n\n6 (11.3)\n\n\n\n24 (45.3)\n\n\n\nNational Skin\nCenter Singapore\n\n\n\n2006\n\n\n\n18\n\n\n\n1999-2001\n\n\n\n45 (21-80)\n\n\n\n2.9 (1.3-4.3)\n\n\n\n3.6 (1.3-5.1)\n\n\n\n4.7 (1.5-9)\n\n\n\n8.7 (3-17)\n\n\n\n14 (77.8%)\n\n\n\n5 (27.7%)\n\n\n\n2 (11.1%)\n\n\n\nSkin Clinic\nHospital Ipoh\n\n\n\n2007\n\n\n\n21\n\n\n\nJan 1996-Jun 2007\n\n\n\n40.1 (20-62)\n\n\n\n2.8 (2.1-3.5)\n\n\n\n3.9 (2.9-5.3)\n\n\n\n2.96 (0.5-8.5)\n\n\n\n14.5 (3.75-28)\n\n\n\n17 (80.9%)\n\n\n\n13 (61.9%)\n\n\n\n5 (23.8%)\n\n\n\n\n\n\n\n\n61\n\n\n\ncountries (i.e. 61.9% in current study vs 27.7% in National\nSkin Center (NSC) Singapore2 vs 11.3% in Spain3) as\nshown in Table 3. As compared to NSC Singapore, our\nseries of patients had a higher rate of hypertension (11.1%\nvs 23.8%) while taking CyA. On the other hand, the\nSpanish study showed that 45.3% of their subjects\ndeveloped hypertension during CyA treatment. This could\nbe attributed to the longer duration of treatment (mean 31.4\nmonths).\n\n\n\nAs a result of the higher risk of renal impairment (raised\nserum creatinine of more than 30%) and new onset\nhypertension in local population, intermittent short course\nCyA as initiated by Berth-Jones in 1996 might be a better\napproach. In this regime, patients received CyA\n5mg/kg/day until achieving 90% reduction in area affected\nor for a maximum of 12 weeks. Those failing to demonstrate\na satisfactory response were withdrawn. When there was a\nrelapse of lesion 75% or more of affected area compared\nwith baseline, CyA was recommenced. This cycle was\nrepeated up to 3 times. Since then, few reports on the use of\nintermittent short course CyA at 2.5-5.0mg/kg/d had well\ndemonstrated that this regime is well tolerated and provides\neffective control of plaque psoriasis4,5,6,7. About 80-85%\ngraded overall response as considerable improvement in the\nstudies. The rate of renal impairment and new onset\nhypertension were 4.4-24% and 1.1-23.7% respectively.\n\n\n\nOther studies had shown that longer term use of CyA as\nmaintenance is indicated in a minority of patients with\nrecalcitrant disease8,9,10,11. In such cases dose should be\nadjusted to provide maximum clinical benefit and minimal\ndrug side effect. The dose should not exceed 5.0mg/kg/d\n(majority <3.5) and the duration of treatment is limited to 2\nyears or less. One retrospective analysis of long-term CyA\ntherapy for psoriasis (n=122) showed that the percentage of\npatients who discontinued CyA due to adverse events\nincreased from 14% at 12 months to 41% at 48 months12.\nReasons for discontinuation included renal dysfunction &\nhypertension (28% & 19% of all patients, respectively). Due\nto the risk of potentially serious cumulative toxicities,\ncurrent guidelines recommend that patients with psoriasis\nshould receive continuous CyA therapy for no more than 2\nyears13. Close monitoring of renal function and blood\npressure is needed. Dose reduction is required if serum\ncreatinine raised more than 30% from baseline (even though\nthe reading is still within normal range) or blood pressure\nrise more than 90mmHg diastolic or 140mHg systolic.\n\n\n\nWe encountered a patient who discovered carcinoma of the\nbreast 2 months after initiation of CyA. She was 62 years\nold and had suffered psoriasis for 13 years before starting\nCyA. Her previous treatment included NBUVB,\n\n\n\nmethotrexate, acitretin and sulfasalazine. We were unsure if\nthere was any family history of breast carcinoma. We believe\nthat the carcinoma of the breast could be a coincidental\nfinding rather than due to CyA therapy. A prospective long\nterm cohort study14 had shown that patients with psoriasis\ntreated with CyA have a significantly higher risk of non-\nmelanoma skin cancer compared with non-psoriatic\npopulation (RR 6:1). This increased risk is observed\nexclusively in patients who have been exposed previously to\nPUVA14,15. There is no significant increase in risk of non-\nskin cancer with CyA compared with general population.\nProlonged exposure to CyA (>2 yrs cumulative treatment)\nwas not associated with higher risk of non-skin cancer.\n\n\n\nLong term continuous cyclosporine is a highly effective\ntreatment modality for severe recalcitrant psoriasis in our\nexperience. However we observed a high rate of reversible\nrenal impairment and new onset hypertension. Furthermore\nrelapses occur frequently and rapidly after cessation\nof treatment. Therefore, intermittent short-course\ncyclosporine therapy could be used as a rapid induction of\nremission for severe psoriasis while another agent such as\nacitretin or narrow band UVB is added to maintain the\nremission. Close monitoring of serum creatinine and blood\npressure is mandatory.\n\n\n\nReferences\n\n\n\n1. Griffiths CEM et al. Ciclosporin in psoriasis clinical practice: an \ninternational consensus statement. Br J Dermatol 2004;\n150(Suppl.67) 11-23.\n\n\n\n2. Theng CTS, Khoo LSW. Ciclosporin in The Treatment Of Psoriasis \n- Our Experience At the National Skin Centre. Dermatology \nBulletin 2006; 17(2): 12-14.\n\n\n\n3. Garcia-Bustinduy M, Escoda M Guimera et al. Safety of long \nterm treatment with cyclosporin A in resistant chronic plaque \npsoriasis: a retrospective case series. JEADV 2004;18:169-172.\n\n\n\n4. Berth-Jones J, Henderson CA, Munro CS et al. Treatment of \npsoriasis with intermittent short-course cyclosporin (Neoral). A \nmulticentre study. Br J Dermatol 1997; 136:527-30.\n\n\n\n5. Ho VCY, Albrecht G, Vanaclocha F et al. Intermittent short \ncourses of cyclosporin (Neoral) for psoriasis unresponsive to \ntopical therapy: a 1-year multicentre, randomised study. Br J \nDermatol 1999; 141: 283-91.\n\n\n\n6. Ho VCY, Griffiths CEM, Berth-Jones J et al. Intermittent short \ncourses of cyclosporine microemulsion for the long-term \nmanagement of psoriasis: a 2-year cohort study. J Am Acad \nDermatol 2001; 44: 643-51.\n\n\n\n7. Faerber L, Braeutigam M, Weidinger G et al. Cyclosporine in \nsevere psoriasis: Results of a meta-analysis. Am J Clin Dermatol \n2001; 2: 41-7.\n\n\n\n8. Powles AV et al. Renal function after 10 years\u2019 treatment with \ncyclosprin for psoriasis. Br J Dermatol 1998; 138, 443-449.\n\n\n\n9. Powles AV et al. Four years of experience with cyclosporine a \nfor psoriasis. Br J Dermatol 1990; 122 (suppl 36), 13-19.\n\n\n\n10. Shupack j, Abel E et al. Cyclosporine as maintenance therapy in \npatients with severe psoriasis. J Am Acad Dermatol 1997; 36:423-\n432.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n62\n\n\n\n11. Mrowietz U, Ruzicka T. Cyclosporin A for psoriasis. Dermatol \nTher 1999; 11:60-6.\n\n\n\n12. Grossman RM et al. Long term safety of cyclosporine in the \ntreatment of psoriasis. Arch Dermatol 1996; 132: 623-629.\n\n\n\n13. Griffiths CEM et al. Ciclosporin in psoriasis clinical practice: an \ninternational consensus statement. Br J Dermatol 2004; 150 \n(suppl.67): 11-23.\n\n\n\n14. Paul CF, Ho VC, McGeown C et al. Risk of malignancies in \npsoriasis treated with cyclosporine: a 5-year cohort study. J \nInvest Dermatol 2003; 120: 211-6.\n\n\n\n15. Marcil I, Stern RS. Squamous-cell cancer of the skin in patients \ngiven PUVA and ciclosporin: nested cohort crossover study. \nLancet 2001; 358: 1042-5.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n63\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nPredictive values of 10% potassium hydroxide \nexamination for superficial fungal infection of the skin\n\n\n\nYap FBB MD MRCP, Wahiduzzaman M MBBS and Pubalan M MBBS MRCP\n\n\n\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\n\n\n\nCorrespondence\n\n\n\nDr Felix BB Yap MD, MRCP\n\n\n\nDepartment of Dermatology\nSarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\nEmail: woodzlamp@yahoo.com\n\n\n\nAbstract\n\n\n\nIntroduction Ten percent potassium hydroxide examination is one of\nthe most frequently performed tests in dermatology. It is usually\nsupplemented by fungal culture for detection of superficial fungal\ninfection of the skin and its appendages. We aim to determine the\npredictive values of 10% potassium hydroxide examination in Sarawak\nGeneral Hospital.\n\n\n\nMaterials and Methods A retrospective review of 292 skin scraping\nresults for 10% potassium hydroxide examination and culture was done\nbetween October 2003 and December 2004. Data for all the scrapings\nwere analysed for predictive values, specificity, sensitivity and likelihood\nratio with fungal culture as the gold standard investigation. Separate\ndata analysis was done for those with onychomycosis.\n\n\n\nResults Positive cultures were noted in 80.8% of skin scrapping cases\nand 85.4% of onychomycosis cases. For the skin scrapping cases, the\npositive predictive value of 10% potassium hydroxide examination was\n67.4%, negative predictive value of 16.9%, sensitivity of 12.3% and\nspecificity of 75%. For those with onychomycosis, the positive\npredictive value was 75%, negative predictive value 13.6%, specificity\n85.7% and sensitivity was 7.3%. The positive likelihood ratio for all\ncases and onychomycosis cases was 0.5 whereas the negative likelihood\nratio was 0.9.\n\n\n\nConclusion Ten percent potassium hydroxide examination has a very\nlow negative predictive value and sensitivity, making it a poor\ninvestigative tool in Sarawak General Hospital. Thus, culture of the\nskin scraping for suspected superficial fungal infection of the skin and\nits appendages is of utmost importance. Steps to improve the quality of\n10% potassium hydroxide examination are important as it is an easy\nand inexpensive test.\n\n\n\nKeywords 10% potassium hydroxide examination, fungal culture,\npredictive values. Financial interests: Nil\n\n\n\nIntroduction\nTen percent potassium hydroxide examination is one of the\nmost frequently performed tests in dermatology. This office\nbased investigative tool allows direct visualization of fungal\nhyphae in keratinized material of the stratum corneum1. It\nis a rapid and inexpensive test. However, it is operator\ndependent and can be influenced by topical treatment.\n\n\n\nIn cases with high suspicion of fungal infection but negative\n10% potassium hydroxide examination, culture of the\nspecimen is usually done.\n\n\n\nTen percent potassium hydroxide examinations and fungal\ncultures are commonly performed among patients with\nsuperficial fungal skin infection and its appendages\nattending the Skin Clinic in Sarawak General Hospital.\nThus, we aim to determine the predictive value of 10%\npotassium hydroxide examination in Sarawak General\nHospital.\n\n\n\nMaterials and methods\nA retrospective review of all the suspected fungal infections\nof the skin and its appendages between October 2003 and\nDecember 2004 in the Skin Clinic, Sarawak General\nHospital was done. Data regarding fungal culture and 10%\npotassium hydroxide examination of the skin and its\nappendages was collected from the central laboratory. Data\nof patients with onychomycosis was extracted from the\npooled data for further analysis.\n\n\n\nAll the specimens collected were subjected to both 10%\npotassium hydroxide examination and fungal culture. The\n10% potassium hydroxide examination and fungal culture\nwas done by trained microbiology technicians.\n\n\n\n\n\n\n\n\n64\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe gold standard test for fungal detection was fungal\nculture in this study. The aim was to determine the\npredictive values for 10% potassium hydroxide compared to\nfungal culture.\n\n\n\nData collected was compiled into the Microsoft Excel\nspreadsheet and subjected to descriptive analysis.\n\n\n\nResults\nFrom October 2003 to December 2004, we collected 292\nscrapings for suspected fungal infection of the skin and its\nappendages. Tables 1 and 2 showed the results for the 10%\npotassium hydroxide examination and culture whereas Table\n3 showed the type of fungus cultured.\n\n\n\nTwo hundred and thirty six cases (80.8%) had a positive\nfungal culture. Of these, 41.5% was Trichophyton, 29.7%\nCandida albicans and 19.1%Microsporum. No\nEpidermophyton was cultured during this period.\n\n\n\nThe 10% potassium hydroxide examination gave a positive\npredictive value of 67.4% and a negative predictive value of\n16.9%. The sensitivity was 12.3% with a specificity of 75%.\nThe positive likelihood ratio was 0.5 whereas the negative\nlikelihood ratio was 0.9.\n\n\n\nFor onychomycosis, 85.4% of the samples had a positive\nfungal culture. Candida albicans was the most frequently\nseen with 46.3%, followed by Trichophyton 39.1% and\nMicrosporum 7.3%.\n\n\n\nTable 1.   Culture and 10% potassium hydroxide examination results\nfor all the cases\n\n\n\nPositive\n\n\n\nNegative\n\n\n\nTotal\n\n\n\n10% potassium \nhydroxide\nexamination\n\n\n\nPositive\n\n\n\n29\n\n\n\n207\n\n\n\n236\n\n\n\nNegative\n\n\n\n14\n\n\n\n42\n\n\n\n56\n\n\n\nTotal\n\n\n\n43\n\n\n\n249\n\n\n\n292\n\n\n\nCulture\n\n\n\nTable 2.   Culture and 10% potassium hydroxide examination results for \nonychomycosis\n\n\n\nPositive\n\n\n\nNegative\n\n\n\nTotal\n\n\n\n10% potassium \nhydroxide\nexamination\n\n\n\nPositive\n\n\n\n3\n\n\n\n38\n\n\n\n41\n\n\n\nNegative\n\n\n\n1\n\n\n\n6\n\n\n\n7\n\n\n\nTotal\n\n\n\n4\n\n\n\n44\n\n\n\n48\n\n\n\nCulture\n\n\n\nTable 3.   Types of fungi grown\n\n\n\nFungus\n\n\n\nTrichophyton\n\n\n\nMicrosporum\n\n\n\nCandida albicans\n\n\n\nAspergillus\n\n\n\nPenicillium\n\n\n\nSuperficial skin\nand its appendages\n\n\n\n98 (41.5%)\n\n\n\n45 (19.1%)\n\n\n\n70 (29.7%)\n\n\n\n18 (7.6%)\n\n\n\n5 (2.1%)\n\n\n\nOnychomycosis\n\n\n\n16 (39.1%)\n\n\n\n3 (7.3%)\n\n\n\n19 (46.3%)\n\n\n\n1 (2.4%)\n\n\n\n2 (4.9%)\n\n\n\nSuperficial skin\n\n\n\n82 (42.1%)\n\n\n\n42 (21.6%)\n\n\n\n51 (26.1%)\n\n\n\n17 (8.7%)\n\n\n\n3 (1.5%)\n\n\n\n\n\n\n\n\n65\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe 10% potassium hydroxide examination gave a\nsensitivity of 7.3%, specificity of 85.7%, positive predictive\nvalue of 75% and negative predictive value of 13.6%. The\npositive likelihood ratio was 0.5 and the negative likelihood\nratio was 0.9.\n\n\n\nDiscussion\nSensitivity of 10% potassium hydroxide examination was\nreported to range from 77% to 88%, and the specificity from\n62% to 95%2,3. Our sensitivity for the 10% potassium\nhydroxide examination was very low at 12.3%. However our\nspecificity of 75% was within the range.\n\n\n\nThe positive predictive value ranges from 59% to 73% and\nnegative predictive value ranges from 79% to 98%2,3. We\nnoted that our negative predictive value of 16.9% was far\nbelow this range.\n\n\n\nWe noted a 33.6% false positive rate with an 83.1% false\nnegative rate for the 10% potassium hydroxide examination.\nThis rate is higher than the normally reported 5% to 15%\nfalse positive rate reported elsewhere4. The high false\nnegative rate explained the low sensitivity and negative\npredictive value in our study. This low pick up by the 10%\npotassium hydroxide examination might be due to poor\npreparation or examination technique by the technicians.\n\n\n\nIn Tehran, Karemzadegan-Nia noted that the sensitivity of\n10% potassium hydroxide examination for onychomycosis\nwas 76.5%, not statistically different from the 80.8%\nsensitivity of histological examination5. We noted a\nsensitivity of only 7.3% and a negative predictive value of\n13.6%. This again is due to the high false negative result of\n86.4%.\n\n\n\nTo improve the 10% potassium hydroxide examination for\nscraping in Sarawak General Hospital, training of the\nlaboratory technicians for proper preparation and\nmicroscopic examination is essential. Besides that, doctors\nsending patients for this examination should also ensure\nthat these patients have not applied any topical antifungal\non the lesions as this will negatively affect the examination.\nImproving this examination is essential as it is a fast and\ncheap investigative tool.\n\n\n\nIn New Delhi, Das and colleagues noted that Trichophyton\nwas the major fungus isolated with over 70% of cases; with\nCandida only contributing 16% of isolates6. We also noted a\npredominance of dermatophytes especially Trichophyton\nbut with a higher yield of Candida with 33.6%.\n\n\n\nDermatophytes especially Trichophyton and yeasts are the\npredominant cause of onychomycosis7,8. We noted\npredominant Candida infection among our patients with\nonychomycosis.\n\n\n\nOur mycologic culture results are similar to that observed\nwith other parts of Asia mainly South and Mideastern Asia.\n\n\n\nWe would like to conclude that 10% potassium hydroxide\nexamination has a high positive predictive value but a very\nlow negative predictive value and sensitivity, making it a\npoor investigative tool in Sarawak General Hospital. Thus,\nculture of the suspected fungal infection of the skin and its\nappendages is of utmost importance. Proper training of the\nlaboratory technicians performing the 10% potassium\nhydroxide examination is needed to improve the quality of\nthe examination.\n\n\n\nReferences\n\n\n\n1. Thomas B. Clear choices in managing epidermal tinea \ninfections. J Fam Pract 2003; 52: 850-62. \n\n\n\n2. Haldane DJ, Robart E. A comparison of calcofluor white, \npotassium hydroxide, and culture for the laboratory diagnosis of \nsuperficial fungal infection. Diagn Microbiol Infect Dis 1990;\n13: 337-339. \n\n\n\n3. Miller MA, Hodgson Y. Sensitivity and specificity of potassium \nhydroxide smears of skin scrapings for the diagnosis of tinea \npedis. Arch Dermatol 1993; 129: 510-511.\n\n\n\n4. Panasiti V, Borroni RG, Devirgiliis V, Rossi M, Fabbrizio L, \nMasciangelo R et al. Comparison of diagnostic methods in the \ndiagnosis of dermatomycoses and onychomycoses. Mycoses \n2006; 49: 26-9.\n\n\n\n5. Karimzadegan-Nia M, Mir-Amin-Mohammadi A, Bouzari N, Firooz \nA. Comparison of direct smear, culture and histology for the \ndiagnosis of onychomycosis. Australas J Dermatol 2007;\n48: 18-21.\n\n\n\n6. Das S, Goyal R, Bhattacharya SN. Laboratory-based \nepidemiological study of superficial fungal infections. J Dermatol \n2007; 34: 248-53. \n\n\n\n7. Gupta M, Sharma NL, Kanga AK, Mahajan VK, Tegta GR. \nOnychomycosis: Clinico-mycologic study of 130 patients from \nHimachal Pradesh, India. Indian J Dermatol Venereol Leprol \n2007; 73: 389-92.\n\n\n\n8. El Sayed F, Ammoury A, Haybe RF, Dhaybi R. Onychomycosis in \nLebanon: a mycological survey of 772 patients. Mycoses 2006;\n49: 216-9.\n\n\n\n\n\n\n\n\n66\n\n\n\n\n\n\n\n\n67\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nEpidemiological characteristics of common secondary \nbacterial skin infection from patients with atopic\ndermatitis\n\n\n\nS T Sim1, H B B Foong2 MBBS FRCP and E M Taylor2 MBBS GDFPD \n\n\n\n1Medical Student (Phase 3A)\nUnikl Royal College of Medicine Perak, Ipoh, Malaysia\n2Foong Skin Specialist Clinic, 33A Persiaran Pearl\n31400 Ipoh, Malaysia\n\n\n\nCorrespondence\n\n\n\nHenry B B Foong MBBS FRCP\n\n\n\nFoong Skin Specialist Clinic\n33A Persiaran Pearl, 31400 Ipoh, Malaysia\nEmail: bbfoong@pc.jaring.my\n\n\n\nAbstract\n\n\n\nIntroduction Atopic dermatitis (AD) is a chronic, highly pruritic,\ninflammatory skin disease that often has a remitting and flaring course,\nwhich may be exacerbated by social, environmental, and biological\ntriggers. The estimated incidence of AD in the general population\nvaries between 1% and 5%. Because of compromised skin barrier, AD\nsufferers frequently develop recurrent bacterial skin infections. These\ninfections can also worsen the disease. The aim of this study is to\nestablish the common types of bacteria found in secondarily infected\nAD patients who attended Foong Skin Specialist Clinic in year 2005-\n2007.\n\n\n\nMaterials and Methods A retrospective study is conducted among\nall the patients with AD who are seen at the Foong Skin Specialist\nClinic in year 2005-2007. Cultures were collected from all AD patients\nwith secondarily infected AD lesions. All their clinical and\nmicrobiology laboratory results are recorded and data obtained from\nthese patients whose specimens of infected sites were processed for the\npresence of types of bacteria.\n\n\n\nResults Out of 52 specimens with an equal sex ratio, 43 (82.7%) of\nthem were positive cultures and among these secondarily infected AD\npatients, 69.2% of them were infected with Staphylococcus aurues and\n61.9% of Staphylococcus aurues were resistant to Penicillin.\n\n\n\nConclusion We found that majority of the AD patients who are\nclinically diagnosed with secondary bacterial infection have positive\ncultures of bacteria and the most common organism isolated from\neczematous lesion at all sites of body is Staphylococcus aureus which is\nconsistent with the results reported by most previous studies. In terms\nof antibiotic sensitivity, more than half (61.9%) of the Staphylococcus\naureus infected AD patients are found resistant to penicillin in this\nstudy which is considered relatively low as compared to previous studies\n(>80%).\n\n\n\nKeywords Atopic dermatitis, bacterial infection, antibiotic sensitivity\n\n\n\nIntroduction\nAtopic dermatitis (AD) is a chronic inflammatory\ngenetically determined disease of the skin marked by\nincreased ability to form reagin (IgE), with increased\nsusceptibility to allergic rhinitis and asthma, and hereditary\ndisposition to a lowered threshold for pruritus1. The\nestimated incidence of atopic eczema in the general\npopulation varies between 1% and 5%2. Over the past few\ndecades there has been a steady increase worldwide in the\nincidence of this disorder3. In Malaysia, 3.7% of the general\npopulation are diagnosed with atopic dermatitis with the\nhighest prevalence among the Malay with the prevalence of\n4.3%4.\n\n\n\nThe pathogenesis of AD is multifactorial; resulting from an\ninteraction between genetic susceptibility, the host's\nenvironment, skin barrier defects and immunological\nfactors5. The condition is characterized by intense pruritus\nand a course marked by exacerbations and remissions6. AD\nis associated with other atopic diseases such as allergic\nrhinitis, bronchial asthma7 and 60% of patients develop AD\nwithin the first year of life, 85% by age 58. Although it is an\ninherited disease, eczema is primarily aggravated by contact\nwith or intake of allergens. It can also be influenced by other\nfactors such as stress or fatigue9. The rapid rise in prevalence\nof AD is thought to be primarily related to changes in our\nenvironment10.\n\n\n\nAtopic dermatitis patients are particularly prone to skin\ninfections11. The percentage of positive culture from skin\nswab of AD patients is more than 90%3,4,8,10,12,13. Heightened\nsusceptibility occurs because the skin of patients with AD\nhas a defective barrier against organisms, depressed immune\nfunction and lacks normal lipophilic bacteria6. As a result\nAD\n\n\n\n\n\n\n\n\n68\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAD patients frequently suffer from boils, folliculitis and\ninfected eczema. The infection causes the eczema to worsen\nand become more resistant to the usual treatment with\nemollients and topical steroids. Antibiotics are often\nrequired to eliminate the infection and control the eczema11.\n\n\n\nThe bacteria that cause infection are also commonly found\non healthy skin like staphylococci and streptococci12,\nEscherichia coli, Enterobacter sp., Klebsiella sp.,\nAcinetobacter sp., Proteus sp14. Coagulase-positive\nstaphylococci (Staph. aureus), which are usually not found\non normal skin, accounted for the majority of organism\nisolated from AD patients\u2019 skin15. According to a study done\nby Donald Leung et al. in London in 2003, Staphylococcus\naureus were found in over 90% of AD skin lesions5. Staph.\nepidermidis which is the predominant organism isolated\nfrom the clinically uninvolved skin of AD patients, was\nsecond to Staph. aureus to be found in lesional skin16. In a\nstudy done by Ihsan et al. in Iraq showed that the\nStaphylococcus epidermidis consisted of 17.13% of bacteria\nisolated from eczematous lesions of 284 AD patients10.\n\n\n\nIn patients with atopic dermatitis, all isolates of  S. aureus\nwere sensitive to cloxacillin, cephalexin, clindamycin, and\nco-trimoxazole; 92% was sensitive to erythromycin, but only\n13% was sensitive to penicillin and ampicillin. As 87% of S.\naureus is resistant to penicillin and ampicillin, antibiotics\nsuch as cloxacillin and cephalexin should be used to\neradicate S. aureus in the skin of atopic dermatitis\nindividuals17.\n\n\n\nTo date there are very few studies conducted specifically on\ncommon secondary bacterial infection of AD patients in\nMalaysia, especially in Ipoh. In view of that, this study is\naimed at determining the bacterial types of each eczematous\n\n\n\nlesion from patients\u2019 skin with AD as well as to\ncorrelate them with the sociodemographic data. Since\nStaphylococcus aureus is the most common organism\nisolated from AD patients according to previous study,\nantibiotic sensitivity of Staphylococcus aureus infection\namong AD patients was determined in this study.\n\n\n\nMaterials and methods\nA retrospective descriptive cross-sectional study was\nconducted among all the patients with AD complicated by\nsecondary bacterial infection over affected skin lesions who\nattended Foong Skin Specialist Clinic in year 2005-2007.\nPatients\u2019 medical records were reviewed for basic\ndemographics, clinical diagnosis and bacteriological culture\nresults. Specimens for bacteriological examination and\nculture were obtained by a sterile swab from the affected\nskin areas of AD patients. SPSS Student version 11.5 was\nused for statistical analysis. Descriptive analysis was done on\neach variable. Chi Square test was employed to compare the\nqualitative data; while Student\u2019s t-test was used to compare\nthe quantitative data, with p value less than 0.05 considered\nas significant.\n\n\n\nResults\nA total of 52 specimens were collected from the patients\nduring the study. 26 women and 26 men were enrolled in\nthe study. The age ranges from 2-80 years with a mean of 22\nyears.\n\n\n\nOut of 52 patients, 43 patients (82.7%) were confirmed to\nhave secondary skin infection by skin swab. The remaining\n9 patients (17.3%) showed negative results on skin swab\nculture. 36 patients (69.2%) were infected with a single type\nof bacteria, compared to 7 patients (13.5%) who had\nmultiple infections.\n\n\n\nFigure 1.   Distribution of patients according to site of swab\n\n\n\nFigure 1 shows the distribution of respondents in relation to site of swab. Most swabs were done on the lower limb 57.7%\n(n=30). This is followed by trunk 15.4% ( n=8). face 13.5% ( n=7), upper limb 7.7% ( n=4) and scalp 5.8% ( n=3).\n\n\n\nP\ner\n\n\n\nce\nn\n\n\n\nta\ng\n\n\n\ne\n\n\n\n\n\n\n\n\nTable 1 shows the comparison between age groups, gender\nand type of infections. Out of 43 patients with secondary\nbacterial infections, 23 (53.5%) were male, and 20 (46.5%)\nwere female. Female of school going age group had the\nhighest infective rate, with 100% (10/10) shown to be\ninfected. This is followed by adult male (90%) and male of\nschool going age (80%).\n\n\n\nIn terms of type of infections, majority of infections were\ncaused by Staph. aureus, representing 69.2% (n=36). Adult\nmale has the highest prevalence of Staph. aureus infection\nwith 16 infected individuals, followed by schooling female\n(9 infected individuals) and adult female (6 infected\nindividuals). Pseudomonas aeruginosa infection is the second\nhighest with 9.6% (n=5). Strep. pyogenes and Enterococcus\nfaecalis each has three infections (5.8%). Group B\nstreptococci and Staph. epidermidis comprising only the\nminority, with 3.8% (n=2) and 1.9% (n=1) respectively.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nBacteria\n\n\n\nNo. examined\n\n\n\nNon-infected\n\n\n\nInfected\n\n\n\nBacteria\n\n\n\nS. aureus\n\n\n\nS. epidermidis\n\n\n\nS. pyogenes\n\n\n\nGroup B \nStreptococcus\n\n\n\nP. aeruginosa\n\n\n\nE. faecalis\n\n\n\nTotal\n\n\n\n52\n\n\n\n9 (17.3%)\n\n\n\n43 (82.7%)\n\n\n\n36 (69.2%)\n\n\n\n1 (1.9%)\n\n\n\n3 (5.8%)\n\n\n\n2 (3.8%)\n\n\n\n5 (9.6%)\n\n\n\n3 (5.8%)\n\n\n\nMale\n\n\n\n1\n\n\n\n0 (0.0%)\n\n\n\n1 (100.0%)\n\n\n\n1 (100.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\nFemale\n\n\n\n2\n\n\n\n1 (50.0%)\n\n\n\n1 (50.0%)\n\n\n\n1 (50.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\nMale\n\n\n\n5\n\n\n\n1 (20%)\n\n\n\n4 (80%)\n\n\n\n3 (60.0%)\n\n\n\n0 (0.0%)\n\n\n\n1 (20%)\n\n\n\n0 (0.0%)\n\n\n\n1 (20%)\n\n\n\n0 (0.0%)\n\n\n\nFemale\n\n\n\n10\n\n\n\n0 (0.0%)\n\n\n\n10 (100.0%)\n\n\n\n9 (90.0%)\n\n\n\n0 (0.0%)\n\n\n\n1 (10.0%)\n\n\n\n0 (0.0%)\n\n\n\n1 (10.0%)\n\n\n\n0 (0.0%)\n\n\n\nMale\n\n\n\n20\n\n\n\n2 (10%)\n\n\n\n18 (90%) \n\n\n\n16 (80%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n2 (10%)\n\n\n\n2 (10%)\n\n\n\nFemale\n\n\n\n14\n\n\n\n5 (35.7%)\n\n\n\n9 (64.3%)\n\n\n\n6 (42.9%)\n\n\n\n1 (7.1%)\n\n\n\n1 (7.1%)\n\n\n\n2 (14.3%)\n\n\n\n1 (7.1%)\n\n\n\n1 (7.1%)\n\n\n\nTable 1.    Comparison between age groups, gender and type of infections. Age is categorized into adult\n(19 year-old and above), schooling (6 to 18 year-old) and pre-schooling (5 year-old and below) groups\n\n\n\nPre-School Schooling\n\n\n\nAge Groups\n\n\n\nAdult\n\n\n\nNumber of bacterial infections\n\n\n\nSpecimens with:\n\n\n\n1. bacteria infection\nStaph aureus\nStaph epidermidis\nStrep. pyogenes\nGroup B Streptococcus\nPseudomonas aeruginosa\nEnterococcal faecalis\nTotal specimens with only one infection\n\n\n\n2. bacteria infections\nStaph. aureus + P.aeruginosa\nStaph. aureus + Strep. pyogenes\nStaph. aureus + E. faecalis\nStaph. epidermidis + E. faecalis\nP. aeruginosa + E. faecalis\nTotal specimens with only two infections\n\n\n\nNumber examined\n\n\n\n31\n0\n1\n2\n2\n0\n\n\n\n36\n\n\n\n2\n2\n1\n1\n1\n7\n\n\n\nTable 2.    Multiplicity of infections\n\n\n\n69\n\n\n\n\n\n\n\n\n70\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 2 displays the multiplicity of infections among\npatients with atopic dermatitis. Majority of patients have\nonly one infection. 67.9% (n=36). Staph. aureus tops the list\nwith 31 patients being infected, while Group B streptococci\nand Pseudomonas aeruginosa have infected two patients\nrespectively. One patient is infected by Strep. pyogenes. Skin\nspecimens from seven patients showed multiple infections.\nThe common combinations of bacteria are Staph. aureus\nwith Pseudomonas aeruginosa and Staph. aureus with Strep.\n\n\n\npyogenes. Other combinations include: Staph. aureus with E.\nfaecalis; S. epidermidis with E. faecalis and P. aeruginosa with\nE. faecalis.\n\n\n\nAssociation between number of infection and age group is\nnot significant statistically since p=0.656. Similar result is\nobtained when associating number of infection with gender\n(p=0.452), hence difference in number of infection between\nmale and female was statistically insignificant.\n\n\n\nAntibiotics\n\n\n\nAugmentin\n\n\n\nCefuroxime\n\n\n\nErythromycin\n\n\n\nFusidic Acid\n\n\n\nMethicilin\n\n\n\nPenicillin\n\n\n\nTetracyclin\n\n\n\nVancomycin\n\n\n\nTotal\n\n\n\nStatus\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nNot Done\nSensitive\nResistant\n\n\n\nPre-school\n\n\n\n0 (0.0%)\n1 (2.8%)\n1 (2.8%)\n\n\n\n0 (0.0%)\n1 (2.8%)\n1 (2.8%)\n\n\n\n0 (0.0%)\n2 (5.6%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n1 (2.8%)\n1 (2.8%)\n\n\n\n0 (0.0%)\n2 (5.6%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n0 (0.0%)\n2 (5.6%)\n\n\n\n0 (0.0%)\n2 (5.6%)\n0 (0.0%)\n\n\n\n1 (2.8%)\n1 (2.8%)\n0 (0.0%)\n\n\n\n2 (5.6%)\n\n\n\nSchooling\n\n\n\n1 (2.8%)\n11 (30.6%)\n0 (0.0%)\n\n\n\n1 (2.8%)\n11 (30.6%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n10 (27.8%)\n2 (5.6%)\n\n\n\n0 (0.0%)\n10 (27.8%)\n2 (5.6%)\n\n\n\n0 (0.0%)\n12 (33.3%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n2 (5.6%)\n\n\n\n10 (27.8%)\n\n\n\n0 (0.0%)\n9 (25.0%)\n3 (8.3%)\n\n\n\n1 (2.8%)\n11 (30.6%)\n0 (0.0%)\n\n\n\n12 (33.3%)\n\n\n\nAdult\n\n\n\n7 (19.4%)\n15 (41.7%)\n0 (0.0%)\n\n\n\n6 (16.7%)\n16 (44.4%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n17 (47.2%)\n5 (13.9%)\n\n\n\n0 (0.0%)\n22 (61.1%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n22 (61.1%)\n0 (0.0%)\n\n\n\n0 (0.0%)\n3 (8.3%)\n\n\n\n19 (52.8%)\n\n\n\n0 (0.0%)\n16 (44.4%)\n6 (16.7%)\n\n\n\n1 (2.8%)\n21 (58.3%)\n0 (0.0%)\n\n\n\n22 (61.1%)\n\n\n\nTotal\n\n\n\n8 (22.2%)\n27 (75.0%)\n1 (2.8%)\n\n\n\n7 (19.4%)\n28 (77.8%)\n1 (2.8%)\n\n\n\n0 (0.0%)\n29 (80.6%)\n7 (19.4%)\n\n\n\n0 (0.0%)\n33 (91.7%)\n3 (8.3%)\n\n\n\n0 (0.0%)\n36 (100.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n5 (13.9%)\n31 (86.1%)\n\n\n\n0 (0.0%)\n27 (75.0%)\n9 (25.0%)\n\n\n\n3 (8.3%)\n33 (91.7%)\n0 (0.0%)\n\n\n\n36 (100%)\n\n\n\np-value\n\n\n\n0.001*\n\n\n\n0.001*\n\n\n\n0.707\n\n\n\n0.022\n\n\n\n-\n\n\n\n0.818\n\n\n\n0.695\n\n\n\n0.084\n\n\n\nTable 3.    Comparison between age groups and antibiotic sensitivity to Staph. aureus\n\n\n\nAge Groups\n\n\n\n\n\n\n\n\n71\n\n\n\nTable 3 shows the cross-tabulation between age groups with\nantibiotic sensitivity to Staphylococcus aureus. Out of 33\nindividuals infected with S. aureus, penicillin shows highest\nincidence of resistance (86.1%), followed by tetracycline\n(25%), erythromycin (19.4%), fusidic acid (8.3%),\naugmentin (2.8%) and cefuroxime (2.8%). There is no\nmethicilin-resistant S. aureus (MRSA) or vancomycin-\nresistant S. aureus (VRSA) infections in this population.\n\n\n\nIn term of age groups, adult has the highest infective rate\n(22 out of 36 patients), followed by schooling and pre-\nschool age groups. Among adult patients, S. aureus is most\nsensitive against methicilin, vancomycin, fusidic acid,\ncefuroxime and augmentin. Erythromycin and tetracycline\nare less sensitive, while penicillin is almost not effective.\nSchool age group had almost similar profile as adults. Pre-\nschool age group had higher resistant rate to most antibiotic\n\n\n\nthan other age groups. Augmentin, cefuroxime and fusidic\nacid are all less effective among pre-school patients while\nmethicilin and vancomycin remain resistance-free.\n\n\n\nDiscussion\nAtopic dermatitis is a chronic relapsing, pruritic\ninflammation of the skin, affecting 10-20% of children and\n1-3% adults worldwide, with increasing prevalence in highly\nindustrialized countries18. In Malaysia, it is estimated that\none-third of the population is currently suffering from some\nform of allergy. A study by Jaafar et al4 in 1993 reported that\nout of 13,524 patients, 4.3% was noted to be affected by\natopic dermatitis and Malays were the highest affected\namong all races. If this trend continues, by the year 2020 it\nis expected that half of the population will be involved.\nHowever, allergy is still not accorded the attention and\npriority that it needs19.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nPrevalence in this\nstudy (%)\n\n\n\nMarwa Abdullah et. al.\n(2007, Egypt)20\n\n\n\nIhsan et al.\n(2006, Iran)10\n\n\n\nJQ. Gong et al.\n(2006, China)21\n\n\n\nYong Kwang Tay et al.\n(1999, Singapore)3\n\n\n\nMustafa et al.\n(1996, Malatya)22\n\n\n\nSample size\n\n\n\n52\n\n\n\n37\n\n\n\n40\n\n\n\n119\n\n\n\n492\n\n\n\n60\n\n\n\nStaph.\naurues\n\n\n\n69.2%\n\n\n\n37\n\n\n\n40\n\n\n\n119\n\n\n\n492\n\n\n\n60\n\n\n\nStaph.\nepidermidis\n\n\n\n1.9%\n\n\n\nN/A\n\n\n\n17.2%\n\n\n\n38.4%\n\n\n\n5.0%\n\n\n\nN/A\n\n\n\nS. pyogenes\n\n\n\n5.8%\n\n\n\n40.0%\n\n\n\n17.1%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\n3.3%\n\n\n\nGroup B\nStreptococci\n\n\n\n3.8%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\n4.1%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nP.\naeruginosa\n\n\n\n9.6%\n\n\n\nN/A\n\n\n\n17.5%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nE.faecalis\n\n\n\n5.8%\n\n\n\n20.0%\n\n\n\n23.1%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nTable 4.    Comparison of infection prevalence with previous studies\n\n\n\nBacterial\n\n\n\nPrevalence in Other Studies (%)\n\n\n\nMost previous studies reported that Staph. aureus is the most\ncommon organism isolated from atopic dermatitis skin\nlesion3,8,10,12,20-22. Staph. epidermidis, Strep. pyogenes,\nEnterococcus faecalis and Pseudomonas aeruginosa infections\nare other common organisms throughout literature review.\nHowever, Staph. epidermidis infection is relatively\nuncommon in this study with only one patient infected\n(1.9%).\n\n\n\nAntibiotic sensitivity profile of Staph. aureus in this study is\ncompared with the literature and tabulated below. It is\nnoted that penicillin has the highest resistance among all\nantibiotics in this study as well as various previous studies.\nCommonly used macrolides such as erythromycin is also\nshown to have high resistant rate ranging from 19.2% to\n77%. Hence, it is recommended that penicillinase-resistant\npenicillin (dicloxacillin, oxacillin, or cloxacillin) and first-\ngeneration cephalosporins might be preferred in the\nmanagement of secondarily infected atopic dermatitis5.\n\n\n\n\n\n\n\n\n72\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nStaph. aureus is recognized as an important triggering factor\nfor the maintenance of skin inflammation and acute\nexacerbations of the genetically determined skin disease\nsuch as atopic dermatitis23-24. Breuer K. et al (2000)25\n\n\n\ndemonstrated that the colonization density of eczematous\nlesions can reach up to 107 CFU/cm2. Many modern\nstudies illustrated the factors whose relevance to the\nincreased colonization of atopic dermatitis skin with Staph.\naureus such as ability to produce exotoxins, ability of bacteria\nto adhere to host cells and optimal pH activity10. Another\nresearch reported that up of 65% of all Staph. aureus strains\nisolated from skin lesion have been shown to produce\nexotoxins with superantigenic properties26.\n\n\n\nFrom this study, we found that majority of the AD patients\nwho were clinically diagnosed with secondary bacterial\ninfection had positive cultures of bacteria. The most\ncommon organism isolated from eczematous lesion at all\nsites of body was Staphylococcus aureus. This result is similar\nto those of the previous studies conducted in various parts\nof the world including developed and developing countries.\nHence antibiotics may have a role in the treatment of atopic\ndermatitis. Although the prevalence of resistance of\nStaphylococcus aureus to Penicillin is relatively low compared\nto previous studies, more than half of the Staphylococcus\naureus infected AD patients were found resistant to\npenicillin in this study. Thus, antibiotics such as cloxacillin\nand cephalexin should be used to eradicate Staphylococcus\naureus in the skin of atopic dermatitis individuals.\n\n\n\nTherefore, further studies on a large scale to estimate the\nexact incidence of the different bacterial organisms found in\nsecondary infection of AD patients as well as bacterial\nculture of specimens should be performed to confirm the\nbacterial etiology so that suitable treatment can be provided.\n\n\n\nIn order to limit the misuse of antimicrobials and prevent\nemergence of resistant bacterial strains, antimicrobial\nsusceptibility testing should be considered when prescribing\nantimicrobial therapy.\n\n\n\nAdvances are likely to need better definitions for the various\nclinical phenotypes of atopic dermatitis, a better\nunderstanding of the immunoregulatory abnormalities\nunderlying it, and new paradigms for preventing relapses of\nthis skin disorder. Recently fillagrin gene mutation mapped\nat the loci 1q21 is responsible for the skin barrier defect.\nSuch advances may lead to the development of\npharmacogenetics and targeting of effective treatments to\nsubsets of patients with atopic dermatitis.\n\n\n\nAcknowledgement\n\n\n\nThe authors would like to thank Dr. Subramania Aiyer,\nAssociate Professor in Microbiology, Department of\nMicrobiology Royal College of Medicine Perak and co-\nsupervisor of the project, for his advice and help throughout\nthe study.\n\n\n\nReferences\n\n\n\n1. Guzman MG  APEC Emerging Infections Network. 2007 \n(http://www.eduserv.hscer.washington.edu/dermUW/lang/\nterm2.html)\n\n\n\n2. Motala C. Atopic Dermatitis. Allergy Soc S Afr :1\n3. TayYK, Khoo BP, Goh CL The profile of atopic dermatitis in a \n\n\n\ntertiary dermatology outpatient clinic in Singapore. Int J \nDermatol 1999:38 (9), 689-692.\n\n\n\n4. Jaafar RB, Pettit JH Atopic eczema in a multiracial country \n(Malaysia). Clin  Exp Dermatol 1993:18 (6), 496-499\n\n\n\n5. Leung DY, Bieber T; Atopic Dermatitis; Lancet2003. Jan 11; \n361(9352); 151-60\n\n\n\n6. Correale CE, Walker C, Murphy L, Craig TJ, Atopic Dermatitis:\nA Review of Diagnosis and Treatment; Am Fam Physician 1999 \nSept 15;60(4): 1191-8\n\n\n\nPrevalence in this\nstudy (%)\n\n\n\nMarwa Abdullah et. al\n(2007, Egypt)20\n\n\n\nBrook I et al.\n(1996, LA)23\n\n\n\nMustafa et al.\n(1996,Malatya)22\n\n\n\nErythromycin\n\n\n\n19.2%\n\n\n\n77.0%\n\n\n\n35.9%\n\n\n\nN/A\n\n\n\nFusidic\nAcid\n\n\n\n7.7%\n\n\n\n12.9%\n\n\n\n22.6%\n\n\n\nN/A\n\n\n\nMethicillin\n\n\n\n1.9%\n\n\n\n9.7%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nPenicillin\n\n\n\n61.9%\n\n\n\n100.0%\n\n\n\n90.0%\n\n\n\n85.9%\n\n\n\nRifampicin\n\n\n\n1.9%\n\n\n\n7.1%\n\n\n\nN/A\n\n\n\n18.7%\n\n\n\nTetracyclin\n\n\n\n25%\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nN/A\n\n\n\nVancomycin\n\n\n\n1.9%\n\n\n\n6.5%\n\n\n\nN/A\n\n\n\n4.7%\n\n\n\nTable 5.    Comparison of antibiotic sensitivity of Staph. aureus with previous studies\n\n\n\nAntibiotic Resistance\n\n\n\nPrevalence in Other Studies (%)\n\n\n\n\n\n\n\n\n73\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n7. Kass DA, Atopic Dermatitis. eMedicine 2006\n8. Pezesk F, et al. Skin Colonization With Staphylococcus Aureus in \n\n\n\nPatients with atopic dermatitis. The Internet Journal of \nDermatology. 2007(5):1. Volume 5 Number 1.\n\n\n\n9. Kl\u00fckenH, WienkerT., Bieber T. Atopic eczema/dermatitis \nsyndrome - a genetically complex disease. New advances in \ndiscovering the genetic contribution. Allergy 2003 Jan;58(1):5-12\n\n\n\n10. Al-Saimary IE, Bacterial Skin Colonization In Patients With \nAtopic Dermatitis/Eczema Syndrome. The Internet Journal of \nDermatology. 2006 (4);2. Volume 4 Number 2.\n\n\n\n11. Stanway A The Causes of Atopic Dermatitis (Eczema); DermNetz, \nNZ; 26th Aug 2007.\n\n\n\n12. Arkwright PD, Daniel TO, Sanyal D, David TJ, Patel L. Age-related \nprevalence and antibiotic resistance of pathogenic \nstaphylococci and streptococci in children with infected atopic \ndermatitis at a single-specialty center. Arch Dermatol 2002 Jul; \n138(7):939-41.\n\n\n\n13. Barbara S. Baker (2006) The role of microorganisms in atopic \ndermatitis.  Clin Exp Immunol 144 (1), 1-9.\n\n\n\n14. Brook I, Frazier E, Yeager J ,Microbiology Of Infected Atopic \nDermatitis; Int J Dermatol 1996: 35 (11), 791-793.\n\n\n\n15. Gloor M, Peters G. and Stoika, D. On the resident aerobic \nbacterial skin flora in unaffected skin of patients with atopic \ndermatitis and in healthy controls. Dermatologica 1982; 164: 258-\n265.\n\n\n\n16. Hauser C., Prins C. and Lacour M. The role of infectious agents in \natopic dermatitis. Leung, D.Y.M. Atopic dermatitis: from \npathogenesis to treatment. Springer Verlag , New York. 1996. 67-\n112.\n\n\n\n17. Goh CL, Wong JS, Giam YC; Skin Colonization of Staphylococcus \naureus in Atopic Dermatitis Patients Seen at The National Skin \nCentre, Singapore; Int J Dermatol 1997 Sep; 36(9);653-7\n\n\n\n18. Roll A, Cozzio A, Fischer B, Schmid-Grendelmeier P. Microbial \ncolonization and atopic dermatitis. Curr Opin Allergy Clin \nImmunol. 2004 Oct;4(5):373-8.\n\n\n\n19. ARanbir Kaulsay. Allergy Alert. Malaysian Society of Allergy and \nImmunology (MSAI) Congress 2007.\n\n\n\n20. Abdallah M, Zaki S, El-Sayed Abeer, Erfan D; Evaluation of \nsecondary bacterial infection of skin diseases in Egyptian in- & \noutpatients & their Sensitivity to antimicrobials; Egyptian \nDermatol Online J 2007: 3;2\n\n\n\n21. Gong JQ, Lin L, Lin T, Skin colonization by Staphylococcus \naureus in patients with eczema and atopic dermatitis and \nrelevant combined topical therapy: a double-blind multicentre \nrandomized controlled trial. Br J Dermatol 2006: 155 (4), 680-687.\n\n\n\n22. Senol Ml. Staphlococcus aureus colonization in atopic skin \ndiseases. J Turgut Ozal Medical Center 3(4): 1996\n\n\n\n23. Leyden J, Marples, R. and Kligman, A Staphylococcus aureus in \nthe lesions of atopic dermatitis. Br. J. Dermatol., 1993, 90: 525-\n530.\n\n\n\n24. Strange, P., Skov., L., Lisby, S. Staphylococcal enterotoxin B \napplied on intact normal and intact atopic skin induces \ndermatitis. Arch. Dermatol, 1996: 132:27-33.\n\n\n\n25. Breuer, K., Wittmann, M., Bosche, B., Kapp, A. and Werfel, T. \nSevere atopic dermatitis in associated with sensitization to \nstaphylococcal enterotoxin B (SEB). Allergy, 2000., 55(6):551-555.\n\n\n\n26. Breuer, K., Haussler, S., Kapp, A., and Werfel, T. Staphylococcus \naureus: colonizing features and influence of an antibacterial \ntreatment in adult with atopic dermatitis. Br. J. Dermatol., 2002., \n147(1):55.\n\n\n\n\n\n\n\n\n74\n\n\n\n\n\n\n\n\n75\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nCutaneous tuberculosis in Penang:\nA 12-year retrospective study\n\n\n\nTan WC1 MD MRCP, Ong CK2 MD MRCP, Lo Kang SC1 MD MRCP and\nAbdul Razak M2 MBBS MMed Msc FCCP AM\n\n\n\n1Department of Dermatology, Penang Hospital\nPenang, Malaysia  \n2Department of Respiratory Medicine, Penang Hospital\nPenang, Malaysia\n\n\n\nCorrespondence\n\n\n\nTan Wooi Chiang MD MRCP\n\n\n\nDepartment of Dermatology, Penang Hospital\nJalan Residensi, 10450 Penang, Malaysia\nEmail: tanwooichiang@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Cutaneous tuberculosis (TB) is a form of extra-\npulmonary tuberculosis. Diagnosis of cutaneous TB is often difficult\nbecause of the diverse clinical presentations. The positive yields from\ncultures are often low. To describe the demographic, clinical,\nhistopathological and bacteriological aspects of cutaneous TB.\n\n\n\nMaterials and Methods This retrospective review looked at cases of\ncutaneous tuberculosis treated at the Respiratory and Dermatology\nunit, Penang Hospital from 1996 to 2007. Data were analysed with\nSPSS 13.0 version.\n\n\n\nResults A total of 23 cases of cutaneous tuberculosis were reviewed.\nThe male to female ratio was 2.3 to 1. The mean age was 37.7 \u00b1 20.7\nyears. There were 10 Malays, 9 Chinese, 2 Indians and 2 Indonesian.\nThe types of cutaneous tuberculosis observed were lupus vulgaris\n(47.8%), tuberculides (17.5%), tuberculosis verrucosa cutis (13.0%),\nscrofuloderma (13.0%) and primary inoculation TB (8.7%). 43.5% of\npatients had systemic involvement. Mantoux tests were positive in\n85.0% of cases. Skin biopsies were performed in 91.3% of patients and\n71.4% of them showed classical histopathologic findings suggestive of\ntuberculosis. Mycobacterium tuberculosis was isolated in the culture\nfrom 28.6% of patients. Localized diseases were found more often in\nBCG-vaccinated individuals. Regional lymphadenopathy was noted\nmore often in patients with disseminated disease. No correlation was\nfound between Mantoux reactivity and the extent of disease.\n\n\n\nConclusion Lupus vulgaris was the commonest form of cutaneous\ntuberculosis. Cultures were positive in only a small proportion of\npatients. Almost half of our patients had systemic involvement. The\npresence of regional lymphadenopathy often indicates disseminated\ndisease. Patients without BCG vaccination were at higher risk of\ndisease dissemination.\n\n\n\nKeywords Tuberculosis, Cutaneous tuberculosis, Lupus vulgaris,\nScrofuloderma, Tuberculide\n\n\n\nIntroduction\nTuberculosis is a chronic granulomatous infection caused by\nMycobacterium tuberculosis. Cutaneous tuberculosis (TB)\nis one of the rarer forms of extra-pulmonary tuberculosis.\nDiagnosis of cutaneous TB is difficult because of the\nprotean clinical presentation and the poor yield from\nculture.\n\n\n\nDespite the attention given to pulmonary tuberculosis, there\nwas very limited data on the epidemiology of cutaneous\ntuberculosis especially in this part of the world. We describe\nthe clinical, histopathological and bacteriological findings\nof patients diagnosed with cutaneous tuberculosis in our\ncentre.\n\n\n\nMaterials and methods\nThis retrospective study looked at cases of cutaneous\ntuberculosis presented to respiratory and dermatology units,\nPenang Hospital from 1996 to 2007. Case records,\nhistological reports and culture results of confirmed cases\nwere retrieved and reviewed. The demographic details,\nclinical features, results of investigation including chest\nradiograph, Mantoux test were recorded and analysed.\n\n\n\nWe have also included cases with negative tissue culture but\nwith clinical features and histological findings compatible\nwith cutaneous tuberculosis, which showed good clinical\nresponse to anti-tuberculous treatment.\n\n\n\nThose patients with Mycobacterium leprae and non-\ntuberculous mycobacterial disease were excluded from this\nstudy. Patients with tuberculous lymphadenitis without\nevidence of skin involvement were also excluded from the\nstudy.\n\n\n\n\n\n\n\n\n76\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nResults\n23 cases of cutaneous tuberculosis were included. The male\nto female ratio was 2.3:1. The mean age of patients was 37.7\n\u00b1 20.7 years (range from 1 to 78 years old). Only 2 children\n(Age <12 years old) were diagnosed to have cutaneous TB\nduring study period. There were 10 Malays, 9 Chinese, 2\nIndians and 2 Indonesian.\n\n\n\nThe types of cutaneous tuberculosis observed in our cohort\nwere lupus vulgaris (47.8%), tuberculides (17.5%),\ntuberculosis verrucosa cutis (13.0%), scrofuloderma (13.0%)\nand primary inoculation TB (8.7%). Among the\ntuberculides that observed in our study, there were 2 cases of\nerythema induratum and 2 cases of papulonecrotic\ntuberculide. (Refer figure 1 & 4)\n\n\n\n9 (39.1%) patients have a contact history of tuberculosis and\n2 (8.7%) patients had had a past history of tuberculosis.\nOnly 9 (39.1%) patients were brought to medical attention\nwithin a year of onset of the disease and 5 (21.7%) patients\nwere diagnosed after more than 5 years of the onset of the\nillness. All our patients were tested for HIV3. (13.0%) out of\n23 patients had concomitant HIV infection.\n\n\n\nSystemic organ involvement\nSystemic involvement was seen in 10 (43.5%) patients. The\nlung was the most common organ involved, in 5 (50.0%)\npatients, followed by lymph nodes in 4 (40.0%) and bone in\n1 (10.0%). There were no cases of TB involving the\ngastrointestinal tract, genitourinary tract, CNS and heart.\nRegional lymphadenopathy was noted more often in\npatients with disseminated disease. (Refer figure 3)\n\n\n\nBCG vaccination\nOf the 23 patients, 11 (47.8%) had been vaccinated and 12\n(52.2%) had no documented BCG vaccination. Among the\nvaccinated group, only 3 patients (27.3%) had disseminated\ndisease. 7 patients (58.3%) in the non-vaccinated group had\ndisseminated disease. Patients with disseminated disease\nwere less often found in those with BCG vaccination.\n(Refer figure 3)\n\n\n\nMantoux reactivity\nInformation regarding Mantoux reactivity was available in\n20 (87.0%) patients, 11 (55.0%) with localized disease and\n9 (45.5%) with disseminated disease. Of the 11 patients\nwith localized disease, 9 (81.8%) were Mantoux positive. 8\n(88.9%) patients with disseminated disease had positive\nMantoux test. No correlation was found between Mantoux\nreactivity and the extent of disease. (Refer figure 2 & 3)\n\n\n\nHistopathology\nHistopathological reports were available for evaluation in 21\npatients (91.3%). Out of which, 15 (71.4%) showed classical\nhistological findings of TB (epithelioid granuloma \u00b1\n\n\n\ncaseation). Tubercle bacilli has been demonstrated in 1/11\n(9.1%) cases with LV and 2/3 (66.7%) cases of SFD. (Refer\nfigure 2)\n\n\n\nAFB culture\nAFB cultures were done for 21 patients (91.3%) but\nMycobacterium tuberculosis was isolated in only 28.6% of\ncases. (Refer figure 2)\n\n\n\nConclusion\nCutaneous tuberculosis is a rare form of extrapulmonary\ntuberculosis. It was reported in 1.0 - 4.4% of all cases of\nTB1-2. In Morocco, cutaneous tuberculosis ranks fifth in\nfrequency after pleural, lymph node, genitourinary and\nintestinal tuberculosis3. Although cutaneous TB only\ncomprises a small proportion of cases, the absolute number\nmay be high, given the high prevalence of TB in many\ndeveloping countries.\n\n\n\nIn our centre, we observed 23 cases of cutaneous TB over a\n12 years period. It is interesting to compare this figures with\nvarious case series around the world: Farina (Spain)4, 11\ncases in 14 years; Chong (Hong Kong)5, 176 cases in 10\nyears; Jerajani, Mumbai (India), 291 cases in 10 years and\nKumar in Chandigarh (India), 402 cases in 25 years. The\nnumbers in these series may reflect true incidence or in\ncertain communities underreporting - a well-known\nproblem in resource-poor areas with a high burden of\ndisease.\n\n\n\nFactors contributing to increasing prevalence of cutaneous\nTB include HIV co-infection, multidrug-resistance,\nimmigrants from countries of higher prevalence and the\nneglect of preventive measures6-8. HIV infection has led to a\n20% increase in the incidence of extra-pulmonary\ntuberculosis in the United States6, of which 1.5% comprised\nof cutaneous tuberculosis9. Although the skin remained a\nrelatively uncommon site of dissemination, several cases of\ncutaneous miliary tuberculosis, scrofuloderma, tuberculous\nulcer, subcutaneous tuberculous abscess and tuberculide in\nHIV-seropositive individuals have been reported. 3 out of\n23 (13.0%) cases from our cohort were HIV infected\npatients.\n\n\n\nTuberculosis of the skin was most commonly reported in\nyoung adults10. In our study, 43.5% of patients were under\n30 years of age. This may be explained by the study\nmethodology. We only looked at the data retrieved from the\nrespiratory unit and dermatology unit which are mainly\nseeing the adult patients. The data in paediatric clinic were\nnot captured in this study. We observed a male\npredominance as noted in other studies4-5,11.\n\n\n\n\n\n\n\n\n77\n\n\n\nSex\n\n\n\nMale\n\n\n\nFemale\n\n\n\nEthnic\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nForeigner\n\n\n\nAge (Mean: 37.7 \u00b1 20.7 yrs )\n\n\n\n<12\n\n\n\n13-20\n\n\n\n21-30\n\n\n\n31-40\n\n\n\n41-50\n\n\n\n51-60\n\n\n\n> 60\n\n\n\nType of cutaneous TB\n\n\n\nTrue cutaneous TBb\n\n\n\nLV\n\n\n\nTVC\n\n\n\nSFD\n\n\n\nPrimary inoculation TB\n\n\n\nTuberculides\n\n\n\nEI\n\n\n\nPNT\n\n\n\nN (%) of patients\n\n\n\n16 (69.6)\n\n\n\n7 (30.4)\n\n\n\n10 (43.5)\n\n\n\n9 (39.1)\n\n\n\n2 (8.7)\n\n\n\n2 (8.7)\n\n\n\n2 (8.7)\n\n\n\n2 (8.7)\n\n\n\n6 (26.1)\n\n\n\n3 (13.0)\n\n\n\n4 (17.4)\n\n\n\n1 (4.3)\n\n\n\n5 (21.8)\n\n\n\n19 (82.5)\n\n\n\n11(57.9)\n\n\n\n3 (15.8)\n\n\n\n3 (15.8)\n\n\n\n2 (10.5)\n\n\n\n4 (17.5)\n\n\n\n2 (50.0)\n\n\n\n2 (50.0)\n\n\n\nFigure 1.    Characteristics of patients with cutaneous TB \nseen at respiratory unit, Penang Hospital\n(1996 to 2007)\n\n\n\nFigure 2.    Mantoux\u2019s test, skin biopsy and AFB culture \nfindings in our cohort\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nLV, lupus vulgaris; TVC, tuberculosis verrucosa cutis; SFD, scrofuloderma;\nEI, erythema induratum; PNT, papulonecrotic tuberculide.\n\n\n\nTest\n\n\n\nMantoux Reactivity\n\n\n\nHistopathology\n\n\n\nAFB Culture\n\n\n\nPerformed (%)\n\n\n\n87\n\n\n\n91.3\n\n\n\n91.3\n\n\n\nPositive (%)\n\n\n\n85\n\n\n\n71.4\n\n\n\n28.6\n\n\n\n\n\n\n\n\n78\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 3.    Clinical predictors of disseminated \n\n\n\nFigure 4.    Papulonecrotic tuberculide\n\n\n\nParametres\n\n\n\nBCG Vaccination  Status\n\n\n\n- Vaccinated \n\n\n\n- Non Vaccinated\n\n\n\nRegional Lymphadenopathy\n\n\n\n- Yes\n\n\n\n- No\n\n\n\nType of Cutaneous TB\n\n\n\n- True Cutaneous TB\n\n\n\n- Tuberculides\n\n\n\nMantoux Reactivity\n\n\n\n- Positive \n\n\n\n- Negative\n\n\n\n- Not done\n\n\n\nLocalised\n(N=13)\n\n\n\n8\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n13\n\n\n\n0\n\n\n\n9\n\n\n\n2\n\n\n\n3\n\n\n\nDisseminated \n(N=10)\n\n\n\n3\n\n\n\n7\n\n\n\n10\n\n\n\n0\n\n\n\n6\n\n\n\n4\n\n\n\n8\n\n\n\n1\n\n\n\n1\n\n\n\nDisease spectrum\n\n\n\n\n\n\n\n\n79\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe development of cutaneous TB depends on several\nfactors, including the patient\u2019s immune status, route of\ninoculation and past sensitization with TB12. In relation to\nhost immunity, cutaneous tuberculosis represents a\ncontinuous spectrum with lupus vulgaris (high degree of\nimmunity) at one end of the spectrum, scrofuloderma and\ntuberculous gumma (low degree of immunity) at the other13.\n\n\n\nThere are two general categories of manifestation of\ncutaneous TB. The first is true tuberculosis, a disease\nevolving from a proliferation of tuberculosis bacilli in the\nskin such as lupus vulgaris, scrofuloderma, tuberculosis\nverrucosa cutis, cutaneous primary tuberculosis, tuberculosis\ncutis orificialis and cutaneous miliary tuberculosis. In true\ninfections, the bacilli reach the skin either from an\nexogenous route or an endogenous focus. Apart from\nmiliary tuberculosis, lesions are mostly single or few in\nnumber and mycobacteria can usually be detected. The\nsecond category is tuberculide, which is diagnosed when the\nskin is involved as a reaction to tuberculous infections in\nother organs. Erythema induratum (Bazin\u2019s disease),\npapulonecrotic tuberculide and lichen scrofulosorum are\ndifferent forms of tuberculide described. Tuberculides\ntypically manifest as recurrent skin eruptions that are\nusually disseminated, symmetrical and show a tendency to\nspontaneous involution. Organisms cannot be isolated from\nthese sites.\n\n\n\nLupus vulgaris (LV) is the commonest form of cutaneous\nTB reported in our cohort. However some studies have\nreported a higher incidence of SCD or equal number of\ncases of LV and SCD4,11. Scrofuloderma is most often\nassociated with active tuberculous lymphadenitis and\npulmonary TB. We observed a similar pattern in our study\npopulation. 17.5% of cutaneous TB cases in our cohort were\ntuberculides. There were an increasing number of\ntuberculide cases being reported in Japan14 and Hong\nKong15.\n\n\n\nDisseminated form of tuberculosis has been reported in 5%\nto 22.1% of patients with cutaneous tuberculosis3,5,16. We\nfound a substantially higher percentage of active\nextracutaneous disease (systemic involvement) in our\npatients (43.5%). Disseminated forms of TB were observed\nin all clinical variants except in tuberculous verrucosa cutis.\n\n\n\nLocalized disease is more commonly seen in a BCG-\nvaccinated individual. Regional lymphadenopathy was\nnoted more often in patients with disseminated disease. No\ncorrelation was found between Mantoux reactivity and the\nextent of disease. Similar findings were also reported by\nKumar B et al10.\n\n\n\nCutaneous tuberculosis continues to be one of the most\nelusive and difficult diagnoses to make for dermatologists\npracticing in developing countries. Not only because they\nhave to consider a wide range of differential diagnoses but\nalso because of the difficulty in obtaining a microbiological\nconfirmation. The culture provides only small diagnostic\nyield in patients with cutaneous TB11,17 as noted in our\nseries.\n\n\n\nA diagnosis of cutaneous TB is typically made\npresumptively based on the presence of active tuberculosis\nelsewhere, clinical history and physical signs, a positive\npurified protein derivative (PPD) skin test reaction, typical\nhistological findings and a therapeutic response to\nantituberculous treatment3,18. Several case reports indicate\nthe usefulness of polymerase chain reaction (PCR) in the\ndiagnosis of cutaneous TB19-20.\n\n\n\nMajority of our patients responded satisfactorily to anti-\ntuberculous therapy. Because most of the cutaneous TB\ncases were related to tuberculous disease of other organs,\nstandard TB treatment regimens is usually sufficient. A\nclinical response could be expected by week 4 or 6 of the\ntherapeutic trial, with lupus vulgaris showing a faster\nresponse than scrofuloderma18. In areas of high TB\nprevalence like Malaysia, a therapeutic trial of anti-TB\nchemotherapy should be considered.\n\n\n\nReferences\n\n\n\n1. Saral Y, Coskun BK, Ozturk P et al. Multiple metastatic \ntuberculosis abscesses in a patient with Pott\u2019s disease and lung \ntuberculosis: a case report. J Cutan Pathol 2005; 32:629-33.\n\n\n\n2. Yates VM, Ormerod LP. Cutaneous tuberculosis in Blackburn \ndistrict (U.K.): a 15-year prospective series, 1981-95. Br J \nDermatol 1997; 136: 483-9.\n\n\n\n3. Kawtar Zouhair, Nadia Akhdari, Fatima Nejjam et al. Cutaneous \ntuberculosis in Morocco. International Journal of Infectious \nDiseases (2007) 11, 209-212\n\n\n\n4. Farina MC, Gegundez MI, Pique E et al. Cutaneous tuberculosis: \na clinical, histopathologic and bacteriologic study. J Am Acad \nDermatol 1995; 33: 433-40.\n\n\n\n5. Chong LY, Lo KK. Cutaneous tuberculosis in Hong-Kong: a 10-year \nretrospective study. Int J Dermatol 1995; 34: 26-29.\n\n\n\n6. Barnes PF, Bloch AB, Davidson PI, Snider DE. Tuberculosis in \npatients with human immunodeficiency virus infection. N Engl J \nMed 1991; 324: 1644-51.\n\n\n\n7. Bass Jr JB, Farer LS, Hopewell PC et al. Treatment of \ntuberculosis and tuberculosis infection in adults and children. \nAmerican Thoracic Society and the Centers for Disease Control \nand Prevention. Am J Respir Crit Care Med 1994; 149: 1359-74.\n\n\n\n8. Beyt BE, Ortbals DW, Santa Cruz DJ et al. Cutaneous \nmycobacteriosis: analysis of 34 cases with a new classification \nof the disease. Medicine (Baltimore) 1980; 66: 95-109.\n\n\n\n9. Gawkrodger DJ. Mycobacterial infections. In: Champion RH, \nBurton JL, Ebling FJG, eds. Textbook of Dermatology, 6th edn, \nVol. 2. London: Blackwell Scientific Publications, 1998; 1181-1214.\n\n\n\n10. Kumar B, Muralidhar S. Cutaneous tuberculosis: a twenty-year \nprospective study. Int J Tuberc Lung Dis 1999; 3: 494-500.\n\n\n\n\n\n\n\n\n80\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n11. Shegal VN, Srivastava G, Rhurana VK, Sharman VK, Bhalla P, \nBeohar PC. An appraisal of epidemiologic, clinical, bacteriologic, \nhistopathologic and immunologic parameters in cutaneous \ntuberculosis. Int J Dermatol 1987; 26: 521-6.\n\n\n\n12. J. E. Lai-Cheong, A. Perez, V. Tang, A et al. Menage. Cutaneous \nmanifestations of tuberculosis. Clinical and Experimental \nDermatology 2007; 32; 461-466.\n\n\n\n13. Sehgal VN, Wagh SA. Cutaneous tuberculosis. Current concepts. \nInt J Dermatol 1990; 29: 237-52.\n\n\n\n14. Hamada M, Urabe K, Moroi Y et al. Epidemiology of cutaneous \ntuberculosis in Japan: a retrospective study from 1906 to 2002. \nInt J Dermatol 2004; 43: 727-31.\n\n\n\n15. Ho CK, Ho MH, Chong LY. Cutaneous tuberculosis in Hong Kong: \nan update. Hong Kong Med J 2006; 12: 272-277.\n\n\n\n16. Ramesh V, Misra RS, Jain RK. Secondary tuberculosis of the \nskin. Clinical features and problems in laboratory diagnosis. Int J \nDermatol 1987; 26: 578-81.\n\n\n\n17. Ramesh V, Misra RS, Saxena U, Mukherjee A. Comparative \nefficacy of drug regimens in skin tuberculosis. Clin Exp Dermatol \n1991; 16: 106-9.\n\n\n\n18. Ramam M, Mittal R, Ramesh V. How soon does cutaneous \ntuberculosis respond to treatment? Implications for a therapeutic \ntest of diagnosis. Int J Dermatol 2005; 44: 121-4.\n\n\n\n19. Margall N, Baselga E, Coll P et al. Detection of Mycobacterium \ntuberculosis complex DNA by the polymerase chain reaction for \nrapid diagnosis of cutaneous tuberculosis. Br J Dermatol 1996; \n135: 231-6.\n\n\n\n20. Arora SK, Kumar B, Sehgal S. Development of a polymerase \nchain reaction dot-blotting system for detecting cutaneous \ntuberculosis. Br J Dermatol 2000; 142: 72-6.\n\n\n\n\n\n\n\n\n81\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nComparison of BBL chromagar MRSA to conventional \nmedia for the detection of methicillin resistant \nstaphylococcus aureus in surveillance nasal swabs \n\n\n\nN Mohd Noor1 MBBS MRCP, S Thevarajah1 MBBS MMed, Zubaidah Abdul Wahab2 MBBS MPath and\nS H Hussein1 MBBS FRCP\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur\nKuala Lumpur\n2Department of Pathology, Hospital Sungai Buloh\nSungai Buloh\n\n\n\nCorrespondence\n\n\n\nN Mohd Noor MRCP \n\n\n\nClinical Specialist\nDepartment of Dermatology\nHospital Kuala Lumpur\n50586 Kuala Lumpur, Malaysia\nEmail : laily124@tm.net.my\n\n\n\nAbstract\n\n\n\nObjectives This study aims to detect MRSA nasal carriers among\nmedical staff and patients in Dermatology ward Hospital Kuala\nLumpur by using two methods, the conventional blood sheep agar\n(BSA) and the novel BBL CHROMagar MRSA (C-MRSA). It also\naims to compare the BSA medium with the C-MRSA medium in\nterms of specificity, sensitivity and time to detection to MRSA.\n\n\n\nMethod A single centre, prospective study where 100 nasal swab\nsamples were taken from medical staff and inpatients, then plated on to\nboth BSA and C-MRSA. After 24 hours incubation, the plates were\nexamined for presence of bacterial colonies, then incubated for another\n24 hours if no colonies were present. All colonies on C-MRSA and\nBSA were subjected to coagulase and susceptibility testing for\nconfirmation of MRSA. MRSA strains produce mauve colonies on C-\nMRSA from hydrolysis of the chromogenic substance, thus C-MRSA\nuses colour as a diagnostic tool.\n\n\n\nResults Mauve colonies were present on nine C-MRSA plates in the\nfirst 24 hours which were all confirmed to be MRSA. Another nine C-\nMRSA plates isolated bluish colonies which were not MRSA. There\nwere colonies on 96 BSA plates, nine of which were MRSA. C-MRSA\nmedium has 100% sensitivity and specificity in detecting MRSA. Both\nculture media had similar detection rates of MRSA from nasal swabs,\nhowever C-MRSA allows for earlier detection of MRSA within 24\nhours compared to BSA which takes 48 hours. 2.2% of ward staff and\n15.7% of inpatients were found to be MRSA carriers.\n\n\n\nConclusion CHROMagar MRSA allows for more rapid\nidentification of MRSA carriers within 24 hours compared to the\nconventional BSA which takes 48 hours. This allows earlier action to\nbe taken to reduce the spread of MRSA infection.\n\n\n\nKeywords MRSA, CHROMagar, nasal carrier\n\n\n\nIntroduction\nMRSA was first reported in 1961 and its prevalence is\nbelieved to be increasing worldwide1. According to the\nNational Nosocomial Infection Surveillance System, the\nmean prevalence of MRSA in US hospitals increased from\n2.4% in 1975 to 36% in 1999 as a percentage of all\nstaphylococcus aureus strains isolated2. In Hospital Kuala\nLumpur the incidence of MRSA infection was reported as\n0.22-0.7% for every 100 admissions a month in 2006, which\nwas amongst the highest of the government hospitals in\nMalaysia.\n\n\n\nMethicillin resistant Staphylococcus aureus (MRSA) is an\nimportant pathogen causing serious nosocomial infections.\nInfections caused by MRSA are associated with increased\nmorbidity and mortality, longer hospital stay, longer course\nof antibiotics therapy and higher costs compared with\ninfections caused by Methicillin susceptible Staphylococcus\naureus (MSSA)3. MRSA infection is often highly\ntransmissible and 20-60% of hospitalized patients who are\nMRSA nasal carriers eventually have MRSA infection4.\n\n\n\nActive surveillance for MRSA in the nares of those at risk\nis an important component of the Society for Healthcare\nEpidemiology of America recommendations for the control\nof nosocomial transmission of MRSA5. Many centres screen\nfor staphylococci in particular MRSA in the nares of at-risk\npopulations, to control nosocomial transmission of MRSA.\nIdentification of patients and healthcare workers colonized\nwith MRSA during outbreaks, as well as contact\nprecautions and strict hand hygiene have reduced the\ntransmission and controlled the spread of MRSA.\n\n\n\n\n\n\n\n\n82\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe number of patients with MRSA infection in the\nDermatology Ward, HKL has increased over the years\ndespite pro-active measures to actively treat MRSA nasal\ncarriers among healthcare personnel and inpatients (Figure\n1). Hence it is of prime importance to develop rapid, highly\nsensitive and cost-effective surveillance methods to identify\nMRSA carriers and take necessary actions to control the\nspread.\n\n\n\nBBL CHROMagar MRSA (C-MRSA) is a selective and\ndifferential medium for the qualitative direct detection of\nnasal colonization by MRSA. C-MRSA medium permits\nthe direct detection and identification of MRSA through\nthe incorporation of specific chromogenic substrates and\ncefoxitin. MRSA strains will grow in the presence of\ncefoxitin and produce mauve-coloured colonies resulting\nfrom hydrolysis of the chromogenic substrate (Figure 2).\n\n\n\nObjectives\nThis study aims to detect MRSA nasal carriers among 100\nhealthcare workers and patients in the Dermatology Ward\n\n\n\nHKL by using two methods, the conventional blood sheep\nagar (BSA) and the novel BBL CHROMagar MRSA. It\nalso aims to compare the BSA medium with the C-MRSA\nmedium in terms of specificity, sensitivity and time to\ndetection to MRSA. The C-MRSA is currently approved\nfor use with nasal swabs.\n\n\n\nMaterial and Methods\nThis was a single centre, prospective study which was\ncarried out from 14th February to 17th March 2006 until\nthe target sample size of 100 was reached. All healthcare\nworkers and inpatients of Dermatology Ward HKL were\nincluded in the study. Healthcare workers included doctors,\nnurses, medical assistants, attendants and hospital support\nservices staff.\n\n\n\nInpatients included all patients warded in the Dermatology\nWard during the study period. The length of hospital stay\nwas noted at the time the nasal swabs were taken. The\npatients\u2019 case notes were also reviewed to obtain\ninformation on the number of ward admissions and clinic\nvisits.\n\n\n\nFigure 1.\n\n\n\nFigure 2.    BBL CHROMagar MRSA showing the growth of MRSA \nwhich appears as mauve colonies - visual identification\n\n\n\n\n\n\n\n\n83\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThere were altogether 100 subjects. A research nurse\nobtained the nasal swabs from all the subjects to ensure\nconsistency and to minimize sampling error. Each subject\nhad two swabs taken from the nares. The swab was initially\nmoistened with sterile saline, then inserted into both the\nanterior nares in a gentle rotating manner and immediately\nput into the Amies transport medium. These samples were\nsent to the microbiology lab, where each sample was plated\nonto the conventional BSA and C-MRSA medium.\n\n\n\nAfter 24 hours of incubation, C-MRSA plates were\nexamined for the presence of mauve-coloured colonies.\nThese colonies were subjected to coagulase and\nsusceptibility testing. Colonies of other colours were also\nsubjected to the same tests to identify the organisms.\nColonies on BSA also underwent coagulase and\nsusceptibility testing. If there were no colonies in the first 24\nhours, the plates would be reincubated for another 24 hours,\nand colonies which grew after that would also be subjected\nto similar tests (Figure 3).\n\n\n\nTube coagulase test\nA Gram smear was done from colonies to confirm that it\nwas a Gram positive cocci. This was followed by the\ncoagulase test which was performed by mixing\n\n\n\nanticoagulated pooled human plasma or rabbit plasma with\nStaph aureus culture. Free (extracellular) coagulase clots\nplasma in the absence of calcium. The tube coagulase test\nwas determined by looking for clot formation after\nincubation for 4 hours. If negative, it was re-examined at 24\nhours because a few strains required a longer time for clot\nformation.\n\n\n\nSusceptibility Test\nSusceptibility to common antibiotics was determined by\ndisc diffusion method according to the Clinical Laboratory\nStandards Institute. The following antibiotic discs were\nused: Erythromycin 15 mcg, Cotrimoxazole 25 mcg,\nFucidic acid 10 mcg, Rifampicin 5 mcg, Vancomycin 30\nmcg, Oxacillin 1 mcg, Mupirocin 10 mcg, Teicoplanin 30\nmcg, Linezolid 30 mcg and Clindamycin 2 mcg. Parameters\nsuch as temperature of 350 C, colony suspension equivalent\nto 0.5 McFarland and prolonged incubation period of 18 to\n24 hours were employed to improve the sensitivity and\nspecificity of the tests. The antibiotic discs were placed on\nMueller Hinton agar plate containing Staph aureus\ninoculum. The diameter of zone surrounding the antibiotic\ndiscs was measured using the Biomic Vision Microbiology\nAnalyser.\n\n\n\nFigure 3.    Workflow and identification of MRSA from CHROMagar MRSA and BSA\n\n\n\nBBL CHROMagar MRSA\n\n\n\nAt 24 hours\nCoagulase and susceptibility test report MRSA\n\n\n\nCoagulase and susceptibility test report MRSA\n\n\n\nCoagulase and susceptibility test report MRSA\n\n\n\nCoagulase and susceptibility test report MRSA\n\n\n\nAt 48 hours\n\n\n\nBSA\n\n\n\nAt 24 hours\n\n\n\nAt 48 hours\n\n\n\n\ufffd \ufffd\n\n\n\n\ufffd \ufffd\n\n\n\n\ufffd \ufffd\n\n\n\n\ufffd \ufffd\n\n\n\n\n\n\n\n\n84\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe detection of methicillin resistance was done by\nperforming the oxacillin disc diffusion test. A 6 mcg\nOxacillin disc was placed on the entire surface of Mueller\nHinton agar plate covered with colony suspension and after\novernight incubation, the diameter of the zone around it\nwas measured. Measurement of less than 10mm indicated\nthat the Staph aureus colonies were resistant to methicillin.\n\n\n\nResults\nThere were a total of 46 ward staff, 51 patients and 3\ncaregivers in this study (Figure 4). The ward staff comprised\nof twenty doctors, seventeen nurses, two Medical\nAssistants, five attendants and two support services staff.\n\n\n\nThere were non-specific colonies on 96 BSA plates within\nthe first 24 hours (Table 1), the organisms isolated are\nshown in Table 2. Mauve colonies were present on 9 C-\nMRSA plates in the first 24 hours, another 9 C-MRSA\nplates had dark purplish and bluish colonies .Coagulase and\nsusceptibility tests confirmed that all the mauve colonies on\nC-MRSA were MRSA. The dark purplish and bluish\ncolonies on C-MRSA were Staph species (resistant to\noxacillin).\n\n\n\nTable 2 shows all the organisms isolated and interestingly\nboth BSA and C- MRSA detected all the MRSA isolates.\nThe BSA medium also isolated MSSA and other non\nMRSA organisms. The growth of MSSA and other non\nMRSA species except for Staph species (resistant to\noxacillin) were suppressed on the C-MRSA medium. The\nsensitivity and specificity of C-MRSA in detecting MRSA\nis 100% \n\n\n\nNine percent (9/100) of the total population studied were\nMRSA nasal carriers. On further analysis, 2.2% (1/46) of\nward staff and 15.7% (8/51) of patients were MRSA\ncarriers. Out of the nine MRSA carriers, eight were patients\nand one was a nurse (Figure 5). Six patients had been in the\nward for more than 72 hours whereas two patients were\nadmitted for less than 72 hours. In the first six patients, two\nhad been on steroids, another two had previous\nhospitalization and the last two were never admitted before.\nThe other two patients had history of hospitalization with\nrecurrent clinic visits in the past one year and had been on\nsteroids.\n\n\n\nTable 1.\n\n\n\nMedia\n\n\n\nBSA\n\n\n\nC-MRSA\n\n\n\nAppearance (after 24 H)\n\n\n\n96 plates - Colonies\n\n\n\n4 plates -  No colonies\n\n\n\n9 plates -  Mauve colonies\n\n\n\n9 plates -  Dark purplish \nand  bluish colonies\n\n\n\n82 plates - No colonies\n\n\n\nAppearance (after 48 H)\n\n\n\n4 plates - No colonies\n\n\n\n82 plates -  No colonies\n\n\n\nFigure 4.\n\n\n\n\n\n\n\n\n85\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nThis was the first study done in HKL to evaluate the\nperformance of the novel C-MRSA in detecting MRSA\nfrom nasal swabs. It showed that the sensitivity and\nspecificity of C-MRSA in detecting MRSA is 100%. Thus\nit may not be necessary to do coagulase and susceptibility\ntests if mauve-coloured colonies are present on C-MRSA,\nas all the mauve colonies were MRSA in this study. This\nwould save money and reduce labour requirements as no\nfurther confirmatory tests are needed. Even if confirmatory\ntests are done for the C-MRSA plates, the number will be\nfar less than the conventional medium (18 C-MRSA plates\nas opposed to 96 BSA plates) as C-MRSA suppresses the\ngrowth of non MRSA species. The conventional BSA still\nrequires coagulase and susceptibility tests for confirmation\nof MRSA. Thus C-MRSA can potentially reduce the\nnumber of confirmatory tests and allows identification of\nMRSA in a single step.\n\n\n\nC-MRSA also allows for rapid identification of MRSA\nwithin 24 hours compared to the traditional BSA which\ntakes 48 hours. This would mean that necessary actions\ncould be taken earlier as MRSA could be identified within\n24 hours. This includes initiating contact precaution which\nwill potentially reduce the spread of MRSA.\n\n\n\nThere was no further recovery of MRSA after reincubating\nspecimens for another 24 hours. Thus an individual may be\ndeclared non MRSA carrier within 24 hours provided no\nmauve colonies were grown on C-MRSA. However due to\nthe small number of specimens in the study, the results need\nto be interpreted with caution. A few other studies with\nlarger sample sizes have shown additional isolates of MRSA\non C-MRSA after 48 hours incubation6. Based on these\nearlier studies, it is still recommended to incubate the\nmedium for 48 hours if there are no colonies present in the\nfirst 24 hours to increase the recovery of MRSA isolates.\n\n\n\nDetecting MRSA nasal carriers is important because\nrelative to other body sites, MRSA nasal colonization poses\na higher risk for subsequent infection in at risk subjects7.\nThose at risk include patients on haemodialysis as well as\ncontinuous ambulatory peritoneal dialysis8. A few studies\nhave monitored MRSA nasal colonization rates in patients\non admission to the hospital. MRSA nasal colonization\nrates were 0.03% in Netherlands, 7.3% in major hospitals in\nthe United States and 7.9% in major hospitals in France9. In\nour study 15.7% of dermatology inpatients were MRSA\nnasal carriers. The number is high as this study was\nconducted during MRSA outbreak in the ward. This study\nalso found that MRSA carriage was more common in\npatients with longer hospital stay, recurrent clinic visits and\non \n\n\n\nTable 2.\n\n\n\nOrganisms isolated\n\n\n\nMRSA\n\n\n\nStaph aureus\n\n\n\nStaph species (sensitive to oxacillin)\n\n\n\nStaph species (resistant to oxacillin)\n\n\n\nDiphtheroids\n\n\n\nNo growth\n\n\n\nBSA\n\n\n\n9\n\n\n\n15\n\n\n\n47\n\n\n\n12\n\n\n\n13\n\n\n\n4\n\n\n\nC- MRSA\n\n\n\n9\n\n\n\n0\n\n\n\n0\n\n\n\n9\n\n\n\n0\n\n\n\n0\n\n\n\nFigure 5.\n\n\n\n\n\n\n\n\n86\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\non steroids. Many studies have shown that decreasing the\nlength and frequency of hospital stays reduces the risk for\nnosocomial MRSA transmission10,11. Netherlands is among\na few countries with very low nosocomial and community\nlevels of MRSA attributed to the \u201csearch and destroy\u201d policy\nfor prevention of MRSA transmission and policy of\nrestrictive antibiotic use9,12.\n\n\n\nHealthcare workers who are MRSA nasal carriers are also at\nrisk of transmitting it to their patients. The colonization\nrate in healthcare workers was 2.5% in the United States\nand 6.2% in France. In our dermatology ward, the\ncolonization rate in healthcare workers was found to be\n2.2%.\n\n\n\nCarriers were treated topically with mupirocin ointment\nthree times a day for 5 consecutive days13 for nasal\ndecolonization to prevent spread to others. Mupirocin is\nvery effective in eradicating nasal carriage and preventing\ninfection over a short term period but long term results are\nless impressive14.\n\n\n\nCertain practices need to be put into place to prevent the\nspread of MRSA. Patients who are colonized or infected\nwith MRSA need to be isolated. There should be use of\nbarrier precautions which include gloves and gowns as well\nas hand washing. Active screening of patients for MRSA\ncarriage should be carried out with patients selection\ndetermined by local infection control team and discussed\nwith appropriate clinical teams. Screening of staff is not\nrecommended routinely unless there is an outbreak of\nMRSA infection in the ward.\n\n\n\nConclusion\nNine percent of the population studied which comprises\nhealthcare workers and patients of dermatology ward HKL\nwere MRSA nasal carriers. Active surveillance for MRSA\nin the anterior nares of those at risk is important to control\nthe nosocomial transmission of MRSA.\n\n\n\nThe novel C-MRSA is as sensitive as BSA in the detection\nof MRSA. C-MRSA also allows identification of MRSA\nisolates within 24 hours with 100% sensitivity and\nspecificity as compared with the conventional BSA which\ntakes 48 hours and requires further coagulase and sensitivity\ntests. This translates into rapid identification of MRSA\nnasal carriers and initiating contact precautions, all of which\nwill potentially reduce the spread of MRSA.\n\n\n\nReferences\n\n\n\n1. Jevons MP. \u2018Celbenin\u2019 resistant staphylococci. Br Med J \n1961;1:124-125\n\n\n\n2. Panlilio AL et al. MRSA in US hospitals 1975-1991. Infect Control \nHosp Epidemiol 1992;13(10):582-586\n\n\n\n3. Engemann et al. Adverse clinical and economic outcomes \nattributable to methicillin resistance among patients with Staph \naureus surgical site infection. Clin Infect Dis 2003;36:592-8\n\n\n\n4. Jernigan JA, Clemence MA, Stott GA et al. Control of methicillin-\nresistant Staphylococcus aureus at a university hospital: one \ndecade later. Infect Control Hosp Epidemiol 1995;16(12):686-96 \n\n\n\n5. Muto et al. SHEA guideline for preventing nosocomial \ntransmission of multidrug-resistant strains of Staph aureus and \nEnterococcus. Infect Control Hosp Epidemiol 2003;24:362-86\n\n\n\n6. Lema et al. Comparison of BBL CHROMagar Staph aureus to \nConventional Media for the Detection of Methicillin Susceptible \nand Methicillin Resistant Staph aureus in Clinical respiratory \nSamples. American Society for Microbiology 2003  \n\n\n\n7. Kluytmans J et al. Nasal carriage of Staphylococcus aureus: \nepidemiology, underlying mechanisms, and associated risks.\nClin Microbiol Rev 1997;10:505-520 \n\n\n\n8. Mupirocin Study Group. Nasal mupirocin prevents \nStaphylococcus aureus exit-site infection during peritoneal \ndialysis. J Am Soc Nephrol 1996;7:2403\u20132408\n\n\n\n9. Wertheim HF et al. Low prevalence of MRSA at hospital \nadmission in the Netherlands: the value of search and destroy \nand restrictive antibiotic use. J Hosp Infect 2004;56:321-325\n\n\n\n10. Lucet JC et al. Successful long-term program for controlling \nMRSA in Intensive Care Units. Intensive Care Med. 2005;\n31:1051-1057\n\n\n\n11. Marshall et al. Acquisition of MRSA in a large ICU. Infect Control \nHosp Epidemiol 2003;24:322-326\n\n\n\n12. Vanderbroucke-Grauls et al. MRSA control in hospitals:\nthe Dutch experience. Infect Control Hosp Epidemiol 1996;\n17:512-513\n\n\n\n13. Coia JE, Duckworth GJ et al. Guidelines for the control and \nprevention of MRSA in healthcare facilities. J Hosp Infection \n2006;635:S1-S44\n\n\n\n14. Laupland KB et al. Treatment of Staph aureus colonization and \nprophylaxis for infection with topical intranasal mupirocin: an \nevidence based review. Clin Infect Dis 2003;37:933-938\n\n\n\n\n\n\n\n\n87\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nD-penicillamine - induced pemphigus in a patient\nwith Wilson disease\n\n\n\nLoh LC1 MBChB MRCP, Goh KL2 MBBS FRCP and Rosnah Zain3 BDSc MSc\n\n\n\n1Dermatology unit, Department of Medicine\nUniversity Malaya, Kuala Lumpur\n2Gastroenterology unit, Department of Medicine\nUniversity Malaya, Kuala Lumpur\n3Department of Oral Pathology, Oral Medicine &\nPeriodontology, Faculty of Dentistry,  University Malaya\nKuala Lumpur\n\n\n\nCorrespondence\n\n\n\nDr LC Loh\nDermatology unit, Department of Medicine\nUniversity Malaya, Kuala Lumpur\nEmail: liewcloh@hotmail.com\n\n\n\nPemphigus is an autoimmune blistering disease characterized by\ncirculating autoantibodies directed against the keratinocyte cell surface.\nMajority of patients with pemphigus develop the disease\nspontaneously. However, there is a small group of patients who develop\npemphigus after treatment with certain medications, of which D-\npenicillamine (DPA) and captopril are the best documented. We report\na case of DPA-induced pemphigus vulgaris in a young Chinese lady\ntreated with DPA for Wilson disease.\n\n\n\nCase Report\nA 26-year-old Chinese lady was referred to the skin clinic\nin June 2003 when she developed blisters on her abdomen,\narms and legs.. She was diagnosed to have Wilson disease\nfollowing an episode of severe hepatitis in January 2000 and\nstarted on D-penicillamine 250mg QDS. She remained\nwell with good control of her Wilson disease until\nNovember 2002 when she developed painful blisters and\nulcers on her buccal mucosa, tongue and lips. She was seen\nin the dental department and treated with dexamethasone\nmouth rinse and fluocononide cream. Her mouth lesions\npersisted and she lost 7 kg within 6 months due to poor oral\nintake secondary to painful mouth lesions. In April 2003\nshe complained of recurrent painful red eyes and was treated\nas conjunctivitis by the ophthalmologist.\n\n\n\nOn further enquiry, apart from ongoing mouth ulcers and\nconjunctivitis, the blisters on her abdomen were only\npresent for 2 weeks and new lesions were developing on the\narms and legs. The lesions were initially small fluid-filled\nvesicles and gradually increased in size. They remained\ntense unless traumatized and became crusted and painful.\nApart from D-penicillamine, she admitted to taking\nprednisolone 5mg daily given by a family physician for the\npast few days for her newly developed blisters. There was no\n\n\n\nother positive past medical history, allergy or family history.\nSystemic enquiry was normal except for weight loss\nsecondary to poor oral intake due to painful mouth lesions.\n\n\n\nOn examination, there were a few discrete tense blisters\nranging from 8 to 12 mm diameter scattered on the\nabdomen, arms and legs. There were also a few crusted\nlesions. Examination of vulva showed some erosion on the\nlabia majora. Mild injected conjunctivae were noted and\nerosion and ulcers were detected on the lips, tongue and oral\nmucosae. Differential diagnosis included D-penicillamine\ninduced pemphigus and erythema multiforme.\n\n\n\nA skin biopsy was carried out and histopathology report\nshowed mild acanthosis and focal perivascular collection of\nlymphocytes and plasma cells. Direct immunofluorescence\nwas positive for IgG and complement was positive in the\nintercellular areas of the lower half of the  epidermis. The\nfeatures  were consistent with pemphigus vulgaris. A biopsy\nof buccal mucosa carried out in July 2003 was also\nconsistent with pemphigus vulgaris. (Figure 3a) Direct\nimmunofluorescence was positive for IgG with intercellular\ndistribution ( Figure 3b).\n\n\n\nDiagnosis of D-penicillamine induced pemphigus was\nexplained to the patient and D-penicillamine was stopped.\nShe was started on zinc sulphate 50mg TDS for Wilson\ndisease and prednisolone 30mg OD for the pemphigus. Her\npemphigus was controlled with slow tapering dose of\nprednisolone which was eventually stopped in Oct 2004.\nShe had no further flare-up of her pemphigus on the\nsubsequent follow up and was eventually discharged from\nthe skin clinic in 2006.\n\n\n\n\n\n\n\n\n88\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nWilson  disease is a recessively inherited, rare disorder of\ncopper metabolism that results in accumulation of copper in\nthe liver and subsequently other organs, mainly the central\nnervous system and kidneys. Treatment of Wilson disease\nincludes chelation therapy using D-penicillamine (DPA)1,\ntrientine and more recently, use of zinc acid.\n\n\n\nDPA was first recognised as a degradation product of\npenicillin more than half a century ago2 . It was first used\nclinically as a copper-chelating agent in the treatment of\nWilson disease1 and in lead poisoning. Subsequently it has\nbeen a therapy for a variety of diseases such as rheumatoid\narthritis, cystinuria, systemic sclerosis, primary biliary\ncirrhosis and many others. However the use of DPA has\nbeen hindered by its many adverse effects. The reported\nnoncutaneous side effects include renal, gastrointestinal,\nhaematologic, pulmonary and autoimmune involvement.\n\n\n\nThe skin reactions are the most common adverse effects of\nDPA. It affects 25% to 50% of patients taking DPA. The\ncutaneous side effects may be divided into several\ncategories, according to their induction mechanisms3. 1.\nDermatoses that result from interference with collagen and\nelastin (penicillamine dermopathy, elastosis perforans\nserpiginosa, excessive wrinkling, cutis laxa, pseudoxanthoma\nelasticum.) 2. Acute sensitivity reactions (urticaria,\nmaculopapular eruptions.) 3. Lesions caused by\nautoimmune mechanisms (bullous pemphigus and\npemphigoid, eruptions of systemic lupus erythematosus and\ndermatomyositis.) 4. Dermatoses that result from an\nuncertain mechanism (lichen planus, psoriasiform\ndermatitis, seborrhoeic dermatitis like, alopecia,\nhypertrichosis and nail changes).\n\n\n\nFigure 1.   Erosions on oral mucosa Figure 2.   Tense blisters on left forearm \n\n\n\nFigure 3.   IIntraepithelial split in pemphigus vulgaris\n\n\n\n\n\n\n\n\n89\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nPemphigus is an autoimmune blistering disease\ncharacterized by circulating autoantibodies directed against\nthe keratinocyte cell surface. The large majority of patients\nwith pemphigus develop the disease spontaneously.\nHowever, there is a small group of patients who develop\npemphigus after treatment with certain medications, of\nwhich DPA and captopril are the best documented 4 .\n\n\n\nDPA-induced pemphigus was first described by Dego et al\nin 1969.5 It is estimated that up to 7% of patients treated\nwith DPA for at least 6 months will acquire pemphigus.\nMost cases of DPA-induced pemphigus appear after an\naverage of 11.7 months (range from 4 weeks to 3 years) 3 .\nIn our patient, it took about three years of treatment with\nDPA before she presented with pemphigus.\n\n\n\nPemphigus foliaceus accounts for 46% of all DPA-induced\npemphigus cases. Approximately one third of the cases are\nof the vulgaris variant, and pemphigus erythematosus\naccounts for up to 20% of the cases 6 . Clinical presentation\nof our patient was one of pemphigus vulgaris. The average\nage of patients with DPA-induced pemphigus was 57 years\n(range from 24 to 78 years old), with a male to female ratio\nof 1.7:1. Blistering was frequently preceded by a pruritic\nurticarial eruption. Oral involvement occured in only 18%\nof DPA-induced pemphigus cases. However, oral mucosal\ninvolvement as the sole manifestation of DPA-induced\npemphigus has been reported 7 . Our patient had oral\ninvolvement of DPA-induced pemphigus which preceeded\nthe cutaneous involvement by more than six months.\n\n\n\nThe histopathology finding that characterizes many cases of\nDPA-induced pemphigus is diffuse acantholysis throughout\nthe epidermis. The cleavage level may vary in different\nlesions as suprabasilar or a high level of intraepidermal\nsplitting. In some reports, dermal infiltrates of DPA-\ninduced pemphigus may consist of neutrophils or\nlymphocytes in a perivascular or diffuse pattern. This is\natypical of spontaneously occurring pemphigus which are\ncharacterized by a mild infiltrate of oesinophils and\nlymphocyte 8 . Most patients with drug induced pemphigus\n\n\n\nhave tissue-bound and/or low-titre circulating\nautoantibodies with the same antigenic specificities at a\nmolecular level as autoantibodies from patients with other\nforms of idiopathic pemphigus. Positive direct\nimmunofluorescence in DPA-induced pemphigus is found\nin about 72.6% while positive indirect immunofluorescence\nwas 52.1% 9 . It is suggested that DPA might exacerbate\nsubclinical pemphigus foliaceus which is associated with\nHLA-DR4. Alleles of HLA-DR4 predispose to pemphigus\nvulgaris and a susceptibility allele is also carried by\nindividuals with drug-induced pemphigus 10 .\n\n\n\nIt is reported that 80% of DPA-induced pemphigus resolve\nwithin 1 year of drug withdrawal, with or without treatment\n6 . Our patient\u2019s DPA-induced pemphigus took more than\na year to resolve despite cessation of DPA and treatment\nwith prednisolone.\n\n\n\nReferences\n\n\n\n1. Walshe JM. Penicillamine: a new oral therapy for Wilson\u2019s \ndisease. Am J Med 1956;2:487-95.\n\n\n\n2. Abraham EP, Chain E, et al. Penicillamine, a characteristic \ndegradation product of penicillin. Nature 1943;151:107-10\n\n\n\n3. Levy RS, Fisher M, Alter JN. Penicillamine: review and \ncutaneous manifestations. J Am Acad Dermatol 1983;8:548-58\n\n\n\n4. Korman NJ, Eyre RW, et al. Drug-induced pemphigus: \nautoantibodies directed against the pemphigus antigen \ncomplexes are present in penicillamine and captopril-induced \npemphigus. J Invest Dermatol. 1991;96(2):273-6.\n\n\n\n5. Dego T, Touraine R, et al. Pemphigus chez un malade traite par \npenicillamine pour malladie de Wilson. Bull Soc Fr Dermatol \nSyphiligr 1969;76:751-3.\n\n\n\n6. Santa Cruz DJ, Prioleau PG, et al. Pemphigus-like lesions \ninduced by D-penicillamine. Am J Dermatopathol 1981;3:85-92. \n\n\n\n7. Hay KD, Muller HK et al. D-Penicillamine-induced \nmucocutaneous lesions with features of pemphigus. Oral Surg \nOral Med Oral Pathol 1978;45:385-95. \n\n\n\n8. Troy JL, Silvers DN, et al. Penicillamine- associated pemphigus: \nIs it really pemphigus? J Am Acad Dermatol 1981;4:547-55.\n\n\n\n9. Brenner S, Wolf R etal. Drug induced pemphigus: I. a survey. Clin \nDermatol 1993;11:501-5.\n\n\n\n10. Matzner Y, Erlich HA, et al. Identical HLA class II alleles \npredispose to drug triggered and idiopathic pemphigus vulgaris. \nActa Derm Venereol 1995;75:12-4.\n\n\n\n\n\n\n\n\n90\n\n\n\n\n\n\n\n\n91\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nCutaneous B-cell pseudolymphoma: Case reports and \nliterature review\n\n\n\nTang JJ MBBS, Chan LC MD MMed and Heng A MBBS MRCP\n\n\n\nDepartment of Dermatology, Ipoh Hospital, Perak, Malaysia\n\n\n\nCorrespondence\n\n\n\nAgnes Heng MBBS MRCP\n\n\n\nDepartment of Dermatology\nIpoh Hospital\n30990 Ipoh, Malaysia\nEmail: agnesheng@gmail.com\n\n\n\nKeywords Cutaneous B-cell pseudolymphoma, lymphocytoma cutis,\n\n\n\ncutaneous lymphoid hyperplasia\n\n\n\nCutaneous B-cell pseudolymphoma (CBPL) is a reactive B-cell\n\n\n\nhyperplasia that clinically and histologically mimics cutaneous B-cell\n\n\n\nlymphoma (CBCL). Many different terms have been used to describe\n\n\n\nthis condition such as lymphocytoma cutis and cutaneous lymphoid\n\n\n\nhyperplasia. This condition typically present as a solitary nodule or\n\n\n\npapule over face (cheek, nose and ear lobe), chest and upper extremities,\n\n\n\nbut multiple lesions may also be present. A variety of stimuli are known\n\n\n\nto induce this condition but most cases have an unknown cause. We\n\n\n\nreport 2 cases of CBPL, the causes of which could not be ascertained.\n\n\n\nCase Reports\nCase 1\nA 60-year-old Indian lady presented with multiple\nasymptomatic erythematous nodules and plaques over her\nface for 3 months. There was no history of any insect bite or\ntrauma. She had no fever, loss of appetite or loss of weight.\nShe was diagnosed to have hypertension for 8 years and has\nbeen on atenolol, prazosin and chlorothiazide. On\nexamination, there were multiple erythematous plaques and\nnodules over her forehead and upper lip (Fig1). Systemic\nexamination was unremarkable. Baseline blood\ninvestigations and chest X-ray were all normal. Skin biopsy\nrevealed dense mature lymphocytes in dermis with\nwidespread lymphoid follicles, some with a germinal center\nformation. (Fig 3a). The germinal centre showed plentiful\ntingible body macrophages (Fig 3b). Immunohistochemical\nstudies revealed a predominantly CD 20+ B-cells in\ngerminal centre and mantle zone area while CD 3+ and CD\n45R0+ cells were present in paracortical area. The B-cells\nexpressed both \ufffd and \ufffd light chains with \ufffd/\ufffd ratio of 4:1.\nThe diagnosis of cutaneous B-cell pseudolymphoma was\nmade and she was started on mometasone furoate 0.1%\n\n\n\ncream. However, the response to treatment was slow and\nshe was subsequently given intralesional triamcinolone\nacetonide and hydroxychloroquine. Her lesions improved\nsignificantly with the treatment but she developed some\nnew eruptions 4 months later which required further\nintralesional corticosteroid injection. Since then, she did not\nhave any recurrences.\n\n\n\nCase 2\nA 57-year-old Malay man presented with multiple\nasymptomatic, slowly progressive, erythematous nodules\nover his face for 1 year. He denied any history of insect bite\nor trauma and did not report any constitutional symptoms.\nHis medical history includes hypertension of 5 years\nduration and was on atenolol. On examination, there were\nerythematous plaques and nodules over his nose, right\ncheek and above his upper lip (Fig 2). He had no\nlymphadenopathy or hepatosplenomegaly. Other systems\nwere normal. Baseline blood investigations and chest X-ray\nwere all normal. Skin biopsy showed that the dermis was\ninfiltrated by a nodular pattern of mature lymphocytes,\nmacrophages, few plasma cell and eosinophils. The\nlymphocytic infiltrates formed follicles with germinal\ncenters and tingible body macrophages which were\nsurrounded by a mantle of small lymphocytes.\nImmunohistochemical studies revealed a mixed B- and T-\nlymphocytes. He was diagnosed as cutaneous B-cell\npseudolymphoma and was started on topical mometasone\nfuroate 0.1% cream. However he did not respond to topical\ntreatment and subsequently intralesional triamcinolone\nacetonide and hydroxychloroquine were added. The lesions\nstarted to improve 6 weeks later and almost disappeared\nafter 9 months of treatment.\n\n\n\n\n\n\n\n\n92\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.   Case 1. A 60-year-old \nlady with erythematous \nplaques and nodules on \nher forehead and \nupper lip\n\n\n\nFigure 3.   (a). Widespread lymphoid follicles with germinal centre formation in dermis and\n(b). The germinal centre shows plentiful tangible body macrophages\n\n\n\nFigure 2.   Case 2. A 57 year-old-\nman with erythematous \nplaques and nodules on \nhis nose, upper lip and \nright cheek.\n\n\n\na b\n\n\n\nDiscussion\nCutaneous pseudolymphoma (CPL) is a group of benign T\nor B lymphocytic infiltrate of the skin which clinically\nand/or histologically simulate cutaneous lymphomas. It can\nbe further divided into T- and B-cell pseudolymphoma\ndepending on the predominant cell type in the infiltrate.\nCPL represents the benign end of a lymphoproliferative\ncontinuum eventuating in true lymphoma at its malignant\nextreme.\n\n\n\nThis condition was first described as sarcomatosis cutis by\nKaposi in 1891. Subsequently various terms have been used\nto describe this condition such as lymphocytoma cutis,\nlymphadenosis benigna cutis, cutaneous lymphoid\nhyperplasia, pseudolymphoma of Spiegler and Fendt. It was\nfinally known as cutaneous pseudolymphoma by Burg et al\nin 1982. Cutaneous pseudolymphoma is a preferred\ndesignation to describe the whole group as it always alerts\none to differentiate these conditions from malignant\ncutaneous lymphoma. Van Vloten et al suggested that it is\nbest to avoid all the various names and to use only cutaneous\nB- or T-cell pseudolymphoma.\n\n\n\n\n\n\n\n\n93\n\n\n\nCutaneous B-cell pseudolymphoma (CBPL) is known to be\ninduced by a variety of stimuli. These include Borrelia\nburgdorferi infection, insect bites, tattoo (predominantly\nred colours), drugs reactions (injected drugs), acupuncture,\ntrauma, vaccination and gold piercing earrings. However,\nmost cases have an unknown cause, as in our 2 patients, and\nthey are termed as idiopathic CBPL. Clinically, CBPL\noften presents as a single nodule or papule (flesh-colored to\nplum-red dermal)  commonly located on face (cheek, nose\nand ear lobe), chest and upper extremities. Scale and\nulceration are generally absent. Multiple lesions and\ngeneralized form is rather infrequent . Both of our patients\npresented with multiple erythematous nodules and plaques\nover the face, which were are rather uncommon. There were\nno identifiable triggering factors in both cases.\n\n\n\nIt may be extremely difficult to differentiate between CBPL\nand cutaneous B-cell lymphoma (CBCL) and a skin biopsy\nis often necessary to differentiate these two conditions.\nCBPL can be differentiated from CBCL by the mixed-cell\ninfiltrate with small mature lymphocytes mainly involving\nthe upper dermis, so called \u201ctop heavy\u201d, in contrast to\nCBCL where the infiltrate is monomorphous, composed of\nmedium to large lymphocytes mainly involving the reticular\ndermis, so called \u201cbottom heavy\u201d. Follicular germinal\ncenters and tingible body macrophages are often present in\nCBPL but are rarely found in CBCL. Furthermore, the\nepithelial and adnexal structures are preserved in CBPL but\nthey are often obliterated in CBCL.\n\n\n\nImmunohistochemical and molecular biological techniques\nenables us more precisely to distinguish CBPLs\nfrom cutaneous malignant B-cell lymphomas.\nImmunohistochemistry in CBPL will show predominance\nof CD 20+ B-cells within reactive follicles and a variable\nnumber of CD3+ T-cells at interfollicular area.\nImmunostaining for kappa (\ufffd) or lambda (\ufffd) light chains\nwill show both chains present in CBPL (polyclonality)\nwhile only one of these will be present in CBCL\n(monoclonality) (\ufffd:\ufffd ratio greater than 10:1 or less than\n0.5:1)2. In our patients, both had the typical\nhistopathological features suggestive of CBPL which\ninclude mature lymphocytic infiltrates in dermis with\nmultiple follicular germinal centers and tingible body\nmacrophages. Immunohistochemical staining also showed\nthat predominance of CD20+ B cells in the germinal centre.\nWe were able to demonstrate polyclonal \ufffd and \ufffd light\nchains in the B-cells in Case 1 while staining for \ufffd and \ufffd\nlight chains was not done in Case 2.\n\n\n\nIn some cases, the possibility of lymphoma cannot be\nexcluded by means of histologic analysis. In such cases,\nmolecular biologic studies which consist of immunoglobulin\nor T-cell receptor genetic rearrangements may provide\nadditional helpful information. If a clone is identified, it\nincreases the likelihood of CBCL. The results of this test\nshould not be considered definitive as clonality is reported\nin occasional pseudolymphomas. This intermediate\ncondition is known as \u201cclonal cutaneous lymphoid\nhyperplasia\u201d which is capable of eventuating into overt\nlymphoma. Antibodies to B burgdorferi may be identified\nin 50% of patients with borrelial lymphocytoma2.\n\n\n\nIn treatment of CBPL, identification of the causative agent\nis very important as removal of the cause generally leads to\nresolution. In cases in which the cause is unknown, the\ncourse varies considerably, but it tends to be chronic and\nindolent. For localized persistent lesions, treatment options\ninclude topical or intralesional corticosteroids, topical\ntacrolimus , cryosurgery, interferon alfa, local radiation and\nsurgical excision. Treatment options for widespread lesions\ninclude antimalarials (Hydroxychloroquine), photodynamic\ntherapy (PDT) with topical 5 aminolevulinic acid (ALA),\nthalidomide   and cytotoxic agents. Borrelia lymphocytoma\ncutis can be treated with oral penicillin 1 gm tds or\ndoxycycline 100 mg bd for 2 weeks. In our case, both\npatients showed good response to combination of\nhydroxychloroquine, topical and intralesional corticosteroid\ntherapy.\n\n\n\nReferences\n\n\n\n1. Van Vloten WA, Willemze R. The many faces of lymphocytoma \ncutis. J Eur Acad Dermatol and Venereol 2003;17:3-6\n\n\n\n2. Ploysangam T, Breneman DL, Mutasim DF. Cutaneous \npseudolymphomas. J Am Acad Dermatol 1998;38: 877-905.\n\n\n\n3. Carr RA, Sanders DSA. Inflammatory dermatoses mimicking \nmalignancy (pseudolymphoma). Curr Diagn Pathol 2005;\n11:245-252\n\n\n\n4. Nihal M, Mikkola D, Horvath N, et al. Cutaneous Lymphoid \nHyperplasia: A lymphoproliferative continuum with \nlymphomatous potential. Hum Pathol 2003; 34:617-622  \n\n\n\n5. El-Dars LD, Statham BN, Blackford S, et al. Lymphocytoma cutis \ntreated with topical tacrolimus, Clin Exp Dermatol 2005;\n30: 294-307\n\n\n\n6. Mikasa K, Watanabe D, Kondo C, et al. Topical 5 aminolevulinic \nacid-based photodynamic therapy for the treatment of a patient \nwith cutaneous pseudolymphoma . J Am Acad Dermatol  \n2005;53:911-912 \n\n\n\n7. Benchikhi H, Bodemer C, Fraitag S, et al. Treatment of cutaneous \nlymphoid hyperplasia with thalidomide: Report of two cases. J \nAm Acad Dermatol 1999;40:1005-1007\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n94\n\n\n\n\n\n"
"\n\n23\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nAcute generalized exanthematous pustulosis:\nA histologic study of forty-five cases\n\n\n\nMai P Hoang1 MD, Meera Mahalingam1,2 MD FRC Path, Jag Bhawan2 MD, Payal Kapur2,3 MD and \nWhitney A High4 MD\n\n\n\n1Department of Pathology, Massachusetts General Hospital\nand Harvard Medical School, Boston, MA\n2Department of Dermatology, Boston University Medical School\nBoston, MA\n3Department of Pathology, University of Texas Southwestern Medical Center\nDallas, Texas\n4Department of Dermatology, University of Colorado Health Sciences Center\nAurora, CO\n\n\n\nCorrespondence\n\n\n\nMai P. Hoang, MD\n\n\n\nMassachusetts General Hospital\nDermatopathology Unit\n55 Fruit Street, Warren 820\nBoston, MA 02114\nEmail: mhoang@partners.org\n\n\n\nAbstract\n\n\n\nBackground Literature on acute generalized exanthematous\npustulosis (AGEP) is restricted to case reports, with only one prior\nseries study. More importantly, a detailed histologic comparison to\npustular psoriasis has not been done.\n\n\n\nObjective To identify discriminatory characteristics, we compared the\nhistologic features of 45 cases of AGEP and 19 cases of pustular\npsoriasis.\n\n\n\nMethods Demographic, historical, clinical, and histologic features of\nAGEP and pustular psoriasis were compared using specimens from 5\ntertiary medical centers.\n\n\n\nResults The age of patients with AGEP ranged from 12 to 91 years\n(mean, 53 years) with a nearly equal M:F ratio. All 45 patients\npresented with a generalized erythematous, pustular eruption (mean\nduration of pustules, 12 days) and fever (present in 25/31 patients).\nRecent drug ingestion was documented in 36/38 (95%) patients. Of\nthe 5 pediatric cases, two had prior upper respiratory tract infection,\nbut were without a history of recent drug ingestion. No patient with\nAGEP had a history of psoriasis. AGEP was distinguished from\npustular psoriasis based upon the following histologic features: necrotic\nkeratinocytes, papillary dermal edema, presence of eosinophils within\nthe dermis, and absence of parakeratosis with neutrophils (p <0.05).\n\n\n\nConclusion While the precise etiology of AGEP remains unknown,\nour findings confirm that most AGEP cases in adults are drug-related.\nCertain histologic features appear to reliably discriminate AGEP from\npustular psoriasis, and awareness of them may increase diagnostic\naccuracy.\n\n\n\nKeywords acute generalized exanthematous pustulosis, AGEP,\npustular psoriasis.\n\n\n\nIntroduction\nIn 1968, Baker and Ryan1 reported 104 cases of generalized\npustular psoriasis; 5 of which occurred in patients without a\nhistory of psoriasis, raising the possibility of infection or\ndrug as a possible etiology. In 1980, Beylot et al2. introduced\nthe term acute generalized exanthematous pustulosis\n(AGEP) to describe pustular eruptions with the following\ncharacteristics: (1) an acute onset without a history of\npsoriasis, infection, or drug ingestion less than one day\nprior; (2) spontaneous resolution of the eruption within 15\ndays; and (3) histologically, non-follicular subcorneal\npustules.\n\n\n\nThe published literature on AGEP exists primarily as case\nreports. A case series has not been described since 1991,\nwhen Roujeau et al. reported on 63 cases3. While textbooks\nmay occasionally note the histologic features of AGEP to be\nindistinguishable from pustular psoriasis, a detailed\ncomparison between AGEP and pustular psoriasis has never\nbeen performed. In this study, we compared the histological\nfeatures of 45 cases of AGEP and 19 cases of pustular\npsoriasis derived from 5 tertiary medical centers.\n\n\n\nMaterials and methods\nThis study was approved by the institutional review boards.\nAll cases with the histologic diagnosis of a pustular eruption\nconsistent with AGEP and pustular psoriasis were obtained\nusing computerized database searches. The clinical history\nof these cases was reviewed. The cases were classified as\neither\n\n\n\n\n\n\n\n\n24\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\neither AGEP or pustular psoriasis based upon the\ncorresponding clinical findings. Histologic specimens of 45\nAGEP and 19 pustular psoriasis cases from 1992 to 2007\nwere retrieved from the pathology files of Massachusetts\nGeneral Hospital and Boston University Medical School,\nBoston, MA; UMass Memorial Medical Center, Worcester,\nMA; University of Texas Southwestern Medical Center,\nDallas, TX; and University of Colorado Health Sciences\nCenter, Aurora, CO. Clinical and histological patient data\nwere catalogued and de-identified.\n\n\n\nClinical Evaluation\nFor all cases, the following information was extracted from\nthe medical records: presentation and distribution of the\nrash; duration of erythema and pustulosis; presence of fever;\nand a history of recent use of medications, prior drug\nreaction(s), psoriasis, recent infection(s), and other relevant\nunderlying diseases.\n\n\n\nHistologic Evaluation\nHistologic sections of all cases were re-reviewed and\nthe diagnoses confirmed independently by two\ndermatopathologists (MPH and MM). For each of 64\ncases, the histologic features outlined in Table 3 were graded\nas either present or absent. The dermal inflammatory\ninfiltrate was graded as sparse (1+), non-brisk (2+) and brisk\n(3+).\n\n\n\nStatistical Analysis\nStatistical differences were confirmed using the Pearson\u2019s\nchi-squared test for non-continuous variables, or where a\ncategory contained less than 5 observations, using the\nFisher\u2019s exact test for non-continuous variables. P-values of\nless than 0.05 were considered significant.\n\n\n\nResults\nDemographic Data\nThe demographic data of 45 AGEP cases from 44 patients\nare summarized in Table 1. All patients presented with a\ngeneralized erythematous and pustular eruption. Most\noften the eruption began upon the face or in the\nintertriginous areas (Figures 1-3). The age of patients with\nAGEP ranged from 12 to 91 years (median, 65 years; mean,\n53 years). The male to female ratio was 4:3.\nAdditional clinical information was available for 38\npatients. Fever was present in 25/31 (81%) patients. The\nduration of pustules was documented in 17 patients (range,\n4 to 30 days; median, 10 days; mean, 12 days). Recent drug\ningestion was documented in 36/38 (95%) patients, with 13\nof these 36 patients having had a prior drug reaction. Two\npediatric patients (Table 2) had a prior upper respiratory\ntract infection, but were without a history of recent drug\ningestion. No patient with AGEP had a history of psoriasis\n(0/38). A family history of psoriasis was not noted (0/13).\nFor the cases of pustular psoriasis, patient age ranged from\n3 to 84 years (median, 60 years; mean, 51 years). The male\nto female ratio was 6:13. Nine of 19 patients had a prior\n\n\n\nhistory of psoriasis. The duration of pustules was\ndocumented in 5 patients and it ranged from 3 weeks to 4\nmonths (median, 3 months).\n\n\n\nHistologic Evaluation\nThe histologic features of AGEP and pustular psoriasis are\nsummarized in Table 3. Necrotic keratinocytes, papillary\ndermal edema, and a significant (>1+) dermal infiltrate of\neosinophils were features more often observed with AGEP\n(p < 0.05) (Figure 4). Follicular involvement was noted in\nfour cases (Figure 4). Fibrin thrombi were rare in AGEP.\nParakeratosis containing neutrophils was observed with\ngreater frequency in pustular psoriasis (p < 0.05).\n\n\n\nDiscussion\nIn the prior series of patients with AGEP, Roujeau et al3.\nnoted significant differences between patients with AGEP\nand pustular psoriasis including: (1) a history of drug\neruption(s), (2) recent drug administration, (3) duration of\npustules, and (4) duration of fever. Further, it was noted that\nAGEP most often began upon the face or intertriginous\nareas and disseminated within a few hours of ingestion of\nthe offending substance. Non-follicular pustules of < 5mm\ndiameter arose upon edematous and erythematous skin.\nPruritis and/or a burning sensation were often noted. Most\npatients (46/63) had more than 100 pustules, and the mean\nduration of the pustules was 9.7 days (range, 4 to 30 days).\nTypically, desquamation followed within a few days.\n\n\n\nBecause of the retrospective nature of our study, we were not\nable to retrieve complete clinical data for all the AGEP and\npustular psoriasis cases studied herein. However, for AGEP\ncases with available clinical information, we noted similar\ndistinguishing features including: the presence of fever\n(81%), the mean duration of the pustules (12 days), and a\nrecent history of drug ingestion (95%). One patient had 2\nepisodes of AGEP within a 2-year period (Cases 43 and\n44).\n\n\n\nFour of our cases occurred in children. Interestingly, only\napproximately 12 cases of pediatric AGEP have been\nreported in the world literature4-11. The clinical features of\nour 4 pediatric cases of AGEP, as compared to the 8\npediatric cases already described in the English-language\nliterature, are summarized in Table 24-7. In our pediatric\ncases the age ranged from 5 months to 16 years (median, 7\nyears). Interestingly, a male predominance was noted among\npediatric AGEP cases. A family history of psoriasis was not\nnoted in two (0/2) pediatric patients. Development of\npsoriasis was not observed 3 years after presentation in one\npatient with available follow-up. Recognized etiologic\nagents for AGEP in children include drugs, infections,\nmercury exposure, and pneumococcal vaccination\n(table 2)4-7. In contrast to our adult population with AGEP,\nin which drug ingestion was the predominant association,\ninfection was equally implicated in our pediatric cases.\n\n\n\n\n\n\n\n\n25\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase #\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\n11\n\n\n\n12\n\n\n\n13\n\n\n\n14\n\n\n\n15\n\n\n\n16\n\n\n\n17\n\n\n\n18\n\n\n\n19\n\n\n\n20\n\n\n\nAge/\nSex\n\n\n\n32F\n\n\n\n32F\n\n\n\n21M\n\n\n\n21M\n\n\n\n48M\n\n\n\n84F\n\n\n\n13M\n\n\n\n35M\n\n\n\n24M\n\n\n\n70M\n\n\n\n82F\n\n\n\n69M\n\n\n\n15M\n\n\n\n72F\n\n\n\n19M\n\n\n\n38M\n\n\n\n86F\n\n\n\n77M\n\n\n\n72F\n\n\n\n69M\n\n\n\nClinical presentation\n\n\n\nGyeneralized vesiculopustular\nrash\n\n\n\nGeneralized erythema and\npustules\n\n\n\nGeneralized erythema and\npustules\n\n\n\nDiffuse maculopapular rash\n\n\n\nGeneralized erythema and\npustules\n\n\n\nGeneralized erythema and\npustules\n\n\n\nGeneralized erythema and\npustules\n\n\n\nGeneralized erythema and\npustules\n\n\n\nDiffuse maculopapular rash\n\n\n\nGeneralized erythema and\npustules\n\n\n\nPustular eruption on trunk and\nextremities\n\n\n\nGeneralized\n\n\n\nDiffuse pruritic eruption with\nsubcorneal pustules\n\n\n\nDiffuse pustules on an\nerythematous base\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nDiffuse rash\n\n\n\nDiffuse erythematous and \ndusky rash\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nFever\n\n\n\nyes\n\n\n\nno\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nDuration\nof\npustules\n\n\n\n5d\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\n9d\n\n\n\nND\n\n\n\n23d\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\n10d\n\n\n\nND\n\n\n\nND\n\n\n\n21d\n\n\n\n5d\n\n\n\nND\n\n\n\nH/o drug\nintake\n\n\n\nClarithromycin\n\n\n\nPenicillin/\nampicillin\n\n\n\nAmoxicillin\n\n\n\nVancomycin\n\n\n\nIbuprofen\n\n\n\nClindamycin\n\n\n\nnone\n\n\n\nPenicillin/\ncefipime\n\n\n\nTegretol\n\n\n\nVancomycin\n\n\n\nBactrim/dilantin\n\n\n\nVancomycin\n\n\n\nnone\n\n\n\nPenicillin\n\n\n\nIbuprofen\n\n\n\nAmoxicillin\n\n\n\nVancomycin\n\n\n\nCefepime\n\n\n\nPlavix\n\n\n\nVancomycin\n\n\n\nPrevious\ndrug\nreaction\n\n\n\nnone\n\n\n\nnone\n\n\n\nyes\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nyes\n\n\n\nnone\n\n\n\nyes\n\n\n\nnone\n\n\n\nyes\n\n\n\nnone\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nH/o \n\n\n\npsoriasis\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nH/o\ninfection\n\n\n\nnone\n\n\n\nnone\n\n\n\nViral versus\nmononucleosis\n\n\n\nosteomyelitis\n\n\n\nnone\n\n\n\nnone\n\n\n\nViral upper\nrespiratory tract\ninfection\n\n\n\nnone\n\n\n\nnone\n\n\n\nStreptococcal\nliver abscess\n\n\n\nnone\n\n\n\nnone\n\n\n\nupper\nrespiratory tract\ninfection\n\n\n\nnone\n\n\n\nUrinary tract\ninfection,\nmononucleosis\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nBacterial\ninfection\n\n\n\nUnderlying\ndisease\n\n\n\nnone\n\n\n\npostpartum\n\n\n\nnone\n\n\n\nStatus post motor\nvehicle accident\n\n\n\nAcute renal failure\n\n\n\nnone\n\n\n\neczema\n\n\n\nSynovial sarcoma\nwith multiple lung\nmetastases\n\n\n\nStatus post motor\nvehicle accident\n\n\n\nChronic\nobstructive\npulmonary disease\n\n\n\nGlioblastoma\nmultiforme\n\n\n\nAortic dissection,\nright empyema\n\n\n\nnone\n\n\n\nRheumatic fever,\naortic and mitral\nvalves impairment\n\n\n\nAsthma, obesity\n\n\n\nnone\n\n\n\nBilateral lower leg\ncellulitis\n\n\n\nClostridium\ndifficile colitis\n\n\n\nAcute myocardial\ninfarction\n\n\n\nRight ankle\nfracture\n\n\n\nTable 1.   Clinical data of 45 cases of acute generalized exanthematous pustulosis\n\n\n\n\n\n\n\n\n26\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase #\n\n\n\n21\n\n\n\n22\n\n\n\n23\n\n\n\n24\n\n\n\n25\n\n\n\n26\n\n\n\n27\n\n\n\n28\n\n\n\n29\n\n\n\n30\n\n\n\n31\n\n\n\n32\n\n\n\n33\n\n\n\n34\n\n\n\n35\n\n\n\n36\n\n\n\n37\n\n\n\n38\n\n\n\n39\n\n\n\n40\n\n\n\n41\n\n\n\nAge/\nSex\n\n\n\n75F\n\n\n\n59F\n\n\n\n12M\n\n\n\n16M\n\n\n\n30F\n\n\n\n48F\n\n\n\n44F\n\n\n\n28F\n\n\n\n36F\n\n\n\n91F\n\n\n\n58M\n\n\n\n86M\n\n\n\n31F\n\n\n\n88M\n\n\n\n81F\n\n\n\n71M\n\n\n\n86M\n\n\n\n88F\n\n\n\n35F\n\n\n\n82F\n\n\n\n79F\n\n\n\nClinical presentation\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nDiffuse erythematous papules\nand pustules\n\n\n\nDiffuse pustules\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\nFever\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nyes\n\n\n\nno\n\n\n\nno\n\n\n\nyes\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nDuration\nof\npustules\n\n\n\n13 d\n\n\n\n6 d\n\n\n\n4d\n\n\n\n14d\n\n\n\n30d\n\n\n\nND\n\n\n\n13 d\n\n\n\n7 d\n\n\n\nND\n\n\n\n5d\n\n\n\nND\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nno\n\n\n\nH/o drug\nintake\n\n\n\nZometa\n(zoledronic acid)\n\n\n\nCardizem\n\n\n\nAcetaminophen;\nibuprofen\n\n\n\nAzithromycin\n\n\n\nIsoniazid\n\n\n\nZoloft, trazodone\n\n\n\nLamisil\n\n\n\nhydroxychloroquine\n\n\n\nAmpicillin\n\n\n\nCephalexin\n\n\n\nItarubicin, araC,\nallopurinol\n\n\n\nMeclizine,\nclonzazepam,\ntimolol, Lanoxin,\ncoumadin, paxil,\nflonase\n\n\n\nLovenox,\ncoumadin,\nheparin, TPA,\nvicodin\n\n\n\nNA\n\n\n\nNA\n\n\n\nLipitor\n\n\n\nUltram\n\n\n\nPlaquenil\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nPrevious\ndrug\nreaction\n\n\n\nyes\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nyes\n\n\n\nnone\n\n\n\nnone\n\n\n\nyes\n\n\n\nnone\n\n\n\nnone\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nH/o \n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone \n\n\n\nnone\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nH/o\ninfection\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nUnderlying\ndisease\n\n\n\nMetastatic breast\ncarcinoma\n\n\n\nDiabetes mellitus,\nendometrial\ncarcinoma\n\n\n\nnone\n\n\n\nnone\n\n\n\nSezary syndrome/\nmycosis fungoides\n\n\n\nDiabetes mellitus,\nhypertension\n\n\n\nAsthma,\nhypertension\n\n\n\nND\n\n\n\nStatus post\ncaesarean section\n\n\n\nND\n\n\n\nAcute\nmyelogenous\nleukemia\n\n\n\nND\n\n\n\nND\n\n\n\nNA\n\n\n\nNA\n\n\n\nND\n\n\n\nND\n\n\n\nLupus\nerythematosus\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\n\n\n\n\n\n27\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase #\n\n\n\n42\n\n\n\n43\n\n\n\n44\n\n\n\n45\n\n\n\nAge/\nSex\n\n\n\n82F\n\n\n\n42F\n\n\n\n71M\n\n\n\nClinical presentation\n\n\n\nGeneralized\n\n\n\nGeneralized\n\n\n\ngeneralized\n(same pt, 2 years later)\n\n\n\nGeneralized\n\n\n\nFever\n\n\n\nno\n\n\n\nno\n\n\n\nno\n\n\n\nNA\n\n\n\nDuration\nof\npustules\n\n\n\n7d\n\n\n\n14d\n\n\n\n14d\n\n\n\nNA\n\n\n\nH/o drug\nintake\n\n\n\nAllopurinol,\ncitalopram,\ntorsemide,\nprotonix, toprol,\nalbuterol,\nprotoniz, Vantin,\nNorvasc,\ncoumadin,\noxycodone,\nheparin,\nsynthroid\n\n\n\nCipro, ceftriaxone\n\n\n\nLevofloxacin\n\n\n\nNA\n\n\n\nPrevious\ndrug\nreaction\n\n\n\nnone\n\n\n\nyes\n\n\n\nyes\n\n\n\nNA\n\n\n\nH/o \n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nNA\n\n\n\nH/o\ninfection\n\n\n\nnone\n\n\n\nnone\n\n\n\nnone\n\n\n\nNA\n\n\n\nUnderlying\ndisease\n\n\n\nhypothyroidism\n\n\n\nnone\n\n\n\nnone\n\n\n\nNA\n\n\n\nCase # (reference)\n\n\n\nCase7\n\n\n\nCase13\n\n\n\nCase23\n\n\n\nCase24\n\n\n\nErsoy #14\n\n\n\nErsoy #24\n\n\n\nErsoy #34\n\n\n\nErsoy #44\n\n\n\nErsoy #54\n\n\n\nSezer5\n\n\n\nLee6\n\n\n\nMeadows7\n\n\n\nAge / Sex\n\n\n\n13yr/M\n\n\n\n15yr/M\n\n\n\n12yr/M\n\n\n\n16yr/M\n\n\n\n5mo/M\n\n\n\n15mo/M\n\n\n\n8yr/M\n\n\n\n15mo/M\n\n\n\n13yr/M\n\n\n\n6yr/M\n\n\n\n6yr/M\n\n\n\n17mo/M\n\n\n\nHistory of drug intake\n\n\n\nnone\n\n\n\nnone\n\n\n\nAcetaminophen;\nibuprofen\n\n\n\nAzithromycin\n\n\n\nNone\n\n\n\nNone\n\n\n\nNone\n\n\n\nNone\n\n\n\nLabetolol\nVancomycin\n\n\n\nAcetaminophen\n\n\n\nNA\n\n\n\nAmoxicillin\n\n\n\nHistory of infection\n\n\n\nViral upper respiratory tract infection\n\n\n\nupper respiratory tract infection\n\n\n\nNone\n\n\n\nNone\n\n\n\nrhinorrhea\n\n\n\nDiarrhea, vaccine (measles, mumps, rubella, diphtheria,\npertussis, tetanus and pneumococcal vaccinations)\n\n\n\nNon-group A beta-hemolytic streptococcal tonsillitis\n\n\n\notitis media\n\n\n\nNone\n\n\n\nNone\n\n\n\nNA\n\n\n\nNone\n\n\n\nTable 2.   Summary of pediatric AGEP cases in the English literature\n\n\n\nNA : not available; ND : not documented \n\n\n\nNA: not available\n\n\n\n\n\n\n\n\n28\n\n\n\nNumber of Cases\n\n\n\nParakeratosis with neutrophils and serum\n\n\n\nParakeratosis with neutrophils\n\n\n\nSubcorneal pustules\n\n\n\nIntraepidermal pustules\n\n\n\nEosinophils within pustule\n\n\n\nEpidermal spongiosis\n\n\n\nAcanthosis\n\n\n\nPsoriasiform hyperplasia\n\n\n\nBasal mitoses (> 1per 10HPFs)\n\n\n\nExocytosis of eosinophils\n\n\n\nNecrotic keratinocytes\n\n\n\nPapillary dermal edema\n\n\n\nVasculitis\n\n\n\nFibrinoid necrosis\n\n\n\nExtravasation of erythrocytes\n\n\n\nFollicular involvement\n\n\n\nDermal eosinophils (>1+)\n\n\n\nDermal neutrophils (>1+)\n\n\n\nDermal lymphocytes (>1+)\n\n\n\nAGEP\n\n\n\n45\n\n\n\n7/45 (15.6%)\n\n\n\n4/45 (8.9%)\n\n\n\n45/45 (100%)\n\n\n\n40/45 (88.9%)\n\n\n\n14/45 (31.1%)\n\n\n\n45/45 (100%)\n\n\n\n44/45 (97.8%)\n\n\n\n8/45 (17.8%)\n\n\n\n30/43 (69.8%)\n\n\n\n16/45 (35.6%)\n\n\n\n41/45 (91.1%)\n\n\n\n43/45 (95.6%)\n\n\n\n0/44 (0%)\n\n\n\n1/44 (2.3%)\n\n\n\n42/45 (93.3%)\n\n\n\n4/45 (8.9%)\n\n\n\n19/44 (43.1 %)\n\n\n\n25/44 (56.8%)\n\n\n\n25/44 (56.8%)\n\n\n\nPustular psoriasis\n\n\n\n19\n\n\n\n1/19 (5.3%)\n\n\n\n16/19 (84.2%)\n\n\n\n18/19 (94.7%)\n\n\n\n18/19 (94.7%)\n\n\n\n1/19 (5.3%)\n\n\n\n14/19 (73.7%)\n\n\n\n19/19 (100%)\n\n\n\n9/19 (47.4%)\n\n\n\n11/19 (57.9%)\n\n\n\n1/19 (5.3%)\n\n\n\n1/19 (5.3%)\n\n\n\n7/19 (36.8%)\n\n\n\n0/18 (0%)\n\n\n\n0/18 (0%)\n\n\n\n10/19 (52.6%)\n\n\n\n1/19 (5.3%)\n\n\n\n0/18 (0%)\n\n\n\n6/18 (33.3%)\n\n\n\n12/18 (66.7%)\n\n\n\nP value\n\n\n\nNS\n\n\n\n0.0001\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\n0.0006\n\n\n\n0.0477\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\nNS\n\n\n\n0.0089\n\n\n\nNS\n\n\n\nNS\n\n\n\nTable 3.   Summary of histologic comparison\n\n\n\nAGEP, acute generalized exanthematous pustulosis; HPF, high power field; NS, not statistically significant\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.   Involvement of the face is frequently \nseen in AGEP cases whereas it is rarely \nseen in pustular psoriasis.\n\n\n\nFigure 2.   Involvement of the body folds is common \nincluding the neck of one patient.\n\n\n\n\n\n\n\n\n29\n\n\n\nacetaminophen3\n\n\n\nallopurinol12\n\n\n\namoxapine13\n\n\n\namoxicillin14\n\n\n\namphotericin B15\n\n\n\nazathioprine16\n\n\n\nanti-HIV protease inhibitors17\n\n\n\nbeta-lactam antibiotics3\n\n\n\nbamifylline18\n\n\n\nbleomycin19\n\n\n\nbufexamac3\n\n\n\nbuphenine20\n\n\n\ncarbamazepine3\n\n\n\ncarbutamide3\n\n\n\nchemotherapy (high dose)21\n\n\n\nchloramphenicol22\n\n\n\nchromium picolinate23\n\n\n\nclemastine24\n\n\n\nclindamycin25\n\n\n\nclobazam3\n\n\n\nclozapine26\n\n\n\ncimetidine27\n\n\n\nciprofloxacin28\n\n\n\nco-amoxiclav29\n\n\n\ncorticosteroids30\n\n\n\ncytarabine31\n\n\n\ndalteparin32\n\n\n\ndextropropoxyphene33\n\n\n\ndiaphenylsulfone27\n\n\n\ndiltiazem34\n\n\n\ndisulfiram35\n\n\n\ndoxycycline36\n\n\n\nenalapril37\n\n\n\neprazinone38\n\n\n\nfluconazole39\n\n\n\nfurosemide40\n\n\n\ngefitinib41\n\n\n\ngentamicin42\n\n\n\ngriseofulvin37\n\n\n\nhydrochlorothiazide43\n\n\n\nhydroxychloroquine44\n\n\n\nibuprofen45\n\n\n\nicodextrin46\n\n\n\nimatinib47\n\n\n\nisoniazid48\n\n\n\nitraconazole49\n\n\n\nlabetolol4\n\n\n\nlansoprazole50\n\n\n\nlincomycin51\n\n\n\nmacrolides antibiotics3\n\n\n\nmetamizole52\n\n\n\nmetronidazole53\n\n\n\nminocycline54\n\n\n\nmorphine55\n\n\n\nnadoxolol3\n\n\n\nnifedipine3\n\n\n\nnifuroxazide56\n\n\n\nnimesulide57\n\n\n\nnystatin58\n\n\n\nparacetamol59\n\n\n\npiperacillin/tazobactam60\n\n\n\npiperazine ethionamide40\n\n\n\nsulbutiamine3\n\n\n\npropafenone61\n\n\n\npropicillin62\n\n\n\nprostaglandin63\n\n\n\npseudoephedrine64\n\n\n\nPUVA65\n\n\n\npyrimethamine40\n\n\n\nquinidine3\n\n\n\nquinolones66\n\n\n\nrifampicin67\n\n\n\nranitidine hydrochloride68\n\n\n\nsalazosulfapyridine69\n\n\n\nsertraline70\n\n\n\nsimvastatin71\n\n\n\nSTI57172\n\n\n\nsulfamethoxazole73\n\n\n\nteicoplanin74\n\n\n\nterbinafine75\n\n\n\ntetracycline3\n\n\n\nthalidomide76\n\n\n\nthallium77\n\n\n\nticlopidine78\n\n\n\nvaldecoxib79\n\n\n\nvancomycin3\n\n\n\nTable 4.   Drugs as causes of acute generalized exanthematous pustulosis (in alphabetical order)\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 3.   Involvement of the thigh inferior to the\ninguinal fold.\n\n\n\n\n\n\n\n\n30\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nIt appears greater than 90% of all AGEP cases in the\nliterature are drug-related, with a wide variety of\nmedications suspected to engender this reaction pattern\n(Table 4)3,4,12-79. AGEP has also been associated with viral\ninfections (specifically adenovirus3, coxsackie B4 virus8,\ncytomegalovirus80, Epstein-Barr virus3, enterovirus3,\nhepatitis B virus3, and human parvovirus B1981) and also\ninfections with mycoplasma pneumoniae3 and\nechinococcosis82. Exposure to mercury was a suspected cause\nfor 8 of 63 patients reported by Roujeau et al3.\nVaccinations4,83, illicit drug use84, herbal medications85, spider\nbite86, intravenous contrast media87, lacquer chicken88, and\nprogesterone89 have also been associated with AGEP.\n\n\n\nRoujeau et al.3 described the main histologic findings of\nAGEP to be spongiform superficial pustules (66%),\npapillary dermal edema (61%), a polymorphous perivascular\ninfiltrate with eosinophils (34%), leukocytoclastic vasculitis\nwith fibrinoid necrosis (20%), and necrotic keratinocytes\n(25%). In most cases, the epidermis was uninvolved or\nexhibited spongiosis without psoriasiform hyperplasia\n(61%). In our large series we found that the presence of\nnecrotic keratinocytes, papillary dermal edema, and dermal\n\n\n\neosinophils were discriminatory features, capable of\ndistinguishing AGEP from pustular psoriasis. In\ncontradiction to the findings of Roujeau et al.3 vasculitis and\nfibrinoid necrosis of the vessel walls were decidedly\nuncommon in our series. Although Beylot et al2 included a\n\u201cnon-follicular\u201d eruption as one criterion of AGEP, four of\nour 45 cases (10%) exhibited follicular involvement\nhistologically, two of which were observed in pediatric\npatients (2/5).\n\n\n\nThe differential diagnosis of AGEP includes subcorneal\npustular dermatosis, pustular contact dermatitis, bullous\nleukocytoclastic vasculitis, drug hypersensitivity syndrome,\nand IgA pemphigus. Subcorneal pustular dermatosis\n(Sneddon-Wilkinson disease) exhibits only subcorneal\npustules; whereas intraepidermal pustules are often noted in\nAGEP. A few cases of pustular contact dermatitis have been\nreported in the literature90,91. While pustular lesions may\narise in some cases of leukocytoclastic vasculitis, we found\nvasculitis to be an uncommon feature of AGEP in our large\nseries. Drug hypersensitivity syndrome, or DRESS (drug\nrash with eosinophilia and systemic syndrome), may present\nwith pustules, but these typically are less pronounced than\nthose\n\n\n\nFigure 4.   Salient histologic features of acute generalized exanthematous \npustulosis include: papillary dermal edema (A, original \nmagnification X 100), necrotic keratinocytes (B, original \nmagnification X 200), prominent dermal infiltrate of eosinophils \n(C, original magnification X 100).  Follicular involvement was \nnoted in occasional cases (D, original magnification X 100) \n(Hematoxylin-eosin)\n\n\n\n\n\n\n\n\n31\n\n\n\nthose seen in AGEP. In addition, patients with drug\nhypersensitivity often have lymphadenopathy, eosinophilia,\nmononucleosis, and significant visceral involvement,\nincluding hepatitis, nephritis, pneumonitis, and/or\nmyocarditis. Mild acanthosis would usually be noted\nin cases of IgA pemphigus. In addition, direct\nimmunofluorescence would demonstrate intercellular IgA\ndeposition.\n\n\n\nAlthough the pathogenesis of AGEP is not well\nunderstood, a combination of different mechanisms likely\ncontributes to its development. It has been suggested that\nan immunologic recall phenomenon, in which particular\nmemory T-cells produce neutrophil-attracting cytokines\nsuch as interleukins 3 and 8 (IL-3, IL-8) may play an\nimportant role92. Britschgi et al.93 showed that significantly\nmore IL-8 is produced from drug-specific T-cells taken\nfrom patients with AGEP in comparison with similar cells\ntaken from patients with other exanthems. Schmid et al.94\n\n\n\ndemonstrated that drug-specific CD4+ cytotoxic CD8+ T-\ncells are activated in AGEP. In addition, perforin or\ngranzyme B, and to a variable degree the Fas/FasL-killing\nmechanism, are involved in the formation of vesicles in\nAGEP. Additional secretion of IL-8 by T cells and\nkeratinocytes attracts neutrophils, filling the vesicles and\ntransforming them into pustules.\n\n\n\nTreatment for AGEP is chiefly symptomatic and\nsupportive. The offending drug must be identified and\ndiscontinued. Antibiotics are not to be given unless there\nis well-documented associated infection. The overall\nprognosis is good, although high fever or superinfection of\nskin lesions may rarely be life-threatening, particularly in\nthe elderly or in immunocompromised individuals.\n\n\n\nUltimately, although the precise etiology of AGEP remains\nunknown, our findings support the theory that most cases of\nAGEP in adults are drug-related, while in pediatric cases\ninfection and drugs appear equally implicated. Salient\nhistologic features of AGEP include necrotic keratinocytes,\npapillary dermal edema, and eosinophils within the dermis.\nIn comparison, these histologic features are reduced or\nabsent in pustular psoriasis, and an awareness of these\nfeatures may likely increase the diagnostic accuracy for\nAGEP.\n\n\n\nReferences\n\n\n\n1. Baker H, Ryan TJ.  Generalized pustular psoriasis: a clinical and \nepidemiological study of 104 cases.  Br J Dermatol 1968;80:\n771-793.\n\n\n\n2. Beylot C, Bioulac P, Doutre MS.  Pustuloses exanthematiques \naigues generalisees: a propos de 4 cas.  Ann Dermatol Venereol \n1980;107:37-48.\n\n\n\n3. Roujeau JC, Bioulac-Sage P, Bourseau C, et al.  Acute \ngeneralized exanthematous pustulosis. Analysis of 63 cases. \nArch Dermatol 1991;127:1333-1338.\n\n\n\n4. Ersoy S, Paller AS, Mancini AJ.  Acute generalized \nexanthematous pustulosis in children. Arch Dermatol 2004;\n140:1172-1173.\n\n\n\n5. Sezer E, Sezer T, Koseoglu D, Filiz NO.  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Acute generalized exanthematous \npustulosis induced by itraconazole. J Am Acad Dermatol \n1997;36:794-796.\n\n\n\n50. Dewerdt S, Vaillant L, Machet L, et al.  Acute generalized \nexanthematous pustulosis induced by lansoprazole.  Acta Derm \nVenereol 1997;77:250.\n\n\n\n51. Otsuka A, Tanizaki H, Okamoto N, Takagaki K.  A case of acute \ngeneralized exanthematous pustulosis caused by lincomycin.  J \nDermatol 2005;32:929-930.\n\n\n\n52. Gonzalo-Garijo MA, Perez-Calderon R, De Argila D, Rodriguez-\nNevado I.  Metamizole-induced acute generalized \nexanthematous pustulosis.  Contact dermatitis 2003;49:47-48.\n\n\n\n53. Watsky KL.  Acute generalized exanthematous pustulosis \ninduced by metronidazole: the role of patch testing.  Arch \nDermatol [Letter] 1999;135:93-94.\n\n\n\n54. Yamamoto T, Minatohara K.  Minocycline-induced acute \ngeneralized exanthematous pustulosis in a patient with \ngeneralized pustular psoriasis showing elevated level of\nsELAM-1.  Acta Derm Venereol 1997;77:168-169.\n\n\n\n55. Kardaun SH, de Monchy JG.  Acute generalized exanthematous \npustulosis caused by morphine, confirmed by positive patch test \nand lymphocyte transformation test.  J Am Acad Dermatol \n2006;55:S21-23.\n\n\n\n56. Machet L, Jan V, Machet MC, et al.  Acute generalized \nexanthematous pustulosis induced by nifuroxazide.  Contact \nDermatitis 1997;36:308-309.\n\n\n\n57. Teixeira M, Silva E, Selores M. Acute generalized exanthematous \npustulosis induced by nimesulide.  Dermatol Online J 2006;12:20.\n\n\n\n58. Kuchler A, Hamm H, Weidenthaler-Barth B, et al.  Acute \ngeneralized exanthematous pustulosis following oral nystatin \ntherapy: a report of three cases.  Br J Dermatol 1997;137:808-811.\n\n\n\n59. Leger F, Machet L, Jan V, et al. Acute generalized exanthematous \npustulosis associated with paracetamol.  Acta Derm Venereol \n1998;78:222-223.\n\n\n\n60. Grieco T, Cantisani C, Innocenzi D, et al. Acute generalized \nexanthematous pustulosis caused by piperacillin/tazobactam.  J \nAm Acad Dermatol 2005;52:732-733.\n\n\n\n61. Huang YM, Lee WR, Hu CH, Cheng KL.  Propafenone-induced \nacyte generalized exanthematous pustulosis.  Int J Dermatol \n2005;44:256-257.\n\n\n\n62. Gebhardt M, Lustig A, Bocker T, Wollina U.  Acute generalized \nexanthematous pustulosis (AGEP): manifestation of drug allergy \nto propicillin.  Contact Dermatitis 1995;33:204-205.\n\n\n\n63. Gallego I, Badell A, Notario J, et al. Toxic pustuloderma induced \nby intracavernous prostaglandin E1 [Letter]. Br J Dermatol \n1997;136:975-976.\n\n\n\n64. Mayo-Pampin E, Florez A, Feal C, et al.  Acute generalized \nexanthematous pustulosis due to pseudoephedrine with positive \npatch test.  Acta Derm Venereol 2006;86:542-543.\n\n\n\n65. Yip J, Sheehan-Dare R, Cotterill J.  Toxic pustuloderma due to \nPUVA treatment [Letter].  Br J Dermatol 1991;125:401-402.\n\n\n\n66. Tsuda S, Kato K, Karashima T, et al.  Toxic pustuloderma induced \nby ofloxacin.  Acta Derm Venereol 1993;73:382-384.\n\n\n\n\n\n\n\n\n33\n\n\n\n67. Azad A, Connelly N. Case of rifampicin-induced acute \ngeneralized exanthematous pustulosis.  Intern Med J \n2006;36:619-620.\n\n\n\n68. Martinez MB, Salvador JF, Aguilera GV, et al. Acute generalized \nexanthematous pustulosis induced by ranitidine hydrochloride.  \nContact Dermatitis 2003;49:47.\n\n\n\n69. Kawaguchi M, Mitsuhashi Y, Kondo S.  Acute generalized \nexanthematous pustulosis induced by salazosulfapyridine in a \npatient with ulcerative colitis.  J Dermatol 1999;26:359-362.\n\n\n\n70. Thedenat B, Loche F, Albes B, et al.  Acute generalized \nexanthematous putulosis with photodistribution pattern induced \nby sertraline.  Dermatology 2001;203:87-88.\n\n\n\n71. Oskay T, Kutluay L.  Acute generalized exanthematous pustulosis \ninduced by simvastatin.  Clin Exp Dermatol 2003;28:558-559.\n\n\n\n72. Brouard MC, Prins C, Mach-Pascual S, Saurat JH.  Acute \ngeneralized exanthematous pustulosis associated with STI571 in \na patient with chronic myeloid leukemia.  Dermatology \n2001;203:57-59.\n\n\n\n73. Anliker MD, Wuthrich B.  Acute generalized exanthematous \npustulosis due to sulfamethoxazol with positive lymphocyte \ntransformation test (LTT).  J Investig Allergol Clin Immunol \n2003;13:66-68.\n\n\n\n74. Chu CY, Wu J, Jean SS, Sun CC.  Acute generalized \nexanthematous pustulosis due to teicoplanin.  Dermatology \n2001;202:141-142.\n\n\n\n75. Beltraminelli HS, Lerch M, Arnold A, et al.  Acute generalized \nexanthematous pustulosis induced by the antifungal terbinafine: \ncase report and review of the literature.  Br J Dermatol \n2005;152:780-783.\n\n\n\n76. Darvay A, Basarab T, Russell-Jones R. Thalidomide-induced toxic \npustuloderma. Clin Exp Dermatol 1997;22:297-299.\n\n\n\n77. Aziz Jalali MH, Mirzazadeh Javaheri S, Salehian P.  Acute \ngeneralized exanthematous pustulosis due to thallium.  J Eur \nAcad Dermatol Venereol 2004;18:321-323.\n\n\n\n78. Cannavo SP, Borgia F, Guarneri F, Vaccaro M.  Acute generalized \nexanthematous pustulosis following use of ticlopidine.  Br J \nDermatol 2000;142:577-578.\n\n\n\n79. Byerly FL, Nelson KC, Granko RP, et al.  Valdecoxib-associated \nacute generalized exanthematous pustulosis. Burns 2005;31:\n383-387.\n\n\n\n80. Haro-Gabaldon V, Sanchez-Sanchez-Vizcaino J, Ruiz-Avila P, et \nal.  Acute generalized exanthematous pustulosis with \ncytomegalovirus infection.  Int J Dermatol 1996;35:735-737.\n\n\n\n81. Ofuji S, Yamamoto O.  Acute generalized exanthematous \npustulosis associated with a human parvovirus B19 infection.  J \nDermatol 2007;34:121-123.\n\n\n\n82. Cannistraci C, Parola IL, Rigano R, et al.  Acute generalized \nexanthematous pustulosis in cystic echinococcosis: \nimmunological characterization.  Br J Dermatol 2003;148:\n1245-1249.\n\n\n\n83. Correia O, Nunes JP, Vaz-da-Silva MJ, et al.  Acute generalized \nexanthematous pustulosis after pneumococcal vaccine [Letter]. \nDermatology 1993;187:217.\n\n\n\n84. Lu LK, High WA.  Acute generalized exanthematous pustulosis \ncaused by illicit street drugs?  Arch Dermatol 2007; 143: 130.\n\n\n\n85. Manzur A, Kiyani KA.  Acute generalized exanthematous \npustulosis triggered by intake of herbal medications.  Int J \nDermatol 2006;45:1247-1248.\n\n\n\n86. Davidovici BB, Pavel D, Cagnano E, et al.  Acute generalized \nexanthematous pustulosis following a spider bite: report of 3 \ncases.  J Am Acad Dermatol 2006;55:525-529.\n\n\n\n87. Peterson A, Katzberg RW, Fung MA, et al.  Acute generalized \nexanthematous pustulosis as a delayed dermatotoxic reaction to \nIV-administered nonionic contrast media.  AJR Am J Roentgenol \n2006;187:W198-201.\n\n\n\n88. Park YM, Park JG, Kang H, et al.  Acute generalized \nexanthematous pustulosis induced by ingestion of lacquer \nchicken.  Br J Dermatol 2000;143:230-232.\n\n\n\n89. Kuno Y, Tsuji T.  Acute generalized exanthematous pustulosis \nupon ingestion of progesterone preparation.  Acta Derm \nVenereol 1998;78:383.\n\n\n\n90. Conde-Salazar L, Guimaraens D, Romero LV, Sanchez Yus E.  \nSubcorneal pustular eruption and erythema from occupational \nexposure to trichloroethylene.  Contact Dermatitis 1983;9:235-237.\n\n\n\n91. Dooms-Goossens A, Loncke J, Michiels JL, et al.  Pustular \nreactions to hexafluorosilicate in foam rubber.  Contact \nDermatitis 1985;12:42-47.\n\n\n\n92. Schaerli P, Britschgi M, Keller M, et al.  Characterization of \nhuman T cells that regulate neutrophilic skin inflammation.  J \nImmunol 2004;173:2151-2158.\n\n\n\n93. Britschgi M, Steiner UC, Schmid S, et al.  T-cell involvement in \ndrug-induced acute generalized exanthematous pustulosis.  J \nClin Invest 2001;107:1433-1441.\n\n\n\n94. Schmid S, Kuechler PC, Britschgi M, et al.  Acute generalized \nexanthematous pustulosis: role of cytotoxic T cells in pustule \nformation.  Am J Pathol 2002;161: 2079-2086.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n34\n\n\n\n\n\n\n\n\n35\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nA 4-year retrospective study of Stevens-Johnson \nsyndrome and toxic epidermal necrolysis \n\n\n\nYap FBB MD MRCP, Wahiduzzaman M MBBS and Pubalan M MBBS MRCP\n\n\n\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\n\n\n\nCorrespondence\n\n\n\nDr Felix Yap Boon Bin MD MRCP\n\n\n\nDepartment of Dermatology\nSarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\nEmail: woodzlamp@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Stevens-Johnson syndrome (SJS) and toxic epidermal\n\n\n\nnecrolysis (TEN) are rare bullous mucocutaneous disease usually\n\n\n\ncaused by drugs. We aim to determine the demographics, causes and\n\n\n\noutcomes of patients admitted with SJS, TEN and SJS-TEN overlap\n\n\n\nin Sarawak General Hospital.\n\n\n\nMaterials and Methods A retrospective review of cases admitted to\n\n\n\nSarawak General Hospital with SJS, TEN and SJS-TEN overlap from\n\n\n\nJanuary 2004 to December 2007 was undertaken. Data regarding the\n\n\n\ndemographic, causes and outcomes were collected from the case folders\n\n\n\nand subjected to descriptive statistical analysis using Microsoft Excel.\n\n\n\nResults Twenty four cases were admitted with 54.2% having SJS, 25%\n\n\n\nhaving SJS-TEN Overlap and 20.8% having TEN. With the mean\n\n\n\nages of more than 40 years, patients with SJS and SJS-TEN overlap\n\n\n\nwere older than patients with TEN, with a mean age of only 25.4 years.\n\n\n\nSeventy nine percent of cases were drugs induced. Anticonvulsants\n\n\n\nwere the main culprit constituting 29.2% followed by allopurinol with\n\n\n\n20.8%. Cases with SJS had the longest incubation period with mean of\n\n\n\n21.6 days whereas cases with TEN had the longest mean hospital stay\n\n\n\nwith 12.4 days. A 12.5% mortality rate was recorded with 2 deaths in\n\n\n\nthe SJS-TEN overlap group and one death in the TEN group. All cases\n\n\n\nwho were given intravenous immunoglobulin (IVIg) survived.\n\n\n\nConclusion SSJS, SJS-TEN Overlap and TEN were mainly drug\n\n\n\ninduced and have high mortality. IVIg treatment seems promising.\n\n\n\nEarly recognition and optimal care in institution with dermatology\n\n\n\nservice is essential in reducing morbidities and mortalities.\n\n\n\nKeywords Stevens-Johnson syndrome (SJS), toxic epidermal\n\n\n\nnecrolysis (TEN), intravenous immunoglobulin (IVIg).\n\n\n\nIntroduction\nStevens-Johnson syndrome (SJS) and toxic epidermal\nnecrolysis (TEN) are rare bullous mucocutaneous disease.\nAlthough rare with an incidence of 0.05 to 2 persons per 1\nmillion populations per year, it has significant impact on the\npublic health in view of its high morbidity and mortality1,2.\nMajority of cases were drug induced3,4,5. They are also\ngrossly under reported worldwide.\n\n\n\nFew studies on SJS and TEN are available in Malaysia due\nto its rarity4. There are no reported studies from East\nMalaysia. Hence, our study aim to determine the causes and\nmanagement outcome of cases with SJS, SJS-TEN Overlap\nand TEN admitted to Sarawak General Hospital for a 4\nyear period from January 2004 to December 2007.\n\n\n\nMaterials and methods\nA retrospective review of cases admitted to the Sarawak\nGeneral Hospital with SJS, SJS-TEN Overlap and TEN\nwas done for a period of 4 years from January 2004 to\nDecember 2007. Data were retrieved from clinical notes in\nthe Medical Records Department.\n\n\n\nA clinical diagnosis of SJS, SJS-TEN and TEN was done\nbased on the clinical features of the cases. No skin biopsy\nwas performed. They were classified as SJS, SJS-TEN\nOverlap and TEN based on Bastuji-Garin et al6. SJS is\ncharacterized by widespread small blisters and skin\ndetachment levels of less than 10% of the body surface area,\nSJS-TEN Overlap by skin detachment levels of 10% to 30%\nof the body surface area, and TEN by skin detachment\nlevels of more than 30% of the body surface area.\n\n\n\nClinical notes were studied in detail regarding the\ndemographics, causative drugs implicated, clinical course\nand management outcome.\n\n\n\nData collected were compiled on a Microsoft Excel sheet\nand subjected to descriptive statistical analysis.\n\n\n\n\n\n\n\n\n36\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nResults\nTable I shows the demographics of patients admitted to\nSarawak General Hospital from January 2004 to December\n2007. A total of 24 cases were admitted with 54.2% having\nSJS, 25% having SJS-TEN Overlap and 20.8% having\nTEN. There was a male preponderance of 58%. The mean\nage for cases with TEN was 23.3, SJS-TEN Overlap 44.5\nand SJS 40.3 years. They range from 8 to 73 years.\n\n\n\nSeventy nine percent of the cases were due to drugs.\nAnticonvulsants and allopurinol were the major culprits,\ncontributing to 7 and 5 cases respectively. Traditional\nmedications were implicated in 2 cases. Other drugs\nincluded antibiotics, non steroidal anti-inflammatory drugs,\nsulpha drugs and antihelmintics (Table II).\n\n\n\nFour cases were given anticonvulsants for pain disorders\nwhile 2 were given for seizure prophylaxis for intracranial\nhaemorrhage. Only one case was on anticonvulsants for\nepilepsy. All the cases on allopurinol were given for\nasymptomatic hyperuricaemia.\n\n\n\nThe mean incubation time i.e. time from drug initiation to\nonset of disease ranging from 4.7 days in TEN to 21.6 days\nin SJS. The hospital stay in cases with TEN were also longer\nwith a mean of 12.4 days compared to only 8.9 days in cases\nwith SJS.\n\n\n\nTable III represents the treatment administered. All the\npatients with SJS and two third of cases with SJS-TEN\nOverlap were given corticosteroids. Eighty percent of cases\nwith TEN were given intravenous immunoglobulins.\n\n\n\nThere were only 3 deaths noted with a mortality rate of\n12.5%. They succumbed to acute respiratory distress\nsyndrome (ARDS) and sepsis. The culprit drug was Jamu\nAsam Urat containing phenylbutazone (a type of\nnonsteroidal antiinlammatory drugs) in one case whereas no\ndrug was implicated in the other two. They were given\ncorticosteroids and cyclosporine on admission. All the cases\nwith TEN given intravenous immunoglobulin (IVIg)\nsurvived.\n\n\n\nMorbidities seen include skin dyspigmentation (52%), nail\ndystrophies (10%) and ophthalmic complications (10%). 2\npatients had visual impairment as a result of severe keratitis.\n\n\n\nDiscussion\nThe spectrum of disease from SJS to TEN is mainly drug\ninduced. We have found that almost 4 out of 5 cases\nadmitted to our centre were drug induced. Regional and\ninternational studies quoted a rate of 50% to 90% of\ncases3,4,5,7.\n\n\n\nAnticonvulsant is one of the commonest culprit agents\nimplicated4,8. The estimated incidence per 10,000 new users\n\n\n\nis 1 to 10 depending on the agents used9. The drug reactions\nare more commonly seen in slow drug metabolizer due of\ngenetic polymorphism. In carbamazepine hypersensitivity,\nthe polymorphism is in position 308 and 328 of the\npromoter region of TNF-a gene10. SJS and TEN are\nconsidered T cell mediated disorders in which activation of\nCD8 T lymphocytes lead to destruction and apoptosis of\nkeratinocytes11. Drugs can activate T cells by acting as a\nhapten, as a prohapten or by direct pharmacologic\ninteraction among the drug, Major Histocompatibility\nComplex (MHC) molecule and a T cell receptor. It is\npostulated that carbamazepine in its chemically inert form\ncan bind with the MHC and T cell receptor causing\nactivation of T cells contributing to SJS and TEN12.\n\n\n\nWe found that 36% of our cases were due to anticonvulsant.\nAmong the anticonvulsant, the majority of cases (71%) were\ndue to carbamazepine. This trend was also seen in India,\nTaiwan, Singapore and northeastern Malaysia4,8,13. The\nincreasing utilization of anticonvulsants in pain\nmanagement and in prophylaxis in neurosurgical patients\nmight explain this. The benefit of prophylactic\nanticonvulsants in neurologic critical care is controversial\nand is often not evidence based14. Carbamazepine induced\nSJS and TEN was also found to be more common in Han\nChinese with HLA-B1502 phenotype in Taiwan15. This\nmight explain the trend in Singapore and some of our cases\nalthough no phenotyping was done.\n\n\n\nCases developing adverse drug reactions to carbamazepine\nshould not be given other aromatic anticonvulsants namely\nphenytoin and phenobarbitone because of cross reaction\namong the drugs. Mockenhaupt et al found that SJS and\nTEN occurred in 1 to 10 per 1000 new user of aromatic\nanticonvulsants and 2.5 per 1000 new user of Lamotrigine,\na newer class of anticonvulsant9. Sodium valproate and\nother newer anticonvulsants rarely cause adverse cutaneous\ndrug reactions. Therefore, we would suggest that aromatic\nanticonvulsants be used cautiously. Safer alternatives for\npain management should be used. They should also be used\nwith care in those with Han Chinese lineage.\n\n\n\nAllopurinol contributed to 26% our cases. Halevy et al\nfound that in Europe and Isreal, allopurinol is the most\ncommon cause of SJS and TEN. They found an increased\nrisk with dosage 200 mg per day or more16. All our cases\nhad taken 300mg per day as it is the only form available in\nMalaysia. Halevy et al also did not find an increased risk of\nallopurinol induced SJS and TEN with comedications with\ndiuretics, aminopenicillins, angiotensin converting enzymes\ninhibitors (ACEI), nonsteroidal anti-inflammatory drugs\n(NSAIDs) and aspirin16. In Han Chinese, HLA-B5801\nallele was strongly associated with severe cutaneous adverse\nreactions to allopurinol17. Allopurinol was administered in\nall our cases for asymptomatic hyperuricaemia. Other\npublished studies also revealed inappropriate indications for\nallopurinol in\n\n\n\n\n\n\n\n\n37\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.   Demographic of Patients\n\n\n\nCases\n\n\n\nMale\n\n\n\nFemale\n\n\n\nMean Age (Years)\n\n\n\nRange Age (Years)\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nIban\n\n\n\nBidayuh\n\n\n\nSJS\n\n\n\n13\n\n\n\n10/13\n\n\n\n3/13\n\n\n\n40.3\n\n\n\n13-70\n\n\n\n4/13\n\n\n\n3/13\n\n\n\n4/13\n\n\n\n2/13\n\n\n\nSJS-TEN Overlap\n\n\n\n6\n\n\n\n2/6\n\n\n\n4/6\n\n\n\n44.5\n\n\n\n8-73\n\n\n\n2/6\n\n\n\n3/6\n\n\n\n0/6\n\n\n\n1/6\n\n\n\nTEN\n\n\n\n5\n\n\n\n2/5\n\n\n\n3/5\n\n\n\n25.4\n\n\n\n10-42\n\n\n\n1/5\n\n\n\n2/5\n\n\n\n1/5\n\n\n\n1/5\n\n\n\nTable 3.   Incubation Period of Drugs\n\n\n\nMean (Days)\n\n\n\nRange (Days)\n\n\n\nSJS\n\n\n\n21.6\n\n\n\n2-40\n\n\n\nSJS-TEN Overlap\n\n\n\n12.4\n\n\n\n1-21\n\n\n\nTEN\n\n\n\n4.7\n\n\n\n2-10\n\n\n\nTable 4.   Duration of Hospital Stay\n\n\n\nMean (Days)\n\n\n\nRange (Days)\n\n\n\nSJS\n\n\n\n8.9\n\n\n\n2-46\n\n\n\nSJS-TEN Overlap\n\n\n\n9.2\n\n\n\n2-23\n\n\n\nTEN\n\n\n\n12.4\n\n\n\n7-19\n\n\n\nTable 2.   Drugs Implicated\n\n\n\nAnticonvulsant\n\n\n\nCarbamazepine\n\n\n\nPhenytoin\n\n\n\nNSAIDs\n\n\n\nIbuprofen\n\n\n\nMefenemic Acid\n\n\n\nTraditional Medications\n\n\n\nAsam Urat\n\n\n\nChinese Herbs\n\n\n\nAnti Gout\n\n\n\nAllopurinol\n\n\n\nOthers\n\n\n\nSulfasalazine\n\n\n\nAmoxycillin\n\n\n\nAlbendazole\n\n\n\nSJS (n=11)\n\n\n\n2\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n4\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\nTEN (n=3)\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\nSJS-TEN Overlap\n(n=5)\n\n\n\n2\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n4\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n\n\n\n\n\n38\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nallopurinol in up to 86% of patients18,19. So, we recommend\njudicious prescription of allopurinol. A proper guideline on\nprescription of allopurinol should be established in Malaysia\nto prevent such inappropriate usage. This will hopefully\nreduce the allopurinol related life threatening adverse drug\nreactions.\n\n\n\nThe highest risk for development of SJS and TEN with\ndrug use occurs within 2 months of initiation9,16. We also\nnoted a similar trend with longest incubation period of only\n40 days. Interestingly, we also observed that the shorter\nmean incubation period was associated with more severe\nclinical presentation. This observation need to be further\nclarified by future studies as it has prognostic significance.\n\n\n\nOur overall mortality was 12.5% with mortality for SJS-\nTEN Overlap of 33.3% and TEN of 20%. The reported\nmortality rate range from 5% to 40%4,5,7,8,20. Two of our 3\ndeaths were children with no apparent drug related cause.\nWe postulate that they had very severe viral infection and\nprobably had secondary bacterial sepsis. Their immunity\nwas further depressed by the administration of\ncorticosteroids and cyclosporine leading to their death.\nHence, immunosuppressive drugs should be used cautiously\nespecially in those with suspected underlying infection.\nSystemic corticosteroids has unproven benefit in early cases\nof SJS and TEN and deleterious in the advanced forms19,20.\n\n\n\nWe noted a 100% survival of the TEN cases given\nintravenous immunoglobulin (IVIg). IVIg is derived from\nplasma pool of several thousand donors and consists mainly\nof IgG. It interferes with Fas-Fas Ligand interactions by\nblocking the Fas binding to its ligand thereby blocking the\napoptosis of the keratinocytes21. Stella et al in Turin noted a\nreduction in mortality from 75% to 26% with the use of\nIVIg22. In a review of 8 studies on the use of IVIG in SJS\n\n\n\nand TEN, French et al found that 6 studies points towards\na benefit of IVIg on mortality associated with TEN23. Thus,\nthe use of IVIg in TEN is very promising. Prospective\nstudies should be done in Malaysia to determine the efficacy\nof IVIg as a first line treatment in TEN.\n\n\n\nReferences\n\n\n\n1. Rzany B, Mockenhunpt M, Baur S et al. Epidemiology of \nerythema exsudativum multiforme majus, Stevens-Johnson \nsyndrome and toxic epidermal necrolysis in Germany (1990-1992): \nStructure and results of a population-based registry. J Clin \nEpidemiol 1996; 49(7): 769-73.\n\n\n\n2. Li LF, MaC. Epidemiological study of severe cutaneous adverse \ndrug reactions in a city district in China. Clin Exp Dermatol 2006; \n31(5): 642-7.\n\n\n\n3. Schopf E, Stuhmer A, Rzany B, Victor N, Zentgraf R, Kapp JF. \nToxic epidermal necrolysis and Stevens-Johnson syndrome. An \nepidemiologic study from West Germany. Arch Dermatol 1991; \n127: 839-42.\n\n\n\n4. Kamaliah MD, Zainal D, Mokhtar N, Nazmi N. Erythema\nmultiforme, Stevens Johnson syndrome and toxic epidermal \nnecrolysis in north eastern Malaysia. Int J Dermatol 1998;\n37: 520-3.\n\n\n\n5. Yamane Y, Aihara M, Ikezawa Z. Analysis of Stevens-Johnson \nsyndrome and toxic epidermal necrolysis in Japan from\n2000-2006. Allergol Int 2007; 56(4): 419-25.\n\n\n\n6. Bastuji-Garin S, Rzany B, Stern RS. A clinical classification of \ncases of toxic epidermal necrolysis, Stevens-Johnson syndrome \nand erythema multiforme. Arch Dermatol 1993; 129: 92-6.\n\n\n\n7. Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schroder \nW. Correlations between clinical patterns and causes of \nerythema multiforme majus, Stevens-Johnson syndrome and \ntoxic epidermal necrolysis. Arch Dermatol 2002; 138: 1019-24.\n\n\n\n8. Devi K, Sandhya G, Criton S, Suja V, Sridevi PK. Carbamazepine \u2013 \nThe commonest cause of toxic epidermal necrolysis and \nStevens-Johnson syndrome: A study of 7 years. Indian J \nDermatol Venereol Leprol 2005; 71: 325-28.\n\n\n\n9. Mockenhaupt M, Messenhaimer J, Tennis P, Schlingmann J. Risk \nof Stevens-Johnson syndrome and toxic epidermal necrolysis in \nnew users of anticonvulsants. Neurology 2005; 64: 1134-8.\n\n\n\nTable 5.   Treatment Outcome\n\n\n\nTreatment\n\n\n\nCorticosteroids\n\n\n\nIVIg\n\n\n\nCyclosporine\n\n\n\nNursing Care only\n\n\n\nOutcome\n\n\n\nSurvive\n\n\n\nSuccumb\n\n\n\nSJS (n=13)\n\n\n\n13\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n13\n\n\n\n0\n\n\n\nTEN (n=5)\n\n\n\n1\n\n\n\n4\n\n\n\n0\n\n\n\n0\n\n\n\n4\n\n\n\n1\n\n\n\nSJS-TEN Overlap\n(n=6)\n\n\n\n4\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n4\n\n\n\n2\n\n\n\n\n\n\n\n\n39\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n10. Pirmohamed M, Lin K, Chadwick D, Park BK. TNF-alpha promoter \nregion gene polymorphism in carbamazepine-hypersensitive \npatients. Neurology 2001; 56: 890-6.\n\n\n\n11. Kehren J, Desvignes C, Krasteva M et al. Cytotoxicity is \nmandatory for CD8 (+) T cell-mediated contact hypersensitivity.\nJ Exp Med 1999; 189: 779-86.\n\n\n\n12. Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern \nMed 2003; 139: 683-93.\n\n\n\n13. Khoo AKM, Foo CL. Toxic epidermal necrolysis in a burns centre: \na 6 year review. Burns 1996; 22: 275-8.\n\n\n\n14. Liu KC, Bhardwaj A. Use of prophylactic anticonvulsants in \nneurologic critical care: A critical appraisal. Neurocrit Care 2007; \n7(2): 175-84.\n\n\n\n15. Chung WH, Hung SI, Hong HS et al. Medical genetics: a marker \nfor Stevens-Johnson syndrome. Nature 2004; 428: 486.\n\n\n\n16. Halevy S, Ghislain PD, Mockenhaupt M et al. Allopurinol is the \nmost common cause of Stevens-Johnson syndrome and toxic \nepidermal necrolysis in Europe and Isreal. J Am Acad Dermatol \n2007 doi:10.1016/j.jaad.2007.08.036. Published online October 3, \n2007.\n\n\n\n17. Hung SI, Chung WH, Liou LB et al. HLA-B5801 allele as a genetic \nmarker for severe cutaneous adverse reactions caused by \nallopurinol. Proc Natl Acad Sci USA 2005; 102: 4134-9.\n\n\n\n18. Bellamy N, Brooks PM, Emmerson BT, Gilbert JR, Campbell J, \nMcCredie M. A survey of current prescribing practices of anti-\ninflammatory and urate lowering drugs in gouty arthritis in New \nSouth Wales and Queensland. Med J Aust 1989; 151: 531-7.\n\n\n\n19. Stuart RA, Gow PJ, Bellamy N, Campbell J, Grigor R. A survey of \ncurrent prescribing practices of anti-inflammatory and urate-\nlowering drugs in gouty arthritis. NZ Med J 1991; 104: 115-7.\n\n\n\n20. Ghislain PD, Roujeau JC. Treatment of severe drug reactions: \nStevens Johnson syndrome, toxic epidermal necrolysis and \nhypersensitivity syndrome. Dermatol Online J 2002; 8(1): 5.\n\n\n\n21. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. \nJ Am Acad Dermatol 2007; 56: 181-200. \n\n\n\n22. Stella M, Clemete A, Bollero D, Risso D, Dalmasso P. Toxic \nepidermal necrolysis (TEN) and Stevens-Johnson syndrome \n(SJS): Experience with high dose intravenous immunoglobulins \nand topical conservative approach. A retrospective review. \nBurns 2006; 33: 452-9.\n\n\n\n23. French LE, Trent JT, Kerdel FA. Use of intravenous \nimmunoglobulin in toxic epidermal necrolysis and Stevens-\nJohnson syndrome: Our current understanding. International \nImmunopharmacology 2006; 6: 543-9.\n\n\n\n\n\n\n\n\n40\n\n\n\n\n\n\n\n\n41\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nLepra reactions: A 10-year retrospective analysis\n\n\n\nTan WC MD MRCP and Lo Kang SC MD MRCP\n\n\n\nFrom the Department of Dermatology\nPenang General Hospital, Malaysia\n\n\n\nCorrespondence\n\n\n\nTan Wooi Chiang MD MRCP\n\n\n\nDepartment of Dermatology\nPenang General Hospital\nJalan Residensi, 10450 Penang\nEmail: tanwooichiang@yahoo.com\n\n\n\nAbstract\n\n\n\nIntroduction Leprosy is a chronic granulomatous infection caused by\nMycobacterium leprae. Drug treatment is effective in eradicating the\nbacilli but does not prevent lepra reaction. Despite much attention\nbeing focused on the problem of lepra reactions, very limited data has\nbeen published on the epidemiology of lepra reactions especially this\npart of the world. The aim of the study is to improve the understanding\nof lepra reaction and to determine the demographics and clinical\npatterns of lepra reactions in Penang General Hospital.\n\n\n\nMaterials and Methods This retrospective study covers a 10-year\nperiod from 1997 to 2006. Demographic characteristic and clinical\npatterns of lepra reactions were analysed with SPSS 13.0 version.\n\n\n\nResults Of the 95 patients who were enrolled in the study, 67 (70.5%)\nwere male and 28 (29.5%) were females. The mean age at presentation\nwas 40.4 \u00b1 17.9 years (range 3-91 years). There were 35 Malays\n(36.8%), 34 Chinese (35.8%), 5 Indians (5.2%) and 21 foreigners\n(22.2%). 35.8% of patients presented with LL (n=34), 18.9% BT\n(n=18), 17.9% TT (n=17), 13.7% BB (n=13) and 13.7% BL (n=13). In\nour series, the lepra reaction rate among leprosy patient was 51.6%\n(n=49). Among those with lepra reaction, 53.1% cases were type 1\nreaction (n=26), 44.9% cases were type 2 reaction (n=22) and 2.0%\ncases were Lucio phenomenon (n=1). Common manifestations\nobserved in lepra reaction were worsening of skin lesions (100%),\ninflammatory oedema of hands, feet and face (53.1%), nerve pain\n(46.9%), fever (20.8%) and nerve tenderness (20.4%). Only 4 cases had\ninvolvement of other organs like the eye and joint. 30.6% of the\nreactions observed in our cohort were severe. Type 1 reaction\ncommonly involved those in borderline spectrum whereas type 2\nreaction commonly involved those in the lepromatous spectrum. Lepra\nreactions occurred before treatment (24.5%), during treatment (71.4%)\nor even after treatment has been stopped (4.1%). Most of the lepra\nreactions occurred during the treatment period especially the first 12\nmonths of therapy.\n\n\n\nConclusion Our study showed a more severe and higher reaction rate\ncompared to other studies. Lepra reaction is a common presentation of\n\n\n\nleprosy. Type 1 reaction commonly involved those with borderline\ndisease but type 2 reaction commonly involved those with lepromatous\nspectrum of disease. Lepra reaction occurred before, during and even\nafter the treatment has stopped. Most of the lepra reactions occurred\nduring treatment period especially the first 12 months of therapy.\n\n\n\nKeywords Leprosy, Lepra Reaction, Reversal reaction, Erythema\nnodosum leprosum, Lucio phenomenon\n\n\n\nIntroduction\nLeprosy is a chronic granulomatous infection caused by\nMycobacterium leprae. The principal manifestations are\nskin lesions and peripheral neuropathy. Drug treatment is\neffective in eradicating the bacilli, but does not prevent\nreactions. Despite much attention  being focused on the\nproblem of lepra reactions, very limited data has been\npublished on the epidemiology of lepra reactions especially\nthis part of the world. The aim of the study is to improve\nthe understanding of lepra reaction  and to determine the\ndemographics and clinical patterns of lepra reaction in\nPenang general hospital.\n\n\n\nMaterials and Methods\nThis retrospective study covered a 10 year period from 1997\nto 2006. Reporting forms were filled up by doctor in-\ncharge. Demographic characteristic and clinical patterns of\nlepra reaction were noted and analysed.\n\n\n\nAll patients (inpatient and outpatient) in the Department of\nDermatology Penang General Hospital, with the diagnosis\nof leprosy within this period were included. Due to paucity\nof cases and difficulty in doing biopsy in young children,\nsome cases were diagnosed clinically without a biopsy. Skin\nsmears were taken from site of lesion and stained with\nZiehl-Neelsen's staining method. Skin biopsy from the site\nof lesion was taken after obtaining an informed consent.\nThe tissue specimens were processed for routine\nhistopathological examination (i.e. staining with\nHematoxylin-Eosin and Fite-Faraco stains).\n\n\n\n\n\n\n\n\n42\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe diagnosis of leprosy is primarily clinical. Anaesthetic /\nhypoesthetic skin lesions with or without thickened\nperipheral nerves are virtually pathognomonic of leprosy. A\nfull thickness skin biopsy from an anaesthetic lesion\nshowing granuloma and lymphocytic infiltration of nerves\nessentially confirms the diagnosis.\n\n\n\nLeprosy is categorized as TT (Tuberculoid Leprosy), BT\n(Borderline Tuberculoid), BB (Borderline Borderline), BL\n(Borderline Lepromatous) and LL (Lepromatous Leprosy)\ntypes according to the Ridley Jopling classification.\n\n\n\nLepra reaction is the term given to a violent but often\nineffective tissue response presenting as an acute\ndeterioration in the clinical lesions of the patient\nundergoing treatment for leprosy.\n\n\n\nSevere reaction is defined as presence of one or more of the\nfollowing signs or symptoms:\n\n\n\n\u2022 Sensory or motor impairment \n\u2022 Ulcerating skin lesions\n\u2022 > 10 reactional skin lesions\n\u2022 Oedema that impair function\n\u2022 Nerve tenderness on palpation\n\u2022 Paraesthesia or nerve pain disturbing sleep or \n\n\n\nimpairing function\n\u2022 Involvement of other organs like eye, joints or \n\n\n\ntestis\n\n\n\nInclusion Criteria:\n\u2022 Patients who were diagnosed to have Leprosy\n\n\n\nBy one or more of the following symptoms and signs:\n1. Hypopigmented or erythematous skin lesion(s) \n\n\n\nwith definite loss of sensation.\n2. Damage to the peripheral nerves as demonstrated \n\n\n\nby palpable thickening with or without \nimpairment of sensation and/or weakness of the \nmuscles of hands, feet or face \n\n\n\n3. Presence of acid-fast bacilli in slit skin smears \n4. Histological changes diagnostic of leprosy in skin \n\n\n\nbiopsy\n\u2022 Receiving standard MDT treatment for leprosy or \n\n\n\ncompleted treatment for leprosy\n\n\n\nExclusion Criteria:\n\u2022 Presence of other skin disorders that may be confused \n\n\n\nwith the clinical picture of leprosy.\n\u2022 On oral corticosteroid or other immunosuppressive \n\n\n\ntreatment for other disorder, not for the purpose of the \ntreatment of lepra reaction.\n\n\n\nStatistical analysis:\nAll analyses were performed using SPSS 13.0 version.\n\n\n\nResults\nA total of 95 patients were diagnosed to have leprosy during\nthis period (1997-2006) in the Dermatology Clinic, Penang\nHospital. The mean age at presentation was 40.4 \u00b1 17.9\nyears (Range3- 91). Of the 95 patients who were enrolled in\nthe study, 67 (70.5%) were male and 28 (29.5%) were\nfemales There were 35 Malays (36.8%), 34 Chinese\n(35.8%), 5 Indians (5.2%) and 21 foreigners (22.2%).\nForeigners are mainly from our neighbouring countries\n(Indonesia, Nepal, Bangladesh and Philippines).\n\n\n\nPatients experienced symptoms for a mean of 21.4 months\nbefore being referred to our clinic. At presentation, patients\nhad a mean Bacteriological Index (BI) of 1.38\u00b11.5 and a\nmean Morphological Index (MI) of 1.00\u00b11.29. Most of\nthem have no family history of leprosy (n=66, 69.5%).\n35.8% of patients presented with lepromatous leprosy\n(n=34), 18.9% BT (n=18), 17.9% TT (n=17), 13.7% BB\n(n=13) and 13.7% BL (n=13).\n\n\n\nIn our series, the lepra reaction rate among leprosy patient\nwas 51.6% (n=49). Among those with a lepra reaction, 26\ncases are type 1 reaction (53.1%), 22 cases are type 2\nreaction (44.9%) and 1 case is Lucio phenomenon (2%).\n49.0% of lepra reactions involved LL patients. Those with\nBT, 16.3% of them developed reaction, followed by BL, BB\nand TT (14.3%, 14.3% and 6.1% respectively).\n\n\n\nCommon manifestations observed in patients who\ndeveloped lepra reaction were worsening of skin lesions\n(100%), inflammatory oedema of hand, feet and face\n(53.1%), nerve pain (46.9%), fever (20.8%) and nerve\ntenderness (20.4%). Only 4 cases had involvement of other\norgans like eye and joint. 30.6% of the reactions observed in\nour cohort were severe, requiring high dose and prolonged\ncourse of systemic corticosteroid and other\nimmunosuppressive agents (Figure 1).\n\n\n\nLepra reactions occurred before, during and even after the\ntreatment has stopped. At presentation, 12 patients (12.6%)\nhad ongoing lepra reaction, majority of them had type 2\nreaction. During treatment, 35 patients experienced a\nreaction, and following treatment cessation an additional 2\npatients experienced a reaction. Lepra reactions seen during\ntreatment were mainly type 1 reaction. Majority of reactions\noccurred within 12 months of MDT and were rarely seen\namong those already on MDT for more than 12 months\n(Figure 2, 3 & 4).\n\n\n\n\n\n\n\n\n43\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.   Reactional signs and symptoms observed in the subjects\n\n\n\nSigns And Symptoms\n\n\n\nSkin Lesions\n\n\n\nNone\n\n\n\nNew site\n\n\n\nPre-existing site\n\n\n\nDegree Of Inflammation\n\n\n\nNone\n\n\n\nErythema\n\n\n\nErythema and raised plaque or nodules\n\n\n\nUlceration*\n\n\n\nReactional Oedema\n\n\n\nNone\n\n\n\nMinimal\n\n\n\nVisible\n\n\n\nAffecting function*\n\n\n\nFever Due To Reaction\n\n\n\n< 37.5\u00b0C\n\n\n\n37.6 - 38.9\u00b0C\n\n\n\n39.0\u00b0C*\n\n\n\nInvolvement Of Other Organ (Eye / Joint / Testis)\n\n\n\nNone\n\n\n\nMild\n\n\n\nDefinite*\n\n\n\nNerve Pain / Paraesthesia\n\n\n\nPresence*\n\n\n\nAbsence\n\n\n\nNerve Tenderness\n\n\n\nPresence* \n\n\n\nAbsence\n\n\n\nSeverity Of Reaction\n\n\n\nMild\n\n\n\nSevere*\n\n\n\nN\n\n\n\n0\n\n\n\n22\n\n\n\n26\n\n\n\n0\n\n\n\n26\n\n\n\n22\n\n\n\n2\n\n\n\n23\n\n\n\n18\n\n\n\n8\n\n\n\n0\n\n\n\n15\n\n\n\n10\n\n\n\n2\n\n\n\n45\n\n\n\n3\n\n\n\n1\n\n\n\n23\n\n\n\n26\n\n\n\n10\n\n\n\n39\n\n\n\n34\n\n\n\n15\n\n\n\n%\n\n\n\n0\n\n\n\n44.9\n\n\n\n55.1\n\n\n\n0\n\n\n\n53.1\n\n\n\n44.9\n\n\n\n4\n\n\n\n46.9\n\n\n\n36.8\n\n\n\n16.3\n\n\n\n0\n\n\n\n30.6\n\n\n\n20.4\n\n\n\n4\n\n\n\n91.8\n\n\n\n6.1\n\n\n\n2.1\n\n\n\n46.9\n\n\n\n53.1\n\n\n\n20.4\n\n\n\n79.6\n\n\n\n69.4\n\n\n\n30.6\n\n\n\nType 1 reaction commonly involved those with borderline\nspectrum. They commonly presented with worsening of\npre-existing skin lesions (i.e the lesion becomes more\nerythematous and oedematous), oedema and tenderness of\nperipheral nerves. The peak time for type I reactions was\nduring the first 3 months of therapy and for up to 12\nmonths. Type 2 reaction mainly involved those with\n\n\n\nlepromatous spectrum of disease. They presented with crops\nof painful erythematous nodules of the skin and\nsubcutaneous tissue. It was associated with fever, malaise,\narthralgias, neuralgia, dactylitis and orchitis. The peak time\nfor type 2 reaction was during the first 6 months and\nfrequently occurred before treatment was started.\n\n\n\n\n\n\n\n\n44\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 2.   Lepra reaction observed among the subjects in the cohort\n\n\n\nFigure 3.   Lepra reactions according to classification of leprosy\n\n\n\nType 1\n\n\n\nBefore treatment\n\n\n\nDuring treatment\n\n\n\nFirst 3/12\n\n\n\n3/12-6/12\n\n\n\n6/12-12/12\n\n\n\n> 1 Yrs\n\n\n\nAfter treatment\n\n\n\nType 2\n\n\n\nBefore treatment\n\n\n\nDuring treatment\n\n\n\nFirst 3/12\n\n\n\n3/12-6/12\n\n\n\n6/12-12/12\n\n\n\n> 1 Yrs\n\n\n\nAfter treatment\n\n\n\nLucio Phenomenon\n\n\n\nNo Reaction\n\n\n\nALL\n\n\n\n26\n\n\n\n4\n\n\n\n21\n\n\n\n13\n\n\n\n6\n\n\n\n2\n\n\n\n0\n\n\n\n1\n\n\n\n22\n\n\n\n7\n\n\n\n14\n\n\n\n7\n\n\n\n3\n\n\n\n2\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n46\n\n\n\nTT\n\n\n\n3\n\n\n\n0\n\n\n\n3\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n14\n\n\n\nBT\n\n\n\n8\n\n\n\n2\n\n\n\n6\n\n\n\n4\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n10\n\n\n\nBB\n\n\n\n5\n\n\n\n1\n\n\n\n3\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n0\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n6\n\n\n\nBL\n\n\n\n4\n\n\n\n1\n\n\n\n3\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n3\n\n\n\n1\n\n\n\n2\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n4\n\n\n\nLL\n\n\n\n6\n\n\n\n0\n\n\n\n6\n\n\n\n2\n\n\n\n3\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n17\n\n\n\n6\n\n\n\n10\n\n\n\n4\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n12\n\n\n\nNUMBER OF PATIENTS\n\n\n\n\n\n\n\n\n45\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nMalaysia achieved WHO\u2019s target for control and\nelimination of leprosy in 19941. However, Leprosy is still\nbeing considered as a public health problem in Malaysia\nbecause of the potential permanent physical disabilities it\nmay cause and social stigma.\n\n\n\nLeprosy is an infectious disease caused by Mycobacterium\nleprae. It is often complicated by the host\u2019s intermittent\nhypersensitivity reactions (the so-called lepra reactions).\nThe skin, superficial peripheral nerves, anterior chamber of\nthe eyes, and testes are the most frequently affected\norgans2-3.\n\n\n\nLeprosy demonstrates a wide spectrum of immunological,\nmicrobiological, histological and clinical sequelae as\nclassified by Ridley and Jopling in 19624. Based on the\nimmunologic response of the host to Mycobacterium leprae,\nLeprosy is classified into a five groups: TT (polar\ntuberculoid), BT (borderline tuberculoid), BB (borderline),\nBL (borderline lepromatous), and LL (polar lepromatous).\nIn 1982, the WHO study group of chemotherapy for\ncontrol programs recommended that the classification of all\npatients be based on Ridley-Jopling classification and the\npositivity of bacilli in skin-slit smears. The type of leprosy\nvaries in different populations. In India and Africa, 90% of\npatients are tuberculoid spectrum of diseases. While in\nMexico 90% are lepromatous spectrum. In our cohort, about\n50% of leprosy patients are in lepromatous spectrum.\n\n\n\nIndolent course of leprosy is sometimes punctuated by acute\nexacerbation of the clinical condition of the patient, in\nterms of worsening of older lesions and appearance of new\nlesions, or other symptoms (\u201cLepra reaction\u201d). Most of the\n\n\n\nstudies reported 20 - 30% rates of lepra reaction of varying\ndegrees of severity during the course of their illness. Our\ncohort had shown a relatively higher reaction rate of 51.6%.\nSimilar findings were also observed in northern India and\nother countries3-4,16.\n\n\n\nLepra reactions consist of type 1 (reversal reaction), type 2\n(Erythema Nodosum Leprosum) and Lucio phenomenon\nreactions. They can cause considerable morbidity and\nmortality. They are also a potential source of confusion to\npatients and clinicians who expect improvement after\nstarting MDT. They may be precipitated by drug\ntherapy (MDT/antimicrobial), intercurrent infection,\nimmunization, pregnancy, parturition or stress5-8. It is\ninteresting to note that there are 6 patients (12.2%)  who\nhad preceding history of broad spectrum antibiotic use prior\nto the lepra reaction. Our cohort did not reveal any other\nobvious precipitating factors.\n\n\n\nType 1 reaction / Reversal reaction is the most common\ntype of reaction. It is mediated by delayed-type\nhypersensitivity directed against M. leprae antigens which\nusually localized to skin and nerve and result in\nmycobacterial elimination. These reactions typically occur\nin \u2018immunologically unstable BT, BB and BL leprosy\npatients2-3. A similar pattern was observed in our cohort\n(76.9% of type 1 reaction occurred among these groups).\nThey manifest clinically as acutely inflamed skin lesions and\nacute neuritis. Type 1 reactions are usually not associated\nwith systemic symptoms such as fever or arthralgias. The\nnerve lesions can manifest as acute painful nerve palsies\nwithin 24\u201336 hours. Involved nerves are usually enlarged\nand tender. Reversal reactions occur most frequently within\n6 to 12 months after starting treatment16.\n\n\n\nFigure 4.   Lepra reaction in relation to timing of treatment and classification of leprosy\n\n\n\n\n\n\n\n\n46\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nType 2 (erythema nodosum leprosum, ENL) reactions\noccur as a result of immune-complex deposition in the\nvascular endothelium and tissues and mediated by type 3\nimmune reactions (immune-complex mediated). ENL\ntends to occur in patients with high antigen load as a result\nof improved / enhanced antibody production in BL and LL\nleprosy. This is not protective in terms of limiting the\ninfection and killing Mycobacterium leprae but it helps to\nclear the tissue of accumulated mycobacterial antigens9.\nENL is usually a systemic disorder. Patients with ENL\npresent with fever, malaise, anorexia, leukocytosis and\nanaemia. Classical clinical manifestations include crops of\nerythematous painful nodules in the skin and subcutaneous\ntissue anywhere in the body but mainly in the face,\nforearms, torso and medial thighs. There may be\naccompanying nerve, ocular, hepatic, splenic, joint,\nmusculoskeletal, reticuloendothelial, testicular (in males),\ncardiac and renal involvement2-3,10-12.The reaction is a\nmanifestation of the disease and not always a complication\nof its therapy4.\n\n\n\nENL is an episodic reaction which occurs in about half of\nborderline lepromatous and lepromatous leprosy patients. It\nfrequently develops within the first 2 years of drug\ntreatment. It may persist and exacerbate even after 5\u201310\nyears in patients who are presumed to be bacteriologically\nnegative. 90.9% of type 2 reaction cases in our cohort\nbelonging to BL and LL leprosy. Data from Brazil show\nthat 30% of the patients diagnosed with MB developed\nENL (Pereira 2003)13, paralleling data from other countries\nsuch as Nepal (Van Brakel & Khawas 1994)14, China (Li et\nal. 1990)15 and north India (Kumar et al. 2004)16. ENL is\ncertainly not rare.\n\n\n\nLucio Phenomenon is a rare occurrence found mainly in\nLatin Americans, especially Mexicans. The condition has\nalso been reported from our region like Singapore20 and\nMalaysia. Patients present as a form of lepromatous leprosy\ndescribed as diffuse lepromatosis, resulting in necrotic\nlesions that ulcerate, especially below the knees. Lesions are\nthe result of dermal ischemic infarction resulting from\nendothelial proliferation and/or thrombosis in small vessels.\nBacilli are often present along with endothelial cells. Unlike\nENL, Lucio is present at the time of initial diagnosis6,17-19.\n\n\n\nOur study showed a more severe and higher reaction rate\ncompared to other studies. Lepra reaction is a common\ncomplication of leprosy. Type 1 reaction commonly involved\nthose with borderline diseases whereas type 2 reaction\ncommonly involved those with lepromatous spectrum of\ndisease. Lepra reaction occurred before, during and even\nafter the treatment has stopped. Most of the lepra reactions\noccurred during treatment period especially the first 12\nmonths of therapy.\n\n\n\nReferences\n\n\n\n1. WHO. Overview and epidemiology review of Leprosy in the WHO \nWestern Pacific Region 1991-2001, pp42.\n\n\n\n2. D. Ridley, W. Jopling, A classification of leprosy for research \npurposes, Lepr. Rev. 1962; 33: 119-129.\n\n\n\n3. R. Hastings, S. Franzblau, Chemotherapy of leprosy, Ann. Rev. \nPharmacol. Toxicol.1988; 28: 231\u2013245.\n\n\n\n4. D. Jolliffe, Leprosy reactional states and their treatment, Brit. J. \nDerm. 1977; 97: 345-352.\n\n\n\n5. World Health Organization. Leprosy Elimination Advisory Group. \nGuide to eliminate leprosy as a public health problem: multidrug \ntherapy cures leprosy, stops transmission and prevents \ndisabilities. Geneva: Leprosy Elimination Group, World Health \nOrganization; 2000.\n\n\n\n6. Guerra JG, Penna GO, de Castro LC, Martelli CM, Stefani MM. \nErythema nodosum leprosum: clinical and therapeutic update. An \nBras Dermatol 2002; 77: 389-407.\n\n\n\n7. Bryceson A, Pfaltzgraff RE. Diagnosis. In: Bryceson A, Pfaltzgraff \nRE. Leprosy. Edinburgh: Churchill Livingstone; 1990: p. 57-75.\n\n\n\n8. Report of the International Leprosy Association Technical Forum. \nDiagnosis and classification of leprosy. Int J Lepr Other \nMycobact Dis 2002; 70: 523-31.\n\n\n\n9. R. Hastings, S. Franzblau, Chemotherapy of leprosy, Ann. Rev. \nPharmacol. Toxicol. 1988; 28: 231-245.\n\n\n\n10. Sehgal VN. Leprosy. Dermatol Clin 1994; 12: 624-44.\n11. Ridley MJ, Ridley DS. The immunopathology of erythema \n\n\n\nnodosum leprosum: the role of extravascular complexes. Lepr \nRev 1983; 54: 95-107.\n\n\n\n12. Bryceson A, Pfaltzgraff RE. Clinical pathology, symptoms and \nsigns. In: Hastings RC, editor. Leprosy. Medicine in the tropics. \n3rd ed. Edinburgh: Churchill Livingstone; 1990. p. 11-55.\n\n\n\n13. Pereira GFM. On thalidomide and WHO policies. Leprosy Review \n2003; 74: 288-290.\n\n\n\n14. Van Brakel WH & Khawas IB. Nerve damage in leprosy: an \nepidemiological and clinical study of 396 patients in west Nepal. \nPart 1. Definitions, methods and frequencies. Leprosy Review \n1994; 65: 204-221.\n\n\n\n15. Li W, Ye G, Yang Z et al. Effect of 3 year multi-drug treatment in \nmulti-bacillary leprosy patients. Proceedings of the Academy of \nMedical Science Peking Union Medical College 1990; 5: 37-40. \n\n\n\n16. Kumar B, Dogra S & Kaur I. Epidemiological characteristics of \nleprosy reactions: 15 years experience from north India. \nInternational Journal of Leprosy 2004; 72: 125-133.\n\n\n\n17. Becx-Bleumink M, Berhe D. Occurrence of reactions, their \ndiagnosis and management in leprosy patients treated with \nmultidrug therapy; experience in the leprosy control program of \nthe All Africa Leprosy and Rehabilitation Training Center (ALERT) \nin Ethiopia. Int J Lepr Other Mycobact Dis 1992; 60: 173-84.\n\n\n\n18. Ortiz Y, Finer M. Lucio\u2019s leprosy (diffuse lepromatous leprosy). II. \nRecent advances, clinical and laboratory data. Dermatol Rev \nMex 1978; 22: 141-63.\n\n\n\n19. Rea TH. Lucio\u2019s phenomenon: an overview. Lepr Rev 1979;\n50: 107-12.\n\n\n\n20. Por Ang, Yong-Kwang Tay, See-Ket Ng, and Chew-Swee Seow. \nFatal Lucio\u2019s phenomenon in 2 patients with previously \nundiagnosed leprosy. J Am Acad Dermatol 2003; 48: 958-61.\n\n\n\n\n\n\n\n\n47\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nComparison of multiple drug therapy in leprosy\n\n\n\nYap FBB MD MRCP, Awang T and Pubalan M MBBS MRCP\n\n\n\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\n\n\n\nCorrespondence\n\n\n\nDr Felix BB Yap\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\nE-mail: woodzlamp@yahoo.com\n\n\n\nAbstract\n\n\n\nIntroduction Multiple drug therapy (MDT) was utilized for the\ntreatment of Hansen\u2019s disease in Sarawak since 1989. MDT Sungai\nBuloh and MDT Sarawak were the 2 major MDT regimens used.\nHence, we aim to compare the outcomes of MDT Sungai Buloh and\nMDT Sarawak.\n\n\n\nMaterials and Methods A retrospective review of 40 cases receiving\nMDT Sungai Buloh and MDT Sarawak from 1993 to 2006 was\nperformed. Data regarding demographics and outcomes were collected\nand analysed. Primary outcome was cure and secondary outcomes were\nrelapse, reactivation, death, leprosy reactions and deformities.\n\n\n\nResults There were no statistically significant differences in the\nprimary outcome among patients on MDT Sungai Buloh and MDT\nSarawak (p=0.41) after adjustment for surveillance rate. We noted that\nsignificantly more patients on MDT Sarawak (40.9%) were still under\nsurveillance compared to MDT Sungai Buloh (5.6%, p=0.01). We also\nnoted a higher rate of erythema nodosum leprosum (ENL) (16.7%)\nand deformities (22.2%) in patients receiving MDT Sungai Buloh\ncompared to 9.1% ENL and 9.1% deformity rate among those on\nMDT Sarawak. However, this did not reach statistical significance.\nOther secondary outcomes were not significantly different between the\ntwo regimens. No recurrence was reported with the two treatment\nregimens. Subanalysis for multibacillary patients did not reveal any\nsignificant differences between the two regimens in the primary\noutcome of cure after adjustment for surveillance rate (p=0.35). Both\nENL and deformity rates of 25% each for MDT Sungai Buloh were\nhigher than the rate of 13.3% each for MDT Sarawak although they\ndid not reach statistical significance. Analysis for paucibacillary\npatients did not show superiority of any one regimen.\n\n\n\nConclusion Both the MDT Sungai Buloh and MDT Sarawak were\neffective in leprosy treatment. Selection of the best treatment regimens\nwill depend on the cost effectiveness, ease of administration and\nduration of treatment that patients can tolerate.\n\n\n\nIntroduction\nLeprosy is one of the oldest diseases in mankind. It was\nreported as early as 600 BC in India and 400 BC in China1.\nIt is caused by Mycobacterium leprae, an acid fast,\npleomorphic, rod-like Gram positive bacteria.\n\n\n\nMultiple drug therapy (MDT) has been introduced by the\nWorld Health Organisation (WHO) in the fight against\nleprosy. In Malaysia, use of MDT was launched in the\n1980s. In Sarawak, the first MDT regime utilized was the\nMDT Sungai Buloh regime in 1989. It was used until 1994\nwhen the MDT Sarawak regime, a modification of the\n1981 WHO MDT regime was introduced. Since 2006, the\nWHO 1997 MDT regime has replaced the MDT Sarawak\nuntil today.\n\n\n\nHere, we aim to compare the outcomes of MDT Sungai\nBuloh and MDT Sarawak, 2 of the most commonly used\nMDT in Sarawak over the years.\n\n\n\nMaterials and Methods\nThis retrospective review aims to compare the outcomes of\npatients receiving MDT Sungai Buloh and MDT Sarawak\nin the Skin Clinic, Sarawak General Hospital from 1993 to\n2006.\n\n\n\nAll the leprosy patients seen between 1993 and 2006 were\nreviewed. Of the 74 cases reviewed, 14 were excluded\nbecause they did not receive either MDT Sungai Buloh or\nMDT Sarawak. Of the remaining 60 patients who were\nreceiving either MDT Sungai Buloh or MDT Sarawak,\nanother 20 patients were excluded as they were transferred\nto other institutions for completion of their treatment.\nThese patients were excluded as we were unable to\ndetermine their treatment outcomes.\n\n\n\nWe collected data on demographics and treatment\noutcomes. The primary outcome was cure. The secondary\noutcomes were recurrence, death, leprosy reactions and\ndeformity.\n\n\n\n\n\n\n\n\n48\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe patients were classified into multibacillary or\npaucibacillary based on 1988 World Health Organisation\n(WHO) classification2,3. The MDT Sungai Buloh and\nMDT Sarawak protocol is shown in Table 1.\n\n\n\nWe define cure as release from surveillance of leprosy\nwithout signs and symptoms of active disease; and\nbacteriologic index (BI) of < 2. The duration of surveillance\ndepends on the MDT regime used (Table 1). Recurrence of\ndisease is defined as appearance of new skin lesions\nconsistent with leprosy and a BI of 2 at any site (21).\nRecurrence of disease during surveillance is termed\nreactivation, whereas recurrence after the surveillance\nperiod is termed relapse.\n\n\n\nLeprosy reactions consist of Erythema Nodosum Leprosum\n(ENL) and lepra reaction. ENL is defined as appearance of\ntender erythematous nodules or plaques on the body\nassociated with constitutional symptoms during and after\ntreatment. Lepra reaction is inflammation of existing\nlesions during and after treatment.\n\n\n\nAll the patients seen between 1989 and 1994 were given\nMDT Sungai Buloh. Those seen after 1994 were all given\nMDT Sarawak.\n.\nData collected were analysed with SPSS version 10. Means,\nstandard deviations (SD) and frequencies were computed\nfor demographic variables. Exploratory analysis using chi-\nsquare test was done to compare the outcomes between the\ntwo MDT regimens. The level of significance was set at\n0.05.\n\n\n\nResults\nTable 2 showed the characteristics of the 40 patients who\nreceived MDT Sungai Buloh and MDT Sarawak. There\nwere 18 patients on MDT Sungai Buloh and 22 receiving\nMDT Sarawak. The baseline characteristics of patients on\nboth MDT regimens were almost similar. Male outnumber\nfemale patients in both the regimens. Almost two third of\nthe patients in both regimens had multibacillary leprosy.\nBoth regimens had predominant Chinese patients. Only 5\n(27.8%) patients on MDT Sungai Buloh were new\ntreatment na\u00efve patients. The rest had had dapsone as a\nsingle agent treatment previously. However, 14 (63.6%)\npatients on MDT Sarawak were treatment na\u00efve on\npresentation.\n\n\n\nTable 3 compared the outcomes of patients treated with\nMDT Sungai Buloh and MDT Sarawak. There was a\nsignificantly better cure rate with MDT Sungai Buloh at\n83.3% compared to MDT Sarawak at 45.5% (p=0.01).\nHowever, significantly more patients on MDT Sarawak\n(40.9%) were under surveillance (p=0.01). Therefore, after\n\n\n\nadjusting for patients who were still under surveillance, we\nnoted that the cure rate between both arms were not\nsignificant (p=0.41). Other outcomes were statistically not\nsignificant although we noted a higher rate of ENL and\ndeformities in patients receiving MDT Sungai Buloh. The\nENL rate was 16.7% among those on MDT Sungai Buloh\ncompared to 9.1% on MDT Sarawak, whereas the\ndeformity rate was 22.2% and 9.1% respectively. There was\nno reported recurrence in both regimens. Two patients on\nMDT Sungai Buloh and 3 on MDT Sarawak succumbed to\nthe disease.\n\n\n\nIn the subanalysis of multibacillary patients, we also noted\nthat the cure rate of 66.7% with MDT Sungai Buloh was\nsuperior to MDT Sarawak at 25% (p=0.02). Again, because\nsignificantly more patients on MDT Sarawak (46.7% versus\n8.3%) were still under surveillance, adjustment for this\nvariable was done. After the adjustment, the cure rate\nbetween the two regimens were not statistically significant\n(p=0.35). There was also no significant difference in other\noutcome measures. We noted that the ENL and deformity\nrates of 25% each with MDT Sungai Buloh were higher\nthan those of MDT Sarawak with 13.3% each. However,\nthese variables did not reach statistical significant\ndifference. In paucibacillary patients, comparison between\nthe two MDT regimens did not show superiority of any one\nagent.\n\n\n\nDiscussion\nGallo et al compared 2 multibacillary MDT regimens i.e.\nregime 1 containing 600mg rifampicin with 100mg dapsone\ndaily for three consecutive months followed by self-\nadministered 100mg dapsone daily for 21 months and\nregime 2 containing 600mg rifampicin with 300mg\nclofazimine once a month under supervision plus self-\nadministered doses of 50mg clofazimine with 100mg\ndapsone daily for 24 months and showed no statistically\nmeaningful differences (p>0.05) in terms of bacilloscopic,\nhistopathological and neuromotor evaluation parameters\nbetween the two regimens4. However, they found that those\non regimen 2 had fewer reaction frequency (p<0.05). This\nimplied that daily rifampicin for 3 months was of no\nbenefit. Jadhav et al also noted that there were no difference\nin the 2 year multibacillary MDT regimen containing daily\nrifampicin for 9 months and the 2 year WHO regimen5.\nHowever, the MDT regimen containing daily rifampicin\nfor 9 months conferred a significantly greater fall in\nbacteriologic index (BI). In our comparison, we also did not\nfind any significant difference between MDT Sungai Buloh\nwhich utilized an intensive 1 month daily rifampicin and\nthe MDT Sarawak regimen which was without. We also\nnoted a higher reaction rate with MDT Sungai Buloh\nwhich utilized 1 month intensive rifampicin therapy.\n\n\n\n\n\n\n\n\n49\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.   MDT regimes used in Sarawak\n\n\n\nRegime\n\n\n\nMDT Sg Buloh*\n\n\n\nPaucibacillary\n\n\n\nMonthly pulse dose\n\n\n\nDaily dose\n\n\n\nMultibacillary\n\n\n\nIntensive phase treatment\n\n\n\nDaily dose\n\n\n\nMaintenance treatment\n\n\n\nMonthly pulse dose\n\n\n\nDaily dose\n\n\n\nMDT Sarawak\n\n\n\nPaucibacillary\n\n\n\nMonthly pulse dose\n\n\n\nDaily dose\n\n\n\nMultibacillary\n\n\n\nMonthly pulse dose\n\n\n\nDaily dose\n\n\n\nMedications\n\n\n\nRifampicin 600 mg\n\n\n\nClofazimine 300 mg\n\n\n\nClofazimine 50 mg\n\n\n\nDapsone 100 mg\n\n\n\nRifampicin 600 mg\n\n\n\nClofazimine 100 mg\n\n\n\nDapsone 100 mg\n\n\n\nRifampicin 600 mg\n\n\n\nClofazimine 300 mg\n\n\n\nClofazimine 50 mg\n\n\n\nDapsone 100 mg\n\n\n\nRifampicin 600 mg\n\n\n\nClofazimine 300 mg\n\n\n\nDapsone 100 mg\n\n\n\nRifampicin 600 mg\n\n\n\nClofazimine 300 mg\n\n\n\nClofazimine 100 mg\n\n\n\nDapsone 100 mg\n\n\n\nDurations\n\n\n\n1 year\n\n\n\n3 years\n\n\n\n1 month or MI+ = 0\n\n\n\n3 years\n\n\n\n6 months\n\n\n\n2 years\n\n\n\nSurveillance\n\n\n\n5 years\n\n\n\n10 years\n\n\n\n5 years\n\n\n\n10 years\n\n\n\nMDT Sg Buloh* = MDT Sungai Buloh          MI+ = morphological inde\n\n\n\nLi et al in Nanjing, China showed that 64.7% of their 303\nmultibacillary patients receiving a 3-year treatment using\nrifampicin, clofazimine and dapsone showed negative skin\nsmears and clinical inactivity6. The rest showed different\ndegree of improvements. 9 out of 11 patients (81.8%) of\npatients in Cebu, Philippines who received the 2 year\nWHO MDT assessed at five or more years after completion\nof treatment had no evidence of relapse7. These 2 studies\nshowed that both the 2 and 3 years regimen were effective\nin leprosy control. In our study, we noted that the cure rate\nafter adjustment for surveillance rate were not significantly\ndifferent between the 2 year MDT Sarawak regimen and\nthe 3 year MDT Sungai Buloh regimen. Moreover, none of\nour patients had relapse.\n\n\n\nGirhdar BK et al found that relapse rates in patients with BI\nof 4 or higher was significantly higher (p < 0.01) in the fixed\ndose regimen of 2 years WHO MDT group as compared to\nthose receiving treatment till the point of smear negativity8.\nAll the relapsed patients responded to retreatment with the\n\n\n\nsame drug combination, indicating that the exacerbation in\ntheir condition was because of insufficient treatment. They\nsuggested that treatment be continued till smear negativity,\nat least in patients with high BI to prevent or reduce\nrelapses. In Cebu, Cellona et al found that the absolute\nrelapse rate was 3% with a cumulative risk estimate of 3.9%\nat 15 yrs among multibacillary patients receiving the 2 year\nWHO MDT regimen. In our study, we did not find any\nrelapses among all our patients on both MDT regimens\nduring the surveillance period of 10 years. All these patients\nwere not followed up after they were discharged from\nsurveillance. As the peak period of relapse is between 12 to\n15 years post treatment, we would not be certain if our\npatients actually have relapse. Thus, as the relapse rate is\nhighest with a high BI, we recommend that multibacillary\npatients with BI of 4 or higher on presentation be\nadministered MDT Sungai Buloh which employed a longer\nduration of treatment and those with lower BI be put on\nMDT Sarawak.\n\n\n\n\n\n\n\n\n50\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nKatoch et al compared 3 paucibacillary MDT regimens i.e.\nregimen 1 consisting of rifampin 600mg once a month for 6\nmonths with dapsone 100mg daily for 6 months, regimen 2\nwith an additional 6 months treatment with dapsone 100\nmg daily on top of regimen 1 and regimen 3 with rifampicin\nadministered daily for the first 7 days on top of regimen 29.\nThey found that 72.2% of the patients in regimen 1, 94.9%\nof the patients in regimen 2, and 97.1% in regimen 3\nbecame inactive. On follow-up for 1 1/2 years, three\nregimen 1 patients and none of the regimen 2 or regimen 3\npatients showed relapses. In our comparison, we noted that\nthere was no statistically significant difference between the\n2 regimens both on cure rate and the relapse rate during the\n5 years surveillance period. We did not see any relapse\namong our patients. Both the MDT Sungai Buloh and\nMDT Sarawak had included clofazimine in the regimens.\nThe addition of clofazimine might be the crucial link in the\nsuccess of these treatments in the paucibacillary patients.\n\n\n\nLimitation of the study\nWe had a small number of patients who received MDT\nSungai Buloh and MDT Sarawak. This affected the\n\n\n\nstatistical power of the study. As this was a retrospective\nreview, a head to head comparison was difficult. Moreover,\npatients received the two MDT regimens on a different\ntime frame; from 1989 to 1994, patients were given MDT\nSungai Buloh and thereafter, were given MDT Sarawak.\nThis might be significant as the pattern and responsiveness\nof the disease might have changed with time. In addition,\n72.2% of patients on MDT Sungai Buloh had dapsone\nmonotherapy previously whereas 63.6% of patients on\nMDT Sarawak were treatment na\u00efve on presentation.\n\n\n\nConclusion\nWe would like to conclude that both the MDT Sungai\nBuloh and MDT Sarawak were effective in leprosy\ntreatment. We would recommend that multibacillary\npatients with BI of 4 or higher on presentation be put on\nMDT Sungai Buloh to prevent recurrence. Otherwise, the\nselection of the treatment regimens will depend on the cost\neffectiveness, ease of administration and duration of\ntreatment that patients can tolerate.\n\n\n\nTable 2.   Baseline demographics and classifications of leprosy cases\n\n\n\nSex\n\n\n\nMale\n\n\n\nFemale\n\n\n\nAge (years)\n\n\n\nMean\n\n\n\nSD\n\n\n\nMin, max\n\n\n\nRace\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nIban\n\n\n\nIndonesians\n\n\n\nPenan\n\n\n\nKenyah\n\n\n\nBidayuh\n\n\n\nKayan\n\n\n\nWHO\n\n\n\nMultibacillary\n\n\n\nPaucibacillary\n\n\n\nNew Cases\n\n\n\nMDT Sg Buloh\n\n\n\n16 (88.9%)\n\n\n\n2 (11.1%)\n\n\n\n36.6\n\n\n\n17.6\n\n\n\n10,74\n\n\n\n10 (55.6%)\n\n\n\n3 (16.8%)\n\n\n\n1 (5.5%)\n\n\n\n1 (5.5%)\n\n\n\n0\n\n\n\n1 (5.5%)\n\n\n\n1 (5.5%)\n\n\n\n1 (5.5%)\n\n\n\n12 (66.7%)\n\n\n\n6 (33.3%)\n\n\n\n5 (27.8%)\n\n\n\nMDT Sarawak\n\n\n\n15 (68.2%)\n\n\n\n7 (31.8%)\n\n\n\n37.7\n\n\n\n20.6\n\n\n\n8,94\n\n\n\n14 (63.6%)\n\n\n\n6 (27.3%)\n\n\n\n1 (4.5%)\n\n\n\n0\n\n\n\n1 (4.5%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n15 (68.2%)\n\n\n\n7 (31.8%)\n\n\n\n14 (63.6%)\n\n\n\n\n\n\n\n\n51\n\n\n\nReferences\n\n\n\n1. Thangaraj RH, Yawalkar SJ. Historical background. In: Leprosy \nfor medical practitioners and paramedical workers. 4th edition. \nCiba-Geigy limited, 1989: 14.\n\n\n\n2. World Health Organization. Leprosy Elimination Advisory Group. \nGuide to eliminate leprosy as a public health problem: multidrug \ntherapy cures leprosy, stops transmission and prevents \ndisabilities. Geneva: Leprosy Elimination Group, World Health \nOrganization; 2000.\n\n\n\n3. D.S. Ridley, W.H. Jopling. Classification of leprosy according to \nimmunity. A five-group system. Int. J. Leprosy 1966; 34: 255-73.\n\n\n\n4. Gallo ME, Alvim MF, Nery JA, Albuquerque EC, Sarno EN. Two \nmultidrug fixed-dosage treatment regimens with multibacillary \nleprosy patients. Indian J Lepr 1996; 68: 235-45.\n\n\n\n5. Jadhav VH, Patki AH, Mehta JM. Comparison of two multidrug \nregimens in multibacillary leprosy. Indian J Lepr 1992; 64: 501-4.\n\n\n\n6. Li W, Ye G, Yang Z, Tao M, Luo J, Wang C, Ji F. Effect of three-\nyear multidrug therapy in multibacillary leprosy patients. Proc \nChin Acad Med Sci Peking Union Med Coll 1990; 5: 37-40.\n\n\n\n7. Villahermosa LG, Fajardo TT Jr, Abalos RM, Cellona RV, Balagon \nMV, Dela Cruz EC, Tan EV, Walsh GP, Walsh DS. Parallel \nassessment of 24 monthly doses of rifampin, ofloxacin, and \nminocycline versus two years of World Health Organization \nmulti-drug therapy for multi-bacillary leprosy. Am J Trop Med \nHyg 2004; 70: 197- 200.\n\n\n\n8. Girdhar BK, Girdhar A, Kumar A. Relapses in multibacillary \nleprosy patients: effect of length of therapy. Lepr Rev 2000; 71: \n144-53.\n\n\n\n9. Katoch K, Ramu G, Ramanathan U, Desikan KV. Comparison of \nthree regimens containing rifampin for treatment of \npaucibacillary leprosy patients. Int J Lepr Other Mycobact Dis \n1987; 55:1-8.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 3.   Outcomes by MDT regimes\n\n\n\nOverall\n\n\n\nCured\n\n\n\nDied\n\n\n\nUnder surveillance\n\n\n\nReactivation/relapse\n\n\n\nENL\n\n\n\nLepra reaction\n\n\n\nDeformities\n\n\n\nMultibacillary\n\n\n\nCured\n\n\n\nDied\n\n\n\nUnder surveillance\n\n\n\nReactivation/relapse\n\n\n\nENL\n\n\n\nLepra reaction\n\n\n\nDeformities\n\n\n\nPaucibacillary\n\n\n\nCured\n\n\n\nDied\n\n\n\nUnder surveillance\n\n\n\nReactivation/relapse\n\n\n\nENL\n\n\n\nLepra reaction\n\n\n\nDeformities\n\n\n\nMDT Sg Buloh\n\n\n\n18 \n\n\n\n15 (83.3%)\n\n\n\n2 (11.1%)\n\n\n\n1 (5.6%)\n\n\n\n0\n\n\n\n3 (16.7%)\n\n\n\n0\n\n\n\n4 (22.2%)\n\n\n\n12\n\n\n\n10 (83.3%)\n\n\n\n1 (8.3%)\n\n\n\n1 (8.3%)\n\n\n\n0\n\n\n\n3 (25%)\n\n\n\n0\n\n\n\n3 (25%)\n\n\n\n6 \n\n\n\n5 (83.3%)\n\n\n\n1 (16.7%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1 (16.7%)\n\n\n\nMDT Sarawak\n\n\n\n22\n\n\n\n10 (45.5%)\n\n\n\n3 (13.6%)\n\n\n\n9 (40.9%)\n\n\n\n0\n\n\n\n2 (9.1%)\n\n\n\n1 (4.5%)\n\n\n\n2 (9.1%)\n\n\n\n15\n\n\n\n6 (40.0%)\n\n\n\n2 (13.3%)\n\n\n\n7 (46.7%)\n\n\n\n0\n\n\n\n2 (13.3%)\n\n\n\n1 (6.7%)\n\n\n\n2 (13.3%)\n\n\n\n7\n\n\n\n4 (57.1%)\n\n\n\n1 (14.3%)\n\n\n\n2 (28.6%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\np value\n\n\n\n0.01\n\n\n\n0.81\n\n\n\n0.01\n\n\n\n0\n\n\n\n0.47\n\n\n\n0.36\n\n\n\n0.25\n\n\n\n0.02\n\n\n\n0.68\n\n\n\n0.03\n\n\n\n0\n\n\n\n0.44\n\n\n\n0.36\n\n\n\n0.44\n\n\n\n0\n\n\n\n0.31\n\n\n\n0.91\n\n\n\n0.16\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0.26\n\n\n\nMDT Sg Buloh* = MDT Sungai Buloh          MI+ = morphological index\n\n\n\n\n\n\n\n\n52\n\n\n\n\n\n\n\n\n53\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nGranular cell tumour - A case series of 9 patients and \nliterature review\n\n\n\nYT Pan MBBS MRCP, HL Tey MBBS MRCP and Chan YC MBBS MRCP FAMS\n\n\n\nDepartment of Dermatology\nNational Skin Centre, Singapore\n\n\n\nCorrespondence\n\n\n\nPan Jiun Yit MBBS, MRCP (UK)\n\n\n\nDepartment of Dermatology\nNational Skin Centre, Singapore\n1 Mandalay Road, Singapore 308205\nEmail: jypan@mail.com\n\n\n\nAbstract\n\n\n\nGranular cell tumours are uncommon benign lesions with a\npredilection for the head and neck region. We report 9 cases of this rare\ntumour seen at the National Skin Centre, Singapore, between 1996 and\n2006. Five patients were female and four were male. Patient ages were\nbetween 15 to 66 years, with a mean of 37.1 years. All 9 patients\npresented with an asymptomatic painless mass varying from a 1 year to\n10 years duration, with a mean duration of 4 years. 6 of the patients\nwere Chinese, 2 were Indian and 1 was Sri Lankan. Five tumors were\nin the head and neck, three were in the groin or genital regions, and one\nwas in the limb. The tumours ranged in size from 0.3 cm (in the\nscrotum) to 2.5 cm (in the neck). On examination, none of the lesions\nhad any features of malignancy. The pre-operative diagnosis was\ndermatofibroma in 3 patients, epidermal cyst in 5 patients, and adnexal\ntumour in 1 case. For 1 of the patients, there were 2 synchronous\ntumours present in the scrotum. Excision biopsy was performed for all\npatients and histology confirmed the diagnosis.\n\n\n\nIntroduction\nGranular cell tumours are relatively rare benign soft tissue\nneoplasms first described by Abrikossoff1 in 1926. They\nappear in two forms: the adult type more commonly found\nin the head and neck region, which occurs more frequently\nin women and blacks; and the congenital type usually\noccuring on the gingiva of the anterior maxillary ridge. The\ngranular cell component of both lesions is identical,\nconsisting of a diffuse infiltrate of large polyhedral cells with\nabundant eosinophilic granular cytoplasm and small central\nnuclei.\n\n\n\nThe origin of granular cell tumours is not completely\nunderstood. They were originally thought to stem from\nstriated muscle cells, macrophages or undifferentiated\nmesenchymal cells, but now are thought to arise from neural\ntissue or Schwann cells. Malignant transformation is rare,\nbut metastatic granular cell myoblastomas have been\nreported2,6.\n\n\n\nGranular cell tumours predominantly arise from the head\nand neck region, with a predilection for the tongue and\n\n\n\nbuccal mucosa3,4. Tumours may be bilateral. Granular cell\ntumours can also uncommonly occur in internal sites e.g.\nmuscle, lip, jaws, parotid gland, pharynx, larynx, trachea,\nbronchus, lung, chest wall, breast, lacrimal sac, orbit, heart,\noesophagus, common bile duct, urinary bladder, spermatic\ncord, male urethra, perineum, anal region, vulva and ovary5.\nThe sites involved are typically superficial tissues, such as\nthe dermis and subcutis, but deep tissue such as muscle and\nabdominal organs may rarely be involved. Because of\nvarious sites of presentation, these tumors are documented\nin the literature of different specialties, including\ndermatology, thoracic surgery7, dental surgery,\notolaryngology, orthopaedic surgery and pathology\npublications.\n\n\n\nMaterials and methods\nWe report a case series of 9 patients with granular cell\ntumour seen from 1996 to 2006 in our centre. Data for this\ncase series was obtained by the medical and histological\nrecords of the National Skin Centre, Singapore.\n\n\n\nCase Series\nNine patients were referred to National Skin Centre,\nSingapore during a 10-year period from 1996 to 2006\n(Table 1). Five patients were female and four were male.\nPatient ages were 15 to 66 years, with a mean of 37.1 years.\nAll 9 patients presented with a primary symptom of an\nasymptomatic painless mass varying from a 1 year to 10\nyears duration, with a mean duration of 4 years. 6 of the\npatients were Chinese, 2 were Indian and 1 was Sri Lankan.\nFive tumors were in the head and neck, three were in the\ngroin (Figure 1) or genital regions, and one was in the\nforearm. The tumours ranged in size from 0.3 cm (in the\nscrotum) to 2.5 cm (in the neck). On examination, none of\nthe lesions had any features of malignancy which included\nrapid growth, large size (> 4 cm), local invasion and\nregional metastases. The pre-operative diagnosis was\ndermatofibroma in 3 patients, epidermal cyst in 5 patients,\nand adnexal tumour in 1 case. For 1 of the patients, there\nwere 2 synchronous tumours present in the scrotum.\nExcision biopsy was performed for all patients.\n\n\n\n\n\n\n\n\n54\n\n\n\nCase\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\nSex\n\n\n\nMale\n\n\n\nFemale\n\n\n\nMale\n\n\n\nFemale\n\n\n\nFemale\n\n\n\nFemale\n\n\n\nMale\n\n\n\nFemale\n\n\n\nMale\n\n\n\nRace\n\n\n\nChinese\n\n\n\nChinese\n\n\n\nChinese\n\n\n\nSri\nLankan\n\n\n\nChinese\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nAge\n\n\n\n56\n\n\n\n17\n\n\n\n52\n\n\n\n12\n\n\n\n35\n\n\n\n59\n\n\n\n22\n\n\n\n66\n\n\n\n15\n\n\n\nFamily\nHx\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nnil\n\n\n\nNo.\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\nSite\n\n\n\nNeck\n\n\n\nLip\n\n\n\nNeck\n\n\n\nLabia Majora\n\n\n\nLip\n\n\n\nGroin\n\n\n\nScrotum and\nPubis\n\n\n\nNose\n\n\n\nForearm\n\n\n\nDuration\n(years)\n\n\n\n4\n\n\n\n2\n\n\n\n5\n\n\n\n1\n\n\n\n3\n\n\n\n6\n\n\n\n10\n\n\n\n3\n\n\n\n2\n\n\n\nPre-operative\ndiagnosis\n\n\n\nEpidermal Cyst\n\n\n\nEpidermal Cyst\n\n\n\nDermatofibroma\n\n\n\nEpidermal cyst\n\n\n\nEpidermal cyst\n\n\n\nAdnexal tumour\n\n\n\nEpidermal cyst\n\n\n\nDermatofibroma\n\n\n\nDermatofibroma\n\n\n\nLongest\ndiameter\n\n\n\n(cm)\n\n\n\n2.5\n\n\n\n0.8\n\n\n\n1\n\n\n\n1\n\n\n\n2\n\n\n\n3.5\n\n\n\n0.3 (scrotum),\n0.4 (pubis)\n\n\n\n0.3\n\n\n\n1.5\n\n\n\nFeatures of\nMalignancy\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nRecurrence?\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nNo\n\n\n\nTable 1.   Characteristics of patients with Granular Cell Tumour\n\n\n\nFigure 1.   Granular Cell Tumour in the Groin. A punch \nbiopsy was carried out which confirmed the \ndiagnosis. The patient opted for excision of \nthe lesion\n\n\n\nFigure 2.   Granular cell tumour. A diffuse infiltrate of \nlarge polyhedral cells with abundant \neosinophilic granular cytoplasm and small \ncentral nuclei is seen\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n55\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAll patient information was obtained from their\ncomputerized and written medical records, and telephone\ncontact was made with all the patients to determine whether\nthey had any evidence of recurrence. All patients contacted\nover the phone were asymptomatic at the time of the\ninterview.\n\n\n\nBiopsy material was fixed in 10% neutral buffered formalin,\nembedded in paraffin, and cut into 5-\u03bcm sections. All\ninterpretations of fine biopsy histologic samples were\nperformed by experienced pathologists, and final pathologic\ndiagnoses were made by histologic examination of\nhematoxylin and eosin stained specimens. The diagnosis\nwas based on the presence of sheets of polygonal cells with\nsmall central pyknotic nuclei and abundant granular\neosinophilic cytoplasm (Figure 2). These eosinophilic\ngranules were periodic acid-Schiff positive and diastase\nresistant. S100 staining was positive in all cases. Epidermal\nacanthosis was noted especially in the more superficial\ntumours. The tumour cells were arranged in lobules or\ntrabeculae in the mid-dermis. Nuclear pleomorphism,\nmultinucleation, and evidence of increased mitoses were not\nnoted in any of the biopsy specimens.\n\n\n\nDiscussion\nGranular cell tumors can be found in several sites, which\ninclude the upper respiratory and gastrointestinal tract, skin\nand viscera3,4. The majority of granular cell tumours are\nfound in the head, neck, trunk and extremities. Genital and\nmultifocal lesions are rare.\n\n\n\nIn our series, all of the lesions were unifocal except one\npatient who had two synchronous granular cell tumours of\nthe scrotum. Only a few cases of scrotal granular tumours\nhave been reported in the literature8,9,10,11,12 and only one out\nof the five reports featured a second synchronous tumour\ninvolving an anatomically adjacent site (the penis)9. The rest\nof the tumours were solitary.\n\n\n\nThe tumour cells almost always stain positively for S-100\nprotein, neuron-specific enolase and NK1-C3, reflecting\ntheir Schwann cell origin13-14. Positivity with stains for\nmyelin-associated P0 and P2 proteins, myelin basic protein\nand Leu-7 is variable. These stains may also be positive\nin a variety of benign and malignant neurogenic\ntumours, including neurofibroma, neurofibrosarcoma,\nneurilemmoma and malignant spindle cell sarcoma15.\nGranular cells are non-immunoreactive for epithelial,\nmuscle and endotheilial cell markers.\n\n\n\nRarely, granular cell tumours may be malignant.\nApproximately 0.5% to 2% of granular cell tumours are\nmalignant4,6. Fewer than 40 cases have been reported in the\nliterature6,16. These occur more often in deep-seated regions\nin adults, with the lesions usually larger (4-15 cm) and\n\n\n\nlocally destructive. They differ from their benign\ncounterparts in that histologically, they have increased\nnuclear and cellular pleomorphism, increased mitotic\nfigures, necrosis, wide cellular sheets, and spindle cell\nstructure16-18. Clinically, decreased rates of survival are\ncorrelated with tumour diameter greater than 4 cm, female\ngender, presence in the lower extremities, intramuscular\nlocation, rapid recent growth, advanced patient age, local\nrecurrence, metastases, Ki67 values greater than 10%, and\np53 immunoreactivity16-18.\n\n\n\nIn benign lesions, recurrence rates are 2-8%, even when the\nresection margins are deemed free of tumour infiltration19.\nThe rates can rise to 21-50% when the margins are positive\nfor tumour involvement. Malignant lesions behave\naggressively and are difficult to eradicate with surgery.\nMetastases are usually detected within 2 years with 40% 3-\nyear survival16,19. Thus, all lesions should ideally undergo a\nwide excision with regular follow-up and examination for\nrecurrence. However, all the cases in our series only\nunderwent an excision biopsy, as granular cell tumours are\nfrequently diagnosed as a benign soft tissue condition (e.g.\nepidermal cyst, dermatofibroma) based on their appearance.\n\n\n\nGranular cell tumour is a rare benign tumour. The presence\nof two synchronous granular cell tumours of the scrotum is\na rare finding. Because of the risk of recurrence and the low\nrisk of malignant transformation, patients should ideally be\nfollowed up regularly with serial physical examinations.\n\n\n\nReferences\n\n\n\n1. Abrikossoff A: Ueber myome ausgehened von der \nquergestreifenten willkuerlichen muskulatur. Virchow Arch \nPathol Anat 1926;260:215-233.\n\n\n\n2. Gamboa LG. Malignant granular cell myoblastoma. AMA Arch \nPathol 1995; 60:663-8.\n\n\n\n3. Curtis BV, Calcaterra TC, Coulson WF: Multiple granular cell \ntumor: A case report and review of the literature. Head Neck \n1997;19:634-637.\n\n\n\n4. Enzinger F, Weiss S: Soft Tissue Tumors. Ed 3. St Louis, Mosby \n1995; 864-875.\n\n\n\n5. Seo IS, Azarelli B, Warner TF et al. Multiple visceral and \ncutaneous granular cell tumours: ultrastructural and \nimmunocytochemical evidence of Schwann cell origin. Cancer \n1984; 53:2104-10.\n\n\n\n6. Sonobe H, Iwata J, Furihata M, Moriki T, Ohtsuki Y: Malignant \ngranular cell tumor: Report of a case and review of the literature. \nPathol Res Pract 1998;194:507-513.\n\n\n\n7. Deavers M, Guinee D, Koss MN, Travis WD: Granular cell tumors \nof the lung. Am J Surg Pathol 1995;19:627-635, \n\n\n\n8. Altman C et al. Multiple cutaneous granular cell tumours of the \nscrotum. Cutis 1999; 63 (2): 77-80\n\n\n\n9. Bryant, J. Granular cell tumour of penis and scrotum. Urology. \n1995;45(2): 332-4\n\n\n\n10. Mendenez, LV, et al. Unusual location of a Granulosa tumour. \nArch Esp Urol 2001;54(4): 374-5.\n\n\n\n11. Medina PM et al. Granular cell tumour of the scrotum with high \npseudoepitheiomatous hyperplasia. Arch Esp Urol 1999; 52(2), \n169-70.\n\n\n\n\n\n\n\n\n56\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n12. E Craig, R Rodiguez, B Ruben. Granular Cell Tumour of the \nScrotum. Dermatology Online Journal 2005, 11(2): 25.\n\n\n\n13. Dhillon AP, Rode J: Immunohistochemical studies of S-100 \nprotein and other neural characteristics expressed by granular \ncell tumor. Diagn Histopathol 1983;6:23-28.\n\n\n\n14. Fisher ER, Weschler M: Granular cell myoblastoma-A misnomer. \nEM and histochemical evidence concerning its schwann cell \nderivation and nature (Granular cell schwannoma). Cancer \n1962;15:936-954.\n\n\n\n15. P. E. Swanson, J. C. Manivel, and M. R. Wick. Immunoreactivity \nfor Leu-7 in neurofibrosarcoma and other spindle cell sarcomas \nof soft tissue. Am J Pathol. 1987 March; 126(3): 546-560.\n\n\n\n16. Fanburg-Smith J, Meis-Kindblom J, Fante R, Kindblom L: \nMalignant granular cell tumor of soft tissue. Am J Surg Pathol \n1998;22:779-794\n\n\n\n17. Menaker G, Sanger J: Granular cell tumor of uncertain malignant \npotential. Ann Plast Surg 1997; 38:658-660.\n\n\n\n18. Tsuchida T, Okada K, Itoi E, Sato T, Sato K: Intramuscular \nmalignant granular cell tumor. Skeletal Radiol 1997; 26:116-121\n\n\n\n19. Scheithauer BW, Woodruff JM, Erlandson RA: Benign granular \ncell tumors and malignant granular cell tumors. In: Tumors of the \nPeripheral Nervous System, Atlas of Tumor Pathology. 3rd ed. \nWashington, DC: Armed Forces Institute of Pathology; 1997;248: \n259, 358-65.\n\n\n\n\n\n"
"\n\nVolume 30   |  July 2013   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.myIndexed in: Western Pacific Research Index Medicus\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\n\n\n\n\niMJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nEditor-in-Chief \nRohna Ridzwan, MRCP\nrohnaridzwan@yahoo.com\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP\nghbelani@hotmail.com\n\n\n\nHenry Foong Boon Bee, FRCP\nbbfoong@pc.jaring.my\n\n\n\nChan Lee Chin, MMed\nlccjess@yahoo.com\n\n\n\nAgnes Heng Yoke Hui, MRCP\nagnesheng2002@yahoo.com\n\n\n\nFelix Yap Boon Bin, Adv M Derm \nwoodzlamp@yahoo.com\n\n\n\nTang Min Moon, Adv M Derm\nminmoon2005@yahoo.com\n\n\n\nChang Chong Chor, Adv M Derm\nccchor@gmail.com\n\n\n\nFounding Editor\nSteven Chow Kim Wing FRCPI\n\n\n\neditorial\nMedical education in dermatology\nin the 21st century\n\n\n\nTeaching of dermatology in medical students varies in\ndifferent universities worldwide. In Malaysia, medical\nstudents\u2019 interest in dermatology is dismal because of\nlack of exposure in medical college. There is a move to\nreinforce dermatology in medical school curriculum\nand standardise the teaching in most if not all\nuniversities in Malaysia. In the beginning of the 21st\ncentury, there were no in-house dermatology teaching\nstaff in local universities. Since the inception of\nAdvance Masters of Dermatology in 2002, there are\nnow four public universities and two private medical\nschools with in-house dermatologists. In the pipeline, a\ncommon website for dermatology slide teaching is\nproposed. Similarly, common lecture notes shall be\nshared among universities even to those medical\ncolleges without dermatology staff. We welcome you\nto share your views and feedback on the article on\nDermatology education in this issue of the MJD.\n\n\n\nExecutive Staff\nNajeeb Ahmad Safdar, MRCP - President\nKoh Chuan Keng, MRCP - Past President\nHenry Foong Boon Bee, FRCP - Vice President\nAgnes Heng Yoke Hui, MRCP - Secretary\nNoor Zalmy Azizan, Adv M Derm - Treasurer\nMd Noh Idris, FRCP, FRCPI\nChan Lee Chin, MMed\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJalan 112, Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2012 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nBAR CODE\n\n\n\n\n\n\n\n\nii MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nNotice to Authors\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts\non all aspects of cutaneous medicine and surgery in the form of\noriginal articles, research papers, case reports and\ncorrespondence.  Contributions are accepted for publication on\ncondition that they are submitted exclusively to the Malaysian\nJournal of Dermatology. The Publisher and Editors cannot be\nheld responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and\nopinions expressed do not necessarily reflect those of the\npublisher and Editors, neither does the publication of\nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:\nrohnaridzwan@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to me at:\nrohnaridzwan@yahoo.com\n\n\n\nContributions should be written for one of the following\ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than three\nillustrations. This category offers a means for rapid\ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation.\nThis category provides rapid publications and is meant to be a\nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five\nreferences. The author may express his or her opinion without\ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and\npathological photographs in color. The diagnosis and legends\nfor the photographs should be listed after the references in the\narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not\nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article\ntypes may include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an\nIntroduction, Materials and Methods , Results, Comment, and\nReferences. A Structured Abstract of not more than 240 words\nmust be included. It should consist of four paragraphs, labelled\nBackground, Methods, Results, and Conclusions. It should\ndescribe the problem studies, how the study was performed, the\nmain results, and what the author(s) concluded from the results. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and\nsummarizes the existing knowledge in a particular field. It\nshould not be an exhaustive review of the literature, and\nreferences should not exceed 100 in number. Tables, diagrams,\nand selected figures are often helpful. The length is left to the\njudgment of the author, although it generally should not exceed\n5000 words. Topics may include updates in clinically relevant\nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the\npaper, the author(s)' name(s), degrees, and affiliation(s), the\ncategory of the article, the number of figures and tables, and\nthree key words for indexing purposes. The name and full postal\naddress (including a street address), phone and fax numbers and\nan email address of the corresponding author who will be\nresponsible for reading the proofs must also be given on the title\npage. The author(s) must also declare any affiliation or\nsignificant financial involvement in any organizations or entity\nwith a direct financial interest in the subject matter or materials\ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. If\nconfusion could result, please include other measurement\nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should\nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in\nthe manuscript. References from journals should include: (1)\nname(s) followed by the initials of the author(s), up to four\nauthors: if more than four authors, include the first three authors\nfollowed by et al.; (2) title of paper; (3) title of the journal as\nabbreviated in the Index Medicus; (4) year of publication; (5)\nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A\nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s);\n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4)\nplace of publication; (5) publisher; (6) year; (7) page(s) referred\nto. \n\n\n\nFor example: \nFoong HBB.  Transcontinental Dermatology: Virtual Grand\nRounds. In: Wootton R and Oakley A, editors. Teledermatology.\nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of\nall references; incomplete references may result in a delay to\npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on\na separate sheet, and should only include essential information.\nDrawings, graphs, and formulas should be submitted on\nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of\nphotomicrographs, the stain type and original magnification\nshould be stated. Each figure should bear a reference number\ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is\nimportant that all electronic artwork is supplied to the Editorial\nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for errors\nor any consequences arising from the use of information\ncontained in this journal; the views and opinions expressed do\nnot necessarily reflect those of the publisher and Editors, neither\ndoes the publication of advertisements constitute any\nendorsement by the publisher and Editors of the products\nadvertised.\n\n\n\n\n\n\n\n\n1MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nPATCH TESTING WITH PRESERVATIVE SENSITIZERS.\nA YEAR RETROSPECTIVE STUDY FROM SELAYANG HOSPITAL\nVoo Sook Yee, MRCP, Rohna Ridzwan, MRCP\n\n\n\nAbstract\n\n\n\nIntroduction: Other than nickel, fragrance and rubber, preservatives are well known sensitizers.\n\n\n\nObjectives: To study the pattern of preservative allergy among patients patch tested at Patch Test\nUnit Selayang Hospital.\n\n\n\nMaterials & Methods: We conducted a retrospective analysis of the data of all the patients patch\ntested with preservative sensitizers present in the European Baseline Series and other commercial\nseries in Selayang Hospital from January 2011 to December 2011.\n\n\n\nResults: 243 patients were patch tested. 28.4% of the patients had a positive reaction to one or more\nof the preservative sensitizers. Paraben mix was the most frequently positive allergen (11.8%).\n17.8% of the Indians had paraben allergy, as compared to 11.3% of Malays and 11.2% of Chinese.\nFemales were more significantly associated with a positive reaction to one or more of the\npreservative sensitizers (p=0.010). A younger age group (<35) was more significantly associated\nwith formaldehyde allergy. \u201cFace and upper limbs combined\u201d presentation was significantly\nassociated with a positive reaction to formaldehyde and methylchloroisothiazolinone/\nmethylisothiazolinone (p=0.042 and p<0.001 respectively).\n\n\n\nConclusion: Our data differ from most other countries in that paraben mix was the most frequently\npositive preservative sensitizer and that younger age group was significantly associated with\nsensitization to formaldehyde.\n\n\n\nKeywords paraben mix, formaldehyde, contact allergy, Malaysia\n\n\n\nCorrespondence\nVoo Sook Yee, MRCP\nDepartment of Dermatology,                         \nSelayang Hospital, Selangor, Malaysia\nE-mail: miyee03@yahoo.com\n\n\n\nmethylisothiazolinone (MCI/MI) in the 1970s and\nmethyldibromo glutaronitrile (MDBGN) in the\n1990s3.\n\n\n\nThere are many studies on the prevalence and trends\nof preservative allergy from the western countries.\nData from South East Asian countries is scarce.\nMalaysia is a multiethnic country comprising of\nMalay, Chinese, Indians and local indigenous\ngroups, each with their own respective unique\ncultures and preferences.\n\n\n\nAim\nThe aims of this study are to study the demographic\ncharacteristic, frequency and pattern of preservative\nallergy among patients patch tested at Patch Test\nUnit Selayang Hospital.\n\n\n\nIntroduction\nMost cosmetics, household and industrial products\ncontain preservatives. Its\u2019 function is to inhibit the\ngrowth of bacteria and fungus, thus enabling these\nproducts to have a longer shelf-life. Unfortunately,\npreservatives are also common sensitizers1. Studies\nhave shown an increased in the prevalence of\nformaldehyde allergy in the 1960s due to\nexposure to cosmetics and textile finishes2. This\nis followed by methylchloroisothiazolinone/\n\n\n\n\n\n\n\n\n2 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMaterials and methods\nThis is a retrospective analysis of all the patients\nthat underwent patch test in Selayang Hospital in\n2011. Patients were patch tested with the European\nStandard Series (ESS) and additional series when\nindicated, using allergens from Chemotechnique\nDiagnostics (Malm\u00f6, Sweden). Preservative\nsensitizers are found in the ESS and the Cosmetic\nSeries (CS) and Hairdressing Series (HDS). \n\n\n\nThe allergens were prepared by using the IQ\nChambers and occluded at the back for 2 days.\nReadings were done on Day 4 and Day 7 in\naccordance to the International Contact Dermatitis\nResearch Group recommendation.\n\n\n\nThe records of the patients patch tested to\npreservative sensitizers were recorded and\nanalyzed, namely formaldehyde 1% aq.,\nquaternium-15 1% pet., methyldibromo\nglutaronitrile (MDBGN) 0.3% pet., paraben\nmix 16% pet., methylchloroisothiazolinone/\nmethylisothiazolinone (MCI/MI) 0.01% aq.,\ndiazolidinyl urea 2% pet., imidazolidinyl urea 2%\npet., dimethylol dimethyl (DMDM) hydantoin 2%\naq., sorbic acid 2% pet., triclosan 2% pet., 2-bromo-\n2-nitropropane-1,3-diol (bronopol) 2% pet.,\niodopropynyl butylcarbamate (IPBC) 0.1% pet.,\nbenzyl alcohol 1% pet., 4-chloro-3-cresol\n(PCMC) 1%pet., 2-phenoxyethanol 1% pet. and\nchloroacetamide 0.2% pet.\n\n\n\nPatients\u2019 presentations were grouped into \u201cface\u201d,\n\u201chands\u201d, \u201cupper limbs\u201d, \u201cface and upper limb\ncombined\u201d, \u201ctrunk\u201d and \u201clower limbs\u201d. Age of the\npatients were grouped into <20, 20-35, 36-50 and\n>50. Positivity is defined as positive reaction to at\nleast one or more preservative sensitizers.\n\n\n\nStatistics\nData obtained were analyzed using SPSS Version\n12.0. Association between categorical variables was\nanalyzed using the chi-squared test. Statistical\nsignificance was set at p <0.05.\n\n\n\nResults\n243 patients were patch tested and the female to\nmale ratio of 1.5:1. One patient had an angry back\nsyndrome. 30 and 8 out of the 243 patients were\nalso patch tested with CS and HDS respectively.\nMalays constituted 55.6%. There were younger\n(<36 years old) than older patients (Table 1).\n\n\n\n28.4% of the patients had a positive reaction to at\nleast one or more preservative sensitizers, with a\nfemale predominance (34.4% vs. 19.3%, p=0.010).\nThe most frequently positive preservative sensitizer\nin this study was paraben mix 11.8%, followed by\nformaldehyde 8.6%, MCI/MI 8.6% and MDBGN\n4.5% (Table 2). \n\n\n\nFemales had 3 times more frequent sensitization to\nMCI/MI as compared to males (11.7% vs. 4.0%,\np=0.038). Proportionately more females had a\npositive reaction to paraben mix, formaldehyde,\nquartenium-15 and MDBGN. However, this is not\nstatistically significant. The percentage of Malay,\nChinese or Indian with a positive reaction to at least\none or more of the preservative sensitizers was\napproximately equal. There were more Indian\npatients sensitized to paraben mix as compared to\nMalays and Chinese. However, this was not\nstatistically significant. Younger patients (less than\n36 years of age), had a significantly more positive\nreaction to formaldehyde (p=0.038) (Table 3).\n\n\n\n\u201cFace & upper limbs\u201d presentation was\nsignificantly more associated with positive reaction\nto one or more preservative sensitizers (p=0.034). It\nwas also significantly associated with positive\nreaction to formaldehyde and MCI/MI (p=0.042\nand p<0.001 respectively). \u201cFace\u201d presentation was\nsignificantly associated with positive reaction to\ndiazolidinyl urea (p=0.016) (Table 4). \u201cHands\u201d\npresentation was significantly associated with\nsensitization to MDBGN (p=0.046)\n\n\n\nDiscussion\nAs only selected patients were patch tested with\nadditional series (CS and HDS), the frequency of\nsensitization of different preservative sensitizers are\nnot directly comparable. Almost a third of patients\nthat underwent patch test in 2011 had positive\nreactions to at least one or more preservative\nsensitizers. It is important to note from this study\nthat without doing the additional series, we would\nhave missed 5% of preservative allergy in this\ncohort of patients.\n\n\n\nThe results show that paraben mix is the most\nfrequently positive preservative allergen in our\nhospital in 2011. This is much higher than reported\nelsewhere. Paraben is an uncommon allergen across\nthe Europe countries 0.1-2.2%4, India 4%5,\nmeanwhile China (Beijing) has a sensitization rate\nof 20%6\n\n\n\n\n\n\n\n\n3MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 1 Demographic characteristic of the patients.\n\n\n\nPatient characteristics \n\n\n\nGender\n\n\n\nEthnic\n\n\n\nAge group\n\n\n\nMale\nFemale\n\n\n\nMalay\nChinese\nIndian\nOthers\n\n\n\n<20\n20-35\n36-50\n>50\n\n\n\nn\n\n\n\n98\n145\n\n\n\n133\n80\n28\n2\n\n\n\n59\n66\n62\n55\n\n\n\n%\n\n\n\n40.3\n59.7\n\n\n\n54.7\n32.9\n11.5\n0.8\n\n\n\n24.2\n27.2\n25.5\n22.6\n\n\n\nTable 2 Frequency of sensitization of common preservative sensitizers in various countries.\n\n\n\nAllergen\n\n\n\nParaben mix\n\n\n\nFormaldehyde\n\n\n\nQuaternium-15\n\n\n\nImidazolidinyl urea\n\n\n\nDiazolidinyl urea\n\n\n\nMCI/MI\n\n\n\nMDBGN\n\n\n\n11.8%\n\n\n\n8.6%\n\n\n\n2.1%\n\n\n\n0.0%\n\n\n\n0.8%\n\n\n\n8.6%\n\n\n\n4.5%\n\n\n\nPresent\nstudy\n\n\n\n10.9%\n\n\n\n4.5%\n\n\n\n2.5%\n\n\n\n1.7%\n\n\n\n3.6%\n\n\n\n4.3%\n\n\n\n5.6%\n\n\n\nThailand7\n\n\n\n20%\n\n\n\n15.8%\n\n\n\n-\n\n\n\n3.0%\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nChina5\n\n\n\n0.1-2.2%\n\n\n\n0.7-5.9%\n\n\n\n0.1-3.2%\n\n\n\n0.4-1.0%\n\n\n\n0.7-1.1%\n\n\n\n1.2-4.2%\n\n\n\n0.3-3.8%\n\n\n\nEuropean4\n\n\n\nCountries\n\n\n\nTable 3 Frequency of sensitization to preservatives.\n\n\n\n*Positive reaction to one or more preservative sensitizers.\n\n\n\nAllergen\n\n\n\nGender\n\n\n\nAge\n\n\n\nEthnic\n\n\n\nPresent\nstudy\n\n\n\nMale\n\n\n\nFemale\n\n\n\np-value\n\n\n\n<20\n\n\n\n20-35\n\n\n\n36-50\n\n\n\n>50\n\n\n\np-value\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndia\n\n\n\nOthers\n\n\n\np-value\n\n\n\nPositivity*\n\n\n\n19 (19.3%)\n\n\n\n50 (34.4%)  \n\n\n\n0.010\n\n\n\n14 (23.7%)\n\n\n\n23 (34.8%)\n\n\n\n16 (25.8%)\n\n\n\n16 (28.5%)\n\n\n\n0.534\n\n\n\n35 (26.3%)\n\n\n\n25 (31.2%)\n\n\n\n8 (28.6%)\n\n\n\n1 (50.0%)\n\n\n\n0.786\n\n\n\nFormaldehyde\n\n\n\n6 (6.1%)\n\n\n\n15 (15.3%)\n\n\n\n0.251\n\n\n\n7 (11.9%)\n\n\n\n10 (15.2%)\n\n\n\n2 (3.2%)\n\n\n\n2 (3.6%)\n\n\n\n0.038\n\n\n\n12 (9.0%)\n\n\n\n6 (7.5%)\n\n\n\n3 (10.7%)\n\n\n\n0 (0.0%)\n\n\n\n0.919\n\n\n\nMCI/MI\n\n\n\n4 (4.0%)\n\n\n\n17 (11.7%)\n\n\n\n0.038\n\n\n\n1 (1.7%)\n\n\n\n9 (13.6%)\n\n\n\n6 (9.6%)\n\n\n\n5 (9.0%)\n\n\n\n0.123\n\n\n\n12 (9.0%)\n\n\n\n8 (10.0%)\n\n\n\n1 (3.5%)\n\n\n\n0 (0.0%)\n\n\n\n0.720\n\n\n\nParaben mix \n\n\n\n10 (10.2%)\n\n\n\n18 (12.4%)\n\n\n\n0.597\n\n\n\n8 (11.8%)\n\n\n\n11 (16.7%)\n\n\n\n9 (14.5%)\n\n\n\n2 (3.6%)\n\n\n\n0.140\n\n\n\n15 (11.3%)\n\n\n\n9 (11.2%)\n\n\n\n5 (17.8%)\n\n\n\n1 (50%)\n\n\n\n0.304\n\n\n\n\n\n\n\n\n4 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nof 20%6 and closer to home, Thailand 10.9%7. Other\ncommon allergens are formaldehyde 8.6% and\nMCI/MI 8.6% respectively. In contrast, a study\nfrom European countries recorded 0.7-5.9% and\n1.2-4.2%8 respectively whereas Thailand recorded\n4.5% and 4.3% respectively7 (Table 2). Another\nmore recent study from Thailand9 recorded\nsensitization rate of 3.5% and 4.3% respectively. On\nthe other hand, North America recorded a higher\nfrequency of sensitization rate of 9% to\nformaldehyde10\n\n\n\nThe mark difference in the positivity rate may be\ndue to 1) Difference in legislation concerning the\nusage of these preservatives in cosmetics,\nhousehold and industrial products in different\ncountries 2) Difference in selection of patients to be\npatch tested. However, this is a finding from a\nsingle centre and may not reflect the whole country.\nParabens are the most commonly used preservatives\nin cosmetic and industrial products, as they are less\ncostly, odourless, colourless, stable and have a wide\nspectrum of antibacterial activity11. Cross-reactions\nwith benzocaine and para-phenylenediamine have\nbeen reported, which are thought to be uncommon.\nOur study found none.\nIn Malaysia, parabens are found not only in the\ninternational, but also in the local domestic\ncosmetics and pharmaceutical products. Parabens\nare also found in certain fruits and vegetables for\nexample olive, carrot and cucumber14. \n\n\n\nCosmetic products in Malaysia are regulated by the\nNational Pharmaceuticals Control Bureau13, where\nthe maximum concentration of formaldehyde and\nMCI/MI is similar to the European countries.\nHowever, there is no specific regulation with\nregards to paraben use. The European countries\nallow the maximum concentration of 0.4% of each\nparaben and a maximum total of 0.8% of all\nparabens in cosmetics, whereas MCI/MI use in\ncosmetics is permitted up to 100ppm4. The\nmaximum concentration of free formaldehyde\npermitted in cosmetics is 0.2%. In addition, all\nfinished products containing formaldehyde or\nformaldehyde releasers must be labelled \u201ccontains\nformaldehyde\u201d whenever concentration exceeds\n0.05%15. MDBGN is banned from being used in\nleave-on products in 2003 and in rinsed-off\nproducts in 2007 in Europe8. In the light of this\nresult, perhaps a study to determine the paraben\nconcentration in various consumer products should\nbe carried out in the near future.\n\n\n\nOn the other hand, it is important to be aware of the\nconcept of \u201cparaben paradox\u201d12. This concept refers\nto two phenomena 1) Patients who are sensitized to\nparabens may continue to use paraben containing\nproducts on intact skin; however, if the same\nproducts are applied to skin with impaired\nepidermal barrier, they may induce a dermatitis 2)\nIndividuals who are sensitized to parabens have\nfalse negative patch test reactions when parabens\nare patch-tested on an intact skin.\n\n\n\nTable 4 Frequency of sensitization to formaldehyde, MCI/MI, diazolidinyl urea, paraben mix with different presentations.\n\n\n\n*46.2% of the patients with \u201cface and upper limbs\u201d presentation has positive reaction to one or more preservative\nsensitizers compared to only 26.2% of the patients with other presentations.\n\n\n\nPatient characteristics \n\n\n\nPositive reaction to one or more\npreservative sensitizer\n\n\n\np-value\n\n\n\nFormaldehyde\np-value\n\n\n\nMCI/MI\np-value\n\n\n\nDiazolidinyl urea\np-value\n\n\n\nParabens mix\np-value\n\n\n\n\u201cFace \u201d vs. others \n\n\n\n36.5% vs. 25.5%\n\n\n\n0.097\n\n\n\n12.6% vs. 7.2%\n0.183\n\n\n\n14.2% vs. 6.7%\n0.064\n\n\n\n3.1% vs. 0%\n0.016\n\n\n\n9.5% vs. 12.2%\n0.564\n\n\n\n\u201cFace & UL combined\u201d vs. others    \n\n\n\n46.2% vs. 26.2%*\n\n\n\n0.034\n\n\n\n19.2% vs. 7.3%\n0.042\n\n\n\n26.9% vs. 6.4%\n<0.001\n\n\n\n0.0% vs. 0.9%\n0.616\n\n\n\n11.4% vs. 11.5%\n0.895\n\n\n\n\n\n\n\n\n5MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nOur study found that 14.2% of the patients who\nwere allergic to formaldehyde had concomitant\ncontact allergy to formaldehyde releasers\n(p=0.001). 14.2% of the patients who were allergic\nto formaldehyde had concomitant positive reaction\nto quaternium-15(p<0.001), whereas 60% of\npatients who were allergic to quaternium-15 were\nallergic to formaldehyde (p<0.001). These almost\nmirror the findings by Lundov et al20 whereby\nconcomitant allergy to quaternium-15 is found in\n23% of patients allergic to formaldehyde, whereas\n74% of patients allergic to quartenium-15 were\nfound to be allergic to formaldehyde as well. This is\nmostly likely because quaternium-15 is a\nformaldehyde releaser that releases the greatest\namount of formaldehyde20.\n\n\n\nFemales had 1.5 times more frequent positive\nreaction to one or more preservative sensitizers as\ncompared to males (34.4% vs. 19.3%, p=0.010).\nProportionately more females are sensitized to\nformaldehyde, quaternium-15, MCI/MI, paraben\nmix and diazolidinyl urea;none of which reached\nstatistical significance. These results are not\nsurprising and most likely due to higher usage of\ncosmetics and other preservative containing\nhousehold products in women. Furthermore, since\nfemales use more cosmetic products, they are more\nlikely to seek medical attention than males. It is\nimportant to note that about one fifth of the males\nwere sensitized to one or more preservative\nsensitizers. A study from UK found sensitization to\nparaben mix as significantly more frequent in men,\nwhereas sensitization to diazolidinyl urea and\nquaternium-15 to be more frequent in women8.\n\n\n\nInterestingly, sensitization to paraben mix was\nfound to be more frequent among Indians as\ncompared to Malay and Chinese although it was not\nstatistically significant. This finding may be related\nto higher use of domestic cosmetics and\ntraditional/herbal liniments amongst the Indians.\n\n\n\nYounger age groups of less than 20 and between 20-\n35 years old had significantly more frequent\nsensitization to formaldehyde as compared to age\ngroups 35-50 and > 50 years old. This finding is in\ncontrast to a Danish study16 where formaldehyde\nallergy was significantly higher amongst the 41-60\nyear-old as compared to those less than 40 and more\nthan 60 years old. A study done in Singapore17 on\nchildren and adolescents as well as another study\nfrom Greece18 done on the patients under 16 years\nold using the European Standard Series reported\n\n\n\nthat formaldehyde and MCI/MI were not  the\ncommon allergens. However, these two studies\nfocused on the common allergens rather than\npreservative allergens. Lundov et al20 found\nmajority of the formaldehyde-allergic patients were\nexposed to cosmetic and household products\ncontaining formaldehyde (78% and 16%\nrespectively). \n\n\n\nOur study shows younger age group between 20-35\nyear-old has about 1.5 times higher rate of\nsensitization to MCI/MI compared to the older age\ngroup (35-50 and >50 years old), though this is not\nstatistically significant. This again contrasts with\nthe study done by Lundov et al19 who found\nMCI/MI allergy to be significantly associated with\nthose above 40 years of age, occupational dermatitis\nand hand eczema. We postulate that the MCI/MI\nallergy in our cohort of patients is mainly due to\nusage of cosmetics in that age group (working\nadults). We only had 9 cases of occupational\ndermatitis in 2011 and they were mainly related to\nrubber allergy.\n\n\n\nOur study found \u201cface and upper limbs combined\u201d\npresentation to be significantly associated with a\npositive reaction to one or more preservative\nsensitizers, which is not surprising as these areas\nhave the highest contact with cosmetics and\nhousehold product. \u201cFace and upper limb\ncombined\u201d presentation was significantly\nassociated with formaldehyde and MCI/CI allergy\nas well. \u201cFace\u201d presentation was significantly\nassociated with diazolidinyl urea allergy. This was\nsimilar with the findings of Schnuch et al8 where\ndiazolidinyl urea allergy was associated with face\ndermatitis. \u201cHands\u201d presentation was significantly\nassociated with MDBGN. Latorre et al15 found the\n\u2018hands\u2019 to be the most common site of dermatitis in\npatients with a positive patch test only to\nformaldehyde, whereas the face and legs were the\nmost usual sites in patients with positive patch test\nreactions to the formaldehyde releasers\n(quaternium-15, imidazolidinyl urea and\ndiazolidinyl urea).\n\n\n\nThe limitation of our study includes 1) it is\nretospective in nature and 2) it does not represent\nthe true prevalence of sensitization of Malaysian\npopulation. The population in this study consisted\nof selected patients with suspected contact allergy.\nOur centre, that is Selayang Hospital, mainly\nreceive referral from Gombak, Rawang and Sentul,\nthus the results may differ from other centres in\nMalaysia.\n\n\n\n\n\n\n\n\n6 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nReferences\n\n\n\n1. Yazar K, Johnsson S, Lind ML et al. Preservatives and\nfragrances in selected consumer-available cosmetics\nand detergents. Contact Dermatitis 2011 May; 64(5):\n256-72\n\n\n\n2. De Groot AC, Le Coz CJ, Lensen GJ et al.\nFormaldehyde-releasers: relationship to formaldehyde\ncontact allergy. Part 2. Formaldehyde-releasers in\nclothes: durable press chemical finishes. Contact\nDermatitis 2010 Jul; 63(1): 1-9\n\n\n\n3. McFadden JP, Ross JS, Jones AB et al. Increased rate of\npatch test reactivity to methyldibromoglutaronitrile.\nContact Dermatitis 2000 Jan; 42(1): 54-5\n\n\n\n4. Uter W, Aberer W, Armario-Hita et al. Current patch\ntest results with the European baseline series and\nextensions to it from the \u2018European Surveillance\nSystem on Contact Allergy\u2019 network 2007-2008.\nContact Dermatitis 2012 Jul; 67(1), 9-19\n\n\n\n5. Sharma VK, Chakrabarti A. Common contact\nsensitizers in Chandigarh, India. Contact Dermatitis\n1998 Mar; 38(3): 127-31\n\n\n\n6. Cheng SW, Cao M, Zhang YL et al. Time trends of\ncontact allergy to a modified European baseline series\nin Beijing between 2001 and 2006. Contact Dermatitis\n2011; Jul 65 (1):22-7\n\n\n\n8. Schnuch A, Lessmann H, Geier J et al.. Contact allergy\nto preservatives. Analysis of IVDK data 1996-2009. Br\nJ Dermatol. 2011 Jun; 164(6): 16-25\n\n\n\n7. Boonchai W, Iamtharachai, Sunthonpalin P. Prevalence\nof allergic contact dermatitis in Thailand. Dermatitis\n2007 May/June; 19(3): 142-45\n\n\n\n8. Jong CT, Statham BN, Green CM et al. Contact\nsensitivity to preservatives in the UK 2004-2005:\nresults of multicenter study. Contact Dermatitis 2007\nSep; 57(3): 165-8\n\n\n\n9. Boonchai W, Desomchoke R, Lamtharachai P. Trend of\ncontact allergy to comestic ingredients in Thais over a\nperiod of 10 years. Contact Dermatitis 2011 Dec;\n65(6):311-6\n\n\n\n10. Zug KA, Warshaw EM, Fowler JF Jr et al. Patch test\nresults of the North American Contact Dermatitis\nGroup 2005-2006. Dermatitis. 2009 May-Jun; 20 (3):\n149-60\n\n\n\n11. Askari SK, Warshaw EM. Parabens. Dermatitis 2006\nDec; 17(4):2\n\n\n\n12. Cashman AL, Warshaw EM. Parabens: A review of\nepidemiology, structure, allergenicity and hormonal\nproperties. Dermatitis 2005; 16: 57-66\n\n\n\n13. National Pharmaceutical Control Bureau. Guidelines\nfor control of cosmetic products in Malaysia Date June\n2010 No 21. Annex VI List of preservatives allowed for\nuse in cosmetic products. ASEAN Cosmetic\nDocuments 1-11\n\n\n\n14. Smith-Becker J, Marois E, Huguet EJ et al.\nAccumulation of salicylic and 4-hydroxybenzoic acid\nin phloem fluids of cucumber during systemic acquired\nresistance is preceded by a transient increase in\nphenylalanine ammonia-lyase activity in petioles and\nstems. Plant Physiol. 1988 Jan; 116(1): 231-8\n\n\n\n15. Latorre N, Borrego L, Fernanadez-Redondo V et al.\nPatch testing with formaldehyde and formaldehyde-\nreleasers: multicentre study in Spain (2005-2009).\nContact dermatitis 2011 Nov; 65(5): 286-92\n\n\n\n16. Thyssen JP, Engkilde K, Lundov MD et al.. Temporal\ntrends of preservative allergy in Denmark (1985-2008).\nContact Dermatitis 2010 Feb; 62(2):102-8\n\n\n\n17. Goon TJ, Goh CL. Patch Testing of Singapore children\nand adolescents: Our experience over 18 years.\nPediatric Dermatol. 2006; 23(2): 117-20\n\n\n\n18. Milingou M, Tagka A, Armenaka M et al. Patch test in\nchildren: A review of 13 years of experience in\ncomparison with previous data.  Pediatrics Dermatol.\n2010; 27(3):325-59\n\n\n\n19. Lundov MD, Thyssen JP, Zachariae C et al Prevalence\nand cause of methylisothiazolinone contact allergy.\nContact Dermatitis 2010 Sept; 63(3):164-67\n\n\n\n20. Lundov MD, Johansen JD, Carlsen BC et al.\nFormaldehyde exposure and patterns of concomitant\ncontact allergy to formaldehyde and formaldehyde-\nreleasers. Contact Dermatitis 2010 Jul; 63(1): 31-36\n\n\n\nConclusion\nParaben mix is most frequently positive\npreservative sensitizer among our patients followed\nby formaldehyde and methylchloroisothiazolinone/\nmethylisothiazolinone (MCI/MI). The younger age\ngroups were more frequently associated with\nsensitization to formaldehyde and MCI/MI.\n\n\n\nAcknowledgement\nThe authors will like to thank the Director General\nof Health, Malaysia for permission to publish this\npaper.\n\n\n\n\n\n\n\n\n7MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nEDUCATION - Original Article\n\n\n\nDEVELOPING A DERMATOLOGY CURRICULUM FOR\nMALAYSIAN MEDICAL UNDERGRADUATES:\nINITIAL RESULTS OF THE DELPHI METHOD \nAdawiyah Jamil, AdvMDerm, Mazlin Mohd Baseri, AdvMDerm, Leelavathi Muthupalaniappen,\nMMed (Fam. Med), Roshidah Baba, FRCP \n\n\n\nAbstract\n\n\n\nBackground: Dermatology in the Malaysian undergraduate medical curriculum is included as a sub-\nspecialty subject in Internal Medicine. The dermatology course content for undergraduate varies\namong the different teaching institutions. A standardized curriculum is required to prepare graduates\nfor clinical dermatological practices in a tropical country and also applicable worldwide.\n\n\n\nMethods: The Delphi method is used to reach a consensus on the curriculum\u2019s core content. A\nquestionnaire with lists of dermatological conditions was developed by a panel of dermatologists and\nfamily physician. A total of 60 participants comprising of 20 dermatologists, 20 family physicians\nand 20 general practitioners are asked to rate the importance of each dermatological conditions\nstated in the questionnaire. The same participants then answers the questionnaire again with results\nof the first round made available to them. The final curriculum content will be identified based on\nthe panel\u2019s collective opinions. \n\n\n\nResults: We present the results of the first part of the study which is the (questionnaire\ndevelopment). Section 1 of the questionnaire lists 20 topics according to the classification of\ndermatological diseases and common dermatological diseases. Section 2 expands each classification\nby listing specific diseases or conditions. There are 4 to 13 diseases identified under each\nclassification. This provides a total of 171 options to be graded by each participant. Section 1 aimed\nto identify important topics based on the classification and common dermatological diseases. The\nlist of specific diseases aimed to identify the important dermatological conditions or diseases under\neach classification.\n\n\n\nConclusion: A standardized appropriate curriculum in dermatology is required for the Malaysian\nundergraduate teaching curriculum which is acceptable both locally and internationally. The finding\nof the study may be used to recommend a standard Malaysian medical undergraduate dermatology\ncurriculum.\n\n\n\nKeywords education, medicine, Malaysia\n\n\n\nCorrespondence\nAdawiyah Jamil, AdrMDerm\nDepartment of Medicine, University Kebangsaan\nMalaysia Medical Center, Bandar Tun Razak, Cheras\n56000 Kuala Lumpur\nE-mail: adda_jamil@yahoo.com\n\n\n\nIntroduction\nDermatology as a subject in the Malaysian\nundergraduate medical curriculum is included as a\nsub-specialty subject in Internal Medicine. This\nsub-specialty area is formally taught in a few local\nuniversities depending on the content of the Internal\nMedicine programme.\n\n\n\n\n\n\n\n\n8 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe course content varies among the different\ninstitutions based on the individuals involved in the\ndevelopment of the academic programme and the\nmodel of the curriculum. There is lack of published\ndata which looks at the suitability and effectiveness\nof the current undergraduate dermatology course\ncontent in Malaysia. Hence there is a need for a\nreview and update of the dermatology curriculum.\n\n\n\nThere are few reports on the availability of a\ndermatology module as a component of the core\nmedical curriculum and the content of the\ncurriculum. In the United Kingdom in year 2000,\n19 out of 24 medical schools had an integrated\ndermatology curriculum1. In 18 of these schools,\nstudents were exposed to patients with\ndermatological conditions in the hospital or\nprimary care setting. In a survey conducted in India,\n3 out of 7 colleges had formal assessments on\ndermatology knowledge2. A survey in the United\nStates of America identified 33 medical schools\nwithout an undergraduate dermatology program3. In\nthe schools that had a program, more than half\nallocated less than 10 hours to dermatology\nteaching.\n\n\n\nThe importance of including dermatology in the\nmedical curricula was illustrated by a few reports.\nSeventy one percent of general practitioners\nsurveyed in the United Kingdom agreed that\ndermatology is an essential part of the medical\ncurriculum and should be included in postgraduate\nprograms4. Thirty seven percent of primary care\nphysicians thought their undergraduate training is\nadequate to prepare them to diagnose common\ndermatological diseases, but only 28% felt they\nwere adequately prepared to treat these diseases5.\nFifty-one percent who completed an undergraduate\ndermatology module felt they were adequately\nprepared to make a diagnosis. Of those who did not\ncomplete the module, only 25% felt they were\nadequately prepared to diagnose common\ndermatological diseases. In terms of the ability to\ntreat common dermatological illnesses, 42% of\nthose who completed their module felt adequate\ncompared to 16% who did not complete their\nmodule5.\n\n\n\nIn 2006, the British Association of Dermatologists\n(BAD) recommended an evidence based core\nundergraduate dermatology curriculum6. Following\nthe introduction of the BAD recommendations, an\naudit of the core curriculum content in the United\n\n\n\nKingdom medical schools was performed in 20097.\nIn terms of hours of exposure, the number of\nseminars or lectures ranged from 0 to 39 with a\nmean of 10, while the number of clinic sessions\nranged from 0 to 18 with a mean of 5. Essential\nclinical skills, background knowledge, skin failure\nand emergency dermatology are included in most\ncurricula. There were still gaps in the\nimplementation of the recommended curriculum.\nThe Canadian dermatology undergraduate\ncurriculum was reviewed in 1983, 1987, and 19968.\nThe average number of hours dedicated to\ndermatology teaching in Canada improved by 7\nhours to 20.5 hours between 1996 and 20088. The\nmain restriction identified in implementing the\ncurriculum in Canada is the small number of\ndermatologists available as teachers.\n\n\n\nIdentification of the core contents is required to\ndevelop a standard medical undergraduate\ndermatology curriculum for the country. This has to\nbe tailored to its usefulness in the local setting,\nespecially taking into consideration the tropical\nclimate, differences in the Asian population and\nskin of color. The curriculum in general must also\nbe applicable worldwide. Additionally, a clearly\ndefined curriculum is important given the very\nlimited time available for the teaching of\ndermatology.\n\n\n\nAim\nThe objective of this study is to identify the\nappropriate course content for the Malaysian\nmedical undergraduate dermatology curriculum. \n\n\n\nStudy design\nThis is a cross sectional study using the Delphi\nmethod to assess the appropriateness of a\ndermatology course content in the medical\nundergraduate curriculum.\n\n\n\nMethodology\nA questionnaire containing lists of dermatological\nconditions to be included in the curriculum was\ndeveloped by 3 dermatologists (2 from an academic\ninstitution, 1 from the Ministry of Health Malaysia)\nand a family physician. The list was created based\non the recommendations of the British Association\nof Dermatologists for a medical undergraduate\ncurriculum6, standard dermatology textbooks9,10,\npublished literature on the subject2-5,8 and personal\nclinical experience. The topics were grouped under\naccepted\n\n\n\n\n\n\n\n\n9MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\naccepted classifications of dermatological diseases.\nThe limited time available for a dedicated\ndermatology teaching is taken into consideration. In\ngeneral about two weeks is allocated for teaching of\ndermatology in a five-year undergraduate program.\nThis is an important point to consider in deciding\nthe curriculum content and it will be highlighted to\nthe participants of this study. The questionnaire\ndevelopment is the first part of the study.\n\n\n\nIn the next part of the study, the questionnaire will\nbe sent via email or snail mail to 20 members of the\nDermatological Society of Malaysia, 20 family\nphysicians and 20 general practitioners who are\nmembers of the Academy of Family Physicians of\nMalaysia. All the members of the Dermatological\nSociety of Malaysia are qualified dermatologists\nwhile members of the Academy of Family\nPhysicians of Malaysia consist of family physicians\nand general practitioners. Participants are asked to\nrate the importance of each disease or condition as\npart of the curriculum content based on a 5-point\nLikert scale (very important, fairly important,\nundecided, fairly unimportant, not important). They\nare given 6 weeks to return the completed\nquestionnaire. Non responders will be reminded\ntwice, at 2 weeks apart using both telephone call\nand mail. Responses from this questionnaire will be\nconsidered as Round 1. The responses will be\nanalyzed and a summary of the results prepared.\n\n\n\nThe results from Round 1 and the questionnaire will\nthen be sent back to the respondents. They will be\nasked to look at the results from Round 1 and\nanswer the questionnaire again (Round 2). They\nmay change their answers or keep to their previous\nanswers. Results from Round 2 will then be\nanalyzed.\n\n\n\nSample size calculation\nThe Delphi group size does not depend on\nstatistical power. It is based on group dynamics in\norder to achieve a consensus among experts. The\nliterature recommends 10-18 experts in a Delphi\npanel12. We decided to have a group consisting of 20\ndermatologists, 20 family physicians and 20 general\npractitioners, a slightly larger group size to account\nfor drop outs. Dermatologists, family physicians\nand general practitioners are chosen as the\nresponders in this study as they manage most\ndermatological cases.\n\n\n\nInclusion criteria consist of dermatologists who are\nmembers of the Dermatological Society of\nMalaysia and registered with the National Specialist\nRegistry, family physicians who are members of the\nAcademy of Family Physicians of Malaysia and\nregistered with the National Specialist Registry, and\ngeneral practitioners who are members of the\nAcademy of Family Physicians of Malaysia. \n\n\n\nFigure 1 Flow chart of study methodology.\n\n\n\nA questionnaire developed by a small group of dermatologists and a family physician\n\n\n\n\uf074\nQuestionnaire sent to 20 dermatologists, 20 general practitioners and 20 family physicians (Round 1)\n\n\n\n\uf074\nAnalysis of results (Round 1)\n\n\n\n\uf074\nSummary of results from round 1 and the same questionnaire sent to the respondents (Round 2)\n\n\n\n\uf074\nAnalysis of results (Round 2)\n\n\n\n\n\n\n\n\n10 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nStatistical analysis\nStatistical analyses will then be performed in the\nsecond part of the study. Analysis will be performed\nin both Round 1 and Round 2. Mode and median\nvalues of each topic will be calculated. Mode values\nthat correlated with median values indicate that the\nresults are a valid representation of the group\u2019s\nview. The level of agreement is determined by\ncalculating the percentage of respondents that\nchoose each answer scale. Responses from the three\ngroups will be analyzed separately and compared.\nThe responses from the groups will also be\nanalyzed together. \n\n\n\nResults\nThe questionnaire was developed by a small group\nof dermatologists and a family physician is shown\nin Appendix 1. Section 1 of the questionnaire\nincludes 20 topics according to the classification of\ndermatological diseases and common\ndermatological diseases. The topics consist of skin\nstructure and function, infection and infestations,\nskin tumours, skin signs of systemic diseases,\ndermatology emergencies, bullous diseases, drug\neruptions, psoriasis, eczema, hair and nail\ndisorders, pigmentary disorders, sexually\ntransmitted infections, leprosy, acne,\ndermatosurgery, genodermatoses, phamacotherapy,\nclinical skills and diagnostic procedures. Section 2\nexpands each classification by listing specific\ndiseases or conditions. There are 4 to 15 diseases\nidentified under each classification. This provided a\ntotal of 175 options to be graded by each\nparticipant. Section 1 aimed to identify important\ntopics based on the classification and common\ndermatological diseases. The list of specific\ndiseases aimed to ascertain the important\ndermatological conditions or diseases under each\nclassification. Respondents are given the\nopportunity to add conditions/diseases which they\nthought important to include in the curriculum. The\nquestionnaire takes about 30 minutes to complete.\n\n\n\nDiscussion\nRealizing the importance of identifying the core\ncontent of a standard dermatology curriculum for\nthe country, the authors have decided to make the\ndevelopment process accessible to all interested\nparties. The Delphi method was chosen as it\nprovides a systematic approach to identify and\nprioritize the curriculum content in order to achieve\na consensus. In addition, it allows contributions of\nexpertise, represents a collective judgment, gives an\nopportunity to revise views, anonymity and avoids\ndirect confrontation11. In this study, Round 1 of the\nquestionnaire will examine the depth and breadth of\ntopics included. It will also narrow down the topics\nconsidered important by the multidisciplinary\npanel. Round 2 allows each responder to revise their\nanswers from Round 1 after considering the panels\u2019\ncollective opinions. The questionnaire that has been\ndeveloped (Appendix 1) provides a framework for\nthese objectives.\n\n\n\nThe British Association of Dermatologists (BAD)\nhad recommended an evidence based core\nundergraduate dermatology curriculum developed\nbased on the Delphi method in 200612. The opinion\nof a panel consisting of 26 consultant\ndermatologists, 9 dermatology specialist registrars,\n33 medical and surgical specialties clinicians, 13\ngeneral practitioners, 8 junior doctors, 10\ndermatology nurses, 4 undergraduate basic sciences\ntutors, 6 pharmacists and 2 members of the Skin\nCare Campaign were evaluated. In our study, we\nselected general practitioners and family physicians\nto be in the panel as invariably, primary care is the\nfirst point of patient contact with health\nprofessionals. They would be able to identify\ncommon and important dermatological conditions\nencountered in daily clinical practice. Furthermore,\nfamily physicians who supervise junior medical\nofficers will be able to identify the knowledge\nlacking in these young doctors and what they\nshould be taught in medical schools.\n\n\n\nIn conclusion, efforts are being made to improve the\nteaching of undergraduate dermatology in\nMalaysia. It is important to develop a curriculum to\nsuit our country and at the same time is relevant\nglobally. The final results of this study may be used\nto recommend a standard Malaysian medical\nundergraduate dermatology curriculum.\n\n\n\n\n\n\n\n\n11MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nPlease place a \uf061 for each topic listed.\nScale: \n\n\n\nSection 1\nA. The topics listed must be included in the medical undergraduate dermatology curriculum. Please grade\nyour opinion according to the scale.\n\n\n\nTOPIC\n\n\n\n1 Skin: structure and function \n\n\n\n2 Infections and infestations\n\n\n\n3 Skin tumours \n\n\n\n4 Skin signs in systemic diseases\n\n\n\n5 Dermatology emergencies\n\n\n\n6 Bullous diseases\n\n\n\n7 Drug eruptions\n\n\n\n8 Psoriasis\n\n\n\n9 Eczema \n\n\n\n10 Hair and nail disorders\n\n\n\n11 Pigmentary disorders\n\n\n\n12 Sexually transmitted infections \n\n\n\n13 Leprosy\n\n\n\n14 Acne\n\n\n\n15 Dermatosurgery\n\n\n\n16 Genodermatoses\n\n\n\n17 Phamacotherapy\n\n\n\n20 Clinical skills and diagnostic procedures\n\n\n\n1 2 3 4 5\n\n\n\n1 2 3 4 5\n\n\n\nVery important Fairly important Undecided Fairly unimportant Not important\n\n\n\nMalaysian Dermatology Curriculum for Medical Undergraduates\nQUESTIONNAIRE\n\n\n\nPlease state if there are other very important topics which you think has not been listed.\n\n\n\n\n\n\n\n\n12     MJD 2011 July Vol 25\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSection 2\n1. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\n\n\n\ngrade your opinion according to the scale.\n\n\n\nStructure and function of the skin \n\n\n\n1. Anatomy of the skin\n\n\n\n2. Physiology of the skin\n\n\n\n3. Functions of the skin\n\n\n\n4. Pathophysiology of skin diseases\n\n\n\n5. Histopathology of common skin diseases\n\n\n\n1 2 3 4 5\n\n\n\n2. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nInfections and infestations\n\n\n\nBacterial infections\n\n\n\n1 Erythrasma\n\n\n\n2 Impetigo\n\n\n\n3 Ecthyma\n\n\n\n4 Folliculitis\n\n\n\n5 Abscess, furuncle, carbuncle\n\n\n\n6 Erysipelas\n\n\n\n7 Cellulitis\n\n\n\n8 Necrotizing fasciitis\n\n\n\n9 Mycobacterium infection\n\n\n\nFungal infections\n\n\n\n10 Tinea pedis and manuum\n\n\n\n11 Tinea corporis, cruris\n\n\n\n12 Tinea capitits, kerion\n\n\n\n13 Pityriasis versicolor\n\n\n\n14 Cutaneous candidiasis\n\n\n\n15 Onychomycosis\n\n\n\n16 Subcutaneous mycoses \n\n\n\n17 Invasive mycoses\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important sub-topics which you think has not been listed above.\n\n\n\n\n\n\n\n\n13MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nInfections and infestations\n\n\n\nViral infections\n\n\n\n18 Molluscum contagiosum\n\n\n\n19 Viral exanthems\n\n\n\n20 Hand, foot and mouth disease\n\n\n\n21 Herpes labialis\n\n\n\n22 Varicella zoster\n\n\n\n23 Herpes zoster\n\n\n\n24 Verruca vulgaris\n\n\n\nInfestations\n\n\n\n25 Pediculosis\n\n\n\n26 Scabies\n\n\n\n27 Cutaneous larva migrans\n\n\n\n28 Insect bite reactions\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n3. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nSkin tumours\n\n\n\n1 Nevomelanocytic nevi\n\n\n\n2 Blue nevus, Spitz nevus, Nevus spilus, \nNevus of Ota, Nevus of Ito,\nMongolian spot, Becker\u2019s nevus\n\n\n\n3 Vascular tumours & malformations\n\n\n\n4 Seborrhoiec keratoses, skin tags\n\n\n\n5 Lipoma, dermatofibroma\n\n\n\n6 Keloids, hypertrophic scar\n\n\n\n7 Syringoma, sebaceous hyperplasia, \ntrichoepithelioma\n\n\n\n8 Actinic keratoses\n\n\n\n9 Cutaneous horn\n\n\n\n10 Squamous cell carcinoma\n\n\n\n11 Basal cell carcinoma\n\n\n\n12 Malignant melanoma\n\n\n\n13 Cutaneous T cell lymphoma,\nSezary syndrome\n\n\n\n1 2 3 4 5\n\n\n\n\n\n\n\n\n14 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nThe skin in systemic diseases\n\n\n\n1 Cutaneous lupus erythematosus\n\n\n\n2 Dermatomyositis\n\n\n\n3 Behcet\u2019s syndrome\n\n\n\n4 Scleroderma\n\n\n\n5 Sarcoidosis\n\n\n\n6 Skin signs of viral hepatitis\n\n\n\n7 Systemic vasculitides\n\n\n\n8 Diabetes mellitus\n\n\n\n9 Internal malignancy/paraneoplastic \nconditions\n\n\n\n10 Dermatitis herpetiformis\n\n\n\n11 Amyloidosis\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n5. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nDermatology emergencies\n\n\n\n1 Acute erythroderma\n\n\n\n2 Staphylococcus scalded skin syndrome\n\n\n\n3 Urticaria, angioedema and anaphylaxis\n\n\n\n4 Eczema herpeticum\n\n\n\n5 Stevens-Johnson Syndrome and\nToxic Epidermal Necrolysis\n\n\n\n6 Psoriasis von Zumbusch\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n\n\n\n\n\n15MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nBullous diseases\n\n\n\n1 Bullous pemphigoid\n\n\n\n2 Pemphigus vulgaris\n\n\n\n3 Hailey hailey disease\n\n\n\n4 Linear IgA disease\n\n\n\n5 Epidermolysis bullosa acquisita\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n7. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nEczema\n\n\n\n1 Atopic eczema\n\n\n\n2 Seborrhoiec eczema\n\n\n\n3 Discoid eczema\n\n\n\n4 Hand and feet eczema\n\n\n\n5 Asteatotic/ craquele\n\n\n\n6 Stasis eczema\n\n\n\n7 Juvenile plantar\n\n\n\n8 Allergic contact dermatitis\n\n\n\n9 Irritant contact dermatitis\n\n\n\n10 Photodermatitis\n\n\n\n11 Phytodermatitis\n\n\n\n12 Photophytodermatitis\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n\n\n\n\n\n16 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nHair, nail and mucosal disorders\n\n\n\n1 Alopecia areata\n\n\n\n2 Androgenetic alopecia\n\n\n\n3 Telogen afluvium\n\n\n\n4 Anagen effluvium\n\n\n\n5 Hirsutism, hypertricosis\n\n\n\n6 Primary cicatricial alopecias\n\n\n\n7 Paronychia\n\n\n\n8 Nail signs in systemic diseases\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n10. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nSexually transmitted infections\n\n\n\n1 Syphillis\n\n\n\n2 Gonorrhoea\n\n\n\n3 Genital herpes\n\n\n\n4 Genital warts\n\n\n\n5 Chlamydia trachomatis infection\n\n\n\n6 Lymphogranuloma venereum \n\n\n\n1 2 3 4 5\n\n\n\n9. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nPigmentary disorders\n\n\n\n1 Vitiligo\n\n\n\n2 Albinism\n\n\n\n3 Melasma\n\n\n\n4 Post inflammatory hypo/hyper pigmentation\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n\n\n\n\n\n17MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSexually transmitted infections\n\n\n\n7 Chancroid\n\n\n\n8 Granuloma Inguinale\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n11. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nPhotodermatoses\n\n\n\n1 Photodermatitis\n\n\n\n2 Porphyrias\n\n\n\n3 Polymorphic light eruption\n\n\n\n4 Photoexacerbated dermatoses\n\n\n\n5 Chronic actinic dermatitis\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n12. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nDrug eruptions\n\n\n\n1 Exanthematous drug eruption\n\n\n\n2 Drug induced hypersensitivity syndrome\n\n\n\n3 Acute generalised exanthematous pustulosis\n\n\n\n4 Fixed drug eruption\n\n\n\n5 Erythema multiforme \n\n\n\n6 Drug induced lupus\n\n\n\n7 Drug induced vasculitis \n\n\n\n8 Drug induced photosensitivity\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n\n\n\n\n\n18 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nGenodermatoses\n\n\n\n1 Ichthyoses\n\n\n\n2 Epidermolysis bullosa\n\n\n\n3 Congenital viral infection\n\n\n\n4 Congenital malformations \n\n\n\n5 Transient dermatoses of the neonate\n\n\n\n6 Vascular malformations/tumours/ \nlymphangiomas\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n14. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nDermatosurgery/procedural skills\n\n\n\n1 Laser\n\n\n\n2 Electrocautery\n\n\n\n3 Cyrotherapy\n\n\n\n4 IL triamcinalone\n\n\n\n5 Skin biopsy, excision\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n15. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nDermatopharmacotherapy\n\n\n\n1 Topical steroids\n\n\n\n2 Topical antibiotics\n\n\n\n3 Topical anti-fungals\n\n\n\n4 Topical tretinoin\n\n\n\n5 Keratolytics\n\n\n\n6 Topical immunomodulators\n\n\n\n7 Emollients\n\n\n\n8 Tar preparations\n\n\n\n1 2 3 4 5\n\n\n\n\n\n\n\n\n19MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDermatopharmacotherapy\n\n\n\n9 Astringents\n\n\n\n10 Wet wraps\n\n\n\n11 Wet dressing\n\n\n\n12 Isotretinoin\n\n\n\n13 Antihistamines\n\n\n\n14 Biologics\n\n\n\n15 Writing a prescription\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n16. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nClinical skills and bedside investigations\n\n\n\n1 Dermatology history taking\n\n\n\n2 Dermatology physical examination\n\n\n\n3 Identification and description of \ncutaneous lesions\n\n\n\n4 Counselling \n\n\n\n5 Tape test\n\n\n\n6 Skin scraping for fungal culture\n\n\n\n7 Microscopic examination with KOH\n\n\n\n8 Tzanck smear\n\n\n\n9 Slit skin smear\n\n\n\n1 2 3 4 5\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\n17. The sub-topics listed must be included in the medical undergraduate dermatology curriculum. Please\ngrade your opinion according to the scale.\n\n\n\nMiscellaneous inflammatory disorders\n\n\n\n1 Lichen planus\n\n\n\n2 Pityriasis rosea\n\n\n\n3 Pityriasis lichenoides\n\n\n\n4 Pyoderma gangrenosum\n\n\n\n1 2 3 4 5\n\n\n\n\n\n\n\n\n20 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nPlease state if there are other very important topics which you think has not been listed above.\n\n\n\nReferences\n\n\n\n1. S Burge. Teaching dermatology to medical students: a\nsurvey of current practice in the U.K. Br J Dermatol\n2002; 146: 295-303.\n\n\n\n2. F Kaliyadan. Undergraduate dermatology teaching in\nIndia: Need for change. Indian J Dermatol Venereol\nLeprol 2010;76:455-457.\n\n\n\n3. PE McCleskey, RT Gilson, RL DeVillez. Medical\nStudent Core Curriculum in Dermatology Survey. J Am\nAcad Dermatol 2009;61:30-35.\n\n\n\n4. OA Kerr, J Walker, M Boohan. General practitioners\u2019\nopinions regarding the need for training in dermatology\nat undergraduate and postgraduate levels. Clin Exp\nDermatol 2005; 31:129-156.\n\n\n\n5. NK. Hansra, P O\u2019Sullivan, CL Chen, et al.\nMedical school dermatology curriculum: Are we\nadequately preparing primary care physicians? J Am\nAcad Dermatol 2008;61:23-29.\n\n\n\n6. Dermatology in the Undergraduate Medical\nCurriculum. Recommendations of the British\nAssociation of Dermatologists. www.bad.org.uk/\nhealthcare.\n\n\n\n7. E Davies, S Burge. Audit of dermatological content of\nU.K. undergraduate curricula. Br J Dermatol 2009;\n160: 999-1005.\n\n\n\n8. C Kirshen, I Shoimer, J Wismer, at el. Teaching\nDermatology to Canadian Undergraduate\nMedical Students. J Cutan Med Surg 2011;15\n(3):150-156.\n\n\n\n9. R Weller, JAA Hunter, J Savin, M Dahl. Clinical\nDermatology. 4th Edition. Wiley-Blackwell 2008.\n\n\n\n10. K Wolff, RA Johnson. Fitzpatrick's Color Atlas and\nSynopsis of Clinical Dermatology. 6th Edition.\nMcGraw-Hill Medical 2009.\n\n\n\n11. C Okoli, SD Pawlowski. The Delphi method as a\nresearch tool: an example, design considerations and\napplications. Information & Management 2004; 42:\n15-29.\n\n\n\n12. R Clayton, R Perera, S Burge. Defining the\ndermatological content of the undergraduate medical\ncurriculum: a modified Delphi study. Br J Dermatol\n2006; 55:137-144.\n\n\n\n\n\n\n\n\n21MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDERMATO-ONCOLOGY - Short Case\n\n\n\nMARJOLIN\u2019S ULCER SECONDARY TO CHRONIC BURN SCAR\nIN 2 PATIENTS\nAzura Mohd Affandi, AdvMDerm, Tan Wooi Chiang, MCRP, Dawn Ambrose, MCRP\n\n\n\nCorrespondence\nAzura Mohd Affandi, AdvMDerm\nDepartment of Dermatology\nHospital Kuala Lumpur, Jalan Pahang\n50586 Kuala Lumpur, Malaysia\nE-mail: affandi_azura@yahoo.co.uk\n\n\n\nIntroduction\nMarjolin\u2019s ulcer is a term used to describe a\nmalignant transformation in a chronic scar, usually\nsecondary to burn injury. The histopathology of the\nmalignant change is usually squamous cell\ncarcinoma. We reported two cases of Marjolin\u2019s\nulcer arising from a chronic burn scar.\n\n\n\nCase report\nCASE 1\nA 59 year-old Myanmar lady presented with 2 years\nhistory of verrucous plaque with ulceration over the\nright posterior ankle. She had no previous history of\npenetrating injury. She gave a history of burn\nsecondary to fire 30 years ago, resulting in a\nchronic scar extending from the lower legs up to the\nthighs. There was a history of similar ulcer over the\nleft leg, which resulted in a left below knee\namputation 3 years ago. There was no family\nhistory of malignancy.\n\n\n\nOn examination, there was a verrucous plaque, with\ncentral ulceration on the right posterior ankle\n(Figure 1). The lesion measured 5x7 cm in\ndiameter. The edges were raised and erythematous.\nThere was also evidence of burn scar extending\nfrom the right lower leg to the thigh. Left leg was\namputated below the knee level. There was no\nevidence of chronic arsenic ingestion.\n\n\n\nSkin biopsy from the ulcer edge showed marked\nparakeratosis, with malignant squamous cells\ninfiltrating into the dermis, arranged in trabeculae\nand nests, surrounded by desmoplastic, inflamed\nstroma (Figure 2).\n\n\n\nThe malignant squamous cells were well\ndifferentiated. There were keratin pearls and\nintercellular bridging. The nuclei were enlarged,\npleomorphic and vesicular, with prominent\nnucleoli. Mitotic figures were easily seen. The\nfeatures were consistent with a well differentiated\nsquamous cell carcinoma.\n\n\n\nKeywords skin cancer, squamous cell carcinoma, chronic skin lesion\n\n\n\nFigure 1\nUlcerated plaque, with raised margin\non the postero-lateral aspect of the right\nankle.\n\n\n\n\n\n\n\n\n22 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTissue for bacterial culture grew Streptococcus\nGroup B and Escherichia coli. Tissue cultures for\nfungus and mycobacterium were negative.\nTuberculous and non-tuberculous mycobacterium\nPolymerase Chain Reaction (PCR) were also\nnegative.\n\n\n\nComputed tomography (CT) scan of the thorax,\nabdomen and pelvis showed focal area of lung\nfibrosis, with two calcified left lung nodules, likely\nto represent granuloma. There was no evidence of\nlung metastases and no lymphadenopathy. \n\n\n\nMagnetic resonance imaging (MRI) of the right leg\nshowed irregular, ill-defined exophytic skin lesion\narising from the postero-lateral aspect of the right\nankle. There was also evidence of local extension\ninto the superficial fascia and superficial part of the\nsubcutaneous fat. The muscles, vessels, bones and\nankle joint were normal.\n\n\n\nFigure 2\nMalignant squamous cells infiltrating into the dermis, arranged in trabeculae and nests, surrounded by\ndesmoplastic, inflamed stroma (haematoxylin & eosin, x4 magnification).\n\n\n\nFigure 3\nUlcerated plaque, with fleshy erythematous\nnodule in the centre of the left forearm.\n\n\n\n\n\n\n\n\n23MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAs patient had amputation of the left leg, she was\nnot keen for further surgical intervention. She was\nhence referred for radiotherapy and is currently\nundergoing treatment.\n\n\n\nCASE 2\nA 53 year-old Indian lady presented with 3 months\nhistory of ulcerated plaque over her left forearm.\nThere was a history of burn injury secondary to hot\nwater scalding at the age of 3 years old. On\nexamination, there was an ulcerated plaque on her\nleft forearm, measuring 5 x 3 cm diameter (Figure\n3). There was no axillary lymphadenopathy.\n\n\n\nSkin biopsy showed malignant squamous cell\ninfiltration into the stroma. The cells were large in\nsize, with pleomorphic vesicular nuclei, prominent\nnucleoli and eosinophilic cytoplasm (Figure 4).\nKeratin pearls and intercellular bridges were also\nseen. The features were consistent with a well\ndifferentiated squamous cell carcinoma. \n\n\n\nShe was referred to the orthopaedic surgeon for\nexcision and grafting.\n\n\n\nDiscussion\nBurn injury occurs with varying depth and\nintensity. The healed burn injury, especially if it\nhealed by secondary intention is at risk for\ncontinued injury during the course of daily\nactivities. This is because the skin has lost the\nnormal architecture of the dermis, nerves, vessels,\nand adnexa. It is less elastic, more easily injured\nand ulcerated compared to normal skin. \n\n\n\nStudies have shown that major burn can lead to\nsignificant depression of both humoral and cell-\nmediated immunity1. The impairment of the\nimmune system is dependent on the extent of burn,\nand increased with the occurrence of superimposed\ninfections2. Individuals who experience chronic\nimmunosuppression are at a greater risk of\ndeveloping a malignancy3.\n\n\n\nFigure 4\nLarge keratinocytes, with pleomorphic vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm.\nMitoses also present (haematoxylin & eosin, x20 magnification).\n\n\n\n\n\n\n\n\n24 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMalignancies arising in burn scar tissue have been\nwell documented. Kowal-Vern et. al reported  412\ncases of cutaneous malignancies from 1923 to\n20044. In a recent study published by Duke J et.al,\n759 cases of solid organ malignancies were\nreported in patients with previous history of\nhospitalization for burn between 1983 to 20085.\nThey also noted that there was a gender effect in\nrelation to incidence of cancer after burn, with a\nsignificant risk of cancer for females5. Examination\nof total incident cancer notifications for females in\nthe burn cohort from 1983 to 2008 found cancer of\nthe breast (26.2%) to be the most common\nnotification, followed by cancers of female genital\nsystem (12.7%), colorectal (9.8%) and lung (9.8%)\ncancers5.\n\n\n\nHistorically, skin neoplasms are known to arise\nwhere chronic exposure to fire or heat injures the\nskin: the \u2018kangri\u2019 burn cancer in India, the \u2018kairo\u2019 of\nthe Japanese, the \u2018kang\u2019 cancer of north-west China\nand erythema ab igne in the British6-8. Celsus was\nthe first to note the development of cancer in burn\nscars9. In 1828, a French surgeon, Jean-Nicholas\nMarjolin, published his description of \u2018warty\u2019\nchanges of chronic ulcers10. It was only in 1903 that\nDa Costa coined the term \u2018Marjolin\u2019s ulcer\u201911.\nHowever, several authors have noted that Marjolin\nwas not the first to describe the entity\u2019s neoplastic\nnature. It was probably Dupuytren, Marjolin\u2019s\ncompetitor, who first described the cancerous\nchanges in an acid burn scar in 18399.\n\n\n\nFor many years the term Marjolin\u2019s ulcer was used\nas a synonym of burn scar neoplasm.  However,\nthere are several pathologies that contribute to\nMarjolin\u2019s ulcer development, such as\nosteomyelitis12, decubitus ulcers12, chronic fistulas13,\nfrost bite14, chronic venous insufficiency15,\nvaccination sites16 and skin graft donor sites17.\n\n\n\nThe histology of Marjolin\u2019s ulcer is usually\nsquamous cell carcinoma (SCC), which accounted\nfor 73% of cases, followed by basal cell carcinoma\n(BCC) in 10% of cases. Other less frequent\nhistological changes are malignant melanoma,\nsarcomas (fibrosarcoma, liposarcoma,\ndermatofibrosarcoma protuberans, mesenchymal\ntumor) and mixed tumors (SCC-BCC and SCC-\nmelanoma)18.\n\n\n\nThere is usually a lag period between the\ndevelopment of Marjolin\u2019s ulcer in a scar tissue and\nthe time of injury. The latency is inversely\nproportional to the patients\u2019 age. The older the\npatient at the time of injury, the shorter the lag\nperiod. The average latency period is 36 years and\nthe average patients\u2019 age at the time of diagnosis is\n5218. Male to female ratio is 2:118. The commonest\naffected sites are the lower extremities, which\naccounted for 36% of cases. This is followed by the\nhead & neck region, upper extremities and the\ntrunk18.\n\n\n\nMarjolin\u2019s ulcer is commonly mistaken for an\ninfected ulceration occurring at the scar tissue sites.\nChanges such as the appearance of painful, non-\nhealing ulcers, enlarging in circumference, with\nelevated and indurated borders, foul-smelling, with\nexudate and bloody discharge suggest a malignant\ntransformation. Biopsy is recommended to confirm\nthe neoplastic transformation. Unfortunately\ndiagnosis is often delayed. Marjolin\u2019s ulcer has a\nhigh metastatic potential and 30% of the cases have\nenlarged lymph nodes with possible distant\nmetastasis at diagnosis18.\n\n\n\nMost researchers agree that the best prevention of\nthese scar malignancies is primary skin grafting of\nthe burn sites. Examination of the effects of burn\nseverity and skin graft amongst burn survivors and\ncancer incidence identified a significant association\nfor those with burns of total body surface area of\n20% or greater, while a non-significant positive\nassociation was found for those who had skin graft5.\nOn the basis that prolonged healing of wounds may\nbe a potential risk factor for carcinoma, it has been\nsuggested that early skin grafting may be important\nwith respect to prevention of cancer.\n\n\n\nTo date, there has not been a consensus reached\nover the treatment protocol. Wide surgical excision\nseems to be the most preferred method.  Defects are\nusually skin grafted either with free flaps or split-\nthickness skin grafts (STSG)19. If there is a\nclinically palpable lymphadenopathy, lymph node\ndissection is recommended with an exception for\nmalignant melanoma, where the sentinel lymph\nnode biopsy should be performed regardless of the\npresence of enlarged lymph nodes. CO2 laser had\n\n\n\nalso been tried successfully in some cases20.\nInoperable cases and recurrences may be treated\nwith radiotherapy alone or combined with\nchemotherapy. \n\n\n\n\n\n\n\n\n25MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nConclusions\nMarjolin\u2019s ulcer may begin as an indolent lesion,\nbut has the potential to become a very aggressive\nmalignancy. Unfortunately the diagnosis and\ntreatment are usually delayed.  In order to reduce\nthe malignant transformation, burns, especially full\nthickness burns, should be skin grafted. Patients\nsuffering from burns or other skin pathologies\nleading to the formation of scar tissue must be\n\n\n\nmonitored regularly. Any suspicious lesions or\nulcerations must be biopsied. Surgical treatment is\nthe mainstay treatment of Marjolin\u2019s ulcer.\nRadiotherapy and chemotherapy can be reserved for\npatients unsuitable for surgery. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director\nGeneral of Health, Malaysia for permission to\npublish this paper.\n\n\n\nReferences\n\n\n\n1. O\u2019Sullivan ST, O\u2019Connor TP. Immunosuppression\nfollowing thermal injury: the pathogenesis of\nimmunodysfunction. Br J Plast Surg 1997;50:615-23.\n\n\n\n2. Jeschke MG, Mlcak RP, Finnerty CC, et al. Burn\nsize  determines the inflammatory and hypermetabolic\nresponse. Crit Care (London England) 2007;11: R90.\n\n\n\n3. Buell JF, Gross TG, Woodle ES. Malignancy after\ntransplantation. Transplantation 2005;80:S254-64.\n\n\n\n4. Kowal-Vern A, Criswell BK. Burn scar neoplasms: a\nliterature review and statistical analysis. Burns\n2005;31:403-13.\n\n\n\n5. Duke J, Rea S, Semmens J et.al. Burn and cancer risk:\nA state-wide longitudinal analysis. Burns 2012;38:340-\n47.\n\n\n\n6. Suryanarayan CR. Kangri cancer in Kashmir valley:\npreliminary study. J Surg Oncol 1973;5:327-33.\n\n\n\n7. Laycock HT. The \u2018\u2018Kang cancer\u2019\u2019 of north-west China.\nBr Med J 1948;1:982.\n\n\n\n8. Peterkin GAG. Malignant change in erythema ab igne.\nBr Med J 1955;2:1599-602.\n\n\n\n9. Treves N, Pack GT. Development of cancer in burn\nscars. Surg Gynecol Obstet 1930;51:749-82.\n\n\n\n10. Marjolin JN: Ulcere: dictionnaire de medecine. Paris,\nBechet, 1828.\n\n\n\n11. Da Costa JC: Carcinomatous changes in an area of\nchronic ulceration, or Marjolin\u2019s ulcer. Ann Surg 1903;\n37: 495-502.\n\n\n\n12. Soo BH, Dong JK, Chang HJ. Clinical study of\nMarjolin\u2019s ulcer. Yonsei Med J 1990; 31: 234-41.\n\n\n\n13. Steffen C: Marjolin\u2019s ulcer. Report of two cases and\nevidence that Marjolin did not describe cancer arising\nin the scars of burns. Am J Dermathopathol 1984; 6:\n187-93.\n\n\n\n14. Fleming MD, Hunt JL, Purdue GF, et al.\nMarjolin\u2019s ulcer: a review and re-evaluation of a\ndifficult problem. J Burn Care Rehabil 1990; 11:460-9.\n\n\n\n15. Thio D, Clarkson JHW, Misra A, et al.\nMalignant change after 18 months in a lower limb\nulcer: acute Marjolin\u2019s revisited. Br J Plast Surg 2003;\n56: 825-8.\n\n\n\n16. Reed WB: Malignant tumors as a late complication of\nvaccination. Arch Dermatolol 1968; 98: 132-5.\n\n\n\n17. Gamatsi E, McCulloch TA, Bailie FB, et al.\nMalignant melanoma in a skin graft: burn scar\nneoplasm or a transferred melanoma. Br J Plast Surg\n2000; 53: 342-52.\n\n\n\n18. Ochenduszkiewicz U, Matkowski R, Szynglarewicz B\net.al. Marjolin\u2019s ulcer: malignant neoplasm arising in\nscars. Rep Pract Oncol Radiother 2006; 11(3): 135-138\n\n\n\n19. Aydogdu E, Yildirim S, Akoz T: Is surgery an effective\nand adequate treatment in advanced marjolin\u2019s ulcer.\nBurns 2005; 31: 421-31.\n\n\n\n20. Hatzis GP, Finn R. Marjolin\u2019s Ulcer: A review of the\nliterature and report of a unique patient treated with a\nCO2 laser. J Oral Maxillofac Surg 2007;65: 2099-2105.\n\n\n\n\n\n\n\n\n26 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDERMATO-ONCOLOGY - Short Case\n\n\n\nSQUAMOUS CELL CARCINOMA ARISING FROM\nHYPERTROPHIC LICHEN PLANUS: A CASE REPORT AND\nREVIEW OF LITERATURE \nTan Wooi Chiang, MRCP, Mohd Affandi, AdvMDerm, Dawn Ambrose, MRCP\n\n\n\nCorrespondence\nTan Wooi Chiang, MRCP (Ire)\nDepartment of Dermatology,\nHospital Kuala Lumpur, Jalan Pahang,\n50586 Kuala Lumpur, Malaysia \nE-mail: tanwooichiang@yahoo.com\n\n\n\nIntroduction\nLichen planus (LP) is a common papulo-squamous\ndisorder involving the skin, mucosa, nails and hair1.\nAlthough it is a benign disorder, malignant changes\nmay occur. There are very few case reports on\nmalignant transformation of cutaneous lichen\nplanus2.\n\n\n\nWe report a case of squamous cell carcinoma (SCC)\nwhich developed over a long standing hypertrophic\nlichen planus (HLP) lesion on the right shin of a\nyoung Indian male. Case is described for the rarity\nof complication arising from a common condition.\n\n\n\nCase report\nA 31-year-old Indian male presented with a chronic\nwarty plaque over both leg since the age of 4. The\nlesion started as red itchy plaques that gradually\nenlarged over time. He was treated with potent\ntopical steroid with or without occlusion and\nintermittent cryotherapy. The lesion improved\nsignificantly but did not disappear completely.\n\n\n\nTwenty-seven years after the initial presentation, a\n5-cent coin size warty growth had appeared at the\ncentre of the plaque. The growth enlarged rapidly\nover 6 weeks and bled on touching. There was no\nhistory of trauma or contact with irritant\nsubstances. He was otherwise well and healthy. He\nis a non-smoker.  \n\n\n\nExamination revealed a well defined, 5 cm by\n3.5 cm, hypertrophic plaque on the anterior aspect\nof the right shin. There was an ulcerated exophytic\ngrowth measuring 1.5 cm by 1.5 cm seen at the\ncentre of the plaque (Figure 1a & Ib). The mucous\nmembranes, hair and nails were normal. Systemic\nexaminations were unremarkable.\n\n\n\nWedge biopsy specimens were obtained from the\nhypertrophic plaque and the exophytic growth.\nHistopathology examination of the plaque lesion\nshowed typical features of hypertrophic LP\n(Figure 2) while the section from the exophytic\ngrowth showed features suggestive of SCC\n(Figure 3). The neoplastic cells were stained\npositive for CK 5 and CK 6 but were negative for\nS100, HMB45 and CD34. MRI of the right lower\nlimb revealed no extension into underlying muscle\nand bone. Other blood tests were normal.\n\n\n\nThe tumour was completely excised. Soft tissue\nreconstruction with flap and skin graft and\ntransposition of the right inguinal dissection were\ndone. Biopsy confirmed no inguinal lymph node\ninvolvement.\n\n\n\nFollow up to 12 months noted, the patient to be well\nwith no local recurrence or distant metastases.\nOther plaques on the left leg and ankle were treated\nwith cryotherapy and potent topical steroid.\n\n\n\nDiscussion\nLichen planus (LP) is a chronic T cell mediated\nmucocutaneous disease. The actual cause of this\ncondition remains unknown. It is characterized by\npruritic, violaceous, polygonal, flat topped papules/\nplaques which are distributed symmetrically over\nthe extremities1.\n\n\n\nKeywords skin cancer, malignant transformation, Malaysia\n\n\n\n\n\n\n\n\n27MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 2\nMarked hyperkeratosis, wedge-shaped hypergranulosis and acanthosis of the epidermis\n(hematoxylin and eosin stain; original magnification x4).\n\n\n\nFigure 1a & 1b (close up view)\nUlcerated growth seen at the centre of the plaque. A few atrophic depigmented lesions were noted\nover both legs (previous site of hypertrophic LP).\n\n\n\n\n\n\n\n\n28 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 3\nFocal ulcerated epithelium with a diffuse neoplastic cell infiltration within the underlying stroma.\nThe neoplastic cells are polygonal to spindle shaped cells with pleomorphic vesicular nuclei,\nprominent nucleoli and variable amount eosinophilic cytoplasm. Mitoses are noted (hematoxylin\nand eosin stain; original magnification x4).\n\n\n\nLP is a common benign inflammatory dermatosis.\nIt occasionally clears within a few weeks. In 50% of\nthe cases, the lesions subside within 9 months. Up\nto 70% of patients may experience spontaneous\nremission within 15 months. Only 12-20% of cases\nwill develop recurrent disease later in life3. Since\nthe first report of malignant transformation of LP in\n1903, its malignant transformation potential\nremained a concern.\n\n\n\nMalignant transformation rate of LP varies widely.\nIt was reported in the literature to be between 0.4\nand 6.5% but in most  studies it do not exceed 1%.\nMeta-analysis of epidemiological studies by Sousa\net al revealed a malignant transformation rate of\n1.63% over 5 years (0.27% per year)4. \n\n\n\nThe incidence of malignancy in LP actually\ndepends on the anatomical site involved and the\ntype of lichen planus. Malignant transformation can\noccur in mucosal lichen planus especially oral LP.\nThe frequency of malignant transformation from\noral LP ranges from 0% to 5.3% with the highest\nrate of 40-60%,  noted in those with erythematous\nand erosive lesions5. World Health Organisation\n(WHO) had classified oral lichen planus as a pre-\nmalignant condition6.\n\n\n\nA long term retrospective epidemiological study of\nmalignancy in patients with LP has demonstrated a\nsignificant association between oral LP and SCC\nwith a relative risk of 5.9%, especially among men\nand smoker. No significant risk of transformation\nof cutaneous LP into SCC had been reported5.\nHowever, the major limitation of this study is both\nchronic and acute LP was included in the review.\nThe result may vary if only the chronic LP form\nwere analyzed. \n\n\n\nMalignant transformation in cutaneous LP is very\nrare2. To date, less than 100 cases of cancers were\nreported. Cutaneous LP related SCC has an\nincidence of 0.4%. Nearly all them  arose from\nhypertrophic LP of the lower leg7. More recent\nreports suggest that the association may be greater\nwith ulcerative LP.\n\n\n\nHypertrophic LP typically present as red brown or\nviolaceous, firm, thick, verrucous plaques on the\nshins and around the ankle. It often persisted for\nmany years and healed with area of pigmentation\nand scarring with degree of atrophy. The chronicity\nof LP appears to be a risk factor for the\ndevelopment of SCC.\n\n\n\n\n\n\n\n\n29MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAll reported LP related malignant cases have long\nlatency periods between the diagnosis of LP and the\ndevelopment of neoplastic transformation (range\nbetween 4 years and 35 years; mean of 12 years)7.\nOur patient also showed long latency period of 27\nyears before the development of malignant\ntransformation.\n\n\n\nThere is a controversy as to whether the cancer\ncomplicating LP has been part of the natural history\nor the result of exposure to external factors like\ntobacco, radiation, arsenic or chronic irritation.\nCancers do occur from the site of chronic\ninflammatory processes such as chronic venous\nstasis ulcer, discoid lupus erythematosus, lupus\nvulgaris or burn scars. \n\n\n\nThe actual mechanism of neoplastic transformation\nis not known. Some authors postulated the  possible\nrole of prolonged chronic inflammation in the\ndevelopment of cancer. Chronic inflammatory\nprocesses will lead to overdrive of the cytokines and\ngrowth factors, which will constantly stimulate\nepithelial cell proliferation and turn into neoplastic\ncondition8-9.\n\n\n\nVery few data are available with regards to LP\nrelated SCC behaviour, although some authors\nsuggest a bad prognosis10. We also observed an\naggressive form of SCC in our patient with rapid\nprogression, ulceration and of a poorly\ndifferentiated type of SCC.\n\n\n\nConclusion\nAlthough cutaneous LP associated SCC is very\nrare, the awareness of the possibility of malignancy\narising on cutaneous LP must be kept in mind.\nWhen treatment fails or new lesion appears, skin\nbiopsy must be done for early diagnosis of\nmalignant transformation. Careful and vigilant\nfollow up for those with long standing hypertrophic\nlichen planus is necessary to allow early detection\nof SCC.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director\nGeneral of Health, Malaysia for permission to\npublish this paper.\n\n\n\nReferences\n\n\n\n1. Sugerman PB, Savage NM, Walsh LJ et al. The\npathogenesis of oral lichen planus. Crit Rev Oral Biol\nMed 2002; 13: 350-365.\n\n\n\n2. Castano E, Lopez-Rios F, Alvarez-Fernandez JG,\nRodriguez-Peralto JL, Iglesias L. Verrucous carcinoma\nin association with hypertrophic lichen planus. Clin\nExp Dermatol 1997; 22: 23-25.\n\n\n\n3. Irvine C, Irvine F, Champion RH. Long term follow up\nof lichen planus. Acta Derm Venereal 1991; 71: 242-\n244.\n\n\n\n4. De Sousa FA, Paradella TC, Carvalho YR, Rosa LE.\nMalignant potential of oral lichen planus: a meta-\nanalysis. Rev Odonto Ci\u00eanc 2009; 24: 194-7.\n\n\n\n5. Sigurgeirsson B, Lindelof B. Lichen planus and\nmalignancy. An epidemiologic study of 2071 patients\nand a review of the literature. Arch Dermatol 1991;\n127: 1684-1688.\n\n\n\n6. World Health Organization Tobacco or health: a global\noverview. In tobacco or health: a global status report.\nWHO, Geneve 1997: 5-65. \n\n\n\n7. Singh SK, Saikia UN, Ajith C, Kumar B. Squamous\ncell carcinoma arising from hypertrophic lichen planus.\nJ Eur Acad Dermatol Venereol 2006; 20: 745-6.\n\n\n\n8. Schottenfeld D, Beebe-Dimmer J. Chronic\ninflammation: a common and important factor in the\npathogenesis of neoplasia. CA Cancer J Clin 2006; 56:\n69-83. \n\n\n\n9. Krasowska D, Bogaczewicz J, Chodorowska G.\nDevelopment of squamous cell carcinoma within\nlesions of cutaneous lichen planus. J Eur Acad\nDermatol Venereol 2007; 17: 447-448.\n\n\n\n10. Ardabili M, Gambichler T, Rotterdam S et al.\nMetastatic cutaneous squamous cell carcinoma arising\nfrom a previous area of chronic hypertrophic lichen\nplanus. Dermatol Online J 2003; 9: 10.\n\n\n\n\n\n\n\n\n30 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDERMATO-ONCOLOGY - Short Case\n\n\n\nCHRONIC ARSENIC POISONING ASSOCIATED WITH\nMULTIPLE SKIN MALIGNANCIES \nLow Zhi Mei1, Tey Kwee Eng2, MRCP, Choon Siew Eng2 FRCP\n\n\n\nCorrespondence\nChoon Siew Eng, FRCP\n2 Department Of Dermatology\nHospital Sultanah Aminah\nJohor Bahru, 80100 Johor, Malaysia\nE-mail: choonse@yahoo.co.uk\n\n\n\n1 Medical Student (Year 4), Monash University\n\n\n\nIntroduction\nChronic arsenic poisoning is rarely seen nowadays.\nIt may develop as a result of long term use of\nChinese herbal medications, drinking high-arsenic\nartesian well water or occupational exposure. The\nmost common manifestations of chronic arsenic\npoisoning are hyperpigmentation or classical\n\"raindrop\" melanosis, punctate hyperkeratosis and\nskin tumours.  \n\n\n\nBowen\u2019s disease is the most common form of skin\ntumour induced by arsenic followed by squamous\ncell carcinoma and basal cell carcinoma. Chronic\narsenic poisoning is also associated with internal\nmalignancy such as carcinoma of lung, stomach,\ncolon, kidney, bladder and hematopoietic system. \n\n\n\nRecognizing signs of chronic arsenic poisoning\nallows early diagnosis and treatment of associated\ncutaneous and internal malignancy. We describe a\nman who developed multiple malignancies namely\nbasal cell carcinoma, squamous cell carcinoma and\nBowen\u2019s disease following exposure to arsenic-\ncontaining traditional Chinese medication given for\nhis childhood asthma.\n\n\n\nCase report\nA 52-year old single Chinese man, first presented to\nthe Department of Dermatology, Sultanah Aminah\nHospital, Malaysia in 2003 with a three-year history\nof multiple brownish plaques on the trunk. Patient\nhad severe childhood asthma which was treated\n\n\n\nwith Sin Lak Pills, a traditional Chinese anti-\nasthmatic preparation, for more than 5 years. He\nhad no history of drinking well water or living close\nto tin mines. There is no family history of\nmalignancies. He was working in the family\ngoldsmith business and stopped since 2003.  \n\n\n\nClinical examination revealed a cutaneous horn on\nhis chest and multiple mildly erythematous plaques\nwith brownish adherent crusts of varying sizes\nranging from 1x1 cm to 5x5 cm on his trunk and\nthighs (Figure 1). He also had multiple punctate\nhyperkeratoses on both the palms and soles\n(Figure 2). Raindrop-like hypomelanosis were\nnoted on his thighs (Figure 3) and upper the back of\nthe trunk.  Biopsies from the plaque on the trunk,\nthigh and cutaneous horn confirmed diagnoses of\nBowen\u2019s disease, basal cell carcinoma (BCC)\n(Figure 4) and squamous cell carcinoma (SCC).\n\n\n\nThe Bowen disease on the trunk, BCC on his left\nthigh and cutaneous horn with underlying SCC\nwere totally excised while the smaller plaques\nassumed to be Bowen disease were treated with\ncryotherapy and acitretin 30mg daily. In spite of the\nacitretin prophylaxis, he continued to develop more\nSCCs. In May 2005, total excision of a fungating\nmass on his right palm by orthopedic team was\nconfirmed to be SCC and in 2006, another SCC on\nthe posterior aspect of the left thigh was removed.\nAt the same time, an enlarged axillary lymph node\nwith metastasis was removed, followed by\nradiotherapy to the affected area.\n\n\n\nIn 2008, after one month history of cough, contrast-\nenhanced CT scan (CECT) of thorax was done. It\nshowed sub-pleural thickening in the left lateral\nchest, associated with fibrosis, likely secondary\nto radiotherapy. Bilateral multiple areas of\nconsolidation were also noted. He sought treatment\nin Singapore and was diagnosed and treated for\npulmonary\n\n\n\nKeywords basal cell carcinoma, squamous cell carcinoma, lung metastasis\n\n\n\n\n\n\n\n\n31MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 1\nLesion on patient\u2019s back.\n\n\n\nFigure 2\nPunctate hyperkeratosis on patient\u2019s soles.\n\n\n\n\n\n\n\n\n32 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 3\nRaindrop-like hypomelanosis on patient\u2019s thighs.\n\n\n\nFigure 4\nBasal cell carcinoma.\n\n\n\n\n\n\n\n\n33MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\npulmonary tuberculosis. He stopped taking acitretin\nfor more than a year but was well till December,\n2011 when he started losing weight again.\n\n\n\nCECT of the thorax showed bilateral upper lobe\nfibrosis, bronchiectasis with scattered small\nnodules and right lung base interlobular septal\nthickening. Tuberculosis workup was negative but\npatient declined bronchoscopy to rule out primary\nor metastatic lung carcinoma and succumbed to his\nillness in May 2012. \n\n\n\nDiscussion\nArsenic is classified as a Class I human carcinogen\nby the International Agency for Research on\nCancer, because of  its association with skin and\nvisceral cancers1. Chronic arsenicism is defined by\nWHO as a chronic health condition arising from\nprolonged ingestion of arsenic above a safe dose for\nat least 6 months, usually manifested by\ncharacteristic skin lesions, with or without the\ninvolvement of internal organs1. Visceral\nmalignancies usually manifest after cutaneous\nonset2.\n\n\n\nArsenic can be found in naturally contaminated\ndrinking water and landfills, traditional Chinese or\nherbal medicines and in occupational settings\n(agricultural chemicals, mining, carpentry and\nmanufacture of gallium arsenide computer\nmicrochips)3,4. Taiwan reported effects of arsenic on\nthe skin in an area with high arsenic concentrations\nin well water5. Ayurvedic and Chinese medicines\nare also known to contain high level of arsenic. Skin\nlesions occurring after the treatment of asthma with\ninorganic arsenic was reported in the United States\nin 19525. \n\n\n\nChronic arsenicism from Sin Lak Pills (Traditional\nChinese medicines) was reported in Singapore6-8.\nThese pills were used to treat asthma and its usage\nhad been linked to various systemic and skin\ndiseases. It was banned in 1972, due to the\nexcessive content of inorganic arsenic sulfide. The\n\n\n\nNational Skin Centre of Singapore reviewed\npatients with cutaneous lesions related to chronic\narsenic intake. Out of 17 patients, 14 took Chinese\nherbal remedies contaminated with inorganic\narsenic8.\n\n\n\nOur patient had severe childhood asthma and was\ntreated with Sin Lak Pills for more than 5 years in\nSingapore. He had no history of drinking well water\nand no history of living close to tin mines. The\nsource of arsenic was likely from the Sin Lak Pills. \n\n\n\nChronic exposure to arsenic can lead to the\ndevelopment of internal malignancies such as lung\nand urinary tract carcinomas, and cutaneous\nmalignancies such as Bowen\u2019s disease, arsenical\nkeratosis, BCC and SCC9-11. Skin manifestations of\nchronic arsenicism include spotted melanosis\ninterspersed with hypopigmentation (raindrop\nappearance), Bowen\u2019s disease, BCC and SCC and\nhyperkeratotic corns or warts on the palms and\nsoles. Lung is a common major site for arsenic-\nrelated cancers. \n\n\n\nBased on WHO 2005 field guide for the detection\nof arsenic poisoning, a urine sample with\nconcentration of arsenic higher than 50\u00b5g/L\nconfirms recent exposure. Since arsenic is rapidly\ncleared from the blood, it is only useful to assess\nrecent high concentration exposures1. Since this\npatient was exposed to arsenic in Sin Lak Pills\nmany years ago, performing the urine test to detect\narsenic would be of no significance.\n\n\n\nHyperkeratosis, hyperpigmentation, and\nhypopigmentation may disappear with time, and\nthis may conceal the possible exposure to arsenic. A\ndiagnosis of arsenic poisoning must be considered\nwhen multiple keratoses or multiple lesions of\nBCC, Bowen\u2019s disease and SCC are found in sun-\nprotected part of the body. Arsenicism has become\nrare, but should still be kept in mind due to\npersistent environmental, occupational exposure\nand the reintroduction of arsenic trioxide as a rescue\ntreatment for promyelocytic leukaemia12.\n\n\n\n\n\n\n\n\n34 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nReferences\n\n\n\n1. Ruiz de Luzuriaga AM, Ahsan H, Shea CR. Arsenical\nKeratoses in Bangladesh-Update and Prevention\nStrategies. Dermatol Clin 2011; 29: 45-51.\n\n\n\n2. Watson K, Creamer D. Arsenic-induced keratoses and\nBowen\u2019s disease. Clin Exp Dermatol 2004; 29: 46-48. \n\n\n\n3. Walvekar RR, Kane SV, Nadkarni MS, et al. Chronic\narsenic poisoning: a global health issue-a report of\nmultiple primary cancers. J Cut Pathol 2007; 34: 203-\n206. \n\n\n\n4. Ernst E. Adverse effects of herbal drugs in\ndermatology. Br J Dermatol 2000; 143: 923-929.\n\n\n\n5. Yu JTHT, Lam WY. Chronic arsenic poisoning: a\nwoman with multiple Bowen\u2019s disease and\npalmoplantar keratosis. Hong Kong J. Dermatol.\nVenereol. 2005; 13: 93-96.\n\n\n\n6. Vitharana K, Pakdeethai J, Tay YK, et al. Chronic\nArsenicism-a forgetten entity? Malaysian J Dermatol\n2007; 19: 123-124.\n\n\n\n7. Tay CH, Seah CS. Arsenic poisoning from anti-\nasthmatic herbal preparations. Med J Austral.\n1975;2:424-428.\n\n\n\n8. Wong SS, Tan KC, Goh CL. Cutaneous manifestations\nof chronic arsenicism: Review of seventeen cases. J\nAm Acad  Dermatol 1998; 38: 179-185. \n\n\n\n9. Col M, Col C, Soran A, et al. Arsenic Related Bowen\u2019s\nDisease, Palmar Keratosis, and Skin Cancer. Environ\nHealth Perspect 1999; 107 (8): 687-689.\n\n\n\n10. Sommers SC, McManus RG. Multiple Arsenical\nCancers of Skin and Internal Organs.  J Am Ca  Soc\n1953; 6 (2): 347-359.\n\n\n\n11. Tsuruta D, Hamada T, Mochida K, et al. Merker cell\ncarcinoma, Bowen\u2019s disease and chronic occupational\narsenic poisoning. Br J  Dermatology 1998; 139: 291-\n294.\n\n\n\n12. Kwong YL. Arsenic trioxide in the treatment of\nhaematological malignancies. Expert Opin Drug Saf\n2004;3:589-597.\n\n\n\n\n\n\n\n\n35MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDERMATOLOGY THERAPEUTIC - Short Case\n\n\n\nSUCCESSFUL MANAGEMENT OF CUTANEOUS POLYARTERITIS\nNODOSA WITH INFECTED ULCERS WITH CLOFAZIMINE AND\nEPIDURAL ANALGESIA \nMichelle Voo Sook Yee1, MRCP, Ng Kim Swan2, MMed (Anaes), Mary Suma Cardosa2, FFPMANZCA,\nSalmi Abdullah3, MMed (Path), Rohna Ridzwan1, MRCP\n\n\n\nCorrespondence\nMichelle Voo Sook Yee, MRCP\n1 Department Of Dermatology,\n\n\n\nHospital Selayang, Selangor, Malaysia\nE-mail: miyee03@yahoo.com\n\n\n\n2 Department of Anaesthesia\nHospital Selayang, Selangor, Malaysia\n\n\n\n3 Department of Pathology\nHospital Selayang, Selangor, Malaysia\n\n\n\nIntroduction\nCutaneous polyarteritis nodosa is an uncommon\nform of cutaneous vasculitis affecting small and\nmedium size arteries. We describe a case of infected\ncutaneous polyarteritis nodosa in a 30-year-old man\nwho responded to antibiotics, steroids and\nclofazimine together with aggressive dressing\nwhich was possible due to effective pain relief.\n\n\n\nCase report\nA 30-year-old Chinese man presented to the\nDermatology clinic with painful ulcers on the ankle\nand dorsum of both feet for one month. There was\nno history of photosensitivity, joint or muscle pain\nor oral ulcers.\n\n\n\nPhysical examination revealed multiple stellate\nshaped ulcers on the dorsum of both feet, which\nwere covered with slough. There was also lace-like\npurplish reticulated rash at both calves suggestive\nof livedo reticularis. There were no subcutaneous\nnodules, oral ulcers nor malar rash. Cardiovascular,\nrespiratory and abdominal examinations were\nunremarkable. There was no sign of peripheral\nneuropathy.    \n\n\n\nA working diagnosis of cutaneous polyarteritis\nnodosa (cPAN) was made with differential\ndiagnosis of livedoid vasculopathy. Skin biopsy\nshowed leucocytoclastic vasculitis, fibrinoid\nnecrosis of the medium size vessel walls and\nluminal thrombi at the capillaries (Figure 1a & b).\nThere was C3 staining along the basal layer and\nblood vessel, with IgM positive at the vessel walls.\n\n\n\nBlood investigations revealed a total white cell\ncount of 13 x103/L , hemoglobin 16g/dL, platelet\ncount  277 x 103/L. Inflammatory markers were\nwithin normal range: Erythrocyte sedimentation\nrate (ESR) 8mm/hr, C-reactive protein 0.4 mg/L.\nRenal profile, liver function and complement levels\nwere normal.  Hepatitis B surface antigen, Anti\nHepatitic C antibody, HIV, antinuclear antibody\n(ANA), Anticardiolipin antibody, anti neutrophil\ncytoplasmic antibody (c-ANCA) and cryoglobulin\nwere negative. \n\n\n\nHe was initially treated as outpatient with oral\nprednisolone 1mg/kg/day, oral cloxacillin and\ncelecoxib. However, he returned a week later and\nwas admitted to the ward for a week because of\nunbearable ulcer pain, which was treated with oral\nTramadol 50mg QID. On discharge he was given\nazathioprine 1mg/kg/day which was subsequently\ntitrated to 2mg/kg/day. Pus swab for culture taken\nduring admission grew no organism.\n\n\n\nKeywords vasculitis, regional anaesthesia, anti-inflammatory drug\n\n\n\n\n\n\n\n\n36 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 1a\nEpidermal necrosis and subcutaneous infiltrates 10x H&E.\n\n\n\nFigure 1b\nFibrinoid necrosis in the vascular wall 400x H&E.\n\n\n\n\n\n\n\n\n37MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nHe was readmitted to hospital one month after\ndischarge because of emergence of new ulcers\nwhich were infected (Figure 2a & b). As the pus\nfrom the ulcers grew Pseudomonas aeruginosa, he\nwas given a 10-day course of intravenous\nceftazidine. Ulcers were dressed daily with alginate\ndressing preceded by acetic acid 3% soak and\npotassium permanganate 5% 1:10000. His pain\nscore reached 8 (on a scale of 0 to 10) especially\n\n\n\nduring dressing, despite being given oral\ndihydrocodeine 60mg BD and morphine 15mg\nsubcutaneously prior to dressing. He was also\nstarted on gabapentin, which was gradually titrated\nup to 300 mg TDS as he had features of neuropathic\npain (burning pain, allodynia and dysaesthesias on\nboth feet). The pain during dressing was so severe\nthat it was not possible to do effective dressing and\nthe ulcers did not show any sign of healing despite\ntwo-week inpatient treatment.\n\n\n\nFigure 2a & 2b\nInfected ulcers following treatment with oral prednisolone 60mg daily and azathioprine 150mg\ndaily for 6 weeks.\n\n\n\n\n\n\n\n\n38 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe Pain Management Team, who had been\nconsulted earlier on the management of his pain,\ndecided to start epidural analgesia using a mixture\nof 0.1% ropivacaine and fentanyl 1mcg/ml at\n5mls/hour using an ambulatory pump. This was\nsubsequently changed to patient controlled epidural\nanalgesia (PCEA) using a mixture of 0.2%\nropivacaine and fentanyl 2 mcg/ml, running as a\nbackground infusion of 3 ml/hour with a 5 ml bolus\non demand, which was mainly used just before and\nduring dressing. Only after starting the epidural\nanalgesia was analgesia adequate to allow\naggressive dressing of the ulcers, which then began\nto heal.\n\n\n\nAzathioprine was stopped as there was no\nimprovement after two-months therapy, and also\nbecause of the active bacterial infection. As he was\nnot suitable for other immunosuppressive agents\ndue to ongoing infection, oral clofazimine 100mg\nonce daily was started as a steroid-sparing agent.\n\n\n\nWith the combination of clofazimine and\naggressive dressing of the ulcers the patient\nimproved rapidly. The ulcers appeared to be clean\nwith healthy granulation tissue within two weeks of\nnew treatment (Figure 3). Epidural analgesia was\nceased after 16 days and analgesia was provided by\naqueous morphine 20 mg before dressing.\n\n\n\nFigure 3\nDay 13 of  clofazimine and epidural analgesia.\n\n\n\nFigure 4\nAfter 6 weeks of clofazimine and prednisolone 25mg\ndaily.\n\n\n\nFigure 5\nAfter 2 months of clofazimine and while on\nprednisolone 5mg daily.\n\n\n\n\n\n\n\n\n39MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe patient was discharged from the ward one\nmonth later with clofazimine 100mg once daily,\ndihydrocodeine 60mg twice daily, gabapentin\n600mg three times a day, aqueous morphine 20mg\nas needed and prednisolone 1mg/kg/day. His\nprednisolone was tapered off by 5mg every two\nweeks. The ulcers continued to reduce in size and\nwere fully healed 6 weeks after discharge (Figure\n4).\n\n\n\nCutaneous polyarteritis nodosa (PAN) is an\nuncommon form of cutaneous vasculitis. It runs a\nchronic relapsing and remitting benign course.\nMost common presentations are tender\nsubcutaneous nodules, livedo reticularis, necrosis\nand ulceration. Most of this features occurs on the\nlower limbs1,2. In a retrospective study of 79 cases,\n80% had painful nodules, 56% had livedo\nreticularis and 49% had ulcers1. \n\n\n\nExtracutaneous manisfestations include myalgia\n(31.2%), arthralgia (69%), neuropathy (22%) and\nfever (25%)1. Our patient presented with livedo\nreticularis, painful ulceration and necrosis at the\nankle and dorsum of both feet as well as\nneuropathic pain; however he denied myalgia or\narthralgia. Common laboratory abnormalities\ninclude mild anemia, moderate leucocytosis and\nelevated ESR2. Our patient had mild leucocytosis\n(WBC 13 x103 u/L), but hemoglobin and ESR were\nnormal. \n\n\n\nDiagnosis of cPAN requires clinicopathological\ncorrection. Clinical presentations such as livedo\nreticularis, tender subcutaneous nodules and or\ncutaneous ulceration and necrosis should prompt\nsuspicion. Skin biopsy shows vasculitis involving\nsmall and or medium sized arteries. The diagnosis\nof cPAN can only be made after the exclusion\nof systemic PAN. In a series of skin biopsies\ndone on 9 cases of cutaneous PAN, direct\nimmnunofluorescence showed C3 and IgM in\n77.8% and 33.3% of the cases respectively3.\nAnother case series reported IgM deposition within\nthe vessel wall in 60%, C3 deposition in 40% and\nboth C3 and IgM deposit in 20%4. Our patient\u2019s\nhistopathology stained positive for both IgM and\nC3.\n\n\n\nMild cPAN responds to topical corticosteroids, non\nsteroidal anti-inflammatory drugs and colchicine2.\nSevere cases require systemic corticosteroids and\n\n\n\nsteroid sparing agents. Drugs reported in the\nliterature that have been used as steroid sparing\nagents are colchicine, hydroxychloroquine,\ndapsone, methrotrexate, sulphapyridine,\npentoxyphyline and intravenous immunoglobulin2.\nHowever there are no prospective randomized\ncontrolled trials evaluating the efficacy of these\nagents.\n\n\n\nOur patient\u2019s ulcers were refractory to 3 months of\nprednisolone 1mg/kg/day and 2 months of\nazathioprine 2mg/kg/day.  This may have been\ncontributed to by the ongoing infection.\nClofazimine as a steroid sparing agent was started\nas he was deemed not suitable for other\nimmunosuppressant because of the ongoing\ninfection. \n\n\n\nClofazimine is a lipophilic rimino-phenazine dye\nwith antimicrobial, anti-inflammatory and\nimmunosuppressive activity. In 1974, a randomized,\ndouble blind controlled trial5 comparing\nclofazimine (100mg per day) with chloroquine\n(250mg per day) in 33 patients with systemic lupus\nerythromatosus with active skin disease showed a\ngood response observed between the clofazimine\ngroup (82.4%) compared with the chloroquine\ngroup (75%). More studies need to be done to\nevaluate the efficacy of clofazimine as a possible\nsteroid sparing agent in cutaneous vasculitic ulcer.\n\n\n\nIncident pain during wound dressing is challenging\nto manage especially when it is severe. Good pain\ncontrol allows proper wound dressing and promotes\nwound healing. A careful history will reveal the\ncharacteristic of pain whether it is nociceptive or\nneuropathic. Successful pain control relies on the\nidentifying the underlying pain mechanism and\ncontinuous pain assessment7. However, pain\nmanagement in chronic leg ulcers maybe\nsuboptimal. In a cross-sectional study of 520\npatients with chronic leg ulcers8, although 26.5% of\nthe subjects reported pain on change of dressing,\nonly 8.6% were given analgesia prior to dressing.\nMild to moderate pain can be easily managed by\noral analgesics. Parenteral strong opioids like\nmorphine may also be necessary to relieve the\nsevere pain during dressing. In this patient however,\nthe wounds were deep and dirty and some\ndesloughing had to be done at each dressing,\nresulting in intolerable pain.\n\n\n\n\n\n\n\n\n40 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nEpidural infusion of local anaesthetics and opioids,\nwhich is commonly used for postoperative\nanalgesia, was started for this patient because of its\nability to provide the necessary somatic block to\nallow dressing to take place without pain. The\npractical problem of requiring additional bolus\ndoses before and during dressing was overcome by\nproviding the patient with the possibility of self-\nadministered bolus doses through a patient-\ncontrolled device. This provided excellent analgesia\nfor dressing and was also useful for post-dressing\npain, thus allowing patient to ambulate at ease.\n\n\n\nIn this patient, good pain control enabled the slough\nand pus to be cleared during wound dressing, thus\nallowing the wounds to heal. An additional benefit\nof the epidural analgesia with continuous infusion\nof low concentration of the local anesthetics was\nsympathetic block of the lower limbs, resulting in\nvasodilatation and improved circulation, which\nmight also have contributed to better wound\nhealing9. \n\n\n\nConclusion\nThis patient who had cPAN with severely infected\nulcers of both feet was successfully managed by\naddressing all aspects of disease management. This\nincludes optimal pain control using epidural\nanalgesia which enabled aggressive wound dressing\nand ulcer healing. We advocate using a\nmultidisciplinary approach when managing\nchallenging cases like this. The use of clofazimine\nas steroid sparing agent in cPAN needs further\nstudy.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director\nGeneral of Health, Malaysia for permission to\npublish this paper.\n\n\n\nReferences\n\n\n\n1. Daoud MS, Hutton KP, Gibson LE. Cutaneous\nperiarteritis nodosa: a clinicopathological study of 79\ncases. Br J Dermatolol 1997; 136: 706-13.\n\n\n\n2. Chen KR. Cutaneous polyarteritis nodosa: a clinical\nand histopathological study of 20 cases. J Dermatol\n1989; 16 : 429-42\n\n\n\n3. Kawakami T, Yamazaki M, Mizoguchi M et al. High\ntiter of anti-phophatidylserine-prothrombin complex\nantibodies in patients with cutaneous polyarteritis\nnodosa. Arthritis Rheum 2007; 57: 1507-13.\n\n\n\n4. Diaz-Perez JL, Schroeter AL, Winkelmann RK.\nCutaneous periarteritis nodosa: immunofluorescence\nstudies. Arch Dermatol 1980; 116: 56-58.\n\n\n\n5. Mackey JP, Barnes J. Clofazimine in the treatment of\ndiscoid lupus erythematosus. Br J Dermatol 1974; 91-\n93-6.\n\n\n\n6. Bezerra EL, Vilar MJ, da Trindade Neto PB, et al.\nDouble-blind, randomized, controlled trial of\nclofazimine compared with chloroquine in patients\nwith systemic lupus erythematosus. Arthrtis Rheum\n2005; 52: 3073-8.\n\n\n\n7. Herberger K, Rustenbach SJ, Grams L et al. Quality-of-\ncare for leg ulcers in the metropolitan area of Hamburg\n- a community-based study. J Eur Acad Dermatol\nVenereol. 2012 Apr;26(4):495-12.\n\n\n\n8. Briggs M, Bennett MI, Closs SJ et al. Painful leg\nulceration. A prospective, longitudinal cohort study.\nWound Rep Reg 2007; 15: 186-191\n\n\n\n9. Visser L. Epidural anaesthesia. Update in Anaesthesia\n2001; 13(11): 1-4.\n\n\n\n1. In reference to article on Pseudocyst of Ear in MJD 2012 Dec; 29\nIt should read as: Pseudocyst of Ear\n\n\n\nSumit Kar, Atul Mohankar, Ajay Krishnan, Nitin Gangane\n\n\n\n2. In reference to back cover of MJD 2012 Dec; 29\nIt should read as: 27 Case Report\n\n\n\nPseudocyst of Ear\nSumit Kar, Atul Mohankar, Ajay Krishnan, Nitin Gangane\n\n\n\nADDENDUM\n\n\n\n\n\n\n\n\n41MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1ST FELLOWSHIP ASIAN ACADEMY OF DERMATOLOGY\nAND VENEROLOGY (DERMATOPATHOLOGY) EXAMINATION\n\n\n\nFAADV (Dermapathology) Examination\n\n\n\nDate: 13th December, 2012\nVenue: Medical Academies of Malaysia, Kuala Lumpur\nOrganizer: Malaysian Dermatological Society (PDM) & Asian Academy of\n\n\n\nDermatology and Venerology (AADV), in collaboration with St John\u2019s \nInstitute of Dermatology (London)\n\n\n\nChairman of the Board of examiners for the FAADV examination: Dr Steven Chow\n\n\n\nFaculty members for this examination:\nProf Alistair Robson (UK)\nDr Catherine Stefanato (UK)\nProf Nopadon Nopakkun (Thailand)\nProf Tetsu Kimura(Japan)\nProf Yu-Hung Wu (Taiwan)\nDr Dawn Ambrose (Malaysia)\nDr Noor Zalmy Azizan (Malaysia)\n\n\n\nCandidates:\nDr Sondang Marisi (Indonesia)\nDr Diah Mira (Indonesia)\nDr Norashikin Shamsudin (Malaysia)\nDr Khalid Al-Aboud (Middle East)\n\n\n\nDAY 1\nWritten - 60 MCQs (60 minutes)\n20 Short answer questions (90minutes)\nSlide reading session - 60 slides (120minutes)\n\n\n\nDAY 2\nViva session - 20 minutes each\n\n\n\nResults of 1st FAADV (Dermapathology) examination:\n1. Dr Norashikin Shamsudin (Distinction)\n2. Dr Khalid Al-Aboud (Distinction)\n\n\n\nThe next FAADV (Dermapathology) examination will be held during the\nRegional Conference of Dermatology in 2014.\n\n\n\nCorrespondence\nNoor Zalmy Azizan\nE-mail: noorzalmy@yahoo.com\n\n\n\n\n\n\n\n\n42 MJD 2013 July Vol 30\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nCONTINOUS MEDICAL EDUCATION\n\n\n\n38th Annual General Meeting\n&\n\n\n\nMalaysia Dermatology\nCongress\n\n\n\nOrganizer\n\n\n\nMalaysian Dermatological Society (PDM)\n\n\n\nTheme\n\n\n\nCurrent advances in Dermatology\n\n\n\nVenue\n\n\n\nKuantan Zenith Hotel, Pahang\n\n\n\nDate\n\n\n\n12th - 15th September 2013\n\n\n\nProgramme website\n\n\n\nwww.dermatology.org.my\n\n\n\nDeadline for abstract submission\n\n\n\n1st August 2013\n\n\n\n\n\n\n\n\n\n\n\n\nGENERAL DERMATOLOGY\n\n\n\nOriginal Article\n1. Patch testing with preservative \n\n\n\nsensitzers. A 1-year retrospective \nstudy from Selayang Hospital\nMichelle Voo Sook Yee, Rohna Ridzwan\n\n\n\nDERMATOLOGY EDUCATION\n\n\n\nOriginal Article\n7. Developing a dermatology \n\n\n\ncurriculum for Malaysian medical \nundergraduates: initial results of \nthe Delphi method\nAdawiyah Jamil, Mazlin Mohd Baseri,\nLeelavathi Muthupalaniappen et al\n\n\n\nDERMATO-ONCOLOGY\n\n\n\nCase Report\n21 Marjolin\u2019s ulcer secondary to \n\n\n\nchronic burn scar in 2 patients \nAzura Mohd Affandi, Tan Wooi Chiang, \nDawn Ambrose\n\n\n\nCase Report\n26 Squamous cell carcinoma arising \n\n\n\nfrom hypertrophic lichen planus:\nA case report and review of \nliterature \nTan Wooi Chiang, Azura Mohd Affandi, \nDawn Ambrose\n\n\n\nCase Report\n30 Chronic arsenic poisoning \n\n\n\nassociated with multiple skin \nmalignancies\nLow Zhi Mei, Tey Kwee Eng,\nChoon Siew Eng\n\n\n\nDERMATOLOGY THERAPEUTIC\n\n\n\nCase Report\n35 Successful management of \n\n\n\nCutaneous Polyarteritis Nordosa  \nwith infected ulcers with \nClofazimine and Epidural \nAnalgesia\nMichelle Voo Sook Yee, Ng Kim Swan, \nMary Suma Cardosa at al\n\n\n\n40 Addendum to MJD 2012 Dec; 29\n\n\n\n41 Fellowship Asian Academy of \nDermatology and Venerology \n(Dermatopathology) Examination \nNoor Zalmy Azizan\n\n\n\nCONTINUOUS MEDICAL EDUCATION\n\n\n\n42 38th Annual General Meeting and \nMalaysian Dermatology Congress \n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n"
"\n\n25MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nKeywords Pemphigoid, mucous membrane\n\n\n\nIntroduction\nMucous membrane pemphigoid is a group of\nputative autoimmune, chronic inflammatory,\nsubepithelial blistering diseases predominantly\naffecting mucous membranes, characterised by\nlinear deposition of IgG, IgA, or C3 along the\nepithelial basement membrane1. This variant of\npemphigoid is rare and encompasses a\nheterogeneous group manifesting a varying\nconstellation of oral, ocular, skin, genital,\nnasopharyngeal, oesophageal and laryngeal lesions.\nIn severe cases, it may lead to blindness due to\nocular involvement and may even be life\nthreatening due to airway obstruction. We report a\ncase of mucous membrane pemphigoid with oral\nand genital involvement.\n\n\n\nCase report\nA 66-years old Chinese gentleman presented with\nrecurring blisters and erosions over the oral cavity\nand genitalia for the past 6 months. The lesions\nstarted as an intact blister that breaks off leaving\npainful erosion with clear discharges. It had started\non the glans and shaft of his penis before involving\nthe oral cavity. There were no eye, skin, respiratory\nand airway complaints. He also denied joint,\ngastrointestinal and neurological involvement.\nThere was no recurring high fever associated with\nthe flare up of the blistering condition. \n\n\n\nHe was on glibenclamide, metformin,\nchlorothiazide, aspirin and lovastatin for his\n\n\n\nAUTOIMMUNE DISORDERS - Case Report\n\n\n\nMucous membrane pemphigoid\n\n\n\nLee CK1, MRCP, Zuraiza MZ2, MDSc, ROKIAH I1, FRCP\n\n\n\ndiabetes, hypertension, hypercholesterolemia and\nischemic heart disease, all of which had been\nconsumed for at least more than 3 years. There was\nno history of ingestion of any traditional\nmedication.\n\n\n\nOn examination, there were numerous well defined\nerosions involving his palate (Figure 1) and buccal\nmucosa. His glans penis was erythematous with\nwell defined erosions discharging serous fluid\n(Figure 2). There were no skin or ocular lesions.\nThe joints were normal. \n\n\n\nA gingival biopsy showed subepithelial blister with\nsubepithelial chronic inflammatory cells mainly\nconsisting of lymphocytes and some plasma cells\n(Figure 3a). Few colloid bodies are seen in the\nepithelium. There was no basal cell degeneration.\nDirect immunofluoresence staining was positive\nwith linear deposition of IgG, fibrinogen and C3 at\nthe basement membrane (Figure 3b). It was stained\nnegative with IgA and IgM.\n\n\n\nThe diagnosis of mucous membrane pemphigoid\nwas made based on the clinical presentation, histo-\npathological findings as well as the direct\nimmunofluoresence staining.\n\n\n\nWe adopted a multidisciplinary approach in the\nmanagement of this patient with the involvement of\nthe dermatology, dental and ophthalmology units.\nThe lesions showed a 50% response to topical\nbetamethasone dipropionate served in a customised\noral tray as well as topical hydrocortisone acetate\n1% to his genital erosions. He was started on\ndapsone initially but unfortunately, he developed\ndrug hypersensitivity syndrome manifesting as\nmaculopapular rash 3 days after starting the drug.\nHe was then started on prednisolone 10mg BD as\nwell as doxycycline 100mg OD with improvement\nof his lesions. Besides the topical and systemic\ntreatment, he was also referred to the\nophthalmology team who excluded ocular\ninvolvement and will follow-up this patient due to\nthe risk of ocular involvement in the disease.\n\n\n\nCorrespondence\nDr Lee CK, MRCP\n1Dermatology Unit, Department of Medicine\nFaculty of Medicine, Universiti Malaya, Kuala Lumpur\n\n\n\n2Department of Oral Pathology\nOral Medicine and Periodontology\nFaculty of Dentistry, Universiti Malaya, Kuala Lumpur\n\n\n\n\n\n\n\n\n26 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nMucous membrane pemphigoid is a rare idiopathic\nand progressing autoimmune blistering disorder\nthat may produce severe sequelae if not detected\naccurately to enable prompt and adequate\ntreatment. It may affect any or all mucous\nmembranes, with or without skin involvement, in\ndecreasing frequency: oral cavity (90%), eye\n(65%), nose, nasopharnyx, anogenital region, skin\n(20-30%), larynx (8-9%), and oesophagus2.\n\n\n\nAutoantibodies involved in this condition are\ndirected to the basement membrane components.\nMany antigens had been identified as the target to\nthis process, including bullous pemphigoid antigen\n1 (BPAg1, 230kD), bullous pemphigoid antigen 2\n(BPAg2, 180kD), laminin 5, laminin 6, a6-integrin\nsubunit, \ufffd4-integrin subunit, collagen VII and other\nproteins of unknown identity and function1,3.\nSeveral studies had reported an increased\noccurrence of HLA-DQB1*0301 allele with this\ncondition1. Cellular immunity and cytokines are\nbelieved to be involved in the pathogenesis of this\ncondition and some studies have indicated that\nchronic inflammation may be responsible for\nprecipitating mucous membrane pemphigoid by an\nepitope spreading phenomenon1.\n\n\n\nThe exact incidence and prevalence of mucous\nmembrane pemphigoid is unknown. It\npredominantly affects elderly women with the mean\nage of onset between 51 to 62 years of age4.\nFemales are affected more than males (2:1). For the\ndiagnosis of mucous membrane pemphigoid,\nclinical and direct immunopathology criteria are\nessential and must be demonstrated before a\ndiagnosis of mucous membrane pemphigoid is\nassigned1.\n\n\n\nIt is important to recognise this entity, as mucous\nmembrane pemphigoid can often lead to scarring\nand may be potentially sight threatening if there is\nocular involvement. Rarely, it may be life\nthreatening when airway or oesophagus is involved.\nWhen the disease occurs in only the oral mucosal or\noral mucosa and skin, the patients are categorised as\na \u201clow-risk patient\u201d1. Some of these patient with\nlocalised disease may remain stable for years,\nwhilst others may develop rapidly progressive\nocular involvement despite immunosuppression5.\nHiggins et al reported an incidence rate of 0.03 per\nperson per year over 5 years for development of\nocular disease in patients with established oral\nmucous membrane pemphigoid5. Due to this\nsignificant risk of developing ocular disease and\nthat many patients may be asymptomatic in the\ninitial\n\n\n\nFigure 1 Erosions over the hard palate Figure 2 Erosions over the glans penis\n\n\n\nFigure 3\n(a) Subepidermal bullae demonstrated in gingival biopsy stained with hematoxylin-eosin stain.\n(b) Direct immunofluorescence microscopy studies demonstrating linear bands of IgG deposited \n\n\n\nat the oral mucous membrane basement membrane\n\n\n\n\n\n\n\n\n27MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ninitial phase of ocular involvement, regular\nophthalmic review is indicated to detect this serious\ncomplication.\n\n\n\nThere are no large-scale, well-controlled studies on\nthe management of mucous membrane pemphigoid.\nThe First International Consensus on Mucous\nMembrane Pemphigoid recommended dividing\npatients into \u201clow-risk\u201d and \u201chigh-risk\u201d groups1.\n\u201cLow-risk\u201d patients are those who have disease\noccurring in only oral mucosa or oral mucosa and\nskin. For this group of patients, a more conservative\napproach was recommended by using either topical\ncorticosteroid of moderate to high potency or\nsystemic therapy like tetracycline, nicotinamide,\ndapsone or low dose prednisolone with or without\nlow doses of azathioprine1. Topical steroids can be\ndelivered orally via a custom tray, as was used by\nthis patient. Successful treatment of mucous\nmembrane pemphigoid with topical tacrolimus has\nalso been reported4.\n\n\n\nPatients with ocular, genital, nasopharyngeal,\noesophageal and laryngeal mucosal involvement\nare defined as \u201chigh-risk\u201d patients1. Treatment\nmodalities for this group of patients include\n\n\n\ndapsone, prednisolone, cyclophosphamide and\nazathioprine1. Methotrexate, mycophenolate mofetil\nand intravenous immunoglobulins are also\nadvocated to treat this condition3. Biologics such as\netanercept and infliximab had been reported to be\nsuccessful in the treatment of recalcitrant mucous\nmembrane pemphigoid3.\n\n\n\nReferences\n\n\n\n1. Chan LS, Ahmed AR, Anhalt GJ, et al. The first\ninternational consensus on mucous membrane\npemphigoid: definition, diagnostic criteria, pathogenic\nfactors, medical treatment and prognostic indicators.\nArch Dermatol 2002; 138:370-379\n\n\n\n2. Eschle-Meniconi Margherita E, Ahmad Sumera R,\nFoster C Stephen. Mucous membrane pemphigoid: an\nupdate. Current Opinion in Ophthalmology\n2005;16(5):303-7\n\n\n\n3. Neff AG, Turner M, Mutasim DF. Treatment strategies\nin mucous membrane pemphigoid. Ther Clin Risk\nManag 2008; 4(3): 617-26\n\n\n\n4. Suresh L, Martinex Calixto LE, Radfar L. Successful\ntreatment of mucous membrane pemphigoid with\ntacrolimus. Spec Care Dentist 2006; 26(2):66-70\n\n\n\n5. Higgins GT, Allan RB, Hall R, et al. Development of\nocular disease in patients with mucous membrane\npemphigoid involving the oral mucosa. Br J Opthalmol\n2006; 90:964-967\n\n\n\n\n\n\n\n\n28 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nANNOUNCEMENT - Continuous Professional Development\n\n\n\nSatellite Meeting\n\n\n\n2009\n\n\n\nOrganizers LADS/ AADV and the Vietnam Dermatological Society \nwith the support of the National Institute for Dermatology and \nVenereology, Vietnam\n\n\n\nTheme Psoriasis and Eczema-a double-edged challenge \n\n\n\nVenue Hilton Hotel, Hanoi \n\n\n\nDate 6 - 9 November 2009\n\n\n\nProgram website: www.asianderm.org \n- Inauguration of the Asian Academy of Dermatology and Venereology \n\n\n\n(AADV)\n- The LADS/AADV will be accepting nominations to the Roll of \n\n\n\nFoundation Members and Charter \n- Members of the AADV in recognition for their contribution and \n\n\n\nsupport for dermatology in Asia.\n- Gala Dinner \u201cA Nite @ the Opera\u201d at the Hanoi Opera House on \n\n\n\n7.11.200\n\n\n\nSecretariat Asian Academy of Dermatology and Venereology / League of Asian \nDermatological Societies\nAcademy House, 210 Jalan Tun Razak, 50400 Kuala Lumpur, Malaysia\nE-mail: secretariat@asianderm.org | webmaster@asianderm.org\n\n\n\n\n\n\n\n\n29MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGRANULOMATOUS DISEASES - Original Article\n\n\n\nRisk factors for type 1 leprosy reaction in a tertiary skin \n\n\n\nclinic in Sarawak\n\n\n\nYap FBB, MRCP, Pubalan M, MRCP\n\n\n\nAbstract\n\n\n\nIntroduction Identifying risk factors for leprosy reactions can preempt clinicians to initiate prompt\ntreatment to prevent associated morbidities. Thus, a retrospective study was done to elucidate the risk\nfactors among 44 newly diagnosed leprosy patients in Sarawak General Hospital from 1993 to 2007.\n\n\n\nMaterials and methods Case folders were searched for demographic data, clinical characteristics,\nslit skin smear results, and the presence of type 1 leprosy reactions, its treatment and outcome.\nAnalysis was done to determine the relative risks for development of this reaction. Student t test was\nused for comparison of means. The level of significance was set at 0.05.\n\n\n\nResults Type 1 reaction was seen in 25% (n=11) of patients. It occurred in 44.4% (n=4) of\nborderline lepromatous (BL), 33.3% (n=1) of mid borderline (BB), 37.5% (n=3) of borderline\ntuberculoid (BT) and 30% (n=3) of tuberculoid (TT) patients. Borderline spectrum of disease gave\na relative risk of 2 (95% CI 0.3-0.9) and age of 40 gave a relative risk of 1.8 (95% CI 0.3-0.9) for\nthe development of type 1 reaction. Older mean age (mean 53.7 years cf. 37.0 years, p = 0.01) and\nearlier presentation to health care workers (mean 5.8 months cf. 11.9 months, p = 0.02) was also\nsignificant risk factors Extent of disease and gender were not identified as risk factors.\n\n\n\nConclusion Risk factors for type 1 leprosy reaction were borderline leprosy, older patients and\nshorter duration of illness on presentation.\n\n\n\nKeywords leprosy, type 1 reaction, risk factors\n\n\n\nCorrespondence\nDr Felix Boon Bin, Yap\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak, Malaysia\nEmail : woodzlamp@yahoo.com\nConflict of interest : Nil\n\n\n\nIntroduction\nType 1 reaction or reversal reaction is caused by\nspontaneous increases in T-cell reactivity to\nmycobacterial antigens1. This reaction typically\noccurs in patients with borderline leprosy\nencompassing mid borderline (BB), borderline\ntuberculoid (BT), and borderline lepromatous (BL)\nleprosy2. These borderline patients are considered\nimmunologically unstable, thus allowing alteration\nof the dynamic immunologic mechanism leading to\nmodifications of the cytokine profiles in the skin\nlesions and nerves causing inflammation3. The\nincidence rate is reported to be 8.7/100 person years\n\n\n\nat risk4. It mainly occurs during treatment.\nClinically, it presents with inflammation of the\nexisting skin lesions causing erythema, oedema,\npain and sometimes ulceration. Accompanying\nacute neuritis is also common. Untreated this will\nlead to deformities and disabilities due to\npermanent nerve damage. Thus, it is important to\ndetermine the risk factors predicting this reaction to\nhelp clinicians anticipate them and start treatment\nearly to prevent the associated morbidities. Here, a\nretrospective study was undertaken to determine the\nrisk factors for type 1 leprosy reaction among all\nthe newly diagnosed patients with leprosy seen in\nthe skin clinic, Sarawak General Hospital between\n1993 and 2007.\n\n\n\nMaterials and methods\nA retrospective review of all the newly diagnosed\npatients with leprosy in the skin clinic, Sarawak\nGeneral Hospital between 1993 and 2007 was\nundertaken. Data regarding the baseline\ndemographics\n\n\n\n\n\n\n\n\n30 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ndemographics, clinical characteristics and slit skin\nsmear results on initial presentation, and the\npresence of type 1 leprosy reactions, its treatment\nand outcome were retrieved from the case folders in\nthe skin clinic.\n\n\n\nClinical characteristics on initial presentation\nretrieved from the case folders included number of\nskin lesions, number of thickened nerves, and\nduration of skin lesions prior to presentation,\nearlobe thickening and loss of lateral third of\nthe eyebrows. The skin lesions consist of\nhypopigmented macules and patches; and\nerythematous macules, papules, patches, plaques\nand nodules with or without loss of sensation.\nThickened nerves included all the superficial\nperipheral nerves namely ulnar, median, radial\ncutaneous, greater auricular, lateral popliteal and\nposterior tibial nerves. \n\n\n\nAll the slit skin smears utilized 6 sites, 1 on each\nearlobe and 4 on the skin lesions on the body.\nBacteriologic index (BI) is a logarithmic scale from\n1+ to 6+ quantifying the density of Mycobacterium\nleprae in the smear. The BI presented in this study\nis the average BI from these 6 sites. Morphological\nindex (MI) is the percentage of regularly stained\nbacilli signifying the percentage of live bacilli in the\nsmear.\n\n\n\nAll the patients in this study were classified based\non the Ridley-Jopling classification5 of\nindeterminate leprosy (IND), tuberculoid leprosy\n(TT), borderline tuberculoid leprosy (BT), mid\nborderline leprosy (BB), borderline lepromatous\nleprosy (BL) and lepromatous leprosy (LL). They\nwere also classified according to the WHO\nclassification6 into multibacillary (MBL) and\npaucibacillary (PBL) leprosy. Patient is considered\nto have borderline leprosy if they have BT, BB or\nBL leprosy. Those with PBL were considered to\nhave IND, TT and BT whereas MBL consisted of\nBB, BL and LL.\n\n\n\nTable 1 Relative risks for type 1 leprosy reaction based on demographics and clinical characteristics in \nSarawak General Hospital\n\n\n\nRR - relative risk, 95%         CI - 95% confidence interval\n\n\n\nRisk Factors\n\n\n\nMale Sex \n\n\n\nAge>40\n\n\n\nBorderline leprosy\n\n\n\nLoss of eyebrow\n\n\n\nEarlobe thickening\n\n\n\nNerve thickening\n\n\n\nSkin lesions>5\n\n\n\nMI>3\n\n\n\nBI>3\n\n\n\nWith reaction (n=11)\n\n\n\n8 (72.7%)\n\n\n\n8 (72.7%)\n\n\n\n8 (72.7%)\n\n\n\n2 (18.2%)\n\n\n\n2 (18.2%)\n\n\n\n7 (63.6%)\n\n\n\n5 (45.5%)\n\n\n\n5 (45.5%)\n\n\n\n3 (27.3%)\n\n\n\nWithout reaction (n=33)\n\n\n\n25 (75.8%)\n\n\n\n13 (39.4%)\n\n\n\n12 (36.3%)\n\n\n\n6 (18.2%)\n\n\n\n9 (27.3%)\n\n\n\n15 (45.5%)\n\n\n\n15 (45.5%)\n\n\n\n11 (33.3%)\n\n\n\n9 (27.3%)\n\n\n\nRR\n\n\n\n0.9\n\n\n\n1.8\n\n\n\n2.0\n\n\n\n1.0\n\n\n\n0.7\n\n\n\n1.4\n\n\n\n1.0\n\n\n\n1.4\n\n\n\n1.0\n\n\n\n95% CI\n\n\n\n0.7-1.6\n\n\n\n0.3-0.9\n\n\n\n0.3-0.9\n\n\n\n0.7-1.4\n\n\n\n0.4-6.3\n\n\n\n0.4-1.3\n\n\n\n0.5-1.9\n\n\n\n0.3-1.7\n\n\n\n0.3-3.2\n\n\n\nType 1 Leprosy Reaction in Sarawak General Hospital\n(n-44)\n\n\n\n\n\n\n\n\n31MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nPatients were deemed to have type 1 leprosy\nreactions or reversal reactions if their original skin\nlesions became inflamed, swollen, painful and\ntender. \n\n\n\nStatistical analysis using SPSS version 15 was done\nto determine the relative risks for development of\ntype 1 reaction. Student t test was utilized for\ncomparison of means in those with or without type\n1 reaction. The level of significance was set at 0.05.\n\n\n\nResults\nDemographics and clinical course\nThere were 44 newly diagnosed patients with\nleprosy in the skin clinic, Sarawak General Hospital\nfrom 1993 to 2007. Six (13.6%) had indeterminate\nleprosy (IND), 10 (22.7%) had tuberculoid leprosy\n(TT), 8 (18.2%) had borderline tuberculoid leprosy\n(BT), 3 (6.8%) had midborderline leprosy (BB), 9\n(20.5) had borderline lepromatous leprosy (BL) and\n8 (18.2%) had lepromatous leprosy (LL). Male\nconstituted 75% (n=33) of the patients. The mean\nage was 41.2 \u00b1 20.0 years, ranging from 8 to 94\nyears old. Twenty five percent (n=11) of patients\ndeveloped type 1 reaction. Type 1 reaction occurred\nin 44.4% (n=4) of BL, 33.3% (n=1) of BB, 37.5%\n(n=3) of BT and 30% (n=3) of TT patients (Figure\n1). None with IND or LL leprosy developed this\nreaction.\n\n\n\nOf the 11 patients with type 1 leprosy reaction, 8\nwere males and 3 were females. Five (45.5%)\npatients had their reactions prior to treatment. The\nremaining 6 had the reaction between 7 and 160\ndays after treatment. The duration of the reactions\nlasted between 1 to 17 months. The mean period\nwas 7 months. All the patients except 2 had oral\ncorticosteroids to treat their reactions. These 2\npatients had only non steroidal anti inflammatory\ndrugs (NSAID). Neuritis was noted in 5 (45.5%)\npatients. However, there were only 2 patients with\npermanent deformity. One had foot drop and\nanother had claw hand. No death was reported.\n\n\n\nRisk factors\nTable 1 shows the relative risks of developing type\n1 leprosy reaction in Sarawak General Hospital. It\nwas noted that borderline spectrum of disease and\nage more than 40 years old gave an increased risks\nof developing type 1 leprosy reaction. Borderline\nspectrum of disease gave a relative risk of 2 (95%\nCI 0.3-0.9) while age more than 40 years old gave a\n\n\n\nrelative risk of 1.8 (95% CI 0.3-0.9). Other\nvariables including gender, MI, BI, presence of\nnerve thickening, number of skin lesions, loss of\nlateral third of the eyebrows and earlobe thickening\nwere not identified as risk factors for development\nof type 1 leprosy reaction.\n\n\n\nAnalysis of means using student t test revealed that\nthose with the reaction was significantly older\n(mean 53.7 years cf. 37.0 years, p = 0.01) and\npresented earlier to the health care workers (mean\n5.8 months cf. 11.9 months, p = 0.02). However,\nthere were no differences in the mean skin lesion\ncount (7.1 cf. 8.2, p = 0.75), mean thickened nerve\ncount (1.3 cf. 0.9, p = 0.48), mean MI (5.8 cf. 4.9,\np = 0.76) and mean BI (1.7 cf. 1.7, p = 0.97) on\ninitial presentation. \n\n\n\nDiscussion\nType 1 leprosy reaction is reported to occur in 8%\nto 32% of patients with leprosy7,8,9. In Penang,\n\n\n\n27.4% of the 95 patients with leprosy seen in the\nPenang General Hsopital developed type 1 reaction,\nwhereas in Hospital Sultanah Aminah, Johor Bahru,\nthe rate was 21.1%10,11. Here, 25% of our leprosy\npatients developed this reaction, similar to regional\nand international figures. Type 1 reaction is seen in\nborderline spectrum of disease. In a tertiary\nhospital in Delhi, the reaction was most commonly\nseen in those with BB followed by BL, BT and LL7.\nIn Thailand, there were a statistically significant\nincreasing proportion of patients with severe\nreversal reaction starting from tuberculoid and\ngoing toward borderline lepromatous12. In\nHyderabad, the reaction was seen mostly in those\nwith BL and BT9. In Penang, it is seen mostly in BT\nfollowed by LL, BB, BL and TT10. Here, the pattern\nwas BL, BT, TT and BB. None of the patients with\nLL developed the reaction. The pattern seen here\nand in Penang corresponded to finding by others in\nthat borderline leprosy comprising BB, BL and BT\nare risk factors for type 1 reaction.\n\n\n\nAmong patients developing type 1 reaction, up to\n60% developed the reaction at the time of\npresentation7,13. In Thailand, among patients with\nPBL developing this reaction, 82% had it during the\ninitial visit while among MBL patients, 35% had it\nbefore treatment12. In Penang, only 15.4% of the 26\npatients developed the reaction prior to treatment10.\nMost of their patients developed the reaction during\nthe\n\n\n\n\n\n\n\n\n32 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nthe first 3 months of therapy10. Here, 45.5% had the\nreaction prior to treatment, 66.7% among patients\nwith PBL and 20% among those with MBL. Our\nrate is much higher than that observed by Tan et al\nin Penang but similar to those reported in India and\nThailand.\n\n\n\nScollard et al noted that type 1 reactions occurred\nwith significantly greater frequency in women, and\ndid not appear to be influenced by age of onset of\nleprosy8. Similarly, female gender was also seen as\na risk factor for reversal reaction in Northern\nIndia13. Widespread disease and multibacillary\ndisease were also identified as risk factors. In West\nNepal, extensive clinical disease and borderline\nleprosy was identified as a risk factor for type 1\nleprosy reaction during the first year of treatment4.\nIn Brazil, among patients with MBL, segmentary\nskin lesions and BI < 3 was significantly associated\nwith reversal reactions14. Higher level of serum\ntumour necrosis factor alpha and interleukin 1 were\nalso identified as a prognostic marker for reversal\nreactions15.\n\n\n\nHere, it was noted that patients with borderline\nspectrum of disease, age more than 40 years old and\nhad shorter duration of illness possessed higher risk\nfor reversal reactions. Extent of disease, measured\nby number of lesions on presentation, MI and BI\nwas not identified as a risk factor. The reason for\nthe shorter duration of illness before presentation\nwas because most of the patients presented with\ntype 1 reaction rather than the disease per se. It is\npostulated that older patients had higher risk for\nreversal reaction because there are more likely to\nhave past infection or exposure to mycobacterium\ntuberculosis, a possible trigger for this reaction16.\nTuberculosis is a major public health problem in\nSarawak.\n\n\n\nThis study is limited by the number of patients and\nthe retrospective nature. Limitation in number of\npatients affected the statistical power. The\nretrospective nature limited the type of data\ncollected. Some of the data are also missing,\nlimiting the scope of the study.\n\n\n\nIn conclusion, risk factors for type 1 leprosy\nreaction were borderline leprosy, older patients and\nshorter duration of illness on presentation. Finding\nthese clinical characteristics in patients with leprosy\ncan forewarn the treating clinician to the possibility\n\n\n\nof reactions in the near future. This will thus\nfacilitate earlier treatment to prevent deformities\nand disabilities.\n\n\n\nReferences\n\n\n\n1. Britton WJ. The management of leprosy reversal\nreactions. Lepr Rev 1998; 69: 225-34\n\n\n\n2. Ridley DS, Radia KB. The histological course of\nreaction in borderline leprosy and their outcome. Int J\nLepr 1981; 49: 383-92\n\n\n\n3. Sehgal VN, Sharma V. Reactions in leprosy. A\nprospective study of clinical, bacteriological,\nimmunological and histopathological parameters in\nthirty-five Indians. J Dermatol 1988; 15: 412-9\n\n\n\n4. Van Brakel WH, Khawas IB, Lucas SB. Reactions in\nleprosy: an epidemiological study of 386 patients in\nwest Nepal. Lepr Rev 1994; 65: 190-203\n\n\n\n5. Ridley DS, Jopling WH. Classification of leprosy\naccording to immunity. Int J Lepr 1966; 34: 255- 73\n\n\n\n6. World Health Organization. Leprosy Elimination\nAdvisory Group. Guide to eliminate leprosy as a public\nhealth problem: multidrug therapy cures leprosy, stops\ntransmission and prevents disabilities. Geneva: Leprosy\nElimination Group, World Health Organization; 2000\n\n\n\n7. Sharma N, Koranne RV, Mendiratta V, et al. A study of\nleprosy reactions in a tertiary hospital in Delhi. J\nDermatol 2004; 31(11): 898-903\n\n\n\n8. Scollard DM, Smith T, Bhoopat L, et al. Epidemiologic\ncharacteristics of leprosy reactions. Int J Lepr Other\nMycobact Dis 1994; 62(4): 559-67\n\n\n\n9. Lockwood DN, Vinayakumar S, Stanley JN, et al.\nClinical features and outcome of reversal (type 1)\nreactions in Hyderabad, India. Int J Lepr Other\nMycobact Dis 1993; 61: 8-15\n\n\n\n10. Tan WC, Lo Kang SC. Lepra reactions: A 10-year\nretrospective analysis. Mal J Dermatol 2008; 21: 41-6\n\n\n\n11. Tey KE, Choon SE, Zainah M, Zabedah I. Management\nof leprosy in the Department of Dermatology, Hospital\nSultanah Aminah, Johor Bahru. Mal J Dermatol 2007;\n19: 95-100\n\n\n\n12. Schreuder PA. The occurrence of reactions and\nimpairments in leprosy: experience in the leprosy\ncontrol program of three provinces in northeastern\nThailand, 1987-1995. Int J Lepr Other Mycobact Dis\n1998; 66: 159-69\n\n\n\n13. Kumar B, Dogra S, Kaur I. Epidemiological\ncharacteristics of leprosy reactions: 15 years experience\nfrom north India. Int J Lepr Other Mycobact Dis 2004;\n72(2): 125-33\n\n\n\n14. Nery JA, Vieira LM, de Matos HJ, et al. Reactional\nstates in multibacillary Hansen disease patients during\nmultidrug therapy. Rev Inst Med Trop Sao Paulo 1998;\n40: 363-70\n\n\n\n15. Parida SK, Grau GE, Zaheer SA, et al. Serum tumor\nnecrosis factor and interleukin 1 in leprosy and during\nlepra reactions. Clin Immunol Immunopathol 1992; 63:\n23-7\n\n\n\n16. Wilkinson RJ, Lockwood DN. Antigenic trigger for\ntype 1 reaction in leprosy. J Infect 2005; 50: 242-3\n\n\n\n\n\n\n\n\n33MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDear Editor,\n\n\n\nWe have encountered a 28 year old Penang lady\npresented with hyperpigmentation and tight skin in\nJuly 2004. She was initially diagnosed as\nscleroderma. However, 2 months after diagnosis,\nshe developed multiple painful nodules on the body.\nExamination showed multiple erythematous tender\nnodules on the body associated with multiple\nhypopigmented anaesthetic lesions and thickened\nearlobes (Figure 1). Slit skin smear showed\npresence of Mycobacterium leprae with a\nmorphological index (MI) of 12 and bacteriologic\nindex (BI) of 5.6. A diagnosis of MBL with ENL\nwas made. She was commenced on the WHO\nmultiple drug therapy (MDT) for a year. She was\nalso given oral prednisolone for her ENL. On\ncompleting of the MDT, her MI was 0 and BI fell to\n3.8. Two years after diagnosis, her ENL worsened\nrequiring addition of azathioprine. Her\nprednisolone was titrated to the maximum of 2\nmg/kg/day. Due to this severe immunosuppresion,\nshe was admitted twice to the hospital because of\nsevere septicaemia. Fortunately, she managed to\nsurvive these episodes. In order to reduce her\ndependence on steroids, oral thalidomide at 400 mg\ndaily was added after discussion of the benefits and\nthe risks, especially teratogenicity, with the\npatient.This helped her for a few months. In\nJanuary 2008, her ENL was again out of control\nrequiring up titration of her steroid. Her BI in April\n2008 went up to 4.0. Skin biopsy for\nmycobacterium culture and sensitivity was sent.  \n\n\n\nSecond line treatment of daily rifampicin 600 mg,\nminocycline 100 mg, ofloxacin 400 mg was\ncommenced. This did not improve her ENL.\nHowever, her BI fell to 2.6 in August 2008. As her\nENL was not improving, pentoxyfylline was added\n\n\n\nGRANULOMATOUS DISEASES - Short Communication\n\n\n\nA lady with complicated erythema nodosum leprosum\n\n\n\nYap FBB, MRCP, Pubalan M, MRCP\n\n\n\nin September 2008. Her azathioprine was changed\nto cyclosporine. This alteration in therapy helped\nthe ENL.\n\n\n\nIn October 2008, her BI fell further to 2.3.\nNevertheless, in December 2008, with an upper\nrespiratory tract infection, her ENL worsened. Her\nprednisolone had to be increased from 0.5\nmg/kg/day to 1 mg/kg/day to control the reaction.\nUp to February 2009, she still has crops of skin\nlesions despite on oral prednisolone 0.5 mg/kg/day,\nthalidomide 400 mg daily, cyclosporine 4\nmg/kg/day and pentoxyfylline 400 mg twice daily\n(Figure 2). Complications of prolonged\ncorticosteroid treatment were apparent.\n\n\n\nCorrespondence\nDr Felix Boon Bin, Yap\nDepartment of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak, Malaysia\nEmail : woodzlamp@yahoo.com\n\n\n\nFigure 1 Presence of multiple erythematous \npapulonodules on the neck with \nthickened earlobes\n\n\n\nFigure 2 Presence of multiple papulonodules\non the upper limbs\n\n\n\n\n\n\n\n\n34 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nTreatment of ENL with immunosuppressive\nmedications is usually successful. In Nepal 48% of\ntheir patients with ENL are successfully treated\nwithin a year3. However, in 13% of cases, ENL can\npersist for more than 5 years3.\n\n\n\nComplicated ENL usually requires the use of more\npotent immunosuppresion. Miller et al had\nsuccessfully treated difficult ENL with\ncyclosporine A4. In our case, the use of cyclosporine\nand azathioprine had limited success.\n\n\n\nThalidomide and pentoxyfylline are used in the\ntreatment of leprosy because of their anti tumour\nnecrosis alpha (TNFa) property. TNFa is found to\nplay a key role in the symptomatology of ENL5. By\nblocking this inflammatory mediator, it is\npostulated that the propagation and progression of\nENL will cease. Thalidomide is proven to be more\nsuperior to corticosteroid and pentoxyfylline6,7.\nThalidomide is drug of first choice in man with\nsevere ENL. However, the use of this highly\nteratogenic drug in women of reproductive age\ngroup is difficult8. The risks and benefits have to be\nweighed and proper discussion between the patients\nand the treating physician is essential to get the\noptimal outcome. The use of thalidomide usually\ncontrols the ENL within 48 hours. However, in our\npatient the use of thalidomide at a recommended\ndosage of 400 mg daily only managed to control the\nreaction for the first few months. Addition of\nanother TNFa blocker, pentoxyfylline also failed to\neffectively control her ENL.\n\n\n\nIn this complicated case of ENL, the use of\nmonoclonal antibody against TNFa e.g. infliximab\nand etanercept might be useful. However, due to the\nhigh cost of this medication and lack of clinical data\non its effectiveness and adverse effects in leprosy\npatients, it was not tried.\n\n\n\nThis case illustrates the difficulty in treating\ncomplicated ENL. Fortunately, complicated ENL\noccurs in the minority of cases.\n\n\n\nReferences\n\n\n\n1. Bhattacharya SN, Vehgal VN. Leprosy in India. Clin\nDermatol 1999; 17: 159-70\n\n\n\n2. Walker SL, Lockwood DNJ. Leprosy. Clin Dermatol\n2007; 25:165-72\n\n\n\n3. Feuth M, Brandsma JW, Faber WR, et al. Erythema\nnodosum leprosum in Nepal: a retrospective study of\nclinical features and response to treatment with\nprednisolone or thalidomide. Lepr Rev 2008 Sep;\n79(3): 254-69\n\n\n\n4. Miller RA, Shen J, Rea TH, et al. Treatment of chronic\nerythema nodosum leprosum with Cyclosporine A\nproduces clinical and immunohistologic remission. Int\nJ Lepr 1987; 55: 441-49\n\n\n\n5. Santos DO, Suffys PN, Bonifacio K, et al. In vitro\ntumour necrosis factor production by mononuclear\ncells from lepromatous leprosy patients and from\npatients with erythema nodosum leprosum. Clin\nImmunol Immunopathol 1993; 67: 199-203\n\n\n\n6. Moreira AL, Kaplan G, Villahermosa LG, et al.\nComparison of pentoxifylline, thalidomide and\nprednisone in the treatment of ENL. Int J Lepr Other\nMycobact Dis 1998; 66: 61-65\n\n\n\n7. Jakeman P, Smith WCS. Thalidomide in leprosy\nreaction. Lancet 1994; 343: 432-33\n\n\n\n8. Britton WJ, Lockwood DNJ. Leprosy. Lancet 2004;\n363: 1209-19\n\n\n\n\n\n\n\n\n35MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDear Editor,\n\n\n\nWe have encountered a 25 year old Malay lady,\nsingle, presented with hyperpigmented raised scaly\nplaque over the left shoulder for 13 years. She\nclaimed that the lesion originated from BCG scar. It\nwas increasing in size and new lesions were noted\non her back and right thigh. No history of contact\nwith tuberculosis and leprosy patient. There is no\nhistory of weight loss, decrease appetite,\nmalignancy nor symptoms of connective tissue\ndisease.\n\n\n\nOn examination there were well demarcated scaly\nplaque with area of atrophy and poikiloderma over\nthe left shoulder (10 x 20cm), back (6 x 5cm) and\nleft thigh (5 x 3cm). Investigation results revealed\nlymphocytosis. Mantoux test was 20mm. CXR was\nnormal. Skin biopsy showed granulomatous\ninflammation.\n\n\n\nA diagnosis of post vaccination lupus vulgaris was\nmade based on the history, skin biopsy and strongly\npositive mantoux test. Patient was put on anti-\ntuberculosis for 6 month (daily doses for 2 months,\nIM Streptomycin 1gm, Isoniazide 250mg,\n\n\n\nGRANULOMATOUS DISEASES - Short Communication\n\n\n\nPost vaccination lupus vulgaris\n\n\n\nMasliza H, MD, Ong CL, MRCP, Zamri, MD, Nor A, MD\n\n\n\nRifampicin 450mg and Pyrazinamide 1250mg\nfollowed by biweekly doses for 4 months of\nRifampicin 450mg and Isoniazide 750mg (Table 1).\nThe skin lesion resolved completely after 6 months\nof therapy.\n\n\n\nDiscussion\nTuberculosis of the skin is caused by\nMycobacterium Tuberculosis, Mycobacterium\nBovis and under certain condition BCG (an\nattenuated strain of M. Bovis used in vaccination).\nFragmented Tuberculosis of the skin has a\nworldwide distribution. The 2 most frequent form\nof skin tuberculosis are lupus vulgaris and\nscrofuloderma1,2,3,4. \n\n\n\nLupus vulgaris is rare whereas scrofuloderma and\nverrucous lesion predominate4. Lupus vulgaris\noccurs more than twice in woman whereas TB\nverrucosa cutis is more often found in men.\nGeneralized milliary TB is seen in infant and adult\nwith severe immunosuppression or AIDS5,6 as is\nprimary inoculation tuberculosis. Scrofuloderma\nusually occurs in adolescents and the elderly\nwhereas lupus vulgaris may affect all age groups.\n\n\n\nCorrespondence\nDr Masliza Hanuni\nDepartment of Dermatology\nHospital Sultanah Nur Zahirah, Pahang\n\n\n\nFigure A & B shows well demarcated scally, hyperkeratotic \nerythematous plaque with area of\npoikiloderma\n\n\n\nFigure C & D After completed treatment\n\n\n\nA B C D\n\n\n\n\n\n\n\n\n36 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nLupus vulgaris is an extremely chronic, progressive\nform of cutaneous tuberculosis occurring in\nindividuals with moderate immunity and high\ndegree tuberculin sensitivity. It is a post primary\npaucibacillary form of tuberculosis - fragmented\nresult from direct extension of underlying\ntuberculous foci of lymphatic or hematogenous\nspread, after primary inoculation, BCG vaccination,\nor in scars of old scrofuloderma. Complete healing\nrarely occurs without therapy.\n\n\n\nLesions are usually solitary and more than 90%\ninvolve the head and neck. Started with small,\nsharply marginated, red-brown papules of\ngelatinous consistency (apple-jelly nodules) slowly\nevolve by peripheral extension and central atrophy\ninto large plaques. However, many clinicians in\nAsian countries who see large numbers of this\nentity have avoided using the descriptive term\n\"apple jelly nodules\" since this is seldom seen in\npigmented patients.\n\n\n\nReappearance of new nodules within previously\natrophic or scarred lesions is characteristic. The\ncartilage (nose, ears) within the affected area is\nprogressively destroyed (lupus vorax); bone\nhowever is usually spared. Buccal, nasal, and\nconjunctival mucosae may be involved primarily or\nby extension.\n\n\n\nClinical variants are numerous and are seen in the\nfollowing forms:\n\n\n\nPlaque forms:\nDisease extension occurs with little central \natrophy. Scaling can occur, especially on the \nlower legs where it may resemble psoriasis. \nIrregular scarring is common and the active \nedge may be thickened and hyperkeratotic.\nUlcerating form:\nScarring and ulceration predominate. Crusts \nform over areas of necrosis. Deep tissues and \ncartilage are invaded by scar tissue that cause \ncontractures and deformity.\nVegetative form:\nNecrosis, ulceration and papillomatous \ngranulation tissue are seen.\nNodular form:\nAbsence of ulceration and scarring. Large soft \ntumors occur, especially on ear lobes.\n\n\n\nHistologically7, the most prominent feature is a\ntypical granulomatous tubercle with epithelioid\ncells, Langhans giant cells and a mononuclear\ninfiltrate. Caseation necrosis is minimal and\ndetection of acid-fast bacilli is rare. Tissue\nhistology varies with secondary changes of abscess.\n\n\n\nTable 1 Guidelines For Mycobacterium Tuberculosis Infection Therapy\n\n\n\nTotal duration of treatment 6 months except in patient with HIV infection, in whom treatment duration is at least 9 months.\n\n\n\nRIFAMPICIN 10mg/kg\n\n\n\nISONIAZIDE 5mg/kg\n\n\n\nPYRAZINAMIDE \n30mg/kg\n\n\n\nETHAMBUTOL \n15mg/kg\n\n\n\nOR\n\n\n\nSTREPTOMYCIN \n15mg/kg\n\n\n\nInitial 8/52\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nThen 16/52\n\n\n\n2-3 X / WEEK\n\n\n\n2-3 / WEEK\n\n\n\nInitial 2/52\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nThen 6/52\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\n2X / WEEK\n\n\n\n2X / WEEK\n\n\n\nThen 16/52\n\n\n\nDAILY\n\n\n\nDAILY\n\n\n\n9/12\n\n\n\n3X / WEEK\n\n\n\n3X / WEEK\n\n\n\n3X / WEEK\n\n\n\n3X / WEEK\n\n\n\n3X / WEEK\n\n\n\nOPTION 1 OPTION 2 OPTION 3\n\n\n\n\n\n\n\n\n37MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiagnosis can be made based on :\n\n\n\n\u2022 Typical LV plaque recognized by the softness of \nthe lesions, brownish red color and slow \nevolution.\n\n\n\n\u2022 The apple jelly nodule revealed by diascopy is \nhighly characteristic.\n\n\n\n\u2022 Strongly positive tuberculin test\n\u2022 Bacteria culture is usually negative\n\u2022 Positive PCR for MTB can support the \n\n\n\ndiagnosis in some cases8.\n\u2022 LV is a chronic disorder. Without therapy it\n\n\n\nprogresses causing functional impairment \nand disfiguration.\n\n\n\nLong standing LV may lead to the development of\ncarcinoma especially squamous cell carcinoma9.\nThe risk of metastases is high. 40% associated with\ntuberculous lymphadenitis. 10 - 20% associated\nwith active pulmonary tuberculosis or tuberculosis\nof bones and joints10. Pulmonary tuberculosis is\n4 - 10 times more frequent in patient with LV than\nin general population10.\n\n\n\nReferences\n\n\n\n1. Chong LY, Lo KK. Cutaneous tuberculosis in Hong\nKong: a 10-year retrospective study. Int J Dermatol.\nJan 1995;34(1):26-9. [Medline]\n\n\n\n2. Farina MC, Gegundez MI, Pique E, et al. Cutaneous\ntuberculosis: a clinical, histopathologic, and\nbacteriologic study. J Am Acad Dermatol. Sep\n1995;33(3):433-40. [Medline]\n\n\n\n3. Tappeiner G, Wolff K. Tuberculosis and other\nmycobacterial infections. In: Fitzpatrick TB, Eisen AZ,\nWolff K, et al, eds. Dermatology in General Medicine.\n4th ed. McGraw-Hill;1993:2370-95\n\n\n\n4. MacGregor RR. Cutaneous tuberculosis. Clin\nDermatol. May-Jun 1995;13(3):245-55. [Medline]\n\n\n\n5. Daikos GL, Uttamchandani RB, Tuda C, et al.\nDisseminated miliary tuberculosis of the skin in\npatients with AIDS: report of four cases. Clin Infect\nDis. Jul 1998;27(1):205-8. [Medline]\n\n\n\n6. Hay RJ. Cutaneous infection with Mycobacterium\ntuberculosis: how has this altered with the changing\nepidemiology of tuberculosis? Curr Opin Infect Dis.\nApr 2005;18(2):93-5. [Medline]\n\n\n\n7. Sehgal VN, Srivastava G, Khurana VK, et al. An\nappraisal of epidemiologic, clinical, bacteriologic,\nhistopathologic, and immunologic parameters in\ncutaneous tuberculosis. Int J Dermatol. Oct\n1987;26(8):521-6. [Medline]\n\n\n\n8. Tan SH, Tan BH, Goh CL, et al. Detection of\nMycobacterium tuberculosis DNA using polymerase\nchain reaction in cutaneous tuberculosis and\ntuberculids. Int J Dermatol. Feb 1999;38(2):122-7.\n[Medline]\n\n\n\n9. Kumar B, Muralidhar S. Cutaneous tuberculosis: a\ntwenty-year prospective study. Int J Tuberc Lung Dis.\nJun 1999;3(6):494-500. [Medline]\n\n\n\n10. Kivanc-Altunay I, Baysal Z, Ekmekci TR, Koslu A.\nIncidence of cutaneous tuberculosis in patients with\norgan tuberculosis. Int J Dermatol. Mar 2003;42(3):\n197-200. [Medline]\n\n\n\n\n\n\n\n\n38 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nAn outbreak of Rove Beetle dermatitis in Penang \n\n\n\nHospital: A report of 37 cases\n\n\n\nTan WC, MRCP, Chan LC, MMed\n\n\n\nAbstract\n\n\n\nBackground Rove beetle dermatitis is a peculiar form of acute irritant dermatitis following the\ncontact with body fluid of an insect which is belonging to genus Paederus. This retrospective study\nis to evaluate the epidemiology and clinical manifestations of rove beetle dermatitis during the\noutbreak of rove beetle dermatitis in Penang (March 2009 - April 2009).\n\n\n\nMethods We describe 37 patients with clinical diagnosis of rove beetle dermatitis presented to our\ndepartment. Only those patients with a definite history of contact with the insect were included in\nthe study. Demographic characteristics, reason for referral and details of skin lesions were\ndocumented and analysed.\n\n\n\nResults Male patients outnumbered female patients - 21 males (56.8%); 16 females (43.2%). The\nmean age of patients was 28.3 years. Of the 37 patients, 18 patients (48.6%) were Malay, 14 Chinese\n(37.8%), 4 Indians (10.8%) and 1 foreigner (2.8%). The mean duration of lesions before presentation\nto our clinic was 3.4 days. The mean duration of lesions before presented to our clinic was 3.4 days.\nSymptom of burning sensation (25, 67.7%) was more pronounced than itching (6, 16.2%). Fourteen\nof our patients (37.8%) reported a positive family history. Clinically, the most common presentation\nconsisted of linear, geographic, erythematous plaques with a \u2018\u2018burnt\u2019\u2019 appearance. In 59.5% of\npatients, more than one lesion was present. Pustules and vesicles were seen in 12 (32.4%) and in 10\n(27.1%) of the patients respectively. \u2018\u2018Kissing lesions\u2019\u2019 were seen in 5 (13.5%) patients. The neck and\narms were the most common sites of involvement. Periorbital involvement occurred in 16.2% of\npatients. Only 8 patients (21.6%) were diagnosed to have \u201cinsect related dermatitis\u201d at initial\npresentation. No one was referred as \u201crove beetle dermatitis\u201d.\n\n\n\nConclusion Rove beetle dermatitis is a common condition. Awareness of these condition and its\nclinical features will prevent misdiagnosis and unnecessary worry.\n\n\n\nKeywords Rove beetle dermatitis, Paederus dermatitis, Dermatitis linearis\n\n\n\nCorrespondence\nDr Tan Wooi Chiang\nDepartment of Dermatology\nPenang Hospital, Jalan Residensi, 10990 Penang\nEmail : tanwooichiang@yahoo.com\n\n\n\nIntroduction\nRove beetle dermatitis (also known as night burn,\npaederus dermatitis, dermatitis linearis, blister\nbeetle dermatitis, whiplash dermatitis) is a specific\nform of acute irritant contact dermatitis caused by\ncontact with the vesicant chemical pederin\ncontained in the body fluids of insects of the genus\nPaederus1. The condition is characterized by\nbullous lesion (vesicles & pustules) on an\n\n\n\nerythematous base with sudden onset of stinging or\nburning sensation on exposed areas of the body2.\n\n\n\nPaederus beetles have been associated with\noutbreak of dermatitis in various countries\nincluding Australia3, Malaysia4, India5, Sri Lanka6,\nIran7 and others8. From literature search, there were\nonly 2 outbreak of rove beetle dermatitis recorded\nin Malaysia. In 1993, Mokhtar N et al reported\npaederus dermatitis among medical students in\nUSM, Kelantan, Malaysia. In September 2002, an\nepidemic of dermatitis linearis caused by rove\nbeetles affected thousands of high rise flat dwellers\nand dormitory students in Penang, Malaysia. In\nMarch 2009, the second outbreak of rove beetle\ndermatitis in Penang state, Malaysia. This study is\nto\n\n\n\n\n\n\n\n\n39MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nto evaluate the epidemiology and clinical\nmanifestations of rove beetle dermatitis during this\noutbreak.\n\n\n\nMaterials and methods\nThis is a retrospective review of 37 patients with\nclinical diagnosis of rove beetle dermatitis who\npresented to dermatology department, Penang\nHospital during the second outbreak of Rove Beetle\ndermatitis in Penang (March 2009 - April 2009).\n\n\n\nThe diagnosis was made clinically and no\nhistopathologic examination was performed. Only\nthose patients with a definite history of contact with\nthe insect were included in the study. Patients with\na doubtful history of contact with the beetle or other\nplausible causes of contact dermatitis were not\nincluded in the study. Patients with a previous\nhistory of chronic skin disease or allergy were also\nexcluded.\n\n\n\nFigure 1\nTypical Rove\n\n\n\nBeetle\n\n\n\nFigure 2 Typical \u201cburnt like\u201d lesion secondary to\nRove Beetle dermatitis\n\n\n\nFigure 3 Typical linear pustular lesion Figure 4 Pustular lesions on the intense\ninflamed area\n\n\n\nFigure 5 Nairobi eye Figure 6 Kissing lesion\n\n\n\n\n\n\n\n\n40 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDemographic characteristics including family\nhistory of similar skin lesions were recorded and\nanalysed. Reason for referral, presenting\nsymptoms, number of skin lesions, site of\ninvolvement, morphology of the lesions, patterns of\ndistribution were also documented and analysed.\nSpecies identification of the Rove Beetles was not\ndone.\n\n\n\nAll the cases of Rove Beetle dermatitis were\nnotified to state health department for further\naction.\n\n\n\nResults\nA total of 37 patients were included in our study.\nMale patients outnumbered female patients - 21\nmales (56.8%); 16 females (43.2%). Their ages\nranged from 5 years to 69 years (mean age, 28.3 \u00b1\n16.6 years, median age 26 years). Of the 37\npatients, 18 patients (48.6%) were Malay, 14\nChinese patients (37.8%), 4 Indian patients (10.8%)\nand 1 patient (2.8%) was foreigner. No significant\ndifference was observed in the clinical features in\nrelation to gender and ethnics.\n\n\n\nThe cutaneous lesions were present from 1 to 10\ndays before presentation (mean 3.4 \u00b1 1.7 days,\nmedian 3 days). The burning sensation was more\npronounced compared to itching. Twenty five\npatients (67.6%) complained of tingling / burning\nsensation over the lesions and 6 (16.2%) had itching\nat the site of lesions. There were 6 (16.2%) patients\nwho were asymptomatic and presented with skin\nlesions only. Fifteen patients (40.5%) presented\nwith a single lesion. The remaining 22 (59.5%)\ncases, 12 (32.4%) had two lesions, 6 (16.2%) had 3\nlesions and 4 (10.8%) had more than 3 lesions.\nFourteen of our patients (37.8%) reported a positive\nfamily history of similar problem.\n\n\n\nThere were various morphological (Table 1) and\ndistribution pattern of the skin lesions observed\n(Table 2). Twelve patients (32.4%) presented with\nerythematous geographic patches with a \u2018\u2018burnt\u2019\u2019\nappearance at the time of initial presentation.\nTwenty two patients (59.5%), had typical linear\nlesions and 5 patients (13.5%) had demonstrated\nstriking feature of \u2018\u2018kissing lesions.\u2019\u2019 The most\ncommon sites of involvement in descending order\nof frequency were the head and neck (24, 64.9%),\nupper extremities (7, 18.9%), trunk (4, 10.8%) and\nlower extremities (2, 5.4%).\n\n\n\nTable 1 Morphological pattern of the skin lesions of rove beetle \ndermatitis observed in our cohort\n\n\n\nMorphology of the skin lesion\n\n\n\nMaculopapular \n\n\n\n\u201cBurnt like\u201d\n\n\n\nPustular\n\n\n\nVesico-bullous\n\n\n\nWheal like\n\n\n\nNo. of cases (%)\n\n\n\n2 (5.4%)\n\n\n\n12 (32.4%)\n\n\n\n12 (32.4%)\n\n\n\n10 (27.1%)\n\n\n\n1 (2.7%)\n\n\n\nTable 2 Pattern of distribution of the skin lesions of rove beetle \ndermatitis observed in our cohort\n\n\n\nMorphology of the skin lesion\n\n\n\nLinear\n\n\n\nHerpetiformis\n\n\n\nBizzarre\n\n\n\nAnnular\n\n\n\nNo. of cases (%)\n\n\n\n22 (59.5%)\n\n\n\n9 (24.3%)\n\n\n\n2 (5.4%)\n\n\n\n4 (10.8%)\n\n\n\n\n\n\n\n\n41MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nLooking at the reasons for referral to Dermatology\nClinic, only 8 patients (21.6%) were referred for\ninsect related dermatitis. Fifteen patients (40.5%)\nwere referred to rule out herpes zoster infection, 6\npatients (16.2%) to rule out contact dermatitis, 4\npatients (10.8%) to rule out herpes simplex\ninfection and other diagnosis in 4 patients (10.8%).\nNo one was referred as \u201crove beetle dermatitis\u201d. \n\n\n\nThere were limitations of this study; species\nidentification of the rove beetles was not done. In\naddition, skin biopsy of the lesions with\nhistopathological examination was not done.\n\n\n\nDiscussion\nRove beetle dermatitis is the result of\nmucocutaneous contact with the haemolymph of\nmembers of the genus Paederus that contain\npederin9. The genus Paederus belongs to family\nStaphyllinidae, order Coleoptae, class Insecta. The\ngenus Paederus consists of more than 600 species,\nwhich are widely distributed worldwide7. The major\nspecies found in Penang is Paederus fuscipes. Local\nMalay name of Paederus fuscipes is \u201cSemut\nSemai\u201d, \u201cSemut Kayap\u201d or \u201cCharlie\u201d.\n\n\n\nThe rove beetle (Fig 1) is less than 1cm long. The\nbody is dark orange and the tip of the abdomen, the\nupper abdomen and the head are black. The upper\nmiddle iridescent greenish region of the abdomen is\nthe hard wings (elytra). A pair of transparent wings\nare neatly folded and hidden under the hard wings.\nDuring the daytime, the beetle will be seen crawling\naround swiftly with hidden wings resembling ants.\nWhen disturbed it raises the abdomen in a\nthreatening gesture like a scorpion and can fly away.\n\n\n\nThe beetle has been observed in the paddy fields\n(since 1919), school fields - within the grass etc. It\nis carnivorous and eats smaller insects. Thus it plays\nan important role as a biological control of \u2018paddy\npests\u2019. During heavy rains / floods, the beetle may\nmigrate to drier areas. They become active after the\nrains6. \n\n\n\nThe haemolymph in the beetle\u2019s entire body (except\nthe wings) contains the most poisonous animal\ncontact toxin in the world called \u2018pederin\u2019 (C24 H43\n\n\n\nO9 N) named in 19527. It is 12 times more\npoisonous than cobra venom. Dried and stored rove\nbeetle for 8 years still retains its toxicity.\n\n\n\nPaederus beetles can fly, but they prefer to run.\nThey neither bite nor sting, but when crushed\nagainst the skin or the eye, they release a toxin\ncalled pederin which will cause irritation and\nblistering1. Acute irritant contact dermatitis which\ncharacterized by \u2018\u2018burn-like\u2019\u2019 lesions occur within\n12-36 hours after exposure9 (Fig 2). The rashes then\ndevelop into vesicles, bullae or pustules10 (Fig 3 &\n4) which dry out to become crusted and scaly\nwithin a week. The lesions correspond in shape and\ndimensions to the area affected by pederin1. These\nbeetles are highly attracted to artificial light sources\nespecially fluorescent lighting at home7. Our cohort\nis somewhat different from others. Our patients are\nmostly from urban area, away from the paddy\nfields. Most of the patients in our cohort sleep with\nthe light on. This may explain why they have rove\nbeetle dermatitis. \n\n\n\nRove beetle dermatitis occurs predominantly on\nexposed parts of the body. Face and neck were\nfound to be the most commonly involved sites in an\nIranian7 and Pakistani study11. Our study also\nobserved a similar finding. The majority of the\nlesions were on the neck and face.\n\n\n\nOcular involvement in the form of periorbital\ndermatitis and keratoconjunctivitis is not\nuncommon. A periorbital predilection was present\nin 6 patients (25%) of the head and neck lesions in\nour study (Fig 5). It is usually secondary to the\ntransfer of the toxic chemical from elsewhere on the\nskin by the fingers. This is similar to reports of\nperiorbital dermatitis and keratoconjunctivitis\ncaused by blister beetle exposure from Tanzania,\nwhich has been named \u2018\u2018Nairobi eye.\u2019\u201912\n\n\n\n\u2018\u2018Kissing lesions\u2019\u2019 can occur from the spread of\npederin to adjacent skin surfaces, usually on\nflexural surfaces13 (Fig 6). However Zargari et al\nreported that 5 percents had kissing lesions,\nwhereas 5 (13.5%) of our patients had kissing\nlesions. The lesions usually heal completely in 10 to\n12 days with transient post-inflammatory\nhyperpigmentation14. \n\n\n\nAn atypical variant of rove beetle dermatitis has\nbeen reported, which is characterized by diffuse\nerythematous and desquamative lesions\npredominantly on the upper body15. Zargari et al\ndescribed diffuse desquamation and epidermal\nnecrosis in 15 percent of cases, which were not\nfound\n\n\n\n\n\n\n\n\n42 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nfound in any of our patients. The severity of the\nreaction probably is attributable to a more potent\ntoxin produced by the species of Paederus sabaeus\nErichson compared with the Malaysian species,\nPaederus fuscipes.\n\n\n\nThe clinical differential diagnoses of rove beetle\ndermatitis include acute allergic or irritant contact\ndermatitis9, herpes zoster9, herpes simplex7, thermal\nburn1, bullous impetigo and phytophotodermatitis9.\nIn the case of rove beetle dermatitis, the uncommon\nassociation of acute dermatitis with minimal or no\ncomplaints facilitates diagnosis2, which is\ncorroborated by the characteristic linear appearance\nof the lesion, their predilection for exposed area, the\npresence of kissing lesions, Nairobi\u2019s eye and\nepidemiological feature (occurrence of similar\ncases in a given are, the seasonal incidence and\nidentification of insect)16. An interesting point to\ntake note, those who sleep with light on may give an\nadditional clue to the diagnosis of rove beetle\ndermatitis.\n\n\n\nThe treatment of rove beetle dermatitis should be\nthe same as irritant contact dermatitis. Removal of\nirritant, washing with soap and water and\napplication of cold wet compression followed by\ntopical steroid are the mainstay of management. If\nsecondarily infected, topical antibiotic or systemic\nantibiotic will be needed17. Prevention is always\nbetter than treatment. Preventing human-beetle\ncontact is the primary method of preventing pederin\nbased trauma.\n\n\n\nMalaysia as an agricultural and tropical country\nmakes rove beetle more prevalent. However the\nreport on this condition is scarce. The incidence of\nrove beetle dermatitis is probably under-reported.\nThe possible explanation to this being lack of\nawareness among the public and healthcare\nworkers. High index of suspicion among the\nmedical practitioners will aid in early diagnosis and\nprompt treatment17.\n\n\n\nConclusion\nRove beetle dermatitis is a common condition. An\noutbreak of rove beetle dermatitis can occur in any\npart of Malaysia and any time especially after rainy\nseason. Awareness of this condition and its clinical\nfeatures will prevent misdiagnosis and prevent\nunnecessary worry. Simple preventive measures can\n\n\n\nbe undertaken based on the behavioural pattern of\nthis nocturnal beetle.\n\n\n\nReferences\n\n\n\n1. Gelmetti C, Grimalt R. Paederus dermatitis: an easily\ndiagnosable but misdiagnosed eruption. Eur J Pediatr\n1993; 152: 6-8\n\n\n\n2. Sendur N, Savk E, Karaman G. Paederus dermatitis: a\nreport of 46 cases in Aydin, Turkey. Dermatology 1999;\n199: 353-5\n\n\n\n3. Banney LA, Wood DJ, Francis GD. Whiplash rove\nbeetle dermatitis in Central Queensland. Australas J\nDermatol 2000; 41: 162-7\n\n\n\n4. Mokhtar N, Singh R, Ghazali W. Paederus dermatitis\namong medical students in USM, Kelantan. Med J\nMalaysia 1993; 48: 403-6\n\n\n\n5. T. Padhi, P. Mohanty, S. Jena, S. Sirka, S. Mishra.\nClinicoepidemiological profile of 590 cases of beetle\ndermatitis in Western Orissa. Indian J Dermatol Lepro\n2007; 73: 333-5\n\n\n\n6. Sateeka D, Kamaladasa SD, Perera WD, Weeratunge L.\nAn outbreak of paederus dermatitis in a suburban\nhospital in Sri Lanka. Int J Dermatol 1997; 36: 34-6\n\n\n\n7. Zargari O, Kimyai-Asadi A, Fathalikhani F, Panahi M.\nPaederus dermatitis in Northern Iran: a report of 156\ncases. Int J Dermatol 2003; 42: 608-12\n\n\n\n8. Veraldi S, Suss L. Dermatitis caused by Paederus\nfuscipes Curt. Int J Dermatol 1994; 33: 277-8\n\n\n\n9. You DO, Kang JD, Youn NH, Paek SD. Bullous contact\ndermatitis caused by self-applied crushed Paederus\nfuscipes for the treatment of vitiligo. Cutis 2003; 72:\n385-8\n\n\n\n10. Uslular C, Kavukcu H, Alptekin D, Acar MA, Denli\nYG, Memisioglu HR, et al. An epidemicity of Paederus\nspecies in Cukurova region. Cutis 2002; 69: 277-9\n\n\n\n11. Kakakhel K. Acute erosive dermatosis of summer?\nPederus Dermatitis. J Pakistan Assoc Derma 2000; 10\n(1): 6-8\n\n\n\n12. Poole TR. Blister beetle periorbital dermatitis and\nkeratoconjunctivitis in Tanzania. Eye 1998; 12: 883-5\n\n\n\n13. Couppie P, Beau F, Grosshans E. [Paederus dermatitis:\napropos of an outbreak in Conakry (Guinea) in\nNovember 1989.] Ann Dermatol Venereol 1992; 119:\n191-5. French\n\n\n\n14. Borroni G, Brazzelli V, Rosso R, Pavan M. Paederus\nfuscipes dermatitis. A histopathological study. Am J\nDermatopathol 1991; 13: 467-74\n\n\n\n15. Todd RE, Guthridge SL, Montgomery BL. Evacuation\nof an Aboriginal community in response to an outbreak\nof blistering dermatitis induced by a beetle (Paederus\naustralis). Med J Aust 1996; 164: 238-40\n\n\n\n16. Vegas FK, Yahr MG, Venezuela C. Paederus dermatitis.\nArch Dermatol 1996; 94; 175-83\n\n\n\n17. Pushpa Gnanaraj, V. Venugopal, M. Kuzhal Mozhi, C.\nN. Pandurangan. An outbreak of Paederus dermatitis in\na suburban hospital in South India: A report of 123\ncases and review of literature. J Am Acad Dermatol\n2007; 57: 297-300\n\n\n\n\n\n\n\n\n43MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDear Editor,\n\n\n\nWe have encountered identical Chinese twin\nbrothers of 17 years of age presented with\nerythematous scaly plaques on the left side of the\noccipital scalp region since 6 months, almost at the\nsame site in both brothers. Patient denied any\nhistory of psoriasis in the family. On examination\nthere were three erythematous mildly scaly plaques,\nover the occipital scalp region with no hair loss. No\nnail changes were appreciated. Blood investigations\nwere within normal limits, especially ANF and a\nfungal culture.\n\n\n\nPunch biopsies from both twins showed similar\nhistopathologic findings of acanthosis and\nparakeratosis with elongation and widening of rete\npegs and an oedematous suprapapillary dermis and\na perivascular lymphoplasmacytic cell infiltrate  in\nthe dermis consistent with a diagnosis of psoriasis.\n\n\n\nDiscussion\nThe unique aspect of this case report is identical\n\n\n\nGENERAL DERMATOLOGY - Short Communication\n\n\n\nTwin psoriasis\n\n\n\nZaigham Mahmood\n\n\n\ntwins  developing scalp psoriasis simultaneously, at\nthe same site and time. A literature search revealed\nonly a few cases with a similar presentation1.\n\n\n\nPsoriasis has been found to be genetically\ndetermined for single-gene autosomal dominant\ninheritance with reduced penetrance. Twin studies\nconfirm a role for inheritance in psoriasis. A study\nof 61 pairs in whom at least one member of each\npair had psoriasis revealed that 73% of\nmonozygotic pairs, compared with only 20% of\ndizygotic pairs had concordant disease. A Danish\nTwin Register, which included analysis of\nconcordance among monozygotic twins does,\nhowever, indicate that environmental factors\ncontribute to the aetiology. The role of the HLA\nsystem in psoriasis is now well recognized and\nHLA-CW6 has been shown to be strongly\nassociated with psoriasis2.\n\n\n\nThe patients responded well to a combination\nregime of calcipotriol and betamethasone 17-\nvalerate ointment and coal tar shampoo.\n\n\n\nReferences\n\n\n\n1. Singh S, Singh VR,Pandey SS. Psoriasis in identical\ntwins: simultaneous occurrence on same sites.\nDermatol Venerol Leprol 1996;62:308-9\n\n\n\n2. Camp RDR,Psoriasis,6th edn.Text of Dermatology :\nU.K, Blackwell Scientific Publications, 1998;1589-\n1650\n\n\n\nCorrespondence\nDr Zaigham Mahmood\nDepartment of Dermatology\nHospital Queen Elizabeth, Karung Berkunci No.2029\n88586 Kota Kinabalu, Sabah, Malaysia\n\n\n\nBoth twin serial sections show skin with acanthosis and parakeratosis. There is elongation and widening of rete\npegs with oedematous suprapapillary dermis. There is moderate perivascular lymphoplasmacytic cell infiltrate\nseen within dermis.\u201d\n\n\n\nFIRST TWIN HPE SECOND TWIN HPE\n\n\n\n\n\n\n\n\n44 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nA\nbacterial infection\nviral infection\nfungal infection\ndermatitis\nnon-infectious disease\nimpetigo\ntinea capitus\ncontact allergy\npsoriasis\nseborrhoeic capitis\n\n\n\nB\nbacterial infection\nviral infection\nfungal infection\ndermatitis\nnon-infectious disease\npustules\ntinea capitus\neczema herpeticum\npsoriasis\nseborrhoeic capitis\n\n\n\nC\nbacterial infection\nviral infection\nfungal infection\ndermatitis\nautoimmune disease\nskin scalding syndrome\nchickenpox\nSLE\ndermatomyositis\nseborrhoeic dermatitis\n\n\n\nSlide A\n\n\n\nTick at the provided space [\ufffd] against answers that correlate to the slide. \nCheck your answer on page 68. Refer to the given criteria in page 69 to discover your clinical diagnostic skill\nstatus.\n\n\n\nSlide B\n\n\n\nSlide C\n\n\n\nGENERAL DERMATOLOGY - Self Assessment\n\n\n\nClinical diagnostic skill test\n\n\n\n\n\n\n\n\n45MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nD\nbacterial infection\nviral infection\nfungal infection\ndermatitis\nautoimmune disease\nskin scalding syndrome\nchickenpox\nSLE\ndermatomyositis\nseborrhoeic dermatitis\n\n\n\nE\nnon-infective inflammation\nADR\nfungal infection\nviral infection\ncontact dermatitis\ndengue\nviral exanthem\ntinea corporis\ncandidiasis\nerythroderma\n\n\n\nF\nnon-infective inflammation\nADR\nfungal infection\nviral infection\ncontact dermatitis\nskin atrophy\necchymoses\ntinea corporis\ncandidiasis\nerythroderma\n\n\n\nG\nnon-infective inflammation\nADR\nfungal infection\nviral infection\ncontact dermatitis\nskin atrophy\necchymoses\ntinea corporis\ncandidiasis\nerythroderma\n\n\n\nSlide D\n\n\n\nSlide E\n\n\n\nSlide F\n\n\n\nSlide G\n\n\n\n\n\n\n\n\n46 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFor good cosmesis (a hidden, fine-lined scar) &\nproper use of cosmetic injectables, surgical\nplanning must include a thorough knowledge of the\nSTLs. The reconstruction of surgical defects should\nbe designed to minimize perceptible scarring. One\nsuch way is to align the long axis of a repair within\nor parallel to the STLs. This places the scar under\nthe least amount of tension, allowing the scar to fall\nwithin a natural wrinkle. Wounds close more easily\nin this orientation, as the skin is approximately\nthree times more distensible perpendicular to the\nSTLs than parallel.\n\n\n\nTension, created by the intermittent contraction of\nthe muscles of facial expression, is transmitted by\nfibrous bands from the SMAS (superficial\nmusculoaponeurotic system) to the skin. The\nelasticity of the skin with youth opposes this\ntension and maintains a smooth appearance. With\n\n\n\nDERMATOSURGERY - Surgical Tips\n\n\n\nKnow your lines - Skin tension lines of the face (STLs)\n\n\n\nGangaram H\n\n\n\nage, the elastic fibers decrease in their ability to\nresist tension, and collagen fibers elongate,\ndecrease in size, and become cross-linked. With\ndamaged collagen and elastin, linear wrinkles form\nalong the attachments of the SMAS to the skin.\n\n\n\nGenerally these wrinkles, termed skin tension lines\n(STLs), run perpendicular to the underlying muscle\nfibers. For example, the STLs of the forehead are\nhorizontal because the frontalis muscle contracts\nvertically. The skin tension lines of the lateral\nperiocular skin (crow\u2019s feet) radiate away from the\nlateral canthus, as the fibers of the ocularis oculi\ncircumferentially wrap from the superior to inferior\neyelid. The horizontal wrinkles of the upper eyelid,\nwhich at first seem to contradict this principle, lie\nperpendicular to the axis of the underlying levator\npalpebrae superioris.\n\n\n\nIn elderly patients with severe damage, the relaxed\nSTLs will be obvious to any observer. However,\ncertain techniques may be utilized to accentuate\nthese lines where the static wrinkles may not be so\nnoticeable. Furrows can be accentuated by asking\npatients to perform exaggerated facial expressions,\nsuch as smiling, frowning, puckering lips, or\nwhistling. Active manipulation of the skin by a\ngentle pinch or massage may also reproduce the\nnatural folds and tension lines.\n\n\n\nSTLs may be softened or eliminated by cosmetic\ninjectable treatments. Injectable botulinum toxin\ntargets the dynamic STLs and moderately fine\nrelaxed STLs by blunting the actions of the\nunderlying musculature. However, deeper relaxed\nSTLs, accentuated by the gravitational pull of sun-\ndamaged skin, are better treated by injectable\nfillers, which replace volume loss.\n\n\n\nCorrespondence\nDr. Gangaram Hemandas\nPrince Court Medical Centre\n39, Jalan Kia Peng, 50450 Kuala Lumpur\n\n\n\nSkin tension lines\n\n\n\nKey points\n- Skin tension lines are the distinctive furrowed or wrinkled lines on the face.\n- Dynamic & relaxed STLs lie perpendicular to the action of underlying muscle fibers.\n- Lines become more visible & deeper with age & sun damage.\n- Knowledge of the skin tension lines is required for successful cutaneous surgery & proper use of \n\n\n\ncosmetic injectables.\n\n\n\n\n\n\n\n\n47MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTHERAPEUTICS - Original Article\n\n\n\nEfficacy and safety of tacrolimus ointment in patients \n\n\n\nwith moderate to severe atopic dermatitis - Malaysian\n\n\n\nexperience                                                               \n\n\n\nNg TG1, Mardziah A2, Roshidah BB3, Heng YH4, Najeeb A5, Lo Kang SC6, Pubalan M7, Loh LC8, Suraiya HH1\n\n\n\nAbstract\n\n\n\nObjectives To evaluate the efficacy and safety of tacrolimus ointment 0.1% in adult and 0.03% in\npediatric patients with moderate to severe atopic dermatitis in Malaysia.\n\n\n\nMethods This is an open-labeled and single arm multi-center study. 36 adult and 37 pediatric\npatients were enrolled. Tacrolimus ointment is applied twice daily for four weeks. The primary\nefficacy outcome is based on the Physician\u2019s Global Evaluation of Clinical Response (PG) at Week\n4. The secondary efficacy outcomes are Eczema Area and Severity Index (EASI) score, changes\nfrom baseline in individual scores of signs and symptoms and body surface area affected and\nPatients Assessment of Treatment Effects.\n\n\n\nResults Overall success rate were 97.1% and 91.2% in the adult and pediatric groups respectively.\nThe decline in EASI, percentage of total BSA affected and patient\u2019s assessment of pruritus were\nsignificant (P<0.001). Of adults and pediatric patients, 97.2% and 75.7% respectively reported\nadverse effect. The most common adverse effect reported was skin burning sensation in 91.7% adult\npatients and pruritus in 67.6% pediatric patients.\n\n\n\nConclusion Tacrolimus ointment 0.1% in adult and 0.03% in pediatric patients is effective for the\ntreatment of moderate to severe atopic dermatitis in Malaysia.\n\n\n\nKeywords tacrolimus, atopic dermatitis\n\n\n\nCorrespondence\nDr Felix Boon Bin, Yap\nDepartment of Dermatology, Kuala Lumpur Hospital\nJalan Pahang, Kuala Lumpur Malaysia\nEmail : @hot tingguanng mail.com\nConflict of interest : Janssen Cilag supported this study\n\n\n\n1Kuala Lumpur Hospital\n2Pediatric Institute, Kuala Lumpur Hospital\n3Melaka General Hospital\n4Ipoh General Hospital\n5Seremban General Hospital\n6Penang General Hospital\n7Sarawak General Hospital\n8University Malaya Medical Center\n\n\n\nIntroduction\nAtopic dermatitis (AD) is a chronic\nrelapsing, intensely pruritic, inflammatory and\nimmunologically-based skin disease with a genetic\npredisposition where symptoms are often triggered\n\n\n\nby various environmental and psychological.\nfactors1. Tacrolimus ointment is a topical\nimmunomodulator which gives a new therapeutic\noption for atopic dermatitis patients.\n\n\n\nIts mode of action suppresses the activation and\nproliferation of antigen-specific T-cells. This is an\nopen-labeled, single arm, multi-center study\nconducted in seven centers in Malaysia. Patients\nwho met entry criteria were given tacrolimus\nointment to be applied twice daily on affected areas\nfor  four weeks. Pediatric patients (2-15 years old)\nwere given 0.03% tacrolimus ointment and adult\npatients (> 16 years old) were given 0.1%\ntacrolimus ointment.\n\n\n\nObjectives of study\nPrimary objective\nTo evaluate the safety and efficacy of tacrolimus\nointment 0.1% in adult and 0.03% in paediatric\npatients with moderate to severe atopic dermatitis.\n\n\n\n\n\n\n\n\n48 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSecondary objectives\n1. To assess improvement in Eczema Area and \n\n\n\nSeverity Index (EASI)\n2. To assess patient\u2019s assessment of overall response \n3. To determine patient\u2019s assessment of itch \n4. To determine the effect of treatment on quality of \n\n\n\nlife of patients with atopic dermatitis\n\n\n\nPatient Selection:\nInclusion criteria\n\u2022 Patients diagnosed with atopic dermatitis using \n\n\n\nHanifin and Rajka criteria and is rated as \nmoderate to severe based on Rajka and \nLangeland criteria \n\n\n\n\u2022 Body surface area must be at least 10% \n\u2022 Patient is at least 2 years of age \n\n\n\nExclusion criteria\n\u2022 Patients having a skin disorder other than atopic \n\n\n\ndermatitis in the areas to be treated and \npigmentation or extensive scarring in the areas to \nbe treated\n\n\n\n\u2022 Clinically infected atopic dermatitis at baseline \n\n\n\nNon-steroidal immunosuppresants (e.g.\ncyclosporine, methotrexate), light treatments (UVA,\nUVB) or sun exposure, systemic corticosteroids\nand other investigational drugs were not allowed for\n4 weeks prior to start of study and restricted through\nout the study period. Intranasal and/or inhaled\ncorticosteroids, if > 2mg prednisone equivalent /day\nrequired were discontinued for at least 2 weeks\nprior to tacrolimus therapy. Terfenadine and other\nnon-sedating systemic antihistamines were not to\nbe taken 1 week prior to the study. Topical\ncorticosteroids, topical antihistamines and other\nmedicated topical agents were also stopped 1 week\nprior to the study.\n\n\n\nTreatment Plan and Outcome measures:\nPatients were evaluated weekly for four weeks. \n\n\n\nPrimary study endpoint:\n\u2022 Physician\u2019s Global Evaluation of Clinical \n\n\n\nResponse at week 4. \n- Investigators were instructed to use \u2018cleared\u2019\n\n\n\nto indicate improvement of 100%, \u2018excellent\u2019\nfor improvement of 90-99%, \u2018marked\u2019 for\n75-89%, \u2018moderate\u2019 for 50-74%, \u2018slight\u2019 for \n30-49%, \u2018no appreciable improvement\u2019 for\n0-29% and \u2018worse\u2019 for worsening of the \ncondition. \nSecondary endpoints\n\n\n\n\u2022 EASI score \n- EASI is a composite score comprising severity \n\n\n\nrating of erythema, odema / induration /\npapulation, excoriations and lichenification \nweighted according to the estimated \npercentage of affected body surface (BSA) of \neach body region. For each body region\n(head / neck, upper limbs, trunk and lower \nlimbs), an affected area score of 0-6 was \nassigned for the percentage of affected BSA \n(0-100%).\n\n\n\n\u2022 Assessment of Itch \n- Assessment of itch was done by using visual \n\n\n\nanalogue score of scale from 0 to 10.\n\n\n\n\u2022 Quality of Life assessment\n- Patients were assessed on the quality of life \n\n\n\nbefore and at week 4 of study using Finlay \nDermatology Life Quality Index. It assessed \nthe physical and psychosocial aspects of the \ndisease state that may affect the patient\u2019s \nfunctioning. The responses to each survey \nitem ranges from 0 reflecting \u2018not at all \naffected\u2019 to 3, reflecting \u2018very much affected\u2019. \nCategory scores are calculated by summing \nthe score of each question corresponding to its \ncategory.\n\n\n\nStatistical Analysis:\nAll statistical tests were two-sided with significance\nlevel of alpha = 0.05. For efficacy endpoints based\non Physician\u2019s Global Evaluation of Clinical\nResponse, EASI score, changes from baseline in\nindividual scores of signs and symptoms and the\nBSA affected and the Patient\u2019s Own Assessment of\nTreatment Effects, the paired t test was used to\nevaluate. The Wilcoxon signed-rank test was used\nfor nonparametric analyses.\n\n\n\nResults\nDemographic and Baseline Characteristics:\nA total of 73 patients were enrolled from seven\nseparate centers in Malaysia. There were 36\n(49.3%) adult patients and 37 (50.7%) pediatric\npatients. Demographics and baseline characteristics\nwere tabulated. (Table 1) \n\n\n\nTreatment efficacy\nPrimary endpoint\nAt Week-4, Physician\u2019s Global Evaluation of\nClinical Response showed that treatment was\neffective in 34/35 (97.1%) adult patients and 31/34\n(91.2%) pediatric patients (Table 2).\n\n\n\n\n\n\n\n\n49MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 1 Demographic and Baseline characteristics\n\n\n\nDemographic\n\n\n\nMale\n\n\n\nFemale\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nDisease Severity\n\n\n\nModerate\n\n\n\nSevere\n\n\n\nTotal %BSA affected\n\n\n\nAdult (N = 36)\n\n\n\n19 (52.8%)\n\n\n\n17 (47.2%)\n\n\n\n12 (33.3%)\n\n\n\n22 (61.1%)\n\n\n\n2 (5.6%)\n\n\n\n23 (63.9%)\n\n\n\n13 (36.1%)\n\n\n\n32.8 +17.3 (12.5 - 76.0)\n\n\n\nPediatric (N =37)\n\n\n\n21 (56.8%)\n\n\n\n16 (45.2%)\n\n\n\n22 (59.5%)\n\n\n\n12 (32.4%)\n\n\n\n3  (8.1%)\n\n\n\n9 (24.3%)\n\n\n\n28 (75.7%)\n\n\n\n52.5 +21.0 (16.4 - 93.1)\n\n\n\nTable 2 Physician\u2019s Global evaluation of Clinical Response, (p<0.001)\n\n\n\n*Response is defined as a rating of better than moderate (50%) improvement\n\n\n\nSecondary endpoints\nThere was significant improvement in the secondary endpoints. These include EASI\nscore, percentage of body surface area, itch score and patient\u2019s assessment of overall\nresponse. (Fig 1-3 and Table 3)\n\n\n\nScores and Rating\n\n\n\n1 = Cleared (100%)\n\n\n\n2 = Excellent Improvement (90 - 99%)\n\n\n\n3 = Marked Improvement (75 - 89%)\n\n\n\n4 = Moderate Improvement (50 - 74%)\n\n\n\n5 = Slight Improvement (30 - 49%)\n\n\n\n6 = No Appreciable Improvement (0 - 29%)\n\n\n\nAdult\n(N = 35)\n\n\n\n3 (8.6%)\n\n\n\n13 (37.1%)\n\n\n\n10 (28.6%)\n\n\n\n8 (22.9%)\n\n\n\n1 (2.9%)\n\n\n\n0 (0.0%)\n\n\n\nPediatric\n(N = 34)\n\n\n\n0 (0.0%)\n\n\n\n8 (23.5%)\n\n\n\n20(58.8%)\n\n\n\n3 (8.8%)\n\n\n\n3 (8.8%)\n\n\n\n0 (0.0%)\n\n\n\n\n\n\n\n\n50 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 1 Changes in EASI  mean score, p <0.001\n\n\n\nFigure 2 Changes in percentage of body surface area, p<0.001\n\n\n\nFigure 3 Changes in patient\u2019s Itch score, p<0.001\n\n\n\nTotal of % Total BSA (Region 1-4)\n\n\n\nAssessment of Itch\n\n\n\n\n\n\n\n\n51MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAdverse events\nAll 73 patients were included in the safety\nevaluation based on the reported adverse events. In\nboth treatment groups, most of the adverse events\nwere mild in severity. 35 (97.2%) of adult patients\nand 28 (75.7%) of pediatric patients reported\nadverse events. Skin burning sensation in 33\n(91.7%) of adult patients was the most common\nadverse events reported. However, these are mild\nand transient and usually decreasing after 2 to 3\ndays of application.  \n\n\n\nQuality of life assessment\nAll 73 patients in the study reported an\nimprovement in the quality of life after the Week-4\ntreatment. To illustrate the QoL burden of atopic\ndermatitis, Figure 5 and 6 show the percentage of\npatients in adult and pediatric age group\nrespectively at baseline and End of Week 4. They\nwere either very much affected/a lot affected/ a little\naffected, or not at all affected by their skin disease\nfor each of the survey items.\n\n\n\nTable 3 Patient\u2019s assessment of overall response (p<0.001)\n\n\n\nResponse\n\n\n\nMuch better\n\n\n\nBetter\n\n\n\nSlightly better\n\n\n\nSame\n\n\n\nSlightly worse\n\n\n\nWorse\n\n\n\nMuch worse\n\n\n\nAdult\n(N = 35)\n\n\n\n20(57.1%)\n\n\n\n12 (34.3%)\n\n\n\n2 (5.7%)\n\n\n\n0(0.0%)\n\n\n\n0 (0.0%)\n\n\n\n1 (2.9%)\n\n\n\n0 (0.0%)\n\n\n\nPediatric\n(N = 34)\n\n\n\n14(41.2%)\n\n\n\n14(41.2%)\n\n\n\n5(14.7%)\n\n\n\n1(2.9%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\n0 (0.0%)\n\n\n\nTable 4 Adverse Events\n\n\n\nEvent\n\n\n\nAll adverse events\n\n\n\nSkin burning/Stinging\n\n\n\nPruritus\n\n\n\nSkin Erythema\n\n\n\nSkin Infection:\n\n\n\nBacterial\n\n\n\nViral\n\n\n\nAcne\n\n\n\nRash\n\n\n\nOthers\n\n\n\nAdult\n(N = 35)\n\n\n\n35 (97.2%)\n\n\n\n33 (91.7%)\n\n\n\n28 (77.8%)\n\n\n\n10 (27.8%)\n\n\n\n4 (11.0%)\n\n\n\n(0.0%)\n\n\n\n11 (30.6%)\n\n\n\n1 (2.8%)\n\n\n\n9 (25.0%)\n\n\n\nPediatric\n(N = 34)\n\n\n\n28 (75.7%)\n\n\n\n18 (48.6%)\n\n\n\n25 (67.6%)\n\n\n\n4 (10.8%)\n\n\n\n7 (18.9%)\n\n\n\n1 (2.7%)\n\n\n\n2 (5.4%)\n\n\n\n0 (0.0%)\n\n\n\n5 (13.5%)\n\n\n\n\n\n\n\n\n52 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nThis report presents the first clinical experience\nwith topical tacrolimus for Atopic Dermatitis (AD)\ntreatment in Malaysia. Our results show that\ntacrolimus is effective and safe for the treatment of\nmoderate to severe AD in both pediatric and adult\npatients.\n\n\n\nAt Week-4, Physician\u2019s Global Evaluation of\nClinical Response showed that treatment was\nsuccessful in 34/35 (97.1%) adult patients and\n31/34 (91.2%) pediatric patients. Our pediatric\npatients had more severe atopic dermatitis with\nhigher mean percentage of body surface area\ninvolvement, pediatric (52.5%) and adult (32.8%)\nand  mean EASI score, pediatric ( 15.6) and adult\n(11.6). There were significant reductions in\n\n\n\npercentage of body surface area involvement and\nmean EASI score, p value <0.001. \n\n\n\nSubjectively, AD patients also appreciated the\nsignificant improvement in itch score in both adult\nand pediatric patients using visual analog scale. The\nmean itch score had reduced by about 50% after one\nweek of treatment in both groups of patients.\nTransient mild to moderate skin burning at the site\nof ointment application occurred more significantly\nin adult than pediatric patients. The sensation of\nskin burning usually lasts for about 10 to 20\nminutes in the first 2 to 3 days of application.\nPrevious studies have reported the sensation of skin\nburning last around 10 minutes. For the majority of\npatients in this study, this discomfort was not\nsufficient to warrant discontinuation of treatment.\nThe\n\n\n\nFigure 5 Adult Quality of life assessment\n\n\n\nFigure 6 Children Quality of life assessment\n\n\n\n\n\n\n\n\n53MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 7 An 18 year adult patient with erythematous, scaly and excoriated patches over his \nposterior neck and back of knee had marked improvement after 4 weeks of topical \ntacrolimus\n\n\n\nBefore After 4 weeks\n\n\n\nFigure 8 A 2 year old girl with severe erythrodermic atopic \ndermatitis with excellent improvement afte 4 weeks of \ntreatment\n\n\n\nBefore Week 4\n\n\n\nFigure 8 A 2 year old girl with severe erythrodermic atopic dermatitis with \nexcellent improvement afte 4 weeks of treatment\n\n\n\nBefore Week 4\n\n\n\n\n\n\n\n\n54 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe heightened local irritation at start of treatment\ncan probably be attributed to the severity of the\nbaseline disease in the patients, and improved later\nas the lesions healed.\n\n\n\nInfections are particular interest with topical\ntreatments containing immunomodulators because\nof possibility of local immunosuppression.\nPediatric patients reported higher incidence of\nbacterial infections. Only one case of viral infection\nwas reported in pediatric patients. A recent analysis\nof the data set for 1554 patients with AD treated\nwith tacrolimus ointment in five clinical trials\nfound that there was no increase in the risk of\ncutaneous bacterial, viral or fungal infections, even\nwith long term treatment.\n\n\n\nThe Food and Drug Administration (FDA) had\nincluded a \u2018black box warning\u2019. This warning, with\nassociated medication guide, implies that\ntacrolimus ointment pose a significant risk to our\npatients over the long term. The black box warnings\nstate that \u201calthough a causal relationship has not\nbeen established, rare cases of malignancy (e.g. skin\nand lymphoma), have been reported in patients\ntreated with topical calcineurin inhibitors\u201d.\n\n\n\nThe aim of any treatment is to improve the health\nand quality of life of the patient. The considerable\nimprovement in the disease symptoms experienced\nby the tacrolimus treated patients in this study\nmeans a substantial improvement in their quality of\nlife. A study conducted in the USA reported\nsignificantly better health related quality of life\nbenefits in adult and children with AD who were\ntreated with 0.03% and 0.1% tacrolimus ointment\nfor a period of 12 weeks. Although our study was\nonly done in 4 weeks, it had already showed\nimprovement in patient\u2019s QoL benefits in adult and\npediatric patients with AD. The QoL benefits were\nobserved across all QoL categories measured,\nincluding symptoms, feeling, daily activities, sleep\nand treatment impact. Patients treated with\ntacrolimus had attended their school, work and\ninvolved in social activities and sports more often.\nParents of children with atopic dermatitis treated\nwith tacrolimus ointment had observed their\n\n\n\nchildren\u2019s sleep was less affected. Our study showed\nthat tacrolimus ointment 0.03% and 0.1% are\neffective for the treatment of both pediatric and\nadult patients respectively. This result are\ncomparable to those previously reported in Europe3,\nUSA2,5,6, Japan4 and Taiwan7.\n\n\n\nConclusion\nThis study demonstrated that tacrolimus ointment\n0.03% and 0.1% are effective for the treatment of\nboth pediatric and adult patients respectively and\nassociated with significant QoL benefits. The 4\nweek treatment was tolerable to both adult and\npediatric patients. Long term study is needed to\nestablish its long term safety profile. In addition,\ntacrolimus ointment is available in different\nconcentrations (0.03% and 0.1%). Further study\nshould develop guidelines on how to use this\nmodality in long term for AD.\n\n\n\nAcknowledgement\nWe thank Janssen Cilag for their support in this\nstudy.\n\n\n\nReferences\n\n\n\n1. Bos JD, Smitt JHS. Atopic Dermatitis. J Eur Acad\nDermatol Venerol 1996; 7:101-141\n\n\n\n2. Paller A, Eichenfeld LF et al. A 12 week study of\ntacrolimus ointment for the treatment of atopic\ndermatitis in children. J Am Acad Dermatol 2001;\n44:47-57\n\n\n\n3. Ruzicka et al. A short term trial of tacrolimus ointment\nfor atopic dermatitis. N Eng J Med 1997; 337:816-21\n\n\n\n4. S. Reitamo et al. A multicentre, Randomized, double-\nblind, controlled study of long term treatment with\n0.1% tacrolimus ointment in adult with moderate to\nsevere AD. Br J Dermatol 2005; 152:1282-1289\n\n\n\n5. Fleischer AB et al. Tacrolimus ointment for the\ntreatment of atopic dermatitis is not associated with\nincrease in cutaneous infection. J Am Acad Dermatol\n2002; 47:562-70\n\n\n\n6. Kelly PA, Burckart GJ, Venkataramana R. Tacrolimus:\nA new immunosuppressive agent. Am J Health-Syst\nPharm 1995; 52:1521-35\n\n\n\n7. Cheng-Che E, Lan et al. Tacrolimus ointment for the\ntreatment of atopic dermatitis: report of first clinical\nexperience in Taiwan. Kaohsiung J Med Sci 2003;\n19:296-304\n\n\n\n\n\n\n\n\n55MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTHERAPEUTICS - Original Article\n\n\n\nA 5-year retrospective study on the outcome of\n\n\n\npatients with acne vulgaris treated with oral isotretinoin \n\n\n\nin Ipoh Hospital\n\n\n\nTang JJ, MRCP, Chan LC, MMed, Heng A, MRCP\n\n\n\nAbstract\n\n\n\nObjective The purpose of this study is to determine the outcome of patients with acne vulgaris\ntreated with oral isotretinoin from January 2003 till January 2008.\n\n\n\nMethodology This is a 5-year retrospective study of patients with acne vulgaris who were started on\noral isotretinoin from January 2003 to January 2008. Only patients who have completed at least 4\nmonths of treatment were included. Case notes were retrieved and analyzed with regards to\ndemographic data, total cumulative dose of oral isotretinoin, duration of treatment, average daily\ndose of isotretinoin, response, relapse and subsequent treatment. Patients who defaulted follow-up\nwere contacted via phone to ascertain if they had any relapse. Laboratory data that were analyzed\nincluded serial liver enzymes, total cholesterol, triglyceride and LDL levels.\n\n\n\nResults A total of 110 case notes were reviewed but only 83 patients fulfilled the inclusion and\nexclusion criteria. Average daily dose of isotretinoin was 0.24 mg /kg/day and mean duration of\ntreatment was 9.56 months. Mean total accumulated dose of isotretinoin was 61.96 \u00b1 34.15 mg/kg\n(range from 11.18 mg/kg to 151.79mg/kg). There were only 6 (7.2%) patients who achieved total\naccumulated dose of more than 120mg/kg/day. All of our patients responded to treatment with 24\n(28.9%) of them were in complete clearance. However, a high percentage (71.2%) of patients\ndeveloped mucocutaneous side-effects out of which 27.7% required dose reduction. Relapse rate\namong those who completed treatment and follow up or contactable for at least 6 months post\ntreatment was 24.2% (8 out of 33 patients). There were only 3 (3.6%) patients who developed raised\ntransaminases during treatment but all were less than twice the upper normal limit. Mean total\ncholesterol, triglyceride and LDL level were significantly raised at 4 months of treatment when\ncompared to the baseline (p<0.05).\n\n\n\nConclusion Low dose Isotretinoin (<0.5mg/kg) is an effective treatment for moderate to severe acne\nvulgaris in our population. All of our patients showed good response to isotretinoin even though\nsome of them relapsed subsequently. Intolerability as a result of mucocutaneous side-effects seems\nto be a challenging issue when starting isotretinoin in our population.\n\n\n\nKeywords Acne vulgaris, Isotretinoin, Response rate, Relapse rate, Side-effect, Tolerability, Dosage\n\n\n\nCorrespondence\nDr Agnes Heng, MRCP\nDepartment of Dermatology, Ipoh Hospital\nJalan Pahang, Kuala Lumpur Malaysia\nEmail: @hot tingguanng mail.com\n\n\n\nIntroduction\nAcne vulgaris is a chronic, inflammatory disease\nwith a multifactorial aetiology affecting the\npilosebaceous units of the skin. It is extremely\ncommon with a prevalence of 80-85% among\n\n\n\nadolescents which leads to significant physical and\npsychological impact1. It has been reported that\n44% of patients had clinically significant anxiety\nwhereas 18% had depression as a result of acne\nvulgaris2. Systemic isotretinoin revolutionized the\ntreatment of acne when it was introduced in 1982. It\nis the most effective sebosuppressive agent that\nstrongly affects all four major pathogenetic factors\nof acne. The response rate of isotretinoin varies\nfrom one centre to another but generally between\n85% to 96.7%3,4,5,6,7. Relapse occur in 10-25% of\npatients\n\n\n\n\n\n\n\n\n56 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\npatients after one isotretinoin cycle, but often shows\na mild severity grade and can be controlled with\ntopical therapy alone or combined with oral\nantibiotics1. Isotretinoin has always been associated\nwith reports of adverse events ranging from the\nserious side effect such as teratogenicity to the\ncommon mucocutaneous side effect. These side\neffects generally increase at higher daily dose4 and\nthus tolerability can be a problem when higher dose\nof isotretinoin is given to patients. Our main\nobjective of this study is to determine the response\nand relapse rates of our patients with acne vulgaris\ntreated with oral isotretinoin. Secondly we would\nlike to ascertain the side-effects and tolerability of\noral isotretinoin in our local population.\n\n\n\nMethodology\nThis is a retrospective study involving patients with\nacne vulgaris started on oral isotretinoin from\nJanuary 2003 to January 2008 who had completed\nat least 4 months of treatment. Case notes were\nretrieved and analyzed with regards to the following\ndata: age, gender, race, previous treatment, site of\nacne, indication of isotretinoin, average daily dose\nof isotretinoin, total cumulative dose of isotretinoin,\nduration of treatment, response,  relapse and time to\nrelapse, subsequent treatment for relapse, side\neffects, tolerability, liver enzymes and lipid profile.\nWe classified the indication of isotretinoin into 5\ngroups according to the \u201cRoaccutane treatment\nguidelines: results of an international survey\u201d by\nCunliffe et al8,9 as follows: 1) severe/ nodulocystic\nacne vulgaris 2) acne unresponsive to conventional\noral and topical therapies 3) acne patients with\nmarked scarring 4) acne patients with psychological\nproblems such as severe depression or\ndysmorphophobia 5) unusual acne variants\nincluding Gram-negative folliculitis, inflammatory\nrosacea and rosacea fulminans. All patients were\ncounselled  about the side effects of oral\nIsotretinoin especially regarding teratogenicity and\ninformed consent was obtained prior to treatment.\nFor female with childbearing potential, pre-therapy\npregnancy test was done and  they must use 2\nmethod of effective contraception during therapy.\nResponse of treatment is classified into 3\ncategories: 1) complete clearance: total or near total\nresolution of lesion; 2) partial clearance: significant\ndegree of improvement/clearance; 3) non-\nresponder: insignificant improvement or\ndeterioration of lesion. However, there is difficulty\nin categorizing them accurately due to the\nretrospective nature of this study. Relapse is defined\nas deterioration in acne sufficient to merit systemic\ntherapy (antibiotic or oral isotretinoin). Patients\nwho had stopped treatment and followed-up for at\n\n\n\nleast 6 months post-treatment will be included for\nanalysis of relapse rate. Patients who defaulted\nfollow-up were contacted via phone or mail to\nascertain if they had any relapse i.e. if they had been\nprescribed systemic therapy for further flares of\nacne. A patient is considered as non-relapser if acne\nremained stable for at least 6 months after stopping\ntreatment. Intolerability is defined as inability to\ntolerate isotretinoin as a result of side-effects which\nrequired dose reduction. Analyses of laboratory\nabnormalities were performed only in patients who\nhad serial alanine aminotransferase (ALT),\naspartate aminotransferase, total cholesterol, LDL\nand triglyceride recordings. These data were\nanalyzed using Student\u2019s t-test.\n\n\n\nResults\nA total of 110 patients were started on isotretinoin\nfrom January 2003 to January 2008 but only 83\npatients completed at least 4 months of treatment.\nPatient characteristics and clinical data are shown in\nTable 1. Majority of our patients were Malay (41%)\nfollowed by Chinese (37.3%) and Indian (16.9%).\nMost of the patients were male (68.7%) and the\nmean age was 19.5 years old (range from 12 to 43\nyears old). Oral isotretinoin was mainly given as\nsecond-line treatment for moderate-severe acne\nunresponsive to conventional treatment (57.8%).\nMajority of our patients had acne lesions on the\nface and trunk (53%) and most of them had been\nstarted on at least 1 type of oral antibiotic before\nisotretinoin (68.2%). Average daily dose of\nisotretinoin was 0.24 mg/kg/day (Range 0.09 to\n0.53) and mean duration of treatment was 9.56\nmonths. Mean total accumulated dose of\nisotretinoin was 61.96 \u00b1 34.15 mg/kg (range from\n11.18 mg/kg to 151.79mg/kg). There were only 6\n(7.2%) patients who achieved total accumulated\ndose of more than 120mg/kg/day. All of our patients\n(100%) responded to treatment at the end of\ntreatment and 24 (28.9%) of them had complete\nclearance. The partial clearance group was found to\nhave higher average daily dose (0.24 mg/kg/day)\nand total accumulated dose (62.25 mg/kg) of oral\nIsotretinoin as compared to complete clearance\ngroup with average daily dose of 0.22 mg/kg/day\nand total accumulated dose of 61.24mg/kg. Side\neffect profile was purely analysed based on the\nrecords in patient\u2019s notes. There was a high\npercentage (71.2%) of patients who had developed\nmucocutaneous side-effect and out of this, about\n27.7% of them were unable to tolerate the side-\neffect which required dose reduction despite\nappropriate preventive measures. The\ncommencement dose among the patients who had\nintolerability due to mucocutaneous side effect\nranged\n\n\n\n\n\n\n\n\n57MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 1 Demographic data\n\n\n\nRace\n\n\n\nGender\n\n\n\nAge\n\n\n\nSite of acne\n\n\n\nPrevious treatment\n\n\n\nIndication of isotretinoin\n\n\n\nMalay\nChinese\nIndian\nOthers\n\n\n\nMale\nFemale\n\n\n\nMean : 19.5 y/o\n\n\n\nFace\nFace+ trunk\nTrunk\n\n\n\nAntibiotic\nIsotretinoin\nNil\n\n\n\nSevere /nodulocystic acne vulgaris\n\n\n\nAcne vulgaris unresponsive to conventional treatment\n\n\n\nAcne vulgaris with scarring\n\n\n\nAcne with psychological distress\n\n\n\nUnusual acne variants\n\n\n\n41.0%\n37.3%\n16.9%\n4.8%\n\n\n\n68.7%\n31.3%\n\n\n\nRange: 12 to 43 y/o\n\n\n\n45.8%\n53.0%\n1.2%\n\n\n\n68.2%\n5.9%\n\n\n\n25.9%\n\n\n\n30.1%\n\n\n\n57.8%\n\n\n\n12.1%\n\n\n\n0%\n\n\n\n0%\n\n\n\nTable 2 Data relating to treatment with isotretinoin\n\n\n\nDuration of treatment (month)\n\n\n\nAverage daily dose (mg/kg/day)\n\n\n\nTotal Accumulated dose (mg/kg)\n\n\n\nResponse rate\n\n\n\nRelapse rate\n\n\n\nTime of relapse (months)\n\n\n\nTreatment of Relapse\n\n\n\nMean : 9.56 \u00b1 4.74\n\n\n\nMean : 0.24 \u00b1 0.09\n\n\n\nMean : 61.96 \u00b1 34.15\n\n\n\nComplete clearance\n\n\n\nPartial clearance\n\n\n\nNonresponder\n\n\n\nOverall\n\n\n\nMean : 7.75\n\n\n\nAntibiotic + Isotretinoin\n\n\n\nIsotretinoin\n\n\n\nRange:  4 to 27\n\n\n\nRange:  0.09 to 0.53\n\n\n\nRange: 11.18 to 151.79\n\n\n\n28.9%\n\n\n\n71.1%\n\n\n\n0\n\n\n\n8 (24.2%)\n\n\n\nRange: 3 to 17\n\n\n\n4 (50%)\n\n\n\n4 (50%)\n\n\n\nTable 3 Side effect profile\n\n\n\nMucocutaneous side-effects\n\n\n\n1. Cheilitis\n\n\n\n2. Dry skin \n\n\n\n3. Bleeding nose\n\n\n\n4. Nil \n\n\n\nLipid Profile Mean Pre Rx\n\n\n\nTotal cholesterol 4.23\n\n\n\nTriglyceride 0.92\n\n\n\nLDL 2.71\n\n\n\n65.5%\n\n\n\n4.6%\n\n\n\n1.1%\n\n\n\n28.7%\n\n\n\nMean Post Rx p value (student t test)\n\n\n\n4.57 p<0.05\n\n\n\n1.28 p<0.05\n\n\n\n2.93 p<0.05\n\n\n\n\n\n\n\n\n58 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nranged from 0.25 to 0.48 mg/kg. The mean daily\ndose of oral Isotretinoin among patients who\ndeveloped mucocutaneous side effect was 0.24\nmg/kg/day whereas it was 0.22 mg/kg/day among\npatients without mucocutaneous side effect\n(p<0.05). Eighteen patients defaulted follow-up and\nwere not contactable after completing 4 months of\ntreatment. Thirty-two patients were still taking\nisotretinoin at the time this study was conducted.\nThese 2 groups of patients were excluded from\nanalysis of relapse rate. As for the remaining 33\npatients who completed treatment and followed-up\nor contactable for at least 6 months post treatment,\n8 (24.2%) of them developed a relapse after\nisotretinoin was stopped. We were unable to\nascertain the correlation between total accumulated\ndose and relapse rate as the sample size was too\nsmall. The mean time to relapse from the time of\ncessation of isotretinoin was about 7.75 months\n(range from 3 months to 17 months). Treatment\noption for relapse was decided by the treating\ndermatologist based on severity of lesion. 4 of them\nwere given systemic antibiotic initially but\nunfortunately they failed to respond and were put\nback on oral Isotretinoin. The remaining 4 were put\non a second course of isotretinoin from beginning\nof relapse. There were only 3 (3.6%) patients who\ndeveloped raised transaminases during treatment\nbut all were less than twice the upper normal limit.\nOn the other hand, the mean total cholesterol,\ntriglyceride and LDL level were significantly raised\nat 4 months of treatment when compared to the\nbaseline (p<0.05). There were 35 (42.2%) patients\nwith raised total cholesterol, 34 (40.9%) with raised\ntiglyceride and 32 (38.5%) with raised LDL level of\nvarious range following treatment with oral\nIsotretinoin.\n\n\n\nDiscussion\nOral isotretinoin is currently the most effective acne\ntreatment available, with reported long-term\nremission rates as high as 70-89%6. It has been\ntraditionally used as a first line treatment for severe\n(nodulocystic, conglobata) acne vulgaris. Over the\nrecent years, dermatologists have increasingly used\noral isotretinoin to treat acne not responding to\ncombination topical therapy and systemic\nantibiotics. In 2003, European Directive was\nlaunched to harmonize the treatment of acne\nvulgaris with isotretinoin in European countries.\nThe new recommendations suggest isotretinoin\nshould only be used as second-line treatment for\nsevere (nodular, conglobate) acne and acne not\nresponding to an appropriate combination treatment\nby a systemic antibiotic and topical therapy10. The\ninference of this being that it should now not be\nused at all as first-line therapy. The recommended\n\n\n\ncommencement dose of isotretinoin therapy is\n0.5mg/kg with titration up to 1 mg/kg depending on\nindividual response and side-effects. A single 4 to 6\nmonths treatment course is adequate and it should\nideally reach a cumulative dose between 120 and\n150 mg/kg to reduce relapse rates1. This\nrecommended dosage is relatively high and was\nchosen to reduce the time of treatment in view of\nthe isotretinoin associated teratogenicity4. It has\nbeen recommended that lower doses less than 0.5\nmg/kg are also clinically effective but resolution\nmay take longer1.\n\n\n\nIn our study, the mean daily dose of isotretinoin was\nonly 0.24 mg/kg/day which was much lower than\nthe recommended dose. However our mean\nduration of treatment (9.56 months) was longer than\nthe recommended regime. There was a wide\nvariation in average daily dose (range 0.09 to\n0.53mg/kg/day) in our study due to lack of\nstandardization with dose regime of Isotretinoin in\nour centre. Despite using a lower dosage with\nlonger duration, our overall response rate was 100%\nwhich is comparable with 96.6% reported by Ng et\nal (mean daily dose of 0.64 mg/kg/day) from\nSingapore3. Our response rate was also higher than\nthe meta-analysis by Wessels F et al which reviewed\n84.22% to 86.71%7. In view of retrospective in\nnature, there was interobserver variation in the\nmethod of treatment response assessment.\nHowever to our surprise, the partial clearance group\nwas found to have higher average daily dose and\ntotal accumulated dose of oral Isotretinoin as\ncompared to complete clearance group. This may be\nbecause the partial clearance group had more severe\nacne lesion as compared to complete clearance\ngroup and thus required higher dose to control the\nlesions.\n\n\n\nLow-dose protocols (<0.5 mg/kg/day) and\nintermittent protocols have been used by many\nauthors in recent years especially for moderate or\nmild acne with promising response rate ranging\nfrom 69% to 94.8%11,12,13,14. The main reason for\nusing these low dose regime was to reduce side-\neffects and improve tolerability of isotretinoin while\nstill inducing sebum suppression11,12,13,14. Low dose\nregime can be associated with a higher relapse rate\nif the cumulative dose of 120 to 150 mg/kg is not\nreached1. Other factors linked with relapse are\nyounger age (less than 25 years at the beginning of\ntherapy), female sex, truncal acne and acne with\nless than nodular lesions1. Our mean total\naccumulated dose was only 61.96 mg/kg which is\nmuch lower than the recommended cumulative dose\nand in fact there were only 7.2% patients who\nachieved total accumulated dose of more than\n120mg/kg. Despite not achieving the target\ncumulative\n\n\n\n\n\n\n\n\n59MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ncumulative dose, our relapse rate (24.2%) is lower\nthan 47.4% by Ng et al  (Singapore)3 and 39% by\nLayton AM et al (UK)6 who had achieved higher\ntotal cumulative dose than ours. On the other hand,\nour relapse rate was comparable with the studies\nusing low dose and intermittent protocol which\nrange between 9.8% to 39%11,12,13,14.\n\n\n\nThe most serious side-effect is teratogenicity. All\nwomen of child-bearing potential must be coupled\nto a pregnancy prevention program that requires the\nuse of 2 effective contraceptive methods and the\nmonitoring for pregnancy before, during, and after\ntherapy15. Mucocutaneous side-effects including dry\nchapped lip, dry skin and dry eyes are the most\ncommon side effect and are experienced by\nvirtually all patients1. Patients who experience\nsevere mucocutaneous adverse effects should have\ntheir dose regime reduced as the majority of these\nside-effects are dose dependant16. There was a high\npercentage of patients (27.7%) who could not\ntolerate isotretinoin and required dose reduction\ndue to mucocutaneous side-effects. We were unable\nto classify the severity of each mucocutaneous side-\neffect due to the retrospective nature of this study.\nFrom this result we could infer that intolerability\ndue to mucocutaneous side-effects was rather\nsignificant among our population as compared to\nother studies which reported that these side-effects\nare generally manageable8. Hypertriglyceridemia,\nhypercholesterolemia, and elevated liver enzymes\noccurred in 15-25% of patients but were rarely of\nclinical significance or severe enough to require\ndose reduction or discontinuation of treatment16.\nLipids rapidly dropped to pre-treatment levels after\ncessation of therapy16. Our study suggested that\nthere was no significant increment of liver enzymes\nas a result of isotretinoin. This might be due to low\ndose regime used in our population. However the\ntotal cholesterol, LDL and triglyceride were\nsignificantly raised following treatment with\nisotretinoin. It is therefore important to monitor\nfasting lipid profile during the treatment with\nisotretinoin.\n\n\n\nConclusion\nLow dose isotretinoin (<0.5mg/kg) is an effective\ntreatment for moderate to severe acne vulgaris in\nour population. All of our patients showed good\nresponse to isotretinoin even though some of them\nrelapsed subsequently. Intolerability as a result of\nmucocutaneous side-effects was a significant\nproblem when commencing isotretinoin in our\npopulation. There are limitations to our study which\nincluded small sample size for analysis of relapse\nrate and the retrospective nature that made analysis\nof certain data difficult. We suggest a well-designed\nprospective study in future to further evaluate the\n\n\n\nefficacy of low dose isotretinoin and relationship\nwith relapse rate in treating acne vulgaris.\n\n\n\nReferences\n\n\n\n1. Anja Thielitz , Andrea K Rauthelm , & Harald\nGollnick,  Update in retinoid therapy of acne.\nDermatologic Therapy 2006 ; Vol. 19 : 272-279\n\n\n\n2. S.C.Kellett , D.J.Gawkrodger; The psychological and\nemotional impact of acne and the effect. British Journal\nof Dermatology 1999; 140: 273\u2013282\n\n\n\n3. Ng, Patricia Pei-Lin; Goh, Chee-Leok Treatment\noutcome of acne vulgaris with oral isotretinoin in 89\npatients. International Journal of Dermatology 1999;\nVol 38 :207-216\n\n\n\n4. B. Hermes, C. Praetel, B.M. Henz Medium dose\nisotretinoin for the treatment of acne J. Eur. Acad.\nDermatol. Venereol. 1998; 11: 117-121 \n\n\n\n5. Ghaffarpour G, Mazloomi S, Soltani-Arabshahi R,\nSeyed KS. J Drugs Dermatol. Oral isotretinoin for\nacne, adjusting treatment according to patient's\nresponse 2006 ;5(9):878-82 \n\n\n\n6. Layton, A M : Knaggs, H : Taylor, J : Cunliffe, W J\nIsotretinoin for acne vulgaris-10 years later: a safe and\nsuccessful treatment. Br-J-Dermatol. 1993 Sep; 129(3):\n292-6 \n\n\n\n7. Wessels F, Anderson AN, Kropman K. The cost-\neffectiveness of isotretinoin in the treatment of acne.\nPart 1. A meta-analysis of effectiveness literature. S Afr\nMed J. 1999 Jul;89(7 Pt 2):780-4\n\n\n\n8. Cunliffe WJ, van de Kerkho PC, Caputo R, Cavicchini\nS, Cooper A, Fyrand OL, Gollnick H, Layton AM,\nLeyden JJ, Mascar\u00f3 JM, Ortonne JP, Shalita A.\nRoaccutane treatment guidelines: results of an\ninternational survey. Dermatology. 1997;194(4):351-7\n\n\n\n9. Alan J Cooper, Treatment of acne with isotretinoin:\nRecommendations based on Australian experience.\nAustralasian Journal of Dermatology 2003;44: 97-105 \n\n\n\n10. AM Layton,B Dreno, HPM Gollnick,,CC Zouboulis. A\nreview of the European Directive for prescribing\nsystemic isotretinoin for acne vulgaris. Journal\nEuropean Academy of Dermatology and Venereology\n2006 ; 20 :773-776\n\n\n\n11. Amichai B, Shemer A, Grunwald MH. Israel. Low-dose\nisotretinoin in the treatment of acne vulgaris. J Am\nAcad Dermatol 2006 Apr;54(4):644-6 \n\n\n\n12. Mandekou-Lefaki I, Delli F, Teknetzis A, Euthimiadou\nR, Karakatsanis G. Low-dose schema of isotretinoin in\nacne vulgaris. Int J Clin Pharmacol Res. 2003;23(2-\n3):41-6\n\n\n\n13. V.Goulden, S.M. Clark, C. Mcgeown and W.J.\nCunliffe.Treatment of acne with intermittent\nisotretinoin British Journal of Dermatology 1997;137:\n106-108 \n\n\n\n14. Y Kaymak,lter The effectiveness of intermittent\nisotretinoin treatment in mild or moderate acne.\nJEADV 2006 ;20 :1256-1260\n\n\n\n15. John McLane, PhD Nutley, New Jersey. Analysis of\ncommon side effects of isotretinoin J Am Acad\nDermatol 2001;45:S188-94\n\n\n\n16. A. M. LAYTON A review on the treatment of acne\nvulgaris.Int J Clin Pract, January 2006 ; 60, 1: 64-72\n\n\n\n\n\n\n\n\n60 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDear Editor,\n\n\n\nWe report two cases of plaque psoriasis which were\nsuccessfully treated with penicillin. \n\n\n\nCase 1\nA 63-year-old Chinese lady attended Tzu Chi\nHospital, Taiwan in December 2008 with multiple\nitchy erythematous skin lesions over her back,\nchest, abdomen, buttocks, bilateral plantar of foot\nand limbs for 10 years. She was diagnosed to have\npsoriasis by a dermatologist and was prescribed\nwith long term topical steroids with no significant\nimprovement and frequent relapses. After the\nconventional treatment failed, she decided to seek\nanother doctor\u2019s opinion and subsequently she came\nto Tzu Chi Hospital.\n\n\n\nOn examination, there were multiple diffuse silvery\nscales over her back, chest, abdomen, buttocks and\nextremities (Figure 1).\n\n\n\nA skin biopsy was done and histopathology\nconfirmed the diagnosis of psoriasis. Her condition\naffected her physically and emotionally. After\nobtaining consent, she was admitted and started on\nparenteral benzylpenicillin 3 million units 6 hourly.\n\n\n\nTHERAPEUTICS - Short Communication\n\n\n\nPenicillin-treated plaque psoriasis: Report of 2 cases\n\n\n\nfrom Taiwan\n\n\n\nAng XX and Wong SM, MRCP\n\n\n\nShe tolerated the therapy well and her skin\ncondition improved after 2 weeks of therapy. She\nwas subsequently discharged and followed up in\nskin clinic.\n\n\n\nCase 2\nA 57-year-old Chinese lady visited Tzu Chi\nHospital with a background history of psoriasis for\nthe past 7 years. Initially it affected her back and\nelbows, extending to the legs gradually. Over the\nyears, her psoriasis was relatively well-controlled\nwith topical corticosteroid treatment. However, her\ncondition worsened over the past few months with\nincreasing plaques which were itchy.\n\n\n\nOn examination, psoriatic plaques were noted over\nthe whole body sparing the face, palms and soles.\n\n\n\nCorrespondence\nS M Wong, MRCP\nDermatology unit, Department of Medicine\nUniversity Malaya Medical Center, Kuala Lumpur\nE-mail : smwong@um.edu.my\n\n\n\nAng XX, Medical student\nMBBS, University Malaya, Kuala Lumpur\n\n\n\nFigure 1 A 63-year-old lady with erythematous plaques on \nthe sole\n\n\n\nFigure 2 Progression of psoriatic plaque on the forearm \nafter penicillin therapy\n\n\n\nInitial lesion\n\n\n\n6 days after treatment\n\n\n\n10 days after treatment\n\n\n\nFigure 3 The back\n\n\n\n(A) Before treatment (B) 10 days after treatment\n\n\n\n\n\n\n\n\n61MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAs she was keen to try on penicillin, she was\nadmitted and started on parenteral benzylpenicillin\n3 million units 4 hourly. She showed excellent\nimprovement after 10 days of treatment and was\nsubsequently discharged (Figure 2 and 3).\n\n\n\nDiscussion\nIn acute inflammatory or exanthematic psoriasis,\nscaling can be minimal and erythema may be the\npredominant clinical sign.\n\n\n\nChronic plaque psoriasis affects approximately 2\npercent of the world's population and may result in\ndisability similar to or exceeding that associated\nwith other major illnesses, such as diabetes\nmellitus, arthritis, depression, and cancer2.\n\n\n\nThere is a strong relationship between guttate\npsoriasis and streptococcus; either a preceding or\nconcurrent infection3. Some authorities have\nclaimed that chronic plaque psoriasis may worsen\nby infection. There is some evidence that\nstreptococcal infection also plays a role in the\npathogenesis of chronic plaque psoriasis1. It is\npostulated that the streptococcus carries a protein\ncalled the M-protein, which acts as a superantigen.\nSuperantigens are bacterial or viral products that\ncan stimulate T cells to proliferate without prior\nintracellular processing by an antigen-presenting\ncell. This leads to polyclonal T-cell activation with\nrelease of immune cytokines such as interleukin-2,\nwhich are important in the pathogenesis of\npsoriasis. The hypothesis is further supported by the\nexperiment where uninvolved skin from psoriasis\npatients grafted on to severe combined immune-\ndeficient mice will develop psoriasis when injected\nwith autologous superantigen-treated leukocytes4.\n\n\n\nOften times, the use of systemic therapies are\nlimited by their toxic effects and cost. The unmet\nneed for safe and effective therapies, coupled with\nan improved understanding of the pathogenesis of\npsoriasis, has prompted clinicians to use other\nalternative treatment. The usage of penicillin in\nplaque psoriasis is based on the postulation that a\ncontinuing sub-clinical streptococcal infection\nmight be responsible for chronic plaque\npsoriasis.Treatment with benzathine penicillin 1.2\n\n\n\nmillion units intramuscularly fortnightly for 24\nweeks, followed by maintanence dose of 1.2 million\nunits monthly showed excellent improvement at two\nyears5. In addition, throat carriage of Streptococcus\npyogenes is common in patients with chronic\nplaque psoriasis. In our case, both patients showed\ngood respond to the usage of penicillin.\n\n\n\nHowever, a literature review by Cochrane stated that\ntwo controlled trials of antistreptococcal\ninterventions, which involved the use of\nphenoxymethylpenicillin or erythromycin with or\nwithout additional rifampicin revealed no clinical\nimprovement of psoriasis in either treatment group\nthroughout the study6.\n\n\n\nIn conclusion, plaque psoriasis is a chronic problem\nwith high morbidity and significant psychosocial\nimpact on an individual. Although the two reported\npatients showed significant improvement after\ntreatment with penicillin, further well designed,\nrandomized controlled trials are needed to establish\nif there is any place for antibiotic therapy in patients\nwith plaque psoriasis.\n\n\n\nReferences\n\n\n\n1. Tervaert WCC, Esseveld H. A study of the incidence of\nhaemolytic streptococci in the throat in patients with\npsoriasis vulgaris, with reference to their role in the\npathogenesis of this disease. Dermatologica 1970;\n140:1-18\n\n\n\n2. Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr,\nReboussin DM. Psoriasis causes as much disability as\nother major medical diseases. J Am Acad Dermatol\n1999; 41:401-407\n\n\n\n3. Telfer NR, Chalmers RJG, Whale K, Colman G. The\nrole of streptococcal infection in the initiation of guttate\npsoriasis. Arch Dermatol 1992; 128: 39\u00b142\n\n\n\n4. Valdimarsson H, Sigmundsdottir H, Jonsdottir I. Is\npsoriasis induced by streptococcal superantigens and\nmaintained by M-protein-specific T cells that cross-\nreact with keratin? Clin Exp Immunol 1997; 107: 21\u00b14\n\n\n\n5. Saxena VN, Dogra J. Long-term use of penicillin for\nthe treatment of chronic plaque psoriasis. Eur J\nDermatol. 2005 Sep-Oct; 15(5):359-62\n\n\n\n6. Owen CM, Chalmers R, O\u2019Sullivan T, Griffiths CEM.\nAntistreptococcal interventions for guttate and chronic\nplaque psoriasis. Cochrane Database of Systematic\nReviews 2000, Issue 2. Art.No.:CD001976.\nDOI:10.1002/14651858. CD 001976\n\n\n\n\n\n\n\n\n62 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswer is given on page 70\n\n\n\nQuiz\n\n\n\nDermatology Care Plan Quiz for nurses\n\n\n\nState the nursing care plan required by each patient.\n\n\n\ne.g.\nNursing problem Nursing intervention Expected Outcome Comment\nWeeping lesion Wet wrap with astringent Dry scaly lesion Stop using astringent \n\n\n\nsolution regularly when lesions are dry\n\n\n\nSlide A Patient has angioedema following penicillin \ningestion. He had contact pustular reaction \nfollowing calamine lotion application\n\n\n\nSlide B Patient has toe web candidiasis\n\n\n\n\n\n\n\n\n63MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDear Editor,\n\n\n\nWe would like to share with you the nursing\nchallenges faced by nurses while nursing a 17-year\nold teenager with pemphigus vulgaris initially\ninvolving about 20% of cutaneous surface area but\nlater progressed to TEN-like lesions on the second\nweek of admission.\n\n\n\nOn examination, patient was in a flexed posture and\nher range of movements were limited due to\nstiffness and pain. There were large erosions on the\nback covered with haemorrhagic and serous crust\nwith scattered flaccid blisters and crusted erosions\non the face, periorbital, perioral, arms, abdomen,\nthighs and involvement of all mucosal surfaces. Her\npain score was 10 on a visual pain score chart.\n\n\n\nShe was commenced on systemic steroids\n(prednisolone 1mg/kg/day) and oral cloxacillin for\nsecondary impetigo. Azathioprine was added on the\nfourth day of admission when the lesions continued\nto evolve. Cloxacillin was suspectd to have\ncontributed to TEN and was withheld. \n\n\n\nShe was subsequently transferred to the burns\nunit and intravenous (IV) immunoglobulin\n(0.4mg/kg/day) was started and completed for four\ndays. Her response was partial with persistence of\n6% of scattered raw erosions. Currently, she\nrequires high dose oral steroid (1.5g/kg per day),\nazathioprine (2mg/kg/day) and oral doxycyline\n(100mg twice a day) to induce remission.\n\n\n\nNURSING - Short Communications\n\n\n\nNursing challenges in a teenager with pemphigus \n\n\n\nvulgaris and toxic epidermal necrolysis\n\n\n\nHazfaneza AH1, Kasmahwati T2, Noradiah J2, Norhasmie R2\n\n\n\nNursing management \nSupportive and nursing care is an important but\noften underreported therapeutic intervention in\npemphigus. \n\n\n\nThere were several specific issues that need to be\ndealt with specifically in this patient, namely: pain\ncontrol, wound dressing, infection control, diet,\nphysiotherapy as well as the psychosocial aspect.\n\n\n\nPain \nThis is a major problem while managing the patient\nbecause of the extensive area of cutaneous\ninvolvement which appears to be directly\nproportional to her pain score. Her pain was\nassessed every four hours with a visual pain score\nchart. Pain score during skin nursing was 9/10\ndespite oral paracetamol (1g four times per day) and\noral tramadol (50mg thrice a day). Oral tramadol\nwas increased to 100mg thrice a day and IV\nfentanyl (50mcg, 10 minutes before dressing) was\nadded. However, the latter was witheld due to the\npain associated with administration. Patient-\ncontrolled analgesia (PCA) morphine was then\nstarted with better results i.e. her pain score\nimproved to 5/10 during wound dressing. As her\nskin condition recovered, her pain was adequately\ncontrolled with non-narcotic analgesia.\n\n\n\nBesides medications, another technique to\nminimize the pain during wound dressing involved\nplanning and organizing dressing and nursing care\nmaterials prior to exposing the wound so as to\nshorten the dressing time. Also, distractions such as\nstory-telling, music-listening and TV watching\nwere helpful in a young patient such as her.\n\n\n\nDressing\nDressing is a very important part of the\nmanagement of pemphigus. The ideal dressing\nwould be able to keep tissue moisture in while\nallowing enough oxygen to penetrate it and\nmaintaining the integrity of reepithelization. Also,\nin view of the denuded skin, thermoregulation is\ncompromised\n\n\n\nCorrespondence\nDr Hazfaneza Ab Halim\n1Department of  Dermatology\nSelayang Hospital, Selangor, Malaysia\nEmail : \n\n\n\n2Dermatology Nurses, Selayang Hospital\n\n\n\n\n\n\n\n\n64 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ncompromised. Therefore, the challenge here is\nfinding the right dressing, using the right dressing\ntechnique as well as keeping the patient warm and\ncomfortable during the dressing procedure. \n\n\n\nThis patient was dressed in 3 layers: Vaseline\nnetted-gauze, sterile gauze and gamgee from the\ninner to the outer layer. Dressings are changed three\ntimes a day preceded by potassium permanganate\n5% diluted 1:10,000 bath for the first two weeks\nuntil lesions are drier. In view of the frequency of\ndressings, silicon based dressings was not used due\nto cost factors.\n\n\n\nDuring the dressing procedures, adequate analgesia\nwas prescribed as mentioned, and care was taken to\nremove the dressing gently while avoiding\ninadvertent removal of reepthelised skin. This is\npossible with the use of Vaseline netted- gauze and\nthe use of warmed distilled water to soak the gauze\nbefore removing it. \n\n\n\nBath and solutions used are warmed before use and\nroom temperature was increased while dressing or\nbathing is performed. These procedures are also\ndone in parts to allow only body area for dressing to\nbe exposed while other areas are covered with warm\nblankets. Attention is also given to ensure doors and\nwindows are closed during dressing. She was\nplaced in a single room with an attached bath to\nfacilitate her intensive dressing regime.\n\n\n\nOther specific dressing techniques are as follows:\nNormal saline wash for the face three times  per\nday. To remove the crusted lesions, Vaseline was\napplied to it 20 minutes before wash to soften it.\nThe hair was washed with 2% cetrimide shampoo\nonce daily. Frequent normal saline eyes toileting\nwas performed following by local application of\nchloramphenicol ointment at periorbital areas.\nGenitals are washed with diluted potassium\npermanganate every two hours and with every\nurination until the erosions dried up.\n\n\n\nFigure 1 Crusted Haemorrhagic lesion\n\n\n\nFigure 3 Apparent fixed flexion on the neck \non admission. Lower limbus seen\n\n\n\nFigure 2 TEN-like\n\n\n\n\n\n\n\n\n65MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nInfection control\nOur patient was assessed regularly for signs of\ninfection such as increased pain or tenderness,\nswelling, erythema, warmth or temperature for\nearly detection and control of infection. For\ninfection prevention, she was put in reverse\nisolation with strict aseptic technique during\ndressing or any form of contact. Contact with\nvisitors is restricted with the same strict aseptic\nrules. Blisters are prophylatically aspirated not only\nto reduce pain, but also to preserve the roof of the\nblisters which acts as a barrier to infection.\n\n\n\nDiet \nAdequate diet in our patient posed a challenge as\nshe had low intake due to pain from her oral ulcers\nand higher output of fluids and albumin due to\nsignificant area of erosions. To reduce pain during\neating, she was given systemic analgesics as well as\nlocal analgesics such as viscous lignocaine. She\nwas also prescribed triamcinolone in orabase to\nreduce oral inflammation. Concomitant oral thrush\nwas treated with syrup nystatin (500,000 unit four\ntimes per day).\n\n\n\nShe was initially given liquid diet as it is better\ntolerated and supplemented with high caloric and\nprotein liquid. Her diet was closely supervised by\nthe attending dietician and her weight was\nmonitored on a daily basis.\n\n\n\nPhysiotherapy\nEarly assistant from Physiotherapist was required in\nrelieving patient\u2019s torticollis (neck stiffness) and\njoint stiffness due to prolonged immobilisation at\nhome. Immediate care with physiotherapist had\nresulted in marked improvement in this patient. She\nwas able to ambulate slowly from bed to the toilet\nwith assistant from the nurse and family members\non the first day of admission. Passive and active\nlimb and joint movement was introduced.\n\n\n\nSubsequently, she was able to fully flex and extend\nthe neck on 3rd day, rotate the neck at 45 degrees\nand sit on the chair on the 4th day, Ambulate to the\ntoilet independently on the day 5th day and stand,\nrotate in standing position on the 10th day of\nadmission. She is able to balance herself on\nstanding. She had been encouraged to walk around\nin the room. At present, she has no limited joint\nmovement and able to move freely.\n\n\n\nPsychosocial \nThe most important psychosocial issue in our\npatient was dealing with the psychological impact\nof having a disfiguring disease. She was suffering\nfrom low self-self esteem and in this situation,\nfamily and friends support was imperative.\n\n\n\nPatient and family education cannot be stressed\nenough especially because of the chronic nature of\nthe disease. They were also educated on the disease,\nmedications and their adverse effects and wound\ncare which was communicated in simple\nunderstandable terms.\n\n\n\nReferences\n\n\n\n1. Janis S.Johnson. Bullous and Vesicular Disease.\nDermatology Nursing 2007. 19 (3). p292-294\n\n\n\n2. Rohna, Riza et al. How Nurses Can Uphold Corporate\nValues in Dermatology Setting: Clinical  Enviroment\nToxic Epidermal Necrolysis 2004. Published by\nSelayang Hospital 2004. p.48-78\n\n\n\n3. Esther Hughes, Julie Van Onselen. Dermatology\nNursing: A Practical Guide. Elsevier Health Sciences,\n2001. p 251-255\n\n\n\n4. Sandra M. Nettina, Lippincott Willi & Wilkins. The\nLippincott Manual of Nursing Practice : Edition 8.\nLippincott Williams & Wilkins. 2005. p.\n\n\n\n5. Alan B. Fleischer, Steven Feldman, Charity\nMcConnell, et al. Emergency Dermatology : Rapid\nTreatment Guide. McGraw-Hill Professional, 2002.\np.46-50\n\n\n\n\n\n\n\n\n66 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSocial Security Organisation (SOCSO), Malaysia\nprovides benefits to its 5 million workers under the\nEmployee Social Security Act 1989 for loss of\nearning capacity. The employment injury scheme\ncovers loss of earnings due to occupational injury\nand diseases including skin diseases. The invalidity\nscheme provides coverage for loss of earnings due\nto whatever reasons.\n\n\n\nThe Medical and Rehabilitation Department,\nSOCSO with the cooperation of occupational health\nand medicine experts produced the Guidelines on\nthe Diagnosis of Occupational Diseases 2007.\nChapter 14 (pages 108 -122) is on Occupational\nSkin Diseases. The objective is to assist medical\nprofessionals concerned with occupational skin\ndiseases to conduct more objective occupational\nand medical history taking, clinical examinations\nand investigations (general, specific and\nconfirmatory).\n\n\n\nFor diagnostic purposes the skin patch test  is ideal.\nHowever if it cannot be performed due to certain\nreasons, especially among the small and medium\nscale industries, an acceptable alternative is to\nprovide photos of working conditions showing\nevidence of significant exposure to the skin disease\ncausing agents.\n\n\n\nThe Guidelines are essential to determine if the risk\nfactors in the workplace caused the skin disease as\nwell as to exclude other non-workplace factors e.g.\nenvironmental, hereditary, lifestyle or other factors.\nAll these have been specified in the prescribed form\n\n\n\nANNOUNCEMENT - Administrative Update\n\n\n\nGuidelines dor diagnosis of occupational skin disease\n\n\n\nand its compensation\n\n\n\nMohammed AAM, LFOMRCP, Zainul AMH, M SC (OM)\n\n\n\nfor application of occupational disease which has to\nbe filled in by the Occupational Health Doctor after\nconducting a walk-though survey. A supporting\nconfirmatory report from a dermatologist is also\nrequired.\n\n\n\nThe risk factors identified during the course of\ninvestigations are emphasized during the preventive\nprogramme for occupational skin disease. This\nGuidelines is important to the independent medical\nboard and appellate medical board members who\nwill finally decide on whether disease is due to\noccupation or not and subsequently determine the\nimpairment rating.\n\n\n\nUnder the Occupational Safety and Health (OSH),\nRegulations 1996 workplaces with more than 40\nworkers must have a Safety & Health Committee to\ncarry out the hazard identification, risk assessment,\ncontrol and investigations. Under the OSH\nRegulations 1997, the Chemical Safety Data Sheet\nproduced by the manufacturer must include 16\nitems including the toxicology of the chemical and\nif is can be absorbed through the skin, it must have\nthe \u2018skin\u2019 notation. For chemicals that cause skin\ndisease, the personal Permissible Exposure Limit\n(PEL) is spelled out in the OSH, 2000. These PELs\nare adopted from the American Congress of\nGovernment Industrial Hygienist publications. The\nhealth and skin effects of chemicals must be\nconducted according to Assessment of the Health\nRisks Arising from the Use Hazardous Chemicals\nin the Workplace 2000.\n\n\n\nCorrespondence\nDr Zainul Abidin Md Hussain\nMedical and Rehabilitation Department\n10th Floor, Menara PERKESO\n281, Jalan Ampang, 50538 Kuala Lumpur, Malaysia\nEmail : drzainul@perkeso.gov.my\n\n\n\n\n\n\n\n\n67MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nIn Malaysia compensation for occupational skin disease is in accordance with The Guidelines on Impairment\nand Disability Assessment of Traumatic Injuries, Occupational Diseases and Invalidity, SOCSO 2006 as in\nTable 1 \n\n\n\nTable 1 SOCSO 2006 Criteria for Rating Permanent Impairment Due to Skin Disorders\n\n\n\nClass 1\n0% - 11%\nWhole Person\nImpairment\n\n\n\nSkin disorder signs\nand symptoms present\nor intermittently\npresent\n\n\n\nand\n\n\n\nFew limitations in\nperformance of\nactivities of daily\nliving\n\n\n\nExposure to certain\nchemical or physical\nagents may\ntemporarily increase\nlimitation\n\n\n\nand\n\n\n\nRequires no or\nintermittent\ntreatment\n\n\n\nClass 2\n12% - 29%\nWhole Person\nImpairment\n\n\n\nSkin disorder signs\nand symptoms present\nor intermittently\npresent\n\n\n\nand\n\n\n\nLimited performance\nof some activities of\ndaily living\n\n\n\nand\n\n\n\nmay require\nintermittent to constant\ntreatment\n\n\n\nClass 3\n30% - 65%\nWhole Person\nImpairment\n\n\n\nSkin disorder signs\nand symptoms present\nor intermittently\npresent\n\n\n\nand\n\n\n\nLimited performance\nof many activities of\ndaily living\n\n\n\nand\n\n\n\nmay require\nintermittent to constant\ntreatment\n\n\n\nClass 4\n66% - 84%\nWhole Person\nImpairment\n\n\n\nSkin disorder signs\nand symptoms\nconstantly present\n\n\n\nand\n\n\n\nLimited performance\nof many activities of\ndaily living, including\nintermittent\nconfinement at home\nor other domicile\n\n\n\nand\n\n\n\nmay require\nintermittent to constant\ntreatment\n\n\n\nClass 4\n85% - 100%\nWhole Person\nImpairment\n\n\n\nSkin disorder signs\nand symptoms\nconstantly present\n\n\n\nand\n\n\n\nLimited performance\nof most activities of\noccasional to constant\nconfinement at home\nor other domicile\n\n\n\nand \n\n\n\nmay require\nintermittent to constant\ntreatment\n\n\n\n\n\n\n\n\n68 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswers to Clinical Diagnositic Skill Test\n\n\n\nSlide A bacterial infection\nviral infection \nfungal infection\ndermatitis\nnon-infectious disease\nimpetigo\ntinea capitus\ncontact allergy\npsoriasis\nseborrhoeic capitis\n\n\n\nSlide B bacterial infection\nviral infection \nfungal infection\ndermatitis\nnon-infectious disease\npustules\ntinea capitus\neczema herpeticum\npsoriasis\nseborrhoeic capitis\n\n\n\nSlide C bacterial infection\nviral infection \nfungal infection\ndermatitis\nautoimmune disease\nskin scalding syndrome\nChickenpox\nSLE\ndermatomyositis\nseborrhoeic dermatitis\n\n\n\nSlide D bacterial infection\nviral infection \nfungal infection\ndermatitis\nautoimmune disease\nskin scalding syndrome\nchickenpox\nSLE\ndermatomyositis\nseborrhoeic dermatitis\n\n\n\nNote the sign of impetiginous skin - golden crust\nand scales radiating from the corner of the mouth\nand lateral canthus. Similar lesion is seen at the\nneck. The patient appears erythematous because of\nthe underlying toxaemia. This patient has skin\nscalding syndrome which needed prompt antibiotic\ntherapy. Delay in diagnosis worsen morbidity and\nmay be fatal.\n\n\n\nThis infant has seborrhoeic dermatitis on the face\nwith accentuation of shiny, dry and erythematous\nskin on the periorbital, nasolabial fold and perioral\nareas when crying.\n\n\n\nThis infant has seborrhoeic capitis complicated by\neczema herpeticum. The latter is recognized by the\nnumerous monomorphic small round superficial\nulcers with secondary crusting. Failing to\nrecognize this viral infection and continuing\ntopical steroid may result in persistent and\nworsening of the herpes infection.\n\n\n\nThis infant has scalp psoriasis but develop contact\ndermatitis to hair care lotion. Topical steroid\nwould have cleared the lesion. Failing to suspect\ncontact dermatitis and stopping the contact\nallergen may result in patient having recurrent\ncontact dermatitis.\n\n\n\n-2\n\n\n\n-2\n\n\n\n-2\n\n\n\n1\n\n\n\n1\n\n\n\n-2\n\n\n\n-2\n\n\n\n2\n\n\n\n1\n-2\n\n\n\n1\n\n\n\n2\n\n\n\n-2\n\n\n\n-1\n\n\n\n-2\n\n\n\n1\n\n\n\n-2\n\n\n\n2\n\n\n\n0\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n2\n\n\n\n1\n\n\n\n-2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\n-2\n\n\n\n-1\n\n\n\n-1\n-1\n\n\n\n\n\n\n\n\n69MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSlide E non-infective inflammation\nADR\nfungal infection\nviral infection\ncontact dermatitis\nskin atrophy\necchymoses\ntinea corporis\ncandidiasis\nerythroderma\n\n\n\nSlide F non-infective inflammation\nADR\nfungal infection\nviral infection\ncontact dermatitis\ndengue\nviral exanthem\ntinea corporis\ncandidiasis \nerythroderma\n\n\n\nSlide G non-infective inflammation\nADR\nfungal infection\nviral infection\ncontact dermatitis\nskin atrophy\necchymoses\ntinea corporis\ncandidiasis\nerythroderma\n\n\n\nThis patient has cushingoid features - truncal\nobesity, thin limbs and buffalo hump. Thus it is not\nsurprising that she has extensive tinea corporis as\nshown by the annular rash with well define red\nscaly edge and central erythema which is non-\nhomogenous.\n\n\n\nPatient has erythroderma in which the cause may\nbe the result of drug reaction, internal malignancy,\nuncontrolled dermatitis or psoriasis.\n\n\n\nThis gentleman has atrophied skin noted on the\ntrunk which tears and bruise easily. He is\nsuspected of having drug induce skin atrophy and\necchymoses. He admitted to chronic consumption\nof Chinese medication which is probably contain\nsteroid taken to relieve his joint pain.\n\n\n\n-2\n\n\n\n-2\n\n\n\n-2\n\n\n\n1\n\n\n\n1\n\n\n\n-2\n\n\n\n-2\n\n\n\n2\n\n\n\n1\n-2\n\n\n\n1\n\n\n\n1\n\n\n\n-2\n\n\n\n-2\n\n\n\n1\n\n\n\n-2\n\n\n\n1\n\n\n\n-2\n\n\n\n-2\n-2\n\n\n\n-2\n\n\n\n-1\n\n\n\n1\n\n\n\n-2\n\n\n\n-1\n\n\n\n-2\n\n\n\n-2\n\n\n\n2\n\n\n\n0\n-1\n\n\n\nHow did you performed? You should aim for correct diagnosis and minimize delayed diagnosis.\n\n\n\nSum up the number of score 2, 1, 0, -1, -2 and -3 that you have collected.\n\n\n\nSCORE\n\n\n\n-3\n\n\n\n-2\n\n\n\n-1\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\nTOTAL NUMBER COLLECTED IMPLICATION\n\n\n\nDelayed diagnosis may result in irreversible outcome / deformity\n\n\n\nDelayed diagnosis may result in prolonged morbidity\n\n\n\nTherapy for wrong diagnosis may worsen the primary skin lesion\n\n\n\nNo effect on outcome of primary skin lesion but cost wastage of \nmedication, investigation kit and money\n\n\n\nTherapy for this diagnosis can have good outcome\n\n\n\nCorrect diagnosis enables appropriate investigations, thearpy and even \nlong term follow-up\n\n\n\n\n\n\n\n\n70 MJD 2009 June Vol 22\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswers to Dermatology Care Plan Quiz\n\n\n\nSlide A\n\n\n\nNursing problem\n\n\n\nAnioedema\n\n\n\nPustular lesion\n\n\n\nDry scaly skin\n\n\n\nNursing intervention\n\n\n\nAntihistamine\nAvoid urticariogenic food \nAdvice patient on urticaria\npreventive measures\nIssue allergy card\n\n\n\nWet wrap with astringent \nsolution regularly\n\n\n\nMoisturising soap\n\n\n\nExpected Outcome\n\n\n\nNo more periorbital swelling\n\n\n\nDry scaly lesion\n\n\n\nMoist non-scaly skin\n\n\n\nComment\n\n\n\nOn discharge, reeducate patient \nregarding his allergy.\n\n\n\nStop using astringent when \nlesions are dry and scaly. On \ndischarge, reeducate patient \nregarding his allergy.\n\n\n\nStop moisturizing soap when\nskin normalise\n\n\n\nSlide B\n\n\n\nNursing problem\n\n\n\nMacerated toe web\n\n\n\nDry scaly toe webs\n\n\n\nNursing intervention\n\n\n\nPaint toe web with                    \nastringent solution\nUse toe spacer to aerate toe \nwebs\n\n\n\nApply antifungal cream\n\n\n\nExpected Outcome\n\n\n\nDry scaly toe webs\n\n\n\nNormal skin\n\n\n\nComment\n\n\n\nStop astringent solution once \nskin dries up\n\n\n\nStop using antifungal cream\n2 weeks after skin normalised\n\n\n\n\n\n"
"\n\n21MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Case Report\n\n\n\nPrimary Cutaneous Anaplastic Large Cell Lymphoma:\n\n\n\nReport of 3 cases from Hospital Kuala Lumpur                    \n\n\n\nTang MM, Adv M Derm, Chang CC, Adv M Derm, Affandi AM, Roshidah B, FRCP\n\n\n\nCorrespondence\nTang Min Moon, MRCP (UK), AdvMDerm (UKM)\nDepartment of Dermatology\nHospital Kuala Lumpur\nWilayah Persekutuan, Malaysia\nE-mail : minmoon2005@yahoo.com\n\n\n\nIntroduction\nPrimary cutaneous anaplastic large cell lymphoma\n(c-ALCL) is an uncommon type of cutaneous T cell\nlymphoma currently classified as one of the CD30+\nlymphoproliferative disorders of the skin under the\nWHO-EORTC classification1. We describe a series\nof three patients with c-ALCL from 2005-2009 in\nthe Department of Dermatology, Hospital Kuala\nLumpur. \n\n\n\nCase 1\nA 23-year-old clerk presented with a two-month\nhistory of two painful ulcerated plaques with\npurulent discharge at the right lateral thigh and\ninguinal region.  He also had intermittent fever, loss\nof appetite and weight loss of 12 kg during the same\nperiod. Clinically the plaques were indurated and\ntender with had dusky erythematous rolled edges\n(Figure 1.1 & 1.2). There was ipsilateral inguinal\nlymphadenopathy.\n\n\n\nThe blood investigations were normal. Computed\ntomography (CT) scan revealed large matted right\ninguinal lymph nodes. Biopsy of an ulcerated\nplaque showed large abnormal lymphocytes with\npleomorphic nuclei and prominent nucleoli but\nscanty cytoplasm. Mitoses was  readily visible. The\ncells were stained positive to CD30 and epithelial\nmembrane antigen (EMA) but negative to CD20,\nCD3, CD15 and anaplastic lymphoma kinase\n(ALK) (Figure 1.3-1.4).\n\n\n\nMulti-agent chemotherapy consisting of\ncyclophosphamide, doxorubicin, vincristine and\nprednisolone (CHOP) was started. All lesions\nresolved completely following completion of four\ncycles of chemotherapy. \n\n\n\nCase 2\nA 60-year-old gentleman presented with multiple\npainful ulcerated plaques over the left foot and left\nleg for 10 years. There were no constitutional\nsymptoms. Clinically, there was an indurated\nannular plaque studded with ulcers of various sizes\nat the left shin and an ulcerated plaque over the left\nsole. There was ipsilateral inguinal\nlymphadenopathy (Figure 2.1 & 2.2).\n\n\n\nThe blood investigations and CT scan of the thorax,\nabdomen and pelvis were normal except for left\ninguinal lymphadenopathy. Skin biopsies of the\nskin lesions demonstrated dense infiltration of large\ncells with pleomorphic nulcei and prominent\nnucleoli but scanty cytoplasm in the dermis and\nsubcutaneous tissue. Frequent mitoses was  evident.\nThe cells were stained positive to CD3 and CD30\nbut negative to CD20 and ALK (Figure 2.3-2.6).\n\n\n\nHis skin lesions partially regressed with six cycles\nof CHOP with bleomycin. However, despite\nadditional six cycles of cyclophosphamide,\nprocabazine, prednisolone and methotrexate, he\nonly achieved partial remission and experienced a\nrelapse later. He subsequently received\nsubcutaneous beta-interferon for a year.\n\n\n\nDuring the last review, he had no new lesions, but\nthe pre-existing lesions had not healed completely.\n\n\n\nKeywords CD30+ lymphoproliferative disorders, cutaneous T cell lymphoma, ulcerated plaques\n\n\n\n\n\n\n\n\n22 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFigure 1.1 & 1.2 Patient 1 has ulcerated plaques at the right inguinal region and right lateral thighs with rolled edges.\nThe hypopigmented depressed patch beside the ulcerated plaque is from a previously healed ulcer. Figure 1.3 Histology of\nthe right inguinal ulcerated plaque showed dense dermal infiltration of large abnormal lymphocytes with pleomorphic\nnuclei and prominent nucleoli. Figure 1.4 The abnormal cells stained positive for CD30.\n\n\n\nFigure 2.1 & 2.2 Patient 2 has multiple indurated annular plaques with shallow ulcers of various sizes at the left shin and\nleft sole. Figure 2.3 & 2.4 Histology of the biopsy on the indurated plaque of left sole showed dense infiltration of large\ncells with prominent nuclei but scanty cytoplasm. Figure 2.5 & 2.6 The abnormal cells stained positive for CD3 and CD30.\n\n\n\n\n\n\n\n\n23MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nCase 3\nCJC was a 69 year-old gentleman presented with 5\nmonth history of widespread pruritic erythematous\npapules, nodules and plaques over the face, neck,\ntrunk, upper and lower limbs. He had intermittent\nfever with night sweats, anorexia and weight loss of\n5 kg in the preceding two months.\n\n\n\nClinically, there were disseminated erythematous\nnodules and plaques on the right temporal area,\nneck, trunk, and extremities. There was no\nhepatosplenomegaly or lymphadenopathy.\n\n\n\nBlood investigations and CT scan revealed no\nabnormality. Skin biopsy demonstrated dense\nintradermal and subcutaneous infiltration of large\nlymphoid cells with prominent nucleoli. Mitoses\nwere abundant. \n\n\n\nThe cells stained positive to CD30, CD3 and EMA\nbut negative to CD20 and ALK.\n\n\n\nMulti-agent chemotherapy consisting of\ncycloposphamide, vincristine, prednisolone and\nsubcutaneous alemtuzumab was administered. This\nwas followed by two cycles of cyclophosphamide,\nvincristine, doxorubicin, dexamethasone,\nintrathecal methotrexate and subcutaneous\nalemtuzumab. Subsequently 3 cycles of\ngemcitabine, dexamethasone and cisplatin were\ngiven. His overall response to treatment was poor.\nSome nodules at the inguinal region became\nulcerated. He died at home 7 months after\ndiagnosis. \n\n\n\nDiscussion\nPrimary cutaneous anaplastic large cell lymphoma\n(c-ALCL) affects mainly adults with a male-to-\nfemale ratio of 1.47-3:11-3. Incidentally, all three of\nour patients were male. The mean age of onset is 52\nyears. Our first patient acquired this disorder at 23\nyears of age. The youngest patient ever reported in\nthe literature was a 2-year-old female2.\n\n\n\nThe clinical presentation range from solitary or\nlocalized lesions to multifocal nodules or tumors,\nsome of which can be ulcerated and some may\nregress spontaneously. The term localized refers to\na few clustered lesions restricted to one anatomic\narea generally not exceeding 15x15cm3. In our\n\n\n\nseries, we described two patients who had localized\nnodules and plaques with only draining lymph\nnodes involvement, and a patient with multifocal\nnodules. In the first patient, the initial ulcerated\nplaque at his right thigh resolved transiently but\nsubsequently recurred. \n\n\n\nPrimary c-ALCL must be distinguished from\nanaplastic transformation of other cutaneous\nlymphoma especially mycosis fungoides, and\ncutaneous infiltration of a systemic anaplastic large\ncell lymphoma (systemic ALCL). Transformed\nmycosis fungoides can be distinguished by the\npresence of patches or plaques for years. There is\nepidermotropism seen histologically. It carries a\npoorer prognosis. Systemic ALCL should be\nsuspected if any extracutaneous disease other than\nregional lymph node involvement is detected.\nALK+ primary systemic ALCL frequently affects\nyounger patients and is more responsive to\nchemotherapy whereas ALK- primary systemic\nALCL carries a poorer prognosis.\n\n\n\nHistological examination of a lesion of cALCL\ntypically shows a diffuse infiltrate composed of\nlarge cells with an anaplastic, pleomorphic, or\nimmunoblastic cytomorphology and expression of\nthe CD30 antigen by more than 75% of the tumor\ncells1. This was demonstrated in all our patients.\nThe tumour cells were CD30+ but ALK-. A\ncomplete immunophenotyping of neoplastic cells\ngenerally show an activated CD4+ T-cell phenotype\nwith variable loss of CD2, CD5, and/or CD3, and\nfrequent expression of cytotoxic proteins\n(granzyme B, TIA-1, perforin)1,5. Some cases (less\nthan 5%) have a CD8+ T-cell phenotype. Unlike\nsystemic CD30+ lymphomas, most c-ALCLs\nexpress the cutaneous lymphocyte antigen (CLA),\nbut do not express epithelial membrane antigen\n(EMA) and anaplastic lymphoma kinase (ALK)\nwhich indicate the 2;5 chromosomal translocation\nor its variants. In contrast to Hodgkin and Reed-\nSternberg cells in Hodgkin disease, staining for\nCD15 is generally negative. Co-expression of CD56\nis observed in rare cases, but does not appear to be\nassociated with an unfavorable prognosis. The\nexpression of differentiation and activation markers\nin various CD30+ lymphoproliferative diseases is\nshown in Table 1.\n\n\n\n\n\n\n\n\n24 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe choice of treatment in c-ALCL is based on the\nsize, the extent, and the clinical behavior of the skin\nlesions. Solitary or localized nodules or plaques can\nbe treated with radiotherapy or surgical excision1.\nPatients with multifocal skin lesions or regional\nlymph node involvement may respond to systemic\ntherapies such as methotrexate, systemic retinoids,\ninterferon-alpha or anti-CD30 monoclonal\nantibody. Single or multiagent chemotherapy may\nbe required in resistant cases. Our first and second\npatients who had localized plaques were treated\nwith multiagent chemotherapy because the\nlocations of the ulcerated plaques were not practical\nfor complete excision or radiotherapy. Besides,\nthere was regional lymph node involvement. Our\nsecond and third patient did not respond well to\nmultiagent chemotherapy. Autologous bone marrow\ntransplantation may be considered in these\npatients4. \n\n\n\nThe prognosis of c-ALCL is reported to be good\nespecially in solitary and localized disease.\nBekkenk et al3 reported excellent prognosis in 79\npatients with primary c-ALCL, with 5- and 10-year\ndisease-related survival rates exceeding 95%. In the\nsame report, the prognosis of 11 patients who had\nregional lymph nodes involvement was also good,\nwith 5- and 10-year disease-related survival rates of\n91%. Our second patient survived the tumour for 14\nyears. The third patient who had disseminated\nlesions succumbed 7 months after diagnosis despite\naggressive multiagent chemotherapy. \n\n\n\nAcknowledgement\nWe would like to thank Dr Lee Bang Rom,\nConsultant Pathologist of Universiti Putra Malaysia\nfor his contribution.\n\n\n\nReferences\n\n\n\n1. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E,\nSwerdlow SH et al. WHO-EORTC classification for\ncutaneous lymphomas. Blood. 2005;105:3768-85\n\n\n\n2. Beljaards RC, Kaudewitz P, Berti E, Gianotti R,\nNeumann C, Rosso R et al. Primary cutaneos CD30-\npositive large cell lymphoma: definition of a new type\nof cutaneos lymphoma with favorable prognosis. A\nEuropean multicenter study of 47 patients. Cancer\n1993;71:2097-2104\n\n\n\n3. Bekkenk M, Geelen FAMJ, van Voorst Vader PC, et al.\nPrimary and secondary cutaneous CD30-positive\nlymphoproliferative disorders: long term follow-up\ndata of 219 patients and guidelines for diagnosis and\ntreatment: a report from the Dutch Cutaneous\nLymphoma Group. Blood. 2000;95: 3653-3661\n\n\n\n4. Shehan JM, Kalaaji AN, Markovic SN, Ahmed I.\nManagement of multifocal primary cutaneous CD30+\nanaplastic large cell lymphoma. J Am Acad Dermatol\n2004;51:103-10\n\n\n\n5. Burg G, Kempf W. Cutaneous Lymphoma. In Taylor &\nFrancis Group Ed. Florida.2005: 61\n\n\n\nDisorders\n\n\n\nLymphomatoid\npapulosis\n\n\n\nPrimary cutaneous\nALCL\n\n\n\nCtaneous infiltration of\nsystemic ALCL\n\n\n\nHodgkin lymphoma\n\n\n\nCD30\n\n\n\n+\n\n\n\n+\n\n\n\n+\n\n\n\n+\n\n\n\nCD15\n\n\n\n+ (50%)\n\n\n\n-\n\n\n\n+\n\n\n\n+\n\n\n\nCD45RO\n\n\n\n+\n\n\n\n+\n\n\n\n-\n\n\n\n-\n\n\n\nALK\n\n\n\n-\n\n\n\n- (rarely +)\n\n\n\n+ (65%)\n\n\n\n-\n\n\n\nEMA\n\n\n\n-\n\n\n\n-\n\n\n\n+\n\n\n\n-\n\n\n\nHOXC5\n\n\n\nn.a.\n\n\n\n++\n\n\n\n+\n\n\n\nn.a.\n\n\n\nTable 1 Expression of differentiation and activation markers in various CD30+ lymphoproliferative diseases5\n\n\n\nAbbreviation: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; EMA, epithelial membrane antigen; CD,\ncluster of differentiation; HOXC5, homeobox C5 expression; n.a., not applicable\n\n\n\n\n\n\n\n\n25MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Short Communication\n\n\n\nCutis Verticis Gyrata Secondary to Congenital\n\n\n\nMelanocytic Naevus - A case report\nPanicker VP, DNB, Dhamramaratnam AD, DVD, Kuruvilla PJ, MD\n\n\n\nCorrespondence\nVinitha Varghese Panicker, MD, DVD, DNB\nDepartment of Dermatology\nAmrita Institute of Medical Sciences, Cochin\nE-mail : vinithavpanicker@aims.amrita.edu\n\n\n\nIntroduction\nCutis verticis gyrata is characterised by hypertrophy\nand folding of skin of scalp leading to gyrated\nappearance. Polan and Butterworth1 classified it\ninto primary and secondary forms. Secondary CVG\nhas been described with a wide variety of causes.\nCongenital melanocytic neavus appears to be the\nmost common2. However it has been described with\nother naevoid abnormalities like Neavus\nlipomatoses, connective tissue nevi, genetic\ndisorders such as neurofibromatoses, and endocrine\ndisorders like acromegaly.\n\n\n\nCase report\nA 3 yr old boy presented with increased folding of\noccipital region of scalp since past 1 year. The\nparents reported that he had a hyperpigmented\n\n\n\nlesion in that area since birth. The developmental\nmilestones were normal. Examination revealed 26 x\n20 cm hyperpigmented plaque covering almost\nwhole occipital region extending to temporal and\nparietal regions (Fig. 1). Parallel folds of skin were\nseen in occipital region, hair growth over the plaque\nwas relatively normal.\n\n\n\nBiopsy from the rugous area showed epidermis with\nprominent acanthosis. The upper dermis show small\nnodules of deeply pigmented naevus cells. The\nnevus cells are seen extending down into deeper\ndermis as single cells insinuating between collagen\nand also going around the follicular structures (Fig.\n2). These features were suggestive of intradermal\nnaevus. Our patient was referred to plastic surgery\nwhere he underwent wide excision and tissue\nexpansion.\n\n\n\nFigure 1 Hyperpigmented plaque on the scalp Figure 2 Histopathological examination indicating\nintradermal naevus\n\n\n\nKeywords scalp lesion, newborn, intradermal naevus\n\n\n\n\n\n\n\n\n26 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nCutis verticis gyrata is hypertrophy of scalp skin\nwith parallel or gyrate folds. Various causes of cutis\nverticis gyrata are: - Hereditary, traumatic,\nendocrinal, inflammatory, tumours and in\nassociation with other conditions. Congenital\nmelanocytic naevus is seen in 1-2 % of newborns3.\nThe naevus cells are derived from epidermal\nmelanocytes4.\n\n\n\nThere are 3 types of congenital melnocytic neavi\naccording to size-small, intermediate and giant.\nCerebriform melanocytic naevus is a rare form of\ngiant naevus5. The naevus may present as a\nconvoluted mass over the scalp.They have high risk\nfor malignancy, the most common is malignant\nmelanoma in 1.8-42% cases6. In cases of\ncerebriform intradermal naevus, treatment is by\nwide surgical excision and plastic reconstruction.\nThis case is being reported because the\nsimultaneous occurrence of these two entities is\nrare.\n\n\n\nReferences\n\n\n\n1. Polan S, Butterworth T. Cutis verticis gyrata: a review\nwith report of seven new cases. Am J Ment Defic 1953;\n57:613-31\n\n\n\n2. de berker DAR, Messenger AG, Sinclair RD. Disorders\nof hair in Burns T, Breathnach S, Cox N, Griffiths C\neditors Rooks textbook of Dermatology & 7th ed USA:\nBlackwell; 2004.p.63.68\n\n\n\n3. Elder D, Elenitsas R. Benign pigmented lesions and\nmalignant melanoma. In: Lever's Histopathology of\nSkin, 8th ed. Elder D et al editors 644-645\n\n\n\n4. Metcalf JS, Maize JC. Melanocytic nevi and malignant\nmelanoma. Dermatologic Clinics 1985; 3: 218\n\n\n\n5. Pai VG, Rao GS. Congenital cerebriform melanocytic\nnaevus with cutis verticis gyrate. Indian J Dermatol.\nVenereol Leprol 2002; 68 p367-8\n\n\n\n6. Zitelli JA, Grant MG. Histologic pattern of congenital\nnevocytic nevi and implication for treatment. J Am\nAcad Dermatol 1984;11:402\n\n\n\n\n\n\n\n\n27MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1a) Tick the possible clinical differential\ndiagnosis\n\n\n\nCellulitis\nCutaneous malignancy\nLupus profundus\nContact dermatitis\nMorphoea\n\n\n\nCase 1\n71year-old, housewife presented with 4 months of progressive painless pruritic indurated plaques at\npreauricular area. There\u2019s history of contact with black hair dye for 5 years, spectacles with metal frame, black\nmetal hair pins. Patch test was positive to Fragrance mix, nickel, Black shampoo with irritation to organic\nacid cleansing foam.\n\n\n\n1b) Tick the possible histopathological \nexamination differential diagnosis\n\n\n\nEosinophilic\nCellulitis\nAngiosarcoma\nLupus profundus\nContact dermatitis\nMorphoea profundus\n\n\n\nGENERAL DERMATOLOGY - Self Assessment\n\n\n\nClinicopatholgical Challenge\nDawn A1, Lee BR2, Latifah3\n\n\n\nCorrespondence\nDawn Ambrose\n1Department of Dermatology, Hospital Kuala Lumpur\n2Department of Dermatology, Universiti Putra Malaysia\n3Department of Pathology, Hospital Kuala Lumpur\n\n\n\n\n\n\n\n\n28 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2a) Tick the possible clinical differential \ndiagnosis\n\n\n\nPsoriasis\nSarcoidosis\nCutaneous tuberculosis\nLichen planus\nSyphilis\n\n\n\nCase 2\n37-year old, lorry driver with a 3 months history of scaly, well demarcated plaques on the face, trunk & legs.\n\n\n\n2b) Tick the possible histopathological \nexamination differential diagnosis\n\n\n\nLichen planus\nCutaneous malignancy\nPsoriasis\nSarcoidosis\nSyphilis\n\n\n\n2c) Tick the possible provisional diagnosis\n\n\n\nLichen planus\nCutaneous malignancy\nPsoriasis\nSarcoidosis\nSyphilis\n\n\n\n\n\n\n\n\n29MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSNIPPETS ON DERMATOLOGY DEVELOPMENT IN THE 1ST DECADE OF THE MILLENIUM\n\n\n\nAsian Academy of Dermatology and Venereology\n\n\n\n(AADV)\nSteven KW Chow\n\n\n\nIn 2002 at the 15th Regional Conference of\nDermatology in Manila, the Council of the LADS\nmet, deliberated and unanimously approved the\nproposal for the formation of the Asian Academy of\nDermatology and Venereology.\n\n\n\nThe executive plan of the AADV calls for a\nstructured program of dermatology CME/CPD\nevents in Asia coordinated regionally to maximize\n\n\n\nPresident: Professor Unandar Budimulya (Indonesia)\n\n\n\nDeputy Vice-Presidents: Madhuri Majumder (Malaysia) / Tranh Hau Khang (Vietnam)\n\n\n\nSecretary-General: Steven KW Chow (Malaysia)\n\n\n\nHonorary Treasurer: Chew Hon Nam (Malaysia)\n\n\n\nBoard members: Nopadon Nopakkun (Thailand)\n\n\n\nYosihki Miyachi (Japan)\n\n\n\nChetan Oberai (India)\n\n\n\nAzer Rashid (Pakistan)\n\n\n\nGeorgina Pastorfide(Philippines)\n\n\n\nSeow Chew Swee (Singapore)\n\n\n\nMardziah Alias (Malaysia)\n\n\n\nTiti Lestari (Indonesia)\n\n\n\nThirty five senior dermatologists were conferred with the Fellowship of the Academy (FAADV).\n\n\n\nthe use of resources within the region. The primary\nobjective of the AADV is to provide the platform to\nmerge all major stakeholders in the field of\ndermatology in Asia.\n\n\n\nIn 20 November 2009 at a simple historical\nceremony at Hilton Opera Hanoi the AADV was\nformally inaugurated with the election of a\nFoundation Board of the AADV consisting of:\n\n\n\nCorrespondence\nSteven KW Chow\nSecretary-General\nAADV\n\n\n\n\n\n\n\n\n30 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe Second Annual Summit of the AADV was held on 20th October 2010 in the city of Kota Kinabalu, East\nMalaysia. It was a meeting incorporated with the 19th Regional Conference of Dermatology (Asian-\nAustralasian).\n\n\n\n70 Foundation Fellows and 10 Honorary Fellows were installed.\n\n\n\nThe FAADV board was further expanded to include Vinchet Chan(Cambodia), Lai Wei (China), Prof Chrang\nShi-Lin(Taipei), Professor Soyun Cho(Korea); JoAnne See (Australia).\n\n\n\nThe Board approved the development of a one year training program for dermatopathology leading to the\naward of a Fellowship in Dermatopathology [FAADV (Dematopathology)] to be initiated in 2011.\n\n\n\nThe Charter of the AADV shall be\n\n\n\n1. To represent and to develop the specialty of dermatology among the members of Asian national \ndermatological Societies/Associations\n\n\n\n2. To enhance the status and the independent development of the various national, regional societies \nand associations like the LADS and the ADA\n\n\n\n3. To act as an avenue to cater for the participation of members of other national dermatological \nsocieties currently not in either the LADS or the ADA\n\n\n\n4. To enhance the development and sharing of best clinical practice in dermatology in Asia\n\n\n\n5. To be the platform for the development of harmonisation of standards in dermatology amongst the \nAsian countries\n\n\n\n6. To enhance cross-border social development, fellowship and technical exchange in dermatology in \nAsia\n\n\n\nMission Statement:\n\"Leadership in sharing and caring for dermatology across borders in Asia\"\n\n\n\nAADV Logo\n\n\n\n\n\n\n\n\n31MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSNIPPETS ON DERMATOLOGY DEVELOPMENT IN THE 1ST DECADE OF THE MILLENIUM\n\n\n\nMalaysian Dermatological Society\u2019s Internet Milestones\nHenry FBB\n\n\n\nCorrespondence\nHenry Foong MBBS FRCP Edin\nUniversiti Kuala Lumpur\nRoyal College of Medicine Perak\nE-mail : bbfoong@gmail.com\n\n\n\nIt is amazing how much we have changed over the\nlast decade. Digital technology has changed the\nworld in profound and exciting ways. The Society\nhas its website established by Dr Allan Yee in 2006\nand was located at www.dermatology.org.my. The\nwebsite gives a brief overview of our mission\nstatement, activities and contributions to continuing\nmedical education for the general public about the\nlargest organ in the body - our skin.\n\n\n\nOne of the most frequently visited pages of the\nwebsite was the list of dermatologists in Malaysia.\nWe have many enquiries from the public requesting\nfor the list of certified dermatologists in their area\nto consult regarding their skin problems. Among\nother frequently visited pages of the website are\nNews and Events which inform members of the\nvarious CME activities in the Society, and Members\nSection where online medical journals are available\nfor viewing. The archives of the Malaysian Journal\nof Dermatology can be accessed through the\nMembers Section of the website. The Psoriasis\nAssociation of Malaysia also maintains a strong\npresence in the society website.\n\n\n\nAccess to online journals is also available to the\nmembers of the Society. The Society has subscribed\nto 2 journals which are Dermatologic Therapy and\nDermatologic Surgery. Members can view and\n\n\n\ndownload the articles from these journals when they\nare reviewing their patient problems and when they\nare writing articles. The latest addition to the list of\nonline journals available to members is Practical\nReviews in Dermatology where one not only can\ndownload commentaries from review articles but\ncan listen to the commentaries from their iPod or\niPad.\n\n\n\nOne of the Society members Dr Henry Foong had\nestablished a virtual grand rounds in dermatology in\n2000 which is a web based global dermatology\nnetwork and gathering place for dermatologists at\nall levels of training to present challenging and\ninteresting cases and to ask questions of colleagues\nwith particular utility for those practising away\nfrom university hospitals and tertiary centres and in\ncountries where resource materials and mentors are\nin short supply. Our members can use this virtual\ngrand round to present challenging and difficult\ncases and get feedback from seasoned\ndermatologists from around the world.\n\n\n\nReferences\nStephanie WH, Henry BBF, David JE\nVirtual Grand Rounds in Dermatology : an 8-year\nexperience in web-based teledermatology. Int J Dermatol\n2009:48; 1313-1319\n\n\n\n\n\n\n\n\n32 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSNIPPETS ON DERMATOLOGY DEVELOPMENT IN THE 1ST DECADE OF THE MILLENIUM\n\n\n\nDermatology Training in Malaysia\nSuraiya HH\n\n\n\nCorrespondence\nSuraiya H Hussein, FRCP\nFormer Head of Dermatology,\nMinistry of Health, Malaysia\nSenior Consultant Dermatologist\nDamansara Specialist Hospital, Kuala Lumpur, Malaysia\n\n\n\nEducation is a continuous process and training of\nspecialist physicians need to be dynamic and\nevolving all the time, responding to current needs\nand standards. The desired outcome of a specialist\ntraining programme in any country is to produce\ncompetent, enthused and committed specialists,\ncapable of independent practice in their own chosen\nfield. It would be a bonus if they also possess the\npotential and ability to contribute knowledge\nthrough their own research, and further enhance the\ndiscipline throughout their career.\n\n\n\nOver the years, training programmes have evolved\nand sometimes even went a full circle. Taking short\ncuts initially, for specific good reasons. Then went\non to expand to be more inclusive and thorough,\ninjecting many prerequisites and service\nrequirements, so that training took the long and\nwinding road. The next phase necessarily, as\ntraining of dermatologists took too long, is to begin\nto streamline - to be more structured, relevant and\nseamless.\n\n\n\nThe challenges of any training programme have\nalways centred on the following considerations\nand priorities:\n\u2022 The duration of training - What is too short, \n\n\n\nwhat is too long, what is just right?\n\n\n\n\u2022 How much of internal medicine training and \nknowledge is required for present day practicing \ndermatologists.\n\n\n\n\u2022 The current number of dermatologists to serve \nthe population of the country. Do we need to \ntrain more dermatologists and fast?\n\n\n\n\u2022 The available expert manpower to train \ndermatologists locally verses the need to go\noverseas.\n\n\n\n\u2022 The attraction that young doctors have towards \ndermatology verses competition with other \nmedical disciplines like cardiology or \nneurology.\n\n\n\n\u2022 The requirement of research during the training\n\n\n\n\u2022 and overseas exposure during or after the \ncompletion of training.\n\n\n\nEach country will weigh and give due consideration\nto the factors above.\n\n\n\nThe Malaysian Journey\nMalaysian specialist dermatology training has\nchanged over the years, particularly in the last\ndecade, and is still evolving, mindful of local needs\nand international practices. In the 1970s, when the\ntotal number of dermatologists in the country was\nso few, training was short, non structured and\nsimple, with no exit assessment. In the 1980s, in\nline with other disciplines of medicine, and efforts\nat introducing the specialist registry by the Ministry\nof Health and the Academy of Medicine,\ndermatologists need to obtain a post graduate\nqualification in internal medicine. This could be the\nMRCP(UK) or equivalent, or Masters Internal\nMedicine, from a Malaysian University, before they\ncan enter a dermatology training period which was\ninitially only one year and later increased to three\nyears in a dermatology department. An overseas\nexposure in the form of a one year Diploma at St\nJohns Institute of Dermatology, London or other\noverseas centres, was often included during or after\nthe 3 years of training. This training programme\nwas still not ideal as it was not structured and\nteaching depended on local conditions at the\nhospitals they worked in.\n\n\n\n\n\n\n\n\n33MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nBy the 21st century, in early 2000, it was deemed\nnecessary to introduce a more structured,\nexperience based training programme, which is well\nsupervised by qualified trainers in recognised\ntraining institutions. A post graduate internal\nmedicine qualification is still the entry requirement.\nA research thesis is included in the training period.\nTrainees undergo an exit examination with local\nand external international examiners at the end of\nthe 3 years. They are then awarded the Advanced\nMasters in Dermatology (UKM). Overseas training\nis offered to specialists after this period so that they\ncan develop their interest in a subspecialty of\ndermatology of their choice. This is a pioneering\ncollaborative effort between Ministry of Health,\nNational University (UKM) and Dermatological\nSociety of Malaysia (PDM) and is the current\npreferred method of training of dermatologists in\nMalaysia.\n\n\n\nStreamlining The Path of Training\nThe quality of specialists that graduate from this\nsystem of training is excellent in that they are\nmature, well rounded and more than capable of\nindependent practice any where in the world.\nNevertheless, we are always mindful that it still\nrequires a very long time to train a dermatologist in\nMalaysia. Therefore, as early as 2004, discussions\nwere already being held between the professional\nbodies, the Ministry of Health and the Universities,\non how we can train more specialists more quickly,\nwithout compromising on the outcome. Two options\nwere considered available, possible and desirable.\nBoth options do not alter the structured programme\nas developed for the Advanced Masters in\nDermatology.\n\n\n\nOption 1, is to telescope the first year of Adv M\nDermatology course into the fourth(final) year of\nMasters in Internal Medicine course, which is the\nsubspecialty rotation year anyway. This will shorten\nthe total duration. Candidates that want to be\ndermatologists could be pre selected before entry,\nor they can decide to do dermatology while in the\nMasters Internal Medicine course.\n\n\n\nOption 2, is to identify candidates for dermatology\ntraining at the outset. The first 2 years of training is\na general internal medical rotation, with an\nexamination in internal medicine, and then the next\n3 years is full time dermatology programme as\nmentioned above. This would shorten the period of\ntraining even more.\n\n\n\nBoth the options are feasible without compromising\nthe quality of dermatologists trained. Furthermore it\nwill address most of the issues, considerations and\npriorities of a training programme that I mentioned\nin my introduction above. This ongoing evolution of\ntraining, however, requires great resolve,\nunderstanding and commitment of all responsible\nfor the direction of specialist training in Malaysia.\n\n\n\nSummary\nWhatever priorities that may exist initially in a\ncountry, training programmes are usually dynamic\nand ever evolving processes. Continuous\nbenchmarking with other centres globally is\nimportant so that the specialists we train are not\nonly relevant for local needs but are able to\nparticipate in the international arena.\n\n\n\nA seamless, structured, experience based and well\nsupervised training programme, with a good mix of\nbasic medical and surgical principles, strong basic\ndermatology and an enticing taste of dermatological\nsubspecialties and research, with appropriate\nassessments during the training is ideal and\nachievable. A period of international/overseas\nexposure to broaden horizons will be invaluable.\n\n\n\nThe new young dermatologist, who will be in their\nearly thirties, will then have ample time in their\ncareer to sub specialise further, contribute\nknowledge through conduct of their own research\nand experiences, to enhance the profession, and to\nteach and train others that come after them. A good\ntraining programme with dedicated mentors\nproduce new specialists who would be better than\ntheir trainers and mentors before them. This is the\naim of any training programme and it augers well\nfor the future of the profession.\n\n\n\n\n\n\n\n\n34 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nCONTINUOUS PROFESSIONAL DEVELOPMENT - Post Graduate Studies\n\n\n\n\u2022 Faculty of Medicine UKM website: http://pkukweb.ukm.my\n\n\n\nAdvanced Master of Dermatology\nCourse Director: Head of Department of Medicine\nCo-chair: National Head of Dermatology, Ministry of Health\n\n\n\nResearch Degree: Thesis required\n\n\n\nTaught Programme: Advanced Master of Dermatology\n\n\n\nProgramme Structure: The Advanced Master of Dermatology is a full-time 3-year programme.\nThe maximum duration allowed is 4 years.\n\n\n\nThe programme consists of 3 years sub-specialty training which is aimed at progressive mastery of\nknowledge, skills and attitude, increasing responsibilities and independence. The programme includes\ntaught courses (lectures, seminars and conference), bedside dermatology procedures and clinical research\nthesis. The written and clinical examinations are conducted at the end of the 3-year programme.\n\n\n\nGENERAL ENTRY REQUIREMENTS\n\u2022 A Masters degree of Internal Medicine from Universiti Kebangsaan Malaysia or other universities \n\n\n\nwhich are recognised by the Senate; or\n\u2022 Other relevant professional qualifications or related experience which are recognised as equivalent\n\n\n\nto a Masters degree by the Senate;\n\u2022 Course is only offered to Malaysians\n\u2022 Government of Malaysia Medical Specialist can apply 1 year after gazettement as a specialist by\n\n\n\nthe Ministry of Health\n\n\n\nLearning outcomes are measured and assessed by the trainers as follows:\n\n\n\n1) Demonstrate advancement of knowledge, comprehension and practical skills and have the \ncapabilities to develop or use ideas in the context of evidence based medicine\n\n\n\n2) Apply knowledge, comprehension and practical skills to solve problems related to fields of study\nin new situations and multidisciplinary approach\n\n\n\n3) Evaluate, develop new approaches and apply knowledge and practical skills in managing\ncomplex problems\n\n\n\n4) Demonstrate leadership skills in managing the clinical team and services\n\n\n\n5) Evaluate and make decision in clinical situations even with limited resources taking into \nconsideration social and ethical issues\n\n\n\n6) Communicate and present the research findings and knowledge to peers and the community\nrelated to the area of expertise\n\n\n\n\n\n\n\n\n35MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7) Develop interest and continue further training in the area of expertise for the purpose of life-long \nlearning\n\n\n\n8) Practice safe clinical skills and recognize own limitation\n\n\n\n9) Formulate and conduct scientific research independently\n\n\n\n10) Demonstrate caring attitude and sensitivities to the needs of self, patients and their families, \ncolleagues and the community\n\n\n\nThe programme is divided into three phases:\n\n\n\nPHASE 1 (Year 1): Clinical training in dermatology. This covers basic dermatology.\nPropose a Research Project for Approval and Conduct Research.\n\n\n\nPHASE 2 (Year 2): Further training in dermatology and introduction to dermatological subspecialty \nareas. Continue research project.\n\n\n\nPHASE 3 (Year 3): Assume responsibilities as \u2018Specialist-in-training\u2019 and complete research project \nand write-up as per requirements of UKM\n\n\n\nCredit hours are not required as candidates will be based in a hospital doing full time clinical posting.\n\n\n\nName of Academic Staff\n\n\n\nLecturers\n\n\n\nDatuk Dr Roshidah Baba, MBBS(Malaya), DipDerm(London), MRCP(UK), FRCP(London)\n\n\n\nDatin Dr Asmah Johar, MD(UKM), MMed(UKM)\n\n\n\nDr Choon Siew Eng, MBBS(Malaya), MRCP(UK), FRCP(London), DipDERM(London),\n\n\n\nDipGUM(London)\n\n\n\nDr Pubalan Muniandy, MBBS(Malaya), MRCP(UK), DGUM(London)\n\n\n\nDr Rohna Ridzwan, MBBS(Malaya), MRCP(UK)\n\n\n\nDr Najeeb Ahmad Mohd Safdar, MBBS(U.P.), MRCP(UK), FRCP(London), DipDerm (Bangkok)\n\n\n\nDr Suganthi Thevarajah, MBBS(Madras), MMed(UKM)\n\n\n\nDr Dawn Ambrose, MD(UKM), MRCP(IRELAND)\n\n\n\nDr Tay Kwee Eng, MD(UKM), MRCP(UK), MMED(Singapore)\n\n\n\nDr Noorzalmy Azizan, MB Bch (NUI), MRCP(UK), Adv MDerm (UKM)\n\n\n\nDr Chang Choong Chor, MBBS(Malaya), MRCP(UK), Adv MDerm(UKM)\n\n\n\nDr Ng Ting Guan, MD(UKM), MRCP(UK), Adv MDerm(UKM)\n\n\n\nDr Chan Lee Chin, MD(USM), MMed(USM)\n\n\n\nInvited Lecturer\n\n\n\nDr. Nopadon Noppakun, BSc in Medical Science (Bangkok), MD(Bangkok),\n\n\n\nCertificate in Dermatopathology\n\n\n\n\n\n\n\n\n36 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nContinuous Professional Development - CME\n\n\n\n36th Annual General Meeting\n& Malaysian Dermatology Congress\n\n\n\nOrganizers  Dermatological Society of Malaysia\n\n\n\nTheme Sun & Skin\n\n\n\nVenue Thistle Hotel, Port Dickson\n\n\n\nDate 22 - 25 September 2011\n\n\n\nProgram website www.dermatology.org.my\n\n\n\nContinuous Professional Development - CME\n\n\n\n11th Asia Pacific Environmental &\nOccupational Dermatology (APEODS)\n\n\n\nOrganizers Asia Pacific Environmental & Occupational Dermatology (APEODS)\n&\n\n\n\nContact & Occupational Dermatoses Forum of India (CODFI)\n\n\n\nVenue Postgraduate Institute of Medical Education & Research, Chandigarh (INDIA)\nRoom No. 5, 4th Floor, F - Block, Nehru Hospital\n\n\n\nDate 14 - 16 October 2011\n\n\n\nDeadline for abstract submission  30th June 2011\n\n\n\nAll submissions should be by e-mail to apeods@yahoo.in\n\n\n\n\n\n\n\n\n37MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nContinuous Professional Development - Book Review\n\n\n\nDoc, Patients\u2019 Outcome is in your Hands.\nImprove your Clinical Skill with\n\n\n\nDermatology Clinical Skill Test Kit\n\n\n\nAuthor Rohna Ridzwan     Email rohnaridzwan@yahoo.com\nPublisher Self\nYear of Publication 2011     ISBN 978-967-10420-0-7\nAvailable at Koperasi Kedaibuku Universiti Malaya Bhd,\nUniversity Malaya Medical Centre\nPrice RM 80 only\n\n\n\n\u201cThe 21st century pushes the use of advance technology into the forefront of\nclinical Medicine, however clinical skills come with experience, recognising\nclinical signs and symptoms. Skin rashes often look the same and confusing to\nthe untrained eye. The author has illustrated the importance of using clinical\nskills in deriving to a precise diagnosis. She has linked the choice of diagnosis\nmade by the clinician to the patient\u2019s predicted outcome. Tips in recognising\n\n\n\nvarious skin conditions have been injected into this book that will assist the reader to assess themselves and\nimprove their clinical skills. This book is recommended to medical students, front-line doctors and even\nspecialist in fields other than Dermatology\u201d.\n\n\n\nDr. Koh Chuan Keng |  President of Dermatological Society of Malaysia\n\n\n\nContinuous Professional Development - CME\n\n\n\ne-Posters Presented at\n22nd World Congress of Dermatology\n\n\n\n1. Mucocutaneous manifestations of Dengue fever among patients in Universiti Kebangsaan Malaysia \nMedical Centre (UKMMC) - Norazirah Md Nor, Mazlin Mohd Baseri, Sharifah Ismail, Saadiah\nSulaiman, Malcolm Greaves (BRONZE AWARD)\n\n\n\n2. Acne myths: Personal experiences of acne patients in Malaysia - Kun Sen Chen\n3. Lipid lowering drugs induced adverse drug reactions - Chew Kek Lee, Yin Yin Lee, Roshidah Baba\n4. Pattern of ADR seen in Tertiary Hospital, Johor, Malaysia between 2001 - 2010\n\n\n\n- Malani Terpiti, Siew Eng Choon\n5. Primary Dapsone resistant Mycobacterium Leprae Infection in Malaysia; A ten year study\n\n\n\n- Norazirah Md Nor, Adawiyah J, Mazlin MB Amrish SO\n6. Clinical skill test kit as a tool to assess housemen ability to recognise skin conditions\n\n\n\n- Raoul Roger Sibert, Rohna Ridzwan\n7. Dilemma in managing skin nodules with sporothricoid spread - Hazfaneza Ab Halim, Rohna Ridzwan\n8. Relationship between skin colour and minimal erythema dose to ultraviolet B radiation in multi-ethnic \n\n\n\nMalaysian population - Yin Yin Lee, Choong Chor Chang, Asmah Johar, Suraiya Hani Hussein\n9. Assessment of skin phototype, skin colour and minimal erythema dose to ultraviolet B radiation in the \n\n\n\nmulti-ethnic Malaysian Population - Yin Yin Lee, Choong Chor Chang, Asmah Johar, Suraiya Hani \nHussein\n\n\n\n10. Quality of life among adult patients with psoriasis: a study using data from the Malaysian Psoriasis \nregistry - Choong Chor Chang, Felix Boon-bin Yap, Hemandas Belani Gangaram, Roshidah Baba\n\n\n\n11. Safety and efficacy of ustekinumab in the treatment of Malaysians with moderate-to severe psoriasis \nincluding erythrodermic psoriasis and patients with past history of pustular flares - Siew Eng Choon\n\n\n\n12. Secondary syphilis infection among patients attending genitor-urinary medicine clinic (GUM), \nHospital Kuala Lumpur (2005-2009) - Yew Thong Chong, Su-ming Wong, Jyh Jong Tang, Felix Boon-bin \nYap, Choong Chor Chang, Asmah Johar, Roshidah Baba\n\n\n\n13. Teledermatology: providing dermatological consultation to remote hospital-based primary care clinics in \nMalaysia - Choong Chor Chang, Min Moon Tang, Asmah Johar, Roshidah Baba\n\n\n\n\n\n\n\n\n38 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nObituary\n\n\n\nDr Allan Yee Kim Chye was Consultant Dermatologist\nand Director of the Hope Skin & Laser Centre at\nGleneagles Medical Centre, Kuala Lumpur. He was\nPresident of the Persatuan Dermatology Malaysia from\n2006 to 2008, and we remember him for his passion and\ncommitment to the affairs of the Society, and his efforts\nin promoting excellence in Dermatology.\n\n\n\nI can recall when Allan attended his first PDM meeting,\nlooking like a well groomed doctor with his disarming\nsmile, and unusually for a Chinese man, a striking thick\nmoustache! He immersed himself fully in the affairs of\nthe Society, serving in the committee, and he\nsubsequently went on to be President of the Society.\nDuring his term as President, he worked unstintingly to\ninstitute several innovative changes, and organised some\nof the most exciting scientific meetings.\n\n\n\nDr Allan Yee was born and grew up in the small town of\nSeremban. He graduated with an MBBS from the\nUniversity of Singapore. A fellow student fondly\nremembers him organizing end-of-exam expeditions to a\nkampong in Kuantan with his usual enthusiasm, and\nleading the way from Singapore in his old battered\nPeugeot! On returning to Malaysia, Allan worked as a\nmedical officer and then Lecturer in Internal Medicine in\nthe University Hospital in Kuala Lumpur. In 1988, after\nobtaining his MRCP, he left for the United Kingdom for\npostgraduate experience and worked with several\nprominent dermatologists including Professor William\nCunliffe in Leeds and Professor John Burton in Bristol.\nHis experience in the UK paved the way for him to invite\nseveral international authorities as guest speakers for our\nscientific meetings in subsequent years.\n\n\n\nAllan returned to Malaysia in 1995 and set up private\npractice initially in Tung Shin Hospital, and subsequently\nin Gleneagles Medical Centre. In 1997 he established the\nHope Skin and Laser Centre, one of the first centres in\nthe country to offer a range of skin laser treatment for\nvarious skin diseases. Allan pioneered the establishment\nof The Cosmetic Dermatology and Laser Medicine\nBoard of the Dermatological Society of Malaysia and\nbecame its first founding president. He believed that\ndermatologists, being experts in skin conditions should\nbe in the forefront of carrying out and ensuring safe\naesthetic procedures. He was also a Fellow of the\nAmerican Society for Laser Medicine and Surgery, as\nwell as a Fellow of the American Academy of\nDermatologists and Fellow of the Royal College of\n\n\n\nPhysicians. He served as the Medical Advisor to the\nPsoriasis Association of Federal Territory & Selangor for\nmany years, working to organize retreats and educational\nevents for the group.\n\n\n\nAllan was greatly interested in research which satisfied\nhis intellectual curiosity. He authored multiple\npublications and was sought after as a speaker at medical\nand public conferences. However, he derived the greatest\nsatisfaction professionally when attending to his patients.\nHis knowledge, compassion, personality and sense of\nhumour shone through when he was with them. He\nbelieved in \u201cgoing the extra mile\u201d for those in need, and\nas a result, formed a special bond with his patients. Many\nbroke down and wept upon hearing of his sudden\npassing, came to his funeral and paid their respects via\nletters, cards, and online postings.\n\n\n\nAllan lived a principled life underpinned by a strong\nsense of right and wrong. He was never one to step back\nfrom a challenge if he saw something wrong. He cared\nenough to act and to take a stand, even if it did sometimes\nruffle feathers. He was a champion of others and was a\nloyal friend who could be counted on and depended on\nalways. He was ever willing to share his expertise and\nknowledge with his colleagues, and always remained a\nstudent of life. He valued tremendously his friends and\ncolleagues.\n\n\n\nDespite such a full professional life, Allan was a devoted\nhusband and father, enjoying every spare moment of free\ntime with his family, He took great pride and joy in\nteaching lessons in life and sharing experiences with his\nson, Jonathan, and wife Anne. Family holidays were a\nwonderful time of leaving stresses and demands behind\nand enjoying time as a close knit family. He is greatly\nmissed by them.\n\n\n\nAllan also held a deep commitment to God. He served\nactively in church and was well-respected and loved by\nhis church brethren as he engaged in church life and\nsought to be of service to those in need. His deep faith\nguided his actions and decisions in life.\n\n\n\nAllan will be missed because he touched so many lives\npositively, and he left behind an amazing legacy. He will\nbe remembered fondly always by his friends and\ncolleagues.\n\n\n\nDato Dr Sushil Kumar Ratti\n\n\n\nALLAN YEE KIM CHYE\n\n\n\n\n\n\n\n\n39MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n\u201cDoc, do you know that Professor Adam passed away 10\ndays ago?\u201d That was the exact words that a patient told\nme at Skin Clinic at University Malaya Medical Centre.\nIt came rather sudden although we know he was ill with\ncancer for some time, the news still came as a shock and\nthe fact 10 days had passed before anyone in the Medical\nfraternity knows about it. He passed away on 31st\nJanuary 2011.\n\n\n\nProfessor Adam obtained his MBBS in 1963 at the then\nUniversity of Malaya in Singapore (Now National\nUniversity of Singapore). He was working in the United\nKingdom and was asked by the then Foundation Dean of\nUM, Tan Sri Professor Dr. T.J . Danaraj, to return as the\nfirst Consultant Dermatologist in University of Malaya. \n\n\n\nProfessor Adam was friend, teacher and mentor to many.\nMany of our current senior Consultant Dermatologists\nhave been taught by him and his advice has been helpful\nearly on in their careers. He has a quiet and gentle\npersonality preferring to be humble, maintaining a low\nprofile despite his many achievements. Chief amongst\nthem is starting the first Immunoflourescence service in\nthe country, whereby blood and tissue from patients with\nautoimmune bullous disorders were sent to the medical\ndepartment at UM instead of pathology. The tissues and\nblood specimens would be processed by a technician\nunder his supervision and he would report on the IMF\nfindins and sent them out to all the skin departments in\n\n\n\nMalaysia including to Jabatan Kulit, Hospital Kuala\nLumpur. This continue until 1997 when by then the\npathology departments took over in providing this\nservice.\n\n\n\nHe worked from 1968 until his retirement from\ngovernment service in 1995. He then proceeded into\nprivate practice wearing three hats, working in Subang\nJaya Medical Centre as a consultant Dermatologist, his\nown clinic in Petaling Jaya Old Town, on top of a session\nevery Tuesdays as a visiting consultant to University\nHospital from 1995 to 2007.\n\n\n\nHe was among the pioneers in the early days of Persatuan\nDermatologi Malaysia and was elected the 3rd President\nof Persatuan Dermatologi Malaysia serving from 1978-\n1980. I had come to know of Professor B.A.Adam during\nmy posting as a Lecturer in Dermatology at the\nDepartment of Medicine at University of Malaya. He\nwas always approachable and helpful and will be missed\nby many who have come to know him.\n\n\n\nProfessor Adam hails from the era of early foundation\nprofessors of the Medical Faculty of University Malaya\nas well as PDM and his contribution to the development\nof Dermatology in Malaysia will be forever etch in our\nmemory.\n\n\n\nDr. Koh Chuan Keng\n\n\n\nPROFESSOR BASHER A ADAM\n\n\n\n\n\n\n\n\n40 MJD 2011 July Vol 26\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAnswers to Clinicopathological Challenge Quiz\n\n\n\n1a) All the above\n\n\n\n1b) Lupus Profundus\n\n\n\nFocal areas of basal cell vacoulation\n\n\n\nDense chronic infiltrates in the dermis &\nsubcutaneous tissue\n\n\n\nPredominantly lymphocytes & eosinophils\n\n\n\nLobular panniculitis.\n\n\n\n2a) All the above\n\n\n\n2b) Secondary syphilis\n\n\n\nPsoriasiform hyperplasia\n\n\n\nLichenoid infiltrate\n\n\n\nPlasma cells & Lymphocytes\n\n\n\n2c) Sarcoidosis\n\n\n\nGranulomatous infiltrates in the dermis\n\n\n\nEpitheloid & giant cells granulomas\nNo necrosis\n\n\n\nGranulomas appear naked\n\n\n\nAsteroid body\n\n\n\nFite/Ziehl - Neelsen & PAS/GMS stains\nnegative\n\n\n\n\n\n\n\n\n\n"
"\n\nVolume 37   |  Dec 2016   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.myIndexed in: Western Pacific Research Index Medicus\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\nM\nA\n\n\n\nLA\nY\n\n\n\nS\nIA\n\n\n\nN\n J\n\n\n\nO\nU\n\n\n\nR\nN\n\n\n\nA\nL O\n\n\n\nF D\nE\n\n\n\nR\nM\n\n\n\nA\nT\n\n\n\nO\nLO\n\n\n\nG\nY\n\n\n\n     Volum\ne 37   |  D\n\n\n\nec 2016  |  ISSN\n: 1511-5356\n\n\n\n\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:\nwoodzlamp@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology \ncan be sent to me at:\nwoodzlamp@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation. \nThis category provides rapid publications and is meant to be a \nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in the \narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods , Results, Comment and \nReferences. A Structured Abstract of not more than 240 words \nmust be included. It should consist of four paragraphs, labelled \nBackground, Methods, Results, and Conclusions. It should \ndescribe the problem studies, how the study was performed, \nthe main results, and what the author(s) concluded from the \nresults. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and \nsummarizes the existing knowledge in a particular field. \nIt should not be an exhaustive review of the literature, and \nreferences should not exceed 100 in number. Tables, diagrams, \nand selected figures are often helpful. The length is left to the \njudgment of the author, although it generally should not exceed \n5000 words. Topics may include updates in clinically relevant \nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author who \nwill be responsible for reading the proofs must also be given on \nthe title page. The author(s) must also declare any affiliation or \nsignificant financial involvement in any organizations or entity \nwith a direct financial interest in the subject matter or materials \ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in \nthe manuscript. References from journals should include: (1) \nname(s) followed by the initials of the author(s), up to four \nauthors: if more than four authors, include the first three authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; (5) \nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A \nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) referred \nto. \n\n\n\nFor example: \nFoong HBB.  Transcontinental Dermatology: Virtual Grand \nRounds. In: Wootton R and Oakley A, editors. Teledermatology. \nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on \nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\nNotice to Authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37\n\n\n\nLETTER TO EDITOR\n\n\n\n1 A Patient With An Unexplained Oily Panniculitis\n That Responded To Doxycycline\n Su P, Ng SK\n\n\n\n3 Gefitinib-Induced Acneiform Eruption\n Long V\n\n\n\n5 Eyelid Thrombus - An Unusual Location, \n An Unusual Differential\n Long V, Liau MM, Huma J\n\n\n\nORIGINAL ARTICLE\n\n\n\n7 Multicleartm Treatment For Striae Distensiae\n Su P, Heng JK, Yang SSY, Aw DCW\n\n\n\n13 Evaluation Of Serum Biotin And Serum Ferritin \n In Women With Diffuse Hair Loss\n Nagesh TS, Misquith A, Silvia WD\n\n\n\n17 Dermatological Diseases Among Octogenarians \n In A Tertiary Center\n Low DW, Adawiyah J, Norazirah MN, \n Leelavathi M\n\n\n\n23 Correlation Between Cumulative Dose Of \n Methotrexate And Methotrexate Induced \n Hepatotoxicity in Psoriasis Patients Undergoing \n Liver Biopsy- A 15 Years Retrospective Study\n Asha G, Tang J J, Chan LC\n\n\n\n28 Pemphigus: A Singapore Perspective\n Valencia L, Tay YK, Teo R\n\n\n\nCASE REPORT\n\n\n\n35 Methotrexate Toxicity\n Long V, Huang JX, Huma J, Aw CW Derrick, \n Nisha SC\n\n\n\n38 A Case Report of Disseminated Porokeratosis \n With Secondary Amyloid Deposition\n Yong AMY, Yang SSY, Tan KB, Sobti AM\n\n\n\n41 The Wrath of the Rengas: A Report Of Severe \n Contact Dermatitis And Implications For Public \n Health In Rural Areas\n Tan ST, Gunawan L, Reginata G\n\n\n\n44 Maxillary Oral Cutaneous Fistula In Diabetes \n Mellitus Patient: A Case Report\n Anisha B, Norashikin S\n\n\n\n47 Leprosy Reaction In Mycobacterium Leprae \n And Mycobacterium Tuberculosis Co Infection: \n A Case Report And Literature Review\n Jamil A, Nik Adeeb NN, Muthupalaniappen L,\n Md Nor N\n\n\n\n51 Young Lady With Recurrent Abdominal Pain, Is It \n Only Gastritis?\n Neoh KK, Tang ASN, Kiing JW, Adam Malik I\n\n\n\n55 A Rare Case Of Multiple Congenital Nevomelanocytic Nevi\n Lestary D, Lestari S, Yenny SW\n\n\n\n58 Linear Basal Cell Carcinoma- A Diagnosis Achieved By\n The Use Of Confocal Microscopy\n Long V, Chen Q, Chuah SY, Thng TGS\n\n\n\n61 Combination Therapy Of Oral Doxycycline With 0.05% \n Tretinoin, 3% Clindamycin, And 0.05% Dexamethasone\n Cream In Severe Acne Vulgaris: Three Case Series\n Sukmawati TT, Gabriela R, Joice GP, Listyani G\n\n\n\n65 A Case Of Verrucous Psoriasis In An Erythrodermic \n Patient\n Bhullar A, Lee BR, Norashikin S\n\n\n\n69 Angiolymphoid Hyperplasia With Eosinophilia Of The\n Eyelid: A Case Report\n Abirami S, MBBS, Gunavathy N, Ho SF, Mazita I, Adil H\n\n\n\n72 Kissing Naevus Of Eyelids - A Report Of Two Cases\n Gupta M\n\n\n\n74 Phenytoin Induced Pellagra- A Case Report\n Gupta M\n\n\n\n76 Linear Lichen Planus Pigmentosus, A Case Report \n And Literature Review\n Anisha B, Norashikin S\n\n\n\nCOMMENTARY\n\n\n\n79 The Pallor Of Biblical Leprosy\n Liau MMQ, Yang SSY\n\n\n\nQUIZ\n\n\n\n81 Asymptomatic Skin Colored Papules On The Limbs\n Of An Adult Female\n Long V, Huang JX\n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 i\n\n\n\nEditor-in-Chief \nAssociate Professor Dr Felix Yap Boon Bin \nMRCP Adv MDerm\nUniversiti Tunku Abdul Rahman\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCPI\nKuala Lumpur\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP\nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed, Penang\n\n\n\nDr Ng Ting Guan MRCP AdvMDerm\nKlang, Selangor\n\n\n\nDr Adawiyah Jamil MMed AdvMDerm\nKuala Lumpur\n\n\n\nDr Tang Jyh Jong MRCP AdvMDerm\nIpoh, Perak\n\n\n\nDr Tarita Taib AdvMDerm\nSelayang, Selangor\n\n\n\nDr Tan Wooi Chiang AvdMDerm\nAlor Setar, Malaysia\n\n\n\nDr Chang Choong Chor AdvMDerm\nKuala Lumpur, Malaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nExecutive Staff\nAgnes Heng Yoke Hui - President\nRohna Ridzwan - Vice President\nNoor Zalmy Azizan - Secretary\nChan Lee Chin - Treasurer\nHenry Foong Boon Bee - Immediate Past President\nDr Azura bt Mohd Affandi - Committee Member\nDr Ruban Satkuna Nathan - Committee Member\nDr Sabeera Begum - Committee Member\nDr Tan Wooi Chiang - Committee Member\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2014 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 371\n\n\n\nLetter to Editor\n\n\n\nA PATIENT WITH AN UNEXPLAINED OILY PANNICULITIS\nTHAT RESPONDED TO DOXYCYCLINE\nSu P, Ng SK1\n\n\n\nCorresponding Author and Reprint Request \nPeiqi SU (MBBS, MRCP (UK))\nNational Skin Centre, Singapore\n1 Mandalay Road, Singapore 308205\nEmail: peiqi_su@nuhs.edu.sg\n\n\n\n1 National Skin Centre, Singapore\n\n\n\nHowever, a week later, there was still persistent pain \nand the patient was referred to us. On examination, \na tender erythematous plaque was seen over her \nleft axilla (Fig. 1). A biopsy was scheduled. During \nthe biopsy, an oily film was seen coming from the \npanniculus (Fig. 2). Histology was consistent with a \nneutrophilic panniculitis. Investigations to rule out \npancreatic disease were negative [amylase 37u/L \n(0-110u/L); lipase 9u/L (8-55u/L)]. Investigations \nto rule out AAT deficiency were also negative [AAT \nlevels measured on two occasions: 141mg/dL and \n132mg/mL (70-180mg/dL]. Other investigations \nthat were negative were bacterial and fungal cultures. \nA Computed Tomography (CT) scan of the thorax \nand abdomen showed non-specific ground glass \nchanges and spirometry was also unremarkable. \nShe was prescribed doxycycline and the response \nwas significant, with a 50% improvement after one \nweek.\n\n\n\nSir,\n\n\n\nIn some cases of panniculitis, an oily discharge \nmay be seen. The important causes of this oily \npanniculitis are pancreatic panniculitis and Alpha-1-\nantitrypsin (AAT) deficiency panniculitis. We report \na 51 year old Chinese lady who presented with a \npainful plaque over her left axilla. On biopsy, a film \nof oil was noted to be coming from the panniculus. \nInvestigations were negative for pancreatic \npanniculitis and AAT deficiency panniculitis. She \nresponded promptly to doxycycline.\n\n\n\nA 52 year old female presented to the Accident \nand Emergency (A&E) department with pain and \nredness over her left axilla. There was no history \nof trauma. She was treated initially for cellulitis \nand concomitant herpes zoster with cloxacillin and \nacyclovir.\n\n\n\nFigure 1. An erythematous indurated plaque over the left \naxilla.\n\n\n\nFigure 2. Oily droplets (arrow) seen during the incisional \nbiopsy.\n\n\n\nWe report a case of an oily panniculitis, with no \nobvious preceding cause, and which responded \nwell to doxycycline. Initial differentials included \npancreatic panniculitis, AAT deficiency panniculitis \nand infective panniculitis. However, serum lipase, \namylase, AAT levels and infective cultures were \nnormal. 25% of patients with AAT panniculitis, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 2\n\n\n\nhowever, may have normal serum AAT levels1. In \naddition, lesions may be induced by low intensity \ntrauma or simply physical activity of the affected \narea in 35% of cases with AAT panniculitis so a \nnegative history for trauma does not exclude the \ndiagnosis2. Other differentials of a neutrophilic \npanniculitis might include factitious, Sweet\u2019s \nsyndrome or neutrophilic panniculitis3 associated \nwith rheumatoid arthritis but features of these were \nhistologically and clinically absent in our patient.\n\n\n\nIt was interesting to note that our patient has \na good response to doxycycline as this has \nbeen used as a treatment for AAT associated \n\n\n\npanniculitis4. It is possible that the anti-\ninflammatory effect of doxycycline contributed \nto the patient\u2019s improvement rather than its anti-\nmicrobial activity.\n\n\n\nIn conclusion, our case represents an idiopathic \noily panniculitis which showed good response \nto doxycycline. Fortunately for the patient, \nthere was no evidence of pancreatic panniculitis \nor AAT deficiency panniculitis which may \notherwise be associated with a less desirable \nprognosis.\n\n\n\nReferences\n \n1. Geraminejad P, DeBloom JR, Walling HW, et al. Alpha-1-\n\n\n\nantitrypsin associated panniculitis: the MS variant. J Am \nAcad Dermatol 2004 51: 645-55.\n\n\n\n2. de Serres F, Blanco I. Role of alpha-1 antitrypsin in human \nhealth and disease. J Intern Med 2014; 276:311\u201335.\n\n\n\n3. Chan MP. Neutrophilic panniculitis: algorithmic approach \nto a heterogeneous group of disorders. Arch Pathol Lab \nMed 2014; 138: 1337-43.\n\n\n\n4. Gross B, Grebe M, Wencker M, et al. New findings in \nPiZZ alpha1-antitrypsin deficiencyrelated panniculitis. \nDemonstration of skin polymers and high dosing \nrequirements of intravenous augmentation therapy. \nDermatology 2009; 218: 370-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 373\n\n\n\nLetter to Editor\n\n\n\nGEFITINIB-INDUCED ACNEIFORM ERUPTION\nLong V\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long MBBS, \nTan Tock Seng Hospital\n11 Jalan Tan Tock Seng, Singapore 308433\nEmail: valencialong@gmail.com \n\n\n\nShe was afebrile. Full blood count, liver, renal \nfunction tests were all within normal limits. \nC-reactive protein was slightly elevated. Cultures \nobtained from the pustule and KOH test of the \ninguinal region were negative.\n\n\n\nGefitinib is a selective EGFR inhibitor. The \nmost common dermatological side effect is an \nacneiform eruption. Although the pathogenesis of \nEGFR-induced skin rash is not well clarified, the \ninhibition of EGFR tyrosine kinase activity seems \nto be responsible. Lichtenberger et al1. showed \nthat EGFR is expressed in the basal layer of the \nepidermis. In papulopustular rash, the main target \nis the epidermal keratinocyte and not the cutaneous \nadnexa. The inhibition of EGFR in keratinocytes \ninduces apoptosis, arrests cell growth, reduces \ncell migration, and increases cell adhesivity and \ncell differentiation. All these processes induce \nkeratinocytes to release inflammatory chemokines \n(such as chemokine (C-C motif) ligand 2 (CCL2), \nchemokine (C-C motif) ligand 5 (CCL5))2. Hence, \ncellular growth arrest and inflammation cause \nxerosis and the most common appearance of a \npapulopustular acneiform rash.\n\n\n\nSir,\n\n\n\nA 70-year-old Asian female with advanced non-\nsmall-cell lung adenocarcinoma with metastasis \nreceiving gefitinib 250mg daily presented with \na progressively worsening pruritic and painful \nerythematous rash after 1 month of therapy. She \ndenied any drug allergy nor usage of traditional \nChinese medications.\n\n\n\nOn examination, there were widespread \nerythematous papules, erosions and crusts on her \nupper limbs and trunk (Figure 1). There were 3 \npustules located on her abdomen (Figure 1, arrows), \nwith an area of maceration and pustulation at the \nleft inguinal region (Figure 2). There was no scalp, \nface, nail involvement nor mucositis. Nikolsky\u2019s \nsign was negative.\n\n\n\nFigure 1. Erythematous patches with 3 non- \nfollicular pustules, erosions and crusts over abdomen \n(arrows).\n\n\n\nFigure 2. Linear pustulation in left inguinal \nregion.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 4\n\n\n\nReferences\n \n1. Lichtenberger BM, Gerber PA, Holcmann M, Buhren BA, \n\n\n\nAmberg N, Smolle V, et al. Epidermal EGFR controls \ncutaneous host defense and prevents inflammation. Sci \nTransl Med. 2013;5:199\n\n\n\n2. Fabbrocini G, Panariello L, Caro G, Cacciapuoti S. \nAcneiform Rash Induced by EGFR Inhibitors: Review \nof the Literature and New Insights. Skin Appendage \nDisorders. 2015;1(1):31-37\n\n\n\n3. Melosky B, Leighl NB, Rothenstein J, Sangha R, Stewart \nD, Papp K. Management of egfr tki\u2013induced dermatologic \nadverse events. Current Oncology. 2015;22(2):123-132. \n\n\n\nmaintained through mild-moderate acneiform rash3 \n(i.e. grade 2 where affected body surface area is \nbetween 10%-30%). Even if the rash progresses to \nstage 3 (>30% body surface area affected), studies \nhave shown that the drug may be temporarily \ndiscontinued (2-4 weeks) and reintroduced at \nphysician\u2019s discretion3. A \u201ctreat-through\u201d approach \nis commonly employed for EGFR TKI induced rash. \n\n\n\nOther side effects include xerosis, telangiectasia, hair \nchanges and paronychia with pyogenic granuloma. \nIn patients presenting with dozens to hundreds of \npustules, the differential diagnosis of AGEP must \nbe considered. However, this patient had insufficient \npustules to qualify.\n\n\n\nGefitinib was withdrawn temporarily and her skin \nlesions resolved without treatment. Gefitinib was \nthen restarted without further development of \nrashes. The dose of EGFR TKI should generally be \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 375\n\n\n\nLetter to Editor\n\n\n\nEYELID THROMBUS - AN UNUSUAL LOCATION,\nAN UNUSUAL DIFFERENTIAL\nLong V1, Liau MM2, Huma J2\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long MBBS\nTan Tock Seng Hospital\n11 Jalan Tan Tock Seng, Singapore 308433\nEmail: valencialong@gmail.com\n\n\n\n1 Tan Tock Seng Hospital, Singapore\n2 National University Hospital, Singapore\n\n\n\nDear Sir, \n\n\n\nWe describe an unusual case of an asymptomatic \npapule found on the eyelid of an otherwise healthy \nmale, with an interesting subsequent diagnosis. \n\n\n\nA 30-year-old male with no past medical history \npresents with an asymptomatic papule on the left \nupper eyelid that has been growing gradually over \n4 months. It is mobile, not tethered to the skin and \nis slightly bluish-tinged. He requested for excision \nas it was not cosmetically pleasing. Histological \nexamination of the lesion revealed a thrombus \ncomposed predominantly of fibrin and admixed \nwith some red blood cells mostly in the periphery \nof the lesion. Coagulation studies were normal. \nAntinuclear antibody (ANA) was also within \nnormal limits. \n\n\n\nEyelid lesions prompt several considerations - \nwhether there is skeletal involvement, anatomically \n\u201cbad\u201d locations, the existence of perineural spread, \nor otherwise aggressive behaviour of \u201cbenign \ntumors\u201d. Many trials1,2 have studied the incidence \nof eyelid tumors with different histopathological \ntypes, citing that up to 86% of lesions were benign, \nincluding squamous cell papilloma, seborrheic \nkeratosis, melanocytic nevi, hidrocystoma and \nxanthoma.  Malignant lesions included basal cell \ncarcinoma, Meibomian gland carcinoma, squamous \ncell carcinoma. \n\n\n\nIt is therefore highly unusual that this lesion turned \nout to be a thrombus, without the patient having any \nhistory of thrombotic or connective tissue disorders. \nThe patient did not sustain any injury or trauma to \nthe eyelid area.\n\n\n\nFigure 1. Clinical image of asymptomatic left upper eyelid \npapule with slight bluish-tinge.\n\n\n\nFigure 2. Histological image of a thrombus \ncomposed predominantly of fibrin and \nadmixed with some red blood cells mostly in \nthe periphery of the lesion.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 6\n\n\n\nEyelid tumors must be taken seriously as there is a \nchance that they could malignant. Amongst benign \neyelid tumors, squamous cell papillomas are most \ncommon. Eyelid thrombus is a rarely reported, \nbut benign lesion. One should not consider an \neyelid thrombus in initial generation of differential \ndiagnoses. Rather, practitioners should first take \n\n\n\ninto consideration the possibility of benign and \nmalignant eyelid skin tumors arising from adnexal \nstructures. It is likely that an isolated eyelid \nthrombus does not signify underlying thrombotic/\ncoagulation/connective tissue disorders, however, it \nmust prompt consideration of these disorders.\n\n\n\nReferences\n \n1. Deprez M, Uffer S, Clinicopathological features of eyelid \n\n\n\nskin tumors. A retrospective study of 5504 cases and review \nof literature, Am J Dermatopathol, 2009, 31(3):256\u2013262.\n\n\n\n2. NI Z, Histopathological classification of 3,510 cases with \neyelid tumor, Zhonghua Yan Ke Za Zhi, 1996, 32(6):435\u2013\n437.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 377\n\n\n\nOriginal Article\n\n\n\nMULTICLEAR\u2122 TREATMENT FOR STRIAE DISTENSIAE\nSu P, Heng JK, Yang SSY, Aw DCW\n\n\n\nAbstract\n\n\n\nIntroduction: Striae distensiae (SD) are common cosmetic complaints. Treatment of SD remains \ndifficult and topical therapies are often disappointing. This study attempts to evaluate the efficacy of \nultraviolet light (UVB/UVA1) therapy using the MultiClear\u2122 (Curelight Ltd, Israel) machine in the \ntreatment of SD.\n\n\n\nMaterials and Methods: Eighteen participants were enrolled into a six-week trial of twice-weekly \ntreatments. Fourteen completed the study. Pre-and post-treatment measurements of the width and \nlength of striae over the abdomen or thighs were taken. Pre- and post-treatment photographs were \nassessed by a blinded investigator and any improvements were rated on a 4-point scale.\n\n\n\nResults: Six participants (42.9%) had reductions in the width of their SD (Mean reduction 0.54mm, p= \n0.0038). Four participants (28.6%) had reductions in the length of their SD (Mean reduction=4.57mm, \np= 0.069). Nine participants (64.3%) did not have any noticeable improvement in the appearance \nof their SD. Ten participants (71.4%) developed tanning as a consequence of treatment. No patients \nexperienced any pain.\n\n\n\nConclusion: Ultraviolet light (UVB/UVA1) therapy may help reduce the width of SD in skin phototypes \nIV-V but tanning is a common side-effect.\n\n\n\nCorresponding Author and Reprint Request \nDr Peiqi SU\nNational University Hospital (NUH)\nSingapore, 1E Kent Ridge Road\nNUHS Tower Block, Level 10, Singapore 119228\nEmail: peiqi_su@nuhs.edu.sg\n\n\n\nto become hypopigmented atrophic scars (striae \nalbae). Several factors are thought to contribute to \nthe pathogenesis of SD. These include mechanical \nstretching of the skin (e.g. in pregnancy, during \nthe adolescent growth spurt), hormonal imbalance \n(hypercortisolic states such as Cushing syndrome) \nand hereditary influence6,7,8.\n\n\n\nStriae distensiae can be cosmetically distressing and \nvarious treatment strategies have been tried.\n\n\n\nUnfortunately, treatment of SD is both frustrating \nand disappointing. Studies evaluating the efficacy of \ntopical agents have been conflicting. Furthermore, \nthe therapeutic outcome may vary according to the \ntype of SD. Tretinoin appears to be more efficacious \nin the treatment of striae rubrae than striae \nalbae9,10,11. It may also be beneficial in preventing or \nreducing the severity of striae gravidarum12. Some \nof these topical agents may have a beneficial effect \non SD through collagen stimulation. Ud-Din et al \ndemonstrated significantly higher collagen levels in \npatients with SD treated with silicone gels13.\n\n\n\nIntroduction\nStriae distensae (SD) or stretch marks are common \ncutaneous lesions, most prevalent amongst \nadolescents, pregnant women and in individuals \nof body mass index (BMI) greater than 271,2,3. Up \nto 88% of adolescence may be affected [1]. In \naddition, the anatomical locations affected may \nvary between different patient population groups. \nThe abdomen and breasts are the most common \nsites for SD in pregnant women4. Although they do \nnot pose any threats to internal health, these dermal \nscars can cause significant psychological burden for \npatients4,5.\n\n\n\nTwo forms of SD have been described: striae rubrae \nand striae albae. The former appears initially as \nlinear erythematous plaques which then progress \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 8\n\n\n\nIn recent years, other treatment modalities have \nbeen tried. These include chemical/mechanical \ndebridement techniques, ablative and nonablative \nlasers, fractional resurfacing, light therapy, \nradiofrequency devices and microneedling therapy. \n4 Pulsed dye laser and intense pulsed light are \nthought to improve the appearance of SD through the \nstimulation of collagen production14,15. Fractional \ncarbon dioxide laser was shown to be more effective \nthan topical treatment with 10% glycolic acid+0.05% \ntretinoin cream in reducing the mean striae area \nin patients with striae alba16. Microdermabrasion \nhas been reported to activate a dermal remodeling \nand wound healing cascade via the elevation of \ntranscription factors, primary cytokines, matrix \nmetalloproteinases and procollagen17.\n\n\n\nThe MultiClear\u2122 machine is a multi-wavelength \nmedical device which can be adjusted to optimal \nnarrow band emission spectra in the UVA and UVB \nrange. Specifically, it emits three different ranges of \nnarrow-band light-UVB (296-315nm), UVA-1(360-\n370nm), and blue light (405-420nm) or blend of \nUVB and UVA1. Thus, it is able to selectively target \nmany skin conditions including psoriasis, acne and \nvitiligo18,19,20. In addition, it may help repigment \nhypopigmented scars and striae alba. To our \nknowledge, only one study using the MultiClear\u2122 \ndevice has been used in the treatment of SD and \nit demonstrated a greater than 50% improvement \nin repigmentation of stretch marks of 67% of \nparticipants at 8 weeks and 56% of participants at \n12 weeks after the last treatment21.\n\n\n\nIn the present study, we evaluate the efficacy and \nsafety of 12 twice-weekly treatments of UVB/\nUVA1 for the treatment of SD in patients of skin \nphototypes IV-V. The study was approved by \nNational Healthcare Group (NHG) Domain Specific \nReview Board.\n\n\n\nMaterials and Methods\nThe study was conducted at the National University \nHospital (NUH) in Singapore with the aim of \nassessing the efficacy of UVB/UVA1 therapy for \nthe treatment of striae alba. Thirty participants were \nconsecutively assessed for eligibility and recruited \naccordingly into the study. Patients with other co-\nexisting dermatoses, who were pregnant, previously \nintolerable to light treatment or treated with light in \nthe last six months and patients with skin type III and \nbelow were excluded. Eligible patients were those \nof either gender aged 21 and above who had striae \nalba, able to attend treatment sessions regularly and \nnot currently using any topical treatment for their \nstriae alba. Eighteen participants were enrolled and \ntwelve excluded. During the first visit, the width \nand length of the widest striae over the abdomen \nor thighs were measured and a baseline photograph \nwas taken. Participants were treated according to the \nMultiClear\u2122 (Curelight Ltd, Israel) manufacturer\u2019s \nprotocol for striae alba with the UVB/UVA1 mode. \nAll treatments started with a minimal erythema \ndose (MED) of 75mJ/cm2 which was increased by \n0.5MED for subsequent treatments. All subjects \nreceived twice-weekly treatments over a period \nof 6 weeks. Normal skin surrounding the striae \ndistensiae was shielded with a UV-blocking stencil. \nEach treated area was a one-inch square which was \nadded up to cover the intended area of treatment.\n\n\n\nUpon completion the course of treatment, \nparticipants were assessed by a doctor and \nmeasurements over the reference stria were \nrepeated. The same doctor performed pre- and \npost-treatment measurements. Any change in pre- \nand post-treatment measurements was calculated \nas a percentage of the pre-treatment measurement. \nPre and post-treatment photographs (with the \nparticipants in standing position) were evaluated by \na blinded investigator. The improvement in striae \n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\nMinimal to no improvement; <25% (stretch marks hardly changed or no obvious change)\n\n\n\nModerate improvement; 26-50% (stretch marks show some improvement in size only)\n\n\n\nGood improvement; 51-75% (stretch marks substantially diminished in size)\n\n\n\nVery good to excellent improvement; >75% (stretch marks disappeared or almost disappeared)\n\n\n\nTable 1. 4-point scale used to grade participant\u2019s striae distensiae (SD) after treatment.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 379\n\n\n\nwas graded on a 4 point scale (Table 1). Presence \nof tanning was recorded. A post-treatment feedback \nform was also distributed to the participants.\n\n\n\nPre- and post-treatment results were analysed using \na one-tailed T test.\n\n\n\nResults\nEighteen participants were enrolled for the study. \nFourteen participants completed the study. Four \ndropped out due to unsightly pigmentation from \ntanning and inability to comply with the treatment \nschedule. Those who dropped out were not included \nin the final analysis of the study \n\n\n\n(i) Patient demographics\nAll participants were female. The median age was \n28 years (Range: 26- 52 years). All but two were of \nskin phototype IV (Table 2). 50% of the participants \nwere Chinese, the remaining were either of Malay, \nFilipino or Indian race.\n\n\n\n(ii) Pre- and Post-treatment measurements\nSix participants (42.9%) had reductions in \nthe width of their SD varying 10-40%(Mean \nreduction 0.54mm, p= 0.0038), the remaining eight \nparticipants showed no change (Table 3). Four \nparticipants (28.6%) had reductions in the length of \ntheir SD (Mean reduction 4.57mm, p= 0.069) whilst \nten participants had no difference.\n\n\n\n(iii) Pre- and Post-treatment appearance of SD\nMost participants (64.3%) did not have any \nnoticeable improvement in the appearance of their \nSD (Graph 1, Figures 1-3). Ten participants (71.4%) \nwere noted to develop tanning as a consequence of \ntreatment. Four patients developed marked tanning \nthat took the form of the stencil shape that was \nexposed to the UV light (Figure 4).\n\n\n\n(iv) Patient Feedback\nClose to half (42.9%) of participants felt that \nthere was no improvement in their stretch marks \nafter treatment. Only four participants (28.6%) \nperceived some improvement. When asked on \naspects of improvement, half of the patients felt \nthat there was improvement in colour . Ten (71.4%) \nparticipants felt warmth during treatment but none \nexperienced any pain. The only reported side-effect \nwas tanning in eight (57.1%) of the participants. \nOnly four participants (28.6%) would recommend \nthe treatment to others. \n\n\n\nPatient No.\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\n11\n\n\n\n12\n\n\n\n13\n\n\n\n14\n\n\n\nAge\n\n\n\n27\n\n\n\n26\n\n\n\n28\n\n\n\n52\n\n\n\n30\n\n\n\n28\n\n\n\n28\n\n\n\n28\n\n\n\n48\n\n\n\n28\n\n\n\n30\n\n\n\n28\n\n\n\n32\n\n\n\n37\n\n\n\nRace\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nChinese\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nFilipino\n\n\n\nFilipino\n\n\n\nChinese\n\n\n\nSkin phototype*\n\n\n\nIV\n\n\n\nIV\n\n\n\nIV\n\n\n\nIV\n\n\n\nV\n\n\n\nIV\n\n\n\nIV\n\n\n\nIV\n\n\n\nIV\n\n\n\nIV\n\n\n\nV\n\n\n\nIV\n\n\n\nIV\n\n\n\nIV\n\n\n\nSite of striae distensiae\n\n\n\nR lower abdomen\n\n\n\nL thigh\n\n\n\nR thigh\n\n\n\nL abdomen\n\n\n\nL abdomen\n\n\n\nR thigh\n\n\n\nR lower abdomen\n\n\n\nR thigh\n\n\n\nR thigh\n\n\n\nR thigh\n\n\n\nL thigh\n\n\n\nL thigh\n\n\n\nL abdomen\n\n\n\nR abdomen\n\n\n\nTable 2. Patient demographics.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 10\n\n\n\nPatient\nNo.\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\n11\n\n\n\n12\n\n\n\n13\n\n\n\n14\n\n\n\nWidth of\nwidest striae\n(pre-treatment \nmm)\n\n\n\n5\n\n\n\n4\n\n\n\n4\n\n\n\n3\n\n\n\n5\n\n\n\n2\n\n\n\n5\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n3\n\n\n\n3\n\n\n\nWidth of\nwidest striae\n(post-treatment \nmm)\n\n\n\n3\n\n\n\n4\n\n\n\n3\n\n\n\n2\n\n\n\n4\n\n\n\n2\n\n\n\n4.5\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n2\n\n\n\n% change\n\n\n\n40\n\n\n\n0\n\n\n\n25\n\n\n\n33.3\n\n\n\n20\n\n\n\n0\n\n\n\n10\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n33.3\n\n\n\n% change\n\n\n\n30.8\n\n\n\n4.4\n\n\n\n0\n\n\n\n10\n\n\n\n10\n\n\n\n11.1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\nLength of\nwidest striae\n(pre-treatment \nmm)\n\n\n\n130\n\n\n\n90\n\n\n\n70\n\n\n\n100\n\n\n\n90\n\n\n\n70\n\n\n\n100\n\n\n\n65\n\n\n\n75\n\n\n\n35\n\n\n\n110\n\n\n\n90\n\n\n\n70\n\n\n\n80\n\n\n\nLength of\nwidest striae\n(post-treatment \nmm)\n\n\n\n90\n\n\n\n86\n\n\n\n70\n\n\n\n90\n\n\n\n80\n\n\n\n70\n\n\n\n100\n\n\n\n65\n\n\n\n75\n\n\n\n35\n\n\n\n110\n\n\n\n90\n\n\n\n70\n\n\n\n80\n\n\n\nTable 3. A summary of the pre- and post- treatment measurements of the width and length of the \nwidest striae. The numbers in bold represent the percentage (%) change in measurements.\n\n\n\nGraph 1. Improvement in striae distensiae (SD) \nappearance as scored by the investigator post-treatment.\n\n\n\nFigure 1. Pre- (A) and post-treatment (B) \nphotographs of a patient rated to have a grade 2 \nimprovement. This patient also had a 33.3% reduction \nin the width of the reference SD and a 10% decrease \nin the length of the longest SD.\n\n\n\nFigure 2. Pre- (A) and post-treatment (B) \nphotographs of a patient rated to have a grade 1 \nimprovement. The patient had a 25% reduction in the \nwidth but no change in the length of the SD.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3711\n\n\n\nhelp improve the appearance of hypopigmented \nstriae alba through increased melanin pigment, \nmelanocyte hypertrophy and an increase in the \nnumber of melanocytes25.\n\n\n\nAlthough our study demonstrated a minute but \nstatistically significant improvement in the width \nof SD after MultiClear\u2122 treatment, the results \ncould be confounded by the small sample size and \ndrop-out bias. Objective scoring of SD is difficult \nand no scales have been validated8. We attempted \nto objectively measure the width and length of the \nwidest striae but we may have missed significant \nimprovement over the other striae.\n\n\n\nThe management of SD remains challenging. Only \na small proportion of our participants showed \nsatisfactory improvement following treatment. \nUnsightly patterned pigmentation from tanning \nwas a common outcome. Less intensive treatment \nregimens may thus be considered in future studies \ninvolving laser/light-treatment of SD in Asian \npatients. \n\n\n\nAcknowledgments\nThe authors would like to thank Madam Peh Bee \nEng for her contribution to the study.\n\n\n\nDiscussion\nOnly 35.7% of our participants were assessed to \nhave an improvement after comparing pre and \npost-treatment clinical photos. Moreover, our \nparticipants were reviewed within 2 weeks after \nthe last treatment. Different treatment regimens \nmay have contributed to the difference observed. \nOur participants completed 12 treatment sessions \nover six weeks whereas in the study by Sadick at \nal21 study, participants completed a maximum of 10 \ntreatments over a longer duration of 22 weeks. In \naddition, their study focused on repigmentation of \nstriae alba in Fitzpatrick skin types II to IV whereas \nwe evaluated the change in width and length of striae \nalba in participants of skin types IV and V only.\n\n\n\nDarker skin types are prone to post-inflammatory \nskin pigmentation which may be evident after skin \nresurfacing treatments22. Ablative laser treatment \nusing the ablative 10 600-nm carbon dioxide (Co2) \nlaser may have some benefit in SD treatment but may \nresult in persistent erythema and post-inflammatory \npigmentation in patients with skin types IV and \nVI 10,23,24. Notably, more than half our participants \ndeveloped tanning as a result of the ultraviolet \ntreatment. Indeed, light sources emitting UVB may \n\n\n\nFigure 3. Pre- (A) and post-treatment (B) photographs of a patient who did not show any \nnoticeable improvement in the appearance of her striae distensiae (SD). There was no change in \nSD measurements after treatment.\n\n\n\nFigure 4. Tanning in a patient who completed \n12-weeks of twice weekly treatment.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 12\n\n\n\nReferences\n \n1. Cho S, Park ES, Lee DH et al. Clinical features and risk \n\n\n\nfactors for striae distensae in Korean adolescents. J Eur \nAcad Dermatol Venereol 2006; 20:1108\u201313.\n\n\n\n2. Chang ALS, Agredano YZ, Kimball AB. Risk factors \nassociated with striae gravidarum. J Am Acad Dermatol \n2004; 51:881\u20135. \n\n\n\n3. Garc\u0131a-Hidalgo L, Orozco-Topete R, Gonzalez-Barranco \nJ et al. Dermatoses in 156 obese adults. Obes Res 1999; \n7:299\u2013302.\n\n\n\n4. Yamaguchi K, Suganuma N, Ohashi K. Quality of life \nevaluation in Japanese pregnant women with striae \ngravidarum: a cross-sectional study. BMC Res Notes \n2012; 21:450.\n\n\n\n5. Al-Himdani S1, Ud-Din S, Gilmore S, Bayat A. Striae \ndistensae: a comprehensive review and evidence-based \nevaluation of prophylaxis and treatment. Br J Dermatol. \n2014 Mar;170(3):527-47.\n\n\n\n6. Kharb S, Gundgurthi A, Dutta MK, Garg MK. Striae \natrophicans: a mimic to Cushing\u2019s cutaneous striae. Indian \nJ Endocrinol Metab 2012;16(Suppl. 1):S123.\n\n\n\n7. Rogalski C, Haustein UF, Glander HJ, Paasch U. Extensive \nstriae distensae as a result of topical corticosteroid therapy \nin psoriasis vulgaris. Acta Derm Venereol 2003; 83:54\u20135.\n\n\n\n8. Garc\u0131a Hidalgo L. Dermatological complications of \nobesity. Am J Clin Dermatol 2002;3(7):497\u2013506.\n\n\n\n9. Hexzel D, Soirefmann M,  Porto MD et al. Superficial \ndermabrasion versus topical tretinoin on early striae \ndistensae: a randomized, pilot study. Dermatol Surg 2014 \nMay;40(5):537-44.\n\n\n\n10. Kang S, Kim KJ, Griffiths CE et al. Topical tretinoin \n(retinoic acid) improves early stretch marks. Arch \nDermatol 1996 May;132(5):519-26\n\n\n\n11. Pribanich S, Simpson FG, Held B et al. Low-dose tretinoin \ndoes not improve striae distensae: a double-blind, placebo-\ncontrolled study. Cutis 1994; 54:121\u20134\n\n\n\n12. Garc\u00eda Hern\u00e1ndez J\u00c11, Madera Gonz\u00e1lez D, Padilla \nCastillo M, Figueras Falc\u00f3nT. Use of a specific anti-stretch \nmark cream for preventing or reducing the severity of \nstriae gravidarum. Randomized, double-blind, controlled \ntrial.Int J Cosmet Sci. 2013 Jun;35(3):233-7.\n\n\n\n13. Ud-Din S, McAnelly SL, Bowring A et al. A double-blind \ncontrolled clinical trial assessing the effect of topical \ngels on striae distensae (stretch marks): a non-invasive \nimaging, morphological and immunohistochemical study. \nArch Dermatol Res. 2013 Sep;305(7):603-17.\n\n\n\n14. Shokeir H, El Bedewi, Sayed S, El Khalafawy G. Efficacy \nof pulsed dye laser versus intense pulsed light in the \ntreatment of striae distensae. Dermatol Surg Jun;40(6):632-\n40.\n\n\n\n15. Naein FF and Soghrati M. Fractional CO2 laser as an \neffective modality in treatment of striae alba in skin types \nIII and IV. J Res Med Sci. 2012 Oct;17(10):928-33.\n\n\n\n16. Karimipour DJ, Kang S, Johnson TM et al. \nMicrodermabrasion: a molecular analysis following a \nsingle treatment. J Am Acad Dermatol 2005; 52:215\u201323.\n\n\n\n17. Suh DH, Chang KY, Son HC, Ryu JH et al. Radiofrequency \nand 585-nm pulsed dye laser treatment of striae distensae: \na report of 37 Asian patients. Dermatol Surg 2007; 33:29\u2013\n34.\n\n\n\n18. Abel EA. 313 as action spectrum for psoriasis. \nPhototherapy.Dermatol Clin 1995;13:841-9.\n\n\n\n19. Noborio R, Nishida E, Kurokawa M, Morita A. A new \ntargeted blue light therapy for the treatment of acne. \n.Photodermatol Photoimmunol Photomed. 2007;23(1):32-\n4.\n\n\n\n20. Sapam R, Agrawalk S and Dhali TK. Systemic PUVA vs. \nnarrowband UVB in the treatment of vitiligo: a randomized \ncontrolled study. Int J Dermatol. 2012;51(9):1107-15.\n\n\n\n21. Sadick NS, Magro C and Hoenig A. Prospective clinical \nand histological study to evaluate the efficacy and safety of \na targeted high-intensity narrow band UVB/UVA1 therapy \nfor striae alba. J Cosmet Laser Ther 2007 Jun;9(2):79-83.\n\n\n\n22. Ho SG and Chan HH. The Asian dermatologic patient: \nreview of common pigmentary disorders and cutaneous \ndiseases. Am J ClinDermatol. 2009;10(3):153-68.\n\n\n\n23. Lee SE, Kim JH, Lee SJ et al. Treatment of striae distensae \nusing an ablative 10 600-nm carbon dioxide fractional \nlaser: a retrospective review of 27 participants. Dermatol \nSurg 2010; 36: 1683\u201390. \n\n\n\n24. Nouri K, Romagosa R, Chartier T et al. Comparison of the \n585 nm pulse dye laser and the short pulsed CO2 laser in \nthe treatment of striae distensae in skin types IV and VI. \nDermatol Surg 1999; 25:368\u201370.\n\n\n\n25. Goldberg DJ, Marmur ES, Schmultset al. Histologic \nand ultrastructural analysis of ultraviolet B laser and \nlight source treatment of leukoderma in striae distensae. \nDermatol Surg. 2005;31(4):385-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3713\n\n\n\nOriginal Article\n\n\n\nEVALUATION OF SERUM BIOTIN AND SERUM FERRITIN\nIN WOMEN WITH DIFFUSE HAIR LOSS\nNagesh TS1,  Misquith A2, Silvia WD3\n\n\n\nAbstract\n\n\n\nIntroduction: Diffuse hair loss is a very common problem in women. The condition has several \ncauses. Anything that interrupts the normal hair cycle can trigger diffuse hair loss. Various studies \nhave shown reduced levels of haemoglobin, serum ferritin, biotin, and thyroid abnormalities to be \ntriggering factors for diffuse hair loss. Supplements of biotin and iron are commonly used in the \nmanagement of diffuse hair loss in females. However contradictory observational data have so far \nfailed to establish a conclusive evidence about the serum levels of biotin and ferritin.\n\n\n\nMaterials and Methods: This study has been planned to evaluate the role of hemoglobin, thyroid \nhormones, serum levels of Biotin and Ferritin in female patients with diffuse hair loss of different \ntypes. 80 female patients presenting with diffuse hair loss were included in the study after considering \nthe inclusion and exclusion criteria. Ethical clearance was taken from the institutional ethics \ncommittee before starting the study. Serum ferritin and serum biotin were estimated using ELISA \nmethod. Haemoglobin was estimated using an auto analyzer. Thyroid function test were evaluated \nusing chemiluminiscence method.\n\n\n\nResults: Reduced haemoglobin was seen in 35 patients. However serum ferritin was reduced in only \none patient. Hypothyroidism was detected in 8 patients. Serum biotin was normal in all the patients. \nHowever serum biotin was towards the lower limit of normal in many patients.\n\n\n\nConclusion: From findings of our study, association of serum ferritin with hair loss is not conclusive \nand also the role of biotin in hair loss has to be evaluated with further larger studies.\n\n\n\nKeywords: Diffuse hair loss, Serum Ferritin, Serum Biotin, Thyroid Profile\n\n\n\nCorresponding Author and Reprint Request \nDr Nagesh TS, MD, DNB  \nNo 1586, \u2018Niharika\u2019, 17th \u2018A\u2019 main, 1st Stage\n5th Block HBR layout, Bangalore - 560043\nE-mail: drnageshts@gmail.com\n\n\n\n1 Department of Dermatology, STD and Leprosy\n2 Department of Biochemistry, Sapthagiri Institute \n of Medical Sciences and Research center, Bangalore, \n Karnataka, India\n3 Department of Biochemistry, Akash Institute of \n Medical Sciences, Bangalore, Karnataka, India\n\n\n\ndiffuse hair loss. The common causes include \ntelogen effluvium (acute and chronic) followed by \nfemale pattern hair loss, anagen effluvium, loose \nanagen hair syndrome, and diffuse type of alopecia \nareata1,2.\n\n\n\nVarious studies have shown reduced levels of \nhaemoglobin, serum ferritin, biotin, and thyroid \nabnormalities to be triggering factors for diffuse hair \nloss. Supplements of biotin and iron are commonly \nused in the management of diffuse hair loss in \nfemales. However contradictory observational data \nhave so far failed to establish a conclusive evidence \nabout the serum levels of biotin and ferritin3. Hence \nthis study has been planned to evaluate the role of \nhemoglobin, thyroid hormones, serum levels of \nferritin and biotin in female patients with diffuse \nhair loss of different types.\n\n\n\nIntroduction\nDiffuse hair loss is a very common problem in \nwomen. The condition has several causes. Anything \nthat interrupts the normal hair cycle can trigger \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 14\n\n\n\nResults\nMost of the patients in our study were in the age \ngroup of 18 to 30 years ( 60%) followed by 31 to 40 \nyears ( 27.5%), 41 to 50 years ( 8.75%) and 51 to \n60 years (3.75%) (Table 1). The average duration of \nhair loss was around 1 year. Reduced haemoglobin \nwas seen in 43.75% of patients. However serum \nferritin was reduced in only five patients (6.25%). \nHypothyroidism was detected in 8 (10%) patients. \nSerum biotin was normal in all the patients. However \nserum biotin was towards the lower limit of normal \nin many patients (22.5%). (Table 2 and 3)\n\n\n\nMaterials and Methods \nThis was a prospective cross sectional study. The \nstudy included 80 female patients aged 18 to 60 \nyears presenting with diffuse hair loss. Ethical \nclearance was taken from the institutional ethics \ncommittee before starting the study. The duration of \nstudy extended for a period of 1 year.\n\n\n\nA detailed history was taken about the onset, \nduration and severity of hair loss. Any precipitating \nfactors were ruled out by taking history suggestive \nof anaemia, thyroid abnormalities, hormonal \nabnormalities, fever, surgery, pregnancy, emotional \nstress and crash dieting. The patients were also \nasked for any drug intake or administration of \nchemotherapy and hair grooming practices (brushing \nwet hair, using hair drier, straightening). Patients \nwho were taking iron or multivitamin supplements, \nany products which influence hair growth or having \nthyroid abnormalities were excluded from the \nstudy. After considering the inclusion and exclusion \ncriterion, the eligible patients were asked to sign \na written informed consent. A thorough clinical \nexamination was done to look for any evidence of \nscarring or patchy hair loss.\n\n\n\nInclusion  criteria :\n\u2022\t Female\tpatients\n\u2022\t Patients\tbetween\t18\t-\t60\tyrs\n\u2022\t Non\tscarring\thair\tloss\tpatients\n\n\n\nExclusion criteria:\n\u2022\t Patients\ton\tiron\tor\tmultivitamin\tsupplements\tfor\t\n at least 3 months\n\u2022\t History\tof\tillness\tlasting\tlonger\tthan\t7\tdays\tover\t\n past 3 months\n\u2022\t Post\tpartum\twomen\twithin\t3\tmonths\n\u2022\t Patients\twho\thave\tapplied\tproducts\tknown\tto\t\n influence hair growth for 6 months\n\u2022\t Scarring\talopecia\n\u2022\t Patient\talready\ton\ttreatment\tfor\thypo-or\t\n hyperthyroidism\n\n\n\nHair shaft abnormalities\n5ml of blood sample was collected. Serum ferritin \nand serum biotin were estimated using ELISA \nmethod. Haemoglobin was estimated using an auto \nanalyzer. Thyroid function test were evaluated using \nchemiluminiscence method.\n\n\n\nAge group\n\n\n\n18 to 30 years\n\n\n\n31 to 40 years\n\n\n\n41 to 50 years\n\n\n\n51 to 60 years\n\n\n\nNumber of patients\n\n\n\n48\n\n\n\n22\n\n\n\n7\n\n\n\n3\n\n\n\nTable 1. Age group of patients with hair loss.\n\n\n\nHaemoglobin\n( 12 \u2013 16 g %)\n\n\n\nSerum ferritin\n(10-125 ng/ml)\n\n\n\nSerum biotin\n(7.8 \u2013 500 pg/ml)\n\n\n\nNormal\n(number of \npatients)\n\n\n\n45\n\n\n\n79\n\n\n\n80\n\n\n\nLow\n(number of \npatients)\n\n\n\n35\n\n\n\n5\n\n\n\nNil\n\n\n\nPercentage \nshowing low \nvalue\n\n\n\n43.8 %\n\n\n\n6.25 %\n\n\n\nNil\n\n\n\nTable 2. Haemoglobin, serum ferritin and serum biotin.\n\n\n\nT\n3\n\n\n\nT \n4\n\n\n\nTSH\n\n\n\nNormal\n(number of \npatients)\n\n\n\n80\n\n\n\n76\n\n\n\n76\n\n\n\nLow\n(number of \npatients)\n\n\n\n0\n\n\n\n4\n\n\n\n4\n\n\n\nPercentage \nshowing low \nvalue\n\n\n\nNil\n\n\n\n5 %\n\n\n\n5 %\n\n\n\nTable 3. Thyroid profile.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3715\n\n\n\nhave shown reduced serum ferritin. This could be \nbecause of the difference in the lower limit of serum \nferritin considered in our study. The lower limit of \nserum ferritin considered in our study was 20ng/ml  \nbased on the studies by Bregy A et al3 and Sinclair13 \ncompared to 40 ng/ml in the above studies. Studies \nby Bregy A et al3, Sinclair13 and Chamberlain AJ et \nal14 also have shown no association of serum ferritin \nwith hair loss in women.\n\n\n\nBiotin is a water soluble B-complex vitamin, \navailable in various dietary sources and is also \nsynthesized by intestinal bacteria. Biotin deficiency \nhas been associated with diffuse hair loss and is often \nused in the management of such cases. However \nthere is no concrete evidence for its association1,15,16. \nNone of the patients in our study showed reduced \nserum biotin. After extensive literature search no \nstudies were found which evaluated the role of \nserum biotin in diffuse hair loss in women.\n\n\n\nDiffuse telogen hair loss may occur in association \nwith thyroid abnormalities. Diffuse scalp \nalopecia occurs in about a third of hypothyroid \npatients. Hyperthyroidism, when severe, is said \nto cause a diffuse alopecia in up to 50% of cases. \nHypothyroidism inhibits cell division both in \nepidermis and in skin appendages. In a proportion of \npatients, this inhibition of mitosis induces catagen \nand delays re-entry of telogen hair into anagen. \nThe mechanism of hair loss in hyperthyroidism is \nunknown. With thyroxine replacement, the hair \nrapidly re-enter anagen and the telogen count falls. \nReplacement therapy generally leads to re-growth \nof hair within a few months. An exception to this \noccurs when the hypothyroidism has been present \nfor many years and the hair follicles have atrophied. \nHair loss in the hyperthyroid patient usually stops \nwithin 3 months of becoming euthyroid8.\n\n\n\nA study by Moltz has shown abnormal thyroid \nfunction tests in 20% of patients11. In our study 10% \nof patients showed features of hypothyroidism.\n\n\n\nConclusion\nBiotin and iron supplements are commonly used in \nthe treatment of hair loss. From the findings of our \nstudy, association of serum ferritin with hair loss is \nnot conclusive and also the role of biotin in hair loss \nhas to be evaluated with further larger studies.\n\n\n\nDiscussion\nHair loss is a common complaint in women and \naffects over 25% of women in developed countries4. \nFemale pattern hair loss (FPHL) and chronic diffuse \ntelogen effluvium (TE) account for majority of cases. \nIncreased shedding of telogen hair results either \nfrom synchronous transition of hair follicles from \nthe growing (anagen) to the resting stage of the hair \ncycle, or from progressive shortening of duration of \nanagen. The former mechanism underlines TE, the \nlater FPHL5,6,7. In TE, the telogen rate is elevated in \nall regions of scalp, including the occipital area; in \nFPHL, the telogen rate is elevated in the frontal and \ncentroparietal scalp region and spares the occipital \nscalp3.\n\n\n\nAnagen effluvium, radiotherapy, drugs, malnutrition, \niron deficiency, hypothyroidism, hyperthyroidism, \ndiffuse alopecia areata, telogen gravidarum are \nsome of the other causes of diffuse hair loss8.\n\n\n\nIron deficiency is the world\u2019s most common \nnutritional deficiency. In premenopausal women, \nthe most common cause of iron deficiency anemia \nare menstrual blood loss, and pregnancy. In \npostmenopausal women, the most common cause of \niron deficiency anaemia are gastrointestinal blood \nloss, and malabsorption. Haemoglobin concentration \ncan be used to detect for iron deficiency, whereas \nserum ferritin concentration can be used to confirm \niron deficiency.\n\n\n\nFerritin is a highly conserved protein complex \nthat plays an important role in iron storage and is \nrecognized as the main iron-binding protein in \nnonerythroid cells. Generally serum ferritin is \ndirectly related to intracellular ferritin and thus total \nbody iron stores. Only iron deficiency causes very \nlow serum ferritin concentrations; therefore a low \nserum ferritin concentration is very specific for iron \ndeficiency. Hence serum ferritin investigation is \nconsidered to be the most powerful screening tool \nfor iron deficiency9.\n\n\n\nA study by Rushton et al. has shown reduced \nhaemoglobin in 6% of patients and reduced serum \nferritin in 72% of patients10. A study by Moltz \nshowed a reduced serum ferritin in 42% of patients11. \nMoeinvaziri et al have also reported reduced serum \nferritin in females with diffuse hair loss12. This is \nin contrast to our study where 6.25% of patients \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 16\n\n\n\nReferences\n \n1. Behari S. Diffuse hair loss in an adult female: Approach \n\n\n\nto diagnosis and management: Indian J Dermatol \nLeprol.2009;75:20-28\n\n\n\n2. Malkud S. A hospital-based study to determine causes \nof diffuse hair loss in women. Journal of clinical and \ndiagnostic research: JCDR. 2015;9(8):1-4.\n\n\n\n3. Bergy A. Trueb R. No association between serum ferritin \nlevels> 10 mg/mL and hair loss activity in women: \nDermatology. 2008;217:1-6\n\n\n\n4. Vujovic A, Del Marmol V. The female pattern hair loss: \nreview of etiopathogenesis and diagnosis. BioMed research \ninternational. 2014; 9:1-9.\n\n\n\n5. Singal A, Sonthalia S, Verma P. Female pattern hair loss. \nIndian J Dermatol Venereol Leprol 2013;79:626-40.\n\n\n\n6. Gilmore S, Sinclair R. Chronic telogen effluvium is due to \na reduction in the variance of anagen duration. Australasian \nJournal of Dermatology. 2010;51(3):163-7.\n\n\n\n7. Malkud S. Telogen Effluvium: A Review. Journal of clinical \nand diagnostic research: JCDR. 2015 Sep;9(9):WE01 - 3.\n\n\n\n8. Sinclair R., \u201cDiffuse hair loss\u201d, International journal of  \nDermatology 1999;38:8-18  \n\n\n\n9. Benjamin L, Fowler W, Calogeras E., \u201cThe diagnosis  and \ntreatment of iron deficiency and its potential relationship to \nhair loss\u201d, J Am Acad Dermatol 2006;54:824-42 \n\n\n\n10. Rushton DH, Ramsay ID, James KC et al. Biochemical \nand trichological characterization of diffuse alopecia in \nwomen: Br J Dermatol. 1990;123(2):187-97.\n\n\n\n11. Moltz L. Hormonal diagnosis in so-called androgenetic \nalopecia in the female. Geburtshilfe Frauenheilkd. \n1988;48(4):203-14.\n\n\n\n12. Moeinvaziri M. Iron status in diffuse telogen hair loss \namong women. Acta Dermatovenerologica Croatica. \n2009;17(4): 279-84.\n\n\n\n13. Sinclair R. There is no clear association between low \nserum ferritin and chronic diffuse telogen hair loss. Br J \nDermatol. 2002;147(5):982-4\n\n\n\n14. Chamberlain AJ, Dawber RP. Significance of iron status \nin hair loss in women. British Journal of Dermatology. \n2003;149(2):428-.\n\n\n\n15. A.Tosti et al. Hair loss in women: Minerva Ginecol \n2009;61:1-8.\n\n\n\n16. Harrison S., Bergfeld W., Diffuse hair loss \u2013Its triggers and \nmanagement: Cleveland clinic journal of medicine 2009; \n76:361-67.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3717\n\n\n\nOriginal Article\n\n\n\nDERMATOLOGICAL DISEASES AMONG OCTOGENARIANS\nIN A TERTIARY CENTER\nLow DW1, Adawiyah J1, Norazirah MN1, Leelavathi M2\n\n\n\nAbstract\n\n\n\nIntroduction: Our country is fast becoming a developed country with improved life expectancy. The \nhealthcare system should be prepared to manage medical conditions which are prevalent in the older \nage group. Skin diseases are commonly observed in the geriatric population. We seek to characterize \nthe dermatological conditions affecting patients at the extremes of age. \n\n\n\nMethods: To determine the types of dermatological diseases affecting patients over 80 years of age, \nand to determine their clinical characteristics and comorbidities.\n\n\n\nObjectives: Subjects with photodamage were older, and had lower education and employment rates \ncompared to subjects without photodamage. There was no significant difference in knowledge on the \nharmful effects of sun exposure and on sun protection or in sun avoidance behaviour (other than use \nof protective sunglasses) between the two groups, though more patients with photodamage felt that \nthey take adequate sun protection measures. Of note, only a low percentage of subjects in both groups \n(24.5% of subjects with photodamage and 23.1% of subjects without photodamage) practise regular \nuse of sunscreen.\n\n\n\nMethods: This was a retrospective study conducted at the Dermatology Unit, University Kebangsaan \nMalaysia Medical Center (UKMMC). All patients aged \u226580 years who attended the Dermatology \nClinic UKMMC in 2015 were identified from the clinic database. Their clinical notes were reviewed. \nDemography, clinical characteristics and dermatological diagnosis were recorded and analyzed using \nSPSS Version 22.\n\n\n\nResults: One hundred and three octogenarians were included in the study. Fifty one (49.5%) were \nfemales, and 52 (50.5%) were males. The age ranged from 80 to 89 years. The majority were Chinese, \n76 (73.8%), 16 (15.5%) were Malays, 6 (5.8%) were Indians and remaining 5 (4.9%) were of other \nethnicities. The most commonly seen diseases were endogenous eczema 46 (44.7%), cutaneous \nmalignancy 10 (9.7%), psoriasis 8 (7.8%), bullous pemphigoid 7 (6.8%) and fungal infection 6 (5.8%). \nMore than half of patients [25 (24.3%)] with endogenous eczema had unclassified eczema. Other \nconditions were seborrheic keratosis 5 (4.9%), adverse drug eruption 5 (4.9%), viral infections 4 \n(3.9%) and lichen amyloidosis 3 (2.9%). Comorbidities of the patients were 48 (46.6%) hypertension, \n29 (28.2%) diabetes, 25 (24.3%) atherosclerosis related disease, 22 (21.4%) dyslipidemia, 9 (8.7%) \nchronic lung disease and 9 (8.7%) non-skin malignancy.\n\n\n\nCorresponding Author and Reprint Request \nAdawiyah Jamil MMed AdvMDerm\nDepartment of Medicine\nUniversiti Kebangsaan Malaysia Medical Center\nBandar Tun Razak, Cheras 56000\nKuala Lumpur, Malaysia \nE-mail: adda_jamil@yahoo.com\n\n\n\n1 Division of Dermatology,\n National University Health System, Singapore\n2 Saw Swee Hock School of Public Health,\n National Health Group, Singapore\n\n\n\nConclusions: Eczema is very common in \nelderly patients. In the majority of patients the \nclinical features of eczema are often not typical \nof endogenous eczema subtypes. We propose \nthe term senectus eczema as a diagnosis, \nhowever its clinical characteristics has yet to \nbe clearly delineated. Skin cancers, psoriasis, \nbullous pemphigoid, fungal infections, drug \neruption and viral infection are other conditions \nwhich should not be missed in assessing these \npatients.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 18\n\n\n\n6 (5.8%) were Indian and the remaining 5 (4.9%) \npatients were of other ethnicities. There were 51 \n(49.5%) were females, and 52 (50.5%) males. Forty \neight (46.6%) had hypertension, 29 (28.2%) had \ndiabetes, 25 (24.3%) had atherosclerosis related \ndisease, 22 (21.4%) had dyslipidemia while 9 (8.7%) \nhad chronic lung disease and another 9 (8.7%) had \nnon-skin malignancy (Table 1).\n\n\n\nThe most common diseases were eczema, 49 \n(47.6%); cutaneous malignancy 10 (9.7%), psoriasis \n8 (7.8%), bullous pemphigoid 7 (6.8%) and fungal \ninfection 6 (5.8%). Other diseases were seborrheic \nkeratosis 5 (4.9%), adverse drug eruption 5 (4.9%), \nviral infections 4 (3.9%) and lichen amyloidosis 3 \n(2.9%).\n\n\n\nEczema was the most frequently diagnosed disorder. \nThe majority of patients had endogenous eczema [46 \n(44.7%)], 3 (2.9%) patients had exogenous eczema. \nOut of 46 patients with endogenous eczema, more \nthan half were diagnosed with unclassified eczema \n[25 (24.3%)]. This was followed by stasis eczema \n[12 (11.7%)], seborrheic eczema [6 (5.8%)] and \nhand and feet eczema [3 (2.9%)].\n\n\n\nIn patients with cutaneous malignancy, the \ncommonest was basal cell carcinoma [5 (4.9%)], \nfollowed by squamous cell carcinoma [4 (3.8%)] \nand Bowen\u2019s disease [1 (1%)]. We did not find \nany association between dermatological diagnoses \nand comorbidities. Table 2 summarizes the \ndermatological diagnoses of our study population.\n\n\n\nTable 3 shows the distribution of cutaneous disease \nin octogenerians according to gender. Drug eruption \nwas more common in male patients. Psoriasis, \nbullous pemphigoid and lichen amyloidosis were \nmore common in females. However, statistically \nsignificant difference was observed only in psoriasis.\n\n\n\nDiscussions\nDermatological diseases affecting the elderly \nhave been described in a few studies. Liao et al \nreviewed 16,924 geriatric patients who attended \ntheir dermatology outpatient clinic4. More than half \nhad dermatitis and about a quarter was diagnosed \nwith fungal infection. Bilgili et al10 and Jindal et \nal11 reported similar findings. Another study in \nTurkey found malignant skin tumours as the second \nmost common condition following eczematous \ndermatitis12. Table 4 summarizes the results of these \nstudies in comparison to this current study.\n\n\n\nIntroduction \nSkin disease affects 45-83% of the geriatric \npopulation1-4. Aging changes the structure and \nphysiology of skin. Lipid content in the stratum \ncorneum is decreased, trans-epidermal water loss \nincreases, there is epidermal and dermal atrophy, \nloss of collagen and elastin, reduced vascularity \nand reduced cytokines and numbers of melanocytes \nand Langerhan cells5-7. These results in impaired \nbarrier function reduced chemical clearance \ncapacity, reduced immune responsiveness and \nwound healing, impaired sensory perception and \nthermoregulation8,9. Inevitable changes such as \ndryness, roughness, fragility, wrinkling and laxity \nare observed in elderly population. Consequently, \nxerosis, eczema, and infections are common in the \ngeriatric population.\n\n\n\nOur country is fast becoming a developed country \nwith improved life expectancy. In 2016, about 1.9 \nmillion of Malaysia\u2019s 31.7 million population are \n\u2265 65 years old8. It is estimated that there would \nbe 5.6 million senior citizens by the year 20358. \nHealthcare services should be prepared to provide \nquality care for patients in this age group. We aimed \nto characterize the dermatological conditions that \naffect patients at the extremes of age in order to \nbetter manage diseases which are prevalent in this \npopulation.  \n\n\n\nMethods \nThis was a retrospective study conducted at the \nDermatology Unit, University Kebangsaan Malaysia \nMedical Center (UKMMC). The primary objective \nwas to determine the types of dermatological \ndiseases affecting patients over 80 years of age. \nSecondary objectives were to determine their clinical \ncharacteristics and comorbidities. All patients \naged \u226580 years who attended the Dermatology \nClinic UKMMC in 2015 were identified from the \nclinic database. Their clinical notes were retrieved \nand reviewed. The dermatological diagnoses \ncaptured were according to the patients\u2019 presenting \ncomplaint. Data on demography, dermatological \ndiagnosis, clinical characteristics and comorbidities \nwere recorded and analyzed using SPSS Version22.\n\n\n\nResults\nA total of 103 octogeriatric patients were seen at \nthe Dermatology outpatient clinic in 2015. The \nmedian age of the study population was 84.6 years \nold. The age range was from 80 to 89 years. Seventy \nsix (73.8%) were Chinese, 16 (15.5%) were Malay, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3719\n\n\n\nCharacteristics\n\n\n\nAge\n\n\n\nGender\n\n\n\n Male\n\n\n\n Female\n\n\n\nEthnicity\n\n\n\n Malay\n\n\n\n Chinese\n\n\n\n Indian\n\n\n\n Others \n\n\n\nCo morbidities\n\n\n\n Hypertension\n\n\n\n Diabetes mellitus \n\n\n\n Atherosclerosis disease\n\n\n\n Dyslipidemia\n\n\n\n Chronic lung disease \n\n\n\n Non-skin malignancy\n\n\n\nMean or n (%)\n\n\n\n 84.6\n\n\n\n 52 (50.5)\n\n\n\n 51 (49.5)\n\n\n\n 16 (15.5)\n\n\n\n 76 (73.8)\n\n\n\n 6 (5.8)\n\n\n\n 5 (4.9)\n\n\n\n 48 (46.6) \n\n\n\n 29 (28.2) \n\n\n\n 25 (24.3) \n\n\n\n 22 (21.4) \n\n\n\n 9 (8.7) \n\n\n\n 9 (8.7)\n\n\n\nTable 1. Characteristics of the study population.\n\n\n\nDermatological disease\n\n\n\nEndogenous eczema\n\n\n\n  Unclassified eczema\n\n\n\n  Statis eczema\n\n\n\n  Seborrheic eczema\n\n\n\n  Hand and feet eczema\n\n\n\nExogenous eczema\n\n\n\nCutaneous malignancy\n\n\n\n Basal cell carcinoma\n\n\n\n Squamous cell carcinoma\n\n\n\n Bowen\u2019s disease\n\n\n\nPsoriasis\n\n\n\nBullous pemphigoid\n\n\n\nFungal infection\n\n\n\nDrug eruption \n\n\n\nSeborrheic keratosis\n\n\n\nViral infection\n\n\n\nLichen amyloidosis\n\n\n\nOthers\n\n\n\nn (%)\n\n\n\n 46 (44.7)\n\n\n\n 25 (24.3)\n\n\n\n 12 (11.7)\n\n\n\n 6 (5.8)\n\n\n\n 3 (2.9)\n\n\n\n 3 (2.9)\n\n\n\n 10 (9.7)\n\n\n\n 5 (4.9)\n\n\n\n 4 (3.8)\n\n\n\n 1 (1.0)\n\n\n\n 8 (7.8)\n\n\n\n 7 (6.8)\n\n\n\n 6 (5.8)\n\n\n\n 5 (4.9)\n\n\n\n 5 (4.9)\n\n\n\n 4 (3.9)\n\n\n\n 3 (2.9)\n\n\n\n 6 (5.8)\n\n\n\nTable 2. Dermatological diseases in the study population.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 20\n\n\n\nDisease\n\n\n\nEndogenous eczema\n\n\n\n Unclassified eczema\n\n\n\n Statis eczema\n\n\n\n Seborrheic eczema\n\n\n\n Hand and feet eczema\n\n\n\nExogenous eczema\n\n\n\nCutaneous malignancy\n\n\n\n Basal cell carcinoma\n\n\n\n Squamous cell carcinoma \n\n\n\n Bowen\u2019s disease   \n\n\n\nPsoriasis\n\n\n\nBullous pemphigoid\n\n\n\nFungal infection\n\n\n\nDrug eruption \n\n\n\nSeborrheic keratosis\n\n\n\nViral infection\n\n\n\nLichen amyloidosis\n\n\n\nOthers\n\n\n\nMale, n (%)\n\n\n\n 26 (25.2)\n\n\n\n 13 (12.6)\n\n\n\n 7 (6.8)\n\n\n\n 4 (3.9)\n\n\n\n 2 (1.9)\n\n\n\n 1 (1)\n\n\n\n 5 (4.8)\n\n\n\n 2 (1.9)\n\n\n\n 2 (1.9)\n\n\n\n 1 (1)\n\n\n\n 1 (1)\n\n\n\n 2 (1.9)\n\n\n\n 3 (2.9)\n\n\n\n 4 (3.9)\n\n\n\n 3 (2.9)\n\n\n\n 3 (2.9)\n\n\n\n 0 (0)\n\n\n\n 4 (3.9)\n\n\n\nFemale, n (%)\n\n\n\n 20 (19.4)\n\n\n\n 12 (11.7)\n\n\n\n 5 (4.8)\n\n\n\n 2 (1.9)\n\n\n\n 1 (1)\n\n\n\n 2 (1.9)\n\n\n\n 5 (4.8)\n\n\n\n 3 (2.9)\n\n\n\n 2 (1.9)\n\n\n\n 0 (0)\n\n\n\n 7 (6.8)\n\n\n\n 5 (4.9)\n\n\n\n 3 (2.9)\n\n\n\n 1 (1)\n\n\n\n 2 (1.9)\n\n\n\n 1 (1)\n\n\n\n 3 (2.9)\n\n\n\n 2 (1.9)\n\n\n\np value\n\n\n\n 0.43\n\n\n\n\n\n\n\n 0.61\n\n\n\n 1\n\n\n\n < 0.05\n\n\n\n 0.26\n\n\n\n 1\n\n\n\n 0.36\n\n\n\n 1\n\n\n\n 0.62\n\n\n\n 0.11\n\n\n\n -\n\n\n\nTable 3. Distribution of skin diseases according to gender.\n\n\n\nAuthors/\nParameters \n\n\n\nNo. (n)\n\n\n\nPopulation/ age\n\n\n\nEczema\n\n\n\nMalignant skin tumor\n\n\n\nPsoriasis\n\n\n\nBullous pemphigoid\n\n\n\nFungal infection\n\n\n\nLiao et al. \n(1993-1999)4\n\n\n\n16924\n\n\n\nTaiwan\n\u2265 65 years\n\n\n\n58.7 %\n\n\n\n2.1%\n\n\n\n3.9%\n\n\n\n0.8%\n\n\n\n38%\n\n\n\nBilgili et al. \n(2007-2010)10\n\n\n\n2217\n\n\n\nTurkey\n\u2265 75 years\n\n\n\n33.2%\n\n\n\n0.8%\n\n\n\n2.1%\n\n\n\n1.8%\n\n\n\n8.4%\n\n\n\nYalcin et al.\n(1999-2003)12\n\n\n\n128\n\n\n\nTurkey\n\u2265 85 years\n\n\n\n14.1%\n\n\n\n12.5%\n\n\n\n-\n\n\n\n2.3%\n\n\n\n6.3%\n\n\n\nJindal et al. \n(2012-2014)11\n\n\n\n1380\n\n\n\nIndia\n\u2265 60 years\n\n\n\n15.3%\n\n\n\n0.8%\n\n\n\n5.4%\n\n\n\n-\n\n\n\n18%\n\n\n\nThis study\n(2015)\n\n\n\n103\n\n\n\nMalaysia\n\u2265 80 years\n\n\n\n47.6%\n\n\n\n8.7%\n\n\n\n7.8%\n\n\n\n6.8%\n\n\n\n5.8%\n\n\n\nTable 4. Skin diseases among geriatric population in various countries.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37\n\n\n\nCutaneous malignancy was the second most \ncommon condition diagnosed in our study \npopulation. Increased cumulative effect of sun \nexposure and carcinogens with age and impaired \ncapacity of DNA repair may be responsible for the \nhigher incidence skin cancers in the older age group. \nThis was illustrated by Yalcin et al12 and our current \nstudy, the geriatric population aged 80 and above \nhad higher percentage of cutaneous malignancy \ncompared to those in their 60s and 70s (Table 4). \nSkin cancer was more common among the Chinese \nin our study population. This is most likely due to \ntheir skin type. In general, Malaysian Chinese has \nskin type III while the Malays and Indians have skin \ntype IV or V. In Turkey there seemed to be a higher \nprevalence of skin cancer in 1999-200312 compared \nto 2007-201010 (Table 4). The authors explained that \nthis finding was because most patients with skin \ntumors were referred to Plastic surgery while their \nstudy population was patients from Dermatology.\n\n\n\nPsoriasis, bullous pemphigoid, fungal infections, \ndrug eruption, viral infection and lichen amyloidosis \nwere diagnosed in less 8% of our study population. \nThese conditions should be considered in evaluating \nelderly patients with skin lesions.\n\n\n\nConclusion\nEczema is very common and should be considered \nfirst in the geriatric population. The clinical features \nof eczema in these patients are often not typical \nof endogenous eczema subtypes. We propose the \nterm senectus eczema as a diagnosis, however its \nclinical characteristics has to be clearly delineated. \nOther conditions like psoriasis, bullous pemphigoid, \nfungal infections, drug eruption and viral infection \nshould not be missed in assessing these patients. \nMalignant skin tumor is more common among the \nChinese compared to other ethnicities. \n\n\n\nEndogenous eczema was the most prevalent \ndisorder in our study population. Eczema affected \nup to 58% of geriatric patients that presented to \ndermatology services4,10-13. Seborrhoeic, asteotatic \nand stasis eczema, and lichen simplex chronicus \nwere the common subtypes described11,13,14. Other \neczematous skin disorders in the elderly has been \ndescribed as non-specific dermatitis4, dermatitis \nnot otherwise specified13, and endogenous eczema \n(grouped separately from other subtypes of \nendogenous eczema)11. Liao et al diagnosed non-\nspecific dermatitis in up to 75% of patients with \ndermatitis4. However, the definitions of these \nterms were not clearly explained. We used the \nterm unclassified eczema as a diagnosis in patients \nwhose rash morphology fitted classical clinical \nfeatures of eczema, but the distribution did not fall \ninto any of the endogenous eczema subtypes. This \ndiagnosis was made after allergic/ irritant contact \ndermatitis and drug induced eczematous reaction \nwere excluded following a thorough history and \nexamination. Patch test was not routinely performed \nif there is no clinical suspicion of allergic contact \ndermatitis from the history. History taking in the \nelderly is challenging as most patients are unable to \nrecall the chronology of the rash and use of possible \nallergens or irritants. Collateral history from care \ngivers is unreliable most of the time.\n\n\n\nUnclassified eczema is common in our patients. \nAssuming the terms non-specific dermatitis and \ndermatitis not otherwise specified are equivalent to \nour unclassified eczema, then this type of eczema is \nvery common in the elderly. A proper name is needed \nfor this condition and its clinical characteristics \nhave to be defined. We propose the name senectus \neczema as its pathophysiology is most likely due to \nthe natural aging process of the skin causing altered \nbarrier function and reduced hydration. In Latin, \nsenectus means old age. Unfortunately we are not \nable to produce a list of clinical characteristics due \nto the retrospective nature of our study.\n\n\n\nReferences\n \n1. Kilic A, Gul U, Aslan E, Soylu S. Dermatologic findings \n\n\n\nin the senior population of nursing homes in Turkey. Arch \nGerontol Geriatr 2008; 47: 93\u201398.\n\n\n\n2. S. Beauregard, Gilchrest BA.  A survey of skin problems \nand skin care regimens in the elderly. Arch Dermatol 1987; \n123: 1638\u20131643.\n\n\n\n3. Cybulski M, Krajewska-Kulak E. Skin diseases among \nelderly inhabitants of Bialystok, Poland. Clin Interv Aging \n2015; 10: 1937\u20131943.\n\n\n\n4. Liao YH, Chen KH, Tseng MP. Pattern of skin diseases \nin a geriatric patient group in Taiwan: A 7-year survey \nfrom the outpatient clinic of a university medical center. \nDermatology 2001; 203: 308\u2013313.\n\n\n\n5. Boss GR, Seegmiller JE. Age-related physiological \nchanges and their clinical significance. West J Med 1981; \n135: 434\u2013440.\n\n\n\n6. Gilchrest BA. Geriatric skin problems. Hosp Prac 1986; \n21(55): 59\u201365.\n\n\n\n21\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37\n\n\n\n7. Haroun MT. Dry skin in the elderly. Geriatrics & Aging \n2003; 6: 41\u201344.\n\n\n\n8. Department of statistics Malaysia official portal. https://\nwww.statistics.gov.my accessed on 29/9/2016.\n\n\n\n9. Farage MA, Miller KW, Elsner P, Maibach HI. Structural \ncharacteristics of the aging skin: a review. Cutaneous and \nOcular Toxicology 2007; 26: 343\u2013357.\n\n\n\n10. Bilgili SG, Karadag AS, Ozkol HU. The prevalence of skin \ndiseases among the geriatric patients in Eastern Turkey. \nJournal of Pakistan Medical Association 2012; 62: 535.\n\n\n\n11. Jindal R, Jain A, Roy S. Skin disorders among geriatric \npopulation at a tertiary care center in Uttarakhand. Journal \nof Clinical and Diagnostic Research 2016; 10(3): WC06-\n08.\n\n\n\n12. Yalcin B, Tamer E, Toy GG. The prevalence of skin \ndiseases in the elderly: analysis of 4099 geriatric patients. \nInternational Journal of Dermatology 2006; 45: 672\u2013676. \n\n\n\n13. Yap KB, Siew MG, Goh CL: Pattern of skin diseases in the \nelderly seen at the National Skin Center (Singapore) 1990. \nSingapore Med J 1994; 35: 147\u2013150.\n\n\n\n14. Jafferany M, Huynh TV, Silverman MA. Geriatric \ndermatoses: a clinical review of skin diseases in an aging \npopulation. International Journal of Dermatology 2012; \n51: 509\u2013522\n\n\n\n22\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3723\n\n\n\nOriginal Article\n\n\n\nCORRELATION BETWEEN CUMULATIVE DOSE OF \nMETHOTREXATE AND METHOTREXATE INDUCED \nHEPATOTOXICITY IN PSORIASIS PATIENTS UNDERGOING \nLIVER BIOPSY - A 15 YEARS RETROSPECTIVE STUDY\nAsha G1, Tang J J1, Chan LC2\n\n\n\nAbstract\n\n\n\nIntroduction: The use of methotrexate in treating moderate to severe psoriasis has been associated \nwith risk of hepatotoxicity. Emerging data suggest that methotrexate may be less hepatotoxic and thus \ncontroversy lies in the role of routine liver biopsy based on cumulative dose to detect hepatotoxicity \nduring treatment.\n\n\n\nObjevtive: The primary objective was to assess the correlation between cumulative dose of methotrexate \nwith hepatotoxicity in terms of liver biopsy grading and serum liver enzymes. Our secondary objective \nwas to establish the possible risk factors for methotrexate induced fibrosis/cirrhosis.\n\n\n\nMethod: A retrospective study was conducted on psoriasis patients who had undergone liver \nbiopsies after certain cumulative dose of methotrexate from year 2000 to 2014 in Department of \nDermatology, Hospital Raja Permaisuri Bainun. Correlation was assessed between total cumulative \ndose of methotrexate with liver biopsy grading (Roenigk classification) and serum liver enzymes. Risk \nfactors for liver fibrosis/cirrhosis (Grade III and IV) including age, gender, ethnicity, diabetes mellitus, \nhypertension, dyslipidemia and ethanol consumption were also assessed. Statistical analysis was done \nby using SPSS version 22.\n\n\n\nResults: Skin areas treated with AEBritening Complex-01 showed significant  degree of lightening \neffect (+1There were 52 patients with a mean age of 49.5 \u00b1 12.9 years. Fifty eight liver biopsies were \ndone with  6 having second biopsies. For the first liver biopsies, 5 had normal finding [mean cumulative \ndose (MCD) = 1629mg]; 29 Grade I (MCD=1701mg); 10 Grade II (MCD=2046 mg); 1 with Grade \nIIIa (MCD=1560mg); 1 Grade IIIb (MCD=1682mg); 2 Grade IV (MCD= 1628 mg). In terms of \nliver enzymes, 6 patients had raised ALT (>41) (MCD= 1333 mg) whereas 46 patients had normal \nALT (<41) (MCD= 1795 mg). 10 patients had raised AST (>40) (MCD= 1641 mg) compared to 42 \npatients with normal AST (<40) (MCD=1766 mg). There were no significant correlation between total \ncumulative dose with liver biopsy grading and serum liver enzymes. Age, gender, ethnicity, diabetes \nmellitus, hypertension, dyslipidemia were also not significant risk factors for liver fibrosis/cirrhosis \n(Grade III and IV). Out of 6 patients who underwent second biopsy, 3 had progression whereas 3 \nshowed no change of liver biopsy grading.\n\n\n\nCorresponding Author and Reprint Request \nDr Asha Govin\nDepartment of Dermatology\nHospital Raja Permaisuri Bainun Ipoh\nEmail: asha.govin@yahoo.com\n\n\n\n1 Department of Dermatology,\n Hospital Raja Permaisuri Bainun Ipoh\n2 Department of Dermatology, Hospital Pulau Pinang\n\n\n\nConclusion: There was no association between \ntotal cumulative dose of methotrexate with \nliver biopsy grading and serum liver enzymes. \nLiver biopsy should be performed according to \nclinical indication instead of purely based on \ncumulative dose of methotrexate.\n\n\n\nKeywords: psoriasis, methotrexate, hepatotoxicity,\nliver biopsy, cirrhosis, fibrosis \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 24\n\n\n\nalkaline phosphatase, albumin, bilirubin, hepatitis \nB and C serology, where available), concomitant \nuse of hepatotoxic drugs, cumulative MTX dose at \nthe time of liver biopsy and liver biopsy findings. \nHistological changes of liver biopsy were graded \naccording to Roenigk Classification6 (Table 1).\n\n\n\nStatistical analysis was performed using SPSS \nversion 22 (IBM). For correlation between \ncumulative dose of MTX with liver biopsy grading \nand serum liver function tests, Spearman\u2019s rank \ncorrelation was used. Multiple logistic regression \nwas used to evaluate the effect of age, gender, \nethnicity, diabetes, hypertension, dyslipidemia \nand cumulative dose of MTX on the liver biopsy \ngrading. Fisher\u2019s Exact test was subsequently used \nfor univariate analyses to ascertain whether any of \nthese risk factors were found to be significantly \nassociated with MTX induced liver fibrosis/\ncirrhosis.\n\n\n\nResults\nDemographics\nOver the period of 15 years, there were 52 psoriatic \npatients who underwent liver biopsy. Out of these 52 \npatients, 4 turned out to be inadequate liver biopsy \nsamples. There were a total of 58 liver biopsies of \nwhich 6 patients had undergone liver biopsies for \nthe second time. The mean age was 49.5 \u00b1 12.9 \nyears (range 20 to 79) with majority males (55.8%) \nand the ethnic breakdown consisting of mainly \nChinese (n = 28, 54%), Malays (n = 14, 27%) and \nIndians (n = 10, 19%). Among the 52 patients, 14 \n(26.9%) had diabetes, 12 (23.1%) had hypertension, \n4 (7.7%) had hyperlipidemia, 1 (1.9%) was obese \nand 1 (1.9%) had chronic alcoholic hepatitis. None \nof our patients had hepatitis B or C infection.\n\n\n\nIntroduction\nMethotrexate (MTX) is indicated in about 20% of \nall patients with psoriasis and continues to be used \ndespite the emergence of newer therapies because \nof the length of experience with its use and its \nundoubted efficacy1,2. Hepatotoxicity associated \nwith MTX in psoriatic patients is well recognized, \nand in some patients can lead to hepatic fibrosis \nand even cirrhosis3. In the past, the prevalence of \nMTX induced liver fibrosis and cirrhosis have \nbeen reported to be as high as 50% and 26% \nrespectively in the west3. Traditionally, serial liver \nbiopsy guided by total cumulative dose of MTX has \nbeen a common practice to detect hepatotoxicity. \nHowever emerging data suggests that MTX may be \nless hepatotoxic than expected and thus controversy \nlies in the role of routine liver biopsy based on \ncumulative dose to detect hepatotoxicity during \ntreatment. The main aim of our study was to assess \nthe correlation between cumulative dose of MTX \nwith hepatotoxicity in terms of liver biopsy grading \nand serum liver enzymes. Our secondary objective \nwas to establish the possible risk factors for MTX \ninduced fibrosis/cirrhosis.\n\n\n\nMaterials and Methods\nA retrospective study was conducted on psoriasis \npatients who had undergone liver biopsies after \ncertain cumulative dose of MTX from year 2000 to \n2014 in Department of Dermatology, Hospital Raja \nPermaisuri Bainun. The case notes of these patients \nwere traced and the following information was \nextracted: age, gender, ethnicity, presence of potential \nrisk factors (diabetes, dyslipidemia, hypertension, \nethanol consumption), standard liver function tests \n(aspartate transaminase, alanine transaminase, \n\n\n\nGrade\n\n\n\nI\n\n\n\nII\n\n\n\nIII a\n\n\n\nIII b\n\n\n\nIV\n\n\n\nFibrosis\n\n\n\nNone\n\n\n\nNone\n\n\n\nMild (septa extending into lobules)\n\n\n\nModerate to severe\n\n\n\nCirrhosis\n\n\n\nFatty infiltration\n\n\n\nMild\n\n\n\nModerate to severe\n\n\n\nModerate to severe\n\n\n\nModerate to severe\n\n\n\nNuclear variability\n\n\n\nMild\n\n\n\nModerate to severe\n\n\n\nModerate to severe\n\n\n\nModerate to severe\n\n\n\nPortal inflammation\n\n\n\nMild\n\n\n\nPortal expansion, lobular necrosis\n\n\n\nPortal expansion, lobular necrosis\n\n\n\nPortal expansion, lobular necrosis\n\n\n\nTable 1. Roenigk classification of liver damage6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3725\n\n\n\nliver biopsy grading and serum liver enzymes \n(P=0.362 and 0.330 respectively). Out of 6 patients \nwho underwent a second biopsy, 3 had progression \nwhereas 3 showed no change of liver biopsy grading.\n\n\n\nRisk factor analysis\nWe used multiple logistic regression to assess \nthe significance of risk factors on the grading \nof liver biopsy. It was found that age, gender, \nethnicity, cumulative dose, diabetes, hypertension \nand dyslipidemia all had no significance on the \ngrading of liver biopsy on multivariate analysis. On \nunivariate analyses with Fisher\u2019s exact test, gender, \nethnicity, and the presence of diabetes, hypertension \nand dyslipidemia were also found to be of no \nsignificance with MTX associated liver fibrosis/\ncirrhosis. However, diabetes shows the highest \nassociation with MTX associated liver fibrosis/\ncirrhosis (p=0.055) but it was still statistically not \nsignificant.\n\n\n\nRelationship between cumulative dose with liver \nbiopsy grading and liver enzymes\nFrom the first series of liver biopsies, 5 showed \nnormal findings at mean cumulative dose (MCD) \nof 1629mg; 29 Grade I (MCD=1701mg); 10 \nGrade II (MCD=2046 mg); 1 with Grade IIIa \n(MCD=1560mg); 1 Grade IIIb (MCD=1682mg); \n2 Grade IV (MCD=1628mg). There was a total \nof 4 patients (8.3%) with liver fibrosis/cirrhosis \n(grade III or IV). Among those who had a \nsecond liver biopsy done, 3 had Grade I finding \n(MCD=2576mg); 2 Grade II (MCD=3885mg); \nand 1 Grade III a (MCD=3635mg). In terms of \nliver enzymes, 6 patients had raised ALT (>41) \n(MCD=1333mg) whereas 46 patients had normal \nALT (<41) (MCD=1795mg). 10 patients had \nraised AST (>40) (MCD=1641mg) compared to 42 \npatients with normal AST (<40) (MCD=1766mg). \nSpearman\u2019s rank correlation showed no significant \ncorrelation between total cumulative dose with \n\n\n\nHistology grade\n\n\n\nNormal\n\n\n\nI\n\n\n\nII\n\n\n\nIII a\n\n\n\nIII b\n\n\n\nIV\n\n\n\nNo.\n\n\n\n5\n\n\n\n29\n\n\n\n10\n\n\n\n1\n\n\n\n1\n\n\n\n2\n\n\n\nMean cumulative dose of MTX (mg)\n\n\n\n1629\n\n\n\n1701\n\n\n\n2046\n\n\n\n1560\n\n\n\n1682\n\n\n\n1628\n\n\n\nTable 2. Distribution of the grades of liver histology and the \nmean cumulative dose at first liver biopsy.\n\n\n\nHistology grade\n\n\n\nNormal\n\n\n\nI\n\n\n\nII\n\n\n\nIII a\n\n\n\nIII b\n\n\n\nIV\n\n\n\nNo.\n\n\n\n0\n\n\n\n3\n\n\n\n2\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\nMean cumulative dose of MTX (mg)\n\n\n\n-\n\n\n\n2576\n\n\n\n3885\n\n\n\n3635\n\n\n\n-\n\n\n\n-\n\n\n\nTable 3. Distribution of the grades of liver histology and the \nmean cumulative dose at second liver biopsy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 26\n\n\n\nRecent studies have reported that MTX cumulative \ndose was not correlated with liver toxicity. Our \npresent study also showed no such correlation. In \nfact, looking at transaminases, our patients with \nnormal ALT had higher MCD (1795mg) compared \nto those with raised ALT (MCD = 1333mg). Those \nwith normal AST had higher MCD (1766mg) \nwhereas patients with elevated AST had a lower \nMCD (1641mg).\n\n\n\nAlcohol consumption, diabetes, obesity, \ndyslipidemia, viral hepatitis, and the use of \nmedications such as arsenic and vitamin A are \nwell recognized risk factors reported to cause \nand accelerate the fibrotic progression in patients \ntreated with MTX7. Surprisingly in our study, it \nwas found that age, gender, ethnicity, cumulative \ndose, diabetes, hypertension and dyslipidemia all \nhad no significance on the grading of liver biopsy. \nAlthough statistically not significant, diabetes \nshows the highest association with MTX associated \nliver fibrosis/cirrhosis (p=0.055). This is because \nfatty liver is a well-known complication of diabetes \nmellitus which in turn can accelerate MTX induced \nhepatotoxicity.\n\n\n\nIn our study, we found that majority of the patients \nwho had undergone liver biopsy were Chinese which \nis most probably a reflection of the population in our \nstudy area. Besides that, more Malays were found to \nhave liver fibrosis (16.7%), however this finding was \nnot statistically significant, hence the cause for this \nis yet to be determined and more research is needed \nto ascertain the correlation between ethnicity and \nliver fibrosis.\n\n\n\nDiscussion\nData on MTX in psoriatic patients is well reported in \nthe western population, however data remains scarce \namong Asians. Very few studies have been conducted \namong Asian patients treated with MTX. A study \non Korean patients with rheumatoid arthritis found \nthat MTX was safe based on fibroscan4. Another \nretrospective study on psoriatic patients treated \nwith MTX in Malaysia showed that hepatotoxicity \nwas uncommon based on serum transaminases5. \nOne study in Singapore among psoriatic patients \non MTX showed that the prevalence of liver fibrosis \nwas comparable to the west and cumulative dose \nwas not significantly associated with liver fibrosis6. \nIn our study, there were only 4 patients (8.3%) with \nliver fibrosis/cirrhosis (grade III or IV). In general, \nour findings are consistent with those of recent \nstudies. Therefore, our findings also suggest that \nMTX induced hepatotoxicity may be less common \nthan previously reported.\n\n\n\nGender\n\n\n\nEthnicity\n\n\n\nDiabetes mellitus\n\n\n\nDyslipidemia\n\n\n\nHypertension\n\n\n\nMale\n\n\n\nFemale\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nYes\n\n\n\nNo\n\n\n\nYes\n\n\n\nNo\n\n\n\nYes\n\n\n\nNo\n\n\n\nRisk factor Proportion of patients with liver fibrosis/cirrhosis\n(Grade III /IV)\n\n\n\n 2/27 (7.4%)\n\n\n\n 2/21 (9.5%)\n\n\n\n 2/12 (16.7%)\n\n\n\n 1/27 (3.7%)\n\n\n\n 1/9 (11.1)\n\n\n\n 3/13 (23.1%)\n\n\n\n 1/35 (2.9%)\n\n\n\n 1/4 (25%)\n\n\n\n 3/44 (6.8%)\n\n\n\n 1/10 (10%)\n\n\n\n 3/38 (7.9%)\n\n\n\nP value\n\n\n\n 0.594\n\n\n\n 0.28\n\n\n\n 0.055\n\n\n\n 0.302\n\n\n\n 1.0\n\n\n\nTable 4. Risk factors analysis for MTX associated liver fibrosis (Univariate comparison \nmade with Fisher\u2019s Exact Test).\n\n\n\nFigure 1. Correlation between cumulative methotrexate \ndose and grades of liver biopsy (Scatter Plot).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3727\n\n\n\nConclusion\nHence, we conclude that there was no association \nbetween total cumulative dose of MTX with liver \nbiopsy grading and serum liver enzymes. On \nthe basis of the findings in this study, we suggest \nthat liver biopsy should be performed according \nto clinical indication instead of purely based on \ncumulative dose of MTX.\n\n\n\nAcknowledgement\nWe are grateful to all the doctors in Department \nof Dermatology, Hospital Raja Permaisuri Bainun \nIpoh, both past and present, who have been \nresponsible for the care of these patients during the \npast 15 years. The authors would like to thank Ms. \nLim Wei Yin from CRC Perak for her contribution \nin statistical analysis of this study. \n\n\n\nCurrently, it remains uncertain whether the use of \nnon-invasive tests can replace liver biopsy. Based \non latest available evidence, use of non-invasive \ntests such as fibroscan, fibrotest and procollagen III \nN-terminal propeptide (P III N P) are not sensitive \nenough to predict the severity of fibrosis8,9,10. At \npresent, in our setting, we do not recommend non-\ninvasive tests as an alternative to liver biopsy as \ndata on Asian psoriatic patients treated with MTX \nis lacking.\n\n\n\nWe acknowledge that our study has some limitations. \nFirstly, the sample size was small and probably \naccounted for the non-significant findings. Besides \nthat, due to the retrospective nature of this study, \nthere were missing or incomplete data. In our case, \nlack of data on patients\u2019 BMI made it not possible \nto assess the impact of obesity. Also, information on \nalcohol consumption was not available for most of \nthe patients in our study. The main strength of our \nstudy is the use of liver biopsy which remains the \ngold standard compared to other non-invasive tests \nwhich have limitations in terms of sensitivity and \nspecificity.\n\n\n\nReferences\n \n1. Bergstresser PR, Screiber SH, Weinstein GD. Systemic \n\n\n\nchemotherapy for psoriasis: a national survey. Arch \nDermatol 1976; 112: 977-981.\n\n\n\n2. Roenigk HH Jr, Auerbach R, Mailbach H, Weinstein \nG, Lebwohl M. Methotrexate in psoriasis: Consensus \nConference. J Am Acad Dermatol 1998; 38: 478-485.\n\n\n\n3. Roenigk H. Methotrexate. In: Dubertret L, editor. Psoriasis. \nBrescia, Italy: ISED, 1994: 162-173.\n\n\n\n4. Park SH, Choe JY, Kim SK. Assessment of liver fibrosis \nby transient elastography in rheumatoid arthritis patients \ntreated with methotrexate. Joint Bone Spine 2010; 77: 588-\n592.\n\n\n\n5. Ng LC, Lee YY, Lee CK, Wong SM. A retrospective review \nof methotrexate-induced hepatotoxicity among patients \nwith psoriasis in a tertiary dermatology center in Malaysia. \nInt J Dermatol 2013; 52: 102-105.\n\n\n\n6. Yeo CM, Chong VH, Earnest A, Yang WL. Prevalence \nand risk factors of methotrexate hepatotoxicity in Asian \npatients with psoriasis. World J Hepatol 2013; 5(5): 275-\n280.\n\n\n\n7. Zachariae H. Have methotrexate-induced liver fibrosis and \ncirrhosis become rare? A matter for reappraisal of routine \nliver biopsies. Dermatology 2005; 211: 307-308. \n\n\n\n8. Chalmers RJ, Kirby B, Smith A, Burrows P, Little R, \nHoran M, Hextall JM, Smith CH, Klaber M, Rogers \nS. Replacement of routine liver biopsy by procollagen \nIII aminopeptide for monitoring patients with psoriasis \nreceiving long-term methotrexate: a multicenter audit and \nhealth economic analysis. Br J Dermatol 2005; 152: 444-\n450.\n\n\n\n9. Berends MA, Snoek J, de Jong EM, van Krieken JH, de \nKnegt RJ, van Oijen MG, van de Kerkhof PC, Drenth JP. \nBiochemical and biophysical assessment of MTX-induced \nliver fibrosis in psoriasis patients: Fibrotest predicts the \npresence and Fibroscan predicts the absence of significant \nliver fibrosis. Liver Int 2007; 27: 639-645.\n\n\n\n10. Poynard T, de Ledinghen V, Zarski JP, Stanciu C, Munteanu \nM, Vergniol J, France J, Trifan A, Le Naour G, Vaillant JC, \nRatziu V, Charlotte F. Relative performances of Fibrotest, \nFibroscan and biopsy for the assessment of the stage of \nliver fibrosis in patients with chronic hepatitis C: a step \ntoward the truth in the absence of a gold standard. J \nHepatol 2012; 56: 541-548.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 28\n\n\n\nOriginal Article\n\n\n\nPEMPHIGUS: A SINGAPORE PERSPECTIVE\nValencia L1, Tay YK2, Teo R3\n\n\n\nAbstract\n\n\n\nBackground: Pemphigus is a group of immunobullous diseases that are diagnosed by histology \nand direct immunofluorescence (DIF).  Two variants are pemphigus vulgaris (PV) and pemphigus \nfoliaceus(PF). It is mediated by autoantibodies directed against desmogleins, namely anti-desmoglein \n1 in PF and anti-desmoglein 3 in PV.\n\n\n\nAims: To review the epidemiology of patients with pemphigus in Singapore.\n\n\n\nMethods: This was a retrospective study of pemphigus: comparative analysis was done for patient \ndemographics, treatment, induction of remission and relapse. Complete and partial remissions were \ndefined according to the definitions proposed by the International Pemphigus Committee.\n\n\n\nResults: All our PV patients had mucocutaneous disease.  Oral/lip involvement was the most frequent \n(100%) followed by genitalia lesions (40%). Only 22.2% of PF patients had mainly cutaneous disease \nwith mild mucosal involvement. In both variants, the cutaneous lesions were typically blisters and \nerosions. Our centre treats PV more aggressively than PF upon initial diagnosis. Higher initial doses \nof prednisolone were given with the use of adjuvants (86.7% in PV vs. 33.3% in PF). PV patients in \nour centre exhibited a shorter average time to disease control (1 month vs. 3 months in PF). 53.3% of \nPV patients went on to achieve complete remission as compared to 33.3% of PF patients.\n\n\n\nLimitations: This study is limited by its retrospective design and small sample size.\n\n\n\nConclusion: Our study shows that more aggressive initial treatment of pemphigus could lead to a \nshorter duration to disease control. PF may run a chronic course similar to PV and cause significant \nmorbidity.\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nDepartment of General Medicine\nTan Tock Seng Hospital, Singapore \nEmail: valencialong@gmail.com\n\n\n\n1 Department of General Medicine,\n Tan Tock Seng Hospital, Singapore \n2 Depertment of Dermatology, Changi General Hospital, \n Simei Street 3 Singapore 529889\n3 Raffles Hospital, Singapore\n\n\n\npemphigus foliaceus (PF). Histologically, there is \nintraepidermal blister formation and acantholysis. \nSuprabasalclefting is seen in pemphigus vulgaris/\nvegetans whereas superficial intra-epidermal bullae \nare found in PF. On direct immunofluorescence, \n(DIF), IgG and/or C3 is deposited in the \nintercellular spaces of the epidermis on the surface \nof keratinocytes in and around the lesions.\n\n\n\nClinically, PV is characterized by both mucosal and \ncutaneous blistering and erosions (Fig.1) while PF \ntends to manifest as solely cutaneous blistering. \n(Fig.2) The mortality rate ranges from 5-10%1 and \nthe mainstay of treatment is systemic corticosteroids. \nOther immunosuppressants may be added for their \nsteroid-sparing effects.\n\n\n\nIntroduction\nPemphigus is an autoimmune bullous disease \ncharacterized by auto- antibodies directed against \ndesmoglein (DG) 1 and desmoglein (DG) 3. Two \nmain subtypes exist -pemphigus vulgaris (PV) and \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3729\n\n\n\nsoftware STATA VERSION 10.1. P values less than \n0.05 were regarded to be statistically significant. \n\n\n\nResults\nThe data of twenty-four patients were retrieved. \nTable 1 shows the patient demographics of patients. \nTable 2 shows the clinical features of PV and PF. \nTable 3 shows the various treatment modalities. \nTable 4 shows the treatment outcomes.\n\n\n\nAlthough PV is generally regarded as a more severe \nform of disease than PF, studies2 have suggested \nthat patients with PV and mucosal involvement may \nhave a higher likelihood of attaining CR off therapy. \nHowever, this has not been assessed in the Asian \npopulation.\n\n\n\nThe aim of this study was to review the clinical \nfeatures and evaluate prognostic factors of adult \npatients diagnosed with pemphigus at Changi \nGeneral Hospital, Singapore from 2006 to 2012. \n\n\n\nMaterials and Methods\nRetrieval of data \nThis was an ethics-approved retrospective study. \nPatients aged 18 and above with a diagnosis of \nPV or PF diagnosed between January 2006 to \nDecember 2012 were included. The diagnosis of \npemphigus was made based on clinical, histology \nand DIF features.\n\n\n\nData collection \nPatient demographics, clinical presentations, \nlaboratory investigations, treatment and eventual \noutcomes were extracted from the patients\u2019 medical \nrecords.\n\n\n\nDefinitions used \nA consensus statement3 has been proposed to \nprovide definitions for stages of disease activity \nas well as to determine therapeutic end points for \npemphigus. These definitions are listed in Table 4.\n\n\n\nStatistical analysis \nFisher\u2019s exact test was used to assess the relationships \nbetween categorical variables. The Mann-Whitney U \ntest was used for the continuous variables. Logistic \nregression analyses were performed with the \n\n\n\nPatient characteristics\n\n\n\nSex \n\n\n\n Male\n\n\n\n Female\n\n\n\nAge (years)\n\n\n\n Range\n\n\n\n Mean\n\n\n\nEthnicity \n\n\n\n Chinese \n\n\n\n Indian \n\n\n\n Malay \n\n\n\n Others\n\n\n\nPV (%)\n\n\n\nn=15 (62.5)\n\n\n\nPV (%)\n\n\n\n6 (40.0)\n\n\n\n9 (60.0)\n\n\n\nPV \n\n\n\n16-63\n\n\n\n45.5\n\n\n\nPV (%)\n\n\n\n8 (53.3)\n\n\n\n1 (6.7)\n\n\n\n5 (33.3)\n\n\n\n1(6.7)\n\n\n\nPF (%)\n\n\n\nn=9 (37.5)\n\n\n\nPF (%)\n\n\n\n2 (22.2)\n\n\n\n7 (77.8)\n\n\n\nPF \n\n\n\n45-82\n\n\n\n60\n\n\n\nPF (%)\n\n\n\n8 (88.9) \n\n\n\n0 (0)\n\n\n\n0 (0) \n\n\n\n1 (11.1)\n\n\n\nTable 1. Patient demographics.\n\n\n\nClinical subtype \n\n\n\nDuration of disease before diagnosis (months)\n\n\n\nRange \n\n\n\nMean \n\n\n\nOverall clinical profile of patient  (%)\n\n\n\nMucocutaneous disease \n\n\n\nCutaneous disease only \n\n\n\nMucousal disease only \n\n\n\nMucosal lesions as initial\npresentation\n\n\n\nMean time before appearance\nof cutaneous lesions (months)\n\n\n\nMucosal lesions same onset\nas cutaneous lesions \n\n\n\nCutaneous lesions before\nmucosal lesions\n\n\n\nClinical manifestations\n\n\n\nMucosal involvement\n\n\n\nOral and/lip involvement \n\n\n\nGenitalia involvement\n\n\n\nConjunctival involvement\n\n\n\nEar, nose, throat (ENT)\ninvolvement \n\n\n\nCutaneous manifestations \n\n\n\nBlisters \n\n\n\nErosions \n\n\n\nKey investigations done \n\n\n\nHSV PCR and/or culture \n\n\n\nConcurrent HSV infection\nwith positive HSV PCR results \n\n\n\nSkin biopsy\n\n\n\nThe enzyme-linked\nimmunosorbent assay\n(ELISA) done \n\n\n\nNumber of positive results \n\n\n\nDirect Immunofluorescence\n(DIF) done\n\n\n\nIndirect immunofluorescence\n(IIF)\n\n\n\nPositive on monkey esophagus\nsubstrate/normal skin substrate\n\n\n\nPositive on transitional rat\nbladder epithelium \n\n\n\nPV (%)\n\n\n\nn - 15 (62.5) \n\n\n\n0.5- 4.0\n\n\n\n1.8 (SD 1.1)\n\n\n\n15 (100)\n\n\n\n0 (0)\n\n\n\n0  (0) \n\n\n\n7 (46.7)\n\n\n\n1.25\n\n\n\n3 (20)\n\n\n\n5 (33.3)\n\n\n\nPV (%)\n\n\n\n15 (100) \n\n\n\n6 (40)\n\n\n\n2 (13.3)\n\n\n\n2  (13.3) \n\n\n\nPV (%)\n\n\n\n15 (100)\n\n\n\n15 (100) \n\n\n\nPV (%)\n\n\n\n8 (53.3)\n\n\n\n3 (37.5)\n\n\n\n15 (100)\n\n\n\n15 (100)\n\n\n\n15 (100)\n\n\n\n15 (100)\n\n\n\n15 (100)\n\n\n\n15 (100) \n\n\n\n0 (0) \n\n\n\nPF (%)\n\n\n\nn = 9 (37.5)\n\n\n\n1.0 \u2013 36.0\n\n\n\n6.4 (SD 11.3)\n\n\n\n2 (22.2)\n\n\n\n7 (77.8)\n\n\n\n0 (0)\n\n\n\n0 (0)\n\n\n\nNA\n\n\n\n0\n\n\n\n2 (22.2)\n\n\n\nPF (%)\n\n\n\n1 (11.1)\n\n\n\n0 (0)\n\n\n\n1 (11.1)\n\n\n\n0 (0)\n\n\n\nPF (%)\n\n\n\n9 (100)\n\n\n\n9 (100)\n\n\n\nPF (%)\n\n\n\n1 (11.1)\n\n\n\n1 (100)\n\n\n\n9 (100)\n\n\n\n9 (100) \n\n\n\n9 (100) \n\n\n\n9 (100)\n\n\n\n9 (100)\n\n\n\n7 (77.8) \n\n\n\n0 (0) \n\n\n\nTable 2. Clinical diagnosis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 30\n\n\n\nPrednisolone monotherapy\n\n\n\nPrednisolone and adjuvant\n\n\n\nDapsone\n\n\n\nAzathioprine \n\n\n\nMycophenolate mofetil  \n\n\n\nIntravenous immunoglobulin  \n\n\n\nRituximab \n\n\n\nMethotrexate\n\n\n\nPatients treated with topical steroids alone \n\n\n\nAverage initial dose of prednisolone to achieve disease control* (mg/day)\n\n\n\nAverage time to disease control (months) \n\n\n\nAverage follow up (months)  \n\n\n\nPV (%)\n\n\n\n2 (13.3)\n\n\n\n13 (86.7)\n\n\n\n2 (13.3)\n\n\n\n13 (86.7)\n\n\n\n3 (20) \n\n\n\n1 (6.7)\n\n\n\n1 (6.7)\n\n\n\n1 (6.7)\n\n\n\n0 (0)\n\n\n\n54.6\n\n\n\n1\n\n\n\n48\n\n\n\nPF (%) \n\n\n\n6 (66.7)\n\n\n\n2 (22.2)\n\n\n\n0 (0)\n\n\n\n1 (11.1)\n\n\n\n0 (0) \n\n\n\n1 (11.1)\n\n\n\n0 (0)\n\n\n\n0 (0)\n\n\n\n1 (11.1)\n\n\n\n28.75\n\n\n\n3\n\n\n\n23\n\n\n\nTable 3. Treatment modalities.\n\n\n\nPatients under complete remission\n\n\n\nCR1\n\n\n\nCR off therapy2\n\n\n\nCR on therapy3 \n\n\n\nAverage time to complete 1st remission (months)\n \nAverage number of relapses7\n\n\n\nPatients under partial remission\n\n\n\nPR4\n\n\n\nPR off therapy5\n\n\n\nPR on therapy6\n\n\n\nAverage time to complete 1st remission (months)\n\n\n\nAverage time required to attain partial remission from previous relapse \n(months)\n\n\n\nAverage number of relapses \n\n\n\nTotal no of patients with complete/partial remission \n\n\n\nPatients with active disease (as of 2013) \n\n\n\nPatients lost to follow up \n\n\n\nPatients who died of other causes \n\n\n\nRelapses (averaged for CR and PR) \n\n\n\nAverage PR and PV maintenance8 dose of prednisolone (mg OD) \n\n\n\nAverage PR and PV control9 dose of prednisolone (mg OD) \n\n\n\nPV (%)\n\n\n\n8 (53.3)\n\n\n\n4 (26.7)\n\n\n\n4 (26.7)\n\n\n\n4.75\n\n\n\n1\n\n\n\nPV (%)\n\n\n\n4 (26.7)\n\n\n\n1 (6.7)\n\n\n\n4 (20)\n\n\n\n21.25\n\n\n\n1.5\n\n\n\n2\n\n\n\n12 (80)\n\n\n\n3 (20)\n\n\n\n0\n\n\n\n1\n\n\n\n1.3\n\n\n\n6.1\n\n\n\n54 \n\n\n\nPF (%) \n\n\n\n3 (33.3)\n\n\n\n1 (11.1)\n\n\n\n2 (22.2)\n\n\n\n5.7\n\n\n\n0\n\n\n\nPF (%) \n\n\n\n4 (44.4)\n\n\n\n2 (22.2)\n\n\n\n2 (22.2)\n\n\n\n8.75\n\n\n\n3\n\n\n\n1\n\n\n\n7 (77.8)\n\n\n\n2 (22.2)\n\n\n\n2 (13.3)\n\n\n\n1\n\n\n\n0.6\n\n\n\n4.6 \n\n\n\n25.6 \n\n\n\nTable 4. Treatment outcomes.\n\n\n\n*disease control defined as the time interval from baseline to the time at which new lesions cease to form and established \nlesions begin to heal.\n\n\n\n1 CR: Complete Remission \u2013 includes both complete remission on and off therapy \n2 CR off therapy: defined as the absence of new and/or established lesions while the patient is off all systemic therapy for at \n least two months\n3 CR on therapy: defined as the absence of new or established lesions while the patient is receiving minimal therapy\n4 PR: Partial remission \u2013 includes both partial remission on and off therapy \n5 PR off therapy: defined as the presence of transient new lesions that heal within one week without treatment and while the  \n patient is off all systemic therapy for at least two months.\n6 PR on therapy: defined as the presence of transient new lesions that heal within one week while the patient is receiving \n minimal therapy, including topical steroids.\n7 Relapse: defined as appearance of 3 or more new lesions a month that do not heal spontaneously within 1 week, or by the \n extension of established lesions, in a patient who has achieved disease control\n8 Maintenance dose: defined as the  lowest possible dose that prevents new lesions from appearing.\n9 Control dose: defined as the dose at which at which new lesions cease to form and established lesions begin to heal. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3731\n\n\n\nClinical features of Pemphigus Foliaceus\nAmongst the PF patients, 1 had oral mucosal lesions \nand another patient had conjunctival mucosal \ninvolvement. All 9 patients presented with cutaneous \nblisters/erosions (Fig.2).\n\n\n\nSignificant investigations \nHerpes Simplex Virus (HSV) Polymerase Chain \nReaction (PCR)/culture HSV PCR/ culture was \ndone in 8 (53.3%) cases. Three (37.5%) were \npositive for HSV 1. For those positive for HSV 1, \ntwo achieved CR on therapy and 1 achieved PR on \ntherapy. All 3 were treated with acyclovir. Where \nthere is a possibility of HSV co-infection in PV, true \nassociation between disease severity and prognostic \nfactors for exacerbation of PV is unclear. \n\n\n\nSome studies have suggested that when patients \npresent PV lesions which are refractory to \ncorticosteroid therapy, herpetic infection should be \nconsidered4. In our centre, repeated tests for HSV \n1 after initial diagnosis of PV were not routinely \nperformed unless the diagnosis of herpetic infection \nwas suspected\n\n\n\nOne patient with PF had a positive HSV PCR and \nculture. At the time of study, she had active disease. \n\n\n\nClinical features of Pemphigus Vulgaris \nIn our study, 7 (46.7%) with PV manifested first with \noral and/or lip lesions followed by cutaneous lesions \n(Fig.1). Three (20%) patients manifested with \nboth simultaneously and five (33.3%) of patients \nmanifested with cutaneous lesions first. The mean \nduration for the onset of cutaneous lesions after oral \nlesions was 1.25 months.\n\n\n\nOral lesions\nIn our study, all had mouth and/or lip lesions. \nThirteen patients (86.7%) had mouth lesions \nof which buccal ulcers, erosions comprised the \nmajority. Eleven patients (73.3%) had lip lesions \ncomprising of erosions, crusting and ulcers. Nine \n(60%) had both mouth and lip lesions. \n\n\n\nGenital lesions \nThe second most common presentation is genital \nerosions (40%)These involved the labia majora in \n100% of the cases for the women and shaft of penis \nfor the men.\n\n\n\nOcular and ENT lesions \nOcular and ENT involvement was seen in 2 (13%) \npatients. The patients with ocular involvement \npresented with discharge and crusting around eyes \nand they were evaluated by opthalmologists. Two \ndeveloped odynophagia and hoarseness of voice. \nThe presence of erosions, consistent with PV were \nconfirmed by an ENT surgeon. \n\n\n\nFigure 1. A patient with pemphigus vulgaris \npresenting as erosions and crusting on the \nback.\n\n\n\nFigure 2. A patient with pemphigus \nfoliaceus showing superficial scales and \ncrusts.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 32\n\n\n\n3rd decade of life formed the second most common \ngroup. In contrast, PF seems to affect the middle \naged- older age group mostly of ages from 6th to \n8th decade followed by 4th to 5th decade. This \ncorrelates well with existing literature5. \n\n\n\nIn patients with PV, oral manifestations are most \ncommon (100%, p <0.01).  More than half presented \nfirst with oral lesions followed by cutaneous blisters. \nOral and/or lip lesions may precede cutaneous \nlesions6 and this was also observed in our study. \nIntra-oral lesions were slightly more common than \nlip lesions, This correlates well with a 2001 study4. \nOur study shows that pain is the most common \nsymptom (80%). \n\n\n\nOur study shows involvement of lining mucosa \n(66.7%) is more common than masticatory mucosa \n(26.7%). Buccal involvement is most common and \ngingival lesions are least common.  This suggests \nthat the type of mucosal involvement in PV is \nrelated to physiological traumatic mechanisms in \npolystratified squamous epithelial structures. A \n2012 study by Fernandez et al15 reports that indeed \nthe most common symptom is pain, and buccal \nmucosal is most common oral mucosal lesion \n(90%). Compared with other studies6,12,13, our study \nshows that lip involvement was the most common \n(73.3%). Genital lesions were the second most \ncommon clinical manifestations (p= 0.05). This \ncorrelates with existing literature7,8 suggesting that \ninvolvement of the female genital tract in PV may \nnot be infrequent. In our study, the genitals are the \n2nd most common mucosal site of PV. A thorough \ngenital examination is needed to avoid missing \nlesions.\n\n\n\nEndoscopic ENT evaluation was not routinely \nperformed in our pemphigus patients. Only patients \nwho were symptomatic were referred to the ENT \nsurgeon. A 2011 study by Kavala et al9 assessing \nENT involvement in pemphigus patients found \nthat up to 13% of patients with PV may have ENT \ninvolvement but may be asymptomatic.\n\n\n\nFor our PF patients, mucosal involvement was noted \nin 2 of our patients - 1 with oral lesions and 1 with \nconjunctival involvement. Here, the \u2018desmoglein \ncompensation theory\u201914 as an explanation for the \nlocalization of blisters in patients with pemphigus \nis challenged. Recent studies14 have suggested that \nthis theory may not be perfect. It may be possible \nfor PF patients to present with mucosal lesions as \nfound in our study. \n\n\n\nTreatment regimens \nSystemic corticosteroids were the mainstay of \ntreatment for both PV and PF. All 15 PV patients \nreceived prednisolone. Thirteen (86.7%) of them \nhad adjuvant therapy. In contrast, 6 (66.7%)  PF \npatients received prednisolone monotherapy. Only \n2 (22.2%) had adjuvant therapy. One PF patient \nachieved complete remission with only topical \ncorticosteroids. \n\n\n\nThe average initial dose of prednisolone required \nfor PV patients to reach disease control was 54 mg/\nday compared to PF patients requiring 25.6 mg/day. \n\n\n\nAzathioprine was the most commonly used adjuvant \ndrug for both PV and PF patients. Other drugs \nused for treatment of PV included mycophenolate \nmofetil (MMF) (n=3), dapsone (n = 2), methotrexate \n(MTX) (n=1).  Recalcitrant cases were treated with \nrituximab (n =1) and intravenous immunoglobulin \n(IVIG) (n=1). Amongst the PF patients, only 1 \npatient required IVIG administration. None of \nthe PF patients required MMF, dapsone, MTX or \nrituximab.\n\n\n\nTreatment outcomes \nTreatment outcomes were classified at the \nrecommendation of the consensus study3. In \nparticular, we were interested in patients who \nattained complete remission off therapy. \n\n\n\nOf the PV patients, 4(26.7%) attained complete \nremission (CR) off therapy and 1 (6.7%) attained \npartial remission (PR) off therapy. Of the PF \npatients, 1 (11.1%)  attained CR off therapy and 2 \n(22.2%)  attained PR  off therapy. CR (off and on \ntherapy) was induced in 7 (46.6%) of PV patients \n5 years after diagnosis, compared to 3 (33.3%) of \nPF patients for the same time period. PV patients \nachieved a higher rate of CR compared to PF \npatients. \n\n\n\nThe mean time taken to attain the first clinical \nremission for PV patients was 4.3 months as \ncompared to 6 months for PF patients. \n\n\n\nThe mean duration of follow up for was 48.8 months \nfor PV patients and 23.3 months for PF patients. \n\n\n\nDiscussion\nIn our study, PV seems to affect mainly two groups \nof individuals, mostly of ages within the 4th to 6th \ndecade. Adolescents and young adults in the 1.5th to \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3733\n\n\n\nOur study reports a lower rate of complete \nremission off therapy than previous studies. This \ncould be attributed to the mindset of our patients \nor dermatologists treating pemphigus. The goal \nof treatment is taper off immunosuppression once \npatient has achieved remission. A significant \nproportion of our patients chose to stay on \nprednisolone at low doses such as 2.5mg/day \neven when they have been considered \u2018cleared\u2019 of \nlesions by physicians. Our study shows that 46.6% \nof patients achieved complete remission within 5 \nyears, comparable to the results of Western studies \nof around 50% for the same period. In a 2003 \nstudy11, only 37% of physicians stated that their goal \nwas to eliminate corticosteroids entirely, implying \nthat most would rather keep patients on a small dose \nof steroids to maintain the complete remission. \n\n\n\nThis study is limited by its retrospective design and \nsmall sample size. Two of our PF patients were lost \nto follow up and their remission status was therefore \nregarded as status during the last hospital visit. The \nrecently published ABSIS (AutoimmuneBullous \nSkin Disorder Intensity Score) and PDAI \n(Pemphigus Disease Area Index) severity scoring \nsystems could not be used in this retrospective study \nsince most of the patients were assessed before the \nrelease of the scoring systems. \n\n\n\nConclusion\nIn conclusion, we present 24 Asian patients with \npemphigus seen at a general hospital in Singapore \nover 6 years. In PV patients, oral mucosal lesions \nwere most common followed by genital lesions. \nOur study also suggests that PF may not run as \nbenign a course as previously thought, and that \ninitial mucosal involvement may be an important \ngood prognostic factor for eventual attainment of \ncomplete remission off therapy for PV.\n\n\n\nHSV has been reported to influence the course \nof PV disease and its presence may be associated \nwith PV flares and clinical exacerbations10. HSV \ninfection may also be a complication of systemic \nimmunosuppression. Clinically it may be difficult to \ndifferentiate cutaneous HSV infection from poorly \ncontrolled PV. A high index of clinical suspicion is \nrequired so that timely antivirals may be given.\n\n\n\nMost of our patients were given oral corticosteroids \nupon diagnosis, often with the addition of an \nadjuvant drug and topical corticosteroids. Two main \nregimens of corticosteroids were given - 0.5mg/kg/\nday and 1mg/kg/day. In general, patients with PV  \nreceived higher doses compared to the patients with \nPF.\n\n\n\nSurprisingly, our study found that that patients with \nPV may do better than PF in terms of  shorter mean \ntime to first clinical remission (4.75 months for \nPV  as opposed to 5.70 months for PF) and  higher \nincidence of CR (53.3% of PV patients achieved \ncomplete remission as compared to 33.3% of PF \npatients). While this phenomenon may be due to the \nfact that patients with PV were treated initially with \nhigher prednisolone doses, it is interesting to note \nthat more recent studies have also begun to challenge \nthe traditional view that PF is more benign than PV. \nDehen et al had previously reported a higher rate of \nrecurrence and relapse (67%) in patients with PF as \ncompared to patients with PV (17%).  \n\n\n\nA study by Almugairen et al reports that the \npresence of mucosal involvement and younger \nage at presentation prognosticates for complete \nremission off therapy (p=0.05) whereby patients \nwith PV and mucosal involvement had a 2.3-fold \nhigher likelihood of achieving complete remission \noff therapy as compared with patients with other \ntypes of pemphigus5. In our study, of the 5 out of \n24 patients who attained complete remission off \ntherapy, 1 had no initial mucosal involvement while \n4 did. While this was not statistically significant, \nit suggests that early mucosal involvement could \nprognosticate for complete remission off therapy. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 34\n\n\n\nReferences\n \n1. Chmurova N, Svecova D. Pemphigus vulgaris: a 11-year \n\n\n\nreview. Bratisl Lek Listy. 2009;110:500-3.\n2. Almugairen N, Hospital V, Bedane C, et al. Assessment \n\n\n\nof the rate of long-term complete remission off therapy in \npatients with pemphigus treated with different regimens \nincluding medium- and high-dose corticosteroids. J Am \nAcad Dermatol. 2013;69:583-8.\n\n\n\n3. Murrell DF, Dick S, Amagai M, et al. Consensus statement \non definitions of disease endpoints and therapeutic response \nfor pemphigus. J Am Acad Dermatol2008;58:1043-6\n\n\n\n4.  Brand\u00e3o ML, Fernandes NC, Batista DP, et al. Refractory \npemphigus vulgaris associated with herpes infection: \ncase report and review. Rev Inst Med Trop Sao Paulo \n2001;53:113-7.\n\n\n\n5. MGorsky, M Raviv, E Raviv, et al. Pemphigus vulgaris \nin adolescence.A case presentation and review of the \nliterature.Oral Surgery Oral Medicine Oral Pathology1994; \n77:620-2. \n\n\n\n6.  Shamim T, Varghese VI, Shameena PM, et al. Pemphigus \nvulgaris inoral cavity: Clinical analysis of 71 cases. Med \nOral Patol Oral Cir Bucal.2008;13:E622-6.\n\n\n\n7. Akhyani M1, Chams-Davatchi C, Naraghi Z, et al. \nCervicovaginal involvement in pemphigus vulgaris: a \nclinical study of 77 cases.Br J Dermatol. 2008;158:478-82.\n\n\n\n8. Fairbanks Barbosa ND, de Aguiar LM, Maruta CW, et \nal. Vulvo-cervico-vaginal manifestations and evaluation \nof Papanicolaou smears in pemphigus vulgaris and \npemphigus foliaceus.J Am Acad Dermatol. 2012;67:409-\n16.\n\n\n\n9. Kavala M1, Alt\u0131nta\u015f S, Kocat\u00fcrk E, et al. Ear, nose and \nthroat involvement in patients with pemphigus vulgaris: \ncorrelation with severity, phenotype and disease activity.J \nEur Acad Dermatol Venereol.2011 ;25:1324-7.\n\n\n\n10. Wilson C, Wojnarowska F, Mehra NK, et al.  Pemphigus \nin Oxford, UK, and New Delhi, India: a comparative study \nof disease characteristics and HLA antigens. Dermatology. \n1994;189 1:108-10.\n\n\n\n11. Mimouni D1, Nousari CH, Cummins DL. Differences and \nsimilarities among expert opinions on the diagnosis and \ntreatment of pemphigus vulgaris. J Am Acad Dermatol. \n2003;49: 1059-62.\n\n\n\n12. Shamim T, Varghese VI, Shameena PM, et al. Oral \npemphigus vulgaris: clinicopathologic study of 20 cases.\nIndian J Pathol Microbiol. 2007;50:498-501.\n\n\n\n13. Iamaroon A, Boonyawong P, Klanrit P, et al. Characterization \nof oral pemphigus vulgaris in Thai patients.J Oral Sci. \n2006 ;48:43-6.\n\n\n\n14.  K. Sardana, V.K. Garg, P. Agarwal. Is there an emergent \nneed to modify the desmoglein compensation theory in \npemphigus on the basis of Dsg ELISA data and alternative \npathogenic mechanisms? British J Dermatol. 2013: 168: \n669-74. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3735\n\n\n\nCase Report\n\n\n\nMETHOTREXATE TOXICITY \nLong V1, Huang JX2, Huma J3, Aw CW Derrick3, Nisha SC3\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nTan Tock Seng Hospital\n11 Jalan Tan Tock Seng, 308433\nEmail: valencialong@gmail.com \n\n\n\n1 Department of General Medicine,\n Tan Tock Seng Hospital, Singapore\n2 Department of Pathology,\n National University Hospital, Singapore\n3 Department of Dermatology,\n National University Hospital, Singapore\n\n\n\nkeratinocytes and epidermal disorganisation. MTX \nwas discontinued and leucovorin was started as \nrescue treatment. In addition, subcutaneous GCSF \nwas given at 300mcg daily for 5 days with eventual \nimprovement of mucositis and blood counts.\n\n\n\nCase report 2: A 51-year old Malay woman with \nchronic RA was treated with long term oral MTX \n22.5mg weekly, leflunamide and prednisolone. \nHer MTX dose was increased to 25mg weekly in \norder to control her persistent joint swelling. Three \nmonths after the dose increment, she developed \ntender, hemorrhagic plaques over the lower limbs \n(Figure 1) and mouth ulcers. A skin biopsy showed \nepidermal atrophy with disorganisation, focal \nvacuolar interface change, rare eosinophils and \nsuperficial perivascular inflammation (Figure 2). \nMTX was stopped with symptom improvement.\n\n\n\nIntroduction\nMethotrexate(MTX) is used as systemic therapy for \nmany rheumatological and dermatological disorders. \nAcute toxicity presents with varied cutaneous \nmanifestations. We review three morphologically \nvaried cases in our centre to highlight the importance \nof early recognition.\n\n\n\nCase Report\nCase report 1: A 60-year old Chinese man with \nchronic plaque psoriasis of affected body surface \narea (BSA) greater than 50% was started on oral \nMTX 7.5mg weekly. Three days after initiation, \nhe was admitted for severe odynophagia. There \nwere extensive ulcers over his lips, with painful, \nscattered erosions over existing psoriatic plaques. \nInvestigations revealed pancytopenia. A skin biopsy \nshowed vacuolar interface dermatitis with apoptotic \n\n\n\nFigure 1. Extensive hemorrhagic plaques over the lower \nlimbs.\n\n\n\nFigure 2. H&E stain showing epidermal atrophy with \ndisorganisation, focal vacuolar interface change, rare \neosinophils and superficial perivascular inflammation.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 36\n\n\n\nuse of omeprazole particularly in patients receiving \nMTX. Previous reports also suggest additional risk \nfactors such as pre-existing folate deficiency, old \nage >75 years old and  poly-pharmacy. Prolonged \nlow-dose MTX toxicity might be chiefly mediated \nby intracellular polyglutamate derivatives, which \nare unmeasurable  by standard assays.\n\n\n\nOf note, 1 patient presented with ulceration of \nexisting psoriatic plaques as a subtle toxicity sign. \nWhile often mistaken as a psoriatic exacerbation \nleading to erroneous dose increment, it is an \nimportant herald for impending pancytopenia. \nThis has been attributed to hyperproliferative \npsoriatic plaques being more susceptible to folate \nantagonism. This case reminds us that ulceration of \npsoriatic plaques even in the presence of an initially \nnormal laboratory profile should not simply be \ndismissed as a flare.\n\n\n\nEarly recognition of clinical MTX toxicity facilitates \nprompt drug discontinuation and leucovorin \nadministration. Treatment is supportive and we \nshow in 2 patients that cutaneous lesions can heal \nrapidly with complete re-epithelization within days \nof MTX discontinuation. Educating the patient on \nthe side effects of MTX and the need for prompt \nclinical consult upon development of symptoms is \nvital to avoid the tragedy of these 3 cases which can \ninvite litigation.\n\n\n\nCase report 3: A 60-year old Chinese woman with \nautoimmune myositis was given prednisolone and \noral MTX 15mg weekly. She mistakenly took 15mg \nof methotrexate for ten days in a row. A week after, \nshe presented with erythematous oedematous facial \nplaques with oral mucositis associated with atypical \ntargets over her trunk (Figure 3a) and thighs with \ngenital erosions (Figure 3b). Investigations showed \nbicytopenia and transaminitis. Skin biopsy also \nshowed vacuolar interface dermatitis, apoptotic \nkeratinocytes and epidermal changes consistent \nwith MTX toxicity. Despite the withdrawal of \nMTX, initiation of leucovorin and empiric antibiotic \ntreatment, she deteriorated rapidly and passed away.\n\n\n\nDiscussion\nAll patients in our series showed prominent oral \nmucosal involvement, but had very different \ncutaneous features. The oral mucosa undergoes \nrapid proliferation/turnover and hence is particularly \naffected by the cytotoxic effects of MTX. All our \npatients had normal MTX levels at the onset and \nserially. A study by Kivity et al1 showed that MTX \nlevels, which are undetectable within 24 hours \nafter administration, do not correlate with clinical \ntoxicity. In addition, most cases of MTX toxicity \nhave been reported2 in patients on low-dose MTX \nlike our patients (7.5-25mg per week). Risk factors \nfor low-dose MTX toxicity include clinically \nsignificant hypoalbuminemia, renal failure and the \n\n\n\nFigure 3a. Atypical target macules over posterior \ntrunk, with positive Nikolsky\u2019s sign.\n\n\n\nFigure 3b. Perianal and genital erosions.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3737\n\n\n\nphysicians to possible acute toxicity. As there is \ncurrently no specific investigation that can confirm \nthe diagnosis, we would like to stress the importance \nof recognizing the highly variable clinical patterns \nof toxicity.\n\n\n\nConclusion\nAcute methotrexate toxicity may present as a variety \nof skin eruptions3, gastrointestinal symptoms and \nmucositis. While cutaneous features may be highly \nvariable, mucositis with cytopenias should alert \n\n\n\nReferences\n \n1. Kivity S, Zafrir Y, Loebstein R, et al. Clinical \n\n\n\ncharacteristics and risk factors for low dose methotrexate \ntoxicity: A cohort of 28 patients. Autoimmunity Reviews. \n2014;13(11):1109-1113.\n\n\n\n2. Hsu M, Chen C. Low-dose methotrexate-induced ulcerated \npsoriatic plaques: A rare case. JAAD Case Reports. \n2015;1(5):264-266.\n\n\n\n3. Scheinfeld N. Three cases of toxic skin eruptions associated \nwith methotrexate and a compilation of methotrexate-\ninduced skin eruptions. Dermatol Online J. 2006;12(7):15.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 38\n\n\n\nCase Report\n\n\n\nA CASE REPORT OF DISSEMINATED POROKERATOSIS\nWITH SECONDARY AMYLOID DEPOSITION\nYong AMY, Yang SSY, Tan KB, Sobti AM\n\n\n\nCorresponding Author and Reprint Request \nAdeline Yong Mei Yen MRCP (UK)\nNational University Health System\n5 Lower Kent Ridge Rd, Singapore 119074\nEmail: Adeline_meiyen@hotmail.com\n\n\n\nranged from approximately 0.5 to 2cm in size, \nand had been present for 3-4 months. There was \nno sensory deficit or other lesions on the body. \nThe patient was otherwise well, with primary \naldosteronism, hypertension and dyslipidemia \nbeing his only medical problems. His medications \nincluded eplerenone and simvastatin. He denied \na history of skin cancer, radiation, or heavy sun \nexposure or family history of a similar rash. There \nwere no changes in the lesions with sun exposure.\n\n\n\nOn examination, there were multiple annular brown \nplaques scattered over his back, as well as upper and \nlower extremities (Fig. 1 and 2). The lesions were \nassociated with a raised border without features \nof scaling or telangiectasia. An initial suspicion \nof disseminated superficial actinic porokeratosis \n(DSAP) was suspected, and the patient was \nempirically treated with topical moisturisers and \nadvised on sun avoidance. However in view of the \nclinical suspicion of an underlying superficial basal \ncell carcinoma, a punch biopsy was performed over \nhis right lower limb. Histology testing revealed a \ncolumn of parakeratosis in the epidermis (cornoid \nlamella) with subjacent amyloid deposits and \nmild lymphocytic infiltrate. (Fig. 3) The patient \nwas treated with one session of cryotherapy to his \nleg lesions. However, he was not keen for further \ntreatment and defaulted follow up subsequently.\n\n\n\nIntroduction\nThe porokeratoses are a group of disorders of \nabnormal epidermal keratinization. This results in \nthe characteristic histologic feature of the cornoid  \nlamella. A variety of subtypes of this disease      \nhave been recognised: porokeratosis of Mibelli, \ndisseminated superficial porokeratosis (DSP), \ndisseminated superficial actinic porokeratosis \n(DSAP), linear porokeratosis, punctuate \nporokeratosis and porokeratosis palmaris et \nplantaris1. Rarely, DSP has been described to be \nin association with dermal amyloidosis in a few \ncase reports worldwide2. We present a case of \ndisseminated porokeratosis with distinct histological \nmanifestations associated with dermal amyloid \ndeposits in an Asian man.\n\n\n\nCase Report\nA 66-year-old Chinese man presented to the \ndermatology clinic with itchy annular lesions over \nhis arms, lower limbs and back. These lesions \n\n\n\nFigure 1. Multiple brown annular plaques over bilateral \nforearms with raised borders.\n\n\n\nFigure 2. Multiple brown annular plaques over legs with \nraised borders.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3739\n\n\n\naction of fibroblasts and dermal macrophages6. These \nauthors state that a mutant clone from keratinocytes, \nresponsible for induction of porokeratotic lesions, \nis presumed to produce dermal amyloid. This \nsupports the fibrillar theory of amyloidosis in which \nabnormal protein aggregation is precipitated from \ndefective keratinocytes.\n\n\n\nIn a retrospective histopathologic study of   30 patients  \non localised cutaneous amyloidosis secondary to \nporokeratosis, Ramirez-Santos et al found that \nadvanced age of the patients and the chronic nature \nof the lesions may have been predisposing factors for \namyloid deposition7. Furthermore, amyloid deposits \nwere observed in mainly skin biopsy samples from \nfemale patients and there was suggestion that racial \nor genetic influences may be involved. In contrast, \nour patient was of male gender, the lesions were \nonly present for 3 to 4 months and he was 66 years \nof age.\n\n\n\nIn conclusion, the coexistence of porokeratosis \nand amyloidosis is a rare occurrence but may be \nunderdiagnosed. The exact mechanisms for its co-\nexistence remain unclear, and this spurs further \nefforts for an optimal therapeutic option in terms \nof targeting the parakeratotic cells at the cornoid \nlamella as well as rectifying keratinization and \ninhibiting cell proliferation. \n\n\n\nDiscussion \nIn 1893, Vittorio Mibelli first described         \nporokeratosis and its characteristic histology of \ncornoid lamellae3. Classically, clinical features \ninclude one or more annular plaques with a \nsurrounding, raised, horny border. Amyloidosis, \non the other hand, refers to a group of sporadic, \nfamilial, degenerative, and infectious disease \nprocesses, linked by abnormal protein folding and \ndeposition of amyloid. In our patient, there was a \nclassical presentation of disseminated brown annular \nplaques with raised borders suggestive of DSP. \nHowever, histology revealed presence of amyloid \ndeposits in the dermis in addition to characteristic \ncornoid lamellae. In primary, localized cutaneous \namyloidosis, this includes macular, lichen, and \nnodular types. Amyloid deposits are limited to the \ndermis without systemic involvement. Interestingly, \nthe material in lichen and macular amyloidosis is \nderived from epidermal keratinocytes [keratinocyte-\nderived amyloid (AK)], whereas that in nodular \namyloidosis is derived from immunoglobulin light-\nchains amyloid (AL)4.\n\n\n\nAmanita et al have suggested a causal link between \nporokeratosis and amyloidosis, with both conditions \ncaused by alterations in the keratinization process5. \nIt has been suggested that necrotic keratinocytes \n(colloid bodies) might transform into amyloid by the \n\n\n\nFigure 3. Photomicrograph of the skin biopsy showing presence of an \nobliquely-oriented column of parakeratosis (cornoid lamella) (arrow) and\nclumps of amyloid deposits in the papillary dermis (arrowheads). \n(Haematoxylin and Eosin, original magnification x 100).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 40\n\n\n\nReferences\n \n1. Sertznig P, von Felbert V, Megahed M. Porokeratosis: \n\n\n\nPresent concepts. Journal of the European Academy of \nDermatology and Venereology : JEADV 2012;26:404-12.\n\n\n\n2. Husein HE, Inmaculada RM, Vicente CA, et al. \nDisseminated superficial porokeratosis with dermal \namyloid deposits in an elderly man: A rare entity. Journal \nder Deutschen Dermatologischen Gesellschaft = Journal of \nthe German Society of Dermatology : JDDG 2015;13:331-\n3.\n\n\n\n3. Biswas A. Cornoid lamellation revisited: Apropos of \nporokeratosis with emphasis on unusual clinicopathological \nvariants. The American Journal of dermatopathology \n2015;37:145-55.\n\n\n\n4. Cornejo KM, Lagana FJ, Deng A. Nodular amyloidosis \nderived from keratinocytes: An unusual type of primary \nlocalized cutaneous nodular amyloidosis. The American \nJournal of dermatopathology 2015;37:e129-33.\n\n\n\n5. Amantea A, Giuliano MC, Balus L. Disseminated \nsuperficial porokeratosis with dermal amyloid deposits: \nCase report and immunohistochemical study of amyloid. \nThe American Journal of dermatopathology 1998;20:86-8.\n\n\n\n6. Touart DM, Sau P. Cutaneous deposition diseases. Part \ni. Journal of the American Academy of Dermatology \n1998;39:149-71; quiz 72-4.\n\n\n\n7. Ramirez-Santos A, Suarez-Amor O, Perez-Perez L, \net al. [localized cutaneous amyloidosis secondary to \nporokeratosis: A retrospective histopathologic study of 30 \npatients]. Actas dermo-sifiliograficas 2008;99:639-43.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3741\n\n\n\nCase Report\n\n\n\nTHE WRATH OF THE RENGAS : A REPORT OF SEVERE \nCONTACT DERMATITIS AND IMPLICATIONS FOR PUBLIC \nHEALTH IN RURAL AREAS \nXavier G1, Yong KY2, Pubalan M3\n\n\n\nCorresponding Author and Reprint Request \nDr Gregory Xavier\nQuality Unit, Sarikei Divisional Health Office\nTingkat 3, Wisma Persekutuan\nJalan Bangunan Kerajaan, 96100 Sarikei, Sarawak\nEmail: gregshc@yahoo.co.uk\n\n\n\n1 Quality Unit, Sarikei Divisional Health Office,\n Tingkat 3, Wisma Persekutuan,\n Jalan Bangunan Kerajaan, 96100 Sarikei, Sarawak\n2 Department of Medicine, Miri Hospital,\n Jalan Cahaya, 98000 Miri, Sarawak\n3 Department of Dermatology,\n Sarawak General Hospital, Jalan Hospital,\n 93586, Kuching, Sarawak\n\n\n\nHe had a similar reaction one month prior to this \nepisode on his legs that was worse on the right foot \nand was treated as cellulitis. This recovered after a \nweek. Similar to the previous reaction the current \npresentation also occurred around 2 to 3 days \nafter returning from the jungle, indicating a type 4 \nhypersensitivity reaction.\n\n\n\nFor the present episode he was again treated as \ncellulitis and was prescribed antibiotics notably \npenicillin. The rash began to worsen and began to \ninvolve the abdomen. The dose of penicillin was \nincreased to its maximum dose. The lesions on the \nabdomen were initially macular and over the next \n5 days it began to coalesce involving almost the \nentire trunk. The rashes were very itchy. The lesions \non the left arm however was beginning to improve.  \nThe diagnosis of a possible Rengas allergy was \nhighlighted to us by the local population although \nthis seemed to be extremely severe. On further \nhistory the patient did note that there was a tree with \nblack spots and he did have contact with it. Some \nof the sap did stain his skin however rinsing it did \nnot readily remove it. Unaware of what it was the \npatient continued his work.\n\n\n\nOn day 5, the presentation included blisters with \nserous discharge that was not foul smelling or \nassociated with fever (Figure 1, 2). Burning \nsensation, itch and pain worsened, and disturbed \nhis sleep. The antibiotic was stopped and he was \ncommenced on steroids and antihistamines. IV \nsteroid was first administered three times daily for \n3 days and followed by oral steroids. Tablet prolase \nwas given to reduce the swelling. Small macular \nrashes began to appear at distal right forearm. \n\n\n\nIntroduction\nThe tropical rainforest consists of a multitude of \nfloral species providing benefits and equally causing \ndetriment to visitors from food to poison. Some tree \nspecies within the family Anacardiaceae (genera \nGluta and Mellanorrhoea), collectively named \nRengas; can cause severe allergic dermatitis to those \nwho come in contact with this plant1.\n\n\n\nSap from the Rengas tree can cause severe irritation \nto the skin. The sap contains urushiol, a biochemical \nallergenic component which affects the skin via \na type 4 hypersensitivity reaction2,3. It is highly \npotent as contact with contaminated surroundings \nincluding water can also cause an allergic response. \nNevertheless the wood is not popularly made into \nfurniture due to its effects1. This tree is similar to the \ncommon mango tree (Mangiferaindica) albeit larger \nand taller with characteristic black blotches on its \nleaves and black sap staining on the trunk4,5. Here, \nwe present a case of a traveler with allergic contact \ndermatitis to Rengas.\n\n\n\nCase Report\nWe present a case of a 24 year old German who came \nwith a chief complaint of left forearm rash. It was \nassociated with itchiness, burning sensation, pain \nand swelling and redness over one week duration. \nPatient was afebrile.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 42\n\n\n\nTrue improvement was seen after one week of \nsteroids which was completed after a 10 days course. \nThere was no scarring.\n\n\n\nDiscussion\nThe potency of rengas is well documented in an \narticle on occupational contact dermatitis to the \nrengas wood7. It describes a group of carpenters \nwith one in particular who worked with Rengas dead \nwood presenting with subacute dermatitis on his \nforearms, antecubital fossae, abdomen and ankles \nof 2 weeks duration. This is a similar presentation \nto our patient who apparently had the signs and \nsymptoms for the same duration.\n\n\n\nA combination of topical agents including \nhydrocortisone, aqueous cream, zinc oxide and \ncalamine cream helped to keep the skin from drying \nand reduce the burning, pain and itch.\n\n\n\nOnce started on steroids the lesions did not \nworsen but its morphology varied showing mixed \nimprovement.\n\n\n\nIn general the morphology, character and the \nspread of the rash underwent dynamic changes but \nwhat stayed consistent is the area of damage. The \nsite of spread began at the left forearm spread to \nthe abdomen and then to the right forearm. Worst \naffected was the abdomen.\n\n\n\nFigure 1. Erythema and erosions on the abdomen.\n\n\n\nFigure 2. Erythema and blisters on the left forearm.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3743\n\n\n\nmonocytes and macrophages leading to a type 4 \nhypersensitivity reaction3,9. Our patient had been \npreviously sensitized to uroshiol with the current \npresentation within 48 hours after exposure.\n\n\n\nThe mainstay of treatment includes steroids and \nantihistamines with avoidance of the plant and its \ncomponents.\n\n\n\nThe rural health clinic in Mulu is equipped with \nbasic antibiotics as well as emergency drugs \nincluding steroids. The presence of a doctor reduces \nthe need for referrals to tertiary centres due to the \nimproved services provided. Allergic reactions are \ncommon presentations to the clinic and this case \nconstitute a very severe allergic reaction to Rengas.\nIn conclusion, early diagnosis, treatment and \nprevention is important in avoiding serious \nhealth consequences of Rengas allergy. Hence, \nthe awareness is crucial especially among rural \nhealthcare staff and nature guides and visitors to \ntropical rainforest. \n\n\n\nAcknowledgement\nWe wish to thank the people of Mulu for their \ninput regarding the effects of Rengas and its \ncharacteristics, and the staff of Mulu Health Clinic \nwho managed to provide good care to this patient. \nWe also acknowledge Mulu National Park on the \nmeasures taken to keep the tourist from harm\u2019s way \nallowing their visit to be comfortable and healthy. \nFinally, we thank the Director General at Ministry \nof Health for approving the publication of this paper.\n\n\n\nHis dermatitis cleared with topical steroids and \navoidance of exposure to the wood. As it has caused \nseveral contacts to have symptoms despite not all \nseeking treatment, it still does demonstrate that it \ncan be a public health concern in particular areas \nof risk such as in a wood factory and in the jungle. \n\n\n\nThe potency as described by locals mentioning that \nby even walking under the tree, coming into contact \nwith contaminated water and rain drops and also \nsmoke from the burning wood4  is well documented \nin a case report of a patient developing allergic \ncontact dermatitis whilst working on dead rengas \nwood7.\n\n\n\nDue to this wrath effects, Rengas was promulgated \nin the Malaysian Camping Online Info with advice \nto stay away from these trees and not to camp nearby \nthem6. It describes the physical appearance of the \ntree, as well as immediate preventive measures \nof washing with soap and water, removal of \ncontaminated clothing and seeking treatment as \nsoon as possible. These measures were explained \nto the national park authorities in order to create \nawareness among its guides, tourist and researchers.\n\n\n\nThe Wood Database has also stated that Rengas \nsap causes blisters, ulcers, fever and constitutional \nsymptoms such as malaise. It mentions of the \nurushiol group of allergens, isolated from poison ivy \nand poison oak plants, which is the common cause \nof this severe contact dermatitis8. The characteristics \nof uroshiol, an immunogenic hapten triggers T cells, \n\n\n\nReferences\n \n1. Rengas | The Wood Database - Lumber Identification \n\n\n\n(Hardwoods) [Internet]. [cited 2016 May 21]. Available \nf r om:h t t p : / /www.wood-da t abase . com/ lumbe r-\nidentification/hardwoods/rengas/\n\n\n\n2.  URUSHIOL - National Library of Medicine HSDB \nDatabase [Internet]. [cited 2016 May 21]. Available \nfrom:https://toxnet.nlm.nih.gov/cgi-bin/sis/search/\na?dbs+hsdb:@term+@DOCNO+7485\n\n\n\n3.  Delayed Hypersensitivity Reactions: Background, \nPathophysiology, Epidemiology. 2016 Apr 27 [cited 2016 \nMay 21]; Available from: http://emedicine.medscape.com/\narticle/136118-overview\n\n\n\n4.  Gluta renghas - Useful Tropical Plants [Internet]. [cited \n2016 May 21]. Available from: http://tropical.theferns.\ninfo/viewtropical.php?id=Gluta+renghas\n\n\n\n5.  The Big Trees: Rengas-attack [Internet]. [cited 2016 \nMay 21]. Available from: http://dbh30cm.blogspot.\ncom/2008/01/rengas-attack.html\n\n\n\n6.  kmnnetwork1. TUMBUHAN BERACUN DI MALAYSIA \n~ Malaysia Camping Online Info [Internet]. [cited 2016 \nMay 21]. Available from: http://camping-malaysia.\nblogspot.com/2009/07/tumbuhan-beracun-di-malaysia.\nhtml\n\n\n\n7.  Goh CL. Occupational allergic contact dermatitis from \nRengas wood. Contact Dermatitis. 1988; 18(5): 300.\n\n\n\n8.  Kalergis AM, L\u00f3pez CB, Becker MI, et al. Modulation \nof fatty acid oxidation alters contact hypersensitivity \nto urushiols: role of aliphatic chain beta-oxidation in \nprocessing and activation of urushiols. J Invest Dermatol. \n1997; 108(1): 57\u201361. \n\n\n\n9.  Kalish RS, Wood JA. Induction of hapten-specific \ntolerance of human CD8+ urushiol (poison ivy)-reactive T \nlymphocytes. J Invest Dermatol. 1997; 108(3): 253\u20137.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 44\n\n\n\nCase Report\n\n\n\nMAXILLARY ORAL CUTANEOUS FISTULA IN DIABETES \nMELLITUS PATIENT: A CASE REPORT \nTan ST, Gunawan L, Reginata G\n\n\n\nCorresponding Author and Reprint Request \nDr Sukmawati Tansil Tan SkpKK, FINSDV\nSerpong Main Street, Ruko Union Square\nNo 9-11, Gading Serpong, Tangerang\n15810 Jakarta, Indonesia\nEmail: sukma_tsl@yahoo.com\n\n\n\nDepartment of Dermatovenereology,\nFaculty of Medicine, Universitas Tarumanagara Jakarta, \nS.Parman Street No. 1, Grogol, West Jakarta\n\n\n\nand had been prescribed antibiotic and analgesic. \nThe pain did improve, but the wound did not. The \npatient was diagnosed with diabetes mellitus 8 years \nago, but never saw his doctor routinely. The patient \nwas then admitted for inpatient care and referred to \noral and maxillofacial surgeon and internist.\n\n\n\nPhysical examination revealed good general \nappearance, blood pressure 130/80 mmHg, \nheart rate 88 x/minute, breathing 18 x/minute, \ntemperature 37.1oC, and body weight 65 kg. \nErythematous plaque with blackish-brown crust, \nnecrotic tissue, edema, and pus were found at facial \nregion. Gangrenous tissue was present at teeth 15, \n16, 24, 25, 26, 27, 28, 38, 43, and 44. Blood test \nrevealed hemoglobin 12.5 g/dL, leukocytes 16.000 \n\u00b5L, eosinophils 4.8, lymphocytes 7.1, segmented \nneutrophils 72.2, monocytes 9.6, and random blood \nglucose 280 mg/dL. Tissue specimen was taken for \npathology anatomy and culture examination. On \nthe first day of treatment, drugs administered were \nintravenous ceftriaxone 1 gram b.i.d., subcutaneous \nnovorapid 8 IU t.d.s., subcutaneous glargine 8 IU \no.n., tablet paracetamol 500 mg t.d.s., also prescribed \nbetadine mouthwash, got the wound compressed, \nand followed diet with 2000 kcal intake. Extraction \nand debridement of teeth was done on the third day. \n\n\n\nDiscussion\nOral cutaneous fistula is a sinus canal connecting \ndental infection focus to facial or neck skin which \nis responsible for extra oral infection spreading1. \nChronic inflammation of the teeth slowly destruct \nalveolar bones and spread to soft tissue to finally \nbreach to the skin surface7-9. Initial clinical \npresentation includes pain at the infected teeth. \nPain would reduce after chronic abscess or oral \ncutaneous fistula has formed1,10. In this case, patient \ncomplained persistent pain since two months before \ncoming to our clinic, which seemed alleviated when \na furuncle-like lesion appeared on the right cheek.\n\n\n\nIntroduction\nChronic infection of the teeth and its adjacent tissue \nmay result in a tunnel-like pathologic structure \ncalled oral cutaneous fistula, which connects dental \ninfection focus with skin of the face or neck1. \nThis condition is preceded by chronic abscess of \nperiapical area, impacted teeth, or radix1,2. Oral \ncutaneous fistula is the most common causes of fixed \nnodulocyst papules and chronic supurative nodules \nof the face and neck which usually is formed in \nthe submandibular and submental region2,3. The \nincidence is higher in over 40 years old age group, \ndominated by male4. Data about oral cutaneous \nfistula in Indonesia is yet to be published.\n\n\n\nOral cutaneous fistula has several differential \ndiagnosis such as local skin infection, pyogenic \ngranuloma, osteomyelitis, congenital fistula, salivary \ngland fistula, infected cyst, and deep mycotic \ninfection1,5. Nevertheless, facial lesion caused \nby oral cutaneous fistula is often an overlooked \ndiagnosis that treatment or surgical intervention not \ndeemed necessary6. \n\n\n\nCase Report\nA sixty-two years old male came to \ndermatovenerology clinic with pain at perioral area \nsince two months ago. Pain alleviated when a blister-\nlike lesion appeared on the right cheek, which then \nengorged and burst out three weeks ago. A week \nbefore the patient came, the wound broadened to \nthe lips and made them looked swollen. The patient \nhad seen several general practitioners beforehand \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3745\n\n\n\nFigure 1. Extraoral presentation of \nodontocutaneous sinus canal at maxillary region \nof the face, consisted of erythematous plaque with \nbrown crust, erythema, necrotic tissue, edema, and \npus pretreatment.\n\n\n\nFigure 3. Minimal hyperpigmented plaque and \ncrust, erosion on Day 7.\n\n\n\nFigure 2. Hyperpigmented plaque with brown \ncrust, edema, and pus on Day 3.\n\n\n\nFigure 4. Wound had closed, a few crusts were still \nvisible 2 weeks post teeth extraction.\n\n\n\nFigure 5. Wound healed completely. Scar seen on \nthe right cheek 3 weeks post teeth extraction and \ndebridement.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 46\n\n\n\nimmunocompromised setting15. In this case, patient \nwas given intravenous ceftriaxone (a broad spectrum \nantibiotic) 1 gram b.i.d., subcutaneous novorapid (a \nrapid-acting insulin) 8 IU t.d.s., and subcutaneous \nglargine (a basal insulin) 8 IU o.n., paracetamol 500 \nmg t.d.s., betadine mouthwash, wound compression, \nand 2000 kcal intake.\n\n\n\nThree days after teeth extraction-debridement, the \nhyperpigmented plaque, brown crust, edema, and \npus had all improved. Seven days after extraction, \nthe lesion dried up, the crust was minimal, an erosion \nwas seen at the lesion site. Patient was sent home \nwith tablet metronidazole 500 mg b.i.d. to eliminate \nanaerobic bacteria, tablet natrium diclofenac 50 \nmg b.i.d. for pain, subcutaneous novorapid 8 IU \nt.d.s., subcutaneous gargline 8 IU o.n., and betadine \nmouthwash to improve oral hygiene11-13. A week \nafter, patient came for the first follow-up, crust was \nvery minimum and lesion had gotten much better. \nOral therapy was continued. A week after first \nfollow-up, all lesion had cleared up and there was \nscar tissue in place of where the lesion was.\n\n\n\nEarly diagnosis and treatment would significantly \nlower complication risk such as sepsis, osteomyelitis, \nand aesthetic problem7.This patient\u2019s prognosis was \nquo ad vitam, quo ad sanam, quo ad cosmeticum \nad bonam. Routine control and treatment helped the \npatient to get better.\n\n\n\nSystemic diseases like malignancy, diabetes, and \nAIDS would aggravate the condition, as was seen in \nthis patient who was first diagnosed with diabetes 8 \nyears ago. Severe gum inflammation and periodontal \nabscess often occurred in diabetes patient who has \npoor oral hygiene11,12. Uncontrolled diabetes mellitus \nmight deteriorate immune system. Susceptibility \nto infection would increase as neutrophil function \nin chemotaxis and phagocytosis were impaired, \nleading to enhanced intracellular bacterial activity \nin causing periodontal destruction11.\n\n\n\nDiagnosis is based on anamnesis, physical \nexamination, blood test, and pathology anatomy \nexamination. In this patient, we found a painful \nwound of 3.5 cm in diameter covered by thick crust \non the right cheek, edema, erythema, and pus. There \nwere multiple gangrenous dental abscesses. Blood \ntest revealed infection and increased blood sugar. \nPathology anatomy showed polymorphonuclear \ncells domination, while culture did not reveal any \nspecific bacteria with Streptococcus being the most \ndominant finding.\n\n\n\nSurgical endodontic treatment or teeth extraction \nis treatment of choice for oral cutaneous fistula9,13, \nbefore which stabilizing general condition and blood \nglucose is imperative in order to limit infection \nspread and ensure maximum antibiotic penetration14. \nOral cutaneous fistula is a local infection in \nwhich systemic antibiotic is only necessary in \n\n\n\nReferences\n \n1. Barrowman RA, Rahimi M, Evans MD, et al. Cutaneous \n\n\n\nsinus tracts of dental origin. 2007; 186(5): p. 264-5.\n2. Zerener T, Bayar GR, Gulses A, et al. Massive cutaneus \n\n\n\nfistula secondary to an odontogenic submandibular abcess \nin an immunocompromised patient: a case report. 2013; \n17(1): p. 11-5.\n\n\n\n3. Ashwin DP, Abhisek M, Anup KG, et al. Chronic \nodontogenic sinus tracts associated with an impacted \ntooth: Report of two cases. 2010; 1(3): p. 205-7.\n\n\n\n4. Miri SS, Atashbar O, Atashbar F. Prevalence of sinus \ntract in patients visiting Department of Endodontics, \nKermanshah School of Dentistry. Global Journal of Health \nScience. 2015; 7(6): p. 271-5.\n\n\n\n5. Alasseri NA, Assari AH. Facial fistula : Long0term \nsequalae of a complicated exodontia. 2015; 35(4): p. 490-\n3.\n\n\n\n6. Ghodsi SZ, Giasi M. Two unusual cases of dental \n(periapical) infection. 2006; 12(4)(15).\n\n\n\n7. Garcia RG,Vera MF, Vera LF. Cutaneous sinus tracts of \nodontogenic origin : Two case reports. 205; 28(6): p. 838-\n40.\n\n\n\n8. Brailo V, Juras DV, Stanimirovic A, et al. Dental infection \nand dermatological diseases: Analysis of ninty-two patients \nand review of the literature. 2015; 54: p. 77-82.\n\n\n\n9. Mahler D, Joachims HZ, Sharon A. Cutaneous dental sinus \nimitating skin cancer. British Journal of Plastic Surgery. \n1971; 24(1): p. 78-81.\n\n\n\n10. Wilson SW, Ward DJ, Burns A. Cautionary Tales Dental \ninfections masquerading as skin lesions. 2001; 54: p. 358-\n60.\n\n\n\n11. Daniel R, Gokulanathan S, Shanmugasundaram N, et al. \nDiabetes and periodontal disease. 2012; 4(2): p. S280-2.\n\n\n\n12. Gandara BK, Morton TH. Non-periodontal oral \nmanifestations of diabetes : A framework for medical care \nproviders. Diabetes Spectrum. 2011; 24(4): p. 199-205.\n\n\n\n13. Abuabara A, Zielak JC, Schramm CA, et al. Dental \ninfection stimulating skin lesion. 2012; 87(4): p. 619-21.\n\n\n\n14. Johnston SL. Clinical immunology review series: An \napproach to the patient with recurrent superficial abscesses. \n2008; 152: p. 397-405.\n\n\n\n15. Ranga U, Aiyappan SK, Veeraiyan S. A case of \nintermittently discharging skin lesion: Oroentocutaneous \nfistula demonstrated on CT fistulography. 2014; 8(8): p. \nZD09-11.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3747\n\n\n\nCase Report\n\n\n\nLEPROSY REACTION IN MYCOBACTERIUM LEPRAE AND \nMYCOBACTERIUM TUBERCULOSIS CO INFECTION: A CASE \nREPORT AND LITERATURE REVIEW \nJamil A1, Nik Adeeb NN1, Muthupalaniappen L2, Md Nor N1\n\n\n\nCorresponding Author and Reprint Request \nDr Adawiyah Jamil, AdvMDerm\nDepartment of Medicine\nUniversiti Kebangsaan Malaysia Medical Center\nBandar Tun Razak, Cheras,\n56000 Kuala Lumpur, Malaysia\nEmail: adda_jamil@yahoo.com\n\n\n\n1 Department of Medicine and\n2 Department of Family Medicine,\n Universiti Kebangsaan Malaysia Medical Center,  \n Bandar Tun Razak, Cheras, 56000 Kuala Lumpur\n\n\n\nLeprosy reactions are a major cause of nerve \ndamage, morbidity and disability. We present case \nof lepromatous leprosy with T1R and pulmonary \ntuberculosis. We reviewed the literature to \ndetermine the relationship between co infection and \ntuberculosis therapy with leprosy reactions.\n\n\n\nCase report\nA 69 year old man with type II diabetes mellitus \nand hypertension presented with numbness of the \nupper and lower limbs with intermittent swelling \nof 2 years duration. Physical examination revealed \nperipheral neuropathy, thickened ulnar nerves \nand multiple neuropathic ulcers. There were no \nhypopigmented or hypoaesthetic patches. Slit \nskin smear morphological index (MI) was 3.7 and \nbacteriological index (BI) was 0.8. Skin biopsy was \nnot performed as there were no definite skin lesions. \nCutaneous tuberculosis is unlikely as there were \nno skin lesions to suggest tuberculosis. Clinical \nfindings were more suggestive of leprosy due to the \npresence of peripheral neuropathy, thickened ulnar \nnerves and neuropathic ulcers. He was diagnosed as \nlepromatous leprosy with recurrent type 1 leprosy \nreaction and was treated with Dapsone, Clofazimine \nand Rifampicin.\n\n\n\nOne month after MDT, he complaint of loss of \nappetite and 10kg weight loss over 3 months. There \nwas no cough, fever or night sweats. On examination, \nthere were bronchial breath sounds at the right upper \nzone of the chest and cervical lymphadenopathy. \nChest radiograph showed consolidation, fibrosis \nand cavitations (Figure 1). Cavitations with ground \nglass and tree in buds appearance were seen on \ncomputed tomography. Broncho alveolar lavage \nculture grew M tuberculosis that was sensitive to all \nfirst line anti tuberculosis drugs. Polymerase chain \nreaction (PCR) isolated M tuberculosis complex. \nEthambutol, isoniazid and pyrazinamide were \nadded for treatment of tuberculosis. Dapsone and \nclofazimine were continued while Rifampicin was \nchanged to daily dose.\n\n\n\nIntroduction\nCo infection by the two oldest diseases known to \nmankind, leprosy and tuberculosis is uncommon. \nA systematic review by Rajagopala et al. in 2012 \nidentified 156 cases in the literature1. In India, it is \nestimated that 0\u00b7019 cases of concomitant infection \nwould be detected per 100,000 population2. The \npathogenesis of simultaneous Mycobacterium \nleprae and Mycobacterium tuberculosis infection \nis unclear. Tuberculosis exposure may be protective \nagainst leprosy, as the Bacillus Calmette-Guerin \n(BCG) vaccination has been demonstrated to confer \nprotection against leprosy3.\n\n\n\nLeprosy reaction occurs in about 25% of \npaucibacillary and 40% of multibacillary leprosy \npatients4. Presence of M leprae antigens or  DNA in \nthe skin or nerves, higher expression of mycobacterial \naccA3 and hsp18 genes and toll - like receptor  (TLR) \ngene polymorphism contribute to development of \nreactions. Risk factors for type 1 reaction (T1R) \nare older age, extensive disease, positive slit skin \nsmear, household contacts, concurrent infection \nand disability at presentation. Risk factors for type \n2 reaction (T2R) are bacteriological index (BI) > 4 \nand lepromatous leprosy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 48\n\n\n\nfirst infection diagnosed in 8 patients, tuberculosis \nwas the first diagnosis in 5 patients. Four patients \nwith leprosy were on prednisolone prior to \ndeveloping tuberculosis. Pulmonary tuberculosis \nwas commonest, other sites reported were the \ncentral nervous system, skin and peritoneum. \nThere were more T2R compared to T1R. The time \nleprosy reaction occurred in relation to diagnosis of \ntuberculosis or duration of anti TB was variable and \nunpredictable. We were not able to determine the \neffect of mycobacterium load and treatment on the \noccurrence of reactions as data from the reviewed \narticles were limited. In most patients with TB as \nthe first infection, leprosy reaction occurred at the \npresentation of leprosy. However, this maybe an \ninaccurate conclusion as the exact time each infection \nis acquired cannot be confirmed. Interestingly, drug \nresistance was not observed except in one patient \nwith multi drug resistant tuberculosis including \nrifampicin10.\n\n\n\nIn the presence of suggestive symptoms, acid fast \nbacilli isolated from a leprosy or tuberculosis patient \nshould be confirmed M leprosy or M tuberculosis. \nLeprosy reactions may complicate the diagnosis \nand treatment of both conditions. It is unlikely that \nacquiring tuberculosis infection or tuberculosis \ntreatment predisposes to leprosy reactions, however \nthis requires further investigation.\n\n\n\nThe patient developed another similar episode \nof T1R a month after anti TB treatment. He was \ntreated with prednisolone 30mg daily (0.5mg/kg) \nfor a month and the dose was tapered off within \n2 months. He remained asymptomatic and well 3 \nmonths after discontinuation of prednisolone.\n\n\n\nDiscussion\nTuberculosis and leprosy co infection is more \ncommon in middle age men with the first infection \nbeing leprosy, in particular lepromatous leprosy1. \nSystemic steroid treatment for leprosy reactions \nwas thought to be a predisposing factor to M \ntuberculosis infection. However, the TRIPOD \nstudies that investigated the effect of 16 weeks \nprednisolone therapy for nerve impairment did \nnot report the occurrence of tuberculosis in their \npatients5. Rajagopalan et al identified malnutrition \nin more than 80% of co infected patients, about 4% \nwere on steroid or immunosuppressive therapy1. \nOnly 1 out of 106 patients had diabetes mellitus1. \nOur patient had diabetes, was well nourished and \nwas not on corticosteroid.\n\n\n\nLeprosy reaction is common in co infected patients, \nwe reviewed the literature to identify the clinical \ncharacteristics and risk factors for leprosy reaction \nin these patients. The findings are summarized \nin Table 1. Most patients were middle aged men. \nLeprosy, mainly the lepromatous type was the \n\n\n\nFigure 1. Chest radiograph showed consolidation, fibrosis and \ncavitations at the right upper zone.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3749\n\n\n\nParameter / \nAuthors\n\n\n\nArgawal et al. 20006\n\n\n\nLee et al. 20037\n\n\n\nArgawal et al. 20078\n\n\n\nSreerama-reddy et \nal. 20079\n\n\n\nMcIver et al. 201110\n\n\n\nPrasad et al. 201011\n\n\n\nTrindade et al. \n201312\n\n\n\nParise-Fortes et al. \n201413\n\n\n\nRawson et al. 20142\n\n\n\nQuyum et al. 201514\n\n\n\nSendrasoa et al. \n201515\n\n\n\nAge,\ngender\n\n\n\n40, M\n\n\n\n63, M\n\n\n\n34, F\n\n\n\n65, M\n\n\n\n50, M\n\n\n\n10, M\n\n\n\n31, M\n\n\n\n31, M\n\n\n\n46, F\n\n\n\n59, M\n\n\n\n18, M\n\n\n\n38, M\n\n\n\n-\n\n\n\n49, M\n\n\n\nDisease\ndiagnosed \nfirst\n\n\n\nTB\n\n\n\nTB\n\n\n\nTB\n\n\n\nLeprosy\n\n\n\nLeprosy\n\n\n\nLeprosy\n\n\n\nLeprosy\n\n\n\nTB\n\n\n\nLeprosy\n\n\n\nBoth\n\n\n\nLeprosy\n\n\n\nLeprosy\n\n\n\nTB\n\n\n\nLeprosy\n\n\n\nDuration to \ndiagnosis of \nsecond disease\n\n\n\nweeks\n\n\n\n4 months\n\n\n\nweeks\n\n\n\nNA\n\n\n\n2 years after \ncompleted MDT\n\n\n\n1 year\n\n\n\n7 months\n\n\n\n3 months\n\n\n\n1 month\n\n\n\nNA\n\n\n\n9 months\n\n\n\n3 years\n\n\n\n6 months\n\n\n\n13 months\n\n\n\nType of\nleprosy\n\n\n\nLL\n\n\n\nBL\n\n\n\nBL\n\n\n\nBL\n\n\n\nLL\n\n\n\n-\n\n\n\nBL\n\n\n\nBB-BT\n\n\n\nBT-BB\n\n\n\nLL\n\n\n\nLL\n\n\n\nLL\n\n\n\nLL\n\n\n\nLL\n\n\n\nSite of\nTB\n\n\n\nPulm\n\n\n\nPulm\n\n\n\nPulm\n\n\n\nPulm\n\n\n\nPulm,\nperitoneal\n\n\n\nPulm\n\n\n\nPulm\n\n\n\nPleura\n\n\n\nPulm\n\n\n\nPerianal\n\n\n\nPulm\n\n\n\nCNS\n\n\n\nSkin\n\n\n\nPulm\n\n\n\nType of \nlepra \nreaction\n\n\n\nII\n\n\n\nI\n\n\n\nI\n\n\n\nNeuritis\n\n\n\nII\n\n\n\nII\n\n\n\nII\n\n\n\nI\n\n\n\nI\n\n\n\nII\n\n\n\nNeuritis\n\n\n\nII\n\n\n\nII\n\n\n\nII\n\n\n\nTime lepra reaction \noccurred\n\n\n\n2 months on \nMDT+anti TB\n\n\n\n4 months on anti \nTB, at diagnosis of \nleprosy\n\n\n\n20 days on anti \nTB, at diagnosis of \nleprosy\n\n\n\nBefore diagnosis \nof TB\n\n\n\nRecurrent before \ndiagnosis of TB\n\n\n\nRecurrent before \nand weeks after anti \nTB\n\n\n\nAt diagnosis of TB, \n6 months on MDT\n\n\n\n3 months on anti \nTB, at diagnosis of \nleprosy\n\n\n\nAt diagnosis of \nleprosy and 6 \nmonths on anti TB\n\n\n\nAt presentation, and \n? recurrent before \ntreatment of both \ndiseases\n\n\n\nNA\n\n\n\nNA\n\n\n\nAt diagnosis of \nleprosy & before \ntreatment of both \ndiseases\n\n\n\n1 month after \ncompleted MDT, \nbefore TB diagnosed\n\n\n\nImuno-\nsuppression\n\n\n\nAzathioprine + \nPrednisolone\n(for renal \ntransplant)\n\n\n\n-\n\n\n\nLeflunomide \n(for rheumatoid \narthritis)\n\n\n\nPrednisolone (for \nneuritis)\n\n\n\nPrednisolone (for \nT2R)\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nPrednisolone (for \nT1R)\n\n\n\nPrednisolone (for \npresumed drug \nreaction)\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nPrednisolone (for \nT2R)\n\n\n\nTable 1. Summary of cases with leprosy and tuberculosis co infection with leprosy reaction.\n\n\n\n\u2013 not available, T2R \u2013 type II leprosy reaction, Pulm-pulmonary\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 50\n\n\n\nReferences\n\n\n\n1. Rajagopala S, Devaraj U, D\u2019souza G, V Aithal V. Co-\ninfection with M. tuberculosis and M. leprae \u2013 case report \nand systematic review. J Mycobac Dis 2012; 2:118. doi: \n10.4172/2161-1068.1000118 \n\n\n\n2. Rawson TM, Anjum V, Hodgson J et al . Leprosy and \ntuberculosis concomitant infection: A poorly understood, \nage-old relationship. Lepr Rev 2014 85, 288\u2013 295.\n\n\n\n3. Zodpey SP, Protective effect of Bacillus Calmette-Guerin \n(BCG) vaccine in the prevention of leprosy: a meta-\nanalysis. Ind J Dermatol Venerol Leprol 2007; 73: 86-93.\n\n\n\n4. WHO Model Prescribing Information: Drugs Used \nin Leprosy. http://apps.who.int/medicinedocs/en/d/\nJh2988e/6.html\n\n\n\n5. Richardus JH, Withington SG, Anderson AM et al. \nTreatment with corticosteroids of long-standing nerve \nfunction impairment in leprosy: a randomized controlled \ntrial (TRIPOD 3). Lepr Rev.2003; 74: 311-318\n\n\n\n6. Agarwal DK, Mehta AR, Sharma AP et al. Coinfection \nwith leprosy and tuberculosis in a renal transplant recipient. \nNephrol Dial Transplant 2000; 15: 1720-1721.\n\n\n\n7. Lee HN, Embi CS, Vigeland KM, White CR, Jr. \nConcomitant pulmonary tuberculosis and leprosy. J Am \nAcad Dermatol 2003; 49: 755-757.\n\n\n\n8. Agrawal S, Sharma A. Dual mycobacterial infection in the \nsetting of leflunomide treatment for rheumatoid arthritis. \nAnn Rheum Dis 2007; 66: 277.\n\n\n\n9. Sreeramareddy CT, Menezes RG, Kishore P. Concomitant \nage old infections of mankind - tuberculosis and leprosy: a \ncase report. J Med Case Reports 2007; 1: 43.\n\n\n\n10. McIver LJ, Parish ST, Jones SP et al. Acute \nglomerulonephritis in a child with multidrug-resistant \ntuberculosis and multibacillary leprosy. MJA 2011; 195(3): \n150-152.\n\n\n\n11. Prasad R, Verma SK, Singh R, Hosmane G. Concomittant \npulmonary tuberculosis and borderline leprosy with type-\nII lepra reaction in single patient. Lung India 2010; 27(1): \n19-23.\n\n\n\n12. Trindade MAB, Miyamoto D, Benard G et al. Case Report: \nLeprosy and Tuberculosis Co-Infection. Clinical and \nImmunological Report of Two Cases and Review of the \nLiterature. Am. J. Trop. Med. Hyg. 2013; 88(2): 236\u2013240.\n\n\n\n13. Parise-Fortes MR, Last\u00f3ria JL, Marques SA et al. \nLepromatous leprosy and perianal tuberculosis: a case \nreport and literature review. Journal of Venomous Animals \nand Toxins including Tropical Diseases 2014; 20: 38\n\n\n\n14. Farhana-Quyum, Mashfiqul-Hasan, Ahmed Z. A case \nof lepromatous leprosy with co-existing tuberculosis \nverrucosa cutis (TVC). Lepr Rev. 2015; 86(2):176-9.\n\n\n\n15. Sendrasoa FA, Ranaivo IM, Raharolahy O et al. Pulmonary \nTuberculosis and Lepromatous Leprosy Coinfection. Case \nReports in Dermatological Medicine, vol. 2015, Article ID \n898410, 4 pages, 2015. doi:10.1155/2015/898410.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3751\n\n\n\nCase Report\n\n\n\nYOUNG LADY WITH RECURRENT ABDOMINAL PAIN,\nIS IT ONLY GASTRITIS?\nNeoh KK1, Tang ASN1, Kiing JW1, Adam Malik I2 \n\n\n\nCorresponding Author and Reprint Request \nDr Neoh Kar Keong\nMedical Department, Sibu Hospital\nBatu 51/2, Jalan Ulu Oya, 96000 Sibu, Sarawak\nEmail: kkneoh@yahoo.com\n\n\n\n1 Medical Department, Sibu Hospital, Sarawak and\n2 Pathology Department, Sarawak General Hospital, \n Sarawak\n\n\n\nnodes up to 0.8cm, with mesenteric fat streakiness, \nmultiple para-aortic lymph nodes and mild ascites. \nTumor marker including beta human chorionic \ngonadotrophin (hCG), Ca19.9, Ca 125, alpha feto \nprotein, and carcinoembryonic antigen (CEA) were \nnormal. A further detailed history by medical team \nin her fourth admission only revealed that she had on \nand off bilateral palpable maculopapular rash over \nbilateral lower limbs, sparing foot and buttock, for \npast 2 years. The rash would spontaneously resolved \nafter a few days, and occasional associated with \nabdominal pain. There was no fever, respiratory, \ncardiovascular, central nervous system and joint \nsymptoms. There was no rash in that admission. \nBlood parameter showed normal full blood count, \nrenal and liver profile, urinalysis, coagulation \nprofile, connective tissue screening and infective \nscreening. \n\n\n\nShe presented again with recurring maculopapular \nrash over bilateral lower limbs 3 weeks after the \ndischarge (Figure 1), and skin biopsy was performed \nand reported as leucocytoclastic vasculitis, with \ndermis layer showing neutrophilic small vessels \nvasculitis, leukocytoclasis and extravasation of red \nblood cells (Figure 2).  \n\n\n\nAfter two years of frequent hospital visits and a \nseries of invasive investigations, we are only able to \nrevise her diagnosis to adult onset Henoch Schonlein \nPurpura (HSP) with gastrointestinal involvement. \nHer symptoms resolved spontaneously and did not \nrequire treatment.\n\n\n\nIntroduction\nHenoch Schonlein Purpura is a systemic vasculitis \ndisease which is associated with lower limb \nmaculopapular rash, abdominal pain, arthritis \nand occasional renal involvement. It is one of \nthe commonest vasculitis in pediatric groups but \nincidence in adult is much rarer. We herein describe \na case of Henoch Schonlein Purpura in a 24 years \nold lady with gastrointestinal involvement.\n\n\n\nCase history\nA 24 year old Chinese lady had recurrent visit to \ndifferent hospitals, over a 2 years duration, with \nthe complaint of abdominal pain. The pain was \ncolicky in nature, over epigastric region, pain score \nup to 8-9/10, lasted for hours, intermittent and may \nspanned over 2-3 weeks duration. The symptoms \nwere associated with vomiting with no bilious \nor food particles. There was no change of bowel \nhabits. She was frequently labelled as acute gastritis \nand discharged with syrup Magnesium Trisilicate \nMixture in casualties. She had history of admission \nto different hospitals for 4 times, and discharged \nwith diagnosis of non specific abdominal pain. \n\n\n\nIn view of her recurrent unexplained symptoms, \nshe was investigated extensively and had undergone \na series of invasive investigation and imaging. \nAbdominal ultrasound, gynecological scan and \noesophagogastroduodenoscopy were normal. \nCECT abdomen showed multiple mesenteric lymph \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 52\n\n\n\nFigure 1. Non thrombocytopaenic purpura of lateral aspect of right thigh, which appeared not at \nsame time with gastrointestinal symptoms.\n\n\n\nFigure 2. Perivascular neutrophilic infiltrations and small \nvessels destruction with leukocytoclasis and extravasation of \nred blood cells in the upper dermis suggesting leukocytoclastic \nvasculitis (H&E, magnification X100).\n\n\n\nFigure 3. Small vessels destruction with leukocytoclasia and red blood cells extravasation (H&E, \nmagnification X 400).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3753\n\n\n\nHSP is confirmed by the presence of IgA by \nimmunofluorescence in purpuric skin lesions. It was \nnot done in our case study due to resource limitation. \nA retrospective studies reviewed by Poterucha T.J, \net.al in 2013 on 68 adults with HSP revealed that \nthose with a positive skin biopsy of leucocytoclastic \nvasculitis or IgA deposition were more likely to \nhave renal involvement (3 fold risk)5. \n\n\n\nMajority of HSP patients recover spontaneously \nand do not require specific treatment6. Care \nof HSP patient will be towards pain relief with \nacetaminophen, nonsteroidal anti-inflammatory \ndrugs or weak opioid.\n\n\n\nUse of steroid in HSP patient is not standardized. \nStudies showed that prednisolone 1mg/kg/day for \n2 weeks, with weaning over subsequent 2 weeks \nis effective in reducing abdominal pain7. Optimal \nmanagement of HSP associated gastrointestinal \nand renal involvement has not been determined. \nSome uncontrolled studies still favor a short course \nof oral steroid for abdominal symptoms relieving8. \nImmunosuppressive medications are not indicated \nunless severe kidney, pulmonary or central nervous \nsystem involvement. \n\n\n\nPrognosis of HSP in childhood is good, with two \nthirds of patient have no recurrent episodes, and \nthe remaining one third may have recurrence9. The \nprognosis of adult onset HSP was not well studied, \nbut Lu S. et al suggested that the risk of chronic \nrenal disease is increased in adult patient with \nHSP, requiring for long term follow up for kidney \nfunction10.\n\n\n\nThe diagnosis of Henoch Schonlein Purpura is \nnot uncommon in Malaysia, and we could be able \nto diagnose her earlier if we had taken a detailed \nhistory in early days, and avoid subjecting this lady \nto multiple invasive test and imaging, and hospital \nadmissions. \n\n\n\nThis case highlights the importance comprehensive \nclinical history as it help us in reaching the diagnosis \nfor this young lady, even though the patient presented \nwith \u201csimple gastritis\u201d.\n\n\n\nDiscussion\nHSP is a systemic small vessel vasculitis \ncharacterized by deposition of IgA complexes in \nvarious tissue. It is frequently self limiting.\n\n\n\nThe annual incidence of HSP in children less than \n17 years old is around 6.2 to 70.3 per 100000, and \nis around 3.4 to 14.3 per million population in \nadult1. Etiology of HSP is unclear, and is postulated \nlinked to bacteria or virus infections, connective \ntissue disease, vaccination, drugs and autoimmune \nmechanisms that lead to antigen-antibody immune \ncomplexes (IgA) formation and deposit in various \ntissues.\n\n\n\nHSP is described as a tetrad of clinical \nmanifestations of non thrombocytopenia palpable \npurpura, arthritis, abdominal pain and renal disease. \nIn adulthood, HSP may present in a more severe \nclinical syndrome, with higher frequency of renal \ninvolvement. However the final outcome of HSP is \nequally good in patients of adulthood or childhood2.\n\n\n\nThe diagnosis criteria of HSP was reviewed by \nEuropean League Against Rheumatism (EULAR) \nand Paediatric Rheumatology European Society \n(PRES) in 2006 as follows : 3\n\n\n\nPalpable purpura (mandatory criterion) in the \npresence of at least one of the following features :\n\u2022\t Abdominal\tpain\t(usually\tdiffuse,\twith\tacute-\n onset)\n\u2022\t Arthritis\tor\tarthralgia\t(acute-onset)\n\u2022\t Renal\tinvolvement\t(proteinuria,\thematuria)\n\u2022\t Histopathological\tfindings\tof\tleukocytoclasis\t\n vasculitis or proliferative glomerulonephritis, \n with predominant immunoglobulin A (IgA) \n deposition\n\n\n\nOur patient had palpable purpura, abdominal pain, \nand leucocytoclastic vasculitis, with all of these \nhappened at a different onset. Some case reports \nshowed that gastrointestinal complaints precede \nthe rash in between 15-30 percents of cases, but \ngastrointestinal symptoms without the appearance \nof skin lesion was also described in isolated case \nreports4. The different onset of abdominal pain and \ncutaneous purpura had cause diagnosis dilemma \nand delay in reaching final diagnosis. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 54\n\n\n\nReferences\n \n1. Sohagia AB, Gunturu SG, Tong TR, Hertan HI, Henoch-\n\n\n\nSchonlein Purpura - A Case Report and Review of the \nLiterature. Gastroenterol Res Pract. 2010 May; Article ID \n597648, 7 pages, 2010. doi:10.1155/2010/597648\n\n\n\n2. Blanco R, Martinez-Taboada VM,  Rodriguez-Valverde \nV, et al. Henoch Schonlein Purpura in adulthood and \nchildhood: two different expressions of the same syndrome. \nArthritis Rheum. 1997 May; 40(5): 859-864.\n\n\n\n3. S.Ozen, Ruperto N, Dillon MJ, et al. EULAR/ PReS \nendorsed consesus criteria for the classification of \nchildhood vasculitis. Ann Rheum Dis. 2006 Jul; 65(7): \n936\u2013941.\n\n\n\n4. Nathan K, Gunasekaran TS, Berman JH. Recurrent \ngastrointestinal Henoch Schonlein Purpira. J Clin \nGastroenterol. 1999 Jul; 29(1): 86-89.\n\n\n\n5. Poterucha TJ, Wetter DA, Gibson LE, et al. Histopathology \nand correlates of systemic disease in adult Henoch-\nSch\u00f6nlein purpura: a retrospective study of microscopic \nand clinical findings in 68 patients at Mayo Clinic. J Am \nAcad Dermatol. 2013 Mar; 68(3): 420-424.\n\n\n\n6. Warit Jithpratuck, Yasmin Elshenawy, Hana Saleh, et al. \nThe clinical implications of adult onset Henoch Scholein \nPurpura. Clin Mol Allergy. 2011 May; 9:9; Article ID \nPMC 3125277, 7 pages, 2011. doi:10.1186/1476-7961-9-9\n\n\n\n7. Ronkainen J, Koskimies O, Ala-Houhaha M, et al. Early \nprednisone therapy in Henoch-Schonlein purpura: a \nrandomized,double-blind, placebo-controlled trial. J \nPediatr. 2006 Aug; 149(2): 241-247.\n\n\n\n8. Szer IS. Gastrointestinal and renal involvement in \nvasculitis: management strategies in Henoch-Sch\u00f6nlein \npurpura. Cleve Clin J Med. 1999 May; 66(5): 312-317.\n\n\n\n9. Saulsbury FT. Henoch-Sch\u00f6nlein purpura in children. \nReport of 100 patients and review of the literature. Med \nBaltim. 1999Nov; 78(6): 395-409.\n\n\n\n10. Lu S, Liu D, Xiao J, et al. Comparison between adults and \nchildren with Henoch-Sch\u00f6nlein purpura nephritis. Pediatr \nNephrol. 2015; 30(5): 791-796.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3755\n\n\n\nCase Report\n\n\n\nA RARE CASE OF MULTIPLE CONGENITAL \nNEVOMELANOCYTIC NEVI\nLestary D, Lestari S, Yenny SW\n\n\n\nCorresponding Author and Reprint Request \nDr Dewi Lestary\nDermatology and Venereology Department\nFaculty of Medicine of Andalas University/\nDr M Djamil Padang Hospital. Padang, Indonesia\nEmail: dewilestary@ymail.com\n\n\n\nHerein, we report a rare case of multiple congenital \nnevomelanocytic nevus.\n\n\n\nCase history\nA girl 6 year old was referred from Payakumbuh \nHospital to us with non-pruritic hairy pigmented \npatches on the right forehead, right scalp, right \ncheek, left temple, arms, chest, abdomen, back, \nbuttock and legs since birth. At birth, blackish coin \nshaped patch was seen only on the right forehead \nwith gradual enlargement and involvement of other \nanatomical sites. The patches did not easily bleed \nand she did not experience headache, seizures nor \nvomiting.\n\n\n\nDermatological examination revealed \nhyperpigmentation hairy plaques with varying size \n(0.5 to 17 cm in diameter) on the right forehead, \nright scalp, right cheek, left temple, arms, chest, \nabdomen, back, buttock, legs (Figure 1). There were \nhair follicles, perifollicular hypopigmentation and \nhomogenous areas on dermoscopy (Figure 2). Skin \nbiopsy showed epidermal atrophy, hyperkeratosis, \nadnexal atrophy and proliferation of nevus cells on \nthe dermis pars reticulare and periadnexally (Figure \n3).\n\n\n\nIntroduction\nCongenital nevomelanocytic nevus (CNN) are \nbenign proliferations of cutaneous melanocytes \nclinically apparent at birth or within the first \npostnatal weeks. The prevalence of CNN appears \nto be slightly higher in non whites with no sexual \npredilections1,2. The estimated incidence is 1 in 100 \nfor small CNN (< 1,5 cm); 1 in 1000 for medium-\nsized CNN (1,5-19,9 cm) and 1 in 20.000 for large \nCNN (> 20 cm) and 1 in 500.000 for giant CNN3,4. \nGiant has been variously defined as a lesion as large \nas the patient\u2019s palm if it occurs on the head and \nneck (and twice that area for other anatomic sites), \n30% of the body surface, or 900 cm2 in adults (or \nsmaller if it involves a major anatomic area)1,5.\n\n\n\nFigure 1. Multiple congenital nevomelanocytic nevus in various parts of the body with \nvarying sizes.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 56\n\n\n\nto UV light5,6. The risk factors for malignant \ntransformation in our patient are continous trauma \nof the scalp lesion due to combing and hair binding. \n\n\n\nGiant congenital melanocytic nevus on the scalp \nand neck may be associated with leptomeningeal \nmelanocytosis and neurologic disorders like \nneurofibromatosis, epilepsy or focal neurologic \nabnormalities, whereas lesions over the vertebral \ncolumn may be associated with spina bifida or \nmeningomyelocele5,6. This associated disorders \nwere not present in the current case.\n\n\n\nDiscussion\nThe diagnosis was made based on the clinical \npresentation and histopathological findings. There \nare three types of congenital melanocytic nevus: \n(a) Giant congenital nevi are more than 20 cm in \ndiameter (adult\u2019s size), (b) small congenital nevi are \nless than 1.5 cm in diameter, and (c) intermediate \nnevi are in between 1.5 and 19.9 cm. The risk of \nmalignant transformation to malignant melanoma is \n8.2%, a 52% higher risk than the general population. \nThe risk factors for malignant melanoma include \ngenetic factor, continuous trauma and long exposure \n\n\n\nFigure 3a. Epidermal atrophy, hyperkeratosis, adnexal \natrophy and proliferation of nevus cells (H & E, \nmagnification X 100).\n\n\n\nFigure 3b. Proliferation of nevus cells in the dermis pars \nreticulare and around the adnexae suggesting congenital \nnevomelanocytic nevus (H & E, magnification X 400).\n\n\n\nFigure 2. Perifollicular hyperpigmentation with \nhomogenous areas seen with dermoscopy.\n\n\n\nHair follicle\n\n\n\nPerifollicular \n\n\n\nHomogenous area\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3757\n\n\n\nThe partial removal of GCMN by procedures \nsuch as dermabrasion, skin curettage, tangential \nexcision, chemical peels and laser treatment is \nmostly employed for cosmesis since only the most \nsuperficial cells of the lesion are removed10. In this \npatient we plan to do punch excision in small lesion \nin combination with carbon dioxide and Q-switched \nruby lasers in the bigger lesions.\n\n\n\nIn conlusion, multiple congenital nevomelanocytic \nnevi are rare and poses problem in management. \nRegular follow ups are important as the risk of \nmalignant transformation is high.\n\n\n\nThe management and treatment of patients with large \nand giant CMN remains controversial. No absolute \nguidelines can be recommended. It depends on a \nnumber of factors, including the size of the lesion, \nthe location of the lesion, the age of patient, the \neffect on cosmesis, and the potential for malignant \ntransformation3,5. The size of the lesions makes their \nremoval difficult. Serial surgical interventions, use of \ntissue expanders, skin flaps, grafts or a combination \nof surgical techniques are frequently required. \nPostoperative complications include contractures, \nseromas especially when tissue expanders are used, \nhematomas, infection, ischemic skin flaps, suture \ndehiscence and formation of keloids7,8,9.\n\n\n\nReferences\n \n1. Grichnik JM, Rhodes AR, Sober AJ. Benign neoplasias \n\n\n\nand hyperplasias of melanocytes. In : Wolff K, Goldsmith \nLA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ eds. \nDermatology in general medicine, Fitzpatrick, 8th ed, vol \n1, New York: McGraw Hill; 2012 : 1377-82.\n\n\n\n2. Nikfarjam J, Chambers E. Congenital melaocytic nevi and \nthe risk of malignant melanoma : Establishing a guideline \nof primary-care physicians. The Einstein Journal of \nBiology and Medicine. 2012: 59-66.\n\n\n\n3. Sharma D, Sharma CM. Large facial congenital \nmelanocytic nevus : A case report. Int J of Research in \nMed Sci. 2013;1(4):576-78.\n\n\n\n4. Sharma S, Sharma N, Sharma V. Giant bathing trunk \nnaevus with multiple congenital melanocytic naevi. The \nInternet J of Pediatric and Neonatology. 2012;14(1):1-5.\n\n\n\n5. Taksande A, Vilhekar K. Congenital giant pigmented \nnevus. Journal of Mahatma Gandhi Institute of Medical \nSciences. 2014;14(1):1-2.\n\n\n\n6. Supit L, Sukasah CL. Surgical management of giant \ncongenital hairy nevi without skin graft or other methods \nof closure. Journal Plastic Reconstrucy. 2012: 106-10.\n\n\n\n7. Tromberg J, Bauer B, Benvenuto-Andrade C, Marghoob \nAA. Congenital melanocytic nevi needing treatment. \nDermatol Ther. 2005;18:136-50.\n\n\n\n8. Warner P, Yakuboff K, Kagan R, et al. An 18-year experience \nin the management of congenital nevomelanocytic nevi. \nAnn Plast Surg. 2008;60:283-7.\n\n\n\n9. Gosain AK, Santoro TD, Larson DL, Gingrass RP. Giant \ncongenital nevi: a 20-year experience and an algorithm for \ntheir management. Plast Reconstr Surg. 2001;108:622-36.\n\n\n\n10. Marghoob AA. Congenital melanocytic nevi. Evaluation \nand management. Dermatol Clin. 2002;20:607-16.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 58\n\n\n\nCase Report\n\n\n\nLINEAR BASAL CELL CARCINOMA - A DIAGNOSIS ACHIEVED \nBY THE USE OF CONFOCAL MICROSCOPY\nLong V, Chen Q, Chuah SY, Thng TGS\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long,MBBS\nNational Skin Centre, Singapore\nEmail: valencialong@gmail.com\n\n\n\nCase history\nAn 86-year-old Chinese female presented with \na 4-year history of a lesion over the left lower \neyelid which was noticed coincidentally after a \ncataract operation. It was mostly asymptomatic \nwith occasional pain but no bleeding. On \nclinical examination, she had a 2cm curvilinear \nhyperpigmented plaque over left lower eyelid \nwith pearly edges with a centrally crusted erosion \n(Figure 1). Dermoscopic features of the lesion \ninclude a small central erosion with scant maple leaf \nstructures scattered along the lesion. There were no \narborizing vessels nor globules seen in dermoscopy. \nA punch biopsy of the plaque was performed near \nthe site of the erosion.\n\n\n\nIntroduction\nLinear basal cell carcinoma (BCC) was first \ndescribed by Lewis in 1985. It is a rare and distinct \nmorphology variant. Since 1985, only 37 cases \nhave been reported. The periocular region was the \nmost affected, especially the lower eyelid and malar \nregion. This report describes a lesion that has few \nclinical and dermoscopic features of basal cell \ncarcinoma and was histopathologically diagnosed \nas an erosion. Only with confocal microscopy \nwas the correct diagnosis clinched \u2013 showing \ntypical features of basaloid islands with peripheral \npalisading and retraction clefting. This report \nemphasizes the importance of selecting the right site \nfor biopsy in a case of linear basal cell carcinoma \nand demonstrates the usefulness of in-vivo confocal \nin such difficult cases when biopsy was not helpful. \n\n\n\nFigure 1. Linear nodule under the left lower eyelid with \ncentral ulceration.\n\n\n\nFigure 2. Histological image shows that the epidermis is \neroded and covered with an inflammed serous crust which \ncontains aggregates of bacteria cocci. Tiny fragments of the \nepidermis are seen at the base of the ulcer and there is no \novert keratinocyte atypia. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3759\n\n\n\nof thin collagen bundles and elastic fibres3. These \nparallel bundles lie perpendicular to the direction of \ncontraction of the underlying muscles3. Hence, the \nlinearity of the tumour may therefore be due in part \nto the stromal interactions with relaxed skin tension \nlines, coupled with muscle contraction constraining \ngrowth in one direction3. There is also thought that \nlinear BCCs arise along embryonic cleavage planes; \nChopra4 et al. suggested that the linearity can be \nexplained by lateral limitations to lesional spread \nresulting from reactive dermal fibrosis. Though \nrare, linear BCC should be considered differential \nfor linear skin lesions.\n\n\n\nDermatoscopically, our case had only 1 feature \nsuggestive of BCC \u2013 the presence of maple-leaf \nlike areas without other characteristic features of \narborizing vessels, globules, telangiectasias or nests. \nAs the lesion was clinically suspicious of a basal \ncell carcinoma, a biopsy was performed to confirm \nthe diagnosis; unfortunately, the histopathological \nfeatures were not helpful as biopsy was performed \non a site that did not have the tumor nests.  The \ndiagnosis was made when an in-vivo confocal \nwas used to scan the length of the lesion. Our \ncase reinforces the important learning point that \nbiopsy may be negative in a case of linear basal \ncell carcinoma as the tumor nests may not extend \nthroughout the linear lesion. Clinical suspicion \nfor basal cell carcinoma must be high, even in the \n\n\n\nHistological examination revealed an eroded \nepidermis covered with an inflamed serous crust \nwhich contained aggregates of bacteria cocci. Tiny \nfragments of the epidermis were seen at the base of \nthe ulcer and there was no overt keratinocyte atypia. \nThere was a dense upper dermal infiltrate of plasma \ncells and lymphocytes in association with pigment \nincontinence (Figure 2). There were no features \nsuggestive of basal cell carcinoma despite clinical \nsuggestion of its diagnosis. \n\n\n\nAs the lesion was clinically suspicious of a basal \ncell carcinoma and histological features may not \nbe representative, an in-vivo confocal examination \nwas performed. Confocal microscopy revealed \ntypical basaloid tumor islands with peripheral \npalisading and retraction clefting consistent with \nBCC (Figure 3). Hence, the diagnosis of linear basal \ncell carcinoma was made. This patient subsequently \nunderwent Moh\u2019s micrographic surgery for complete \nclearance and resection of the basal cell carcinoma.\n\n\n\nDiscussion\nLinear BCC is a rare morphological variant first \ndescribed by Lewis1 in 1985; since then, 37 cases \nhave been reported. Most of these cases reported were \naligned along relaxed skin tension lines. Pierard2 et \nal. suggested that in the reticular dermis, skin tension \nlines have an anatomical counterpart consisting of a \npreferential parallel orientation and a straightening \n\n\n\nFigure 3. Confocal microscopic image shows the \npresence of basaloid tumor islands with elongated cord-\nlike structures (red asterisk) and peripheral palisading \nand clefting (thin blue arrows). Aggregates of plump-\nbright stellate structures (white circle), characteristic of \nmelanophages, can also be seen.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 60\n\n\n\nReferences\n \n1. Lewis JE. Linear basal cell epithelioma. Int J Dermatol \n\n\n\n1985; 24: 124\u20135\n2. Pierard GE, Lapiere CM. Microanatomy of the dermis in \n\n\n\nrelation to relaxed skin tension lines and Langer\u2019s lines. \nAm J Dermatopathol 1987; 9: 219\u201324.\n\n\n\n3. Al-Niaimi F, Lyon CC. Linear basal cell carcinoma: a \ndistinct condition? Clin Exp Dermatol. 2011 April; 36(3): \n231\u2013234.\n\n\n\n4. Chopra KF, Cohen PR. Linear basal cell carcinomas: report \nof multiple sequential tumors localized to a radiotherapy \nport and review of the literature. Tex Med 1997; 93: 57\u20139\n\n\n\n5. Segura S, Puig S, Carrera C, et al. Dendritic cells in \npigmented basal cell carcinoma: a relevant finding by \nreflectance-mode confocal microscopy. Arch Dermatol \n2007; 143:883\u20136.\n\n\n\n6. Ono I, Sakemoto A, Ogino J, et al. The real-time, three-\ndimensional analyses of benign and malignant skin tumors \nby confocal laser scanning microscopy. J Dermatol Sci \n2006; 43:135\u201341.\n\n\n\n7. Cinotti E, Jaffelin C, Charriere V, et al. Sensitivity of \nhandheld reflectance confocal microscopy for the diagnosis \nof basal cell carcinoma: A series of 344 histologically \nproven lesions. J Am Acad Dermatol. 2015; 73(2): 319-20. \n\n\n\nindex of suspicion must exist. In cases like these, \nan in-vivo focal microscopy would be useful as one \ncan scan through the whole lesion to look for the \ntumor nests. In areas where in-vivo confocal is not \navailable, a repeat biopsy would be needed.\n\n\n\nabsence of every single typical feature including  \narborizing vessels, tumor nests or globules. In this \ncase, there were subtle hints of maple-leaf like areas \nand focal ulceration/erosion seen on histological \nexamination. Though not fully conclusive, a high \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3761\n\n\n\nCase Report\n\n\n\nCOMBINATION THERAPY OF ORAL DOXYCYCLINE WITH 0.05% \nTRETINOIN, 3% CLINDAMYCIN, AND 0.05% DEXAMETHASONE \nCREAM IN SEVERE ACNE VULGARIS: THREE CASE SERIES\nSukmawati TT, Gabriela R, Joice GP, Listyani G\n\n\n\nCorresponding Author and Reprint Request \nDr Gabriela Reginata\nJalan Raya Serpong, Ruko Union Square No.9-11 \nGading Serpong, Tangerang, Indonesia  15810\nEmail: sukma_tsl@yahoo.com,\ngabrela.reginata@gmail.com\n\n\n\n0.05% tretinoin, 3% clyndamycin, and 0.05% \ndexamethasone at night. At one month follow up, \nthere was marked reduction in inflammatory lesions. \nHe was commenced on combination of 0.05% \ntretinoin and 3% clindamycin for another 3 months.\n\n\n\nCase 2\nA 25 year old man presented with severe \nnodulocystic acne for 3 months. He has acne since \nthe age of 17 and was intermittently taking oral \nand topical anti-acne without much improvement. \nExamination showed erythematous papules, \npustules, nodulocysts, comedones and scars on face. \nHe was given oral doxycyclin 100 mg twice daily for \n10 days and cream containing 0.05% tretinoin, 3% \nclyndamycin, and 0.05% dexamethasone at night. \nAt two weeks follow up, most inflammatory lesions \nhad improved. Once the inflammation settled, he \nwas commenced on combination of 0.05% tretinoin \nand 3% clindamycin for another 3 months.\n\n\n\nCase 3\nA 19 year old woman presented with severe \nnodulocystic acne on the face and neck for 1 year. \nShe depended heavily on topical herbal products for \nher AV.  On examination, there were multiple \ncomedones, papules and pustules distributed on her \nface and neck. She was given oral doxycyclin 100 \nmg twice daily for 10 days and cream containing \n0.05% tretinoin, 3% clindamycin, and 0.05% \ndexamethasone at night. At one month, her lesions \nimproved tremendously. She was changed to a \ncombination cream of 0.05% tretinoin and 3% \nclindamycin for another 3 months..\n\n\n\nIntroduction\nAcne vulgaris (AV) is a chronic inflammatory \ndisease affecting pilosebaceous unit marked by the \npresences of comedones, papules, pustules, and \nnodules1,2. This is commonly found among teenagers \naged from 12-15 years old and peaks in age of 17-\n21 years old1. Despite being a self-limiting disease, \nAV causes scarring leading to severe aesthetical and \nphysiological disturbances3.\n\n\n\nThere are many factors causing acne eg. races, \ngenetics, hormones, diet, psychologic stressors, \ncosmetics use, climates, drugs, pregnancy, and \nsmoking behavior4,5. Four major pathogenesis of AV \nare increase of sebum production, pilosebaceous \nfollicular hyperploriferation, colonization of P. \nacnes, and inflammatory process6.\n\n\n\nThe goal of therapy is to accelerate recovery, inhibit \nnew lesions, and prevent scarring1. Treatment \nof nodulocystic and conglobata acne remains \nchallenging. We present three cases of severe AV \ntreated with a combination of oral doxycycline \nand combo cream containing treninoin 0.05%, \nclyndamycin 3%, and dexamethasone 0.05%.\n\n\n\nCase 1\nA 20 year old man had severe nodulocystic acne for 2 \nyears which failed to respond to antibiotics and over \nthe counter topical anti-acne. Examination showed \nmultiple comedones, papules, nodulocysts and scars \non the face. He was given oral doxycycline 100 \nmg twice daily for 10 days and cream containing \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 62\n\n\n\nFigure 1a. Erythematous papules, \npustules, nodulocysts and scars on \nface.\n\n\n\nFigure 2a. Papules, pustules and \nnodulocysts on the face.\n\n\n\nFigure 3a. There were multiple \ncomedones, papules, pustules on the \nface and neck.\n\n\n\nFigure 1b. After 1 month of therapy, \nthere was marked reduction of \ninflammatory lesions.\n\n\n\nFigure 2b. After 2 weeks of therapy, \nthere was reduction in inflammatory \nlesions.\n\n\n\nFigure 3b. After 1 month of therapy, \nthere was reduction in inflammatory \nlesions.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3763\n\n\n\nTopical antibiotic is also commonly utilized in \ninflammatory acne14 Clindamycin is a semisynthetic \nmolecule derived from lyncomycin. It lowers free \nlipid acid concentration and P. acnes population \nin the pilosebaceous units15. It also possesses anti-\ninflammatory property by suppressing leukocytes \nchemotaxis15,16. It is much favoured compared to the \noral due to its superior side effect profile.  \n\n\n\nCorticosteroid has anti-inflammatory, \nimmunosupresive, anti-proliferative, and \nvasoconstrictive properties. As anti-inflammatory \nagent, corticosteroid inhibits A2 phospolipase \nrelease, an enzyme responsible for synthesis of \nprostaglandin, leukotriene, and other arachidonic \nacid derivates that could damage dermal collagenous \ntissue and leads to formation of permanent scars12. \nTherefore steroid administration is important \nespecially for severe cases such as nodulocystic acne \nand acne conglobata for scar prevention2. The most \npreferred topical corticosteroid is dexamethasone. \nDexamethasone has not widely used as topical \ntherapy for skin because it is poorly absorbed. \nNevertheless, in severe acne, the higly inflamed \nskin allows better absorption17. Thus, topical \ndexamethasone works well in severe inflammatory \nacne. This phenomenon is called \u201cfocal specific \neffect\u201d, which not only minimize general adverse \neffects of corticosteroids, but also heal the inflamed \nskin area and prevent the occurrence of post-\ninflammation hyperpigmentation18. However topical \ncorticosteroid has double-edged sword, where long \ntime use could induce comedogenesis, leading to \nincreased concentration of free fatty acids in skin \nsurface lipids and increased numbers of bacteria in \nthe pilosebaceous duct19.\n\n\n\nOur three patients responded excellently with the \ncombination of oral doxycycline and the combo \ncream. Steroid use was stopped after inflammatory \nlesions disappeared. For maintenance, the three \npatients treated by combination cream 0.05% \ntretinoin and 3% clindamycin for 3 months.\n\n\n\nIn conclusion, severe AV therapy using short \ncourse oral doxycycline with combination cream \nof tretinoin, clindamycin and dexamethasone is \npromising in the treatment of severe AV.  \n\n\n\nDiscussions\nAV is one of dermatological disease that is commonly \nfound among teenagers and adults. Despite not \nbeing a life-threatening condition, its sequelae \nundermined patient\u2019s confidence and self esteem1,2. \nNowadays, self medication of AV take centrestage. \nThe three patients reported had tried multiple over \nthe counter products to no avail. This has become \nchallenging for dermatologist, especially in dealing \nwith severe scarring acne.\n\n\n\nIn the three cases presented before, all patients \nsuffered severe acne vulgaris based on clinical \nassessment. All our patients satisfied the Lehman \net al classification of severe acne (>5 cysts, >100 \ncomedones, >50 inflammatory lesions, >125 total \nlesions)7.\n\n\n\nEffective therapy in AV significant improves the \nquality of life in AV sufferers. The understanding \nof four mechanism of AV pathophysiology formed \nthe foundation of treatment: refinement of follicular \nproliferation, suppression of sebaceous gland \nactivity, reduction of P. acnes population, and \ninhibition of local inflammation2.  For mild AV, \ntopical retinoid or topical antibiotic suffice but \nmoderate to severe AV require systemic antibiotics \nand topical retinoid1,8. The three patients were \ntreated using oral doxycyclin 100 mg twice daily for \n10 days and cream containing 0.05% tretinoin, 3% \nclindamycin, and 0.05% dexamethasone at night. \nContinuing use of oral or topical broad spectrum \nantibiotics increases the risk of P. acnes resistence8, \nand this circumstance could cause AV treatment \nfailure.\n\n\n\nTetracycline had been used widely in the past to treat \ninflammatory lesions9. It is able to reduce free fatty \nacid concentration and supress P. acnes growth2. Due \nto the high resistance rate, doxycycline, a derivative \nof tetracycylines, has been recommneded2,9.\n\n\n\nTopical medications given to the our patients \nwere a combination of tretinoin, clyndamycin, \nand dexamethasone. The topical retinoids has \ncomedolytic activity, preventing formation of \nmicrocomedones by normalizing follicular epithelial \ndesquamation. In addition to targeting abnormal \nproliferation and differentiation of keratocytes, \nretinoids also possesses anti-inflammatory effects10. \nThe main topical retinoids are tretinoin, tazarotene, \nand adapalene11,12. These properties make topical \nretinoids highly favoured among dermatologists. It \nis also safer than the oral isotretinoin treatment13.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 64\n\n\n\nReferences\n \n1. Sitohang IBS, Wasitaatmadja SM. Akne vulgaris. In: \n\n\n\nMenaldi SLS, Bramono K, Indriatmi W, editors. Ilmu \npenyakit kulit dan kelamin. 7th ed. Jakarta: Badan Penerbit \nFakultas Kedokteran Universitas Indonesia; 2015.p.288-\n92.\n\n\n\n2. Zaenglein AL, Graber EM, Thiboutot DM, Strauss JS. In: \nWolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, \nLeffel DJ, editors. Fitzpatrick\u2019s dermatology in general \nmedicine. 7th ed. New York: McGraw Hill Companies; \n2008.p.690-703.\n\n\n\n3. Aurora MK, Yadav A. Role of hormones in acne vulgaris. \nClin Biochem. 2011;44:1035-40.\n\n\n\n4. Williams HC, Dellavalle RP. Acne vulgaris. Lancet. \n2012;379:361-72.\n\n\n\n5. Shaw JC. Persistant acne in adult women. Arch Dermatol. \n2001;137:1252-3.\n\n\n\n6. Szabo K. Studying the genetic predisposing factors in \nthe pathogenesis of acne vulgaris. Human Immunol. \n2011;72:766-73.\n\n\n\n7. Lehmann HP, Robinson KA, Andrews JS, Holloway V. \nAcne therapy: a methodologic review. J Am Acad Dermato. \n2002;47:1035-40.\n\n\n\n8. Thiboutot DM, Gollnick HP, Betolli V, Dreno B, Kang S, \nLeyden JJ, et al. New insight into the management of acne: \nan update from the Global Alliance to improve outcome \nin acne group. J Am Acad Dermatol. 2009 May;60(5 \nSuppl):S1-50.\n\n\n\n9. Harper JC. An update on the pathogenesis and management \nof acne vulgaris. J Am Acad Dermatol. 2004;51(1):536-8.\n\n\n\n10. Rathi SK. Acne vulgaris treatment: the current scenario. \nIndian J Dermatol. 2011 Jan-Feb; 56(1):7-13.\n\n\n\n11. Keri J, Shiman M. An update on the management of acne \nvulgaris. Clin Cosmet Investig Dermatol. 2009;2:105-10.\n\n\n\n12. Haider A,Shaw JC. Treatment of acne vulgaris. JAMA. \n2004;292(6):726-35.\n\n\n\n13. Costa CS, Bagatin E. Evidence on acne therapy. Sao Paulo \nMed J. 2013;131(3):193-7.\n\n\n\n14. Cunliffe WJ, Gollnick HPM. Topical therapy. In: \nCunliffe WJ, Gollnick HPM, editors. Acne diagnosis and \nmanagement. London: Martin Dunitz Ltd, 2001.p.107-14.\n\n\n\n15. Katsamba A, Dessinioti C. New and emerging treatments \nin dermatology. Acne Dermatol Ther. 2008;21(2):86-95.\n\n\n\n16. Golnick HPM, Krautheim Andrea. Topical treatment in \nacne: current status and future aspects. Dermatology. \n2003;206(1):29-36.\n\n\n\n17. Dhar S, Seth J, Parikh D. Sistemic side-effects of topical \ncorticoseroids. Indian J Dermatol. 2014 Sep-Oct; \n59(5):460-4.\n\n\n\n18. Abraham A, Roga G. Topical steroid-damaged skin. Indian \nJ Dermatol. 2014 Sep-Oct; 59(5):456-9.\n\n\n\n19. Coondoo A, Phiske M, Verma S, et al. Side-effects of \ntopical steroids: A long overdue revisit. Indian J Dermatol. \n2014; 5(4): 416-25.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3765\n\n\n\nCase Report\n\n\n\nA CASE OF VERRUCOUS PSORIASIS IN\nAN ERYTHRODERMIC PATIENT\nBhullar A1, Lee BR2, Norashikin S1\n\n\n\nCorresponding Author and Reprint Request \nDr Anisha Bhullar\nDepartment of Medicine, Faculty of Medicine\nand Health Sciences, Universiti Putra Malaysia\n43300 Serdang, Malaysia\nEmail: anishabhullar@gmail.com\n\n\n\n1 Department of Medicine and\n2 Department of Pathology, Faculty of Medicine and \n Health Sciences, Universiti Putra Malaysia,\n 43300 Serdang, Malaysia\n\n\n\non the dorsum of both feet which did not respond \nto methotrexate (Figure 1).These lesions were \nasymptomatic but were progressively growing. \nMethotrexate was given for a duration of 2 months \nat the dose of 10mg/week.\n\n\n\nA 6 mm punch biopsy was taken from these plaques \nto confirm the diagnosis of verrucous plaque \npsoriasis. As his condition was severe, we planned \nfor biologic therapy to control both his cutaneous \nand joint disease.\n\n\n\nHistopathology examination of the skin specimen \nshowed a grossly acanthotic epidermis. Psoriasiform \nhyperplasia with elongation of the rete ridges was \nseen. Dilated capillary loops in the papillary dermis \nwas also present (Figure 2). There were neutrophilic \nexudates with microabscesses collections within \nthe epidermis and parakeratosis with corresponding \nhypogranulosis (Figure 3). Patchy superficial \nlymphocytic perivascular exudates were also seen. \nPAS staining was negative for fungal bodies. These \nchanges were consistent with verrucous plaque \npsoriasis.\n\n\n\nIn the meantime methotrexate was discontinued \nas he had developed acute hepatitis and he was \njust maintained on topical corticosteroids. As his \ncondition was severe, we planned for biologic \ntherapy to control both his cutaneous and joint \ndisease. He was commenced on ustekinumab \nshortly afterwards, which resulted in flattening of \nhis verrucous plaques as well as improvement in his \npsoriasis after 2 doses. This was the drug of choice \nin our patient as we had limited resources to finance \nother biologics at that time (TNF \u2013 alpha inhibitors).\nHe completed 4 doses of ustekinumab. We stopped \nthis drug as the overall PASI score has increased \nafter 4 doses. The PASI score before the initiation \nof ustekinumab was 30, rising to 39 after 4 doses. \nOur next choice of treatment was adalimumab, for \nwhich we were able to secure funding. Our patient \nhas been on this medication for 1 year, with good \nclinical response seen overall (Figure 4).\n\n\n\nIntroduction\nVerrucous psoriasis is an uncommon variant \nof psoriasis characterized by the presence of \nhypertrophic verrucous papules or plaques. The \nwarty appearance of the lesions is more suggestive \nof dermatoses such as verruca vulgaris .These cases \nare usually seen in patients with longstanding plaque \npsoriasis. It may be difficult to diagnose, therefore \na skin biopsy with histopathology correlation is \nwarranted.\n\n\n\nWe report a case of verrucous psoriasis seen on lower \nextremities in a patient with pre-existing plaque \npsoriasis and a review of the relevant literature.\n\n\n\nCase Report\nA 51 year old Malay male presented to our center \nwith a history of extensive chronic plaque psoriasis \nspanning 10 years. He was initially treated with \nacitretin and NBUVB but due to poor clinical \nresponse was switched to methotrexate. He has \nhad several episodes of erythroderma precipitated \nby poor compliance to systemic medications. His \ncondition has also been complicated with psoriatic \narthropathy with involvement of the small joint \nof the hands for the last 3 years. Throughout our \nclinical assessments, he had been persistently \nerythrodermic with flexion deformities of his distal \ninterphalangeal joints bilaterally. \n\n\n\nTwo years ago he presented with symmetrical, \nmoderately thick warty brownish hyperkeratotic \nplaques occurring on pre-existing psoriatic plaques \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 66\n\n\n\nFigure 1. Brownish warty hyperkeratotic plaques symmetrically distributed on the lower legs \nextending to the dorsum of the feet and soles.\n\n\n\nFigure 2. The epidermis showed psoriasiform hyperplasia with elongation of the rete ridges and \nprominent hypogranulosis. Dilated capillary loops were noted at the papillary dermis.\n\n\n\nFigure 3. Neutrophils collection forming microabcessess within the stratum corneum and papillary \ndermis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3767\n\n\n\nFigure 4. The excellent clinical \nimprovement seen in both soles resulting \nin complete resolution of plaques.\n\n\n\ncommon in men, affecting 13 of the patients with \n7 female patients. The common sites involved \nare the trunk and the extremities. Some of these \nlesions have arisen on a background of pre-existing \nchronic plaque psoriasis. One case had concomitant \nnon melanoma skin cancer3. We also came across \na case treated as multiple verrucous carcinoma, \nwhich was possibly VP based on the distribution \nand morphology, biopsy and response to acitrenin. \nThese lesions were hyperkeratotic plaques on dorsal \nof feet, ankles and thigh10.\n\n\n\nThe cause of verruca psoriasis is unknown. It has \nbeen postulated to occur from obstruction in the \nlymphatic drainage leading to the development of \nextensive cutaneous papillomatosis which gives the \nclinical warty appearance9,11. No studies have been \ndone to confirm this.\n\n\n\n The occurrence of the verrucous lesions in psoriasis \npatients is uncommon. Some of the possible causes \ninclude poor hygiene and poor compliance to \ntreatment. A similar case of verrucous skin eruptions \nin a patient with hepatitis C during interferon \ntreatment suggests that ongoing immunosuppressive \ntherapy may promote and lead to the development \nof verrucous psoriasis5.\n\n\n\nDiscussions\nPsoriasis is a T-cell mediated immune disease \nwhich affects 2-3% of the general population. \nThe common subtypes of psoriasis are defined as \nplaque, guttate, flexural or inverse, pustular and \nerythrodermic psoriasis. Verrucous psoriasis was \ninitially considered to be a more severe form of \npsoriasis rather than a separate entity. Over time, it \nhas been discussed in the literature and is accepted \nas a clinical variant. It has not shown to have any \nparticular site predilection and can occur by itself as \nwell as in patients with psoriasis vulgaris .Clinically \nthe lesions appear thickened and hypertrophic \nmimicking the appearance of other dermatosis \nlike verruca vulgaris. In our patient the verrucous \nappearance of the feet also resembled mossy foot, \na term usually used in conditions with chronic \nlymphatic obstruction such as elephantiasis where \nthe lesions are grossly papillomatous. \n\n\n\nSo far there have been 20 cases reported in the \nliterature1-9. The first clinical case description \nwas documented by Nakamura et al in 1994 in a \n60 year old male of Japanese origin with chronic \nplaque psoriasis1. The largest and only case series \nof 12 patients was reported by Khalil et al in the \nwestern population, mostly of Caucasian patients2. \nThe overall distribution of cases seems to be more \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 68\n\n\n\nbiologics have only been approved for the plaque \nvariant of psoriasis and the current use to biologics \nin erythrodermic patients is limited.\n\n\n\nThis case report presents a rare and atypical \nmanifestation of psoriasis in a patient with \nchronic plaque psoriasis despite being on oral \nimmunosuppressive therapy. Verrucous lesions \noften reflect poor control of the underlying psoriasis \nand helps to guide clinical decision making with \nrespect to therapeutic management options.\n\n\n\nAs our patient was suffering from refractory chronic \nplaque psoriasis with extensive body surface \ninvolvement, we decided on biologic therapy \nusing ustekinumab, a monoclonal antibody which \ntargets interleukin 12 and 23. Other novel treatment \nmodalities that have been successful in other \npatients are radiation treatment and adalimumab4,6. \nA retrospective study by Pescitelli et al   had shown \nustekinumab to be effective in the management \nof erythrodermic psoriasis with very rapid and \nquick resolution of cutaneous disease12. Thus far, \n\n\n\nReferences\n \n1. Nakamura S, Mihara M, Hagari Y, Shimao S. Psoriasis \n\n\n\nverrucosa showing peculiar histologic features. J Dermatol \n1994; 21: 102-105.\n\n\n\n2. Khalil FK. Keehn CA, Saeed S, Morgan MB. Verrucous \npsoriasis: a distinctive clinicopathologic variant of \npsoriasis. Am J Dermatopathol 2005; 27: 204-207.\n\n\n\n3. Monroe HR, Hillman JD, Chiu MW. A case of verrucous \npsoriasis.Dermatol OnlineJ 2011; 17: 10.\n\n\n\n4. Maejima H, Katayama C, Watarai A, et al. A case of \npsoriasis verrucosa successfully treated with adalimumab. \nJ Drugs Dermatol 2012; 11: e74-75.\n\n\n\n5. Scavo S, Gurrera A, Mazzaglia C, et al. Verrucous psoriasis \nin a patient with chronic C hepatitis treated with interferon. \nClini Drug Investig 2004; 24: 427-429. \n\n\n\n6. Larsen F, Menter A, Cockerell CJ, Wilcox BN. Verrucous \nlinear (segmental) psoriasis of the right leg responding to \nradiation therapy. J Drugs Dermatol 2008; 7: 969-971.\n\n\n\n7. Curtis AR, Yosipovitch G. Erythrodermic verrucous \npsoriasis. J Dermatolo Treat 2012; 23: 215-218.\n\n\n\n8. Erkek E, Bozdogan O. Annular verrucous psoriasis with \nexaggerated papillomatosis. Am J Dermatopathol 2001; \n23: 133-135.\n\n\n\n9. Okuyama, R, Tagami H. Psoriasis verrucosa in an obese \nJapanese man; A prompt clinical response observed with \noral etretinate. J  Eur Acad DermatolVenereol 2006; 20: \n1359-1361.\n\n\n\n10. Larsen F, Susa JS, Cockerell CJ, Abramovits W. Case of \nmultiple verrucous carcinomas responding to treatment \nwith acetretin more likely to have been a case of verrucous \npsoriasis. J Am Acad Dermatol 2007; 57: 534-535.\n\n\n\n11. Zoubolis CC, Biczo S, Gollnick H, et al. Elephantiasis \nnostrasverrucosa: beneficial effect of oral etretinate \ntherapy. Br J Dermatol 1992; 127: 411-416.\n\n\n\n12. Pescitelli L, Dini V, Gisondi P, et al. Erythrodermic \npsoriasis treated with ustekinumab: An Italian multicenter \nretrospective analysis. Journal of dermatological science. \n2015 May 1;78(2):149-51.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3769\n\n\n\nCase Report\n\n\n\nANGIOLYMPHOID HYPERPLASIA WITH EOSINOPHILIA OF\nTHE EYELID: A CASE REPORT\nAbirami S, MBBS1, Gunavathy N2, Ho SF2, Mazita I3, Adil H1\n\n\n\nCorresponding Author and Reprint Request \nAbirami Shavani a/p Sanmugam\nOphthalmology Department, School of\nMedical Sciences, Universiti Sains Malaysia\n16150 Kubang Kerian, Kelantan, Malaysia\nEmail: aby2099@gmail.com\n\n\n\n1 Department of Ophthalmology, School of Medical \n Sciences, Universiti Sains Malaysia,\n 16150 Kubang Kerian, Kelantan, Malaysia\n2 Department of Ophthalmology, Hospital Raja \n Permaisuri Bainun, 30990 Ipoh, Perak, Malaysia\n3 Department of Pathology, Hospital Raja Permaisuri \n Bainun, 30990 Ipoh, Perak, Malaysia\n\n\n\nleft preseptal region extending to the subcutaneous \nregion at the left temporal region which enhances \nafter omnipaque infusion (Figure 2). As these \nfindings correlated with the initial diagnosis, he was \ncontinued on intravenous ceftriaxone for 3 days. \nHowever, there was no improvement.\n\n\n\nSubsequently, a biopsy with debulking of the left \nupper eyelid lesion was performed. Intraoperatively, \nyellowish hard materials were removed and sent \nfor histopathological examination. Histopathology \nresults showed fragments of fibromuscular tissue \ndisplaying scattered blood vessels surrounded by \nmature lymphocytes and eosinophils forming a \nnodular pattern (Figure 3). The stroma and muscular \nlayer is infiltrated by dense eosinophils. There were \nno areas of necrosis or neoplastic lymphoid cells \nseen. Peripheral eosinophil cunt was 3.36 X 108, \nwhcih was within normal range. These features \nwere suggestive of Angiolymphoid hyperplasia with \neosinophilia and the diagnosis was revised.\n\n\n\nPost-operatively, he was started on intravenous \ndexamethasone for 3 days followed by topical \nsteroids. He responded well with gradual \nimprovement of the upper lid swelling over the \ncourse of 3 months.\n\n\n\nDiscussion\nALHE arising from orbital region is a rare \npresentation. The presenting features are usually \nvague and nonspecific especially when it involves \nthe ocular adnexa or orbit5. This leads to a delay \nin diagnosis in most cases2,10. In the case of orbital \ninvolvement, the common clinical features are lid \nswelling, ptosis, proptosis, periorbital swelling, \ndiplopia, watering, pruritis around the eyes and \nblurring of peripheral vision5,9,10. In our case, the \nclassical presenting features of proptosis and \ndiplopia were missing. This is because there were \nno extraconal lesion or recti muscle displacement. \nThe usual sites of periorbital ALHE involvement are \nlacrimal glands, eyelids, conjunctiva, medial and \nlateral canthal region, intra- and extraconal orbital \nspaces5.\n\n\n\nIntroduction\nAngiolymphoid hyperplasia with eosinophilia \n(ALHE) is an uncommon benign vascular disorder \ndescribed by Wells and Whimster in 19691,3,4. It \nis characterized by marked vascular proliferation \nand inflammation primarily involving the head \nand neck region5-7,9-11. It has a predilection towards \nwomen mainly in the third and fifth decade of \nlife6,9,11. Although involvement of the ocular adnexa \ninvolving orbit has been reported in the literature \npreviously, it remains a rare site of occurrence5,9,10,12. \nWe report a case of orbital involvement of ALHE.\n\n\n\nCase Report\nA 39 year old Malay gentleman who was an ex-\nillicit drug user (non-injecting type) presented with \npainless, progressive left upper lid swelling for 3 \nweeks following an insect bite (Figure 1). There \nwere no history of fever, eye discharge, skin rashes, \ntrauma or blurring of vision. On examination, \nthere was a non tender, diffuse, non fluctuant and \nerythematous swelling of the left upper lid leading \nto total mechanical ptosis. Bilateral ocular findings \nwere normal. An initial diagnosis of left preseptal \ncellulitis secondary to insect bite was made. He was \nempirically started on oral Augmentin for one week. \nOn follow up at one week, the swelling remained \nthe same and he was admitted for intravenous \nceftriaxone. Blood investigations including full blood \ncount were normal. Plain and contrasted computed \ntomography of the orbit showed thickening of the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 70\n\n\n\nALHE has been called the western cousin of \nKimura\u2019s disease (KD) for the similarities they \nshare in clinical presentation5. They were previously \nconsidered as the same disease in different stages. \nCurrently, they are distinguishable as separate \nentities6-7,9-10. In contrast to ALHE, Kimura disease \nhas a predilection to Asian men and commonly \npresents with painless subcutaneous masses in \nthe head and neck, lymphadenopathy, peripheral \nblood and tissue eosinophilia6,7,9. Histologically, \nthe salient features of KD are, florid lymphoid \nfollicles with germinal center formation, \neosinophilic microabscesses, eosinophilic infiltrates \nand eosinophilic folliculolysis. It does not have \nepitheliod cells characteristic of ALHE7.\n\n\n\nAlthough the exact pathogenesis of ALHE remains \nobscure, various theories have been proposed in \nprevious studies3,5,7,9,10,12. The hypotheses include a \nneoplastic process, reactive process and infectious \nmechanism7. There has been data suggesting \nALHE may have lymphoproliferative changes as \nevidenced by presence of T-cell gene rearragements. \nPresence of blood and tissue eosinophilia and raised \nserum IgE concentration instead suggests reactive \netiology. It has also been postulated that ALHE can \ndevelop following injury, insect bites, infections \nor administration of tetanous toxoid vaccines2,10,12. \nArteriovenous shunts are also believed to be \nassociated with development of ALHE2,5-7. Another \npostulation is that renin, via the angiotensin II, may \nprompt proliferation of vessels thus being associated \nwith the etiology of ALHE5.\n\n\n\nFigure 1. showing initial presentation \nof left upperlid swelling with complete \nmechanical ptosis.\n\n\n\nFigure 2. Transverse Orbital CT scan \nshowing thickened preseptal region of \nthe left eye prior to excision biopsy.\n\n\n\nFigure 3. Blood vessels (black arrow) surrounded by \neosinophils (red arrow) and lymphocytes (Hematoxylin & \nEosin stain, x10 magnification).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3771\n\n\n\nrecurrence2,5. Other treatment modalities for ALHE \ninclude intralesional corticosteroids, cryotherapy, \nphotodynamic therapy, application of tacrolimus/\nimiquimod, systemic corticosteroid treatment, \nirradiation, interferon alpha-2a, cytotoxic agents \nand laser treatment with pulsed dye or carbon \ndioxide2,3,5-7,9,10,12. In our patient, we preferred the \nchoice of debulking as it was done simultaneously \nwith the biopsy to aid in diagnosis. An alternative \napproach is to observe the patient for 3 to 6 months \nfor possibility of spontaenous involution2,10.\n\n\n\nConclusion\nIn conclusion, a high index of suspicion is needed \nto diagnose ALHE particularly in an atypical \npresentation. Histopathologic studies are essential \nfor diagnosing ALHE given the unspecific clinical \npresentation and for subsequent management.\n\n\n\nAnother condition with close similarities to orbital \nALHE is idiopathic orbital inflammatory disease \n(IOID) which has similar clinical presentation with \nproptosis, pain, ptosis, lacrimal gland swelling, \nand thickened extraocular muscles5. However they \ncan be distinguished histopathologically where a \nclassic case of IOID has cellular infiltrate consisting \nmainly of mature lymphocytes, with plasma \ncells, macrophages, histiocytes, eosinophils, and \ninfrequently neutrophils5.\n\n\n\nAs much as it is a challenge to diagnose, so is the \ntreatment of ALHE. Many literatures have proposed \nsurgical excision or debulking of the lesion as \nthe preferred choice of treatment5,7. However, \nthere is a high recurrence rate following surgical \nintervention as high as 33%2,3,5,7,9,10,12. Incomplete \nsurgical margins has been said to contribute to the \n\n\n\nReferences\n \n1. Wells GC, Whimster IW. Subcutaneous angiolymphoid \n\n\n\nhyperplasia with eosinophilia. Br J Dermatol 1969;81:1-\n14.\n\n\n\n2. I Zaraa, M Mlika, S Chouk,et al. Angiolypmphoid \nhyperplasia with eosinophilia: A study of 7 cases. \nDermatology Online Journal 17(2):1.\n\n\n\n3. Paolo Esteves, Marcella Barbalho, Tiago Lima, et al. \nAngiolymphoid Hyperplasia with Eosinophilia: A case \nreport. Case Rep Dermatol 2015;7:113-116.\n\n\n\n4. Chacon a, Mercer J. Successful management of \nangiolymphoid hyperplasia with eosinophilia in a split-\nface trial of topical tacrolimus and timolol solution. G Ital \nDermatol Venereol 2016 aug;151(4):436-40 .\n\n\n\n5. Bipasha Mukherjee, Jayant Kadaskar, Omega \nPriyadarshini, et al. Angiolymphoid Hyperplasia with \nEosinophilia of the Orbit and Adnexa. Ocular Oncology \nand Pathology 2016;2:40\u201347.\n\n\n\n6. Pedro Leonardo Briggs. Kimura disease is not \nangiolymphoid hyperplasia with eosinophilia: clinical \nand pathological correlation with literatute review and \ndefinition of diagnostic criteria. An Bras Dermatol \n2006;(2):167-73.\n\n\n\n7. Ruifeng Guo, Alde Carlo P. Gavino. Angiolymphoid \nHyperplasia with Eosinophilia. Arch Pathol Lad Med \n2015;139:683-686.\n\n\n\n8. Nouchi A, Hickman G, Battistella M, et al. Treatment of \nangiolymphoid hyperplasia with eosinophilia (ALHE) \nusing topical tacrolims : Two cases. Ann Dermatol Venereol \n2015 May;142(5):360-6.\n\n\n\n9. Bangal SV, Chitgopekar RP, Gupta AK, Karle R. Orbital \nextension of supraorbital angiolymphoid hyperplasia with \neosinophilia. AMJ 2011,4,3,111-113.\n\n\n\n10. Amir A, Azari, Mozhgan R. Kanavi,et al. Angiolymphoid \nHyperplasia with Eosinophilia of the Orbit and Ocular \nAdnexa: Report of Five Cases. JAMA Ophthalmol 2014 \nMay;132(5):633-636.\n\n\n\n11. Serena Lembo, Anna Balato, Teresa Cirillo, Nicola Balato. \nA Long-term Follow-up of Angiolymphoid Hyperplasia \nwith Eosinophilia Treated by Corticosteroids: When \na Traditional Therapy is Still Up-to-Date. Case Rep \nDermatol 2011; 3:64-67.\n\n\n\n12. Prathyusha Chitrapu, Mahir Patel, Allison Readinger, Alan \nMenter. Angioplymphoid hyperplasia with eosinophilia. \nProc (Bayl Univ Med Cent) 2014;27(4):336-337.\n\n\n\n13. Pankaj Kumar Doloi, Swagata Khanna. Angiolymphoid \nHyperplasia with Eosinophilia \u2013 A Case Report. \nInternational Journal of Otolaryngology and Head & Neck \nSurgery 2012, 1, 44-47.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 72\n\n\n\nCase Report\n\n\n\nKISSING NAEVUS OF EYELIDS - A REPORT OF TWO CASES\nGupta M\n\n\n\nCorresponding Author and Reprint Request \nDr Mrinal Gupta, MBBS, MD, DNB\nSudhaa Skin Centre, Tawi Vihar, Sidhra\nJammu, India 180019.\nEmail: drmrinalgupta@yahoo.com\n\n\n\nThe patient had approached us for cosmetic concern. \nThe patient was advised a biopsy of the lesion which \nhe refused. He was counselled about the nature of \nthe lesion and was advised regular follow-up for \nmonitoring the lesion. After one year of follow-up, \nthere was only mild increase in pigmentation of the \nlesion and the patient is still under regular follow-up \nwithout any significant change in the lesion.\n\n\n\nCase 2\nThe second case, a 35 year old female, also presented \nwith a kissing naevus over the right eyelid since \nbirth which was a hyperpigmented, velvety plaque \nto begin with but had later on became nodular with \nincreasing pigmentation and hair growth over time. \nAs the lesion was not in the line of the visual axis in \nchildhood, the vision was normal but gradually with \nthe increase in size and nodularity of the naevus, \nthe visual axis was being obstructed, causing lateral \nvisual field obstruction. On examination, the patient \nhad two well developed hyperpigmented nodular \nlesions over the lateral aspect of right eyelids. The \nupper eyelid lesion was larger measuring about 4cm \nX 2cm while the lower lid lesion was about 1.5cm X \n1cm. The lesions showed irregular nodular surface \nwith increased terminal hair and follicular dilatation \n(Figure 2). On ophthalmological examination, the \nvisual acuity was normal but the field of vision was \nreduced laterally due to mechanical obstruction by \nthe naevus.\n\n\n\nThe patient was advised a biopsy and surgical \nexcision of the naevus but, unfortunately, the patient \nwas lost in follow-up.\n\n\n\nIntroduction\nKissing naevus or divided naevus is a rare form of \ncongenital naevus which appears over two adjacent \nsites which are fused together in-utero in the early \nstages of development but get separated later on \nlike the two eyelids. The naevus is present on two \nadjacent sites in such a manner as when the two are \napposed together, the naevus appears as a single \nlarge naevus1,2. Kissing naevus have mostly been \nreported over the eyelid but kissing naevi of the \npenis and fingers have also been reported.\n\n\n\nKissing naevus of the eyelid was first reported \nby Von Micheal in 1908, and the name was first \nused by Fuchs in 1919. Most of the cases appear \nin childhood but may rarely appear in adulthood. \nThe lesions usually present a cosmetic concern but \nlarger lesions may lead to impaired vision due to \nmechanical ptosis or obstruction of visual axis1,2. \nHerein we report two cases of kissing naevus of \neyelids who presented with the complaints of \ncosmesis and visual disturbance.\n\n\n\nCase History\nCase 1 \nThe patient, a 22 years old male, presented with \na hyperpigmented melanocytic naevus on right \neyelids since birth. The naevus was gradually \nbecoming more pigmented and thickened but had \nremained asymptomatic throughout the course. On \nexamination, a hyperpigmented velvety plaque of \nsize 3.5cm X 2cm was present on the lateral aspect \nof the right upper eyelid while a similar lesion \nof size 2cm X 1.5cm was present on the lateral \naspect of lower eyelid (Figure 1). On closure of \nthe eyelids, the lesions resembled a single naevus. \nThe conjunctiva and the cornea were not involved \nand the vision was normal. There was no systemic \ncomplaint and no family history was present either.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3773\n\n\n\nFigure 1. Kissing naevus of eyelid presenting as velvety \nplaque.\n\n\n\nFigure 2. Kissing naevus of eyelid presenting as nodular \nmass.\n\n\n\nThe smaller naevi that do not cause any significant \nmorbidity can be left untreated under observation but \nthe larger naevi or those causing significant cosmetic \nconcern or visual complaints will require a surgical \nprocedure. In view the development of deprivation \namblyopia and the malignant potential, early \nsurgical treatment is recommended for all medium \nand large congenital melanocytic naevi of the \neyelid. The most appropriate type of reconstructive \nprocedure should be selected according to the size \nand anatomical units / segmental distribution of \nnaevus. A lesion that is smaller than 1/4 of the upper \nand lower eyelids can be excised with adjacent flap \nadvancement for reconstruction. A lesion that is \nlarge can be reconstructed with a full-thickness graft \nusing a retroauricular or contralateral eyelid flap. A \nlarge lesion on the forehead and the isthmus area \ncan be reconstructed via local flap surgery using a \ntissue expander4,5.\n\n\n\nDiscussion\nKissing naevus or divided naevus is a rare form of \ncongenital naevus which usually appears during \ninfancy but may rarely appear during adulthood. \nUsually they are seen on the medial aspect of the \neyelids but may rarely be seen laterally or in the \ncanthal region. The symmetrical borders and the \ncontiguous pattern of the kissing naevus are related \nto the embryological mechanism of its development. \nThe kissing naevi are believed to arise at the time \nwhen the eyelids are fused in-utero. The eyelids \nappear as ectodermal protrusions at the age of six \nweeks. Gradually they grow towards each other and \nbegin to fuse and are completely fused by the age of \nnine weeks. They remain fused till 24 weeks after \nwhich they gradually separated. Hence the kissing \nnaevus appears somewhere during 9-24 weeks of \ngestation wherein the melanoblasts accumulate \nat the fused eyelid, which on separation leads to \nformation of two distinct naevi, one each on both \nupper and lower lids3.\n\n\n\nReferences\n \n1. McDonnell PJ, Mayou BJ. Congenital divided naevus of \n\n\n\nthe eyelids. Br J Ophthal 1988;72:198-201. \n2. Aslan G, Terzioglu A. Divided Nevus of the Eyelids \n\n\n\n(Report of two cases). T Klin J Med Sci 2000;20:172-4.\n3. Hatem AT, Mohamed HA, Yousef AF, Jonathan JD. \n\n\n\nEmbryologic and Fetal Development of the Human Eyelid. \nOphthal Plast Reconstr Surg 2016;32:407\u201314\n\n\n\n4. Margulis A, Adler N, Bauer BS. Congenital melanocytic \nnevi of the eyelids and periorbital region. Plast Reconstr \nSurg 2009;124: 1273-83. \n\n\n\n5. Soo AL, An YR, Dong LL, Yong IY. Treatment of \nCongenital Divided Nevus of the Eyelid with Excision and \nBlepharoplasty. Arch Plast Surg. 2012; 39(4): 437\u20139. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 74\n\n\n\nCase Report\n\n\n\nPHENYTOIN INDUCED PELLAGRA \u2013 A CASE REPORT\nGupta M\n\n\n\nCorresponding Author and Reprint Request \nDr Mrinal Gupta, MBBS, MD, DNB\nSudhaa Skin Centre, Tawi Vihar, Sidhra\nJammu, India 180019.\nEmail: drmrinalgupta@yahoo.com\n\n\n\nlimits. The routine hematological and biochemical \ninvestigations were within normal limits. Due to \nunavailability, estimation of serum niacin or its \nurinary metabolites could not be performed.\n\n\n\nBased on history, presence of skin lesions with burnt \nout appearance, and investigations, a diagnosis \nof drug-induced pellagra like dermatitis was \nestablished. Patient was started on nicotinamide (300 \nmg/day) in three divided doses with multivitamin B \ncomplex while continuing phenytoin therapy. There \nwas complete resolution of the symptoms within \nfour weeks of the therapy after which she was given \na maintenance daily dose of 50 mg of nicotinamide. \nThe patient remained symptom free and there was \nno recurrence of symptoms over a six month follow \nup period.\n\n\n\nDiscussion \nLong recognized as a disease due to dietary \ndeficiency of nicotinic acid or its precursor \ntryptophan, pellagra is now known to be of \nmultifactorial origin, with concomitant deficiency \nof pyridoxine, riboflavin, thiamine, and proteins. \nGenerally, pellagra is a disease of a maize-eating \npopulation with an insufficient intake of animal \nprotein, fruits, and vegetables and has also been \nreported in some jowar (Sorghum vulgare) eating \npopulations1.\n\n\n\nCutaneous lesions resembling sunburn with a \nburnt-out appearance are the hallmark of pellagra. \nDermatitis seen in pellagra begins as symmetric \nerythema that later becomes hyperpigmented \nassociated with desquamation and rarely crusting \nmay occur. It is predominantly located on the face, \ndorsal surfaces of the hands and arms known as \nGauntlet of Pellagra and around the neck known \nas Casal\u2019s necklace. Cheilosis (dry fissured lips), \nangular stomatitis, and oral and perirectal sores \nare seen. In late stages, the entire tongue and oral \nmucosa, including the gingival mucosa, become \ninflamed, swollen, and ulcerated, and assume a bright \nscarlet color (scarlet glossitis and stomatitis). Poor \nappetite, epigastric discomfort, gastritis, nausea, \nvomiting and diarrhea are the common granular cell \n\n\n\nIntroduction\nPellagra is a nutritional deficiency disorder of \nniacin or its precursor tryptophan, characterized \nby classical 3Ds (dermatitis, diarrhea and \ndementia)1. This classic clinical presentation is \nrarely seen nowadays and most of the cases are \nborderline or less typical. It usually occurs in \nmalnourished persons or with alcohol abuse. Apart \nfrom nutritional deficiency, certain conditions like \nmalabsorption syndrome, metabolic disorders like \nHartnup disease, carcinoid syndrome, and drugs \nlike isoniazid, 6-mercaptopurine, 5-fluorouracil, \npyrazinamide, phenytoin, chloramphenicol, \nazathioprine, phenobarbitone, ethionamide are \nalso known to cause pellagra1,2. We report a case \nof pellagra in 23-year old female, taking phenytoin \nfor generalized tonic clonic seizures for the last \n16 years, who showed complete clearance of skin \nlesions with nicotinamide therapy.\n\n\n\nCase Report\nA 23-year old female presented with itchy skin \nlesions over the dorsa of hands and feet for the past \ntwo weeks. Lesions were gradually progressive and \nshe also complained of mild to moderate burning \nand itching over lesions while going out in sun. The \npatient had a history of generalized tonic clonic \nseizures for the last 16 years and had been taking \nphenytoin for the same and was presently taking \n200 mg/day phenytoin. There was no history of \nany other drug intake or any exposure to chemical \nagents and contact allergens. There was no history \nof memory loss or diarrhea or decreased appetite \nor any similar lesions in the past. On examination, \nwell demarcated, hyperpigmented, reddish brown, \nscaly plaques were present over the dorsa of both \nhands and feet [Figure 1]. There were no lesions \non the V area of neck, glossitis or cheilitis. Rest \nof the patient\u2019s systemic examination including \nher neurological examination was within normal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3775\n\n\n\nFigure 1. Symmetric, hyperpigmented, well-defined plaques \nwith desquamation surrounded by dusky discoloration over \ndorsa of hands and feet.\n\n\n\nNicotinamide is the preferred drug over niacin in \nthe management of pellagra as it does not cause \nvasomotor disturbances. World Health Organization \n(WHO) recommends a dose of nicotinamide 300 \nmg orally in divided doses or 100 mg parentally \nin divided doses for 3-4 weeks with vitamin B \ncomplex supplementation and high protein diet. \nUsually, neurological symptoms are the earliest \nto resolve and improve within 24 to 48 hours, but \nskin lesions may take 3 to 4 weeks to resolve. A \nmaintenance dose with nicotinamide 50 to 100 mg/\nday is recommended3,5.\n\n\n\nWe present this case to highlight this under reported, \neasily treatable adverse effect which may occur with \nprolonged anticonvulsant use.\n\n\n\nlayer loss, and architectural disarray with \ndysmaturation. Sebaceous glands and hair follicles \nare often atrophic.\n\n\n\nVarious drugs have been implicated in manifesting \nniacin deficiency which include antitubercular \ndrugs (isoniazid, ethionamide, pyrazinamide), \n5-fluorouracil, mercaptopurine and anticonvulsants \n(phenobarbital, carbamazepine, phenytoin). The \nexact mechanism of drug induced pellagra is not \nknown, although there have been various hypotheses. \nAntitubercular drugs, isoniazid, pyrazinamide, \nand ethionamide, are structurally similar to NAD, \ntherefore, they competitively replace NAD from \nthe metabolic pathways leading to pellagra. \n5-flourouracil inhibits conversion of tryptophan to \nniacin, whereas, 6-mercaptopurine causes inhibition \nof NAD phosphorylase thereby leading to deficiency \nof niacin. Phenytoin, chloramphenicol, azathioprine \nand phenobarbital interfere in the tryptophan-niacin \npathway causing pellagroid dermatitis4.\n\n\n\nReferences\n \n1. Karthikeyan K, Thappa DM. Pellagra and Skin. Int J \n\n\n\nDermatol 2002;41:476-81. \n2. Kaur S, Goraya JS, Thami GP, Kanwar AJ. Pellagrous \n\n\n\ndermatitis induced by phenytoin. Pediatr Dermatol \n2002;19:93.\n\n\n\n3. Dhawan AK, Grover C, Sharma S. Phenytoin induced \npellagroid dermatitis. Indian J Dermatol 2014;59:520-1.\n\n\n\n4. Garg G, Khopkar U. Ethionamide-induced pellagroid \ndermatitis resembling lichen simplex chronicus: A \nreport of two cases. Indian J Dermatol Venereol Leprol \n2011;77:534.\n\n\n\n5. Soni BP, McLaren DS, Sherertz MF. Cutaneous changes in \nnutritional disease. In: Freedberg IM, Eisen AZ, Wolf K, \nAusten KF, Goldsmith LA, Katz SL, editors. Dermatology \nin General Medicine. 5th ed. New York: McGraw-Hill; \n1999. p. 1725-37.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 76\n\n\n\nCase Report\n\n\n\nLINEAR LICHEN PLANUS PIGMENTOSUS, A CASE REPORT \nAND LITERATURE REVIEW\nAnisha B, Norashikin S\n\n\n\nCorresponding Author and Reprint Request \nDr Ansiha Bhullar, AdvMDerm\nFaculty of Medicine and Health Sciences\nUniversiti Putra Malaysia, Serdang, 43300 Malaysia\n\n\n\nsurface atrophy without mucosal, hair and nail \ninvolvement or other skin lesions. Our differential \ndiagnoses included LPP, zosteriform or linear \nlichen planus, lichen striatus and post-inflammatory \nhyperpigmentation.\n\n\n\nA skin biopsy showed atrophic epidermis with a \nband-like lymphocytic infiltrates at the dermo-\nepidermal junction and basal cell vacuolation (Figure \n3). There was prominent pigmentary incontinence \nand presence of melanophages with perivascular \nlymphocytic infiltrates (Figure 4). These features \nare consistent with a lichenoid interface dermatitis \nreaction such as lichen planus pigmentosus. This \npatient was initiated on super potent topical steroids \nbut despite being on treatment for months, the \nlesions did not regress. \n\n\n\nDiscussion\nLichen planus pigmentosus, a variant of lichen \nplanus is a pigmentary disorder with unknown \netiology mostly affecting adults and sometimes \nchildren. These patients are usually darker skinned \nindividuals and the first case was reported in the \nIndian literature1. Subsequently we found similar \ncases being reported in the Japanese and Koreans \nas well. In a large study by Kanwar et al of 124 \npatients, it showed a slight female preponderance3.\n\n\n\nThis condition has been commonly described as \nhyperpigmented brownish macules and patches \nbut occasionally slate grey or brownish black in \ncolour, typically distributed on sun-exposed areas.  \nThere have been varying patterns of presentations \nincluding flexural, zosteriform, segmental and \nlinear patterns. It is mostly diffuse but can also be \nreticular, blotchy and perifollicular3. There have also \nbeen reports of classical LP coexisting with LPP5. \nThe linear pattern of LPP is unique with only a few \nreports thus far in the current literature, mainly in \nOriental patients.\n\n\n\nIntroduction\nLichen planus pigmentosus (LPP) is a pigmentary \ndisorder first reported in 1974 in India in dark skinned \nindividuals by Bhutani et al1. Since then, it has also \nbeen reported in other racial and ethnic groups \nworldwide. It mainly affects women, and commonly \npresents on sun exposed areas with a morphological \nappearance of brownish hyperpigmented macules. \nThese lesions are asymptomatic. Histologic features \nof LPP are vacuolar basal cell layer degeneration with  \nband-like lichenoid infiltration of inflammatory cells \nseen hugging the dermo-epidermal junction and \nprominent melanin incontinence. Unlike classical \nlichen planus, involvement of the scalp, nail or \nmucosal area is rare. The linear form of LPP has \nfeatures of LPP and linear lichen planus, exhibiting \na linear pattern of distribution along the lines of \nBlaschko. There have been only a few reports in \nthe dermatologic literature on linear LPP, mostly in \nOrientals. Herein we report a case of linear LPP on \nthe face along the review the relevant literature.\n\n\n\nCase Report\nA 48 year old healthy Indian female presented \nwith several months history of hyper pigmented \nmacules on the right side of the chin. The macules \nhad coalesced and seemed to spread backwards in a \nlinear pattern along the right mandible. There was no \nhistory of trauma or new medication. There was also \nno preceding history of erythema on the affected \narea. Our patient denied the use of aromatic oils, \nperfumes or herbal medication and new cosmetics.\n\n\n\nClinical examination revealed reticulated dark \nbrown linear patches along the right mandible \nmeasuring 2 cm at the widest diameter and 10.5 cm \nin length (Figure 1 and Figure 2). There was visible \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3777\n\n\n\nFigure 1. Reticulated dark brown linear patches \nalong the right mandible measuring 2 cm at the \nwidest diameter and 10.5 cm in length.\n\n\n\nFigure 3. Atrophic epidermis with a band-like \nlymphocytic infiltrates at the dermo-epidermal \njunction and basal cell vacoulation.\n\n\n\nFigure 2. Linearly distributed brownish macules \nand patches extending along the right mandible.\n\n\n\nFigure 4. Heavy pigmentary incontinence and \npresence of melanophages with perivascular \nlymphocytic infiltrates.\n\n\n\nCase Report\n\n\n\nHong S et al 20044\n\n\n\nAkagi et al 20045\n\n\n\nSeo JK et al 20106\n\n\n\nVachiramon V et al 20102\n\n\n\nKim JE et al 20127\n\n\n\nZhang et al 20128\n\n\n\nI Hassan et al 20129\n\n\n\nMonteaqudo B et al 201410\n\n\n\nNo. of Cases\n\n\n\n2\n\n\n\n3\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\nAge of Onset\n\n\n\n23 years\n\n\n\n16 years\n\n\n\n32 years\n\n\n\n22 years\n\n\n\n30 years\n\n\n\n60 years\n\n\n\n33 years\n\n\n\n61 years\n\n\n\n25 years\n\n\n\n30 years\n\n\n\n39 years\n\n\n\nGender\n\n\n\nfemale\n\n\n\nfemale\n\n\n\nfemale\n\n\n\nfemale\n\n\n\nfemale\n\n\n\nmale\n\n\n\nmale\n\n\n\nmale\n\n\n\nfemale\n\n\n\nmale\n\n\n\nfemale\n\n\n\nEthnicity\n\n\n\nKorean\n\n\n\nKorean\n\n\n\nJapanese\n\n\n\nJapanese\n\n\n\nJapanese\n\n\n\nKorean\n\n\n\nThai\n\n\n\nKorean\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nSpanish\n\n\n\nSite Involved\n\n\n\nLeft leg\n\n\n\nLeft arm\n\n\n\nRight gluteal region to right leg\n\n\n\nRight shoulder to right upper arm\n\n\n\nRight shoulder to right arm and forearm\n\n\n\nAnterior neck and chin\n\n\n\nBilateral arms and forearms\n\n\n\nForehead\n\n\n\nRight mandibular region\n\n\n\nLeft forehead and face\n\n\n\nRight axilla, Inframammary sulcus\n\n\n\nTable 1. Clinical characteristics of linear LPP seen in case reports.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 78\n\n\n\nhyperpigmented lesions without a preceding history \nof erythema does not support the diagnosis of \nlichen striatus. The histology of lichen striatus \ndemonstrates lichenoid interface changes, but lacks \nthe pigmentary incontinence. In zosteriform LP the \nlesions are flat topped, polygonal, purplish papules \narranged in a dermatomal pattern with pruritus, \nunlike LPP where the lesions are completely \nasymptomatic. Histologically also zosteriform \nLP would show characteristic LP histology which \nwere not seen in our case. The histology findings \nin post inflammatory hyperpigmentation on the \nother hand, lack features of interface dermatitis \nand mainly show pigmentary incontinence. EDP \nclinically presents as ash coloured asymptomatic \nmacules with a raised erythematous border initially. \nOver time, the border disappears leaving behind a \ngrayish lesion. Histopathologically EDP has mild \nbasal vacuolar degeneration with perivascular \nmononuclear infiltrates, pigment incontinence. The \nmelanin is deposited in the deeper dermis in EDP \nunlike LPP where it is in the superficial dermis \ninstead11. Together with the clinical features and \nhistopathology results we were able to clinch the \ndiagnosis of LPP.\n\n\n\nTopical steroids, topical calcineurin inhibitors and \nND YAG laser have been used as treatment options \nbut with little improvement seen. We report this \nunusual presentation of LPP as it is not commonly \nencountered.\n\n\n\nLinear LPP predominantly involves the head and \nneck region and the extremities. Linear LPP occurs \nby itself and its association with underlying illness \nhas not been established. In our review we identified \n11 case reports of linear LPP patients of more than \n16 years of age. There were 7 cases of women and \n4 cases of men with majority of the patients in early \nadulthood. One patient with underlying hepatitis C \ninfection presented with bilateral lesions and another \nhad facial nerve palsy but there was no established \nlink between these conditions and LPP3,6. Most of \nthe cases reported so far are in the Asian population \nwith a single case found in the Spanish population. \nTable 1 summarizes all cases of linear LPP reported \nin the literature.\n\n\n\nThe upper limbs was the major site of presentation \nat 44.5%, followed by the head and neck region \n(36.4%) and  the lower limbs (18.1%).Histopathology \nexamination of all 11 cases demonstrated basal \ncell vacuolar degeneration, lymphocyte infiltrates, \npigmentary incontinence and dermal melanophages. \nIn our patient, we had considered zosteriform/\nlinear lichen planus (LP), lichen striatus and post \ninflammatory hyperpigmentation as differential \ndiagnoses. Erythema dyschromicum perstans \n(EDP) is another important differential diagnosis \nto be considered .Due to the rarity of this disease, \na careful history was essential to determine the \ninitial presentation. Of these diseases, the linearity \nof lichen striatus bears a similar morphological \nappearance to linear LPP. The onset of asymptomatic \n\n\n\nReferences\n \n1. Bhutani LK, Bedi TR, Pandhi RK, Nayak NC. Lichen \n\n\n\nplanus pigmentosus. Dermatologica 1974; 149: 43-50.\n2. Vachiramon V, Suchonwanit P, Thadanipon K. Bilateral \n\n\n\nlinear lichen planus pigmentosus associated with hepatitis \nC virus infection. Case Rep Dermatol 2010; 2 :169-172 \n\n\n\n3. Kanwar AJ, Dogra S, Handa S, Parsad D, Radotra \nBD. A study of 124 Indian patients with lichen planus \npigmentosus. Clini Exp Dermatol 2003; 28: 481-485. \n\n\n\n4. Hong S, Shin JH, Kang HY. Two cases of lichen planus \npigmentosus presenting with a linear pattern. J Korean \nMed Sci 2004; 19: 152-154.\n\n\n\n5. Akagi A, Ohnishi Y, Tajima S, Ishibashi A. Linear \nhyperpigmentation with extensive epidermal apoptosis: a \nvariant of linear lichen planus pigmentosus? J  Am Acad \nDermatol 2004; 50: 78-80.\n\n\n\n6. Seo JK, Lee HJ, Lee D, Choi JH, Sung HS. A case of linear \nlichen planus pigmentosus.Ann Dermatol 2010; 22: 323-\n325.\n\n\n\n7. Kim JE, Won CH, Chang S, Lee MW, Choi JH, Moon KC. \nLinear lichen planus pigmentosus of the forehead treated \nby neodymium: yttrium\u2013aluminum\u2013garnet laser and \ntopical tacrolimus. J Dermatol 2012; 39: 189-191.\n\n\n\n8. Zhang R, Zhu W. One case of unilateral linear lichen \nplanus pigmentosus. Open Dermatol J 2012; 6: 25-28.\n\n\n\n9. Hassan I, Rather PA, Sajad P. Linear lichen planus \npigmentosus and coincidental ipsilateral facial nerve \npalsy: An unusual observation.Our Dermatol Online 2012; \n3: 361-362.\n\n\n\n10. Monteagudo B, Suarez-Amor O, Cabanillas M, de \nLas Heras C, Alvarez JC. Superimposed lichen planus \npigmentosus. Dermatology Online J 2014; 20: 22639\n\n\n\n11. Ghosh A, Coondoo A. Lichen planus pigmentosus: The \ncontroversial consensus. Indian journal of dermatology. \n2016 Sep;61(5):482.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3779\n\n\n\nCommentary\n\n\n\nTHE PALLOR OF BIBLICAL LEPROSY\nLiau MMQ, Yang SSY\n\n\n\nCorresponding Author and Reprint Request \nLiau MeiQi May\n6 Countryside Road, Singapore 789772\nEmail: maylmq@gmail.com\n\n\n\nNational University Health System,\nSingapore Department of Dermatology,\n1E Kent Ridge Road, Tower Block, Level 10,\nSingapore 119228\n\n\n\nto diagnose someone as a leper was made by a priest. \nHe, or she, was then physically segregated from \nthe community - this was more to prevent moral \ncontamination, rather than physical contamination4. \n\n\n\nLeprosy - Biblical vs Modern \ninterpretation \nIt is interesting that the priests were given the \npower to diagnose these conditions, as this very \nsame \u201cpower\u201d is what we, as dermatologists and \nphysicians, strive so hard to obtain and be good at. \nIn the modern day clinician\u2019s assessment of this \nentity, five categories of leprosy using clinical, \nhistopathological and immunological criteria \ncan be identified. These include, from the least \nto the most severe (i.e. greatest to least immune \nresponse): tuberculoid polar leprosy, borderline \ntuberculoid, midborderline, borderline lepromatous \nand lepromatous polar leprosy. Essentially, this \nmethod of classification correlates with the immune \nresponse to M.leprae infection. \n\n\n\nWe now know that patients with borderline forms \nof the disease can experience either upgrading (i.e. \nimprovement) or downgrading (i.e. worsening) of \ntheir conditions. Upgrading is often experienced \nduring treatment, and downgrading can occur during \nduring systemic illness, chemotherapy, pregnancy \nand emotional stress. In biblical times, if the leprosy \nsufferer had an \u201cupgrading\u201d of the clinical picture \nwith clinical resolution, he or she could return to \nsociety. Otherwise, the quarantine would continue \nindefinitely. \n\n\n\nMedical knowledge during that era was limited and \nthere is a growing consensus2,5 that the term leprosy \nused in the Bible referred to a diverse group of skin \ndiseases that bears no resemblance to Hansen\u2019s \ndisease as we know it today. These include psoriais, \nfungal infections, seborrheic dermatitis, atopic \ndermatitis, pityriasis rosea, syphilis, scabies, lupus \nerythematosus and sarcoidosis. \n\n\n\nLeprosy, also known as Hansen\u2019s disease, is a \ndisease that has been known to man since time \nimmemorial. It is amongst the world\u2019s oldest and \nmost dreaded diseases and also one of the most \nimportant dermatologic diseases from the sociologic \nviewpoint. This disease probably originated in \nEgypt and other Middle Eastern countries as early \nas 2400 BC.  It played a unique role in the history \nof mankind due to many centuries of rejection and \nsegregation of individuals and whole communities \nafflicted with this condition. \n\n\n\nFamous as a cause of the leonine facies, it is \nclinically characterised by one or more of the three \ncardinal features: hypopigmented or erythematous \nplaques with loss of sensation, thickened peripheral \nnerves and acid-fast bacilli detected on skin smears \nor biopsy.  Lack of knowledge about the disease \nand its treatment facilitated its spread throughout \nthe world. Those who were unfortunate enough to \ncontract it were isolated, stigmatised and excluded \nfrom society.  Mycobacterium leprae, the causative \nagent of leprosy was finally discovered by G.H. \nArmauer Hansen in 1873, making it the first \nbacterium to be identified as causing disease in \nhumans1.\n\n\n\nBook of Leveticus\nChapters 13-14 of the Book of Leviticus, the third \nbook of the Old Testament of the Christian Bible, \ndescribes skin afflictions2,3. The Hebrew term \ntzaraat, originally used in chapter 13 of Leveticus, \nis the root word. It referred to a collective group \nof skin diseases, including biblical leprosy, which \nreferred to a person who was unclean. The decision \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 80\n\n\n\nSoutheast Asia\nSince the introduction of multi-drug therapy (MDT) \nin the early 1980s, the global burden has significantly \nreduced and many countries have achieved World \nHealth Organisation\u2019s (WHO) goal of reducing \nprevalence to less than 1:10\u2019000 of the population. \nDespite so, South-east Asia (SEA) remains a hotbed \nfor leprosy. In 2012, the SEA region accounted for \n71% of new cases detected worldwide with 166 445 \ncases reported6. Of these, more than 7% presented \nwith visible deformities. The highest prevalence was \nnoted in Indonesia, India, Bangladesh, Myanmar6. \n\n\n\nConclusion\nToday, this disease still affects large populations \naround the world. This epidemiological picture \nhighlights continued transmission of infection and \ndelayed detection of the disease. The main challenges \nin the control of leprosy is the delay in detection \nof new cases and stigma surrounding this ancient \ndisease. The WHO Global Leprosy Srategy 2016-\n2020 was launched as a result, calling for stronger \ncommitments and accelerated efforts to eradicate the \ndisease7. The main goals of this global strategy is to, \nby 2020, reduce the number of children diagnosed \nwith leprosy and related physical deformities to \nzero; reduce the rate of newly-diagnosed leprosy \npatients with visible deformities to less than one per \nmillion; and ensure that all legislation that allows for \ndiscrimination on the basis of leprosy is overturned. \nLeprosy is very much still a public health concern, \nas it was thousands of years ago.\n\n\n\nWhite leprosy\n\u201cWhite leprosy\u201d as described in the bible was \ncharacterised by bright white hypopigmented \npatches of the skin associated with white hair. \nThere was a possibility this was mistaken for other \nconditions with a combination of hypopigmented \nlesions and loss of melanin in the hair (i.e. \npoliosis). This includes vitiligo which can manifest \nwith leukotrichia. Piebaldism, a rare autosomal \ndominant disorder of melanocyte development, is \ncharacterised by symmetrical hypopigmented white \nforelock and hypopigmented patch of the central \nportion of the forehead. It is one of the defining \nfeatures of Waardenburg syndrome (together with \nheterochromia iridis) and Ziprkowski-Margolis \nsyndrome. It is also observed in tuberous sclerosis, \nYaws and Vogt Koyanagi Harada Disease.  \n\n\n\nIndeed, the \u201cpallor\u201d of white leprosy was likened \nto the skin tone of the dead, a terrifying thought \nespecially to those with darker skin at the time. It \nis through this similarity to the dead that the horror \nderived from benign forms of leprosy traces its \nreligious roots. The Bible discloses a close and \nimportant relationship in the biblical times was that \nbetween sin and sickness, the ultimate consequence \nof sin being death. In 1 Corinthian 11:27-32: \n\u201cWhoever, therefore, eats the bread or drinks the \ncup of the Lord in an unworthy manner will be \nguilty concerning the body and blood of the Lord. \nLet a person examine himself, then, and so eat of the \nbread and drink of the cup. For anyone who eats and \ndrinks without discerning the body eats and drinks \njudgment on himself. That is why many of you are \nweak and ill, and some have died.\u201d Physical Illness, \nmany of which has manifestations in the skin, is \ndescribed as the sequel to sin and the prologue to \ndeath. \n\n\n\nReferences\n \n1. G. H. A. Hansen, \u201cInvestigations concerning the etiology \n\n\n\nof leprosy,\u201d Norsk Magazin for L\u00e6gevidenskaben, vol. 4, \npp. 1\u201388, 1874 (Norwegian).\n\n\n\n2. Freilich AR. Tzaraat-biblical leprosy. J Am Acad Dermatol. \n1982;6:131-134.\n\n\n\n3. Lloyd Davies M, Lloyd Davies TA. Biblical leprosy: A \ncomedy of errors. J R Soc Med. 1989;82:622-623.\n\n\n\n4. Mathew SK, Pandian JD. Newer insights to the neurological \ndisease among biblical characters of old testament. Ann \nIndian Acad Neurol. 2010;13:164-166.\n\n\n\n5. Goldman L, Moraites R, Kitzmiller K. White spots in \nbiblical times. Arch Dermatol. 1966;93:744-753.\n\n\n\n6. \u201cLeprosy Situation in South-East Asia Region 2012\u201d. \nWorld Health Organisation, South-East Asia Regional \nOffice. Retrieved from http://www.searo.who.int/entity/\nleprosy/data/NCDR2012/en/. Accessed 28/7/16.\n\n\n\n7. Golden leprosy strategy 2016-2020: Accelerating towards \na leprosy-free world. World Health Organisation. Retrieved \nfrom \u201chttp://www.searo.who.int/entity/global_leprosy_\nprogramme/documents/global_leprosy_strategy_2020/\nen/\u201d. Accessed 28/7/16.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 3781\n\n\n\nQuiz\n\n\n\nASYMPTOMATIC SKIN COLORED PAPULES ON THE LIMBS\nOF AN ADULT FEMALE\nLong V1, Huang JX2\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nDepartment of Medicine\nTan Tock Seng Hospital Singapore\n11 Jalan Tan Tock Seng, Singapore 308433\nEmail: valencialong@gmail.com\n\n\n\n1 Department of Medicine, Tan Tock Seng Hospital, \n Singapore 11 Jalan Tan Tock Seng, 308433 \n2 Department of Pathology, National University \n Hospital, Singapore, 5 Lower Kent Ridge Rd, 119074\n\n\n\nDiscussion\nLaboratory investigations showed raised thyroxine \nlevels 17.7 pmol/L, low thyroid stimulating \nhormone levels <0.02 mIU/L. A skin biopsy of the \nskin colored papules revealed dermal mucinosis \nwith vacuolar interface and superficial perivascular \ndermatitis suggestive of localized myxedema \n(Figure 2a).\n\n\n\nThere was also presence of superficial perivascular \ndermatitis with extravasated red blood cells and \nvacuolar interface change (Figure 2b) suggestive of \nconcomitant pigmented purpuric dermatosis (PPD).\n\n\n\nHistory\nA 60-year-old woman with a history of Graves\u2019 \ndisease and thyroid eye disease presents with a \n6-month history of asymptomatic skin colored \npapules on her shins, amongst few scattered \nerythematous macules (Figure 1).\n\n\n\nExamination\nOn examination, she had eight flesh colored \ndiscrete papules localized to the anterior shin, some \ncoalescing to form a plaque. There were also a few \nerythematous macules. The papules were non tender \nnor pruritic. She had evidence of mild active thyroid \neye disease with periorbital swelling, but otherwise \nwithout chemiosis, nor limitation in extraocular \nmovements. She did not have any finger clubbing. \nShe was clinically euthyroid.\n\n\n\nQuestion 1: What is the diagnosis? \nA. Cutaneous mucinosis \nB. Pretibial myxedema \nC. Scleromyxedema \nD. Fibrosing dermopathy \nE. Elephantiasis\n\n\n\nQuestion 2: What is the treatment of choice? \nA. Topical steroids \nB. Oral steroids\nC. Plasmapheresis \nD. Surgical excision\nE. Intravenous immunoglobulin\n\n\n\nFigure 1\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Dec Vol 37 82\n\n\n\nFigure 2a Figure 2b\n\n\n\nlimbs \u2013 this can be best explained by mechanical \nfactors as low level dermopathy is likely a systemic \nprocess and dermopathy can also occur in upper \nbody if traumatized. Treatment of the underlying \nhyperthyroidism does not necessarily eradicate \nthe skin lesions of pretibial myxedema, which \nmay occasionally become more pronounced after \nthe treatment of the thyrotoxicosis, particularly \nwith radioactive ablation therapy3. First line \ntreatment usually involves topical or intralesional \ncorticosteroids with compression bandages giving \nadditional benefit. Pentoxyfylline has also been \nshown to be effective4. This patient\u2019s dermopathy \nimproved with use of topical clobetasol ointment. \nThat this patient has concomitant PPD is interesting, \nalthough an association between pretibial myxedema \nand PPD is unknown.\n\n\n\nDiagnosis:\nPretibial myxedema with concomitant pigmented \npurpuric dermatosis.\n\n\n\nPretibial myxedema is a rare and late dermopathy \nof Graves\u2019 disease, usually developing after the \nonset of opthalmopathy and affecting women \nmore commonly than men (3.5:1). Both nodular \nand plaque forms are recognized, whilst polypoid \nand elephantiasic variants are rarer1. Important \ndifferentials to consider for pretibial myxedema are \nchronic edema with secondary skin changes may \nmimic non pitting pretibial myxedema. Mucinosis \nassociated with obesity2, or as a result of underlying \nchronic venous insufficiency, hypertrophic lichen \nplanus should also be considered in the appropriate \nsetting. Interestingly, pretibial myxedema tends to \naffect dependent areas and less commonly the upper \n\n\n\nReferences\n \n1. Dutta P, Shah VN. Pretibial myxedema mimicking \n\n\n\nelephantiasis. International Journal of Case Reports and \nImages 2013;4(12):695\u2013697.\n\n\n\n2. Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. \nDermopathy of Graves\u2019 disease (pretibial myxedema): \nlongterm outcome. J Clin Endocrinol Metab 2002; 87 : \n438-46\n\n\n\n3. Gopie P, Naraynsingh V. Severe pretibial myxedema. Int J \nLow Extrem Wounds. 2011 Jun;10(2):91-2\n\n\n\n4. Engin B, G\u00fcm\u00fc\u015fel M, Ozdemir M et al. Successful \ncombined pentoxifylline and intralesional triamcinolone \nacetonide treatment of severe pretibial myxedema. \nDermatol Online J. 2007 May 1;13(2):16.\n\n\n\nAnswers \nQuestion 1 : B. Pretibial myxedema \nQuestion 2 : A. Topical steroids \n\n\n\n\n\n"
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"\n\n95\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nEctodermal dysplasia in a pair of siblings\n\n\n\nSM Wong MBChB MRCP and LC Loh MBChB MRCP\n\n\n\nDermatology Unit, Department of Medicine\nUniversity Malaya Medical Center, Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nS M Wong MBChB MRCP\n\n\n\nDermatology Unit\nDepartment of Dermatology\nUniversity Malaya Medical Centre\nKuala Lumpur\nEmail: suming1@yahoo.com\n\n\n\nEctoderrmal dysplasias are a heterogenous group of disorders, in which\n\n\n\nmore than 150 different syndromes have been identified. It is defined\n\n\n\nby primary defects in the development of two or more tissues derived\n\n\n\nfrom embryonic ectoderm, characterized by abnormalities in the skin,\n\n\n\nsweat glands, hair, teeth and nails. Other parts, including the lens of the\n\n\n\neye, parts of the inner ear, or nerves, may also fail to develop normally.\n\n\n\nCase Report\nWe report a case of a pair of siblings, X and her younger\nbrother Y, aged 10 and 6 respectively. They were referred to\nthe dermatology clinic for dry skin and eczema.\n\n\n\nX was born in Hospital Kuala Lumpur and Y was born in\nthe University Hospital. Y was initially referred to the\ngeneticist because the doctors noticed he had skin problems\nand that his sister also had similar problems with\ncharacteristic physical features.\n\n\n\nOn further questioning, they both gave a history of lack of\nsweating. They also had multiple hospital admissions in the\npast for recurrent respiratory tract infections and asthma.\nDiagram 1 shows their family tree. Their parents were of\nconsanguineous marriage. They had two other older siblings\nwho were normal.\n\n\n\nOn physical examination, both revealed dry, eczematous\nskin. The hair was thin and sparse and the teeth were peg-\nshaped and reduced in number. The nails were normal and\nexamination of the cardiovascular, respiratory and\ngastrointestinal systems were normal. (see Picture 1 & 2)\n\n\n\nTogether with the clinical findings, equally affected male\nand female siblings and the presence of consanguinity\nsupported the diagnosis of hypohydrotic ectodermal\ndysplasia with an autosomal recessive mode of inheritance.\n\n\n\nDiscussion\nEctodermal dysplasias (ED) have long been recognized as\ndistinct entities and the description of affected individuals\nwere first described by Darwin. They have been defined by\nthe clinical characteristics and mode of inheritance.\n\n\n\nMany ED syndromes have been identified. The more\ncommon ones include hypohidrotic EC, hidrotic ED,\nankyloblepheron-ectodermal dysplasia-clefting (AEC)\nsyndrome, ectodermal dysplasia-ectrodactyly-clefting\n(EEC) syndrome, Rapp-Hodgkin and Tooth and Nail\n(Witkop) syndrome1. They each have their own mode of\ninheritance and clinical features.\n\n\n\nHypohidrotic ectodermal dysplasia (HED) is the most\ncommon ED. It is also known as anhidrotic ectodermal\ndysplasia and Christ-Siemens-Touraine Syndrome. The\nincidence is approximately 1:100,000 live births and it\noccurs in all races and ethnic groups.\n\n\n\nED are often inherited as an X-linked disorder (XLEDA),\nbut autosomal recessive and dominant forms are\nrecognized2. The appearance of affected males and females\nin autosomal recessive HED is clinically indistinguishable\nfrom that seen in males with X-linked HED. Children with\nED may be diagnosed at birth. But more often diagnosis is\ndelayed until the teeth fail to erupt at the expected age (6-9\nmonths) or the teeth that erupt are conical in shape.\n\n\n\nEctodermal dysplasias are caused by genetic defects in the\nectodysplasin signal transduction pathway. This pathway is\nutilized by epithelial cells in the development of tooth, hair\nfollicles and eccrine sweat glands. Therefore, genetic defects\nin this pathway result in aplasia, hypoplasia or dysplasia of\nthese structures.\n\n\n\n\n\n\n\n\n96\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.\n\n\n\nDiagram 1.    Family tree\n\n\n\nFigure 2.\n\n\n\n\n\n\n\n\n97\n\n\n\nThe genes involved, ED1 or EAD (which codes for the\nligand, ectodysplasin) is associated with X-linked\nhypohidrotic ectodermal dysplasia (HED). It is located at\nXq12-13 on the X chromosome3. 95% of individuals with\nHED have the X-linked form. The genes EDAR\n(ectodysplasin-A receptor) EDARADD (an intracellular\nadaptor protein), are associated with both autosomal\ndominant and recessive forms of HED. Mutation of these\ngenes account for 5% of HED. In addition, defects in a gene\nNEMO (NF-__ essential modulator) is associated with\nHED and immunodeficiency4.\n\n\n\nSkin biopsy is not usually necessary for the diagnosis of\nHED. However, if biopsy were to be done, histologic\nfindings would include a flattened and thinned epidermis, a\nreduction in hair follicles and sebaceous glands and eccrine\nglands which are incompletely developed or entirely absent.\n\n\n\nThe three cardinal features associated with ED include\nhypotrichosis (thin, sparse hair), hypohydrosis (absent or\nreduced sweating leading to inability to maintain core body\ntemperature and consequently hyperpyrexia) and\nhypodontia (absent or reduced number of teeth). The teeth\nthat are present are peg-shaped or conical. In addition, they\nmay have dry skin and eczema, periorbital\nhyperpigmentation, saddle nose, frontal bossing5, full\neverted lips and brittle nails. They are also likely to have\nrecurrent upper and lower respiratory tract infections due to\nthick nasal secretions. Hearing as well as ocular problems\nmay also occur.\n\n\n\nThe management of patients with ED include taking a\ndetailed medical history and family history. Careful\nexamination of the affected individual, affected siblings and\npotential carriers for clinical manifestations of HED should\nbe done. They should then be referred to a geneticist to aid\nin diagnosis and management.\n\n\n\nCurrently, no pharmacological treatment is available. The\nmanagement of the affected individuals targets the three\ncardinal features and is directed at optimizing psychosocial\ndevelopment, establishing optimal oral function and\npreventing hyperthermia.\n\n\n\nWigs or special hair care formulas and techniques to\nmanage dry, sparse hair may be useful. For hypohydrosis,\nensure an adequate supply of water, and if possible, stay in a\ncool environment. This may mean being in an air-\nconditioned room, wearing a wet T shirt or having a spray\nbottle of water. For hypodontia, dental restoration, for\nexample with dentures, should be offered, not only for good\noral function but also for psychological and social reasons.\nThey should be followed up by respiratory specialists and/or\nENT specialists for asthma, recurrent infections and nasal\nconcretions as well as getting appropriate dermatological\ncare for dry skin and eczema. If appropriate, they should be\nlinked with other individuals with ED and be referred to\nsupport groups where available.\n\n\n\nReferences\n\n\n\n1. Bolognia J, Jorizzo JL, Rapini RP. Dermatology 2003 ed. Elsevier; \np906-907.\n\n\n\n2. Munoz F, Lestringant G, Sybert V et al. Definitive evidence for an \nautosomal recessive form of hypohidrotic ectodermal dysplasia \nclinically indistinguishable from the more common X-linked \ndisorder. Am J Hum Genet 1997 Jul;61(1):94-100.\n\n\n\n3. Mortier K, Wackens G. Ectodermal dysplasia anhidrotic. \nOrphanet encyclopedia. September 2004.\n\n\n\n4. Wolff K, Katz LAG, Gilchrest BA. Fitzpatrick\u2019s Dermatology in \nGeneral Medicine. 2008, 7th ed; p1339-1342.\n\n\n\n5. Johnson ER, Roberts MW, Guckes AD et al.Analysis of \ncraniofacial development in children with hypohydrotic \nectodermal dysplasia. Am J Med Genet 2002;112:327-324.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n98\n\n\n\n\n\n\n\n\n99\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nAn unusual case of naevus of Ota and\nIto associated with port wine stain\n\n\n\nChong YT MD, MRCP, Tey KE MD, MMed, MRCP and Choon SE MBBS, FRCP\n\n\n\nDepartment of Dermatology\nHospital Sultanah Aminah\nJohor Bahru\n\n\n\nCorrespondence\n\n\n\nDr. Chong YT, MD, MRCP\n\n\n\nDepartment of Dermatology\nHospital Sultanah Aminah\n80100 Johor Bahru, Johor, Malaysia\nEmail: cytusm@yahoo.com\n\n\n\nNaevus of Ota is a dermal melanocytic pigmentary disorder that affects\npredominantly females. It occurs most frequently in Asian populations.\nIts association with naevus of Ito and a port wine stain is very rare. We\nreport a rare occurrence of these three conditions in a male patient.\n\n\n\nKeywords Naevus of Ota, Naevus of Ito, Port wine stain.\n\n\n\nIntroduction\nNaevus of Ota is a hamartoma of dermal melanocytes which\nappears clinically as a blue or grey discoloration on the\nface, occurring over the distribution of the ophthalmic\nand maxillary branches of the trigeminal nerve. Various\nbenign cutaneous and leptomeningeal conditions, such as,\nnaevus of Ito, phakomatosis pigmentovascularis, naevus\nflammeus, Sturge-Weber Syndrome, neurofibromatosis and\nleptomeningeal melanosis have been reported to occur in\nassociation with naevus of Ota.\n\n\n\nWe report a male patient with bilateral naevus of Ota and\nIto in association with a port wine stain.\n\n\n\nCase Report\nA 26-year-old Chinese man, with no previous medical\nproblem, presented to our hospital with a complaint of\nfrontal headache of two days duration. His blood pressure\nwas found to be high during a medical check-up in a private\nclinic. He did not have any neurological symptoms such as\ndizziness, blurring of vision, vertigo, tinnitus, limb weakness\nor numbness. Systemic review was unremarkable. Clinically,\nhis blood pressure was 180/110 mm Hg and his heart rate\nwas 80 beats per minute. He had an ill-defined confluent\nbluish pigmentation on the face bilaterally in the\ndistribution of the first and second branch of the trigeminal\nnerve. There was also a dark-red pigmented lesion noted\nover the left upper forehead, consistent clinically with port\nwine stain (fig 1). Dark brown discoloration was also noted\nover both sclera (fig 2). In addition, he has ill-defined bluish\nconfluent pigmented lesion over the back of the shoulder\n\n\n\n(fig 3). Cardio-respiratory, per abdomen and neurological\nexamination did not reveal any significant findings. His\nvisual acuity was good; however, detail eye examination was\nnot done. His blood result did not reveal any abnormalities.\nMagnetic Resonance Imaging (MRI) and Magnetic\nResonance Angiography (MRA) of the brain did not reveal\nany abnormalities either. He was diagnosed to have naevus\nof Ota and Ito with an associated port wine stain and no\nevidence of neurological involvement.\n\n\n\nDiscussion\nAn oculodermal melanosis was first described by Hulkey in\n18611, and similar lesion was also reported by Halbe in\n18692,3. In 1939, Ota further described several cases of\npigmented nevus of the skin and eye and named them\n\u201cnevus fuscoceruleus ophthalmomaxillaris of Ota\u201d4. Nevus\nof Ota is a dermal melanocytic harmatomas that present as\nbluish or gray hyperpigmentation occurring along the\nophthalmic (V1), mandibular (V2) and very rarely maxillary\n(V3) branches of the trigeminal nerve. The nevus of Ota\noccurs most frequently in Asian populations, with an\nestimated prevalence of 0.014-0.034%, as well as in Black\npersons and has a strong predilection to occur in females\n(male-to-female ratio of 1:4.8)5,6. In more than half of the\npatients, this condition is associated with \u201cocular\nmelanocytosis\u201d involving the conjuctiva, sclera, uveal tract\nand possibly the optic nerve20. Other extracutaneous\ninvolvement such as the oral and nasal mucosa, external\nauditory canal, tympanic membrane, meninges and the\nbrain have been reported7,8. The dermal hyperpigmentation\nis usually noticed at birth, however, it may also develop or\nbecome noticeable only later in life. Hidano et al reported\ntwo peaks of onset, one during infancy and the second peak\nin the second decade6. Most cases of nevus of Ota are\nunilateral, although pigmentation is present bilaterally in\n4-20%1,9,14. Tanino has further classified the nevus of Ota\ninto four clinical types based on the distribution and various\nregions of involvement (table 1)10.\n\n\n\n\n\n\n\n\n100\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.   Figure 3.   \n\n\n\nFigure 2.   \n\n\n\nTable 1.   Types of naevus of Ota1,10\n\n\n\nType 1\n\n\n\nType 2\n\n\n\nType 3\n\n\n\nType 4\n\n\n\nIA. Mild orbital type: Distribution over the upper and lower\neyelids, periocular and temple region.\n\n\n\nIB. Mild zygomatic type: Pigmentation is found in the\ninfrapalpebral fold, nasolabial fold and the zygomatic region.\n\n\n\nIC. Mild forehead type: Involvement of the forehead alone.\n\n\n\nID: Involvement of ala nasi alone.\n\n\n\nModerate type: Distribution over the upper and lower eyelids,\nperiocular, zygomatic, cheek and temple regions\n\n\n\nThe lesions involve the scalp, forehead, eyebrow and nose.\n\n\n\nBilateral types: Both sides are involved.\n\n\n\n\n\n\n\n\n101\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nNevus of Ito, initially described by Minor Ito in 1954, is a\ndermal melanocytic condition with similar feature as naevus\nof Ota, but it occurs over the shoulder, side of neck and\nsupraclavicular areas in the distribution of the posterior\nsupraclavicular and lateral cutaneous branchial nerves. The\noccurrence of both naevi of Ota and Ito in a patient is very\nrare11. There has been rare report of association of bilateral\nnevus of Ota with nevus of Ito12.\n\n\n\nOther cutaneous disorders and leptomeningeal conditions\nreported to occur in patient with nevus of Ota\ninclude phakomatosis pigmentovascularis, nevus flammeus,\nneurofibromatosis, leptomeningeal melanosis and Sturge-\nWeber syndrome13.\n\n\n\nPort wine stain is a capillary vascular malformation with an\nincidence of 0.3 percent15. Clinically, port wine stain appears\nas a pinkish red to deep purple homogenous congenital\nlesion with a geographic contour or a dermatomal\ndistribution. Fifty percent of the capillary malformations\nare located in the face in the distribution of the trigeminal\nnerve16. Facial port wine stain is mainly unilateral and\npreferentially distributed over the maxillary branch of the\ntrigeminal nerve17. Port wine stains of the eyelids, bilateral\ndistribution of the birthmark, and unilateral lesions\ninvolving all three branches of the trigeminal nerve are\nassociated with significant higher likelihood of having eye\nand/or central nervous system complications18. In\ncombination with another vascular malformation, port wine\nstain can be part of a syndrome, such as Sturge-Weber,\nphakomatosis pigmento-vascularis, Klippel-Trenaunay or\nServelle-Martorell16.\n\n\n\nNaevus of Ota, naevus of Ito and port wine stain can\ncause considerable cosmetic disfigurement to patients,\noccasionally resulting in emotional and psychological\ndistress. There is a concern of elevated intraocular pressure\nand glaucoma in about 10% of patients with naevus of\nOta4,21. Other risks include malignant melanoma19,23 and\nmeningeal melanocytoma22.\n\n\n\nThe current treatment of choice for naevi of Ota and Ito is\npulsed Q-switched laser surgery. It works by selective\nphotodermal and photomechanical destruction of the\ndermal melanocytes and melanophages. Good success rate\nand minimal side effects have been reported with the Q-\nswitched ruby, Q-switched alexandrite and Q-switched\nNd:YAG lasers24,25,26.\n\n\n\nIn summary, naevus of Ota occurs mainly in females, usually\nunilaterally distributed and is rarely associated with naevus\nof Ito or port wine stain. Our male patient who has all three\nfeatures is extremely rare. Although port wine stain can be\nassociated with other vascular malformation such as Sturge-\nWeber syndrome, we did not find any abnormality in his\n\n\n\ncentral nervous system. However, he needs further eye\nevaluation to assess the extend of the ocular melanocytosis\nas well as periodic follow up to detect the possible\nassociation of increased intraocular pressure or glaucoma\nwhich can be as high as 10%.\n\n\n\nReferences\n\n\n\n1. Sekar S, Kuruvila M, Pai HS. Nevus of Ota: A series of 15 cases. \nIndian J Dermatol Venereol Leprol. 2008; 74:125-8.\n\n\n\n2. Hulke JW. Series of cases of carcinoma of the eye-ball (case 2), \nOphthalmol Hosp Rep. 1861; 3:279-86.\n\n\n\n3. Lee H, Choi SS, Kim SS, Hong YJ. A case of glaucoma associated \nwith Sturge-Weber Syndrome and Nevus of Ota. Korean J \nOphthalmol. 2001; 15:48-53.\n\n\n\n4. Ota M. Nevus fuscoceruleus ophthalmomaxillaris. Tokyo Med J. \n1939; 63:1243-1245.\n\n\n\n5. Chan HH, Kono T. Nevus of Ota: clinical aspects and \nmanagement. Skinmed. 2003; 2 (2):89-96.\n\n\n\n6. Hidano A, Kajima H, Ikeda S, Mizutani, Miyasato H, Niimura M. \nNatural history of nevus of Ota. Arch Dermatol 1967; 95:187-195.\n\n\n\n7. Bisceglia M, Carosi I, Fania M, Di Ciomo A, Lomuto M. Nevus of \nOta. Presentation of a case associated with a cellular blue nevus \nwith suspected malignant degeneration and revuew of literature. \nPathologica 1997; 89(2):168-74.\n\n\n\n8. Wilcox JC. Melanomatosis of skin and central nervous system. \nAJDC 1939; 57:391.\n\n\n\n9. Teekhasaenee C, Ritch R, Rutnin U, Leelawongs N. Ocular \nfindings in oculodermal melanocytosis.  Arch Ophthalmol 1990; \n108:1114-20.\n\n\n\n10. Tanino H. Nevus fuscoceruleus opthalmomaxillaris Ota. Jpn J \nDermatol 1939; 46:435-451.\n\n\n\n11. Mukhopadhyay AK. Nevus of Ota associated with nevus of Ito. \nIndian J Dermatol Venereol Leprol 2004; 70:112-113.\n\n\n\n12. Hidano A, Kajima H, Ikeda Y, Endo Y. Bilateral nevus of Ota \nassociated with nevus of Ito. Arch Dermatol 1965; 91:357-9.\n\n\n\n13. Recupero SM, Abdolrahimzadeh S, De Dominis M, Mollo R. \nSturge-Weber syndrome associated with naevus of Ota. Eye \n1998; 12(Pt 2):212-3.\n\n\n\n14. Kaufmann R, Vranes M. Bilateral nevus of Ota, a case report. Z \nHautkr 1986 Aug 15; 61(16):1152-8.\n\n\n\n15. Jacobs AH, Walton RG: The incidence of birthmarks in the \nneonate. Pediatrics 58:218, 1976.\n\n\n\n16. Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ. \nFitzpatrick\u2019s Dermatology in General Medicine. McGraw-Hill,\n7th ed., 2008;vol 2: page 1652-1666.\n\n\n\n17. Bioxeda P, de Misa RF, Arrazola JM, Perez B, Harto A, Ledo A. \nFacial angioma and the Sturge-Weber syndrome: a study of 121 \ncases. Med Clin (Barc) 1993;101(1)1-4.\n\n\n\n18. Tallman B, Tan OT, Morelli JG, Piepenbrink J, Stafford TJ, Trainor \nS, Weston WL. Location of port wine stains and the likelihood of \nophthalmic and/or central nervous syytem complications. \nPediatrics 1991;87(3):323-7.\n\n\n\n19. Bisceglia M, Carosi I, Fania M, Di Ciommo A, Lomuto M. Naevus \nof Ota. Presentation of a case associated with cellular blue \nnaevus with suspected malignant degeneration and review of \nthe literature. Pathologica 1997;89(2):168-74).\n\n\n\n20. Kono T, Kurome H, Shibuya Y, Hayasaka S. Ocular findings in \nJapanese women with naevus of Ota. Graefes Arch Clin Exp \nOphthalmo 1995 Nov;233(11):667-71.\n\n\n\n21. Liu JC, Ball SF. Naevus of Ota with glaucoma: report of three \ncases. Ann Ophthalmol 1991 Aug;23(8):286-9.\n\n\n\n22. Rahimi-Movaghar V, Karimi M. Meningeal melanocytoma of the \nbrain and oculodermal melanocytosis (naevus of Ota): case \nreport and literature review. Surg Neurol 2003 Mar;59(3):200-10.\n\n\n\n\n\n\n\n\n102\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n23. Patel BC, Egan CA, Lucius RW, et al. Cutaneous malignant \nmelanoma and oculodermal melanocytosis (naevus of Ota): \nreport of a case and review of literature. J Am Acad Dermatol \n1998 May;38(5 Pt 2):862-5.\n\n\n\n24. Watanabe S, Takahashi H. Treatment of naevus of Ota with the \nQ-switched ruby laser. N Eng J Med 1994 Dec;331 (26):1745-50.\n\n\n\n25. Wang HW, Liu YH, Zhang GK, Jin HZ, Zuo YG, Jiang GT, Wang JB. \nAnalysis of 602 Chinese cases of naevus of Ota and the \ntreatment results treated by Q-switched alexandrite laser. \nDermatol Surg 2007 Apr;33(4):455-60.\n\n\n\n26. Chan HH, Leung RS, Ying SY, et al. A retrospective analysis of \ncomplications in the treatment of naevus of Ota with the Q-\nswitched alexandrite and Q-switched Nd:YAG lasers. Dermatol \nSurg 2000 Nov;26(11):1000-6.\n\n\n\n\n\n\n\n\n103\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nLepromatous leprosy - The deceptive and the obvious\n\n\n\nKader B Mohamed MBBS Dip Derm\n\n\n\nDepartment of Dermatology\nHospital Pulau Pinang   \n10990 Penang\n\n\n\nCorrespondence\n\n\n\nDr Kader B Mohamed\nDepartment of Dermatology \nHospital Pakar Sultanah Fatimah \n84000 Muar, Johor\n\n\n\nLeprosy is a chronic granulomatous disease with which mankind has\nbeen struggling for thousands of years. It is a disease of the superficial\nnerves where the Mycobacterium leprae, the causative microbe, enters\nthe Schwann cells and triggers a chain of immunological reactions.\nAlthough M. leprae  was discovered by Armauer Hansen from Norway\nin 1872, we have yet to find a (in vitro) culture medium for its growth;\nwe depend on animals such as mice, and armadillos for testing\nsensitivity pattern against antibiotics. If not detected early or reactions\nin leprosy are not identified promptly and managed adequately, patients\ncan  suffer severe deformities, disfigurement and be subjected to social\nstigma.\n\n\n\nAwareness and suspicion are two elements necessary for early detection\nof leprosy. One patient who eluded the diagnosis of leprosy because of\nits resemblance to an important systemic disease and another  with\nprominent clinical features walked around freely undetected in a busy\nmetropolis are reported here to draw attention to this important\nchronic infectious disease.\n\n\n\nCase Report\nCase 1\nA 45-year-old Chinese lady who was referred to us\npresented with an erythematous patch on the face for the\npast 1 year. The rash was bilateral, over the cheek,\ninfraorbital and along the mandibular regious but not\ninvolving the nose (Figure 1). It was not itchy or warm.\nThere were no pustules and the earlobes were seemingly\nnormal. There were no systemic symptoms such as fever,\nfatigue, or myalgia. Since the rash was of \u2018butter-fly type\u2019;\nshe was extensively investigated for systemic lupus\nerythematosus (SLE) elsewhere with negative results. On\nexamination, there was mild sensory impairment. The rash\nwas mildly indurated. Slit skin smear for AFB was positive;\nB.I. 1.5+, M.I. 2.5% and skin biopsy confirmed lepromatous\nleprosy (LL). She also had thyroid enlargement  and\nsymptoms of thyrotoxicosis. Her thyroxine  level  was\nelevated. After checking for possible interaction between\nanti-thyroid and anti-leprosy drugs she was put on\nmultidrug therapy (MDT) for multibacillary (MB) leprosy,\n\n\n\ncarbimazole and metoprolol. She was on combined follow-\nup with the medical unit for about 5 years when the smear\nbecame negative, thyroid function test were fairly restored\nand symptoms of target organs well under control. This\npatient was an example of non-noduler, diffuse infiltrated\nlepromatous leprosy.\n\n\n\nCase 2\nA 50-year-old Chinese woman presented with indurated,\nnodular plaque-like lesions on the face of 2 years duration\n(Figure 2). The lesions were distributed over the chest, and\nlower limbs. The appearance was very suspicious of leprosy\nbut sensation was intact. Slit skin smear for AFB was\nstrongly positive. B.I. 2.5+, M.I. 3.5%. Fite-Faraco stain of\nthe skin biopsy specimen showed the bacilli in globi. She\nwas treated with MDT for MB leprosy.\n\n\n\nDiscussion\nA common misconception among the non-dermatologists\nis that in leprosy, there should be impaired or loss of\nsensation at the time of presentation. It must be emphasized\nhere that in tuberculoid leprosy sensory involvement is\nearly; in lepromatous type it is late and therefore in LL, in\nthe early stage, cotton-wool and pin-prick tests may be\nnormal. This author has reported few diseases which\nresemble leprosy such as granuloma multiforme,\nepidermolysis bullosa (dystrophic type), and mycosis\nfungoides (nodular type)1. In pre-senile hyperplasia of the\nsebaceous glands, the facial skin can be thrown into folds,\near-lobes red and thickened and fore-head in wrinkles\nresembling leonine facies2. Seldom do we see patients with\nleprosy who do not seek advice early, go into reactional state\n(upgrading) without treatment, with swelling of the lips face\nand the skin diffusely erythematous Sometimes, patients\ncan present with a histoid type of leprosy (Figure 3). In\nlepromatous leprosy the lesions are more extensive, nodular\nand erythematous, since the immunity is low. But single\nlesion of lepromatous leprosy has been documented3.\n\n\n\n\n\n\n\n\n104\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAlthough the prevalence of leprosy has reduced, the dream\nof eliminating the disease is far ahead. One of the the\ngreatest achievement of medicine is the eradication of\nsmall-pox. Can that goal be reached?\n\n\n\nFirst of all we should expose medical students to this\nsubject4. While patients resembling leprosy receive anti-\nleprosy treatment, patients with leprosy are not detected\nearly and do not get the treatment. This paradoxical\nsituation should change. In prevalent countries any patient\nwith thickening of the ear lobes should evoke suspicion of\nleprosy; the other conditions which should be borne in\nmind are lymphoma and cutaneous leishmaniasis.\n\n\n\nReferences\n\n\n\n1. Mohamed KB. Dermatological disorders resembling leprosy. Sing  \nMed J. 1989; 30:265 - 268\n\n\n\n2. Mohamed KB. Facial Lesions resembling leprosy. Int J Lep 2001; \n71:35-37\n\n\n\n3. Mohamed KB. A dough-nut shaped facial lesion in lepromatous \nleprosy. Br J Dermatol 1998;138:560-561\n\n\n\n4. Kawuma JH. Reflections of Global Forum on Leprosy Control. \nLepr Rev 2006;77:172-174\n\n\n\nFigure 1.   Facial erythema involving the right side. \nNote the ear-lobe\n\n\n\nFigure 3.   Histoid leprosy. This patient with chronic renal failure \npresented with nodular lesions on the face, trunck and \nlimbs. Smear for AFB was positive. Skin biopsy \nshowed spindle-shaped macrophages arranged whorl \npattern. This type of leprosy was described by Wade. \nNote the annular borderline lesion at the back of the \nleft arm\n\n\n\nFigure 2.   Nodular lesions of LL on the face. \nNote the thickened ear-lobe\n\n\n\n\n\n\n\n\n105\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nCutis laxa associated with xanthogranuloma\n\n\n\nKE Tey MD MRCP MMed AM and SE Choon MBBS FRCP AM \n\n\n\nDepartment Of Dermatology\nHospital Sultanah Aminah, Johor Bahru\n\n\n\nCorrespondence\n\n\n\nKE Tey MD MRCP MMed\n\n\n\nDepartment Of Dermatology\nHospital Sultanah Aminah\nJohor Bahru, 80100 Johor\nEmail: ketey08@yahoo.com\n\n\n\nCutis laxa (CL) is a rare inherited or acquired connective tissue\ndisorder in which the skin becomes inelastic and hangs loosely in folds.\nAutosomal dominant, autosomal recessive and X-linked recessive\nforms have been described. In both the inherited and acquired types,\nthe internal organs are frequently involved. We describe a 2-year-old\ngirl with congenital cutis laxa, presenting with multiple\nxanthogranulomata.\n\n\n\nCase Report\nA 2-year-old Malay girl was referred to us in August 2004\nwith multiple skin nodules of 2 months duration. She was\ndelivered full term in the breech position, and was a product\nof a non-consanguineous marriage. Her birth weight was\n2.6 kg , and she  was hairless at birth. She was noted to have\nwrinkled skin since the age of seven months. Her motor\ndevelopmental milestones were markedly delayed. She\ncould only sit with support at the age of 14 months, and she\ncould not even walk by the age of two years. She had failure\nto thrive, and experienced poor weight gain since birth. Her\nother family members, including a 3-year old sister were\nnormal, but her paternal great-grandfather had multiple\nsimilar skin lesions during his youth.\n\n\n\nTwo months prior to referral, she developed multiple\nnodules on her abdomen, back and right cheek.\n\n\n\nExamination revealed a thin and emaciated baby girl\nweighing only 5.6kg. She possessed sparse hair, with gross\nlaxity of facial skin and sagging cheeks. Bluish discoloration\nof both nasal ala was noted. (Fig1). As a result of excessive\nwrinkling, she appeared older than her chronological age.\nThere were crusted, moderate-sized discrete nodules on her\nright cheek, abdomen and back. Her skin was generally\nloose and inelastic, with excessive wrinkles. (Fig 2 ) Chest\nexamination revealed pectus carinatum. On auscultation,\ncrepitations and rhonchi were present, but no murmur was\nnoted. She had bilateral inguinal hernia. She was\nmaintained on continuous bladder drainage for urinary\nincontinence. Bilateral foot drop was noted.\n\n\n\nShe received an initial clinical diagnosis of Hutchinson\nGilford syndrome with squamous cell carcinoma, with\ndifferential diagnosis of Cutis laxa and Ehlers Danlos\nsyndrome. The differential diagnosis of skin nodules\nincludes keratoacanthoma, dermatofibroma protuberance ,\nsquamous cell carcinoma and basal cell carcinoma.\n\n\n\nHer blood count revealed mild anaemia with haemoglobin\nof 9.6 g/dl and leucocytosis. Chest x-ray showed pneumonic\nchanges but no evidence of emphysema or bronchiectasis.\nMagnetic resonance brain imaging revealed generalized\ncerebral atrophy.\n\n\n\nOther investigations including liver function test, renal\nfunction and serum cortisol were normal. Serology tests for\nsyphilis, HIV, and Hepatitis B were non-reactive.\n\n\n\nSkin histology from the wrinkled skin showed reduction\nand fragmented elastic fibres consistent with a diagnosis of\ncutis laxa. The skin nodules were excised, and histology was\nreported as xanthogranuloma. The excision wound healed\nwith a normal scar (Fig 3). The parents were informed\nabout the diagnosis. The patient died at home after\ndischarge from hospital in December 2004.\n\n\n\nDiscussion\nCutis laxa (CL) is an uncommon disorder of generalized\nelastolysis in which the skin becomes inelastic and hangs\nloosely in folds, resulting in the appearance of premature\naging. It may be inherited or acquired. Inherited forms of\nCL are more common. Autosomal dominant, autosomal\nrecessive and X-linked recessive forms have been described.\n\n\n\nThe autosomal recessive form is the most frequent and also\nthe most severe. It is often associated with severe internal\ncomplications, such as genitourinary and gastrointestinal\ndiverticula, diaphragmatic hernia, and emphysema leading\nto cor pulmonale and death in the first few years of life.\nRecently, a serine to proline amino acid substitution in the\nfibulin 5 (FBLN5) gene has been associated with problems\nin normal elastogenesis, resulting in a recessive form of CL\nin humans1.\n\n\n\n\n\n\n\n\n106\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOur patient presented as early as 7 months of age with\nexcessively wrinkled skin, delayed developmental\nmilestones, multiple xanthogranulomata, bilateral inguinal\nherniae and genitourinary system involvement. The severity\nof involvement and rapid progression of her disease\nresembled the autosomal recessive form of congenital CL.\nHer magnetic resonance brain scan revealed cerebral\natrophy, suggesting probable cerebral dysgenesis. Although\nthere was no consanguinity and no documented family\nhistory of similar disease, we postulated gene mutation as\nthe cause for CL in this patient. Unfortunately, genetic\nstudies of both parents and patient were unavailable.\n\n\n\nThe X-linked recessive variant of CL is rare, with skin laxity\nand skeletal and genitourinary tract abnormalities. X-linked\nCL is identical to Ehlers-Danlos syndrome type IX, and\nboth conditions are now known as the occipital horn\nsyndrome.\n\n\n\nThe autosomal dominant form of CL has a later onset than\nthe autosomal recessive form. This runs a benign course;\nskin involvement is present, with few, if any systemic\ncomplications, and a normal life expectancy.\n\n\n\nFigure 1.   Sparse hair, gross laxity of facial skin \nwith sagging cheek, bluish discoloration \nof ala nasi. Xanthogranuloma  R cheek\n\n\n\nFigure 2.   Generalized loose , inelastic skin with \nexcessive wrinkles\n\n\n\nFigure 3.   The excision  wound healed with \nnormal scar\n\n\n\n\n\n\n\n\n107\n\n\n\nOur patient presented with features compatible with\npremature aging syndrome that led to the clinical\ndifferential diagnosis of Hutchinson Gilford syndrome, CL\nand Ehlers Danlos syndrome. Hutchinson Gilford\nsyndrome presents with premature aging, sclerodermatous\nskin, hair loss and early development of multiple squamous\ncell carcinomata. The diagnosis of Hutchinson Gilford\nsyndrome became unlikely in our patient as skin histology\nfrom the nodules was reported as xanthogranulomata.\nPatients with Ehlers Danlos syndrome have generalized\nloose inelastic skin which is fragile, easily bruised, and heal\npoorly. The excision wound in our patient healed nicely,\nwhich favored the diagnosis of CL clinically. This was\nfinally confirmed with skin histology, which showed a\nreduction and fragmented elastic fibres.\n\n\n\nAcquired CL often begins in adulthood . Fifty percent of\nacquired CL cases are associated with a preceding\ninflammatory eruption, such as eczema, erythema\nmultiforme, urticaria or vesicular eruption, as well as\nreactions to penicillin or other drugs. The patient may have\nfever, malaise, and leukocytosis. The cutaneous laxity that\nfollows is confined to areas of previous inflammation.\n\n\n\nPatients with Wilson\u2019s Disease are at particular risk because\nof the elastolytic effects caused by long-term use of high\ndoses of the copper chelation agent penicillamine2.\n\n\n\nAcquired CL can also occur in association with systemic\nlupus erythematosus, complement deficiency (C3 and C4),\nsarcoidosis3, multiple myeloma4,5,6, and systemic\namyloidosis7. More recently, a case of CL has been\nassociated with immunoglobulin G (IgG)-4 heavy-chain\ndeposition disease of the kidneys8. Visceral involvement\nwhich includes the lungs, the gastrointestinal tract, the\nheart and the urogenital system, is common in acquired CL.\n\n\n\nRecent studies have shown that several factors, including\ncopper deficiency, lysyl oxidase, elastases and elastase\ninhibitors contribute to abnormal elastin degradation9.\nLysyl oxidase, a copper-dependent enzyme, is important in\nthe synthesis and cross-linking of elastin and collagen.\nTherefore, low levels of serum copper could lead to\ndiminished elastin synthesis. However, only a few patients\nwith CL have demonstrated low serum copper levels.\nDefective copper utilization may also lead to decreased\nactivity of elastase inhibitor alpha-1 antitrypsin, resulting in\ndestruction of elastic fibers.\n\n\n\nNo specific histological abnormality is seen on routine\nstains with hematoxylin and eosin. On elastic fiber stains, all\ntypes of CL show a reduction in the number of elastic fibers\nthroughout the dermis, with remaining fibers being\nshortened, clumped, granular, or fragmented. In severe\ncases, no elastic fibers may be present, but only fine, dust-\nlike particles scattered throughout the dermis can be seen.\nThere is no effective treatment currently to prevent disease\nprogression. Surgical correction of excessive skin folds,\nprolapses, or hernias produce only temporary benefit.\n\n\n\nBotulinum toxin injections are being considered for\nimproving the aged appearance and dysmorphisms seen in\npersons with CL10. CL increases the risk for aortic\naneurysms, so regular cardiology follow-up is recommended\nto avert a potentially fatal aortic rupture.\n\n\n\nReferences\n\n\n\n1. Loeys B, Van Maldergem L, Mortier G, Coucke P, Gerniers S, \nNaeyaert JM, et al. Homozygosity for a missense mutation in \nfibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol \nGenet. Sep 1 2002;11(18):2113-8.\n\n\n\n2. Hill VA, Seymour CA, Mortimer PS. Pencillamine-induced \nelastosis perforans serpiginosa and cutis laxa in Wilson's \ndisease. Br J Dermatol. Mar 2000;142(3):560-1.\n\n\n\n3. Lewis FM, Lewis-Jones S, Gipson M. Acquired cutis laxa with \ndermatitis herpetiformis and sarcoidosis. J Am Acad Dermatol. \nNov 1993;29(5 Pt 2):846-8.  \n\n\n\n4. Ting HC, Foo MH, Wang F. Acquired cutis laxa and multiple \nmyeloma. Br J Dermatol. Mar 1984;110(3):363-7.\n\n\n\n5. McCarty MJ, Davidson JM, Cardone JS, Anderson LL. Cutis laxa \nacquisita associated with multiple myeloma: a case report and \nreview of the literature. Cutis. Apr 1996;57(4):267-70.\n\n\n\n6. Gupta A, Helm TN. Acquired cutis laxa associated with multiple \nmyeloma. Cutis. Feb 2002;69(2):114-8.\n\n\n\n7. Newton JA, McKee PH, Black MM. Cutis laxa associated with \namyloidosis. Clin Exp Dermatol. Jan 1986;11(1):87-91.\n\n\n\n8. Tan S, Pon K, Bargman J, Ghazarian D. Generalized cutis laxa \nassociated with heavy chain deposition disease. J Cutan Med \nSurg. Sep-Oct 2003;7(5):390-4.\n\n\n\n9. Khakoo A, Thomas R, Trompeter R, Duffy P, Price R, Pope FM. \nCongenital cutis laxa and lysyl oxidase deficiency. Clin Genet. \nFeb 1997;51(2):109-14.\n\n\n\n10. Tamura BM, Louren\u00e7o LM, Platt A, Pertel P, Santos LF, Levites J. \nCutis laxa: Improvement of facial aesthetics by using botulinum \ntoxin. Dermatol Surg. Dec 2004;30(12 Pt 2):1518-20.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n108\n\n\n\n\n\n\n\n\n109\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nPyoderma gangrenosum associated with malignancy: \nA report of three cases\n\n\n\nHuma K, KE Tey MD MRCP MMed AM and SE Choon MBBS FRCP AM\n\n\n\nDepartment Of Dermatology \nHospital Sultanah Aminah, Johor Bahru\n\n\n\nCorrespondence\n\n\n\nDr Huma Khurrum\nDepartment Of Dermatology \nHospital Sultanah Aminah, Johor Bahru\nEmail : dr_hkaf4@yahoo.com\n\n\n\nPyoderma Gangrenosum (PG) is a rare, painful and often rapidly-\nprogressive ulcerative cutaneous condition1. Fifty percent of cases are\nassociated with underlying diseases2.\n\n\n\nThe associated underlying disease may occur prior to, concurrently\nwith or following PG. About 7% may have an associated underlying\nmalignancy5. Leukemia, usually acute myeloid leukemia and chronic\nmyeloid leukemia are the malignancies most commonly reported.\nThree cases of pyoderma gangrenosum associated with malignancies\nare described.\n\n\n\nCase Report\nCase 1\nA 58-year-old Malay man, a chronic smoker, with no\nsignificant past medical history presented in June 1993 with\na one month history of recurrent, multiple, non healing\npainful ulcers on both legs.\n\n\n\nHe did not have fever or other constitutional symptoms. He\nhad no significant bowel or urinary symptoms or any weight\nloss. There was no history of trauma or insect bite. His\nfamily and social history were non contributory.\n\n\n\nThe initial skin lesion was a boil on the right leg which\nbroke down rapidly and became ulcerated. Other similar\nlesions began to develop on his body subsequently. He was\nadmitted to the ward several times for recurrent painful\nulcers and has been treated with multiple broad spectrum\nantibiotics. On examination, there were multiple ulcerated\nplaques with red beefy base on the chest and arms (Fig 1).\nCribriform hypertrophic scarring of previous ulcers were\nseen on both upper limbs and face. There was no\nlymphadenopathy or organomegaly.\n\n\n\nBiopsy of ulcer showed non specific inflammation.\nThere was no evidence of vasculitis although some\nperivascular inflammation was present (Fig 2). Cultures for\nmycobacterium and subcutaneous fungal infections  were\n\n\n\nnegative. Investigations including a full blood count, liver\nfunction test, renal profile, antinuclear factor, rheumatoid\nfactor were normal. Serology tests for syphilis, HIV, and\nHepatitis B and C were non-reactive. Screening for\nunderlying malignancies including serial chest x rays, tumor\nmarkers, endoscopy, colonoscopy were unremarkable.\n\n\n\nHe was diagnosed to have pyoderma gangrenosum and\ntreated intermittently with dapsone and prednisolone for\neach episode of eruptions. The ulcers healed with multiple\ndisfiguring scars. In June 2004, he developed multiple ulcers\non the chest wall. On repeated chest X ray in early 2005, an\nopacity was noted in right mid zone which was treated\ninitially as pneumonia but the lesion did not resolve with\nantibiotics.\n\n\n\nSubsequent chest X ray, done after two months showed the\nmass becoming more pronounced. CT scan thorax revealed\na definite mass in right lateral segment of middle lobe,\nsuggestive of carcinoma of the lung.\n\n\n\nHistopathology of the lung tissue was reported as\nadenocarcinoma of lung. He was referred to the oncology\nteam for further management.\n\n\n\nCase 2\nA 58-year-old Chinese woman was referred to us by the\nHematology Department in March 2005, for multiple skin\nlesions on both wrists and left ankle of one week duration.\nShe was known to have myelodysplastic syndrome\ndiagnosed in Feb 2005 and was on chemotherapy.\n\n\n\nShe presented with a one-month history of painful,\nenlarging ulcer on both wrists and left ankle. The skin lesion\nstarted as a small blister which rapidly enlarged and became\nulcerated over two to three days. She was febrile, pale and\nemaciated. She had multiple cervical and axillary\nlymphadenopathy.\n\n\n\n\n\n\n\n\n110\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThree skin lesions were noted on the left ankle, and left and\nright wrists, measuring 7x6 cm, 5x4 cm and 5x5 cm\nrespectively (Fig 3). Skin lesions were characterized by\nruptured bullae and, ulcerated plaques with sloughing base.\nThe edges were violaceous with surrounding erythema.\n\n\n\nOn histopathology, intraepidermal bullae, filled with\nnuclear debris and neutrophils were noted. The dermis was\nheavily infiltrated with neutrophils, some mononuclear cells\nand red blood cells. It was consistent with pyoderma\ngangrenosum.\n\n\n\nShe was treated with IV methylprednisolone 500 mg. The\nskin lesions improved after 2 weeks of high dose steroids,\nfollowing which steroids were tapered.\n\n\n\nCase 3\nA 50-year-old Chinese man was diagnosed to have\ncarcinoma of the lung in August 2002. Eight months later,\nhe presented to us with pustular skin lesions on both wrists\nof one week duration. It evolved rapidly into ulcerated\nlesions. Examination revealed a thin, emaciated and pale\ngentleman with generalized lymphadenopathy. There was\ndecreased  breath sounds on the right side of the chest.\n\n\n\nThere were multiple ulcerated plaques with purplish edge\nand central haemorrhagic crusts, on the dorsal aspects of\nboth hands. Other systems were unremarkable. On tissue\nhistopathology, subcorneal bullae with underlying dermis\ncontaining areas of necrosis, debris and acute inflammatory\ncells were noted. The lower dermis showed presence of\nperiappendageal and perivascular chronic inflammatory\ncells. There was no evidence of malignancy.\n\n\n\nFigure 1.   Pyoderma gangrenosum. Showing beefy red ulcers with hypertrophic margins\n\n\n\nFigure 2.   Histopathology of skin biopsy specimen\n\n\n\n\n\n\n\n\n111\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nHe was diagnosed to have pyoderma gangrenosum. He was\ntreated and responded well to a tapering dose of\nprednisolone.\n\n\n\nDiscussion\nPG was first described in 1930 by Brunsting et al1.\nPyoderma Gangrenosum is a destructive necrotising, non\ninfective ulceration of the skin which presents as a furuncle-\nlike nodule, pustule or haemorrhagic bulla. Incidence is\nreported as 1 in 100,000 people/year in United States.\nPathergy, induced by trauma to the skin of susceptible\npersons, is reported in 25% of patients7. It manifests\nclinically as deep painful subcutaneous nodule, pustules,\nulcers or bullae.\n\n\n\nFour types of PG have been described and this includes\nulcerative, vegetative, pustular  and bullous type.\n\n\n\nThe cause is unknown. In half of the cases, it is reported as\nidiopathic2, while in 50% of cases, it is associated with\nulcerative colitis, Crohn's disease, rheumatoid arthritis,\nseronegative polyarthritis and monoclonal gammopathy. It\nis rarely associated with chronic active and persistent\nhepatitis, Behcet's disease and internal malignancies. It has\nbeen reported in patients with polycythemia vera,\npostoperative states, immunocompromised states and\nWegener's granulomatosis2.\n\n\n\nThe associated underlying disease may occur prior to,\nconcurrently with or following PG.\n\n\n\nThe first case was followed up for about twelve years. He\nhad multiple episodes of pyoderma gangrenosum before he\n\n\n\ndeveloped the carcinoma of lung. Our second patient\nalready had myeloproliferative disorder when she developed\nPG at the same time. Our third case was known case of lung\ncarcinoma, developed PG after eight months of his primary\nillness. Therefore, it is quite interesting to establish the link\nbetween onset of PG and underlying disease in three of our\ncases.\n\n\n\nThere is 7% malignant disease association5. Leukemia,\nusually acute myeloid leukemia and chronic myeloid\nleukemia are the most commonly reported malignancies6.\nBullous PG is the most commonly reported variety.\nUlcerative type of PG is noted with myeloma (IgA type)\nand Walderstrom\u2019s macroglobulinemia. Other reported\nassociations were myelofibrosis, lymphomas and solid\ntumours5.\n\n\n\nThe diagnosis is made by exclusion. Histopathologic\nfindings are not specific but crucial to rule out other causes\nof skin ulcers. Differential diagnosis can be infection, insect\nbite or contact dermatitis8.\n\n\n\nThere is no specific treatment. In patients with an\nassociated underlying disease, the effective therapy of the\nassociated condition may be associated with a control of the\ncutaneous process as well2,7. No specific randomized clinical\ntrial has been done but the gold standard in treatment is\nsystemic corticosteroids. Steroid sparing agents such as\ndapsone, cyclosporin or azathioprine may be used. Local\ntreatment includes corticosteriod (intralesional),\ncyclosporin (topical, intralesional), tacrolimus (topical,\nintralesional), macrophage colony stimulating factors\n(intralesional) and  skin grafts.\n\n\n\nFigure 3.   Ruptured bullae, ulcerated plaques with slough  & violaceous undermined edges\nand surrounding erythema\n\n\n\n\n\n\n\n\n112\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReferences\n\n\n\n1. Brunsting LA, Goeckerman WH, O'Leary PA. Pyoderma (ecthyma) \ngangrenosum: clinical and experimental observations in five \ncases occurring in adults. Arch Dermatol Syph 1930;22:655-680. \n\n\n\n2. Schwaegerle SM, Bergfeld WF, Senitzer D, Tidrick RT. Pyoderma \ngangrenosum: a review. J Am Acad Dermatol 1988;18:559-568. \n\n\n\n3. Fitzpatrick TB,et al sixth edition, chapter 98.\n4. Von Den Driesh P: Pyoderma gangrenosum: A report of 44 cases \n\n\n\nwith follow up. Br J Dermatol 1997;137:1000-1005.\n\n\n\n5. Jacobs P, Palmer S, Gordon-Smith EC: Pyoderma gangrenosum \nin myelodysplasia and acute   leukaemia. Postgrad Med J \n1985;61:689-694.\n\n\n\n6. Lewis SJ, Poh-Fitzpatrick MB, Walther RR: Atypical pyoderma \ngangrenosum with leukemia. JAMA 1978;239:935-938. \n\n\n\n7. Powell FC, Schroeter AL, Su WPD, Perry HO. Pyoderma  \ngangrenosum: a review of 86 patients. Q J Med 1985;55:173-186.  \n\n\n\n8. Weenig RH, Davis MD, Dahl PR, Daniel Su WP: Skin ulcers \nmisdiagnosed as pyoderma gangrenosum. N Engl J Med \n2002;347(18):1412-1418.\n\n\n\n\n\n\n\n\n113\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nIncontinentia pigmenti: Report of 3 cases from Sarawak\n\n\n\nLeong KF1 MBBS MRCPCH, Pubalan M2 MBBS MRCP and Yap FBB2 MD MRCP\n\n\n\n1Paediatric Institute, Kuala Lumpur General Hospital\n2Department of Dermatology, Sarawak General Hospital\nJalan Hospital, 93586 Kuching, Sarawak\n\n\n\nCorrespondence\n\n\n\nDr Felix BB Yap\nDepartment of Dermatology\nSarawak General Hospital\n\n\n\nKeywords Incontinentia Pigmenti, X linked dominant, Blaschko\u2019s\n\n\n\nline\n\n\n\nIncontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is\na rare X- linked dominant multisystem disease involving ectodermal\nstructures namely cutaneous, ocular, dental, neurological and skeletal\nsystems1. Mutation of the nuclear factor kappa B essential modulator\n(NEMO) gene in chromosome Xq28 is determined to cause this rare\ngenodermatosis2. The cutaneous manifestations are the most\ncharacteristic features of this disorder3. We would like to report 3 cases\nof incontinentia pigmenti seen in the skin clinic, Sarawak General\nHospital.\n\n\n\nCase Report\nCase 1\nA newborn Malay girl was admitted to the nursery in 2005\nwith vesicular skin eruption distributed along the Blaschko\u2019s\nlines, more prominent on the left side of the body, sparing\nthe nails and mucous membrane (Figure 1a). The lesions\nevolved into verrucous lesions and later into\nhyperpigmented macules few months later. At 18 months\nfollow up, vertex alopecia and peg teeth were noted; without\neyes or neurological abnormalities and normal\ndevelopmental milestones. She has 3 elder sisters with\nsimilar skin lesions and dental abnormalities, with one\nhaving alopecia (Figure 1b). No parental consanguinity was\nnoted. No skin biopsy was performed but we noted high\nblood eosinophils count in the first week of life.\n\n\n\nCase 2\nA newborn baby girl was referred to the dermatology unit\nin 2006 for vesicular lesions along the Blaschko\u2019s lines\nbilaterally associated with hypereosinophilia. The lesions\nprogressed to whorled, macular and linear\nhyperpigmentation in the next few months (Figure 2). She\nhad no dental, neurological and opthalmological\nabnormalities at 8 months follow up. Her developmental\nmilestones were normal. No skin biopsy was done.\n\n\n\nCase 3\nA 3-month-old Iban girl was referred in June 2008 for\nvesicular and verrucous hyperpigmentation along the\nBlaschko\u2019s lines, predominantly right sided (Figure 3). She\nwas born full term to a non-consanguineous parent and had\nbullous lesions since birth. No family history was elicited.\nHer mother never had any abortion or miscarriage before\nthis. None of her other family members from both her\nmaternal and paternal sides have these skin abnormalities.\nNo skin biopsy was done for her. She also had\nhypereosinophilia.\n\n\n\nDiscussion\nIncontinentia pigmenti is an X-linked dominant\ngenodermatosis seen almost exclusively in females. The\nmutation in the NEMO gene is lethal for affected males,\nusually resulting in abortion of male foetuses2. The affected\nfemales survive because of lyonisation3. Female carriers will\nusually have a distorted sex ratio of 2 females to 1 male\noffspring2. Up to half the cases are spontaneous mutation4.\nIn 1993, Landy and Donnai recommended a diagnostic\ncriteria for the disorder5. They recommended that for\nsporadic cases, a diagnosis of incontinentia pigmenti can be\nmade if one or more of the three major criteria is present.\nThe major criterias are typical neonatal vesicular rash with\neosinophilia; typical blaschkoid hyperpigmentation in\nadolescence; and linear atrophic hairless lesions. For those\nwith at least one positive first degree female relative,\ndiagnosis can be made with minor criterias. The minor\ncriterias include dental anomalies, alopecia and wooly hair.\nAll three patients we presented fulfilled the criteria.\n\n\n\nThe cutaneous manifestations of incontinentia pigmenti are\nclassically described in 4 sequential stages1,3,4. Stage 1 is the\nvesicular or inflammatory stage with linear vesicles, pustules\nand bullae along the Blaschko\u2019s line usually seen at birth.\nStage 2 is the verrucous or proliferative stage characterised\nby warty keratotic papules and plaques usually seen between\nthe ages\n\n\n\n\n\n\n\n\n114\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nthe ages of 2 to 8 weeks. Stage 3 is the hyperpigmented\nstage manifested by macular hyperpigmentation in a swirled\npattern along the lines of Blaschko seen between ages 12\nand 40 weeks. The final stage, stage 4 is the hypopigmented\nstage characterised by hypopigmented streaks and patches\nand cutaneous atrophy seen from infancy through\nadulthood.\n\n\n\nAll these stages might occur simultaneously, in sequential\norder or overlap with each other. Any stage can present as\nan initial presentation1. In Singapore, 54% of patients had\ncoexistence of 2 or more stages simultaneously and 14% had\nwhorled pigmentation as the initial and solitary clinical\npresentation3.\n\n\n\nCase 1 illustrates the typical progression of the disease from\nthe vesicular stage at birth progressing to the verrucous and\nlater hyperpigmented stage. Case 2 did not have the\nverrucous stage. Meanwhile, case 3 presented with\noverlapping bullous and verrucous stage. All our cases have\nyet to manifest stage 4.\n\n\n\nHair abnormalities are noted in 40% of patients1. The most\ncommon anomaly is alopecia usually with scarring. Dental\nanomalies occur in 70% of patients, affecting both the\ndeciduous and permanent teeth. The most common\nabnormalities include missing teeth, small teeth,\nabnormally-shaped teeth such as peg or conical teeth, and\ndelayed eruption of both deciduous and permanent teeth.\nCase 1 and her siblings showed these anomalies.\n\n\n\nOcular anormalities is seen in one third of patients and\nincludes retinal and nonretinal findings1. Nail dystrophy is\nseen in 40-60% of affected individuals4. Neurological\nabnormalities are the most disabling manifestation of\nincontinentia pigmenti. It is seen in 10% to 40% of patients.\nThe manifestations include seizures, mental retardation,\nspasticity, hemiparesis, and encephalopathy1,4. We have yet\nto detect such anomalies in our patients and will vigilantly\nlook for them during their subsequent follow up.\n\n\n\nFigure 1a Figure 1b\n\n\n\nFigure 2 Figure 3\n\n\n\n\n\n\n\n\n115\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nBlood investigations reveal eosinophilia in a third of cases4.\nSkin biopsy findings depend on the stage of the disease.\nStage 1 shows eosinophilic spongiosis; stage 2 shows\npapillated epidermal hyperplasia; stage 3 reveals thickened\npapillary dermis, many melanophages, deposits of melanin\nin the dermis, and vacuolar alteration of epidermal basal cell\nlayer; and stage 4 has increased melanin in the upper dermal\nlayers, hyperkeratosis, acanthosis, atrophy, scarring, and an\nabsence of skin appendages1,4. All our case had\nhypereosinophilia but did not have a skin biopsy.\n\n\n\nNo specific treatment is available for incontinentia\npigmenti1,3,4. Prevention of infection in stage 1, good dental\nhygiene and meticulous dental intervention for dental\nanomalies and neurological consultation for patients with\nneurological complications is needed. Genetic counselling\nshould be offered for affected families.\n\n\n\nReferences\n\n\n\n1. Francis JS, Sybert VP. Incontinentia pigmenti. Semin Cutan Med \nSurg 1997; 16: 54-60.\n\n\n\n2. Smahi A, Courtois G, Vabres P, et al. Genomic rearrangement in \nNEMO impairs NF-kappaB activation and is a cause of \nincontinentia pigmenti. The International Incontinentia Pigmenti \n(IP) Consortium. Nature 2000; 405: 466-72.\n\n\n\n3. Chan YC, Giam YC. A retrospective study of incontinentia \npigmenti seen at the National Skin Centre, Singapore over a 10 \nyear period. Ann Acad Med Singapore 2001; 30: 409-13.\n\n\n\n4. Chang CH. Incontinentia pigmenti. eMedicine 2007.\n5. Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger \n\n\n\nsyndrome). J Med Genet 1993; 30: 53-9.\n\n\n\n\n\n\n\n\n116\n\n\n\n\n\n\n\n\n117\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nPrimary cutaneous anaplastic large cell lymphoma\nin a young woman\n\n\n\nYap FBB MD MRCP and Pubalan M MBBS MRCP\n\n\n\nDepartment of Dermatology\nSarawak General Hospital\nJalan Hospital, 93586, Kuching, Sarawak\n\n\n\nCorrespondence\n\n\n\nDr Felix BB Yap\nDepartment of Dermatology\nSarawak General Hospital\nJalan Hospital , 93586 Kuching\nEmail: woodzlamp@yahoo.com\n\n\n\nPrimary cutaneous anaplastic large cell lymphoma (ALCL) constitutes\naround 1% of all cutaneous lymphomas1. It is defined as predominance\n(>75%) of large clusters of CD 30+ blast like cells in the skin biopsy\nwith no clinical evidence of lymphomatoid papulosis, extracutaneous\nlocalization at presentation or previous or concurrent mycosis\nfungoides or other cutaneous lymphoma2. It is usually seen in males\nwith a median age of 40 years3. It classically presents as a solitary\nulcerated tumour on the trunk or extremities. Twenty two percent of\ncases are multifocal3. Extracutaneous dissemination occurs in\napproximately 10%, mainly to regional lymph nodes3. Skin restricted\ndisease has an excellent prognosis with 96% 5 year survival4.\n\n\n\nHere, we report a case of primary cutaneous anaplastic large cell\nlymphoma (ALCL) in a 32-year-old woman.\n\n\n\nCase Report\nA 32-year-old Chinese woman presented with one year\nhistory of an ulcerated nodular lesion on her right mid\nthigh. It started as a small papule which progressively\nenlarged and ulcerated. She was seen by her general\npractitioner who did a skin biopsy which was reported as\npseudolymphoma. She failed to respond to topical\ncorticosteroids. She was then referred to us for further\nmanagement. There was no significant past medical history.\n\n\n\nExamination of the skin showed an irregular nodular lesion\non her right mid thigh measuring 16 x 13 cm with an\noverlying ulceration measuring 5 x 4 cm at one end, with a\nfoul smelling discharge. There were satellite lesions\nmeasuring 1 x 1 cm surrounding the tumor (Figure 1). Two\n3 x 2 cm erythematous plaque lesions on her left forearm\nand back were also noted. There was no significant\nlymphadenopathy.\n\n\n\nA 6 mm punch biopsy done showed diffuse dermal\ninfiltration by large neoplastic cells with no\n\n\n\nepidermotropism. These neoplastic cells had abundant\neosinophilic cytoplasm with large horseshoe nuclei and\nprominent nucleoli (Figure 2 and 3). Frequent mitoses were\nnoted. The whole dermis and panniculus were infiltrated by\nthese cells. Immunohistochemistry showed prominent\nstaining with CD 30 (80%) and Leukocyte Common\nAntigen (60%). Staining for CD3, CD8, CD 20, anaplastic\nlarge cell lymphoma (ALCL) tyrosine kinase (ALK) and\nepithelial membrane antigen (EMA) were negative.\n\n\n\nHer blood investigations including HIV test were normal.\nComputered tomography (CT) scanning of the neck, chest,\nabdomen and pelvis showed no lymphadenopathy or\norganomegaly. Bone marrow was clear of the tumour.\n\n\n\nShe was thus diagnosed to have primary cutaneous ALCL\nStage 1E (solitary or grouped lesions confined to 1\nanatomic site less than 15 cm2). Her skin tumour responded\nto 22 fractions of localized radiotherapy but was\ncomplicated by worsening of the ulcer. Nevertheless, the\nulcer responded to hydrogel and silver dressing.\n\n\n\nDiscussion\nOur patient is interesting because she is a woman in her\nearly 30s. Bekkenk et al in the Netherlands found only 1\npatient younger than 20 years old among 79 patients with\nprimary cutaneous CD 30+ large cell lymphoma3. Most\nstudies found the mean ages in the mid 40s3,5.\n\n\n\nThe histological findings in our patient showed neoplastic\nCD30+lymphocytes with no predilection for either T (CD3\nand 8) or B (CD20) cells. We suspect that she had null cell\nprimary cutaneous ALCL, although CD43, another T cell\nmarker was not done. Null cell primary cutaneous ALCL is\nrarely seen. Liu et al reported that 3 out of 25 patients with\nprimary cutaneous ALCL in Stanford had null cell primary\ncutan\n\n\n\n\n\n\n\n\n118\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ncutaneous ALCL5. The main differential diagnoses\nhistopathologically are secondary cutaneous manifestation\nof systemic ALCL and type C lymphomatoid papulosis\n(LyP). In our case the infiltration of the neoplastic\nlymphocytes was until the level of the panniculus, ruling out\nLyP which does not infiltrate the subcutis. Moreover, the\npatient presented with tumoural lesion and not papular\nlesion as commonly seen with LyP. The absence of ALK\nand EMA staining in our case ruled out cutaneous\ninvolvement of systemic ALCL. De Coteau showed that\nsystemic CD30+ ALCL express ALK and EMA whereas\nLyP and primary cutaneous ALCL lack these markers6.\n\n\n\nAnother differential diagnosis to entertain is the large cell\ntransformation of mycosis fungoides (MF). It is of utmost\nimportance to differentiate the two because large cell\ntransformation of MF has a more aggressive clinical course\nand warrants aggressive therapy5. Clinical presentation\nusually is helpful in differentiating the two entities.\n\n\n\nTumoural lesions developing within patches or plaques of\nMF favour large cell transformation5,7. Our patient\npresented with tumoural nodules without plaques or\npatches. This is more in keeping with primary cutaneous\nALCL. Histopathologically, presence of small,\nintermediate, and large atypical lymphocytes in addition to\nthe large anaplastic cells would favour large cell\ntransformation of MF7. In our patient, the large neoplastic\ncells were prominently seen without presence of atypical\nlymphocytes favouring a diagnosis of primary cutaneous\nALCL.\n\n\n\nStage 1E consisting of solitary or few localized lesions are\ntreated with local radiotherapy or excision3,4,5. Multifocal\ndisease is best treated with radiotherapy or low dose\nmethotrexate3,5. Multiagent chemotherapy is only indicated\nin full-blown disease of lymph nodes involvements3. Our\npatient responded completely to the localized radiotherapy.\n\n\n\nFigure 1.   Irregular nodular lesion on the right \nmid thigh with an overlying ulcer and \nmultiple satellite lesions\n\n\n\nFigure 2.   Diffuse dermal infiltration by large \nneoplastic cells with no \nepidermotropism (H&E stain. X10 \nmagnification)\n\n\n\nFigure 3.   Large neoplastic lymphoid cells had \nabundant eosinophilic cytoplasm \nwith large horseshoe nuclei and \nprominent nucleoli (H&E stain. X40 \nmagnifications)\n\n\n\n\n\n\n\n\n119\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nLiu et al in Stanford reported that their patients with null\ncell phenotype had a worse outcome compared to T cell\nphenotype5. They added that those with null cell\nphenotypes were more resistant to treatment. We would\ncontinue to follow our patient to monitor the progress of\nher disease.\n\n\n\nReferences\n\n\n\n1. Zackheim HS, Vonderheid EC, Ramsay DL, LeBoit PE et al. \nRelative frequency of various forms of primary cutaneous \nlymphomas. J Am Acad Dermatol 2000; 43: 793-6.\n\n\n\n2. Beljaards RC, Kaudewitz P, Berti E, Gianotti R et al. Primary \ncutaneous CD 30-positive large cell lymphoma: definition of a \nnew type of cutaneous lymphoma with a favorable prognosis. \nCancer 1993; 71: 2097-104.\n\n\n\n3. Bekkenk MW, Geelen FAMJ, van Voorst Vader PC, Heule F et al. \nPrimary and secondary cutaneous CD 30+ lymphoproliferative \ndisorders: a report from the Dutch Cutaneous Lymphoma Group \non the long-term follow-up data of 219 patients and guidelines for \ndiagnosis and treatment. Blood 2000; 95(12): 3653-61.\n\n\n\n4. Whittaker SJ, Marsden JR, Spittle M. Joint British Association of \nDermatologist and U.K. Cutaneous Lymphoma Group  guidelines \nfor the management of primary cutaneous T-cell lymphoma. Br J \nDermatol 2003; 149: 1095-107.\n\n\n\n5. Liu HL, Hoppe RT, Kohler S, Harvell JD et al. CD30+ cutaneous \nlymphoproliferative disorders: The Stanford experience in \nlymphomatoid papulosis and primary cutaneous anaplastic large \ncell lymphoma. J Am Acad Dermatol 2003; 49: 1049-58.\n\n\n\n6. De Coteau JF, Butmarc JR, Kinney MC, Kadin M. The t(2;5) \nchromosomal translocation is not a common feature of primary \ncutaneous CD30+ lymphoproliferative disorders: Comparison with \nanaplastic large-cell lymphoma of nodal origin. Blood 1996;\n87: 3437-41. \n\n\n\n7. Diamandidou E, Colome-Grimmer M, Fayad L, Duvic M et al. \nTransformation of mycosis fungoides/Sezary syndrome: clinical \ncharacteristics and prognosis. Blood 1998; 92: 1150-9.\n\n\n\n8. Sheehan JM, Kalaaji AN, Markovic SN, Ahmed I. Management of \nmultifocal primary cutaneous CD 30+ anaplastic large cell \nlymphoma. J Am Acad Dermatol 2004; 51(1): 103-10.\n\n\n\n9. Beljaards RC, Kaudewitz P, Berti E et al. Primary cutaneous CD \n30-positive large cell lymphoma: definition of a new type of \ncutaneous lymphoma with a favorable prognosis. Cancer 1993; \n71: 2097-104.\n\n\n\n10. Bekkenk MW, Geelen FAMJ, van Voorst Vader PC et al. Primary \nand secondary cutaneous CD 30+ lymphoproliferative disorders: \na report from the Dutch Cutaneous Lymphoma Group on the \nlong-term follow-up data of 219 patients and guidelines for \ndiagnosis and treatment. Blood 2000; 95(12): 3653-61.\n\n\n\n11. Whittaker SJ, Marsden JR, Spittle M. Joint British Association of \nDermatologist and U.K. Cutaneous Lymphoma Group  guidelines \nfor the management of primary cutaneous T-cell lymphoma. Br J \nDermatol 2003; 149: 1095-107.\n\n\n\n12. Sagaert X, De Wolf-Peeters C. Anaplastic large cell lymphoma. \nCurrent Diagnostic Pathology 2003; 9: 252-8.\n\n\n\n\n\n\n\n\n120\n\n\n\n\n\n\n\n\n121\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nCutaneous tuberculosis confirmed by PCR in a patient \nwith culture negative for mycobacterium tuberculosis\n\n\n\nLee YY1 MD MRCP MMed, Loh LC1 MBChB MRCP and SC Peh2 MBBS MPath FRCPath FRCPA AM FAMM PhD \n\n\n\n1Dermatology Unit, Department of Medicine\n2Department of Pathology\nUniversity Malaya Medical Centre, Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nLee Yin Yin MD MRCP MMed\n\n\n\nDermatology Unit\nDepartment of Medicine\nUniversity Malaya Medical Centre\nKuala Lumpur\nEmail: yleemd@yahoo.com\n\n\n\nCutaneous tuberculosis is an old and rare infectious disease. Laennec\nreported the first case of cutaneous tuberculosis in 1826 and M.\ntuberculosis was discovered by Koch in 18821.\n\n\n\nSince then, many cases of cutaneous tuberculosis have been described\nand classified. The different forms of diseases correlate with the\nimmunologic status of the host, host\u2019s prior sensitization, route of\ndisease transmission, layer of skin primarily involved and rate of disease\nprogression. Nevertheless, the most widely accepted classification is\nbased on the mechanism of disease propagation which can be via direct\ninoculation, through contiguous infection or via hematogenous route2.\nBacterial load has also been used to categorize this disease into\nmultibacillary and paucibacillary forms.\n\n\n\nDiseases under the multibacillary forms include primary inoculation\ntuberculosis (tuberculous chancre), scrofuloderma, tuberculous\nperioficialis, acute miliary tuberculosis and tuberculous gumma.\nPaucibacillary forms include lupus vulgaris, tuberculosis verrucosa cutis\nand tuberculids.\n\n\n\nStrains of M. Tuberculosis complex that can be isolated include M.\ntuberculosis, M. africanum, M. canetti and M. bovis, M. microti and M.\nbovis BCG.\n\n\n\nCase Report\nA 50-year-old Indian woman presented with a rapidly\nenlarging and painless plaque on her right knee of more\nthan 3 years duration. She had a history of a small laceration\nat the same site thirty years ago, which did not heal\ncompletely. She is otherwise healthy, without any\nconstitutional symptoms. She was previously employed as a\nclinic assistant more than ten years ago. Clinically, there was\na firm, well demarcated, erythematous, scaly plaque on her\nright knee with raised, hyperkeratotic edge. (Figure 1)\n\n\n\nSkin biopsies performed at two different occasions showed\nchronic granulomatous inflammation. (Figure 2a and 2b)\n\n\n\nHowever, mycobacterium could not be seen or isolated by\nsmear examination or conventional culture methods from\nthe skin specimens.\n\n\n\nBlood counts and biochemistry was unremarkable. Her\nESR was 32 mm/hr and mantoux test was 30 mm. Her\nchest X Ray was normal \n\n\n\nHer clinical features were highly suggestive of cutaneous\ntuberculosis, although cultures were negative. She was\noffered empirical treatment with anti-tuberculous therapy\nwhich she declined pending an absolute diagnosis.\n\n\n\nWe  proceeded to PCR technique to detect M. tuberculosis\nDNA. The result was positive for detection of M.\ntuberculosis complex. She was subsequently initiated on\nintensive anti-tuberculous therapy consisting of oral\nRifampicin 600mg daily, Pyrazinamide 1.5gm daily,\nIsoniazid 300mg daily and Pyridoxine 10mg daily for 2\nmonths followed by maintenance regime for six months.\nThis resulted in marked clinical improvement of her\nhyperkeratotic plaque.\n\n\n\nDiscussion\nThe worldwide incidence of tuberculosis is on a steady rise\nin recent years. Cutaneous tuberculosis represents only a\nminute proportion of tuberculosis. Nonetheless, due to the\nhigh prevalence of tuberculosis particularly in developing\ncountries, this small percentage becomes significant.\n\n\n\nEffective management of cutaneous tuberculosis requires\nrapid detection and confirmation of the etiologic agent.\nUnfortunately, obstacles in the diagnosis of cutaneous\ntuberculosis arise due to varied clinical manifestations of the\ncutaneous lesions and also low culture yield for M.\ntuberculosis, especially from chronic lesions and in patients\nwith a high degree of cell mediated immunity3.\n\n\n\n\n\n\n\n\n122\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTraditionally, the accepted \u2018gold standard\u2019 laboratory\nmethods for detecting and identifying M. tuberculosis in skin\ninclude direct acid-fast bacteria (AFB) smear with Ziehl-\nNeelsen (ZN) stain, Lowenstein-Jensen (LJ) based culture\nmedia, radiometric BACTEC system and histopathological\nexamination.\n\n\n\nAdvances in research have led to the discovery of newer\ntechniques including molecular diagnostic tests over the\npast two decades. Majority of these investigations focused\non detection of nucleic acids (RNA and DNA), which are\nspecific to M. tuberculosis by amplification techniques such\nas PCR.\n\n\n\nHistorically, investigators concentrated on the identification\nof purin and pyrimidine base content of mycobacterial\ngenomes, which was followed by DNA re-association\nkinetics, restriction of endonuclease analysis and sequence-\nspecific DNA hybridization with radioactively labeled\n\n\n\nprobes4. This technique is further enhanced with the\nincorporation of PCR, which assisted in sequence-specific\namplification of mycobacterium target sequence before their\nmolecular analysis.\n\n\n\nAmplified M. tuberculosis direct test (MTD) (Gen-Probe\nInc., San Diego, CA, USA) is a rapid technique of nucleic\nacid amplification which can be used directly on processed\nclinical specimens. It is based on enzymatic amplification of\nribosomal RNA via DNA intermediates. Detection of\namplified product is then facilitated by an acridinium-ester-\nlabeled DNA probe5.\n\n\n\nThis kit is available under a special research purpose in the\nmicrobiology laboratory in \u2018Hospital Sungai Buluh\u2019. An\narrangement was made to send our skin biopsy sample there\nfor further investigation. This proved to be a valuable\nexperience for both our patient and ourselves when the\nreport was positive for M. tuberculosis complex.\n\n\n\nFigure 1.\n\n\n\nFigure 2a & 2b.   Epidermis show hyper- and parakeratosis.  The subepidermal areas show \ngranulomas composed of collections of lymphocytes, epitheloid cells and \nmultinucleated Langhans\u2019 type giant cells. Special histochemical stains \n(Ziehl-Neelsen, Giemsa and Periodic Acid Schiff stains) do not reveal \npresence of acid fast bacilli or fungus\n\n\n\n\n\n\n\n\n123\n\n\n\nDetection of M. tuberculosis DNA by PCR in fresh tissue is\na reliable method for diagnosis and confirmation of\ncutaneous tuberculosis, particularly when this\nmicroorganism is not detected by conventional methods.\n\n\n\nMultiple trials have been conducted comparing\nconventional versus new diagnostic modalities. A\ncomparative study of PCR, smear examination and culture\nfor diagnosis of cutaneous tuberculosis conducted by Negi\net al in 2005 found PCR to be more superior to other\ninvestigative modalities, with a sensitivity and specificity\nrates of 95.2% and 100% respectively6. PCR is also more\nsuperior due to its rapid detection of positive results, ie. 1\nday for PCR, < 1 day for smear examination23.42 days for\nBACTEC culture and 38.02 days for LJ culture.\n\n\n\nOur patient is a classic example of a case of diagnostic\ndilemma that benefited from this rapid, sensitive and\nprecise investigation. This enables us to initiate immediate\ntreatment with tremendous clinical improvement after six\nmonths of combined anti tuberculous therapy.\n\n\n\nWe hope that this DNA amplification technique will be\nmade readily available in our local setting to assist in\nproviding a rapid and informative tool for detection and\nimmediate initiation of appropriate treatment against M.\ntuberculosis.\n\n\n\nReferences\n\n\n\n1. MacGregor RR. Cutaneous Tuberculosis. Clinics in Dermatology. \n1995;13:245-255.\n\n\n\n2. Bravo FG and Gotuzzo E. Cutaneous tuberculosis. Clinics in \nDermatology (2007) 25, 173-180.\n\n\n\n3. Farina M, Gegundez I, et al. Cutaneous tuberculosis: A clinical, \nhistopathologic, and bacteriologic study. J Am Acad Dermatol. \nSeptember 1995. Volume 33, Number 3. \n\n\n\n4. Klaus, D. Detection of Mycobacterial DNA in the Skin: Etiologic \nInsights and Diagnostic Perspectives. Arch Dermatol. \n1996;132:71-75.\n\n\n\n5. Cho, SN and Brennan, PJ. Tuberculosis: Diagnostics. \nTuberculosis. 2007:Aug;87 Suppl 1:S14-7.\n\n\n\n6. Negi SS, Basir SF, Gupta S, Pasha ST, Khare S, Lal S. \nComparative study of PCR, smear examination and culture for \ndiagnosis of cutaneous tuberculosis. J Commun Dis. 2005 \nJun;37(2):83-92.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\n124\n\n\n\n\n\n\n\n\n125\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCommentary\n\n\n\nManagement of naevus of Ota\n\n\n\nHC Ting MBBS MRCP\n\n\n\nTing Skin Specialist Clinic, Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nDr Ting Hoon Chin\nTing Skin Specialist Clinic\n78A, Jalan Imbi\n55100 Kuala Lumpur\nEmail: hoonchin@streamyx.com\n\n\n\nTherapy with Q-switched lasers which can deliver light\npulses with high fluences and very short pulse durations is\nthe treatment of choice for naevus of Ota. The target of\ntreatment is the melanosome and this has a thermal\nrelaxation time of 0.5 - 1 microsecond. The pulse duration\nof the light from Q-switched lasers is in the range of 10-50\nnanoseconds which is within the limits of this thermal\nrelaxation time, thus allowing selective photothermolysis,\nwith minimal injury to the surrounding tissue. Melanin has\na broad absorption spectrum (from 250-1200 nm). The\nthree Q-switched lasers known to be effective for naevus of\nOta produce light with wavelengths within this absorption\nspectrum (Q-switched ruby 694 nm, Q-switched\nAlexandrite 755 nm and Q-switched Nd-YAG 1064 nm).\n\n\n\nOf the three lasers the Q-switched Nd-YAG has the least\nabsorption by melanin and is considered to be safer than the\nother two  lasers for patients with darker skin types in\nwhom the complications of hypopigmentation and\nhyperpigmentation are always a concern. However, there are\nonly few reports in the literature on the use of Q-switched\n\n\n\nNd-YAG in darker skin individuals. This retrospective\nstudy by Tang, Gangaram and Hussein shows that the use\nof Q-switch Nd-YAG laser produces good results with no\ncomplications and no recurrences in 50 patients with type\nIV and type V skin1. Previous studies from Hong Kong of\npatients treated with Q-switched lasers (Q-switched Nd-\nYAG alone, Q-switched Alexandrite alone or the 2\ncombined) have reported instances of hypopigmentation,\nhyperpigmentation, texture change and scarring, as well as\nrecurrences2. Perhaps further studies on larger groups of\npatients, preferably prospective in nature, will clarify the\nissue with regard to complications and recurrences.\n\n\n\nReferences\n\n\n\n1. Tang MM, Gangaram HB, Hussein SH. Treatment of naevus of \nOta with Q-switched 1064nm Nd:YAG laser. Malay J Dermatol \n2007: 21: 34-36\n\n\n\n2. Chan HH, Leung RS, Ying SY, et al. A retrospective analysis of \ncomplications in the treatment of nevus of Ota with Q-switched \nalexandrite and Q-switched Nd:YAG lasers. Dermatol Surg \n2000;26: 1000-1006.\n\n\n\n\n\n\n\n\n126\n\n\n\n\n\n\n\n\n127\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCorrespondence\n\n\n\nCorrespondence\n\n\n\nTemptations of dermatologists\n\n\n\nDermatologists face temptations in the course of their work.\nI can think of a few areas where dermatologists have to\nthread cautiously so as to avoid regrets later or even for the\nrest of their lives.\n\n\n\n1) When the clinic is busy and lesions look like fungal\ninfections, it is very tempting to start antifungal treatment\nwithout mycological confirmation. But when lesions do not\nclear, we have a problem. Microscopic examination then\nusually is negative, which may mean it is not a fungal\ninfection all along, or it may be negative because of\nsuppression of fungus by the antifungal agents, which due to\ncertain reasons, is unable to clear it.\n\n\n\nTherefore, to avoid confusion, it is always safer to follow the\ngolden rule of not starting antifungals without mycological\nconfirmation.\n\n\n\n2) All dermatologists know the name Tinea versicolor is a\nmisnomer, but not all take the trouble to stop others from\nusing it. Some may conveniently use it themselves. This may\nbe costly to patients and health care providers since oral\ngriseofulvin is often prescribed by non-dermatologists for\n'Tinea' infections. I come across this error again and I am\nsure other dermatologists have come across it too. So let us\nset a good example besides teaching non-dermatologists to\ncall it Pityriasis versicolor since it is a yeast infection which\nwill not respond to griseofulvin.\n\n\n\n3) Sometimes lesions are removed and discarded by\nconfident doctors without taking the trouble to send them\nfor histopathological examination. This can be dangerous\nsince seeing can be misleading! Assuming our visions are\nperfect and we are not colour blind, lesions can still mimic\none another. Research has shown that consultants perform\nbetter than junior doctors in clinically differentiating\nmalignant skin lesions from benign ones. But neither groups\ncan achieve a perfect score! They can still mistake malignant\nmelanoma for seborrhoeic keratosis and vice versa.\nPigmented basal cell carcinoma only adds to the\nuncertainty.\n\n\n\nSo, think twice before confidently and conveniently\ndiscarding tissues. Once gone, they cannot be recovered.\nAnd a later dispute may arise.\n\n\n\n4) You may have heard this one. A doctor was heard asking\na lawyer during a party, \u201cHow can I prevent people from\ncoming to me for their medical problems in public places? \"\n\n\n\n\u201cVery simple, just send them bills for consultation and they\nwill stop bothering you\" said the wise lawyer with a smile.\n\u201cHow come I have never thought of that\u201c the doctor\nwondered.\n\n\n\n\u201cDon\u2019t worry, I'll send you the bill for this consultation\nsoon.\" The lawyer said with a bigger smile.\n\n\n\nThe professional hazard of any dermatologist includes\npeople coming to them in the corridor for consultation.\nDermatologists are hereby warned to avoid entertaining the\npublic by making \u201ccorridor diagnoses\"! This is not just about\nmoney. Other reasons include:-\n\n\n\na) You cannot take a proper history with so many people in\nthe hearing range whether they want to eavesdrop or not.\nPatients may later turn around and accuse you of\nembarrassing them by asking sensitive questions in the\npublic, i.e. you are not professional enough to uphold\nprofessional secrecy!\n\n\n\nb) You cannot possibly carry out any proper physical\nexamination either. Without proper lighting, nursing\nassistance, privacy for patients to be adequately exposed for\nproper examination, you are doomed to make a blunder.\n\n\n\nc) No medical records means no protection!\n\n\n\nd) More people will line up for your \u201cmobile charity clinic\n\u201conce you start with the first patient.\n\n\n\nRemember, resist making a corridor diagnosis at all costs. It\nmay be more costly if you neglect this advice!\n\n\n\nDr Ong Cheng Leng MBBS, MRCP\n\n\n\nConsultant Dermatologist\n\n\n\nKuantan General Hospital, Kuantan\n\n\n\nCutaneous manifestations of lymphomas:\n\n\n\nReport of 3 cases\n\n\n\nLymphomas are malignant disorders of the lymphoid\ntissues which  arise either from B or T lymphocytes. Skin is\nan important organ where early symptoms of the disease\nmanifest and prompts investigations. Three disorders,\nHodgkin\u2019s disease (HD), Non-Hodgkin\u2019s lymphoma\n(NHL) and Mycosis Fungoides (MF) seen by the author\nover the past several years are reported and their unique\npresentations discussed.\n\n\n\n\n\n\n\n\n128\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Reports\nCase 1\nA 61-year-old Chinese man presented with a large tumour,\nulcerative plaque and multiple nodular lesions over the left\nthigh of insidious onset (Figure 1). There was no history of\nweight loss, fever or pruritus. The spleen was not palpable\nand there was no significant superficial lymphadenopathy.\nA skin biopsy showed features of Hodgkin\u2019s disease,\nlymphocytic predominant with dense mononuclear cells in\nthe dermis with few diagnostic binucleate (mirror-image)\nReed-Sternberg cells. He was referred for staging of the\ndisease and further treatment but he died two months later.\n\n\n\nCase 2\nA 56-year-old Chinese woman was seen with nodular\nlesions on the lower leg for the past 6 months. She\nexperienced mild itch. She had no other constitutional\nsymptoms. Her inguinal lymph nodes were enlarged but\nnon-tender. A skin biopsy showed lymphoid cell which\nwere immature with ovoid nuclei surrounding the blood\nvessels and skin appendages. Histochemical tests showed\nthe cell were LCA and L 26 positive. Patient was referred\nfor chemotherapy and responded well.\n\n\n\nCase 3\nA 40-year-old Malay woman presented with a large tumour\nover the left axilla and diffuse plaques over  the abdomen\nand chest associated with pruritis for the past 6 months. She\nhad taken some traditional medicine but was of no help in\nthe progress of the disease. A skin biopsy showed\npolymorphic infiltrate consisting of lymphoid cells,\nhistiocytes in the dermis seen marching towards and\n\n\n\ninvading the epidermis forming collections of Pautrier\u2019s\nmicroabscess which consists of a small group of\nmononuclear cells surrounded by halo-like clear space\n(Figures 2). Patient was ill and did not survive long.\n\n\n\nThe cutaneous manifestations of  lymphoma may vary from\npruritus and pigmentation to ulcerative plaques and\nnodules. The lymphomas arise in the lymph nodes or in the\nlymphoid tissues of the parenchymal organs such as the gut,\nlung or skin. Ninety percent of HD originate from the\nlymph nodes and 10% are of extra-nodal origin. Primary\ncutaneous HD is rare but has been well documented. In\n1832, Thomas Hodgkin of Guy\u2019s Hospital, London\ndescribed the autopsy findings of 7 patients who died of\ngeneralized lymphadenopathy and splenomegaly. The\nhistopathological features of HD was described by\nGreenfield in 1878. In 1892, Sternberg described the\ncharacteristic giant cells and areas of necrosis. The\nrecognition of giant cells as the diagnostic component of\nHD was made by Dorothy Reed of John Hopkin\u2019s Hospital\nin 1902. Ever since, much progress has been made in the\nclassification and management of the desease.\n\n\n\nThe clinical features, constitutional symptoms,\nhistopathological types, staging and curative treatmant of\nHD are well established. Skin lesions are part of general\ninvolvement of organs and lymph nodes. When the skin is\ninvolved histopathologically the prognosis is thought to be\npoor as in the reported case and tends to occur in areas of\nthe skin distal to the lymph node(s) containing tumour. In\nmost patients it is manifested initially by the appearance of\nerythematous nodules which grow continuously and\nbecome ulcerated as in the first patient.\n\n\n\nFigure 1.   HD. Tumours, ulcerative lesions over the thigh Figure 2.   Pautriers microabscesses (H&E X 400)\n\n\n\n\n\n\n\n\n129\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nNon-Hodgkin\u2019s lymphoma (NHL) refers to the malignant\ndisorders of lymphoid tissues which lack the characteristic\nhistopathological features of HD, that is absence of Reed-\nSternberg cells. NHL has several subtypes but basically it is\ndivided into high and low grades according to the rate of\ncell division. High-grade lymphomas are potentially curable\nwhereas the low-grade is considered incurable.\n\n\n\nMF is a cutaneous T-cell lymphoma which has variable\nclinical manifestations ranging from multiple or solitary\npatches, generalised hyperpigmentation and excoriation,\ninfiltrative plaque, erythematous nodules to pruritic\nerythroderma or exfoliative dermatitis  and large tumours.\nPruritus is a common symptom as in other lymphomas. It is\ndivided into patch, plaque and tumour stages. The\ncutaneous lesions range from round, oval patches or plaques\nto infiltrative nodules. MF can spread to the lymph nodes\nand visceral organs.\n\n\n\nKader B Mohamed MBBS, Dip Dermatology\n\n\n\nDepartment of Dermatology\n\n\n\nHospital Pakar Sultanah Fatimah\n\n\n\n84000 Muar, Johor\n\n\n\nReferences\n\n\n\n1. Gordon RA, Donald P. Skin Infiltrations in Hodgkin\u2019s Disease. \nArch Dermatol 1980; 116:1038-1040.\n\n\n\n2. SzurL, Levene GM, Harrison CV Samman PD. Primary Cutaneous \nHodgkin\u2019s Disease. Lancet 1970; 1:1016-1020.\n\n\n\n3. Lymphomas. In Clinical Medicine, Kumar P, Clark M, editors. 6th \ned. London, W.B Saunders 2005, p367-369.\n\n\n\n4. Leslie Smith J, Butler JJ. Skin Involvement in Hodgkin\u2019s Disease. \nCancer 1980; 45:354-361.\n\n\n\n5. Randle et al. Cutaneous Granulomas in Malignant Lymphoma. \nArch Dermatol 1980; 116:441-443.\n\n\n\n\n\n\n\n\n130\n\n\n\n\n\n"
"\n\nNotice to Authors\n\n\n\nThe Malaysian Journal of Dermatology welcome manuscripts \non all aspects of cutaneous medicine and surgery in the form of \noriginal articles, research papers, case reports and correspondence. \nContributions are accepted for publication on condition that they \nare submitted exclusively to the Malaysian Journal of Dermatology. \nThe Publisher and Editors cannot be held responsible for errors or \nany consequences arising from the use of information contained in \nthis journal; the views and opinions expressed do not necessarily \nreflect those of the publisher and Editors, neither does the \npublication of advertisements constitute any endorsement by the \npublisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following categories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than three \nillustrations. This category offers a means for rapid communication \nabout a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and pathological \nphotographs in color. The diagnosis and legends for the \nphotographs should be listed after the references in the article. The \narticle should be no more than 2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an Introduction, \nMaterials and Methods, Results, Comment and References. A \nStructured Abstract of not more than 240 words must be included. \nIt should consist of five paragraphs, labelled Background, \nMethods, Results, Discussion and Conclusion. It should describe \nthe problem studies, how the study was performed, the main \nresults, and what the author(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and \nsummarizes the existing knowledge in a particular field. It should \nnot be an exhaustive review of the literature, and references should \nnot exceed 100 in number. Tables, diagrams, and selected figures \nare often helpful. The length is left to the judgment of the author, \nalthough it generally should not exceed 5000 words. Topics may \ninclude updates in clinically relevant basic science and cutaneous \nbiology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of the paper, \nthe author(s)\u2019 name(s), degrees, and affiliation(s), the category of \nthe article, the number of figures and tables, and three key words \nfor indexing purposes. The name and full postal address (including \na street address), phone and fax numbers and an email address of \nthe corresponding author who will be responsible for reading the \nproofs must also be given on the title page. The author(s) must also \ndeclare any affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the subject \nmatter or materials discussed in the manuscript on this page.\n\n\n\nAll measurements should be according to the metric system. If \nconfusion could result, please include other measurement systems \nin parentheses.\n\n\n\nRefer to patients by number or letters; names or initials should not \nbe used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear in the \nmanuscript. References from journals should include: (1) name(s) \nfollowed by the initials of the author(s), up to six authors: if more \nthan six authors, include the first six authors followed by et al.; (2) \ntitle of paper; (3) title of the journal as abbreviated in the Index \nMedicus; (4) year of publication; (5) volume number; (6) first and \nfinal page numbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); (2) \nchapter (if any) book titles; (3) edition, volume, etc.; (4) place of \npublication; (5) publisher; (6) year; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual Grand \nRounds. In: Wootton R and Oakley A, editors. Teledermatology. \nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication.\n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on separate \npages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of photomicrographs, \nthe stain type and original magnification should be stated. Each \nfigure should bear a reference number corresponding to a similar \nnumber in the text.\n\n\n\nTo minimise the publication time of your manuscript it is important \nthat all electronic artwork is supplied to the Editorial Office in the \ncorrect format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for errors or \nany consequences arising from the use of information contained in \nthis journal; the views and opinions expressed do not necessarily \nreflect those of the publisher and Editors, neither does the \npublication of advertisements constitute any endorsement by the \npublisher and Editors of the products advertised.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39\n\n\n\nContents\n\n\n\nREVIEW ARTICLES\n\n\n\n1 Generalized Pustular Psoriasis\n          Choon SE\n\n\n\n2 Contact Allergic Dermatitis to Cosmetics and Topical \nAnti-ageing Products\n\n\n\n          R Ridzwan, BH Zainudin\n\n\n\nORIGINAL ARTICLES\n\n\n\n1 Vascular Anomalies: A 3-Year Review in the \nPaediatric Institute Hospital Kuala Lumpur Between \n2013 And 2015\n\n\n\n           Ng FY, Tang MM, S Begum, Leong KF\n\n\n\n2 Prevalence of Co-infection with Gonorrhoea and \nNon-Gonococcal Urethritis in Males with Urethral \nDischarge Genitourinary Clinic, Hospital Kuala \nLumpur: A 5-year study between 2011 \u2013 2015\n\n\n\n          V Krishnasamy, A Johar\n\n\n\n3 The Utilization of Cutaneous Laser Therapy at \nthe Department of Dermatology, Hospital Kuala \nLumpur: A 5-year review\n\n\n\n          S Robinson, Tang MM, NZ Azizan\n\n\n\nCASE REPORT \n\n\n\n1 Gardner \u2013 Diamond Syndrome\n          Ellie Choi, Sam Yang, Ng SK \n\n\n\n2 Dialysis-associated Pseudoporphyria: An Often \nOverlooked Cause of Bullous Photosensitivity\n\n\n\n          R Ramalingam\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n3 Angiosarcoma Mimicking Rhinophymatous Rosacea\n          RSA Raja Mohd Radzi, Tey KE, Choon SE, Lee MY\n\n\n\n4 Atypical Presentation of Cutaneous Larva Migrans: \nA Case Report & Literature Review\n\n\n\n          Ong KP, Tan WC, Chong YT, Khor YH, Chan LC \n\n\n\n5 The Immunocompromised Patient with Peri-Anal \nLesions\n\n\n\n          Tang ASN, Neoh KK, Joshua MD, P Muniandy \n\n\n\n6 Blistering Eruption and Fulminant Hepatitis: A \nFatal Coinfection of Leptospirosis and Disseminated \nHerpes Simplex\n\n\n\n          R Ramalingam\n\n\n\n7 Case Series of Acrodermatitis Enteropathica in \nLangkawi Hospital\n\n\n\n          Lee SW, Ooi SY, Tan WC\n\n\n\n8 From Red Herring to Malignancy\n          Loo CH, Tang MM, Z Faizah Baharom, Lee BR, S \n\n\n\nThevarajah\n\n\n\n9 Surgical Correction of Pincer-Nail Deformity using \nAutologous Full Thickness Skin Graft: A Case \nReport\n\n\n\n          MY Ahmad Muslim, Chuah CK\n\n\n\nACKNOWLEDGEMENT\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 1\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office \nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nExecutive Committee\nAgnes Heng Yoke Hui, MRCP - President\nRohna Ridzwan, MRCP - Vice President\nNoor Zalmy Azizan, Adv M Derm - Secretary\nChan Lee Chin, MMed - Treasurer\nHenry Foong Boon Bee, FRCP - Past President\nSabeera Begum, MMed - Committee Member\nTan Wooi Chiang, Adv M Derm - Committee \nMember\n\n\n\nAzura Mohd Affandi, Adv M Derm - \nCommittee Member\nDr. Ruban Nathan, FRCP - Committee Member\n\n\n\nDermatological Society of Malaysia \n(Rumah Dermatology)\nG1, Medical Academics of Malaysia, 210, \nJalan Tun Razak, 50400 Kuala Lumpur, \nMalaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise \n723E 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang.\nTel : 04-658 4515 / 04-657 8515    Fax : 04-658 4505\n\n\n\n\u00ae2017 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 392\n\n\n\nREVIEW\n\n\n\nGeneralized Pustular Psoriasis\nSiew Eng Choon, FRCP\n\n\n\nDepartment of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\nJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor Bahru, Johor, Malaysia\n\n\n\nSummary:\nGeneralized Pustular Psoriasis (GPP) is a dermatological emergency that often requires hospitalization \nbecause of possible life-threatening complications, including heart failure, renal failure and sepsis. It \nis a chronic recalcitrant disease in which acute pustular flares frequently recur on exposure to classic \ntriggers. This review article is aimed to update the new insights into the genetic basis of GPP and \nhighlighted the central role IL1 and IL36 in the pathogenesis of GPP. \n\n\n\nKey words: Generalized Pustular Psoriasis, Acute GPP of von Zumbusch, Annular Pustular Psoriasis, Localized variant of GPP, \nExanthematic GPP, Interleukin-36 receptor antagonist, CARD14 mutations\n\n\n\nIntroduction\nPustular psoriasis may be localized or generalized.1,2 \nIn localized pustular psoriasis, the pustular lesions \nare confined to the hands and feet. The two clinical \nvariants are i) palmoplantar pustulosis (PPP) and ii) \nacrodermatitis continua of Hallopeau (ACH). PPP \nis a disease of adults with a female preponderance. \nIt is characterized by erythematous plaques studded \nwith sterile pustules in various stages of evolution \non both palms and soles (Figure 1a). Unlike PPP, \nACH affects both children and adults.  ACH start as \nchronic sterile pustules affecting tips of fingers or \ntoes but tend to extend slowly to surrounding skin \nand can affect the whole palms and soles (Figure \n1b). ACH may evolve into generalized pustular \npsoriasis (GPP). \n\n\n\nGPP is a rare and potentially life-threatening variant \nof psoriasis which is characterized by widespread \nerythema and sterile pustules. GPP was first reported \nin 1910 by Ludwig von Zumbusch who described \na patient with psoriasis vulgaris (PV) who suffered \nnine episodes of widespread pustular eruption over \na period of 20 years.3 Although there were many \n\n\n\nsubsequent case reports/series of GPP, only two \nincluded more than 100 patients.4-5 The earliest \nand largest case series with detailed clinical review \nof 104 GPP from all over Britain was published \nin 1968 by Baker and Ryan.4 Baker and Ryan \nclassified GPP into 4 clinical variants i) Acute GPP \nof von Zumbusch, ii) Annular Pustular Psoriasis, \niii) Localized variant of GPP and iv) Exanthematic \nGPP. \n\n\n\nClincal Variants of Generalized Pustular \nPsoriasis\n\n\n\nAcute Generalized Pustular Psoriasis\nAcute GPP of von Zumbusch is the most severe and \npotentially lethal variant of GPP.1-7 It is characterized \nby waves of widespread, fiery redness studded with \nsterile pustules that may coalesce to form lakes \n(Figure 1c-f). Affected skin is often painful and \ntender. Patients are usually uncomfortable, ill and \nfebrile with leucocytosis. Mucosal involvement \nmanifests clinically as cheilitis and geographic \ntongue (Figure 1g). Arthralgia/arthritis are \npresent in about 30% of patients.5 Complications \ninclude sepsis, renal, hepatic, respiratory and \ncardiac failure.1,2,6-8 GPP may remit and relapse \nspontaneously. The skin may revert to normal or \npatient may remain erythrodermic for weeks to \nmonths before achieving normal skin. Acute GPP \nmay or may not be associated with PV. About \n30% to 70% of patients had preceding psoriasis \nvulgaris.5 During the course of GPP, patients may \npresent with various subtypes of psoriasis including \n\n\n\nCorresponding Author\nAssociate Professor Dr Choon Siew Eng\nDepartment of Dermatology, Hospital Sultanah Aminah, \nJalan Persiaran Abu Bakar Sultan, 80100 Johor Bahru,\nJohor, Malaysia.\nEmail: choonse@yahoo.co.uk\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 3\n\n\n\npsoriasis vulgaris (PV), inverse, erythrodermic \nand annular pustular psoriasis suggesting common \npathophysiological mechanisms. Acute GPP, \nregardless of age at onset, is a chronic recalcitrant \ndisease in which acute pustular flares frequently \nrecur on exposure to classic triggers and also \nfor unknown reasons even when patients are on \nsystemic or biologic therapy.1-5,9\n\n\n\nAcute GPP is often provoked and the most \ncommon precipitating factor is the use of systemic \ncorticosteroid.4-5,7-12 Other systemic drugs reported \nto provoke GPP include but are not limited \nto lithium, progesterone, phenybutazone and \nantimalarial, fluoxetine, ustekinumab, infliximab \nand adalimumab.1,2,5,6,13-18 Other precipitating \nfactors include infections particularly upper \nrespiratory infections (URTI), sunlight, pregnancy, \nmenstruation and hypocalcemia.1,2,5,6,19 Excessive \nuse of irritant topical preparation such as coal tar \nmay cause GPP and use of potent topical steroid had \nalso been implicated.1,2,20 \n\n\n\nImpetigo Herpetiformis \nImpetigo herpetiformis or pregnancy-induced acute \nGPP is now believed to be the same disease as \nacute GPP since the majority of patients have other \ntriggers besides pregnancy.5,21-22\n\n\n\nAnnular Pustular Psoriasis (APP)\nAPP is a less acute variant of GPP characterized by a \nsubacute or chronic eruption of annular/serpiginous \nplaques with erythematous scaly or pustular margins \n(Figure 1h). 1,2,4-6,9,23 \n\n\n\nPatients are usually constitutionally well without \nfever, leucocytosis, arthritis or other organ \ninvolvement. Common aggravating factors are \nstress, URTI and menstruation. APP is known to be a \nmore benign variant of GPP that responds to topical \nagents4,5,9,19,21 but severe juvenile APP that failed \nconventional systemic therapy and conversion into \nacute GPP had been documented.5,9,23,24 \n\n\n\nLocalized Variant of GPP \nBaker and Ryan described localized pattern of \nGPP as pustulosis that occur in and around discoid \npsoriatic plaques which have glazed, deep red and \nnon-scaly surface overlying flat pustules. The most \ncommon trigger is superimposed bacterial infection \nand pustules usually settled promptly with systemic \nantibiotics.4 It is not uncommon for patients with \npsoriasis vulgaris to have pustular lesions during \nperiods of heightened disease activity, particularly \n\n\n\nfollowing the use of irritant topical agents or URTI.2,4,25 \nHowever, these patients are constitutionally well, \neven when they have widespread psoriatic plaques \nstudded with numerous pustules (Figure 1i). This \ngroup of patients would be more appropriately \ncalled psoriasis with pustulosis, which represent a \ntransient unstable phase of psoriasis vulgaris with \ngood prognosis and should not be lumped together \nwith GPP, a classic recalcitrant psoriasis. \n\n\n\nExanthematic GPP \nExanthematic GPP was described by Baker and \nRyan as sudden onset of sterile pustules in patients \nwith no previous history of psoriasis. It usually \nfollows an URTI or after ingestion of drugs used for \ntreating the URTI. Exanthematic GPP is self-limiting \nand resolves completely within a few weeks.4 This \ndescription is reminiscent of acute generalized \nexanthematous pustulosis (AGEP). AGEP is a \nrare, cutaneous reaction characterized by sudden \nonset of numerous, discrete, non-follicular, sterile \npustules on oedematous erythematous skin (Figure \n2a).26-27 AGEP is predominantly drug-induced but \nmay follow infections. Skin lesions appear rapidly \nwithin 1-3 days of drug exposure and upon drug \nwithdrawal, resolve rapidly within 15 days.\n\n\n\nMost dermatologists accept exanthematous GPP \nas AGEP. However, prevalence of psoriasis is \nhigher in patients with AGEP27-28 and association of \nAGEP with GPP had been documented. 29 IL36RN \nmutations which were reported in both AGEP \nand GPP may explain the clustering of these two \npustular eruptions.29 Although difficult, it is possible \nto distinguish AGEP from GPP in a patient with PV. \nFigure 3 showed characteristic features of acute \nGPP, namely widespread erythema studded with \npustules that form lakes of pus. Pustules in AGEP \nare pinpoint and discrete although they may rarely \ncoalesce to form sub-centimeter pustules. Unlike \nAGEP that resolves completely after 2 weeks, GPP \nusually lasts 2-3 months if left untreated.3-5,7,19 AGEP \ndoes not recur unless patients is re-exposed to culprit \ndrug but recurrent pustular flares is common in GPP. \nFever and neutrophilia are common to both AGEP \nand GPP but eosinophilia seen in 30% of AGEP is \nnot a feature of GPP.26-28 \n\n\n\nGPP and AGEP also share similar histologic \nfeatures. Spongiform epidermal micro-abscesses \nare seen in both GPP and AGEP (Figure 3a & b). \nHowever, in GPP, the micro-abscesses composed \nof only neutrophils whereas micro-absceseses in \nAGEP contain both neutrophils and eosinophils. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 394\n\n\n\nNecrotic keratinocyte reported in AGEP is also not \na feature of GPP. Neutrophil exocytosis and mild \ndermal edema are features of both conditions but \nsevere dermal oedema favours a diagnosis of AGEP. \nDermal infiltrate in GPP are usually more superficial \nthan in AGEP and composed of only lymphocytes. \nNeutrophils, if present, are few and confined to \npapillary dermis. Dermal infiltrate of AGEP are \nmixed neutrophil-rich infiltrate with conspicuous \neosinophils.28 Presence of typical histologic \nfeatures of psoriasis such as hyperkeratosis, regular \nacanthosis, hypogranulosis, suprapapillary plate \nthinning and the presence of tortuous, dilated blood \nvessels support a diagnosis of GPP but their absence \ndoes not rule out acute GPP. \n\n\n\nPathogenesis of GPP\nThe pathogenesis of GPP is unclear but is assumed \nto be similar to that of PV with an exaggerated \nresponse. Development of psoriasis is believed to \nbe due to complex interactions between genetic \nfactors, environmental factors and the dysregulated \nimmune response. In genetically predisposed \nindividuals, various environmental triggers or \nautoantigen namely LL37 stimulate keratinocytes \nto produce pro-inflammatory cytokines, including \nIL-1 which activate dendritic cells. Activated \ndendritic cells produce IL12 and IL23 which \npromotes differentiation of na\u00efve T cells to Th1 and \nTh17 cells respectively. The downstream cytokines \n(IL17, IL22, TNF\u03b1, IFN) released, further stimulate \nkeratinocytes to produce more pro-inflammatory \ncytokines and chemokines providing a positive \nfeedback to this inflammatory loop. \n  \nOver the past several years, IL36 has emerged \nas another important cytokine in psoriasis \npathogenesis.30 IL36 molecules are overexpressed \nin psoriatic plaques. IL36 belongs to IL1 family \nand like all IL1 family members, IL36 molecules \nare potent inducer of NF kappa B cytokine network \nwhich is also upregulated in psoriatic skin. Studies \nshowed that cytokines important in psoriasis \npathogenesis such as IL17, IL22, TNF\u03b1 and IFN \ncan induce human keratinocyte to produce IL36. \nSimilarly, it has been shown that IL-36 can stimulate \nhuman keratinocytes and induce the recruitment of \nimmune cells such as neutrophils, dendritic cells \nand T cells resulting in enhanced production of \npro-inflammatory cytokines and chemokines. The \nresultant mutually reinforcing inflammatory loop \namplifies and perpetuates the chronic inflammation \nseen in psoriasis.\n\n\n\nIL36 has 3 isoforms, IL36\u03b1, \u03b4 and \u03b3 and all three \nhave same biological activity because they bind \nto the same receptors (IL36R). All 3 isoforms are \nelevated in psoriasis. Activity of IL36 is modulated \nby IL36 receptor antagonist (IL36Ra) which \nis encoded by IL36RN gene. In 2011, IL36RN \nmutations were reported in 9 Tunisian families with \nfamilial acute GPP22 and also in 3 out of 5 unrelated \npatients with sporadic acute GPP.31 This lead to an \ninteresting observation that overexpression of IL36 \nis associated with PV whereas deficiency of its \nantagonist causes acute GPP. \n\n\n\nIL36RN mutations\nIL36RN codes for IL36Ra which modulates the \nactivities of IL36. Loss of function mutation \nabolishes the antagonistic effect of IL36Ra and allow \nuninhibited IL36 signalling. IL36RN mutations \nwere also detected in patients with ACH and PPP, \nproviding a genetic link between localized and \ngeneralized pustular psoriasis.32 Our group found \nIL36RN variants in 22% of ACH, 5% of PPP and \n15% of GPP. Ten Malaysians in this study harbour \nmutations but the allele affected, c.115+6T>C, is \ndifferent from British patients, p.Ser113Leu. 32 \n  \nc.115+6T>C variant was also the most prevalent \nallele in Han Chinese with GPP. This disease variant \nwas detected in 48% of 68 acute GPP patients \ncompared to only 3.6% of 365 normal controls in \na study from Shanghai.33 Homozygous mutation, \nwhich should result in disease, was identified in 2 \nnormal controls aged over 40-year-old, suggesting \nthat environmental triggers or mutations in additional \ngenes may be required for disease onset. This study \nshowed no IL36RN mutation in 113 patients with \nPV. Similar results were observed in another study \nfrom China.34 Disease variant c.115+6T was seen in \n46.7% of 62 sporadic GPP, 6.9% of PV and 6% of \nnormal controls. These studies confirmed the results \nof another study of 349 unrelated British patients \nwith familial PV which also showed no association \nof IL36RN variants with PV.35 \n\n\n\nSubsequent studies attempted to correlate IL36RN \ngenotype with clinical presentation of GPP. A small \nJapanese study showed that the majority of GPP \nwithout associated PV is due to IL36RN mutations \nwhich was seen in 82% of 11 patients with GPP \nalone compared to only 10% of 20 GPP patients with \nassociated PV.36 Similar finding was documented in \nanother small study from Germany where IL36RN \nmutations were present in 46% of 13 patients with \nGPP alone compared to only 17% of 6 patients with \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 5\n\n\n\nGPP and associated PV.37 Our group did a systematic \nreview of the clinical features and genetic status of \nan extended case series of 233 GPP patients and \nfound that the majority of patients with GPP alone \nharbour IL36RN mutations, thus validating the \nfindings of both the Japanese and German studies.38 \n\n\n\nRecessive IL36RN alleles were present in 49 \npatients (21% of 233 GPP). Prevalence of recessive \nIl36RN was highest among Asian (73.8% of \n172 patients) followed by European (21% of 49 \npatients) and African (5.2% of 12 patients). Single \ndisease alleles were present in 18 patients (7.7% \nof 233 patients). We showed that homozygous \nIL36RN mutations define a more severe phenotype \ncharacterized by early onset, low prevalence of PV \nand high-risk of systemic inflammation (defined as \nfever >380C and leucocytosis >12 X 109/L).38 We \nalso found that heterozygous IL36RN mutations \nincrease disease risk compared to normal population \ncontrols. Although high prevalence of systemic \ninflammation were seen in both groups of patients \nwith one or two disease alleles, disease onset was \nsignificantly delayed in heterozygous patients. \nThus, heterozygous patients may require a longer or \nmore intense exposure to environmental triggers to \nmanifest disease.\n\n\n\nIn our subsequent analysis of 27 Malaysians with \njuvenile GPP, 8 out of 20 patients (40%) screened, \nhave IL36RN mutations; 5 homozygous (115+6T>C/ \nc.115+6T>C), 1 compound heterozygous \n(c.115+6T>C/p.Ser113Leu) and 2 heterozygous \n(c.115+6T>C/negative).9  Within this small subset \nof 20 patients, we observed similar characteristics; \ni) prior PV was uncommon in IL36RN-positive \npatients (12.5% versus 66.6%, p=0.028), ii) disease \nonset was earlier in homozygous patients (median \nage at onset: 3.5 years versus 11.5 years, p=0.031) \nand  iii) 85.7% of patients with one or two disease \nalleles had systemic inflammation compared to \n27.3% of IL36RN-negative patients (p=0.050). \nAdditionally, we found that IL36RN-positive \npatients required long-term systemic maintenance \ntherapy. All eight IL36RN-positive patients, with a \nmean follow-up duration of 23.5 years (range 3.3 to \n45 years), were still dependent on systemic agents \nto prevent frequent relapses compared to 50% of \nIL36RN-negative patients (p=0.042). \n\n\n\nA very recent study from Taiwan, showed that 52% \nof 57 patients with various type of PP have IL36RN \nmutations.39 Mutations were seen in 75% 32 GPP, \n22% of 9 patients with localised GPP, and 14% \n\n\n\nof PPP but none of 2 patients with erythrodernic \npustular psoriasis. The authors identified early onset, \nrecurrent disease (more than two attacks) inverse \npsoriasis, a family history of pustular psoriasis and \nassociated ACH as correlates for IL36RN mutations. \nMutation rate was highest among patients with \nassociated ACH (93.8% vs 56.3% in those without \nACH).\n\n\n\nCARD14 mutations\nThe CARD14 (Caspase Recruitment Family \nMember 14) is a scaffold protein that mediates \nNF-kB signalling in keratinocytes. CARD14 \nmutations have been reported in familial psoriasis \nand pityriasis rubra pilaris.29 A systematic analysis \nof CARD14 mutation in 416 patients, done by \nour group, observed no disease alleles in subjects \nwith familial PV (n=159), erythrodermic psoriasis \n(n=23), acral pustular psoriasis (n=100) or sporadic \nPRP (n=29).40 Recently, CARD 14 mutation was \nidentified as a risk factor for GPP with associated \nPV in a Japanese population.41 Sugiura et al found \nCARD14 mutations with pASp176His substitution \nin 21 % of 19 GPP patients with associated PV, \nwhich was significantly higher than the 3% observed \nin 100 normal controls. No CARD14 mutation was \nfound in all 11 patients with GPP alone. \n\n\n\nOur group also found similar CARD14 variant \n(pASp176His) in 4 Chinese Malaysians with GPP. \nBut the association of CARD14 with PV concurrence \nis unconvincing as only two of our GPP patients \nwith mutations have associated PV. One patient \ninherited the variant from a maternal aunt. Although \nCARD14 mutations were detected in only a small \nnumber of patients, its frequency is significantly \nhigher than in normal controls.40 A meta-analysis of \nthe Japanese and our studies found that CARD14 \nmutations are significantly associated with GPP \nonly in the Chinese and Japanese populations. \nHowever, a recent Chinese study of 62 GPP and \n174 PV showed no association of CARD14 variants \nwith GPP or PV.42 More data is required to validate \nthe role of this low frequency CARD14 mutations in \nthe pathogenesis of GPP.\n\n\n\nTreatment of GPP\nThere is a lack of high quality evidence to guide \ntreatment of patients with GPP.  Furthermore, \nefficacy of administered treatment is difficult to \nassess because of the spontaneously self-limiting \nnature of this disease. A systematic review on \nthe treatment of pustular psoriasis, performed \nby the Medical Board of the National Psoriasis \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 396\n\n\n\nFoundation, USA, concluded that good quality data \non the treatment of pustular psoriasis is extremely \nlimited. The Medical Board recommends acitretin, \nmethotrexate, cyclosporine and infilximab as first \nline drug for patients with adult-onset GPP, based \non case reports, case series and uncontrolled open \nlabel trials.43 \n\n\n\nAcitretin is the preferred first-line agent. However, \nmethotrexate and cyclosporine are recommended \nas good alternatives. Infliximab is recommended \nto bring about a rapid response in patients with \nsevere acute disease. The recommended second-line \ntherapy for adult-onset GPP includes adalimumab, \netanercept and PUVA particularly in combination \nwith acitretin. Topical agents are only recommended \nfor limited disease or as adjunctive treatment. First-\nline drug recommended for GPP in children are \nsimilar except that etanercept is recommended \ninstead of infliximab. \n\n\n\nA more recent systematic review on the safety \nand efficacy of biologic therapy in erythrodermic \nand pustular psoriasis concluded that, although \nevidence is limited, biologics including infliximab, \nadalimumab, etanercept, ustekinumab and anakinra \nare effective in treating GPP.44 Secukinumab is \nregistered for the treatment of GPP in Japan after a \nphase III, open-label, multicentre, single arm study \ndemonstrated the efficacy and safety of secukinumab \nin 12 Japanese patients with GPP.45\n\n\n\nConclusion\nGPP is a chronic recalcitrant disease in which \nacute pustular flares frequently recur on exposure \nto classic triggers and also for unknown reasons \neven when patients are still on systemic or biologic \ntherapy. New insights into the genetic basis of \nGPP highlighted the central role IL1 and IL36 in \nthe pathogenesis of GPP. This has encouraged \nthe use of IL1 inhibitors46-48 in treating GPP. Both \nhomozgygous and heterozygous mutations in \nIL36RN confer disease risk. But IL36RN mutation \nis only found in a proportion of patients with GPP. \nOur group identified a clinical triad that may be used \nto prioritise IL36RN screening and targeted therapy \nwith IL36R antagonists. It would be interesting to \nsee discovery of additional genes or environmental \ntriggers that could explain the occurrence of GPP \nin patients without IL36RN mutations and the \npresence of homozygous mutations in in normal \ncontrols. Good quality randomised control trials are \nneeded to guide treatment of this potentially life-\nthreatening variant of psoriasis.\n\n\n\nConflict of Interest Declaration\nThe author has no financial/conflict of interest to \ndisclose.  \n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Johann E. Gudjonsson; James T. Elder. Psoriasis. \nFitzpatrick\u2019s Dermatology in General Medicine, 8th ed, \nchapter 18, McGraw-Hill Medical, New York, 2012.\n\n\n\n2. Griffiths CEM, Barker JNWN. Psoriasis. Rook\u2019s Textbook \nof Dermatology. 8th ed, Chichester, England: Wiley \nBlackwell 2010:20.1-20.60.\n\n\n\n3. von Zumbusch LR. Psoriasis and pustuloses exanthem. \nArch Derm Syph 1910;99:335-346.\n\n\n\n4. Baker H, Ryan TJ. Generalised pustular psoriasis: a clinical \nand epidemiological study of 104 cases. Br J Dermatol \n1968;80:771-93.\n\n\n\n5. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey \nKE, Chew SF. Clinical profile, morbidity, and outcome of \nadult-onset generalized pustular psoriasis: analysis of 102 \ncases seen in a tertiary hospital in Johor, Malaysia. Int J \nDermatol 2014;53:676-84.\n\n\n\n6. Zelickson BD, Muller SA. Generalized pustular psoriasis: \nA review of 63 cases. Am Acad Dermatol 1991;127:1339-\n45.\n\n\n\n7. Borges-Costa J, Silva R, Goncalves L, Filipe P, Soares de \nAlmeida L, Marques Gomes M. Clinical and laboratory \nfeatures in acute generalised pustular psoriasis: a \nretrospective study of 34 patients. Am J Clin Dermatol \n2011;12:271-6.\n\n\n\n8. Ryan TJ, Baker H. The prognosis of generalised pustular \npsoriasis. Br J Dermatol 1971;85:407-11. \n\n\n\n9. Lau BW, Lim DZ, Capon F, Barker JN, Choon SE.  Juvenile \ngeneralized pustular psoriasis is a chronic recalcitrant \ndisease: an analysis of 27 patients seen in a tertiary hospital \nin Johor, Malaysia. Int J Dermatol 2017;56:392-9.\n\n\n\n10. Baker H. Corticosteroids and pustular psoriasis. Br J \nDermatol 1976;94:83-7. \n\n\n\n11. Brenner M, Molin S, Ruebsam K, Weisenseel P, Ruzicka \nT, Prinz JC. Generalised pustular psoriasis induced by \nsystemic glucocorticosteroids: 4 cases and recommendation \nfor treatment. Br J Dermatol 2009;161:964-6.\n\n\n\n12. Ohkawara A, Yasuda H, Kobayashi H, Inaba Y, Ogawa H, \nHashimoto I et al. Generalized pustular psoriasis in Japan: \ntwo distinct groups formed by differences in symptoms and \ngenetic background. Acta Derm Venereol 1996;76:68-71.\n\n\n\n13. Hay RA, Pan JY. Paradoxical flare of pustular psoriasis \ntriggered by ustekinummab, which responded to \nadalimumab therapy. Clin Exp Dermatol 2014;39:751-2.\n\n\n\n14. Caca-Biljanovska N, V\u2019lckova-Laskoska M, Laskoski \nD. Successful management of ustekinumab-induced \npustular psoriasis without therapy discontinuation. Acta \nDermatovenerol Croat 2013;21:202-4.\n\n\n\n15. Wenk KS, Claros JM, Ehrlich A. Flare of pustular \npsoriasis after initiating ustekinumab therapy. J Dermatol \nTreat 2012;23:212-4.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 7\n\n\n\nFigure 1. (a) Palmoplantar pustulosis with characteristic pustules in various stages of evolution on both soles; (b) Acrodermatitis \nsuppurativa of Hallopeau with characteristic acral pustules that had extended to palms; (c)-(f) Acute generalized pustular psoriasis with \ncharacteristic wide-spread erythema studded with pustules and lakes of pus; (g) Geographic tongue and cheilitis seen in a patient with \nacute generalized pustular psoriasis; (h) Annular pustular psoriasis with characteristic lesions; (i) Psoriasis with pustulosis (also known \nas localized variant of generalized pustular psoriasis).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 398\n\n\n\nFigure 3. (a) & (b) Acute generalized pustular psoriasis showing spongiform intra- and sub-corneal micro-abscesses, acanthosis, supra-\npapillary plate thinning, tortuous papillary vessels and superficial infiltrate of lymphocytes (Haematoxylin-eosin stain). \n\n\n\nFigure 2. (a) Acute generalized exanthematous pustulosis with characteristics numerous discrete, pin-head sized pustules on erythematous \nand oedematous skin.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 9\n\n\n\n16. Gregoriou S, Kazakos C, Christofidou E, Kontochristopoulos \nG, Vakis G, Rigopoulos D. Pustular Psoriasis development \nafter initial ustekinumab administration in chronic plaque \npsoriasis. Eu J Dermatol 2011;21:104-5.\n\n\n\n17. Kato Y, Yamamoto T. Generalized pustular psoriasis \ntriggered by infliximab in two patients with Crohn\u2019s \ndisease. J Dermatol 2013;40:932-3.\n\n\n\n18. Kimura U, Kinoshita A, Haruna K, Mizuno Y, Sekigawa \nI, Takamori K et al. Generalized pustular  psoriasis-like \neruptions induced after the first use of adalimumab in the \ntreatment of psoriatic arthritis. J Dermatol 2012;39:286-7.   \n\n\n\n19. Jin H, Cho HH, Kim WJ, Mun JH, Song M, Kim HS et \nal. Clinical features and course of generalized pustular \npsoriasis in Korea. J Dermatol 2015;42:674-8.  \n\n\n\n20. Saeki H, Wanatabe A, Tada Y, Kakinuma T, Komine M, \nIhn H et al. Juvenile pustular psoriasis associated with \nsteroid withdrawal syndrome due to topical corticosteroid. \nJ Dermatol 2008;35:601-3. \n\n\n\n21. Chang SE, Kim HH, Choi JH, Sung KJ, Moon KC, Koh \nJK. Impetigo herpetiformis followed by generalised \npustular psoriasis: more evidence of same disease entity. \nInt J Dermatol 2003;42:754-5. \n\n\n\n22. Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei \nXY, Fraitag S et al. Interleukin receptor 36 antagonist \ndeficiency and generalized pustular psoriasis. N Engl J \nMed 2011;365:620-8. \n\n\n\n23. Liao PB, Rubinson R, Howard R, Sanchez G, Frieden \nIJ. Annular pustular psoriasis\u2014most common form of \npustular psoriasis in children: report of three cases and \nreview of the literature. Pediatr Dermatol 2002;19:19-25.\n\n\n\n24. Popadic S, Nikolic M. Pustular Psoriasis in Childhood and \nAdolescence: A 20-Year Single-Center Experience. Pediatr \nDermatol 2014;31:575-9.\n\n\n\n25. Naldi L, Gambini D. The clinical spectrum of psoriasis. \nClin Dermatol 2005;25:510-8.\n\n\n\n26. Sidoroff A, Halevy S, Bavinck JNB, Vaillant L, Roujeau \nJC. Acute generalized exanthematous pustulosis (AGEP) \n\u2013 A clinical reaction pattern. J Cut Pathol 2001;28:113-9.\n\n\n\n27. Sidoroff A, Dunant A, Viboud C, Halevy S, Bavinck \nJN, Naldi L et al. Risk factors for acute generalized \nexanthematous pustulosis (AGEP)-results of a \nmultinational case-control study (EuroSCAR). Br J \nDermatol. 2007;157:989-96.\n\n\n\n28. Halevy S, Kardaun SH, Davidovici B, Wechsler J. The \nspectrum of histopathological features in acute generalized \nexanthematous pustulosis: a study of 102 cases. Br J \nDermatol. 2010;163:1245-52.\n\n\n\n29. Sugiura K. The genetic background of generalized \npustular psoriasis: IL36RN mutations and CARD14 gain \nof function variants. J Dermatol Sci 2014;74:187-92.\n\n\n\n30. Towne JE, Sims JE. IL36 in psoriasis. Current Op \nPharmacol 2012;12:486-90.\n\n\n\n31. Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith \nCH, Pullabhatla V et al. Mutations in IL36RN/IL1F5 are \nassociated with the severe episodic inflammatory skin \ndisease known as generalized pustular psoriasis. Am J \nHum Genet 2011;89:432-7.\n\n\n\n32. Setta-Kaffetzi N, Navarini AA, Patel VM, Pullabhatla \nV, Pink AE, Choon SE et al. Rare pathogenic variants \nin IL36RN underlie a spectrum of psoriasis-associated \npustular phenotypes. J Invest Dermatol 2013;133:1366-9.\n\n\n\n33. Li M, Han J, Lu Z, Li H, Zhu K, Cheng R et al. Prevalent \nand rare IL36RN mutations in Chinese patients with \ngeneralized pustular psoriasis and psoriasis vulgaris. J \nInvest Dermatol 2013;133:2637-9.\n\n\n\n34. Li X, Chen M, Fu X, Zhang Q, Wang Z, Yu G et al. \n\n\n\nMutation analysis of the IL36RN gene in Chinese patients \nwith generalized pustular psoriasis with/without psoriasis \nvulgaris. J Dermatol Sci 2014;76:132-8. \n\n\n\n35. Berki DM, Mahil SK, Burden AD, Trembath RC, Smith \nCH, Capon F et al. Loss of IL36RN function does \nnot confer susceptibility to psoriasis vulgaris. J Invest \nDermatol 2014;134:271-3.\n\n\n\n36. Sugiura K, Takemoto A, Yamaguchi M, Takahashi H, \nShoda Y, Mitsuma T et al. The majority of generalized \npustular psoriasis without psoriasis vulgaris is caused by \ndeficiency of interleukin-36 receptor antagonist. J Invest \nDermatol 2013;133:2514-21.\n\n\n\n37. Korber A, Mossner R, Renner R, Sticht H, Wilsmann-\nTheis D, Schulz P et al. Mutations in IL36RN in patients \nwith generalized pustular psoriasis. J Invest Dermatol \n2013;133:2634-7.\n\n\n\n38. Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, \nArostegui JI et al. IL36RN mutations define a severe \nautoinflammatory phenotype of generalized pustular \npsoriasis. J Allergy Clin Immunol 2015;135:1067-70.\n\n\n\n39. Wang TS, Chiu HY, Hong JB, Chan CC, Lin SJ, Tsai TF. \nCorrelation of IL36RN mutation with different clinical \nfeatures of pustular psoriasis in Chinese patients. Arch \nDermatol Res 2016;308:55-63.\n\n\n\n40. Berki DM, Liu L, Choon SE, David Burden A, Griffiths \nCEM, Navarini AA et al. Activating CARD14 mutations \nare associated with generalized pustular psoriasis but \nrarely account for familial recurrence in psoriasis vulgaris. \nJ Invest Dermatol 2015;135:2964-70. \n\n\n\n41. Sugiura K, Muto M, Akiyama M. CARD14 c.526G4C \n(p.Asp176His) is a significant risk factor for generalized \npustular psoriasis with psoriasis vulgaris in the Japanese \nCohort. J Invest Dermatol 2014;134:1755-7.\n\n\n\n42. Qin P, Zhang Q, Chen M, Fu X, Wang C, Wang Z et al. \nVariant analysis of CARD14 in a Chinese Han population \nwith psoriasis vulgaris and generalized pustular psoriasis. \nJ Invest Dermatol 2014;134:2994-6.\n\n\n\n43. Robinson A, Voorhees ASV, Hsu S, Korman NJ, Lebwohl \nMG, Bebo BF Jr et al. Treatment of pustular psoriasis: From \nthe Medical Board of the National Psoriasis Foundation. J \nAm Acad Dermatol 2012;67:279-88.\n\n\n\n44. Levin EC, Debbaneh M, Koo J, Liao W. Biologic \ntherapy in erythrodermic and pustular psoriasis. J Drugs \nDermatol. 2014;13:342-54.\n\n\n\n45. Imafuku S, Honma M, Okubo Y, Komine M, Ohtsuki \nM, Morita A et al. Efficacy and safety of secukinumab in \npatients with generalized pustular psoriasis: A 52-week \nanalysis from phase III open-label multicenter Japanese \nstudy. J Dermatol 2016;43:1011-7.\n\n\n\n46. Viguier M, Guigue P, Pag\u00e8s C, Smahi A, Bachelez H. \nSuccessful treatment of generalized pustular psoriasis \nwith the intereukin-1-receptor antagonist anakinra: lack \nof correlation with IL1RN mutations. Ann Intern Med \n2010;153:66-7.\n\n\n\n47. Huffmeier U, Watzold M, Mohr J, Schon MP, Mossner \nRSuccessful therapy with anakinra in a patient with \ngeneralized pustular psoriasis carrying IL36RN mutations. \nBr J Dermatol 2014;170:202-4. \n\n\n\n48. Rossi-Semerano L, Piram M, Chiaverini C, De Ricaud \nD, Smahi A, Kon\u00e9-Paut I. First clinical description \nof an infant with interleukin-36-receptor antagonist \ndeficiency successfully treated with anakinra. Pediatrics \n2013;132:e1043-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3910\n\n\n\nREVIEW\n\n\n\nContact Allergic Dermatitis to Cosmetics and Topical Anti-ageing \nProducts\nRohna Ridzwan1, MRCP, Badrul Hisyam Zainudin2, Bachelor of Science\n\n\n\n1Department of Dermatology, Selayang Hospital, Selangor Darul Ehsan, Malaysia\n2Cocoa Downstream Research Division, Malaysian Cocoa Board, Negeri Sembilan, Malaysia\n\n\n\nSummary:\nThe main objective of this review article is to provide an update of the literature concerning delayed-\ntype reactions or contact allergic dermatitis caused by cosmetic and anti-ageing ingredients. We scan \nfor tips on how to recognize these reactions from the history and clinical signs. The common allergens \nreported include fragrances and preservatives. Be aware of the new allergens. There is a need to patch \ntest with some of the heavy metals because of their presence in cosmetics but besides nickel, cobalt \nand occasional mercury, heavy metals do not frequently cause allergic contact dermatitis.  They are \ndangerous because of their systemic toxicity on other internal organs. It is important to recognize \nthe source of the contact allergens that have been documented in various continents. Reports from \nAsian countries (India, China, Korea, Singapore, Malaysia and Japan) have been included to increase \nthe awareness of cosmetic induced contact allergic dermatitis in this region. This knowledge upon \nreflections may assist us in our own daily practice.\n\n\n\nKey words: Facial dermatitis, Hand dermatitis, Hair care dermatitis, Cosmetic intolerance, Antiageing\n\n\n\nIntroduction\nThe Oxford dictionary defines cosmetic as a \npreparation applied to the body, especially the \nface, to improve its appearance. The range covers \neverything from the latest cosmetics to skin, oral, \nnail and hair care. As for anti-ageing product, it is \ndesigned to prevent the appearance of ageing. Some \npatients do develop contact reactions to cosmetics \nand anti-ageing products by presenting with either a \ncosmetic intolerance syndrome or status cosmeticus, \nan immediate type I hypersensitivity reaction \n(contact urticaria or angioedema), contact irritant \nreaction or a delayed type IV hypersensitivity \nreaction (allergic dermatitis and photoallergic \ndermatitis). In this review, we focused on the last \nreaction.\n\n\n\nMaterials and Methods\nDifferent databases were searched: ScienceDirect, \nScopus, SpringerLink, Wiley, Taylor and Francis. \nA literature review was performed with the search \nterms [contact dermatitis] and [cosmetics], [contact \ndermatitis] and [anti-ageing product], [heavy \nmetal] and [personal care products], [cosmetic \nintolerance]. Parameters reviewed include burden \nof contact dermatitis, diagnosis, contact allergen, \nsource of the allergen and patient outcome. The \npublished literatures reviewed were from the year \n1987 to 2017.\n\n\n\nBurden and risk of Contact allergic \ndermatitis\nDe Groot1 et al studied 1609 individuals (838 men, \n771 women) in Netherlands. 196 (12.2%) of them \nclaimed to have suffered from side effects, none \nof the 20 tested patients showed any cosmetic \nallergy. De Groot2 et al also studied on 982 female \nclients of beauticians. 254 (25.9%) claimed to have \nexperienced cosmetic-related side effects in the \npreceding 5 years. \n\n\n\nCorresponding Author\nDr Rohna Ridzwan\nDepartment of Dermatology, Selayang Hospital,\nLebuhraya Selayang-Kepong, Batu Caves 40400, \nSelangor, Malaysia\nEmail: rohnaridzwan@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 11\n\n\n\nOne hundred and fifty women were tested with the \nEuropean standard patch test tray and cosmetic \nseries. Allergic reaction was considered \u201cproven\u201d \nin 3 patients (2%) and \u201cpossible\u201d in 7 (4.7%). The \nauthors concluded that allergy is responsible for less \nthan 10% of all reactions to cosmetics and toiletries2. \n\n\n\nIn Sweden, Lindberg3 noted out of 1075 patients \nattending patch test clinics, 509 reported or had \nprevious adverse reactions to cosmetics or skin \ncare products. Only 26.9 % (290/1075) had positive \npatch tests to cosmetic allergen3. The occurrence of \ncosmetic related contact dermatitis based on patch \ntest clinic studies varies from countries. It ranges \nfrom 6.7% in China4, 25.1% in Spain5, 74.2% in \nTurkey6 to 76% in India7.\n\n\n\nDefective skin barrier and a frequent application \nof skin care products could increase the risk of \ndeveloping contact allergy to such products3. \nIncrease use of cosmetics carries increase risk for \nadverse effects3. \n\n\n\nClinical features\nContact dermatitis is classified into irritant, \nallergic and photo contact dermatitis. Photocontact \ndermatitis is dermatitis that occurs on sun-exposed \nskin resulting from contact with photosensitizers. \nMaibach8 has termed cosmetic intolerance syndrome \nin people who present with burning, itching, stinging \nor tightness sensation to a range of cosmetic products \nbut have negative patch test results.\n\n\n\nDiagnostic Tools \nHistory\nCosmetic Contact dermatitis (CCD) is suspected \nif patient gives an obvious history of developing \ndermatitis at site of application of the cosmetics. \nSupporting evidence include clearance of dermatitis \nwhen usage is stopped (dechallenge) and recurrent \nof dermatitis upon applying the same cosmetic \n(rechallenge).\n\n\n\nFor patients who are unable to give the above history, \nthe site of the dermatitis (Table 1) can be used to \nalert the dermatologist to have a high suspicion \nof cosmetic/anti-ageing products causing contact \ndermatitis. CCD is commonly seen on the head \n(79.4%)5, scalp (10.53%)7, face (39.8% - 68.8%)4,6, \neyelids (32.5%)5, face and neck (10.7% - 21.05%) \n4,7, hands (9.68% - 36.6%) and extremities (11.8%).6\n\n\n\nInvestigations\nContact allergic dermatitis to cosmetics is suspected \nif there is a positive patch test to the leave-on \nproduct as is, to the diluted rinse off products and \nif patient has positive regular open application test \non the leave-on product. Diagnosis is confirmed \nif patient has positive patch test to the specific \ningredients in the product. Table 2 and 3 illustrate \nthe CCD presentations and the unsuspected contact \nallergens identified in the cosmetic and anti-ageing \ningredients respectively that include preservatives, \nfragrances, dyes, vitamin and new chemical \nadditives and other ingredients.\n\n\n\nIn instances where patients are not sure which \ncosmetics and anti-ageing products are the triggering \nfactor for their dermatitis, the dermatologist could \ninvestigate using a different approach; recognizing \nthe pattern of contact dermatitis, choosing additional \ncosmetic, preservatives, fragrance, hairdressing and \nmetal series that are relevant for patch testing. Patch \ntesting with additional substances related to cosmetic \nand skin care products, increases the chances of \nidentifying the cosmetic allergen in patients who do \nnot react to standard series.3 The cosmetic allergens \ndetected in the Western and Eastern countries varied \nslightly (Table 4).\n\n\n\nAmong the common preservatives used in cosmetics, \ncontact dermatitis to isothiazolinones especially \nmethylchloroisothiazolinone/methylisothiazolinone \n(MCI/MI or Kathon CG), parabens formaldehyde \nand  Methyldibromoglutaronitrile (MDBGN) are \ndocumented in the 3 continents4-5,7,9-10,30-34 (Table 4). \nNow in Europe,36 the use of MBDGN is prohibited \nin cosmetic products  and in Japan,37 the use of MCI/\nMI is prohibited in leave-on products. \n\n\n\nIt is interesting to note that Abitol, Gallate and \nThimerosal allergy are mainly noted in Asians4,7,10,32 \n\n\n\nTable 5 is highlighted to increase the clinicians\u2019 \nawareness and enables them to trace the source of \nthese 3 allergens. The specific fragrance allergens \napart from cinnamates have been identified in \ncentres where fragrance series is available for patch \ntest.9, 30-32\n\n\n\nFor the past few years, positive patch test to nickel, \ncobalt and occasionally mercury was noted in \npatients presenting with facial dermatitis. (Table 6). \nAre they relevant? Goh40 et al in 1989 documented \ncontact dermatitis from nickel in eye shadow. Then, \nWeldon41 et al in 2000 reported mercury poisoning \nassociated with a Mexican beauty cream.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3912\n\n\n\nTable 1. Sites of dermatitis associated with cosmetic dermatitis.\n\n\n\nSite of dermatitis Source of allergen Authors\n\n\n\nScalp Hair dyes, permanent waves, shampoos, hair sprays and perfumes Kumar7, Ortiz9, Vazquez5.\n\n\n\nFace Face cream, shaving creams, cosmetics\nMake\u2013up, moisturizer, nail and hair-care\n\n\n\nKumar7, Lee10, Ada6, Li4, Ortiz9, Lindberg3 \n\n\n\nEars Hair dyes, permanent waves, shampoos, hair sprays, and perfumes Ortiz9 \n\n\n\nEyelids Eye and nail cosmetics Lee10, Ada6, Ortiz9, Vazquez5 \n\n\n\nLips Lipsticks, oral hygiene products (toothpaste, mouthwash and dental \nfloss), gum, and mints \n\n\n\nKumar7, Lee10, Ortiz9 \n\n\n\nNeck Perfumes, nail varnish Kumar7, Lee10, Lindberg4 Ortiz9\n\n\n\nFace, lips and Neck Hair dye, skin care and make up Kumar7, Lee10 \n\n\n\nScalp, face, neck and upper \nlimbs \n\n\n\nHair dye Li4 \n\n\n\nHands Hair care, soap cosmetics, moisturizers, cleansing products, \nperfumes, make-up, nail and hair care products\n\n\n\nKumar7, Ada6, Li4, Ortiz9\n\n\n\nTrunk Hair care, soap, moisturizers, cosmetics, cleansing products, \nperfumes, \n\n\n\nOrtiz9 \n\n\n\nExtremities Cleansing products Ada6\n\n\n\nWidespread Skin care products Li4\n\n\n\nTable 2. Presentations of CCD and identification of new or unsuspected contact allergens in the cosmetic ingredients. \n\n\n\nCosmetic allergen Reaction pattern Authors\n\n\n\n3-iodo-2- propynyl \nbutylcarbamate (IPBC) \n\n\n\nRecurrent itchy papular facial dermatitis noted in a lady after using a cosmetic \ncream preserved with Glycacil-L. Her dermatitis resolved completely after she \nstopped using this cream. Patch test showed positive reactions to thimerosal 1% \npetrolatum. Glycacil-L 0.1% aqua and Glycacil-L 0.01% aqua and also Iodopropynyl \nbutylcarbamate 0.1% petrolatum (Chemotechnique Diagnostics\u00ae). IPBC is the active \ningredient of Glycacil-L (Lonza\u00ae Inc., Fair Lawn, NJ), a cosmetic preservative. \n\n\n\nPazzaglia11 1999 \n\n\n\nPlant extracts High prevalence of allergy to plant extracts in patients with cosmetic dermatitis when \ntested to a plant series. Plant extracts are frequently used as perfume ingredients in \ncosmetic products e.g. shampoo, mouthwash, soaps, deodorant and sunscreen. Most \ncommon plant allergy seen was to tea-tree oil. \n\n\n\nThomson12 2000 \n\n\n\nSodium dihydroxycetyl \nphosphate (SDP)\n\n\n\nAcute severe confluent oedematous eczema localized to the face, neck and hands in a \nlady after using 3 different herbal moisturizing creams. Patch test was positive to Dr. \nScheller, Arnica, herbal blossom, hand cream (Apotheker Dr. Scheller, G\u00f6ppingen, \nGermany). The concentration of sodium dihydroxycetyl phosphate (Dragophos S \n2/918501, Dragoco Inc., PA, USA) in the cream was given as in the range of 1\u20135%. \nPatch tests showed a reaction to SDP only and to SDP allergen extract.\n\n\n\nLomholt13 2001\n\n\n\nSodium myristoyl sarcosinate \nand sodium myristoate mixture \n\n\n\nFacial dermatitis in a lady after using Oil of Ulay gentle foaming facial wash. She \nreacted only to Oil of Ulay gentle foaming face wash 1% aqua, with erythematous \ninfiltration on Day 4. She develops severe local irritating reaction on Day 3 of \nRepeated open application test (ROAT) with Oil of Ulay gentle foaming face wash. \nShe reacted only to sodium myristoyl sarcosinate (SMS) 1% in water with red \ninfiltration seen on Day 2 and Day 4 when patch tested with the ingredients of Oil of \nUlay gentle foaming face wash.\n\n\n\nMalanin14 2002\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 13\n\n\n\nAnti-ageing allergen Reaction pattern   Authors\n\n\n\nVitamin C in anti-ageing cream Oedematous erythematous lesions on the eyelids that spread to the remainder of the \nface and neck in a woman. She had positive reactions to chromate, which was not \nrelevant, and to a cosmetic cream, Active C dry skin\u00ae (La Roche Posay Laboratory) \nthat had been used before onset of the eczema. Subsequent patch tests with the \ningredients of this cream showed positivity only to ascorbic acid 5% aqua.\n\n\n\nBelhadjali22 2001\n\n\n\nTable 3. Presentations of CCD and identification of new or unsuspected contact allergens in the antiageing ingredients.\n\n\n\nVitamin K Facial especially periorbital dermatitis 4 months after using topical cosmetic \nAuriderm K2\u00ae cream (Auriga International S.A., Waterloo, Belgium), a mixture \ncontaining vitamin K1 and retinol to decrease periorbital hyperpigmentation. Patch \ntests with the ingredients of this product were positive to vitamin K1 2% petrolatum \nand trans-vitamin K 2% petrolatum. \n\n\n\nVeneziano15 2005 \n\n\n\nOxybenzone Photoallergic contact cheilitis after applying lip cosmetic. Veysey16 2006 \n\n\n\nCopolymers Perioral itching and eczematous dermatitis, which had spread to the cheeks and ears \nin a lady who had used several cosmetic products, including 2 purple-colored lipsticks \nand 2 lip balms. Patch test positive reaction to 1 of the purple-colored lipsticks only. \nPositive patch test reactions to ingredients of the lipstick polyvinylpyrrolidone \n(PVP)/ hexadecene copolymer diluted 10% (++), 5% (++), and 1% (+) in petrolatum. \n\n\n\nQuartier17 2006\n\n\n\nHydrolyzed wheat protein Intense burning over face, neck, and scalp in a lady several hours after applying \na new moisturizing cosmetic cream. Negative patch test result to the standard, \ncosmetic, hairdressing, and facial series. Noted positive patch test to own \u2018gel pour le \ncol\u2019 Gatineau\u00ae cream. She also had positive patch tests to hydrolyzed wheat protein \n50% aqua, the diluted constituents of the cosmetic \u2018neck cream\u2019. \n\n\n\nHann18 2007\n\n\n\nPentylene glycol Facial dermatitis with swelling of the eyelids occurred after using toleriane riche \ncream (La Roche Posay Laboratories, La Roche Posay, France) and L. Widmer body \nlotion. Patch test was positive to L. Widmer body lotion as is and to its ingredient \npropylene glycol (5% aqua). Patch test was also positive to Toleriane riche cream as \nis but patch test was negative to its ingredient, pentylene glycol (5% in aqua). ROAT \nto pentylene glycol (5% in aqua) was positive on Day 3.\n\n\n\nKerre19 2008 \n\n\n\nDiazolidinyl urea or \nimidazolidinyl urea \n\n\n\nDermatitis on the hands with occasional spread to the face and neck in a lady after \nusing for almost a month, body cream, Deliplus leche limpiadora\u00ae (Cosme \u0301ticos \nRNB\u00ae). She used Deliplus regeneradora\u00ae and Deliplus Aloe Vera\u00ae (Cosme \u0301ticos \nRNB\u00ae S.L.; Valencia, Spain) as moisturizer since onset of symptoms. Patch test \npositive to diazolidinyl urea, imidazolidinyl urea, and her own products  \u2018as is\u2019. \nDeliplus leche limpiadora\u00ae and Deliplus regeneradora\u00ae contains diazolidinyl urea. \nDelilpus Aloe Vera\u00aecontains imidazolidiny urea. \n\n\n\nGarc\u0131a-Gav\u0131n20 2010 \n\n\n\nMenthoxypropanediol Perioral erythema and scaling noted after applying lip balm (Blistex Med plus). \nROAT and Patch test positive to Blistex Med plus tested as is. Patch test positive \nto 5% Menthoxypropanediol in petrolatum (Blistex Med plus ingredient). Patch test \nnegative for rest of ingredients of Blistex Med plus\u00ae. \n\n\n\nFranken21 2013   \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3914\n\n\n\nHydroxydecylubiquinone \n(idebenone) \n\n\n\n1) 47-year-old Caucasian woman developed a severe, oedematous and vesicular \ndermatitis of the face, ears, and neck within 24 hrs. after receiving facial treatment \nwith an anti-ageing\u2019 cream.  Positive patch test reaction only to the anti-ageing \ncream. Positive patch test reaction was also noted to idebenone 0.5%, one of the \nindividual ingredients of the cream premixed in petrolatum at the concentration \nused in the finished product. \n2) Sudden onset of a red, itchy, burning, swollen face in a 38 year-old lady after a 2nd \napplication of Prevage MD\u00ae, an anti- ageing facial cream manufactured by Elizabeth \nArden, Inc. (New York, NY, USA). Positive patch test reactions at D4 and D7 with \nnickel sulfate 0.5%, propolis 10% and Prevage MD. The components of Prevage \nMD did not include propolis. A positive reaction (+++) to hydroxydecylubiquinone \n(idebenone) 1%, in a pet. from Pharma Cosmetix Research, LLC, Richmond, VA, \nUSA, at D4 and D7 readings. \n3) Itchy rash noted on the face and neck 2 days after facial treatment Prevage anti-\nageing cream (Elizabeth Arden, London, UK) applied at a Beauty salon. Positive \npatch test reaction to her Prevage anti-ageing cream and to nickel. Patch testing to \nthe individual ingredients of the Prevage anti-ageing cream premixed in petroleum \nat the concentrations used in the final product provided by manufacturer showed \nreaction to 0.5% idebenone.\n\n\n\nSasseville23 2007\n\n\n\nAleer24 2008\n\n\n\nNatkunarajah25 2008 \n\n\n\nTetrahydroxypropyl ethylenediamine Recurrent eyelid dermatitis, which extended to the face and \u2018V\u2019 of her neck after \napplication of Roc anti-ageing creams. Patch test positive to i) tetrahydroxypropyl \nethylenediamine in Roc anti-ageing creams ii) methylisothiazolinone in a shampoo \nand a hair and body cleanser\n\n\n\nGoossens26 2011\n\n\n\nGlycofilm\u00d2 1.5P Eczematous lesions involving the face, neck, and trunk in a lady that developed \n2 months after the daily application of an anti-wrinkle cream. Positive path test \nreactions to colophonium and to the anti- wrinkle cream \u2018as is\u2019. Patch test with the \ningredients of the cream, which were provided by the manufacturer, gave positive \nreactions to Glycofilm\u00ae 1.5P (Solabia, Pantin, France), an aqueous solution \ncontaining biosaccharide gum-4 (CAS no. 283602-75-5), and phenoxyethanol. \n\n\n\nFoti27 2013\n\n\n\nMagnolia of cinalis 1) A lady develop acute vesicular, oedematous and pruritic dermatitis of the face \na few days after applying a new \u2018anti-ageing\u2019 day care cream on her face. She had \nused a similar cream for night care a few months earlier, but had stopped using \nit after 3 months because of redness and itching. Both products contained the \nsame key ingredient, Magnolia of cinalis bark extract. Positive patch test to facial \nanti-ageing cream, EucerinTM Volume-Filler Day Care Dry Skin, tested \u2018as is\u2019. \nA repeated open application test with the suspected cream (twice daily, 5 \u00d7 5-cm \napplications) on the volar aspect of the forearm; this was strongly positive at D3. \nPatch test was positive to only one of the ingredients of the cream Magnolia of \ncinalis bark extract 0.5% petrolatum.  \n2) A 2nd lady developed itchy eczematous lesions on the neck, V-neck and face \nfor 2 months. Positive reactions were observed to Eucerin\u00ae volume ller day \ncream (Beiersdorf, Hamburg, Germany), Magnolia of cinalis bark extract 0.5% \nin petrolatum as provided by the company and to tixocortol pivalate. No clinical \nrelevance could be found for the latter reaction. She also had Positive patch \ntest reactions to Magnolia grandi ora bark extract (INCI) [0.05% in petrolatum \nprovided by Clinique, Estee Lauder (Brussels, Belgium)] cosmetics. \n3) A lady developed scaling erythematous lesions on the face, mainly on the \nforehead and the temporal area. She was using several cosmetic products (including \nEucerin\u00ae volume ller night cream) and she dyed her hair regularly. Patch test was \npositive to only Eucerin\u00ae volume ller night cream and to Magnolia of cinalis bark \nextract 0.5% petrolatum.\n4) A lady presenting with itchy and scaly erythematous lesions on the face and \nV-neck region, as well as recurrent oedema of the eyelids for 4 months. Lesions \ncompletely disappeared after stopping her cosmetics. Patch test were performed \nwith Nivea\u00ae Cellular anti-age day cream SPF 15 (Beiersdorf) which contain \nMagnolia of cinalis bark. There were positive reactions to the cream tested \u2018as is\u2019 \nand to the Magnolia of cinalis bark extract. This patient also reacted positively to \nMagnolia grandi ora bark extract in eye cream and serum from the same brand.\n\n\n\nRaison-Peyron28 2015\n\n\n\nGhys29 2015\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 15\n\n\n\nSensitizers Americans (United States9) Caucasian (Spain5, Germany30, 31) Asian                                                                     \n(China4, India7, Korea10 \nMalaysian32, Singaporean,33-34 \nJapan35)\n\n\n\nPreservatives MCI/MI \n\n\n\nParabens\n\n\n\nFormaldehyde \n\n\n\nImidazolidinyl urea  \n\n\n\n                                                                         \nCocamidopropyl betaine \n\n\n\n\n\n\n\nThimerosal\nBronopol            \nGlycerylthioglycolate                 \n\n\n\nMCI/MI5,30-31                \n\n\n\nParabens5,30-31                                     \nFormaldehyde resin5,30-31                \nFormaldehyde donors30-31 \nImidazolidinyl urea30-31 \nDiazolidinylurea30-31 \nDMDM hydantoin30-31 \nCocamidopropyl betaine30-31 \nMBDGN5,30-31  \nIodopropynyl butylcarbamate30-31 \nQuaternium-1530-31\n\n\n\nBronopol30-31 \nGlycerylthioglycolate30-31 \nPropylene glycol30-31\n\n\n\nMCI/MI10,32-34                                               \n\n\n\nParaben mix32-34                                               \nFormaldehyde4,32\n\n\n\nImidazolidinyl urea4 \nDiazolidinylurea33 \n\n\n\n                                                                                                           \nMBDGN10, 32-34                                               \nIodopropynyl butylcarbamate32                    \nQuaternium-1510, 32-34                                               \nThimerosal4, 7, 10,32  \n\n\n\nBronopol10                        \n\n\n\nAbitol5,10,32                            \nGallate mix8, 10\n\n\n\nDodecyl Gallate32                    \nOctyl Gallate4                          \nSorbitan monooleate4         \nSorbitan sesquioleate32       \nIsopropyl myristate4,32 \nBenzalkonium chloride10        \nCrotan BK10                   \nChlorphenesin10                 \nTriethanolamine10                    \nPovidone iodine32                    \nSodium disulfide32           \n\n\n\nFragrances Fragrance mix \nBalsam of Peru \nCinnamic aldehyde             \nEssential oil \n\n\n\nFragrance Mix5,30-31                \n\n\n\n                                                  \nBalsam of Peru5 \nJasmine5                           \nIsoeugenol5 \nOak moss absolute5 \n\n\n\nFragrance mix4, 7, 10, 32 \n\n\n\nFragrance Mix I34                    \n\n\n\nFragrance Mix II32, 34                  \nBalsam of Peru32                  \nJasmine32                             \nAbsolute Eugenol32              \nCinnamic aldehyde32                  \nCinnamic alcohol32                     \nAmyl cinnamic alcohol32 \nBenzyl alcohol32                            \nD Limonene32                  \nHydroperoxide of linalool32       \nHydroperoxide of limonene \nEgyptian32\n\n\n\nLyral32\n\n\n\nDyes PPD PPD30                                   PPD4,7,10,32-34\n\n\n\nEmulsifiers Lanolin alcohol Lanolin & derivatives30-31 Amerchol L 1014,10,32\n\n\n\nSunscreen Oxybenzone   Avobenzone UV filters30-31\n\n\n\nSkin whitening agent Kojic acid35\n\n\n\nNail polishes  \n                                               \nArtificial nails\n\n\n\nToluene sulfonamide \n\n\n\nformaldehyde resin                         \n\n\n\nMethyl methacrylate \n\n\n\nOthers Aloe botanical products Tocopherol linoleate, Vitamin E \n\n\n\nderivative (antioxidants) 30-31\n\n\n\nCetrimide7\n\n\n\nTable 4. Common cosmetic allergens in Americans, Caucasian and Asian.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3916\n\n\n\nTable 5. Preservative allergens in cosmetic products noted in mainly in Asians.\n\n\n\nPreservatives Allergens Products38-39\n\n\n\nAbitol (plasticizer)\n\n\n\n\n\n\n\nHair colour, conditioner, lightener, relaxer, straightener Eye shadow, eyeliner, mascara, \nconcealer, makeup remover \nLip balm, lip colour, lip colour remover\nTeeth whitener\nSkin whitening cream Shaving cream and gel\nFacial cleaner, powder and anti-ageing product\nFace, body & hand cream\nBody lotion, cleanser and wipes\nSunscreen\n\n\n\nGallate mix (antioxidant) Hair conditioners \nLipstick\nFacial moisturizers, foundation, facial cleanser\nBody wash, cleansers, lotions\n\n\n\nThimerasol (preservative) Make-up removers\nEye moisturizers\nEye shadows                                                                   \nMascaras\n\n\n\nIn Malaysia, Ong and Rohna32 also noted patch test \npositivity to heavy metals in patients with facial \ndermatitis and cheilitis after using cosmetics. The \nauthors suspect these patients sustain facial and \nperioral dermatitis because of contact to cosmetics \ncontaining the metal allergen. The presence of heavy \nmetals in cosmetics and personal care products \nhave been proven and documented in the literatures \n(Table 6). The fear of presence of heavy metals \nin cosmetics is mainly in the toxicity following \nsystemic absorption rather than them causing \nallergic contact dermatitis with the exception of \nnickel and cobalt. The latter are present in standard \nallergen series. \n\n\n\nAuthors\u2019 view: If we do not patch test patients with \nother metals that are present in cosmetics, we will \nprobably miss the contact allergic dermatitis to \nthese metals. \n\n\n\nNickel salts are used as dye mordant and pigments. \nChromium may be intentionally added to cosmetics \nas dyes.49 Copper compound are used as biocides in \nmedicated cream and soap.49 Cobalt and arsenic are \npresent as impurities. Lead is not an ingredient of \nthe lipsticks; it might be present as impurities in the \ncolor additives. Ayenimo et al stated that an impurity \nis a substance not intentionally added to a product, \nbut rather is either a byproduct of the manufacturing \nprocess, formed by the breakdown of ingredients, or \nan environmental contaminant of raw ingredients.49 \n\n\n\nZinc oxide have characteristics ideal for use as a \nbroad-spectrum inorganic ultraviolet (UV) radiation \n\n\n\nblocking material in personal-care products.49, 55 \n\n\n\nMercury is used in skin whiteners because the metal \nblocks production of melanin, which gives hair and \nskins their pigmentation. Mercury salts inhibit the \nformation of melanin by competing with copper \nin the action of the enzyme tyrosinase.41 Al-Saleh \net al.53 noted facial whitening creams produced in \nThailand, Lebanon and England contained the \nhighest levels of mercury, ranging from 1,281 to \n5,650 ppm. \n\n\n\nIn Mexico, phenyl mercury and its salts as well as \nthimerosal, are allowed as cosmetic preservatives \nonly in eye make-up to a maximum permissible \nmercury concentration of 0.007% (w/v)56, whereas \nas color additives, mercury and its compounds are \nallowed up to 1 ppm.57 There is a risk of hazard if their \npresent in cosmetics exceeds the allowed regulation \nlimits observed in each country. Chromium and \ncadmium are prohibited in cosmetics.58 Patient \nwho is already sensitized to these metals, contact \ndermatitis may occur even at lower permissible \nconcentration.44 \n\n\n\nManagement\nAfter identifying the contact allergen from the \npositive patch or photo patch test, the relevance \nof the positive patch test needs to be ascertained.  \nCurrent vs. past relevance or unknown relevance \nhave to be determined. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 17\n\n\n\nTable 6. Presence of heavy metals in cosmetics.\n\n\n\nHeavy metals Products Authors\n\n\n\nAluminum Lipstick \nCompact powder, foundation\n\n\n\nLiu42 \nMutaz43\n\n\n\nArsenic Eye shadow                                          \nLipsticks, lip glosses, skin whitening creams \n\n\n\nSainio44\n\n\n\nAdepoju-Bello45\n\n\n\nBarium Lipstick\nEye shadow \nFacial powder\nBody lotion\nSunscreen\n\n\n\nMutaz43\n\n\n\nAbabneh46\n\n\n\nBismuth Eye shadow \nLipstick\nFacial powder\nFace, body and hand cream\nBody lotion\nSkin whitening cream\nSunscreen\n\n\n\nAbabneh46\n\n\n\nCadmium Lipstick \nLipsticks (brown) lip glosses \nCompact powder\nSkin whitening creams \n\n\n\nMutaz43 Amit47\n\n\n\nLiu42 Adepoju-Bello45 Ziarati48   \n\n\n\nMutaz43\n\n\n\nAdepoju-Bello45 Ayenimo49 \n\n\n\nChrome Eyeshadow                                                                     \nLipstick                                                     \nHenna                                                      \nCompact powder, foundations              \nmoisturizing creams  \nSkin whitening cream, Sunscreen              \nSoap \n\n\n\nSainio44 Mutaz43 Ababneh46\n\n\n\nLiu42 Ababneh46 Ullah51\n\n\n\nMutaz43\n\n\n\nMutaz43 Ababneh46\n\n\n\nAbabneh46 \nAyenimo49 \n\n\n\nCobalt Eyeshadow\nCompact powder, foundations             \nMoisturizing creams\nSunscreen\n\n\n\nSainio44 Ababneh46\n\n\n\nMutaz43Ababneh46Ullah50  \n\n\n\nMutaz43 Ullah50  \n\n\n\nAbabneh46\n\n\n\nCopper Hair cream and non-medicated cream\nEye shadow\nLipstick\nFacial powder\nFace, body and hand cream\nBody lotion\nSunscreen\n\n\n\nLiu42Ayenimo49 \n\n\n\nAbabneh46\n\n\n\nIron Face, body and hand cream\nEye shadow\nLipstick\nFacial powder\nBody lotion\nSkin whitening cream\nSunscreen\n\n\n\nAbabneh46 Ullah50 \n\n\n\nAbabneh46\n\n\n\nLead Eyeliner, eye pencil \nEye shadow \nHenna, compact powder                        \nLipsticks (pink) n, lip glosses                     \nSkin whitening creams                                \nSoap, shampoo\n\n\n\nUllah50Nnorom51 \n\n\n\nMutaz43 Sainio44 \n\n\n\nMutaz43\n\n\n\nLiu42 Adepoju-Bello45 Ziarati48Piccinini52\n\n\n\nLiu42 Adepoju-Bello45\n\n\n\nAmit47\n\n\n\nManganese Lipstick\nEye shadow \nFacial powder\nSkin whitening cream\nSunscreen\n\n\n\nLiu42\n\n\n\nAbabneh46\n\n\n\nMercury Lipsticks, lip glosses skin \nWhitening creams\n\n\n\nAdepoju-Bello45\n\n\n\nAdepoju-Bello45 Al-Saleh et al.53 \n\n\n\nPeregrino 54\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3918\n\n\n\nNickel Eyeshadow                                                                         \nLipsticks, lip glosses                                \nHenna, compact powder                                                           \nSkin whitening cream                                    \nFace, body and hand cream, body lotion \nSunscreen\n\n\n\nGoh40 Mutaz43 Ababneh46\n\n\n\nMutaz43 Ababneh43                                     \n\n\n\nAbabneh46Adepoju-Bello45  \n\n\n\nAbabneh46\n\n\n\nSelenium Eye shadow \nFacial powder\nFace, body and hand cream\nBody lotion\nSkin whitening cream\nSunscreen\n\n\n\nAbabneh46\n\n\n\nStrontium Eye shadow \nFacial powder\nFace, body and hand cream\nBody lotion\nSunscreen\n\n\n\nAbabneh46\n\n\n\nZinc Shampoo\nHair cream\nEye shadow\nLipstick\nFacial powder\nFace, body and hand cream\nBody lotion\nSkin whitening cream\nSunscreen\nSoap\n\n\n\nUllah50\n\n\n\nAyenimo49\n\n\n\nAbabneh46\n\n\n\nIf the positive patch test is relevant to patient\u2019s \ncurrent dermatitis, then the patient needs to be \ninformed and educated on the possible sources \nof the allergen because allergen avoidance can \nprevent recurrent or improve symptoms of contact \ndermatitis. Thus it is prudent to know the source of \nthe contact allergen (Table 1, 2, 3, 5 and 6). Contact \ndermatitis to cosmetic or anti-ageing products \nusually resolved after stopping using these products \nand avoiding other products that contain similar \nallergen.\n\n\n\nAuthors\u2019 view: Early resolution is possible if patient \navoid all relevant or abstain from all cosmetics \nfor a month especially during the acute attack \nof dermatitis. In some patients, with severe and \nwidespread contact dermatitis, a short course of \nsystemic steroid is required for dermatitis to resolve. \n\n\n\nContact dermatitis to pseudo cosmetics\nFisher59, Helbling60, Beck60 and Fujiko Soga et \nal61 reported allergic contact dermatitis simulating \ncosmetic dermatitis caused by contact dermatitis to \nrubber sponge applicator for cosmetics.\n\n\n\nDiethyldithiocarbamate was one of the rubber \nchemicals responsible for the contact dermatitis.60\n\n\n\nChallenges to diagnosis\nIn most instances especially in local setting, patient \nchanges their skin and hair care products frequently \nand are unable to ascertain which product causes \ntheir dermatitis. The habit of throwing products \nimmediately when contact dermatitis occurs prevents \nfurther patch test on patient\u2019s own product and \nidentifying the contact allergen.  Thus often we have \nto rely on positive patch test to commercial patch \ntest series to identify the allergen.  Unfortunately in \nthe local setting not all Dermatology centres have \nfacilities for patch testing and unable to perform \npatch testing to confirm allergic contact dermatitis \nfrom cosmetic ingredients e.g. preservative, \nfragrance, hairdressing etc.\n\n\n\nSimilarly, not many centres have the expertise and \nlaboratory facilities to perform cosmetics product \ndilution, extraction and thin layer chromatography \nfor patch testing. Thus the actual contact allergen \nin patient\u2019s own product cannot often be identified. \n\n\n\nTo prevent the occurrence of similar adverse \nreaction from cosmetics and anti-ageing products \nwe also analysed for presence of heavy metals, \nretinols, hydroquinone and banned chemicals. Once \nthese chemicals are detected, the cosmetic products \nwill be deregistered as cosmetic product and then \nconfiscated.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 19\n\n\n\nPatients may know the allergen after patch test that\nthey should avoid but often they do not know the \nsources of the allergen.  They need to be educated \non which product to avoid because of the absence of \ningredients labelling. Avoidance is also difficult in \nallergens that display the synonyms on product label. \nPatients are unaware that hypoallergic cosmetics \nmay have preservatives and fragrance that can \ncause contact dermatitis. Many essential oils were \nnot classed by the cosmetics industry as a source of \nfragrance and these accounted for a large proportion \nof the plant extracts found in those products labeled \nas fragrance-free.12\n\n\n\nAuthors view: Individuals with severe fragrance \nallergy, it is advisable for them to avoid cosmetics \ncontaining plant extracts.\n\n\n\nBernedo62 et al highlighted the possibility of the \n\u201cconnubial\u201d contact dermatitis where the source of \ncontact allergen comes from direct contact with a \nclose partner. Thus it is useful to enquire whether \npatient\u2019s consort uses cosmetic that contains the \nallergen. A detail history of exposure to allergen in \nshared cosmetics at home, work and hotel or among \nfriends should be sought. Avoidance of contact to \nthe allergen is the key to prevention of recurrent \ncontact dermatitis.\n\n\n\nConclution\nPrevention of recurrent or persistent dermatitis as \na result of contact allergic dermatitis to cosmetics \nrequires identification of the causative allergen, \ndetermining the relevance of the positive patch test \nallergen and finally tracing the source of allergen \nand educating the patient to avoid the allergen. \nIn patients with suspected CCD, we recommend \nadding preservatives, fragrance and metal allergens \nthat are common in the local region for patch testing \nto achieve higher diagnostic yield.\n\n\n\nConflict of Interest Declaration\nThe author declared no conflict of interests.\n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n1. Groot AC, Nater JP, Lender R, Rijcken B. Adverse effects \n\n\n\nof cosmetics and toiletries: a retrospective study in the \ngeneral population. Int J Cosmet Sci 1987;9:255-9.  \n\n\n\n2. De Groot A, Beverdam E, Ayong C, Coenraads P, Nater \nJ. The role of contact allergy in the spectrum of adverse \neffects caused by cosmetics and toiletries. Contact \nDermatitis 1988;19:195-201.\n\n\n\n3. Lindberg M, Tammela M, Bostrom A, Fischer T, Inerot A, \nSundberg K et al. Are adverse skin reactions to cosmetics \nunderestimated in the clinical assessment of contact \ndermatitis? A prospective study among 1075 patients \nattending Swedish patch test clinics. Acta Derm Venereol \n2004;84:291-5.\n\n\n\n4. Lin-Feng Li, Guangren Liu, Jing Wang.  Patch test \nin Chinese patients with allergic contact dermatitis to \ncommon cosmetic from a European Cosmetic series.  \nContact Dermatitis 2007;57:50-4.\n\n\n\n5. Gomez Vazquez M, Fernandez-Redondo V, Toribio J. \nAllergic contact eczema/dermatitis from cosmetics. \nAllergy 2002;57:268-9. \n\n\n\n6. Ada S, Seckin D. Patch testing in allergic contact dermatitis: \nis it useful to perform the cosmetic series in addition to the \nEuropean standard series? JEADV 2010;24:1192-6.\n\n\n\n7. Kumar P, Paulose R.\n \nPatch testing in suspected allergic \n\n\n\ncontact dermatitis to cosmetics. Hindawi Publishing \nCorporation Dermatology Research and Practice. http://\ndx.doi.org/10. 1155/2014/695387.\n\n\n\n8. Maibach H, Engasser P. Management of cosmetic \nintolerance syndrome. Clin Dermatol 1988;6:102-7. \n\n\n\n9. Ortiz KJ, Yiannias JA. Contact dermatitis to cosmetics, \nfragrances, and botanicals. Dermatologic Therapy \n2004;17:264-71.\n\n\n\n10. Lee SS, Hong DK, Jeong NJ. Multicenter study of \npreservative sensitivity in patients with suspected cosmetic \ncontact dermatitis in Korea. Journal of Dermatology \n2012;39:677-81.\n\n\n\n11. Pazzaglia M, Tosti A. Allergic contact dermatitis from \n3-iodo-2- propynyl butylcarbamate in a cosmetic cream. \nContact Dermatitis 1999;41:290-304.\n\n\n\n12. Thomson KF, Wilkinson SM. Allergic contact dermatitis \nto plant extracts in patients with cosmetic dermatitis. BJD \n2000;142:84-8.\n\n\n\n13. Lomholt H, Suresh C, Rastogi, Klaus E Andersen. Allergic \ncontact dermatitis from sodium dihydroxycetyl phosphate, \na new cosmetic allergen? Contact Dermatitis 2001;45:143-\n5.\n\n\n\n14. Malanin KEN. Contact dermatitis caused by a mixture of   \nsodium myristoyl sarcosinate and sodium myristoate in \ncosmetic product. Contact dermatitis 2002;47:50.\n\n\n\n15. Veneziano L, Silvani S, Voudouris S, Tosti A. Contact \ndermatitis due to topical cosmetic use of Vitamin K. \nContact Dermatitis 2005;52:113-4.\n\n\n\n16. Veysey EC, Orton DI. Photoallergic contact cheilitis \ndue to oxybenzone in a lip cosmetic. Contact Dermatitis \n2006;55:54. \n\n\n\n17. Quartier S, Garmyn M, Becart S, Goossens A. A contact \ndermatitis to copolymers in cosmetics. Contact Dermatitis \n2006;55:257-67.\n\n\n\n18. Hann S, Hughes M, Stone N. Contact Dermatitis Allergic \ncontact dermatitis to hydrolyzed wheat protein in a \ncosmetic cream. Contact Dermatitis 2007;56:119-20.\n\n\n\n19. Stefan Kerre. Allergic contact dermatitis to pentylene glycol \nin a cosmetic cream. Contact Dermatitis 2008;58:122-3.\n\n\n\n20. Garc\u0131a-Gav\u0131n J, Gonzalez-Vilas D, Fernandez-Redondo V, \nToribo J. Allergic contact dermatitis in a girl due to several \ncosmetics containing diazolidinyl urea or imidazolidinyl \nurea. Contact Dermatitis 2010;63:49-50. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3920\n\n\n\n21. Franken L, de Groot A, Laheij-de Boer AM.  Allergic \ncontact dermatitis caused by menthoxypropanediol in a lip \ncosmetic. Contact Dermatitis 2013;69:375-85. \n\n\n\n22. Belhadjali H, Giordano- Labadie F, Bazex J. Contact \ndermatitis from Vitamin C in a cosmetic anti-ageing cream. \nContact Dermatitis 2001;45:31.\n\n\n\n23. Sasseville D, Moreau L, Al-Sowaidi M. Allergic contact \ndermatitis to idebenone used as an antioxidant in an anti-\nwrinkle cream. Contact Dermatitis 2007;56:117-8.\n\n\n\n24. Mc Aleer MA, Collins P. Allergic contact dermatitis \nto hydroxydecyl ubiquinone (idebenone) following \napplication of an anti-ageing cosmetic cream.  Contact \nDermatitis 2008; 59:178-9.\n\n\n\n25. Natkunarajah J, Ostlere L. Allergic contact dermatitis \nto idebenone in an over-the-counter anti-ageing cream. \nContact Dermatitis 2008;58:239. \n\n\n\n26. Goossens A, Baret I, Swevers A. Allergic contact \ndermatitis caused by tetrahydroxypropyl ethylenediamine \nin cosmetic products. Contact Dermatitis, 2011;64:158-84. \n\n\n\n27. Foti C, Romita P, Guida S, Antelmi A, Bonamonte D. \nAllergic contact dermatitis caused by Glycofilm\u00d2 1.5P \ncontained in an anti-wrinkle cream. Contact Dermatitis \n2013;69:181-91.\n\n\n\n28. Raison-Peyron N, C\u00e9saire A, Du-Thanh A, Dereure \nO. Allergic contact dermatitis caused by Magnolia of \ncinalis bark extract in a facial anti-ageing cream. Contact \nDermatitis 2015;72:398-421.\n\n\n\n29. Ghys K, De Palma A, Vandevenne A, Werbrouck J, \nGoossens A. Magnolia of cinalis bark extract, a recently \nidentified contact allergen in \u2018anti-ageing\u2019 cosmetics. \nContact Dermatitis 2015;73:119-32.\n\n\n\n30. TL Diepgen, E Weisshaar. Contact dermatitis: \nepidemiology and frequent sensitizers to cosmetics. J Eur \nAcad Dermatol Venereol 2007;21(S2):9-13.\n\n\n\n31. White IR, de Groot AC. Cosmetics and skin care products. \nIn: Frosch PJ, Menne T, Lepoitevin JP. Contact Dermatitis, \n4th ed. Berlin-Heidelberg-New York, Springer, 2006:493-\n506. \n\n\n\n32. Ong SB, Rohna R. A 2\u2013year restrospective study of contact \ndermatitis to cosmetics in a public hospital. 2017. Paper \npresented at Malaysian Annual Dermatology Conference \nin 2017 August at Kuala Lumpur.\n\n\n\n33. Cheng S, Leow YH, Goh CL, Goon A. Contact sensitivity to \npreservatives in Singapore: frequency of sensitization to 11 \ncommon preservatives 2006-2011. Dermatitis 2014;25:77-\n82.\n\n\n\n34. Ochi H, Cheng SW, Leow YH, Goon AT. Contact allergy \ntrends in Singapore - a retrospective study of patch test \ndata from 2009 to 2013. Contact Dermatitis 2017;76:49-\n50.\n\n\n\n35. Mikio N, Keiichi K, Kyozo K. Contact dermatitis to kojic \nacid in skin care products. Contact dermatitis 1995;32:9-\n13.\n\n\n\n36. Urwin R, Wilkinson M. Methylchloroisothiazolinone and \nmethylisothiazolinone contact allergy: a new \u2018epidemic\u2019. \nContact Dermatitis 2013:68:253-5. \n\n\n\n37. Scherrer MAR, Rocha VB. Increasing trend of sensitization \nto methylchloroisoth- iazolinone/methylisothiazolinone \n(MCI/MI). An Bras Dermatol 2014:89:527. \n\n\n\n38. Dermnet New Zealand website. https://www.dermnetnz.\norg/topics/contact-allergy-to-preservatives/\n\n\n\n39. US Department of Health library website. https://www.\nnih.gov/research-training/library-resources.\n\n\n\n40. Goh CL, Ng SK, Kwok SF. Allergic contact dermatitis from \nnickel in eyeshadow. Contact Dermatitis 1989;20:380-1. \n\n\n\n41. Weldon MM, Smolinski MS, Maroufi A, Hasty BW, Gilliss \n\n\n\nDL et al. Mercury poisoning associated with a Mexican \nbeauty cream, West J Med 2000;173:15-8. \n\n\n\n42. Liu S, Hammond SK, Rojas-Cheatham A. Concentrations \nand potential health risks of metals in lip products, \nEnvironmental Health Perspectives 2013;121:705-10.\n\n\n\n43. Al-Qutob MA, Alatrash HM, Abol-Ola S. Determination \nof different heavy metals concentrations in cosmetics \npurchased from the Palestinian markets by ICP/MS. AES \nBioflux 2013;5:289-93.\n\n\n\n43. Sainio EL, Jolanki R, Hakala E, Kanerva L. Metals and \narsenic in eye shadows. Contact Dermatitis 2000;42:5-10.\n\n\n\n44. Adepoju-Bello AA, Oguntibeju OO, Adebisi RA, Okpala \nN, Coker HAB. Evaluation of the concentration of \ntoxic metals in cosmetic products in Nigeria. African J \nBiotechnology December 2012;11:16360-4. \n\n\n\n45. Ababneh, FA, Abu-Sbeih KA, Al-Momani IF. Evaluation \nof allergenic metals and other trace elements in personal \ncare products, Jordan J Chem 2013;8:179-90.\n\n\n\n46. Amit SC, Rekha B, Atul KS, Sharad SL, Dinesh KC, \nVinayak ST. Determination of Lead and Cadmium in \ncosmetic products. J Chemical and Pharmaceutical \nResearch 2010;2:92-7.\n\n\n\n47. Ziarati P, Moghimi S, Arbabi-Bidgoli S, Oomi M. Risk \nAssessment of heavy metal contents (lead and cadmium) \nin lipsticks in Iran. Int J Chemical Engineering and \nApplications 2013;3:6.\n\n\n\n48. Ayenimo JG, Yusuf AM, Adekunle AS, Makinde OW. \nHeavy metal exposure from personal care products. Bull \nEnviron Contam Toxicol 2010;84:8-14.\n\n\n\n50. Ullah H, Noreen S, Fozia, Rehman A, Waseem A, Zubair \nS et al. Comparative study of heavy metals content \nin cosmetic products of different countries marketed \nin Khyber Pakhtunkhwa, Pakistan, Arabian J Chem \n2017;10:10-8.\n\n\n\n51. Nnorom IC, Igwe JC, Oji-Nnorom CG. Trace metal \ncontents of facial (make-up) cosmetics commonly used in \nNigeria. African J Biotech 2005;4:1133-8.\n\n\n\n52. Piccinini P, Piecha M, Torrent SF. European survey on \nthe content of lead in lip products. J Pharm and Biomed \nAnalysis 2013;76:225-33.\n\n\n\n53. Al-Saleh I, Al-Doush I.  Mercury content in skin lightening \ncreams and potential health hazards to the health of Saudi \nwomen. J. Toxicol. Environ. Health 1997;51:123-30. \n\n\n\n54. Peregrino CP, Moreno MV, Miranda SV, Rubio AD, Leal \nLO. Mercury levels in locally manufactured Mexican \nskin lightening creams. Int. J Environ Res Public Health \n2011;8:2516-23.\n\n\n\n55. Yabe S, Yamashita M, Momose S, Tahira K, Yoshida S, \nRuixing Li et al. Synthesis and UV-shielding properties \nof metal oxide doped ceria via soft solution chemical \nprocesses. Int J Inorg Mater 2001;3:1003-8.\n\n\n\n56. Health Ministry. Agreement that defines the banned and \nrestricted substances in the manufacture of perfumes and \nbeauty. Official Journal of the Mexican Federation, 21 May \n2010. \n\n\n\n57. Raw Materials for Food, Perfume and Beauty Products. \nDyes and Pigments. Sanitary Specifications; Official \nMexican Norms, NOM-118-SSA1-1994, Goods and \nServices. http://www.salud.gob.mx/unidades/cdi/\nnom/118ssa14.html.\n\n\n\n58. Council Directive 76/768/EEC of 27 July 1976 on the \napproximation of the laws of the Member States relating to \ncosmetic products (that cosmetic must not contain Cd and \nCr), Official Journal L 1976;262:169-200.\n\n\n\n59. Fisher AA. Allergic contact dermatitis stimulating cosmetic \ndermatitis. Cutis 1993; 51:320-1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 21\n\n\n\n60. Helbling I, Beck M H. Rubber sponge applicator \nresponsible for cosmetic facial dermatitis. Contact \nDermatitis 1998;39:43.\n\n\n\n61. Soga F, Katoh N, Inoue T, Kishimoto S. Allergic contact \ndermatitis as a result of diethyldithiocarbamate in a rubber \ncosmetic sponge. Contact Dermatitis 2008;58:116-7. \n\n\n\n62. Bernedo N, Audicana MT, Uriel O, Velasco M, Gastaminza \nG, Fern\u00e1ndez E et al. Contact dermatitis from cosmetic \napplied by the patient\u2019s girlfriend. Contact dermatitis \n2004;50:252-3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3922\n\n\n\nORIGINAL ARTICLE\n\n\n\nVascular Anomalies: A 3-Year Review in the Paediatric Institute \nHospital Kuala Lumpur Between 2013 And 2015\nFei Yin Ng1, MRCP, AdvMDerm, Min Moon Tang1, MRCP, AdvMDerm, Sabeera Begum2, MMed, Kin Fon Leong2, \nMRCPCH\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Paediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nVascular anomalies, regardless of tumour or malformation, may result in significant morbidity. The \ndiagnosis of vascular anomalies in the paediatric group is always challenging. We aim to describe the \npattern of vascular anomalies referred to the Paediatric Institute Kuala Lumpur Hospital (PIKLH). \n\n\n\nMethods: \nThis is a 3-year retrospective review on vascular anomalies among children referred to PIKLH between \n2013 and 2015.\n\n\n\nResults: \nThere were 289 children; male to female ratio of 1:2.1; aged from birth to 14 years with median age of \n5 months recruited. The referring diagnoses included haemangioma (71.3%), capillary malformation \n(13.8%), lymphatic malformation (1.7%), kaposiform hemangioendothelioma (1.0%) and others. A \nhundred and sixty-one (55.7%) had lesions located at the head and neck region, followed by trunk \n(14.2%), lower limbs (9.3%), upper limbs (7.6%), perineum (3.8%) and multiple sites (6.9%). In 197 \npatients (68.2%), there were no further investigations performed, 13.5% had ultrasonography, 7.3% \nhad MRI, 4.8% had both ultrasonography and MRI; 4.1% had skin biopsy, 0.3% had angiogram. \nThe final diagnoses were haemangioma (72.3%) of which 10 were ulcerated; capillary malformations \n(17.6%), combined vascular malformations (2.4%), kaposiform hemangioendothelioma (2.8%), \nlymphatic malformations (2.1%); venous malformations (1.4%); tufted angioma (1.0%) and \narteriovenous malformations (0.3%). One hundred and nine patients (37.7%) received beta-blockers; \n71(24.6%) underwent laser, 16(5.5%) received sirolimus, 9(3.1%) received systemic corticosteroids \nwith vincristine, 4(1.4%) had systemic corticosteroids, 3(1.0%) had excision and 2(0.7%) had \nsclerotherapy. The remaining patients were put under observation.  \n\n\n\nConclusion:\nThree-quarters of the vascular anomalies referred were hemangioma followed by vascular   \nmalformations. Vascular anomalies have a large variation in clinical presentation. Expertise in \nthe diagnosis and management modalities are essential to achieve optimum outcomes. Therefore \nvascular anomalies are best managed in a multidisciplinary setting. \n\n\n\nKey words: Vascular anomalies, Hemangioma, Vascular malformation, Vascular tumour\n\n\n\nCorresponding Author\nDr Ng Fei Yin\nDepartment of Dermatology, Hospital Kuala Lumpur, \n50586 Jalan Pahang, Kuala Lumpur\nEmail: willow_fy02@yahoo.com\n\n\n\nIntroduction\nVascular anomalies encompass a spectrum of \nendothelial disorders ranging from benign, self-\nlimiting birthmark to lethal neoplasms. The overall \nincidence of vascular anomalies is conventionally \nconsidered rare as there is no registry on vascular\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 23\n\n\n\nanomalies available to accurately describe the \nepidemiology. Most of the current epidemiological \ndata reported in the literature are subjected to \nchallenge mainly due to the inconsistency of \ndiagnostic criteria and nomenclature1. In addition, \nmany specialties are actively involved in the \ndirect care to these groups of patients. Hence the \nprevalence data audited by various disciplines are \nprobably bound to interest bias. \n\n\n\nAccording to the International Society for the Study \nof Vascular Anomalies (ISSVA), vascular anomalies \nwere divided into two main groups which included \nvascular malformation and vascular tumour.2,3 \nBriefly, vascular malformation is a congenital error \nof endothelial morphogenesis with stable endothelial \nturnover. It differs from vascular tumour, which is \ncharacterized by endothelial cell hyperplasia.4 In the \npast, misnomers were common in the description \nof vascular anomalies. Hemangioma was often \nmisused to label vascular malformations.5\n\n\n\nManaging children with vascular anomalies is \nchallenging. Vascular anomalies can result in \nnot only physical complications such as severe \npain, ulcerations, infection, bleeding, thrombosis, \ndisfigurement, soft tissue overgrowth, local structure \ncompression, growth retardation, but with great \npsychosocial impact as well.5  An accurate diagnosis \nand proper management of vascular anomalies \nwould most often require a multidisciplinary \nteam approach. In this retrospective review, we \naim to describe the nomenclature of the vascular \nanomalies presented to our center based on the latest \nclassification together, the demographic data and \nthe management approach.\n\n\n\nMaterials and Methods\nA retrospective review on all cases with a diagnosis \nof vascular anomalies referred to the Paediatric \nInstitute Kuala Lumpur Hospital between 2013 and \n2015 was performed. The patients\u2019 medical records \nwere manually retrieved from the record office. \nData was obtained by reviewing patients\u2019 case notes \nand further analyzed by simple statistics using IBM \nSPSS\u00ae Statistics version 23.\n\n\n\nResults\nThere were a total of 289 children with a diagnosis \nof vascular anomalies recruited in this audit. As \nshown in Table 1, the age of patients at the point \nof referral ranged from 0 (at birth) till 14 years. \nTwo-third of the subjects were females. Majority \n\n\n\nwere Malays (63%) followed by Chinese (25.3%) \nand Indian (8%). This was similar to the Malaysian \nethnic composition.\n\n\n\nMore than half of the vascular anomalies presented \non the head and neck region (Table 2). Approximately \n7% of the patients had lesions on multiples sites \nof the body. In the objective assessment of the \nvascular anomalies, radio-imaging was required in \none-quarter of the cases as demonstrated in Table \n2. Ultrasonography was performed in 13.5% of \npatients, magnetic resonance imaging (MRI) in \n7.3% of patients and angiogram in 0.3% of patients. \nAbout 4% of the patients underwent skin biopsy.\n\n\n\nFollowing a proper physical examination by \nconsultant pediatric dermatologists, radiological \nand laboratory investigations, hemangioma (95%) \nwas found to be the most common vascular tumor, \nas demonstrated in Table 3. Female patients \nwere twice the number of males in the vascular \ntumour group. There were 8 cases of kaposiform \nhemangioendothelioma and 3 cases of tufted \nangioma in this cohort. Of these, two patients \ndeveloped Kasabach-Merritt Phenomenon. PHACE \nsyndrome was recognized in 3 patients with \nsegmental haemangioma. Capillary malformation \n(73.9%) was the most frequent vascular \nmalformation noted, followed by combined vascular \nmalformations (10.1%), lymphatic malformations \n(8.7%), venous malformation (5.8%) and arterio-\nvenous malformation (1.4%).\n\n\n\nPatients were treated with various treatment \nmodalities. About 40% of patients with vascular \ntumours were counseled and were followed up \nwith observation. About two-fifth of patients with \nvascular tumor received solely beta-blocker. The rest \nunderwent laser treatment, systemic corticosteroids, \nsirolimus, vincristine or combination treatment. \nHowever, nearly 92% of those with vascular \nmalformation required intervention (Table 4). \nTwo-third of patients with vascular malformations \nreceived laser treatment, and were mainly those \nwith capillary malformation.\n\n\n\nDiscrepancy in the diagnosis between the referring \nclinicians and the paediatric dermatologists was \nidentified in 10% of cases as shown in Table 5. These \nincluded inability to recognize vascular anomalies, \ninability to differentiate between vascular tumours \nand vascular malformation, and finally inability to \nrecognize the aggressiveness of the tumour. The \nreferring clinicians were paediatricians.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3924\n\n\n\nDiscussion\nThe complexity and heterogeneity of vascular \nanomalies often leads to misdiagnosis, under-\ndiagnosis and mismanagement. Based on literature \nreview on vascular anomalies, imprecise use of \nterminology was prevalent in both medical and \nsurgical disciplines.4 The term \u201chemangioma\u201d was \nused erroneously in up to 70% of the literature \nand almost 20% of patients received incorrect \nmanagement due to incorrect nomenclature used.4 \nEven in a center with an interest in handling \nvascular anomalies, the understanding of the \nterminology was found to be inconsistent.6 Virchow \nfirst classified vascular anomalies using the terms \nsimple, cavernous or racemose \u201cangiomas\u201d based \non each histological characteristics in 1863.7 In \n1982, Mulliken and Glowacki recommended a \nbinary classification of vascular anomalies based \non the endothelial characteristics.1 The International \nSociety for the Study of Vascular Anomalies \n(ISSVA), officially founded in 1992, adopted the \nbinary classification in 1996. The updated ISSVA \nclassification system in 2014 expanded the scope \nto genetic and pathologic characteristics of the \nvascular anomalies.2 The simplified version of \nISSVA classification for vascular anomalies is \nshown in Table 6.\n\n\n\nThe Pediatric Institute Kuala Lumpur Hospital is \nthe tertiary referral center for pediatric vascular \nanomalies in Malaysia. Vascular tumors (76.1%) \nwere more commonly observed compared to \nvascular malformations in this audit. Similar to other \nstudies shown in Table 7, infantile hemangioma was \nthe commonest vascular tumor encountered and \nwas associated with female predominance.  Data \nfrom China showed that the male to female ratio of \nvascular malformation was comparable to our audit.8 \nStudy from Canada however had an equal gender \ndistribution for vascular malformation.9 Amongst \nthe vascular malformations 73.9% were capillary \nmalformations. Mixed low-flow malformations \nwere the next most frequently seen vascular \nmalformations. In other studies, apart from capillary \nmalformation, venous and lymphatic malformations \nwere diagnosed more often. 10-12 \n\n\n\nComprehensive clinical history and physical \nexamination are important in the diagnosis of vascular \nanomalies as observed in our setting. Diligent use \nof radio-imaging are helpful in the management \nof vascular anomalies, not only in diagnosis, but \nalso for assessing the extent of lesions, evaluating \ncomplications and response to therapy.13,14 MRI \n\n\n\nimaging are helpful for large and extensive lesions, \nlesions in and around joints, visceral involvement \nand complex and syndromic vascular anomalies.15,16 \nTissue biopsy and histopathological examination \n(HPE) is the gold standard for diagnosis of locally \naggressive and malignant vascular tumor. Careful \ninterpretation of radio-imaging and HPE from tissue \nbiopsy is crucial to initiate an appropriate treatment \nplan.\n\n\n\nInfantile hemangioma located at non-vital areas of \nthe body are managed conservatively i.e. \u201cactive \nnon-intervention\u201d. This includes education of care \ntakers on the natural history of infantile hemangioma, \nserial photographic documentation of lesions \nand close monitoring of patients every 2-4 weeks \nespecially during the first 3 months of age.  \u201cActive \nnon-intervention\u201d was nevertheless provided \nto only about 9% of our patients with vascular \nmalformation. Most of the vascular malformations, \nespecially capillary malformation, in our cohort \nrequired vascular laser and interestingly none of \nthe patients with vascular malformation underwent \nsurgical intervention. \n\n\n\nHistorically, treatment of complicated vascular \nanomalies was mainly surgical, and medical therapies \nincluding corticosteroids and chemotherapy were \nless effective.17 Nevertheless, oral propranolol \nand sirolimus have been recently recognized to be \neffective in the management of vascular anomalies. \nOral propranolol and sirolimus have been used as a \ntreatment option for vascular anomalies since 2012 \nin our center. Since its approval by United States \nFood and Drug Administration (FDA) in 2014, \npropranolol has replaced systemic corticosteroids \nas first line therapy for complicated infantile \nhemangioma. A number of general paediatricians \nhowever, as observed in our audit, had initiated \noral propranolol inappropriately for patients with \nvascular malformation before referring to us, \nassuming a diagnosis of haemangioma. Sirolimus \nwas used alone and as combination with other \nagents for both vascular tumor and malformation \nin our cohort. Sirolimus, with its anti-proliferative \nand antiangiogenic effects was used initially for \nrecalcitrant Kaposi hemangioendothelioma with \nKasabach-Merritt phenomenon.18 Subsequently, it \nwas also reported to be useful in the treatment of \nlymphatic malformation, capillary lymphatic venous \nmalformation, phosphatase and tensin homolog \n(PTEN)-associated vascular anomalies and venous \nlymphatic malformations.19-21 More recently, it \nwas also reported to be effective for complicated \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 25\n\n\n\ninfantile hemangioma refractory to conventional \ntherapy.22\n\n\n\nMatilla KA et al reviewed 480 patients who were \nreferred as vascular anomalies and noted majority \n(89.2%) of the vascular tumors were diagnosed \ncorrectly. Nevertheless most of the vascular \nmalformations (62.0%) were misdiagnosed. The \nreferring parties had great difficulty in establishing \nan accurate diagnosis in conditions such as venous \nmalformations, arteriovenous malformations \nand combined slow\u2013flow malformations. Most \nmisdiagnosed cases were labelled as hemangioma.12 \nIn another retrospective review of 5621 patients \nreferred with vascular anomalies, Greene AK et al \nillustrated that only 53.0% of patients had a correct \nreferral diagnosis. Vascular tumors were more likely \nto be accurately diagnosed (70.4%) than vascular \nmalformations (45.6%).23 MacFie et al then again \nobserved inaccurate diagnosis was given to 69% of \ntheir patients with vascular lesions.24\n\n\n\nOverall, we had about 10% of patients in our \ncohort with incorrect referral diagnosis. This is \nmuch lower as compared to other reports.4,12,23,24 \nThis could be because the referring clinicians \nin our cohort were pediatricians and majority \nof them had had prior communications with \nthe receiving paediatric dermatologists before \nsending the patients to our center.  Establishing an \naccurate diagnosis of vascular anomalies can be \nchallenging for many clinicians who have limited \nexperience in this field. Differentiating vascular \ntumours from vascular malformations can be \ndifficult especially in infancy. Further classification \nof the subtypes of vascular malformation \nrequires additional expertise like imaging and \nskin biopsy. Besides, treatment of patients with \nvascular anomalies frequently involves numerous \nsubspecialties namely neonatologist, surgeon, \n\n\n\noncologist, hematologist, interventional radiologist, \ngeneticist, dermatologists, otorhinolaryngologist, \nophthalmologist, neurosurgeon, cardiologist, \npathologist, physiotherapists, occupational therapist \netc.  Vascular anomalies clinic that provides a \ncomprehensive and multidisciplinary care would be \nthe forward in future.\n\n\n\nSince it is a retrospective review, some demographic \nand clinical data were incomplete. This is the major \nlimitation. There were patients who were followed \nup in other centers after the initial diagnosis was \nmade with treatment plan outlined, thus data on the \nprogress of these patients were regrettably unable to \nbe traced. This audit nevertheless highlights the lack \nof understanding and confusion among clinicians in \nthe diagnosis of vascular anomalies. We recommend \nthat a national registry on pediatric vascular \nanomalies to be designed in order to accurately \ndescribe these conditions in our nation and to \nimprove the understanding among the practitioners.\n\n\n\nConclusion \nThree-quarters of the vascular anomalies in our \ncohort were hemangioma followed by vascular   \nmalformations. Management of patients with \nvascular anomalies is extremely challenging and the \ncritical step is by establishing an accurate diagnosis. \nPatients are best managed in a multidisciplinary \nsetting.\n\n\n\nConflict of Interest Declaration\nThe authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement \nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3926\n\n\n\nTable 1. Demography data of the 289 pediatrics with vascular anomalies.\n\n\n\nCharacteristics n=289\n\n\n\nM:F 1:2.1\n\n\n\nMean age of onset in days (range) 18.5 (0 -1825)\n\n\n\nEthnic Malay  182 (63%)\n\n\n\nChinese  73 (25.3%)\n\n\n\nIndian 23 (8%)\n\n\n\nOthers 11 (3.8%)\n\n\n\nReferring diagnosis Vascular tumour 213 (73.7%)\n\n\n\nVascular malformation 54 (18.7%)\n\n\n\nOthers (nevi, cyst, skin tag, diaper dermatitis) 4 (1.4%)\n\n\n\nDiagnosis not given/missing data 18 (6.2%)\n\n\n\nTable 2. Assessment of 289 patients with vascular anomalies in the Pediatric Institute Hospital Kuala Lumpur.\n\n\n\nAssessment in Hospital Kuala Lumpur n (%)\n\n\n\nAnatomical site of lesions Head and neck 161 (55.7)\n\n\n\nTrunk 41 (14.2)\n\n\n\nUpper limb 22 (7.6)\n\n\n\nLower limbs 27 (9.3)\n\n\n\nMultiple sites 20 (6.9)\n\n\n\nPerineum 11 (3.8)\n\n\n\nMissing data 7 (2.4)\n\n\n\nInvestigations None 197 (68.2)\n\n\n\nUltrasound 39 (13.5)\n\n\n\nMRI 21 (7.3)\n\n\n\nUltrasound + MRI 14 (4.8)\n\n\n\nAngiogram 1 (0.3)\n\n\n\nBiopsy 12 (4.1)\n\n\n\nMissing data 15 (5.2)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 27\n\n\n\nTable 3. Final diagnoses of the vascular anomalies presented by 289 patients.\n\n\n\n Vascular tumour\nn=220\n\n\n\nVascular malformation\nn=69\n\n\n\nFinal diagnosis Type n (%) Type n (%)\n\n\n\nHaemangioma 209 (95) Capillary 51 (73.9)\n\n\n\nKaposiform hemangio-endothelioma 8 (3.6) Lymphatic 6 (8.7)\n\n\n\nTufted angioma 3 (1.4) Venous 4 (5.8)\n\n\n\nKasabach-Merritt phenomenon \u2013 2 cases\nPHACE syndrome \u2013 3 cases\n\n\n\nArterio-venous 1 (1.4)\n\n\n\nCombined (Venolymphatic) 7 (10.1)\n\n\n\nM:F 1 : 2.3 1 : 1.4\n\n\n\nAge range of \nlesion onset in \ndays  \n\n\n\n0 \u2013 300 0 \u2013 1825\n\n\n\nAge of diagnosis \nin months (range)\n\n\n\n0 \u2013 144 0 - 168\n\n\n\nTable 4. Treatment modalities treatment modalities provided to 289 patients. \n\n\n\nTypes of treatment Vascular anomalies\n\n\n\nVascular tumour\n\n\n\nn=220 (%)\n\n\n\nVascular malformation\n\n\n\nn=69 (%)\n\n\n\nExpectant management 88 (40) 6 (8.7)\n\n\n\nBeta-blocker  93 (42.3) 1 (1.4)\n\n\n\nLaser 11 (5)  46 (66.7) \n\n\n\n\u0392-blocker + laser 12 (5.5) 1 (1.4)\n\n\n\nSystemic corticosteroids 4 (1.8) 0\n\n\n\nExcision  3 (1.4) 0\n\n\n\nSclerotherapy 0 2 (2.9)\n\n\n\nSirolimus  4 (1.8) 9 (13)\n\n\n\nSirolimus + laser 0 1 (1.4)\n\n\n\nSirolimus + B-blocker 0 2 (2.9)\n\n\n\nVincristine + Systemic corticosteroids  8 (3.6) 0\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3928\n\n\n\nTable 5. Discrepancies of referring and final diagnosis.\n\n\n\nType of discrepancies n\n\n\n\nUnable to recognize vascular anomalies 4\n\n\n\nUnable to differentiate between vascular \ntumour and vascular malformation\n\n\n\nHemangioma referred as vascular malformation 4\n\n\n\nVascular malformation referred as hemangioma 9\n\n\n\nVenous malformation referred as capillary malformation 1\n\n\n\nCombined malformation 2\n\n\n\nUnable to recognize the criteria of aggressiveness of vascular tumour 1\n\n\n\nTable 6. The simplified version of ISSVA classification for Vascular Anomalies by International Society for the Study of Vascular \nAnomalies. (adopted from http://www.issva.org/UserFiles/file/Classifications-2014-Final.pdf).\n\n\n\nVascular anomalies\n\n\n\nVascular tumors Vascular malformation\n\n\n\nBenign Locally aggressive Malignant Simple Combined\n\n\n\nInfantile hemangioma Karposiform hemangio- \nendothelioma\n\n\n\nAngiosarcoma Capillary malformation (CM) CVM, CLM\n\n\n\nCongenital \nhemangioma\n\n\n\nRetiform hemangio-\nendothelioma\n\n\n\nEpithelioid hemangio-\nendothelioma\n\n\n\nLymphatic malformation (LM) LVM, CLVM\n\n\n\nTufted angioma PILA, Dabska tumor Others Venous malformation (VM) CAVM\n\n\n\nSpindle-cell \nhemangioma\n\n\n\nComposite hemangio-\nendothelioma\n\n\n\nArteriovenous malformation (AM) CLAVM\n\n\n\nEpithelioid \nhemangioma\n\n\n\nKaposi sarcoma Arteriovenous fistula\n\n\n\nPyogenic granuloma Others\n\n\n\nOthers\n\n\n\nPILA: papillary intralymphatic angioendothelioma; CVM: capillary-venous malformation; CLM: capillary-lymphatic malformation; \nLVM: lymphatic-venous malformation; CLVM: capillary-lymphatic-venous malformation; CAVM: capillary-arteriovenous \nmalformation; CLAVM: capillary-lymphatic-arteiovenous malformation.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 29\n\n\n\nSt\nud\n\n\n\ny\n\n\n\nC\nha\n\n\n\nra\nct\n\n\n\ner\nis\n\n\n\ntic\ns\n\n\n\nFr\nan\n\n\n\nki\ne \n\n\n\net\n a\n\n\n\nl, \nC\n\n\n\nan\nad\n\n\n\na \n20\n\n\n\n12\nB\n\n\n\nin\n y\n\n\n\nan\ng \n\n\n\net\n a\n\n\n\nl, \nC\n\n\n\nhi\nna\n\n\n\n 2\n01\n\n\n\n5\nH\n\n\n\nos\npi\n\n\n\nta\nl K\n\n\n\nua\nla\n\n\n\n L\num\n\n\n\npu\nr\n\n\n\n(C\nur\n\n\n\nre\nnt\n\n\n\n a\nud\n\n\n\nit,\n 2\n\n\n\n01\n7)\n\n\n\nVa\nsc\n\n\n\nul\nar\n\n\n\n T\num\n\n\n\nou\nr\n\n\n\nn=\n62\n\n\n\n1\nVa\n\n\n\nsc\nul\n\n\n\nar\n M\n\n\n\nal\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\nn=\n31\n\n\n\n1\nVa\n\n\n\nsc\nul\n\n\n\nar\n T\n\n\n\num\nou\n\n\n\nr\nn=\n\n\n\n39\n04\n\n\n\nVa\nsc\n\n\n\nul\nar\n\n\n\n \nM\n\n\n\nal\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\nn=\n25\n\n\n\n44\n\n\n\nVa\nsc\n\n\n\nul\nar\n\n\n\n T\num\n\n\n\nou\nr\n\n\n\nn=\n22\n\n\n\n0\nVa\n\n\n\nsc\nul\n\n\n\nar\n M\n\n\n\nal\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\nn=\n69\n\n\n\nM\nal\n\n\n\ne:\nfe\n\n\n\nm\nal\n\n\n\ne\n1:\n\n\n\n 2\n.2\n\n\n\n1:\n1\n\n\n\n1:\n1.\n\n\n\n86\n1:\n\n\n\n1.\n47\n\n\n\n1:\n2.\n\n\n\n3\n1:\n\n\n\n 1\n.4\n\n\n\nC\nom\n\n\n\nm\non\n\n\n\nes\nt t\n\n\n\nyp\ne \n\n\n\n(%\n)\n\n\n\nH\nem\n\n\n\nan\ngi\n\n\n\nom\na \n\n\n\n(1\n00\n\n\n\n%\n)\n\n\n\nVe\nno\n\n\n\nus\n m\n\n\n\nal\nfo\n\n\n\nrm\nat\n\n\n\nio\nn \n\n\n\n(3\n8.\n\n\n\n9%\n)\n\n\n\nIn\nfa\n\n\n\nnt\nile\n\n\n\n h\nem\n\n\n\nan\ngi\n\n\n\nom\na \n\n\n\n(7\n0.\n\n\n\n5%\n)\n\n\n\nC\nap\n\n\n\nill\nar\n\n\n\ny \nm\n\n\n\nal\nfo\n\n\n\nrm\nat\n\n\n\nio\nn \n\n\n\n(7\n6.\n\n\n\n0%\n)\n\n\n\nH\nem\n\n\n\nan\ngi\n\n\n\nom\na \n\n\n\n(9\n5%\n\n\n\n)\nC\n\n\n\nap\nill\n\n\n\nar\ny \n\n\n\nm\nal\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn \n(7\n\n\n\n3.\n9%\n\n\n\n)\n\n\n\nA\nna\n\n\n\nto\nm\n\n\n\nic\nal\n\n\n\n si\nte\n\n\n\nH\nea\n\n\n\nd \n&\n\n\n\n n\nec\n\n\n\nk\nLo\n\n\n\nw\n-fl\n\n\n\now\n- H\n\n\n\nea\nd \n\n\n\n&\n n\n\n\n\nec\nk\n\n\n\nAV\nM\n\n\n\n-E\nxt\n\n\n\nre\nm\n\n\n\niti\nes\n\n\n\nH\nea\n\n\n\nd \n&\n\n\n\n n\nec\n\n\n\nk\nN\n\n\n\nA\nH\n\n\n\nea\nd \n\n\n\n&\n n\n\n\n\nec\nk\n\n\n\nH\nea\n\n\n\nd \n&\n\n\n\n n\nec\n\n\n\nk\n\n\n\nA\nss\n\n\n\noc\nia\n\n\n\nte\nd \n\n\n\nsy\nnd\n\n\n\nro\nm\n\n\n\nes\n (%\n\n\n\n)\nPH\n\n\n\nA\nC\n\n\n\nES\n 0\n\n\n\n.3\n2%\n\n\n\nK\nTS\n\n\n\n 8\n%\n\n\n\nN\nA\n\n\n\nK\nTS\n\n\n\n 3\n.2\n\n\n\n%\nPH\n\n\n\nA\nC\n\n\n\nES\n1.\n\n\n\n4%\nK\n\n\n\nTS\n 1\n\n\n\n.4\n%\n\n\n\nC\nom\n\n\n\npl\nic\n\n\n\nat\nio\n\n\n\nns\n (%\n\n\n\n)\nN\n\n\n\nA\nN\n\n\n\nA\nK\n\n\n\nM\nS \n\n\n\n1.\n7%\n\n\n\nN\nA\n\n\n\nK\nM\n\n\n\nP \n0.\n\n\n\n9%\nN\n\n\n\nA\n\n\n\nTa\nbl\n\n\n\ne \n7.\n\n\n\n T\nhe\n\n\n\n c\nha\n\n\n\nra\nct\n\n\n\ner\nis\n\n\n\ntic\ns o\n\n\n\nf v\nas\n\n\n\ncu\nla\n\n\n\nr a\nno\n\n\n\nm\nal\n\n\n\nie\ns o\n\n\n\nf t\nhr\n\n\n\nee\n d\n\n\n\niff\ner\n\n\n\nen\nt c\n\n\n\nou\nnt\n\n\n\nrie\ns.\n\n\n\nK\nH\n\n\n\nE:\n K\n\n\n\nap\nos\n\n\n\nifo\nrm\n\n\n\n h\nem\n\n\n\nan\ngi\n\n\n\noe\nnd\n\n\n\not\nhe\n\n\n\nlio\nm\n\n\n\na;\n K\n\n\n\nM\nP:\n\n\n\n K\nas\n\n\n\nab\nac\n\n\n\nh-\nM\n\n\n\ner\nitt\n\n\n\n P\nhe\n\n\n\nno\nm\n\n\n\nen\non\n\n\n\n; K\nTS\n\n\n\n: K\nlip\n\n\n\npe\nl T\n\n\n\nre\nna\n\n\n\nun\nay\n\n\n\n S\nyn\n\n\n\ndr\nom\n\n\n\ne;\n P\n\n\n\nH\nA\n\n\n\nC\nES\n\n\n\n: P\nos\n\n\n\nte\nrio\n\n\n\nr f\nos\n\n\n\nsa\n b\n\n\n\nra\nin\n\n\n\n m\nal\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn,\n h\n\n\n\nem\nan\n\n\n\ngi\nom\n\n\n\na,\n a\n\n\n\nrte\nria\n\n\n\nl a\nno\n\n\n\nm\nal\n\n\n\nie\ns, \n\n\n\nca\nrd\n\n\n\nia\nc \n\n\n\nde\nfe\n\n\n\nct\n/c\n\n\n\noa\nrc\n\n\n\nta\ntio\n\n\n\nn \nof\n\n\n\n a\nor\n\n\n\nta\n, e\n\n\n\nye\n &\n\n\n\n e\nnd\n\n\n\noc\nrin\n\n\n\ne \nan\n\n\n\nom\nal\n\n\n\nie\ns, \n\n\n\nst\ner\n\n\n\nna\nl c\n\n\n\nle\nft/\n\n\n\nsu\npr\n\n\n\nau\nm\n\n\n\nbi\nlic\n\n\n\nal\n ra\n\n\n\nph\ne;\n\n\n\n A\nV\n\n\n\nM\n: a\n\n\n\nrti\ner\n\n\n\nio\n-v\n\n\n\nen\nou\n\n\n\ns m\nal\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn;\n N\n\n\n\nA\n: n\n\n\n\not\n a\n\n\n\nva\nila\n\n\n\nbl\ne\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3930\n\n\n\nReferences \n\n\n\n1.   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Role of sirolimus in advanced kaposiform \nhemangioendothelioma. Pediatr Dermatol \n2016;33:e88-e92.\n\n\n\n21. Adams DM, Trenor CC III, Hammill AM, Vinks AA, Patel \nMN, Chaudry G et al. Efficacy and safety of sirolimus in \nthe treatment of complicated vascular anomalies. Pediatrics \n2016;137:e20153257.\n\n\n\n22. Hutchins KK, Ross RD, Kobayashi D, Martin A, Raipurkar \nM. Treatment of Refractory Infantile Hemangiomas and \nPulmonary Hypertension with sirolimus in a Pediatric \nPatient. J Pediatr Hematol Oncol 2017;39:e391-3.\n\n\n\n23. Greene AK, Liu AS, Mulliken JB, Chalache K, Fishman \nSJ. Vascular anomalies in 5621 patients : guidelines for \nreferral. J Pediatr Surg 2011;46:1784-9.\n\n\n\n24. MacFie CC, Jeffery SL. Diagnosis of vascular skin \nlesions in children: an audit and review. Pediatr Dermatol \n2008;25:7-12.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 31\n\n\n\nORIGINAL ARTICLE\n\n\n\nPrevalence of Co-infection with Gonorrhoea and Non-Gonococcal \nUrethritis in Males with Urethral Discharge Genitourinary Clinic, Hospital \nKuala Lumpur: A 5-year study between 2011 \u2013 2015\n\n\n\nVijayaletchumi Krishnasamy MD, Dip. STD/AIDS, Asmah Johar, MMed\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nDual infection with Neisseria gonorrhoeae and Chlamydia sp has been reported in several studies worldwide \nin men presenting with urethral discharge. The rate of co-infection has been reported to be between 1.5 to 51%. \nThis study aims to determine the demographic characteristics and sexual behaviour of men diagnosed to have \nurethritis.\n\n\n\nMethods: \nThis is a retrospective study on all men who presented with urethral discharge and diagnosed to have \ngonococcal (GU) and non-gonococcal urethritis (NGU) for the year 2011 to 2015 in Genito-Urinary \nMedicine Clinic (GUM), Hospital Kuala Lumpur. The case notes were retrieved and reviewed.\n\n\n\nResults: \nThere were a total of 307 men who attended the GUM clinic with urethral discharge. The mean age \nof patients was 26.4 years (range 16-57 years). Majority (64.5%) were in the age group between 20-\n29 years. Around 95% were Malaysians and of these about 80% were Malays. Thirty-seven patients \n(12%) completed their tertiary education. There were 24 patients (8%) documented to have substance \nabuse. Majority (78%) were heterosexual. About 36% of patients had 2 or more partners (range 2-10) \n6 months before the symptoms developed. The most common cause of urethritis was gonococcal \nurethritis (66.4%), followed by NGU (24.4%). Among the NGU, nine were detected to have Chlamydia \nsp infection (12%). Co-infection with Neisseria gonorrhoea and Chlamydia sp were detected in 28 \nmen (9.1%). Seven (2.3%) were HIV seropositive. \n\n\n\nConclusion:\nMajority of males diagnosed with gonorrhoea were heterosexuals acquired mainly via casual partners. \nAbout 10% had co-infection with Neisseria gonorrhoeae and Chlamydia sp.\n\n\n\nKey words: Urethritis, Neiserria gonorrhoeae, Chlamydia sp, Non-gonococcal urethritis\n\n\n\nCorresponding Author\nDr Vijayaletchumi Krishnasamy \nDepartment of Dermatology, Hospital Kuala Lumpur, \n50586 Jalan Pahang, Kuala Lumpur\nEmail: vkrishnasamy44@gmail.com\n\n\n\nIntroduction\nDual infection with Neisseria gonorrhoeae \nand chlamydia sp. has been reported in several \nstudies worldwide in men presenting with urethral \ndischarge. The rates of co-infection have been \nreported to be around 1.5-51%.1-8 In Malaysia, GU \nand NGU is commonly diagnosed in men presenting \nwith urethral discharge and dual therapy has been \nthe mainstay of treatment in all primary care \ncenters. Despite its common occurrence, the data \non NGU and its co-infection in Malaysia is lacking. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3932\n\n\n\nIn this study we aim to determine the demographic \ncharacteristics, behavior traits and the prevalence of \nthese infections.\n\n\n\nMaterials and Methods\nWe retrieved and reviewed all case notes of males \ndiagnosed to have gonococcal urethritis, non-\ngonococcal urethritis and chlamydia infection for \nthe year 2011 to 2015. Information including age, \nethnicity, level of education, employment status, \nsexual orientation, type or partner, number of \npartners in the last 6 months and other concomitant \nsexually transmitted infections were extracted and \nanalysed.\n\n\n\nA diagnosis of gonococcal urethritis is made if the \ngram stain of urethral discharge shows the presence \nof gram negative intracellular diplococcus or the \nsmear culture is positive for Neisseria gonorrhoeae. \nNon-gonococcal urethritis is diagnosed when gram \nstaining of urethral discharge in a symptomatic \nman shows inflammatory cells without the presence \nof gram negative diplococcic and Chlamydia \ninfection was confirmed using chlamydia \nimmunofluorescence test.\n\n\n\nResults\nFor the year 2011 to 2015, a total of 307 cases \nwhich fulfilled the criteria were analysed using \nSPSS version 20. The demographic data is shown \nin Table 1. The age ranged from 16 to 57 years old \nand the mean age of patients is 26.4 years. Majority \nof patients (64.5%) fell in the age group of 20 to 29 \nyears followed by those within the range of 30 to 39 \nyears (32.6%). The minority were in the range of 50 \nto 59 years.  Around 12% was less than 20 years of \nage.\n\n\n\nAround 95% were Malaysians and the rest were \nforeigners comprising of Indonesians, Bangladeshis \nand Arabs etc.  The Malays formed the largest \nethnic group with the aforesaid infections followed \nby Indians (9.8%) and Chinese (4.2%). Only about \n1% of patients were from East Malaysia.\n\n\n\nMajority of them were educated and about 72.3% \nhad studied until secondary school whilst 12% had \ncompleted tertiary education. Substance abuse was \ndocumented in 24 (8%) patients and most of which \nwere taking marijuana and amphetamine.\n\n\n\nAround 78.8% of men claimed that they were \nheterosexual, 11.4% bisexual and homosexual \n\n\n\nwas documented in about 9.8% of men. About half \n(59.3%) had sex with casual partners, 30% with \nsteady partners and about 10% with sex workers \nprior to the onset of symptoms.  About 36% of \npatients had 2 or more partners (range 2-10) over the \nlast 6 months. The most common cause of urethritis \nwas gonococcal urethritis (66.4%), followed by non-\ngonococcal urethritis (24.4 %). Among the NGU, \nnine were detected to have Chlamydia sp infection \n(12%). Co-infection with Neisseria gonorrhoeae \nand Chlamydia sp were detected in 28 men (9.1%). \nSeven (2.3%) were HIV seropositive.\n\n\n\nDiscussion\nThis study was carried out in Genito-Urinary \nMedicine Clinic Hospital Kuala Lumpur which \nis the biggest government tertiary referral centre \nsituated in the capital city of Kuala Lumpur and \nis easily accessible via public transport.  Genito-\nUrinary Medicine Clinic, a division of the \ndepartment of dermatology is situated within the \nvicinity of the hospital amongst other specialized \ndepartments.  It caters to walk-in clients and those \nwho have been referred from other departments, \nneighbouring hospitals and health clinics. The clinic \nhas its own satellite laboratory whereby simple \nsexually transmitted infections (STIs) tests such as \ngram stain, urine tests, dark ground microscopy and \nrapid plasma reagent tests (RPR) for syphilis could \nbe done immediately.\n\n\n\nThe striking demographic characteristic in these \npatients was nearly 80% of them were in the age \ngroup of 20 to 40 years.  They were probably at \nthe age whereby men have higher sexual urge and \nwith financial independence which enabled them to \nengage in unhealthy sexual practices thus resulting \nin STIs.  According to the national HIV census the \nnumber of adolescents with HIV is increasing in an \nalarming rate.11,12 Even though sexual education has \nbeen incorporated in school curriculum, sensitive \nissue like homosexuality is not acknowledged by \nthe school authorities.  About 12% of our patients \nwere less than 20 years which is unsurprising and \nit adds on to the gravity of the situation mentioned \nabove. Therefore, adolescent\u2019s ignorance on the \ntransmission facts of HIV and other STIs causes \nthem to continually engage in unsafe sex.\n\n\n\nHistory of substance abuse has been documented \nin a minority of patients and the kinds of substance \nused were amphetamine-based stimulants and \nmarijuana.15,16\n\n\n\n. The recreational drugs are becoming \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 33\n\n\n\npopular among the adolescents and young adults in \nMalaysia.  Research showed that the social pressure \nto be accepted into a peer group impels them to \nstart trying out drugs thus leading to other high risk \nactivities like unsafe sex.14,15\n\n\n\nSeveral prevalence studies3,5,6,8 on GU and Chlamydia \nco-infection have looked into the number of partners \nby an individual prior to infection. One study5 \nnoted a significant association with the number of \npartners for the risk of co-infection. In our study, \nthe proportion of patients who\u2019s had more than 2 \npartners within 6 months is about 36.2% which is \nrelatively high.\n\n\n\nAccording to World Health Organization (WHO) in \n200811, the estimated global incidence of Neisseria \ngonorrhoeae and Chlamydia trachomatis were \n106.1 and 105.7 million cases respectively. The \nnumbers of reported cases were in increasing trend \nfrom the year 2005 for both. In Malaysia, we are able \nto monitor the incidence of Neisseria gonorrhoeae \nsince it is a notifiable disease.  The incidence of \ngonorrhoea for Malaysia was 4.7 per 100,000 \npopulation in 201111, increasing over the years to \n7.53 per 100,000 in 2015.12 The rise in incidence of \ngonorrhoea could be consistent with the global rise \nor it could due to the increase in the awareness of \nnotification among the clinicians.\n\n\n\nNon-gonococcal infection is not in the list of \nnotifiable infections in Malaysia.  Non-gonococcal \nurethritis (NGU) may be caused by Chlamydia \ntrachomatis, Mycoplasma sp, Urea plasma sp and \nothers.13 Non-gonococcal urethritis is diagnosed \nwhen staining of urethral discharge in a symptomatic \nman shows inflammatory cells without the presence \n\n\n\nof gram negative diplococcic. All men diagnosed to \nhave NGU need to be tested further for its aetiology.  \nHowever, the diagnostic tests for Mycoplasma sp \nand Ureaplasma sp are not available in our setting. \n\n\n\nCo-infection of gonococcal and non-gonococcal \nurethritis especially Chlamydia trachomatis has \nbeen observed in different countries as shown in \nTable 3.1-7 The rates of co-infection were reported \nto be between 1.5-51%.1-8 In our cohort of \ngonococcal urethritis, about 12% was also infected \nwith Chlamydia trachomatis. This low rate of co-\ninfection is however cannot fully justify the policy \nof epidemiological treatment of chlamydia in all \ncases of gonococcal urethritis in Malaysia. Future \nprospective study is needed to determine other \naetiology of NGU in order to characterize better the \nrate of co-infection in this country. \n\n\n\nConclusion \nMajority of heterosexual males with gonorrhoea \nhad casual partners. Co-infection with Neisseria \ngonorrhoeae and Chlamydia sp. was 9.1%.\n\n\n\nConflict of Interest Declaration\nThe authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement \nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3934\n\n\n\nTable 1. The demographic data and sexual history of 307 men with urethritis.\n\n\n\nPatients Characteristics n=307\n\n\n\nMean age in years (range) 26.4 (16-56)\n\n\n\nAge group in years (%) <20 37 (12)\n\n\n\n20-29 198 (47.8)\n\n\n\n30-39 51 (32.6)\n\n\n\n40-49 11 (12.0)\n\n\n\n50-59 10 (3.4)\n\n\n\nEthnicity (%) Malay 245 (79.8)\n\n\n\nChinese 13 (4.2)\n\n\n\nIndians 30 (9.8)\n\n\n\nBumiputera 3 (1.0)\n\n\n\nForeigners 16 (5.2)\n\n\n\nHighest Education level (%) Primary 45 (14.7)\n\n\n\nSecondary 222 (72.3)\n\n\n\nTertiary 37 (12.0)\n\n\n\nMissing data 3 (1.0)\n\n\n\nEmployment history (%) Student 43 (14)\n\n\n\nEmployed 238 (77.5)\n\n\n\nUnemployed 26 (8.5)\n\n\n\nNumber with documented substance abuse (%) 24 (7.8)\n\n\n\nSexual orientation (%) Heterosexual 242 (78.8)\n\n\n\nBisexual 35 (11.4)\n\n\n\nHomosexual 30 (9.8)\n\n\n\nType of partner (%) Casual 182 (59.3)\n\n\n\nSteady 92 (30.0)\n\n\n\nCommercial 31 (10.0)\n\n\n\nNumber of patients with 2 or more partners in the past 6 months (%) 111 (36.2)\n\n\n\nNumber with other concomitant sexually transmitted infections (%) 18 (5.9)\n\n\n\nConcomitant sexually transmitted infections apart \nfrom Urethritis\n\n\n\nSyphilis 4 (1.3)\n\n\n\nGenital warts 3 (1.0)\n\n\n\nHerpes genitalis 2 (4.1)\n\n\n\nHepatitis B 2 (4.1)\n\n\n\nHepatitis C 1 (1.0)\n\n\n\nHuman Immunodeficiency virus  7 (2.3)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 35\n\n\n\nTable 2. The etiology of urethritis in 307 men with urethral discharge.\n\n\n\nAge group Neisseria gonorrhoea only n=204 Non gonococcal \nurethritis n=75\n\n\n\nNeisseria gonorrhoea &\n Chlamydia trachomatis n=28\n\n\n\nTotal n=307\n\n\n\n<20 27 (8.7%) 4 (1.3%) 6 (1.9%) 37\n\n\n\n20-29 132 (28%) 54 (8.7%) 12 (4.0%) 198\n\n\n\n30-39 32 (7.8%) 11 (2.6%) 8 (1.9%) 51\n\n\n\n40-49 5 (1.0%) 5 (1.6%) 1 (0.3%) 11\n\n\n\n50-59 8 (1.6%) 1 (0.3%) 1 (0.32%) 10\n\n\n\nTable 3. The reported rate of co-infection of gonococcal and non-gonococcal urethritis in different countries.\n\n\n\nAuthor, year  Countries Age  (yrs) Sexual behaviour NG (%) NGU (%) CT(%) NG and CT (%)\n\n\n\nCreighton et al\n20031\n\n\n\nUK 22.4 (mean) - 3.8 - 8.1 1.5\n\n\n\nKhan et al\n20052\n\n\n\nUS 15-16 - 1.3 - 5.9 51\n\n\n\nSatyajit et al\n20053\n\n\n\nUK 20-25 1 partner  43.7%\n2 partners  32.3%\n\n\n\n\u22653 28.7%\n\n\n\n- - - 16.1\n\n\n\nTongtoyai et al, 20154 Thailand MSM 4.6 11.6 2.9\n\n\n\nDonati. et al\n20095\n\n\n\nItaly 33.7 (mean) - - - 74.5 30.1\n\n\n\nBarbosa et al\n20106\n\n\n\nBrazil 26.5 (mean) 1partner 85.4% 18.4 13.1 4.4\n\n\n\nLim et al, 20157 Singapore 14-19 Heterosexual male with \nSTI\n\n\n\n33.1 23.6 10.2\n\n\n\nKrishnasamy et al 2017 HKL\nMalaysia\n\n\n\n26.4 (mean) > 2 Partners - 36.2% 66.4 24.4 3 9.1\n\n\n\nNG: Neiserria gonorrhoeae; NGU: non gonococcal urethritis; CT: Chlamydia trachomatis; MSM: men having sex with men; STI: \nSexually transmitted infections; HKL: Hospital Kuala Lumpur; UK: United Kingdom; US: United State of America.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3936\n\n\n\nReferences\n\n\n\n1. Creighton S, Tenant-Flowers M, Taylor CB, Miller R, \nLow N. Co-infection with gonorrhoea and chlamydia: how \nmuch is there and what does it mean? Int J STD AIDS \n2003;14:109-13.\n\n\n\n2. Khan RH, Mosure DJ, Blank S, Kent CK, Chow JM, \nBoudov MR et al. Chlamydia trachomatis and Neisseria \ngonorrhoeae Prevalence and Coinfection in Adolescent \nEntering Selected US Juvenile Detention Centers, 1997 \n-2002. Sex Transm Dis 2005;32:255-9.\n\n\n\n3. Das S, Sabin C, Wade A, Allan S. Sociodemography of \ngenital co-infection with Neisseria Gonorrhoeae and \nChlamydia Trachomatis in Coventry, UK. Int J STD AIDS \n2005;16:318-22.\n\n\n\n4. Tongtoyai J, Todd CS, Chonwattana W, Pattanasin S, \nChaikummao S, Varangrat A et al. Prevalence and Correlate \nof Chlamydia trachomatis and Neisseria gonorrhoeae by \nAnatomic Site Among Urban Thai men who have sex with \nMen. Sex Transm Dis 2015;42:440-9.\n\n\n\n5. Donati M, Di Francesco A, D\u2019Antuono A, Pignanelli S, \nShurdhi A, Moroni A et al. Chlamydia trachomatis serovar \ndistribution and other concurrent sexually transmitted \ninfections in heterosexual men with urethritis in Italy. Eur \nJ Clin Microbiol Infect Dis 2009;28:523-6.\n\n\n\n6. Barbosa MJ, Moherdaui F, Pinto VM, Ribeiro D, \nCleuton M, Miranda AE et al.      Prevalence of Neisseria \ngonorrhoeae and Chlamydia trachomatis infection in men \nattending STD clinics in Brazil.  Rev Soc Bras Med Trop \n2010;43:500-3.\n\n\n\n7. Lim RB, Wong ML, Cook AR, Brun C, Chan RK, Sen P et \nal. Determinants of Chlamydia, Gonorrhea and Coinfection \nin Heterosexual Adolescents Attending the National Public \nSexually Transmitted Infection Clinic in Singapore. Sex \nTransm Dis 2015;42:450-6.\n\n\n\n8. SSuN Special Focus Report, Gonorrhoeae/Chlamydia \nCo-infection, Feb 2013. http://www.vdh.virginis.gov/\nepidemiology/DiseasePrevention/data, accessed on 6 \nNovember 2017. \n\n\n\n9. Forward KR. Coinfection with Chlamydia trachomatis \nand Neisseria gonorrhoeae in Nova Scotia. Can J Infect \nDis Med Microbio 2010;21:e84-6.\n\n\n\n10. World Health Organization Global Prevalence and \nincidents of selected curable sexually transmitted infection: \noverview and estimates. GENEVA: WHO 2012. http://\nwww.who.int/reproductivehealth/publications/rtis/2008_\nSTI_estimates.pdf, accessed on 6 November 2017.\n\n\n\n11. Incidence Rate and Mortality Rate of Communicable \nDiseases 2011. MOH Malaysia. Health Fact 2012. http://\nwww.moh.gov.my/images/gallery/stats/heal_fact/health_\nfact_2012_page_by_page.pdf, accessed on 6 November \n2017.\n\n\n\n12. Incidence Rate and Mortality Rate of Communicable \nDiseases 2014. MOH Malaysia.     Health Fact 2015. \nhttp://www.moh.gov.my/images/gallery/publications/\nKKM%20HEALTH%20FACTS%202016.pdf, accessed \non 6 November 2017.\n\n\n\n13. Centres for Disease Control and Prevention. Diseases \ncharacterized by Urethritis and Cervicitis. MMWR \n2015;64:51-2.\n\n\n\n14. Singh D, Chawarski MC, Schottenfeld R, Vicknasingam \nB. Substance Abuse and HIV situation in Malaysia. J Food \nDrug Anal 2013;21:S46-S51. \n\n\n\n15. Chie QT, Tam CL, Bonn G, Dang HM, Khairuddin R. \nSubstance Abuse, Relapse, and Treatment Program \nEvaluation in Malaysia:Perspective of Rehab Patients and \nstaff Using The mixed Method Approach. Front Psychiatry \n2016; doi: 10.3389/fpsyt.2016.00090. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 37\n\n\n\nORIGINAL ARTICLE\n\n\n\nThe Utilization of Cutaneous Laser Therapy at the Department of \nDermatology, Hospital Kuala Lumpur: A 5-year review\n\n\n\nSuganthy Robinson, MRCP, AdvMDerm, Min Moon Tang, MRCP, AdvMDerm, Noor Zalmy Azizan, MRCP, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nThe Department of Dermatology, Hospital Kuala Lumpur has been providing cutaneous laser therapy \nservices for over 20 years. We aim to describe the utilization of cutaneous laser therapy at the Department \nof Dermatology, Hospital Kuala Lumpur and the post treatment complications.\n\n\n\nMethods: \nWe reviewed all patients who received cutaneous laser therapy at the Department of Dermatology, Hospital \nKuala Lumpur from January 2012 till December 2016. Complications were defined as dyspigmentat ion, \ninfection, scarring, blisters, ulcerations, skin textural changes or contact dermatitis secondary to post/ pre-laser \ntopical therapy.\n\n\n\nResults: \nA total of 1190 patients with a male to female ratio of 1:2.21 and a mean age of 35.8 years received single, \nrepeated or combination cutaneous laser therapy from 2012 till 2016 for 48 different skin conditions. Annually, \nan average of 1314 laser sessions were performed. Indications included seborrhoeic keratosis (249, 20.9%), \nport wine stain (162, 13.6%), solar lentigines (144, 12.1%), syringoma (105, 8.8%), viral warts (88, 7.4%), \nand Naevus of Ota (82, 6.9%) among others. Majority underwent Q-switched Nd:YAG laser (36.5%) followed \nby pulsed dye laser (33.6%), ablative conventional carbon dioxide laser (29.2%) and fractional carbon dioxide \nlaser (0.7%). Over the past 5 years, 3 patients developed severe complication post laser therapy which was \nblisters. Pain was tolerable with application of topical 5% EMLA\u00ae (lidocaine 2.5% and prilocaine 2.5%) cream \npre-laser treatment. \n\n\n\nConclusion:\nQ-switched Nd:YAG laser therapy was the most frequently employed laser in the Department of \nDermatology, Hospital Kuala Lumpur. Our centre has a high volume of cases with a low rate of post \ntreatment complication.\n\n\n\nKey words: Laser, Medical dermatology, Q-switched Nd:YAG, Pulse dye laser, Carbon dioxide laser\n\n\n\nCorresponding Author\nDr Suganthy Robinson\nDepartment of Dermatology, Hospital Kuala Lumpur, \n50586 Jalan Pahang, Kuala Lumpur\nEmail: suganthyr@yahoo.com\n\n\n\nIntroduction\nLaser technology has rapidly evolved over the \nlast six decades and with this comes a demand \nfor cutting edge knowledge on the attributes and \nindications of the various types of laser apparatus.1 \nAlthough cutaneous laser therapy has received \nmuch attention for its cosmetic implications, major \nadvances have revolutionized the use of lasers in \nmedical dermatology.\n\n\n\nCutaneous laser therapy has been applied widely \nin the fields of dermatology and plastic surgery for \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3938\n\n\n\nthe treatment of vascular lesions, including port-\nwine stain, capillary and cavernous hemangiomas, \nand telangiectasias. Moreover, both malignant and \nbenign pigmented lesions such as tattoos, cafe-au-\nlait spots, pigmented naevi, and small basal cell \ncarcinomas are also amenable to laser therapy.2 \nLaser is also now acknowledged as a recognized \nsurgical instrument in enabling bloodless surgeries \nas carbon dioxide lasers are extensively used \nfor cutting, ablating and cauterizing with good \nhemostatic effects.3 The indication range for \ncutaneous laser therapy continues to broaden with \nimproved outcomes and safety profiles along with \nthe advancement and refinement of laser technology.\n\n\n\nThe Department of Dermatology, Hospital Kuala \nLumpur has been providing cutaneous laser therapy \nservices for almost two decades and focusses on \nmedical and aesthetic dermatology indications. The \nlaser unit is currently equipped with an ablative \nconventional carbon dioxide laser which is useful \nfor vapourizing lesions and applying incisions, a \nQ-switched neodymium- doped yttrium aluminium \ngarnet (Nd:YAG) laser for pigmented lesions, a \npulsed dye laser (PDL) for treatment of vascular \nlesions and a fractional carbon dioxide machine for \nacne scar resurfacing. Cutaneous laser services are \nprovided three times a week for local patients as \nwell as referrals from the whole country.\n\n\n\nMaterials and Methods\nA retrospective, descriptive study was conducted \nwhere medical records of all patients who received \ncutaneous laser therapy at the Department of \nDermatology, Hospital Kuala Lumpur from January \n2012 till December 2016 were reviewed. The \nobjective was to describe the utilization of cutaneous \nlaser therapy and the post treatment complications.\n\n\n\nThe laser machines used were a Sharplan CO2 \n1030 30Watt Laser System, a Medlite C6 by \nHoyaConBio, a V-beamPerfecta, 595nm by \nCandela Corp. Wayland, USA and a MiXto SX\u00ae \n\n\n\nfractional CO2 Laser by Lasering, USA. Carbon \ndioxide laser is effective for the treatment of various \nskin disorders by virtue of its specific wavelength \n(10600 nm) and duration of output which can be \nmanipulated to be continuous or pulsed.4 Whereas, \nfor the treatment of a various vascular lesions, the \nPDL with a wavelength of 595 nm and equipped \nwith a dynamic cooling device is used at our centre \nowing to its favourable efficacy and safety profile.\n\n\n\nComplications were defined as dyspigmentation, \n\n\n\ninfection, scarring, blisters, ulcerations, skin \ntextural changes or contact dermatitis secondary \nto post/pre-laser topical therapy. The data which \nincluded demographics, indication and type of laser \ntreatment and number of treatment sessions received \nwas collected using a standardized clinical research \nform and stored electronically on Microsoft Excel \nspreadsheet. Descriptive analysis was performed \nusing SPSS version 21.\n\n\n\nResults\nA total of 1190 patients received single, repeated or \ncombination cutaneous laser therapy from 2012 till \n2016 for 48 different skin conditions. About 27.1% \nof the patients (322 of 1190 patients) had one laser \nsession as opposed to 868 patients who had multiple \nlaser sessions. There were 194 patients who received \ncombination laser treatments and 996 had one type \nof laser performed on them. The demographic data is \nshown in Table 1. The mean age was 35.8 years with \nthe youngest patient only 9 days old and the oldest \npatient to undergo skin laser treatment was 90 years. \nMajority of the patients were female (68.8%). The \nmean number of laser sessions received per patient \nwas 5.3 with one patient receiving up to 46 sessions \nfor resistant viral warts. The ethnic distribution of \nthe study population corresponded with the national \npopulation distribution. \n\n\n\nFigure 1 illustrates the number of laser sessions \nprovided per year. Annually, an average of 1314 \nlaser sessions were performed. The highest \nnumber of laser sessions (1635) was performed in \n2015 and an increasing trend was noted from 2013. \nHowever, the decline in the number of laser sessions \nin 2016 was due to the breakdown of the PDL and \nQ-switched Nd:Yag machines. \n\n\n\nFigure 2 shows the number of laser sessions provided \nby each laser machine. Q-switched Nd:YAG was the \nmost frequently employed laser (36.5%) followed \nby PDL (33.6%), ablative conventional CO2 \n(29.2%) and fractional CO2 (0.7%). The fractional \nCO2 laser service was initiated since September \n2013 mainly for acne scars in skin phototype III and \nIV and recorded the least number of laser sessions. \nAlthough the fractional CO2 laser has many \ntreatment indications which encompasses treatment \nof wrinkles, facial rejuvenation, dyschromia, \nmelasma, etc., in our dermatology clinic of a public \nhospital which is heavily funded by government, its \nuse is limited to the sole indication of severe acne \nscar treatment. Apart from this, there was only one \ndermatologist credentialed to perform fractional CO2 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 39\n\n\n\nlaser at that period. The lack of dermatologists who \nare trained in dermatosurgery and limited allocated \nslots for laser surgery (three half-day sessions per \nweek) were factors that accounted for the low usage \nof the fractional CO2 laser. \n\n\n\nTable 2 demonstrates the indications of laser therapy \nin the current cohort. The top three indications for \nlaser therapy included seborrheic keratosis (20.9%), \nport wine stains (capillary malformations) (13.6%) \nand solar lentigines (12.1%). \n\n\n\nTable 3 shows the clinical indications for ablative \nconventional CO2 laser treatment at our centre. \nPulsed dye laser was performed for 18 different \nskin lesions and this is presented in Table 4. For the \nnumerous pigmented lesions which are demonstrated \nin Table 5, a Q-switched Nd:YAG laser was used. \nLast but not least, our fractional CO2 laser was used \nonly for acne scars in patients with Fizpatrick skin \ntype III or IV.\n\n\n\nOver the past 5 years, only 3 (0.3%) patients \ndeveloped severe complication post laser therapy \nwhich was blisters. All three had PDL, 2 of them \nfor port wine stains and 1 for keloid scars. Pain was \ntolerable with the application of topical 5% EMLA\u00ae \n(lidocaine 2.5% and prilocaine 2.5%) cream prior \nto laser treatment. Anticipated side effects such as \nerythema and post inflammatory hyperpigmentation \nwere experienced by almost all our patients who \nunderwent laser treatment. They were nevertheless \nmild, tolerable and transient. Post-inflammatory \nhyperpigmentation was particularly common for \nthose who underwent Q-switched Nd:YAG  and \nCO2 lasers. Post inflammatory hyperpigmentation \nthat developed after treatment with Q-switched \nNd:YAG  and CO2 lasers on the face of our patients \nresolved within 6 to 12 weeks as careful selection \nof patients and pre-laser counselling had been \nperformed meticulously. Furthermore, these patients \nhad been advised on strict sun avoidance 3 months \nprior to laser surgery, mandatory use of sunscreen \ntogether with careful skin care pre and post laser \ntreatment which included topical whitening agents. \nNone of our patients developed permanent post \ninflammatory hyperpigmentation. Patients who had \nhistory of herpes simplex infection were prescribed \nsystemic antiviral as prophylaxis. Fortunately, we \ndid not encounter any infections post laser therapy \nin our patients over the past 5 years.\n\n\n\nNone of the 18 patients who underwent fractional CO2 \nskin resurfacing for acne scars developed any severe \n\n\n\nadverse reaction though all of them experienced \ntemporary erythema, hyperpigmentation and \nwarmth followed by crusting which resolved in 7 to \n14 days. Their skin care regime post laser included \nregular emollient application, avoidance of harsh \nsoaps and application of make-up or other topicals \nand strict sun protection as mentioned above.\n\n\n\nDiscussion\nGranted that the spotlight has been mainly on laser \nusage for aesthetic purposes, lasers also play an \nimportant role in medical dermatology. Literature \non the usage of skin lasers in medical dermatology \nis by far less discussed than cosmetic dermatology.1 \nThus there is a clear need to further explore and \ndevelop this area.\n\n\n\nWater is the only chromophore for CO2 laser at \n10600nm and therefore can be used to ablate \npigmented and non-pigmented lesions. It can incise, \nexcise, vapourize or coagulate or combine any of \nthese modes in its application. Conventional clinical \nindications for CO2 laser application includes \nmoles, seborrheic keratosis, skin tags, viral warts, \nsyringoma, xanthelasma, basal cell epithelioma and \nviral warts.5 Of late, the treatment of toenail disease \nlike onychodystrophy and painful ingrown toenail \nwith CO2 laser has fascinated many. By applying \na wedge resection method, postoperative bleeding \nand pain were very much reduced compared the \ntraditional technique of complete nail avulsion.5-7 \nIn the treatment of refractory skin diseases such \nas hidradenitis suppurativa and pilonidal sinus, \nderoofing with CO2 laser and hair follicle removal \nwith long pulse Nd:YAG laser is a useful minimally \ninvasive tissue saving technique.1, 8 In addition, \nfractional CO2 laser treatment appears to be useful \nin the treatment of genodermatoses such as Darier-\nWhite disease and Hailey-Hailey disease.9 10 With \nsuch fascinating advancement, we plan to maximize \nthe usage of the fractional CO2 laser at our centre in \nfuture.\n\n\n\nQ-switched lasers deliver very short pulses in \nnanoseconds with high peak power.4 The clinical \nindications that are amenable to Q switched \nNd:YAG lasers are diverse and many. Treatment \nwith wavelengths of either 532nm or 1064nm \nof epidermal and dermal pigmented lesions \nsuch as tattoos, lentigines, caf\u00e9-au lait macules, \nephilides, Nevus of Ota, Nevus of Ito, Hori\u2019s \nnevus and epidermal melasma to name a few are \nwell established.11 When Q-switched frequency \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3940\n\n\n\ndoubled 532nm is used with low fluence and large \nspot size, a medium depth laser peel effect with a \nshort downtime is achieved and this is excellent for \ntreating photoaging. However, for darker skin types, \npost inflammatory hyperpigmentation may pose a \nproblem.12\n\n\n\nThe PDL is an effective first-line treatment modality \nfor vascular lesions.1,13 Vascular lesions that may \nbe treated with PDL are port wine stains (outcome \ndepends on location of the lesion and vessel size and \ndepth), facial telangiectasias, spider naevi, scars and \nulcerated haemangiomas.1,14 Other than these well \nacknowledged clinical indications, a small study  by \nErceg et all has shown that recalcitrant discoid lupus \nerythematosus lesions in 12 patients treated with \nPDL improved in terms of disease area and severity \nindex after 6 weeks of treatment (P<0.0001).15 A few \ncase reports have also demonstrated the efficacy of \nPDL for the treatment of granuloma faciale.16,17 Our \ncentre has treated a patient with granuloma faciale \nwith 14 sessions of PDL. Cutaneous sarcoidosis \ntreated with CO2 laser and PDL have been reported \nto be efficacious by a few.18,19 PDL have also been \napplied as adjunctive treatment in small basal \ncell carcinomas particularly where surgery is not \nplausible.1,20\n\n\n\nApart from the lasers available at our centre, the \nexcimer laser has been proven to be effective in \nthe treatment of psoriasis, vitiligo, hypopigmented \ndisorders (leukoderma, halo naevi, naevus \ndepigmentosus and pityriasis alba), alopecia areata, \natopic dermatitis and lymphoproliferative disorders \n(early stage mycosis fungoides, lymphomatoid \npapulosis and primary cutaneous CD30+).1,21-24 The \n308-nm excimer laser has demonstrated efficacy for \nthe treatment of mild to moderate localized plaque \npsoriasis, scalp and intertriginous psoriasis.21,25-29 In \ngeneral, plaque lesions required 10 to 11 sessions \nto clear while scalp lesions needed over 20 sessions \nfor 50-90% improvement.27,28,30,31 When compared \nwith narrow-band UVB (NB-UVB), Bonis et \nal found that the excimer laser mandated less \ntreatment sessions and a lower cumulative dose of \nUVB to achieve clearance of psoriatic lesions.21 \nMoreover, Novak et al showed that the excimer \nlaser induced a higher rate of T-cell apoptosis \ncompared to NB-UVB.32 Findings of a recent meta-\nanalysis suggested that targeted UVB light sources \nlike the excimer laser can be used to treat psoriasis \nwhen topical therapy has been unsuccessful.33 For \ntreatment of vitiligo with the excimer laser, better \noutcomes were seen in Fitzpatrick skin types of \n\n\n\nIII and above. Vitiligo patches over the face, neck \nand axilla responded better compared to lesions \non the joints and acral sites.24,34 Additionally, the \nexcimer laser has also been used to treat granuloma \nannulare, Langerhans cell histiocytosis, lichen \nplanus, localized scleroderma and acquired reactive \nperforating collagenosis .24 , 35\n\n\n\nRecent advances in laser technology such as \nlaser assisted drug delivery (LADD) have shown \npromising potential for treatment of a wide variety \nof dermatology conditions.36 Laser assisted drug \ndelivery involves three important components and \nutilizes an ablative fractional laser. Firstly, the laser \nis used to disrupt the skin barrier. Next, a laser may \nbe used to exert a therapeutic effect (optional). \nLastly, the therapeutic drug is delivered via laser \nchannels to augment the therapeutic effect. This \nmethod offers the benefit of efficacy, alternative \nroute of administration which is less invasive \nwith good safety profiles and therefore leading to \nbetter compliance.37-38 Lasers such as CO2, Erbium: \nyttrium\u2013aluminum\u2013garnet (Er:YAG), Nd:YAG, \nArgon-fluoride excimer, Erbium-doped 1,550 nm, \n1,927-nm diode and Q-switched Ruby have been \napplied to enhance transdermal uptake of drugs, \ncosmeceuticals, and fillers.37 Laser assisted drug \ndelivery also allows the drug to either remain within \nthe layers of the skin or to be absorbed systemically \nby altering the laser parameters. Some of the \ndermatological disorders treated with LADD that \nhave been studied are actinic keratosis and non-\nmelanoma skin cancers where 5-aminolevulinic \nacid (ALA), methyl-5-aminolevulinate (MAL), \nimiquimod, ingenol mebutate and methotrexate \nwere used. Others include hemangioma (timolol), \nalopecia areata (minoxidil and diphencyprone), \nonychomycosis (topical amorolfine), photoaging \n(botulinum toxin), post inflammatory \nhyperpigmentation (corticosteroid), psoriasis \n(methotrexate) and scars (triamcinolone acetonide, \n5-fluorouracil, poly-L-lactic acid, vitamin C, \nbimatoprost and stem cells).38 As this is a relatively \nnew treatment modality, there is still a lot of \nuncertainty with regards to efficacy, safety, ideal \nlaser device and settings, dosing and formulation of \nthe drugs for the respective treatment indications. \nThus, extensive research is much needed to answer \nthese questions.\n\n\n\nThe complications and side effects for each \ntype of laser and skin lesion treated are distinct. \nComplications from skin laser surgery may occur \nas a result of one or a combination of three factors \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 41\n\n\n\nnamely operator technique, mechanical defect of the \nmachine or patient adherence to pre and post laser \nskin care.39 However, it is pertinent to differentiate \ncomplications as they are uncommon from anticipated \nside effects which may develop in all patients who \nundergo laser treatment such as erythema, purpura, \nedema, moderate pruritus, warmth, exudative \nareas, etc.40 Post inflammatory hyperpigmentation \n(PIH) ensuing from photothermolysis is due to \nmelanin deposits. This is generally momentary \nand reported in essentially all laser surgeries but \nis more prevalent and may be prolonged in higher \nphototype skin, suntanned patients and in lasers \nthat exploit melanin or exogenous pigments as \nchromophores.40,41 For Q-switched Nd:YAG lasers, \ntemporary responses include erythema, physical \nurticaria, acneiform eruption, petechiae, whitening \nof hair and hyperpigmentation. These are usually \nmild and consequent treatment sessions may \nbe continued. However, cessation of treatment \nshould be considered or laser settings adjusted if \nmottled hypopigmentation and hyperpigmentation, \nleukoderma, severe urticaria, severe acneiform \neruption or reactivation of herpes simplex infection \ndevelops post laser therapy. For tattoos treated \nwith high power, scarring and ghost shadow may \ndevelop.11\n\n\n\nA few studies have shown that albeit treatment \nwith antiviral prophylaxis, herpes reactivation still \noccurs in 2% to 7% of all patients who undergo laser \nprocedures.42,43 In a study involving 2064 Korean \npatients who were treated with a single session of \nQ-switched Nd:YAG  for small melanocytic naevi, \nKim et al did not observe any post procedure infection \nor remarkable complications such as atrophy, \nscarring, hypopigmentation or hyperpigmentation.44 \nMoreover, Younes et al who performed 3 sessions  of \nQ-switched Nd:YAG laser treatment on 50 patients \nwith skin phototype II,III and IV for freckles in \nEgypt found that 2 patients (4%) developed post \ninflammatory hyperpigmentation and 3 patients \n(6%) developed hypopigmentation apart from \ntransient erythema experienced by 6 patients.45 \nThese small variations in complication rates are \ndependent on many factors such as stacking pulses, \nmultiple passes, high fluence and skin phototype \nwhich is also compounded by non-compliance to \nskin care post laser.41\n\n\n\nThe most evident side-effect of PDL is purpura \nwhich appears during treatment and can persist for \nup to 2 weeks post therapy. Other complications that \nmay occur with PDL therapy are blistering, crusting, \nulceration, bleeding, hyperpigmentation, atrophic \nand hypertrophic scarring and hypopigmentation.14,46 \nA study by Wlotzke et al. showed that in a hundred \npatients who received flashlamp-pumped pulsed \ndye laser for port wine stain (PWS) treatment, 1% \n\n\n\ndeveloped bullae.47 Furthermore, Thajudheen et al \nconducted a study on 75 patients with Fitzpatrick \nskin types IV and V who had PWS. They received \nmultiple treatments with PDL monthly for six years. \nThirty percent of his patients encountered PIH which \nlasted six to eight weeks and two patients developed \nsuperficial scarring.48 These studies indicate that \ncomplications from treatment with pulse dye laser \nare low and comparable to our centre.\n\n\n\nComplications arising from fractional CO2 \nresurfacing that have been reported include \nhypertrophic scarring, viral, bacterial and fungal \ninfections, dyspigmentation, acne, milia and textural \nskin changes.46 49 In general, hyperpigmentation \npost fractional  and full beam ablative resurfacing \noccurs approximately 30 days after and can persist \nfor up to 4 months.50 Treatment of PIH should be \ninstituted early and includes adequate application \nof broad spectrum sunscreen, abstaining from \nsun exposure 6 to 8 weeks pre and post laser and \nuse of topical whitening agents such as topical \nhydroquinone, tretinoin, kojic, azelaic and glycolic \nacids.40 An extended period of 3 months for skin \npreparation is recommended for those with added \nrisk of hyperpigmentation.51 Neaman et al reviewed \n97 patients (majority Fitzpatrick skin types II and \nIII) who underwent 101 sessions of fractional CO2 \nlaser resurfacing over 19 months at his centre. \nHe reported 93% of his patients experienced \nhyperemia less than 5 weeks, 5.9% had hyperemia \nlasting between 5 to 8 weeks and 0.9% for more \nthan 8 weeks. Other side effects described were \nhyperpigmentation (9.9%), milia (6.9%), acne \neruption (5.9%), and transient ectropion (0.9%).52 \nIn 13 Asian patients with skin phototype IV and \natrophic acne scars treated with 3 sessions of \nCO2 fractional resurfacing laser over 6 months, \nManuskiatti et al reported 92.3% incidence of PIH \nwhich resolved between 2 to 16 weeks facilitated by \nonce a day application of hydroquinone 4% cream. \nOther reported side effects were acneiform eruption \n(31%, 4 of 13 subjects), allergic contact dermatitis \n(15%, 2 of 13), and herpes simplex infection (7.7%, \n1 of 13).53 Again we observe inconsistent side effect \nand complication reporting rates between these two \nstudies due to different skin phototypes, selection \nof patients, operator techniques, fluence, number of \npasses and post procedure care.\n\n\n\nWith adequate number of trained specialists \nand funding, it is our hope that we would be \nable to expand our services for wider medical \ndermatological indications as mentioned above.  \nWe hope to include an intense pulsed light machine \nand an excimer laser among others and embark \non further service and research for indications in \nmedical dermatology.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3942\n\n\n\nTable 1. The demographic characteristics of 1190 patients who had laser treatment in the Department of Dermatology Hospital Kuala \nLumpur between 2012 and 2016.\n\n\n\nCharacteristics n=1190 \n\n\n\nMean age in years (range) 35.8 (9 days to 90 years)\n\n\n\nGender, n (%) Female 891 (68.8)\n\n\n\nMale 371 (31.2)\n\n\n\nEthnicity, n (%) Malay 698 (58.7)\n\n\n\nChinese 347 (29.2)\n\n\n\nIndian 124 (10.4)\n\n\n\nIban 1 (0.1)\n\n\n\nOthers 20 (1.7)\n\n\n\nMean number of laser session (range) 5.3 (1-46)\n\n\n\nFigure 1. The number of laser sessions provided per year in the Department of Dermatology, Hospital Kuala Lumpur.\n\n\n\n\n\n\n\nConclusion\nOur center treats a high volume and wide variety \nof dermatological disorders with four types of \ncutaneous laser devices. Nevertheless, we have a \nlow rate of post laser treatment complication. We \nwish to further exploit the utility of our current \nlasers for a broader range of medical dermatology \nindications. The fractional CO2 machine is currently \nonly used for acne scar resurfacing and LADD is \none possibility among other indications that can be \nexplored and researched.\n\n\n\nConflict of Interest Declaration\nThe authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health, Malaysia for his permission to \npublish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 43\n\n\n\nFigure 2. Number of sessions provided by different types of lasers in the Department of Dermatology Hospital Kuala Lumpur.\n\n\n\nTable 2. Indications for laser therapy in the Department of Dermatology Hospital Kuala Lumpur between 2012 and 2016.\n\n\n\nIndications n % Indications n %\n\n\n\nSeborrhoeic keratosis 249 20.9 Melanocytic naevus 17 1.4\n\n\n\nPort Wine Stain 162 13.6 Angiofibroma 16 1.3\n\n\n\nSolar lentigines 144 12.1 Pyogenic granuloma 16 1.3\n\n\n\nSyringoma 105 8.8 Post inflammatory hyperpigmentation 15 1.3\n\n\n\nViral wart 88 7.4 Trichoepithelioma 15 1.3\n\n\n\nNaevus of Ota 82 6.9 Ephilides 14 1.2\n\n\n\nSkin tags 78 6.6 Inflammatory acne 14 1.2\n\n\n\nTattoo removal 68 5.7 Cherry angioma 13 1.1\n\n\n\nMelasma 66 5.5 Rosacea 11 0.9\n\n\n\nKeloid scar 63 5.3 Comedones 11 0.9\n\n\n\nSebaceous hyperplasia 51 4.3 Telangiectasia 11 0.9\n\n\n\nHaemangiomas 48 4.0 Vascular malformations 10 0.8\n\n\n\nMilia 41 3.4 Caf\u00e9 au lait macules 6 0.5\n\n\n\nHori\u2019s naevus 41 3.4 Angiokeratoma 6 0.5\n\n\n\nLinear epidermal naevus 30 2.5 Naevus spilus 5 0.4\n\n\n\nBecker\u2019s naevus 22 1.8 Molluscum contagiosum 5 0.4\n\n\n\nXanthelasma 22 1.8 Actinic keratosis 4 0.3\n\n\n\nAcne scars 18 1.5 Calluses and corns 4 0.3\n\n\n\nSegmental lentigines 18 1.5 Others* 17 1.4\n\n\n\n* Steatocystoma multiplex, epidermal cyst, porokeratosis, rhinophyma, vasculitic ulcers, lymphocytoma cutis, granuloma facialis, \nlichen planus, capillaritis, pigmentary mosaicism and nodular prurigo\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3944\n\n\n\nTable 3. Clinical indications for ablative carbon dioxide laser.\n\n\n\nSeborrhoeic keratosis\nSolar lentigines\nSyringoma\nViral wart\nSkin tags\nSebaceous hyperplasia\nMilia\nLinear epidermal naevus\nMelanocytic naevus\nAngiofibroma\nPyogenic granuloma\nTrichoepithelioma\nComedones\nMolluscum contagiosum\nActinic keratosis\nCalluses and corns\nSteatocystoma multiplex\nEpidermal cyst\nPorokeratosis\nRhinophyma\nNodular prurigo\n\n\n\nTable 4. Clinical indications for PDL\n\n\n\nPort Wine Stain\nKeloid scar\nHaemangiomas\nRhinophyma\nVasculitic ulcers\nAngiofibroma\nAngiokeratoma\nPyogenic granuloma\nInflammatory acne\nCherry angioma\nRosacea\nTelangiectasia\nVascular malformations\nMolluscum contagiosum\nXanthelasma\nLymphocytoma cutis\nGranuloma facialis\nCapillaritis\n\n\n\nTable 5. Clinical indications for Q-switched Nd:YAG. \n\n\n\nSolar lentigines\nNaevus of Ota\nTattoo removal\nMelasma\nHori\u2019s naevus\nSegmental lentigines\nBecker\u2019s naevus\nEphilides\nCaf\u00e9 au lait macules\nNaevus spilus\nLichen planus\nPigmentary mosaicism\nPost inflammatory hyperpigmentation\n\n\n\nReferences\n\n\n\n1. Han G. Applications of lasers in medical dermatology. \nCutis 2014;94:E20-3.\n\n\n\n2. Abergel RP, Meeker CA, Lam TS, Dwyer RM, Lesavoy \nMA, Uitto J. Control of connective tissue metabolism by \nlasers: recent developments and future prospects. J Am \nAcad Dermatol 1984;11:1142-50.\n\n\n\n3. Arndt KA, Noe JM, Northam DB, Itzkan I. Laser therapy. \nBasic concepts and nomenclature. J Am Acad Dermatol \n1981;5:649-54.\n\n\n\n4. Gianfaldoni S, Tchernev G, Wollina U, Fioranelli M, \nRoccia MG, Gianfaldoni R et al. An Overview of Laser in \nDermatology: The Past, the Present and ... the Future (?).  \nMaced J Med Sci 2017;5:526-30.\n\n\n\n5. Omi T, Numano K. 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Darier-White disease treated \nwith fractional CO2 laser in two cases. Dermatol Ther \n2015;28:254-7.\n\n\n\n11. Goel A. Clinical applications of Q-switched NdYAG laser. \nIndian J Dermatol Venereol Leprol 2008;74:682-6.\n\n\n\n12. Anderson RR, Margolis RJ, Watenabe S, Flotte T, Hruza \nGJ, Dover JS. Selective photothermolysis of cutaneous \npigmentation by Q-switched Nd: YAG laser pulses at \n1064, 532, and 355 nm. J Invest Dermatol 1989;93:28-32.\n\n\n\n13. Landthaler M, Hohenleutner U. Laser therapy of vascular \nlesions. Photodermatol Photoimmunol Photomed \n2006;22:324-32.\n\n\n\n15. Erceg A, Bovenschen HJ, van de Kerkhof PC, de Jong \nEM, Seyger MM. Efficacy and safety of pulsed dye laser \ntreatment for cutaneous discoid lupus erythematosus. J Am \nAcad Dermatol 2009;60:626-32.\n\n\n\n16. Welsh JH, Schroeder TL, Levy ML. Granuloma faciale in \na child successfully treated with the pulsed dye laser. J Am \nAcad Dermatol 1999;41:351-3.\n\n\n\n17. Cheung ST, Lanigan SW. Granuloma faciale treated with \nthe pulsed-dye laser: a case series. Clin Exp Dermatol \n2005;30:373-5.\n\n\n\n18. Roos S, Raulin C, Ockenfels HM, Karsai S. Successful \ntreatment of cutaneous sarcoidosis lesions with the \nflashlamp pumped pulsed dye laser: a case report. Dermatol \nSurg 2009;35:1139-40.\n\n\n\n19. O\u2019Donoghue NB, Barlow RJ. Laser remodelling of nodular \nnasal lupus pernio. Clin Exp Dermatol 2006;31:27-9.\n\n\n\n20. Karsai S, Friedl H, Buhck H, Junger M, Podda M. The role \nof the 595-nm pulsed dye laser in treating superficial basal \ncell carcinoma: outcome of a double-blind randomized \nplacebo-controlled trial. Br J Dermatol 2014;172:677-83.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 45\n\n\n\n21. Bonis B, Kemeny L, Dobozy A, Bor Z, Szabo G, Ignacz \nF. 308 nm UVB excimer laser for psoriasis. Lancet \n1997;350:1522.\n\n\n\n22. Jin SP, Jeon YK, Cho KH, Chung JH. Excimer laser therapy \n(308 nm) for mycosis fungoides palmaris et plantaris: a \nskin-directed and anatomically feasible treatment. Br J \nDermatol 2010;163:651-3.\n\n\n\n23. Deaver D, Cauthen A, Cohen G, Sokol L, Glass F. Excimer \nlaser in the treatment of mycosis fungoides. J Am Acad \nDermatol 2014;70:1058-60.\n\n\n\n24. Beggs S, Short J, Rengifo-Pardo M, Ehrlich A. \nApplications of the Excimer Laser: A Review. Dermatol \nSurg 2015;41:1201-11.\n\n\n\n25. Feldman SR, Mellen BG, Housman TS, Fitzpatrick RE, \nGeronemus RG, Friedman PM et al. Efficacy of the 308-\nnm excimer laser for treatment of psoriasis: results of a \nmulticenter study. J Am Acad Dermatol 2002;46:900-6.\n\n\n\n26. Mafong EA, Friedman PM, Kauvar AN, Bernstein LJ, \nAlexiades-Armenakas M, Geronemus RG. Treatment of \ninverse psoriasis with the 308 nm excimer laser. Dermatol \nSurg 2002;28:530-2.\n\n\n\n27. Gupta SN, Taylor CR. 308-nm excimer laser for the \ntreatment of scalp psoriasis. Arch Dermatol 2004;140:518-\n20.\n\n\n\n28. Morison WL, Atkinson DF, Werthman L. Effective \ntreatment of scalp psoriasis using the excimer (308 \nnm) laser. Photodermatol Photoimmunol Photomed \n2006;22:181-3.\n\n\n\n29. Carrascosa JM, Soria X, Domingo H, Ferr\u00e1ndiz C. \nTreatment of inverse psoriasis with excimer therapy and \ntacrolimus ointment. Dermatol Surg 2007;33:361-3.\n\n\n\n30. .Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand \nJM, Gordon KB et al. Guidelines of care for the management \nof psoriasis and psoriatic arthritis: Section 5. Guidelines of \ncare for the treatment of psoriasis with phototherapy and \nphotochemotherapy. J Am Acad Dermatol 2010;62:114-\n35.\n\n\n\n31. Mudigonda T, Dabade TS, Feldman SR. A review of \ntargeted ultraviolet B phototherapy for psoriasis. J Am \nAcad Dermatol 2012;66:664-72.\n\n\n\n32. Novak Z, Bonis B, Baltas E, Ocsovszki I, Ignacz F, Dobozy \nA et al. Xenon chloride ultraviolet B laser is more effective \nin treating psoriasis and in inducing T cell apoptosis than \nnarrow-band ultraviolet B. J Photochem Photobiol B \n2002;67:32-8.\n\n\n\n33. Almutawa F, Thalib L, Hekman D, Sun Q, Hamzavi I, Lim \nHW. Efficacy of localized phototherapy and photodynamic \ntherapy for psoriasis: a systematic review and meta-\nanalysis. Photodermatol Photoimmunol Photomed \n2015;31:5-14.\n\n\n\n34. Alhowaish AK, Dietrich N, Onder M, Fritz K. Effectiveness \nof a 308-nm excimer laser in treatment of vitiligo: a review. \nLasers Med Sci 2013;28:1035-41.\n\n\n\n35. Matsui A, Nakano H, Aizu T, Sawamura D. Treatment of \nacquired reactive perforating collagenosis with 308-nm \nexcimer laser. Clinical and Experimental Dermatology \n2016;41:811-22.\n\n\n\n36. Sklar LR, Burnett CT, Waibel JS, Moy RL, Ozog DM. \nLaser assisted drug delivery: a review of an evolving \ntechnology. Lasers Surg Med 2014;46:249-62.\n\n\n\n37. Zaleski-Larsen LA, Fabi SG. Laser-Assisted Drug \nDelivery. Dermatol Surg 2016;42:919-31.\n\n\n\n38. Waibel JS, Rudnick A, Shagalov DR, Nicolazzo DM. \nUpdate of Ablative Fractionated Lasers to Enhance \nCutaneous Topical Drug Delivery. Adv Ther 2017;34:1840-\n9.\n\n\n\n39. AlNomair N, Nazarian R, Marmur E. Complications in \nlasers, lights, and radiofrequency devices. Facial Plast \nSurg 2012;28:340-6.\n\n\n\n40. Costa FB, El Ammar ABPC, Campos VB, Kalil CLPV. \nComplications in laser dermatologic surgery. Part II: \nfractional and nonfractional ablative laser and fractional \nnon-ablative laser. Surgical And Cosmetic Dermatology \n2011;3:135-46.\n\n\n\n41. El Ammar ABPC, Costa FB, Kalil CLPV, Campos VB. \nComplications in laser dermatologic surgery Part I: \nNon-fractional non-ablative lasers Surgical Cosmetic \nDermatology 2010;3:47-53.\n\n\n\n42. Nanni CA, Alster TS. Complications of carbon dioxide \nlaser resurfacing. An evaluation of 500 patients. Dermatol \nSurg 1998;24:315-20.\n\n\n\n43. Alster TS, Nanni CA. Famciclovir prophylaxis of herpes \nsimplex virus reactivation after laser skin resurfacing. \nDermatol Surg 1999;25:242-6.\n\n\n\n44. Kim YJ, Whang KU, Choi WB, Kim HJ, Hwang JY, Lee \nJH et al. Efficacy and safety of 1,064 nm Q-switched \nNd:YAG laser treatment for removing melanocytic nevi. \nAnn Dermatol 2012;24:162-7.\n\n\n\n45. Younes AKH, Mohammed EE, Tawfik KM, Mohamed \nRR, Abdo Y. The Effect of 3 Sessions of Q Switched \nNeodymium: Yttrium\u2013Aluminum\u2013 Garnet Laser in the \nTreatment of Freckles. Pigmentary Disorders. Journal of \nPigmentary Disorders 2015;2:193.\n\n\n\n46. Willey A, Anderson RR, Azpiazu JL, Bakus AD, Barlow \nRJ, Dover JS et al. Complications of laser dermatologic \nsurgery. Lasers Surg Med 2006;38:1-15.\n\n\n\n47. Wlotzke U, Hohenleutner U, Abd-El-Raheem TA, Baumler \nW, Landthaler M. Side-effects and complications of \nflashlamp-pumped pulsed dye laser therapy of port-wine \nstains. A prospective study. Br J Dermatol 1996;134:475-\n80.\n\n\n\n48. Thajudheen CP, Jyothy K, Priyadarshini A. Treatment of \nport-wine stains with flash lamp pumped pulsed dye laser \non Indian skin: a six year study. J Cutan Aesthet Surg \n2014;7:32-6.\n\n\n\n49. Ramsdell WM. Fractional CO2 Laser Resurfacing \nComplications. Semin Plast Surg 2012;26:137-40.\n\n\n\n50. Sullivan SA, Dailey RA. Complications of laser \nresurfacing and their management. Ophthal Plast Reconstr \nSurg 2000;16:417-26.\n\n\n\n51. Zhang AY, Obagi S. Diagnosis and management of skin \nresurfacing-related complications. Oral Maxillofac Surg \nClin North Am 2009;21:1-12.\n\n\n\n52. Neaman KC, Baca ME, Piazza RC, VanderWoude DL, \nRenucci JD. Outcomes of fractional CO2 laser application \nin aesthetic surgery: a retrospective review. Aesthet Surg J \n2010;30:845-52.\n\n\n\n53. Manuskiatti W, Triwongwaranat D, Varothai S, Eimpunth \nS, Wanitphakdeedecha R. Efficacy and safety of a carbon-\ndioxide ablative fractional resurfacing device for treatment \nof atrophic acne scars in Asians. J Am Acad Dermatol \n2010;63:274-83.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3946\n\n\n\nCASE REPORT\n\n\n\nGardner \u2013 Diamond Syndrome\nEllie Choi1, MMed, Sam Yang1, MRCP, See Ket Ng2, MMed\n\n\n\n1Division of Dermatology, Department of Medicine, National University Hospital, Singapore\n2National Skin Centre, Singapore\n\n\n\nSummary\nGardner\u2013Diamond syndrome (GDS), or autoerythrocyte sensitisation, is a rare cause of recurrent \npainful bruising with a typical anamnesis and prodrome. We describe a patient with GDS and discuss \nthe literature surrounding this unique condition.\n\n\n\nKey words: Autoerythrocyte sensitisation, Gardner Diamond Syndrome, Painful bruising\n\n\n\nCorresponding Author\nDr Ellie Choi\n5, Lower Kent Ridge Road, 119074 Singapore\nEmail: Ellie_choi@nuhs.edu.sg\n\n\n\nIntroduction\nGardner\u2013Diamond syndrome (GDS), also known \nas autoerythrocyte sensitisation or painful bruising \nsyndrome, is said to be an autoimmune vasculopathy \ncaused by sensitization to phosphatidylserine, a \ncomponent of erythrocyte stroma.\n\n\n\nUnlike typical bruising, patients with GDS \nmay experience generalized malaise, fever and \ngastrointestinal symptoms. There is an interesting \nprodromal phase of burning and itching sensation of \nthe skin, before erythematous plaques and swelling \nappear. The lesions evolve to become blue-yellowish \nand then greenish before disappearing in 7-10 days \nas the erythema and swelling subside. Lesions may \narise after an event of mild mechanical provocation, \nbut commonly after emotional stress without \nphysical injury, or spontaneous development.1\n\n\n\nThere is an association with the female gender and \nhysterical personality traits, with psychoemotional \ndisorders being a characteristic finding in these \npatients.1\n\n\n\nWe highlight a case of Gardner-Diamond syndrome \nin a lady with painful bruising. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 47\n\n\n\nCase Reports\nA 65-year-old lady presented to the dermatology \nclinic with a 10 months history of a mildly pruritic \nrash. This affected her thighs and abdomen. Bruises \nwere seen, and occurred without an antecedent \nhistory of trauma. \n\n\n\nHer symptoms would start with pain and itching, \nfollowed by bruising. New lesions would develop on \naverage once every week, and each would last for 1 \nmonth before spontaneously resolving.  There were \nno triggering factors such as trauma or emotional \nstress.\n\n\n\nShe had a past medical history of a breast carcinoma \nand was in remission after excision. Of note, she \nhad no psychiatric history.\n\n\n\nOn examination, there were irregular ecchymotic \npatches over the limbs of different ages (Figure \n1a&b). Blood counts and coagulation profile were \nnormal.\n\n\n\nThe diagnosis of GDS was made based on the \ncharacteristic history and skin findings. She \nwas treated with cetirizine for itch, and topical \nbetamethasone valerate 0.025% cream and menthol. \nShe continued to develop recurrent itching and \nbruising, but at a reduced frequency of once per \nmonth. She was not keen for further confirmatory \ntesting for GDS as she was clinically improving.\n\n\n\nFigure 1. (a) Over the left thigh, an irregular, ecchymotic patch; (b) Right popliteal fossa showing an area of resolving ecchymosis. \n\n\n\nDiscussion\nGDS was first described in 1955 by Frank Gardner \nand Louis Diamond2 in four women with an \nabnormal pain bruising response to minor trauma, \nwith an intradermal sensitivity to autologous red \ncells stroma but not autologous plasma. Gouch et \nal.3 subsequently went on to identify phosphatidyl \nserine in the cell membrane as the provocative \nfactor.\n\n\n\nA postulated theory for the development of \nautoerythrocyte sensitisation is that extravasation \nof erythrocytes triggers specific antibodies of the \nIgE class to cardiolipin and phosphatidylserine. \nThese induce redistribution of erythrocyte \nphosphatidylserine onto the outer surface of the cell \nmembrane resulting in autosensitisation.4\n\n\n\nThe presence of a prodromal stage with malaise \nand fatigue, as well as pain, itching, and edematous \nplaques is consistent with an inflammatory phase. \nThis is typically followed by the development of \necchymoses as the inflammatory infiltrate regresses.1\n\n\n\nDespite the strong association with underlying \npsychological and emotional factors, the \nunderstanding and pathogenesis of these factors \nin the development of GDS is still uncertain. The \ndiagnosis is made by typical anamnestic data, \nclinical features, and a positive intracutaneous test \nwith autoerythrocytes. In this test, 1ml of the patients \nwashed erythrocytes is injected intracutaneously, \nand if positive, the typical inflammatory lesions \nprogressing to bruising would develop with 24 \nhours, demonstrating autosensitisation to own \nerythrocytes.1\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3948\n\n\n\nDifferential diagnosis to consider, especially when \nconfirmatory tests are not performed as in our \npatient, would include an underlying coagulopathy \nsuch as hemophilia, or thrombocytopenia.5 Where \nlaboratory investigations are normal, non accidental \ntrauma,5 Munchausen\u2019s syndrome,6 Cushings \nsyndrome,7 and collagen vascular diseases8 such as \nEhlera-Danlos syndrome should be considered in a \npatient with recurrent bruising.\n\n\n\nTreatment is overall limited, with minimal evidence \nfor oral medications.  Psychotherapy has been trialed \nwith good results in some case studies9,10 The course \nof GDS may last years, with periods of remission, \nand relapses associated with stress. \n\n\n\nAn understanding of the characteristic findings \nwould help to difference this from differential \ndiagnoses such as bleeding disorders and physical \nabuse.\n\n\n\nConclusion\nAlthough rare, GDS is an important diagnosis to \nkeep in mind in the assessment of a patient with \nrecurrent bruising. A suspicion of this condition \nshould prompt further evaluation of underlying \npsychological or emotional factors, which may be \nmore distressing for the patient than the dermatologic \nmanifestations.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Ivanov OL, Lvov AN, Michenko AV, K\u00fcnzel J, Mayser \nP, Gieler U. Autoerythrocyte sensitization syndrome \n(Gardner-Diamond syndrome): review of the literature. J \nEur Acad Dermatol Venereol 2009;23:499-504. \n\n\n\n2. Gardner FH, Diamond LK. Autoerythrocyte sensitization: \na form of purpura producing painful bruising following \nautosensitization to red blood cells in certain women. \nBlood 1955;10:675-90. \n\n\n\n3. Groch GS, Finch SC, Rogoway W, Fischer DS. Studies \nin the pathogenesis of autoerythrocyte sensitization \nsyndrome. Blood 1966;28:19-33. \n\n\n\n4. Struneck\u00e1 A, Krpejsov\u00e1 L, Palecek J, M\u00e1cha J, \nMaturov\u00e1 M, Rosa L et al. Transbilayer redistribution \nof phosphatidylserine in erythrocytes of a patient with \nautoerythrocyte sensitization syndrome (psychogenic \npurpura). Folia Haematol Int Mag Klin Morphol Blutforsch \n1990;117:829-41.\n\n\n\n5. Sibert J. Bruising, coagulation disorder, and physical child \nabuse. Blood Coagul Fibrinolysis Int J Haemost Thromb \n2004;15:S33-9. \n\n\n\n6. Clark GD, Key JD, Rutherford P, Bithoney WG. \nMunchausen\u2019s syndrome by proxy (child abuse) presenting \nas apparent autoerythrocyte sensitization syndrome: \nan unusual presentation of Polle syndrome. Pediatrics \n1984;74:1100-2. \n\n\n\n7. Pluta RM, Burke AE, Golub RM. JAMA patient \npage. Cushing syndrome and Cushing disease. JAMA \n2011;306:2742. \n\n\n\n8. De Paepe A, Malfait F. Bleeding and bruising in patients \nwith Ehlers-Danlos syndrome and other collagen vascular \ndisorders. Br J Haematol 2004;127:491-500. \n\n\n\n9. Silny W, Marciniak A, Czarnecka-Operacz M, Zaba R, \nSchwartz RA. Gardner-Diamond syndrome. Int J Dermatol \n2010;49:1178-81. \n\n\n\n10. Ingen-Housz-Oro S, Viguier M, Guitera-Rovel P, Verola O, \nDe Kerviler E, Girault N et al. [Painful bruising syndrome \nmimicking cellulitis of the leg]. Ann Dermatol Venereol \n2002;129:1029-32. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 49\n\n\n\nCASE REPORT\n\n\n\nDialysis-associated Pseudoporphyria: An Often Overlooked Cause \nof Bullous Photosensitivity\nRajalingam Ramalingam, MRCP, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nPseudoporphyria is a condition clinically and histologically similar to porphyria cutanea tarda (PCT) \nbut without abnormalities in porphyrin metabolism. Pseudoporphyria has also been described in \npatients with chronic renal failure, with or without accompanying dialysis. Herein we report a case \nof dialysis-associated pseudoporphyria in the hopes that increased awareness of this condition may \nultimately lead to improved outcomes with the institution of specific treatment measures.\n\n\n\nKey words: Pseudoporphyria, Dialysis, Photosensitivity\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology, Hospital Tengku Ampuan \nAfzan, Jalan Tanah Putih, 25100 Kuantan, Pahang, \nMalaysia\nEmail: raj.blueheart@gmail.com\n\n\n\nIntroduction\nPseudoporphyria is a condition clinically and \nhistologically similar to porphyria cutanea tarda \n(PCT) but without abnormalities in porphyrin \nmetabolism. Numerous causes have been \nreported in the literature, among them, excessive \nultraviolet A (UVA) exposure, drugs (nonsteroidal \nantiinflammatory drugs [NSAIDs], retinoids, \nantibiotics, diuretics) and chronic hepatitis C \ninfection.1 Pseudoporphyria has also been described \nin patients undergoing dialysis for chronic renal \nfailure.2,3 Increased awareness of dialysis-associated \npseudoporphyria may ultimately lead to improved \noutcomes with the institution of prompt as well as \nspecific treatment measures.\n\n\n\nCase Report \nA 33-year-old lady on hemodialysis for the past one \nyear for end-stage renal disease (ESRD), was referred \nto us for a nonpruritic, scarring, blistering rash over \nher face and dorsal surface of both hands. The rash \nbegan approximately four months after initiation \nof dialysis and was associated with erythema and \nsubsequent vesicular eruption following exposure \nto sunlight. She wears a hijab, long-sleeved blouses \nand socks whenever she is outdoors. There was no \nsignificant family history.\n\n\n\nThe cause of her ESRD was presumed to be \nsecondary to chronic glomerulonephritis in view of \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3950\n\n\n\nbilaterally contracted kidneys on ultrasonography. \nPrimary disease of autoimmune and infective \netiology had been ruled out. She is presently only \non folic acid, calcium carbonate and B complex \nvitamin supplements, in addition to subcutaneous \nerythropoietin-beta replacement. She denies \nconsuming any over-the-counter or traditional \nherbal medicines.\n\n\n\nExamination revealed photo-distributed \nhyperpigmentation and deep dermal scarring, \npredominantly over her face and dorsal surface of \nboth hands (Figures 1a-d). Intact vesicles were also \nnoted over two of her digits (Figure 1e).\n\n\n\nFigure 1. (a)-(d) Clinical presentation of the patient showed dyspigmentation and scarring over the sun exposed skin; (e) Bullae noted \non the fingers.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 51\n\n\n\nBlood investigations were in keeping with ESRD. \nSkin biopsy showed a cell-poor subepidermal \ncleft with festooning (Figure 2a-b). Direct \nimmunofluorescence studies were negative. As the \npatient was anuric, blood for porphyria screening \nwas done instead, which did not detect any gene \nmutation for the enzyme hydroxymethylbilane \nsynthase (HMBS). Nor did it show elevated \nporphyrin levels, therefore ruling out acquired PCT. \n\n\n\nAs such, we concluded that this lady has dialysis-\nassociated pseudoporphyria. She was prescribed \na moderate potency topical corticosteroid and \nsunscreen, and advised appropriately regarding \nsun protection measures. We will consider oral \nN-acetylcysteine should she not improve.\n\n\n\nDiscussion\nPseudoporphyria may occur in patients with chronic \nkidney disease irrespective of dialysis status. \nPostulated theories include inadequate clearance \nof porphyrins due to renal failure, porphyrins \nhaving too high a molecular weight to be cleared \nby hemodialysis membranes4, azotemia reducing \nthe activity of uroporphyrinogen decarboxylase \nresulting in increased plasma porphyrins5 and \nconcomitant administration of photosensitizing \ndrugs such as diuretics, statins, aluminum hydroxide \nand antihypertensive agents.6 None of these drugs \nwas being taken by our patient.\n\n\n\nThe role of erythropoietin in association with \npseudoporphyria is controversial. At least one \nreport seemed to suggest that erythropoietin might \nlead to photosensitization7, while other authors \nhave successfully used erythropoietin as a treatment \nfor hemodialysis-associated PCT8,9 by effectively \n\n\n\nreducing iron stores. In our patient, her blisters began \nprior to the initiation of erythropoietin replacement, \nthus ruling out erythropoietin as a cause of bullous \nphotosensitization.\n\n\n\nThe management of psedoporphyria in the context \nof ESRD can be very challenging. In most cases \nurine for porphyrins cannot be analyzed due to \nanuria, and the diagnosis is dependent on blood \nand stool porphyrin levels in addition to typical \nhistopathological findings. Several treatment \nmodalities have been reported in the literature with \nvariable success, including N-acetylcysteine3,4,10,11, \ndeferoxamine12, chloroquine13 and small-volume \nphlebotomy14 among other anecdotal therapies. \nPatients with ESRD are prone to oxidative stress \ndue to reduced glutathione levels in plasma \nand circulating erythrocytes, which increases \nsusceptibility to the effects of ultraviolet exposure \nat even lower porphyrin levels.13 Administration \nof N-acetylcysteine increases intracellular \nbiosynthesis of glutathione, a potent antioxidant, \nthereby reducing the oxidative stress.3\n\n\n\nConclusion\nPseudoporphyria should be suspected in any \npatient with chronic kidney disease having bullous \nphotodermatoses, with or without accompanying \ndialysis.\n\n\n\nConflict of Interest Declaration\nThe author has no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nFigure 2. (a) & (b) Histology of the skin biopsy revealed cell-poor subepidermal blister filled with fibrin.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3952\n\n\n\nReference\n\n\n\n1. Green JJ, Manders SM. Pseudoporphyria. J Am Acad \nDermatol 2001;44:100-8.\n\n\n\n2. Bergler-Czop B, Brzezi\u0144ska-Wcis\u0142o L. Pseudoporphyria \ninduced by hemodialysis. Postep Derm Alergol 2014;1:53-\n5.\n\n\n\n3. Tremblay JF, Veilleux B. Pseudoporphyria associated with \nhemodialysis treated with N-acetylcysteine. J Am Acad \nDermatol 2003;12:1189-90.\n\n\n\n4. Vadoud-Seyedi J, de Dobbeleer G, Simonart T. Treatment \nof hemodialysis-associated pseudoporphyria with \nN-acetylcysteine: report of two cases. Br J Dermatol \n2000;142:580-1.\n\n\n\n5. Day RS, Eales L. Porphyrins in chronic renal failure. \nNephron 1980;26:90-5.\n\n\n\n6. Beer K, Applebaum D, Nousari C. Pseudoporphyria: \ndiscussion of etiologic agents. J Drugs Dermatol \n2014;13:990-2.\n\n\n\n7. Harvey E, Bell CH, Paller AS. Pseudoporhyria cutanea \ntarda: two case reports on children receiving peritoneal \ndialysis and erythropoietin therapy. J Pediatr 1992;121:749-\n52.\n\n\n\n8. Sarkell B, Patterson JW. Treatment of porphyria cutanea \ntarda of end-stage renal disease with Erythropoietin. J Am \nAcad Dermatol 1993;29:499-500.\n\n\n\n9. Peces R. Enriquez de Salamanca R, Fontenellas A. \nSuccessful treatment of haemodialysis -related porphyria \ncutanea tarda with erythro poietin. Nephrol Dial Transplant \n1994;9:433-5.\n\n\n\n10. Fevang SAM, Kroon S, Skadberg O. Pseudoporphyria \nor Porphyria Cut\u00e1nea Tarda? Diagnostic and Treatment \nDifficulties. Acta Derm Venereol 2008;88:426-7.\n\n\n\n11. Katoulis AC, Ferra D, Toumbis E, Papadavid E, Kanelleas \nA, Panayiotides I et al. Pseudoporphyria Associated with \nNonhemodialyzed Renal Insufficiency, Successfully \nTreated with Oral N-Acetylcysteine. Case Reports in \nDermatol Med 2013;2013:1-3.\n\n\n\n12. Labidi J. Porphyria Cutanea Tarda in a Chronic \nHemodialysis Patient. Saudi J Kidney Dis Transpl \n2010;21:919-22.\n\n\n\n13. El Kabbaj D, Laalou A, Alouane Z, Bahadi A, Oualim Z. \nHemodialysis-Associated Pseudoporphyria Resistant to \nN-acetylcysteine. Saudi J Kidney Dis Transpl 2011;22:311-\n4.\n\n\n\n14. Shieh S., Cohen J. L., Lim H. W. Management of porphyria \ncutanea tarda in the setting of chronic renal failure: A case \nreport and review. J Am Acad Dermatol 2000;42:645-52. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 53\n\n\n\nCASE REPORT\n\n\n\nAngiosarcoma Mimicking Rhinophymatous Rosacea\nRaja Siti Aishah Bt Raja Mohd Radzi 1, MD, Kwee Eng Tey1, MRCP, Siew Eng Choon1, FRCP, Meng Yen Lee 2, MPath\n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia\n2Department of Pathology, Hospital Sultanah Aminah, Johor Bahru, Malaysia\n\n\n\nSummary\nCutaneous angiosarcoma is a rare, highly malignant vascular tumor. More than 50% of them are \nlocalized to the skin of the head and neck regions. It usually present as nodules with ulceration, plaques, \nor bruise-like lesions. However, the clinical features may vary. We reported this case due to its atypical \nclinical presentation, which presented with rhinophyma-like features, making it a diagnostic challenge \nto the clinicians. \n\n\n\nKey words: Angiosarcoma, Rhinophymatous Rosacea\n\n\n\nCorresponding Author\nDr Tey Kwee Eng\nDepartment of Dermatology, Hospital Sultanah Aminah, \nJalan Persiaran Abu Bakar Sultan, 80100 Johor Bahru, \nJohor, Malaysia. \n\n\n\nIntroduction\nCutaneous angiosarcoma is a rare, highly malignant \nvascular tumor. More than 50% of them are \nlocalized to the skin of the head and neck regions.1 \nAngiosarcomas are aggressive lesions which tend to \nrecur locally and spread widely. They have a high \nrate of lymph nodes and systemic metastases, as \nwell as tumor related-death. The reported 5-year \nsurvival of angiosarcoma is between 10% to \n35%.5 Angiosarcomas of the face usually present \nas nodules with ulceration, plaques, or bruise-like \nlesions. However, the clinical features may vary and \noccasionally cellulitis-like lesion, angioneurotic \nedema, and scarring alopecia have been described.1\n\n\n\nCase Report \nA 73-years-old gentleman presented with reddish \ndiscoloration with mild swelling on the tip of his \nnose for 2 months duration. The lesion was non-itchy \nand painless in nature. Initially the lesion started as \na red papule over the right nostril associated with \nnose swelling. He had no prior history of irradiation. \nExamination revealed erythematous to violaceous \ninfiltrative plaque with superficial telangiectatic \nvessels and diffuse swelling of the nose (Fig. 1). \nCervical lymphadenopathy was not detectable. \nSystemic review was unremarkable. Initial \ndifferential diagnoses include rhinophymatous \nrosacea, lupus pernio and angiosarcoma.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3954\n\n\n\nFigure 1. Erythematous to violaceous infiltrative plaque with \nsuperficial telangiectatic vessels and diffuse swelling of the \nnose.\n\n\n\nSkin histology showed proliferation of tortuous, \nanastomosing vasculature network with dissecting \nstroma. These vessels were lined by plump, atypical \nendothelial cells with vesicular chromatin and \noccasional prominent nucleoli. Multinucleated \ntumour cells were seen. There was focal area of \nnecrosis noted (Fig. 2a). The atypical endothelin \ncells were stained positive for CD31 (Fig. 2a) and \nCD34. It was negative for S-100 protein, SMA \nand HHV-8. Ki67 stains showed about 10% of the \ntumour cells.\n\n\n\na b\n\n\n\nFigure 2. (a) (X100) Histological image of proliferation of tortuous, anastomosing vasculature network with dissecting stroma and focal \narea of necrosis; (b)(X400) Tumour cells were stained positive for CD31.\n\n\n\nDiagnosis of cutaneous angiosarcoma was made \nbased on clinical presentation and skin histology. \nLaboratory indices were normal. PET scan showed \nno distant metastasis. Patient was referred to \nplastic surgery team, however surgical intervention \nwas deemed not feasible. Thereafter, patient was \nreferred to oncology team for further management. \nHe received 30 doses of radiotherapy but failed to \ncontrol the tumour. Unfortunately, he succumbed 10 \nmonths after the diagnosis was made. \n\n\n\nDiscussion \nWhile soft tissue angiosarcomas have a similar \ndistribution between sexes and can develop at any \nage, cutaneous angiosarcoma is most commonly \nseen in elderly adult males. Most lesions which \npresent on the face and scalp are sporadic cases \nwhile cutaneous angiosarcoma presenting in other \n\n\n\nlocations can be associated with previous radiation \ntherapy or chronic lymphoedema.\n\n\n\nThe link between radiotherapy and angiosarcoma \nwas first reported in 1981 when angiosarcoma was \nobserved in the mammary skin of a woman, years \nafter lumpectomy and radiotherapy done for breast \ncancer. \n\n\n\nAngiosarcoma is a rare complication of radiotherapy \nwith a cumulative incidence of 0.9 per 1000 cases \nover 15 years. A Surveillance of Epidemiology and \nEnd Results (SEER) data study demonstrated a peak \nincidence of 5 - 10 years after treatment.3\n\n\n\nThe majority of radiation-induced cutaneous \nangiosarcomas occur in the breast, but they are \nalso observed in the head and neck or other sites. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 55\n\n\n\nReferences\n\n\n\n1. Rich AL, Berman P. Cutaneous angiosarcoma presenting \nas an unusual facial bruise. Age Ageing 2004;33:512-4.\n\n\n\n2. Thomas Mentzel, Heinz Kutzner, Uwe Wollina. Cutaneous \nangiosarcoma of the face: Clinicopathologic and \nimmunohistochemical study of a case resembling rosacea \nclinically, J Am Acad Dermatology, 1998;38:837-40.\n\n\n\n3. Dossett LA, Harrington M, Cruse CW, Gonzalez RJ. \nCutaneous angiosarcoma. Curr Probl Cancer 2015;39:258-\n63.\n\n\n\n4. Lo Presti M, Mazzella C, Monfrecola A, Falleti J. \nAngiosarcoma mimicking rhinophyma. Dermatol Res \nPract 2010;2010:1-3.\n\n\n\n5. Aguila LI, S\u00e1nchez JL. Angiosarcoma of the face \nresembling rhinophyma. J Am Acad Dermatology \n2003;49:530-1.\n\n\n\n6. Gallardo MA, Bosch RJ, Vidal L, Cabra B, Rodrigo AB, \nDe Galvez MV et al. Angiosarcoma arising on rhinophyma. \nEur J Dermatol. 2000;10:555-8.\n\n\n\nChronic lymphoedema of any origin - post-\nlymphadenectomy, Milroy\u2019s disease (hereditary \nlymphoedema) and chronic infection - is also \nassociated with the development of angiosarcoma \n(Stewart-Treves syndrome).3\n\n\n\nOur patient presented with skin lesions mimicking \nrhinophymatous rosacea with no prior history \nof irradiation. Diagnosis was confirmed after \nskin biopsy. In the literature, both angiosarcoma \nresembling rhinophyma and angiosarcoma \ndeveloping on rhinophyma had been reported. The \nformer was described by Aguila and S\u00e1nchez5 and \nthe latter by Gallardo et al.6\n\n\n\nConclusion\nTherefore, it is important to have a high index \nof suspicion in order not to miss the diagnosis of \nangiosarcoma. Therapeutical approach comprises \nwide resection in localised neoplasms while for \nlarger tumors, radiotherapy or chemotherapy can be \nused.4\n\n\n\nConflict of Interest Declaration\nThe author has no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3956\n\n\n\nCASE REPORT\n\n\n\nAtypical Presentation of Cutaneous Larva Migrans: A Case Report & \nLiterature Review\nKean Pan Ong1, MBBS, Wooi Chiang Tan1, MRCP, AdvMDerm, Yew Thong Chong2, MRCP, AdvMDerm, Yek Huan Khor1, \nMRCP, AdvMDerm, Lee Chin Chan1, MMed, FRACGP\n\n\n\n1Department of Dermatology, Hospital Pulau Pinang, Georgetown, Penang, Malaysia\n2Gleneagles Penang, Georgetown, Penang, Malaysia\n\n\n\nSummary\nCutaneous larva migrans, also known as \u201cmigrant linear epidermitis\u201d, \u201cbeach worm\u201d, \u201cmigrant \nhelminthiasis\u201d, \u201cdermatitis serpiginosus\u201d or \u201ccreeping eruption\u201d. It is a zoonosis which caused by \naccidental percutaneous inoculation of helminth larvae, usually parasites of the small intestines of cats \nand dogs. It typically presents as an itchy, erythematous, serpiginous, cutaneous eruption. We describe \na case of disseminated and extensive infection of cutaneous larva migrans in a 21-year-old traveler, \nleading a delay in diagnosis and treatment.\n\n\n\nKey words: Cutaneous larva migrans, Creeping eruption, Hookworm infection, Dermatitis serpiginosus.\n\n\n\nCorresponding Author\nDr Chan Lee Chin\nDepartment of Dermatology, Hospital Pulau Pinang, \nJalan Residensi, 10990 Georgetown, Malaysia.\nEmail: lccjess@yahoo.com\n\n\n\nIntroduction\nCutaneous Larva migrans (CLM) is caused by \npercutaneous penetration and migration of larvae \nof nematode parasite.1-2 It is most commonly found \nin tropical and subtropical areas like the Caribbean, \nSouth and Central America, Southeast Asia and \nAfrica. The infestation has no prevalence in term of \nrace, sex and age but higher risk in those who walk \nbarefoot or expose without wearing shirt to soil or \nsandy beach contaminated with animal feces.3-4\n\n\n\nDiagnosis is usually made clinically based on the \ntypical appearance of intensely pruritic serpiginous \nor linear erythematous lesions that advances. We \nreport a case of atypical presentation of cutaneous \nlarva migrans causing a delay in diagnosis and \ntreatment.\n\n\n\nCase Report \nBS is a 21 years old man from Germany. He was \nhere for a month doing his internship at one of \nthe factory in Penang Island. He presented with \ngeneralised pruritic rashes over his trunk and limbs \nof two days duration. Two weeks prior to onset of \nhis symptoms, he had traveled to Pulau Perhentian, \na resort Island in East Penisular, Malaysia. He had \nsunbathed on the beach. There was no significant \ndrug or contact history. He did not have any atopy \nhistory.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 57\n\n\n\nClinically, he was noted to have extensive excoriated \nerythematous scaly papules and small plaques all \nover his trunk and limbs (Figure.1a&b). He was \ntreated as papular eczema with systemic steroid as \nwell as a course of anti-scabetic. However, there was \nno response and in the subsequent days the lesions \nbecame more papulo-vesicles. His full blood count, \nrenal profile and liver function test were within \nnormal limit.\n\n\n\nOver the next ten days, the lesions progressively \nappeared more serpiginous (Figure. 1c-f). It was \nthen obvious clinically that he had cutaneous larva \nmigrans. He was treated with oral albendazole \n400mg once daily for three days and resulted in \nrapid improvement of pruritus and rashes within 3 \ndays.\n\n\n\nDiscussion\nCLM is caused by larvae of animal nematode \nespecially hookworm. Common nematodes involved \nare Ancylostoma braziliense, Ancvlostoma caninum \nand Uncinaria stenocephala.1 The adult worms live \nin the intestines of dogs and cats. The parasite\u2019s \neggs (ova) are discharged in the animal feces. The \nova hatch into larvae that mature into infective \nfilariform larvae, which will penetrate human skin \nwhen a person comes in contact with infected soil \nor sand. The infective larvae can migrate freely \nin sandy soils especially in areas where warm \ntemperatures and moisture (like tropical beaches \nincluding Malaysia) are optimal for it\u2019s viability.2-4 \nBy secreting proteases and hyaluronidase, larvae \npenetrate through follicles, fissures or intact skin of \nthe new host.\n\n\n\nFigure 1. (a) & (b) Erythematous papules and small scaly plaques with excoriation on anterior chest & back; (c) & (d) appearance of \nserpiginous, erythematous and slightly raised lesions on back; (e) & (f) appearance of serpiginous, erythematous lesions on right hand \nand forearm.\n\n\n\nOnce transmission has occured, the larvae stay \nconfined to the epidermis and less often the upper \ndermis. If the larvae manage to penetrate into the \ndermis then they may transport via the lymphatic and \nvenous systems to the lungs and other internal organ \nlike intestines. It can stay in the skin for a period \nof 2 to 50 weeks. It migrates at the rate of a few \nmillimeters to a few centimeters per day forming the \ntypical lesions of tortuous, serpiginous tunnel rising \nabove the skin surface (usually tract advancement \nof 1-2 cm/day). The humans are accidental hosts, \nand the larvae are usually not able to complete their \nnatural cycle. Permanent infection does not occur in \nthe human host.5\n\n\n\nTypically, CLM presents as a pruritic raised \nerythematous linear, serpiginous or curvilinear \ntrack that keep advancing. The pruritic symptoms \noccur secondary to an immune response to both \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3958\n\n\n\nthe larvae and their products.6 The condition may \nbe complicated by an impetiginized or eczematous \nprocess. In most cases, the diagnosis of CLM \nis based on the typical skin findings (creeping \neruption) and the recent travel history (it usually \nappears a few days after infestation). Laboratory \ninvestigations or biopsy is indicated only for those \ncomplex or diagnosis in doubt cases. \n\n\n\nTreating physician need to be aware and familiar \nwith atypical presentation of CLM as it is easily \ntreatable. Some of the atypical presentations of \nCLM reported include late onset CLM, unusual \nlocalization like scalp, multiple tracks, diffuse \nmultifocal papulo-vesicular eruption localized \nmainly on the chest, back and abdomen (like in \nour patient), hair follicle inflammation (hookworm \nfolliculitis) most frequently in the buttocks area and \nmigrating urticaria.1,3-6\n\n\n\nEven though CLM is self-limiting, the intense \npruritus and risk of infection mandate treatment. \nPrevention of CLM infestation by avoidance of \ndirect skin contact with fecally contaminated soil is \nthe key of treatment.\n\n\n\nTreatment options are as follows:\na. Oral Albendazole 400mg daily for 3\u20137 days is \nusually well tolerated.\n\n\n\nb. Ivermectin, a single dose of 200ug/kg bodyweight \n(average dose of 12mg) is well tolerated and highly \neffective but is contraindicated in children less than \n5 years. It is not available in Malaysia.\n\n\n\nc. Cryotherapy by freezing the tip of the lesion \nis another commonly used method but it is not \neffective as the tip of the serpiginous track does \nnot indicate the actual site of the moving larva. \nComplications like ulcerations and blisters may \noccur with cryotherapy.\n\n\n\nd. Ethyl chloride spray has been tried but was found \nto be ineffective.\n\n\n\nPrognosis of cutaneous larva migrans is good. It is \na self-limiting disease. Humans are dead end hosts \nwhere larvae will eventually die, resulting in lesions \nclearance within 4-8 weeks in most cases, but could \nbe as long as 1 year in rare cases.\n\n\n\nDelay in diagnosis or inadequate treatment often \nresults in complications which include secondary \nbacterial infection (10% of cases7) usually by caused \n\n\n\nstreptococus pyogenes, cellulitis, allergic reactions \nand even Loeffler syndrome.5\n\n\n\nConclusion\nCutaneous larva migrans should be kept in mind \nespecially in patients presenting with pruritic rashes \nafter a history of walking barefoot or bare-body \ncontact with sandy beaches or soil in endemic areas, \nas the appearance of the typical red and serpiginous \nskin lesions maybe delayed.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare\n\n\n\nAcknowledgement\nThe authors would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nReferences\n\n\n\n1. Jelinek T, Maiwald H, Nothdurft HD, Loscher T. \nCutaneous larva migrans in travellers: synopsis of \nhistories, symptoms, and treatment of 98 patients. Clin \nInfect Dis 1994;19:1062-6.\n\n\n\n2. Nurjahan MI, Tevaraj P. Rash in a foreign worker. Malays \nFam Physician 2016;11;39-41.\n\n\n\n3. Tekely E, Szostakiewicz B, Wawrzycki B, K\u0105dziela-\nWypyska G, Juszkiewicz-Borowiec M, Pietrzak A et al. \nCutaneous larva migrans syndrome: a case report. Postepy \nDermatol Alergol. 2013;30:119-21.\n\n\n\n4. Malvy D, Ezzedine K, Pistone T, Receveur MC, Longy-\nBoursier M. Extensive cutaneous larva migrans with \nfolliculitis mimicking ultimetameric herpes zoster \npresentation in an adult traveler returning from Thailand. J \nTravel Med 2006;13:244-7. \n\n\n\n5. Podder I, Chandra S, Gharami RC. Loeffler\u2019s Syndrome \nfollowing cutaneous larva migrans: An uncommon sequel. \nIndian J Dermatol 2016;61:190-2.\n\n\n\n6. Veraldi S, Persico MC, Francia C, Schianchi R. Chronic \nhookworm-related cutaneous larva migrans. Int J Infect \nDis 2013;17:e277-9.\n\n\n\n7. Caumes E, Danis M. From creeping eruption to \nhookworm-related cutaneous larva migrans. Lancet Infect \nDis 2004;4:659-60.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 59\n\n\n\nCASE REPORT\n\n\n\nThe Immunocompromised Patient with Perianal Lesions\nAngelina Siing Ngi Tang1, MD, Kar Keong Neoh2, MD, Joshua Mohanraj Daniel3, MPath, Pubalan Muniandy 4, MRCP\n\n\n\n1Department of Internal Medicine, Sibu Hospital, Sibu, Sarawak, Malaysia\n2Faculty of Medicine, SEGI University, Malaysia\n3Quantum Diagnostic Sdn Bhd, Malaysia\n4Department of Dermatology, Sarawak General Hospital, Sarawak, Malaysia\n\n\n\nSummary\nGenital Herpes Simplex Virus (HSV) is a major global public health issue where the number of patients \nincreases every year. It has a variety of clinical presentations, and a tendency to recur when the immune \nsystem is compromised. Patients with human immunodeficiency virus (HIV) have a higher chance of \nbeing infected with HSV possibly due to their high risk attributes. We reported a case of a 19-year-\nold homosexual male who was recently diagnosed with HIV and presented with perianal lesions for a \nduration of three months. This case is presented with the aim to highlight the differential diagnosis of \nrash in immunocompromised patients and how to approach them.\n\n\n\nKey words: Genital Herpes Simplex Virus, Human Immunodeficiency Virus, Sexually Transmitted Disease\n\n\n\nCorresponding Author\nDr Angelina Tang Siing Ngi\nDepartment of Internal Medicine, Sibu Hospital, Batu \n51/2, Jalan Ulu Oya, 96000 Sibu, Sarawak\nEmail: angeltsn88@yahoo.com\n\n\n\nIntroduction\nGenital Herpes Simplex Virus (HSV) is a major \nglobal public health issue where the number of \npatients increases every year. It is an incurable but \nsuppressible disease. It has a variety of clinical \npresentations, and a tendency to recur when the \nimmune system is compromised. Patients with HIV \nhave a higher chance of being infected with HSV \npossibly due to their high risk attributes.\n\n\n\nCase Report \nWe reported a case of a 19-year-old male who was \nrecently diagnosed with HIV and presented with \npainful perianal lesions for three months duration. \nHe was actively engaged in unprotected homosexual \nrelationships. He had a CD4 count of 18 cells/\nmm3 and was recently commenced on Highly Anti \nRetroviral Therapy (HAART) for one month. \n\n\n\nHe reported that the perianal lesions started three \nmonths prior to seeking treatment, initially only \na few in number, painful and itchy. The lesions \nhad progressively increased in size and numbers, \nand occasionally produced pus. He had no fever, \nabdominal, urinary or gastrointestinal complaint.\n\n\n\nClinical examination revealed that he was not \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3960\n\n\n\nseptic looking with normal vital signs. There were \nmultiple dome-shaped, flesh coloured papules and \nnodules with size ranging from 0.5 cm to 2 cm over \nthe perianal region (Figure 1a). Ulcers were seen \non some of the nodules (Figure 1b). There was no \npus discharge. There were multiple nodules on the \nshaft of penis, with a few ulcerations seen (Figure \n1c). Bilateral inguinal lymph nodes were palpable. \nHe also had multiple ulcerated papules and nodules \nranging between 0.5 cm and 1.5 cm over the ventral \nsurface of the right arm. (Figure 1d). \n\n\n\nHis laboratory investigations revealed normal full \nblood count, renal and liver profile. His hepatitis B \nsurface antigen, Hepatitis C antibody and venereal \ndisease research laboratory were non reactive. \n\n\n\nBiopsies from perianal lesions showed ulceration of \nepidermis and chronic inflammation of underlying \ndermis. There were areas where the epidermis \n\n\n\nwas acanthotic and showed marked hyper and \nparakeratosis. The underlying dermis showed \ngranulation tissue which was infiltrated by a mixture \nof plasma cells, lymphocytes, neutrophils and \neosinophils. There were intranuclear viral inclusions \nin keratinocytes in focal areas (Figure 2a-c). There \nwas no typical molluscum body, multinucleated \ngiant cells, granuloma or malignancy change. The \nspecial stain for fungal and acid-fast bacilli was \nnegative. The findings from the right arm biopsy \nwas similar. The histology of the skin biopsies \nwere consistent with Herpes Simplex Virus (HSV) \ninfection.\n\n\n\nHe defaulted follow up for the past nine months \nwithout taking HAART and treatment for HSV. \nHealth inspectors had identified him lately and he \nwas advised to follow up in nearby hospital. \n\n\n\nFigure 1. (a) Multiple papules and nodules over the perianal region; (b) a closer view of perianal lesions showed that some of the \npapules and nodules were ulcerated, but there was no pus discharge; (c) multiple nodules were noted over the shaft of penis; (d) multiple \nulcerated, flesh colour pustules over the ventral surface of right arm Figure 1. (a) Multiple papules and nodules over the perianal region; \n(b) a closer view of perianal lesions showed that some of the papules and nodules were ulcerated, but there was no pus discharge; (c) \nmultiple nodules were noted over the shaft of penis; (d) multiple ulcerated, flesh colour pustules over the ventral surface of right arm.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 61\n\n\n\nFigure 2. (a) H&E (X40) showed a low power view of full thickness ulceration of the epidermis. The adjacent intact epidermis showed \nmarked acanthosis; (b) H&E (X 100, medium power view) showed marked acanthosis and spongiosis of the epidermis. Intranuclear \nviral inclusion bodies were seen within the keratocytes; (c) H&E (X400, high power) showed full thickness ulceration of the epidermis. \nThe ulcer bed and underlying dermis were replaced by granulation tissue, a dense infiltrate of lymphocytes and plasma cells and a lesser \nnumber of neutrophils and eosinophils. There were intranuclear viral inclusion bodies within the keratinocytes.\n\n\n\nDiscussion\nPerianal lesions are common in HIV-infected \npatient, especially in those who practice homosexual \nrelationships. Wexner (1986) reported that 34% of \nhis 340 HIV-infected patients had perianal lesions \nover 4 years of observation.1\n\n\n\nSome of the perianal lesions look alike, and it is \ndifficult to differentiate them clinically. To make a \ncorrect diagnosis of perianal lesions in HIV-infected \npatients, a detailed history, thorough clinical \nexamination, histology sample and serology testing \nis required. The common differential diagnosis of \nperianal lesions in HIV- infected patients are shown \nin Table 1.\n\n\n\nThere are shortfalls in our case study as no serology \ntesting for HSV was done due to resource limitation, \nand the patient was not started on HSV treatment. \nHis diagnosis was made on clinical ground only.\n\n\n\nThe identification of the typical histological \nfeatures of HSV (large multinucleated cells, with \nnuclear moulding, margination of chromatin \nand a homogeneous ground glass appearance) is \nchallenging in immunocompromised patients. The \ncytopathic changes in this case were focal and largely \nobscured by a dense infiltrate of inflammatory cells \nand granulation tissue. However, the presence of \nkeratinocytes with viral inclusion and epidermal \nulceration (most likely due to intraepidermal blister) \nwould favour a HSV infection. \n\n\n\nHSV infections are common worldwide. Both HSV \n\n\n\ntype 1 and 2 cause genital herpes. Langenberg \n(1999) reported that the rates of new HSV-1 and \nHSV-2 infections were 1.6 and 5.1 cases per 100 \nperson-years respectively. Of these, around 40% \nof new HSV-2 infections and 65% of new HSV-1 \ninfections were symptomatic.10 \n\n\n\nA recent study by Bernstein (2013) found out \nthat HSV-1 is now more common than HSV-2 in \ncausing oral and genital mucosa infections in young \nwoman.11 His study had overturned our common \nbelief that HSV-2 is the most common cause for \ngenital herpes. Patients with HSV have subclinical \nor asymptomatic shedding of virus over oral or \ngenital mucosa even in the absence of active lesions, \nand thus have a higher risk of disease transmission.\n\n\n\nHSV infections are classically described in three \nclinical designations:\n\n\n\nA) Primary: New infection in patients without \nantibody to HSV 1 or 2. The primary infections \nwere reported to be associated with more systemic \nsymptoms than non-primary and recurrent \ninfections, in which 98% patients had local pain, \n80% had tender lymphadenopathy and 63% had \ndysuria.12\n\n\n\nB) Non-Primary: New HSV infection in patients \nwho have antibodies to the other type of HSV. These \npatients have less systemic effects and some were \nasymptomatic.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3962\n\n\n\nTable 1. Common differential diagnosis of perianal lesions in HIV- infected patients.\n\n\n\nNo Disease Organism Description Histology\n\n\n\n1 Molluscum contagiosum Poxvirus Chronic, firm, dome shaped papules\n\n\n\nOccasionally polypoid with stalk like \nbase\n\n\n\nLobulated endophytic hyperplasia that \nproduces a circumscribed intradermal \npseudotumor, and the presence of \nmolluscum bodies.2\n\n\n\n2 Syphilis (primary) Treponema pallidum Painless, indurated, clean-based ulcer Diffuse plasma cell infiltration with \nendothelial swelling and proliferation \nin blood vessels. Definite diagnosis is \nby identification of organism, dark field \nexamination, polymerase chain reaction \n(PCR) testing or serology testing \n\n\n\n3 Condyloma Lata\n(Secondary syphilis)\n\n\n\nTreponema pallidum Wart-like growths over genitalia Prominent epidermal hyperplasia with \nchronic inflammatory cells infiltration. \nDefinite diagnosis is similar to primary \nsyphilis.\n\n\n\n4 Chancroid Haemophilus ducreyi Deep, undermined, purulent ulcer, \nsometimes with painful inguinal \nlymphadenitis\n\n\n\nSimilar to syphillis. Definite diagnosis is \nby gram stain (gram negative coccobacilli), \nculture or PCR.3\n\n\n\n5 Fungal infection Fungal Fungal infections are able to colonize \ndifferent tissue layers (Epidermis, \ndermis, subcutaneous tissues, muscle \nand fascia)\n\n\n\n-\n\n\n\n6 Condylomata Acuminata Human papillomavirus Single or multiple warts, flat, \ndome-shaped, cauliflower-shaped, \nfiliform, fungating, pendunculated, \ncerebriform, plaque-like, smooth, \nverrucous, lobulated, with various \ncolours \n\n\n\nAcantosis, papillomatosis, hyperceratosis, \nparaceratosis and koilocytosis.4 Definite \ndiagnosis is by filter hybridization or PCR \nfor HPV typing.\n\n\n\n7 Tuberculosis infection Mycobacterium \ntuberculosis\n\n\n\nInflammatory papules, verrucous \nplaques, suppurative nodules, chronic \nulcers\n\n\n\nTuberculoid granuloma inflammation, with \npresence of acid fast bacilli in Ziehl-Neelson \nstaining 5\n\n\n\n8 Squamous Cell Carcinoma - Non-healing ulcerative lesion or \nfungating mass \n\n\n\nSquamous phenotypic differentiation\n\n\n\n9 Genital Herpes Herpes simplex virus Multiple, shallow, tender and \nrecurrent ulcers \n\n\n\nMultinucleated keratinocytes, acanthosis \nwith presence of inclusion body formation. \nDefinite diagnosis is by tube culture \nisolation, viral antigen or HSV DNA \ndetection followed by HSV typing by \nmonocloncal antibody reagents6\n\n\n\n10 Scabies Sarcoptes scabiei \nhominis\n\n\n\nExcoriations and burrows Epidermal layer : hyperkeratosis, acanthosis \nand spongiotic edema and vesiculation. \nDermal layer: perivascular and diffuse cell \ninfiltration with mainly mononuclear cells.7\n\n\n\nDefinite diagnosis is by identification of \nscabies mite or eggs under microscope.\n\n\n\n11 Lymphogranuloma \nvenereum\n\n\n\nChlamydia trachomatis Genital ulcers or papules with painful \ninguinal lymphadenopathy\n\n\n\nHistology is not specific. Definite diagnosis \nis by nucleic acid amplification test of swab \nsample or lymph node aspirate. It is not \nalways possible to culture the organism.8\n\n\n\n12 Granuloma inguinale Klebsiella granulomatis Painless ulcers with minimal or \nabsent inguinal lymphadenopathy\n\n\n\nDefinite diagnosis by tissue smear and \nvisualization of Donovan body- the \norganism is found within cytoplasm of \nhistiocytes and exhibit bipolar staining.9\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 63\n\n\n\nC) Recurrent: Recurrent presentations are typically \nless severe than primary or non-primary. Benedetti \n(1994) reported that almost all patients with \nsymptomatic HSV-2 infections had symptomatic \nrecurrence, and the recurrence rates were higher for \nthose who had more severe or prolonged duration \nduring the primary infection, regardless of receiving \nanti-viral or not.13 \n\n\n\nHSV infections usually manifest as ulcers in \nimmunocompetent hosts. The clinical manifestations \nof HSV infections in HIV-infected patients are \natypical and they are influenced by patient\u2019s \nimmunological status:\ni) Ulcerative disease: common presentation \nis shallow, painful and erosive genital ulcers. \nProlonged, deep genital or perianal ulceration \nand fissures are seen in those with very low CD4 \n(<50cells/mm \u201c3\u201d).14\n\n\n\nii) Hypertrophic masses: Hypertrophic lesions are \nfrequently confused with malignancies or HPV \ninfection (condylomata acuminata) and lead to \ndelay in diagnosis. They are more frequently seen in \nHIV-infected patients with low CD4 count.\n\n\n\niii) Unusual manifestations: HSV infections are also \nreported to cause extra-genital presentations such as \nesophagitis, hepatitis, pneumonitis, retinal necrosis, \naseptic meningitis, urinary retention secondary to \nsacral autonomic nervous systemic dysfunction, and \ndistant skin lesions namely erythema multiforme. \nDistant HSV lesions from the primary site in \nimmunocompetent patients are rare. \n\n\n\nAn interesting study by Ameli (2006) that included \n1796 HIV-infected women found that 18% were \nseropositive to HSV-1, 20% to HSV-2 and 58% were \npositive to both. The risk of getting HSV in HIV-\ninfected women was higher with increasing age, \nmore sexual partners, earlier sexual experiences, \nlower education level and lower income.15\n\n\n\nA meta-analysis of 31 studies by Wald (2002) \nrevealed that the HSV-2 infection increased the \nrisk estimate of HIV acquisition by 2.1 to 3.9.16 The \nmechanisms of increased risk of HIV transmission \namong HSV-2 infected patients were postulated to \nbe :\nA) HSV-2 ulcers facilitate HIV-1 entry during \nsexual intercourse \nB) increase in local recruitment of CD4 cells , which \nare targets of HIV-1.\n\n\n\nThere is no curative treatment for HSV to date. \nStudies support the early initiation of antivirals \nwithin 72 hours of lesions as it reduces the \nduration, severity, and complications of genital \nherpes.17 Acyclovir is as efficient as famciclovir \nand valacyclovir in terms of reducing duration of \nshedding and to recovery, and severity of lesions. \nThe drawback for acyclovir is its frequent dosing of \n5 times per day due to its poor bioavailability.18\n\n\n\nCenter for Disease Control (CDC) had suggested \nthe following treatment regimes for HSV in 2015:\nA) Acyclovir 400mg - 3 times daily or 200mg - 5 \ntimes daily\nB) Famciclovir 250mg - 3 times daily\nC) Valacyclovir 1000mg - 2 times daily\nDuration of treatment: 7-10 days\n\n\n\nIn HIV-infected patients, the treatment dosage \nof HSV infections is similar to the above CDC \nrecommendation, but the treatment duration should \nbe prolonged to a minimum of 5 days, or until lesion \nresolution.19\n\n\n\nMost of the superficial lesions are responsive to \noutpatient treatment and oral antivirals. However, \nadmission and parenteral antivirals may be warranted \nfor those with involvement of central nervous \nsystem, end-organ damage and disseminated HSV. \n\n\n\nLebrun-Vignes (2007) reported that in his meta-\nanalysis of fourteen trials, the mentioned three \nantivirals were equally effective in suppressing the \nnumber of recurrence, but the long term side effects \nand costs of antivirals were not addressed.20\n\n\n\nAs for suppressive therapy, CDC recommended the \nfollowing regime:\nA) Acyclovir 400 mg to 800 mg orally twice to three \ntimes daily\nB) Famciclovir 500 mg twice daily\nC) Valacyclovir 500 mg twice daily19\n\n\n\nRoutine screening of HSV in asymptomatic \npopulations is not recommended as confirmatory \ntests are not routinely available and there is also \nno curative treatment. However, counseling and \nscreening of sexual partners of patients with HSV \nare recommended with the aim to reduce disease \ntransmission.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3964\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Wexner SD, Smithy WB, Milsom JW, Dailey TH. The \nsurgical management of anorectal diseases in AIDS and \npre-AIDS patients. Dis Colon Rectum 1986;29:719-23.\n\n\n\n2. Molluscum contagiosum. PathologyOutlines.com \nwebsite. http://www.pathologyoutlines.com/topic/\nskinnontumormolluscum.html, Accessed September 24th, \n2017.\n\n\n\n3. Inamadar AC, Palit A. Chancroid: An update. Indian J \nDermatol Venereol Leprol 2002;68:5-9.\n\n\n\n4. Dias EP, Gouvea ALF, Eyer CC. Condyloma acuminatum: \nits histopathological pattern. Sao Paulo Med J 1997; \n115:1383-9.\n\n\n\n5. Ibn Majdoub Hassani K, Ait Laalim S, Toughrai I, Mazaz \nK. Perianal Tuberculosis: A Case Report and a Review \nof the Literature. Case Reports in Infectious Diseases \n2012;2012:1-4. \n\n\n\n6. Singh A, Preiksaitis J, Ferenczy A, Romanowski B. The \nlaboratory diagnosis of herpes simplex virus infections. \nCan J Infect Dis Med Microbiol 2005;16:92-8.\n\n\n\n7. Falk ES, Eide TJ. Histologic and clinical findings in human \nscabies. Int J Dermatol 1981;20:600-5.\n\n\n\n8. Coevic R, Gulin SJ. Lymphogranuloma venereum: \ndiagnostic and treatment challenges. Infect Drug Resist \n2015;8:39-47.\n\n\n\n9. Sehgal VN, Shyamprasad AL, Beohar PC. The \nhistopathological diagnosis of donovanosis. Br J Vener Dis \n1984;60:45-7.\n\n\n\n10. Langenberg AG, Corey L, Ashley RL, Leong WP, \nStraus SE. A prospective study of new infections with \nherpes simplex virus type 1 and type 2. N Engl J Med \n1999;341:1432-38.\n\n\n\n11. Bernstein DI, Bellamy AR, Hook EW 3rd, Levin MJ, Wald \nA, Ewell MG, et al. Epidemiology, clinical presentation, \n\n\n\nand antibody response to primary infection with herpes \nsimplex virus type 1 and type 2 in young women. Clin \nInfect Dis 2013;56:344-51.\n\n\n\n12. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex \nviruses. Clin Infect Dis 1998;26:541-53.\n\n\n\n13. Benedetti J, Corey L, Ashley R. Recurrence rates in genital \nherpes after symptomatic first-episode infection. Ann \nIntern Med 1994;121:847-54.   \n\n\n\n14. Bagdades EK, Pillay D, Squire SB, O\u2019 Neil C, Johnson \nMA, Griffiths PD. Relationship between herpes simplex \nvirus ulceration and CD4+ cell counts in patients with HIV \ninfection. AIDS 1992;6:1317-20.\n\n\n\n15. Ameli N, Bacchetti P, Morrow RA, Hessol NA, Wilkin T, \nYoung M, et al. Herpes simplex virus infection in women \nin the WIHS: epidemiology and effect of antiretroviral \ntherapy on clinical manifestations. AIDS 2006;20:1051-8. \n\n\n\n16. Wald A, Link K. Risk of human immunodeficiency virus \ninfection in herpes simplex virus type 2-seropositive \npersons: a meta-analysis. J Infect Dis 2002;185:45-52. \n\n\n\n17. Corey L, Fife KH, Benedetti JK, Winter Ca, Fahnlander A, \nConnor JD, et al. Intravenous acyclovir for the treatment of \nprimary genital herpes. Ann Intern Med 1983;98:914-21.\n\n\n\n18. Fife KH, Barbarash RA, Rudolph T, Degregorio B, Roth \nR. Valaciclovir versus acyclovir in the treatment of first-\nepisode genital herpes infection. Results of an international, \nmulticenter, double-blind, randomized clinical trial. The \nValaciclovir International Herpes Simplex Virus Study \nGroup. Sex Transm Dis 1997;24:481-6. \n\n\n\n19. Workowski KA, Bolan GA. Centers for Disease Control \nand Prevention. Sexually transmitted diseases treatment \nguidelines, 2015. MMWR Recomm Rep 2015;64:1-137. \n\n\n\n20. Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume \nJC, Lechat P, Chosidow O. A meta-analysis to assess \nthe efficacy of oral antiviral treatment to prevent genital \nherpes outbreaks. J Am Acad Dermatol 2007;57:238-46. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 65\n\n\n\nCASE REPORT\n\n\n\nBlistering Eruption and Fulminant Hepatitis: A Fatal Coinfection of \nLeptospirosis and Disseminated Herpes Simplex\nRajalingam Ramalingam, MRCP, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nLeptospirosis has a wide spectrum of nonspecific clinical manifestations ranging from mild disease \nto multiorgan failure with variable cutaneous manifestations. Disseminated herpes simplex virus \ninfection usually occurs in the setting of immunosuppression. Both these infections are rare infective \ncauses of fulminant hepatitis. Herein, we report a case of fatal leptospirosis and disseminated herpes \nsimplex virus coinfection, in the hopes that this report will increase awareness among health care \nproviders for relevant investigation and prompt management.\n\n\n\nKey words: Disseminated herpes simplex, Leptospirosis, Malaysia\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology, Hospital Tengku Ampuan \nAfzan, Jalan Tanah Putih, 25100 Kuantan, Pahang, \nMalaysia\nEmail: raj.blueheart@gmail.com \n\n\n\nIntroduction\nLeptospirosis has a wide spectrum of nonspecific \nclinical manifestations ranging from a self-\nlimiting mild disease to severe multiorgan failure \n(Weil\u2019s disease). Cutaneous manifestations include \ntransient macular erythema, petechiae and purpura \nfulminans. Disseminated herpes simplex virus \n(DHSV) infection is rare and usually occurs in the \nsetting of immunosuppression. Mucocutaneous \nfindings are typically generalized vesicles, pustules \nand superficial erosions. Multiorgan involvement \nhas also been known to occur in DHSV.1-2 While \nboth diseases can cause acute fulminant hepatitis, \nwe the authors believe that this is the first incident \nof a coinfection in an immunocompetent individual \nwith dire consequences.\n\n\n\nCase Report \nA 52-year-old gentleman, a hawker by profession \nand a recent flood evacuee with no past medical \nillness or recent travels, presented to a district \nhospital with an abrupt onset of a nonpruritic, \npainless, generalized vesicular eruption. Crops of \nclear vesicles appeared over his face and scalp, \nwhich eventually generalized. The rash was \npreceded by high-grade fever, severe myalgia and \nexcruciating back pain of one day duration. There \nwere no respiratory or gastrointestinal symptoms. \nThere was no history of a primary herpes simplex \ninfection. A similar history among family members \nand coworkers was not found. He denied ingesting \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3966\n\n\n\nany over-the-counter drugs or traditional herbal \nremedies. Physical examination revealed a \nnormotensive patient with generalized vesicles and \nno orogenital mucosal involvement. Apart from \nmild leukocytosis (14.7 x109/L), all other blood \nparameters, including renal and liver profiles, were \nwithin normal limits. He was subsequently referred \nto our hospital the next morning for evaluation of \nhis rash.\n\n\n\nHowever, upon admission to our hospital, we found \nhim to be ill and hypotensive. There were generalized \ncrops of clear vesicles on an erythematous base \n(Figures 1a-b). Erosions were also noted over \nhis hard palate. Bedside Tzanck smears showed \nnumerous multinucleated giant cells (Figure 1e). An \nurgent skin biopsy was performed.\n\n\n\nFigure 1. (a) & (b) Clinical presentation of the patient showed generalized clear vesicles which also involved the (d)hard palate; (c)the \nvesicles later turned hemorrhagic; (d) Tzanck smear showed numerous multinucleated giant cells.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 67\n\n\n\nBlood investigations revealed leukocytosis \n(33.87 x 109/L) with predominantly neutrophilia, \nthrombocytopenia (74 x 109/L), coagulopathy \n(INR 2.7, APTT 107.3s), markedly elevated liver \ntransaminases (alanine aminotransferase 1,655 U/L; \naspartate aminotransferase 3,774 U/L) and severe \n\n\n\nmetabolic acidosis (serum bicarbonate 10 mmol/L). \nCreatine kinase was only modestly elevated (346 \nU/L). Renal profile remained normal. HIV rapid \ntest was nonreactive. He was empirically initiated \non broad spectrum antibiotics for septicemic shock, \nand intravenous acyclovir for DHSV infection.\n\n\n\nFigure 2. (a) & (b) Histopathological examination showed multinucleated keratinocytes with ground-glass appearance.\n\n\n\ndistrict hospital as well as in ours did not grow any \norganism. Thus, we concluded that this gentleman \nsuccumbed to fulminant hepatic failure from \nleptospirosis and DHSV coinfection.\n\n\n\nDiscussion\nThe World Health Organization recognizes \nleptospirosis as the only epidemic-prone infection \nwhich can be transmitted directly from rodent \nurine-contaminated water. This is especially true \nfollowing natural disasters such as flooding3, to \nwhich our patient was exposed to. \n\n\n\nIn Weil\u2019s disease, one would expect renal \ndysfunction, respiratory embarrassment and only \nmodest elevations in hepatic transaminases, which \nrarely exceed 200 U/L.4 Our patient had markedly \nelevated liver enzymes without renal impairment, \nwhich is unusual if this were only leptospirosis. \n\n\n\nWithin three hours, the vesicles had turned \nhemorrhagic (Figure 1c) with large, confluent \necchymotic patches appearing over most of his \ntrunk. He was also disoriented and agitated. He was \npromptly and aggressively resuscitated but to no \navail. He eventually passed away, less than 24 hours \nafter his initial presentation to the district hospital. \nHis family refused a post-mortem examination.\n\n\n\nHistopathological examination, which was only \navailable after his death, revealed multinucleated \nkeratinocytes with ground-glass appearance (Figures \n2a&b). Indirect immunofluorescent antibody (IFA) \ntest was positive. Skin biopsy tissue for bacterial \nculture was negative. Unfortunately, tissue for viral \nculture or viral polymerase chain reaction (PCR) \nwas not done. Leptospira immunoglobulin M \nenzyme-linked immunosorbent assay (IgM-ELISA) \nwas positive, as was the microscopic agglutination \ntest (MAT). Blood and urine cultures taken in the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3968\n\n\n\nWe believe the raised hepatic transaminases was due \nto herpes simplex virus infection. We did consider \nthe fact that the markedly elevated liver enzymes \nmight be due to ischemic hepatitis as the patient \nwas hypotensive upon admission to our hospital. \nHowever, the normal renal profile and therefore a \nlack of acute kidney injury makes ischemic hepatitis \na less likely cause of the raised liver enzymes.\n\n\n\nDHSV infection is well known to cause fulminant \nhepatitis, although this commonly occurs in an \nimmunocompromised or pregnant individual. \nFulminant hepatitis due to herpes simplex virus \ninfection in an apparently immunocompetent \nindividual however, is postulated to be due to \nundiagnosed or subclinical complex primary \nimmunodeficiencies involving particular \nsusceptibility to herpes viruses.5-7\n\n\n\nThere have been multiple reports of fatal \ncoinfections of leptospirosis with melioidosis9, \ndengue10, chikungunya11 and scrub typhus.12 To \nour knowledge, there have been no reported cases \nof a fatal leptospirosis and DHSV coinfection. We \nbelieve that our patient\u2019s immunity may have been \ncompromised by leptospirosis8, thus making him \nvulnerable to an overwhelming infection of herpes \nsimplex virus.\n\n\n\nConclusion\nIt is not unlikely for a fatal coinfection of \nleptospirosis and disseminated herpes simplex \nvirus to occur. Hence, awareness of such lethal \ncoinfections is crucial for early laboratory testing \nas well as for the prompt initiation of treatment in \norder to reduce morbidity and mortality.\n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, thank the Director-General of \nHealth, Malaysia, for his permission to publish this \narticle.\n\n\n\nReferences \n\n\n\n1. Farr RW, Short S, Weissman D. Fulminant hepatitis \nduring herpes simplex virus infection in apparently \nimmunocompetent adults: report of two cases and review \nof the literature. Clin Infec Dis 1997;24:1191-4.\n\n\n\n2. Prellner T, Flamholc L, Haidl S, Lindholm K, Widell \nA. Herpes Simplex virus \u2013 the most frequently isolated \npathogen in the lungs of patients with severe respiratory \ndistress. Scand J Infec Dis 1992;24:283-92.\n\n\n\n3. Watson JT, Gayer M, Connolly MA. Epidemics after \nnatural disasters. Emerg Infect Dis 2007;13:1-5.\n\n\n\n4. Edwards GA, Domm BM. Leptospirosis. Med Times \n1966;94:1086-95.\n\n\n\n5. Watanabe D, Kuhara T, Ishida N, Takeo T, Tamada Y, \nMatsumoto Y. Disseminated mucocutaneous herpes \nsimplex virus infection in an immunocompetent woman. \nInt J STD AIDS 2010;21:213-4.\n\n\n\n6. Zahariadis G, Jerome KR, Corey L. Herpes simplex \nvirus-associated sepsis in a previously infected \nimmunocompetent adult. Ann Intern Med 2003;139:153-4.\n\n\n\n7. Milman N, Zhu J, Johnston C, Cheng A, Magaret A, \nKoelle DM et al. In Situ Detection of Regulatory T Cells \nin Human Genital Herpes Simplex Virus Type 2 (HSV-2) \nReactivation and Their Influence on Spontaneous HSV-2 \nReactivation. J Infect Dis 2016;214:23-31.\n\n\n\n8. Zipfel PF, Wurzner R, Skerka C. Complement evasion \nof pathogens: common strategies are shared by diverse \norganisms. Mol Immunol 2007;44:3850-7.\n\n\n\n9. How SH, Ramalingam R, Kuan YC, Ahmad N, Ab \nRahman J, Mohamed MS. Case Report: Fatal Co-\nInfection\u2013Melioidosis and Leptospirosis. Am J Trop Med \nHyg 2012;87:737-40.\n\n\n\n10. Sharp TM, Bracero J, Rivera A, Shieh WJ, Bhatnagar \nJ, Rivera-Diez I et al. Fatal Human Co-infection with \nLeptospira spp. and Dengue Virus, Puerto Rico, 2010. \nEmerg Infect Dis 2012; 18:878-80.\n\n\n\n11. Nahn TX, Bonnieux E, Rovery C, De Pina JJ, Musso D. \nFatal leptospirosis and chikungunya co-infection: Do not \nforget leptospirosis during chikungunya outbreaks. ID \nCases 2016;5:12-4.\n\n\n\n12. Ho YH, Chen LK, Tsai PJ, Wang LS. Coinfection with \nLeptospirosis and Scrub Typhus - A Report of Four Cases. \nTzu Chi Med J 2006;18:237-40.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 69\n\n\n\nCASE REPORT\n\n\n\nCase Series of Acrodermatitis Enteropathica in Langkawi Hospital\nShen Wei Lee1, MRCP, Shin Yi Ooi1, MRCP, Wooi Chiang Tan2, MRCP, AdvMDerm\n\n\n\n1Department of Medicine, Hospital Langkawi, Kedah, Malaysia\n2Department of Dermatology, Hospital Pulau Pinang, Penang, Malaysia\n\n\n\nSummary\nAcrodermatitis enteropathica (AE) is a rare genetic autosomal recessive disorder characterised by \nperiorificial inflammatory rash, diarrhoea and hair loss. Hereby, we report 3 cases of acrodermatitis \nenteropathica.\n\n\n\nKey words: Acrodermatitis enteropathica, Zinc deficiency, Acral and periorificial dermatitis.\n\n\n\nCorresponding Author\nDr Lee Shen Wei \nDepartment of Medicine, Hospital Langkawi, Bukit \nTekuh, Jalan Padang Matsirat, 07000 Langkawi, Kedah, \nMalaysia\nEmail : shenweijojo@gmail.com\n\n\n\nIntroduction\nAcrodermatitis enteropathica (AE) is a rare \ndermatosis related to zinc deficiency, manifests \nas acral and periorificial dermatitis, alopecia, \nintractable diarrhoea and failure to thrive. It can \nbe classified into primary zinc deficiency, which is \ngenetically based and acquired secondary deficiency. \n\n\n\nCase report\nWe report 3 cases of AE, presented as symmetrical \nerythematous, squamous or eczematous lesions, \nlocated around perioral, anogenital and acral areas. \nTwo of them are siblings, diagnosed in Malacca and \nlater transferred to Langkawi hospital for follow up; \nand a newly diagnosed infant who developed AE \ndue to nutritional zinc deficiency. \n\n\n\nPatient 1: A 10-year-old Malay girl, presented with \npsoriasiform plaques at lower limbs at 3 years of age. \nHer younger brother (Patient 2) also suffered from \nsimilar unresolved psoriasiform skin lesions. There \nwere no hair changes and no chronic diarrhoea. \nOral zinc was given to both siblings with serial zinc \nlevel monitoring, and skin lesions resolved after \nthat. They were transferred to Langkawi hospital \nfor continuation of follow up since 2015, and their \nconditions remained stable up to date.\n\n\n\nPatient 3, An eight-month old baby boy, presented \nwith generalized itchy scaly rash for 3 weeks \nduration. The rash started on bilateral calf and \nexpanded to trunk and head involving face and \nscalp, gradually progress to superficial blistering \nassociated with weepy excoriation over groin and \nperianal region. Further history revealed that the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3970\n\n\n\nchild has poor social & financial support. He was \ntaken cared by his mother together with a 3-year-old \nsister, father being imprisoned. He was breastfed for \nfirst 2 months then subsequently he was fed with \ndiluted condensed milk without proper weaning \ndiet. \n\n\n\nWe saw a generalized oedematous baby having \nextensive skin desquamation and hypopigmentation \nover limbs, with tender weepy erosion over groin \narea. He had scanty short brittle hair over scalp. He \nwas first treated as possible staphylococcus scalded \nskin syndrome. Upon referral to dermatology team \non day 3 admission, the diagnosis was revised to \nAE with possible kwashiorkor disease and was later \nconfirmed by a low serum zinc level of 10ug/dl. \n\n\n\nHe was assessed by dietician and started on formula \nmilk (lactogen), which delivers around 4mg of \nelemental zinc per day; on top of the introduction \nof solid diet. His skin lesion improved within a \nweek of diet modification, and completely resolved \nupon discharge in one week\u2019s time, leaving post \ninflammatory hypopigmentation.\n\n\n\nDiscussion \nAcrodermatitis enteropathica is related to zinc \ndeficiency, either primary deficiency or acquired \nsecondary deficiency.1 Hereditary AE is caused by \nautosomal recessive mutation of SLC39A4 gene on \nchromosome 8q24.3 which encodes the ZIP4 zinc \ntransporter, leading to impaired zinc absorption \nmainly from small intestine.2\n\n\n\nAcquired form is more common than hereditary form, \nwhich occur in poor dietary intake such as anorexic \nand alcoholics; malabsorption conditions such as \ninflammatory bowel disease and coeliac disease; \nan excess of phytate diet (cereal grains); increase \nin metabolic demands such as malignancy, burns; \nmedications-induced; pregnancy and renal disease.3 \n\n\n\nZinc deficiency is frequently found in premature \ninfants due to increased demand, insufficient \nstores, impaired absorption and increased urinary, \ngastrointestinal tract and cutaneous losses of zinc.4\n\n\n\nClinical findings of AE include characteristic \neczematous, bullous cutaneous lesions on \nperiorificial and acral sites, alopecia, and intractable \ndiarrhoea. However the triad is only complete \nin 20% of AE patients. If left untreated, the \noutcome can be devastating, ranging from growth \nretardation, neuropsychiatric features, secondary \nimmunodeficiency, delayed wound healing and \n\n\n\nsecondary bacterial/fungal infection with sepsis \noften leading to death.5\n\n\n\nAcrodermatitis enteropathica is diagnosed primarily \nby clinical manifestations and further supported \nwith low plasma zinc level. Good recovery with zinc \nsupplement confirmed the diagnosis of AE. The cut-\noff point of plasma zinc level is 50ug/dl. However, in \n30% of diagnosed AE, the zinc deficiency occur with \nnormal level of plasma zinc, due to the impairment \nof zinc biologic action at the actual site where zinc \nis released from blood to microenvironment, thus \nreducing the actual bioavailability of zinc.6\n\n\n\nHistopathology findings are usually consistent \nwith nutritional deficiency dermatitis, include \ncytoplasmic pallor, vacuolization, ballooning \ndegeneration causing subcorneal & intraepidermal \nclefts, and subsequent confluent necrosis of \nkeratinocytes within the superficial stratum \nspinosum and stratum granulosum of the epidermis.  \nIn chronic or resolving AE, the fully developed \nnecrolysis is minimal; psoriasiform hyperplasia, \nparakeratosis with variable neutrophils are often \nindistinguishable with psoriasis and other chronic \ndermatitis.5\n\n\n\nRapid recovery is usually observed with prompt \nzinc supplement, generally started at 2-3 mg/kg/day \nof elemental zinc, most patients require 1-10mg/kg/\nday of oral zinc preparation.7 Plasma zinc levels and \nzinc-dependent enzyme levels should be monitored \nevery 3 to 6 months for appropriate dose adjustment.5\n\n\n\nAnother important differential diagnosis in this patient \nis Kwashiorkor disease, as the initial presentation of \ngeneralised desquamation of skin in an oedematous \ninfant. However, there was no hepatomegaly, no \nnail changes, and blood investigations did not show \nanaemia, hypoglycaemia, and metabolic acidosis to \nsupport Kwashiorkor disease.  \n\n\n\nThe limitation of our case is that skin biopsy was \nnot performed to further support the diagnosis. This \nis due to the young age of the patient and our lack of \nexperience in performing a skin biopsy in this age \ngroup. However, skin biopsy is just an adjunct to the \ndiagnosis of AE. On top of that, our patient defaulted \nfollow up, thus we were not able to monitor his \nprogression and final outcome.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 71\n\n\n\nFigure 1. (a), (b) & (c) Case 3: Acral and periorificial dermatitis with alopecia on presentation.\n\n\n\nFigure 2. (a) & (b) Case 3: Resolution of skin desquamation and growth of hair after 1 week post-treatment.\n\n\n\n\n\n\n\n   \nFig 1: Case 3 : acral and periorificial dermatitis with alopecia on presentation \n\n\n\nConclusion\nOur case emphasises that one should think broadly \nwhen treating childhood skin disorders.  Diagnosis \non AE requires a high index of suspicion. AE is \ndiagnosed primarily by clinical manifestation, low \nserum zinc level, and good recovery with zinc \nsupplementation.  An early diagnosis and prompt \ntreatment of AE reduces mortality and prevents the \nlong-term consequences of zinc deficiency.\n\n\n\nConflict of Interest Declaration\nThe authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\n   \nFig 2: Case 3 : resolution of skin desquamation and growth of hair after 1 week \n\n\n\nReferences\n\n\n\n1. Michaellson G. Zinc therapy in acrodermatitis \nenteropathica. Acta Derm Venereol 1974;54:377-81.\n\n\n\n2. Kambe T, Fukue K, Ishida R, Miyazaki S. Overview of \nInherited Zinc Deficiency in Infants and Children. J Nutr \nSci Vitaminol 2015;61:S44-6.\n\n\n\n3. Lakdawala N, Grant-Kels JM. Acrodermatitis enteropathica \nand other nutritional diseases of the folds (intertriginous \nareas). Clinics in dermatology 2015;33:414-9.\n\n\n\n4. Chue CD, Rajpar SF, Bhat J. An acrodermatitis \nenteropathica-like eruption secondary to acquired zinc \ndeficiency in an exclusively breast-fed premature infant. \nInt J Dermatol 2008;47:372-3.\n\n\n\n5. Maverakis E, Fung MA, Lynch PJ, Draznin M, Michael \nDJ, Ruben B et al. Acrodermatitis enteropathica and \nan overview of zinc metabolism.J Am Acad Dermatol \n2007;56:116-24.\n\n\n\n6. Lee SY, Jung YJ, Oh TH, Choi EH. A case of acrodermatitis \nenteropathica localized on the hands and feet with a normal \nserum zinc level. Ann Dermatol 2011;23:S88-90.\n\n\n\n7. Wessells K.R., King J.C., Brown K.H. Development of a \nplasma zinc concentration cutoff to identify individuals \nwith severe zinc deficiency based on results from adults \nundergoing experimental severe dietary zinc restriction \nand individuals with acrodermatitis enteropathica. J. Nutr \n2014;144:1204-10.\n\n\n\na b c\n\n\n\na b\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3972\n\n\n\nCASE REPORT\n\n\n\nFrom Red Herring to Malignancy\nChai Har Loo1, MRCP, Min Moon Tang1, MRCP, AdvMDerm, Zuliatul Faizah Baharom2, MPath, Bang Rom Lee3, MPath, \nSuganthi Thevarajah1, MMed \n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Department of Pathology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n3Department of Pathology, Gleneagles, Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nAngiosarcoma is a rare but aggressive malignant tumor of vascular endothelial cells accounting for \n1-2% of soft tissue sarcoma. Due to its rarity and heterogeneity in clinical presentation, delay in \ndiagnosis and treatment is not uncommon. Hence, prognosis is usually guarded. Here we report a \ncase of primary cutaneous angiosarcoma arising from the right cheek which progressed rapidly and \nresulted in perforation of buccal mucosa despite combination therapy of paclitaxel and propranolol. \n\n\n\nKey words: Angiosarcoma, Vascular tumor, Propranolol, Paclitaxel\n\n\n\nIntroduction\nAngiosarcoma is a rare but very aggressive soft tissue \nsarcoma arising from malignant vascular endothelial \ncells. It accounts for approximately  1-2% of soft \ntissue sarcomas and frequently affects the head \nand neck region.1-3 Predisposing factors include \nultraviolet radiation, chronic ulceration (especially \nat the arteriovenous fistula sites)4 and chronic \nlymphoedema (namely Stewart-Treves syndromes \nwhich develops in long-standing lymphoedema \nof the arm of patient post radical mastectomy or \npost irradiation therapy for breast cancer).5 Local \nrecurrence of cutaneous angiosarcoma is high, \nranging from 35-86%6,7 with frequent metastasis to \nregional lymph nodes or the lung. Prognosis remains \ndismal, attributed to diagnostic and treatment delay. \nHistorically, the 5-year survival rates range from 10 \nto 35%.8-10\n\n\n\nHere we report a case of primary cutaneous \nangiosarcoma arising from right cheek which \nprogressed rapidly and resulted in perforation of \nbuccal mucosa despite therapy with paclitaxel and \npropranolol.\n\n\n\nCase Report\nA 52-year-old Chinese gentleman, a heavy smoker, \npresented with a progressively enlarging painless \n\u201cbruise\u201d over his right cheek 4 months before he was \nreferred to the Department of Dermatology Hospital \nKuala Lumpur. It started with a small erythematous \n\n\n\nCorresponding Author\nDr Loo Chai Har \nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586 Kuala Lumpur, Malaysia\nEmail: chaihar@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 73\n\n\n\nviolaceous nodule which developed concurrently \nwith severe gingivitis. The nodule expanded \ngradually from mid maxillary to infraorbital \nregion and later affecting more than a half of the \nright cheek in less than two months (Figure 1a). \nThe plaque subsequently ulcerated spontaneously \nwith pus discharge. The patient denied any \nconstitutional symptoms or prior trauma to the \naffected area. Systemic review was unremarkable. \nHe sought treatment at multiple medical facilities \nwith no improvement. He was initially treated for \nabscess with multiple courses of antibiotics and \nunderwent dental extraction for severe dental caries \nand gingivitis before being referred to a tertiary \ndermatology center. \n\n\n\nClinical examination revealed a large ulcer with \nnecrotic tissue sagging over his right cheek. Right \nperiorbital swelling and ectropion were seen. \n(Figure 1b) Poor oral hygiene was noted. There was \nno lymphadenopathy or hepatosplenomegaly. \n\n\n\nAt this juncture, differential diagnosis including soft \ntissue infections like actinomycosis, lupus vulgaris, \nnon-tuberculous mycobacterial infection and \nsubcutaneous fungal infections were considered. In \naddition, we also included pyoderma gangrenosum \nas well as autoimmune granulomatous vasculitis like \nWegener granulomatosis in the list of differential \ndiagnosis. Cutaneous malignancy such as \nangiosarcoma, cutaneous lymphoma and malignant \nmelanoma were additional important considerations \nfor this gentleman. \n\n\n\nBlood investigations including full blood count, \nrenal and liver profile and inflammatory markers \n(erythrocytes sedimentation rate and C-reactive \nprotein) were unremarkable. Antinuclear antibody \nand anti-neutrophil cytoplasmic antibodies were \nnon-reactive. Serological tests for viral infections \nsuch as human immunodeficiency virus, hepatitis B \n& C were also non-reactive. Swab culture showed \nStenotrophomonas maltophilia. Skin biopsy tissue \nfor bacterial, fungal and mycobacterial cultures \nwere all negative. \n\n\n\nThe chest radiography revealed no evidence of active \ntuberculosis or metastases. Computed tomography \nshowed soft tissue lesion on the right cheek with \npossible malignancy without any evidence of \ndistant metastasis. Cerebral angiogram performed \nat another hospital showed features suggestive of \nbilateral orbital arteriovenous malformation with \nright external carotid artery involvement. However, \na repeat cerebral angiogram in our centre revealed \nno vascular abnormalities. Magnetic resonance \nimaging (MRI) showed a rim of enhancing collection \nat right maxillary region, measures 1.1cm (AP) x \n3.9cm (w) x 2.8cm (Ht) which led to the impression \nof right sided facial cellulitis with multi-loculated \ncollection and muscle involvement.\n\n\n\nHistopathological examination (Figure 2a) \ndemonstrated dermal proliferation of endothelial \ncells that exhibit abundant, eosinophilic cytoplasm, \nvesicular nuclei and prominent nucleoli. In the \nupper dermis there were slit like vascular spaces \ndissecting the dermal collagen. The spaces were \nlined by atypical endothelial cells which displayed \nhyperchromatic nuclei with irregular nuclear \noutline. The atypical cells were immunoreactive \ntoward CD31, CD34, ERG and FLI 1(Figure 2b-d). \nImmunofluorescence test was negative.\n\n\n\nA diagnosis of cutaneous angiosarcoma was made \n4 months after the onset of lesion. The patient \nwas started on a combination therapy of paclitaxel \n80mg/m2 and propranolol 120mg per day. After 6 \nweeks of oral propranolol and 2 doses of paclitaxel, \nthe necrotic tissue sloughed off revealing a 4 x 3 \ncm perforation on his right cheek (Figure 1c). It \nwas later complicated by secondary infection. Oral \nfeeding was challenging due to the huge buccal \ndefect and a nasogastric tube was inserted for the \npatient. Reassessment of disease after 2 doses of \npaclitaxel unfortunately showed no regression but \nfurther advancement of tumor with involvement of \nright cervical lymph nodes (Figure 1e-f). At the last \nreview, palliative care was provided with emphasis \non pain relief. Palliative chemotherapy with another \n2 doses of paclitaxel was given as well.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3974\n\n\n\nFigure 1: (a) Firm violaceous swelling over the right cheek with involvement of infraorbital region (May 2017); (b) Huge ulceration \nwith necrotic tissue sagging over the right cheek (Aug 2017); (c) Perforation of right cheek when the necrotic tissue was sloughed-off \nexposing the inner oral structure. (Oct 2017); (d) Progressive local invasion of tumour after 2 doses of paclitaxel with huge right cervical \nlymph node enlargement (Nov 2017); (e) Computed tomography showed large ulcerative soft tissue mass in the right sided face with \ncommunication into the oral cavity (solid arrow) and (f) right infratemporal space with cervical and supraclavicular nodal metastasis \n(dotted arrow).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 75\n\n\n\nFigure 2. (a) (H&E x200) (b) (H&E x 800) Atypical epithelioid endothelial cells with single/ multinucleated large, round nuclei and \nhyperchromatic nucleoli with abundant cytoplasm dissecting through dermal collagen. Extravasation of red blood cells noted; (c) ERG \nstain \u2013 nuclear staining of the endothelial cells; (d) CD31 stain \u2013 highlight the endothelial cells with cytoplasmic stains.\n\n\n\nDiscussion\nAngiosarcoma may arise from cutaneous or non-\ncutaneous structures (breast, heart, liver, spleen) and \ndeep tissue. Approximately one-third occur in the \nskin, one-fourth in soft tissue and the rest in other \nsites.11 It has a male preponderance and typically \naffects the elderly with a median age of 70-75 \nyears old. Caucasians and the fair skin population \nare more frequently affected.12 It can manifest as \necchymosis, violaceous papules or nodules, chronic \nulceration and rosacea-like lesions,13 giving rise to \ndiagnostic challenge. Ten to twenty-five percent \nexhibits distant metastatic disease at the time of \ndiagnosis.14\n\n\n\nThe diversity of clinical presentations may result in \ndelay in referral by other health care providers to \ndermatologists, leading to late diagnosis and poor \noutcome. This is illustrated by our patient, a middle \naged man who presented with recurrent gingivitis \nwhich was managed by dentists. Despite multiple \ncourses of antibiotics and dental extraction, the \nlesion progressed relentlessly from bruise to \nnodule to ulcerated plaque. Computed tomographic \nangiogram and MRI findings were red herrings as \nthey suggested either an arteriovenous malformation \nor multiple collections of abscess. \n\n\n\nThe role and importance of histopathological \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3976\n\n\n\nexamination is undebatable and cannot be \nemphasized more with regards to diagnosing any \nmass lesion. An early biopsy in the course of disease \nwould have expedited the management leading to a \nbetter outcome. This case highlighted the importance \nof cross referral to specialists when in doubt and the \nimportance of multidisciplinary clinics. \n\n\n\nHistopathological examination is the gold standard \nin the diagnosis of angiosarcoma. The recognition \nand confirmation of malignant endothelial \ncells which are abnormal, pleomorphic with \nhyperchromatic nuclei and mitotic features remains \ncrucial. The endothelial cells may appear round or \npolygonal with epithelioid appearance. Most of the \ncases are well-differentiated angiosarcoma which \nshows irregular or slit-like vascular channels with \nsingle-layered endothelial cells lining, functioning \nvascular sinusoids continuous with normal vascular \nchannels, permeating the dermal collagen.7,15 The \ncellular pleomorphism may be minimal and easily \nmissed. The extreme end of poorly differentiated \nangiosarcoma shows continuous sheets with necrosis \nand little or no evidence of luminal differentiation. \nImmuno-histochemical staining is useful to confirm \nthe endothelial origin of the abnormal cells. Markers \nfor endothelial differentiation include cytoplasmic \nstains of CD31 and CD34 and FLI-1.7 CD31 is the \nmost specific and is considered as the gold standard \nfor endothelial differentiation in angiosarcoma. \nMoreover, only epithelioid angiosarcoma is positive \nfor pancytokeratin stains and epithelial membrane \nantigen (EMA).16,17\n\n\n\nTreatment of cutaneous angiosarcoma remains a \nchallenge. Available options consist of wide surgical \nresection, radiotherapy and chemotherapy. Clearly, \nsurgical resection is advantageous in early localized \ndisease with even a possible cure. Unfortunately, \nonly 50% of the patients had resectable tumor \nat presentation.18 Up to 30-40% of patients who \nhad undergone tumor resection, had positive \nmicroscopic margin with unfavorable survival \noutcome.18,19 Anatomic limitation and cosmetic \nconsideration often make wide surgical resection \nnot feasible in angiosarcoma of the head and face. \nHence, combination therapy with adjuvant radiation \nis often recommended especially in reducing local \nrecurrence. \n\n\n\nChemotherapy is used for palliative measure but can \nalso serve as neoadjuvant therapy prior to resection. \nThe recent multi-center angiosarcoma study in Asia \nby Quek R et al.20 highlighted the chemo-sensitive \n\n\n\nnature of angiosarcoma and the improved overall \nsurvival with chemotherapy (11.5 months versus 4.4 \nmonths). Paclitaxel was used as the first-line therapy \nfor 71.4% of cutaneous angiosarcoma and 100% \nof non-cutaneous angiosarcoma in a study done in \nSingapore.3 An overall response rate of 56% was \nachieved.3 Based on a 14-year retrospective study \nby Fury MG et al, doxorubicin based chemotherapy \nachieved progression-free survival of 3.7-5.4 months \nwith a response rate of 40-65% while paclitaxel \nyielded 6.8 months progression-free survival for \nnon-operable scalp angiosarcoma.10 Prospective \nstudies on paclitaxel also showed promising results \nwith median overall survival ranging from 8 to 18.6 \nmonths.21,22  Overall survival at one-year was 58%.23\n\n\n\nIn 2008, there was a paradigm shift in the management \nof benign vascular tumor after a landmark study24 \nwhich repositioned the role of propranolol in \ntreating infantile haemangioma. Preclinical study25 \nrevealed that propranolol is able to selectively \ninhibit proliferation, survival and migration of \na panel of malignant vascular tumor cells which \noncogenic mechanisms are believed to be driven by \nbeta adrenergic signaling. Furthermore, malignant \nvascular tumors are found to have upregulation \nof beta adrenergic receptors. Encouraging results \ninclude significant reduction in proliferative index \nby up to 34% within the first week of propranolol (at \n1 to 1.5mg/kg) in angiosarcoma patient, implicating \nthat early mitigation with propranolol may halt \ntumor progression.26 Pasquier E et al27 concluded that \nthe combination of propranolol with vinblastine-\nbased metronomic chemotherapy had a promising \noutcome for recurrent or metastatic angiosarcoma \nwith a 100% response rate.\n\n\n\nAdverse predictors of survival include high mitotic \ncounts, metastatic disease at presentation, local \nrecurrence, positive surgical margins, visceral or \ndeep soft tissue tumor location, tumor size >5cm, \ntumor necrosis, absence of surgical excision, \nmultifocal disease and depth of invasion of more \nthan 3mm.12,28,29 Our patient had a large inoperable \ntumor measuring more than 5cm with tumor necrosis \nand deep invasion that conferred a poor prognosis. \nRequena et al recently highlighted that it is important \nto diagnose angiosarcoma i.e. to biopsy bruise-like \nlesion before it progressed to tumor which carries \npoor prognosis.30 Hence, all clinicians should have \na high index of suspicion for angiosarcoma and low \nthreshold to perform a biopsy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 77\n\n\n\nConclusion\nAngiosarcoma is an aggressive soft tissue sarcoma \nwith poor outcome. The heterogeneity of clinical \npresentations makes the diagnosis a challenge. \nEarly recognition of suspicious lesions including \nnon-resolving bruise-like lesion, together with \ntissue biopsy is crucial in establishing the diagnosis \nso that definitive treatment can be initiated early. \n\n\n\nConflict of Interest Declaration\nThe authors have no financial/conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Mendenhall WM, Mendenhall CM, Werning JW, Reith \nJD, Mendenhall NP. Cutaneous Angiosarcoma. Am J Clin \nOncol 2006;29:524-8\n\n\n\n2. Lahat G, Dhuka AR, Hallevi H, Xiao L, Zou C, Smith KD \net al. Angiosarcoma: clinical and molecular insights. Ann \nSurg 2010;251:1098-106.\n\n\n\n3. Farid M, Ong WS, Marcus Lee JF, Feevan R, Ho ZC, Sairi \nAN et al. Cutaneous versus Non-Cutaneous Angiosarcoma: \nClinicopathologic Features and Treatment Outcomes in \n60 Patients at a Single Asian Cancer Centre. Oncology \n2013;85:182-90.\n\n\n\n4. Oskrochi Y, Razi K, Stebbing J, Crane J. Angiosarcoma and \nDialysis-related Arteriovenous Fistulae: A Comprehensive \nReview. Eur J Vasc Endovasc Surg 2016; 51:127-33.\n\n\n\n5. Depla AL, Scharloo-Karels CH, de Jong MA, Oldenborg \nS, Kolff MW, Oei SB et al. Treatment and prognostic \nfactors of radiation-associated angiosarcoma (RAAS) after \nprimary breast cancer: a systematic review. Eur J Cancer \n2014;50:1779-88\n\n\n\n6. Ogawa K, Takahashi K, Asato Y, Yamamoto Y, Taira K, \nMatori S et al. Treatment and prognosis of angiosarcoma of \nthe scalp and face: A retrospective analysis of 48 patients. \nBr J Radiol 2012; 85:e1127-33.\n\n\n\n7. Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. \nAngiosarcoma. Lancet Oncol 2010;11:983-91.\n\n\n\n8. Perez MC, Padhya TA, Messina JL, Jackson RS, Gonzalez \nRJ, Bui MM et al. Cutaneous angiosarcoma: a single-\ninstitution experience. Ann Surg Oncol 2013;20:3391-7.\n\n\n\n9. Fayette J, Martin E, Piperno-Neumann S, Le Cesne \nA, Robert C, Bonvalot S et al.  Angiosarcomas, a \nheterogeneous group of sarcomas with specific behavior \ndepending on primary site: a retrospective study of 161 \ncases. Ann Oncol 2007;18:2030-6.\n\n\n\n10. Fury MG, Antonescu CR, van Zee KJ, Brennan MF, Maki \nRG. A 14-year retrospective review of angiosarcoma: \nclinical characteristics, prognostic factors and treatment \noutcomes with surgery and chemotherapy. Cancer J \n2005;11:241-7.\n\n\n\n11. Nagao K, Suzuki K, Yasuda T, Hori T, Hachinoda J, \nKanamori M et al. Cutaneous angiosarcoma of the buttock \n\n\n\ncomplicated by severe thrombocytopenia: a case report. \nMol Clin Oncol 2013;1:903-7.\n\n\n\n12. Tenjarla S, Sheils LA, Kwiatkowski TM, Chawla S. \nCutaneous Angiosarcoma of the Foot: A Case Report \nand Review of the Literature. Case Rep Oncol Med \n2014;2014:1-5. \n\n\n\n13. Mentzel T, Kutzner H, Wollina U. Cutaneous angiosarcoma \nof the face: clinicopathologic and immunohistochemical \nstudy of a case resembling rosacea clinically. J Am Acad \nDermatol 1998;38:837-40.\n\n\n\n14. Yang JC, Rosenberg SA, Glatstein EJ, Antman KH. \nSarcomas of soft tissues in: VT DeVita, S Hellman, SA \nRosenberg (Eds.) Cancer: Principles and Practice of \nOncology. 4th ed. JB Lippincott, Philadelphia; 1993:1436-\n88.\n\n\n\n15. Shustef E, Kazlouskaya V, Prieto VG, Ivan D, Aung PP. \nCutaneous angiosarcoma: a current update. J Clin Pahtol \n2017;70:917-25. \n\n\n\n16. Bacchi CE, Silva TR, Zambrano E, Plaza J, Suster S, Luzar \nB et al. Epithelioid angiosarcoma of the skin: A study of \n18 cases with emphasis on its clinicopathologic spectrum \nand unusual morphologic features. Am J Surg Pathol. \n2010;34:1334-43.\n\n\n\n17. Al-Abbadi MA, Almasri NM, Al-Quran S, Wilkinson EJ. \nCytokeratin and epithelial membrane antigen expression \nin angiosarcomas: an immunohistochemical study of 33 \ncases. Arch Pathol Lab Med 2007;131:288-92. \n\n\n\n18. Lydiatt WM, Shaha AR, Shah JP. Angiosarcoma of the \nhead and neck. Am J Surg 1994;168:451-4.\n\n\n\n19. Espat NJ, Lewis JJ, Woodruff JM, Antonescu C, Xia \nJ, Leung D et al. Confirmed angiosarcoma: prognostic \nfactors and outcome in 50 prospectively followed patients. \nSarcoma 2000;4:173-7. \n\n\n\n20. R Quek, HH Loong, V Sriuranpong, M Farid, SH Tan, \nWL Goh et al. Epidemiology, real world treatment and \noutcomes of 423 patients with angiosarcoma (AS) in Asia: \nA report from the Asian Sarcoma Consortium (ASC). Ann \nOncol 2016;27:ix163-8.\n\n\n\n21. Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard \nI, Piperno-Neumann S et al. Phase II trial of weekly \npaclitaxel for unresectable angiosarcoma: the ANGIOTAX \nstudy. J Clin Oncol 2008;26:5269-74.\n\n\n\n22. Apice G, Pizzolorusso A, Di Maio M, Grignani G, Gebbia \nV, Buonadonna A et al. Confirmed Activity and Tolerability \nof Weekly Paclitaxel in the Treatment of Advanced \nAngiosarcoma. Sarcoma 2016;2016:1-7.\n\n\n\n23. Ray-Coquard IL, Domont J, Tresch-Bruneel E, Bompas \nE, Cassier PA, Mir O. Paclitaxel given once per week \nwith or without bevacizumab in patients with advanced \nangiosarcoma: a randomized phase II trial. J Clin Oncol \n2015;33:2797-802.\n\n\n\n24. Leaute-Labreze C, Dumas de la Roque E, Hubiche T, \nBoralevi F, Thambo JB, Taieb A. Propranolol for severe \nhemangiomas of infancy. New Engl J Med 2008;358:2649-\n51.\n\n\n\n25. Stiles JM, Amaya C, Rains S, Diaz D, Pham R, \nBattiste J et al. Targeting of Beta Adrenergic Receptors \nResults in Therapeutic Efficacy against Models of \nHemangioendothelioma and Angiosarcoma. PLoS ONE \n2013;8:e60021.\n\n\n\n26. Chow W, Amaya CN, Rains S, Chow M, Dickerson EB, \nBryan BA. Growth attenuation of cutaneous angiosarcoma \nwith propranolol-mediated \u03b2-Blockade. JAMA Dermatol. \n2015;151:1226-9.\n\n\n\n27. Pasquier E, Andre N, Street J, Chougule A, Rekhi B, Ghosh \nJ et al. Effective Management of Advanced Angiosarcoma \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3978\n\n\n\nby the Synergistic Combination of Propranolol and \nVinblastine-based Metronomic Chemotherapy: A Bench to \nBedside Study. E Bio Medicine 2016;6:87-95.\n\n\n\n28. Morgan MB, Swann M, Somach S, Eng W, Smoller B. \nCutaneous angiosarcoma: a case series with prognostic \ncorrelation. J Am Acad Dermatol 2004;50:867-74.\n\n\n\n29. Buehler D, Rice SR, Moody JS, Rush P, Hafez GR, Attia \nS et al. Angiosarcoma Outcomes and Prognostic Factors: \nA 25-Year Single Institution Experience. Am J Clin Oncol \n2014;37:473-9.\n\n\n\n30. Requena C, Sendra E, Llombart B, Sanmartin O, Gull\u00e9n \nC, Lavernia J et al. Cutaneous Angiosarcoma: Clinical \nand Pathology Study of 16 cases. Actas Dermosifiliogr \n2017;108:457-65.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 79\n\n\n\nCASE REPORT\n\n\n\nSURGICAL CORRECTION OF PINCER-NAIL DEFORMITY USING \nAUTOLOGOUS FULL THICKNESS SKIN GRAFT: A CASE REPORT \nMuhammad Yasir B Ahmad Muslim, MBBCh, Chee Kheng Chuah, MS Ortho \n\n\n\nHand & Upper Limb Unit, Department of Orthopaedic and Traumatology, Hospital Kuala Lumpur, Kuala Lumpur, \nMalaysia\n\n\n\nSummary\nPincer nail deformity is often undertreated although it is a cause of pain and disfigurement. \nThis may be attributed to underdiagnosis and lack of awareness of the available treatment \noptions especially surgical options. Not many centres offer surgical correction of pincer nail \ndeformity in Malaysia. We would like to describe a surgical method of correcting this deformity.\n \n\n\n\nKey words: Pincer nail, Nail deformity, Surgical correction\n\n\n\nCorresponding Author\nDr Muhammad Yasir Bin Ahmad Muslim\nDepartment of Orthopaedics & Traumatology, Kuala \nLumpur Hospital, Jalan Pahang, 50586 Kuala Lumpur, \nMalaysia\nEmail: drmyasir132@gmail.com\n\n\n\nIntroduction\nPincer-nail deformity or unguis constringens \nis characterized by an extreme transverse \novercurvature of the nail that increases along the \nlongitudinal axis of the nail and reaches its greatest \nproportion towards the tip. At this point, the lateral \nborders tighten around the soft tissues, which \nare pinched without necessarily disrupting the \nepidermis.1 It is a disturbing deformity especially if \npresent in the finger nails as compared to toe nails. It \naffects not only the appearance but also the function \nbesides being painful. Somehow, in our region, it \nis overlooked and rarely do people go for surgical \ncorrection. We report the first case of pincer-nail \ndeformity correction using autologous full thickness \nskin graft in our center.\n\n\n\nCase Report\nA 36 years old security guard developed an idiopathic \npincer nail deformity over his right middle and ring \nfingers. Plain radiographs showed no deformity or \nosteophyte on the distal phalanges. The deformity \nwas severe (Figure 1a); hence he was counselled for \nsurgical correction, which he agreed for on his ring \nfinger, which was the one more deformed.\n\n\n\nThe surgery was performed under digital block \nanaesthesia and finger tourniquet. The deformed \nnail plate was removed2. A small transverse incision \nwas made on each side of the hyponychium. A \nhypodermic syringe needle was introduced through \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3980\n\n\n\nthe incision directed proximally to exit just proximal \nto the eponychial fold to create a tunnel between \nthe distal phalanx and the paronychium. Another \nparallel one was inserted beside that. A nylon suture \nwas passed through the needle hole (Figure 1b). \nThe full thickness skin graft was harvested from \nthe medial aspect of the ipsilateral arm, rolled and \ntied to the suture at one end. The suture was pulled \nthrough along with the graft which was drawn into \nthe tunnel thus elevating the paronychial fold and \ncorrecting the transverse overcurvature. The same \nsteps were repeated on the other side. The incisions \nwere then closed with nylon sutures (Figure 1c). The \noriginal deformed nail plate was divided vertically \nto allow it to flatten to be interposed in between \n\n\n\nthe nail bed and the eponychial fold to prevent \nformation of synechiae between them.\n\n\n\nThis method gives immediate correction of the \npincer deformity of the nail bed (Figure 1c) with \nrelief of pain. The future nail would then regenerate \nin this new normal transverse curvature of the nail \nbed (Figure 1d&e).\n\n\n\nSurgical correction for the middle finger was also \ndone 5 months later using the same methods. The \npatient was followed up for 1 year postoperatively. \nThe fingers were painless with no recurrence of the \npincer deformity. \n\n\n\nFigure 1. (a) The pincer nail deformity prior to surgical correction; (b) Tunnels were created underneath the nail bed on both sides, and \nnylon sutures were passed through to facilitated insinuation of the skin grafts inside the tunnels; (c) Pincer nail deformity is corrected \nimmediately after the skin grafts were insinuated; (d) New nail plate growing in a normal transverse curvature; (e) Six months post \noperatively, the new nail is a bit thickened, but the transverse curvature is improved. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 39 81\n\n\n\nDiscussion\nPincer nail deformity is a condition that develops \nwith accompanying pain and discomfort, interfering \nwith quality of life. Neglected cases result in eventual \nsoft tissue defect which sometimes accompanied \nby bone resorption1. In extreme cases, besides the \nunsightly nail deformity, the associated pain can \nbe provoked by the lightest of touch, such as the \nweight of a bedsheet.1\n\n\n\nNon-surgical treatment with a plastic device has \nshown good results in decreasing the transverse \novercurvature of the nail and associated pain3, but \ntreatment may take months and compliance issues \nmay arise, besides there being high recurrence rates.4\n\n\n\nCorrection of pincer-nail deformity with autograft \ndermis is a simple and short procedure and has been \nshown to be effective in correcting the deformity \nand relief of pain.\n\n\n\nConclusion\nPincer-nail deformity should be picked up and \ntreated. Surgical correction with full thickness skin \ngraft offers promising results.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences \n\n\n\n1. Baran R, Dawber R, Haneke E, Tosti A, Bristow I, Thomas \nL et al. A Text Atlas of Nail Disorders: Techniques in \nInvestigation and Diagnosis; 3rd ed; Florida; CRC Press; \n2005:18-22.\n\n\n\n2. Zook EG, Chalekson P, Brown RE, Neumeister MW. \nCorrection of pincer-nail deformities with autograft or \nhomograft dermis: modified surgical technique; J Hand \nSurg 2005;30;400-3.\n\n\n\n3. Di Chiacchio N, Kadunc BV, de Almecida ART, Madeira \nCL. Treatment of transverse overcurvature of the nail with \na plastic device: Measurement of response. J Am Acad \nDermatol 2006;55:1081-4.\n\n\n\n4. Baran R, Haneke E, Richert B. Pincer Nails: Definition \nand Surgical Treatment. Dermatol Surg 2001;27;261-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 Dec Vol 3982\n\n\n\nACKNOWLEDGEMENT\nDecember Issue 2017\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Assoc Professor Dr Adrian Yong Sze Wai\n3. Dr Agnes Heng Yoke Hui\n4. Datin Dr Asmah Johar\n5. Dr Ch\u2019ng Chin Chwen\n6. Dr Chan Lee Chin\n7. Dr Chang Choong Chor\n8. Dr Chong Yew Thong\n9. Dr Colin Theng Thiam Seng\n10. Dr Dawn Ambrose\n11. Assoc Professor Dr Felix Yap Boon Bin\n12. Professor Goh Chee Leok\n13. Dr Henry Foong Boon Bee\n14. Dr Khor Yek Huan\n15. Dr Lee Bang Rom\n16. Dr Lo Kang Shang Chit\n17. Dr Michelle Voo Sook Yee\n18. Dr Ng Su Yuen\n19. Dr Ng Ting Guan\n20. Dato\u2019 Dr Noor Zalmy Azizan\n21. Assoc Professor Dr Norashikin bt Shamsudin \n22. Dr Sabeera Begum\n23. Dr Tang Jyh Jong\n24. Dr Tarita Bt Taib\n25. Dr Wee Ai Leen\n\n\n\n\n\n"
"\n\nZi Ling Hun 1, Najeeb Ahmad B. Mohd. Safdar 2, Chen Hsiung Liang 3, Vaani Valerie  A/P \n\n\n\nVisuvanathan 2, Prakash A/L Balasubramaniam 2, Khar Weoi Low 3\n1 International Medical University Clinical School, Seremban, Malaysia\n2 Department of Dermatology, Hospital Tuanku Ja'afar Hospital, Seremban, Malaysia\n3 Klinik Kesihatan Kahang Batu 22, Kluang, Johor, Malaysia\n\n\n\nINTRODUCTION\nAcne is a common dermatological condition that \nimpacts approximately 85 percent of those between \nages of 12 and 24\u00b9 . However, it is often viewed as a \ncosmetic condition. Treatment of acne is often sidelined \nby health care administrators resulting in poor resource \nallocations in the treatment of acne.\n\n\n\nOBJECTIVE\nTo determine the impact of severity of acne on quality \nof life and psychological health among acne patients in \nHospital Seremban.\n\n\n\nMATERIALS AND METHOD\n\uf09f A cross-sectional study on acne patients visiting \nDermatology clinic in Hospital Tuanku Jaa\u2019far, \nSeremban, Malaysia from August 2016 to January 2017 \nwas carried out. All patients with acne vulgaris aged 13 \nyears and above were invited to participate in this study.\n\uf09f Data was collected with standardized questionnaire\nforms namely Global Acne Grading System (GAGS), \nDermatology Life Quality Index (DLQI) and Patient \nHealth Questionnaire for Depression and Anxiety (PHQ-\n4).\n\uf09f The data was analyzed with T test, using statistical \nanalysis IBM SPSS.\n\n\n\nDISCUSSION\n\uf09f A higher prevalence of males (55%) having \n\n\n\nmoderate-severe acne than females, similar as had \nbeen demonstrated in other studies\u00b2. \n\n\n\n\uf09f Mean DLQI score of 9.60 indicates patients in \nSeremban Hospital experienced moderate \nimpairment in quality of life due to their acne.\n\n\n\n\uf09f Mean PHQ-4 score was 4.14, indicating mild \nsymptoms of depression and/or anxiety in the past \ntwo weeks. \n\n\n\n\uf09f No significant difference between acne severity and \ndermatology life quality index (p= 0.104). This implies \nthat effect on quality of life should not be judged \nbased on acne severity alone. Lack of coping \nstrategies, for example, increased cosmetics usage \nand hairstyles to partly conceal the presence of acne, \nare other factors which may influence the quality of \nlife in patients, besides the severity of acne. \n\n\n\nLIMITATIONS\n\uf09f Small sample size\n\uf09f Cross sectional design\n\n\n\nCONCLUSION\nAcne has a profound effect on quality of life and the \npsychological well being of patients. However these \neffects are not related to the severity of acne per se.\nQuality of life and psychological health issues must be \naddressed in all patients with acne vulgaris regardless \nof acne severity. \n\n\n\nRESULTS\n\n\n\nRESULTS\n\u2022 There was no significant difference between gender \n\n\n\nand acne severity (p= 0.242), as well as between \nethnic and acne severity (p= 0.369).\n\n\n\n\uf09f The mean DLQI score was 9.60 \u00b1 5.16. There was no   \nsignificant difference between acne severity and the\nDLQI score (p= 0.104). \n\n\n\n\uf09f The mean for PHQ-4 score was 4.14 \u00b1 3.63. There \nwas no significant difference between acne severity \nand psychological health. (p= 0.425).\n\n\n\n\uf09f No significant difference between gender and \ndermatology life quality index (p= 0.866), as well as \npsychological health ( p= 0.215). No significant \ndifference between ethnic and dermatology life quality \nindex (p= 0.208), as well as with psychological health \n( p= 0.792).\n\n\n\nImpact of Acne Vulgaris Severity on Quality of Life \nand Psychological Health in Hospital Tuanku \nJaa\u2019far, Seremban, Malaysia\n\n\n\nPoster \nNo.1\n\n\n\nREFERENCES\n1. Bhate K, Williams H. Epidemiology of acne vulgaris. \n\n\n\nBr. J. Dermatol. 2013;168(3):474-485.\n2. Aktan S, Ozmen E, S B. Anxiety, depression, and \n\n\n\nnature of acne vulgaris in adolescents. Int J Dermatol. \n2000;39(5):354-357.\n\n\n\n3.  Yap F. The impact of acne vulgaris on the quality of \nlife in Sarawak, Malaysia. SSDDS. 2012;16(2):57-60.\n\n\n\n4. Hanisah A, Omar K, Shah SA. Prevalence of acne \nand its impact on the quality of life in school-aged\nadolescents in Malaysia. J Prim Health Care. \n2009;1:20-5. \n\n\n\n5. Tanghetti, E. A., Kawata, A. K., Daniels, S. R. \nYeomans, K., Burk, C. T., Callender, V. \nD.Understanding the Burden of Adult Female Acne. J\nClin Aesthet Dermatol. 2014:7(2):22-30.\n\n\n\nCharacteristics N=40 (%)\nGender\nMale \nFemale\n\n\n\nEthnicity\nMalay\nChinese\nIndian\nOthers\n\n\n\nAcne severity using Global Acne \nGrading System (GAGS)\nMild\nModerate\nSevere\n\n\n\n22 (55%)\n18 (45%)\n\n\n\n27 (67.5%)\n7 (17.5%)\n3 (7.5%)\n3 (7.5%)\n\n\n\n21 (52.5%)\n17 (42.5%)\n2 (5%)\n\n\n\nTable 1: Socio-demographic data and clinical \ncharacteristics of patients  \n\n\n\nTable 2: Quality of life and psychological health of \nacne patients\n\n\n\nQuality of life and psychological \nhealth\n\n\n\nN=40 (%)\n\n\n\nQuality of life measured with \nDermatology Life Quality Index (DLQI)\nNo effect\nMild effect\nModerate effect\nVery large effect\nExtremely large effect\n\n\n\nPsychological Health measured using \nPatient Health Questionnaire for \nDepression and Anxiety (PHQ-4)\nNone\nMild\nModerate\nSevere\n\n\n\n1 (2.5%)\n8 (20%)\n15 (37.5%)\n15 (37.5%)\n1 (2.5%)\n\n\n\n16 (40%)\n9 (22.5%)\n9 (22.5%)\n6 (15%)\n\n\n\n\n\n\n\n\nZulaiha A. Jalil, Siti Khalijah M. Zulkefli, Rajalingam Ramalingam\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan\n\n\n\nINTRODUCTION\n\n\n\nThere are many types of cutaneous adverse drug reactions (CADR), from mild pruritus to severe life-threatening conditions such as\nStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with significant morbidity and mortality. Awareness of local\nepidemiology of CADR may play a vital role in future clinical management protocols.\n\n\n\nMETHODOLOGY\n\n\n\nA retrospective review of all patients referred to the Department of Dermatology of Hospital Tengku Ampuan Afzan (HTAA), Kuantan,\nPahang with CADR from 2013 to 2016 was carried out to determine the epidemiology of CADR in the local population.\n\n\n\nDISCUSSION\n\n\n\n1. Huang H. Y., et al. Clin & Exp Dermatol 2010; 36: 135-141 2. Choon S. E., et al. Ind J Dermatol Venereol Leprol 2012; 78(6): 734-739 3. Talib N. H., et al. S Afr Fam Pract 2015; 57(4): 227-230 4. Garg H. K., et al. Int J Med\nRes Prof 2016; 2(5): 45-49 5. Mokhtari F., et al. J Res Med Sci 2014; 19: 720-5 6. Janardhan B., et al. Int J Res Dermatol 2017; 3(1): 74-78 7. Borch J. E., et al. Acta Derm Venereol 2006; 86: 523-527 8. Zaraa I., et al. Int J\nDermatol 2011; 50: 877-880 9. Lim K. S. et al. Neurol Asia 2008; 13: 15-21 10. Chang C. C., et al. Int J Dermatol 2011; 50: 221-4\n\n\n\nRESULTS\n\n\n\nType of CADR (n=62) Culprit Group of Drug\n\n\n\nA comparison of clinicoepidemiological studies on CADR in Malaysia and various Asian countries\n\n\n\nCONCLUSION\n\n\n\nSJS was the commonest CADR encountered in our center, while the commonest culprit drug was allopurinol. Antibiotics as a group\ncaused the most CADR.\n\n\n\nWe would like to thank the Director General of Health, Malaysia for permission granted to present this report.\n\n\n\nACKNOWLEDGEMENT\n\n\n\nREFERENCES\n\n\n\nRates of CADR among both genders \nand various ethnic groups\n\n\n\nNo. of new \npatients\n\n\n\nN (%)\n\n\n\nNo. with \nCADR\nN (%)\n\n\n\nCADR \nrate\n(%)\n\n\n\nGender\nMale\n\n\n\nFemale\n3567 (48.5)\n3786 (51.5)\n\n\n\n37 (62.7)\n22 (37.3)\n\n\n\n1.04\n0.58\n\n\n\nEthnicity\nMalay\n\n\n\nChinese\nIndian\n\n\n\nIndigenous\n\n\n\n5697 (77.5)\n1176 (16.0)\n\n\n\n322 (4.4)\n158 (2.1)\n\n\n\n41 (69.5)\n11 (18.6)\n\n\n\n3 (5.1)\n4 (6.8)\n\n\n\n0.72\n0.94\n0.93\n2.53\n\n\n\nTotal 7353 59 0.80\n\n\n\nStevens-Johnson syndrome\n\n\n\nMaculopapular Eruption\n\n\n\nToxic Epidermal Necrolysis\n\n\n\nPhotodermatitis\n\n\n\nUrticaria/Angioedema\n\n\n\nAcute Generalized Exanthematous Pustulosis\n\n\n\nExfoliative Dermatitis\n\n\n\nErythema Multiforme\n\n\n\nFixed Drug Eruption\n\n\n\nErythroderma\n\n\n\nDrug-related Eosinophilia with Systemic Symptoms\n\n\n\nLichenoid Drug Eruption\n\n\n\nBullous Drug Eruption\n\n\n\nDapsone Hypersensitivity syndrome\n\n\n\nNo Data\n\n\n\n24%\n\n\n\n21%\n\n\n\n10%\n8%\n\n\n\n8%\n\n\n\n3%\n\n\n\n3%\n\n\n\n3%\n\n\n\n3%\n\n\n\n2%\n2%\n\n\n\n2%\n2%\n\n\n\n2%\n\n\n\n8%\n\n\n\nAntibiotics\n\n\n\nAllopurinol\n\n\n\nAnalgesics\n\n\n\nAntiepileptics\n\n\n\nAntimitotics\n\n\n\nTraditional &\nComplimentary Medicine\n\n\n\nAntiretroviral Therapy\n\n\n\nUnknown\n\n\n\nOthers/Miscellaneous\n\n\n\n48%\n\n\n\n15%\n\n\n\n10%\n\n\n\n3%\n\n\n\n3%\n\n\n\n3%\n\n\n\n2% 5%\n\n\n\n11%\n\n\n\nHuang HY, et al1\n\n\n\n(2004-2008)\nShanghai, China\n\n\n\nN=734\n\n\n\nChoon SE, et al2\n\n\n\n(2001-2010)\nJohor Bahru, Malaysia\n\n\n\nN=362\n\n\n\nTalib NH, et al3\n\n\n\n(2009-2010)\nKuala Lumpur, Malaysia\n\n\n\nN=134\n\n\n\nGarg HK, et al4\n\n\n\n(2010-2012)\nAjman, UAE\n\n\n\nN=43\n\n\n\nMokhtari F, et al5\n\n\n\n(2006-2013)\nIsfahan, Iran\n\n\n\nN=282\n\n\n\nJanardhan B, et al6\n\n\n\n(2013-2014)\nHyderabad, India\n\n\n\nN=481\n\n\n\nOur Study\n(2013-2016)\n\n\n\nKuantan, Malaysia\nN=62\n\n\n\nMale:Female ratio 1:1.97 1.14:1 1.1:1 1:1.15 1:1.55 1.78:1 1.68:1\n\n\n\nMean age (years) 43.9 (8-93) 39.6 (1-98) 47.0 (14-91) 30.0 29.48 (0.4-90) 42 (1-64) 47.2 (3-92)\n\n\n\nMedian latency (days) 7.64\u00b18.32 NA NA 5.63\u00b10.5 NA 4 (1-120) 6\n\n\n\nIncidence/\nPrevalence (%)\n\n\n\nNA Incidence: 0.86 Prevalence: 0.2 NA NA Prevalence: 1.08 Incidence: 0.8\n\n\n\nCommonest CADR (%) 1. EM (34.7)\n2. Urticaria (26.2)\n3. MPE (21.7)\n\n\n\n1. MPE (42.3)\n2. SJS (24.3)\n3. DRESS (9.4)\n\n\n\n1. MPE (22.4)\n2. SJS (9.7)\n3. FDE (8.9)\n\n\n\n1. MPE (48.8)\n2. Erythroderma \n\n\n\n(18.6)\n3. Urticaria (11.7)\n\n\n\n1. SJS (31.9)\n2. MPE (24.5)\n3. TEN (11.0)\n\n\n\n1. MPE (35.6)\n2. Urticaria (26.2)\n3. FDE (17.9)\n\n\n\n1. SJS (24.2)\n2. MPE (21.0)\n3. TEN (9.7)\n\n\n\nCommonest Groups of \nCulprit Drugs\n\n\n\n1. Antimicrobials \n(48.3)\n\n\n\n2. Allopurinol (6.0)\n\n\n\n1. Antimicrobials\n(40.3)\n\n\n\n2. AEDs (22.4)\n3. Allopurinol (13.8)\n\n\n\n1. Antimicrobials \n(36.6)\n\n\n\n2. TCM (17.9)\n3. Analgesics (13.4)\n\n\n\n1. Antimicrobials \n(48.8)\n\n\n\n2. Analgesics (32.5)\n3. TCM (4.6)\n\n\n\n1. AEDs (51.8)\n2. Antimicrobials \n\n\n\n(33.7)\n3. Analgesics (5.7)\n\n\n\n1. Antimicrobials \n(56.3)\n\n\n\n2. NSAIDs (19.5)\n3. AEDs (16.6)\n\n\n\n1. Antimicrobials \n(48.4)\n\n\n\n2. Allopurinol (14.5)\n3. Analgesics (9.7)\n\n\n\n\u2022 A total of 62 CADR involving 59 patients \nwere seen among 7,353 new patients, \nyielding an incidence rate of 0.80% (yearly \nCADR rate range: 0.16 \u2013 1.89%)\n\n\n\n\u2022 The highest CADR rate was seen among \nindigenous peoples\n\n\n\n\u2022 Two-thirds of patients with CADR were \nbetween 21 and 60 years old, with a mean \nage of 47.3 years (range: 3 \u2013 92)\n\n\n\n\u2022 Two patients died, one each from dapsone\nhypersensitivity syndrome and TEN, \nresulting in a mortality rate of 3.39%\n\n\n\n\u2022 More females (80.0%) had SJS than males \n(20.0%), while TEN showed a reverse \npattern (83.3% males vs 16.7% females)\n\n\n\n\u2022 Allopurinol was the commonest culprit \ndrug causing SJS (7/15) and TEN (2/6)\n\n\n\n\u2022 Cotrimoxazole and Cloxacillin were the two \ncommonest antimicrobials implicated in \nCADR, while the commonest analgesic was \nCelecoxib\n\n\n\n\u2022 One-third of our patients only took a single \ndrug, while the average number of drugs \ntaken by a patient was three.\n\n\n\n\u2022 Severe CADR, namely SJS and TEN, were among the commonest CADRs observed in the Malaysian hospitals above, including ours. \nThis could be due to a referral bias, being dermatology referral centers accepting serious CADRs. This could also explain the lower \nCADR rate in our cohort compared to 1.38% and 1.5% of dermatology referrals in Denmark7 and Tunisia8, respectively.\n\n\n\n\u2022 We now know that there are specific genetic markers for carbamazepine- and phenytoin-induced CADRs9,10, and that these alleleic\nmarkers occur with varying frequency in different ethnic populations. Whether this holds true for the indigenous peoples of the \nstate of Pahang resulting in higher CADR rates among them, requires further pharmacogenomic studies.\n\n\n\n\u2022 Antimicrobials being the predominant culprit group in almost all of the studies above not only reflects the high infectious diseases \nburden in tropical and subtropical Asia, but also serves to remind us of more judicious prescriptions of these agents in the future.\n\n\n\nEM: erythema multiforme; MPE: maculopapular exanthem; SJS: Stevens-Johnson syndrome; DRESS: drug-related eosinophilia with systemic symptoms; FDE: fixed drug eruption; TEN: toxic epidermal necrolysis; AEDs: \nanti-epileptic drugs; TCM: traditional and complimentary medicine; NSAIDs: non-steroidal anti-inflammatory drugs; NA: not available\n\n\n\n2\n\n\n\n* There is no conflict of interest for all authors *\n\n\n\n\n\n\n\n\nINTRODUCTION\n\n\n\nFungal infections of the skin is one the most common diseases encountered in dermatology. As a tertiary referral center in the state of\nPahang, we sought to determine the clinicoepidemiology pattern of patients with cutaneous fungal infections.\n\n\n\nMETHODS\n\n\n\nA retrospective review of all cutaneous specimens sent for fungal culture from the Department of Dermatology of Hospital Tengku\nAmpuan Afzan (HTAA), Kuantan, Pahang between 2011 to 2016 was carried out to determine the local pattern of cutaneous mycology.\n\n\n\nDISCUSSION\n\n\n\n\u2022 More than half of all samples did not isolate any fungus despite a clinical diagnosis of cutaneous mycosis. This could be due to\nseveral possible factors:\n\n\n\ni. a wrong diagnosis of cutaneous mycosis\nii. delayed specimen transportation to the lab; it is recommended that specimens for fungal culture should be transported to\n\n\n\nthe lab preferably within 2 hours to ensure optimum recovery of fungi1\n\n\n\niii. improper sampling methods without the aid of direct microscopy using potassium hydroxide (KOH) or Wood\u2019s lamp\nexamination, especially for onychomycosis and superficial mycoses\n\n\n\n\u2022 Ideally, as described in previous studies, micro-drilling, proximal sampling and subungual curettage2 yield better results than simple\nnail clipping for nail fungal cultures. A recent meta-analysis concluded that the accuracy of KOH and cultures was lower compared\nto nail biopsy with Periodic Acid-Schiff (PAS)-staining3, something worth considering in patients with recalcitrant onychomycosis.\n\n\n\n\u2022 For suspected tinea capitis, hair root and scalp skin scraping should be obtained by vigorously rubbing over the erythematous, scaly\nor alopecic region with a moistened cotton swab or gently rubbing with a sterile toothbrush4.\n\n\n\n\u2022 While skin biopsy and tissue culture remains the gold standard in diagnosing subcutaneous and deep fungal infection, occasional\nspecimens can be difficult to culture either due to low fungal burden or heavy secondary infections, and may require multiple\nsampling, subcultures and/or extended incubation5. Furthermore, there may be histopathologic identification of fungal elements\ndespite skin tissue culture failing to show fungal growth6. As such, future studies may want to look at the discrepancy rate between\nboth methods of fungal identification.\n\n\n\n\u2022 We advocate proper prospective studies in the future addressing mycological patterns of cutaneous fungal infection with important\nassociated factors such as comorbidities, immunosuppression, occupation, social habits and chronic medication usage in addition\nto improved sampling techniques.\n\n\n\n\u2022 The utilization of polymerase chain reaction (PCR) or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry\n(MALDI-TOF)7 for a more accurate identification of fungal species should also be considered in future clinicoepidemiological studies.\n\n\n\n1. Chaya A. K., et al. Ind J Dermatol Venereol Leprol 2007; 73(3): 2002-2005 2. Shemer A., et al. J Dermatol 2009; 36: 410-414 3. Velasquez-Agudelo V., et al. BMC Infectious Diseases 2017; 17(166): 2-\n11 4. Friedlander S. F., et al. Pediatrics 1999; 104(2): 276-279 5. Barros M. B., et al. Clin Microbiol Rev 2011; 24(4): 633-654 6. Gonzalez Santiago T. M., et al. J Am Acad Dermatol 2014; 71: 293-301 7.\nChalupov\u00e1 J., et al. Biotechnol Adv 2013; 1-12\n\n\n\nRESULTS\n\n\n\nCONCLUSION\n\n\n\nThe predominant fungi isolated from nail samples were non-dermatophyte molds, whereas samples of skin scraping and hair mainly\nisolated dermatophytes. Apart from onychomycosis, both superficial and subcutaneous mycoses of the skin and hair showed a male\npreponderance.\n\n\n\nWe would like to thank the Director General of Health, Malaysia for permission granted to present this report.\n\n\n\nACKNOWLEDGEMENT\n\n\n\nREFERENCES\n\n\n\nPositive Cultures Nail Skin Scraping Hair Skin Biopsy\n\n\n\nPatients\nN\n\n\n\nMale : Female\n\n\n\nMalay\nChinese\n\n\n\nIndian\nIndigenous\n\n\n\nMean age (years)\n\n\n\n135\n\n\n\n1 : 1.33\n\n\n\n82 (60.7%)\n33 (24.4%)\n19 (14.1%)\n\n\n\n1 (0.7%)\n\n\n\n53.5 (2 \u2013 90)\n\n\n\n31\n\n\n\n1.21 : 1\n\n\n\n24 (77.4%)\n5 (16.1%)\n2 (6.4%)\n\n\n\n0\n\n\n\n47.9 (2 \u2013 80)\n\n\n\n19\n\n\n\n1.7 : 1\n\n\n\n18 (94.7%)\n0\n0\n\n\n\n1 (5.3%)\n\n\n\n8.9 (3 \u2013 28)\n\n\n\n8\n\n\n\n1.67 : 1\n\n\n\n5 (62.5%)\n3 (37.5%)\n\n\n\n0\n0\n\n\n\n66.1 (27 \u2013 83)\n\n\n\nSamples\nN\n\n\n\nCommonest \nfungus isolated\n\n\n\n150\n\n\n\nA. niger: 62 (41.3%)\nT. rubrum: 10 (6.7%)\n\n\n\nPenicillium sp: 9 (6.0%)\n\n\n\n40\n\n\n\nM. canis: (6 (15.0%)\nT. rubrum: 5 (12.5%)\n\n\n\nT. interdigitale: 3 (7.5%)\n\n\n\n27\n\n\n\nM. canis: 20 (74.1%)\nM. audouinii: 5 (18.5%)\nE. floccosum: 1 (3.7%)\n\n\n\n9\n\n\n\nS. schenckii: 3 (33.3%)\nC. cladosporioides: 1 (11.1%)\n\n\n\nPenicillium sp: 1 (11.1%)\n\n\n\nA total of 496 samples from 413 patients were sent, out of which 62.9% were nail clipping, 19.0% skin scraping, 12.9% hair and 5.2%\nskin biopsy tissue. Cultures were positive in 226 (45.6%) samples from 193 patients. Overall, non-dermatophyte molds were the\npredominant fungus isolated (74.0%), followed by yeasts (14.7%) and dermatophytes (11.3%).\n\n\n\nA. niger: Aspergillus niger; T. rubrum: Trichophyton rubrum; T. interdigitale: Trichophyton interdigitale; M. canis: Microsporum canis;  M. audouinii: Microsporum audouinii; E. floccosum: Epidermophyton floccosum; \nS. schenckii: Sporothrix schenckii; C. cladosporioides: Cladosporum cladosporioides\n\n\n\n* There is no conflict of interest for all authors *\n\n\n\n3\n\n\n\nNail\n\n\n\nFingernail\n\n\n\nToenail\n\n\n\nFingernail &\nToenail\nNot specified\n\n\n\nSkin scraping\n\n\n\nFeet\n\n\n\nScalp\n\n\n\nTrunk\n\n\n\nGroin\n\n\n\nNot specified\n\n\n\n14%\n\n\n\n9%\n\n\n\n1%\n\n\n\n76%\n\n\n\n15%\n\n\n\n15%\n\n\n\n10%\n\n\n\n2%\n\n\n\n58%\n\n\n\n\n\n\n\n\nSyringocystadenoma papilliferum\narising in a naevus sebaceous\n\n\n\nPoster \nNo. 4\n\n\n\nNik Aimee Azizah Faheem MB BCh BAO1, Zhenli Kwan Adv M Derm1, Adrian Sze Wai Yong \nMRCP (Dermatology)1, Chin Chwen Ch\u2019ng Adv M Derm1, Leng Leng Tan Adv M Derm1, \nJayalakshmi Pailoor FRCPath2, Kim Kwan Tan MBBS2, Manimalar Naicker MPath2\n\n\n\n1 Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, \nKuala Lumpur, Malaysia\n2 Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n\n\n\nIntroduction\n\n\n\nNaevus sebaceous is a cutaneous hamartoma with \nhyperplasia of the epidermis, sebaceous glands \nand apocrine glands. It usually occurs in the head \nand neck region and is present since birth. Naevus\nsebaceous has been well documented to have the \npotential of developing into both benign and \nmalignant neoplasms. 18.9% of patients with \nnaevus sebaceous have secondary benign \nneoplasms while another 2.5% have malignant \nneoplasms.1 We report a case of \nsyringocystadenoma papilleferum (SCAP) arising \nfrom a naevus sebaceous.\n\n\n\nCase Report\n\n\n\nA 56-year-old Malay lady with underlying type 2 \ndiabetes mellitus, hypertension and gout was \nreferred to our Dermatology clinic by her local \ngovernment clinic with a lesion over her right \ntemporal scalp. This lesion had been present since \nbirth but increasing in size with intermittent \nbleeding over the past two months. She was \ninitially treated with oral antibiotics and dressings \nwithout improvement. \n\n\n\nOn physical examination, there was a fleshy \npapillomatous exophytic mass measuring 3 cm x 2 \ncm over her right temporal scalp with surrounding \nmaceration and pus discharge. There was no \npalpable lymphadenopathy. An excisional biopsy \nwas performed.\n\n\n\nHistopathological examination revealed \npapillomatosis with cystic invaginations extending \ndownwards from the epidermis. Numerous papillary \nprojections were extending into the lumina of these \ninvaginations. The invaginations and papillary \nprojections were lined by glandular epithelium \nconsisting of an outer layer of small cuboidal cells \nand inner layer of tall columnar cells. Underlying \napocrine metaplasia was also seen, suggesting the \npresence of a naevus sebaceous.\n\n\n\nFigure 1: Fleshy papillomatous mass on temporal \nscalp, measuring 3 x 2 cm\n\n\n\nFigure 2: Syringocystadenoma papilliferum (H&E. stain, x4)\n\n\n\nFigure 3: Apocrine metaplasia (blue arrow), a feature of \nnaevus sebaceous (H&E. stain, x10)\n\n\n\nDiscussion\n\n\n\nSCAP is a hamartoma derived from apocrine eccrine\nglands. It is the second commonest benign neoplasm \narising from a pre-existing naevus sebaceous after \ntrichoblastoma.1 However in Taiwan, SCAP is more \ncommon in patients with naevus sebaceous \ncompared to trichoblastoma.2\n\n\n\nKatoulis and Bozi have described 3 types of SCAP. 3\nOur patient had the first type, namely the plaque type, \nwhich presents as a hairless lesion on the scalp and \nis often associated with naevus sebaceous. It is \ngenerally apparent at birth and gradually enlarges \nafter puberty. The other types are the linear and \nsolitary nodule types. Malignant transformation of \nSCAP to basal cell carcinoma, squamous cell \ncarcinoma, or syringocystadenocarcinoma\npapilliferum may occur. The treatment options for \nSCAP include surgical excision, Mohs micrographic \nsurgery and carbon dioxide laser excision.3 For \nnaevus sebaceous, surgical excision may be delayed \ntill after adolescence as risk of malignancy is low.4\n\n\n\nReferences\n1. Idriss MH, Elston DM. Secondary neoplasms associated with nevus \n\n\n\nsebaceus of Jadassohn: A study of 707 cases. J Am Acad Dermatol 2014; \n70: 332-7.\n\n\n\n2. Hsu MC, Liau JY, Hong JL, et al. Secondary neoplasms arising from nevus \nsebaceus: A retrospective study of 450 cases in Taiwan. J Dermatol\n2016;43:175-80.\n\n\n\n3. Chandramouli M, Sarma D, Tejaswy K, Rodrigues G. Syringocystadenoma\npapilliferum of the scalp arising from a nevus sebaceous. J Cutan Aesthet\nSurg 2016;9:204-6.\n\n\n\n4. Lowell G, Katz S, Gilchrest B, Paller A, Leffell D, Wolff K. Fitzpatrick\u2019s \nDermatology in General Medicine, 8th ed. United States of America: \nMcGraw-Hill; 2012.\n\n\n\n\n\n\n\n\nIchthyosis and fragile hair:  \nWhat say you? \n\n\n\n1Voo SYM, 1Yusof DSY, 2Leong KF \n\n\n\n1Department  of  Dermatology,  Hospital Queen Elizabeth \n2Department of Pediatrics, Pediatric Institute Hospital Kuala Lumpur \n\n\n\nPoster \n5 \n\n\n\nIntroduction \n\n\n\nCase report \n\n\n\nDiscussion \n\n\n\nFig 4 \n\n\n\nFig 3a Fig 1a Fig 2a Fig 1b \n\n\n\nFig 2b \n\n\n\n\n\n\n\n \n \nNetherton syndrome (NS) is a rare autosomal recessive ichthyosiform disorder characterized by ichthyosis, atopic \ndiathesis and hair shaft abnormalities1. Here, we present a family of NS. \n \n\n\n\n\n\n\n\n \nThe index case was referred at the age of 13 years for management of erythroderma. He had generalized scaling \nand desquamation since day 3 of life and was follow-up at a district hospital however defaulted review since 10 \nyears ago. Both his parents were distant cousins. He was refused for schooling because of his skin condition. His \neldest sister, one aunt (Fig 1b) and two of his uncles had similar skin changes at newborn. However, except his \naunt, they passed away during early infancy. His family tree is shown in Figure 4. \n \n\n\n\nClinically his hair was sparse with loss of eyebrow and mild ectropian (Fig 1). He was erythrodermic with \npolycyclic erythematous serpiginous patches with double edge scales at his trunk (Fig 2a). His weight and height \nwere below 95% centile. Dermoscopic examination of his hair showed bamboo hair (Fig 2b). Histopathological \nexamination of the skin biopsy showed psoriasiform hyperplasia, hyperkeratosis with focal parakeratosis with lack \nof granular layer (Fig 3b and 3c). There was almost absence of lymphoepithelial kazal-type related inhibitor \n(LEKTI) staining at the granular layer the epithelium(Fig 3a). His total Ig E was > 5000 kU/L.The diagnosis of NS \nwas made based on clinical signs and symptoms as well as immunofluorescence staining results. \n \n\n\n\nHis aunt\u2019s skin biopsy for LEKTI staining is still pending. The index patient\u2019s skin and symptoms improved after \nstarted acitretin and he plans to start schooling.  \n\n\n\n\n\n\n\n\n\n\n\n \nNear to one fifth of a study of newborn with erythroderma had NS2. The \nclinical hallmark of NS are non bullous ichthyosiform erythroderma, \nichthyosis linearis circumflexa (ILC) and hair shaft abnormalities3 which \ninclude trichorrhexis invaginata (TI). \n \n\n\n\nThe challenge of the diagnosis is that the characteristic hair may appear \nlate due to delayed hair growth. It is not uncommon for hundreds of hair \nsamples to be examined before TI is found. Furthermore ILC is \nintermittent and may not be present during examination.  \n \n\n\n\nNS is due to mutation in SPINK5 gene located in chromosome 5q31-32 \nwhich encodes for serine protease inhibitor LEKTI. As a result of loss of \nfunction of LEKTI, there is increased skin proteolytic activity affecting skin \nbarrier function. This syndrome is also associated with metabolic \ndisturbance (for example aminoaciduria), immunological disorders and \ngrowth retardation.  \n\n\n\nNetherton syndrome should be considered in any neonate presenting with \nerythroderma or ichthyosis, growth failure and recurrent infection and \nprompt us to look for additional clues. The most important period is the \nneonatal period whereby supportive therapy is the mainstay of treatment \nas mortality is high due to intercurrent infection4. \n  \n\n\n\n\n\n\n\n\n\n\n\nConclusion \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nReferences \n1.Emre S et al. Two siblings with Netherton Syndrome. Turk J Med Sci 2010; 40(5): 819-23 \n2.Pruszkowski A et al. Neonatal and infantile erythrodermas: a retrospective study of 51 patients. Arch Dermatol. 2000; 136: 875-80 \n3.Bittencourt MdeJ et al. Trichoscopy as a diagnostic tool in trichorrhexis invaginata and Netherton Syndrome. An Bras Dermatol 2015 Jan Feb; \n90(1): 114-6 \n4.Craiglow BG. Icthyosis in newborn. Semin Perinatal 2013 Feb; 37(1): 26-1 \n \nAcknowledgement  \nThe authors would like to thank Dr Lee Bang Rom for interpreting and providing the images of the skin histopathology, Dr Dwi for performing and providing the images of the \nLEKTI staining as well as the Director General of Health for giving the permission to present this case report. \n \n\n\n\nFig 3b \n\n\n\nFig 3c \n\n\n\nFig 4 \n\n\n\n\n\n\n\n\nClinical pattern and treatment response of Syphilis among \nHuman Immunodeficiency Virus (HIV)-infected Men \n\n\n\nWho Have Sex with Men (MSM) in Malaysia: \na 5-year Multi-centre retrospective study (2011-2015)\n\n\n\nSiaw Yen Ong*, Min Moon Tang*, Izzaty Dalawi\u00a5, Vijayaletchumi Krishnasamy*, Wooi Chiang Tan\u00a7, Chin Aun Yeoh\u00a7, Wee Meng Kho\u2020, \nPubalan Muniandy\u2020, Pui Li Wong#, Rukumani Devi Velayuthan\u00b6, Zhenli Kwan\u2021, Chin Chwen Ch\u2019ng\u2021, Norli Marwyne Mohd Noor\u00a4, Asmah Johar*\n\n\n\n*Department of Dermatology, Hospital Kuala Lumpur; \u00a5Clinical Research Centre, Hospital Kuala Lumpur; \u00a7Department of Dermatology, Hospital Sultanah Bahiyah; \n\u2020Department of Dermatology, Hospital Umum Sarawak; #Infectious Disease Unit, University Malaya Medical Center; \n\n\n\n\u00b6Department of Medical Microbiology, University Malaya Medical Centre; \u2021Dermatology Unit, University Malaya Medical Centre\n\u00a4Department of Dermatology, Hospital Sungai Buloh\n\n\n\nINTRODUCTION\n\n\n\nRESULTS\n\n\n\nMETHODOLOGY\n\n\n\nThis is a retrospective study on all HIV-infected MSM with syphilis\nbetween 2011 and 2015. Data was collected from five centres which\nincluded Department of Dermatology Hospital Kuala Lumpur; Department\nof Dermatology Hospital Sultanah Bahiyah; Department of Dermatology\nHospital Umum Sarawak; Dermatology Unit and Infectious Disease Unit\nUniversity Malaya Medical Centre; and Department of Dermatology\nHospital Sungai Buloh.\n\n\n\nDISCUSSION\n\n\n\nCONCLUSION\n\n\n\nREFERENCES ACKNOWLEDGEMENT\n\n\n\nThe most common subtype of syphilis among MSM with HIV was latent syphilis. Approximately 43.8% of the patients defaulted after treatment.\nAbout 8.5% failed treatment at 1-year follow up.\n\n\n\nTable 1. Demography of 294 HIV seropositive MSM with syphilis\n\n\n\nTable 2 Characteristics of Syphilis in 294 HIV-infected MSM\n\n\n\nHigh rates of syphilis have been reported worldwide among men who\nhave sex with men (MSM). Co-infections between human\nimmunodeficiency virus (HIV) and other sexually transmitted infections\n(STI) are common due to shared routes of sexual transmission. As a\nnotifiable disease in Malaysia, the data of syphilis among MSM and\namong those infected with HIV is lacking. This study aims to describe\nthe clinical pattern and treatment response of syphilis among HIV-\ninfected MSM.\n\n\n\n\u2022 A total of 294 HIV seropositive MSM with the mean age of 31.2\nyears (range 16-66) were confirmed to have syphilis. Nearly half\n(47.6%) were in the age group of 20-29 years. The demography is\nshown in Table 1.\n\n\n\n\u2022 Less than 10% was documented to have substance abuse. Only\nabout 13% was documented to use condom consistently.\n\n\n\n\u2022 About a quarter was previously infected with syphilis.\n\u2022 The most frequent concomitant sexually transmitted infection was\n\n\n\ngenital wart.\n\u2022 More than half (55%) were diagnosed to have syphilis and HIV\n\n\n\nconcurrently.\n\n\n\nCharacteristics] n=294 p\nType of syphilis Early syphilis\n\n\n\n(n=149)\nPrimary 8 (2.7%) 0.861\n\n\n\n(early vs \nlate)\n\n\n\nSecondary 83 (28.2%)\nEarly Latent 58 (19.7%)\n\n\n\nLate syphilis\n(n=145)\n\n\n\nLate latent 65 (22.1%)\nLatent  of unknown \nduration\n\n\n\n72 (24.5%)\n\n\n\nTertiary 8 (2.7%)\nMedian Pre-treatment \nVDRL/RPR titer (range)\n\n\n\nEarly syphilis 1:64 (0-1:2048) <0.0001\nLate syphilis 1:8 (1:1-1:1024)\n\n\n\nMedian CD4 count \n(range), cell/\u03bcl\n\n\n\nEarly syphilis 341 (2-998) 0.315\nLate syphilis 312 (3-978)\n\n\n\nNumber of patients with \nCD4 < 200/\u03bcl (%)\n\n\n\nEarly syphilis 30 (20.1%) 0.402\nLate syphilis 36 (24.3%)\n\n\n\nType of treatment, n (%) Early syphilis Benzathine penicillin 131 (44.6%) -\nDoxycycline 41 (13.9%)\nCrystalline penicillin 2 (0.7%)\nProcaine penicillin G 3 (1%)\n\n\n\nLate syphilis Benzathine penicillin 135 (45.9%)\nDoxycycline 11 (3.7%)\nCrystalline penicillin 3 (1%) \nProcaine penicillin G 1 (0.3%)\nCeftriaxone 1 (0.3%)\n\n\n\nTreatment outcome with serological response Early syphilis\n\n\n\nn=149\n\n\n\nLate \nsyphilis\nn=145\n\n\n\nTotal\n\n\n\nn=294\nResponded \nto \ntreatment \n\n\n\n4-fold drop at 1 year 8 10 18 (6.1%)\nSerology non-reactive 15 15 30 (10.2%)\nSerofast (1:8 or less) 35 37 72 (24.5%)\n\n\n\nFail treatment 8 6 14 (4.8%)\nFour fold drop at 6 months but re-infected 17 11 28 (9.5%)\nTreated and\nDefaulted\n\n\n\nDefaulted right after treatment 36 46 82 (27.9%)\nTreated with 4-fold drop at 6 months & defaulted 23 14 37 (12.5%)\nTreated with no 4-fold drop at 6 months & \ndefaulted\n\n\n\n7 3 10 (3.4%)\n\n\n\nDied before completed treatment 0 3 3 (1%)\n\n\n\nTable 3. The treatment outcomes with serological responses at one year after treatment\n\n\n\nCharacteristics n=294\nMean age in years (range) 31.2 (16-66)\nAge group in years, n (%) <20 10 (3.4%)\n\n\n\n20-29 140 (47.6%)\n30-39 95 (32.3%)\n40-49 37 (12.6%)\n50-59 10 (3.4%)\n60-69 2 (0.7%)\n\n\n\nEthnicity, n (%) Malay 165 (56.7%)\nChinese 100 (34.0%)\nIndian 9 (3.1%)\nBumiputra (Iban, Bidayuh, Bajau, Melanau) 18 (6.1%)\nForeigner (Philippines & Indonesian) 2 (0.7%)\n\n\n\nNumber with documented substance abuse, n (%) 25 (8.5%)\nNumber of bisexual, n (%) 75 (25.5%)\nType of partners, n (%) Casual 164 (55.8%)\n\n\n\nSteady 96 (32.7%)\nCommercial 16 (5.4%)\n\n\n\nNumber of patients with 2 or more partners in the past 6 months, n (%) 164 (55.8%)\nNumber with documented consistent use of condom in the past 6 \nmonths, n (%)\n\n\n\n39 (13.3%)\n\n\n\nNumber with previous history of sexually transmitted infections, n (%) 184 (62.6%)\nType of previous\nsexually transmitted \ninfection (STI),\nn (%) \n\n\n\nSyphilis 71 (24.1%)\nGonorrhoea 26 (8.8%)\nGenital warts 19 (6.5%)\nHerpes genitalis 18 (6.1%)\nHepatitis B 8 (2.7%)\nNon-gonococcal urethritis 4 (1.4%)\n\n\n\nNumber with other concomitant STI, n (%) 80 (27.5%)\nConcomitant STI apart \nfrom syphilis, n (%)\n\n\n\nGenital warts 50 (17.0%)\nHerpes genitalis 24 (8.2%)\nGonorrhoea 12 (4.1%)\nHepatitis B 10 (3.4%)\nChlamydia 3 (1.0%)\nNon-gonococcal urethritis 1 (0.3%)\n\n\n\nMedian CD4 count (range) 334 (2 \u2013 998)\n\n\n\nAuthor, year Country n % \nMSM\n\n\n\nEarly syphilis (%) Late syphilis (%) % responded \nto treatment \n\n\n\nat 1 year*\nPrimary Secondary Early \n\n\n\nlatent\nLate \n\n\n\nlatent\nLatent of \nUnknown \nduration\n\n\n\nTertiary\n\n\n\nManavi et al, 200712 UK 129 82 31 21 - - - - 70\n48 undetermined stage\n\n\n\nJinno et al, 201313 US 560 96.7 14 26 60 - - - 90.9\n\n\n\nTsai et al, 201414 Taiwan 349 94.9 8.9 55.3 35.8 - - - 67.8\n\n\n\nYang et al, 201415 Taiwan 573 94.1 8.9 57.8 33.3 - - - 70.9\n\n\n\nNishijima et al, 201616 Japan 112# 100 62 unspecified 4 18 - - -\n\n\n\nCurrent study 2017 Malaysia 294 100 2.7 28.2 19.7 22.1 24.5 8 Early syphilis  -\n87.9\n\n\n\nOverall-89.6\n\n\n\n\u2022 Syphilis and HIV co-infection has been labelled as a dangerous\nduo1,2. Syphilis enhances the risk of contracting HIV infection\nand HIV may alter the natural course of syphilis3.\n\n\n\n\u2022 HIV may result in higher rate of asymptomatic primary syphilis\nor more aggressive disease manifestations in early syphilis4,5.\nNeurosyphilis may occur more frequently, at a much earlier\nstage and progress more rapidly in the presence of HIV\ninfection6,7. Treatment failure is noted to be higher and\nserological cure has been shown to be slower in HIV-infected\npatients with syphilis8-10.\n\n\n\n\u2022 The burden of syphilis among the MSM is known to be\ninexplicably high worldwide11.\n\n\n\n\u2022 The clinical characteristics and treatment outcome of syphilis\namong HIV-infected MSM have been described in a few studies\nas shown in Table 4. Most papers did not study late syphilis.\n\n\n\nTable 4. The characteristics and treatment outcome of syphilis among HIV-infected MSM reported in other countries\n\n\n\n* Excluding patients who re-infected with syphilis, defaulted after treatment and died; #-incident syphilis infection\n\n\n\n\u2022 The characteristics of syphilis and the type of treatment received are\nshown in Table 2.\n\n\n\n\u2022 The number of early and late syphilis in our cohort were almost equal.\nHowever about 2/3 of the patients (66.3%) had latent syphilis. The pre-\ntreatment non-treponemal antibody titre (VDRL or RPR) for early\nsyphilis was significantly higher than the late syphilis. The median CD4\ncounts and the number of patients with CD4 <200/\u03bcl in early syphilis\nwere comparable to late syphilis.\n\n\n\n\u2022 The treatment outcome is shown in Table 3. Excluding those who were\nre-infected and defaulted follow up or died, the rate of treatment\nfailure were 12.1% and 8.8% for early and late syphilis respectively\n(p=0.582).\n\n\n\nWe would like to thank the Director General of Health, \nMalaysia for permission to present this report.\n\n\n\n1. Lynn et al. Lancet Infect Dis 2004;4:456-66\n2. Karumudi et al. Expert Rev Anti Infect Ther 2005;3:825-\n\n\n\n31\n3. Kenyon et al. BMC Infect Dis 2017;17:111\n4. Kassutto et al. Emerg Infect Dis 2004;10:1471-3\n5. Schofer et al. Genitourin Med 1996;72:176-81\n\n\n\n6. Flood et al, J Infect Dis 1998;177:931-40\n7. Marra et al. Clin Infect Dis 2004;38:1001-6. \n8. Ghanem et al. Sex Transm Infect 2007;83:97-101\n9. Malone et al. Am J Med 1995:55-63\n10.Smith et al. South Med J 2004;97:379-82\n11.Abara et al. PLoS One 2016;11:e0159309\n\n\n\n12.Manavi et al. Int J STD AIDS 2007; 18: 814\u2013818\n13.Jinno et al.  BMC Infect Dis. 2013;13:605\n14.Tsai et al. PLoS One 2014;9: e109813\n15.Yang et al. PLoS One 2014;9:e109667\n16.Nishijima et al. PLoS ONE. 2016;11(12):e0168642\n\n\n\n\u2022 The treatment and the response rate of early syphilis in our cohort were\ncomparable to other studies.\n\n\n\n\u2022 Future prospective study is needed to describe the effect of HAART on the\nnatural history and treatment outcome of syphilis in HIV-infected MSM.\n\n\n\n6\nMinistry of Health\n\n\n\nMalaysia\n\n\n\n\n\n\n\n\nPrevalence of Co-infection of Gonorrhoea and Non Gonococcal Urethritis \n\n\n\nin Males with Urethral Discharge \n\n\n\nat Genitourinary Clinic, Hospital Kuala Lumpur: \n\n\n\na 5-year study between 2011 - 2015\nVijayaletchumi Krishnasamy, Asmah Johar\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur\n\n\n\nMajority of males diagnosed with urethritis were heterosexual. Two third of the\n\n\n\nurethritis were gonorrhea. About 10% had co-infection with Neisseria\n\n\n\ngonorrhoea and Chlamydia trachomatis.\n\n\n\nWe would like to thank the doctors and allied health personals from GUM clinic for their contribution to this study.  We \nwould also like to thank the Director of Health Malaysia for the permission to present the poster\n\n\n\nIntroduction\n\n\n\nMethodology\n\n\n\nDual infection with Neisseria gonorrhoeae and chlamydia has been reported in\nseveral studies worldwide in men presenting with urethral discharge. The rates\nof co-infection have been reported to be 1.5-51%5-11. In Malaysia there is limited\ndata on the prevalence of gonorrhoea, non gonococcal urethritis and its co-\ninfection. This study aims to determine the demographic characteristics and\nbehavior traits of men diagnosed to have the above infections.\n\n\n\nThis is a retrospective study was done at GUM clinic, HKL. All case notes of men\nwho had presented with urethral discharge and diagnosed to have gonococcal\nand non gonococcal urethritis from the year 2011 to 2015 were retrieved and\nreviewed.\n\n\n\nResults\n\n\n\n\u2022 There were a total of 307 men who had attended the GUM clinic with urethral\ndischarge. The demographic data is shown in Table 1.\n\n\n\n\u2022 The mean age of the patients was 26.4 years(range 16-57). Majority of the\npatients (64.5%) were in the age group between 20-29 years.\n\n\n\n\u2022 About 95% were Malaysian and of these about 80% were Malay.\n\u2022 Thirty-seven patients (12%) completed their tertiary education.\n\u2022 There were 24 patients (8%) documented to have substance abuse.\n\u2022 Majority (78%) were heterosexual. About 36% of patients had 2 or more\n\n\n\npartners (range 2-10) 6 months before the symptoms developed.\n\u2022 The most common cause of urethritis was gonococcal urethritis (66.4%),\n\n\n\nfollowed by non-gonococcal urethritis (NGU; 24.4%).\n\u2022 Among the NGU, nine were detected to have Chlamydia sp infection (12%).\n\u2022 Co-infection of Neisseria gonorrhoeae and Chlamydia sp were detected in 28\n\n\n\nmen (9.1%).\n\u2022 Seven (2.3%) were HIV seropositive.\n\n\n\nTable 1. The demographic data and sexual history of 307 men with urethritis\n\n\n\nCharacteristics n=307\n\n\n\nMean age in years (range) 26.4 (16-56)\n\n\n\nAge group in years (%) <20 37 (%)\n\n\n\n20-29 198 (47.8%)\n\n\n\n30-39 51 (32.6%)\n\n\n\n40-49 11 (12.0%)\n\n\n\n50-59 10 (3.4%)\n\n\n\nEthnicity Malay 245 (79.8%)\n\n\n\nChinese 13 (33.7%)\n\n\n\nIndian 30 (9.8%)\n\n\n\nBumiputra 3 (1%)\n\n\n\nForeigner 16 (5.2%)\n\n\n\nHighest education level Primary 45 (14.7%)\n\n\n\nSecondary 222 (72.3%)\n\n\n\nTertiary 37 (12.0%)\n\n\n\nMissing data 3 (1.0%)\n\n\n\nEmployment history Student 43 (14.0%)\n\n\n\nUnemployed 26 (8.5%)\n\n\n\nEmployed 238 (77.5%)\n\n\n\nNumber with documented substance abuse (%) 24 (7.8%)\n\n\n\nSexual orientation Heterosexual 242 (78.8%)\n\n\n\nBisexual 35 (11.4%)\n\n\n\nHomosexual 30 (9.8%)\n\n\n\nType of partners Casual 182 (59.3%)\n\n\n\nSteady 92 (30.0%)\n\n\n\nCommercial 31 (10.1%)\n\n\n\nNumber of patients with 2 or more partners in the past 6 months (%) 111 (36.2%)\n\n\n\nNumber with other concomitant sexually transmitted infections (%) 18 (5.9%)\n\n\n\nConcomitant sexually \n\n\n\ntransmitted infections apart \n\n\n\nfrom Urethritis\n\n\n\nSyphilis 4 (1.3%)\n\n\n\nGenital warts 3 (1.0%)\n\n\n\nHerpes genitalis 2 (4.1%)\n\n\n\nHepatitis B 2 (3.4%)\n\n\n\nHepatitis C 1 (0.3%)\n\n\n\nHuman immunodeficiency virus 7 (2.3%)\n\n\n\nConclusion\n\n\n\nReferences\n\n\n\nAcknowledgement \n\n\n\nTable 2 . The etiology of urethritis in 307 men with urethral discharge\n\n\n\nAge group Neisseria \n\n\n\ngonorrhoea only\n\n\n\nN=204\n\n\n\nNon gonococcal \n\n\n\nurethritis\n\n\n\nN=75\n\n\n\nNisseria\n\n\n\ngonorrhoea &\n\n\n\nChlamydia\n\n\n\ntrachomatis\n\n\n\nN=28\n\n\n\nTotal\n\n\n\nN=307\n\n\n\n<20 27(8.7%) 4(1.3%) 6(1.9%) 37\n\n\n\n20-29 132(28%) 54(8.7%) 12(1.0%) 198\n\n\n\n30-39 32(7.8%) 11(2.6%) 8(1.9%) 51\n\n\n\n40-49 5(1.0%) 5(1.6%) 1(0.3%) 11\n\n\n\n50-59 8(1.6%) 1(0.3%) 1(0.32%) 10\n\n\n\nDiscussions\n\n\n\nAuthor, year  Countries Age  (yrs) Sexual behaviour NG (%) NGU (%) CT(%) NG and CT\n(%)\n\n\n\nSarah et al\n20035\n\n\n\nUK 22.4 \n(mean)\n\n\n\n- 3.8 - 8.1 1.5\n\n\n\nKhan et al\n20056\n\n\n\nUS 15-16 - 1.3 - 5.9 51\n\n\n\nSatyajit et al\n20057\n\n\n\nUK 20-25 1 partner  43.7%\n2 partners  32.3%\n\n\n\n\u22653 28.7%\n\n\n\n- - - 16.1\n\n\n\nDonati. et al\n20098\n\n\n\nItaly 33.7 \n(mean)\n\n\n\n- - - 74.5 30.1\n\n\n\nBarbosa et al\n20109\n\n\n\nBrazil 26.5\n(mean)\n\n\n\n1partner 85.4% 18.4 13.1 4.4\n\n\n\nTongtoyai et \nal, 201510\n\n\n\nThailand MSM 4.6 11.6 2.9\n\n\n\nLim et al, \n201511\n\n\n\nSingapore 14-19 Heterosexual \nmale with STI\n\n\n\n33.1 23.6 10.2\n\n\n\nKrishnasamy\net al 2017\n\n\n\nHKL\nMalaysia\n\n\n\n26.4\n(mean)\n\n\n\n> 2 Partners -\n36.2%\n\n\n\n66.4 24.4 3 9.1\n\n\n\n\u2022 According to the WHO1, the estimates global incidence of Nisseria gonorrhoea and\nChlamydia trachomatis were 106.1 and 105.7 millions cases respectively in 2008. The\nnumber of reported cases were in increasing trend from the 2005 report for both.\n\n\n\n\u2022 Nesseria gonorrhoea infection is a notifiable in Malaysia. The incidence of gonorrhoea for\nMalaysia was 4.7 per 100,000 population in 20112, increasing over the years to 7.53 per\n100,000 in 20153. Nevertheless, NGU is not in the list of notifiable infections in\nMalaysia. The rise of incidence of gonorrhoea could be consistent with the global rise or\nit could due to the increase in the awareness of notification among the clinicians.\n\n\n\n\u2022 Non-gonoccocal urethritis (NGU) may be caused by Chlamydia trachomatis, Mycoplasma\nsp, Ureaplasma sp and others4. NGU is diagnosed when staining of urethral secretion in\na symptomatic man shows inflammation without gram negative diplococcic. All men who\nare confirmed to have NGU need to be tested further for the etiology. However, the\ndiagnostic tests for Mycoplasma sp and Ureaplasma sp are not available in our setting.\n\n\n\n\u2022 Co-infection of gonococcal and non-gonococcal urethritis especially Chlamydia\ntrachomatis has been observed in different countries5-11 as shown in Table 3. The rates of\nco-infection were reported to be between 1.5-51%.\n\n\n\n\u2022 In our cohort of gonococcal urethritis, about 12% was also infected with Chlamydia\ntrachomatis. This may not justify the policy of epidemiological treatment of chlamydia in\nall cases of gonococcal urethritis in Malaysia. Future prospective study is needed to\ndetermine other aetiology of NGU in order to characterize better the rate of co-infection\nin this country.\n\n\n\n1. WHO 2012. ISBN: 978 92 4 150383 9\n2. MOH Malaysia. Health Fact 2012.\n3. MOH Malaysia. Health Fact 2015.\n4. CDC. MMWR 2015;64:51-52 \n5. Sarah et al. Int J STD AIDS 2003;14:109-113\n6. Khan et al. Sex Transm Dis 2005;32:255-259\n7. Satyajit et al. Int J STD AIDS 2005;16:318-322\n8. Donati et al. Eur J Clin Microbiol Infect Dis 2009;28:523-526\n9. Barbosa et al. Rev Soc Bras Med Trop 2010;43:500-503\n10. Tongtoyai et al. Sex Transm Dis 2015;42:440-449\n11. Lim et al. Sex Transm Dis 2015;42:450-456\n\n\n\nTable 3 . The reported rate of co-infection of gonococcal and NGU  urethritis in \ndifferent countries\n\n\n\nNG \u2013 Neisseria gonorrhoea; NGU- non gonococcal urethritis; CT \u2013 Chlamydia trachomatis; MSM- man having sex with man; STI \u2013 sexually transmitted infections\n\n\n\nPoster \nNo :07\n\n\n\n\n\n\n\n\n70.3 %\n\n\n\n27.9 %\n\n\n\n1.1 %\n0.7 %\n\n\n\n1 type of STI\n\n\n\n2 types of STIs\n\n\n\n3 types of STIs\n\n\n\n4 types of STIs\n\n\n\nWe would like to extend our sincere gratitude to the doctors, allied health personnels from GUM,HKL for their contributions in this study and as well as \nNooraishah Ngah Saaya for helping to compose the data. We would also like to thank Director General of Heath Malaysia for permission to present this poster. \n\n\n\nThe latest WHO update in August 2016 reported more than 1 million\nsexually transmitted infections (STIs) acquired every day worldwide.\nEach year, there is an estimated 357 million new infections with either 1\nof these 4 STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. HIV\npatients are high risk group for STIs. However, data regarding the current\ntrend of STIs among HIV patients in Malaysia is limited .\n\n\n\nBACKGROUND\n\n\n\nOBJECTIVE\n\n\n\nTo describe the pattern of STIs and profile of patients with HIV in GUM\nclinic, HKL.\n\n\n\nThis was a retrospective study carried out from 2011 until 2015 in GUM\nclinic, HKL. Case notes of patients with HIV positive were retrieved and\nreviewed. Demographic data such as: gender, ethnicity, age, occupation\nand sexual orientation were analysed. Clinical presentations and types of\nSTIs were identified.\n\n\n\nACKNOWLEDGEMENT\n\n\n\nRESULTS\n\n\n\nCONCLUSION\n\n\n\nMETHODOLOGY\n\n\n\nFigure 4 : Types of syphilis in patients with HIV\n\n\n\nFigure 3 : Types of sexually transmitted infections in \n\n\n\npatients with HIV\n\n\n\nBased on the data from GUM, HKL, STIs were commonly seen in males\nsuffering from HIV. Almost half of the patients were in the blue collar\noccupation. More than half of the patients were homosexuals. Syphilis\nwas the commonest type of STI in HIV patients and secondary syphilis\nwas the most common presentation. It was noted that 29.3% of patients\nsuffered from 2 or more types of STIs.\n\n\n\nFigure 1 : Clinical presentation of sexually transmitted  \n\n\n\ninfections in 276  HIV seropositive patients \n\n\n\nThere were a total of 276 HIV seropositive patients, which were\nconfirmed to have STIs and have sought treatment at the GUM clinic\nbetween 2011 - 2015. Most of the patients were males (267, 96.7%) and\nthe remaining were females (3, 3.3%). As for ethnic distribution, the\nMalays accounted for 55.8%, followed by Chinese (30.8%), Indians\n(8.0%) and 5.4% belong to the other groups. 46.4% of patients\u2019\noccupation were blue collar, followed by white collar (21.0%), students\n(12.7%) and there were no available data for 19.9%.\nThe mean age of patients that was diagnosed to have STIs was 31.1 \u00b1\n9.9 years. More than half were homosexual (55.8%), followed by\nheterosexual (22.1% ) and bisexual (13.8%). There were 147 valid CD4\ncount and 129 missing data, of which 20.4% patients had a CD4 count of\n>500 cells/\u03bcL, 55.7% patients with CD4 count between 200-500 cells/\u03bcL\nand 22.4% patients with CD4 < 200 cells/\u03bcL. Almost half of patients\npresented with warts (40.1%), with the remaining presenting with rash\n(19.6%), ulcer (16.3%), discharge (7.2%) and pruritus (0.4%) (Figure 1).\n70.3% patients had 1 type of STI, 27.9% had 2 types of STIs, 1.1% had 3\ntypes of STIs and 0.7 % had 4 types of STIs during the follow up period\nof 5 years (Figure 2).\nThe most common STIs among HIV patients were syphilis (139, 44.2%),\nfollowed by genital wart (95, 34.4%), herpes (31, 11.2%), gonorrhea (9,\n3.3%), chlamydia (2, 0.7%), others (17, 6.2%) being non specific\nurethritis and chancroid (Figure 3). Among the patients with syphilis, the\nmost common presentations were secondary syphilis (44.6%), followed\nby early latent (23.0%), late latent (12.9%), primary (5%) and tertiary\n(2.2%). (Figure 4).\n\n\n\n6.2\n\n\n\n0.7\n\n\n\n3.3\n\n\n\n11.2\n\n\n\n34.4\n\n\n\n44.2\n\n\n\n0 10 20 30 40 50\n\n\n\nOTHERS\n\n\n\nCHLAMYDIA\n\n\n\nGONORRHEA\n\n\n\nHERPES\n\n\n\nGENITAL WART\n\n\n\nSYPHILIS\n\n\n\nPercentage, %\n\n\n\n1.8\n14.1\n\n\n\n0.4\n7.2\n\n\n\n16.3\n\n\n\n19.6\n40.6\n\n\n\n0 10 20 30 40 50\n\n\n\nNOT AVAILABLE\n\n\n\nOTHER\n\n\n\nPRURITIS\n\n\n\nDISCHARGE\n\n\n\nULCER\n\n\n\nRASH\n\n\n\nWARTS\n\n\n\nPercentage, %\n\n\n\n12.2\n\n\n\n2.2\n\n\n\n12.9\n\n\n\n23.0\n\n\n\n44.6\n\n\n\n5.0\n\n\n\n0 10 20 30 40 50\n\n\n\nNOT SPECIFIED\n\n\n\nTERTIARY SYPHILIS\n\n\n\nLATE LATENT\u2026\n\n\n\nEARLY LATENT\u2026\n\n\n\nSECONDARY SYPHILIS\n\n\n\nPRIMARY SYPHILIS\n\n\n\nPercentage, %\n\n\n\nFigure 2 : Number of concomitant  sexually transmitted  \n\n\n\ninfections\n\n\n\n08\nPATTERN OF SEXUALLY TRANSMITTED INFECTIONS (STI) AMONG PATIENTS WITH HIV \n\n\n\nIN GENITOURINARY MEDICINE (GUM) CLINIC, HOSPITAL KUALA LUMPUR (HKL)\n\n\n\nShir Nee Tan, Swee Kuan Heah, Azura Mohd Affandi, Asmah Johar\nDepartment of Dermatology, Hospital Kuala Lumpur\n\n\n\n\n\n\n\n\nPoster \n\n\n\nNo.9\n\n\n\nPrevalence of Sexually Transmitted Infections (STI) in \n\n\n\nGenito-Urinary Medicine Clinic (GUM), Hospital Kuala Lumpur\n\n\n\nHR Hariyadurai, SR Syed Nong Chek, A Johar\nDepartment of Dermatology, Hospital Kuala Lumpur\n\n\n\nBACKGROUND\n\n\n\nEfforts by the Ministry of Health and non-governmental organisations (NGOs) has\nseen the incidence of human immunodeficiency virus (HIV) on the downtrend.\nNevertheless, the opposite can be said with syphilis and gonorrhea1-3. Earlier age of\nsexually debut and lack of sexual education exposure has led to STIs further\nspreading to others as patients fail to realise that they are disease carriers resulting\nin complications such as infertility and spread of HIV4-5.\n\n\n\nOBJECTIVES\n\n\n\nTo determine the prevalence of reported STIs within the Genitourinary Medicine (GUM)\nClinic, HKL between 2015-2016.\n\n\n\nMETHODS\n\n\n\nThis is a retrospective study of patients age more than 10 years attending the GUM Clinic,\nHKL between 2015-2016. Data was obtained by reviewing patients\u2019 case notes and further\nanalysed using SPSS version 18.0.\n\n\n\nCONCLUSION\n\n\n\nThe three commonest STI presented to GUM clinic were genital wart, syphilis and\ngonorrhoea.\n\n\n\nACKNOWLEDGEMENT\n\n\n\nRESULTS\n\n\n\nREFERENCES\n\n\n\n1. Cheng et al. Sexually Transmitted Disease (STD). WebmedCentral INFECTIOUS DISEASE\n2011;2:WMC002611\n\n\n\n2. Anwar et al. BMC Public Health 2010;10:47.\n3. Planning Division, Health Informatics Centres, MOH. Sexually Transmitted Diseases.\n4. Incidence Rate & Mortality Rate of Communicable Diseases,Health Facts 2012-2016\n5. Low WY. JUMMEC 2009;12:3-14.\n6. Zulkifli et al. J Adolesc Health 2000;27:276-80.\n\n\n\nTable2: Literature review on the Prevalence of Sexually Transmitted Infections  in other \nregions \n\n\n\n0\n\n\n\n50\n\n\n\n100\n\n\n\n150\n\n\n\n200\n\n\n\n250\n\n\n\nN\nu\n\n\n\nm\nb\n\n\n\ne\nr \n\n\n\no\nf \n\n\n\np\na\nti\n\n\n\ne\nn\n\n\n\nts\n\n\n\n0-12\n\n\n\n13-19\n\n\n\n20-29\n\n\n\n30-39\n\n\n\n40-49\n\n\n\n50-59\n\n\n\n60-69\n\n\n\n70 >\n\n\n\nWe would like to thank all doctors and allied health personnel from the GUM Clinic, Hospital Kuala Lumpur. We also acknowledge the support of Ministry of Health Malaysia and Director \nGeneral of Health, Malaysia.\n\n\n\nFigure 2:Sexually Transmitted Infections presented to GUM Clinic Hospital Kuala Lumpur\n\n\n\nTable1: Demographic characteristics  GUM Clinic attendees\n\n\n\nA total of 1361 patients had attended the clinic of which 1296 (95.2%) diagnosis of STDS\nwere made. The most common age group attending the clinic are between 20-29. This\nconsisted 472 (48.3%) males and 182 (47.5%) females.\n\n\n\n\u2022 Table 1 represents the demographic characteristics of the patients.\n\u2022 Figure 1 constitutes age group versus type of STIs.\n\u2022 Figure 2 depicts top 5 STIs in our study. HIV screening was performed in all the patients\n\n\n\npresenting to the clinic. There were 129 (9.5%) patients diagnosed with HIV although the\ndata for the mode of transmission is not available\n\n\n\nFigure 1:SexuallyTransmitted Infections  according to Age Group\n\n\n\nRegion Country Author/Year Number (subjects) Top 5 STI\n\n\n\nAsia Thailand Rugpao et al,\n\n\n\n1997\n\n\n\n195 Chlamydia, gonorrhea, warts, \n\n\n\nmolluscum contagiosum,\n\n\n\ntrichomoniasis\n\n\n\nMalaysia Rohani et\n\n\n\nal,2002\n\n\n\n435 Gonorrhea, syphilis, \n\n\n\nnon specific urethritis (NSU), \n\n\n\nOther STDs, Herpes genitalis\n\n\n\nIndonesia Hamzah et al,\n\n\n\n2009\n\n\n\n278 NSU, gonorrhea, warts, \n\n\n\nvulvovaginal candidiasis, \n\n\n\nbartholinitis\n\n\n\nMalaysia Hariyadurai et al,\n\n\n\n2017\n\n\n\n1361 Warts, latent syphilis, \n\n\n\ngonorrhea, \n\n\n\nprimary herpes, \n\n\n\nnon specific urethritis\n\n\n\nWHO Americas, African \n\n\n\nregions, European\n\n\n\nregions, Eastern \n\n\n\nMediterranean, Western \n\n\n\nPacific, South East Asia\n\n\n\nRowley et al,\n\n\n\n2008\n\n\n\nTrichomoniasis -276.4 million\n\n\n\nGonorrhea-106.1 million\n\n\n\nChlamydia-105.7 million\n\n\n\nSyphilis-10.6 million\n\n\n\nTrichomoniasis, gonorrhea, \n\n\n\nchlamydia, syphilis\n\n\n\nNorth \n\n\n\nAmerica\n\n\n\nUS Satterwhite 2013 19.7 million Warts, Chlamydia, \n\n\n\nTrichomoniasis, \n\n\n\nGonorrhea, Herpes Genitalis\n\n\n\nCharacteristics n=1361 %\nGender Male 978 71.9\n\n\n\nFemale 383 28.1\n\n\n\nMean age in years (range)\n\n\n\nAge group in years (%) <20 78 5.7\n\n\n\n20-29 654 48.1\n\n\n\n30-39 366 26.9\n\n\n\n40-49 118 8.7\n\n\n\n50-59 84 6.2\n\n\n\n60-69 40 2.9\n\n\n\n>70 21 1.5\n\n\n\nEthnicity Malay 801 58.9\n\n\n\nChinese 234 17.2\n\n\n\nIndian 216 15.9\n\n\n\nOthers 82 6.0\n\n\n\nForeigner 28 2.1\n\n\n\nSexual orientation Heterosexual 1059 77.8\n\n\n\nBisexual 245 18.0\n\n\n\nHomosexual 57 4.2\n\n\n\nSource of referrals Government Hospital 586 43.1\n\n\n\nGovernment Clinic 311 22.9\n\n\n\nSelf referred 209 15.4\n\n\n\nGeneral Practioner 116 8.5\n\n\n\nPusat Darah Negara 83 6.1\n\n\n\nEmergency Department 39 2.9\n\n\n\nOthers 17 1.2\n\n\n\nReason for visits Symptomatic 968 71.1\n\n\n\nPositive VDRL 176 12.9\n\n\n\nContact 117 8.6\n\n\n\nSTI Check Up 98 7.2\n\n\n\nNegative VDRL 1 0.1\n\n\n\nOthers 1 0.1\n\n\n\nDiagnosis Sexually Transmitted Infections (STIs) 1296 95.2\n\n\n\nNon STI 65 4.8\n\n\n\n30.2%\n\n\n\n21.7%13.8%\n\n\n\n11.4%\n\n\n\n7.9%\n\n\n\n14.9%\n\n\n\nWarts\n\n\n\nSyphilis\n\n\n\nGonorrhea\n\n\n\nPrimary Herpes\n\n\n\nNSU\n\n\n\nOthers\n\n\n\n\n\n\n\n\nCutaneous manifestations in patients infected with  \nHuman Immunodeficiency Virus:  An audit in Hospital Kuala Lumpur \n\n\n\nBACKGROUND \n\n\n\nIndividuals infected with human immunodeficiency virus (HIV) may \nsuffer from various cutaneous diseases.  Local surveillance data \ndemonstrate that HIV is still confined within the key populations1, and \nthat the prevalence among relatively low risk populations is between \n0.02 to 0.11%2. This audit aims to describe the pattern of cutaneous  \nmanifestations of patients infected with HIV, whom were referred to \nthe Department of Dermatology, Hospital Kuala Lumpur.   \n\n\n\nMETHODS \n\n\n\nThis is a retrospective study on all newly referred HIV-infected patients \nwho presented to the Department of Dermatology, Hospital Kuala \nLumpur in year 2016. Patients case notes were retrieved and reviewed.  \n\n\n\nDISCUSSION & CONCLUSION \n\n\n\n\u2022 The pattern of HIV transmission in Malaysia has changed \nsignificantly from primarily via Intravenous Drug-Use (IVDU), to \ntransmission via sexual routes.  \n\u2022 IVDU to sexual transmission ratio declined from 4 in year 2000 to 0.2 \n\n\n\nin 2015, owing to efforts made in opioid-replacement therapy and \nneedle exchange programme2.  \n\n\n\n\u2022 However, HIV prevalence among the MSM population has since \nincreased2.  \n\n\n\n\u2022 While the majority of referrals were from outpatient sources, \nlow CD4+ counts  complicated with opportunistic infections \nincurred a greater need for inpatient treatment.  \n\n\n\n\u2022 The types of dermatoses among the HIV infected patients in \nvarious Asian countries were shown in Table 2. \n\n\n\n\u2022 Interestingly, psoriasis was encountered more often than \nseborrheic dermatitis in our cohort similar to an Indian study3. \nThe latter being more commonly seen in other similar studies4,6 \nalong with xerosis.  \n\u2022 Seborrheic dermatitis in HIV infected patients may be more \n\n\n\ncommonly managed by primary care doctors in our setting. \n\u2022 Our cohort showed that 9.5% of patients with kaposi sarcoma \n\n\n\namong those with CD4+ counts less than 200 similar to a report \nfrom Taiwan \n\u2022 Lower threshold to perform skin biopsy is advocated \n\n\n\n\u2022 Oral candidiasis which is commonly encountered in HIV cohorts \nas demonstrated by other studies in Asia6 (up to 70%), showed a \nmuch lower prevalence in this study (5.5%).  \n\u2022 Most patients had received treatment for oral candidiasis at primary \n\n\n\ncare, dental clinics as well as from their ID physicians.  \n\n\n\n\u2022 In conclusion, majority of  HIV infected patients in our cohort \npresented with infective skin diseases, of which, viral causes \nwere most frequently encountered.  \n\n\n\n\u2022 The results of this study, add to the increasing evidence of \ncutaneous manifestations in HIV. Further local studies are \nneeded to analyse the evolution of skin disease through the \ndifferent stages of HIV and their treatment outcome.  \n\n\n\nRESULTS \n\n\n\nREFERENCES \n\n\n\n\u2022 There were a total of 110 new HIV-infected patients referred to us \nwith skin diseases. The demographic characteristics are shown in \nTable 1. \n\n\n\n\u2022 The mean age of the patients was 33.6 years (range 15-72). Majority \nof the patients (43.6%) were from the 20-29 years age category.  \n\n\n\n\u2022 About a third (31.8%) of cases were in-patient referrals.  \n\u2022 Fifty-nine patients (53.6%) were men who had sex with men (MSM).  \n\u2022 Nine patients (8.2%) were documented to have substance abuse.  \n\u2022 Majority (59%) had CD4+ counts of more than 200/\u03bcL. About 80% of \n\n\n\nin-patient cases had CD4+ counts of less than 200/\u03bcL whereas about \nthree-quarters of out-patient cases had CD4+ counts of more than \n200/\u03bcL. \n\n\n\n\u2022 There were 46 patients (41.8%) who were on HAART.  \n\u2022 A total of 152 skin diagnosis were made. Of these, 103 were infective \n\n\n\nand 49 were non infective diseases.  \n\u2022 The commonest infection observed was viral infections (52.4%) with \n\n\n\ngenital human papilloma virus infection being the most frequently \nencountered.   \n\n\n\n\u2022 The most common non-infective skin disease was papulosquamous \ndisorders such as psoriasis (44.7%) followed by pruritic papular \neruption of HIV (21.1%).  \n\n\n\n\u2022 Six patients had severe adverse cutaneous drug reactions i.e. Stevens-\nJohnson Syndrome (SJS)/SJS-Toxic Epidermal Necrolysis overlap \nsyndrome to Co-trimoxazole, carbamazepine, Akurit-4 and \nlevofloxacin.  \n\n\n\nTable 1. Demographic Data of 110 HIV infected patients in 2016  \n Characteristics  n = 110 (%) \n Mean Age in Years (range) 33.62 (15-72)  \n Age (years) 11-20 4 (3.6) \n\n\n\n21-30 51 (46.4) \n31-40 28 (25.5) \n41-50 16 (14.5) \nAbove 50 11 (10.0) \n\n\n\n Gender Male 104 (94.5) \nFemale 6 (5.5) \n\n\n\nSexual Orientation Heterosexual 26 (23.6) \nHomosexual 51 (46.4) \nBisexual 8 (7.3) \n\n\n\n Ethnicity Malay 65 (59.1) \nChinese 32 (29.1) \nIndian 8 (7.3) \nOthers 5 (4.5) \n\n\n\n Concomitant Illness Pulmonary tuberculosis 23 (20.9) \nFungal infections 7 (6.4) \nHepatitis B 2 (1.8) \nHepatitis C 3 (2.7) \nBipolar Mood Disorder 1 (0.9) \nAsthma 2 (1.8) \nDiabetes mellitus 1 (0.9) \n\n\n\n Referral Category Inpatient referral 35 (31.8) \nOutpatient referral 75 (68.2) \n\n\n\nMode of HIV Transmission Heterosexual 26 (23.6) \n\n\n\nHomosexual 51 (46.4) \nBisexual 8 (7.3) \nIVDU 9 (8.2) \nBlood Transfusion 1 (0.9) \nNot available 15 (13.6) \n\n\n\nMeena Nithianandan, Anisha Bhullar, Suganthi Thevarajah, Min Moon Tang \nDepartment of  Dermatology, Hospital Kuala Lumpur \n\n\n\n0\n\n\n\n10\n\n\n\n20\n\n\n\n30\n\n\n\n40\n\n\n\n50\n\n\n\n60\n\n\n\n70\n\n\n\n80\n\n\n\n90\n\n\n\n< 200 200 - 500 > 500\n\n\n\nN\nu\n\n\n\nm\nb\n\n\n\ne\nr \n\n\n\no\nf \n\n\n\np\nat\n\n\n\nie\nn\n\n\n\nts\n \n\n\n\nCD4 Count \n\n\n\nInpatient referral Outpatient referral\n\n\n\nFigure 1.   CD4+  Count  versus  referral category \n\n\n\n12.2% \n\n\n\n79.6% \n\n\n\n8.2% \n\n\n\nAdverse cutaneous drug reaction\nNon-infective dermatoses\nMalignancy\n\n\n\nFigure 3. Non-Infective causes (n=49) skin lesions among HIV \ninfected patients \n\n\n\nWe would like to thank all doctors and allied health personnel from the Department of Dermatology, \nHospital Kuala Lumpur. We would also like to thank the Director of Health Malaysia for the permission \nto present the poster. \n\n\n\n\n\n\n\nFigure 2.   Infective causes  (n=103) skin lesions among HIV infected \npatients \n\n\n\n1. MOH. Malaysia Global AIDS Response Progress Report 2016 \n2. MOH. Malaysia National Strategic Plan for Ending AIDS 2016-2030 (2015) \n3. Sud et at. Int J STD AIDS 2009;20:771-4 \n4. Dwiyana et al. Acta Med Indones 2009;41 Suppl 1:18-22 \n5. Wiwanitkit V. Int J Dermatol 2004;43: 265-8. \n6. Tzung et al. Kaohsiung J Med Sci 2004;20:216-24 \n\n\n\nCountry India3 Indonesia4 Thailand5 Taiwan6 Current \n\n\n\nstudy \n\n\n\nNo of Cases (n) 150 121 96 45 110 \n\n\n\nTotal Diagnosis \n\n\n\nInfective (%) \n\n\n\nNon-Infective (%) \n\n\n\n473 195 322 158 152 \n\n\n\n46.5 31.8 32.9 62.0 67.8 \n\n\n\n53.5 68.2 67.1 38.0 32.2 \n\n\n\n% of CD4+<200 59.3 71.7 37.5 79 38.2 \n\n\n\nTable 2.  Cutaneous diseases among HIV infected subjects in \ndifferent Asian countries  \n\n\n\n29.1% \n\n\n\n52.4% \n\n\n\n16.5% \n1.9 \n\n\n\nBacterial infections\nViral infections\nFungal infections\nArthropod Infestation\n\n\n\nACKNOWLEDGEMENT \n\n\n\nNon infective  Type (number) \nInflammatory \ndermatoses \n\n\n\nPsoriasis (15) \nPruritic papular eruptions in HIV (7) \nContact dermatitis (4) \nPhotodermatitis (4) \nPapular urticaria (1) \nEosinophilic folliculitis (1) \nDiscoid eczema (1) \nNodular prurigo (1) \nPapular eczema (1) \nXerosis (1) \nHydradenitis suppurativa (1) \n\n\n\nCutaneous \nadverse drug \nreactions \n\n\n\nSevere cutaneous adverse drug \nreactions (6)  \nMaculopapular (2) \n\n\n\nMalignancy Kaposi sarcoma (4) \n\n\n\n Infection Type (number) \nViral  Genital wart (31) \n\n\n\nHerpes genitalis (11) \nHerpes zoster (6) \nMolluscum contangiosum (2)  \nHerpes labialis (1) \nCommon wart (1) \nHairy leukoplakia (1) \n\n\n\nBacterial Syphilis (20) \nGonorrhea (4) \nCellulitis (3) \nAbscess (2)  \nFolliculitis (1) \nLupus Vulgaris  (1) \n\n\n\nFungal Oral candidiasis (6) \nPenicilliosis (4) \nHistoplasmosis (2) \nOnychomycosis (1) \nTinea corporis (1) \nTinea pedis (1) \n\n\n\nArthropod Scabies (2) \n\n\n\n10 \n\n\n\n\n\n\n\n\nA retrospective review of patch test results using the European \nStandard series in University Malaya Medical Centre between \n\n\n\n2016 and 2017\nKelvin Shenq Woei Siew1, Zhenli Kwan1, Chin Chwen Ch\u2019ng1, Leng Leng Tan1, Faridah Muhamad2, Norhazah\n\n\n\nHalim2, Adrian Sze Wai Yong1\n\n\n\n1Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya\n2Division of Dermatology, Department of Medicine, University Malaya Medical Centre\n\n\n\nPoster \n\n\n\nNo.11\n\n\n\nPatch test is an essential tool to aid in the diagnosis of  \nallergic contact dermatitis, which is characterised by type \nIV hypersensitivity, and used to identify potential \ncausative allergens. \n\n\n\nNickel had the highest frequency of contact \nsensitisation, possibly due to the ubiquitous use of \nnickel in many products, including electronics and \ncostume jewellery. This is consistent with previous \nMalaysian, Singaporean and Thai data.1,2 The high \nfrequency of contact sensitisation to fragrance and \nBalsam of Peru were consistent with previous \nstudies1,2,3 and may be due to leave-on and self-\nhygiene products such as perfumes and cosmetics.4,5\n\n\n\nAlthough positive reactions to cobalt are often \nattributed to co-sensitisation with nickel or \nchromium, these associations were not statistically \nsignificant in our study.\n\n\n\nThe association between facial involvement and \ncontact sensitization to neomycin could be due to the \nuse of topical neomycin for various cutaneous\ninfections and also in eye drop preparations. \nFragrances may be found not only in cosmetics and \nhygiene products, but also in food, beverages and \nscented detergents used for laundry purposes, thus \nleading to the association between truncal involvement \nand contact sensitization to fragrance mix.\n\n\n\nIntroduction\n\n\n\nObjectives \n\n\n\nTo evaluate the frequency of contact sensitisation to \ndifferent allergens among patients who were suspected to \nhave allergic contact dermatitis. \n\n\n\nMaterial and methods\n\n\n\nThis is a retrospective observational study on contact \nsensitisation using the European Standard Series with the \nallergEAZE\u2122 patch test system conducted in the \nDermatology clinic between 2016 and 2017. The \ninterpretation of outcomes were according to the \nInternational Contact Dermatitis Research Group (ICDRG) \nrecording system. Positive patch test reactions were \ndefined as those with +, ++ or +++. Statistical analysis was \nperformed using SPSS version 21.0. Frequencies of \npositive patch test reactions were calculated. The \nPearson\u2019s chi-squared test, or Fisher\u2019s exact test where \nnecessary, was performed to evaluate possible \nassociations between demographic factors, site of \ninvolvement and contact sensitisation to allergens. \n\n\n\nResults\nA total of 62 subjects (M:F = 1:2.44; median age 44 years) \nwere patch-tested and the majority were ethnic Chinese \n(Table 1). 90.3% (n=56) had suspected allergic contact \ndermatitis, 3.2% (n=2) had atopic eczema, 1.6% (n=1) had \ndiscoid eczema and 4.8% (n=3) had other forms of \neczema. The most common site of involvement was on the \nface (29.0%, n=18) (Table 1). \n\n\n\nFigure 1: Top five most common sensitising allergens\n\n\n\nCharacteristics Number of subjects, n (%)\n\n\n\nAge group\nAdult (18-64 years old)\nGeriatric (65 years old and above)\n\n\n\n54 (87.1)\n8 (12.9)\n\n\n\nGender\nFemale \nMale\n\n\n\n44 (71.0)\n18 (29.0)\n\n\n\nEthnicity\nChinese\nMalay \nOthers\nIndian\n\n\n\n42 (67.7)\n17 (27.4)\n2 (3.2)\n1 (1.6)\n\n\n\nOccupation\nUnemployed/retiree\nWhite collar\nStudent\nHomemaker\nBlue collar\nNot stated\n\n\n\n13 (21.0)\n11 (17.7)\n7 (11.3)\n6 (9.7)\n2 (3.2)\n23 (37.1)\n\n\n\nSite of involvement\nFace\nHands\nLower limbs\nTrunk\nArms or forearms\nLips\nNipples\nNeck\nNot stated\n\n\n\n18 (29.0)\n14 (22.6)\n11 (17.7)\n10 (16.1)\n7 (11.3)\n4 (6.5)\n1 (1.6)\n1 (1.6)\n12 (19.4)\n\n\n\nDiscussion\n\n\n\n1. How KN, Tang MM, Roshnee K, Johar A. Contact sensitization in \nadults: a 5-year retrospective review in hospital Kuala Lumpur. \nMed J Malaysia 2017; 72:113-8.\n\n\n\n2. Ochi H, Cheng SWN, Leow YH, Goon ATJ. Contact allergy trends in \nSingapore \u2013 a retrospective study of patch test data from 2009 to \n2013. Contact Dermatitis 2016; 76: 49-50.\n\n\n\n3. Dararattanoroj W, Pootongkam S, Rojanawatsirivej N, \nWongpiyabovorn J. Patterns and risk factors of causative contact \nallergens in Thai adult patients with contact dermatitis. Asian Pac \nJ Allergy Immunol 2017; 35: 27-32. \n\n\n\n4. \u017bukiewicz-Sobczak WA, Adamczuk P, Wr\u00f3blewska P, et al. Allergy \nto selected cosmetic ingredients. Postepy Dermatol Alergol 2013; \n30: 307-10. \n\n\n\n5. Warshaw EM,  Buchholz HJ, Belsito DV, J et al. Allergic patch test \nreactions associated with cosmetics: Retrospective analysis of \ncross-sectional data from the North American Contact Dermatitis \nGroup, 2001-2004. J Am Acad Dermatol 2009; 60: 23-38.\n\n\n\nReferences\n\n\n\n66.1% (n=41) had reaction to one or more allergens. The  \nmost common allergens causing contact sensitisation \nare as summarised in Figure 1. \n\n\n\nTable 1: Demographics of study population and site of  involvement\n\n\n\n25.8% (n=16) \n\n\n\n16.1% (n=10)\n12.9% (n=8) 11.3% (n=7)\n\n\n\n9.7% (n=6)\n\n\n\n0\n2\n4\n6\n8\n\n\n\n10\n12\n14\n16\n18\n\n\n\nNickel Sulfate \nHexahydrate \n\n\n\n5%\n\n\n\nFragrance \nmix 8%\n\n\n\nFragrance \nMix II 14%\n\n\n\nCobalt (II) \nChloride \n\n\n\nHexahydrate \n1%\n\n\n\nBalsam of \nPeru 25%\n\n\n\nThe authors have no conflict of interest to declare.\n\n\n\nContact sensitisation to neomycin was associated with \nfacial involvement (odds ratio, OR = 12.286, 95% \nconfidence interval, 95% CI: [1.266, 119.250]) while \ncontact sensitisation to fragrance mix was associated \nwith truncal involvement (OR = 5.111, 95% CI: \n[1.113, 23.477]). A history of atopic eczema was \nassociated with contact sensitisation to colophony 20% \n(OR = 30.500, 95%CI: [7.805, 119.190]).\n\n\n\n\n\n\n\n\nSYMMETRICAL POLYARTHRITIS \n\n\n\nWITH SUBCUTANEOUS NODULES  \n\n\n\nIN AN INDONESIAN LADY \n\n\n\n \n1Tan WF, 2Voo SYM, 3Faizal AS \n\n\n\n1 Department of Internal Medicine, Hospital Queen Elizabeth \n2 Department of Dermatology, Hospital Queen Elizabeth \n\n\n\n3 Department of Pathology, Hospital Queen Elizabeth \n\n\n\n\n\n\n\n\n\n\n\n12 \n\n\n\n \nLeprosy and tuberculosis are chronic granulomatous \ndiseases. Leprosy has a predilection for the skin and \nperipheral nerves, whereas tuberculosis mainly involves \nthe lungs, and occasionally extrapulmonary organs. The \ncoexistence of leprosy and cutaneous tuberculosis is \ninfrequently reported even in countries where both of \nthese diseases are endemic. \n \n \nWe described a case of a 30-year-old Indonesian lady \nwith a 6 months history of symmetrical polyarthritis \ninvolving her hands and feet, associated with morning \nstiffness and weight loss. She denied any contact history \nwith leprosy or tuberculosis.  \n \nOn examination, she had multiple ill-defined \nhypoaesthetic, hypopigmented patches over her face (Fig \n1). She also has thickened earlobes with palpable nodules \nover the pinna. There were hypertrophied scars and \nnodules over the axillary and inguinal areas. The deep \nnodules at the inguinal areas had sinus tracts which were \nexuding purulent discharge (Fig 2).There were active \nsynovitis over her proximal interphalangeal and \nmetacarpophalangeal joints bilaterally, and nail dystrophy \n(Fig 3).Ulnar nerves were thickened bilaterally with no \nevidence of ulnar neuropathy.  \n \n \n  \n \n \n \n \n \n \n \n \n \n\n\n\n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n She was diagnosed to have borderline lepromatous \nleprosy with erythema nodosum leprosum and \ncutaneous tuberculosis (scrofuloderma). WHO \nMultidrug therapy (MDT), antituberculous treatment \nand oral prednisolone for treatment of erythema \nnodosum leprosum, were given. She received blood \ntransfusion and hematinics for iron deficiency anemia.  \n \nDuring the clinic reviews, her joint symptoms have \nresolved and her skin lesions have healed with \nhypertrophic scars.  \n \n \n \nMusculoskeletal involvement is the third most common \nclinical presentation of leprosy1. Joint involvement can \nbe due to lepra reaction, direct infiltration of the \nsynovium by Mycobacterium leprae or Charcot\u2019s \nneuropathy.2 Among the five subtypes, lepromatous \nleprosy is most commonly associated with arthritis and \ninvolvement is polyarticular in nature3.  \n  \nNumerous reviews have reported coinfection of leprosy \nand pulmonary tuberculosis in patients where both of \nthese diseases are endemic. This is postulated to be \ndue to a mycobacterial genera-specific anergy that \npredisposes an individual to both mycobacterial \ninfections4. However, coinfection of leprosy and \ncutaneous tuberculosis is rarely reported.  \n  \nWe need to consider leprosy in patients presenting with \nrheumatic manifestations and the possibility of \ncoinfection with tuberculosis in endemic areas. Delay in \ndiagnosis and treatment may lead to permanent nerve \ndamage or physical deformities. With coinfection, we \nneed to avoid monotherapy treatment of tuberculosis \nwhich may lead to rifampicin resistant tuberculosis. \n \n \n \n1. Paira S.O, Roverano S. The rheumatic \nmanifestations of leprosy. Clin Rheumatol. 1991; 10: \n274-276 \n2. Alam F et al. Case of arthritis secondary to leprosy. \nSpringerplus 2014 Dec 15;3:732 \n3. Pereira H.L, Ribeiro S.L, Pennini S.N, Sato E.I. \nLeprosy-related joint involvement. Clin Rheumatol. \n2009; 28: 79-84 \n4.Rajagopala S, Devaraj U, D\u2019Souza G, V Aithal V. Co-\nInfection with M. tuberculosis and M. leprae-Case \nReport and Systematic Review. J Mycobac Dis. 2012; \n2:118 \n \n \n \n\n\n\nLaboratory investigation showed microcytic hypochromic \nanemia (haemoglobin 5.7g/dL) and elevated C-reactive \nprotein. White cell count, platelet, renal and liver profile \nwere normal. Antinuclear antibodies and anti-cyclic \ncitrullinated peptide antibodies were negative, with a low \ntitre (1:8) of rheumatoid factor. Chest and hand \nradiographs were normal. HIV status was negative. \n \nSlit skin smear showed BI 4 and MI 0. Histopathology of \nthe earlobes and inguinal nodule revealed macrophage \ngranuloma (Fig 4, 5) Additionally, the inguinal nodule also \nhad epithelioid granuloma with chronic inflammatory \ninfiltrates (Fig 5). Wade Fite stain of both samples showed \nabundant acid fast bacilli  (Fig 7). Mycobacterium \ntuberculosis culture of the inguinal nodule grew acid fast \nbacilli but was insufficient for further testing.  \n \n \n \n\n\n\nIntroduction \n\n\n\nCase Report \n\n\n\nDiscussion \n\n\n\nReferences \n\n\n\nFig 1 Fig 2 \n\n\n\nFig 3 \n\n\n\nFig 4 Fig 5 \n\n\n\nFig 6 \n\n\n\n\n\n\n\n\nA Rare Case of Langerhans Cell Histiocytosis\n\n\n\nin an Infant\nR. Parvathy, WM Kho, HN Ling, M. Pubalan1\n\n\n\n1Dermatology Department, Sarawak General Hospital, Kuching, Sarawak\n\n\n\nPoster \nNo. 13\n\n\n\nFigure 1: Multiple erythematous papules with\n\n\n\nhemorrhagic crusts and erosion scattered over the\n\n\n\nanterior abdominal and chest wall\n\n\n\nFigure 2A: Neoplastic\n\n\n\ncells infiltrating in the\n\n\n\ndermis dispersedly.\n\n\n\n(Magnification X40, H&E\n\n\n\nstain)\n\n\n\nFigure 2B: Large\n\n\n\nirregular neoplastic cells\n\n\n\nwith abundant\n\n\n\ncytoplasm, indistinct\n\n\n\ncell membranes and well\n\n\n\ndemarcated lobulated\n\n\n\nnuclei seen.\n\n\n\n(Magnification X100,\n\n\n\nH&E stain)\n\n\n\nINTRODUCTION\n\n\n\nOn admission to the pediatric department, renal profile, liver\nfunction test, urinalysis, biohazard screening, chest and skull X-ray\nwere normal, except for depressed hemoglobin of 7.8 g/dl and\nplatelet of 43 uL, elevated white cell count of 13.8 uL and lactate\ndehydrogenase of 593 uL. Blood for culture and sensitivity showed\nStaphylococcus infection with a body temperature of 38.50C.\nTreatment was initiated with syrup Cloxacillin and intravenous C-\npenicillin.\n\n\n\nA 3mm diagnostic punch biopsy from the abdomen was obtained.\nMicroscopically, sections were stained with hematoxylin and eosin\nshowed ulcerated epidermal surface replaced by inflammatory debris\nand degenerating polymorphs. The upper dermis, there are\naggregates of histiocytic cells with round to lobulated nuclei,\ninconspicuous nucleoli and pale eosinophilic cytoplasm (Figure 2).\nMitosis are frequent up to 4/HPF. The cells are positive for CD1a and\nS100 stain (Figure 3). A diagnosis of LCH with multi-system\ninvolvement was confirmed. The pediatric team started the patient\nwith metylprednisolone with topical application of bethamethasone\ncream 0.05% to the skin and 1% cetrimide solution was used for\nbathing. The lesions subsequently dried up and improved within few\nweeks.\n\n\n\nLangerhans cell histiocytosis (LCH) is an idiopathic, rare\ndisorder which is characterized by primary infiltration and\naccumulation of histiocytes in various tissue organs.1 The Histiocyte\nSociety clinically classifies LCH into single and multi-system, where\nsingle-system involves one organ, usually the bone, skin, lymph node,\nlungs, thyroid or pituitary gland and multi-system with two or more\norgan involvement, which can be with or without risk organs involved.\nThe liver, spleen, lungs and bone marrow are considered high risk\norgans as associated mortality rates are high in those who do not\nrespond to treatment.2 Here we describe a case of an infant with\nmulti-system LCH presenting with anemia, thrombocytopenia,\nhepatosplenomegaly, together with an infection.\n\n\n\nREFERENCES\n\n\n\nDISSCUSSION\n\n\n\nThe initial manifestation of LCH is often the cutaneous\nhistiocytosis, which may mimic chronic dermatitis. However, high\nindex of suspicion should be raised when the use of conventional\ntopical creams becomes a failure. The incidence of LCH is rare with an\nestimate of 2 to 5 cases per million populations with a male\npredominance and most common in children aged 1 to 4 years.3 The\netiology is unclear with a neoplasm versus inflammatory disorder\nwhich is often debated. Mutation of oncogenic BRAF V600E indicates\na neoplastic disorder while the participation of proinflammatory\nchemokines in LCH suggests a reactive disorder.4\n\n\n\nTreatment varies according to disease extension, sites and number\nof lesion. It is aimed to increase survival rate and prevent late\nsequelae.3, 4 Single system skin diseases is often self-limiting, which\ndo not require any therapy; however topical corticosteroid may be\nused. Local nitrogen mustard application and PUVA are utilized as\nsecond-line.1 Multi-system diseases are treated with systemic\nprednisolone, chemotherapy such as vinblastine, methotrexate and 6-\nmercaptopurine.3 Progressive disease with risk organ involvement\nwho does not respond to first-line treatment, a salvage therapy with\ncombination of Ara-C and cladribine or clofarabine, single agent\nshould be considered.4 The prognosis depends on age of onset,\nextent of disease and vital organ failure.3\n\n\n\nCASE REPORT\n\n\n\nA female infant at 3 months of age, born at term with a birth\nweight of 2.55kg was referred from primary care for multiple visits of\ngeneralized rash for the past 1 month, which was worsening after\ntreatment of various topical creams. Before transfer to the tertiary\ncentre, patient had blood transfusion due to low hemoglobin level of\n5.7g/dl and treated for infection. The lesions were pruritic\nerythematous papules, which later became crusted, eroded and some\nforming pustules (Figure 1). The rash started over the scalp, spreading\nto the upper limbs, trunk and lower limbs, which involved the palms,\nsoles and lower gum. The child was clinically pale with a palpable liver\nand spleen. Patient had a history of admission to the hospital for\natypical pneumonia previously. Furthermore, there was no history of\nconsanguineous marriage or family history of similar condition. A\ndifferential diagnosis of LCH, acrodermatitis enteropathica, leukemia\ncutis and scabies were made.\n\n\n\n1.Satter EK, High WA. Langerhans cell histiocytosis: a review of the\ncurrent recommendations of the Histiocyte Society. Pediatric\ndermatology. 2008 May 1; 25(3):291-5.\n\n\n\n2. Histiocyte Society. Langerhans cell histiocytosis: evaluation and\ntreatment guidelines, 2009 April 15. Available from URL:\nhttp://www.histiocytesociety.org/document.doc?id=290.\n\n\n\n3. Hu S, Wang W, Wang C, Ma R, Xiao Z, Dong H. Langerhans cell\nhistiocytosis presenting as a multi\u2010system disorder in an infant.\nInternational journal of dermatology. 2012 Jun 1; 51(6):709-12.\n\n\n\n4. Morimoto A, Oh Y, Shioda Y, Kudo K, Imamura T. Recent advances in\nLangerhans cell histiocytosis. Pediatrics International. 2014 Aug 1;\n56(4):451-61.\n\n\n\n2A 2B\n\n\n\nFigure 3A: CD1a stain Figure 3B: S100 stain\n\n\n\n3A 3B\n\n\n\n\n\n\n\n\n0\n\n\n\n5\n\n\n\n10\n\n\n\n15\n\n\n\n20\n\n\n\n25\n\n\n\n30\n\n\n\nA TWO-YEAR RETROSPECTIVE STUDY OF \n\n\n\nCONTACT DERMATITIS TO COSMETICS IN \n\n\n\nPUBLIC HOSPITAL\nOng Sai Beng, Rohna Ridzwan\n\n\n\nDepartment of Dermatology, Selayang Hospital, Malaysia\n\n\n\nMethodology\nThis is a retrospective observational study of patients who \npresented to Dermatology clinic at Selayang Hospital with \nfacial dermatitis with or without involvement of other part of \nthe body and with positive patch test to preservative, \nfragrance and/or metal allergen between year 2015 and \n2016. These sensitizers were obtained from the Standard \nEuropean series and additional series from \nChemotechnique Diagnostics\u00ae (Fragrance, Metal, \nCosmetic, Dental series) while Preservative series was \nfrom AllergEAZE\u00ae. Parameters studied include \ndemography and patch test positive allergens. Patients \nwho had developed angry back syndrome will be excluded \nfrom the analysis. Angry back syndrome is defined as more \nthan 5 patch test positive allergen s in one particular series\n\n\n\nResult\n125 patients were studied with male to female ratio of 1:2. The age ranges from 7 to 77 years old with mean age of 41. \nWe noted 44% of sensitizers detected are preservative, where 37% and 19% for fragrance and metal respectively. In \nthis study we also look at allergens positive in lips dermatitis. Total of 18 patients with lips dermatitis with male to \nfemale ratio of 1:8. \n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\nCommon Allergen in Lip Dermatitis\n\n\n\nPreservativeMetalFragrance\n\n\n\nDiscussions\nThe commonest preservative in cosmetic induced contact allergic is Kathon CG which is also noted in other Asian \ncountries, Europe and America. Cosmetic allergy to arbitol and gallate (preservatives) are documented in the Asian \ncountries only .Cosmetic contact dermatitis to Iodopropynyl butylcarbamate is in an uprising trend and it is noted in \nEurope and this study.\n\n\n\nIn Selayang Hospital, individual fragrance allergen that causes cosmetic allergy were identified due to the availability of \nFragrance series. In other Asian country, only Fragrance Mix I is documented.\n\n\n\nHeavy metal such as chrome, lead or palladium are not suppose to be present in the cosmetics. But during the \nproduction of cosmetic product, these heavy metals might be produced as part of a by-product due to impurities in the \nraw materials. There are multiple chemistry papers that reported trace of heavy metals in cosmetics such as eyeliners, \nlipstick, powder and others. In this study, metal allergen in cosmetic  induced \ncontact allergic dermatitis was also detected from patch test.\n\n\n\nIn this retrospective study we were able to identified the contact allergens but unable to confirm the sources. Future \nprospective patch test study on patient\u2019s own product is preferable to identify the sources of the allergens.\n\n\n\nConclusion\nFor all patient with suspected cosmetic dermatitis, we suggest patch test is perform with additional preservative, \nfragrance and metal series in addition to individual sensitizer from patient\u2019s own products.\n\n\n\nCommon Allergen in Facial Dermatitis\nNumber of patients\n\n\n\nNumber of patients\n\n\n\nFigure 2. Top 10 allergens in lip dermatitisFigure 1. Top allergens in cosmetic induce contact\n\n\n\nPreservativeMetalFragrance\n\n\n\nIntroduction\nCosmetics are products intended to be used on the skin, \nteeth and oral cavity for cleaning, perfuming, changing \ntheir appearance, and/or correcting body odours, and/or \nprotecting or keeping them in good condition. Hence \ncosmetics include make-up and personal care products. \nThere have been an increase in incidence of contact \nallergic dermatitis to cosmetics for the past decade. It \nnot only affect the patient\u2019s psychologically in social \nactivities but also will reduce the productivity due to \nabsent from work.\n\n\n\nObjective of this study is to determine the common \ncosmetic allergens in this region.\n\n\n\n\n\n\n\n\nAntibiotic Resistance Pattern of Neisseria Gonorrhoeae at the Genitourinary\n\n\n\nMedicine Clinic, Hospital Kuala Lumpur (2011-2015)\nMeena Nithianandan, Azura Mohd Affandi\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nIn the era of super-bugs, there is a need to monitor antibiotic resistance patterns.\nDue to the emergence of antimicrobial resistance worldwide, local antibiotic\nresistance patterns should be monitored periodically to alert early intervention.\nThis audit was conducted to analyse the antibiotic resistance patterns among the\ngonococcal urethritis cases that presented to the GUM Clinic, HKL.\n\n\n\nINTRODUCTION\n\n\n\nThis is a retrospective study on the antibiotic resistance patterns based on 370\nculture-positive gonorrhoea obtained from urethral swab samples sent between\n2011 and 2015. Antimicrobial susceptibility testing by standard disc diffusion\nmethod was performed to detect sensitivity to penicillin, tetracycline,\nciprofloxacin, cefuroxime, azithromycin and ceftriaxone. All data was obtained\nfrom patient records.\n\n\n\nCONCLUSION\n\n\n\nREFERENCES\n\n\n\nA total of 370 positive culture isolates of N.gonorrhoeae (new and recurrent)\nfrom 2011 to 2015 were reviewed. Highest level of resistance detected was to\nazithromycin 100% (64/64) followed by tetracycline 82.8% (293/354).\nResistance to penicillin was noted in 60.9% (224/368) of all isolates. Both\npenicillin and tetracycline showed a decreasing resistance trend from 2011-\n2015. The third commonest antibiotic resistance was to ciprofloxacin at 46.5%\n(158/340), followed by cefuroxime 2.7% (6/219). Resistance to ceftriaxone was\n0.8% (3/364), although reviews previously in 2001-2005 showed no\nresistance1. The results were compared to data obtained from the Gonococcal\nResistance to Antimicrobials Surveillance Programme (GRASP)3.\n\n\n\nHigh rates of resistance to Penicillin and Tetracycline have been\ndocumented in HKL and in the Western Pacific region. Within 10 years, a\nmarked increase in Ciprofloxacin resistance (10% to 46.5%) is evident.\nResistance to Cefuroxime and Ceftriaxone was discovered, not found in\nthe previous study. In view of the comparative susceptibility profile of\nCefuroxime, further studies should be carried out within the region to\ndocument its possible use against Neisseria sp. Ceftriaxone remains the\nfirst line antimicrobial in treating Gonorrhoea at HKL.\n\n\n\nRESULTS\n\n\n\nMETHODOLOGY\n\n\n\nTable 1: Demographic Characteristics of GUM Clinic HKL Patients\n\n\n\nVariables\n(n = 98)\n\n\n\nn %\nAge (years):\n\n\n\n11-20 24 24.5\n21-30 57 58.2\n31-40 13 13.3\n41-50 0 0.0\n\n\n\nAbove 50 4 4.1\nMean \u00b1 SD \n\n\n\n(Range)\n25.70 \u00b17.89\n\n\n\n(15,56)\nEthnicity:\n\n\n\nMalay 82 83.7\nChinese 0 0.0\nIndian 9 9.2\nOthers 7 7.1\n\n\n\nClinic Visit: \n1 89 90.8\n\n\n\n2-3 4 4.1\n>3 0 0.0\n\n\n\nOrientation:\nBisexual 11 11.2\n\n\n\nHeterosexual 72 73.5\nHomosexual 14 14.3\n\n\n\nunknown 1 1.0\nHIV status: \n\n\n\nPositive 5 5.1\nNegative 91 92.9\nUnknown 2 2.0\n\n\n\n0\n\n\n\n10\n\n\n\n20\n\n\n\n30\n\n\n\n40\n\n\n\n50\n\n\n\n60\n\n\n\n70\n\n\n\n80\n\n\n\n90\n\n\n\n100\n\n\n\nResistant\n\n\n\nIntermediate\n\n\n\nSensitive\n\n\n\nFigure 1: Overall Antibiotic Susceptibility for Neisseria gonorrhoeae (2011-2015, HKL)\n\n\n\n0\n\n\n\n10\n\n\n\n20\n\n\n\n30\n\n\n\n40\n\n\n\n50\n\n\n\n60\n\n\n\n70\n\n\n\n80\n\n\n\n90\n\n\n\n100\n\n\n\n2011 2012 2013 2014 2015\n\n\n\nCiprofloxacin\n\n\n\nCefuroxime\n\n\n\nPenicillin\n\n\n\nTetracycline\n\n\n\nColistin\n\n\n\nCeftriaxone\n\n\n\nAzithromycin\n\n\n\nErythromycin\n\n\n\nAmpicillin\n\n\n\nPolymyxin B\n\n\n\nFigure 2:  Antibiotic Resistance Pattern for Neisseria gonorrhoeae (2011-2015)\n\n\n\n1. Affandi AM, Gangaram HB, Hussein SH. Antibiotic Resistance Pattern\nof Neisseria gonorrhoeae in Hospital Kuala Lumpur, Malaysia (2001-\n2005).\n\n\n\n2. World Health Organization. Baseline report on global sexually\ntransmitted infection surveillance. Geneva: WHO. 2012.\n\n\n\n3. Public Health England: Gonococcal Resistance to Antimicrobials\nSurveillance Programme (GRASP) 2013 Report.\n\n\n\nYear/Antibiotics 2011 2012 2013 2014 2015\nOverall \n\n\n\n(5 years)\n\n\n\nPenicillin\n82.2%\n\n\n\n(83/101)\n53.4%\n\n\n\n(55/103)\n54.9%\n\n\n\n(28/51)\n49.1%\n\n\n\n(28/57)\n53.6%\n\n\n\n(30/56)\n60.9%\n\n\n\n224/368\n\n\n\nTetracycline\n87.1%\n\n\n\n(88/101)\n86.0%\n\n\n\n(80/93)\n80.9%\n\n\n\n(38/47)\n63.2%\n\n\n\n(36/57)\n91.1%\n\n\n\n(51/56)\n82.8%\n\n\n\n293/354\n\n\n\nCiprofloxacin\n10.0%\n\n\n\n(10/100)\n70.5%\n\n\n\n(67/95)\n67.4%\n\n\n\n(29/43)\n39.2%\n\n\n\n(20/51)\n62.7%\n\n\n\n(32/51)\n46.5%\n\n\n\n158/340\n\n\n\nCefuroxime ND\n1.5%\n\n\n\n(1/68)\n2.2%\n\n\n\n(1/46)\n0%\n\n\n\n(0/55)\n8.0%\n\n\n\n(4/50)\n2.7%\n6/219\n\n\n\nAzithromycin\n100%\n\n\n\n(64/64)\nND ND ND ND\n\n\n\n100%\n64/64\n\n\n\nCeftriaxone\n0%\n\n\n\n(0/100)\n0%\n\n\n\n(0/103)\n5.8%\n\n\n\n(3/52)\n0%\n\n\n\n(0/55)\n0%\n\n\n\n(0/54)\n0.8%\n3/364\n\n\n\nTable 2:  Summary of antibiotic resistance patterns of N.gonorrhoeae (2011-2015)  in HKL\n\n\n\nAntibiotic \n%Resistance\n\n\n\nPenicillin Tetracycline Ciprofloxacin Cefuroxime Azithromycin Ceftriaxone\n\n\n\nHKL\n(2011-2015)\n\n\n\n(n = 370)\n60.9 82.8 46.5 2.7 100.0 0.8\n\n\n\n1HKL\n(2001-2005)\n\n\n\n(n = 416)\n64.4 86.8 10.4 0 N/A 0\n\n\n\n3England & \nWales\n\n\n\n(n= 1568 )\n22.6 82.8 37.3 N/A 1.0 0.0\n\n\n\n2Singapore\n(n= 86)\n\n\n\nN/A N/A 10.0 N/A 0 0.0\n\n\n\n2Philippines\n(n= 160 )\n\n\n\nN/A N/A 74.4 N/A N/A 0.0\n\n\n\n2Thailand\n(n=720)\n\n\n\nN/A N/A 97.6 N/A N/A 19.9\n\n\n\n2Australia\n(n=3220 )\n\n\n\nN/A N/A 34.7 N/A <1.0 2.0\n\n\n\n2China\n(n= 1026 )\n\n\n\nN/A N/A 100.0 N/A N/A 36.9\n\n\n\nTable 3: Comparison of N.gonorrhoeae Antibiotic Resistance Patterns in HKL with other Countries\n\n\n\n3GRASP (England & Wales) \u2013 2014\nN/A - not available\n\n\n\n1Affandi AM et al.HKL - 2005\n2WHO (Global Report) - 2012\n\n\n\nPe\nrc\n\n\n\nen\nta\n\n\n\nge\nPe\n\n\n\nrc\nen\n\n\n\nta\nge\n\n\n\n15\n\n\n\n\n\n\n\n\nPOSITIVE\tPATCH\tTEST\tTO\tCOPPER\t\nSULPHATE\tAND\tCOPPER\tOXIDE,\t\tIS\t\n\n\n\nTHERE\tANY\tRELEVANCE?\nNasuha\tR1,\tSalwa R1,\t\tTeoh\tTY1,\tRohna\tR1,\tWan\tSyameen\tAfira\tWA2\t\n\n\n\n1Dermatology\tof\tDepartment,\tHospital\tSelayang\t2UITM\n\n\n\nCopper is a metal that is commonly used in coin, jewelry, plumbing, dental applications, ceramic glazes,\nelectrical wires, intrauterine contraceptive devices (IUDs) and pesticide. Allergic contact dermatitis to\ncopper is a type IV hypersensitivity reaction and is infrequently reported although humans are widely\nexposed to copper on the skin. Positive patch test to copper sulphate and copper oxide is controversial in its\nsignificance.\nTherefore, through this study, we seek to assess the prevalence of allergic contact dermatitis to copper\nbased on our local patch test data and to investigate the most probable sources of copper allergy among\nour patients.\n\n\n\nINTRODUCTION\n\n\n\nThis is a cross sectional study involving patients had\npositive patch test to copper sulphate and copper oxide\nbetween January 2015 until December 2016. Parameters\nstudied include patient\u2019s demography and site of\ndermatitis. Patients from year 2016 with cheilitis were\ncalled back to answer the questionnaire to determine the\npossible source of exposure to copper.\n\n\n\nMETHODOLOGY\n\n\n\nRESULTS\nThere were 21 patients aged between 19 to 55 years old\nwith positive patch test to copper sulphate and copper\noxide with a female preponderance.\nNine patients had cheilitis, while 6 (67%) of them were\nable to provide relevant history suggesting contact\ndermatitis to copper containing food, personal care\nproducts and cosmetics.\n\n\n\nCopper is a known weak sensitizer as compared to other\nmetal compounds, yet it is relevant in some patients,\nespecially those with cheilitis. Our findings should be\nconsidered exploratory and hypothesis generating. A\nlarger trial with an extended follow-up period would be\nideal to prove a causal relationship between copper and\ncertain cases of allergic contact dermatitis.\n\n\n\nCONCLUSION\n\n\n\nREFERENCES\n1..Zug KA, Kornik R, Belsito DV, et al. Patch-testing north american lip dermatitis patients:\ndata from the North American Contact Dermatitis Group, 2001 to 2004. Dermatitis.\n2008;19(4):202-208.\n2.Strauss RM, Orton DI.Allergic contact cheili- tis in the United Kingdom: retrospective\nstudy. Am J Contact Dermat. 2003;14(2):75-77.\nZoli V, Silvani S, Vincenzi C, Tosti A. Allergic contact cheilitis. Contact Dermatitis.\n2006;54(5):296-297.\n3.Lim SW, Goh CL. Epidemiology of eczematous cheilitis at a tertiary dermatological referral\ncentre inSingapore. ContactDermatitis. 2000;43(6):322-326.\n4.Jun Ma.Nancy M. Betts.Zinc and Copper Intakes and Their Major Food Sources for Older\nAdults in the 1994\u201396 Continuing Survey of Food Intakes by Individuals (CSFII).Journal of\nNutrition.2000: 2838-2843\n5. VilaplanaJ,RomagueraC. New developments in jewellery and dental materials. Contact\nDermatitis 1998: 39: 55\u201357.\n6.Ali Sani, Maryam Bello Gaya et al , Determination of some heavy metals in selected\ncosmetic products sold in KanoMetropolis, Nigeria . Toxicology Reports 3 (2016) 866\u2013869 .\n\n\n\nSOURCES\n\n\n\nMALE\n38%\n\n\n\nFEMALE\n62%\n\n\n\nGENDER\n\n\n\nMALE FEMALE\n\n\n\nProducts\t Case\tReported\n\n\n\nPineapple 2\n\n\n\nNoodle 2\n\n\n\nChocolate\t 2\n\n\n\nSunflower\tseed 1\n\n\n\nLipstick\t/lip\tgloss 2\n\n\n\ntoothpaste 3\n\n\n\nDental filling 1\n\n\n\nDental\tbraces 1\n\n\n\nDISCUSSION\nIn 2015, we noted copper sulphate to be the 12th most\ncommon sensitizers among our patients. We further looked\ninto specific sites involved and noted 42% of our patients\nwith positive patch testing to copper had chelitis.\nAllergic contact chelitis has usually been described to be\nsecondary to fragrance mix, balsam of Peru, nickel sulphate,\nsodium gold thiosulfate and neomycin sulphate as reported\nby The North American Contact Dermatitis Group (NACDG)1\n\n\n\nand groups from the United Kingdom2, Italy3 and Singapore4.\nA study on Zinc and Copper Intakes showed that certain food\ngroups such as nuts and seeds, legumes, potato and potato\nproducts, beef, pasta, pasta dishes and chocolate have high\ncontent of copper. Pineapple is also a very good source of\ncopper.\nCopper is also commonly and increasingly used in dental\napplications in concentrations of 5% to almost 100%7.\nAnother study in Nigeria showed that copper ranked third\nbehind manganese and nickel in terms of the highest\nconcentration of the heavy metals analysed in cosmetic\nproducts8. Interestingly 67% of our patients were able to\nidentify food, dental and personal care products as a cause\nof their cheilitis which contains copper.\n\n\n\n0\n\n\n\n5\n\n\n\n10\n\n\n\n15\n\n\n\n15-20 21-58 >59\n\n\n\nAGE GROUP\n\n\n\n0 2 4 6 8 10\n\n\n\nCheilitis\n\n\n\nUpper limbs\n\n\n\nLower limbs\n\n\n\nTrunk \n\n\n\nFace\n\n\n\nHand and feet\n\n\n\nExposure\nSITE OF DERMATITIS\n\n\n\n16\n\n\n\n\n\n\n\n\nDrug Reaction with Eosinohpilia and Systemic (DRESS). A  4-year  \nretrospective study from Selayang Hospital, Malaysia\n\n\n\nSharifah FSNM,  Teoh TY, Rohna R, Ng HW  \nDepartment Dermatology Selayang Hospital, Selangor, Malaysia\n\n\n\nIntroduction\nDRESS (Drug reaction with eosinophilia and systemic syndrome), also known as Drug induced hypersensitivity syndrome\n(DIHS) is a severe cutaneous adverse reaction (SCAR), and carries a mortality rate of up to 10%.\n\u2022 It is characterized by fever, skin rash, lymphadenopathy and multi-organ involvement. Diagnosis is based on Naranjeet\u2019s\n\n\n\ncriteria. The onset of symptoms usually occurs 2-12 weeks after drug ingestion which is delayed when compared to other\ntypes of drug reactions.\n\n\n\nMethodology: This is a retrospective study. All patients\u2019 medical records with the diagnosis of DRESS from year 2013 to\n\n\n\n2016 in Selayang Hospital were retrieved and included in this study. Parameters studied included demography, clinical\n\n\n\npresentation, laboratory results and patients\u2019 outcome.\n\n\n\nResult: There were 34 patient were included in this study, from 2013 till December 2016. (male 26 , female 8) .Majority\n\n\n\nwere Malays (64.7%) followed by Chinese (29%).Their age ranged between 20-90 years old. Majority (97%) of patient\n\n\n\npresented with macular papular rash ((Figure 1) as well as hyper eosinophilia. The rashes could be seen as early as 2 days\n\n\n\nafter starting the culprit drug. The commonest drug is phenytoin (Figure 2). The culprit drug that causes death were\n\n\n\nallopurinol, duramine and akurit-4. The anti-TB medications, and duramine have higher latency time (range 28 \u2013 60 days).\n\n\n\n17 \n\n\n\nRoujeau and Stern7\n\n\n\nWalsh S Chen YC Wongkitisophon Voo SYM\n\n\n\nEt al \nPresent study\n\n\n\net al10 et al1 et al12\n\n\n\nNumber of patients - 27 60 27 22 34\n\n\n\nMost frequent drug Anticonvulsant Anticonvulsant Allopurinol Phenytoin Allopurinol Phenytoin\n\n\n\nFever (%) 87 100 87 88.9\n\n\n\n10=29.41%\n\n\n\nMost frequent rash Exanthem\nUrticated papular \n\n\n\nexanthem\nExanthem Macular papular Macular papular Macularpapular\n\n\n\nFacial edema (%) - 85.1 - 74.1 11.76%\n\n\n\nLymphadenopathy (%) 75 88 31 22.2 77.30%\n8.82%\n\n\n\nEosinophilia (%) 30 93 52 70.4 91.42%\n33=97.1%\n\n\n\nHepatic involvement (%) 51 100 80 96.3 90.90%\n\n\n\n13= 38.23%\n\n\n\nRenal involvement (%) 11 7 40 7.4 22.70%\n35.29%\n\n\n\nMortality (%) 10 11 10 3.7 22.70%\n4=11.76%\n\n\n\nDiscussion\n\n\n\nThis study was conducted as a follow up study by Voo SYM in 2014 (poster presentation) who looked at DRESS cases in\n\n\n\nSelayang Hospital from 2006-2012. In the first study, we noted a high mortality rate which we thought was due to late\n\n\n\npresentation and also misdiagnosis. A series of awareness activity was carried out to educate healthcare professionals in our\n\n\n\nhospital and also healthcare centres around Selayang Hospital.\n\n\n\nIn our study, we noted a decrease of mortality rate to 11.76% from 22.7% from the previous study. This mortality rate is still\n\n\n\nhigher compared to other studies. All 4 death in our study was due to liver failure, 2 patients were actually referred from other\n\n\n\nmedical centres to hepatology department which is the national referral centre for hepatology with severe liver impairment.\n\n\n\nInterestingly, our current finding noted there is a decrease in the incidence of hepatitis in our DRESS patient while an increase in\n\n\n\nrenal impairment. We are unsure of the reason for this phenomenon. due to poor documentation and lack of awareness\n\n\n\nFacial oedema and lymphadenopathy has been noted to be a prominent feature in DRESS. However, in our study, the number of\n\n\n\npatient with these feature is low probably awareness of these signs in medical officers. Reference from other study are shown in\n\n\n\ntablet 1 .\n\n\n\nThe most common causative drug for DRESS in our study differs from Voo SYM could be due to the awareness of allopurinol\n\n\n\nbeing a highly sensitized drug in causing multiple severe cutaneous adverse drug reaction and the cautious use of it. On top of\n\n\n\nthat, ministry of health Malaysia has also made allopurinol a controlled drug to be prescribed only by specialist.\n\n\n\nFigure 1 Clinical features of DRESS\n\n\n\nConclusion\nDRESS training is important to extent to health care beyond our hospital to increase the awareness and further reduction in\n\n\n\nDRESS complication.\n\n\n\nTable 1  previous and current studies :Roujeau and Stern, Walsh S , Chen YC , Wongkitisophon, Voo SYM\n\n\n\nFigure 2 Drug causes DRESS\n\n\n\n\n\n\n\n\nThe difference of sensitization detection rates by routinely patch-testing \n1,3-Diphenylguanidine, N-Cyclohexyl-N-phenyl-4-phenylenediamine, \n\n\n\nN-Cyclohexylthiophthalimide and Ylang Ylang Oil in addition to \nEuropean Baseline Series in Hospital Selayang \n\n\n\nFei Yin Ng1, Min Moon Tang1, Asmah Johar1, Rohna Ridzwan2\n\n\n\n1Department of Dermatology Hospital Kuala Lumpur\n2Department of Dermatology, Hospital Selayang\n\n\n\nINTRODUCTION\n\n\n\nRESULT\n\n\n\nMETHODOLOGY\n\n\n\nEuropean Baseline Series(EBS) is used in most Dermatology Centres in\nMalaysia in the assessment of allergic contact dermatitis. This study aims\nto assess the difference of sensitization detection rates by routinely\npatch-testing 1,3-Diphenylguanidine(DPG), N-Cyclohexyl-N-phenyl-4-\nphenylenediamine(CPPD), N-Cyclohexylthiophthalimide(N-CHTP), and\nYlang-ylang oil in addition to the EBS.\n\n\n\nThis is a prospective study done in the Department of Dermatology\nHospital Selayang between July 2015 and December 2016. All patients\nscheduled for patch tests were routinely patch-tested with the 4\nadditional allergens along with the EBS.\n\n\n\n\u2022 A total of 292 patients were recruited with majority females(59.6%).\n\u2022 The median age was 41 years.\n\u2022 The overall sensitization rate was 67.1% using EBS and it increased to\n\n\n\n70.5% with the addition of the 4 allergens.\n\u2022 The 10 most common sensitizing allergens were shown in Table 2.\n\n\n\nAmong these, females were more sensitized to nickel, fragrance mix I,\ntextile dye mix, DGP and Methylisothiozolinone. Males were more\nsensitized to nickel, textile dye mix, paraben mix, DPG and Balsam of\nPeru.\n\n\n\n\u2022 Rubber sensitization detection rate was significantly increased with\nthe addition of DPG(from 23.1% to 76.9%, p<0.00001). The addition\nof CPPD and N-CHTP improved the detection of rubber sensitization\nby 4.6%.\n\n\n\n\u2022 The addition of Ylang-ylang improved the detection of fragrance\nsensitization by 6.5%.\n\n\n\n\u2022 The allergens with the low sensitization rates < 1.0% were lyral (0.7%),\nmercapto mix (0.7%), primin (0.7%), budesonide (0.3%) and N-\nIsopropyl-N-phenyl-4-phenylenediamine (0.3%).\n\n\n\nDISCUSSION\n\n\n\nCONCLUSION\n\n\n\nREFERENCES ACKNOWLEDGEMENT\n\n\n\nThe sensitization detection rate was improved slightly with addition of the\n4 allergens. The routine patch-testing of DPG along with EBS improved the\ndetection rate of rubber allergy significantly. Larger muticentre studies are\nrequired to provide more data to reflect the prevalence of DPG allergy\nwithin the nation.\n\n\n\nWe would like to thank the \nDirector General of Health, \nMalaysia for permission to \npresent this study.\n\n\n\n\u2022 Although previous data showed that the sensitization rate of these 4\nallergens were high in the same center between 2011-2013, their\nsensitization rate in the current cohort became significantly lower for\nCPPD(3.9% vs 1.4%; p=0.047) and ylang-ylang (14.6% vs 3.4%,\np=0.00002); insignificantly lower for N-CHTP (3.6% vs 1.4%, p=0.064).\nThe sensitization of DPG remained high (11.1% vs 10.6%, p=0.824).\n\n\n\n\u2022 In the process of manufacturing rubber products, 1,3\nDiphenylguanidine is an important rubber accelerator, while N-\n(Cyclohexylthio)phthalimide functions as a retarder and N-Cyclohexyl-\nN-phenyl-4-phenylenediamine plays its role as an antidegradant1.\n\n\n\n\u2022 The prevalence of diphenylguanidine allergy had been gradually rising.\nMost cases have been reported with exposure to synthetic gloves2.\n\n\n\n\u2022 An 8-year retrospective review on patch test using rubber allergens\ndemonstrated that the positive rate of reaction to diphenylguanidine\nranged from 1% to 7.5%3. The rate of sensitisation to N-\n(Cyclohexylthio)phthalimide (5.2%) and N-Cyclohexyl-N-phenyl-4-\nphenylenediamine (1.3%) was comparable to our data3.\n\n\n\n\u2022 Ylang ylang oil, also known as Cananga odorata flower oil was first\ndiscovered as a cosmetic sensitizer in 1971, Its usage has expanded in\naromatherapy, food preparations and ethnomedicine4. Ylang ylang oil\nhas been incorporated into the North American baseline screening\nseries5. Studies which have included Ylang ylang oil in the routine\ntesting of patients with contact dermatitis have revealed prevalence\nrates of 0.7% to 2.6% 6,7\n\n\n\nCharacteristics n=292\nGender, n(%) Male 118 (40.4)\n\n\n\nFemale 174 (59.6)\nAge, median 41 \nEthnic, n(%) Malay 157 (53.8)\n\n\n\nChinese 96 (32.9)\nIndian 37 (12.7)\nOthers 2 (0.7)\n\n\n\nTable 1.  Patient demography\n\n\n\nPatch Test Series Rate of positive reaction (%)\nn=292\n\n\n\nP value\n\n\n\nEuropean Baseline Series 196 (67.1%)\n0.37European Baseline Series + 4 \n\n\n\nadditional allergens\n206 (70.5%)\n\n\n\nTable 3. Comparison of rate of positive reactions using the European\nBaseline Series (EBS) and with 4 additional allergens\n\n\n\nTest allergens Detection rate,\nn (%)\n\n\n\np value\n\n\n\nEuropean Baseline Series rubber allergens\n15 (23.1) -\n\n\n\nEuropean Baseline Series rubber allergens + \n3 Additional rubber allergens 50 (76.9) <0.00001\n\n\n\nEuropean Baseline Series rubber allergens + \n1,3 Diphenylguanidine 47 (72.3) <0.00001\n\n\n\nEuropean Baseline Series rubber allergens + \nN-Cyclohexyl-N-phenyl-4-phenylenediamine 18 (27.7) 0.545\n\n\n\nEuropean Baseline Series rubber allergens + \nN-(Cyclohexylthio) phthalimide 18 (27.7) 0.545\n\n\n\nTable 2.  Top 10 common allergens detected using modified EBS\n\n\n\nTable 4.  Sensitivity of rubber allergy detection\n\n\n\nAllergen Positive reactions, n (%) \nTotal\n\n\n\nn=292\nFemale\nn=174\n\n\n\nMale\nn=118\n\n\n\nNickel Sulfate 67 (22.9) 47 (27.0) 20 (16.9)\nTextile Dye Mix 38 (13.0) 19 (10.9) 19 (16.1)\nN,N-Diphenylguanidine 31 (10.6) 19 (10.9) 12 (10.2)\nFragrance Mix l 29 (9.9) 20 (11.5) 9 (7.6)\nMethylisothiazolinone 23 (7.9) 15 (8.6) 8 (6.8)\nCobalt Chloride Hexahydrate 20 (6.8) 14 (8.0) 6 (5.1)\nBalsam of Peru 20 (6.8) 9 (5.2) 11 (9.3)\nParaben Mix 19 (6.5) 6 (3.4) 13 (11.0)\nFormaldehyde 16 (5.5) 11 (6.3) 5 (4.2)\nPotassium Dichromate 16 (5.5) 12 (6.9) 4 (3.4)\n\n\n\nTable 5. Sensitivity in fragrance allergy detection\n\n\n\nHOSPITAL SELAYANG p value\n2011-2013 2015-2016\n\n\n\nDuration of study period 36 months 18 months -\nTotal number of study subjects 705 292 -\nRate of positive reaction using EBS 466 (66.1%) 196 (67.1%) 0.755\nRate of positive reaction using EBS + \nAdditional series\n\n\n\n546 (77.4%) 229 (78.4%) 0.736\n\n\n\nRate of positive \nreaction to \nspecific rubber \nallergen\n\n\n\n1,3 Diphenylguanidine 52 (11.1%)\nn=468\n\n\n\n31 (10.6%)\nn=292\n\n\n\n0.824\n\n\n\nN-Cyclohexyl-N-\nphenyl-4-\nphenylenediamine\n\n\n\n18 (3.9%)\nn=462\n\n\n\n4 (1.4%) \u2193\u2193\nn=292\n\n\n\n0.047\n\n\n\nN-Cyclohexylthio\nphthalimide\n\n\n\n17 (3.6%)\nn=472\n\n\n\n4 (1.4%) \u2193\nn=292\n\n\n\n0.064\n\n\n\nRate of positive reaction to Ylang ylang\noil in total number of patients tested \nwith Ylang ylang oil\n\n\n\n21 (14.6%)\nn=144\n\n\n\n10 (3.4%) \u2193\u2193\nn=292\n\n\n\n0.00002\n\n\n\nTable 6. Comparison of data between the current study and the previous \nstudy in Hospital Selayang \n\n\n\n1. Warburton et al. Contact Dermatitis 2016:1-9.\n2. Notre-dame P. Eur J Dermatol 2016;26(6):523-30.\n3. Bendewald et al. Dermatitis. 2010;21(1):33-40.\n4. Tan et al. Evidence-Based Complement Altern Med.\n\n\n\n2015;2015:1-30.\n5. de Groot et al Dermatitis. 2016;27(4):170-5\n6. Uter et al. Contact Dermatitis. 2010;63(5):277-283.\n7. Wetter et al. J Am Dermatology. 2007;63(5):789-798.\n\n\n\nTest allergens Detection rate, n \n(%)\n\n\n\np value\n\n\n\nEuropean Baseline Series fragrance allergens 48 (62.3%) -\nEuropean Baseline Series + \nYlang ylang oil 52 (68.8%) 0.499\n\n\n\n\u2022 The current data was compared to a previous study held in the same\ncentre between 2011 and 2013. The 36-month study had a total of 705\nsubjects. Rate of positive reaction to at least one allergen was similar in\nboth studies when using EBS alone or along with additional series.\n\n\n\n\u2022 In the former study, subjects were tested with additional rubber and\nfragrance series only when suspected to have rubber and fragrance\nallergy. When tested in a random population, there was a significant\nreduction in the rate of positive reaction to N-Cyclohexyl-N-phenyl-4-\nphenylenediamine and Ylang ylang oil . There was no significant\ndifference in the results for diphenylguanidine and N-\nCyclohexylthiophthalimide. However, the number of positive reactions\nto N-Cyclohexylthiophthalimide was small.\n\n\n\n\u2022 In the previous study, lyral (0.0%) had the lowest positive rate of\nreaction, followed by fragrance mix II (1.0%).\n\n\n\n18\nMinistry of Health\n\n\n\nMalaysia\n\n\n\n\n\n\n\n\nPatch testing in children and adolescents: \n7 years\u2019 experience\n\n\n\nSharifah Rosniza SNC1, MM Tang1, Asmah J1, KF Leong2, Sabeera B2\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n2Paediatrics Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nPoster no:\n\n\n\n19\n\n\n\nIntroduction\nAllergic contact dermatitis is thought to be infrequent in children.\nHowever, recent reports have proven otherwise. Positive patch test\nreaction has been detected in children in 26.6% to 95.6% of patients1.\nThis study aims to explore the pattern of allergic contact dermatitis in\nchildren and adolescents in Hospital Kuala Lumpur.\n\n\n\nMaterials and methods\nThis is a retrospective review of all children and adolescent patients\nbetween the age of 5 to 19 year-olds who underwent patch test in\nHospital Kuala Lumpur between January 2010 to December 2016. Patch\ntest was performed using IQ chambers and allergens purchased from\nChemotechnique Diagnostics. Patients were patch tested with European\nBaseline Series, other appropriate series and patients\u2019 own products as\ndirected from history. Readings were recorded according to the\nrecommendations by the International Contact Dermatitis Research\nGroup.\n\n\n\nResults\n\u2022 There were 116 children and adolescent patients who underwent\n\n\n\npatch test (Table 1).\n\u2022 Based on age definitions by World Health Organization, 19 (16.4%)\n\n\n\npatients were categorized as children (<10 years) and 97 (83.6%)\npatients were adolescents (10-19 years).\n\n\n\n\u2022 Seventy four patients (63.8%) had at least one positive patch test\nreaction.\n\n\n\n\u2022 There were 11 (57.9%) positive patch test in children and 63 (64.9%) in\nadolescent patients and this difference is not statistically significant\n(p=0.56).\n\n\n\n\u2022 The most common allergens in this study were nickel sulfate, fragrance\nmix, potassium dichromate, cobalt chloride, MCI/MI (Kathon CG) and\nthimerosal (Table 2).\n\n\n\n\u2022 In patients with upper limb involvement, 54(78.3%) patients had hand\neczema.\n\n\n\n\u2022 Positive patch test was recorded in 53.7% of patients with hand\neczema.\n\n\n\nCharacteristics n=116\n\n\n\nMedian age in years (range) 14 (5-19)\n\n\n\nMale : female ratio 1 : 2.7\n\n\n\nEthnicity, n (%) Malay 75 (64.7)\n\n\n\nChinese 25 (21.6)\n\n\n\nIndian 15 (12.9)\n\n\n\nOthers 1   (0.9)\n\n\n\nSite of lesions, n (%) Upper limbs 68 (59.5)\n\n\n\nLower limbs 61 (52.6)\n\n\n\nFace and ears 36 (31.0)\n\n\n\nTrunk 31 (26.7)\n\n\n\nGeneralized 2   (1.7)\n\n\n\nClinical diagnosis, n (%) Contact dermatitis 87 (75.0)\n\n\n\nEczema 6  (5.2)\n\n\n\nAtopic eczema 5 (4.3)\n\n\n\nHand and foot eczema 5  (4.3)\n\n\n\nFoot eczema 4 (3.4)\n\n\n\nHand eczema 3  (2.6)\n\n\n\nDiscoid eczema 3  (2.6)\n\n\n\nPompholyx 1  (0.9)\n\n\n\nFacial eczema 1  (0.9)\n\n\n\nLip eczema 1  (0.9)\n\n\n\nSeries used, n (%) European Baseline 115 (99.1)\n\n\n\nShoe 31 (26.7)\n\n\n\nRubber 29 (25.0)\n\n\n\nCosmetic 20 (17.2)\n\n\n\nPlastic and glue 10 (8.6)\n\n\n\nTextile and dye 9 (7.8)\n\n\n\nMetal 7 (6.0)\n\n\n\nMedicaments 3 (2.6)\n\n\n\nDental 3 (2.6)\n\n\n\nPhotoallergen 1 (0.9)\n\n\n\nPositive patch test n (%)\n\n\n\nNickel sulfate 29 (39.2)\n\n\n\nFragrance mix 13 (17.6)\n\n\n\nPotassium dichromate 11 (14.9)\n\n\n\nCobalt chloride 9  (12.2)\n\n\n\nMCI/MI (Kathon CG) and thimerosal 6 each (8.1)\n\n\n\nColophony, neomycin, formaldehyde 5 each (6.8)\n\n\n\n4-phenylenediamine base and SQL mix 4 each (5.4)\n\n\n\nDisperse orange 3, acid yellow 36, 4-aminobenzene, \nepoxy resin, mercaptobenzothiazole\n\n\n\n3 each (4.1)\n\n\n\nMercapto mix, dibutylthiourea, paraben mix, \npalladium chloride, cocomidopropylbetaine, \ntixocortol-21-pivalate, N-isopropyl N-phenyl \nparaphenylanadiamine, thiuram mix\n\n\n\n2 each (2.7)\n\n\n\nBalsam of Peru, primin, disperse yellow 9, benzoyl \nperoxide, MDBGN, mercury ammonium chloride, \ndisperse red 1, wool alcohol, 4-ter-butylphenol \nformaldehyde resin, benzocaine, amalgam, mercury, \ncopper oxide, copper sulphate, lead chloride, \nchlorocresol, dimethylamino propylamine, \ngoldsodium thiosulphate, hexamethylenetetramene, \ndisperse blue mix 106/124, dithiodimorpholine, \namalgam alloying metal\n\n\n\n1 each (1.4)\n\n\n\nDiscussion & Conclusion \n\u2022 Around 60% of our patients had a positive patch test reaction.  \n\u2022 The most common allergen is nickel sulfate, and this finding is similar\n\n\n\nto other studies2 (Table 3).\n\u2022 Our female patients had higher positive patch test reaction and this\n\n\n\ncould be due to the increased exposure to nickel from jewellery and\near piercing.\n\n\n\n\u2022 Cobalt chloride and potassium dichromate are also one of the\ncommon allergens in this study. Patients who are sensitized to nickel\nare more prone to be sensitized to other metals such as cobalt and\nchromium and this may explain the high sensitization to cobalt\nchloride and potassium dichromate in our patients3.\n\n\n\n\u2022 Fragrances and preservatives were also found to be common\nallergens in this study and this could be caused by exposure to\nincreasing number of toiletries and cosmetic products aimed at\nchildren and adolescent population.\n\n\n\n\u2022 In conclusion, allergic contact dermatitis is not rare in our children\nand adolescent population as more than 60% positive reaction were\nrecorded during patch test.\n\n\n\n\u2022 Our top 3 sensitizing allergens are nickel, fragrance mix and\npotassium dichromate.\n\n\n\n\u2022 Findings from this study could contribute to the development\nof paediatric baseline series suited for Malaysian population.\n\n\n\nReferences\n1. Simonsen et al.  Contact Dermatitis.  2011; 65: 254\u2013265\n2. Rodrigues et al.  An Bras Dermatol.  2016; 91(1): 64-72\n3. Brand\u00e1o et al.  An Bras Dermatol.  2012; 87(2): 269-76\n4. Jacob et al.  Pediatr Dermatol.  2008; 25: 520-7\n5. Clayton et al.  Br J Dermatol.  2006; 154: 114-7\n6. Goon et al.  Pediatr Dermatol.  2006; 23: 117-20\n7. Kobata.  S\u00e1o Paulo (SP): Universidade de S\u00e1o Paulo; 2010.79p\n\n\n\nMCI/MI-methylcholoroisothiozolinone/methylisothiozolinone; \nMDBGN- methyldibromoglutaronitrile; SQL-sesquiterpine lactone \n\n\n\nTable 1: Characteristics of patients who underwent patch test\n\n\n\nTable 2. The sensitization pattern  of current cohort\n\n\n\nAuthor\nCountry\n\n\n\nStudy\nperiod\n\n\n\nNo of \npatients\n\n\n\nAge Positive\nreaction \n\n\n\nTop  two \nallergens\n\n\n\nOur study\nMalaysia\n\n\n\n2010-\n2016\n\n\n\n116 5-19 \nyears\n\n\n\n63.8% Nickel\nFragrance mix\n\n\n\nJacob et al4\n\n\n\nUSA\n2001-\n2006\n\n\n\n65 1-18 \nyears\n\n\n\n83.0% Nickel\nThimerosal\n\n\n\nClayton et al5\n\n\n\nUK\n1995-\n2004\n\n\n\n500 <16 \nyears\n\n\n\n27.0% Nickel\nFragrance mix I\n\n\n\nGoon et al6\n\n\n\nSingapore\n1986-\n2003\n\n\n\n2340 <20 \nyears\n\n\n\n45.4% Nickel\nThimerosal\n\n\n\nKobata7\n\n\n\nBrazil\n2007-\n2009\n\n\n\n62 2-12\nyears\n\n\n\n61.0% Nickel\nThimerosal\n\n\n\nTable 3. Patch-test results from literature review\n\n\n\n\n\n\n\n\nGow Pei Min1, Latha Selvarajah1, Choon Siew Eng2 \n \n\n\n\n1Department of Dermatology, Hospital Sultan Ismail Johor Bahru, Johor, Malaysia \n2Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia \n\n\n\n20 \n\n\n\nFig 2: Post treatment - \nLeft shin healed \ncutaneous lesion with \nflat hyperpigmentation \n(yellow arrow)  \n\n\n\nFig 1: Pre treatment  - \nLeft shin cutaneous \nlesion with hyper \npigmented nodule \n(yellow arrow)  \n\n\n\n\u00be Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is rare, comprising approximately 1-3% of all \ncutaneous lymphomas.  \n\n\n\n\u00be It usually affects elderly females, and has a poor prognosis.  \n\u00be There is a well established association between lymphoproliferative disorders and autoimmune rheumatological diseases \n\n\n\nsuch as systemic lupus erythematosus (SLE).  \n\u00be The risk of non-Hodgkin\u2019s lymphoma (NHL) is particularly increased in SLE, with diffuse large B-cell identified as the \n\n\n\ncommonest associated subtype.  \n\u00be However, the risk of primary cutaneous lymphomas in patients with SLE is not known.  \n\u00be We report a case of PCDLBCL-LT in an elderly lady with longstanding SLE and Sjogren\u2019s syndrome. \n \n\n\n\n\u00be A 56 year-old Malay lady with underlying long standing SLE and Sjogren\u2019s syndrome on Azathioprine presented with a \npainless nodule over her left shin for 6 months (Figure 1) with multiple soft nodules with atrophic skin changes over \nthighs.  \n\n\n\n\u00be There was history of intermittent fever and loss of weight. There were no palpable lymph nodes or hepatosplenomegaly.  \n\u00be A punch biopsy of the nodule revealed findings consistent with diffuse large B-cell lymphoma of non-germinal center B-\n\n\n\ncell\u2013like (non GCB) type.  \n\u00be Computed tomography of thorax, abdomen and pelvis excluded visceral organ involvement.  \n\u00be A trephine biopsy done showed no evidence of infiltration by primary disease.  \n\u00be She was commenced on chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and \n\n\n\nprednisolone), and is currently responding to treatment (figure 2). \n \n \n \n \n \n \n\n\n\n\u00be Association of autoimmune disease such as Sjogren and SLE with NHL is well known.  \n\u00be The common sites of involvement are lymph node, bone marrow, mucosal associated lymphoid tissue and in specific for \n\n\n\nSjogren syndrome the salivary gland.  (1) (2) Cutaneous involvement is rare.  \n\u00be It is extremely rare when cutaneous DLBCL manifest in this patient with mixed Sjogren Syndrome and SLE.  \n\u00be There are similar case reported in either isolated Sjogren Syndrome or isolated SLE (3) (4), but not in the case of mixed \n\n\n\nSjogren Syndrome and SLE.  \n\u00be However, development NHL in these patients seems to share the same pathogenesis.(5) \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nThis case highlights the possibility that patients with autoimmune disease have increased risk of not only the classic forms \nof NHL but also primary cutaneous B-cell lymphomas. \n\n\n\nPrimary Cutaneous Diffuse Large B-cell \nLymphoma-Leg Type In A Patient With Mixed \nConnective Tissue Disease  \n\n\n\n1. Bernatsky S et al. Hodgkin\u2019s lymphoma in systemic lupus erythematosus. Rheumatol Oxf Engl. 2007 May;46(5):830\u20132.  \n2. Nocturne G et al. Sj\u00f6gren Syndrome-associated lymphomas: an update on pathogenesis and management. Br J Haematol. 2015 Feb;168(3):317\u201327.  \n3. Zarins A et al. A Case of Cutaneous B-Cell Lymphoma in Longstanding Systemic Lupus Erythematosus. J Cutan Med Surg. 2016 Nov;20(6):579\u201381.  \n4. Selva-O\u2019Callaghan A et al. Primary cutaneous large B-cell lymphoma of the legs in a patient with primary Sj\u00f6gren\u2019s syndrome. Clin Exp Rheumatol. 2003 \n\n\n\nOct;21(5):672.  \n5. Fallah M et al. Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study. Ann Oncol Off J Eur Soc Med Oncol. 2014 \n\n\n\nOct;25(10):2025\u201330.  \n \n\n\n\nFig 3: Dense lymphoid \ninfiltrate in lower dermis \nand subcutis (H&E X4) \n\n\n\nFig 4: The infiltrate consist of malignant \nlymphoid cells, characterized by large \ncells with irregular vesicular nuclei, \nprominent nucleoli and conspicuous \neosinophilic cytoplasm. Multiple mitoses \nare present. (H&E  X 40) \n \n\n\n\nFig 5: The malignant cells stain positive for CD20 (left),  Bcl6 (middle) \nand MUM1 (right) [X40]  \n \n\n\n\nIntroduction \n\n\n\nCase Report \n\n\n\nDiscussion \n\n\n\nConclusion \n\n\n\nReferences \n\n\n\n\n\n\n\n\nResult and discussion\n18 patients were studied with age ranging from 10 to 77 years with a mean age of 32. The were more female patients (72%) than\nmale patients (28%). The positivity rate for the short contact patch test is 50%.\n\n\n\nConclusion\nWe propose that all urticaria patients with history of adverse drug reaction, contact dermatitis and atopy should have short contact \npatch test done to identify the cause of urticaria\n\n\n\nSHORT CONTACT PATCH TEST PROFILE IN PATIENTS WITH  \n\n\n\nHISTORY OF URTICARIA AND CONTACT DERMATITIS IN \n\n\n\nSELAYANG HOSPITAL FROM JANUARY TO DECEMBER 2016\nOng SB1, Rohna R1, Nur Ashikin A2\n\n\n\n1Department of Dermatology Hospital Selayang, 2UiTM Selayang\n\n\n\nPoster \nNo. 21\n\n\n\nIntroduction\nContact urticaria is an immediate hypersensitivity reaction\nthat occurs after direct contact with an allergen.To\ndetermine the cause of contact urticaria remains a\nchallenge due to the diversity of causes and the complexity\nof diagnostic procedures. There are increasing reports of\npositive patch test in contact urticaria patients and little is\nknown about its mechanism.\n\n\n\nObjective of this study is to determine the short contact \npatch test (SCPT) sensitization rate and the clinical \ncharacteristic of patient with history of urticaria in \nsuspected contact dermatitis.\n\n\n\nMethodology\nThis is a retrospective  study of patients who had history of urticaria \nand  suspected of contact dermatitis in Selayang Hospital from \nJanuary to December 2016. These patients had a 30 minutes of  \nSCPT followed by European baseline series.The allergens tested  \nwere  Balsam of Peru, Benzoic acid, Cinnamic alcohol, Cinnamic \naldehyde, Fragrance mix I and Nickel sulphate. Parameters studied \ninclude demographic data , frequency of contact  allergens and \nsource of allergen , SCPT adverse reactions , association between \ncontact urticaria with contact dermatitis, history of adverse drug \nreaction and  frequency of atopy diathesis .\n\n\n\n0 1 2 3 4 5 6 7 8 9\n\n\n\nBenzoic Acid\n\n\n\nBalsam of Peru\n\n\n\nCinnamic Aldehyde\n\n\n\nNickel Sulphate\n\n\n\n Cinnamic Alcohol\n\n\n\nFragrance mix 1\n\n\n\nAllergens\n\n\n\nWe were unable to identify  the allergen source as the patients were unable to recall possible causative  food and personal care\nproduct that  contained either 1 or more of the 6 allergens tested. Two out of 18 patients developed adverse reaction during short \ncontact patch test and closed patch test was not done on them. One patient developed giddiness during SCPT. Another patient \ndeveloped urticaria after completed the short contact patch test and follow by wheezing at 60 minutes post SCPT.\n\n\n\nNo. of patient\n\n\n\nFigure 1: SCPT result \n\n\n\nWe noted the possible association of contact urticaria allergen with adverse drug reaction, contact dermatitis and atopy as \nillustrated in Table 1. In view of this is a retrospective observation study with small sample size, we were unable to determine the \nsignificant of this finding. We would like to recommend further prospective study with bigger sample size to verify this finding.\n\n\n\nAllergen History of adverse drug \nreaction\n\n\n\nPositive patch test result Allergic \nRhinitis\n\n\n\nBronchial \nasthma\n\n\n\nAtopic \neczema\n\n\n\nBalsam of Peru Diclofenac\nMefenamic acid\nBactrim\n\n\n\nAlfa Isomethyl Ionone\nAnise Alcohol\nBalsam of Peru\nBenzoic acid\nCinnamic Alcohol\nCoblat chloride\nFarnesol\nFragrance Mix II\nPovidone iodine 10%\nNeomycin sulphate\n\n\n\n3 1 1\n\n\n\nBenzoic acid Diclofenac\nBactrim\nErythromycin\nTetracycline\n\n\n\nAlfa Isomethyl Ionone\nAnise Alcohol\nBalsam of Peru\nBenzoic acid\nCinnamic Alcohol\nCoblat chloride\nFarnesol\nFragrance Mix II\nIsopropyl Myristate\nKathon CG\nMethylisothiazolinone\nNeomycin sulphate\nPovidone iodine 10%\n\n\n\n5 1 1\n\n\n\nCinnamic alcohol Mefenamic acid\nBactirm\n\n\n\n0 0 0\n\n\n\nCinnamic aldehyde Diclofenac\nMefenamic acid\nBactrim\nErythromycin\nTetracycline\n\n\n\nCoblat chloride\nIsopropyl Myristate\nKathon CG\nMethylisothiazolinone\nNeomycin sulphate\n\n\n\n2 1 0\n\n\n\nNickel sulphate None None 1 0 1\n\n\n\nTable 1: Association of contact urticaria allergens with other type of allergy\n\n\n\n\n\n\n\n\nSun exposure among patients with \natopic dermatitis and its relationship \nwith disease severity\n\n\n\nArumugam M1, Adawiyah Jamil1, Norazirah Md Nor1, Norlaila Mustafa1, Mazlin Baseri1, Thevarajah S2, Shamsul Azhar\nShah3\n\n\n\n1 Dermatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Center. 2 Department of \nDermatology, Hospital Kuala Lumpur. 3 Department of Community Health, Universiti Kebangsaan Malaysia \nMedical Center\n\n\n\nPoster: \n\n\n\n22\n\n\n\nConclusion\nSun exposure was very limited in the majority of both AD and controls. The\nSEI was similar between the 2 groups. Severity of AD was not related to the\namount of sun exposure. Higher SEI observed in males and Chinese are\nmost likely due to culture and religious influences.\n\n\n\nIntroduction\nSun exposure has been reported to be beneficial for atopic\ndermatitis (AD). Patrizi et al. 1 showed that 74.4% of patients with\nmild-moderate AD had complete resolution during summer, 16.3%\nimproved while 9.3% had no change in disease severity. Ultraviolet\nA1 and narrowband ultraviolet B are established AD treatments. In\nthe tropics it is often assumed that AD patients shun the sun to\nprevent sweating which worsens the symptoms of AD. This study\ncompared sun exposure between AD with healthy controls and\ndetermine the relationship between sun exposure with AD severity,\nethnicity and gender.\n\n\n\nMaterials and Methods\nThis was a case- control study involving 38 AD patients and an equal number\nof healthy controls matched for age, gender, ethnicity, Fitzpatrick skin type\nand body mass index. Subjects on systemic immunosuppressive agents\nwithin the last 4 weeks of recruitment, those with renal or hepatic impairment,\nsubjects on vitamin D/ calcium supplements in the last 6 months, and those\nwith parathyroid diseases were excluded from the study. A clinical\nexamination was performed on the cases to determine their eczema severity\nusing SCORAD. Sun exposure was calculated as the number of hours per\nweek spent outside without sun protection multiplied by percentage body part\nexposed to sunlight3,4.\n\n\n\nResults\n\n\n\nTable 1. Characteristics of the study population\nParameters Case, n=38\n\n\n\n((%)) or median \n(IQR)\n\n\n\nControls, n=38\n\n\n\n((%)) or median \n(IQR)\n\n\n\nMWU p \nvalue\n\n\n\nAge (years) 27.5 (22.8-38.0) 28.0 (24.0-38.0) 681.5 0.673\n\n\n\nGender\nMale 14 ((36.8)) 14 ((36.8))\nFemale 24 ((63.2)) 24 ((63.2))\n\n\n\nEthnicity\nMalay 20 ((52.6)) 20 ((52.6))\nChinese 10 ((26.3)) 10 ((26.3))\nIndian 8 ((21.1)) 8((21.1))\n\n\n\nFitzpatrick skin type\n\n\n\nIII 2((5.3)) 2((5.3))\nIV 31(81.6) 33((86.8))\nV 4((10.5)) 3((7.9))\nVI 1((2.6)) -\n\n\n\nBMI (kg/m2) 23.6 (21.2-29.5) 24.7 (21.4-29.7) 685.0 0.701\n\n\n\nNormal 20((52.6)) 23((60.5))\nObese 8((21.1)) 8((21.1))\nOverweight 9((23.7)) 7((18.4))\n\n\n\nUnderweight 1((2.6)) -\n\n\n\nSEI 9.3(5.7-17.9) 9.1(4.5-19.0) 705.0 0.864\n\n\n\nAdequate(SEI\u226518.3) 9((23.7)) 11((28.9))\n\n\n\nInadequate(SEI\u226418.3)\n\n\n\nSubjects using \nsunscreen\n\n\n\n29((76.3))\n\n\n\n0\n\n\n\n21((71.1))\n\n\n\n0\n\n\n\nTable 4. Interethnic comparison of SEI between AD and controls\n\n\n\nParameter Male Female \u03c72 p value\n\n\n\nSEI \u2013 AD \n\n\n\nMedian(IQR)\n\n\n\nKruskal-Wallis \nTest Ranks\n\n\n\n19.36(9.6-26.8)\n\n\n\n26.04\n\n\n\n8.23(5.5-12.6)\n\n\n\n15.69\n\n\n\n7.689 .006*\n\n\n\nSEI - Control\n\n\n\nMedian(ICR)\n\n\n\nKruskal-Wallis \nTest Ranks\n\n\n\n19.00(12.81-24.39)\n\n\n\n28.68\n\n\n\n5.95(3.30-9.32)\n\n\n\n14.15\n15.159\n\n\n\n<.001**\n\n\n\nParameter Malay Chinese Indian \u03c72 p value\n\n\n\nSEI \u2013 AD \nMedian(IQR)\n\n\n\nKruskal-Wallis \nTest Ranks\n\n\n\n7.59 (3.2-9.7)\n\n\n\n15.40\n\n\n\n14.97(12.8-32.0)\n\n\n\n29.05\n\n\n\n9.85(3.6-20.2)\n\n\n\n17.81\n\n\n\n10.32 .006*\n\n\n\nSEI - Control\n\n\n\nMedian(IQR)\n\n\n\nKruskal-Wallis \nTest Ranks\n\n\n\n6.51(3.3-14.1)\n\n\n\n15.45\n\n\n\n14.32(12.6-24.6)\n\n\n\n27.75\n\n\n\n7.89(4.7-21.4)\n\n\n\n19.31\n\n\n\n8.19\n.017*\n\n\n\nFigure 1. Severity of atopic dermatitis in cases\n\n\n\nTable 3. Intergender comparison of SEI between AD and controls\n\n\n\nParameter Mild AD Moderate AD Severe AD \u03c72 p \nvalue\n\n\n\nSEI (IQR) 8.78(5.6-22.3) 8.78(6.2-14.2) 14.97(2.8-25.3) .362 .835\n\n\n\nAnalyses were performed using the Kruskal-Wallis H test\n\n\n\nTable 2. SEI and AD severity\n\n\n\nAnalyses were performed using the Mann-Whitney U test.\n\n\n\nAnalyses were performed using the Kruskal-Wallis H test. **. Kruskal-Wallis test is significant at the 0.01 level. *. Kruskal-\nWallis test is significant at the 0.05 level.\n\n\n\nDiscussion\nSun exposure in AD patients was similar to healthy individuals contrary to\ncommon assumption that they avoid the sun more than people without skin\ndiseases. However, SEI of both AD and controls were generally inadequate\nsuggesting that the majority of the study population avoided the sun. Sun\navoidance is a typical behaviour among Asians who value fairer skin. The\nSEI in this study in fact may reflect just the amount of unavoidable sun\nexposure in an Equatorial country.\nThe lack of association between sun exposure and AD severity maybe\nexplained by the low SEI across the board. The amount of sun exposure is\nnot sufficient for a positive effect on AD. Culture and religion influence the\nhigher SEI in males compared to females and in Chinese compared to other\nethnicities. Men in general wear clothes that cover less of the body and\nlimbs while Muslim women\u2019s clothing covers more than others. Low SEI in\nMalays is because the majority were females. Malay ladies generally have\nless skin exposed as they wear hijabs, long sleeved tops with long skirts or\ntrousers.\n\n\n\nReferences\n1. Patrizi A, Savoia F, Giacomini F, Tabanelli M, Gurioli C. The effect of summer holidays and sun exposure on atopic dermatitis. G Ital Dermatol Venereol. 2009;144(4):463-6.\n2. Holick MF, MacLaughlin JA, Doppelt SH.  Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. Science1981;211(4482):590-593.\n3. Dawodu A, Zalla L, Woo JG, Herbers PM, Davidson BS, Heubi JE, Morrow AL. Heightened attention to supplementation is needed to improve the vitamin D status of breastfeeding mothers and infants when sunshine exposure is restricted. Matern Child \n\n\n\nNutr. 2014;10(3): 383-97.\n4. Dawodu A, Davidson B, Woo JG, Peng YM, Ruiz-Palacios GM, de Lourdes Guerrero M, Morrow AL. Sun exposure and vitamin D supplementation in relation to vitamin D status of breastfeeding mothers and infants in the global exploration of human milk study. \n\n\n\nNutrients. 2015 ;7(2):1081-93.\n5. Parisi AV, Wilson CA. Pre-vitamin D effective ultraviolet transmission through clothing during simulated wear. Photodermatol Photoimmunol Photomed. 2005 ;21(6):303-10.\n\n\n\n\n\n\n\n\nRESEARCH POSTER PRESENTATION DESIGN \u00a9 2015\n\n\n\nwww.PosterPresentations.com\n\n\n\nClique Clinic   4, Jalan 19/36, Seksyen 19, 46300 Petaling Jaya, Selangor, Malaysia. www.cliqueclinic.com\n\n\n\nThis study aims to evaluate the efficacy and safety of combine treatment \n\n\n\nbetween MFU-V and CaHA for the treatment of facial skin laxity in lower \n\n\n\nface.\n\n\n\nIntroduction\n\n\n\nResults\n\n\n\nCase 1\n\n\n\nLeft: Before treatment. Right: 1 month post treatment (Centre)\n\n\n\nDiscussion\n\n\n\nCase 1\n\n\n\nLeft: Before treatment. Right: 1 month post treatment (Left side) Conclusion\n\u2022 Combinative treatment with MFU-V and CaHA is effective for \n\n\n\nimproving facial skin laxity giving natural facial rejuvenation.\n\n\n\n\u2022 Both are adjunct to production of new collagen.\n\n\n\n\u2022 The safety profile is consistent with the safety profiles of the \n\n\n\nindividual treatments. \n\n\n\n\u2022 Further follow up is needed to study the long term safety and \n\n\n\nlongevity of the results.\n\n\n\nMing Chun Goh, Hui Qian Yeow, Bob John, Ting Song Lim\n\n\n\nDepartment of Aesthetic Medicine, Clique Clinic\n\n\n\nCase series: Combining Micro-focused Ultrasound with Visualization (MFU-V) with \nCalcium Hydroxylapatite (CaHA) with Integral Lidocaine as a Novel Approach for Reversing \n\n\n\nFacial Aging\n\n\n\nObjective\n\n\n\nFacial involving many factors across multiple layers of the face. It is a \n\n\n\ndynamic process involving the aging of soft-tissue and bony structures.\n\n\n\nSkin tendons, retaining ligaments and superficial musculoaponeurotic \n\n\n\nsystem (SMAS) form a structural complex that supports the tethering of the \n\n\n\nskin to the skull.  As part of the aging process, these structures, along with \n\n\n\nthe skin, undergo collagen depletion, loss of elasticity and weakening of \n\n\n\ncomponents, leading to skin laxity and facial sagging.\n\n\n\nCombinative aesthetic interventions often leads to better results than \n\n\n\nsingle modalities alone. However, combining Micro-focused ultrasound \n\n\n\nwith visualization (MFU-V) with biostimulators such as Calcium \n\n\n\nhydroxylapatite (CaHA) with integral lidocaine have not been fully \n\n\n\nexplored.\n\n\n\nMethodology\n\n\n\n\u2022 8 healthy patients ( 30-65 years old) with mild to moderate skin laxity \n\n\n\nwere enrolled. \n\n\n\n\u2022 MFU-V with transducer DS4-4.5 and DS7-3.0  were used . 240 lines, 0.3J, \n\n\n\nDS4-4.5 transducer followed by 200 lines, 0.45J, DS 7-3.0.\n\n\n\n\u2022 Then 1.5 ml of CaHA with integral lidocaine was injected over the \n\n\n\ncorner of the mouth, nasolabial fold, marrionatte line and mandible \n\n\n\nangle. \n\n\n\n\u2022 All pre treatment photos were taken using 3D LifeViz.\n\n\n\n\u2022 All patients were follow up at post treatment 1 week and 1 month.\n\n\n\n\u2022 MFU-V is a transcutaneous heat delivery system that focuses \n\n\n\nultrasound waves to specific areas in dermal and subcutaneous \n\n\n\ntissues. These depths target structures such as SMAS layer and \n\n\n\nretaining ligaments and skin tendons complex. The immediate \n\n\n\nresponse is a tightening of the collagen and stimulating subsequent \n\n\n\nlong-term neocollagenesis seen within at least 3 months after \n\n\n\ntreatment. \n\n\n\n\u2022 Calcium hydroxyapatite is a white substance filler and biostimulator. \n\n\n\nIt is supposed to induce neocollagenesis during the first 6 months \n\n\n\nafter injection. It can be used as volumizer in the subcutaneous \n\n\n\nlayers or in the dermis to correct dermal atrophy.\n\n\n\n\u2022 Theoretically, the heating process by MFU-V could initiate an \n\n\n\ninflammatory response and might lead to a foreign body reaction \n\n\n\nor change in the appearance and characteristics of the filler after \n\n\n\nbeing heated.\n\n\n\n\u2022 Inflammatory response eg. Swelling is seen over treated area. This is \n\n\n\nexpected as CaHA is a biotimulator with volumizing properties.\n\n\n\n\u2022 Clinically no visual or palpable nodule present.\n\n\n\n\u2022 Both procedures were well tolerated and no major adverse effect is \n\n\n\nseen.\n\n\n\nReference\n\u2022 Casabona, Gabriela MD; Pereira, Greg\u00f3rio MD. Microfocused\n\n\n\nUltrasound with Visualization and Calcium Hydroxylapatite for \n\n\n\nImproving Skin Laxity and Cellulite Appearance. Plastic and \n\n\n\nReconstructive Surgery - Global Open. July 25, 2017.\n\n\n\n23\n\n\n\nCase 1\n\n\n\nLeft: Before treatment. Right: 1 month post treatment (Right side)\n\n\n\nCase 2\n\n\n\nLeft: Before treatment. Right: 1 month post treatment (Centre)\n\n\n\nCase 2\n\n\n\nLeft: Before treatment. Right: 1 month post treatment (Left side)\n\n\n\nCase 1\n\n\n\nLeft: Before treatment. Right: 1 month post treatment (Right side)\n\n\n\n\n\n\n\n\nCase Report: Blastic Plasmacytoid \nDendritic Cell Neoplasm \nCT Koot, P Gunabalasingam \nDepartment of Dermatology, Hospital Melaka, Melaka, Malaysia \n\n\n\n24 \n\n\n\nINTRODUCTION \nBlastic plasmacytoid dendritic cell neoplasm is a rare \nform of cutaneous lymphoma. It accounts for 0.44% of \nhaematological malignancies and 0.7% of cutaneous \nlymphoma1.   \n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nCASE REPORT \nA 32-year-old man presented with a rash on his trunk \nfor the past one month, which progressively involved \nhis limbs. There were no other constitutional \nsymptoms. Clinically, there were multiple \nerythematous indurated plaques noted at the trunk \nand limbs (Figure 1). There were no \nhepatosplenomegaly or lymphadenopathy.  \n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nDISCUSSION \nBlastic plasmacytoid dendritic cell neoplasm (BPDCN) \nis a rare form of cutaneous lymphoma and is classified \nunder the prescursor of haematological neoplasm. This \nneoplasm has been reclassified numerous times  as \nclinical and pathological techniques improve. Currently \nit is classified as BPDCN by WHO in 20082. \n \nBPDCN usually affects elderly patients, aged between \n60 to 70 years old. However, it can present at any age \nalbeit rare as the case of our patient. It has a \npredilection for men (male to female ratio, 3:1)3. It \ncommonly presents in the skin with either solitary or \nmultiple nodules / tumours. About half of the patients \nmay have nodal or bone marrow involvement at \npresentation. Most patients presenting with only skin \nlesions will rapidly develop involvement of bone marrow, \nperipheral blood, lymph nodes and extranodal sites4. \n \nBPDCN is an aggressive lymphoma with poor \nprognosis. Median survival rate is 12 - 14 months3. \nSystemic chemotherapy usually results in complete \nremission, but quick relapses unresponsive to further \nchemotherapy follows. Allogenic haemotopoetic stem \ncell transplantation may improve survival rates from 12 \nmonths to 31 months1. As our patient was young this \noption was discussed with him. Unfortunately, our \npatient defaulted follow up and further treatment \nmodalities could not be discussed.  \n \nOther novel treatment options in development include \nmonoclonal antibodies, chimeric antigen receptor T-cell \ntherapies, dual-targeting agents or bispecific molecules. \nThese treatment modalities have the ability to target \nCD123, CD56 and other antigens that may be \napplicable to patients with BPDCN5.  \n \n \n\n\n\nCONCLUSION \nBPDCN is a rare and aggressive form of cutaneous \nlymphoma that may initially present in the skin with \nmultiple contusiform plaques, with or without leukaemic \ninfiltration. Skin biopsy with triple positive \nCD4+CD56+CD123+ phenotype confirms the diagnosis. \nEarly treatment is essential as initial chemotherapy \ncombined with allogenic haemotopoetic stem cell \ntransplantation may improve survival. Novel targeted \nagents could represent the next direction in therapeutic \ndrug development. We present this case to add to the \ngrowing body of literature on BPDCN. \n \n \n \n\n\n\n\n\n\n\n\n\n\n\nREFERENCES \n1. L Pagano et al, Blastic plasmacytoid dendritic cell neoplasm \nwith leukemic presentation: an Italian multicenter study, \nHaematologica, 2013;98(2).  \n2. W Kempf, CA Sander, Classification of cutaneous \nlymphomas \u2013 an update, Histopathology, 2010;56(57-70). \n3. Y Shi, E Wang, Blastic plasmacytoid dendritic cell neoplasm, \nArch Patho Lab Med, 2014;138(564-569). \n4. Willemze et al, WHO-EORTC classification for cutaneous \nlymphoma, Blood, 2005;105(10). \n5. N Pemmaraju, Blastic plasmacytoid dendritic cell neoplasm, \nCllinical Advances in Hematology & Oncology, 2016;14(4). \n \n \n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nBlood investigations, computer tomographic scan, \nbone marrow aspiration and trephine biopsy were \nnormal. Skin biopsy showed scattered periadnexal \nnodules of neoplastic aggregates in the papillary and \nreticular dermis (Figure 2A). These cells are \nadmixture of small to medium sized pleomorphic \nblasts with high nucleo-cytoplasmic ratio and \nexhibiting fine chromatin clumps with occasional \nsmall nucleoli (Figure 2B). They stained positive for \nCD4, CD56 and CD123, features in keeping with \nblastic plasmacytoid dendritic cell neoplasm. (Figure \n3).  \nThe patient was started on chemotherapy and \ncompleted one cycle of cytarabine and etoposide \nprotocol, which led to the improvement of cutaneous \nmanifestations. He was also counselled regarding the \noption of allogenic haemotopoetic stem cell \ntransplantation. \n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n Figure 1: Multiple indurated plaques at the trunk \n\n\n\nFigure 2A: Scattered periadnexal nodules in the dermis \nFigure 2B: Clusters of small to medium sized \npleomorphic blast with  high nucleo-cytoplasmic ratio \n\n\n\nFigure 3: Positive stains for CD4, CD56 and CD123 \n\n\n\nCD56+ CD4+ CD123+ \n\n\n\nACKNOWLEDGEMENT \nWe would like to thank the Department of Pathology, \nHospital Melaka  and Queen Elizabeth Hospital for \nproviding the histopathology images. \n \n\n\n\n\n\n\n\n2A 2B \n\n\n\n\n\n\n\n\n23 \n\n\n\nIntroduction \n\n\n\nMastocytosis is a rare disease characterized by a \ndisorderly mast cell accumulation in various organs, \nmanifesting through a wide range of clinical alterations \nand varies from indolent cutaneous forms to malignant \nand systemic conditions. The variants of cutaneous \nmastocytosis are urticaria pigmentosa, mastocytoma, \ndiffuse cutaneous mastocytosis (DCM), and \ntelangiectasia macularis eruptiva perstans. Bullous \nmastocytosis is a severe variant of diffuse cutaneous \nmastocytosis with approximately 30% cases manifesting \nwithin 6 months of age. It causes extensive blisterings \nand can be confused with other forms of infantile \nbullous disorders. \n \n\n\n\nCase Report \n\n\n\nA 6 month of girl was admitted with acute respiratory \ndistress, requiring ventilatory support after 2 days \nhistory of fever and cough. She was tachycardic and \nhypotensive, compounded by multiple episodes of \nvomiting and diarrhea. The child was small for her age, \nweighing 3.9 kg upon admission. Her birth weight was \n2.8 kg. At 1 month of age, she had asymptomatic brown \nmacules on her body. These lesions subsequently \nprogressed to pruritic red-brown plaques over the whole \nbody about 4 months later. The cutaneous lesions \neventually developed to tense blisters which became \nhemorrhagic and eroded 2 weeks after presentation. \nSystemic examination did not reveal any abnormality. \nDarier\u2019s sign was positive. \n \n\n\n\nDiscussion \n\n\n\nBullous mastocytosis is a rare and severe variant of \ncutaneous mastocytosis. It is associated with both \nlocal and systemic symptoms that are caused by the \nexcessive production of mast cell-secreted mediators \nsuch as histamine,  leukotrienes, proteases and \nheparin. Apart from the skin, gastrointestinal tract, \nspleen, liver and bones are commonly affected. Patients \nsuffering from mastocytosis often have cardiovascular \nmanifestations such as flushing, hypotension, \ntachycardia, syncope, as was noted in this child. The \ncommonest symptoms affecting gastrointestinal tract are \nvomiting and diarrhoea. This patient may also have \nmalabsorption as  she had poor weight gain. The main \ngoal of treatment is to control signs and symptoms caused \nby release of mast cells mediators. Combinations of H1 \nand H2 blocking agents have been the mainstay of \ntreatment for most of the uncomplicated bullous \nmastocytosis cases. Oral steroids have been reported in a \nfew case reports, to be useful in GI malsabsorption. This \nchild was started on cetirizine and ranitidine as well as a \n2 week course of prednisolone. There was improvement \nin the GI symptoms with no progression of the disease \nover a month period thereafter. Despite the relative rarity \nof bullous mastocytosis, the diagnosis of this disease is \nimportant. Patients with extensive blistering, neonatal \nonset and symptoms of vasodilatation are at a potential \nrisk of developing severe complications and death. It is \nimportant to distinguish this rare form of cutaneous \nmastocytosis from other blistering conditions in children. \n\n\n\nReferences \n\n\n\n1. Ko W.L, Lee W.R, Chou C.L. Bullous mastocytosis. J Exp Clin Med 2013;5(4):160-161 \n2. Ghosh A, Choudhury J, Dhar S. An infant with bullous mastocytosis: A rare form of bullous disorder. Indian J Paediatr Dermatol 2017;18:122-124 \n3. Asati DP, Tiwari A. Bullous mastocytosis in a 3-month-old infant. Indian Dermatol Online J 2014;5:497-500. \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nDiffuse Cutaneous Mastocytosis, \n\n\n\nBullous Variant,  \n\n\n\nIn A 6 Month Old Infant \n \n\n\n\nYoong Wei Lee1, Kwee Eng Tey1, Krishna Premalatawati2, Md Shah Md Shariman2 \n\n\n\n1Department of Dermatology, Sultanah Aminah Hospital Johor Bahru,  \n\n\n\nJohor, Malaysia \n2Department of Pathology, Sultanah Aminah Hospital Johor Bahru,  \n\n\n\nJohor, Malaysia \n25 \n\n\n\nLaboratory Results \n\n\n\nThe serum total tryptase level was elevated at 46.8 \u00b5g/L \n(normal level < 10 \u00b5g/L). Result of the child\u2019s complete \nblood cell count and differential was normal. Skin \nbiopsy showed a subepithelial bulla with aggregates of \nCD117 positive stained mast cells at the base and \nGiemsa stain highlighting cytoplasmic metachromatic \ngranules. These cells stained negative for Cd1a, S-100 \nand HMB-45. The clinical and histologic features were \ncompatible with the diagnosis of bullous mastocytosis. \n \n\n\n\nA B \n\n\n\nC D \n\n\n\nA. Subepidermal bulla (H&E \uf0b440) \nB. Mast cells densely filling the dermis below the bulla \n\n\n\n(H&E \uf0b4400) \nC. Positive CD117 stain (\uf0b440) \nD. Positive Giemsa stain highlighting intracytoplasmic \n\n\n\nmetachromatic granules in mast cells (\uf0b4400) \n\n\n\n\n\n\n\n\nTHE LIPS DON\u2019T LIE \u2013 A CASE OF \nOROFACIAL TUBERCULOID LEPROSY  \n\n\n\n\n\n\n\nTee Fuei Shian1, Latha Selvarajah1, Choon Siew Eng2 \n1Department of Dermatology, Hospital Sultan Ismail Johor Bahru, Johor, Malaysia \n\n\n\n2Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia \n\n\n\n26 \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFigure 3. Numerous foci of large granulomas seen \nbetween muscle bundles (H&E  X4) \n \n\n\n\nINTRODUCTION \n\u2022 Leprosy is a chronic granulomatous infectious disease with an insidious onset1.  \n\u2022 The clinical presentation varies from few to widespread lesions, while oral manifestations are rare2. \n\u2022 We report a case of tuberculoid leprosy in a middle-aged Malaysian gentleman with orofacial swelling. \n\n\n\nCASE REPORT \nThis is a 43 year-old Malaysian Indian gentleman who presented with a painless swelling over his lips and \nface for 6 months. There was no preceeding trauma. He denied any close contact with leprosy patients.  \nClinically there was a firm, non tender erythematous swelling extending from the area below the left side of \nhis nose to his left upper lip (Figure 1). There were no thickened nerves or hypoaesthetic patches. He was \notherwise well. \nA biopsy was taken from the mucosal area of the left side of his upper lip. Histopathological examination \nrevealed tuberculoid granulomatous inflammation, but acid-fast bacilli stain was negative (Figure 2 & 3). \nTissue cultures for fungal and mycobacterium tuberculosis, and tissue for mycobacterium leprae PCR were \nall negative. Slit skin smear was also negative.  \nA diagnosis of tuberculoid leprosy with type 1 reaction was made. He was commenced on paucibacillary \nregime with oral prednisolone, and is responding well to treatment.  \n\n\n\nFigure 1: Erythematous swelling over left side of upper lip extending to area below left side of nose (left). Image on right shows the \nclinical improvement after 2 months of treatment. \n\n\n\nFigure 2: Oral mucosal biopsy showing numerous foci of \nlarge granulomas between muscle bundles (H&E  X4) \n \n\n\n\nFigure 3: These granulomas compose of well-formed epitheloid \nhistiocytes and multinucleated giant cells, and are surrounded \nby lymphocytes (H&E  X10). AFB stain was negative. \n\n\n\nDISCUSSION / CONCLUSION \n\u2022 Leprosy is usually characterized by erythematous or hypopigmented macules with peripheral sensorimotor \n\n\n\nneuropathies, and rarely affects the oral mucosa3. \n\u2022 This case emphasizes the importance of high index of suspicion for leprosy in cases with atypical presentation.  \n\u2022 Clinical diagnosis is paramount, especially with leprosy reactions, where histopathological changes may be subtle with \n\n\n\nnegative mycobacteria staining.   \n\n\n\nREFERENCES \n1. Walker SL, Lockwood DN. Leprosy. Clin Dermatol 2007;25:165\u201372. \n2. de Abreu MA, Michalany NS, Weckx LL, Neto Pimentel DR, Hirata CH, de Avelar Alchorne MM. The oral mucosa in leprosy: a clinical and \n\n\n\nhistopathological study. Braz J Otorhinolaryngol. 2006;72:312-6. \n3. Chimenos K\u00fcstner E, Pascual Cruz M, Pinol Dansis C, Vinals Iglesias H, Rodr\u00edguez de Rivera Campillo ME, L\u00f3pez L\u00f3pez J. Lepromatous leprosy: a \n\n\n\nreview and case report. Med Oral Patol Oral Cir Bucal. 2006;11:E474-9. \n\n\n\n\u2022 Special thanks to Dr Nur Fazilah Mohd Tahir, Department of Oral Surgery, Hospital Sultan Ismail Johor Bahru, and Dr Shariman, \nDepartment of Pathology, Hospital Sultanah Aminah Johor Bahru for their contributions.  \n\n\n\n\u2022 No conflict of interest declared. \n\n\n\n\n\n\n\n\nJenny TYL1, Leong KF1, Baharom ZF2, Sabeera BKI1\t\n\r\n1Department of Paediatric Dermatology, Institute Pediatric Hospital Kuala Lumpur\t\n\r\n2Department of Pathology, Hospital Kuala Lumpur\t\n\r\n\n\n\n28 \nSelf healing Infantile Familial \nCutaneous Mucinosis: Case Report\t\n\r\n\n\n\nIntroduction \nSelf- healing Cutaneous Mucinosis is a rare disease characterized by transient cutaneous lesions and sometimes mild \ninflammatory symptoms. In this report, we describe one of the youngest patient with this condition.   \n\n\n\nCase Report \n Patient is a 2 month old Malay boy who presented with \n\n\n\ngeneralise skin lesions that begin at 1 month old. Lesions initially only \ninvolving bilateral cheek but progressively increasing involving the \nwhole body. The lesions were asymptomatic and patient otherwise \nwas well.  \n\n\n\n He was born full term with birth weight of 3.33kg. \nAntenatally, mother had gestational diabetes mellitus on diet control \nand anemia. Postnatal, he was observed in ward for 5 days for being \nG6PD deficiency. His growth and development were appropriate for \nhis age. \n  He was the youngest of 4 siblings, product of non \nconsanguinous marriage. His eldest brother had similar skin lesions \nduring neonatal period which totally resolved by 1 year old. \n\n\n\n Physical examination revealed generalize skin lesions, more \nprominent over the face and acral region with involvement of the \npalms and soles. There was no involvement of the scalp and mucous \nmembrane. Skin lesions consist of erythematous non follicular \npapules which coalesce forming plaques. Lesions were blanchable \nand there were no overlying epidermal changes. These lesions \nresolve with post inflammatory hyperpigmentation. \n\n\n\n The clinical differential diagnosis included congenital \nsyphilis, langerhan cell histiocytosis and neonatal lupus \nerythomatosus. \n\n\n\n Laboratory workup including complete blood cell count, C-\nreactive protein, antistreptolysin O titer, erythrocyte sedimentation \nrate, liver transaminases, creatinine and urinalysis were within normal \nlimits. Immunologic workup included antinuclear antibody, anti-Ro, \nanti-La, C3, C4, IgA, IgG, IgM, complement factor and rheumatoid \nfactor. All were within normal limits. \n\n\n\n A punch biopsy of the left thigh was performed. Results \nrevealed mild acanthosis and mild increased in melanocytes in the \nepidermis. There is no lichenoid reaction. Scattered melanin pigment \nladen macrophages are seen at the superficial dermis extending \ndown to the deep dermis. There were extracellular mucin \ndemonstrated in the papillary dermis. Immunofluorescence study \nshowed no antibody deposition (IgG, IgA, IgM, C3). \n\n\n\n At 5 months follow up, the patient was noted to have \nresolution of some lesions and development of some new lesions. He \nhas subsequently been lost to follow up. \n\n\n\nH&E x100. Normal epidermis with sparse \nperivascular lymphocytic infiltration. \n\n\n\nAlcian blue x200. There is superficial dermal \nmucin deposition in the papillary dermis \n  \n\n\n\nAlcian blue x400. Mucin deposition in the \npapillary dermis \n\n\n\nDiscussion \n The cutaneous mucinoses are a heterogenous group of \n\n\n\ndisorders in which mucin accumulate in the skin or within the hair \nfollicle.  \n\n\n\n Depending on the clinical manifestations, cutaneous \nmucinoses may be divided into localized or diffuse forms. In addition, \nthey may he classified as primary or secondary to neoplastic or \ninflammatory disorders. Furthermore, cutaneous mucinoses may \ninvolve only the skin or may be associated with other systemic \npathology such as thyroid disorders, diabetes mellitus, lymphoma, or \nmucoplysaccharidosis.  \n\n\n\n This case is unique in its presentation with coexisting \nprogressive and self healing lesions which present during infancy. In \naddition, its familial with 2 brothers having similar skin lesions. \n \nConclusion \n\n\n\n Awareness of this condition is important because its course \nis benign, no treatment is required, and parents can be reassured.  \n\n\n\nReferences \n1.\u202f Rongioletti F, Rebora .A. The new cutaneous mucinoses: a review with an \n\n\n\nup-to-dale classification of cutaneou.s mu- cinoses. J Am Acad Dermalol \n1991.24:265-270. \n\n\n\n2.\u202f Stokes K.S, Rabinowitz LG, Segura AD, Esterly NB. Cu- taneous mucinosis \nof infancy. Pediatr Dermatol 1994;! 1: 246-251.  \n\n\n\n3.\u202f  Pucevich .MV, Latour DL, Bale GF. King LE. Self-healing juvenile \ncutaneous mucinosis. J .Am Acad Dermatol 1984: 11:327-3.32.  \n\n\n\n\n\n\n\nFigure 1: Generalise symmetrical, erythematous \npapules and plaques involving palms and soles. \nSparing of scalp and mucous membrane. \n\n\n\n\n\n\n\n\nMulticentric Reticulohistiocytosis: A Rare Case Report\n\u2022YC Teh1, WM Kho2, Azah Syahrina3, Pubalan M2\n\n\n\n\u20221Medical Department, Miri Hospital\n\u20222Dermatology Department, Sarawak General Hospital\n\n\n\n\u20223Pathology Department, Sarawak General Hospital\n\n\n\n29\n\n\n\nIntroduction\nMulticentric reticulohistiocytosis (MRH) is a rare \nmultisystem disorder of unknown aetiology that is \ncharacterized by erosive arthritis and papulonodular \nlesions on the skin, mucous membranes, and \ninternal organs. Females are affected more than \nmales, with ratio of 3:1.1\n\n\n\nCase Report\nA 57-year-old man, presented with generalised skin \nrash and multiple small hand joints pain  for 4 years. \nH e  h a d  a r t h r a l g i a  o v e r  b o t h  h a n d  d i s t a l \ninterphalangeal joint, proximal interphalangeal joint \nand wrist joint. There was no morning stiffness of \nthe joints. On examination, there are multiple non \npruritic reddish-brown paulonodular skin lesion over \nbody trunk, head, ear helices, both upper and lower \nlimbs without any mucosal involvement (Fig 1,2). \nHis blood test revealed dyslipidemia. There was no \nanemia, ESR was not raised, ANA and rheumatoid \nfactor were negative. Histopathological examination \nrevealed nodular proliferation of histiocyte and \nmultinucleated giant cells at superficial dermis \n(slides 1&2). Immunohistochemical study shows the \ncells are positive for CD68 and negative to CD10. \nBilateral hand radiograph revealed symmetrical \nmarginal erosion over hand joints(Fig 3). Ultrasound \nof the abdomen revealed no mass.\n\n\n\nFigure 1: Multiple reddish brown papulonodule over limbs, \ntrunk\n\n\n\nFigure 2: reddish-brown papulonodule over acral\n\n\n\nDiscussion \nMRH is  a c lass I I  or  non-Langerhans ce l l \nhistiocytosis, characterized by local proliferation of \nresident mononuclear phagocytes other than \nLangerhans cell. It consist of nonpruritic, flesh \ncoloured to reddish brown yellow papules and \nnodules that may be found anywhere in the body \nwith a predilection for face, hand and around joints.  \nSmall papules are found around nail folds which \nare called \u2018coral beads\u2019 represent typical clinical \nsign.\u00a0There is association with malignancy, \ntuberculosis, dyslipidemia and autoimmune \nd isease.  Mal ignancy can occur  in  25% of \npatients.2,3\n\n\n\nConclusion\nMRH is a rare disease. High index of suspicion is \nneeded to diagnose MRH in patient presented \nwith erosive arthritis with papulonodular skin \nlesions, and to exclude underlying malignancy.\n\n\n\nReference:\n1. Shah SP, Shah AM, Prajapati SM, Bilimoria FE. Multicentric \n\n\n\nreticulohistiocytosis. Indian Dermatol Online J. 2011 Jul-Dec; 2(2): \n85\u201387\n\n\n\n2. Snow L,  Mul ler  SA.  Mal ignancy-associated mul t icent r ic \nreticulohistiocytosis: a clinical, histological and immunophenotypic \nstudy. Br J Dermatol 1995;133(1): 71-76\n\n\n\n3. Han L, Huang Q, Liao KH. Multicentric reticulohistiocytosis \nassociated with liver carcinoma: report of a case. Case Rep \nDermatol. 2012 May-Aug; 4(2): 163\u2013169\n\n\n\nSlide 1 and  2 (x400):  Section of skin show unremarkable \nepidermis. There is nodular  proliferation of histiocytes \nand multinucleated giant cells at superficial  dermis.\n\n\n\nFig 3: Symmetrical marginal erosion on bilateral \nhand xray\n\n\n\n\n\n\n\n\nCase Series of Acrodermatitis Enteropathica\nin Langkawi Hospital\n\n\n\nSW Lee1, SY Ooi1, WC Tan2\n\n\n\n1Deparment of Medicine, Hospital Langkawi, Kedah, Malaysia\n2Department of Dermatology, Hospital Pulau Pinang, Penang, Malaysia\n\n\n\n30\n\n\n\nINTRODUCTION\nAcrodermatitis enteropathica is a rare dermatosis related to zinc deficiency, manifests as acral and periorificial dermatitis, \nalopecia, intractable diarrhoea and failure to thrive. It can be classified into primary zinc deficiency, which is genetically based \nand acquired secondary deficiency. \n\n\n\nCASE REPORT\nWe report 3 cases of AE, presented as symmetrical \nerythematous, squamous or eczematous lesions, located around \nperioral, anogenital and acral areas. Two of them are siblings, \ndiagnosed in Malacca and later transferred to Langkawi hospital \nfor follow up; and a newly diagnosed infant who developed AE \ndue to nutritional zinc deficiency. \n\n\n\nPatient 1: A 10 year old Malay girl, who presented with \npsoriasiform plaques at lower limbs at 3 years old. Her younger \nbrother (Patient 2) also suffered from similar unresolved \npsoriasiform skin lesions. There were no hair changes and no \nchronic diarrhoea. Oral zinc was given to both siblings with serial \nzinc level monitoring, and skin lesions resolved after that. They \nwere transferred to Langkawi hospital for continuation of follow \nup since 2015, and disease remain stable up to date. \n\n\n\nPatient 3, an eight-month old baby boy, presented with \ngeneralized itchy scaly rash for 3 weeks duration. The rash  \nstarted on bilateral calf and expanded to trunk and head \ninvolving face and scalp, gradually progress to superficial \nblistering associated with weepy excoriation over groin and \nperianal region. Further history revealed a child with poor social \n& financial support. He was taken care by his mother together \nwith a 3-year-old sister, father being imprisoned. Breastfeeding \nwas given for first 2 months then followed by diluted condensed \nmilk without proper weaning diet. \n\n\n\nWe saw a generalized oedematous baby having extensive skin \ndesquamation and depigmentation over limbs, with tender \nweepy erosion over groin area. Scanty short brittle hair over \nscalp. He was first treated as possible staphylococcus scalded \nskin syndrome. Upon referral to dermatology team on day 3 \nadmission, the diagnosis was revised to acrodermatitis\nenteropathica with possible kwashiorkor disease and was later \nconfirmed by a low serum zinc level of 10 ug/dl. \n\n\n\nHe was assessed by dietician and started on formula milk \n(lactogen), which deliver around 4mg of zinc per day; on top of \nintroduction of solid diet. His skin lesion improved within a week \nof diet modification, and completely resolved upon discharge \nafter 1 week time, leaving post inflammatory hypopigmentation. \n\n\n\nDISCUSSION \nAcrodermatitis enteropathica is related to zinc deficiency, \neither primary deficiency or acquired secondary deficiency. \n\n\n\nHereditary AE is caused by autosomal recessive mutation of \nSLC39A4 gene on chromosome 8q24.3 which encodes the \nZIP4 zinc transporter, leading to impaired zinc absorption \nmainly from small intestine. \n\n\n\nAcquired form is more common than hereditary form, which \noccur in poor diets such as anorexic and alcoholics; \nmalabsoprtion conditions such as inflammatory bowel \ndisease and coeliac disease; an excess of phytate diet (cereal \ngrains); increase in metabolic demands such as malignancy, \nburns; medications-induced; pregnancy and renal disease.\nZinc deficiency is frequently found in premature infants due \nto increased demand, insufficient stores, impaired \nabsorption and increased urinary, gastrointestinal tract and \ncutaneous losses of zinc.\n\n\n\nClinical findings of AE include characteristic eczematous, \nbullous cutaneous lesions on periorificial and acral sites, \nalopecia, and intractable diarrhoea. However the triad is only \ncomplete in 20% of AE patients. If left untreated can be \ndevastating, ranging from growth retardation, \nneuropsychiatric features, associated immunodeficiency, \ndelayed wound healing and secondary bacterial/fungal \ninfection with sepsis often lead to death.\n\n\n\nAE is diagnosed primarily by clinical manifestations and \nfurther supported with low plasma zinc level. Good recovery \nwith zinc supplement confirmed the diagnosis of AE. The cut-\noff point of plasma zinc level is 50ug/dl. However, in 30% of \ndiagnosed AE, the zinc deficiency occur with normal level of \nplasma zinc, due to the impairment of zinc biologic action at \nthe actual site where zinc is released from blood to \nmicroenvironment, thus reducing the actual bioavailability of \nzinc.\n\n\n\nHistopathology findings usually consistent with deficiency \ndermatitis, include cytoplasmic pallor, vacuolization, \nballooning degeneration causing subcorneal &\nintraepidermal clefts , and subsequent confluent necrosis of \nkeratinocytes within the superficial stratum spinosum and \nstratum granulosum of the epidermis. In chronic or resolving \nAE, the fully developed necrolysis is minimal; psoriasiform\nhyperplasia, parakeratosis with variable neutrophils are often \nindistinguishable with psoriasis and other chronic dermatitis. \n\n\n\nRapid recovery is usually observed with prompt zinc \nsupplement, generally started at 2-3 mg/kg/d of elemental \nzinc, most patients require 1-10mg/kg/day of oral zinc \npreparation. Plasma zinc levels and zinc-dependent enzyme \nlevels should be monitored every 3 to 6 months for \nappropriate dose adjustment.\n\n\n\nThe limitations of our case report are that skin biopsy was \nnot performed in view of the young age of patients with \ndifficult sedation and also the patient defaulted follow up.\n\n\n\n\n\n\n\n   \nFig 1: Case 3 : acral and periorificial dermatitis with alopecia on presentation \n\n\n\n   \nFig 2: Case 3 : resolution of skin desquamation and growth of hair after 1 week \n\n\n\nReferences \n1. Michaellson G. Zinc therapy in acrodermatitis enteropathica, Acta Derm Venereol 1974.\n2. Kambe T et al. Overview of Inherited Zinc Deficiency in Infants and Children. J Nutr Sci Vitaminol (Tokyo) 2015.\n3. Lakdawala N et al. Acrodermatitis enteropathica and other nutritional diseases of the folds (intertriginous areas) Clinics in dermatology 2015.\n4. Chue CD et al. An acrodermatitis enteropathica-like eruption secondary to acquired zinc deficiency in an exclusively breast-fed premature infant. Int J Dermatol 2008.\n5. Maverakis E et al. Acrodermatitis enteropathica and an overview of zinc metabolism. JAAD 2007.\n6. Lee SY et al. A case of acrodermatitis enteropathica localized on the hands and feet with a normal serum zinc level. Ann Dermatol 2011\n\n\n\nCONCLUSION\nOur case emphasises that one should think broadly when treating childhood skin disorders.  Diagnosis on AE requires a high index of \nsuspicion. AE is diagnosed primarily by clinical manifestation, low serum zinc level, and good recovery with zinc supplementation. An \nearly diagnosis and prompt treatment of AE reduces mortality and prevents the long-term consequences of zinc deficiency.\n\n\n\n\n\n\n\n\nIntroduction \n\n\n\nCase report \n\n\n\nAngioimmunoblastic T Cell Lymphoma ( AITL) \n\n\n\nremains a diagnostic challenge due to its \n\n\n\nconstellation of diverse presentations which \n\n\n\ninclude diffuse lymphadenopathy, \n\n\n\nhepatosplenomegaly and constitutional \n\n\n\nsymptoms1-3. The polymorphism of cutaneous \n\n\n\npresentations of AITL causes a diagnostic dilemma \n\n\n\nto dermatologists. Furthermore, the non specific \n\n\n\nhistological features from the skin often leads to \n\n\n\ndelayed diagnosis4. The common histological skin \n\n\n\ncharacteristics seen in AITL include perivascular \n\n\n\ninfiltrate, vascular hyperplasia or proliferation and \n\n\n\nvasculitis4. Other uncommon cutaneous \n\n\n\nhistological findings include granulomatous \n\n\n\ndermatitides, prurigo eruptions,atypical linear IgA \n\n\n\ndermatosis form and epidermotropic form \n\n\n\nmimicking myocosis fungoides4. Therefore AITL is \n\n\n\ndiagnosed by lymph node biopsy which remains \n\n\n\nthe gold standard5. To our knowledge, this is the \n\n\n\nfirst case in Malaysia where the skin biopsy has \n\n\n\nconclusively diagnosed AITL. Given the lack of \n\n\n\ndiagnostic clinical and histological characteristics \n\n\n\nof cutaneous AITL, dermatologists must maintain a \n\n\n\nhigh index of suspicion when skin lesions are \n\n\n\nrefractory to standard treatment and continue to \n\n\n\nascertain an accurate clinical diagnosis in order to \n\n\n\nimprove survival. \n\n\n\n \n1. Lachenal F et al. Angioimmunoblastic T-cell lymphoma: \n\n\n\nclinical and laboratory features at diagnosis in 77 patients. \n\n\n\nMedicine (Baltimore). 2007 Sep;86(5):282-92. \n\n\n\n2. Balaraman B et al. Evaluation of cutaneous \n\n\n\nangioimmunoblastic T-cell lymphoma. J Am Acad Dermatol. \n\n\n\n2011 Oct;65(4):855-62.  \n\n\n\n3. Ocampo-Garza J et al. Angioimmunoblastic T-cell \n\n\n\nlymphoma: a diagnostic challenge. Case Rep Dermatol. \n\n\n\n2014 Dec 17;6(3):291-5. \n\n\n\n4. Kaffenberger B et al.Extranodal Marginal Zone Lymphoma-\n\n\n\nlike Presentations of Angioimmunoblastic T-Cell Lymphoma: \n\n\n\nA T-Cell Lymphoma Masquerading as a B-Cell \n\n\n\nLymphoproliferative Disorder. Am J Dermatopathol. 2015 \n\n\n\nAug;37(8):604-13. \n\n\n\n5. Sachsida-Colombo E et, al. A difficult case of \n\n\n\nangioimmunoblastic T-cell lymphoma to diagnose. Rev Bras \n\n\n\nHematol Hemoter.2016 Jan-Feb;38(1):82-5. \n\n\n\nAcknowledgement \n\n\n\nPicture 1 \n\n\n\n\n\n\n\nA Case Report of Angioimmunoblastic T Cell Lymphoma \n\n\n\nand The Skin: A Diagnostic Challenge \nSuthananthan CA, Gunabalasingam P \n\n\n\nDepartment of Dermatology, Hospital Melaka, Melaka, Malaysia \n\n\n\n\n\n\n\n31 \n\n\n\nAngioimmunoblastic T Cell Lymphoma (AITL) is a \n\n\n\ndistinct form of peripheral T cell lymphoma that presents \n\n\n\nwith diffuse lymphadenopathy,hepatosplenomegaly and \n\n\n\nB cell symptoms1,2.  Skin manifestations occur in up to \n\n\n\n50% of patients with AITL and usually presents as a non \n\n\n\nspecific macularpapular rash. The other plethora of \n\n\n\ndermatological presentations include petechiae,purpura, \n\n\n\nnodules and urticaria1-3 .The histological features of AITL \n\n\n\nin the skin are subtle therefore the gold standard for the \n\n\n\ndiagnosis of AITL remains excisional lymph node \n\n\n\nbiopsy4,5. \n\n\n\nA 78 year old Chinese gentleman with a history of \n\n\n\nhearing difficulties and hypertension presented with a \n\n\n\none year duration of indurated hyperpigmented plaques \n\n\n\nover his back with associated right cervical \n\n\n\nlymphadenopathy. His initial skin biopsy showed chronic \n\n\n\ninflammation without the evidence of malignancy.  Initial \n\n\n\nrepeated biopsies demonstrated  granulomatous \n\n\n\ninflammation without the evidence of malignancy. He \n\n\n\nsubsequently progressed to develop nodular lesions on \n\n\n\nhis trunk, face and limbs( Picture 1) with hepatomegaly \n\n\n\nand multiple lymph nodes involving his axilla, cervical \n\n\n\nand inguinal region. The cervical lymph node biopsy \n\n\n\nshowed features of dermatopathic lymphadenopathy. A \n\n\n\nCT Scan of his thorax, abdomen and pelvis revealed \n\n\n\nbilateral axillary and inguinal nodal and liver \n\n\n\ninvolvement. In view of the high index of suspicion \n\n\n\nrepeated biopsies was done and finally demonstrated \n\n\n\nfeatures of cutaneous angioimmunoblastic T cell \n\n\n\nlymphoma. The patient was started on Narrow Band \n\n\n\nUltra Violet B(NBUVB) by the dermatologist and on a \n\n\n\npalliative regimen of cyclophosphamide and \n\n\n\ndexametasone/prednisolone by the hematologist. \n\n\n\nUnfortunately he progressively deteriorated and passed \n\n\n\naway secondary to aspiration pneumonia with an acute \n\n\n\nstroke.  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFigure 1                              Figure 2 \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nHistopathology \n\n\n\nThe diagnostic skin biopsy demonstrated irregular \n\n\n\nperivascular nodules of atypical lymphoid cells \n\n\n\naggregates. These cells are large, moderately \n\n\n\npleomorphic and exhibiting vesicular nuclei with \n\n\n\nprominent nucleoli. These atypical lymphoid cells \n\n\n\nexpress almost all T-markers (Pan-T markers) (strong & \n\n\n\ndiffuse: CD2+;CD3+;CD5+;CD4+, lesser CD7+ & CD8+ \n\n\n\nand CD 56-. Strong & diffuse PD1+) The lesion shows \n\n\n\nmoderate proliferation rate (Ki67 in between 20-30% \n\n\n\nonly). \n\n\n\nDiscussion/Conclusion \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFigure 1:CD34 negative, CD21 negative and PD1 positive \n\n\n\nneoplastic cells \n\n\n\nFigure 2: Neoplastic cells are expressing all T-cell markers. \n\n\n\nWe would like to thank the Department of Pathology \n\n\n\nHospital Melaka and Queen Elizabeth Hospital for \n\n\n\nproviding the histopathology images. \n\n\n\nReferences: \n\n\n\nPicture 1: \n\n\n\nHyperpigmented \n\n\n\nplaques and \n\n\n\nnodules over the \n\n\n\npatients back  \n\n\n\n \n\n\n\n\n\n\n\n\nRESEARCH POSTER PRESENTATION DESIGN \u00a9 2015\n\n\n\nwww.PosterPresentations.com\n\n\n\nClique Clinic   4, Jalan 19/36, Seksyen 19, 46300 Petaling Jaya, Selangor, Malaysia. www.cliqueclinic.com\n\n\n\nThis case series aims to investigate the safety and efficacy of utilizing the \n\n\n\nCutera Enlighten 1064Nm picosecond laser with Multi Lens Array (MLA) for \n\n\n\nthe treatment of acne scarring. \n\n\n\nIntroduction\n\n\n\nResults\n\n\n\nResults\n\n\n\nCase 3 \n\n\n\nLeft: Before treatment. Right: Follow up visit at 8 weeks post 2 treatments \n\n\n\nDiscussion\n\n\n\nCase 4\n\n\n\nLeft: Before treatment. Right: Follow up visit at 4 weeks post 1 treatment session\n\n\n\nConclusion\n\u2022 This study shows that treatment of facial acne scars by 1064nm \n\n\n\npicosecond laser with a diffractive lens array produced \n\n\n\nimprovement in appearance and texture during a 5 months follow \n\n\n\nup. \n\n\n\n\u2022 Minimal adverse affects were reported. \n\n\n\n\u2022 A longer duration of treatment and follow up as well as a larger \n\n\n\nnumber of subjects is recommended for a better understanding of \n\n\n\nthe effects of Picosecond laser with MLA for treatment of acne \n\n\n\nscars.  \n\n\n\nCase 1\n\n\n\nLeft: Before treatment. Right: Follow up visit after 5 months post 5 treatments \n\n\n\nDr Bob Klajo anak Edmund John, Dr Tingsong Lim\n\n\n\nDepartment of Aesthetic Medicine, Clique Clinic\n\n\n\nCase series: The use of Cutera Enlighten Picosecond Laser with \n\n\n\nMulti Lens Array (MLA) in Treatment of Facial Acne Scarring\n\n\n\nObjectives\n\n\n\nAcne is a common disease that affects mostly adolescents. More often \n\n\n\nthan not, acne is associated with acne scarring which is permanent. \n\n\n\nTreatment for acne scarring has been well studied, but novel treatments \n\n\n\nare emerging. One of the most recently introduced treatment for acne \n\n\n\nscars would be the use of Picosecond laser with lens array.\n\n\n\nMethodology\n\u2022 Subjects who are affected by acne scarring are recruited into the \n\n\n\nstudy. Four subjects are enrolled, three males and one female, age \n\n\n\nranging from 22 to 30 years old. \n\n\n\n\u2022 Subjects are screened for any contraindications for treatment including \n\n\n\nuse of oral isotretinoin. They provided informed consent to be involved \n\n\n\nin this study. \n\n\n\n\u2022 Post laser care including the application of sun protection was \n\n\n\nreinforced to the subjects. \n\n\n\n\u2022 Photos were taken before treatment as well as for every subsequent \n\n\n\nvisits for comparison and monitoring the progress. \n\n\n\n\u2022 Pain management include the use of numbing cream Lidocaine \n\n\n\n10.56%.\n\n\n\nCase 2\n\n\n\nLeft: Before treatment. Right: Follow up after 5 months post 7 treatment sessions\n\n\n\n\u2022 Lasers, intense pulsed light, and other energy devices are also \n\n\n\nregularly used in the treatment of scarring and fractional \n\n\n\nresurfacing, whether with ablative or nonablative devices, and \n\n\n\nhave become the current standard of care. \n\n\n\n\u2022 Brauer et al previously described the use of a picosecond 755-nm \n\n\n\nlaser (Cynosure) with a diffractive lens array in the treatment of \n\n\n\nfacial acne scarring. This specialized optic affects more surface \n\n\n\narea, has a greater pattern density per pulse, and may improve the \n\n\n\nappearance of acne scars. \n\n\n\n\u2022 This current study has the objective to study safety and efficacy of \n\n\n\nusing the Cutera Enlighten picosecond laser with patented Multi \n\n\n\nLens Array for treatment of acne scars. \n\n\n\n\u2022 The adverse affects reported were mainly pain during procedure \n\n\n\nand petechiae that lasted for 7-10 days. No other significant \n\n\n\nadverse affects were reported, including Herpes Simplex \n\n\n\nreactivation. \n\n\n\nReferences\n\u2022 Brauer, J.A., Kazlouskaya, V., Alabdulrazzaq, H., Bae, Y.S., Bernstein, \n\n\n\nL.J., Anolik, R., Heller, P.A. and Geronemus, R.G., 2015. Use of a \n\n\n\npicosecond pulse duration laser with specialized optic for treatment \n\n\n\nof facial acne scarring. JAMA dermatology, 151(3), pp.278-284.\n\n\n\nAcknowledgement\n\n\n\n\u2022 Special thanks to Clique Clinic and to all individuals who have \n\n\n\ncontributed whether directly or indirectly to this study\n\n\n\n32\n\n\n\n\n\n\n\n\n  Lest\t\r \u00a0we\t\r \u00a0forget:\t\r \u00a0Lucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0\n\t\r \u00a0 \t\r \u00a0Voo\t\r \u00a0SYM1,\t\r \u00a0Teoh\t\r \u00a0XY2,\t\r \u00a0Tan\t\r \u00a0WC3,\t\r \u00a0Chan\t\r \u00a0LC5,\t\r \u00a0Ramalingan\t\r \u00a0R5,\t\r \u00a0Tang\t\r \u00a0MM6\t\r \u00a0\n\n\n\n\t\r \u00a0 \t\r \u00a01Department\t\r \u00a0of\t\r \u00a0Dermatology,\t\r \u00a0Hospital\t\r \u00a0Queen\t\r \u00a0Elizabeth,\t\r \u00a0Kota\t\r \u00a0Kinabalu,\t\r \u00a0Sabah,\t\r \u00a0Malaysia\t\r \u00a0\n\t\r \u00a0 \t\r \u00a02Department\t\r \u00a0of\t\r \u00a0Medicine,\t\r \u00a0Hospital\t\r \u00a0Queen\t\r \u00a0Elizabeth,\t\r \u00a0Kota\t\r \u00a0Kinabalu,\t\r \u00a0Sabah,\t\r \u00a0Malaysia\t\r \u00a0\n\t\r \u00a0 \t\r \u00a03Department\t\r \u00a0of\t\r \u00a0Dermatology,\t\r \u00a0Hospital\t\r \u00a0Sultanah\t\r \u00a0Bahiyah,\t\r \u00a0Alor\t\r \u00a0Setar,\t\r \u00a0Kedah,\t\r \u00a0Malaysia\t\r \u00a0\n\t\r \u00a0 \t\r \u00a04Department\t\r \u00a0of\t\r \u00a0Dermatology,\t\r \u00a0Hospital\t\r \u00a0Pulau\t\r \u00a0Pinang,\t\r \u00a0Malaysia\t\r \u00a0\n\t\r \u00a0 \t\r \u00a05Department\t\r \u00a0of\t\r \u00a0Dermatology,\t\r \u00a0Hospital\t\r \u00a0Tengku\t\r \u00a0Ampuan\t\r \u00a0Afzan,\t\r \u00a0Kuantan,\t\r \u00a0Pahang,\t\r \u00a0Malaysia\t\r \u00a0\n\t\r \u00a0 \t\r \u00a06Department\t\r \u00a0of\t\r \u00a0Dermatology,\t\r \u00a0Hospital\t\r \u00a0Kuala\t\r \u00a0Lumpur,\t\r \u00a0Kuala\t\r \u00a0Lumpur,\t\r \u00a0Malaysia\t\r \u00a0\n\n\n\n33 \n\n\n\nFigure\t\r \u00a02a:\t\r \u00a0\t\r \u00a0\nWaxy\t\r \u00a0infiltraTon,\t\r \u00a0\t\r \u00a0\t\r \u00a0\n\n\n\nloss\t\r \u00a0of\t\r \u00a0eyebrows\t\r \u00a0and\t\r \u00a0\nnecroTc\t\r \u00a0crusted\t\r \u00a0ulcers\t\r \u00a0\n\n\n\nFigure\t\r \u00a02b:\t\r \u00a0\t\r \u00a0\nConfluent\t\r \u00a0reTculate\t\r \u00a0purpuric\t\r \u00a0\npatches\t\r \u00a0with\t\r \u00a0bullae\t\r \u00a0at\t\r \u00a0the\t\r \u00a0\n\n\n\nlower\t\r \u00a0extremiTes\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\n\n\n\nINTRODUCTION\t\r \u00a0\n\t\r \u00a0\n\n\n\nLucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0is\t\r \u00a0an\t\r \u00a0uncommon\t\r \u00a0presentaTon\t\r \u00a0of\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\nleprosy,\t\r \u00a0which\t\r \u00a0is\t\r \u00a0characterized\t\r \u00a0by\t\r \u00a0reTculate\t\r \u00a0purpura\t\r \u00a0and\t\r \u00a0or\t\r \u00a0\ngeometrical\t\r \u00a0ulcers\t\r \u00a0that\t\r \u00a0heal\t\r \u00a0with\t\r \u00a0atrophic\t\r \u00a0stellate\t\r \u00a0scarring.\t\r \u00a0\nThe\t\r \u00a0aim\t\r \u00a0of\t\r \u00a0this\t\r \u00a0study\t\r \u00a0is\t\r \u00a0to\t\r \u00a0review\t\r \u00a0the\t\r \u00a0clinical\t\r \u00a0presentaTons\t\r \u00a0\nand\t\r \u00a0outcome\t\r \u00a0of\t\r \u00a0paTents\t\r \u00a0with\t\r \u00a0lucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0seen\t\r \u00a0in\t\r \u00a0\nfive\t\r \u00a0dermatology\t\r \u00a0referral\t\r \u00a0hospitals.\t\r \u00a0\n\n\n\n\t\n\rMETHODOLOGY\t\r \u00a0\n\t\r \u00a0\n\n\n\nThis\t\r \u00a0is\t\r \u00a0a\t\r \u00a0retrospecTve\t\r \u00a0review\t\r \u00a0on\t\r \u00a0all\t\r \u00a0the\t\r \u00a0paTents\t\r \u00a0with\t\r \u00a0lucio\u2019s\t\r \u00a0\nphenomenon\t\r \u00a0diagnosed\t\r \u00a0and\t\r \u00a0managed\t\r \u00a0in\t\r \u00a0Hospital\t\r \u00a0Queen\t\r \u00a0\nElizabeth\t\r \u00a0Hospital,\t\r \u00a0Sabah,\t\r \u00a0Hospital\t\r \u00a0Sultanah\t\r \u00a0Bahiyah,\t\r \u00a0\nKedah,\t\r \u00a0Hospital\t\r \u00a0Pulau\t\r \u00a0Pinang,\t\r \u00a0Penang,\t\r \u00a0Hospital\t\r \u00a0Tengku\t\r \u00a0\nAmpuan\t\r \u00a0Afzan,\t\r \u00a0Pahang\t\r \u00a0and\t\r \u00a0Hospital\t\r \u00a0Kuala\t\r \u00a0Lumpur,\t\r \u00a0Kuala\t\r \u00a0\nLumpur\t\r \u00a0over\t\r \u00a0the\t\r \u00a0last\t\r \u00a015\t\r \u00a0years\t\r \u00a0from\t\r \u00a02003\t\r \u00a0to\t\r \u00a02017.\t\r \u00a0\n\t\r \u00a0\n\n\n\n\t\r \u00a0\n\n\n\n\n\n\n\nRESULTS\t\r \u00a0\n\t\r \u00a0\n\n\n\n\u2022\u202f There\t\r \u00a0were\t\r \u00a018\t\r \u00a0paTents\t\r \u00a0with\t\r \u00a0male\t\r \u00a0to\t\r \u00a0female\t\r \u00a0raTo\t\r \u00a02:1\t\r \u00a0\t\r \u00a0\n\u2022\u202f Four\t\r \u00a0were\t\r \u00a0non\t\r \u00a0Malaysians\t\r \u00a0\n\u2022\u202f The\t\r \u00a0ethnic\t\r \u00a0distribuTon\t\r \u00a0is\t\r \u00a0displayed\t\r \u00a0in\t\r \u00a0Figure\t\r \u00a01\t\r \u00a0\n\u2022\u202f Mean\t\r \u00a0age\t\r \u00a0of\t\r \u00a0presentaTon\t\r \u00a0was\t\r \u00a041\t\r \u00a0\n\u2022\u202f Mean\t\r \u00a0duraTon\t\r \u00a0of\t\r \u00a0presentaTon\t\r \u00a0was\t\r \u00a021\t\r \u00a0days\t\r \u00a0and\t\r \u00a0median\t\r \u00a0\n\n\n\n10.5\t\r \u00a0days\t\r \u00a0(range\t\r \u00a04-\u00ad\u201060)\t\r \u00a0\n\u2022\u202f Mean\t\r \u00a0bacteriological\t\r \u00a0index\t\r \u00a0(BI)\t\r \u00a0and\t\r \u00a0morphological\t\r \u00a0index\t\r \u00a0\n\n\n\n(MI)\t\r \u00a0were\t\r \u00a04.2\t\r \u00a0and\t\r \u00a02.1\t\r \u00a0respecTvely\t\r \u00a0\n\t\r \u00a0\n\t\r \u00a0\n\n\n\n\n\n\n\nTable\t\r \u00a02:\t\r \u00a0Clinical\t\r \u00a0presentaFons,\t\r \u00a0Treatment\t\r \u00a0and\t\r \u00a0Outcome\t\r \u00a0\n\n\n\nPresenTng\t\r \u00a0\nsymptoms\t\r \u00a0\n\n\n\nUlcers\t\r \u00a0 \t\r \u00a0\t\r \u00a05\t\r \u00a0(27.8%)\t\r \u00a0\n\n\n\nPurpura\t\r \u00a0and\t\r \u00a0ulcers\t\r \u00a0 13\t\r \u00a0(72.2%)\t\r \u00a0\n\n\n\nType\t\r \u00a0of\t\r \u00a0leprosy\t\r \u00a0 Diffuse\t\r \u00a0non\t\r \u00a0nodular\t\r \u00a0 17\t\r \u00a0(94.4%)\t\r \u00a0\n\n\n\nLepromatous\t\r \u00a0leprosy\t\r \u00a0 \t\r \u00a0\t\r \u00a01\t\r \u00a0\t\r \u00a0(5.6%)\t\r \u00a0\n\n\n\nWHO\t\r \u00a0disability\t\r \u00a0 Grade\t\r \u00a02\t\r \u00a0 13\t\r \u00a0(72.2%)\t\r \u00a0\n\n\n\nHistopathology \nfindings\t\n\r\n\n\n\nEndothelial\t\r \u00a0proliferaTon\t\r \u00a0 \t\r \u00a0\t\r \u00a0\t\r \u00a04\t\r \u00a0(22%)\t\r \u00a0\n\n\n\nColonizaTon\t\r \u00a0of\t\r \u00a0endothelial\t\r \u00a0cells\t\r \u00a0by\t\r \u00a0\nAFB\t\r \u00a0\n\n\n\n\t\r \u00a017\t\r \u00a0(94%)\t\r \u00a0\n\n\n\nThrombosis\t\r \u00a0 \t\r \u00a014\t\r \u00a0(77%)\t\r \u00a0\n\n\n\nTreatment\t\r \u00a0 MDT\t\r \u00a0alone\t\r \u00a0 \t\r \u00a0\t\r \u00a02\t\r \u00a0(11.1%)\t\r \u00a0\n\n\n\nMDT+\t\r \u00a0systemic\t\r \u00a0steroid\t\r \u00a0 \t\r \u00a0\t\r \u00a09\t\r \u00a0(50.0%)\t\r \u00a0\n\n\n\nMDT+\t\r \u00a0systemic\t\r \u00a0steroid\n+pentoxyphylline\t\r \u00a0\n\n\n\n\t\r \u00a0\t\r \u00a07\t\r \u00a0(38.9%)\t\r \u00a0\n\n\n\nOutcome\t\r \u00a0 Survived\t\r \u00a0 15\t\r \u00a0(83.3%)\t\r \u00a0\n\n\n\nDied\t\r \u00a0due\t\r \u00a0to\t\r \u00a0lucio\u2019s\t\r \u00a0related\t\r \u00a0\ncomplicaTon\t\r \u00a0\n\n\n\n\t\r \u00a0\t\r \u00a02\t\r \u00a0(11.1%)\t\r \u00a0\n\n\n\nDied\t\r \u00a0due\t\r \u00a0to\t\r \u00a0other\t\r \u00a0cause\t\r \u00a0 \t\r \u00a0\t\r \u00a01\t\r \u00a0(5.6%)\t\r \u00a0\n\n\n\nCurrent\t\r \u00a0status\t\r \u00a0 Treatment\t\r \u00a0in\t\r \u00a0progress\t\r \u00a0 \t\r \u00a0\t\r \u00a07\t\r \u00a0(39.0%)\t\r \u00a0\n\n\n\nSurveillance\t\r \u00a0 \t\r \u00a0\t\r \u00a03\t\r \u00a0(16.7%)\t\r \u00a0\n\n\n\nCompleted\t\r \u00a0treatment\t\r \u00a0and\t\r \u00a0\nsurveillance\t\r \u00a0\n\n\n\n\t\r \u00a0\t\r \u00a01\t\r \u00a0(5.6%)\t\r \u00a0\n\n\n\nTransfer\t\r \u00a0back\t\r \u00a0to\t\r \u00a0home\t\r \u00a0country\t\r \u00a0 \t\r \u00a0\t\r \u00a01\t\r \u00a0(5.6%)\t\r \u00a0\n\n\n\nDefaulted\t\r \u00a0 \t\r \u00a0\t\r \u00a03\t\r \u00a0(16.7%)\t\r \u00a0\n\n\n\n\t\r \u00a0\n\t\r \u00a0\n\n\n\n\n\n\n\n0\" 20\" 40\" 60\" 80\" 100\"\n\n\n\nMalaysian\"\n\n\n\nNon\"Malaysian\"\nMalay\"\n\n\n\nChinese\"\n\n\n\nIndigenous\"\n\n\n\n22.2%\"\n\n\n\n77.8%\"\n\n\n\nTable\t\r \u00a01:\t\r \u00a0Referring\t\r \u00a0team\u2019s\t\r \u00a0diagnosis\t\r \u00a0\t\r \u00a0 n=18\t\r \u00a0\nConnecTve\t\r \u00a0Tssue\t\r \u00a0disease\t\r \u00a0 \t\r \u00a0\t\r \u00a02\t\r \u00a0\n\n\n\nVasculopathy/vasculiTs/purpura\t\r \u00a0 \t\r \u00a0\t\r \u00a04\t\r \u00a0\n\n\n\nSteven\t\r \u00a0Johnson\t\r \u00a0syndrome\t\r \u00a0 \t\r \u00a0\t\r \u00a02\t\r \u00a0\n\n\n\nOthers\t\r \u00a0(Gangrene\t\r \u00a0toes/celluliTs/necroTzing\t\r \u00a0\nfaciiTs/ulcers/cutaneous\t\r \u00a0tuberculosis)\t\r \u00a0\n\n\n\n\t\r \u00a0\t\r \u00a06\t\r \u00a0\n\n\n\nNot\t\r \u00a0stated\t\r \u00a0 \t\r \u00a0\t\r \u00a02\t\r \u00a0\t\r \u00a0\n\n\n\nLucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0 \t\r \u00a0\t\r \u00a01\t\r \u00a0\n\n\n\nLeprosy\t\r \u00a0 \t\r \u00a0\t\r \u00a01\t\r \u00a0\n\n\n\n\t\r \u00a0\n\n\n\nDISCUSSION\t\r \u00a0\t\r \u00a0\n\t\r \u00a0\n\n\n\n\u2022\u202f We\t\r \u00a0found\t\r \u00a0male\t\r \u00a0preponderance\t\r \u00a0\t\r \u00a0similar\t\r \u00a0to\t\r \u00a0other\t\r \u00a0\nstudies1,2,3\t\r \u00a0\t\r \u00a0\n\n\n\n\u2022\u202f Only\t\r \u00a0one\t\r \u00a0paTent\t\r \u00a0was\t\r \u00a0known\t\r \u00a0to\t\r \u00a0have\t\r \u00a0leprosy\t\r \u00a0prior\t\r \u00a0to\t\r \u00a0\npresentaTon\t\r \u00a0and\t\r \u00a0more\t\r \u00a0than\t\r \u00a0two\t\r \u00a0thirds\t\r \u00a0of\t\r \u00a0our\t\r \u00a0paTents\t\r \u00a0\nalso\t\r \u00a0had\t\r \u00a0WHO\t\r \u00a0grade\t\r \u00a02\t\r \u00a0disability\t\r \u00a0indicaTng\t\r \u00a0late\t\r \u00a0\nrecogniTon\t\r \u00a0of\t\r \u00a0leprosy\t\r \u00a0\n\n\n\n\u2022\u202f All\t\r \u00a0except\t\r \u00a0one\t\r \u00a0paTent\t\r \u00a0all\t\r \u00a0had\t\r \u00a0diffuse\t\r \u00a0non-\u00ad\u2010nodular\t\r \u00a0\nleprosy\t\r \u00a0which\t\r \u00a0contributes\t\r \u00a0to\t\r \u00a0under-\u00ad\u2010recogniTon\t\r \u00a0as\t\r \u00a0there\t\r \u00a0\nis\t\r \u00a0absence\t\r \u00a0of\t\r \u00a0the\t\r \u00a0typical\t\r \u00a0patches,\t\r \u00a0plaques\t\r \u00a0or\t\r \u00a0nodules.\t\r \u00a0\n\n\n\n\u2022\u202f Our\t\r \u00a0paTents\t\r \u00a0have\t\r \u00a0significant\t\r \u00a0morbidity\t\r \u00a0as\t\r \u00a0indicated\t\r \u00a0by\t\r \u00a0\nhigh\t\r \u00a0proporTon\t\r \u00a0of\t\r \u00a0disability\t\r \u00a0however\t\r \u00a0this\t\r \u00a0phenomenon\t\r \u00a0\ncan\t\r \u00a0also\t\r \u00a0have\t\r \u00a0aggressive\t\r \u00a0course\t\r \u00a0with\t\r \u00a0the\t\r \u00a0development\t\r \u00a0\nof\t\r \u00a0secondary\t\r \u00a0sepsis2,3,4.\t\r \u00a0\t\r \u00a0\n\n\n\n\t\r \u00a0\nCONCLUSION\t\r \u00a0\n\t\r \u00a0\n\n\n\n\u2022\u202f Lucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0mimics\t\r \u00a0connecTve\t\r \u00a0Tssue\t\r \u00a0diseases\t\r \u00a0\nand\t\r \u00a0vasculopathy,\t\r \u00a0hence\t\r \u00a0this\t\r \u00a0diagnosis\t\r \u00a0should\t\r \u00a0be\t\r \u00a0\nconsidered\t\r \u00a0when\t\r \u00a0paTents\t\r \u00a0presents\t\r \u00a0with\t\r \u00a0reTculate\t\r \u00a0\npurpura\t\r \u00a0or\t\r \u00a0bizzare\t\r \u00a0geometrical\t\r \u00a0shaped\t\r \u00a0ulcers\t\r \u00a0and\t\r \u00a0\nprompt\t\r \u00a0us\t\r \u00a0to\t\r \u00a0look\t\r \u00a0for\t\r \u00a0further\t\r \u00a0clues\t\r \u00a0including\t\r \u00a0diffuse\t\r \u00a0\ninfiltraTon,\t\r \u00a0maldrosis,\t\r \u00a0hypoesthesia\t\r \u00a0and\t\r \u00a0peripheral\t\r \u00a0\nneuropathy\t\r \u00a0\n\n\n\n\u2022\u202f Awareness\t\r \u00a0of\t\r \u00a0this\t\r \u00a0enTty\t\r \u00a0facilitates\t\r \u00a0diagnosis\t\r \u00a0and\t\r \u00a0\nimproves\t\r \u00a0paTents\u2019\t\r \u00a0outcome\t\r \u00a0\n\n\n\n\n\n\n\nReference\t\r \u00a0\n1.\t\r \u00a0Rea\t\r \u00a0TH\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0Lucio\u2019sphenomenon\t\r \u00a0and\t\r \u00a0diffuse\t\r \u00a0non\t\r \u00a0nodular\t\r \u00a0\nlepromatous\t\r \u00a0leprosy.\t\r \u00a0Arch\t\r \u00a0Dermatol\t\r \u00a01978.\t\r \u00a0\n2.\t\r \u00a0Ang\t\r \u00a0P\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0Fatal\t\r \u00a0Lucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0in\t\r \u00a02\t\r \u00a0paTents\t\r \u00a0with\t\r \u00a0previously\t\r \u00a0\nundiagnosed\t\r \u00a0leprosy.\t\r \u00a0J\t\r \u00a0Am\t\r \u00a0Acad\t\r \u00a0Dermatol.\t\r \u00a02003.\t\r \u00a0\n3.\t\r \u00a0Choon\t\r \u00a0Se\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0Lucio\u2019s\t\r \u00a0phenomenon:\t\r \u00a0a\t\r \u00a0report\t\r \u00a0of\t\r \u00a03\t\r \u00a0cases\t\r \u00a0seen\t\r \u00a0in\t\r \u00a0\nJohor\t\r \u00a0Malaysia.\t\r \u00a0Int\t\r \u00a0J\t\r \u00a0Dermatol.\t\r \u00a02009.\t\r \u00a0\n4.\t\r \u00a0Costa\t\r \u00a0IM\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0Lucio\u2019s\t\r \u00a0phenomenon\t\r \u00a0a\t\r \u00a0case\t\r \u00a0report\t\r \u00a0and\t\r \u00a0review\t\r \u00a0of\t\r \u00a0\nliterature.\t\r \u00a0Int\t\r \u00a0J\t\r \u00a0Dermatol.\t\r \u00a02015.\t\r \u00a0\n\t\r \u00a0\nAcknowledgement\t\r \u00a0\nWe\t\r \u00a0would\t\r \u00a0like\t\r \u00a0to\t\r \u00a0thank\t\r \u00a0the\t\r \u00a0Director\t\r \u00a0General\t\r \u00a0of\t\r \u00a0Health\t\r \u00a0for\t\r \u00a0giving\t\r \u00a0us\t\r \u00a0the\t\r \u00a0\npermission\t\r \u00a0to\t\r \u00a0present\t\r \u00a0this\t\r \u00a0data.\t\r \u00a0\n\t\n\r\n\n\n\nFigure\t\r \u00a01:\t\r \u00a0NaTonality\t\r \u00a0and\t\r \u00a0Ethnic\t\r \u00a0DistribuTon\t\r \u00a0\n\n\n\n\n\n\n\n\n \nConclusion \n\n\n\n \nThis case clearly illustrates that clinical presentation and response to oral zinc is more \nimportant to clinch the diagnosis; even though the zinc level was normal. The role of \ninvestigations including serum zinc level and histopathology examinations may support \nthe diagnosis of acrodermatitis enteropathica but they are not compulsory criteria. \n \n \n\n\n\nAcrodermatitis Enteropathica with  \nNormal Zinc Level: A case report  \n\n\n\nAi Leen Wee \nHospital Melaka, Melaka, Malaysia \n\n\n\nIntroduction \n \n          Acrodermatitis enteropathica or zinc deficiency can be divided into genetic or acquired \ntype.  Both clinical presentations are the same, presenting with well demarcated \nerythematous patches around the mouth, anus, limbs including hands and feet.  Diagnosis is \nreadily made with typical clinical features and low serum zinc.  We  illustrate here a case of \nacrodermatitis enteropathica with normal zinc level. \n \n\n\n\nDiscussion \n        \n\n\n\n          Acrodermatitis enteropathica is a disease related to zinc deficiency caused by an \nabnormality of intestinal zinc absorption, which is classified into hereditary congenital \ntype (inherited as an autosomal recessive trait) and acquired type.  Possible causes of the \nacquired type include inadequate intake zinc caused by prematurity or insufficient zinc \nabsorption.  The acquired types can be further classified into classic acrodermatitis \nenteropathica with low serum zinc levels and a variant type that presents with \ncharacteristic clinical features but normal serum zinc level(1).  In cases diagnosed with \nacrodermatitis enteropathica, approximately 30% of cases show a normal or higher serum \nzinc level(2). Hence, the level of serum zinc is not reflected in the actual bioavailability of \nzinc. Zinc deficiency can occur when zinc is released from blood to a microenvironment \nwhere the actual site of zinc biologic action is impaired, even when serum zinc level is \nnormal(3). Both the inherited and acquired type presents with similar clinical features. The \nonly way to differentiate the two is the resurgence of clinical manifestation with the \ncessation of zinc supplement in the inherited type.  \n \n          The cutaneous manifestation is characterized by of erythematous patches with well \ndefined borders over the periorificial, perineum, perianal, and limbs including the hands \nand feet. These patches evolve into crusted, blistered pus-filled and eroded lesions(3) \n(Figure 1). Other cutaneous manifestations include alopecia, red glossy tongue with \nmouth ulcers, nail changes and secondary cutaneous infections. The babies affected are \nusually irritable as witnessed in this patient as well. Intractable diarrhoea, failure to thrive \nand conjunctivitis are other non-cutaneous clinical features. The diagnosis of this \ncondition comprises of characteristic clinical features and rapid resolution to zinc \nsupplement. Low serum zinc level further supports the diagnosis. Another supportive \ninvestigation would be histopathological examination (HPE) showing psoriasiform \nepidermis, confluent parakeratosis and upper epidermal pallor(3) (Figure 3). This patient\u2019s \nbiopsy showed focal parakeratosis, acanthotic and spongiotic epidermis. No bullous lesion \nor cytoplasmic pallor of keratinocytes seen. These findings can still be in keeping with \nearly changes acrodermatitis enteropathica.  \n \n          In the case presented above, the fact that the patient is an ex-premature gives an \nimportant clue to the diagnosis. With the added typical skin lesions, both distribution and \nmorphologically; the clinical diagnosis of acrodermatitis enteropathica can be confidently \nmade despite of normal serum zinc level. The commencement of oral zinc leading to rapid \nclinical response and resolution further supports this diagnosis. In the above reported \ncase, after commencing oral zinc, her irritability resolved within a day and skin lesions \nresolved in about two weeks\u2019 time.  \n \n\n\n\nReferences:  \n\n\n\n \n1. Aggett PJ. Acrodermatitis enteropathica. J. Inherit Metab Dis 1983; 6 (suppl 1): 39-43. \n2. Mack D, Koletzko B, Cunnane S et al. Acrodermatitis enteropathica with normal serum zinc \n\n\n\nlevels: diagnostic value if small bowel biopsy and essential fatty acid determination. Gur 1989; \n30: 1426-1429. \n\n\n\n3. Lee SY, Jung YJ, Oh TH et al. A Case of Acrodermatitis Enteropathica Localized on the Hands and \nFeet with a Normal Serum Zinc Level. Ann Dermatol 2011; 23: 599-590  \n\n\n\n\n\n\n\nCase report \n           \n          NAH is a 5-month-old girl presented with one month history of rashes associated with \nirritability.  She was treated as eczema by general practitioners with no improvement seen; \nbefore referring to us.  Physical examination revealed erythematous patches with well-\ndefined borders seen along the periorificial, perianal, perineal, scalp, limbs including hands \nand feet.  She had alopecia but no nail changes and mucous membranes involvement.  Apart \nfrom cutaneous manifestation, she was also very irritable, crying incessantly since the skin \ncondition began.  However, she has no conjunctivitis, intractable diarrhoea and failure to \nthrive.  \n           \n          Baseline blood investigations were normal.  Skin biopsy was performed; serum zinc was \nsent and commenced on oral zinc 1mg/kg.  Zinc level was normal and the histopathological \nexamination is supportive but not pathognomonic of acrodermatitis enteropathica.  \nIrritability resolved within a day and skin lesions resolved in about two weeks\u2019 time. \n \n\n\n\nAt presentation After 2 weeks of zinc \n\n\n\nAt presentation After 2 weeks of zinc After 1 day of zinc \n\n\n\nAt presentation \n\n\n\n Progression/ Resolution \n\n\n\nTypical Histopathological Examinations (3) \n\n\n\nFigure 3: The typical histopathology examination findings(3)  \n(A) Acute spongiotic dermatitis and infiltration of upper dermal inflammatory cells (H&E, \u00d7200)  \n(B) Cytoplasmic pallor, intraepidermal vesicle formation in the upper epidermis (H&E, \u00d740) \n\n\n\nFigure 1: Clinical findings of patient at presentations; erythematous, well defined crusted  \n                 patches over periorificial, perineum, perianal, limbs including hands and feet \n\n\n\nFigure 2: Rapid improvement/ resolution of cutaneous lesions, significantly seen over the  \n                 periorificial and perineum areas. \n\n\n\n\n\n\n\n\nGENERALIZED GRANULOMA ANNULARE: \nA report of 2 cases and literature review\nKang Nien How1, Ikmal Hisyam Bakrin2, Norashikin Shamsudin1\n\n\n\n1Department of Medicine, Faculty of Medicine and Health Sciences,  UPM\n2Department of Pathology, Faculty of Medicine and Health Sciences, UPM\n\n\n\n35\nINTRODUCTION\nGranuloma annulare (GA) is an idiopathic benign granulomatous skin disease, characterized by annular dermal\nplaques or papules. We are reporting two patients with generalized GA (GGA), with different clinical features, disease\nmorphology and histology pattern.\n\n\n\nCASE\tREPORT\t1\nA 26 years old Malay gentleman with no known medical\nillness, presented with asymptomatic, skin-coloured, large\nannular plaques over the upper limb, dorsal hands, upper\nback and trunk of 8 months duration (figure 1a & 1b). He\nwas otherwise well without any constitutional symptoms.\nApart from granuloma annulare, our differential diagnoses\nincluded erythema annulare centrifugum, lepromatous\nleprosy, and cutaneous sarcoidosis. Histology (figure 1c)\nshowed perivascular and periadnexal lymphocytic infiltrate\nwith foci of epithelioid granulomas in an interstitial pattern\n(arrow). Muciramine stain was negative. No necrobiosis\nwas seen. Negative wade-fite stain and slit skin smear\nexamination excluded leprosy. His fasting blood sugar,\nthyroid function test and fasting serum lipids were all\nwithin normal range. On follow up, there was spontaneous\npartial resolution of skin lesions.\n\n\n\nCASE\tREPORT\t2\nA 67 years old Malay lady with underlying diabetes\nmellitus (DM) presented with 2 months history of pruritic\nerythematous discrete papules over the forearms, dorsal\nhands, upper back and lower limbs (figure 3). She denied\nany constitutional symptoms. Clinical diagnoses of lichen\nplanus, cutaneous sarcoidosis and GA were considered.\nHistology showed palisading granuloma with central area\nof necrobiosis in the dermis (figure 1c). Grenz zone was\npresent. The granuloma consisted of epithelioid cells and\nLanghans type multinucleated giant cells. Alcian-blue stain\ndemonstrated mucin deposition within the central area of\ndead collagen (figure 1d). Her fasting serum lipid and\nthyroid function test were unremarkable. In view of\nextensive lesions and poor response to topical\ncorticosteroids, hydroxychloroquine was commenced.\n\n\n\nDISCUSSION\nThe prevalence of GA is unknown1. It is estimated about 0.1-0.4% of new patients presented to dermatologists were\ndiagnosed as GA2. The reported age of onset is at the third and fifth decades with female predominance (1-2:1). The\nvariants, presentation, frequency and histology are stated in Table 1. Though debatable, the association with diabetes\nand dyslipidemia is most widely reported. Other associated diseases includes HIV, malignancies, thyroid disease and\nsystemic infections3. GA typically produce minimal symptoms, and frequently self-resolved. 50% of LGA has a tendency\nto remit within 2 years3. Treatment is desired in view of its appearance, tendency to recur and occasional widespread\ndistribution3, however evidence is minimal. Intralesional triamcinolone can be used for LGA3. Antimalarial drug or\nphototherapy are suggested for treatment of GGA3. Our case reports, demonstrate an early and late onset GGA. The first\ncase showed classical clinical morphology but had interstitial type GA on histology, whereas our second case did not\nshow typical morphology but had classical histology of GA.\nType Classic description Frequency Note Histology\nLocalized\n(LGA)\n\n\n\nAnnular plaques, limited \nclassically on hands or \nfeet \n\n\n\n+++++ Most common and well recognized Mucin coupled with a palisading \n(26%) or interstitial (71%)1\n\n\n\npattern of granulomatous \ninflammation represents the \nprinciple findings in all subtypes \nof GA\n\n\n\nGeneralized\n(GGA)\n\n\n\nAnnular plaques, or \npapules, diffuse, classically \non the extremities and \ntrunk\n\n\n\n+++ Extensive involvement of the limbs \nprobably fits into this type.  \n\u201cdisseminated\u201d GA is best thought \nto be as a form of GGA in the \nabsence of better data.\n\n\n\nSubcutaneous\n(SGA)\n\n\n\nSubcutaneous nodules +++ Exclusively in children Involving the reticular dermis or \nsubcutaneous layer. \n\n\n\nother rare variants include, perforating GA, palmoplantar, blackolinear, pustular, visceral and actinic granuloma.\nTable\t1:\tVariants,\tmorphology,\tfrequency\tand\thistology\tof\tGA1\n\n\n\nREFERENCES\n1. Piette et al. J Am Acad Dermatol. 2016; 75.3: 457-465.\n2. Muhlbauer JE. J Am Acad Dermatol. 1980;3:217-230.\n3. Piette et al. J Am Acad Dermatol 2016; 75.3: 467-479.\n\n\n\nCONCLUSION\nGA is not uncommon, yet under researched. Additional studies are\nnecessary to better elucidate the cause, triggers, associations, and\ntreatment of this condition.\n\n\n\n(b)(a)\t\n\n\n\n(c) (d)\n\n\n\nFigure\t2\n(a)\tLeft\tforearm\n(b)\tRight\tupper\tback\n(c)\tH&E\tstain\t(x\t100)\n(d)\tAlcian-blue\tstain\t(x\t400)\n\n\n\n(a)\t (b)\n\n\n\n(c)\n\n\n\nFigure\t1\n(a)\tLeft\tforearm\n(b)\tRight\tflank\n(c)\tH&E\tstain\t(x\t100)\n(d)\tMuciramine stain\t\n(x400)\n\n\n\n(d)\n\n\n\n\n\n\n\n\nTitle\nAuthors, Institution\n\n\n\nPoster \nNo. Institutional \n\n\n\nlogo\n(optional)\n\n\n\nTHE\tDISFIGURING\tULCERATED\tNODULE\nKang Nien How1, Ikmal Hisyam Bakrin2, Kim Wah Ho3, Norashikin Shamsudin1\n\n\n\n1Department of Medicine, Faculty of Medicine and Health Sciences, UPM.\n2Pathology Department, Faculty of Medicine and Health Sciences, UPM\n3Hematology Department, Hospital Ampang, Kuala Lumpur\n\n\n\n36\nINTRODUCTION\nPrimary cutaneous CD30+ lymphoproliferative disorder is a group\nof primary cutaneous T cell lymphoma (P-CTCL) that consists of\nlymphomatoid papulosis (LyP), borderline disease and primary\ncutaneous anaplastic large cell lymphoma (C-ALCL). It is the\nsecond most common cutaneous lymphoma after mycosis\nfungoides (MF), comprising about 30% of all CTCL1. We herein\nreport a case of primary cutaneous anaplastic large cell\nlymphoma which regressed completely without any treatment.\n\n\n\nCASE\tREPORT\nA 45 years old Malay gentleman presented with a rapidly\nenlarging, painless solitary facial nodule of 2 months\nduration. He denied any prior trauma or insect bites. He\nwas also well with no history of fever, constitutional or B\nsymptoms. Clinical examination revealed a 3x3 cm\nerythematous juicy ulcerated tumour (figure 1A), with no\nenlargement of regional lymph nodes or\nhepatosplenomegaly. Clinical differential diagnoses\nincluded lymphocytoma cutis, fixed plaque sporotrichosis,\ndeep fungal infection, mycobacterium and atypical\nmycobacterium infection. Histological examination from an\nincisional skin biopsy showed a diffuse and dense\nproliferation of large neoplastic lymphoid cells with\nmarkedly pleomorphic nuclei in the dermis. Occasional\nhorseshoe (\"hallmark\") cells were also present (arrow)\n(figure 2a). Apoptotic bodies were frequently seen. The\nneoplastic cells were immunopositive for CD2 (figure 2c),\nCD3 and CD30 (figure 2d). A subpopulation of neoplastic\ncells were CD4 and CD8 positive. The Ki-67 proliferative\nindex was high, at 90%. The neoplastic cells showed\naberrant loss of CD5 and CD7 expression (figure 2e & 2f).\nImportantly, the ALK-1 stain was negative (figure 2b). A\ndiagnosis of cutaneous anaplastic large cell lymphoma was\nmade. A staging computed tomography revealed cervical\nlymph node enlargement with no distant metastases. He\ndeclined any active intervention and had complete\nspontaneous regression after 3 months of initial\npresentation, leaving an atrophic scar over the site of\nprevious tumour (figure 1B).\n\n\n\nFigure\t1\t(A)\tFebruary\t2017.\t(B)\tJuly\t2017\t\n\n\n\n(A) (B)\n\n\n\nDISCUSSION\nC-ALCL comprise 8% of P-CTCL2. They typically present as\nnodules or papules with ulceration. Histologically, there is\ndiffuse, non-epidermotropic infiltrate with cohesive sheets\nof large CD30+ tumour cells. The tumour cells have round,\noval or irregularly shaped nuclei, with prominent\neosinophilic nucleoli and abundant cytoplasm,\nrepresenting typical anaplastic cells. Immunophenotype.\nThe neoplastic cells shows CD4+ expression with variable\nloss of CD2, CD5, and/or CD3. Cytotoxic proteins (granzyme\nB, TIA-1, perforin) are commonly positive. More than 75%\nof neoplastic T cells should express CD30+ to be defined as\nC-ALCL. CLA is usually positive. EMA and ALK negativity\ndifferentiate C-ALCL from systemic CD30+ lymphoma. Co-\nexpression of CD56 is rare, indicating a poor prognosis.2 As\nin our case, C-ALCL may show partial or complete\nspontaneous regression2. They frequently relapse in the\nskin (41%) but rarely disseminate (10%)3. Patient with\nmultifocal skin lesions and only regional lymph nodes\ninvolvement have similar prognosis to patient with just one\nskin lesion3. It is an indolent disease, with an excellent\nprognosis, demonstrating 10 years disease-specific survival\nin over 90% of patients3. Treatment of C-ALCL is\nsummarized in Table 1. Though regional lymph nodes are\ninvolved, doxorubicin-based multi-agent chemotherapy is\nnot required, as demonstrated in our case.\n\n\n\nType First Line\n\n\n\nSolitary/ few localized \nnodule \n\n\n\nExcision\nRadiotherapy\n\n\n\nMultifocal skin therapy Radiotherapy \nLow dose MTX \n\n\n\nExtracutaneous disease/ \nrapid progressing\n\n\n\nDoxorubicin-based \nmultiagent chemotherapy\n\n\n\nTable\t1:\tTreatment\tfor\tP- ALCL2\n\n\n\nCONCLUSION\n\u2022 C-ALCL is an indolent disease with a good 10 year\n\n\n\ndisease survival. It may show partial or complete\nspontaneous regression. Doxorubicin-based\nmultiagent chemothrapy is rarely needed.\n\n\n\nREFERENCES\n1. Groves FD et al. J Nati Cancer Inst. 2000; 92: 1240-\n\n\n\n1251.\n2. Willemze R et al. Blood. 2005; 105.10: 3768 \u2013 3784.\n3. Bekkenk M et al. Blood. 2000; 95: 3653-3661\n\n\n\na b\n\n\n\nc d\n\n\n\nfe\n\n\n\nFigure 2: (a) H&E stain (b) negative ALK-1 (c) CD2+ (d) \nCD30+ (e & f) abberent loss of CD5 and CD7\n\n\n\noriginal\tmagnification\tx\t400\t\n\n\n\noriginal\tmagnification\tx\t400\t\n\n\n\noriginal\tmagnification\tx\t400\t\n\n\n\n\n\n\n\n\n  \nCASE REPORT: TUMORAL CALCINOSIS  \n\n\n\n HL Wong1, KF Leong1, Sabeera BKI1, Zuliatul F2 \n\n\n\n1 Paediatric Dermatology Department, Institut Pediatrik Hospital Kuala Lumpur \n2 Pathology Department, Hospital Kuala Luumpur \n\n\n\nPoster \nNo. \n37 \n\n\n\n\n\n\n\n\n\n\n\nIntroduction \nTumoral calcinosis  (TC),also known as Teutschlaender disease or calcifying bursitis, is a rare condition which is characterized \nby  deposition of calcium phosphate and calcium hydroxyapatite within periarticular soft tissues. We report a case of TC in an \nadolescent who presented with typical presentation and histological findings. \n\n\n\n  \n ML is a 14-year-old boy who presented with multiple \n\n\n\n swellings around bilateral elbows and knees for 2 years  \nduration. The number and size of the swellings have increased  \n\n\n\ngradually. Some have ruptured with chalky white discharge. The \nmovement of the affected joints remained normal despite  \n\n\n\nthe swellings. It was not associated with pain. He is  \notherwise well with no known medical illness or history of  \n\n\n\nhospital admission. He performs fairly well at school and he \n plays football for his school.  There is no similar history in \n\n\n\n the family.  \n On examination, multiple masses of  \n\n\n\nvarious sizes ( smallest one measures about 1x1cm whereas \n the largest one measure 5x7cm) and consistencies, ranging \n\n\n\n from firm to hard, were noted around bilateral knees and  \nelbows. The overlying skin was normal. The masses were not  \nattached to the  overlying skin and were not warm, tender or     \n\n\n\nmobile.  Examination of other joints were normal  with no \n weakness.  \n\n\n\n \n Laboratory  investigations  revealed normal renal  \n\n\n\nprofile, Calcium, phosphate, thyroid function and parathyroid \n function. The connective tissue diseases screening was  \n\n\n\nnegative and inflammatory markers were not raised.  \nEchocardiography  revealed mild dilatation of the aortic root.   \nOphthalmology and hearing  assessment was normal. Plain \n\n\n\n radiographs showed multiple  multilobulated, calcified masses \nat bilateral knees and elbows. There was no evidence of  \n\n\n\n fractures, periosteal changes or soft tissue changes.  \n Ultrasound of bilateral elbows and knees showed multiple well-\n\n\n\ndefined cystic lesions with complex fluid component,  \nespecially in both knees. Some of the lesions have foci of  \ncalcification within.  Internal Doppler did not suggest high  \nvascularity.  There was no intra-articular  extension or joint \n\n\n\n effusion noted.  \n\n\n\n\n\n\n\nTC mainly presents in childhood or adolescences as painless, firm, single or multiple  masses around the joints that may lead to \njoint function limitation especially when it is large in size. The commonest reported joints affected are  soft tissues of peri-\n\n\n\narticular upper limb (shoulder and elbow), knees and hip regions as in our case. Differential diagnoses of soft-tissue \ncalcification include mixed connective tissue diseases, dermatomyositis and  calcific bursitis. However, malignancies e.g. \n\n\n\nparosteal osteosarcoma, chondrosarcoma, and synovial sarcoma should also be considered. \n \n \n   \n\n\n\nTC is a distinct clinico-radio-pathological entity characterised by soft tissue periarticular calcinosis which mimics neoplasm. \nHence, a multidisciplinary approach should be exercised in terms of  making a precise diagnosis.  \n\n\n\n1. Kathryn M et al. Tumoral Calcinosis: Pearls, Polemics, and Alternative Possibilities. RSNA May-June volume  2006: volume 28 issue 3. \n2. Sridevi et al. Idiopathic Tumoral Calcinosis \u2013 Rare Clinico Pathological Entity: A Report of Two Cases. J Clin Diagn Res 2017 Jun; 11(6): ED06\u2013ED07. \n3. Yuen et al. Tumoral calcinosis: a case reportJournal of Orthopedic Surgery 2011;19(1):108-12 \n\n\n\n\n\n\n\n\n\n\n\nMultiple swellings of various sizes and consistencies at \nbilateral knee joints.  \n\n\n\nPresence of calcium discharge at the joint \n\n\n\nHPE findings \n\n\n\nThere is a  large \nuniform basophilic \ncalcium deposit at \ndermis \n\n\n\nH&E x 40 \n \n\n\n\nH&E x 200\n  \n\n\n\nCase Report \n\n\n\nmultiple  multilobulated, calcified masses at bilateral knees and \nelbows ( early changes) \n\n\n\nConclusion \n\n\n\nDiscussion \n\n\n\nClassifications of TC Type 1-Primary normo-phosphatemic)  Type 2- Primary hyper-phosphatemic   Type 3-Secondary TC \n\n\n\nLaboratory \nCharacteristics \n\n\n\n\u2022  Normo-calcemia and normo-\nphoshpatemia \n\n\n\n\u2022 Normo-calcemia and hyper-phosphatemia  \u2022 Hyper-calcemia  and \nphosphatemia secondary or \ntertiary hyperparathyroidism \ndue to Chronic renal failure \n(CRF) \n\n\n\nNumber of \ncalcifications \n\n\n\n\u2022  usually solitary calcifications.  \u2022 Usually multiple calcifications \u2022 Usually multiple \ncalcifications \n\n\n\nGenetic \npreponderance \n\n\n\n\u2022 no evident familial pattern in this \nentity \n\n\n\n\n\n\n\n\u2022 Genetic predisposition is a feature  \n\u2022 hyperphosphatemia arises due to reduced urinary phosphate \n\n\n\nexcretion caused by recessive mutations in GalNAc \ntransferase 3 gene, GALNT3, and KLOTHO, that causes the \ninactivation of FGF23, a phosphoturic hormone \n\n\n\nThe diagnosis of TC  is mainly based on typical radiologic features and biochemical profile, with the exclusion of the presence of  \nconnective tissue diseases. The normal laboratory results and the presence of multiple calcifications make our case most likely an \nidiopathic case since there is no family history of such complaint. Conservative treatment  remains the mainstay of treatment for \nprimary TC unless symptomatic whereas a combination of surgical excision and medical treatment for phosphate deprivation is \n\n\n\nthe best approach for TC with secondary causes. \n\n\n\nRt Elbow \n\n\n\nRt knee \nLft knee \n\n\n\nRt knee- \nmedial \naspect \n\n\n\nRt knee \n\n\n\nReference \n\n\n\nRt knee Rt Elbow \nLft knee \n\n\n\nseveral small \ncalcified \nnodules in the \ndermis. \n \n\n\n\n\n\n\n\n\nBLUE RUBBER BLEB NAEVUS SYNDROME \nPRESENTING AS AN IN UTERO FACIAL MASS \n\n\n\nHL Wong1, KF Leong1, Sabeera BKI1, Zuliatul F2 \n\n\n\n1 Paediatric Dermatology Department, Institut Pediatrik Hospital Kuala Lumpur \n2 Pathology Department, Hospital Kuala Luumpur \n\n\n\nPoster \nNo. \n38 \n\n\n\n\n\n\n\n\n\n\n\nIntroduction \nBlue rubber bleb naevus syndrome (BRBNS) is a rare multifocal venous malformation syndrome involving predominantly the skin \nand gastrointestinal tract.  It has been reported to be associated with iron deficiency anaemia and fatal bleeding. We report a case \nof BRBNS presenting as a facial tumour in utero for its rarity and atypical presentation which cast a diagnostic dilemma. \n\n\n\nCase Report \n\n\n\n  \nQ is a 6 month-old Malay girl who was  \n\n\n\nreferred to us during her antenatal period  for a facial mass  \nfound during antenatal scan at 35 weeks of gestation. A fetal  \n\n\n\nMRI done showed an  exophytic mass with features  \nsuggestive of  vascular tumour. At birth, there was a \n\n\n\n pedunculated violacious mass found at the  right forehead  \nextending to the right upper eyelid, measuring 7x8cm. It was  \n\n\n\nsoft in consistency and non tender. The clinical impression was  \nhaemangioma and oral propranolol was started at day 4 of life. \n\n\n\n \n However, the tumour increased in size  \n\n\n\ndisproportionately to growth and she developed one episode of  \nfresh per rectal bleed despite treatment with propranolol for 2 \n\n\n\n months and hence it  was stopped. MRI of brain, orbit and  \nface was repeated at 4 months of age and there was  \n\n\n\nevidence of slow flow vascular malformation which was  \nconfirmed by angiogram. In view of the development of new  \n\n\n\nbluish naevi over other parts of the body and further  \nepisode of bleeding from the mass, which resulted in anaemia       \nrequiring packed cell  transfusion, the diagnosis was revised  \n to Blue Rubber Bleb Naevus Syndrome which was supported  \n\n\n\nby HPE findings. Oral sirolimus was started subsequently \n with satisfactory response. \n\n\n\n\n\n\n\n\n\n\n\nHPE findings \n\n\n\nThe dermis shows \npresence of dilated \nvascular channels.  \n\n\n\nDiscussion \n BRBNS is a rare vascular anomaly syndrome consisting of multifocal venous malformations . The confusing \nterminology or misnomer has historically obscured the diagnosis and treatment of vascular anomalies. BRBNS has been \nthought to have an inheritance pattern of autosomal dominant. However, most case reports revealed otherwise and most of them \nare sporadic as in our case.  \n \n The venous malformation in BRBNS is different from proliferative tumors e.g. haemangiomas and hence it is expected \nnot to respond to antiangiogenic agents such as corticosteroids and interferon. The cutaneous lesions of BRBNS are generally \nsmall, measuring less than 1\u20132 cm, and blue to violacious in color. The number of  these compressible cutaneous lesions can \nvary from several to hundreds at any age.  In our case, a large facial mass during antenatal period as the sole presentation is the \nfirst case ever reported in history and hence a diagnostic challenge. The site of this lesion ( extending from the right forehead to \nthe upper eyelid) makes the biopsy or excision difficult. The biopsy was only done at 6 months of age when she started to \ndevelop other cutaneous lesions around her body and the HPE results cinched the diagnosis of venous malformation. \n  \n  In comparison to cutaneous lesion, the lesions along the gastrointestinal ( GI) tracts are  usually more clinically \nrelevant than the skin and soft tissue lesions as they can cause chronic bleeding which leads to iron deficiency anaemia. Most of \nthe time, patients exhibit GI bleeding at an early age and it continues throughout their life. Massive sudden hemorrhage is rare. \n \n A multidisciplinary approach, involving Paediatrician, Dermatologist, and Surgeon should be adopted in terms of \nmanagement of complications of BRBNS. Medical treatment with oral antiangionenic agent ,Sirolimus has recently gained \npopularity among treating paediatricians/dermatologists. To date, there are several case reports  that demonstrated good \nresponse among Paediatric patients diagnosed to have BRBNS i.e. the shrinking of the size of the venous malformation and the \nreduction in incidence of GI bleed in patients . Endoscopic approaches are generally reserved for acute bleeding. Surgical \nresection is deemed to be overly aggressive and unhelpful because of the belief that lesions would recur after removal. \n\n\n\nConclusion \nBRBNS has various presentations, and can even present during the antenatal period. Therefore, it is important to correlate the \nclinical and HPE findings to come to a definitive diagnosis.  \n\n\n\nReference \n1. Steven J Fishman et al.Blue Rubber Bleb Nevus Syndrome Surgical Eradication of Gastrointestinal Bleeding  Ann Surg. 2005 Mar; 241(3): 523\u2013528. \n2. Domini M et al. Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment Eur J Pediatr Surg. 2002 Apr;12(2):129-33. \n3. Dobru D. et a; Blue rubber bleb nevus syndrome: case report and literature review. Rom J Gastroenterol. 2004 Sep;13(3):237-40. \n\n\n\n\n\n\n\n\nComparison of  Clinical Characteristic and Treatment Outcome of  \nSyphillis between HIV and Non-HIV-infected patients \u2013\n\n\n\n5-years retrospective study\nSathiah D,  Lee HL, Tang JJ  \n\n\n\nDepartment of Dermatology, Raja Permaisuri Bainun Hospital, Ipoh\n\n\n\nINTRODUCTION:\nSyphilis and HIV are both sexually transmitted diseases and commonly\ncoexistist especially among high risk populations. Co-infection of these\ntwo condition can alter the course of both diseases. Syphilis may\nincrease the risk of HIV transmission and accelerate development of\nimmunodeficiency in HIV patients. On the other hand, HIV may\ninfluence the manifestation of syphilis and increase the treatment\nfailure. Treatment response in syphilis is defined as 4-fold decline of\nnon-treponemal antibody titres and /or seroreversion to non reactive\nin 12 months. However this response may be delayed in syphilis\npatients with coinfection of HIV.\n\n\n\nOBJECTIVES\nThe aim of the study is to analyze demography , clinical characteristic\nand treatment outcome of syphilis among HIV and non HIV patients.\n\n\n\nMETHODS\nThis was a retrospective study involving patients with syphilis treated\nin Department of Dermatology, Hospital Raja Permaisuri Bainun from\nyear 2012-2016. Medical records were traced and following data\nwere analyzed: demography, sexual preference, CD4 count, HAART\ntherapy, stage of syphilis,, RPR level and the rate of decline after\ntreatment. Data were analyzed using SPSS version 20.\n\n\n\nRESULTS\n\n\n\nIn term of treatment outcome, rate of 4-fold reduction in RPR within 12\nmonths is higher among\n\u2022 N-HIV (90%, 36 out of 40,) as compare to HIV (67.7%, 21 out of 31)\n\n\n\n(Figure 1 ).\n\u2022 Baseline RPR titer <1:32 (90%, 38 out of 42) as compare to baseline\n\n\n\nRPR titer > 1:32 (65%, 19 out of 29) (Table 2)\n\u2022 latent syphilis (87%, 49 out of 56 patients as compared to primary\n\n\n\n(67%, 2 out of 3) secondary syphilis (75% 6 out of 8) or tertiary\nsyphilis( 0%, 0 out of 4 patients)\n\n\n\n\u2022 HIV with CD4 counts > 350 cells/mm3 (90% ,10 out of 11) as\ncompared to HIV with CD4 counts < 350 cells/mm3 (55% ,11 out of\n20) (Table 2)\n\n\n\nDISCUSSION:\nHIV infection can coexist with syphilis, as both pathogens are sexually\ntransmitted and presence of one may facilitate infection with the other\n[1]. Ahn Jy et al revealed that co-infection of syphilis and HIV\npredominantly affect young male patients (n=933,92.4%) with median\nage group 38 years old and most of these patients were MSM\n(n=636,63%) [2]. This finding was consistent with our study which\nshowed syphilis and HIV co-infection commonly affect male patients\n(93.5%) with median age of 34 years old and mostly were MSM (61.3%)\ntoo.\n\n\n\nIt has been well accepted that 4-fold decline on RPR titers by 12 months\nof follow up is considered as appropriate response to therapy regardless\nof the treatment regime for patients with syphilis [3,4]. There are\nmultiple factors which may influence the rate of decline in RPR. Ghanem\net al. showed that failure of 4-fold decline of serological response within\n12 months after treatment was higher in HIV group ( 22 out of 129\npatients) as compared to non-HIV group (5 out of 168 patients)\n(p<0.001)[6]. We observed similar result in our study whereby the rate\nof 4-fold reduction in RPR within 12 months is higher among N-HIV\n(90%) as compare to HIV group (67.7%).\n\n\n\nApart from that, baseline RPR level may affect the rate of decline in RPR.\nArlene C.sena et al revealed that baseline of RPR<1:32 was associated\nwith higher rate of seroreversion within 12months as compare to\npatients with baseline RPR of > 1:32 (41.1% v 5.0%,) [5]. Similar result\nwas noted in our study in which of higher percentage of patients with\nbaseline RPR <1:32 showed decline of titer to 4-fold within 12 months as\ncompared to patients with baseline RPR of >1:32 (90% vs 65%) .\n\n\n\nTreatment outcome of patients with syphilis may be related to the stage\nof disease too. Ghanem et al study showed that early syphilis was\nassociated with delaying in 4 fold reduction of RPR as compared to late\nsyphilis[6]. In our study, latent syphilis (87%, 49 out of 56 patients as has\nis associated with highest percentage of 4 fold reduction in RPR as\nfollowed by secondary syphilis (75% 6 out of 8) , primary (67%, 2 out of\n3) and tertiary syphilis( 0%, 0 out of 4 patients).\n\n\n\nIn patients with co infection of syphilis and HIV, baseline CD4 count will\naffect the treatment outcome too. Marra et al. showed that HIV-infected\npatients with CD4 cell counts \u2a7d200 cells/\u00b5L were 3.7 times less likely to\nnormalize CSF\u2013Venereal Disease Research Laboratory (VDRL) test results\nthan were those with CD4 cell counts >200 cells/\u00b5L [7,8] In our study, it\nwas noted that 55% (11 out of 20) of patients with CD4 < 350 as\ncompared to 90% (10 out of 11) of patients with CD4 >350 achieved 4\nfold decline of RPR within 12 months.\nIt has been shown that the prevalence of neurosyphilis is higher in HIV\npatients as compared to non HIV patients (23.5% versus 10%) [9]. Nicola\nM.Zetola et al also revealed significant association of neurosyphilis with\nCD4 count < 350 cells/mm3 and baseline RPR >1:32. It was\nrecommended to perform CSF examination for HIV infected patients\nwith RPR titre >1:32, regardless of syphilis stage or those with CD4 count\n<350 cells/mm3 regardless of titre[4].\n\n\n\nREFERENCES :\n1. Neuza S. Sato et al. Serogical response to treatment to syphilis.\n2. Ahn et al.Incidence of syphilis seroconversion among HIV infected persons In ASIA . Jounal of \ninternational AIDS society 2016.\n3. K Manavi et al.The oucome of treatment of early latent syphilis and with undetermined duration in HIV \ninfected and noninfected patients.International jounal of STD and AIDS 2007.\n4. Nicola M. Zetola .Syphilis and HIV infection . \n5.Arlene C.Sena .Rate of decline in nontreponomal antibody titres and seroconversion after treatment of \neary syphilis.\n6.Khalil G. Ghanem .Antiretroviral Therapy Is Associated with Reduced Serologic Failure Rates for Syphilis \namong HIV-Infected Patients.\n7. Farhi D et al.Clinical and serological baseline and follow up features of syphilis according to HIV status \nin the post -HAART.. \n8.Marra CM,  Maxwell CL,  Tantalo L, et al. Normalization of cerebrospinal fluid abnormalities after \nneurosyphilis therapy: does HIV status matter.\n9. J. Bord\u00f3n et al.European Journal of Clinical Microbiology and Infectious disease.\n\n\n\n.\n\n\n\nA total of 71 patients with syphilis were recruited [HIV (n=31); N-HIV\n(n=40)] (Table1) . Demography pattern of both group were quite similar\nwith majority being male and median age of 34 years old. Majority of\npatients with HIV were MSM (61.3%) while most of patients with N-HIV\nwere heterosexual (47.5%). Patients in both group mostly had latent\nsyphilis but the number is higher in N-HIV (87.5%) as compare to HIV\n(70.9%). However primary and secondary syphilis were more common\nin HIV (21.6%) as compare to Non HIV (10%). On the other hand, HIV\ngroup has higher number of tertiary syphilis (7.5%) as compare to N-\nHIV (2.5%). All of the HIV-infected patients were given HAART.\n\n\n\nPoster \nNo. 39\n\n\n\nClinical characteristic HIV (n=31) N-HIV (n=40)\n\n\n\n1) Age \n\u2022 Median (years)\n\u2022 Range ( years)\n\n\n\n34.13 \n18-40\n\n\n\n34.38\n18-40\n\n\n\n2) Gender\n\u2022 Male\n\u2022 Female\n\n\n\n29 (93.5%)\n2 (6.5%)\n\n\n\n30 (75%)\n10 (25%)\n\n\n\n3) Sexual preference\n\u2022 MSM\n\u2022 Heterosexual\n\u2022 Bisexual\n\n\n\n19 (61.3%)\n8 (25.8%)\n4 (25.7%)\n\n\n\n5 (12.5%)\n19 (47.5%)\n16 (40%)\n\n\n\n4) Stage of syphilis\n\u2022 Primary\n\u2022 Secondary\n\u2022 Latent\n\u2022 Tertiary\n\n\n\n2 (5.5%)\n5 (16.1%)\n21 (70.9%)\n3 (7.5%)\n\n\n\n1 (2.5%)\n3 (7.5%)\n35 (87.5%)\n1 (2.5%)\n\n\n\nTable 1: Demography pattern among HIV and non-HIV patients\n\n\n\nFigure 1 : Rate of 4-fold reduction in RPR  after treatment among HIV and non-HIV.\n\n\n\n0%\n\n\n\n10%\n\n\n\n20%\n\n\n\n30%\n\n\n\n40%\n\n\n\n50%\n\n\n\n60%\n\n\n\n70%\n\n\n\n80%\n\n\n\n90%\n\n\n\n100%\n\n\n\nHIV N-HIV\n\n\n\n4 fold decline < 12 m 4 fold decline > 12 m\n\n\n\n90%\n67.7%\n\n\n\nn=31 n=40\n\n\n\nFactors HIV (n=31) N-HIV (n=40)\n\n\n\n4 x decline \n<12m\n\n\n\n4 x decline \n>12 m\n\n\n\n4 x decline \n<12m\n\n\n\n4 x decline     \n> 12 m\n\n\n\n1) Baseline RPR\n\u2022< 1:32\n\u2022>1:32\n\n\n\n13\n8\n\n\n\n3\n7\n\n\n\n25 \n11\n\n\n\n1 \n3\n\n\n\n2) Stages of \ndisease\n\u2022Primary\n\u2022Secondary\n\u2022Latent\n\u2022Tertiary\n\n\n\n1\n4\n\n\n\n16\n0\n\n\n\n1\n1\n5\n3\n\n\n\n1\n2\n\n\n\n33\n0\n\n\n\n0\n1\n2\n1\n\n\n\n3) CD 4 count\n\u2022< 350\n\u2022>350\n\n\n\n11\n10\n\n\n\n9\n1\n\n\n\nCONCLUSION : Syphilis with HIV co-infection is common especially\namong young male who are MSM. Factors associated with failure to\nachieve 4-fold decline in RPR within 12 months include HIV co-\ninfection, early syphilis and higher baseline RPR of >1:32\n\n\n\nTable 2: Factors associated with rate of decline in RPR after treatment in HIV and N-HIV group\n\n\n\n\n\n\n\n\nThe Great Imitator: A Case Report of Bullous \nSystemic Lupus Erythematosus\n\n\n\nSabrina Ab Wahab\n1\n, WSA Wan Ahmad Kamal\n\n\n\n1\n, Nur Ashikin A\n\n\n\n1\n, Teoh TY\n\n\n\n2\n, Tarita T\n\n\n\n1\n, Rohna \n\n\n\nRidzwan\n2\n\n\n\n1\nDermatology Unit, Universiti Teknologi MARA, Selangor, Malaysia\n\n\n\n2\nDepartment of Dermatology, Selayang Hospital, Selangor, Malaysia\n\n\n\nPoster \nNo. 40\n\n\n\nBullous SLE is a rare autoimmune bullous disease\nthat occurs in established cases of SLE . Less than\n5% of patients with SLE, either in isolation or in\naddition to other cutaneous manifestations have\nthis condition.1 Therefore , there is need to exclude\nother primary bullous diseases such as bullosa\nacquisita (EBA), pemphigus vulgaris (PV) or bullous\npemphigoid (BP) on first presentation. The\nassociation of bullous SLE with lupus nephritis is\ncontroversial and is reported in this case as a\nconcomitant presentation.\n\n\n\nLS, a 60 year-old Chinese lady, housewife, who\nwas previously well presented with itchy\nerythematous patches for 2 weeks. However, her\ncondition became worsened into extensive\ngeneralized blisters that spread from face, then\nspread to trunk , limbs and also developed oral\nulcers . It occurred as flaccid painful blisters and\nevolved into raw and crusted erosions with\npresence of nonblanchable purpuras on trunks and\nlimbs . There was no genital or eye involvement .\nShe reported alopecia but no joint pains . She was\ninitially treated as pemphigus vulgaris with\nintravenous hydrocortisone and topical potent\nsteroids. Skin biopsy showed subepidermal bullous\nwith neutrophilic dominant inflammation consistent\nwith clinical diagnosis of lupus erythematosus. The\nIF study shows IgG (3+), IgA (2+), IgM(1+), C3(1+),\nC1q (3+) and fibrin (3+). The immune deposits were\nseen within the vessels wall as well. Her diagnosis\nwas revised to bullous systemic lupus\nerythematous. Results later revealed that her ANA\nwas positive 1:160 mix pattern, AntiDsDNA positive,\nlow C3 (0.14), low C4 (<0.08) , and raised ESR\n44mm/Hr . AntiRNP and antiSM was also positive.\nHer condition was complicated with newly\ndiagnosed lupus nephritis requiring hemodialysis\nand was treated with intravenous immunoglobulin\nfor 5 days. She deteriorated due to sepsis with\nmultiorgan failure and did not manage to undergo\nrenal biopsy . We report a case of concomitant\nlupus nephritis with newly diagnosed bullous SLE\nwho succumbed to death due to overt sepsis.\n\n\n\nBullous SLE is rare as first presentation of SLE and\nhas possible association with lupus nephritis .1,2\n\n\n\nTreatment of cutaneous LE depends on disease\nseverity. Our patient fulfilled bullous SLE criteria\nand lupus nephritis. Bullous SLE is caused by\nautoantibodies to type VII collagen at the\ndermoepidermal junction.3 The association between\nblistering diseases and renal impairment is still\ncontroversial. The relationship between lupus\nnephritis and bullous SLE was reported in few case\nstudies, and was associated with type VII collagen\nwhich is usually not present in normal glomeruli. 2,4\n\n\n\nType VII collagen was described as actively\nsynthesized and incorporated in areas of\nglomerular and/or tubular scarring, irrespective of\nthe underlying disease including SLE nephritis. The\nde novo expression of fibrillary collagens in the\ndiseased renal extracellular matrix and type VII\ncollagen is the major component of anchoring fibrils\nat the dermal-epidermal junction and the main\ntarget of immune system in bullous SLE.4\n\n\n\nUNIVERSITI \n\n\n\nTEKNOLOGI \n\n\n\nMARA\n\n\n\nFigure 1 :Generalized erythematous             Figure 2 : Blistering eruptions on chest      \n\n\n\nplaques with blistering eruptions on trunk\n\n\n\nFigure 3 : Figure 4:\n\n\n\nNonblanchable purpura on the thigh Nonblanchable purpura on the trunk ,with\n\n\n\nblistering eruptions on arms/forearms\n\n\n\nFigure 5: Skin biopsy shows subepidermal bullous, and neutrophilic dermal\n\n\n\ninfiltration.\n\n\n\nIn conclusion, differentiation between bullous SLE with\nprimary bullous disease is important . There is possible\nassociation of autoantibodies to Type VII collagen in both\nbullous SLE and lupus nephritis due to the concomitant\npresentation, however there is not enough evidence to\nsupport the link . Furthermore, bullous SLE may be a risk for\nthe development of lupus nephritis and may relate to worse\nprognosis and refractory disease.\n\n\n\n1. Dhir R, Desylva P, Gehi N, Malik A, Singh YD, Jagannayakulu H,\net al. Pericardial effusion with vesiculobullous lesions in a young\nfemale. Bullous systemic lupus erythematosus (bullous SLE). Indian\nJ Dermatol Venereol Leprol 2006 Mar-Apr;72(2):175-177.\n2. Fujimoto W, Hamada T, Yarmada J, Matsuura H, Iwatsuki K:\nBullous systemic lupus erythematosus as an initial manifestation of\nSLE. J Dermatol 2005, 32:1021-27.\n3. Ng, Yee Yung & Ter Chang, I & Chen, wei-tsen & N Liou, H &\nYang, AH & Yang, Wu-Chang. (1999). Concomitant lupus nephritis\nand bullous eruption in SLE. Nephrology, dialysis, transplantation :\nofficial publication of the European Dialysis and Transplant\nAssociation - European Renal Association. 14. 1739-43.\n10.1093/ndt/14.7.1739.\n4. Onetti Muda A, Ruzzi L, Bernardini S, Teti A, Faraggiana T.\nCollagen VII expression in glomerular sclerosis. J Pathol 2001\nOct;195(3):383-390.\n\n\n\n**The authors declare that there is no conflict of interests.**\n\n\n\nIntroduction\n\n\n\nCase Report\n\n\n\nDiscussion\n\n\n\nReferences\n\n\n\nConclusion\n\n\n\n\n\n\n\n\nPoster \nNo. 41 Lichen Planus : A 7 year retrospective study in \n\n\n\nHospital Raja Permaisuri Bainun, Ipoh \nMadiha MS, SS Ong, JJ Tang \nDepartment of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh, \nPerak \n\n\n\nINTRODUCTION\t\r \u00a0\n\n\n\nMATERIAL\t\r \u00a0&\t\r \u00a0METHODS\t\r \u00a0\n\n\n\nRESULTS\t\r \u00a0\n\n\n\nDISCUSSION\t\r \u00a0\t\r \u00a0\n\n\n\nCONCLUSION\t\r \u00a0\n\n\n\nREFERENCES\t\r \u00a0\n\n\n\nLichen\t\r \u00a0planus\t\r \u00a0(LP)\t\r \u00a0 is\t\r \u00a0an\t\r \u00a0inflammatory\t\r \u00a0disorder\t\r \u00a0that\t\r \u00a0can\t\r \u00a0affect\t\r \u00a0\nthe\t\r \u00a0 skin,\t\r \u00a0mucous\t\r \u00a0membrane\t\r \u00a0and\t\r \u00a0nail.\t\r \u00a0 It\t\r \u00a0 typically\t\r \u00a0presents\t\r \u00a0 as\t\r \u00a0\npruriKc,\t\r \u00a0 polygonal,\t\r \u00a0 violaceous\t\r \u00a0 flat-\u00ad\u2010toppped\t\r \u00a0 papules\t\r \u00a0 or\t\r \u00a0\nplaques.\t\r \u00a0 Study\t\r \u00a0 regarding\t\r \u00a0 LP\t\r \u00a0 in\t\r \u00a0Malaysia\t\r \u00a0 is\t\r \u00a0 sKll\t\r \u00a0 very\t\r \u00a0 few.\t\r \u00a0 This\t\r \u00a0\nstudy\t\r \u00a0 presents\t\r \u00a0 the\t\r \u00a0 epidemiology\t\r \u00a0 and\t\r \u00a0 clinical\t\r \u00a0 paRern\t\r \u00a0 among\t\r \u00a0\npaKents\t\r \u00a0 aRending\t\r \u00a0 Dermatology\t\r \u00a0 Clinic,\t\r \u00a0 Hospital\t\r \u00a0 Raja\t\r \u00a0\nPermaisuri\t\r \u00a0Bainun,\t\r \u00a0Ipoh.\t\r \u00a0\n\n\n\nAll\t\r \u00a0 paKents\t\r \u00a0 with\t\r \u00a0 biopsy\t\r \u00a0 proven\t\r \u00a0 LP\t\r \u00a0 from\t\r \u00a0 2010\t\r \u00a0 to\t\r \u00a0 2016\t\r \u00a0 were\t\r \u00a0\nrecruited.\t\r \u00a0Epidemiology\t\r \u00a0and\t\r \u00a0clinical\t\r \u00a0data\t\r \u00a0were\t\r \u00a0obtained\t\r \u00a0from\t\r \u00a0\nmedical\t\r \u00a0records\t\r \u00a0retrospecKvely.\t\r \u00a0\n\n\n\nLP\t\r \u00a0 affected\t\r \u00a0mostly\t\r \u00a0 Indian\t\r \u00a0 in\t\r \u00a0 our\t\r \u00a0 populaKon\t\r \u00a0with\t\r \u00a0 classical\t\r \u00a0 LP\t\r \u00a0\nbeing\t\r \u00a0 the\t\r \u00a0 most\t\r \u00a0 common\t\r \u00a0 presentaKon.\t\r \u00a0 Majority\t\r \u00a0 of\t\r \u00a0 paKents\t\r \u00a0\nachieved\t\r \u00a0 remission\t\r \u00a0 following\t\r \u00a0 treatment\t\r \u00a0 with\t\r \u00a0 topical\t\r \u00a0 and\t\r \u00a0\nsystemic\t\r \u00a0steroid\t\r \u00a0with\t\r \u00a0few\t\r \u00a0requiring\t\r \u00a0other\t\r \u00a0systemic\t\r \u00a0agents\t\r \u00a0for\t\r \u00a0a\t\r \u00a0\nbeRer\t\r \u00a0control\t\r \u00a0of\t\r \u00a0the\t\r \u00a0disease.\t\r \u00a0\n\n\n\nTable\t\r \u00a01:\t\r \u00a0Clinical\t\r \u00a0characterisKc\t\r \u00a0in\t\r \u00a0paKents\t\r \u00a0with\t\r \u00a0LP\t\r \u00a0\n\n\n\nCharacteris*cs\t\r \u00a0 N\t\r \u00a0(%)\t\r \u00a0\n\n\n\nGender\t\r \u00a0\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Male\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Female\t\r \u00a0\n\n\n\n\t\r \u00a0\n24\t\r \u00a0(52.2)\t\r \u00a0\n22\t\r \u00a0(47.8)\t\r \u00a0\n\n\n\nAge\t\r \u00a0(years)\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Median\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Min,Max\t\r \u00a0\n\n\n\n\t\r \u00a0\n56\t\r \u00a0\n15,84\t\r \u00a0\n\n\n\nEthnicity\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Malay\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Chinese\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Indian\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Others\t\r \u00a0\t\r \u00a0\n\n\n\n\t\r \u00a0\n8\t\r \u00a0(17.4)\t\r \u00a0\n4\t\r \u00a0(8.7)\t\r \u00a0\n33\t\r \u00a0(71.7)\t\r \u00a0\n1\t\r \u00a0(2.2)\t\r \u00a0\n\n\n\nTable\t\r \u00a02:\t\r \u00a0Disease\t\r \u00a0characterisKcs\t\r \u00a0in\t\r \u00a0paKents\t\r \u00a0with\t\r \u00a0LP\t\r \u00a0\n\n\n\nCharacteris*cs\t\r \u00a0 N\t\r \u00a0(%)\t\r \u00a0\n\n\n\nDisease\t\r \u00a0duraKon\t\r \u00a0(months)\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Median\t\r \u00a0\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Min,\t\r \u00a0Max\t\r \u00a0\n\n\n\n\t\r \u00a0\n10\t\r \u00a0\t\r \u00a0\n1,120\t\r \u00a0\n\n\n\nSymptoms\t\r \u00a0\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Itchy\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Itchy\t\r \u00a0&\t\r \u00a0pigmentaKon\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0PigmentaKon\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0AsymptomaKc\t\r \u00a0\t\r \u00a0\n\n\n\n\t\r \u00a0\n23\t\r \u00a0(50.0)\t\r \u00a0\n19\t\r \u00a0(41.3)\t\r \u00a0\n3\t\r \u00a0(6.5)\t\r \u00a0\n1\t\r \u00a0(2.2)\t\r \u00a0\n\n\n\nSite\t\r \u00a0\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Genital\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Trunk\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Limbs\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Trunk\t\r \u00a0and\t\r \u00a0Limbs\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Groin\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Face\t\r \u00a0and\t\r \u00a0neck\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Trunk\t\r \u00a0and\t\r \u00a0neck\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Face\t\r \u00a0and\t\r \u00a0limbs\t\r \u00a0\n\n\n\n\t\r \u00a0\n1\t\r \u00a0(2.2)\t\r \u00a0\n5\t\r \u00a0(10.9)\t\r \u00a0\n13\t\r \u00a0(28.3)\t\r \u00a0\n20\t\r \u00a0(43.5)\t\r \u00a0\n1\t\r \u00a0(2.2)\t\r \u00a0\n2\t\r \u00a0(4.3)\t\r \u00a0\n2\t\r \u00a0(4.3)\t\r \u00a0\n2\t\r \u00a0(4.3)\t\r \u00a0\n\n\n\nFamily\t\r \u00a0History\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0Yes\t\r \u00a0\n\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0\t\r \u00a0No\t\r \u00a0\n\n\n\n\t\r \u00a0\n1\t\r \u00a0(2.2)\t\r \u00a0\n45\t\r \u00a0(97.8)\t\r \u00a0\n\n\n\n78%\t\n\r\n\n\n\n5%\t\n\r\n\n\n\n2%\t\n\r\n\n\n\n2%\t\n\r\n\n\n\n9%\t\n\r\n\n\n\n4%\t\n\r\n\n\n\nSubtype\t\n\r\n\n\n\nclassical\t\n\r\n\n\n\nhypertrophic\t\n\r\n\n\n\npigmentosus\t\n\r\n\n\n\nactinic\t\n\r\n\n\n\nLPP\t\n\r\n\n\n\nLPLK\t\n\r\n\n\n\nFigure\t\r \u00a01:\t\r \u00a0Subtype\t\r \u00a0of\t\r \u00a0LP\t\r \u00a0in\t\r \u00a0our\t\r \u00a0paKent\t\r \u00a0\n\n\n\nIn\t\r \u00a0 our\t\r \u00a0 study,\t\r \u00a0 we\t\r \u00a0 found\t\r \u00a0 predominantly\t\r \u00a0 Indian\t\r \u00a0 paKents\t\r \u00a0\ncompared\t\r \u00a0 to\t\r \u00a0other\t\r \u00a0ethnicity\t\r \u00a0which\t\r \u00a0was\t\r \u00a0similarly\t\r \u00a0observed\t\r \u00a0by\t\r \u00a0\nNorazirah\t\r \u00a0MN\t\r \u00a0et\t\r \u00a0al\t\r \u00a0and\t\r \u00a0Vijayasingam\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0This\t\r \u00a0suggest\t\r \u00a0some\t\r \u00a0\ngeneKc\t\r \u00a0predominant\t\r \u00a0 to\t\r \u00a0 get\t\r \u00a0 LP\t\r \u00a0 in\t\r \u00a0 Indian.\t\r \u00a0We\t\r \u00a0also\t\r \u00a0 found\t\r \u00a0 that\t\r \u00a0\nthe\t\r \u00a0 classical\t\r \u00a0 LP\t\r \u00a0was\t\r \u00a0 the\t\r \u00a0most\t\r \u00a0 common\t\r \u00a0 consKtuKng\t\r \u00a0 71.7%\t\r \u00a0of\t\r \u00a0\ntotal\t\r \u00a0cases\t\r \u00a0followed\t\r \u00a0by\t\r \u00a0lichen\t\r \u00a0planus\t\r \u00a0pigmentosus\t\r \u00a0(LPP)\t\r \u00a0(8.7%)\t\r \u00a0\nand\t\r \u00a0 hypertrophic\t\r \u00a0 LP\t\r \u00a0 (4.3%).\t\r \u00a0 A\t\r \u00a0 similar\t\r \u00a0 finding\t\r \u00a0 of\t\r \u00a0 dominant\t\r \u00a0\nclassical\t\r \u00a0 LP\t\r \u00a0 over\t\r \u00a0 other\t\r \u00a0 subtype\t\r \u00a0 had\t\r \u00a0 been\t\r \u00a0 reported\t\r \u00a0 in\t\r \u00a0 other\t\r \u00a0\nliterature\t\r \u00a03,4,5.\t\r \u00a050%\t\r \u00a0of\t\r \u00a0our\t\r \u00a0paKents\t\r \u00a0were\t\r \u00a0seen\t\r \u00a0in\t\r \u00a0the\t\r \u00a0age\t\r \u00a0group\t\r \u00a0\nof\t\r \u00a040-\u00ad\u201060\t\r \u00a0years\t\r \u00a0old.\t\r \u00a0However\t\r \u00a0in\t\r \u00a0India\t\r \u00a0it\t\r \u00a0mostly\t\r \u00a0affected\t\r \u00a0younger\t\r \u00a0\nage\t\r \u00a0 group\t\r \u00a0 between\t\r \u00a0 20-\u00ad\u201040\t\r \u00a0 years\t\r \u00a0 old\t\r \u00a0 3,4.\t\r \u00a0 We\t\r \u00a0 also\t\r \u00a0 found\t\r \u00a0 that\t\r \u00a0\nthere\t\r \u00a0was\t\r \u00a0no\t\r \u00a0gender\t\r \u00a0preponderance\t\r \u00a0compared\t\r \u00a0to\t\r \u00a0Indian\t\r \u00a0study\t\r \u00a0\nwhich\t\r \u00a0 showed\t\r \u00a0 female\t\r \u00a0were\t\r \u00a0more\t\r \u00a0 commonly\t\r \u00a0 affected\t\r \u00a0 3,4,5.\t\r \u00a0 In\t\r \u00a0\nour\t\r \u00a0 paKents,\t\r \u00a0 the\t\r \u00a0 most\t\r \u00a0 common\t\r \u00a0 site\t\r \u00a0 affected\t\r \u00a0 in\t\r \u00a0 classical\t\r \u00a0 LP\t\r \u00a0\nwas\t\r \u00a0limbs\t\r \u00a0(75%)\t\r \u00a0which\t\r \u00a0was\t\r \u00a0similarly\t\r \u00a0observed\t\r \u00a0by\t\r \u00a0BhaRacharya\t\r \u00a0\net\t\r \u00a0 al.\t\r \u00a0 and\t\r \u00a0 Pariha\t\r \u00a0 A\t\r \u00a0 et\t\r \u00a0 al.\t\r \u00a0 Pruritus\t\r \u00a0 was\t\r \u00a0 the\t\r \u00a0 most\t\r \u00a0 common\t\r \u00a0\nsymptom\t\r \u00a0 of\t\r \u00a0 LP\t\r \u00a0 in\t\r \u00a0 91.3%\t\r \u00a0 of\t\r \u00a0 our\t\r \u00a0 paKents\t\r \u00a0 which\t\r \u00a0 similarly\t\r \u00a0\nexperienced\t\r \u00a0 by\t\r \u00a0 Indian\t\r \u00a0 study\t\r \u00a0 (\t\r \u00a0 90.0%\t\r \u00a0 4\t\r \u00a0 and\t\r \u00a0 82.6%\t\r \u00a0 5\t\r \u00a0 ).\t\r \u00a0 There\t\r \u00a0\nwere\t\r \u00a0 two\t\r \u00a0paKents\t\r \u00a0with\t\r \u00a0 lichenoid\t\r \u00a0drug\t\r \u00a0erupKon\t\r \u00a0secondary\t\r \u00a0 to\t\r \u00a0\nImaKnib\t\r \u00a0 and\t\r \u00a0 Glimepiride\t\r \u00a0 (anKdiabeKc)\t\r \u00a0 respecKvely\t\r \u00a0 which\t\r \u00a0\nwere\t\r \u00a0two\t\r \u00a0main\t\r \u00a0implicated\t\r \u00a0drugs\t\r \u00a0causing\t\r \u00a0lichenoid\t\r \u00a0reacKon\t\r \u00a06\t\r \u00a0.\t\r \u00a0\nThe\t\r \u00a0 lower\t\r \u00a0 number\t\r \u00a0 of\t\r \u00a0 paKents\t\r \u00a0 with\t\r \u00a0 lichenoid\t\r \u00a0 drug\t\r \u00a0 erupKon\t\r \u00a0\nmay\t\r \u00a0 be\t\r \u00a0 due\t\r \u00a0 to\t\r \u00a0 less\t\r \u00a0 likelihood\t\r \u00a0 of\t\r \u00a0 performing\t\r \u00a0 skin\t\r \u00a0 biopsy\t\r \u00a0 in\t\r \u00a0\nadverse\t\r \u00a0drug\t\r \u00a0reacKon\t\r \u00a0hence\t\r \u00a0this\t\r \u00a0group\t\r \u00a0of\t\r \u00a0paKent\t\r \u00a0may\t\r \u00a0not\t\r \u00a0be\t\r \u00a0\ncaptured\t\r \u00a0 in\t\r \u00a0 our\t\r \u00a0 series.\t\r \u00a0 Our\t\r \u00a0 paKents\t\r \u00a0 had\t\r \u00a0 higher\t\r \u00a0 complete\t\r \u00a0\nremission\t\r \u00a0 rates\t\r \u00a0 which\t\r \u00a0 was\t\r \u00a0 64%\t\r \u00a0 compared\t\r \u00a0 to\t\r \u00a0 systemaKc\t\r \u00a0\nreview\t\r \u00a0 and\t\r \u00a0 meta-\u00ad\u2010analysis\t\r \u00a0 done\t\r \u00a0 by\t\r \u00a0 Atzmony\t\r \u00a0 L\t\r \u00a0 et\t\r \u00a0 al,\t\r \u00a0 which\t\r \u00a0\nfound\t\r \u00a0that\t\r \u00a0 the\t\r \u00a0complete\t\r \u00a0remission\t\r \u00a0rates\t\r \u00a0ranges\t\r \u00a0 from\t\r \u00a013.04%\t\r \u00a0\nto\t\r \u00a0 59.26%.\t\r \u00a0 This\t\r \u00a0 may\t\r \u00a0 be\t\r \u00a0 due\t\r \u00a0 to\t\r \u00a0 early\t\r \u00a0 iniKaKon\t\r \u00a0 of\t\r \u00a0 treatment\t\r \u00a0\nincluding\t\r \u00a0systemic\t\r \u00a0steroid\t\r \u00a0which\t\r \u00a0 lead\t\r \u00a0to\t\r \u00a0beRer\t\r \u00a0control\t\r \u00a0of\t\r \u00a0the\t\r \u00a0\ndisease.\t\r \u00a0\n\t\r \u00a0\n\n\n\n1.\u202f Norazirah\t\r \u00a0 MN,\t\r \u00a0 Mazlin\t\r \u00a0 MB,\t\r \u00a0 Adawiyah\t\r \u00a0 J\t\r \u00a0 et\t\r \u00a0 al.\t\r \u00a0 Lichen\t\r \u00a0 planus\t\r \u00a0 and\t\r \u00a0 HepaKKs\t\r \u00a0 C\t\r \u00a0 infecKon\t\r \u00a0 :\t\r \u00a0\nExploring\t\r \u00a0the\t\r \u00a0associaKon\t\r \u00a0among\t\r \u00a0Malaysian\t\r \u00a0paKents.\t\r \u00a0MJD\t\r \u00a02013;\t\r \u00a031:8-\u00ad\u201012.\t\r \u00a0\n\n\n\n2.\u202f Vijayasingam\t\r \u00a0SM,\t\r \u00a0Lim\t\r \u00a0KB,\t\r \u00a0Yeoh\t\r \u00a0KH\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0Lichen\t\r \u00a0planus:\t\r \u00a0a\t\r \u00a0study\t\r \u00a0of\t\r \u00a072\t\r \u00a0cases\t\r \u00a0in\t\r \u00a0Singapore.\t\r \u00a0Ann\t\r \u00a0\nAcad\t\r \u00a0Med\t\r \u00a0Singapore.1988\t\r \u00a0Oct;\t\r \u00a017(4):541-\u00ad\u20104.\t\r \u00a0\t\r \u00a0\n\n\n\n3.\u202f BhaRacharya\t\r \u00a0 M,\t\r \u00a0 Kaur\t\r \u00a0 I,\t\r \u00a0 Kumar\t\r \u00a0 B.\t\r \u00a0 Lichen\t\r \u00a0 planus:\t\r \u00a0 a\t\r \u00a0 clinical\t\r \u00a0 and\t\r \u00a0 epidemiological\t\r \u00a0 study\t\r \u00a0 of\t\r \u00a0\ncutaneous\t\r \u00a0lichen\t\r \u00a0planus.\t\r \u00a0J\t\r \u00a0Dermatol.\t\r \u00a02000;\t\r \u00a019\t\r \u00a0(1):21-\u00ad\u20106.\t\r \u00a0\n\n\n\n4.\u202f Parihar\t\r \u00a0A,\t\r \u00a0Sharma\t\r \u00a0S\t\r \u00a0et\t\r \u00a0al.\t\r \u00a0A\t\r \u00a0clinicopathological\t\r \u00a0study\t\r \u00a0of\t\r \u00a0cutaneous\t\r \u00a0LP.\t\r \u00a0J\t\r \u00a0Dermatol\t\r \u00a0&\t\r \u00a0Dermatol\t\r \u00a0\nSurg.\t\r \u00a02015;\t\r \u00a027(9):576-\u00ad\u2010582.\t\r \u00a0\n\n\n\n5.\u202f Ireddy\t\r \u00a0SG,\t\r \u00a0Udbalkar\t\r \u00a0G.\t\r \u00a0Epidemiological\t\r \u00a0study\t\r \u00a0of\t\r \u00a0lichen\t\r \u00a0planus.\t\r \u00a0BMR\t\r \u00a0Journal.\t\r \u00a02014;\t\r \u00a01(1):1-\u00ad\u20109.\t\r \u00a0\n6.\u202f Farzam\t\r \u00a0 G,\t\r \u00a0 Parastoo\t\r \u00a0 D,\t\r \u00a0 Nasim\t\r \u00a0 F.\t\r \u00a0 Cutaneous\t\r \u00a0 and\t\r \u00a0 mucosal\t\r \u00a0 lichen\t\r \u00a0 planus:\t\r \u00a0 a\t\r \u00a0 comprehensive\t\r \u00a0\n\n\n\nreviewof\t\r \u00a0clinical\t\r \u00a0subtypes,\t\r \u00a0risk\t\r \u00a0factors,\t\r \u00a0diagnosis\t\r \u00a0and\t\r \u00a0prognosis.\t\r \u00a0Sci\t\r \u00a0World\t\r \u00a0J.\t\r \u00a02014.\t\r \u00a0\n7.\u202f AtzmonyL,\t\r \u00a0 Reiter\t\r \u00a0 O,\t\r \u00a0 Hodak\t\r \u00a0 E\t\r \u00a0 et\t\r \u00a0 al.\t\r \u00a0 Treatments\t\r \u00a0 for\t\r \u00a0 cutaneous\t\r \u00a0 lichen\t\r \u00a0 planus:\t\r \u00a0 a\t\r \u00a0 systemaKc\t\r \u00a0\n\n\n\nreview\t\r \u00a0and\t\r \u00a0meta-\u00ad\u2010analysis.\t\r \u00a0Am\t\r \u00a0J\t\r \u00a0Clin\t\r \u00a0Dermatol.\t\r \u00a02015.\t\r \u00a0\n\n\n\n\t\r \u00a0\n\n\n\n\u2022\u202f Male\t\r \u00a0and\t\r \u00a0female\t\r \u00a0were\t\r \u00a0equally\t\r \u00a0affected\t\r \u00a0in\t\r \u00a0our\t\r \u00a0study.\t\r \u00a0\n\u2022\u202f Most\t\r \u00a0of\t\r \u00a0our\t\r \u00a0paKents\t\r \u00a0did\t\r \u00a0not\t\r \u00a0have\t\r \u00a0nail\t\r \u00a0changes\t\r \u00a0(93.5%)\t\r \u00a0or\t\r \u00a0\n\n\n\noral\t\r \u00a0lesions\t\r \u00a0(89.1%)\t\r \u00a0\n\u2022\u202f Only\t\r \u00a02\t\r \u00a0paKents\t\r \u00a0had\t\r \u00a0lichenoid\t\r \u00a0drug\t\r \u00a0erupKon\t\r \u00a0secondary\t\r \u00a0to\t\r \u00a0\n\n\n\nImaKnib\t\r \u00a0and\t\r \u00a0Glimepiride\t\r \u00a0\n\u2022\u202f All\t\r \u00a0 paKents\t\r \u00a0 received\t\r \u00a0 topical\t\r \u00a0 corKcosteroid,\t\r \u00a0 19\t\r \u00a0 paKents\t\r \u00a0\n\n\n\nrequired\t\r \u00a0 only\t\r \u00a0 topical\t\r \u00a0 corKcosteroid\t\r \u00a0 and\t\r \u00a0 27\t\r \u00a0 paKents\t\r \u00a0\nrequired\t\r \u00a0addiKonal\t\r \u00a0systemic\t\r \u00a0steroid.\t\r \u00a0\n\n\n\n\u2022\u202f Out\t\r \u00a0of\t\r \u00a0 these\t\r \u00a027\t\r \u00a0paKents,\t\r \u00a03\t\r \u00a0paKents\t\r \u00a0 required\t\r \u00a0addiKonal\t\r \u00a0\nHydroxychloroquine,\t\r \u00a0 1\t\r \u00a0 paKent\t\r \u00a0 required\t\r \u00a0 addiKonal\t\r \u00a0\nreKnoic\t\r \u00a0 acid\t\r \u00a0 and\t\r \u00a0 1\t\r \u00a0 paKent\t\r \u00a0 was\t\r \u00a0 treated\t\r \u00a0 with\t\r \u00a0\nHydroxychloroquine,\t\r \u00a0Methotrexate\t\r \u00a0 and\t\r \u00a0 Azathioprine\t\r \u00a0 to\t\r \u00a0\ncontrol\t\r \u00a0the\t\r \u00a0disease.\t\r \u00a0\n\n\n\n\u2022\u202f 1\t\r \u00a0 paKent\t\r \u00a0 had\t\r \u00a0 addiKonal\t\r \u00a0 PUVA\t\r \u00a0 and\t\r \u00a0 2\t\r \u00a0 paKents\t\r \u00a0 had\t\r \u00a0\nNBUVB.\t\r \u00a0\n\n\n\n\u2022\u202f DuraKon\t\r \u00a0 before\t\r \u00a0 complete\t\r \u00a0 remission\t\r \u00a0 was\t\r \u00a0 between\t\r \u00a0 7\t\r \u00a0\nmonths\t\r \u00a0to\t\r \u00a05\t\r \u00a0years.\t\r \u00a0\n\n\n\n\u2022\u202f For\t\r \u00a0 25\t\r \u00a0 paKents\t\r \u00a0 who\t\r \u00a0 are\t\r \u00a0 sKll\t\r \u00a0 under\t\r \u00a0 our\t\r \u00a0 follow\t\r \u00a0 up,\t\r \u00a0 16\t\r \u00a0\npaKents\t\r \u00a0(64%)\t\r \u00a0of\t\r \u00a0them\t\r \u00a0achieved\t\r \u00a0complete\t\r \u00a0remission.\t\r \u00a0\n\n\n\n\n\n\n\n\nPoikiloderma : \nA Diagnostic Challenge of Two Case Reports \n\n\n\n\n\n\n\n42 \n Narayanan D, Tang JJ \n\n\n\nDepartment of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh \n\n\n\nINTRODUCTION \nPoikiloderma is a descriptive term referring to a combination of \ncutaneous atrophy, telangiectasia and varied pigmentary changes in a \nreticulate pattern1. It may pose a diagnostic challenge to clinicians due \nto similarity in presentation even though the underlying causes are \nvaried. Herein, we describe 2 patients with poikiloderma caused by \nmycosis fungoides (MF) and subacute cutananeous lupus erythematosus \n(SCLE) respectively, both of whom had similar clinical presentation. \n\n\n\nCASE 1 \nA 36 year old man presented with a 6 year history of erythematous, \nscaly plaques over his trunk, bilateral upper and lower limbs. His rash \nwas asymptomatic. His past medical history was not significant and he \nwas not a smoker. On physical examination, violaceous plaques in a \nreticulated pattern were noted predominantly over the trunk and limbs \nwith thick plaques over the inner aspect of the thighs (Fig. 1A). His face, \nneck and scalp were spared. His liver, spleen and lymph nodes were not \npalpable. A skin biopsy done showed epidermotropism and \nintraepidermal collections of atypical lymphocytes (Fig. 1B) which \nstained positive for CD2, CD3, CD4 and CD5 (Fig. 1C) with loss of CD7 \nand CD8 (Fig. 1D). All other blood investigations were normal. CT scan \nfor staging showed bilateral axillary and inguinal lymphadenopathy. A \nfinal diagnosis of poikilodermatous MF (Stage IB) was made and he was \ncommenced on a combination of psoralen plus ultraviolet A therapy \n(PUVA) and acitretin. All lesions resolved within 2 years of treatment \nand he continues to be in remission. \n\n\n\nCASE 2 \nA 52 year old man presented with a 2 month history of diffuse rash \nwhich started from the thighs then gradually spread to involve his \ntrunk, upper limbs, face and neck. The rash was mildly itchy. His past \nmedical history was not significant. He worked as a bus driver and was \nexposed to the sun for many hours in a day. On examination, there \nwere erythematous to violaceous, confluent papules and plaques with \nareas of cutaneous atrophy, hypopigmentation and hyperpigmentation \n(Fig. 2A) in a reticulated pattern involving his face, trunk and limbs but \nworse over the sun exposed areas. There was no heliotrope rash, \nGottron sign or proximal myopathy. His systemic examination was \nunremarkable. Skin biopsy showed psoriasiform hyperplasia with \ninterface dermatitis (Fig 2B). Immunofluorescence (IF) studies showed \ngranular deposition of IgM antibody along the dermoepidermal \njunction (DEJ) (Fig 2C). Antinuclear antibody (ANA) test was positive \nwith a titre of 1:640. However, no extractable antinuclear antibodies \nwere detected. His creatine kinase was normal as was his other blood \ninvestigation results. On the basis of the clinical, histopathological and \nserological findings, a diagnosis of poikilodermatous SCLE was made. \nHe was started on oral prednisolone, hydroxychloroquine and topical \ncorticosteroids and showed good response to treatment. \n\n\n\nCONCLUSION \nPoikiloderma may look confusingly similar despite its varying \netiologies. Although the importance of good history taking and \nthorough physical examination should not be overlooked, the final \ndiagnosis depends on a good clinicopathological correlation with the \nskin biopsy result.  \n\n\n\nDISCUSSION \nPoikilodermatous MF is a rare variant of MF. Typically, the lesions \nconsist of large plaques of hypopigmentation and hyperpigmentation \nwith atrophy and telangiectasia, located predominantly over the trunk \nand flexural areas.2 Due to cutaneous atrophy, the skin appears \nwrinkled and resembles a \u201ccigarette paper\u201d. It has an early stage (IA-IIA) \nat diagnosis and a male predominance.2 As opposed to classic MF, \npoikilodermatous lesions are generally asymptomatic or mildly pruritic \nand are usually stable or slowly increasing in size.2 A retrospective \nstudy by Abbott et al found the incidence to be 11.2% with younger age \nat onset when compared to classic MF.3  \n    Histologically it is similar to classic MF with an atypical T-cell \ninfiltrate in the papillary dermis, evidence of epidermotropism, \nepidermal atrophy, dilated blood vessels in the dermis, melanophages, \nand melanin incontinence.2 Pautrier microabscesses are not as common. \nImmunophenotypic studies are consistent with a mature helper T-cell \nphenotype and typically demonstrate a CD2+, CD3+, CD4+, CD45RO+, \nCD7-, CD8- pattern.4 However, other studies have found a \npredominance of a CD8+, CD4- immunophenotype instead.2 \nPoikilodermatous MF has an excellent prognosis and most patients \nrespond well to phototherapy (PUVA).3 \n    Poikilodermatous SCLE was first reported by Pramatarov et al in the \nyear 2000. They described a patient who presented with generalized \npoikiloderma in a photo distributed pattern and attributed it to a \nprevious episode of sunburn.5 Since then, there have only been 2 other \narticles published on the matter.6,7 One of them was a retrospective \nstudy by Marzano et al, who reviewed 54 patients with established \nSCLE. They found the prevalence of poikilodermatous SCLE to be 7.4% \n(4 out of 54 patients). Interestingly, 3 of the 4 patients also reported an \nepisode of sunburn or excessive sun exposure followed by rapid \ndevelopment of generalized poikiloderma.6 Excessive sun exposure had \nbeen noted in our second case due to his job as a bus driver which \ncould have predisposed him to develop SCLE. \n   Histologically characteristic features of SCLE include marked \northokeratosis, interface dermatitis with basal cell vacuolation, Civatte \nbody formation and melanin incontinence.7 Direct \nimmunofluorescence may show granular deposits of complement \nand/or immunoglobulin along the DEJ but this is only positive in 60% of \npatients.7 Likewise, a positive ANA with positive anti-Ro/SSA is highly \nsuggestive of SCLE but may be absent in up to 20% of patients, as was \nthe case with our patient who tested positive for ANA but negative for \nanti-Ro/SSA. Frequently, a combination of topical corticosteroids, oral \nanti-malarial and immunosuppressive therapy is required to achieve \nremission. \n\n\n\nReferences \n1. Nofal A, Salah E. Acquired poikiloderma: proposed classification and diagnostic approach. J \nAm Acad Dermatol. 2013;69(3):e129-40 \n2. Bloom B, Marchbein S, Fischer M, Kamino H, Patel R, Latkowski JA. Poikilodermatous mycosis \nfungoides. Dermatol Online J. 2012;18(12):4. \n3. Abbott RA, Sahni D, Robson A, Agar N, Whittaker S, Scarisbrick JJ. Poikilodermatous mycosis \nfungoides: a study of its clinicopathological, immunophenotypic, and prognostic features. J Am \nAcad Dermatol. 2011;65(2):313-9. \n4. Farley-loftus R, Mandal R, Latkowski JA. Poikilodermatous mycosis fungoides. Dermatol \nOnline J. 2010;16(11):8. \n5. Pramatarov K, Vassileva S, Miteva L. Subacute cutaneous lupus erythematosus presenting with \ngeneralized poikiloderma. J Am Acad Dermatol. 2000;42(2 Pt 1):286-8. \n6. Marzano AV, Facchetti M, Alessi E. Poikilodermatous subacute cutaneous lupus \nerythematosus. Dermatology (Basel). 2003;207(3):285-90. \n7. Kuhn, Lehmann, et al. \u201cChapter 21.\u201d Cutaneous Lupus Erythematosus, Springer, 2014, pp. \n297\u2013303. \n\n\n\nFigure 1. (A) Poikilodermatous MF with reticulated  lesions (inset); (B) Epidermo -\ntrophism with atypical lymphocytes which are CD4+ (C) and CD7- (D) \n\n\n\nFigure 2. (A) Pokilodermatous SCLE with cutaneous atrophy and dyspigmentation \n(inset); (B) Interface dermatitis; (C) Positive IF with granular pattern \n\n\n\n\n\n\n\n\nLOCAL EXPERIENCE OF USTEKINUMAB IN THE TREATMENT OF \n\n\n\nPLAQUE PSORIASIS: A CASE SERIES\n\n\n\nAzlin T, Rohna R, Teoh TY, Ong SB\n\n\n\nSelayang Hospital, Malaysia\n\n\n\nINTRODUCTION\n\n\n\nPsoriasis is a chronic relapsing inflammatory skin disorder affecting about 1 to 3% of the population worldwide, and is often\nassociated with significant morbidity and impaired quality of life.\n\n\n\nIn the treatment of psoriasis, topical therapy is sufficient in the majority of patients. However, a number of patients experience\nsevere symptoms and may require systemic treatment such as methotrexate, cyclosporine, oral retinoid, or phototherapy 1.\nIntroduction of biologic agents has changed the landscape of psoriasis treatment worldwide. In Malaysia, biologic agents are\nused as a 3rd line treatment.\n\n\n\nDISCUSSION\n\n\n\nBiologics agent has changed the paradigm of treatment for psoriasis\nand psoriatic arthropathy2. Malaysia psoriasis CPG recommends\nthat biologics agent to be considered when BSA >20% or PASI >30\nor DLQI >20 and a failure or intolerant or contraindication to all 2nd\nline therapy: methotrexate, cyclosporin, acitretin and phototherapy3.\nOur experience is consistent with PHOENIX 1 and 2 where\nmaximum response is noted at 6 months and the response rate\nstabilized there on4,5. All our patient attained at least PASI 50 at 6\nmonths. PHOENIX 2 noted only a 5-7% of poor responders who\nachieved less than PASI 504,5. Three of our patient had mild URTI\nwhile on ustekinumab. PHOENIX 2 documented of up to 10.4% of\nURTI in patients on 8 weekly dosing of ustekinumab. Interestingly,\nour experience noted that weight may not play a significant role in\nresponse to ustekinumab. Both patient 1 and 2 were below 90kg\nwhile patient 3 and patient 4 were above 100kg, yet patient 3 and 4\nhad better response at 6 months. PHOENIX 2 had 20% of partial\nresponders and they were noted to be of higher body weight and\nlonger duration of skin disease4. Patient 4 had a worsening of\nresponse towards the end of his treatment which could be\ncontributed to a stressful life and URTI. The 3 patients who\ncompleted one year of ustekinumab had gradual recurrence of\npsoriasis, as was noted in PHOENIX 15.\nOne interesting observation we noted was that patient 1 and patient\n3 developed psoriatic arthropathy few months after completing 1\nyear of ustekinumab. After following up patient for 36 weeks in\nPHOENIX 1, there was no similar report of psoriatic arthritis in its\npopulation. This observation may be a coincidental finding as part of\nthe disease progression, or a \u201cside effect\u201d of the treatment. A larger\npopulation study is needed to ascertain this effect.\n\n\n\nREFERENCES\n\n\n\n1. Necas M and Vasku V, 2010, Ustekinumab in the treatment of severe rupioid psoriasis: A case report. Acta Dermatoven, APA, Vol 19, \n23 \u2013 27.\n\n\n\n2. Menter A, Papp KA, et al, 2016, Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results \nfrom the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Journal of the European Academy of Dermatology and \nVenereology.  30(7), 1148-58.\n\n\n\n3. Ministry of Health Malaysia, Clinical Practice Guidelines: Management of Psoriasis Vulgaris, 2013.\n4. Papp KA, Langley RG, Lebwohl M, et al, 2008, Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in \n\n\n\npatients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet, \n371(9625):1675\u20131684.\n\n\n\n5. Leonardi CL, Kimball AB, Papp KA et al 2008. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in \npatients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). \n\n\n\nCASESERIES\n\n\n\nFour patients had Ustekinumab and completed 12 months of therapy. One patient just completed his therapy in April 2017.\nMean baseline body surface area (BSA) was 66%, Psoriasis Area Severity Index (PASI) 24.8, and Dermatology Life Quality\nIndex (DLQI) of 11.5. Three patients developed mild infection during the course of Ustekinumab therapy.\n\n\n\nPatient 1 is a 43 year-old male, who was diagnosed with plaque psoriasis at 26\nyears old. He has failed phototherapy and methotrexate, and had contraindication\nto cyclosporin. His BSA, PASI and DLQI improved at the end of therapy but had\ngradual rebound after 1 year. (Figure 1) However, he developed psoriatic arthritis\nwith sacroiliitis during our post one year follow up observation.\n\n\n\nPatient 2 is a 32 year-old male, who suffers from plaque psoriasis since 18 years of\nage. He had a slow response to phototherapy and acitretin, and developed an\nadverse effect to methotrexate and cyclosporine. He was started on ustekinumab\nin 2015 for 1 year. His BSA, PASI and DLQI were significantly reduced. (Figure 2)\n\n\n\nPatient 3 is a 33 year-old male, who has plaque psoriasis since 13 years of age.\nHe also has underlying steatohepatitis. He developed erythroderma secondary to\nphototherapy and had transaminitis with acitretin and methotrexate. His BSA, PASI\nand DLQI improved significantly and was maintained for another 1 year. (Figure 3)\n\n\n\nHe developed psoriatic arthropathy during our post one year follow up observation.\n\n\n\nPatient 4 is a 43 year-old male, who was diagnosed with plaque psoriasis at 29\nyears old. He has an underlying metabolic syndrome with gouty arthritis. He\ndeveloped transaminitis with acitretin. His BSA, PASI and DLQI were noted to be\nreduced after 6 months of therapy (Figure A-D) but worsened at 12 months. (Figure\n\n\n\n4)\n\n\n\nFigure A: Before therapy        Figure C: 6 months of \n\n\n\n(Front)                                       therapy (Front)\n\n\n\nFigure B: Before therapy        Figure D: 6 months of\n\n\n\n(Back)                                        therapy (Back)\n\n\n\nFigure A\n\n\n\nFigure B Figure D\n\n\n\nFigure C\n\n\n\n43\n\n\n\nCONCLUSION\n\n\n\nTreatment with ustekinumab was fully indicated in our\npatients, resulting in very good and rapid therapeutic\neffect without any severe adverse events. However,\nthe development of arthritis in 2 of our patients after\ncompleting 1 year of ustekinumab remains to be\nexplained.\n\n\n\n\n\n\n\n\nEfficacy of Using Topical Immunotherapy with Squaric Acid \nDibutylester  in the Treatment of Alopecia Areata \u2013 \n\n\n\nA case series of 11 patients\n\n\n\nAng TS,   Tang JJ  \nDepartment of Dermatology, Raja Permaisuri Bainun Hospital, Ipoh\n\n\n\nPoster \nNo. 44\n\n\n\nINTRODUCTION\nAlopecia areata (AA)  is a common autoimmune mediated non scarring hair \nloss directed at anagenic hair follicle, most commonly on the scalp. The \nseverity ranges from alopecia areata to severe form of alopecia totalis (AT) \nand alopecia universalis (AU). Squaric acid dibutylester (SADBE) is a form of \ncontact sensitizer used as immunotherapy in AA with promissing outcome \nand good tolerablility with less side effects.   \nOBJECTIVES\nTo determine the demography, treatment outcome and  side effects of \nSABDE in the treatment of AA at the Department Of Dermatology, Hospital \nRaja Permaisuri Bainun, Ipoh.\nMETHODS\nThis was a retrospective review from December 2015 to July 2017 for \npatients with AA who undergone SADBE treatment in our department after \nfailed conventional treatment. All patients who completed SADBE for at \nleast 3 months were recruited and the following clinical data were \nanalyzed : age, sex, gender,duration of presentation to initial SADBE, disease \nsubtype, side effect and  treatment response. Good response of treatment \nis defined as regrowth of terminal hair with patches of alopecia (Mcdonald \nHull and Norris Grade 3).\nAs for the SADBE protocol, all patients are sensitized with 2% SADBE first \nand then 0.001% SADBE wi l l  be used dur ing the in it iat ion.  This \nconcentration is gradually increased to 0.01%, 0.1%, 0.2%, 0.5% , 1% and 2% \nuntil mild dermatitis develop manifesting as mild erythema and pruritus. \nThis treatment is carried out at weekly basis until significant hair growth is \nnoted.\nRESULTS\nA total of 11 patients with AA of varying severity in the treatment of SADBE \nwere recruited that consist of 8 females (72%) and 3 males (28%). There \nwere 6 Malays (55%) and 5 Chinese (45%). The means age was 20 years old \n(range from 4 years old to 60 years old) and the means duration of \npresentation to initial SADBE was 2 years 5 months (range from 5 months to \n7 years). As for previous treatment, all 11 patients had failed topical \ncorticosteroid and 4 had failed topical psoralen and ultraviolet A therapy \nPUVA, intralesional corticosteroid (IDK) respectively and 3 had failed short \ncourse of oral prednisolone. \n\n\n\nThere was three subtypes of AA been identified which were 5 patients had \nAA affecting less than 50% of the scalp and 6 had severe form, including 1 \npatient with AT and 5 patients with AU. \nA total of 8 patients (72%.) achieved overall good response with regrowth of \nterminal hair with residual patches of alopecia. In patients with less than \n50% scalp involvement; the response rate was better (80%) compare to \nthose with severe form of AA (66%) -Figure 1 -4. The mean duration taken \nto achieve good response was 6.5 months ( range from 3.5 months to 16 \nmonths). Among 8 responders, 4 of them require 10 sessions of SADBE to \nelicit the regrowth of vellus hair at the concentration of 0.1-0.5% and the \nremaining 4 responders required more than 10 session before vellus hair \nformation. Among 3 non responders, 2 patients were unable to be \nsensitized at the concentration of 2% and one responsed with formation \nvellus hair but failed to develop terminal hair. Among 8 patients who failed \ntopical PUVA and/or IDK previously, 5 of them (62.5%) responded well to \nSADBE.  Only 3 patients  suffered from minor side effects like persistant \nirritation, vesicle and blister formation. Table 1\n\n\n\nTable 1: Clinical characteristic and Treatment outcome of patients on \nSADBE  F-Female, M-Male, TCS-topical corticosteroid, PUVA-topical psoralen and ultraviolet A \ntherapy, IDK-intralesional corticosteroid, CS-oral corticosteroid, y-year, m-month, GR-Good response, \nNR-Non response\nDISCUSSION\nAA is a common autoimmune disease, mediated by autoreactive CD8+ T \ncells,characterized by  non scarring hair loss involving commonly on the \nscalp and the life time risk is 2%. [1,2,3] . AA predominantly affects female \nas in our study (72% female) which was consistent with a study by Dall\u2019oglio \net al (53% female).[1] \nSADBE is  a form of contact allergens of topical immunotherapy in treatment \nof AA whereby the recruited suppressor CD8+ T cells generate an inhibitory \neffect on the immune process against hair follicles, thus allowing hair \ngrowth. SADBE is an  nonmutagenic ideal sensitizer as it is not widely found \nin nature , does not cause significant adverse events and does not cross \nreaction with other chemicals.[2,3]\n\n\n\nCONCLUSION \nSADBE is an effective and well tolerable therapeutic \nimmuno therapy in treatment of AA.\n\n\n\n[1]F. Dall\u2019oglio, M. R. Nasca et al.Topical immunomodulator therapy with squaric acid \ndibutylester (SADBE) is effective treatment for severe alopecia areata (AA): Results of an open-\nlabel, paired-comparison, clinical trial 2005; 16: 10\u201314\n[2]Nikki D Hill, Kristin Bunata et al. Treatment of alopecia areata with squaric dibutylester \n2015; 33,300-304\n[3]Anup K. Tiwary, Dharmendra K. Mishra et al.Comparative study of efficacy and safety of \ntopical squaric Acid dibutylester and diphenylcyclopropenone for the treatment of  alopecia \nareata 2016 Jun; 8(6): 237\u2013242.\n[4]Gurcharan Singh, MS Lavanya et al.Topical immunotherapy in alopecia areata  2010; 2:36-39\n[5]Van der Steen, Van Baar et al. Treatment of alopecia areata with diphenylcyclopropenone \n1991; 24:253-257\n[6]Takashi Yoshimasu, Fukumi Furukawa et al. Modified immunotherapy for alopecia areata \n2016;15 (7), 664-667. \n\n\n\nThe clinical response to SADBE was according to a grading system \nproposed by Mcdonald Hull and Norris [4]\nGrade 1 - Regrowth of vellus hair\nGrade 2 - Regrowth of sparse pigmented terminal hair\nGrade 3 - Regrowth of terminal hair with patches of alopecia \nGrade 4 - Regrowth of terminal hair on scalp \n\n\n\nOur study showed 72% of patients with AA responded to SADBE and \nthe response is better with less severe form of AA (80%) as \ncompared to severe form AA (AT/AU) (66%). This result is supported \nby Case et al which also showed AA responded better than AT and \nAU at 73% and 30% respectively. Another study by Micali et al \nshowed that 80% with less severe type of AA had good response to \nSADBE compared to 49% of more severe form of AA. Dall\u2019oglio also \nshowed that 80% of the treatment group had experienced hair \ngrowth compared to 50% of the control group. Ajith et al too showed \nhigher success rate in patients < 50% scalp involvement (68%) \ncompared to diffuse type (29%) .However, Caserio et al only had \n28.5% patients had hair growth after using SADBE. [2]. The non \nresponder rate in our series was 28% which is consistent with  20% \nof non responders in study by Case et al.[2]\n\n\n\nSeverity of alopecia , duration of disease and presence of nail factor \npredicted a poorer response by Van der Steen et al.[5] Our study \nshowed that 2 patients suffered from AU did not respond to SADBE. \nHowever, early development of contact dermatits (sensitization \ninduces contact dermatits within 10 weeks of application) is a good \nprognostic factor.[4] In our study, 4 patients who formed vellus hair \nat minimal of 10 sessios of SADBE showed good response to \ntreatment.\n\n\n\nEczema, auto-eczematization, blistering, swelling of regional lymph \nnodes, urticaria and contact leukoderma are the most common side \neffects.[2,4] In our study , only 3 patients suffered minor side effects \nlike persistant irritation, vesicle and blister formation. \n\n\n\nMeanwhile, Takashi et al revealed that modified immunotherapy \nstarting with a concentration of 0.01% SADBE without sensitizationis \nas effective as conventional  immunotherapy start ing with \nsensitization with 2% SADBE or DPCP.[6] \n\n\n\nFigure 1 & 2 -  60 years old lady with progressively worsening of  \n                          AA which hair regrowth after 4 months of SADBE \n                          \n                         \n\n\n\n  Figure 3 & 4 - AA in a 4 years old girl which failed topical steroid\n                           responded well after 4 months of  SADBE\n\n\n\nFig 1 Fig 2\n\n\n\nFig 3 Fig 4\n\n\n\nSex Age \n \n\n\n\nSubtype\n \n\n\n\nPrevious \nTreatment\n\n\n\n\n\n\n\nDisease \nDuration\n\n\n\nOutcome \nof SADBE \n\n\n\nDuration to \nachieve good \nresponse \n\n\n\nSide effect \n\n\n\n1 F 6 AA TCS 1 y GR 7 m  -\n2 F 33 AU TCS, PUVA, CS 2 y GR 7m -\n3 F 10 AU TCS, PUVA 4 y GR 16m -\n4 M 13 AA TCS 7 y GR 4 m -\n5 F 42 AU TCS, PUVA 7 y NR - -\n6 F 4 AA TCS 5 m GR 3.5 m Irritation\n7 F 32 AT TCS, PUVA, IDK 2 y GR 5 m Blister\n\n\n\n8 F 9 AU TCS, CS 5 m NR - -\n9 M 12 AA TCS, IDK 1 y NR - Vesicle\n\n\n\n10 M 31 AU TCS, IDK, CS 1 y GR 6 m -\n\n\n\n11 F 61 AA TCS, CS 1 y GR 4 m -\n\n\n\n\n\n\n\n\nA 5-year clinico-etiological study of erythroderma \nin a tertiary hospital of Ipoh\n\n\n\nAsha G, Tang JJ, Hospital Raja Permaisuri Bainun\n\n\n\nPoster\n45\n\n\n\nINTRODUCTION\n\n\n\nErythroderma is a condition characterized by generalized scaling and\n\n\n\nerythema involving 90% or more of the body surface area.\n\n\n\nErythroderma poses a diagnostic challenge as it can be caused by a\n\n\n\nwide range of cutaneous or systemic diseases.\n\n\n\nOBJECTIVE\n\n\n\nThe aim of this study was to evaluate the demographic pattern, clinical\n\n\n\nfeatures and etiology of erythroderma. We also assessed the\n\n\n\ncorrelation between clinical diagnosis and histopathological findings as\n\n\n\nwell as duration of erythroderma and complications of acute skin\n\n\n\nfailure.\n\n\n\nMETHOD\n\n\n\nA retrospective study was conducted in the Department of\n\n\n\nDermatology, Hospital Raja Permaisuri Bainun. All patients with\n\n\n\nerythroderma who had undergone skin biopsies from year 2012 to 2016\n\n\n\nwere studied. Relevant data was collected and data analysis was done\n\n\n\nusing SPSS version 22.\n\n\n\nRESULTS\n\n\n\nOver the period of 5 years, there were 48 erythroderma cases who had\n\n\n\nundergone skin biopsy. Majority were males and male to female ratio\n\n\n\nwas 3.8:1. The duration of erythroderma ranged from 2 weeks to 2\n\n\n\nyears. The demographic data and clinical features are shown in Table 1\n\n\n\nand 2 .\n\n\n\nThe most common etiology in our cohort was eczema (n=34, 70.8%),\n\n\n\nSpearman\u2019s rank correlation showed very good correlation between\n\n\n\ninitial clinical impression and histopathological findings (P=0.962). The\n\n\n\netiological distribution is illustrated in figure 1.\n\n\n\nAge (years) Mean 66\nRange 22-88\n\n\n\nGender Male n=38 (79.2%)\n\n\n\nFemale n=10 (20.8%)\n\n\n\nEthnicity Malay n= 15 (31.3%)\n\n\n\nChinese n= 27 (56.3%)\n\n\n\nIndian n= 6 (12.5%)\n\n\n\nDuration of \n\n\n\nerythroderma\n\n\n\n< 3 months n= 21 (43.8%)\n\n\n\n3-12 months n= 18 (37.5%)\n\n\n\n> 1 year n= 9 (18.8%)\n\n\n\nPrevious history of \n\n\n\ndermatoses\n\n\n\nEczema n= 9 (18.8%)\n\n\n\nPsoriasis n= 2 (4.2%)\n\n\n\nNil n= 37 (77.1%)\n\n\n\nTable 1: \nDemographic \npattern\nof patients with \nerythroderma \n\n\n\nTable 2: \nClinical features  of \npatients with erythroderma\n\n\n\nAmong the complications noted were, hypoalbuminemia (n=22,\n45.8%), mild skin infection (n= 17, 35.4%), severe skin infection such as\neczema herpeticum and carbuncle (n=3, 6.3%) and sepsis (n=6, 12.5%).\nStatistical analysis using Fisher\u2019s exact test showed that the duration of\nerythroderma had no significant correlation with the complications\nencountered. Although, hypoalbuminemia had the highest association\nwith shorter duration of erythroderma of less than 3 months\n(p=0.078), this was still statistically not significant.\n\n\n\nVarious treatment modalities were used in the treatment of\nerythroderma including topicals, phototherapy (NBUVB) and systemic\nagents such as oral prednisolone or steroid sparing agents\n(azathioprine, cyclosporine, methotrexate and acitretin) or\ncombination of these treatments depending on the underlying cause\n(Table 3). 4 patients were lost to follow up and 2 passed away, both of\nwhich were cases of mycosis fungoides and their deaths were not\ndirectly related to erythroderma.\n\n\n\nTreatment n (%) Outcome n(%)\nRemission Partial remission Default/ death\n\n\n\nTopicals alone 11 (22.9%) 1 (9.1%) 6 (54.5%) 4 (36.4%)\nTopicals + \n\n\n\nSystemic agent\n\n\n\n32 (66.7%) 26 (81.3%) 4 (12.5%) 2 (6.3%)\n\n\n\nPhototherapy 5 (10.4%) 4 (80%) 1 (20%) 0\n\n\n\nTable 3: Treatment modalities and outcome\n\n\n\nDISCUSSION\n\n\n\nThe estimated annual incidence of erythroderma is 1-2 patients per\n\n\n\n100,000 population.1 There is a male predominance in most studies\n\n\n\nwith a ratio ranging from 2:1 to 4:1.2 Our study observed similar\n\n\n\nfindings with a male to female ratio of 3.8:1. Erythroderma usually\n\n\n\noccurs in the 6th decade.3,4 This was consistent with our study\n\n\n\nwhereby patients presented at mean age of 68 years. Majority of our\n\n\n\npatients were Chinese (56.3%) which was in contrast to another\n\n\n\nstudy done in Malaysia which reported a Malay predominance at\n\n\n\n57.3%.5 This is most likely a reflection of the population in our study\n\n\n\narea which is of predominant Chinese ethnicity.\n\n\n\nIn this study we found that most of the patients had a duration of\nerythroderma of less than 3 months which is supported by a recent\nstudy done by Gouthami SK et al, whereby 88% of their cases had\ndisease duration of less than 3 months.7 Besides, eosinophilia and\nhypoalbuminemia were commonly reported at 54.2% and 45.8%\nrespectively. This finding was supported by a study by Grace FL Tan et\nal with eosinophilia (58.2%) and hypoalbuminemia (45.3%).435.4% of\nour study population had anemia which was comparable to a recent\nstudy in Portugal which showed 30.1% having anemia.10\n\n\n\nPre-existing dermatosis is the commonest etiology as determined by\nmost studies with an incidence of 50-70%.1,2,4,7-10 The prevalence of\ndrug induced erythroderma was 12-24% according to most\nstudies.2,8,9 These findings were unlike our study whereby the\ncommonest etiology was eczema accounting for 70.8% of cases. In\nour study, pre-existing dermatosis was only seen in 22.9% of cases\nand only 6.3% of drug induced erythroderma were reported. This\ndiscordance can probably be explained by the fact that our study\npopulation only included cases of erythroderma who had undergone\nskin biopsy. Skin biopsies are less often performed in drug induced\nerythroderma and pre-existing dermatosis hence explaining the\nfewer cases in these categories.\n\n\n\nThe initial management of erythroderma is mainly symptomatic.\nSystemic steroids may be used in severe cases. 68.8% of our cases\nrequired systemic steroids. From this study we gathered that the\noverall prognosis was good with 64.5% achieving remission and 23%\npartial remission. Contrary to previous studies which reported high\nmortality rates (11%-64%),11,12 there was a low mortality rate of 4.2%\nin our study. This may be due to intensive inpatient care given to all\nerythrodermic patients which reduce the mortality in our centre.\n\n\n\nIn general, acute erythroderma is associated with more complications\ndue to acute skin failure.13 However, we did not find such correlation\nbetween duration of erythroderma and the complications in our\nstudy. Hypoalbuminemia had the highest association with shorter\nduration of erythroderma of less than 3 months (p=0.078), but this\nwas statistically not significant. The correlation between clinical\ndiagnosis and histopathological findings was very good and\ncomparable to Gouthami SK et al with 64% and Artur C et al with\n66.3%.7,10\n\n\n\nCONCLUSION\nIn all cases of erythroderma it is essential that a thorough history and\nclinical examination as well as relevant laboratory investigations\nincluding skin biopsy are performed in order to arrive at an accurate\ndiagnosis. The commonest cause of erythroderma in our series was\neczema and there was a very good clinico-pathological correlation.\nOur study suggested that the prognosis of erythroderma may be\ngood with a low mortality rate if intensive inpatient care is given to\nthese patients.\n\n\n\nREFERENCES\n\n\n\n1) Sigurdsson V, Steegmans PH and Van Vloten WA. The incidence of erythroderma: a survey among all dermatologists\n\n\n\nin The Netherlands. J Am Acad Dermatol 2001; 45:675-678\n\n\n\n2) Sehgal VN and Srivastava G. Exfoliative dermatitis: A prospective study of 80 patients. Dermatologica 1986;\n\n\n\n173(6):278-284\n\n\n\n3) Hulmani M, Nandakishore B, Bhat MR, Sukumar D, Martis J, Kamath G, Srinath MK. Clinico-etiological study of 30\n\n\n\nerythroderma cases from tertiary center in south India. India Dermatol online J. 2014; 5:25-29\n\n\n\n4) Grace Tan FL, Kong YL, Andy Tan SL, Tey HL. Causes and features of erythroderma. Ann Acad Med Singapore 2014;\n\n\n\n43:391-394\n\n\n\n5) Peter Ch\u2019ng WB, Adam B, Rohna R. Erythroderma- A retrospective study with special emphasis on good prognosis.\n\n\n\nMJD 2011; 26:1-5\n\n\n\n6) Khaled A, Sellami A, Fazaa B, Kharfi M, Zeglaoui F, Kamour MR. Acquired erythroderma in adults: a clinical and\n\n\n\nprognostic study. J Eur Acad Dermatol Venereol. 2010; 24:781-788\n\n\n\n7) Gouthami SK, Rama Krishna KV, Chandra SRI, Amareshwar B. A clinico-etiological study of erythroderma. Indian J of\n\n\n\nApplied Research. 2017; 7:98-100\n\n\n\n8) Akhyani M, Ghodsi ZS, Toosi S, Dabbaghian H. Erythroderma: a clinical study of 97 cases. BMC Dermatol 2005; 5:5\n\n\n\n9) Li J, Zheng HY. Erythroderma: a clinical and prognostic study. Dermatology 2012; 225:154-162. Epub 2012/10/06\n\n\n\n10) Artur C, Maria C, Alberto M, Filomena A. Erythroderma. A clinical and etiological study of 103 patients. J Dermatol\n\n\n\nCase Rep 2016; 10(1):1-9\n\n\n\n11) Abraham I, McCarthy CJ, Sanders SL. 101 cases of exfoliative dermatitis. Arch Dermatol 1963; 87:96-101\n\n\n\n12) Sigurdsson V, Toonstra J, Hezermans Boer M et al: Erythroderma: a clinical and follow up study of 102 patients, with\n\n\n\nspecial emphasis on survival. JAAD 1996; 35: 53-57\n\n\n\n13) Nick J. Levell. Erythroderma. Medicine June 2013; 41(6):356\u2013359\n\n\n\nClinical feature n (%)\n\n\n\nScaling and erythema 48 (100%)\n\n\n\nPruritus 47 (97.9%)\n\n\n\nFever 12 (25%)\n\n\n\nPedal edema 19 (39.6%)\n\n\n\nPalmo-plantar keratoderma 15 (31.3%)\n\n\n\nNail changes 7 (14.6%)\n\n\n\nLymphadenopathy 10 (20.8%)\n\n\n\nEosinophilia 26 (54.2%)\n\n\n\nAnemia 17 (35.4%)\n\n\n\n\nhttps://www.bing.com/images/search?view=detailV2&ccid=mYZgjH1%2b&id=E00CC8AAC24F65BAC5ECF33CB07CCDFD22DF742F&thid=OIP.mYZgjH1-Tlrsv-ZFk3YuZwEsB0&q=Hospital+raja+permaisuri+bainun+ipoh+logo&simid=608029807266367719&selectedIndex=0\n\n\nhttps://www.bing.com/images/search?view=detailV2&ccid=mYZgjH1%2b&id=E00CC8AAC24F65BAC5ECF33CB07CCDFD22DF742F&thid=OIP.mYZgjH1-Tlrsv-ZFk3YuZwEsB0&q=Hospital+raja+permaisuri+bainun+ipoh+logo&simid=608029807266367719&selectedIndex=0\n\n\n\n\n\n\nThe Utilization of Cutaneous Laser Therapy at the\nDepartment of Dermatology, Hospital Kuala Lumpur-\n\n\n\nA 5 year review\nSuganthy Robinson, Min Moon Tang, Sharifah A Alhabshi, Nadiah A Fuad, Sam R R Tamilarsan, Noor Zalmy Azizan\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur\n\n\n\nINTRODUCTION\n\n\n\nThe Department of Dermatology, Hospital Kuala Lumpur has been\nproviding cutaneous laser therapy services for almost two\ndecades. The laser unit is currently equipped with an ablative\ncarbon dioxide laser which is useful for vapourizing lesions and\napplying incisions, a Q-switched neodymium-YAG (NdYAG) for\npigmented lesions, a pulsed dye laser (PDL) for treatment of\nvascular lesions and a fractional carbon dioxide machine for acne\nscar resurfacing.1 Cutaneous laser services are provided three\ntimes a week for local patients as well as referrals from the whole\ncountry.\n\n\n\nDISCUSSION\n\n\n\nOBJECTIVES\n\n\n\nTo describe the utilization of cutaneous laser therapy at the\nDepartment of Dermatology, Hospital Kuala Lumpur and the post\ntreatment complications.\n\n\n\nMATERIALS AND METHOD\n\n\n\nA retrospective, descriptive study was conducted where medical\nrecords of all patients who received cutaneous laser therapy at\nthe Department of Dermatology, Hospital Kuala Lumpur from\nJanuary 2012 till December 2016 were reviewed. Complications\nwere defined as hypopigmentation, infection, scarring, blisters,\nulcerations, skin textural changes or contact dermatitis secondary\nto post/ pre-laser topical therapy.\n\n\n\nRESULTS\n\n\n\nREFERENCES\n\n\n\n\u2022 A total of 1190 patients received single, repeated or\ncombination cutaneous laser therapy from 2012 till 2016 for 48\ndifferent skin conditions. The demographic data is shown in\nTable 1.\n\n\n\n\u2022 Figure 1 illustrates the number of laser sessions provided per\nyear. The decline in the number of laser sessions in 2016 was\ndue to the breakdown of the PDL machine.\n\n\n\n\u2022 Figure 2 shows the number of laser sessions provided by each\nlaser machine. Q-switched NdYag was the most frequently\nemployed laser. The fractional CO2 laser service was initiated\nsince September 2013 mainly for acne scars in fair skin\nphototype.\n\n\n\n\u2022 Table 2 demonstrates the indications of laser therapy in the\ncurrent cohort.\n\n\n\n\u2022 Over the past 5 years, 194 (16.3%) patients underwent\ncombination laser therapy and only 3 (0.3%) patients developed\nsevere complication post laser therapy which was blisters.\n\n\n\n\u2022 Pain was tolerable with the application of topical EMLA prior to\nlaser treatment.\n\n\n\n1. Dixon et al. Wet J Med 1985;143:758-63\n2. Han G. Cutis 2014; 94:E20-E3\n3. Jain et al. J Cutan Aesthet Surg.\n\n\n\n2012;5:190-2\n4. Falto-Aizpurua et al. J Eur Acad Dermatol\n\n\n\nVenereol 2015;29:1045-52\n5. Raszewska-Famielec et al. Dermatol Ther\n\n\n\n2015;28:254-7\n6. Landthaler et al. Photodermatol\n\n\n\nPhotoimmunol Photomed 2006; 22:\n324\u201332\n\n\n\n7. Sklar et al. Lasers Surg Med,\n2014;46:249\u201362.\n\n\n\n1337\n1237\n\n\n\n1449\n1635\n\n\n\n910\n\n\n\n0\n\n\n\n200\n\n\n\n400\n\n\n\n600\n\n\n\n800\n\n\n\n1000\n\n\n\n1200\n\n\n\n1400\n\n\n\n1600\n\n\n\n1800\n\n\n\n2012 2013 2014 2015 2016\nYear\n\n\n\nNumber of \nsession n=6568\n\n\n\nTable 2: Indications for laser therapy \n\n\n\nCONCLUSION\n\n\n\n\u2022 Granted that the spotlight has been mainly on laser usage for\naesthetic purposes, lasers also play an important role in\nmedical dermatology.\n\n\n\n\u2022 In the treatment of refractory skin diseases such as\nhidradenitis suppurativa and pilonidal sinus, deroofing with\nCO2 laser and hair follicle removal with long pulse NdYAG laser\nis a useful minimally invasive tissue saving technique.2,3\n\n\n\n\u2022 In addition fractional CO2 laser treatment appears to be useful\nin the treatment of genodermatoses such as Darier-White\ndisease and Hailey-Hailey disease4,5.\n\n\n\n\u2022 The PDL and Intense pulsed light sources (IPLS) are effective\nfirst-line treatment modalities for vascular lesions.2,4\n\n\n\n\u2022 Lasers have also been applied as adjunctive treatment in small\nbasal cell carcinomas and early stage mycosis fungoides.2\n\n\n\n\u2022 Recent advances such as laser assisted drug delivery have\nshown promising potential for a wider variety of dermatology\nconditions.\n\n\n\n\u2022 With adequate number of trained specialists and funding, it is\nour hope that we would be able to expand our services for\nwider medical dermatological indications as mentioned above.\n\n\n\n\u2022 We hope to include an IPL machine and an excimer laser\namong others and embark on further research for indications\nin medical dermatology.\n\n\n\nOur center treats a high volume and wide variety of cases with\ncutaneous lasers. Nevertheless we have a low rate of post laser\ntreatment complication.\n\n\n\nIndications n % Indications n %\nSeborrhoeic keratosis 249 20.9 Melanocytic naevus 17 1.4\nPort Wine Stain 162 13.6 Angiofibroma 16 1.3\nSolar lentigines 144 12.1 Pyogenic granuloma 16 1.3\nSyringoma 105 8.8 Post inflammatory \n\n\n\nhyperpigmentation\n\n\n\n15 1.3\n\n\n\nViral wart 88 7.4 Trichoepithelioma 15 1.3\nNaevus of Ota 82 6.9 Ephilides 14 1.2\nSkin tags 78 6.6 Inflammatory acne 14 1.2\nTattoo removal 68 5.7 Cherry angioma 13 1.1\nMelasma 66 5.5 Rosacea 11 0.9\nKeloid scar 63 5.3 Comedones 11 0.9\nSebaceous hyperplasia 51 4.3 Telangiectasia 11 0.9\nHaemangiomas 48 4.0 Vascular malformations 10 0.8\nMilia 41 3.4 Caf\u00e9 au lait macules 6 0.5\nHori\u2019s naevus 41 3.4 Angiokeratoma 6 0.5\nLinear epidermal naevus 30 2.5 Naevus spilus 5 0.4\nBecker\u2019s naevus 22 1.8 Molluscum contagiosum 5 0.4\nXanthelasma 22 1.8 Actinic keratosis 4 0.3\nAcne scars 18 1.5 Calluses and corns 4 0.3\nSegmental lentigines 18 1.5 Others* 17 1.4\n\n\n\nPoster \nNo. 46\n\n\n\nCharacteristics n= 1190\nMean age in years (range) 35.8 (9 days to 90 years)\nGender, n(%) Female 891 (68.8)\n\n\n\nMale 371 (31.2)\nEthnicity, n(%) Malay 698 (58.7)\n\n\n\nChinese 347 (29.2)\nIndian 124 (10.4)\nIban 1 (0.1)\nOthers 20 (1.7)\n\n\n\nMean number of laser session (range) 5.3 (1-46)\n\n\n\nTable 1. The demographic characteristics of 1190 patients\n\n\n\nFigure 1. The number of laser sessions provided per year\n\n\n\nFigure 2 . Number of sessions provided by different types of \nlasers\n\n\n\n0\n\n\n\n500\n\n\n\n1000\n\n\n\n1500\n\n\n\n2000\n\n\n\n2500\n\n\n\nAblative CO2 PDL Q-switched\nNdYAG\n\n\n\nFractional CO2\n\n\n\n1915 2207\n2399\n\n\n\n47\n\n\n\nN\nu\n\n\n\nm\nb\n\n\n\ne\nr \n\n\n\no\nf \n\n\n\nLa\nse\n\n\n\nr \nSe\n\n\n\nss\nio\n\n\n\nn\ns \n\n\n\nType of Laser\n\n\n\nN=6568\n\n\n\n* Steatocystoma multiplex, epidermal cyst, porokeratosis, rhinophyma, \nvasculitic ulcers, lymphocytoma cutis, granuloma facialis, lichen \nplanus, capillaritis, pigmentary mosaicism and nodular prurigo\n\n\n\n\n\n\n\n\nPOROKERATOSIS  PTYCHOTROPICA\nLee Hock Leng1, Azmin Azila Abdul Aziz2, Tang Jhy Jong1\n\n\n\n1. Dermatology Derpartment, Hospital Raja Permaisuri Bainun\n2. Pathology Derpartment, Hospital Raja Permaisuri Bainun\n\n\n\nPoster \n\n\n\nNo. 47\n\n\n\nPorokeratosis is an epidermal keratinization disorder\ncharacteristic with central atrophy and distinctive ridge-like\nedge. It is commonly subdivided into 6 distinguished variants\ni.e. disseminated superficial actinic porokeratosis (DSAP),\ndisseminated superficial porokeratosis (DSP), porokeratosis of\nMibelli (PM), linear porokeratosis (LP), punctate porokeratosis\n(PP) and porokeratosis palmaris et plantaris disseminata\n(PPPD). Porokeratosis ptychotropica (PPt), a seventh subtype\nwas first termed by Lucker et al in 1995 for a pruritic\ndermatoses confined to gluteal cleft with histology of multiple\ncornoid lamella. (Lucker et al, 1995).\n\n\n\nCornoid lamella is an unify histological feature of all\nporokeratotic variants characterized by 3 microscopic\nfeatures i.e. vertical column of parakeratosis with\nunderlying diminish granular layer and presence of\ndyskeratotic cell. (Wade & Ackerman, 1980) Most of the\ncommon porokeratosis are characterized by central\natrophy and a hyperkeratotic edge. Variants with central\nhyperkeratosis or even verrucae surface may be found in\nporokeratosis of Mibelli, linear porokeratosis and\nporokeratosis ptychotropica.\n\n\n\nPtychotropica derived from Greek i.e. Ptyche meaned\n\u201cfold\u201d and Trope mean \u201ca turning\u201d to describe verrucae\nhyperkeratotic lesion on genitourinary region. Unlike other\nvariants, porokeratosis ptychotropica is clinically\ncharacterized by pruritic, papulosquamous, and\nverrucous lesions. It is easily missed diagnose as inverse\nor plaque psoriasis, fungal infection, lichen simplex\nchronica or verrucae vulgaris. (Cockerell, 1991) Because\nof the unusual clinical and pathological appearances, a\ndiagnosis of porokeratosis ptychotropica is often delayed.\nIt may spend many years of failed treatment and multiple\nbiopsies is often taken prior to the confirmation of the\ndiagnosis. (Malek et al, 2009) Superimposed lichen\nsimplex chronica and viral infection have been proposed\nas the possible pathogenesis. Histologically, it is\ndistinguished from other variants by the presence of\nmultiple and sometimes confluent cornoid lamellae\nspanning the entire lesion. Porokeratosis is well known to\nthe risk of malignant transformation especially squamous\ncell carcinoma. (Sasson M & Krain AD, 1996) The first\ncase of porokeratosis ptychotropica associated invasive\nsquamous cell carcinoma has been reported by Mazori in\n2017. (Mazori, 2017)\n\n\n\nFigure 1: A, Multiple symmetrical raised hyperpigmented\ndiscrete papules at peripheral and coalesced into plaque\ntowards the centre on bilateral gluteal. B, Polarized\ndermoscopy showing hyperkeratosis and well-defied edge C,\nMultiple cornoid lamella with column of parakeratosis,\nhypogranulosum and dyskeratosis.\n\n\n\nA B C\n\n\n\nFeature DSAP DSP PM LP PP PPPD PPt\n\n\n\nNumber Multiple Same as DSAP Single/ few Few to multiple Multiple Same as PP Multiple\n\n\n\nSize <1cm Same as DSAP plaque Papule to plaque Small papule Same as PP Papular plaque\n\n\n\nShape annular Same as DSAP Annular annular Seed like spiny \nprotrusion\n\n\n\nSame as PP Round papule\n\n\n\nDistribution Extensor of \nextremities & \nshoulder\n\n\n\nNot related to sun \nexposure area\n\n\n\nNon sun exposure \narea esp extremities\n\n\n\n2 forms: \n- Localized at \nextremities\n- generalized \npapuloplaque in \nBlaschkoid pattern\n\n\n\nRestricted to palm \nand sole\n\n\n\nSpreading from \npalm and sole to \nother body part\n\n\n\ngenitalgluteal \ninvolvement,  \nsymmetrical later \n\n\n\nMorphology Atropic lesion with \nperipheral  \nhyperkeratotic \nridge\n\n\n\nSame as DSAP atrophic center and a \nslender and guttered \nkeratotic rim\n\n\n\nKeratotic/ veruccae Tender keratotic \npapules\n\n\n\nTender keratotic \npapules\n\n\n\npruritic, \npapulosquamous\nand verrucous\nlesions\n\n\n\nHPE 2 cornoid lamella \non both side, \nperivascular \nmononuclear cell, \nlichenoid band \n\n\n\nSame as DSAP Ridge-like \npronounced \nepidermal \ninvagination at site of \ncornoid lamella, mild \npapulomatosis\n\n\n\nMultiple cornoid\nlamella\n\n\n\nWell defined but \nnon marginated\ncornoid lamella with \nlichenid\ninflammation\n\n\n\nWell defined \npunctate cornoid \nlamella lacking \nmargination\n\n\n\nMultiple \nconfluent cornoid \nlamellae \nspanning the\nentire surface \n\n\n\nAssociation Aggravated  by \nsun, risk of \nmalignancy \ntransformation\n\n\n\nOnset younger \nthan DSAP\n\n\n\n- -Rare\n-onset at birth or \nchildhood\n- highest risk of \nmalignancy \ntransformation\n\n\n\nrare rare Frequent \ndelayed \ndiagnosis\n\n\n\nIntroduction\n\n\n\nCase Report\nA 50 year-old lady without comorbid presented with intensely\npruritic papules over bilateral gluteal area since 9 years ago. It\ngradually progressive to be extensive and hyperpigmentation.\nShe was treated as lichen simplex chronica and verrucous\nepidermal naevus but no responding to topical salicylate acid\nor superpotent steroid.\n\n\n\nDifferential diagnosis of plaque psoriasis, lichen simplex\nchronica, verrucae vulgaris, cutaneous amyloidosis and\nepdermodysplasia veruciformis were made. A repeated\nhistology showed orthokeratosis, mild acanthosis,\npapilomatosis and multiple cornoid lamella with invagination of\nthe epidermis filled with columnar parakeratosis. The granular\nlayer beneath the cornoid lamella was reduced. Epidermal\nkeratinocytes revealed no perinuclear halos or blue-gray pallor.\nVessel at papillary dermis were dilated with some perivascular\nlymphocytic infiltration and no obvious fibrosis seen at papillary\ndermis. Deep dermis and subcutaneous fat were\nunremarkable. The rest were normal with no atypical\nmalignancy cell or koilocytes seen. Congo red stain for amyloid\nshowed negative. The histology findings not fulfilled all the\nlisted differential diagnosis but only porokeratosis\nptychotropica.\n\n\n\nDiscussion\n\n\n\nConclusion\nAwareness of porokeratosis ptychotropica as one of the\npossibility differential diagnosis of the gluteal verrucae\nhyperkeratotic lesion could be important as it is\npremalignant.\n\n\n\nTable 1: Summary of each variant of porokeratosis\n\n\n\nReference:\nMazori, D. R., et al. (2017). \"Transformation of porokeratosis ptychotropica into invasive squamous cell carcinoma.\" Int J Dermatol 56(6): 679-680.\nVeasey, J. V., et al. (2016). \"Porokeratosis ptychotropica: a rare manifestation with typical histological exam.\" An Bras Dermatol 91(4): 496-498.\nMalek J, Chedraoui A, Kibbi AG, et al. (2009) Genitogluteal porokeratosis: 10 years to make the diagnosis! Am J Dermatopathol. 31:604\u2013606\nSasson M, Krain AD. (1996) Porokeratosis and cutaneous malignancy. A review. Dermatol Surg 22: 339\u2013342.\nLucker, G. P., et al. (1995). \"An unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica?\" Br J Dermatol 132(1): 150-151.\nCockerell CJ. (1991) Induction of disseminated superficial actinic porokeratosis by phototherapy for psoriasis. J Am Acad Dermatol. 24:301\u2013302\nWade TR, Ackerman AB. (1980) Cornoid lamellation: a histologic reaction pattern. Am J Dermatopathol. 1980;2:5\u201315\n\n\n\n\n\n\n\n\nPrevalence and Clinical Characteristics of Non-\nAlcoholic Fatty Liver Disease (NAFLD) in Patients \nwith Psoriasis \nMoonyza Akmal Kamil1, Norazirah Md Nor2, Ngiu Chai Soon3, Mohd Rizal Abdul Manaf4\t\n\r\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\t\n\r\n2Dermatology Unit, Department of Medicine, University Kebangsaan Malaysia Medical Centre, Malaysia\t\n\r\n3Gastroenterology Unit, Department of Medicine, University Kebangsaan Malaysia Medical Centre, Malaysia\t\n\r\n4Community Health Department, University Kebangsaan Malaysia Medical Centre, Malaysia \n\n\n\nPoster \nNo. 48 \n\n\n\n\n\n\n\n\n\n\n\nPsoriasis is recognized as a systemic inflammatory \ncondition linked to obesity and metabolic syndrome, \nwhich are risk factors for Non-Alcoholic Fatty Liver \nDisease (NAFLD). NAFLD is a spectrum of condition \nranging from hepatosteatosis to steatohepatitis, which \ngive rise to fibrosis and cirrhosis.   \n\n\n\nThis is an observational cross sectional study involving \npatients with chronic plaque psoriasis who attend the \nUKM Medical Centre and Hospital Kuala Lumpur \nDermatology Outpatient clinics, from November 2015 \nuntil May 2016. NAFLD was diagnosed using ultrasonic \nelastography measured as Controlled Attenuated \nParameter (CAP) in dB/m on fibroscan examination. \n \nWe exclude patients who had secondary causes of \nchronic liver disease, those who were on hepatotoxic \nmedications, alcohol consumption above the safety limit, \nand those who had contraindication for fibroscan \nprocedure.  \n \nThe sociodemographic data and the cl in ical \ncharacteristics of psoriasis patients were compared \nbetween patients with and without NAFLD. \n\n\n\nFrom 109 patients, the prevalence of NAFLD in our \nstudy is 85.3%, with 43% having mild NAFLD while \nanother 57% were in the moderate to severe group.  \n\n\n\nTo determine the prevalence and clinical characteristics \nof psoriasis patients with NAFLD. \n\n\n\nTo our knowledge, this study is the first in psoriasis \npopulation detecting NAFLD using Fibroscan. The higher \nprevalence of NAFLD in our patients maybe due to the \nhigher sensitivity and specificity of fibroscan in detecting \nsteatosis, compared to abdominal ultrasound (Table 3). It \ncould also be attributed to the fact that most of our \npatients are in the overweight and obese group. \n\n\n\nStudy Population \n(n) \n\n\n\nPrevalence Diagnosis \nof NAFLD \n\n\n\nOur study \n \n\n\n\n109 85.3% Fibroscan  \n\n\n\nMiele et al \n(Italy, 2009)1 \n\n\n\n142  59.2% Ultrasound  \n\n\n\nVan Der \nVoort, et al.  \n\n\n\n(Netherlands, \n2013)2 \n\n\n\n118 46.2% Ultrasound  \n\n\n\nMadanagobal\nane et al \n\n\n\n(India, 2012)3 \n\n\n\n330 17.4% Ultrasound  \n\n\n\nTable 3: Psoriasis and NAFLD -  a comparison \n\n\n\nReferences:\t\n\r\n1.Miele, L., et al., Prevalence, characteristics and severity of non-alcoholic fatty \nliver disease in patients with chronic plaque psoriasis. J Hepatol, 2009. 51(4): p. \n778-86\t\n\r\n2.van der Voort, E.A., et al., Psoriasis is independently associated with \nnonalcoholic fatty liver disease in patients 55 years old or older: Results from a \npopulation-based study. J Am Acad Dermatol, 2014. 70(3): p. 517-24.\t\n\r\n3.Madanagobalane, S. and S. Anandan, The increased prevalence of non-\nalcoholic fatty liver disease in psoriatic patients: a study from South India. \nAustralas J Dermatol, 2012. 53(3): p. 190-7.\t\n\r\n\n\n\nCharacteristic Psoriasis \npatients \n\n\n\nwith \nNAFLD, \n\n\n\nn=93 \nMedian \n(IQR) or \n\n\n\nn(%)  \n\n\n\nPsoriasis \npatients \nwithout \nNAFLD, \n\n\n\nn=16 \nMedian \n\n\n\n(IQR)  \nOr n(%) \n\n\n\nP-value \n\n\n\nBMI (kg/m2) 26.23 (4) 22.76 (4) *<0.0005 \n\n\n\nWC (cm) 93 (11) 80 (19) *<0.0005 \n\n\n\nMetS \u00a051 \n(54.8%) \n\n\n\n2 (12.5%) 0.002 \n\n\n\nALT (U/L) 28.5 (26) 15.0 (6) 0.001 \n\n\n\nTG  (mmol/L) 1.40 (0.8) 0.79 (0.2) *<0.0005 \n\n\n\nFBG(mmol/L) 5.30 (1.8) 4.90 (0.4) 0.010 \n\n\n\nHDL-chol (mmol/L) 1.2 (1.01) 1.47 (1.22) 0.010 \n\n\n\n\n\n\n\nTable 1: Clinical and biochemical parameters between \npatient with and without NAFLD. \n\n\n\nBMI \u2013 body mass index, WC \u2013 waist circumference, MetS \u2013 Metabolic \nSyndrome,  ALT \u2013 Alanine Transaminase,  TG \u2013 Triglyceride,  FBG \u2013\nFasting Blood Glucose, HDL-chol \u2013HDL-cholesterol, PASI \u2013 Psoriasis \nArea and Severity Index,  SBP \u2013 Systolic Blood Pressure\t\n\r\n\n\n\nPredictors  Wald p-value OR (95% CI) \nBMI 6.736 *0.009 1.630 (1.127 \u2013 \n\n\n\n2.357) \n\n\n\nTG  6.336 *0.012 130.737 (2.94 \n-5812.75) \n\n\n\nPASI 4.087 *0.043 1.138 (1.004 \u2013 \n1.290) \n\n\n\nMetS 0.425 0.515 0.457 (0.044 - \n4.805) \n\n\n\nHDL-chol 2.405 0.121 10.693 (0.535 \u2013 \n213.738) \n\n\n\nALT 0.245 0.620 1.018 (0.947 \u2013 \n1.095) \n\n\n\nSBP 0.251 0.616 0.987 (0.937 \u2013 \n1.039) \n\n\n\nFBG 1.421 0.233 2.958 \n(0.497-17.595) \n\n\n\nTable 2: Multivariate analysis \u2013 predictors of NAFLD in \npsoriasis patients \n\n\n\nPsoriasis patients especially those with high BMI, high \nTG and severe disease need to be screened for NAFLD, \ndespite having normal liver enzymes.  \n\n\n\nSignificant positive correlations were seen between \nseverity of NAFLD with SBP (rs=0.191, p=0.047), and the \nseverity of psoriasis using PASI (rs=0.202, p=0.035).  \n\n\n\n\n\n\n\n\nVancomycin-induced Toxic Epidermal Necrolysis \n\n\n\n1.       Department of Medicine, Hospital Sibu, Sarawak. \n2.       Department of Dermatology, Sarawak General Hospital. \n3.       Department of Pathology, Sarawak General Hospital. \n\n\n\nResults \n\n\n\nIntroduction \n\n\n\nMethodology and Objectives \n\n\n\nAndy Ko TY1, Tan SW1, Teo Yan1, Chuah SL1, Wong TM1, Kho WM2,Suhashini G3,Pubalan M2  \n\n\n\nConclusion \n\n\n\nReferences \n \n1. Bahar F. Firoz, Jeffrey Scott Henning, Lee Ann Zarzabal, Brad H. Pollock. Toxic epidermal necrolysis: Five years of treatment experience from a burn unit. Journal of the American Academy of Dermatology \n2012; 67(4): 630-635 \n2. Mahar PD, Wasiak J, Hii B, Cleland H, Watters DA, Gin D, Spinks AB. A systematic review of the management and outcome of toxic epidermal necrolysis treated in burns centres. Burns. 2014 \nNov;40(7):1245-54 \n3. Bastuji-Garin S1, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993 \nJan;129(1):92-6. \n4. Halevy S1, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A, Naldi L, Dunant A, Viboud C, Roujeau JC;EuroSCAR Study Group. Allopurinol is the most common cause of Stevens-Johnson \nsyndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008 Jan;58(1):25-32. \n5. Peggy Sekula, Ariane Dunant, Maja Mockenhaupt, Luigi Naldi, Jan Nico Bouwes Bavinck, Sima Halevy, Sylvia Kardaun, Alexis Sidoroff. Comprehensive Survival Analysis of a Cohort of Patients with Stevens\u2013\nJohnson Syndrome and Toxic Epidermal Necrolysis. Journal of Investigative Dermatology. 2013; 133(5) : 1197-1204 \n6. Thomas Harr, Lars E French. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet Journal of Rare Diseases20105:39 \nHannah BA1, Kimmel PL, Dosa S, Turner ML. Vancomycin-induced toxic epidermal necrolysis. South Med J. 1990 Jun;83(6):720-2. \n7. Vidal C , Gonz\u00e1lez Quintela A , Fuente R . Toxic epidermal necrolysis due to vancomycin. Annals of Allergy. 1992; 68(4):345-347 \n8. Stephen I-Hong Hsu. Biopsy-Proved Acute Tubulointerstitial Nephritis and Toxic Epidermal Necrolysis Associated with Vancomycin. Pharmacotherapy 2001; 21(10): 1233\u20131239 \n9. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, Auquier A, Bastuji-Garin S, Correia O, Locati F: Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J \nMed. 1995, 333: 1600-1607. \n10. Fournier S, Bastuji-Garin S, Mentec H, Revuz J, Roujeau JC: Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection. Eur J Clin Microbiol Infect Dis. 1995, 14: 558-559.  \nMulvey JM, Padowitz A, Lindley-Jones M, Nickels R: Mycoplasma pneumoniae associated with Stevens Johnson syndrome. Anaesth Intensive Care. 2007, 35: 414-417. \n11. Schalock PC, Dinulos JG: Mycoplasma pneumoniae-induced Stevens-Johnson syndrome without skin lesions: fact or fiction?. J Am Acad Dermatol. 2005, 52: 312-315. \n12. Forman R, Koren G, Shear NH: Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of 10 years' experience. Drug Saf. 2002, 25: 965-972. \n13. Garcia-Doval I, LeCleach L, Bocquet H, et al. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol2000;136:323\u2013\n7 \n15. Nassif A1, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P, Bagot M, Roujeau JC. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol. 2004 \nNov;114(5):1209-15. \n16. Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, Chin SW, Chiou CC, Chu SC, Ho HC, Yang CH, Lu CF, Wu JY, Liao YD, Chen YT. Granulysin is a key mediator for disseminated keratinocyte death in \nStevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med. 2008 Dec;14(12):1343-50. \n17. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad \nDermatol 2013;69:173. \n18. Huang YC, Li YC, Chen TJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol 2012;167:424\u201332 \n19. Dorafshar AH1, Dickie SR, Cohn AB, Aycock JK, O'Connor A, Tung A, Gottlieb LJ. Antishear therapy for toxic epidermal necrolysis: an alternative treatment approach. Plast Reconstr Surg. 2008 \nJul;122(1):154-60. \n \n \n \n \n \n \n\n\n\nThis report suggests that Vancomycin can be a possible cause of \nTENS.  \n \n\n\n\nToxic Epidermal Necrolysis (TEN) is a severe mucocutaneous lesion \ncommonly associated with drug. It carries a high mortality rate of \n30%. (2) Early withdrawal of causative agents can reduce mortality \nfrom 26% to 5%. (5) \n\n\n\nWe described a case of Vancomycin induced TEN.  \n \n\n\n\nA 30 year old lady at 18 weeks gestation presented with \nsymptoms of heart failure with pulmonary hypertension \nsecondary to atrial septal defect. She developed acute dyspnea \nrequiring ventilator support. Subsequently she had a miscarriage \nshortly after admission. Upon admission sildenafil was started for \npulmonary hypertension. \nHer long intensive care unit (ICU) stay was complicated by \nmethicillin resistant Staphylococcus Aureus bacteremia and she \nwas treated with intravenous vancomycin. On day 5 of \nvancomycin, she developed macular rashes over her bilateral \npalms, upper limbs and lower limbs followed by her trunk. (Figure \n1a to Figure 1c). On day 7, the macular rash progressed to \nbecome blisters which ruptured with denuded skin involving more \nthan 30% of her body surface area. There were orogenital \ninvolvement. (Figure 2a to 3d) Nikolsky\u2019s sign was positive. She did \nnot have any history of autoimmune symptoms or family history \nof bullous disease.  \nA diagnosis of Vancomycin induced TENs was made. Her SCORTEN \nwas 1 for BSA of more than 10%. Eosinophil count was raised at \n0.9 x 106/L. Serology for ANA, HIV, Hep B and C was negative. Skin \nbiopsy was taken confirming TEN. (Figure 6a to 6c) \nVancomycin and sildenafil were stopped immediately upon \ndiagnosis. Patient was given intravenous immunoglobulin for a  \ncumulative dose 2.1g/kg in view of extensive skin involvement. \nDaily dressing and compression was done. Her wound healed \nwell. (Figure 5a to 5c) Subsequently, sildenafil was reintroduced \nwith no new rashes.  \n \n\n\n\nDiscussions \n\n\n\nTEN is a severe cutaneous drug eruptions with two muco-\ncutaneous involvement and more than 30% of BSA. It occurs \nmore commonly in woman with a male to female ratio of 0.6. (5) \nThe diagnosis is made clinically and supported by histological \nfeatures which revealed necrotic epidermis involving all layers.(6)  \nOur patient is a female. She did not have prior history of drug \nallergy. The generalized macular rash developed on day 5 of \nintroduction of vancomycin and worsened with subsequent \ndevelopment of erosions involving more than 30% of her body \nsurface area and mucous membrane involvement. Her disease \nonset was slightly earlier as compared to those reported from \nliteratures with a mean onset of 6 days to 2 weeks from drug \nexposure. (18) She was diagnosed clinically as TEN. Although her \nblood culture grew Staphylococcal Aureus, this is unlikely \nStaphylococcal Scalded Skin (SSS) syndrome in view of mucosal \ninvolvement. Skin biopsy later confirmed the diagnosis of TEN. \nOne single-centered, five years study reported that the \ncommonest cause of TEN is Trimethoprim/sulfamethoxazole.(1) \nAnother multinational study showed that the most common drug \nthat attributed to TENS is Allopurinol. (4) Nonetheless, isolated \ncases of drugs other than the aforementioned had been \nreported. The rashes in our patient developed on day 5 of \nvancomycin. There are isolated case reports of vancomycin \ninduced TENS. (7-9) Mycoplasma and Herpes Simplex infection \nhad also been associated with TEN. (11-14) HIV conferred a 1000 \nincreased risk of TENS. (10) Our patient\u2019s HIV serology test was \nnegative. \nSCORTEN is a prognosis marker and can aid clinician\u2019s decision on \nthe proper setting for further care namely intensive care burn \nunit or non- specialized wards. (15) Our patient had extensive \nskin involvement and SCORTEN of 1. Due to our resource limited \nsetting, she was nursed in a non-specialized ward with close \nmonitoring. \nThe treatment of TEN is mainly supportive which includes \nmeticulous skin care, pain control, fluid balance, nutritional \nsupport and prevention of infection. In terms of wound care, \nsome literature suggested wound debridement and others kept \nthe necrotic skin as a biological dressing. One study reported no \ndifference in wound healing between the 2 approaches. (20) \nProphylactic antibiotic is not recommended. Intravenous \nImmunoglobulin and other adjunctive therapy had been \nproposed however there are conflicting evidence on their \nbenefit. (19)   \n\n\n\nDay 5 Vancomycin  \n\n\n\nDay 7 Vancomycin \nDay 1 Iv Ig  \n\n\n\n \nDay 5 Iv Ig  \n\n\n\n \nDay 10 Iv Ig  \n\n\n\n \nDay 20 Iv Ig  \n\n\n\nFigure 1a Figure 1b \nFigure 1c \n\n\n\nFigure 2a Figure 2b \nFigure 2c \n\n\n\nFigure 2d \n\n\n\nFigure 3a \n\n\n\nFigure 3b \nFigure 3c \n\n\n\nFigure 3d \n\n\n\nFigure 4a \n\n\n\nFigure 4b  \npredebridement \n\n\n\nFigure 4c  \npostdebridement \n\n\n\nFigure 5a \n\n\n\nFigure 5b \nFigure 5c \n\n\n\nFigure 6a \nFigure 6a \nSkin biopsy HPE \nH&E x 40 Section \nshows subepidermal \nsloughing of epidermis \n \n\n\n\nFigure 6b and 6c \nSkin biopsy HPE  \nH & E x 400 The epidermis shows confluent \nnecrosis with overlying basket weave stratum \ncorneum \n \n\n\n\nFigure 6c Figure 6b \n\n\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttp://www.sciencedirect.com/science/article/pii/S0190962211022808\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mahar PD[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mahar PD[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mahar PD[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mahar PD[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wasiak J[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wasiak J[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wasiak J[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Hii B[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Hii B[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Hii B[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Cleland H[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Watters DA[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Gin D[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Spinks AB[Author]&cauthor=true&cauthor_uid=24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/24685065\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bastuji-Garin S[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bastuji-Garin S[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bastuji-Garin S[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bastuji-Garin S[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bastuji-Garin S[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bastuji-Garin S[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Rzany B[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Rzany B[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Rzany B[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Stern RS[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Shear NH[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Naldi L[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Naldi L[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Naldi L[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Roujeau JC[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Roujeau JC[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Roujeau JC[Author]&cauthor=true&cauthor_uid=8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/8420497\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Halevy S[Author]&cauthor=true&cauthor_uid=17919772\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Ghislain PD[Author]&cauthor=true&cauthor_uid=17919772\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Ghislain PD[Author]&cauthor=true&cauthor_uid=17919772\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Ghislain PD[Author]&cauthor=true&cauthor_uid=17919772\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mockenhaupt M[Author]&cauthor=true&cauthor_uid=17919772\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mockenhaupt M[Author]&cauthor=true&cauthor_uid=17919772\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Mockenhaupt 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BA[Author]&cauthor=true&cauthor_uid=2356503\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Kimmel PL[Author]&cauthor=true&cauthor_uid=2356503\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dosa S[Author]&cauthor=true&cauthor_uid=2356503\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dosa S[Author]&cauthor=true&cauthor_uid=2356503\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dosa S[Author]&cauthor=true&cauthor_uid=2356503\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Turner ML[Author]&cauthor=true&cauthor_uid=2356503\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/2356503\n\n\nhttp://europepmc.org/search?query=AUTH:\"Vidal+C\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Vidal+C\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Gonz%C3%A1lez+Quintela+A\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Gonz%C3%A1lez+Quintela+A\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Gonz%C3%A1lez+Quintela+A\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Gonz%C3%A1lez+Quintela+A\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Gonz%C3%A1lez+Quintela+A\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Fuente+R\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Fuente+R\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Fuente+R\"&page=1\n\n\nhttp://europepmc.org/search?query=AUTH:\"Fuente+R\"&page=1\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Nassif A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Nassif A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Nassif A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Nassif A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bensussan A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bensussan A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bensussan A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Boumsell L[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Boumsell L[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Boumsell L[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Deniaud A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Deniaud A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Deniaud A[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Moslehi H[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Moslehi H[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Moslehi H[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wolkenstein P[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wolkenstein P[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wolkenstein P[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bagot M[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bagot M[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Bagot M[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Roujeau JC[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Roujeau JC[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Roujeau JC[Author]&cauthor=true&cauthor_uid=15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/15536433\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chung WH[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Hung SI[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Yang JY[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Su SC[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Huang SP[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wei CY[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chin SW[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chiou CC[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chiou CC[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chiou CC[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chu SC[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Ho HC[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Yang CH[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Lu CF[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wu JY[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Liao YD[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Chen YT[Author]&cauthor=true&cauthor_uid=19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/19029983\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dorafshar AH[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dorafshar AH[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dorafshar AH[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dorafshar AH[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dickie SR[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dickie SR[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Dickie SR[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Cohn AB[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Aycock JK[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Aycock JK[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Aycock JK[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=O'Connor A[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Tung A[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Gottlieb LJ[Author]&cauthor=true&cauthor_uid=18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/18594400\n\n\nhttps://www.ncbi.nlm.nih.gov/pubmed/18594400\n\n\n\n\n\n\nTOPICAL CORTICOSTEROIDS PHOBIA AMONG \nDERMATOLOGY OUTPATIENT IN UiTM \nSPECIALIST CLINIC\nIsma A.S , Luqman A.J,  Alina P.H, Athirah M.M, Sofea H.R, T Taib\nFaculty of Medicine, Universiti Teknologi MARA\n\n\n\nPoster \nNo. 50\n\n\n\nINTRODUCTION\nCorticosteroid phobia is certainly a misnomer because the\nterm 'phobia' defines an irrational fear. In fact, corticosteroid\nphobia is the dedicated term to describe all types of fear about\nsteroid use. TOPICOP, a new scale in evaluating topical\ncorticosteroid phobia help us assess the severity of steroid\nphobia among patient who use topical corticosteroid for\ntreatment and the causes of topical corticosteroid phobia.\n\n\n\nAIM\n\u2022 To evaluate the degree of corticosteroids phobia in\n\n\n\npatients who are on the usage of topical corticosteroids.\n\u2022 To evaluate the causes of corticosteroids phobia in\n\n\n\npatients who are currently being treated with topical\ncorticosteroids.\n\n\n\nMETHODOLOGY\nA cross-sectional study involving 80 topical\ncorticorticosteroid user, diagnosed with eczema in outpatient\nUiTM Dermatology clinic. All respondents completed a\ndemographic and TOPICOP questionnaire. For peadiatric\npatient, the form was fill up by their parent.\n\n\n\nRESULTS\nMean age of study cohort was 43.8 (1 \u2013 86) yrs. \nN=80\n\n\n\nCharacteristics Variable %\n\n\n\nGender Male 53.8\n\n\n\nFemale 46.2\n\n\n\nEthnicity Malay 81.2\n\n\n\nChinese 15\n\n\n\nIndian 3.8 \n\n\n\nEducation Primary school 12\n\n\n\nSecondary school 28\n\n\n\nGraduated 35\n\n\n\nOccupational Status Employed 26.3\n\n\n\nStudent 27.5\n\n\n\nHousewife 10\n\n\n\nRetiree 27.5\n\n\n\nOther 8.8\n\n\n\nClinical Characteristic (corticosteroid usage)\n\n\n\nDuration of Use \uf03c 5 yrs 80\n\n\n\n\uf03e 5 yrs 20 \n\n\n\nNumber of Different \n\n\n\nType (CS)\n\n\n\n1 33.8\n\n\n\n2-4 38.8\n\n\n\n\uf03e 4 27.5\n\n\n\nSeverity of Phobia None 1.3\n\n\n\nMild (1-11) 57.5\n\n\n\nModerate (12-22) 37.5\n\n\n\nSevere (23-33) 3.8\n\n\n\nN=227 (total number of varied topical corticosteroid use)\n\n\n\nClobetasol propionate 0.01% cream 0.5%\n\n\n\nClobetasol propionate 0.05% ointment 2.7%\n\n\n\nClobetasol propionate 0.05% cream 3.2%\n\n\n\nClobetasol propionate 0.15% cream 0.9%\n\n\n\nClobetasone butyrate 0.05% ointment 11.5%\n\n\n\nClobetasone butyrate 0.05% cream 5.8%\n\n\n\nHydrocortisone 1% ointment 15.0%\n\n\n\nHydrocortisone 1% cream 17.2%\n\n\n\nHydrocortisone 2% cream 0.1%\n\n\n\nBetamethasone dipropionate 0.05% \n\n\n\nointment\n\n\n\n18.5%\n\n\n\nBetamethasone dipropionate 0.05% cream 3.5%\n\n\n\nBetamethasone valverate 0.01% cream 7.1%\n\n\n\nMomethasone furoate 0.1% cream 13.7%\n\n\n\nFigure 1: Distribution of topical \n\n\n\ncorticosteroid phobia \n\n\n\n*CS \u2013 corticosteroid, Yrs - years\n\n\n\nAll 3 respondents who reported severe\ncorticosteroid - phobia were graduates.\nrespondents. However there were no significant\ncorrelation between degree of phobia with\neducational level, age and gender\n\n\n\nFinally , 38% of study cohort found that\nreassurance for usage of topical CS was\nunnecessary, 33% thought reassurance was\nsometimes needed, 9% opted for often reassurance\nand 21% always need reassurance in using topical\nCS.\n\n\n\nDISCUSSION  &  CONCLUSION\n\u2022 Majority of study cohort had at least degree\n\n\n\nof steroid phobia which might affect their\ntreatment compliance or resulted from\nimproper topical corticosteroid application.\n\n\n\n\u2022 Despite this, many of our patients are not\naware of importance of reassurance and\neducation from medical professionals.\n\n\n\n\u2022 Proper technique of steroid application may\nalleviate anxiety among patients.\n\n\n\n\n\n\n\n\nPREVALENCE OF ACNE AND ITS EFFECTS ON THE QUALITY OF \nLIFE AMONG ADOLESCENTS - A SUNGAI BULOH SECONDARY \nSCHOOL EXPERIENCE\n\n\n\nLiyana R, Pennie C.P,  Nur Syhuhada S, Solihin M.M, Nur Amanina Z.H, Taib T\nFaculty of Medicine, Universiti Teknologi MARA (UiTM)\n\n\n\nPoster \nNo. 51\n\n\n\nINTRODUCTION\n\n\n\nAcne vulgaris is common among adolescents. It may\ncause them some negative implications including\nstress, low self-esteem and poor relationship with\nothers. The severity of acne was assessed using GAGS\nscore whereby CADI score was used to assess the\nquality of life.\n\n\n\nAIMS\n\n\n\nTo determine the prevalence of acne, categorized its\nseverity and its impact on quality of life of study cohort.\n\n\n\nMETHODOLOGY\n\n\n\nA cross sectional study was performed at secondary\nschool students at Sg Buloh involving 271 students\naged from 14-17 years old. Data collection including\ndemographic, CADI score and GAGS score.\n\n\n\nRESULTS\n\n\n\nMean age of study cohort was 15.5 (13.6-17.4) \u2013 yrs old\n\n\n\nTable 1: Demographic characteristics of study cohort\n\n\n\n0\n5\n\n\n\n10\n15\n20\n25\n\n\n\nMild \ndisability\n\n\n\nModerate \ndisability\n\n\n\nSevere \ndisability\n\n\n\n31\n\n\n\n37 42\n32\n\n\n\n67\n\n\n\n62\nP\n\n\n\ne\nrc\n\n\n\ne\nn\n\n\n\nta\nge\n\n\n\n (\n%\n\n\n\n)\n\n\n\nCADI Score\n\n\n\nThe Impact Of Acne On The Quality Of Life\n\n\n\nMale Female\n\n\n\nGender N Mean (\u00b1) Ind T-score\n\n\n\nGAGS \n\n\n\nScore\n\n\n\nMale 108 12.70 (\u00b18.11) p=0.001\n\n\n\nFemale 153 9.61 (\u00b17.18)\n\n\n\nMild :1-18 , Moderate :19-30  , Severe : 31-38 , Very severe : >39\n\n\n\n0\n10\n20\n30\n40\n50\n\n\n\nMild Moderate Severe Very \nsevere\n\n\n\n87\n\n\n\n17\n3 2\n\n\n\n134\n\n\n\n16\n2 0\n\n\n\nGAGS Score\n\n\n\nAcne Assessment\n\n\n\nMale Female\n\n\n\nP\ne\nrc\n\n\n\ne\nn\n\n\n\nta\ng\n\n\n\ne\n (\n\n\n\n%\n)\n\n\n\nCONCLUSION\nIn conclusion, adolescents should be given an\nearly health education regarding skin care\nbecause acne has significant negative impacts in\ntheir quality of life.\n\n\n\nVariable Frequency, n (%)\n\n\n\nGender \n\n\n\n1. Male \n2. Female \n\n\n\n110 (40.6%) \n161 (59.4%) \n\n\n\nEthnicity\n\n\n\n1. Malay \n2. Chinese \n3. Indian \n4. Others \n\n\n\n215 (79.3%) \n25 (9.2%)\n16 (5.7%)\n15 (5.3%) \n\n\n\nFamily income\n\n\n\n1. < RM 500 \n2. RM 500- RM 1500 \n3. RM 1500- RM 2000 \n4. > RM 2000 \n\n\n\n9 (3.3%) \n88 (32.5%) \n65 (24.0%) \n109 (40.2%) \n\n\n\nOut of a total study cohort, 96.3%(n=261) were\ndiagnosed to have acne. 59.4% were girls and 40.6%\nboys. These was further analyzed using GAGS and\nCADI score. Clinically mild, moderate, severe and very\nsevere degree of acne were seen in 81.5%, 12.2%,\n1.8% and 0.7% respectively, out of 261 students.\n\n\n\nFigure 1 : Acne severity distribution by gender.\n\n\n\nOut of 261, majority of them has moderate (38.4\n%) or severe disability (38.4%) while only 23.3 %\nhas mild disability. Mean CADI score slightly\nhigher in female compared to male (9.27\u00b13.47)\nbut statistically not significant.\n\n\n\nThere was a weak but significant correlation \nbetween GAGS and CADI score (r=-0.2).  \n\n\n\nDISCUSSION\n\n\n\nDespite the majority of them found to be\nclinically mild by GAGS score, they reported\nsignificantly impaired quality of life with majority\nin the moderate or severe. They reported more\nadversely affected in social life or relationship,\nand causing behaviour modification in public. A\nrecent study conducted by KM Padmavathy et al\n(2014), there was a significant positive\ncorrelation of the impact of acne in their quality of\nlife. Males showed significant correlation of\nclinical severity of acne to stress and atrophic\nscar.[1] In CADI score the definition of behaviour\nmodification in public may not be adaptive in\nmalays predominant secondary school.\nInterestingly, more male students reported\nsevere disability as compared to female\ncounterpart and they had higher mean of GAGS\nscore. Hence, acne affected the quality of life in\nboth gender.\n\n\n\nREFERENCES\n1. KM Padmavathy et al. (2014). Evaluation of Acne \n\n\n\nSeverity and Its Impact on Young Adults.\n\n\n\n2. F. Boon Yap (2012). Cardiff Acne Disability Index \n\n\n\nin Sarawak, Malaysia, 2012.\n\n\n\n3. R. J. Motley, A. Y. Finlay 19. Cardiff Acne \nDisability Index.\n\n\n\nABBREVIATION\nCADI \u2013 Cardiff Acne Disability Index\nGAGS- Global Acne Grading System\n\n\n\n\n\n\n\n\nPSYCHOLOGICAL IMPACT OF INFANTILE   \n      HAEMANGIOMA ON CHILDREN  \n\n\n\nAND THEIR PARENTS  \nAbdullah R1, Angsar A1 & Sabeera BKI2 \n\n\n\n1Paediatric Dermatology Nursing, 2 Paediatric Dermatology Unit \nInstitute Of Paediatrics Hospital Kuala Lumpur \n\n\n\n\n\n\n\n52  \n\n\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nS \n\n\n\n \n \nInfantile haemangiomas (IHs) are common, benign \nvascular tumours in children that appear soon after birth \nand regress before the age of 12 years. It is estimated \nthat only 31\u201350% of children exhibit satisfactory \ncosmetic healing after involution. In the remaining \nchildren, natural regression of IHs can result in skin \natrophy, scarring, fibro-fatty tissue, hyper and \nhypopigmentation, and laxity. \nDuring consultations, parents usually express their \nfeelings and worries about their child\u2019s lesion, \nparticularly when present on the face.  \nPhysicians have always been concerned about the \nconsiderable psychosocial impact these lesions might \nhave on children and their parents. \n \n\n\n\n \n \nThis is a prospective cross sectional study inviting \nparents of children who were treated for facial \nhaemangiomas to participate in answering a \nquestionnaire which had been validated called - \nInfantile Haemangioma Quality of life (IH-QoL) \nquestionnaire1. The questionnaire consist of  20 \nquestions that addressed the emotional attitudes of the \nparent and child toward the disease and the related \ntreatment. The psychosocial consequences in these \nparents impact on their emotions, experiences and life-\nstyle were analysed. The study was conducted at the \nBirthmark Clinic, Institut Pediatrik Hospital Kuala \nLumpur between April to June 2017. All patients with \nfacial hamangioma were recruited and haemangioma \non other sites were excluded. \n\n\n\n1. SL Chamlin et al. Development and validation of a Quality-of-Life Instrument for Infantile Haemangiomas.  \n    Journal of Investigative Dermatology 2015; 135, 1533\u20131539  \n2. Jeffery Z et al. The Psychological impact of haemangioma on children and their parents \n    Arch Dis Child 2012;97:922\u2013926.  \n\n\n\nINTRODUCTION \n\n\n\n \n \nThe objective of the study was to assess the \npsychosocial impact of haemangiomas and their \ntreatment on children and their parents  \n \n\n\n\nOBJECTIVE \n\n\n\n \n \nDermographic data: There were total 103 patients with \ninfantile haemangioma treated during the study period. \nFifty six (54%) patients had facial haemagioma but only \n40 parents consented to participated in the study. Five  \nques t i onna i res were exc luded because o f \nincompleteness and finally only 35 questionnaires were  \nanalysed. There were more female (71%) patients. Most \nwere infants less than 1 year old (70%) but 4 patients \nwere aged more than 3 years old. The onset of \nhaemangioma was within 4 weeks of life in 68% of \npatients. Sixty percent of the haemangiomas were \nsuperficial, 22% were mixed and rest were deep \nh a e m a n g i o m a s . T h e c o m m o n l o c a t i o n o f \nhaemangiomas were around the periorbital region in \n35% of patients followed by  lips (18%), forehead \n(17%), cheek (14%), nose (11%) and  chin (5%) in \ndecreasing order on frequency. \n \nIH-QoL results: Nearly 90% of the parents were \nsatisfied with treated received and only 4 infants with \nperiorbital haemangioma had slow response. Despite of \nhigh treatment satisfactions about 60% of parents still \nneed further reassurance and information on the \ndisease. Most worrying issues for parents were during \nthe proliferative phase, when it growing too fast. \n\n\n\nRESULTS \n\n\n\n \nFacial haemangiomas are associated with parental reactions of  \nsad, fear, and mourning, particularly in the growth phase.  \nAccurate measurement of the quality of life is critical to the \nultimate goal of improving this outcome for affected infants and \ntheir families. \nImportantly, IH-QoL can be used in practice to identify parents \nneeding additional support and education.  \n \n\n\n\nHospital Kuala Lumpur \n\n\n\n\n\n\n\nRESULTS - IH QoL \n\n\n\nNo. of patients \n\n\n\nSeventy five percent parents are bothered when their child are \nstared by strangers and more than half are sad and sometime \ndepressed about the child\u2019s haemangioma. Other common \nissues raised were that their child would be teased at school and \nthat their self esteem would suffer (63%). Sixty five  percent had \nissues of self blame and worried that haemangioma may occur in \nsubsequent children. One third of the parents were accused of \nabusing their children because of haemangioma which then led \nfew parents hiding the haemangioma. Generally most parents \nfelt that haemangioma had no negative impact on their social \nfunction such as visiting public places, being with friends and \nrelatives or even how the child looked. And finally it had no \nissues in the relationship between spouses. \n \n \n \nThe clinical characteristics of hemangiomas with a greater \nnegative impact on IH-QoL, include hemangiomas located on the \nface and those in the proliferative stage. Those with infants with \nhemangiomas in the proliferative stage have worse impact on the \nparent emotional functioning but less effect on social functioning. \nThese characteristics alone may be useful in identifying parents \nin clinical practice requiring more intensive hemangioma \neducational efforts, emotional support, and hemangioma \ntreatment. \nLimitations of the study include selection bias, where most \npatients referred for treatment of severe haemangioma. Most  \nparents who are concerned about the visibility of facial \nhaemangioma. Interpretability of the IH-QoL scores which may \nimprove with clinical use. And lastly, the study sample was small \nin number. \nCONCLUSION \n\n\n\nDISCUSSION \n\n\n\nMETHODOLOGY \n\n\n\nFigure 1 \n\n\n\nFigure 1 & 2:  The bar chart show the significant difference between parent emotional/\npsychosocial functioning and child social interactions, elaborated in detail below. \n\n\n\n\n\n\n\n\nA Cohort Study of Nurses\u2019 Knowledge on Bullous \nCellulitis and Its Management:\n\n\n\nPre- and Post Dermatology Training in Public Hospital\n\n\n\nPoster \nNo. 53\n\n\n\nAshiela S, Noradiah J, Rohna R\nDepartment of Dermatology, Selayang Hospital \n\n\n\nINTRODUCTION\nCellulitis in adults is a common medical\ncondition.1 Appropriate antibiotic is essential\naccording to type and sensitivity to microbial\norganism. However, skin nursing also plays a\nvital role to speed up the recovery. Thus,\nnurses play an integral part in bullous cellulitis\nmanagement.2 Multiple incidence of improper\nskin nursing and inadequate skin nursing\ncausing adverse event have been documented.\n\n\n\nThe British Dermatological Nursing Group has\ndeveloped a competency-based guideline to\ndevelop dermatology nurses from novice to\nexpert, focusing on the nurse\u2019s educational\ndevelopment in combination with knowledge\nand skills. 3 This study is to determine nurses\nknowledge of bullous cellulitis and its\nmanagement before and after training.\n\n\n\nMATERIALS & METHOD\nA prospective comparative study of nurses\nknowledge on nursing management of bullous\ncellulitis before and after dermatology training\nwas conducted in Selayang Hospital between\nApril to June 2017. A total of 40 staff nurses\nwas chosen randomly using convenience\nsampling methods.\n\n\n\nInclusion Criteria\n\u2022All nurses in intensive care unit, medical,\ndermato-rheumato and paediatric ward who\nconsented in this study.\n\n\n\nExclusion Criteria\n\u2022All nurses from other department who do not\nperform skin nursing and those who not keen\nto participate.\n\n\n\nAll Participants were asked to answer a survey\nform before and after receiving Dermatology\ntraining. Training will be given by Sister in-\ncharge in respective ward by using the same\npower point slide and cellulitis nursing tools\n(Figure 2). Training will be given within 2 weeks\nafter nurses answered the questionnaire. The\nsame nurses will complete the same\nquestionnaire in a week after training.\n\n\n\nA Total of 14 questions with category A mainly\ndemographic and experience background.\nWhereby category B, a multiple choices\nquestionnaire about clinical data that divided\ninto pharmacology management, non-\npharmacology management and monitoring. 1\nmark was given for a correct answer and zero\nmark for wrong answer. Total of 11 marks will\nbe given if participant able to answer all\nquestions. The result will be divided into 3\ngroups : satisfactory 1-3 marks, good 4-6 and\nexcellent 7-11.\n\n\n\nData Analysis were done using SPSS 16.0.\n\n\n\nFigure 1: Leg Cellulitis Figure 2:Cellulitis nursing tools\n\n\n\nCharacteristic\nNo %\n\n\n\nGender\n\n\n\nMale 1 2.5\nFemale 39 97.5\n\n\n\n0\n\n\n\n5\n\n\n\n10\n\n\n\n15\n\n\n\nMedical Ward Derm-Rheum \nWard\n\n\n\nPediatric ICU\n\n\n\n10 8 10 10\n\n\n\n2\n0\n\n\n\n0 0\n\n\n\nExperience No Experience\n\n\n\nSatisfactory\n2%\n\n\n\nGood, 52.5, \n53%\n\n\n\nExcellent\n45% Satisfactory\n\n\n\nGood\n\n\n\nExcellent\n\n\n\nDISCUSSION & CONCLUSION\n1. Experience working in dermatology department was an\n\n\n\nadvantage as participant has higher pre dermatology survey\nscore. Although 90% of participant had experience managing\npatient with cellulitis, only 45% had excellent score before the\ntraining thus the increase of risk of improper skin nursing\nperformed.\n\n\n\n2. There is currently no post basic course in dermatology. The\ntraining and teaching intervention positively influenced post\ntraining scores significantly. The need for intensive continuing\neducation and staff development in dermatology to improve\npatient outcome.\n\n\n\nCharacteristic\nNo %\n\n\n\nEthnic\nMalay 38 95\nChinese 0 0\nIndian 2 5\n\n\n\n0\n2\n4\n6\n8\n\n\n\n10\n12\n\n\n\nMedical Ward Derm-Rheum \nWard\n\n\n\nPediatric ICU\n\n\n\n1\n\n\n\n8\n\n\n\n1 1\n\n\n\n11 9 9\n\n\n\nNo  Experience Experience\n\n\n\n1. Guidelines On The Management Of Cellulitis In Adults by CREST ; www.crestni.org.uk\n2. Courtenay M, Carey N; A review of the impact and effectiveness of nurse-led care in dermatology ;BJD. 2006;154(1):1-6.\n3. Dermatology Nursing Competencies by the British Dermatological Nursing Group.\n\n\n\nCONCLUSION\nDermatology training for nurses should be implemented in all centers with dermatology service and regular training\nshould be done as it has significantly improved nurses knowledge in managing bullous cellulitis. Having a post basic\ntraining in dermatology nursing improves patient care.\n\n\n\nRESULT\nTable 1 : Demographic Data\n\n\n\nFigure 3 : Staff With Dermatology Experience \n\n\n\nFigure 4 : Treating Cellulitis Experience\n\n\n\nFigure 5 : Pre Dermatology Link Nurse Training Result\n\n\n\nPost Dermatology Training, all participant obtained excellent \nresult. p-value in Paired t-test comparing Total Pre & Post \nDermatology Training Score is significant . (p = 0.00001)\n\n\n\nCharacteristic\nNo %\n\n\n\nGender\n\n\n\nMale 1 2.5\nFemale 39 97.5\n\n\n\n0\n\n\n\n5\n\n\n\n10\n\n\n\n15\n\n\n\nMedical Ward Derm-Rheum \nWard\n\n\n\nPediatric ICU\n\n\n\n10 8 10 10\n\n\n\n2\n0\n\n\n\n0 0\n\n\n\nExperience No Experience\n\n\n\nSatisfactory\n2%\n\n\n\nGood, 52.5, \n53%\n\n\n\nExcellent\n45% Satisfactory\n\n\n\nGood\n\n\n\nExcellent\n\n\n\nCharacteristic\nNo %\n\n\n\nEthnic\nMalay 38 95\nChinese 0 0\nIndian 2 5\n\n\n\n0\n2\n4\n6\n8\n\n\n\n10\n12\n\n\n\nMedical Ward Derm-Rheum \nWard\n\n\n\nPediatric ICU\n\n\n\n11 9 9\n\n\n\n1\n\n\n\n8\n\n\n\n1 1\n\n\n\nNo  Experience Experience\n\n\n\n\n\n\n\n\nKnowledge of topical application among \npsoriasis patients in Dermatology Department \n\n\n\nHospital Pulau Pinang: A clinical audit\nLay Fang Phang1,  Mohd Ali Nor Azlima1, Nurul Shafaril Niza2, Yek Huan Khor1, Wooi Chiang Tan1, Lee Chin Chan1\n\n\n\n1Department of Dermatology, Hospital Pulau Pinang, Malaysia\n2Department of Pharmacy, Hospital Pulau Pinang, Malaysia\n\n\n\nNo.  \n54 \n\n\n\n\n\n\n\nINTRODUCTION \nTopical treatment is the first line therapy for psoriasis. \nEfficacy of topical therapies can be enhanced by \nadherence and proper application of medications\u00b9. \nTherefore an audit was carry out to assess the \nknowledge of topical application in psoriasis patients.  \n\n\n\nMETHODOLOGY \nA cross-sectional study was done. Using convenient \nsampling, adult psoriasis patients who were follow up \nin Dermatology clinic Hospital Pulau Pinang from 1st \nJune 2017 to 15th June 2017 were included. Patients \nwho were under 18 years old and newly diagnosed \npsoriasis patients were excluded from the study.  \n\n\n\nTable 1: Criteria with standard of 80% each \n\n\n\n1.\u202f Able to recognize different types of topical \nmedications. \n\n\n\n2.\u202f Able to apply topical medications at correct sites \nof body. \n\n\n\n3.\u202f Able to recognize frequency of topical \napplications. \n\n\n\n4.\u202f Able to differentiate the strength of topical \nsteroid. \n\n\n\n26.7%\n\n\n\n63.3%\n\n\n\n53.3%\n\n\n\n36.7%\n\n\n\n83.3%\n\n\n\n93.3%\n\n\n\n83.3%\n80.0%\n\n\n\n0%\n\n\n\n10%\n\n\n\n20%\n\n\n\n30%\n\n\n\n40%\n\n\n\n50%\n\n\n\n60%\n\n\n\n70%\n\n\n\n80%\n\n\n\n90%\n\n\n\n100%\n\n\n\nMedication \ntype\n\n\n\nCorrect site Frequency Steroid \nstrength\n\n\n\nn = 30First audit Re-audit\n\n\n\nDISCUSSION \n\u2022\u202f Poor knowledge about topical medications indicates \n\n\n\ninsufficient counseling provided by the physician. \nMore time should be spent to explain the treatment \nand demonstrate how to apply the medications.  \n\n\n\n\u2022\u202f To create better understanding of topical \nmedications, patients should be provided with \ncomprehensive but easi ly understandable \ninstructions and labels to improve adherence.  \n\n\n\n\u2022\u202f Patients\u2019 understanding of their topical medication is \nimproved after using color and picture labelling \nsystem with individual counseling. \n\n\n\n\u2022\u202f Limitation includes language barrier and different \neducational background. \n\n\n\nCONCLUSION \nThe knowledge on topical application was suboptimal. \nThe results from remedial measures demonstrate that \nuse of color and pictorial labeling system and detail \npersonal counsel ing by pharmacist improve \nunderstanding of topical application. A larger study is \non the way. And we plan to introduce colour and \npicture labeling for topical medications in our hospital. \n\n\n\nREFERENCES \n1.\u202f Kircik L. Skin Therapy Letter. Topical Treatment Adherence for \n\n\n\nPsoriasis. Updated August 2014. \n2.\u202f Roberto Cardarelli, Christopher Mann, Kimberly G Fulda, \n\n\n\nElizabeth Balyakina, Anna Espinoza and Sue Lurie. Improving \naccuracy of medication identification in an older population \nusing a medication bottle color symbol label system. BMC \nFamily Practice 2011;12:142. \n\n\n\nOut of the thirty patients in our cohort, more than half  \nof them are able to apply topical medications at \ncorrect sites of body and almost half of them can \nrecognize the frequency of the topicals. However only \n36.7% of them are able to differentiate strength of \ntopical steroids prescribed to them and only  26.7% of \npatients able to recognize the various types of topical \nmedications (Chart 1).  \n\n\n\nRESULTS \nWe have a total of 30 patients. Fairly equal sex \ndistribution with 16 (53.3%) male and 14 (46.7%) \nfemale patients. In term of race distribution; Malay 8 \n(26.7%), Chinese 13 (43.3%), Indian 8 (26.7%) and \nKadazan 1 (3.3%) \n\n\n\nPOST-REMEDIAL AUDIT RESULTS \nPercentage of patients who can recognize types of \nmedications, correct site of application, frequency and \nability to differentiate strength of steroid have improved \nsignificantly to 83%  ,93%, 83% and 80% respectively \n(Chart 1) \n\n\n\nChart 1: Patient\u2019s understanding on topical application -         \n              Pre & Post-remedial audit results \n\n\n\nPITFALLS IDENTIFIED \n1.\u202f Most patients were unable to remember the name \n\n\n\nof medications, especially those on multiple \ntopical medications. \n\n\n\n2.\u202f The containers that were used for various types of \ntopical medications were almost identical in \nappearance, making it hard for patients to \ndifferentiate them. \n\n\n\n3.\u202f Inadequate counseling time by physicians in clinic.   \n\n\n\nPatients fulfilled criteria and consented \n\n\n\nConsultation & Counseling done.Prescription given \n\n\n\nCollection of medication  \n\n\n\nAudit of patients' knowledge on the prescribed \nmedication based on the criteria listed in Table 1 \n\n\n\nPitfalls identified \n\n\n\nImplementation of remedial measures done \n\n\n\nRe-audit done at the next visit, 2-3 weeks later  \n\n\n\nREMEDIAL MEASURES \n1.\u202f Colour and picture labeling on the containers of their \n\n\n\ntopical medications were introduced to identify types \nof medication, site of application as well as to \nrecognize strength of steroid\u00b2 (Figure 1) \n\n\n\n2.\u202f Patients are counseled individually by an assigned \npharmacist.  \n\n\n\nFigure 1: Colour & Picture Labeling \n\n\n\nKurang \nKuat \n\n\n\nS  Steroids \n\u00a7\u202f Sangat Kuat \n\u00a7\u202f Kuat \n\u00a7\u202f Sederhana kuat \n\u00a7\u202f Kurang kuat \n\n\n\n     Keratolytics/ Tar \n\n\n\n     Emollients \n\n\n\n\n\n\n\n\nSelf-Reported Generalised Pruritus Among \nCommunity-Dwelling Older Adults in the \n\n\n\nMalaysian Elders Longitudinal Research Study\nShin Shen Yong1, Zhenli Kwan1, Chin Chwen Ch\u2019ng1, Adrian Sze Wai Yong1, Leng Leng Tan1, Shahrul \n\n\n\nBahyah Kamaruzzaman2, Ai Vyrn Chin2, Maw Pin Tan2\n\n\n\n1Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia\n2Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia\n\n\n\n55\n\n\n\nINTRODUCTION\nGeneralised pruritus may be associated with \nsystemic diseases and requires a comprehensive \napproach. This cross-sectional study aimed to \nidentify the burden of pruritus and the factors \nassociated with the presence of generalised \npruritus and its severity among older adults. \n\n\n\nOBJECTIVE\nTo determine the prevalence and severity of \ngeneralised pruritus with selected factors in the \nolder Malaysian population. \n\n\n\nMATERIALS AND METHOD\nStudy design: Cross-sectional study\nStudy sample: 770 subjects aged 55 years and \nabove from Petaling Jaya North, Petaling Jaya \nSouth and Pantai Valley. \nData collection period: 2012-2015\nMethod: The presence or absence of generalised \npruritus for all individuals was recorded with \nseverity rated using a numerical rating scale. The \nPearson\u2019s chi-square test was used to determine \npossible associated factors while multivariate \nlogistic regression analysis was performed to \nidentify significant predictors of generalised \npruritus. \n\n\n\nRESULTS\n46 subjects (5.97%) reported generalised pruritus, \nof whom only 43 rated severity.\n\n\n\nUnadjusted analysis revealed that dementia was \nassociated with the presence of generalised \npruritus (Table 1). \n\n\n\nDISCUSSION AND CONCLUSION\n\u2022 The behavioural and psychological manifestations of \n\n\n\ndementia such as psychosis and obsessive behaviour \ncan lead to constant scratching.1 However, only one \nsubject with dementia reported having generalised \npruritus. This could be due to a small number of \npeople reporting the presence of generalised pruritus.\n\n\n\n\u2022 Ageing female skin is prone to dryness and pruritus \ndue to reduction of collagen production and a lower \nlevel of glycosaminoglycans that prevents \ntransdermal water loss2. Females have a lower \nthreshold to scratch due to the differences in itch \nperception when compared to men.3\n\n\n\n\u2022 The association between generalised pruritus and \ngout could be due to the side effects of medications \nsuch as non-steroidal anti-inflammatory drugs \n(NSAIDS).4\n\n\n\n\u2022 The presence of iron deficiency should be explored \nas it is often regarded as a cause of pruritus, even in \nthe absence of anemia.5\n\n\n\n\u2022 Generalised pruritus affects the sleep quality by \ncausing sleep onset insomnia, increased night-time \nawakening, and decreased total sleep hours.6 Drugs \nused in the treatment of pruritus may also lead to \nsleep disturbance.7 These phenomena contribute to a \npoor Pittsburgh Sleep Quality Index in the study.\n\n\n\n\u2022 Further research to define the dermatoses and risk \nfactors associated with generalised pruritus will be \nuseful in the planning of appropriate management \nstrategies for older adults affected by pruritus. \n\n\n\nREFERENCES\n1. Cohen-Mansfield, J., M.S. Marx, and A.S. Rosenthal, A \n\n\n\ndescription of agitation in a nursing home. J Gerontol, 1989. \n44(3): p. M77-84.\n\n\n\n2. Ganceviciene, R., et al., Skin anti-aging strategies.\nDermatoendocrinol, 2012. 4(3): p. 308-19.\n\n\n\n3. Stumpf, A., et al., Sex differences in itch perception and \nmodulation by distraction--an FMRI pilot study in healthy \nvolunteers. PLoS One, 2013. 8(11): p. e79123.\n\n\n\n4. Stevenson, D.D., M. Sanchez-Borges, and A. Szczeklik, \nClassification of allergic and pseudoallergic reactions to drugs \nthat inhibit cyclooxygenase enzymes. Ann Allergy Asthma \nImmunol, 2001. 87(3): p. 177-80. \n\n\n\n5. Yonova, D., Pruritus in certain internal diseases. Hippokratia, \n2007. 11(2): p. 67-71. \n\n\n\n6. Yosipovitch, G., et al., The prevalence and clinical \ncharacteristics of pruritus among patients with extensive \npsoriasis. Br J Dermatol, 2000. 143(5): p. 969-73 \n\n\n\n7. Ciriaco, M., et al., Corticosteroid-related central nervous system \nside effects. J Pharmacol Pharmacother, 2013. 4(Suppl 1): p. \nS94-8.\n\n\n\n9.3%\n(n=4)\n\n\n\n18.6%\n(n=8) 16.3%\n\n\n\n(n=7)\n\n\n\n7.0%\n(n=3)\n\n\n\n14.0%\n(n=6)\n\n\n\n21.0%\n(n=9)\n\n\n\n4.7%\n(n=2)\n\n\n\n9.3%\n(n=4)\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\nThree Four Five Six Seven Eight Nine Ten\nNumerical Rating Scale for Pruritus\n\n\n\nFrequency of severity of generalised \npruritus (n=43)\n\n\n\nFactors\nGeneralised pruritus\n\n\n\nTotal\n\u03c72or Fisher\u2019s \nexact test\n\n\n\np-value\nYes No\n\n\n\nDementia\n\n\n\n4.013 0.045*Yes 1 (33.3%) 2 (66.7%) 3\n\n\n\nNo 45 (5.9%) 722 (94.1%) 767\n\n\n\nGeneralised \npruritus\n\n\n\nPSQI (n=749)\nTotal\n\n\n\n\u03c72or Fisher's \nexact test\n\n\n\np-value\nPoor Good\n\n\n\nYes\n26(56.5%) 20(43.5%)\n\n\n\n46\n4.201 0.04\n\n\n\nNo 292(41.1%) 418(58.9%) 710\n\n\n\nTable 1. Association between presence of dementia and \ngeneralised pruritus\n\n\n\nFigure 1. Frequency of severity of generalised pruritus.\n\n\n\nFigure 3. Association between generalised pruritus and \nsleep quality.\n\n\n\nMultivariate analysis found that female gender \n(OR=2.149, p=0.029), dementia (OR=10.963, p=0.058) \nand gout (OR=2.729, p=0.040) were significant \nindependent predictors of generalised pruritus. \nSubjects with generalised pruritus had significantly \nlower levels of haemoglobin compared to those without \n(13.14 g/dL and 13.71 g/dL respectively). \n\n\n\nThe\tauthors\thave\tno\tconflict\tof\tinterest\tto\tdeclare.\n\n\n\n\n\n\n\n\nRESEARCH POSTER PRESENTATION DESIGN \u00a9 2015 \n\n\n\nwww.PosterPresentations.com \n\n\n\nClique Clinic   4, Jalan 19/36, Seksyen 19, 46300 Petaling Jaya, Selangor, Malaysia. www.cliqueclinic.com \n\n\n\nIn our clinical setting, we observed that among the Malaysians coming \nfor aesthetic procedures, there is an increasing number of those \ndeveloping Facial Overfilled Syndrome (FOS). They typically have \ndistorted pointy chin, overly broad noses, and overwhelmingly bloated \ncheeks. Many of them are not aware of it and are not able to \nappreciate the distortion. It is also sometime overlooked by aesthetic \npractitioners giving the injections. \nThis article aim to bring awareness of such overfilled syndrome to the \nmedical aesthetic community to prevent further facial distortion cause \nof facial overfilling with fillers. \n\n\n\nIntroduction \n\n\n\nResults \n\n\n\nDiscussions \n\n\n\nConclusion \n\n\n\nOverfilled Syndrome can be appreciated by palpating the areas overly filled with gel \nlike fluid regardless of the chronological period the fillers were placed. In many \ninstances, fillers could be placed more than 5 years and still palpable as liquid fluid \ninside the skin. \n\n\n\n\n\n\n\nDr Tingsong Lim \nDepartment of Aesthetic Medicine, Clique Clinic \n\n\n\nFacial Overfilled Syndrome in Malaysia \n\n\n\nObjectives \n\n\n\nFacial aging is characterised by dynamic, cumulative changes of the \nface structure due to the combined effects of gravity, progressive \nbone resorption, decreased tissue elasticity, and the redistribution of \nsubcutaneous fullness. Volume depletion, especially in the mid face, is \none of the earliest and most common sign of facial aging.  \n \nAlthough Asian patients tend to be endowed with more collagen \nreserve, early deflation of the mid face can exaggerate the forming of \neye bags, peri-orbital fine lines, tear troughs, nasolabial folds and jowls. \nOn top of that, temple hollowing and forehead volume loss could lead \nto droopy eyelids leading to an exhausted look. A relatively weak \nmidline also makes the Asian face look round and flat.  \n \nAesthetic practitioners attempt to treat these volume depletions and \nmidline weaknesses with hyaluronic acid dermal fillers or biostimulators. \nHowever, as dermal filler procedures become more widely acceptable \nand available in Malysia,  we also observed increasing numbers of \npeople developing facial overfilled syndrome.  \n\n\n\nMethodology \n\u2022\u202f Subjects who developed overfilled syndrome were recruited. Photos \n\n\n\nwere taken and analysis was done based on the photos to assess on \nthe volume distribution, topography, symmetry and gender, ethnicity \nand cultural appropriateness. \n\n\n\n\u2022\u202f The overfilled condition is categorized according to the areas that is  \ninappropriately proportionated compare to the whole face. \n\n\n\n\u2022\u202f The overfilled areas were palpated to feel the fluidity of the substance \nplaced. \n\n\n\n\u2022\u202f Overfilled areas are being managed by using hyaluronidase to \nattempt to dissolve the volume being placed. \n\n\n\n\u2022\u202f The after photo is taken once week after hyaluronidase is placed. \n\n\n\nThe overfilled syndrome is typically volume overload in the mid face, \nforehead, chin and nose. Mid-face overload are commonly known \nas pillow face, butt cheek, or flying saucer facies. This phenomenon \ncould be due to incorrectly placed dermal fillers, poor selection of \nfiller products, overzealous attempts by the injectors, and overly \nenthusiastic clients who \u201cchase the lines\u201d. \n \nMid-face over-filling is more commonly seen in Malaysian patients \ndue to the smaller frame of asian skull structures, which makes the \nexaggeration of volume more pronounced compare to their \ncaucasoid or negroid counterparts. The strong malar structure is too \neasily over-emphasized, giving the whole face a flying saucer look, \nwhere the middle third of the face is overloaded compare to the \nupper and lower third of the face. \n \nOverfilled syndrome is more commonly done by practitioners who \ndepend solely on a single modality for treatment. The tendency of \noverfilling patients with fillers, coupled with botulinum toxin misuse is \ncommonly seen in smaller practices where understanding of the \nartistry are more focused on commercial values and business \noriented settings. \n \nAlso, it is tied to certain local community values where an \nexaggerated look is the preference. The obsession with getting \ndrastic results with fillers could be a very dangerous practice in terms \nof safety and could possibly result in permanent distortion to the \nnatural structure of one\u2019s face. \n \nOnce a face is overfilled and the structure is distorted, diminishing \nthe volume with hyaluronidase will help to minimize the distortion, but \nwill not necessarily restore the face to its natural look. Therefore, it is \nvery important for the medical aesthetic community to bring up the \nawareness of overfilled syndrome and prevent this from happening \nin the first place. Having the conscience to not overfill, aesthetic \npractitioners will learn to be more cautious of the amount of product \nthey use, the products they select, and the right placement of the \nproduct. \n \nWith more awareness to prevent the practitioners from doing harm, it \ncould bring the overall quality of work to another level. \nUnderstanding the interdependent play of 5 layers structures, \nnamely: skin, fat, SMAS and retaining ligaments, muscles and bones \nis extremely crucial for aesthetic physicians to combat the signs of \naging.  It is vital to target all 5 layers of aging by combining different \nmodalities. Combination therapy has become a necessity rather \nthan a trend.  \n\n\n\nReplenishing volume to attain a more youthful appearance has yielded \nexcellent results, enabling the deflating face regain volume and \nfirmness. However, overzealous filling of faces with dermal fillers can \nresult in distortion of the face structure resulting in overfilled syndrome. \nThis phenomenon of mild to severe facial distortion due to the \nincorrectly placed dermal fillers either at the wrong plane, wrong \nlocation, or wrong amount of products, is especially apparent among \nAsian patients, due to the smaller bone frame of the mongoloid skulls. \nHaving the awareness of the overfilled syndrome is crucial among \naesthetic practitioners to prevent the mistake of producing distorted, \nunnatural and aesthetically unappealing faces. \n\u00a0 \n\n\n\n56 \n\n\n\nOverly-bloated cheeks is a common phenomenon \nof overfilled syndrome. Overfilled cheek is a result \nof chasing the lifting effect with fillers and over-\nemphasize the beauty of an \u201capple cheek\u201d. \n\n\n\n \n\n\n\n\n\n\n\n\nRESEARCH POSTER PRESENTATION DESIGN \u00a9 2015 \n\n\n\nwww.PosterPresentations.com \n\n\n\nClique Clinic   4, Jalan 19/36, Seksyen 19, 46300 Petaling Jaya, Selangor, Malaysia. www.cliqueclinic.com \n\n\n\nUnderstanding the pathophysiological changes of the facial aging is \ncritical in the course of restoring volume, and could racalibrate the \nmanner in which the maturing face is treated. \nThe five facial structures, in 5 different layers, undergo aging \ninterdepently: \n\u2022\u202f Skin (Layer 1) : epidermal atrophy, dermal elastosis \n\u2022\u202f Fat (Layer 2 & 4): fat atrophy, displacement and downward -shifting \n\u2022\u202f Anchoring Complex (Layer 3, 4, 5): skin tendons, SMAS & retaining \n\n\n\nligaments become fragile and weak \n\u2022\u202f Muscle (Layer 3): muscle atrphy, and secondary hyperactivity \n\u2022\u202f Bones (Layer 5): bone resorptions \n\n\n\n                      skin \n subcutaneous fat \n\n\n\n         superficial musculo-aponeurotic  \n               facial muscle \n               retaining ligaments & space \n\n\n\n periosteum and bone \n\n\n\n \n                         Figure 1: The Five Structures of Facial Aging in 5 different layers \n\n\n\n \nThe Anchoring Complex of the face, namely, skin tendons, superfical \nmuscular aponeurotic system (SMAS), and retaining ligaments, forms \nan achoring support of the soft tissues to the skull of the face. The \nweakening of these deep structures lead to stretching and loosening of \nfundamental structural support, contributing to facial sagging. Skeletal \nchanges due to bone resorption causes flattening of the forehead, \nhollowing of the orbit, receding of nasal bone, mida face bine atrophy, \nchin bone atrphy and or mandibular bone atrophy. These changes \nalong with fat loss of the deep fat pads, contributed to further \ndeterioration of the structural support of the face. Aesthetic practioners \ncan do more harm than good if they overlook the right layers and \nstructures that require attention. \n \n \n \n\n\n\n  Dermis \n  Subcutaneous Fats \n  Retinacular cutis  \n  (Skin Tendons) \n   \n\n\n\n                                                                                     SMAS\n  \n    Retaining Ligaments \n\n\n\n \n  \n  Periosteum \n\n\n\n \n Figure 2: The Anchoring Complex of the Face \n \n\n\n\nIntroduction Discussions \nAn awareness of the characters of fillers -- their \"rheology\" \u2013 is very \nimportant in producing predictable results. Placement of fillers of the \nwrong rheology in the wrong plane at the wrong place with the wrong \namount can cause great distortion to the natural look of a face. One \nsuch example is overfilled syndrome, which is very often overlooked \nby even the most experienced aesthetic physicians.  \n \nTherefore, it is proposed to look beyond filling the face with volume, \nbut using the right filler rheology at the right place, with the optimal \namount to give support to the underlying structures and to restore to \nwhat it used to be. The idea of structural support takes a multitude of \nfactors into consideration, including how treatments should be \nindividualized based on gender, ethnicity, age and the cultural \nperception of youth and beauty. Together, these factors create a \ntreatment procedure that suits the individual patient, thus providing \nbetter outcomes while maintaining a natural appearance.  \n\u00a0 \nWith the numerous filler types and brands currently available in the \nmarket, deciding which facial filler to use, when, where, why to use it, \nits longevity and safety, is not a straightforward process. The various \ntypes of fillers in the market can be broadly divided into three simple \ngroups: the voluminizing, enhancing and refining fillers. \n\u00a0 \nThe \u2018voluminizing\u2019 fillers are those with great lifting capacity, with \ncertain features of plasticity, and generally do well in deeper layers \nsuch as supra-osteal and subcutaneous layers. Generally, a small \namount is enough to create the needed lifting and voluminizing \nresults. Ideal areas for placement include, but are not limited to, \ninfraorbital areas along the orbicularis retaining ligaments, temporal \nareas (i.e., between the superficial and deep temporal fascia), and \nprejowl sulcus, just medial to the mandibular cutaneous ligaments. \n\u00a0 \nThe \u2018enhancing\u2019 fillers require high elasticity and cohesivity with \nminimum characteristic of plasticity, in order for them to stay in shape, \nwithout fearing its migration and losing its shape. Such fillers are best in \nregions such as the nasal bridge, nasal spine, canine fossa, chin and \nmandibular augmentation. \n\u00a0 \nThe \u2018refining\u2019 fillers require high cohesivity with low viscosity to enable \nthem to \u201cblend in\u201d and integrate with the soft tissues, without breaking \ndown into pieces. Such fillers spread well while not breaking down, \nmaking them ideal for highly dynamic and mobile areas of the face, \nincluding the periorbital and perioral regions.  \n\u00a0 \nUnderstanding the rheological properties of fillers allows the physician \nto make informed decisions on the best layer and area to apply the \nproduct. This is executed by targeting the retaining ligaments, \nrestoring structure, particularly in areas such as the orbicularis retaining \nligament and the zygomatic cutaneous ligament, among others. This \nunderscores the importance of understanding volume loss of the \nspecific layers of facial tissue, and the need for structural support.  \n\n\n\nDr Tingsong Lim \nDepartment of Aesthetic Medicine, Clique Clinic \n\n\n\nInjectology \u2013 Bringing Fillers Rheology into Clinic Settings \n\n\n\nDiscussions \n\n\n\nAesthetic Medicine is a rapidly evolving field. Over the last decade, \nthere has been a conceptual shift in rejuvenation, from removal and \nreconstructive surgeries to volume restoration and facial lifting using \nmultiple modalities. While we strive to move the profession forward with \nnew technologies and products, it is very important for us to revisit the \nbasics, and to understand the principal physiological changes of facial \ntissues that come into play as a result of aging. Furthermore, \nunderstanding the rheology of dermal fillers, and making full use of its \ncharacters, is important to ensure predictable and reproducible results. \n\n\n\n57 \n\n\n\nConclusion \nThe challenge for an aesthetic physician is where to draw the limit in our \nquest to develop a rejuvenated face. Injectology is not only confined \nto techniques and safety of injection. Understanding the functional \nanatomy, deep structures and layers, danger zones, and rheology of \nthe fillers are equally important to excel in the art of filler-based face \nsculpting these days. While preventing distorted faces and overfilled \nsyndrome in the long run is vital, patient satisfaction and well-being \nshould always be a priority. \n\u00a0 \n\n\n\n\n\n\n\n\n59.\tThe prevalence and clinical \t\n\tcharacteristic of chronic urticaria \t\n\tin a tertiary center\t\nDy-Win Low, Norazirah Md Nor,  Adawiyah Jamil, Leelavathi Muthupalaniappen\t\nDermatology Unit, Department of Medicine, University Kebangsaan Malaysia Medical Center, Kuala Lumpur \t\n\n\n\nIntroduction: \t\nChronic urticaria (CU) is defined as urticaria rash that \npersisted beyond six weeks duration. Up to date, \nthere is sparse epidemiological data on this condition \nin Malaysia. \t\n\t\nObjectives:\t\nTo identify the prevalence and clinical characteristics \nof patients with CU.\t\n\t\nMaterials and methods: \t\n\u00a7\u202f Study design:  Retrospective study.\t\n\u00a7\u202f Study site: Dermatology outpatient clinic, \n\n\n\nUniversiti Kebangsaan Malaysia Medical Center.\t\n\u00a7\u202f Inclusion criteria: Patients diagnosed with CU from \n\n\n\nJanuary 2014 to June 2017.\t\n\u00a7\u202f Methods:  Clinical notes reviewed. Demography \n\n\n\nand clinical characteristic were recorded and \nanalysed with SPSS version 21.\t\n\n\n\nResults:\t\nTable 1: Demographic Data of Study Population \t\n(n= 133)  \t\n\n\n\nDemographics \t Numbers (%)\t\nAge (Median (years))\t 46\t\n\n\n\nAge of Onset ( Median (years))\t 44\t\n\n\n\nGender\t\nMale\t\nFemale\t\n\n\n\n\t\n44 (33.1)\t\n89 (66.9)\t\n\n\n\nEthnicity\t\nMalay\t\nChinese\t\nIndian\t\nOthers\t\n\n\n\n\t\n77 (57.9)\t\n50 (37.6)\t\n4 (3.0)\t\n2 (1.5)\t\n\n\n\nTable 2: Clinical characteristics of chronic urticaria in \nstudy population   \t\n\n\n\nClinical Characteristics \t Numbers (%)\t\nType of Chronic Urticaria\t\n\n\n\nIdiopathic\t\nInducible\t\n\n\n\nSymptomatic \nDemographism\t\nDelayed pressure\t\nCold\t\nCholinergic\t\nAquagenic\t\n\n\n\n\t\n113 (85)\t\n20 (15)\t\n\t\n\n\n\n11 (8.3)\t\n3 (2.3)\t\n3 (2.3)\t\n2 (1.5)\t\n1 (0.8)\t\n\n\n\nPresentation\t\nUrticaria alone\t\nUrticaria with angioedema\t\n\n\n\n\t\n105 (78.9)\t\n28 ( 21.1)\t\n\n\n\nSeverity\t\nMild\t\nModerate\t\nSevere\t\n\n\n\n\t\n100 ( 75.2)\t\n22 ( 16.5)\t\n11 (8.3)\t\n\n\n\nClear in 1 year\t 50 (37.6)\t\n\n\n\nLab Investigations\t\nANA positive\t\nThyroid dysfunction\t\n\n\n\n\t\n11 (8.3)\t\n5 (3.8)\t\n\n\n\nCharacteristics \t Numbers (%)\t\nTreatment options:\t\n\n\n\nNon-sedating H1 \nantihistamine ( nsAH)\t\n\n\n\nLicensed dose\t\nTwo folds\t\nThree folds\t\nFour folds\t\n\n\n\nLeukotriene antagonist\t\nCyclosporine\t\n\n\n\n\t\n133 (100)\t\n\t\n\n\n\n67 (50.4)\t\n42 (31.6)\t\n2 (1.5)\t\n\n\n\n22 (16.5)\t\n6 (4.5)\t\n1 (0.8)\t\n\n\n\n\t\nDiscussion:\t\n\u00a7\u202f The prevalence of CU at our center is \n\n\n\napproximately 0.8% which is similar to other \nstudies (0.5\u20131%). 1\t\n\n\n\n\u00a7\u202f Median age of onset in our study is 44 year which \nis slightly higher than other studies. (20-40 years of \nage).1 The reason was not apparent. \t\n\n\n\n\u00a7\u202f Most of our CU patients were chronic idiopathic \nurticaria which was similar to other studies (69 \u2013 \n93%). 1,2\t\n\n\n\n\u00a7\u202f 37.6% of our CU patients had remission within 1 \nyear which was almost similar to other studies \n(20\u201347%). 1-3\t\n\n\n\n\u00a7\u202f Non-sedating H1-antihistamines (nsAH) are the \nmainstay of symptomatic therapy, but treatment \nwith licensed doses relieves symptoms effectively \nin <50% of patients. 1 In our study, 50.4% of CU \npatients responded to licensed doses of nsAH.\t\n\n\n\n\t\nConclusions:\t\n\u00a7\u202f Majority of patients were females, Malay and \n\n\n\nmiddle age.\t\n\u00a7\u202f Chronic idiopathic urticaria is the most common \n\n\n\ntype.\t\n\u00a7\u202f Majority of patients has mild disease which \n\n\n\npersisted for more than 1year.\t\n\n\n\n\t\nReferences:\t\n1.\u202f Maurer M et al.  Unmet clinical needs in chronic \n\n\n\nspontaneous urticaria. A GA2LEN taask forse \nreport.  Allergy 2011; 66: 317-330.\t\n\n\n\n2.\u202f Kulthanan K et al. Chronic idopathic urticaria: \nprevalence and clinical course. Journal of \nDermatology 2007; 34: 294-301.\t\n\n\n\n3.\u202f Kozel et al. Natural course of physical and chronic \nurticaria and angioedema in 220 patients. J Am \nAcad Dermatol 2001; 45: 387\u2013391.\t\n\n\n\nTable 3:  Treatment required for disease control\t\n\n\n\n\n\n\n\n\nAn Infant with Variegated Skin Lesions \u2013\nA Case Report of Phacomatosis \n\n\n\nPigmentovascularis Type II \nKit Wan Wong, Kwee Eng Tey \n\n\n\nDepartment of Dermatology, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia\n\n\n\n60\nIntroduction\n\n\n\nPhacomatosis pigmentovascularis (PPV) is a rare syndrome \nfirst described by Ota et al., in 1947. It is characterized by a \ncombination of capillary malformation and other pigmented \nnaevi.1 It arises sporadically, with no sex predilection. \n\n\n\nCase Report\n\n\n\nWe report a 3-week old Malay male infant who is a product\nof a non-consanguineous marriage. He was born full term\nvia spontaneous vagina delivery, weighing 3.8kg. This is a\nfirstborn and there is no family history of any vascular or\npigmentary disorder.\n\n\n\nThe child presented with extensive erythematous to\nviolaceous patches on his face, trunk and limbs with\naberrant blue patches noted since birth. On examination, he\nwas found to have port-wine stain (naevus flammeus)\ninvolving the left side of his face, bilateral upper limbs,\ntrunk and back (Figure 1 and 2). He also has extensive\naberrant Mongolian spots over a large part of the trunk,\nback, gluteal and all four limbs (Figure 3). There were\nbilateral oculocutaneous melanoses (Naevi of Ota) (Figure\n4). A mild degree of soft tissue hypertrophy of the left limb\nwas also noted (Figure 5).\n\n\n\nUltrasound cranium, left arm and hepatobiliary system was\nnormal. There is an increase in left arm muscle bulk with\nantero-posterior diameter on the left measuring 1.1cm\ncompared to the right which measures 0.6cm. No definite\ncollection was seen and colour Doppler study was normal.\n\n\n\nFigure 1\n\n\n\nDiscussion\n\n\n\nPPV had originally been classified into four major\ntypes.1 A fifth type, in which the vascular lesion is\ncutis marmorata telangiectatica congenita (CMTC),\nwas subsequently added.2 In 2005, Happle proposed\na new, simplified classification using descriptive\nterms encompassing four groups.3\n\n\n\n*All subtypes, in accordance with Hasegawa, are subdivided into\ntypes (a) or (b) - with and without systemic involvement\n\n\n\nThe pathogenesis of PPV is not fully known,\nhowever it has been linked to abnormal development\nand migration of vasomotor nerves and melanocytes\nderived from the neural crest. A genetic\nphenomenon called twin spotting which was\ndescribed by Happle and Steijen has been\nhypothesized to explain this.3\n\n\n\nAll patients with PPV must be investigated for\nsystemic complications depending on the sites\ninvolved. Central nervous system, eye and skeletal\nabnormalities are the most common systemic\ncomplications in PPV. Neurologic conditions include\npsychomotor retardation, seizures and cerebral\natrophy; with symptoms typically presenting within\nthe first few months of life. The most common\nophthalmologic associations include conjunctival\nmelanocytosis, episcleral vascular malformation and\nglaucoma. Assessment for Klippel-Trenaunay\nsyndrome should also be done if there is limb\ninvolvement.\n\n\n\nPPV without systemic involvement has a naturally\nbenign course. However, a patient\u2019s quality of life\nand self\u2013esteem may be improved by treating\nnaevus flammeus with pulsed dye laser and by\ntreating pigmentary naevus with Q-switched laser.\nMedical treatment of PPV with systemic\ncomplications requires individualized plans and\nmultidisciplinary management from other specialties\nsuch as ophthalmologist, neurologist and vascular\nspecialist.\n\n\n\nReferences\n\n\n\n1. Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis\ntype Iva, Arch Dermatol, 1985;121:651-5.\n\n\n\n2. Torrelo A, Zambrano A, Happle R. Cutis marmorata\ntelangiectatica congenita and extensive Mongolian spots:\ntype 5 phacomatosis pigmentovascularis, Br J Dermatol,\n\n\n\n2003;148:342-5.\n3. Happle R1, Steijlen PM. Phacomatosis pigmentovascularis\n\n\n\ninterpreted as a phenomenon of twin spots, Hautarzt,\n\n\n\n1989;40:721-4.\n\n\n\nFigure 2\n\n\n\nType \n\n\n\n(according \n\n\n\nto Happle)\n\n\n\nType \n\n\n\n(according to \n\n\n\nHasegawa*)\n\n\n\nVascular lesion Pigmentary lesion\n\n\n\nExcluded I Nevus flammeus Verrucous and\npigmented nevus\n\n\n\nCesio-\nflammea II Nevus flammeus\u00b1\n\n\n\nanemic nevus Mongolian spot\n\n\n\nSpilorosea III Nevus flammeus\u00b1\nanemic nevus Nevus spilus\n\n\n\nNon-\nclassifiable IV Nevus flammeus\u00b1\n\n\n\nanemic nevus\nMongolian spot, \nNevus spilus\n\n\n\nCesio-\nmarmorata V\n\n\n\nCutis marmorata\ntelangiectatica\ncongenita\n\n\n\nMongolian spot\n\n\n\nFigure 3\n\n\n\nFigure 4\n\n\n\nFigure 5\n\n\n\nThis case presents manifestations that classify it as PPV \nType II, which is characterized by extensive bilateral lesions \nof capillary malformation and aberrant Mongolian spots.\n\n\n\nNevus of Ota\n\n\n\n\nhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962015000700010\n\n\nhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962015000700010\n\n\n\n\n\n\n61 \nLeprosy and tuberculosis co-infection: a review of \n\n\n\ncases in Dermatology Clinics in Malaysia \nMin Moon Tang1, Shir Nee Tan1, Kwee Eng Tey2,  Yee Ting Lim2, Wooi Chiang Tan3,  \nLee Chin Chan4, Choo Khoon Ong5,  Michelle Sook Yee Voo6, Suganthi Thevarajah1 \n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur; 2Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru; \n3Department of Dermatology, Hospital Sultanah Bahiyah, Alor Setar; 4Department of Dermatology, Hospital Pulau Pinang; \n\n\n\n5Department of Respiratory, Hospital Pulau Pinang; 6Department of Dermatology, Hospital Queen Elizabeth, Sabah \n\n\n\nINTRODUCTION \n\n\n\nRESULTS \n\n\n\nMETHODOLOGY \n\n\n\nDISCUSSION \n\n\n\nCONCLUSION \n\n\n\nREFERENCES ACKNOWLEDGEMENT \n\n\n\nLeprosy and tuberculosis are both chronic granulomatous \ndiseases caused by Mycobacterium leprae and Mycobacterium \ntuberculosis respectively. We aim to describe the clinical \ncharacteristics and the management of patients who had leprosy \nand tuberculosis co-infection. \n\n\n\nThis is a retrospective study on all patients with leprosy and \ntuberculosis co-infection managed in 5 dermatology clinics in \nMalaysia between 1999 and 2017. Data was obtained by \nreviewing patients\u2019 medical records. \n\n\n\nDemographic characteristics n=22 \nMean age in years (range) 43.6 (19-80) \nGender, n(%) Male 19 (86.4) \n\n\n\nFemale 3 (13.6) \nNationality, n(%) Malaysian 10 (45.5) \n\n\n\nForeign born 12 (54.5) \nEthnicity among \nMalaysian, n(%) \n\n\n\nMalay 5 (50) \nChinese  2 (20) \nIndian 1 (10) \nOrang asli 2 (20) \n\n\n\nCountry of origin of \nforeign born, n(%) \n\n\n\nIndonesia 9 (75) \nMyanmar 3 (25) \n\n\n\nLeprosy characteristics n=22  \nType of cases, n(%) New case 20 (90.9) \n\n\n\nRelapse case 2 (9.1) \nDisease classification \nby Ridley & Jopling, \nn(%) \n\n\n\nTuberculoid 1 (4.5) \nBorderline tuberculoid 1 (4.5) \nBorderline borderline 2 (9.1) \nBorderline lepromatous 2 (9.1) \nLepromatous leprosy 16 (72.7) \n\n\n\nMedian baseline slit \nskin smear (range) \n\n\n\nBacteriological index (BI) 3.2 (0-5) \nMorphological index (MI) 1.3 (0-8) \n\n\n\nType of treatment \nprescribed, n(%) \n\n\n\nSungai Buloh Augmented \nRegime  (multibacillary)- at \nleast 36 months \n\n\n\n14 (63.6) \n\n\n\nWHO regime \u2013 6 months  1 (4.5) \nWHO regime \u2013 12 months 2 (9.1) \nWHO regime \u2013 18 months 1 (4.5) \nWHO regime \u2013 24 months 3 (13.6) \n\n\n\nSecond line agent \nused, n(%) \n\n\n\nOfloxacin 9 (40.9) \nMinocycline 2 (9.1) \n\n\n\nType of reactions, \nn(%) \n\n\n\nReversal 2 (9.1) \nErythema nodosum leprosum 13 (59.1) \nLucio\u2019s phenomenon 1 (4.5) \nNo reactions 6 (27.3) \n\n\n\nTuberculosis (TB) characteristics n=22 \nType of TB, n(%) Pulmonary tuberculosis 20 (90.9) \n\n\n\nTuberculosis lymphadenopathy 1 (4.5) \nScrofuloderma 1 (4.5) \n\n\n\nTiming of TB in \nrelation to leprosy, n \n(%) \n\n\n\nBefore leprosy 4 (18.2) \nConcurrently 11 (50.0) \nAfter leprosy 7 (31.8) \n\n\n\nMedian duration between the diagnosis of leprosy and \nTB in months (range) \n\n\n\n6  \n(-46 to  11) \n\n\n\nInvestigation \nevidence of TB \ninfection , \nn(%) \n\n\n\nOpacities in chest radiograph 11 (50) \nPositive sputum for acid fast bacilli 13 (59.1) \nPositive tuberculosis PCR 2 (9.1) \nPositive tuberculosis culture  8 (36.4) \n\n\n\nPositive GeneXpert\u00ae rapid TB test 1 (4.5) \nTreatment of \nTB, n(%) \n\n\n\nIntensive phase Rifampicin 21 (95.5) \nIsoniazid 21 (95.5) \nPyrazinamide 21 (95.5) \nEthambutol 16 (95.5) \nStreptomycin 2 (9.1) \nAkurit 4 1 (4.5) \n\n\n\nMaintenance \nphase \n\n\n\nRifampicin 14 (63.6) \nIsoniazid 14 (63.6) \n\n\n\nMedian duration of TB treatment received  in months \nat last follow up (range) \n\n\n\n6 (1-15) \n  \n\n\n\nStatus at \nlast follow \nup, n(%) \n\n\n\nCompleted both TB and Leprosy treatment \nand under surveillance \n\n\n\n6 (27.3) \n\n\n\nCompleted both TB and Leprosy treatment \n& released from surveillance \n\n\n\n1 (4.5) \n\n\n\nCompleted TB treatment but still on \nleprosy treatment \n\n\n\n2 (9.1) \n\n\n\nTransfer care to other center 4 (18.2) \nCompleted TB treatment but defaulted 5 (22.7) \nDefaulted before completed TB treatment 3 (13.6) \nCompleted both TB and Leprosy treatment \nbut died during surveillance \n\n\n\n1 (4.5) \n\n\n\nMajority of our patients had lepromatous leprosy with pulmonary tuberculosis. Most tolerated both treatments well. \n\n\n\n\u2022 A total of 22 patients were diagnosed to have leprosy and \ntuberculosis co-infection (Table 1&2) \n\n\n\n\u2022 Sungai Buluh Augmented Regime was the most frequently \nprescribed treatment regime.  \n\n\n\n\u2022 Erythema nosodum leprosum was the most frequent reaction \nexperienced by the cohort. \n\n\n\n\u2022 All patients received anti-tuberculosis with 16 (72.7%) \ncompleted for at least 6 months duration.  \n Table 1. The demography and characteristics of leprosy in 22 \n\n\n\npatients \nTable 2. The characteristics of tuberculosis, investigations, \nmanagement & outcome in 22 patients \n\n\n\n\u2022 The median reduction of bacteriological index (BI) at 6 and 12 \nmonths were 0.4 and 0.6 respectively among those who \ncompleted at least 6 months of anti-tuberculosis in addition \nto the leprosy treatment.  \n\n\n\n\u2022 The documented adverse events that were directly related to \nthe concurrent leprosy and tuberculosis treatments included \nhepatitis(1); lethargy(1) and transient maculopapular \neruption(1). \n \n\n\n\nWe would like to thank the Director General of \nHealth, Malaysia for permission to present this \nreport. \n\n\n\n\u2022 Previous reports have shown that 6-54.7% of death in leprosy \nwere due to TB.1,2 Co-infection does occur. \n\n\n\n\u2022 The estimated incidence of TB in Malaysia was 89/100,000 in \n2015.3 The incidence of leprosy in Malaysia was 0.7 per 100,000 \nin 2015.4  \n\u2022 Based on probability calculator, It is estimated to detect 0.0006 cases \n\n\n\nof TB and leprosy co-infection per 100,000 population in Malaysia.  \n\n\n\n\u2022 Rifampicin is the key agent in the treatment of leprosy and TB. \nOfloxacin is a second line anti-TB treatment and Clofazimine is \nused to treat rifampicin resistant or multidrug resistant TB.5,6  \n\n\n\n\u2022 In those who had the SSS monitored while receiving \ntreatment for both leprosy & TB, concurrent treatment did \nnot seem to reduce the BI at a greater rate. \n\n\n\n\u2022 In 7 patients who had TB after the leprosy, the leprosy \ntreatment did not seem to protect them from getting TB.  \n\u2022 Five received long term prednisolone to treat their leprae reactions; \n\n\n\nwhich may be a risk factor to develop TB in these patients.   \n\n\n\n\u2022 Future research is needed to study the immuno-genetic host \nfactors which predispose to TB & leprosy co-infection and the \nantimicrobial resistance pattern in all concomitant infections. \n\n\n\n1.Gatner et al. Lepr Rev 1980;51:5-10 \n2.Rawson et al. Lepr Rev 2014;85:288-95 \n3.WHO. Global Tuberculosis Report 2016 \n4.WHO. WER 2016;91:405-20 \n\n\n\n5.WHO Treatment of tuberculosis guideline 4th Edition 2010 \n6.WHO. WHO Treatment guidelines for drug-resistant tuberculosis \n\n\n\n2016 Update \n\n\n\n\n\n\n\n\n62\n\n\n\nCLM (creeping eruption) is caused by larvae of animal nematode. The adult\nworms live in the intestines of dogs and cats. The parasite\u2019s eggs (ova) are\ndischarged in the animal feces. The ova hatch into larvae that mature into infective\nfilariform larvae, which will penetrate human skin when a person comes in contact\nwith infected soil or sand. The infective larvae can migrate freely in sandy soils\nespecially in areas where warm temperatures and moisture (like tropical beaches)\nare optimal for it\u2019s viability.\nOnce transmission has occured, the larvae stay confined to the epidermis and less\noften the upper dermis. It can stay in the skin for a period of 2 to 50 weeks. It\nmigrates at the rate of a few millimeters to a few centimeters per day forming the\ntypical lesions of tortuous, serpiginous tunnel rising above the skin surface. The\nhumans are accidental hosts, and the larvae are usually not able to complete their\nnatural cycle. Permanent infection does not occur in the human host. The parasite\nmigration causes severe pruritus, epidermal damage and secondary infections.\nSome of the atypical presentations of CLM reported include diffuse multifocal\npapulo-vesicular eruption localized mainly on the chest, back and abdomen (like in\nour patient), hair follicle inflammation (hookworm folliculitis) most frequently in the\nbuttocks area and migrating urticaria.\nEven though CLM is self-limiting, the intense pruritus and risk of infection mandate\ntreatment. Treatment options are as follows;\na. Oral Albendazole 400mg daily for 3\u20137 days is usually well tolerated.\nb. Ivermectin, a single dose of 200ug/kg bodyweight (average dose of 12mg) is\nwell tolerated and highly effective but contraindicated in children less than 5 years.\nc. Cryotherapy, freezing the tip of the lesion has been tried but is not effective\nbecause the tip of the serpiginous track does not indicate the actual site of the\nmoving larva. May cause ulcerations and blisters\nd. Ethyl chloride spray has been tried but was found to be ineffective\nComplication of CLM infection include secondary bacterial infection usually\nStreptococus pyogenes, may lead to cellulits, Allergic reactions and even Loeffler\nsyndrome have been reported\n\n\n\nClinically, noted to have extensive excoriated erythematous scaly papules and\nsmall plaques all over his trunk and limbs (Fig.1-3). He was treated as papular\neczema with systemic steroid as well as a course of anti-scabetic. However,\nthere was no response and in the subsequent days the lesions became more\npapulo-vesicles. His full blood count, renal profile and liver function test were\nnormal within normal limit.\n\n\n\nAtypical Presentation of Cutaneous Larva Migrans:               \n\n\n\nA Case Report & Literature Review\nKean Pan Ong1, Yew Thong Chong2, Wooi Chiang Tan1, Yek Huan Khor1, Lee Chin Chan1\n\n\n\n1Department of Dermatology, Hospital Pulau Pinang, Georgetown, Penang, Malaysia\n2Gleneagles Penang, Georgetown, Penang, Malaysia\n\n\n\nINTRODUCTION\n\n\n\nCutaneous Larva migrans (CLM) is caused by percutaneous penetration and\nmigration of larvae of nematode parasite. It is most commonly found in tropical and\nsubtropical areas like the Caribean, South and Central America, Southeast Asia and\nAfrica. The infestation has no prevalence in term of race, sex and age but higher\nrisk in those who walk barefoot or expose without wearing shirt to soil or sandy\nbeach contaminated with animal feces.\nDiagnosis is usually made clinically based on the typical appearance of intensely\npruritic serpiginous or linear erythematous lesions that advances. We describe a\ncase of atypical presentation of cutaneous larva migrans causing a delay in\ndiagnosis and treatment.\n\n\n\nCONCLUSION\n\n\n\nCutaneous larva migrans should be kept in mind especially in patients presenting\nwith pruritic rashes after a history of walking barefoot or bare-body contact with\nsandy beaches or soil in endemic areas, as the appearance of the typical red and\nserpiginous skin lesions maybe delayed.\n\n\n\nCASE REPORT\n\n\n\nREFERENCES\n\n\n\n1. Nurjahan MI, Tevaraj P. Rash in a foreign worker. Malays Fam Physician. 2016.\n2. Podder I, Chandra S, Gharami RC. Loeffler's Syndrome Following Cutaneous Larva Migrans: An Uncommon Sequel. Indian J Dermatol. 2016.\n3. Tekely E et al. Cutaneous larva migrans syndrome: a case report. Postepy Dermatol Alergol. 2013.\n4. Malay et al. Extensive Cutaneous Larva Migrans with Folliculitis Mimicking ultimetameric Herpes Zoster Presentation in an Adult Traveler Returning from Thailand. J Travel Med 2006.\n\n\n\nFigure 1-3: Day 2 of presentation\n\n\n\nBS is a 21 years old man from Germany. He was here for a month doing his\ninternship at one of the factory in Penang. He presented with generalised pruritic\nrashes over his trunk and limbs of two days duration. Two weeks prior to onset of\nhis symptoms, he had travelled to Pulau Perhentian, a resort Island in East\nPenisular, Malaysia. He had sunbathed on the beach. There was no significant drug\nor contact history. He did not have any atopy history.\n\n\n\nFigure 1 & 2: Erythematous papules and small scaly plaques with excoriation \n\n\n\non anterior chest & back\n\n\n\nFigure 3  Close up view of lesion at the back\n\n\n\nFigure 4-7: Day 10 of presentation\n\n\n\nFigure 4 & 5: Appearance of serpiginous, erythematous and slightly raised \n\n\n\nlesions on back \n\n\n\nFigure 6 & 7: Appearance of serpiginous, erythematous lesions on right hand\n\n\n\nand forearm\n\n\n\nDISCUSSION\n\n\n\nOver the next ten days, the lesions progressively appeared more serpiginous\n(Fig. 4-7). It was then obvious clinically that he had cutaneous larva migrans. He\nwas treated with oral albendazole 400mg once daily for three days and resulted\nin rapid improvement of pruritus and rashes within 3 days.\n\n\n\n\n\n\n\n\nAntibiotic Prescribing Pattern in Skin and Soft Tissue \n\n\n\nInfections in Medical Wards Hospital Pulau Pinang \n\n\n\nEvelyn Chan, CT Leong, CK Yoon, PS Wong, TS Chow, KN Leong\nDepartment of Medicine, Hospital Pulau Pinang, Georgetown, \n\n\n\nPenang, Malaysia\n\n\n\n63\nINTRODUCTION\nSkin and soft tissue infections (SSTIs) range from mild\ninfections which only require outpatient treatment to\nmoderate to severe infections like abscesses, cellulitis and\nnecrotizing fasciitis which require hospitalizations and\nintravenous antibiotics. To date , data on epidemiology and\nantibiotic usage in patients with SSTIs in Malaysian\nhospitals is scarce. The aim of our study is to analyze the\nepidemiological aspect and antibiotic prescribing pattern in\npatients who are admitted with SSTIs to our medical wards\nin Hospital Pulau Pinang.\n\n\n\nRESULTS\nTable 1: Demographic data  (n=144)\n\n\n\nMATERIALS AND METHODS\nThis is a retrospective cross-sectional study involving adult\nin-patients admitted for skin and soft tissue infections to the\nmedical wards in Hospital Pulau Pinang from January to\nDecember 2016.\n\n\n\nTable 5: Blood culture results                                    \n\n\n\nTable 4: Change of antibiotics                                \n\n\n\nDiscussion\nPoor response and worsening clinical condition were assessed\nsubjectively by the treating clinicians. Future studies would\nneed to have objective criteria like temperature, tachycardia,\nWBC and increase of CRP from the baseline to assess\nresponse to treatment.\n\n\n\nThe yield in blood culture from SSTIs is known to be low (less\nthan 5% worldwide) We had a higher culture positivity rate\nas our cohort were inpatients. The most common organisms\nfound were streptococcus , staphylococcus aureus and other\ngram negative pathogens . This could explain the choice of\nampicillin/sulbactam as the most commonly prescribed\nantimicrobial.\n\n\n\nThirteen percent of SSTIs in the medical wards underwent\nsurgical intervention i.e wound debridement, incision and\ndrainage , deroofing and amputation. Few were\nmisdiagnosed and wrongly admitted to the medical wards\nwhich later was taken over by our orthopaedic counterpart.\n\n\n\nConclusion\nWe were able to establish certain epidemiological and\nmicrobiological aspects as well as antibiotic prescribing\npattern in SSTIs admitted to medical wards in our hospital.\n\n\n\nAcknowledgement \nSpecial thanks to all individuals who have made this study a \nsuccessful one.  \n\n\n\nProgress in the ward :\nMedian length of hospital stay was 5 days (3 to 11 days).\nNineteen patients (13%) underwent surgical intervention.\nTen patients died (6.9%) of which 5 deaths were attributable\ntoSSTIs.\n\n\n\nTable 6: Pus culture results\n\n\n\nThe commonest type of SSTIs is cellulitis ( 93%) followed by \nnecrotizing fasciitis (3.5%) and others(3.5%). The commonest \nsite was the lower limbs ( 94%) with 135 patients followed by \n8 patients (5%) with upper limb involvement and 1 (1%) patient\nwith both. \n\n\n\nReferences\n\u2022 Clinical and epidemiological characteristics of adult patients hospitalized for erysipelas and cellulitis \n\n\n\nM.-R. Perell\u00f3-Alzamora Euro Clinical Microbio Oct. 2011\n\u2022 Erysipelas and cellulitis: clinical and microbiological spectrum in an Italian tertiary care Hospital  Luca Lazzarini Journal of Infection Jan 2005\n\u2022 Practice Guidelines for the Diagnosis and Management of  Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America\n\n\n\n\n\n\n\n\n\n\n\n\nNo.\nof \n\n\n\nptss\n\n\n\n\n\n\n\n\n\n\n\n\nMICROCYSTIC ADNEXAL CARCINOMA: A CASE REPORT\n\n\n\nCASE REPORT\n\n\n\nREFERENCES\n\n\n\n\u2022Jiu Wen Kiing, Hani Ramlan Aznim, Wee Meng Kho, Muniandy Pubalan. \nSarawak General Hospital Kuching  (SGH)\n\n\n\nINTRODUCTION\n\n\n\nMicrocystic Adnexal Carcinoma is a rare cutaneous\nneoplasm can mimic benign adnexal tumour. According to\nSurveillance, Epidemiology, and End Results (SEER), the\nincidence rate is 6.5 per 10 million white population, 1.9 per\n10 million for black subjects and 1.6 per 10 million for\nAsian/Pacific Islanders (1).\n\n\n\nCONCLUSION\nMicrocystic adnexal carcinoma should be kept in mind as one\nof the differential diagnosis for benign looking papules or\nnodular or plaque like lesions over the head and neck\nregions. In any doubt, the lesion should be biopsied for HPE.\n\n\n\nDISCUSSION\nMicrocystic adnexal carcinoma is a rare aggressive locally\ninfiltrating cuteneous malignancy. It commonly affects middle\nand elderly group with median age of onset is 68 years old (1,\n2). It had been suggested that UV radiation and UVB\nsignature P53 mutations are important culprits for the\ncancer(3).\nPatients typically present with papules or plaques or nodules\nwith or without telangiectasias and commonly over head and\nneck area (4).\nDiagnosis is based on clinical & histo-pathological findings,\nmainly the presence squamous nests and cysts, variable\nductular differentiation, and perineural growth(5). MAC\nstaging is by American Joint Committee on Cancer\nStaging(6).\nTreatment guideline for Microcystic modalities is lacking due\nto rarity of the disease but there is some case series report\nregarding their way of treatment. Treatment options are Mohs\nmicrographic surgery, radiotherapy, or chemotherapy. (7, 8).\nThe 10-year overall survival was 86.4% (1). There is risk of\nrecurrence with recurrent rate about 18%(9), thus long term\nfollow-up is needed.\n\n\n\nA 64 year old man with underlying type 2 diabetes mellitus\nand chronic hypertension presented with a painless left\nperiorbital swelling and excessive tearing for one week.\nPhysical examination revealed multiple erythematous\npapules at left periorbital and left nasal bridge. There was no\nocular involvement. He consulted ophthalmologist and was\ntreated with one week course of oral Augmentin and topical\ntetramycin but failed to improve his condition. Subsequently\nhe was referred to dermatology team with 3mm punch\nbiopsy done over the left nasal bridge.\n\n\n\n1) Yu JB, Blitzblau RC, Patel SC, Decker RH, Wilson LD. Surveillance, Epidemiology, and End\nResults (SEER) database analysis of microcystic adnexal carcinoma (sclerosing duct\ncarcinoma ) of the skin. Am J Clin Oncol. 2010 Apr;33(2):125-7.\n\n\n\n2) Ohtsuka H, Nagamatsu S. Microcystic Adnexal Carcinoma: Review of 51 Japanese Patients.\nDermatology. 2002;204(3):190-3.\n\n\n\n3) Smith KJ, Williams J, Corbnett D, Skelton H. Am J Surg Pathol.2001;25(4):464.\n4) Wetter R, Goldstein GD. Dermatol Ther.2008 Nov;21 (6):452-8.\n5) Cooper PH, Mills SE. J Am Acad Dermatol. 1984 May; 10(5 Pt 2): 908-14.\n6) Edge SF, Byrd DR, Compton CC, et al. AJCC cancer staging manual, 7th ed, Springer, New\n\n\n\nYork 2010.\n7) Chiller K, Passaro D, Scheuller M, Singer M, McCalmont T, Grekin RC. Arch Dermatol. 2000\n\n\n\nNov;136(11):1355-9.\n8) Robyn W, Glenn DG. Microcystic Adnexal Carcinoma: a diagnostic and therapeutic\n\n\n\nchallenge.Dermatology Therapy.Nov/Dec 2008;Vol 21(6):452-458.\n9) Katarina C, Douglas P et. al. Microcystic Adnexal Carcinoma. Forty-eight Cases, Thier\n\n\n\nTreatment, and Their Outcome. Arch Dermatology.Nov 2000;Vol 136:1355-1399.\n\n\n\nHISTOPATHOLOGICAL  EXAMINATION: \n\n\n\nPhoto taken on 16 Dec 2015\n\n\n\nLeft Periorbital And Nasal Bridge Lesions\n\n\n\nCT imaging showed small subcutaneoous soft tissue\nthickening at left cheek with the size of 0.6 x 1.5cm\nextending to left periorbital region. Soft tissue thickening at\nleft periorbital soft tissue. Remaining area were normal. The\nTNM staging was T1N0M0 which was stage 1.\nIn view of left periorbital lesion progressively increasing in\nsize, the patient was then referred to plastic team for\nexcision and then referred for radiotherapy.\n\n\n\nPhoto taken on 12 April 2016\n\n\n\nPhoto taken on 12 April 2016\n\n\n\n64\n\n\n\nX4 Magnification\n\n\n\nX20 MagnificationX40 Magnification\n\n\n\nX40 Magnification PanCK\n\n\n\nX20 Magnification\n\n\n\nX40 Magnification CK7\n\n\n\nX40 Magnification\n\n\n\nHPE showed skin tissue with unremarkable epidermal layer.\nThe underlying dermis composed of small nests and ducts\nof malignant cells displaying enlarged cells with pleomorphic\nhyperchromatic nuclei and eosinophilic cytoplasm. Focal\nvascular spaces invasion is seen. Immunohistochemical\nstudies show tumour cells with positivity towards\npancytokeratin (CKWSS) and cytokeratin 7 (CK7).\n\n\n\n\n\n\n\n\n\n\n\n\nA. Mohd Affandi\n1\n, N. Ngah Saaya\n\n\n\n1\n, N. Baharum\n\n\n\n2 \n\n\n\n1 \nDepartment of Dermatology, Hospital Kuala Lumpur \n\n\n\n2 \nBiostatistics Unit, National Clinical Research Centre, Kuala Lumpur, Malaysia \n\n\n\n\n\n\n\nCO-MORBIDITIES AND RISK FACTORS  \n\n\n\nIN ADULT PATIENTS WITH  \n\n\n\nPSORIATIC ARTHRITIS IN MALAYSIA\n\n\n\nINTRODUCTION \n\n\n\nThe aim of this study is to determine the co-morbidities & risk factors in \nadult patients (aged >18 years) with PsA in Malaysia. \n\n\n\nPsoriatic arthritis (PsA) is an inflammatory arthritis associated with \npsoriasis. It is considered to be one of the spondyloarthritides and as such \nhas both spinal and peripheral joint involvement as well as enthesitis and \ndactylitis. PsA patients have a higher prevalence of co-morbidities like \ndiabetes mellitus, hypertension, hyperlipidaemia and obesity.  \n\n\n\nOBJECTIVE \n\n\n\nMETHOD \n\n\n\nData was obtained from the Malaysian Psoriasis Registry.  \n\n\n\nRESULTS \n\n\n\nA total of 15,794 adult patients were notified to the registry between July \n2007 to December 2016. However, only 14,181 patients had complete \ndata, and of these, 13.4% patients had PsA. 51.9% were females and 22.6% \nwere Indian (Figure 1). The commonest type of arthropathy reported was \noligo/monoarthropthy, which accounted for 37.9% of cases (Figure 2). PsA \npatients were found to have increased co-morbidities such as diabetes \nmellitus, hypertension, hyperlipidaemia and obesity (p<0.001)(Table 1). 9 \nfactors were found to be significantly (p<0.05) associated in adult patients \nwith PsA. These were older patients (age > 40 years), younger age of onset \n(<40 years), longer duration of disease (>5 years), female gender, Indian \nethnicity, body surface area > 10%, total skin score \u2265 10, presence of nail \ninvolvement and DLQI > 10 (Table 2). Patients with PsA also have reduced \nproductivity as evidenced by increased in DLQI, hospital visits, days off \nwork and  hospital admissions (Table 3 ). \n\n\n\nFigure 2  Types of psoriatic arthropathy \n\n\n\nTable 2  Factors associated with psoriatic arthritis in adults patients \n\n\n\n*Result was based on available information \n\n\n\nCONCLUSION \n\n\n\n13.4% of psoriasis patients in Malaysia have PsA. Patients with PsA also have \nincreased cardiovascular co-morbidities and reduced quality of life. \nIndependent risk factors for PsA were older patients, younger age of onset, \nlonger duration of disease, female gender, Indian ethnicity, severe disease, \npresence of nail involvement and DLQI > 10. \n\n\n\nACKNOWLEDGEMENT \n\n\n\nWe would like to thank all doctors and allied health personnel from the \nparticipating centres. We also acknowledge the support of Clinical Research \nCentre, Ministry of Health Malaysia and Dermatological Society of Malaysia. \n\n\n\nCo-morbidities \n\n\n\nArthritis \nPresent \n\n\n\nArthritis Absent \nSimple Logistic Regression* \n\n\n\n(n=1,905) (n=11,967) \n\n\n\nn % n % Crude OR (95% CI) P-value \n\n\n\nDiabetes Mellitus 403 16.0 2,116 84.0 1.25 1.11, 1.40 <0.001 \n\n\n\nHypertension 632 16.9 3,106 83.1 1.41 1.27, 1.57 <0.001 \n\n\n\nHyperlipidaemia 492 18.7 2,146 81.3 1.60 1.43, 1.79 <0.001 \n\n\n\nIschaemic heart \ndisease \n\n\n\n125 15.4 685 84.6 1.15 0.94, 1.40 0.168 \n\n\n\nCerebrovascular \ndisease \n\n\n\n29 12.6 201 87.4 0.90 0.61, 1.33 0.590 \n\n\n\nBMI\u226530 (obesity \nWHO) \n\n\n\n529 16.0 2,777 84.0 1.27 1.14, 1.42 <0.001 \n\n\n\nTable 1  Co-morbidities associated with psoriatic arthritis patients \n\n\n\nVariable \n\n\n\nArthritis \nPresent \n\n\n\nArthritis Absent \nMultiple Logistic Regressiona \n\n\n\n(n=1,905) (n=11,967) \n\n\n\nn % n % Adj. OR (95% CI) P-value \n\n\n\nAge:             <0.001 \n17-40 years 612 10.7 5,122 89.3 1.00 (ref.) \n41-60 years 963 17.7 4,472 82.3 1.98 1.61, 2.45 <0.001 \n>60 years 330 12.2 2,373 87.8 1.62 1.20, 2.19 0.002 \n\n\n\nAge of onset: \n\u226440 years (Type 1) 1,268 14.3 7,610 85.7 1.32 1.05, 1.64 0.015 \n>40 years (Type 2) 596 12.6 4,153 87.4 1.00 (ref.) \n\n\n\nDuration of disease:               \n\u22645 years 539 9.6 5,093 90.4 1.00 (ref.) \n>5 years 1,325 16.6 6,670 83.4 1.40 1.14, 1.72 <0.001 \n\n\n\nGender:               \nMale 917 11.7 6,927 88.3 1.00 (ref.) \nFemale 988 16.4 5,040 83.6 1.90 1.61, 2.24 <0.001 \n\n\n\nEthnicity:               \nIndian 431 18.0 1,965 82.0 1.69 1.39, 2.06 <0.001 \nNon-Indian 1,474 12.8 9,997 87.2 1.00 (ref.) \n\n\n\nObesity group (WHO):             NS \nBMI <30 1,376 13.0 9,190 87.0 \nBMI \u226530 529 16.0 2,777 84.0 \n\n\n\nType of psoriasis:             NS \nErythrodermic 53 22.8 179 77.2 \nNon-erythrodermic 1,741 13.4 11,219 86.6       \n\n\n\nBody surface area:               \n\u226410% 904 12.2 6,484 87.8 1.00 (ref.) \n>10% 424 18.9 1,822 81.1 1.29 1.06, 1.57 0.011 \n\n\n\nTotal skin score:               \n<10 1,682 13.2 11,046 86.8 1.00 (ref.) \n\u226510 178 19.9 717 80.1 1.90 1.40, 2.59 <0.001 \n\n\n\nNail involvement:               \nAbsence 465 8.3 5,152 91.7 1.00 (ref.) \nPresence 1,405 17.2 6,754 82.8 2.19 1.81, 2.64 <0.001 \n\n\n\nDLQI:               \n\u226410 685 13.9 4,250 86.1 1.00 (ref.) \n>10 417 17.4 1,982 82.6 1.30 1.09, 1.55 0.004 \n\n\n\n*Result was based on available information. \nAdj. OR = Adjusted odds ratio;  ref. = Reference; NS = Not significant \na Forward LR was applied. \nMulticollinearity was checked and not found. \nHosmer-Lemeshow test (P=0.152), classification table (overall correctly classified percentage=85.5%) and \narea under the ROC curve (68.2%) were applied to check the model  \n\n\n\nParameters \n\n\n\nArthritis \nPresent \n\n\n\nArthritis Absent \nSimple Logistic Regression** \n\n\n\n(n=1,905) (n=11,967) \nn % n % Crude OR (95% CI) P-value \n\n\n\nDLQI, mean (SD)   \n\u226410 685 13.9 4,250 86.1 1.00 (ref.) \n>10 417 17.4 1,982 82.6 1.31 1.14, 1.49 <0.001 \n\n\n\nNo. of clinic visit*, \nmedian (IQR)  \n\n\n\n<0.001 \n\n\n\n0 time 362 12.7 2,481 87.3 1.00 (ref.) \n1-2 times 953 12.8 6,466 87.2 1.01 0.89, 1.15 0.879 \n3-10 times 450 16.9 2,210 83.1 1.40 1.20, 1.62 <0.001 \n11-48 times 24 22.6 82 77.4 2.01 1.26, 3.20 0.004 \n\n\n\nNo. of days off work\n*\n, \n\n\n\nmedian (IQR) \n<0.001 \n\n\n\n0 day 1,576 13.1 10,451 86.9 1.00 (ref.) \n1-3 days 98 17.8 454 82.2 1.43 1.14, 1.79 0.002 \n4-10 days 49 25.3 145 74.7 2.24 1.61, 3.11 <0.001 \n11-90 days 35 31.2 77 68.8 3.01 2.01, 4.51 <0.001 \n\n\n\nNo. of hospital \nadmissions*, \nmedian (IQR) \n\n\n\n<0.001 \n\n\n\n0 time 1,708 13.4 11,009 86.6 1.00 (ref.) \n1-2 times 69 26.6 190 73.4 2.34 1.77, 3.10 <0.001 \n3-15 times 10 31.2 22 68.8 2.93 1.39, 6.20 0.005 \n\n\n\nTable 3  QOL and productivity parameters observed in patients with psoriatic arthritis \n\n\n\n*Over a 6-month period. \nIQR = 75th \u2013 25th percentile. \n**Result was based on available information. \n\n\n\n13.4 % of patients had \npsoriatic arthropathy \n\n\n\nFigure 1    Ethnicity in patients with PsA \n\n\n\nPoster no. 65 \n\n\n\n\n\n\n\n\nA. Mohd Affandi, I. Khan, N. Ngah Saaya \n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur \n \n\n\n\n\n\n\n\nEPIDEMIOLOGY AND CLINICAL FEATURES IN  \n\n\n\nADULT PATIENTS WITH PSORIASIS IN MALAYSIA\n\n\n\nINTRODUCTION \n\n\n\nFigure 1   Types of psoriasis \n\n\n\nTo determine the epidemiology and clinical characteristics in adult patients \n(aged > 18 years) with psoriasis in Malaysia. \n\n\n\nPsoriasis is a chronic disease affecting the skin  and joints. It can have a \nsignificant impact on the physical, emotional, and, psychosocial wellbeing of \nthe patients.  \n\n\n\nOBJECTIVE \n\n\n\nMETHOD \n\n\n\nData was  obtained from the Malaysian Psoriasis Registry between July 2007 \nand Dec 2016. \n\n\n\nRESULTS \nA total of 15,794 adult patients were notified to the registry between July \n2007 and December 2016. 56.6% of the patients were male and 50.5% of \nthe patients were Malay. Mean age of the patients was 36.1 \u00b1 17.1 years. \n23.2% of patients had positive family history of psoriasis. Plaque psoriasis \nwas the commonest type of psoriasis (85.1%), followed by guttate psoriasis \n(2.9%) and erythrodermic psoriasis (1.7%)(Figure 1). Psoriatic arthropathy \nwas reported in 13.7% of patients (Figure 2). 57.1% patients had nail \ninvolvement (Figure 3). Most of the patients (93.3%) were on topical \ntreatment (Figure 4). Only 2.8% of patients received phototherapy and \nNBUVB was the commonest used (87.5%) (Figure 5). Systemic therapy was \ngiven in 18.4% of patients and the commonest systemic agent used was \nmethotrexate (74.0%) (Figure 6). The mean DLQI score was 8.5 \u00b1 6.6 \n(Figure 7). \n\n\n\n57.1% of patients had nail \npsoriasis \n\n\n\nFigure 3   Types of nail psoriasis \n\n\n\n13.7% of patients had \npsoriatic arthropathy \n\n\n\nFigure 2   Types of psoriatic arthropathy \n\n\n\nFigure 4   Types of topical  therapy \n\n\n\n2.8% of patients had nail \npsoriasis \n\n\n\nFigure 5   Phototherapy \n\n\n\n93.3% of patients had \ntopical therapy \n\n\n\n18.4% of patients had \nsystemic treatment \n\n\n\nFigure 6   Systemic therapy \n\n\n\nMean DLQI : 8.50 \u00b1 6.58 \n\n\n\nFigure 7   Quality of life in adult patients with psoriasis \n\n\n\nFigure 8   QoL impairment in adult psoriasis patients based on category of DLQI \n\n\n\nCONCLUSION \n\n\n\nData from the Malaysian Psoriasis Registry reported a slight male \npreponderance among adult patients with psoriasis in Malaysia. Plaque \npsoriasis contributes to 85.1% of adult patients with psoriasis, and 13.7% of \npatients had psoriasis arthritis. Majority of the patients were on topical \ntreatment (93.3%), followed by systemic agents (18.4%) and phototherapy \n(2.8%). It is important to note the moderate impairment in the quality of life \nin adult patients with psoriasis. \n\n\n\nACKNOWLEDGEMENT \n\n\n\nWe would like to thank all doctors and allied health personnel from the \nparticipating centres. We also acknowledge the support of Clinical Research \nCentre, Ministry of Health Malaysia and Dermatological Society of Malaysia. \n\n\n\nPoster No. 66 \n\n\n\n\n\n\n \nPoster 1\n\n\nPoster 2\n\n\nPoster 3\n\n\nPoster 4\n\n\nPoster 5\n\n\nPoster 6\n\n\nPoster 7\n\n\nPoster 8\n\n\nPoster 9\n\n\nPoster 10\n\n\nPoster 11\n\n\nPoster 12\n\n\n \nSlide Number 1\n\n\n\n\nPoster 13\n\n\nPoster 14\n\n\nPoster 15\n\n\nPoster 16\n\n\nPoster 17\n\n\nPoster 18\n\n\n \nThe difference of sensitization detection rates by routinely patch-testing \ufffd1,3-Diphenylguanidine, N-Cyclohexyl-N-phenyl-4-phenylenediamine, \ufffdN-Cyclohexylthiophthalimide and Ylang Ylang Oil in addition to \ufffdEuropean Baseline Series in Hospital Selayang \ufffdFei Yin Ng1, Min Moon Tang1, Asmah Johar1, Rohna Ridzwan2\ufffd1Department of Dermatology Hospital Kuala Lumpur\ufffd2Department of Dermatology, Hospital Selayang\n\n\n\n\nPoster 19\n\n\nPoster 20\n\n\nPoster 21\n\n\nPoster 22\n\n\nPoster 23\n\n\nPoster 24\n\n\nPoster 25\n\n\nPoster 26\n\n\nPoster 28\n\n\nPoster 29\n\n\nPoster 30\n\n\nPoster 31\n\n\nPoster 32\n\n\nPoster 33\n\n\nPoster 34\n\n\nPoster 35\n\n\nPoster 36\n\n\nPoster 37\n\n\nPoster 38\n\n\nPoster 39\n\n\nPoster 40\n\n\nPoster 41\n\n\nPoster 42\n\n\nPoster 43\n\n\nPoster 44\n\n\nPoster 45\n\n\nPoster 46\n\n\nPoster 47\n\n\nPoster 48\n\n\nPoster 49\n\n\nPoster 50\n\n\nPoster 51\n\n\nPoster 52\n\n\nPoster 53\n\n\nPoster 54\n\n\nPoster 55\n\n\nPoster 56\n\n\nPoster 57\n\n\nPoster 59\n\n\nPoster 60\n\n\nPoster 61\n\n\nPoster 62\n\n\nPoster 63\n\n\nPoster 64\n\n\n \nSlide Number 1\n\n\n\n\nPoster 65\n\n\nPoster 66\n\n\n\n"
"\n\nVolume 21   |  August 2008   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.my\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA    DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\n\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcomes manuscripts on all\naspects of cutaneous medicine and surgery in the form of original articles,\nresearch papers, case reports and correspondence. Contributions are\naccepted for publication on condition that they are submitted exclusively\nto the Malaysian Journal of Dermatology. The Publisher and Editors\ncannot be held responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and opinions\nexpressed do not necessarily reflect those of the publisher and Editors,\nneither does the publication of advertisements constitute any\nendorsement by the publisher.\n\n\n\nManuscripts should be submitted via email: bbfoong@pc.jaring.my\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology can be sent\nto:\n\n\n\nHenry Foong Boon Bee, MBBS, FRCP\nEditor-in-Chief\nFoong Skin Specialist Clinic\n33A Persiaran Pearl, Fair Park, Ipoh 31400, Malaysia\nTel: +60 5 5487416    Fax: +60 5 5487416\nEmail: bbfoong@pc.jaring.my\n\n\n\nContributions should be written for one of the following categories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than three illustrations.\nThis category offers a means for rapid communication about a single\nsubject.\n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation.This category\nprovides rapid publications and is meant to be a succinct presentation with\na minimum of graphs and tables.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five references.\nThe author may express his or her opinion without complete\ndocumentation.\n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and pathological\nphotographs in color. The diagnosis and legends for the photographs\nshould be listed after the references in the article. The article should be no\nmore than 2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not exceed\n600 words, two figures, and 10 references.\n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article types may\ninclude Review, Report or Case Report Format.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an Introduction,\nMaterials and Methods, Results, Comment, and References. A\nStructured Abstract of not more than 240 words must be included. It\nshould consist of four paragraphs, labeled Background, Methods, Results,\nand Conclusions. It should describe the problem studies, how the study\nwas performed, the main results, and what the author(s) concluded from\nthe results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and summarizes\nthe existing knowledge in a particular field. It should not be an exhaustive\nreview of the literature, and references should not exceed 100 in number.\n\n\n\nTables, diagrams, and selected figures are often helpful. The length is left\nto the judgment of the author, although it generally should not exceed\n5000 words.Topics may include updates in clinically relevant basic science\nand cutaneous biology.\n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the paper, the\nauthor(s)' name(s), degrees, and affiliation(s), the category of the article,\nthe number of figures and tables, and three key words for indexing\npurposes. The name and full postal address (including a street address),\nphone and fax numbers and an email address of the corresponding author\nwho will be responsible for reading the proofs must also be given on the\ntitle page. The author(s) must also declare any affiliation or significant\nfinancial involvement in any organizations or entity with a direct financial\ninterest in the subject matter or materials discussed in the manuscript on\nthis page.\n\n\n\nAll measurements should be according to the metric system. If confusion\ncould result, please include other measurement systems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials should not be\nused.\n\n\n\nReferences must be listed in the order in which they appear in the\nmanuscript. References from journals should include: (1) name(s)\nfollowed by the initials of the author(s), up to four authors: if more than\nfour authors, include the first three authors followed by et al.; (2) title of\npaper; (3) title of the journal as abbreviated in the Index Medicus; (4) year\nof publication; (5) volume number; (6) first and final page numbers of the\narticle.\n\n\n\nFor example:\nFoong H, Ibrahimi O, Elpern D, Tyring S, Rady P and Carlson JA.\nSeborrhoeic keratosis-like lesions in a young woman with\nepidermodysplasia verruciformis. Int J Dermatol 2008; 47(5):476-8\n\n\n\nReferences to books should include: (1) author(s) or editor(s);\n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) place of\npublication; (5) publisher; (6) year; (7) page(s) referred to.\n\n\n\nFor example:\nFoong H. Transcontinental Dermatology: Virtual Grand Rounds.\nIn: Wootton R and Oakley A, editors. Teledermatology. London.\nRoyal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of all\nreferences; incomplete references may result in a delay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, each on a separate\nsheet, and should only include essential information. Drawings, graphs,\nand formulas should be submitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of photomicrographs, the\nstain type and original magnification should be stated. Each figure should\nbear a reference number corresponding to a similar number in the text.\nTo minimise the publication time of your manuscript it is important that\nall electronic artwork is supplied to the Editorial Office in the correct\nformat and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for errors or any\nconsequences arising from the use of information contained in this\njournal; the views and opinions expressed do not necessarily reflect those\nof the publisher and Editors, neither does the publication of\nadvertisements constitute any endorsement by the publisher and Editors\nof the products advertised.\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n\n\n\n\n\nEditorial Board\n\n\n\nEditor-in-Chief\nHenry Foong Boon Bee, MBBS, FRCP \n\n\n\nEditorial Office\nFoong Skin Specialist Clinic\n33A Persiaran Pearl\nIpoh 31400 Malaysia\nEmail : bbfoong@pc.jaring.my \n\n\n\nAssociate Editors\nChoon Siew Eng, MBBS, FRCP\n\n\n\nGangaram Hemandas, MBBS, FRCP\n\n\n\nAgnes Heng Yoke Hui, MBBS, MRCP\n\n\n\nTing Hoon Chin, MBBS, MRCP\n\n\n\nFounding Editor\nSteven Chow Kim Weng, MBBS, FRCPI (1987-1993)\n\n\n\nEditors Emeritus\nRoshida Baba, MBBS, FRCP (1994-1998)\n\n\n\nMadziah Alias, MD, MMed (1999-2002)\n\n\n\nKoh Chuan Keng, MBBS, MRCP (2003-2004)\n\n\n\nNajeeb Ahmad Mohd Safdar, MBBS, MRCP (2005-2006)\n\n\n\nPresident\nAllan Yee Kim Chye, MBBS FRCP\n\n\n\nVice President\nMadziah Alias, MD MMed\n\n\n\nSecretary\nKoh Chuan Keng, MBBS MRCP\n\n\n\nTreasurer\nNajeeb Ahmad Mohd Safdar, MBBS MRCP\n\n\n\nImmediate Past President\nGangaram Hemandas, MBBS FRCP\n\n\n\nCommittee Members\nAgnes Heng Yoke Hui, MBBS MRCP\nOng Cheng Leng, MBBS MRCP\nHenry Foong Boon Bee, MBBS FRCP\n\n\n\nPersatuan Dermatologi Malaysia\n\n\n\nMalaysian Journal of Dermatology\nJurnal Dermatologi Malaysia\n\n\n\nThe Official Publication for Persatuan Dermatologi Malaysia\n\n\n\nPublished by PERSATUAN Dermatologi Malaysia - Dermatological, Society of Malaysia\n\n\n\nPrinted by Cetak Sri Jaya, 11, Jalan Ambong Kanan 3, Kepong Baru, 52100 Kuala Lumpur, Malaysia\nTel / Fax : 603-6275 9514   Email : cetak_s_j@yahoo.com.my\n\n\n\n\u00ae 2008 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without written permission from the editorial board\n\n\n\n\n\n\n\n\ni\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nVOLUME 21  |  AUGUST 2008  |  ISSN: 1511-5356\n\n\n\nContents\nEditorial\n\n\n\n1 Should dermatologists perform more \ndermatologic surgery? \nHenry B.B. Foong, MBBS, FRCP \n\n\n\nReview\n3 Skin rejuvenation procedures - An update\n\n\n\nGoh Chee Leok, MBBS, MD, FAMS, FRCP\n\n\n\n9 Evidence-based dermatology - A brief \nintroduction\nDavid A Barzilai, MD, PhD\n\n\n\nOriginal Articles\n13 Treatment of naevus of Ota with\n\n\n\nQ-switched 1064nm Nd:YAG laser\nMM Tang, MBBS, MRCP,\nHB Gangaram, MBBS, FRCP and\nSH Hussein, MBBS, FRCP\n\n\n\n19 A retrospective study of Q-switched \nNd:YAG laser in the treatment of Hori\u2019s \nnaevus\nYY Lee, MD, MRCP, MMed,\nHB Gangaram, MBBS, FRCP and\nSH Hussein, MBBS, FRCP\n\n\n\n23 Acute generalized exanthematous\npustulosis: A histologic study of\nforty-five cases \nMai P Hoang, MD,\nMeera Mahalingam, MD, FRCPath,\nJag Bhawan, MD, Payal Kapur, MD and  \nWhitney A High, MD \n\n\n\n35 A 4-year retrospective study of\nStevens-Johnson syndrome and toxic \nepidermal necrolysis\nYap FBB, MD, MRCP,\nWahiduzzaman M, MBBS and\nPubalan M, MBBS, MRCP\n\n\n\n41 Lepra reactions: A 10-year retrospective \nanalysis\nTan WC, MD, MRCP and\nLo Kang SC, MD, MRCP\n\n\n\n47 Comparison of multiple drug therapy\nin leprosy\nYap FBB, MRCP, Awang T and\nPubalan M, MRCP\n\n\n\n53 Granular cell tumour - A case series of\n9 patients and literature review\nYT Pan, MBBS, MRCP,\nHL Tey, MBBS, MRCP and\nChan YC, MBBS, MRCP, FAMS\n\n\n\n57 Use of cyclosporine in the treatment of \npsoriasis\nMM Tang, MD, MRCP,\nLC Chan, MD, MMed and\nA Heng, MBBS, MRCP\n\n\n\n63 Predictive values of 10% potassium \nhydroxide examination for superficial \nfungal infection of the skin\nYap FBB, MD, MRCP,\nWahiduzzaman M, MBBS and\nPubalan M, MBBS, MRCP \n\n\n\n67 Epidemiological characteristics of \ncommon secondary bacterial skin \ninfection from patients with atopic \ndermatitis\nS T Sim, H B B Foong, MBBS, FRCP and\nE M Taylor, MBBS, GDFPD\n\n\n\n75 Cutaneous tuberculosis in Penang:\nA 12-year retrospective study \nTan WC, MD, MRCP, Ong CK, MD, MRCP,\nLo Kang SC, MD, MRCP and\nAbdul Razak M, MBBS, MMed, MSc, FCCP,\nAM\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nii\n\n\n\n81 Comparison of BBL chromagar MRSA to \nconventional media for the detection of \nmethicillin resistant staphylococcus aureus\nin surveillance nasal swabs \nN Mohd Noor, MBBS, MRCP,\nS Thevarajah, MBBS, MMed,\nZubaidah Abdul Wahab, MBBS, MPath and\nS H Hussein, MBBS, FRCP\n\n\n\nCase Reports\n87 D-penicillamine-induced pemphigus in a \n\n\n\npatient with Wilson\u2019s disease \nLoh LC, MBChB, MRCP,\nGoh KL, MBBS, FRCP and Rosnah Zain\n\n\n\n91 Cutaneous B-cell pseudolymphoma:\nCase reports and literature review\nTang JJ, MBBS, Chan LC, MD, MMed and\nHeng A, MBBS, MRCP\n\n\n\n95 Ectodermal dysplasia in a pair of siblings\nSM Wong, MBChB, MRCP and\nLC Loh, MBChB, MRCP\n\n\n\n99 An unusual case of naevus of Ota and Ito \nassociated with port wine stain\nChong YT, MD, MRCP,\nTey KE, MD, MMed, MRCP and\nChoon SE, MBBS, FRCP\n\n\n\n103 Lepromatous leprosy - The deceptive and \nthe obvious\nKader B Mohamed, MBBS, Dip Derm\n\n\n\n105 Cutis laxa associated with \nxanthogranuloma\nKE Tey, MD, MRCP, MMed, AM and\nSE Choon, MBBS, FRCP, AM\n\n\n\n109 Pyoderma gangrenosum associated with \nmalignancy: A report of three cases\nHuma K, MBBS, Dip Derm,\nKE Tey, MD, MRCP, MMed, AM and\nSE Choon, MBBS, FRCP\n\n\n\n113 Incontinentia pigmenti: Report of 3 cases \nfrom Sarawak\nLeong KF, MRCPCH, Pubalan M, MRCP and\nYap FBB, MRCP\n\n\n\n117 Primary cutaneous anaplastic large cell \nlymphoma in a young woman\nYap FBB, MRCP and Pubalan M, MRCP\n\n\n\n121 Cutaneous tuberculosis confirmed by\nPCR in a patient with culture negative for \nmycobacterium tuberculosis\nLee YY, Loh LC, MBChB, MRCP and SC Peh   \n\n\n\nCommentary\n125 Management of naevus of Ota\n\n\n\nTing Hoon Chin, MBBS, MRCP\n\n\n\nCorrespondence\n127 Temptations of dermatologists\n\n\n\nOng Cheng Leng, MBBS, MRCP\n\n\n\n127 Cutaneous manifestations of lymphomas:\nReport of 3 cases  \nKader B Mohamed, MBBS, Dip Derm\n\n\n\n\n\n\n\n\n1\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nEditorial\n\n\n\nShould dermatologists perform more dermatologic \nsurgery?\n\n\n\nThe clinical practice of dermatology has changed during the\npast 25 years. Dermatologists are performing more skin\nsurgeries than before1. When I was a medical student\nattending the skin clinic in University Hospital, we saw\nmainly patients with medical dermatology problems.\nToday, if one visits a modern dermatology centre, one would\nbe able to see an array of dermatologic procedures. It is not\nsurprising since dermatologists have been pioneers in\ndermatologic surgery for many years. They have not only\ncreated Mohs micrographic surgery but have developed and\nenhanced many new technologies including cryosurgery,\nbotulinum toxin injection, laser surgery, soft tissue\naugmentation, tumescent liposuction, hair transplant and\nreconstructive surgery for skin cancers. Over the last 25\nyears, new technologies have change dramatically the way\ndermatologists practice. They use laser to treat nevus of Ota\nand tattoos, botulinum toxin injection to improve wrinkles\nand fractional resurfacing laser to treat acne scars. They also\nuse intense pulsed light (IPL) to rejuvenate the face, radio\nfrequency devices to tighten skin, hyaluronic acid injection\nto replace volume loss in the photoaging skin and many\nothers not to mention microdermabrasion, chemical peels,\nhyfrecating seborrheic keratosis and applying topical acids\nto treat xanthelasma.\n\n\n\nIn fact dermatologists perform more surgical procedures on\nthe skin than any other specialty based on data from the\nCentre for Medicare and Mediaid services in United\nStates2. Mohs micrographic surgery remains the \u2018gold\nstandard\u201d as a technique that has the highest cure rate for\nthe treatment of most skin cancers. They result in smaller\nscars for defects that are important in functional and\ncosmetic areas of the face. These data are interesting\nbecause they show that the incidence of skin cancers are\nprobably increasing. Reported incident rates vary, but in the\nUnited States the combined incidence for basal cell\ncarcinoma, squamous cell carcinoma, and melanoma is\nreported to be about 1 million new cases in 2007.\n\n\n\nDermatology is broadly recognized as a comprehensive\norgan based specialty and this include training in the\nfundamental understanding of the structure, function and\npathophysiology of the skin. Despite the increase in skin\nsurgeries, training program in the country has not evolved\nat the same rate. In fact, dermatopathology is generally\ngiven more emphasis for differential diagnosis and regarded\nas more important than skin surgery during training and\ndifferential diagnosis is usually regarded as the heart and\ncore of dermatologic training. Dermatologic surgery topics\n\n\n\nare usually relegated to the last chapter of any multivolume\ntext of dermatology\n\n\n\nHowever, for better or for worse, dermatology is now a\nmedical and surgical field3. The issue is not whether\ndermatologists perform such procedures but whether they\ncontinue to train, educate and research in the surgical\naspects of dermatology. As such, it is important that\ntraining and research in dermatologic surgery should play\nan important role in the academic program of dermatology.\nAll dermatology trainees must become competent to\nperform basic dermatologic surgery upon graduation from\ntheir training. Good surgical skills must be taught early in\ntheir training to ensure that, in the absence of adequate\nguidance, they do not habituate to poor technique which is\nsubsequently difficult to alter. Patients may be better served\nby a dermatologist with surgical skills who is able to provide\nall their dermatologic care, thus eliminating the need for\nfrequent referrals to a surgeon. Finally, if excellent surgical\ntraining were the norm in dermatology education, patients\nwould regard their dermatologists as the expert in skin\ncancers and skin surgeries. There is no doubt that the true\nexperts in any field of medicine are those that do the same\nprocedure over and over again. High-risk surgeries are\nbetter done by surgeons who do lots of them4.\n\n\n\nHenry B.B. Foong, MBBS, FRCP Edin\n\n\n\nEditor-in-Chief\nMalaysian Journal of Dermatology\nIpoh, Malaysia\n\n\n\nReferences\n\n\n\n1. Roenigk RK.  Dermatologists Perform More Skin Surgery Than \nAny Other Specialist: Implications for Health Care Policy, \nGraduate and Continuing Medical Education. Dermatol Surg \n2008; 34 : 293-300.\n\n\n\n2. Physician/Supplier Procedure Summary Master File. Centers for \nMedicare & Medicaid Services, U.S. Department of Health & \nHuman Services. \n\n\n\n3. Alam M. Dermatologic surgery training during residency: room \nfor improvement. Dermatol Surg 2001; 27 : 508-9.\n\n\n\n4. Alam M. The Case for Procedure-Specific Volume Requirements. \nDermatol Surg 2001; 27 : 2-4\n\n\n\n\n\n\n\n\n2\n\n\n\n\n\n\n\n\n3\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReview\n\n\n\nSkin rejuvenation procedures - An update\n\n\n\nGoh Chee Leok MBBS MD FAMS FRCP\n\n\n\nNational Skin Centre, Singapore\n\n\n\nCorrespondence\n\n\n\nGoh Chee Leok MBBS, MD, FAMS, FRCP\n\n\n\nSenior Consultant Dermatologist\nNational Skin Centre\n1 Mandalay Road, Singapore\nEmail: cheeleok@yahoo.com.sg\n\n\n\nIntroduction\nSkin aging, presenting with rhytides/sagging and\nphotodamage, and scarring from severe acne, surgery, or\ntrauma are cosmetic disfigurements which may cause\npsychologic damage and prompt patients to seek advice\nabout treatment. Solar damage of the skin leads to\nepidermal abnormalities, such as lentigenes and actinic\nkeratoses, and the degeneration of collagen, which results in\nthe formation of rhytides and telangiectasias. A variety of\ndifferent treatments have been used for the rejuvenation of\nsun-damaged skin, including topical retinoids, bleaching\nagents, chemical peeling, dermabrasion, lasers and light\ndevices. The optimum resurfacing laser provides precise skin\nvaporization with minimal postoperative morbidity, which\ndepends significantly on the depth of ablation and energy\nfluence.\n\n\n\nThe ablative lasers era:\nIn the early 1980s, the CO2 laser was the most commonly\nused ablative laser in dermatology practice. It was initially\nused for the treatment of benign tumours, and soon gained\npopularity as a resurfacing technique for correcting\nphotodamaged skin including wrinkles, dyspigmentation\nand scars1. Ablative lasers including the CO2 laser and\nEr:YAG lasers resurfacing remains the most effective\ntreatment for photodamage and intrinsic wrinkling, acne\nscars, chickenpox scars and traumatic scars to date. It has\nbeen used for many years since the introduction of scanners\nthat allow resurfacing of large skin areas. These traditional\nablative laser resurfacing procedures offer reliable and\npredictable positive outcome2. Unfortunately, CO2 ablative\nlasers are associated with unacceptable morbidity and\ncomplications e.g. severe pain, prolong erythema,\npostinflammatory hyperpigmentation (especially in Asians),\nlate onset hypopigmentation and scarring. Transient\nerythema is the result of the natural healing process of the\nresurfaced skin. On the other hand, persistent erythema is a\ntroublesome complication to the patient and laser surgeon,\nas the patient wishes to return to normal activities in the\nshortest possible time. HSV Infections is a dreaded\ncomplication as it may cause severe scarring. Downtime is\n\n\n\nlong and patient requires long leave to recover from the\nablative laser procedures. Another major disadvantage of\nablative laser resurfacing is the need of local or general\nanaesthesia. As a result, over the last few years, ablative laser\nbecame less popular among patients3,4.\n\n\n\nThe pulsed Er:YAG laser with the unique feature of\nmaximal water absorption (water absorption coefficient 16\ntimes greater than the CO2 laser), and therefore minimal\noptical penetration depth and thermal damage, has been\nshown to be efficacious in the treatment of mild to\nmoderate superficial rhytides and scars2. This infrared\nspectrum (2940=nm), has been shown to provide very\nprecise ablation, because of its high selectivity to tissue\nwater and negligible thermal damage. The characteristics of\na wavelength with maximal water absorption, a sufficiently\nshort time duration (< 1 ms), and sufficient energy fluence\nplace the Er:YAG laser as the optimum ablative device for\nfine and superficial resurfacing of the skin. Pinpoint\nbleeding appears after several passes (4-5 passes depending\non the spot size and energy fluence) with exposure of the\ndermo-epidermal junction, and the laser treatment is\nusually stopped. Therefore, bleeding is a problem in the\ntreatment of deeper wrinkles with the Er:YAG laser5. The\nmain advantages of the Er:YAG over the CO2 laser are the\nreduced thermal damage, shorter recovery time, less\npostoperative erythema, and fewer anesthesia requirements.\nThe absence of thermal damage using the Er:YAG laser\nmeans less profound clinical and histologic improvement in\nphotodamaged skin. In a bilateral comparison study of 20\npatients using the CO2 and Er:YAG lasers in the treatment\nof facial rhytides, there were no significant differences in\npostoperative erythema, pain, and healing time when equal\ndepths of tissue coagulation and ablation were achieved\nwith each type of laser6. However, the same study showed\nthat, Er:YAG ablation is associated with less efficacy. Fine\nlines responded very well to this laser, whereas deeper\nrhytides showed a greater response to CO2 laser resurfacing.\nAnother study on 21 subjects with facial rhytides showed\nrelatively better wrinkle improvement with the CO2 laser,\nbut quicker recovery with the Er:YAG laser7.\n\n\n\n\n\n\n\n\n4\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe nonablative lasers era:\nIn 1983, Anderson and Parrish introduced the theory of\nselective photothermolysis8. It was realize that specific lasers\nwavelength can be harnessed to cause selective destruction\nof unwanted chromophores in cutaneous lesions.\n\n\n\nThis theory paved the way for the development and\napplication of various laser systems that aim at destroying\nclinical lesions with minimal injury to the surrounding and\noverlying skin structures. Newer lasers were developed to\nachieve tissue remodelling by modifying collagen and\nconnective tissue properties in the dermis while preserving\nthe integrity of the epidermis. Nonablative procedures\nbecame fashionable and promoted in the early 2000s. These\ndevices were touted to be able to stimulate nonablative\ncollagen remodeling and promoted to be used for skin\nrejuvenation to treat wrinkles and scars (acne scars and\ntraumatic scars)9,10. Numerous laser devices are developed\nfor this purpose. Nonablative lasers use laser energy to\nstimulate collagen synthesis in the dermis without\ndamaging the epidermis. Various light wavelengths have\nbeen harnessed in nonablative lasers. These lasers have long\npulse width to generate continuous spread of heat through\nreflection, refraction and scattering in the dermis. The\nprerequisites are epidermal cooling and wavelengths\nsufficiently long to penetrate and injure the dermis. Laser\nheat in the dermis stimulates collagen remodelling and\ncorrect scars and wrinkles. These nonablative lasers\ntreatment cause minimal downtime and patients are able to\nreturn to work the next day. The disadvantages of the\nprocedure include uncertain treatment outcome, slow\nresponse, multiple treatments needed at monthly intervals,\nrisk of postinflammatory hyperpigmentation (especially in\nAsians) and even blistering eruptions. Nonablative\nresurfacing works rather slowly that the patient may not\nnotice much improvements if at all. Because it produces\nminimal improvement for skin rejuvenation, its use\ndeclined over the years.\n\n\n\nThe Vascular Lasers:\nA possible role for PDLs in the treatment of photoaged skin\nhad long been suggested by the apparent clinical and\nhistologic collagen changes induced in PDL-treated\nhypertrophic scars, striae distensae, and acne scars11-13. The\nfirst to be utilized for wrinkle reduction was the 585-nm\nPDL (N-lite) at 350-microsecond and subpurpuric\nfluences. A clinical study using single PDL treatments\n(585-nm, 450-microsecond) demonstrated a clinical\nimprovement in 75% to 90% of mild to moderate wrinkles\nand 40% in moderate to severe rhytides14. Histologic\nexamination of the treated areas showed an increased\namount of normal staining in elastin and collagen fibers in\nthe papillary dermis, with increased cellularity and mucin\n\n\n\ndeposition. Although another initial study demonstrated\nsignificant reduction in rhytides, further studies were unable\nto reproduce these findings and demonstrated only minimal\neffects15. Generally, only modest results have been observed\nwith these short wavelengths, presumably because of\npredominantly vascular targeting and superficial\npenetration to the papillary dermis.\n\n\n\nThe Intense pulsed light (IPL)\nUnlike the laser that emits a single wavelength of light\nenergy that targets a specific chromophore, IPL devices\nharness a broad spectrum of light wavelength to target a\nwide range of chromophores on the skin. The IPL source is\na flashlamp that emits wavelengths of non-coherent light in\na spectrum from 500 to 1100 nm. Filters are used to block\nemission below a selection of threshold wavelengths that\nmay cause damage to the epidermis. Because of its shorter\nwavelengths and broad spectrum of light, it is used mainly\nfor treating Type 1 photoageing (i.e. superficial pigmentary\ndisorders such as lentigenes, solar lentigo and freckles, and\nsuperficial telangiectasia). It is not very effective against\nwrinkles and not effective against acne scars. It is useful for\nlight assisted hair removal in fair skin individuals. IPL\nshould be used with caution in dark skin individuals e.g.\nskin type V-VI as the epidermal melanin absorb a\nsubstantial amount of the light energy to cause burn and\nblisters.\n\n\n\nThere are numerous reports on the efficacy of IPL in skin\nrejuvenation recently. One study reported 38% of patients\nnoticed a 75% or better improvement of telangiectasias but\nonly 18% of the patients experienced a 75% or better\nimprovement in the fine wrinkles. 59% had improvement in\nerythema, 60% improvement in flushing, 67% improvement\nin pores by 50%; 70% improvement in telangiectasia; 72%\nimprovement in skin texture smoothness; 75% overall\nimprovement and in one patient with histological\nexamination showed new collagen deposition. 61% stated\nthe improvements to be very satisfactory16. In a report from\nAsia, 97 Asians patients that was treated with an IPL device\nfollowed up for 1 month after last treatment reported >90%\nimprovement in pigmentation; >83% improvement in\ntelangiectasia and >65% improvement in skin texture17.\n\n\n\nOur experience with the IPL of 139 patients treated for\nmelasma at 4 weekly interval for 6 treatments in skin type\n4-5 gave an overall fair reduction in pigmentation of 34%.\nHowever the reduction in pigmentation is short-lived and\ntends to recur within 3-6 months. Hence it is important to\nget patients to continue on maintenance sunscreen, sun\navoidance and topical bleaching creams during and after\nIPL treatment.\n\n\n\n\n\n\n\n\n5\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nNewer Skin Rejuvenation Procedures:\nNewer devices recently developed for skin rejuvenation aims\nat improve its efficacy and associated with little downtime.\nThe following devices were recently introduced.\nPreliminary results have shown them to be better than the\ntraditional non-ablative lasers for treating wrinkles and\nscars but still less efficacious than the ablative lasers. It has\nless downtime compared to the ablative lasers but slightly\nmore downtime compared to the non-ablative lasers.\n\n\n\n1. Fractional Phothermolysis:\n\n\n\n(a) Non-Ablative Fractional Lasers:\n\n\n\nThe newest technology to enter the laser arena is fractional\nresurfacing or fractional photothermolysis18. The concept\nbehind this approach is to thermally alter a fraction of the\nskin, leaving intervening areas of normal skin untouched,\nwhich rapidly repopulate the ablated columns of tissue. The\n1550-nm erbium-doped mid-infrared fiber laser induces\ncylindrical areas of thermal damage to the epidermis and\nupper dermis spaced at 2000 microscopic treatment zones\nof photothermolysis per cm2.\n\n\n\nFractional photothermolysis is a relatively new and gradual\nlaser procedure to rejuvenate the aging skin. This laser\ntreatment causes multiple laser-puncture holes, which have\nbeen termed \u201cmicrothermal treatment zones\u201d (MTZ) of\nthermal injury, to the skin. Each MTZ has a diameter of\n30-70 microns and depth of about 400-700 microns. These\nzones comprise approximately 15% to 25% of the skin\nsurface area per treatment session. These small laser-\npuncture holes appear as faint tiny spots on the skin after\nthe laser treatment. Because there is lots of normal skin in\nbetween the puncture holes, the cells from the normal skin\nrapidly repairs the holes and the skin heals rapidly. And as\na result of this healing process, new collagen is formed and\nimprovements in wrinkle scar and pigmented spots are seen.\nCompared to ablative resurfacing, fractional resurfacing\nresults in faster recovery and fewer side effects. Erythema\nand edema resolve within a few days in most patients but\nthe improvement in rhytides and photodamage is not as\nimpressive as with ablative resurfacing. Mild to moderate\nimprovement is observed, requiring multiple treatment\nsessions, totaling 5 to 6 and spaced at 1- to 4-week intervals.\nSun-induced pigmentary alteration improves more quickly,\nwhile wrinkles require more treatments to result in a\nsignificant improvement.\n\n\n\nFollowing the introduction of the Fraxel fractional lasers,\nseveral new nonablative fractional photothermolysis laser\ndevices were introduced. The Lux IR (Palomar Medical\nTechnologies) Fractional infrared handpiece attachment for\nthe StarLux pulsed light and laser system technology\ndelivers an array of small beams that create a periodic lattice\nof isolated hyperthermic columns ranging from 1.5 to 3.0\n\n\n\nmm in diameter to the reticular dermis. The Lux 2940\nfractional laser handpiece has been added, using delivery of\nerbium laser light to deliver very deep ablative columns.\nAnother nonablative fractional resurfacing device is the\nAffirm laser (Cynosure Inc), which sequentially emits\n1320-nm and 1440-nmwavelengths at fixed intervals. A\nmicrolens array is employed to diffuse the laser light into a\nlattice of microbeams,with targeting of superficial and\ndeeper penetration depths through the two wavelengths.\nMatisse (Quanta System) is another nonablative fractional\nskin resurfacing laser using the Er:Glass 1540 nm\nwavelength. The 1540 nm laser wavelength is absorbed by\nthe water of skin tissue by means of its lens array,\nstimulating the deep, the superficial dermis and epidermis\nat different temperature grades. It produces an evenly low\nlevel of thermal neocollagen and elastin stimulation on all\nthe treatment areas and in addition, a high level thermal\nheating and coagulation within the fractional areas.\n\n\n\n(b) Ablative Fractional Lasers\n\n\n\nTo induce more thermal injury with the hope it enhancing\nneocollagengenesis and improve the efficacy of the\nfractional lasers for skin rejuvenation, ablative fractional\nlasers were introduced recently. These lasers include those\nusing CO2 laser system e.g. Mixto SX(Lasering USA),\nEncore(Lumenis) and the Fraxel Re:pair(Reliant\nTechnologies) and those using the Er:YAG lasers system\ne.g. Pixel Alma Laser (Nexgen Lasers Inc) and Profactional\nlaser system(Sciton Inc). The efficacy and side effects of\nthese lasers remains to be seen.\n\n\n\nThe Fractional Resurfacing Procedure methods\n\n\n\nPatients with dyspigmentation and lentigines require 2 to 3\ntreatments, whereas those with significant rhytides require\nat least 5 or more treatment sessions. Patients with melasma\nrequire multiple treatments at low fluence and density to\nprevent post inflammatory hyperpigmentation.\n\n\n\nIt has been recommended that patient receives prophylactic\noral antivirals, such as acyclovir, famciclovir, or valacyclovir,\nstarting 1 day before fractional resurfacing and continuing\nfor 5 days postoperatively or until reepithelialization is\ncomplete. Oral antibiotics, such as dicloxacillin or\nazithromycin, may be prescribed to patients with a history\nof bacterial infections of the facial skin to reduce the chance\nof secondary bacterial infection.\n\n\n\nAnesthesia. Topical anesthesia is required. Application\nEMLA or LMX cream for 60 minutes before the procedure\nis recommended. During the procedure, cold air cooling\n(Zimmer Medizin Systems, Irvine, Calif ) is required to\nminimize discomfort. Some of the newer fractional\nresurfacing devices are reportedly painless.\n\n\n\n\n\n\n\n\n6\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDuring the laser procedure, tiny spots of the epidermis are\ncoagulated and collagen in the adjoining dermis is\ndenatured. Clinically there are no obvious exudates and\ncomplete re-epithelization occurs within 24 hours of the\nprocedure.\n\n\n\n2. Plasma skin resurfacing\n\n\n\nA novel device for performing ablative resurfacing has been\ndeveloped which works by passing radiofrequency into\nnitrogen gas. The \u2018\u2018nitrogen plasma\u2019\u2019 causes rapid heating of\nthe skin with limited tissue ablation and minimal collateral\nthermal damage. Several reports indicate improvement in\nfacial rhytides and scars following treatment. Epidermal\nregeneration occurs by 7 days postoperatively with\nneocollagenesis visible on histologic analysis at 90 days(19).\nComparative studies are needed to evaluate the safety and\nefficacy of this device as compared to CO2 and Er:YAG\nlaser resurfacing. Results appear to be similar to gentle CO2\n\n\n\nand Er:YAG laser resurfacing. The more aggressive the\ntreatment-that is, the higher the fluence-the more\nimpressive the results. Just where plasma resurfacing fits in\nthe spectrum of resurfacing devices, however, remains to be\nseen.\n\n\n\n3. Pigment Lasers\n\n\n\nPigmentary disorders are common and form a major part of\ncosmetic dermatological problems of Asian patients. In the\nmid 1990s, the Q-switched Nd-YAG laser was introduced\nand has remained one of the most widely used laser system\nfor treating pigmentary disorders until today. When\nfrequency-doubled at 532nm, it is used mainly to remove\nepidermal pigmentary lesions such as freckles, solar\nlentigines and caf\u00e9-au-lait macules and red coloured tattoos.\nThe 1064nm wavelength is used mainly for more dermal\npigmentary disorders such as Hori\u2019s nevus, nevus of Ota and\nblack coloured tattoos. Other pigment lasers include the\nQ-switched Alexandrite (755nm) and Ruby (694nm) lasers.\nHowever these shorter wavelength lasers are best used on\nlight skin type (Fitzpatrick skin type I-III). The shorter\nwavelengths tend to be cause epidermal burn and\nhypopigmentation as the epidermal melanin tends to take\nup the laser energy before it reaches the target\nchromophores. Recent reports have indicated that the\npulsed dye laser at 595nm (under occlusion pressure) is just\nas effective in removing superficial pigmentation disorders\nsuch as lentigenes20.\n\n\n\nOther Devices/Procedures for Skin Rejuvenation\n\n\n\nIn recent years many new devices have been introduced to\nrejuvenate the skin viz skin tightening, photomodulation\nand photodynamic therapy.\n\n\n\n1. Skin Tightening:\n\n\n\n(a) Radiofrequency Devices\n\n\n\nThe radiofrequency wavelengths devices were introduced a\nfew years ago to induce tissue heating and tightening for a\n\n\n\n\u201cmedical facelift\u201d as a form of non-ablative skin\nrejuvenation. These devices (e.g. Thermacool\u201a) utilizes\nradio-frequency (RF) energy to cause tissue resistance to\nflow of electrons to generate heat in tissues. It provides a\nuniform, intense and sustained heating in the dermis while\ncooling and protecting the epidermis. It is designed to cause\nimmediate collagen contraction followed by new collagen\nproduction which occurs over a period of time. It is\ncurrently used predominantly for treating periorbital\n(around the eye) wrinkles, jowl line and neck skin sagging,\nA single treatment with this RF tissue tightening (RFTT)\ndevice produces objective and subjective reductions in\nperiorbital wrinkles, measurable changes in brow position,\nand acceptable epidermal safety. These changes were\nindicative of a thermally induced early tissue-tightening\neffect followed by additional tightening over a time course\nconsistent with a thermal wound healing response. The\nlongevity of clinical results has yet to be determined.\n\n\n\nRuiz-Esparza et al21 reported that 14/15 patients obtained\ncosmetic improvement from facial skin tightening21. Alster\net al22 reported that there were significant improvement in\ncheek and neck skin laxity in the majority of patients treated\nwith the radio-frequency device22. Kushikata et al23 from\nJapan reported that radio-frequency treatment was effective\nfor nasolabial folds, marionette lines, and jowls with 70% of\nhis patients reporting good or very good improvement23.\n\n\n\nSide effects from the radio-frequency devices included,\npain, erythema, swelling (seen in >90%). Occasionally\nburns, blistering and skin discoloration (seen in about 5%\nof the patients) occur. Serious side effects reported\ninclude permanent depressions from treatment induced\nsubcutaneous fat necrosis. Finzi et all reported that reducing\nthe fluence and performing multipasses will help reduce\nside-effects and improve treatment outcome24.\n\n\n\n(b) Infra Red devices\n\n\n\nThe infra-red skin tightening devices works principally to\nincrease in skin firmness/tightening by utilizing the infra-\nred energy to heat up the dermal tissue. It is used for\nreversal of skin laxity, lifting of sagging skin esp along the\njowl line and underchin, reduction in skin crease lines (e.g.\nnasolabial folds) & wrinkles. An example of such a device is\nthe Titan\u201a (Cutera) device. The light source has a\nwavelength of between 1200nm-1800nm that is delivered\nin an integrated hand piece which provides contact cooling\nand infra-red light that deliver a uniform and prolonged\nheating of the deeper dermis (volumetric heating) of up to\nseveral seconds duration. The heating initiates 2 processes\nviz., collagen contraction which produce an immediate\nclinical effects followed by collagen remodelling over next\n3-6 months resulting in longer term clinical results. The\nepidermis is protected via epidermal cooling. In a report\nfrom Singapore, xxx% experience improvements following\ntreatment25. Its long term effects remains to be elucidated.\n\n\n\n\n\n\n\n\n7\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n2. Photomodulation\n\n\n\nPhotomodulation utilizes a process where light delivered\nthrough light emitting diodes are used to activate cells\ncausing them to produce collagen and elastin26. The light\nmanipulates or regulates cell activity without thermal effect.\nPhotomodulation has been reported to help improve skin\ntexture and histological evidence of induction of increased\ncollagen deposition with reduced MMP-1 (collagenase)\nactivity in the papillary dermis. It has been used to treat a\nwide range of photoaged skin with a specific sequence of\npulsing. In one study, subjects were evaluated at 4, 8, 12, 18\nweeks and 6 and 12 months after a series of 8 treatments\ndelivered over 4 weeks. Data collected included stereotactic\ndigital imaging, computerized optical digital profilometry,\nand peri-ocular biopsy histologic evaluations for standard\nstains and well as collagen synthetic and degradative\npathway immunofluorescent staining. The result reported a\nreduction of signs of photoaging in 90% of subjects with\nsmoother texture, reduction of peri-orbital rhytids, and\nreduction of erythema and pigmentation. Optical\nprofilometry showed a 10% improvement by surface\ntopographical measurements. Histologic data showed\nmarkedly increased collagen in the papillary dermis of 100%\nof post-treatment specimens. Staining with anti-collagen I\nantibodies demonstrated a 28% (range: 10%-70%) average\nincrease in density while staining with anti-\nmatrixmetalloproteinase (MMP)-1 showed an average\nreduction of 4% (range: 2%-40%). No side effects or pain\nwere noted26.\n\n\n\n3. Photodynamic Therapy (PDT)\n\n\n\nPhotodynamic therapy is a procedure whereby topical\nphotosensitizer e.g. amino-levulanic acid(ALA) is applied\non the skin prior to photostimulation with a certain\nwavelength of lights. The process is used for treating acne\nvulgaris by destroying P. acnes and sebaceous glands. It is\nused for treating actinic keratosis and recently used to\nenhance the effects of IPL in treatment photoaged skin\n(dyspigmentation, telangiectasia and superficial rhytides).\n\n\n\nThere are several variables in PDT procedures.\nPhotosensitizers used in PDT includes 5-ALA and methyl-\nALA in various vehicles. The skin is incubated with the\nALA which is usually painted on the skin and left for about\n30 mins to 3 hours. Various light sources have been used\nincluding red light, blue light, IPL and PDL. Patients\nshould avoid sun exposure for 24 hours after the procedure.\n\n\n\nPDT has recently be used to enhance the effect of IPL for\nphotorejuvenation. Recent reports indicated that topical\nPDT using ALA + IPL gives good results for rejuvenation\nthen IPL alone. Better improvements in \u201ccrow feet\u201d,\ntelangiectasia and skin texture with rejuvenation was carried\nout on PDT than IPL alone27. Improvements has been\nreported after one treatment alone.\n\n\n\nAdverse effects of PDT includes photodermatitis, hence the\nneeds for complete sun avoidance after PDT for at least 24\nhours\n\n\n\nConclusions\nOver the past 2 decades there have been significant\nadvances in the skin rejuvenation procedures. Advances in\nlasers ranging from ablative skin resurfacing lasers which is\nassociated with prolong post-operation downtime to\nfractional resurfacing with short post-operation downtime\nhas encouraged more patients to seek skin rejuvenation\ntreatment. Radiofrequency devices and infra-red devices has\nallow skin tightening to complement resurfacing procedure\nto further enhance the effects of skin rejuvenation.\nHowever the efficacy and long term effects of many of these\nprocedures remains uncertain and awaits further studies.\nHence it may be prudent to adopt a conservative approach\nwhen offering and carrying out these procedures for our\npatients.\n\n\n\nReferences\n\n\n\n1. Bailin PL. Lasers in dermatology: 1985. J Dermatol Surg Oncol \n1985;11:328-334.\n\n\n\n2. Goh CL, Khoo L. Laser skin resurfacing treatment outcome of \nfacial scars and wrinkles in Asians with skin type III/IV with the \nUnipulse CO2 laser system. Singapore Med J 2002;43:28-32.\n\n\n\n3. Tanzi EL, Alster TS. Single-pass carbon dioxide versus multiple-\npass Er:YAG laser skin resurfacing: a comparison of \npostoperative wound healing and side-effect rates. Dermatol \nSurg 2003;29:80-84.\n\n\n\n4. Fulton JE Jr. Complications of laser resurfacing: methods of \nprevention and management. Dermatol Surg 1998;24:91-99.\n\n\n\n5. Perez MI, Bank DE, Silvers D. Skin resurfacing of the face with \nthe Erbium:YAG laser. Dermatol Surg 1998; 24: 653\u2013659.\n\n\n\n6. MacDaniel DH, Lord J, Ash K, Newman J. Combined CO2/Er:YAG \nlaser resurfacing of peri-oral rhytides and side-byside\ncomparison with carbon dioxide laser alone. Dermatol Surg 1999; \n25: 285\u2013293.\n\n\n\n7. Tanzi EL, Alster TS. Single-pass carbon dioxide versus multiple-\npass Er:YAG laser skin resurfacing: a comparison of \npostoperative wound healing and side-effect rates. Dermatol \nSurg. 2003;29:80-4.\n\n\n\n8. Anderson RR, Parrish JA. Selective photothermolysis: precise \nmicrosurgery by selective absorption of pulsed radiation. \nScience 1983;220:524-527.\n\n\n\n9. Ang P, Barlow RJ. Nonablative laser resurfacing: a systematic \nreview of the literature. Clin Exp Dermatol 2002;27:630-635.\n\n\n\n10. Chua SH, Ang P, Khoo LS, Goh CL. Nonablative 1450-nm diode \nlaser in the treatment of facial atrophic acne scars in type IV to \nV Asian skin: a prospective clinical study. Dermatol Surg. 2004;\n30:1287-91.\n\n\n\n11. Alster TS, McMeekin TO. Improvement of facial acne scars by \nthe 585-nm flashlamp-pumped pulsed dye laser. J Am Acad \nDermatol 1996;35:79-81.\n\n\n\n12. McDaniel DH, Ask K, Zubowski M. Treatment of stretch marks \nwith the 585-nm flashlamp pumped pulsed dye laser. Dermatol \nSurg 1996;22:332-7.\n\n\n\n13. Alster TS, Williams CM. Improvement of hypertrophic and \nkeloidal median sternotomy scars by the 585 nm \nflashlamppumped pulsed dye laser: A controlled study. Lancet \n1995;345:1198-200.\n\n\n\n\n\n\n\n\n8\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n14. Tanghetti EA, Sherr EA, Alvarado SL. Multipass treatment of \nphotodamage using the pulse dye laser. Dermatol Surg. 2003;\n29:686-90.\n\n\n\n15 Zelickson BD, Kilmer SL, Bernstein E, Chotzen VA, Dock J, \nMehregan D, et al. Pulsed dye therapy for sundamaged skin. \nLasers Surg Med 1999;25:229-36.\n\n\n\n16. Bitter PH. Noninvasive rejuvenation of photodamaged skin using \nserial, full-face intense pulsed light treatments. Dermatol Surg. \n2000 ;26:835-42.\n\n\n\n17. Negishi K, Wakamatsu S, Kushikata N, Tezuka Y, Kotani Y, Shiba \nK. Full-face photorejuvenation of photodamaged skin by intense \npulsed light with integrated contact cooling: initial experiences \nin Asian patients. Lasers Surg Med. 2002;30:298-305.\n\n\n\n18. Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. \nFractional photothermolysis: a new concept for cutaneous \nremodeling using microscopic patterns of thermal injury. Lasers \nSurg Med 2004;34:426-38.\n\n\n\n19. Gonzalez MJ, Sturgill WH, Ross EV, Uebelhoer NS. Treatment of \nacne scars using the plasma skin regeneration (PSR) system. \nLasers Surg Med. 2008;40:124-7.\n\n\n\n20. Galeckas KJ, Collins M, Ross EV, Uebelhoer NS. Split-face \ntreatment of facial dyschromia: pulsed dye laser with a \ncompression handpiece versus intense pulsed light. Dermatol \nSurg. 2008;34:672-80.\n\n\n\n21. Ruiz-Esparza J, Gomez JB. The medical face lift: a noninvasive, \nnonsurgical approach to tissue tightening in facial skin using \nnonablative radiofrequency. Dermatol Surg. 2003;29:325-32.\n\n\n\n22. Alter TS, Tanzi F. Improvement of neck and cheek laxity with a \nnonablative radiofrequency device: a lifting experience.  \nDermatol Surg. 2004;30:503-7.\n\n\n\n23. Kushikata N, Negishi K, Tezuka Y, Takeuchi K, Wakamatsu S.  \nNon-ablative skin tightening with radiofrequency in Asian skin. \nLasers Surg Med. 2005 ;36:92-7.\n\n\n\n24. Finzi E, Spangler A. Multipass vector (mpave) technique with \nnonablative radiofrequency to treat facial and neck laxity. \nDermatol Surg. 2005;31:916-22.\n\n\n\n25. Chua SH, Ang P, Khoo LS, Goh CL. Nonablative infrared skin \ntightening in Type IV to V Asian skin: a prospective clinical study. \nDermatol Surg. 2007;33:146-51.\n\n\n\n26. Weiss RA, McDaniel DH, Geronemus RG, Weiss MA, Beasley KL, \nMunavalli GM, Bellew SG.  Clinical experience with light-emitting \ndiode (LED) photomodulation. Dermatol Surg. 2005;31:1199-205.\n\n\n\n27. Dover JS, Bhatia AC, Stewart B, Arndt KA. Topical 5-\naminolevulinic acid combined with intense pulsed light in the \ntreatment of photoaging. Arch Dermatol. 2005;141:1247-52.\n\n\n\n\n\n\n\n\n9\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReview\n\n\n\nEvidence-based dermatology - A brief introduction\n\n\n\nDavid A Barzilai MD PhD\n\n\n\nDepartment of Dermatology\nRhode Island Hospital, Brown University\nProvidence, RI, USA\n\n\n\nCorrespondence\n\n\n\nDavid Barzilai MD, PhD\n\n\n\nDepartment of Dermatology\nRhode Island Hospital, Brown University\nProvidence, RI, USA\nEmail: david@skinresearch.org\n\n\n\nIntroduction\nSince \u201cevidence-based medicine\u201d (EBM) was coined in\n1992, much information and misinformation has been\ncirculated about what evidence-based medicine is and isn\u2019t1.\nThis is perhaps particularly true in dermatology where we\nhave only recently begun to appreciably introduce its\nlanguage and tools into our residency programs and\npractices2. David Sackett defines EBM as \u201cintegration of\nthe best research evidence with our clinical expertise and\nour patient\u2019s unique values and circumstances3.\u201d This\ndescription emphasizes that EBM is not a \u201ccookbook\nmedicine.\u201d Rather, EBM combines the \u201cstate of the science\u201d\n(which is often lacking in dermatology), with sound clinical\njudgment and knowledge of what makes our patients\nunique.\n\n\n\nClinicians have incorporated evidence into practice since\nlong before Hippocrates. What makes EBM unique as a\nparadigm is the formalization of the process by which we\nassimilate, evaluate, and employ data1. EBM can be\nformalized into a series of logical steps4:\n\n\n\n1. Formalizing your question into a well-built\nanswerable question\n\n\n\n2. Systematically searching out for the best evidence \navailable \n\n\n\n3. Critically appraising the evidence\n4. Integrating the data with clinical expertise and \n\n\n\npatient values\n5. Archiving the results and learning from 1-4\n\n\n\nStep 1 helps formalize your question, making your inquiry\nmore explicit, and fosters the next step to search for the\nevidence. Most clinical questions are in PICO format,\ninvolving a Patient, an Intervention, a Comparison, and a\nclinical Outcome. For example, \u201cIn a 22 year old female\nwith mild chronic non-comedonal acne (the Patient) is\nprescription strength benzoyl peroxide monotherapy\n(Intervention) superior to over the counter salicylic acid\nmonotherapy (Comparison) in preventing inflammatory\npapules from developing?\u201d Online resources helpful in\n\n\n\ndesigning well-built clinical questions include Anatomy of a\nwell-built clinical question  (University of Sheffield) and\nconstructing a well-built clinical question using PICO\n(University of Washington).\n\n\n\nStep 2 involves systematically searching for relevant data to\nanswer our questions5. The objective is to have a\ncomprehensive search that will not miss the highest quality\nsources. When better sources are available, this step shuns\ntextbooks and \u201cexperts\u201d which tend to be outdated and\nvulnerable to bias. This search thus is geared preferentially\ntowards the pinnacle of the \u201chierarchy of evidence.\u201d The\nbest source of information, when available, is the systematic\nreview (particularly comprised of randomized controlled\ntrials when the clinical query pertains to therapy).\nSystematic reviews answer focused study questions through\nexplicit a priori methods, and are exhaustive searches\nincorporating study quality when appropriate. In\ndermatology, Cochrane Systematic Reviews compiled by\nthe Cochrane Skin Group (Figure 1) generally provide the\nbest answers6. When these are not available and the\nquestion of interest pertains to a common skin condition,\nsecondary journals such as Evidence-Based Medicine and\nACP Journal Club provide structured abstracts to high\nquality studies and commentary helpful in their critical\nappraisal. Four times a year Archives of Dermatology\nfeatures an evidence-based dermatology section with similar\ncontent. PubMed Medline is the most popular primary\nsource, but most searches have a high noise to signal ratio.\nPubmed\u2019s clinical query database is designed for searches\nwith fewer false positive (undesired or irrelevant) references\n(Figure 2). In recent years there has been increased\nattention to evidence-based references, which in contrast to\ntraditional textooks formally integrate quality of evidence\nand are frequently updated. These include UpToDate and\nClinical Evidence. A high-quality text, Evidence-Based\nDermatology7 is also available, and can provide an excellent\nstarting point for an up-to-date search. General and\ndermatology-specific guides on how to perform evidence-\nbased searches are available1,5,7-9.\n\n\n\n\n\n\n\n\n10\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.   Cochrane Skin Group (CSG)\n\n\n\nCSG is part of the Cochrane Collaboration, dedicated to preparing, maintaining and promoting the\naccessibility of systematic reviews on the effects of health care interventions. This site features\nabstracts of Cochrane systematic reviews which by design meet the highest review standards.  \n\n\n\nFigure 2.   PubMed Clinical Query Tool\n\n\n\nPubMed\u2019s Clinical Query tool was designed to clinical searches relevant to practice. Clinical searches\ncan focus on etiology, diagnosis, therapy, prognosis, or clinical prediction rules. A narrow (specific)\nsearch will display the most relevant results whereas, a broad (sensitive) search prioritizes\ncomprehensiveness. For most dermatology searches a narrow search is most appropriate to avoid\nbeing overwhelmed with the number of results.\n\n\n\n\n\n\n\n\n11\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nStep 3 involves critical analysis of the data collected in\nstep 2 to determine overall quality. For this purpose it is\nimportant to familiarize yourself with the basic terminology\nand concepts in clinical epidemiology as it pertains to study\nquality10-12. A good study is reasonably free from bias and\nconfounding errors (systematic errors), includes an adequate\nnumber of patients (i.e., is adequately powered to detect\nclinically important differences), and is relevant to your\npatient. Although a full review of critical appraisal is beyond\nthe scope of this overview (entire books are published on the\nsubject), the hierarchy of evidence offers a general rule to\nstart with: systematic reviews of randomized trials are\nsuperior to randomized trials, which are superior to cohort\nand other study designs, which in turn are superior to case\nreports and expert opinion. It is important to emphasize\nhere that this rule by itself is inadequate since well-designed\nobservational study may be more meaningful than a poorly\ndesigned or executed trial. For further reading on critical\nappraisal of study design, the Centre for Health Evidence\n(CHE) offers an online User Guide (based on a JAMA\nseries by the same title).\n\n\n\nStep 4 relates to individualizing care and critically\nevaluating the context of the clinical problem13-15. In step 3,\nwe examined internal validity (how free it is from bias), but\njust as important is external validity, or how generalizable it\nis to your patient group and setting, which may be very\ndifferent. Your 25 year old patient with mild 10% BSA\npsoriasis probably won\u2019t respond the same as a 50 year old\nfemale patient in a tertiary care setting. Incorporating\npatient preferences and social settings into clinical decisions\nis imperative for compliance, patient rapport, and better\noutcomes. The Centre for Health Evidence offers a brief\nchecklist to assist with these considerations.\n\n\n\nStep 5 has us ask ourselves what we have learned from\nSteps 1-4 in order to improve our next search. Storing our\nresults for future reference is also valuable. Citation\nmanagers like EndNote store this information electronically\nand permit efficient sorting and searching of references.\n\n\n\nOnline, the most comprehensive listing of evidence-based\ndermatology resources can be found at the United\nKingdom\u2019s National Library of Health Skin Disorders\nSpecialist Library. This massive initiative, funded by the\nUnited Kingdom\u2019s National Health Service (NHS) indexes\nhigh quality, evidence-based information on all of aspects of\nskin disorders for patients and providers.\n\n\n\nebDerm.org  is another online evidence-based dermatology\nresource with a slightly different focus- a mission to teach\nand disseminate evidence-based dermatology. While the\ncurrent version of this website includes an annotated guide\nto selected web-based evidence-based dermatology\nresources and PowerPoint guide, it is undergoing a major\nexpansion with grant support from the Sulzberger Institute.\nThis update will permit multimedia resources and\ncollaborative evidence-based learning projects on August\n1st 2007. This will include ebDerm Learning, a\ncomprehensive guide to web-based resources, ebDerm\nLibrary, a digital library of evidence-based dermatology\n\n\n\nmaterials, and the ebDerm Community. A key highlight of\nthis expansion will be the teaching of EBM via participation\nin a Critically Appraised Topic (CAT) clinical query based\nlearning tool. Residents, dermatologists, and dermatology\ntraining programs interested in participating may contact\nthe author of this publication at david@skinresearch.org.\n\n\n\nLike any other skill, proficiency in EBM searches (and\nefficiency obtaining your answer!) increases with consistent\npractice. This brief informal narrative was not intended to\nbe comprehensive, but rather to whet your appetite for\nfurther reading on how EBM can be operationalized into\npractice. The author sincerely hopes that this most\nimportant learning objective was encouraged by the\noverview presented. Of the references below, 8 and 9\nprovide EBM guides focused on dermatology.\n\n\n\nReferences\n\n\n\n1. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson \nWS. Evidence Based Medicine: what it is and what it isn\u2019t. BMJ \n1996;312:71-72. \n\n\n\n2. Dellavalle RP, Stegner DL, Deas AM, Hester EJ, McCeney MH, \nCrane LA, Schilling LM. Assessing evidence-based dermatology \nand evidence-based internal medicine curricula in US residency \ntraining programs: a national survey. Arch Dermatol 2003 \nMar;139 (3):369-72; discussion 372. \n\n\n\n3. Straus SE, Richardson WS, Glasziou P, Haynes RB. Evidence-\nBased Medicine: How to Practice and Teach EBM. 3rd ed.\nNew York; 2005. \n\n\n\n4. Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-\nbuilt clinical question: a key to evidence-based decisions. ACP J \nClub 1995;123(3):A12-3. \n\n\n\n5. Oxman AD, Sackett DL, Guyatt GH. Users' guides to the medical \nliterature. I. How to get started. The Evidence-Based Medicine \nWorking Group. JAMA 1993;270(17):2093-5. \n\n\n\n6. Williams H, Adetugbo K, Po AL, Naldi L, Diepgen T, Murrell D. The \nCochrane Skin Group. Preparing, maintaining, and disseminating \nsystematic reviews of clinical interventions in dermatology. Arch \nDermatol 1998;134(12):1620-6.\n\n\n\n7. Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany.  \nEvidence-based dermatology. London: BMJ Books; 2003.\n\n\n\n8. Bigby M. Evidence-based medicine in dermatology. Dermatol Clin \n2000;18(2):261-76. \n\n\n\n9. URL: ebDerm.org Accessed 1-16-07.\n10. Williams HC, Strachan DP. The Challenge of Dermato-\n\n\n\nEpidemiology. New York: CRC Press; 1997. \n11. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical \n\n\n\nliterature. II. How to use an article about therapy or prevention. \nB. What were the results and will they help me in caring for my \npatients? Evidence-Based Medicine Working Group. JAMA \n1994;271(1):59-63. \n\n\n\n12. Barzilai DA, Freiman A, Dellavalle RP, Weinstock MA, Mostow \nEN. Dermatoepidemiology. J Am Acad Dermatol 2005;52(4):559-\n73; quiz 574-8. \n\n\n\n13. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical \nliterature. II. How to use an article about therapy or prevention.\nA. Are the results of the study valid? Evidence-Based Medicine \nWorking Group. JAMA 1993;270(21):2598-601. \n\n\n\n14. McAlister FA, Straus SE, Guyatt GH, Haynes RB. Users' guides to \nthe medical literature: XX. Integrating research evidence with \nthe care of the individual patient. Evidence-Based Medicine \nWorking Group. JAMA 2000;283(21):2829-36. \n\n\n\n15. Williams HC. Applying trial evidence back to the patient. Arch \nDermatol 2003;139(9):1195-200.\n\n\n\n\n\n\n\n\n12\n\n\n\n\n\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nTreatment of naevus of Ota with Q-switched 1064nm\nNd:YAG laser\n\n\n\nMM Tang MBBS MRCP, HB Gangaram MBBS FRCP and SH Hussein MBBS FRCP\n\n\n\nDepartment of Dermatology\nHospital Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nTang Min Moon MRCP (UK)\n\n\n\nDepartment of Dermatology\nKuala Lumpur Hospital\n50586 Kuala Lumpur\nWilayah Persekutuan\nMalaysia\nEmail: minmoon2005@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Naevus of Ota was first described in 1939 by Ota M.\nIt is characterized by a bluish-gray mottled hyperpigmentation in the\ndistribution of the trigeminal nerve. It affects between 0.014 - 0.6% of\nthe Asian population. It is not only physically disfiguring but may be\nassociated with tremendous psychosocial impact on the patient. The\naim of the study is to determine the demographic data of local patients\nwith naevus of Ota, their response to treatment with Q-switched\n1064nm Nd:YAG laser, complications and recurrence.\n\n\n\nMaterials and Methods A retrospective analysis of all patients with\nnaevus of Ota treated with Q-switched 1064nm Nd:YAG laser\nbetween January 1998 to December 2007 was conducted at the\ndermatology clinic, Kuala Lumpur Hospital. Patients\u2019 demographic\ndata, clinical characteristics, response to Q-switched 1064nm Nd:YAG\nlaser and the complications were reviewed.\n\n\n\nResults A total of 50 patients with naevus of Ota were treated with\nQ-switched 1064nm Nd:YAG laser. There were 42 female and 8 male\npatients with a F : M ratio of about 5:1. The mean age of presentation\nwas 31 years old (11-60 years). More than half were Chinese patients\n(56%) followed by Malays (38%), Indian (2%) and others (4%). Seventy\nfour percent of the patients had Fiztpatrick skin-type IV and the rest\nskin type V. Ninety two percent of the patients had unilateral\ntrigeminal dermatomal involvement while 8% had bilateral trigeminal\ndermatomal involvement. Of the 15 patients who were referred to the\nophthalmologist, 10 were found to have scleral involvement and none\nhad glaucoma. Patients who had 2 treatments (13 patients) did not\nhave any significant lightening of their lesions. In the remaining 37\npatients who had 3 sessions (mean = 5.7, range 3 -15 sessions), 9\npatients (24.3%) reported the response as good (51-75% lightening); 17\npatients (45.3%) as excellent (>75% lightening) and 8 patients (22%)\nhad near complete lightening (>90%). None reported any\ncomplications or recurrence.\n\n\n\nConclusion Q-switched 1064nm Nd:YAG laser is an effective and\nsafe treatment modality for patients with naevus of Ota.\n\n\n\nKeywords Naevus of Ota, Q-switched 1064nm Nd:YAG laser,\nFitzpatrick skin-type IV and V\n\n\n\nIntroduction\nIn 1939 Ota M reported \u201cnevus fusco-caeruleus\nophthalmomaxillaris and melanosis bulbi\u201d or naevus of Ota,\nwhich was described as a bluish-gray mottled\nhyperpigmentation along the first and second divisions of\nthe trigeminal nerve with frequent mucosal involvement. It\naffects between 0.014 - 0.6% of the Asian population1-3.\nThere is a female predominance with a female to male ratio\nof 3 to 5:1. Extracutaneous involvement in naevus of Ota\nincludes ocular pigmentation affecting the sclera, iris and\nconjunctiva; glaucoma, uveitis, cataract and rarely orbital\nand cerebral melanoma1,3. However, they are uncommon.\nMost patients with naevus of Ota suffer from tremendous\ncosmetic disfigurement and psychological impact due to the\nhighly visible distribution of the lesions and their\npersistence over time. This has encouraged patients to seek\ntreatment. Prior to the advent of laser surgery, dermabrasion\nand cryotherapy were the main therapeutic options but they\nusually result in scar formation and post treatment\nhyperpigmentation. Laser treatment of naevus of Ota on\nthe other hand has been shown to be very safe and effective.\n\n\n\nMaterials and methods\nThis is a retrospective study of all patients with naevus of\nOta who were treated with Q-switched 1064nm\nneodymium:yttrium-aluminium-garnet (Nd:YAG) laser\nbetween January 1998 to December 2007 at the\nDepartment of Dermatology, Kuala Lumpur Hospital.\nDiagnosis of naevus of Ota was made clinically by a\ndermatologist. Study parameters reviewed included\npatients\u2019\n\n\n\n13\n\n\n\n\n\n\n\n\n14\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\npatients\u2019 demographic data, their clinical characteristics,\nclinical response to Q-switched Nd:YAG laser and\ncomplications.\n\n\n\nQ-switched 1064nm Nd:YAG laser (Versa Pulse Aesthetic)\nwas used in this centre. Informed consent was obtained\nfrom all patients before their laser treatment.\n\n\n\nThe degree of response to laser treatment was graded by\npatients according to the lightening of lesions. \u201cExcellent\u201d\nresponse was defined as more than 75% lightening; \u201cGood\u201d\nresponse as lightening of between 50-75%; \u201cModerate\u201d\nresponse as lightening of between 25-50% while \u201cPoor\u201d\nresponse as less than 25% lightening. The data findings\nwere analyzed using SPSS 16.0 statistical analysis for\nWindows.\n\n\n\nResults\nFifty patients seen at the dermatology clinic Hospital Kuala\nLumpur with a diagnosis of naevus of Ota were treated with\nthe Q-switched 1064nm Nd:YAG laser during the period of\nJanuary 1998 to December 2007. The demographic data of\nall the patients are summarized in Table 1. There were 42\nfemale and 10 male patients with a female to male ratio of\n5.25:1. The mean age of presentation was 31 years old. The\nyoungest patient treated was 11 years old while the oldest\npatient was 60 years old. Of the 50 patients, more than half\n28 (56%) were Chinese, followed by Malays 19 patients\n(38%), Indian (2%) and two foreigners (4%). Thirty seven\npatients (74%) had Fiztpatrick skin type IV and the rest had\nskin type V. The facial areas involved in our group of\npatients are shown in Table 2. Ninety two percent of the\npatients had unilateral trigeminal dermatomal involvement\nwhile 8% had bilateral trigeminal dermatomal involvement.\nThe color of the nevus at first presentation included brown,\n\n\n\nblue, black or grey.\n\n\n\nSixty percent of the patients developed the nevus at birth or\nwithin the first year of life. None had any other concomitant\ncongenital skin lesions such as port wine stain or\nhemangioma. Only 4 patients had tried other treatments\nincluded depigmentation cream, carbon dioxide laser and\nQ-switched Nd:YAG in private clinics before presenting to\nus. Only one patient had a family history of a similar lesion.\nFifteen patients were referred to the ophthalmologist\nfor assessment. Ten were found to have scleral\nhyperpigmentation, 1 conjunctival involvement but none\nhad glaucoma.\n\n\n\nMajority of the patients were treated at intervals between 2-\n4 months (ranging from 2 months to 2 years). The affected\narea was treated at energy fluences of 3.8-5J/cm2 with a spot\nsize diameter of 3mm.\n\n\n\nThe clinical results of laser treatment are demonstrated in\nTable 3. Of the 50 patients treated, 7 (14%) had only one\ntreatment while 6 (12%) had 2 treatments and all of them\ndid not have significant lightening of their lesions (<50% of\nlightening of lesions). In the remaining 37 patients who had\n3 sessions (mean = 5.7, range 3-15 sessions), 9 patients\n(24.3%) reported the response as good (51-75% lightening);\n17 patients (45.9%) as excellent (>75% lightening). Eight\npatients (22%) had near complete clearance (>90%). Twenty\none out of 27 patients (78%) with Fiztpatrick skin type IV\nreported to have good or excellent result. On the other\nhand, 50% of patients with Fiztpatrick skin type V had\ngood or excellent result. The different treatment result\nbetween the 2 groups of patients however was not\nstatistically significant.\n\n\n\nCharacteristic\n\n\n\nMean age in years (range)\n\n\n\nEthnic\n\n\n\nF : M ratio\n\n\n\nMean duration of  lesion in years (range)\n\n\n\nFiztpatrick skin type\n\n\n\nTable 1.   Patient demographics and baseline clinical characteristics\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nIV\n\n\n\nV\n\n\n\nN=50\n\n\n\n31.1 (11-60)\n\n\n\n19 (38%)\n\n\n\n28 (56%)\n\n\n\n1 (2%)\n\n\n\n2 (4%)\n\n\n\n5.25:1\n\n\n\n27.2 (7-59)\n\n\n\n37 (74%)\n\n\n\n13 (26%)\n\n\n\n\n\n\n\n\n15\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTrigeminal nerve dermatone\n\n\n\nV1\n\n\n\nV1, 2\n\n\n\nV2\n\n\n\nV1, 2, 3\n\n\n\nTotal (%)\n\n\n\nTable 2.   Distribution of naevus of Ota\n\n\n\nLeft\n\n\n\n1\n\n\n\n10\n\n\n\n9\n\n\n\n1\n\n\n\n21 (42)\n\n\n\nRight\n\n\n\n4\n\n\n\n14\n\n\n\n6\n\n\n\n1\n\n\n\n25 (50)\n\n\n\nBilateral\n\n\n\n1\n\n\n\n2\n\n\n\n1\n\n\n\n0\n\n\n\n4 (8)\n\n\n\nTotal (%)\n\n\n\n6 (12)\n\n\n\n26 (52)\n\n\n\n16 (32)\n\n\n\n2 (4)\n\n\n\n50 (100)\n\n\n\nV1 - Ophthalmic branch; V2 - Maxillary branch; V3 - Mandibular branch\n\n\n\n0 - no response; 1 - Poor response (<25% lightening); 2 - Moderate response (25-50% lightening);\n3 - Good response (50-75% lightening); 4 - Excellent response (>75% lightening)\n\n\n\nNo of\nlaser\ntreatment\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n>6\n\n\n\nTotal\n\n\n\nTOTAL\n(%)\n\n\n\n7 (14)\n\n\n\n6 (12)\n\n\n\n8 (16)\n\n\n\n8 (16)\n\n\n\n4 (8)\n\n\n\n17 (34)\n\n\n\n50\n\n\n\nFitzpatrick Skin type IV\n\n\n\nResponse\n(patient assessment)\n\n\n\nTable 3.   Results of treatment with the Q-Switched 1064nm Nd:YAG laser according to Fiztpatrick skin type\n\n\n\nFigure 1.   A 44-year-old Chinese woman with naevus of Ota of right \nophthalmic and maxillary dermatome before and after \n9 laser treatments, near complete clearance can be noted.\n\n\n\nBefore Laser treatment After 9 sessions of Q-switched\n1064nm Nd:YAG\n\n\n\nNo\nof pt\n\n\n\n6\n\n\n\n4\n\n\n\n4\n\n\n\n6\n\n\n\n3\n\n\n\n14\n\n\n\n37\n\n\n\n0\n\n\n\n5\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n9\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n3\n\n\n\n2\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n4\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n4\n\n\n\n6\n\n\n\n4\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n2\n\n\n\n10\n\n\n\n15\n\n\n\nFitzpatrick Skin type V\n\n\n\nResponse\n(patient assessment)\n\n\n\nNo\nof pt\n\n\n\n1\n\n\n\n2\n\n\n\n4\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n13\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n4\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n3\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n3\n\n\n\n4\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n2\n\n\n\n\n\n\n\n\n16\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAll patients had topical anesthetic EMLA (eutectic mixture\nof local anesthetics) cream one hour before laser therapy.\nDespite the EMLA, all patients experienced a certain\namount of pain with 62% reporting as moderate and 10% as\nsevere. Two patients (4%) developed significant edema at\nthe site of treatment. Topical chloramphenicol ointment\nwas applied to the area treated immediately after the laser\ntherapy in all patients, unless they are allergic to it. Twenty\npercent of patients (10) were treated with a course of\nsystemic antibiotic such as erythromycin, cefuroxime and\ncephalexin to prevent any cutaneous infection from the raw\nwound. None of our patients developed late complications\nsuch as hypo- or hyperpigmentation, textural changes or\nscar formation. None have experienced any recurrence as\nyet.\n\n\n\nDiscussion\nNaevus of Ota is a benign oculodermal melanocytosis which\nis commonly seen in Asians. The cause of the naevus is not\nfully known. More than 50% of lesions are present at birth\nwhereas 40% manifest during puberty1. Some have\nhypothesized that sex hormones play a role in its\npathogenesis, given the female predominance, the\nappearance of lesion at the onset of puberty in many cases\nand reports of color variation with the menstrual cycle4.\n\n\n\nIn naevus of Ota, spindle-shaped dendritic melanocytes\nwhich contain large amount of melanin are present in the\ndeeper layers of the reticular dermis. Laser treatment of\nnaevus of Ota is based on the destruction of melanosomes\nand melanocytes by absorption of laser light of specific\nwavelengths. This is explained by the concept of selective\nphotothermolysis where the most selective thermal damage\noccurs when energy is delivered faster that the rate of\ncooling, or thermal relaxation time of a given target\n(\u201cchromophore\u201d)6. The family of Q-switched lasers is the\ncurrent standard therapy for naevus of Ota, achieving\nselective photothermolysis by having a pulse duration\nbriefer than the thermal relaxation time of melanosomes\n(less than 1msec)5-7. Q-switched 1064nm Nd:YAG laser has\nthe longest wavelength and is associated with the deepest\npenetration into the skin and consequently may be of\ntheoretically greater benefit in individuals with darker skin\nsuch as Fiztpatrick IV and V.\n\n\n\nThe clinical efficacy of Q-switched 1064nm Nd:YAG laser\nwas demonstrated in our center. Patients who had had only\none or two treatment sessions had only poor or moderate\nresponse. Therefore, the patient and the treating\ndermatologist should not expect much lightening of lesion\n\n\n\nin the first 2 treatment sessions. In our series, all good and\nexcellent responses were the result of three or more\ntreatments. Seventy percent of those who had 3 or more\ntreatment sessions had good or excellent results. There was\nno difference in the clinical response between patients with\nFiztpatrick skin type IV and V.\n\n\n\nPain and bleeding are common immediately after the laser\ntreatment. All patients should be well informed about the\nimmediate reactions. Long term complications such as scar\nformation, pigmentation and textural changes were not seen\nin our series of patients. None of our patients has reported\nany relapse of their lesions.\n\n\n\nThree types of Q-switched lasers have been used widely to\ntreat naevus of Ota. These include the Q-switched 694nm\nRuby laser, Q-switched 755nm Alexandrite laser and the\nQ-switched 1064nm Nd:YAG laser8. Previous studies have\nshown that all of them were able to provide excellent results\nin treating naevus of Ota10-14. The first prospective study\ncomparing the clinical efficacy of Q-switched Alexandrite\nand Q-switched 1064nm Nd:YAG laser in the treatment of\nnaevus of Ota among Hong Kong patients was done by\nChan HH et al9. Their findings indicate that Q-switched\n1064nm Nd:YAG laser is more effective than Q-switched\nalexandrite in the lightening of naevus of Ota. In darker-\nskinned (Fiztpatrick skin type IV-VI), the Q-switched\nNd:YAG laser at 1064nm is usually the safest laser to\nlighten a naevus of Ota. In lighter-skinned patients, Q-\nswitched ruby laser at 694nm and Q-switched alexandrite\nlaser at 755nm can also be used. Currently there is no\neffective treatment for the scleral pigmentation of naevus of\nOta.\n\n\n\nGenerally, the interval between laser treatments should be at\nleast 2-3 months in order to permit maximal lightening\nfrom each treatment and allow time for post inflammatory\nhyperpigmentation to clear if it has developed after\ntreatment15. In our series of patients, the interval between\nthe treatments ranged from 2 months to 2 years. Longer\ntreatment intervals of more than 6 months were arranged\naccording to patients\u2019 preference and conveniencet. Study\nhas shown that maximum and stable lightening of the\nlesions is usually seen 1-2 years after the last treatment12.\nTherefore the clinical response would not be greatly\naffected by longer interval between laser treatments.\n\n\n\nQ-switched 1064nm Nd:YAG laser is a safe and effective\ntreatment modality for naevus of Ota in patients with\nFitzpatrick skin types IV and V. Three or more laser\ntreatment is required for any significant clinical response.\n\n\n\n\n\n\n\n\n17\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReferences\n\n\n\n1. Hidano A, Kajama H, Ikeda S, et al. Natural history of naevus of \nOta. Arch Dermatol 1967; 95:187-195. \n\n\n\n2. Leung AK, Kao CP, Cho HY, et al. Scleral melanocytosis and \noculodermal melanocytosis in Chinese children. J Pediatr 2000; \n137: 581-584. \n\n\n\n3. Henry HLC, Taro K et al. Nevus of Ota: Clinical aspects and \nManagement. SKINmed 2003; 2: 89-98\n\n\n\n4. Ferguson REH, Vasconez HC. Laser Treatment of Congenital Nevi. \nJ Craniofacial Surg 2005; 16: 908-914.\n\n\n\n5. Goldberg DJ. Laser removal of pigmented lesions. Dermatol Clin \n1997; 15: 397-407.\n\n\n\n6. Stratigos AJ, Dover JS. Overview of lasers and their properties. \nDermatol Ther 2000; 13: 2-16\n\n\n\n7. Alam M, Arndt KA et al. Laser treatment of nevus of Ota. \nDermatol Ther 2001; 14: 55-59\n\n\n\n8. Carpo BG, Grevelink JM et al. Laser treatment of pigmented \nlesions in children. Semin Cutan Med Surg 1999; 18: 233-243\n\n\n\n9. Chan HH, Leung RSC et al. A retrospective analysis of \ncomplications in the treatment of nevus of Ota with the Q-\nswitched Alexandrite and Q-switched Nd:YAG Lasers. Dermatol \nSurg 2000; 26: 1000-1006.\n\n\n\n10. Wang HW, Zhang GK et al. Analysis of 602 Chinese cases of \nnevus of Ota and the treatment results treated by Q-Switched \nAlexandrite laser.  Dermatol Surg 2007; 33: 455-460. \n\n\n\n11. Chang CJ, Nelson JS et al. Q-Switched Ruby Laser Treatment of \nOculodermal Melanosis (Nevus of Ota). Plastic & Reconstructive \nSurgery 1996; 98: 784-790.\n\n\n\n12. Taylor, C. R., Flotte, T. J., Gange, R. W., and Anderson, R. R. \nTreatment of nevus of Ota by Q-switched ruby laser. J Am Acad \nDermatol 1994; 30: 743.\n\n\n\n13. Lowe NJ, Wieder JM, Sawcer D, Burrows P, Chalet M. Nevus of \nOta: treatment with high energy fluences of the Q-switched ruby \nlaser. J Am Acad Dermatol 1993; 29: 997-1001.\n\n\n\n14. Watanabe, Shinichi et al. Treatment of nevus of Ota with the Q-\nSwitched Ruby laser. New Eng J of Med 1994. 331(26):1745-1750.\n\n\n\n15. Raulin C, Schonermark MP et al. Q-switched ruby laser \ntreatment of tattoos and benign pigmented skin lesions: a critical \nreview. Ann Plast Surg 1998; 41: 555-565.\n\n\n\n\n\n\n\n\n18\n\n\n\n\n\n\n\n\n19\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nA retrospective study of Q-switched Nd:YAG laser in \nthe treatment of Hori\u2019s naevus\n\n\n\nYY Lee MD MRCP MMED, HB Gangaram MBBS FRCP and SH Hussein MBBS FRCP\n\n\n\nDepartment of Dermatology\nHospital Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nLee Yin Yin MD (Canada), MRCP (UK), MMED (Malaya)\n\n\n\nDepartment of Dermatology\nHospital Kuala Lumpur\n50586 Kuala Lumpur\nWilayah Persekutuan, Malaysia\nEmail: yleemd@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Hori\u2019s naevus is an acquired bilateral naevus of Ota-like\nmacules (ABNOM). It was first reported by Hori et al in 1984. It is\ncommon among Asians and has a female preponderance. Hori\u2019s naevus\nis characterised by blue-brown macules typically on the malar region of\nthe face.\n\n\n\nObjectives To evaluate the clinical characteristics of patients with\nHori\u2019s naevus seen at Hospital Kuala Lumpur and the efficacy of Q-\nswitched neodynium-yttrium-aluminium-garnet (Nd:YAG) laser in\nthe treatment of this condition.\n\n\n\nMethod A retrospective analysis of 16 patients diagnosed clinically\nwith Hori\u2019s naevus and treated with Q-switched Nd:YAG laser was\ncarried out. Patient\u2019s demographic data and clinical characteristics,\nresponse to Q-switched Nd:YAG laser, complications and recurrence\nwere reviewed.\n\n\n\nResults A total of 16 patients diagnosed clinically with Hori\u2019s naevus\nand treated with Q-switched Nd:YAG laser were reviewed. Fifteen of\nthe patients were female with one male. Their ages ranged from 33-61\nyears old (mean age = 47). Nine of these patients were Chinese with\nseven Malays. All had Fitzpatrick skin phototype IV. The age of onset\nranged from 15-45 years old. The most common clinical presentation\nwas bilateral brown macules on the malar region of the face. Eleven\npatients received treatment with Q-switched 1064nm Nd:YAG and\nfive combination treatment with Q-switched 532nm Nd:YAG\nfollowed by 1064nm laser. Two patients were lost to follow up after a\nsingle treatment. After a single treatment, 13 patients graded their\nclinical response as \u2018poor\u2019 (0-25% improvement) and 1 as \u2018fair\u2019 (26-50%\nimprovement). Six patients received a total of two treatments of whom\n4 graded their response as \u2018fair\u2019 (26-50% improvement) and 2 as \u2018good\u2019\n(51-75% improvement). Two patients who received a total of\nfour treatments graded their responses as \u2018good\u2019 and \u2018excellent\u2019 (76-\n100% improvement) respectively. 10 patients had significant\nhyperpigmentation post laser treatment. However, none reported any\nrecurrences.\n\n\n\nConclusion There is no difference in pigment clearance between\nconcurrent use of Q-switched 532nm Nd:YAG laser followed by\n1064nm laser and Q-switched 1064nm Nd:YAG laser for Hori\u2019s\nnaevus. However, there is only minimal improvement after a single\ntreatment, and multiple sessions are required to achieve satisfactory\nimprovement. Post inflammatory hyperpigmentation was the main\ncomplication seen.\n\n\n\nKeywords Hori\u2019s naevus; Q-switched Nd:YAG laser; Fitzpatrick skin\ntype IV\n\n\n\nIntroduction\nHori\u2019s naevus is an acquired bilateral naevus of Ota-like\nmacules (ABNOM). It was first described in the Japanese\npopulation by Hori et al in 19841. It is one of two primarily\ndermal dyschromasia seen in Asian population, the other\nbeing naevus of Ota. The prevalence of Hori\u2019s naevus is\nabout 0.8% in the Asian population2. There is a higher\npreponderance among the female population, with an age of\nonset ranging from 4th to 5th decades of life3. Hori\u2019s naevus\nis characterized by blue-brown and or slate grey macules,\nmost frequently on the malar region of the face. Other areas\nof involvement include bilateral forehead, temples, eyelids,\nnasal alae and nasal root4. Unlike the naevus of Ota, Hori\u2019s\nnaevus does not involve the ocular or mucous membranes.\n\n\n\nThere has been a dearth of reported treatment modalities\nutilized to manage this disfiguring, psychologically\ndistressing cosmetic condition. However, Hori\u2019s naevus is\nknown for its recalcitrance to conventional treatments.\n\n\n\nCryotherapy has been found to produce unpredictable\nresults. Dermabrasion showed promising results after a\nsingle session, but the major disadvantage of this technique\nis the risk of bloodborne contamination and uncontrolled\ndepth of ablation4.\n\n\n\n\n\n\n\n\n20\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nQ-switched Nd:YAG laser has been reported in the\nliterature to produce excellent results with minimal risk of\ncomplications. This review was designed to evaluate the\nclinical characteristics of patients with Hori\u2019s naevus seen at\nHospital Kuala Lumpur and the efficacy and safety of Q-\nswitched Nd:YAG laser in the treatment of this condition in\nour local setting.\n\n\n\nMaterials and methods\nA retrospective analysis of 16 patients from Hospital Kuala\nLumpur with a clinical diagnosis of Hori\u2019s naevus was\nperformed. Patients received treatment with either Q-\nswitched 1064nm Nd:YAG or combination treatment with\nQ-switched 532nm Nd:YAG followed immediately by\n1064nm laser. Patient\u2019s demographic data and clinical\ncharacteristics, response to Q-switched Nd:YAG laser,\ncomplications and recurrence were reviewed.\n\n\n\nThe degree of clearance following laser treatment was\ncategorized into 4 grades, ranging from excellent to poor.\n\u2018Excellent\u2019 response was defined as 76-100% clearance;\n\u2018Good\u2019 as 51-75% clearance, \u2018Fair\u2019 as 26-50% clearance and\n\u2018Poor\u2019 as 0-25% clearance.\n\n\n\nResults\nA total of 16 patients diagnosed clinically with Hori\u2019s\nnaevus and treated with Q-switched Nd:YAG laser were\n\n\n\nreviewed. There is a predilection for female gender, with 15\nfemale and 1 male in our series. Their ages ranged from 33-\n61 years old (mean age = 47). Of the 16 patients, 9 (56%)\nwere Chinese and 7 (44%) were Malays. All of them had\nFitzpatrick skin phototype IV. The age of onset of Hori\u2019s\nnaevus ranged from 15-45 years old (Table 1).\n\n\n\nThe most common colour at presentation was brown 11\n(68.7%), followed by blue 3 (18.8%) and black 2 (12.5%).\nAll the patients presented with either macules (75%) or\npatches (25%) on the malar region of the face. Five (31.3%)\nof the patients reported a positive family history of a similar\nfacial condition, which primarily affected a first degree\nrelative, mainly their mothers or sisters. Four (25%) patients\ntried various topical depigmenting agents bought over-the-\ncounter without much success prior to their laser therapy.\n\n\n\nEleven (68.7%) patients received treatment with Q-\nswitched 1064nm Nd:YAG whilst the remaining 5 (31.3%)\nreceived a combination treatment with Q-switched 532nm\nNd:YAG followed by 1064nm laser. Two patients were lost\nto follow up after a single treatment. The rest of the patients\nhave received treatments ranging from 1-4 sessions. The\nlaser treatments and outcomes are summarized in Table 2\nand Table 3. Six (37.5%) patients received only a single laser\ntreatment, six (37.5%) received 2, while the remaining four\nreceived 3 and 4 laser sessions respectively.\n\n\n\nCharacteristics\n\n\n\nMean age in years (range)\n\n\n\nEthnic\n\n\n\nFemale : Male ratio\n\n\n\nAge of onset in years (range)\n\n\n\nTable 1.   Patient demographics and baseline clinical characteristics\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nN=16\n\n\n\n47.0 (33-61)\n\n\n\n7 (44%)\n\n\n\n9 (56%)\n\n\n\n0\n\n\n\n15:1\n\n\n\n14-45\n\n\n\nNo of laser \ntreatments\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\nTotal \n\n\n\nTable 2.   Result of treatment with Q-switched 532nm Nd:YAG followed \nby 1064nm laser (n=5)\n\n\n\nNo of\npatients\n\n\n\n2\n\n\n\n2\n\n\n\n1\n\n\n\n0\n\n\n\n5\n\n\n\nPoor\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\nFair\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\nGood\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\nExcellent\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\nResponse (Patient assessment)\n\n\n\n\n\n\n\n\n21\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nNo of laser \ntreatments\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\nTotal\n\n\n\nTable 3.   Result of treatment with Q-switched 1064nm Nd:YAG laser (n=11)\n\n\n\nNo of\npatients\n\n\n\n4\n\n\n\n4\n\n\n\n1\n\n\n\n2\n\n\n\n11\n\n\n\nPoor\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\nFair\n\n\n\n0\n\n\n\n3\n\n\n\n0\n\n\n\n0\n\n\n\n3\n\n\n\nGood\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n3\n\n\n\nExcellent\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n1\n\n\n\nUnknown\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\nResponse (Patient assessment)\n\n\n\n**Response 1. Poor = 0-25% improvement 2. Fair = 26-50% improvement\n3. Good = 51-75% improvement 4. Excellent = 76-100% improvement\n\n\n\nFigure 1.   A 45-year-old Malay female, before and after 2 laser treatments, with \u2018fair\u2019 response\n\n\n\nBefore After Before After\n\n\n\nFigure 2.   A 34-year-old Chinese, before and after 3 laser treatments with \u2018good\u2019 response\n\n\n\nBefore After After\n\n\n\n\n\n\n\n\n22\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAfter a single treatment, 13 patients graded their clinical\nresponse as \u2018poor\u2019 (0-25% improvement) and 1 as \u2018fair\u2019 (26-\n50% improvement). Out of the 6 patients who received a\ntotal of 2 treatments, 4 graded their response as \u2018fair\u2019 (26-\n50% improvement) and 2 as \u2018good\u2019 (51-75% improvement).\nThe 2 patients who received a total of 3 laser treatments\nreported the degree of clearance as \u2018good\u2019 and \u2018excellent\u2019 (76-\n100% improvement) respectively. The other 2 patients who\nreceived a total of 4 laser treatments reported the same\nresults, i.e. \u2018good\u2019 and \u2018excellent\u2019 respectively.\n\n\n\nThere is no significant difference in response between\ntreatment with Q-switched 1064nm Nd:YAG and\ncombination treatment of Q-switched 532nm Nd:YAG\nfollowed by 1064nm laser. As for complications, majority,\ni.e. 10 (62.5%) patients reported hyperpigmentation\ndeveloping within a week post laser therapy. One patient\n(6.25%) developed hypopigmentation, but none reported\nscarring, erythema or textural changes related to laser\ntreatment. So far, none of our patients had reported any\nrecurrences.\n\n\n\nDicussion\nHori\u2019s naevus is an acquired dermal melanocytosis occurring\nmore commonly among the Asian population. Three\nmechanisms have been postulated to be involved in the\npathogenesis of this dyschromasia: (i) Epidermal\nmelanocyte migration; (ii) Hair bulb melanocyte migration;\nand (iii) Reactivation of immature resting dermal\nmelanocytes triggered by an unknown event. In addition,\nultraviolet exposure has been postulated to induce\nmelanogenesis via induction of tyrosinase activity and\nhormonal disequilibrium in pregnancy has been implicated\ndue to reactivation of latent melanocytes in the dermis5.\n\n\n\nHistopathologic examination shows active melanin\nsynthesizing melanocytes dispersed mainly in the papillary\nand mid dermis6. Epidermal hyperpigmentation is a\nprominent feature in Hori\u2019s naevus and as a result, an\nimportant cause of post-laser hyperpigmentation.\n\n\n\nSeveral types of laser modalities have been widely used for\nthe management of Hori\u2019s naevus. These include Q-\nswitched 694nm ruby laser, Q-switched 532nm Nd:YAG\nlaser, Q-switched 1064nm Nd:YAG laser, Q-switched\n755nm Alexandrite laser and Scanned CO2 laser followed\nby Q-switched 694nm ruby laser.\n\n\n\nH.L. Ee et al had done a prospective study among\nSingaporeans comparing the effectiveness of monotherapy\nwith Q-switched 1064nm Nd:YAG laser versus concurrent\nuse of Q-switched 532nm Nd:YAG laser in combination\n\n\n\nwith the 1064nm laser. They concluded that the latter is\nmore effective7. Our study did not show any significant\ndifference between the 2 regimens, but this could be due to\nour relatively small sample size.\n\n\n\nIn our centre, we observed that patients did not fare so\nwell after a single laser treatment. However, all of\nthem recorded \u2018good\u2019 or \u2018excellent\u2019 responses after 3 to 4\nsessions of laser treatment. Ten (62.5%) patients developed\nhyperpigmentation within a week post-laser therapy, which\nwas similar to other studies with incidences ranging\nfrom 50%-73%2. One patient (6.25%) reported both\nhyperpigmentation and hypopigmentation post-laser, but\nnone developed scarring, erythema or textural changes.\n\n\n\nPatients are treated at two monthly intervals. This is to\nallow any post inflammatory hyperpigmentation that may\ndevelop to resolve adequately. So far, none of our patients\nhas reported any recurrences of their lesions.\n\n\n\nConclusion\nThere is no difference in pigment clearance between\nconcurrent use of Q-switched 532nm Nd:YAG laser\nfollowed by 1064nm laser and Q-switched 1064nm\nNd:YAG laser for Hori\u2019s naevus. A single treatment only\nresult in minimal improvement and multiple treatments are\nneeded for total clearance. An important issue associated\nwith Q-switched Nd:YAG laser treatment of Hori\u2019s naevus\nis post inflammatory hyperpigmentation, which remains a\nchallenge to dermatologists managing this condition.\n\n\n\nReferences\n\n\n\n1. Hori Y, Kawashima M, Oohara K, Kukita A. Acquired, bilateral \nnevus of Ota-like macules. J Am Acad Dermatol 1984; 10:961-4.\n\n\n\n2. J. Y. Lin and H. H. Chan. Pigmentary Disorders in Asian Skin: \nTreatment With Laser and Intense Pulsed Light Sources. Adv \nDermatol Surg 2006; 11:8.\n\n\n\n3. Hori Y, Takayama O. Circumscribed dermal melanoses: \nclassification and histologic features. Dermatol Clin 1988;\n6:315-26.\n\n\n\n4. Woraphong Manuskiatti, Apichati Sivayathorn et al. Treatment of \nacquired bilateral nevus of Ota-like macules (Hori\u2019s nevus) using \na combination of scanned carbon dioxide laser followed by Q-\nswitched ruby laser. J Am Acad Dermatol 2003; 48:584-91.\n\n\n\n5. H.L. Ee, H.C. Wong, C.L. Goh and P. Ang. Characteristics of Hori \nNevus: a prospective analysis. Br J Dermatol 2006; 154:50-53.\n\n\n\n6. F. Murakami, Y. Soma and M. Mizoguchi. Acquired symmetrical \ndermal melanocytosis (naevus of Hori) developing after \naggravated atopic dermatitis. Br J Dermatol 2005; 152:903-908.\n\n\n\n7. Hock Leong Ee, Chee Leok Goh et al. Treatment of Acquired \nBilateral Nevus of Ota-Like Macules (Hori\u2019s Nevus) with a \nCombination of the 532nm Q-switched Nd:YAG Laser Followed \nby the 1064nm Q-switched Nd:YAG Is More Effective: \nProspective Study. Dermatol Surg 2006; 32:34-40.\n\n\n\n\n\n"
"\n\nCONSTITUTION\n\n\n\nPERSATUAN DERMATOLOGI MALAYSIA (DERMATOLOGICAL SOCIETY OF MALAYSIA)\n\n\n\nCLAUSE 1 NAME\n\n\n\n1.  The Association shall be known as\n\n\n\nPERSATUAN DERMATOLOGI MALAYSIA (DERMATOLOGICAL SOCIETY OF \nMALAYSIA)\n\n\n\n\u00a0\u00a0\u00a0\u00a0Hereinafter referred to as \"the Association\".\n\n\n\n2. Meaning of name : DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n3. Level : Kebangsaan\n\n\n\nCLAUSE 2 ADDRESS\n\n\n\n1. The registered address is\n\n\n\nUNIT 1-6, LEVEL 1 ENTERPRISE 3B, JALAN INNOVASI 1 TECHNOLOGY \nPARK MALAYSIA LEBUHRAYA PUCHONG-SG BESI BUKIT JALIL, 57000 \n\n\n\nKUALA LUMPUR \n57000 WILAYAH PERSEKUTUAN KUALA LUMPUR\n\n\n\nor at such other place as may from time to time be decided by the Committee; and \nthe postal address is\n\n\n\nUNIT 1-6, LEVEL 1 ENTERPRISE 3B, JALAN INNOVASI 1 TECHNOLOGY \nPARK MALAYSIA LEBUHRAYA PUCHONG-SG BESI BUKIT JALIL, 57000 \n\n\n\nKUALA LUMPUR\n57000 WILAYAH PERSEKUTUAN KUALA LUMPUR\n\n\n\n2. The registered and postal addresses shall not be changed without the prior \napproval of the Registrar of Societies.\n\n\n\nCLAUSE 3 OBJECTIVE\n\n\n\nThe Objects of The Society shall be: \na) To advance the knowledge and practice of dermatology; \nb) To promote research in dermatology; \nc) To promote regional and international co-operation in dermatology; \nd) To acquire and publish literature and scientific works; \ne) To organise clinical meeting, seminars, conventions and all such acts and things \n\n\n\n1\n\n\n\n\n\n\n\n\nincidental or subsidiary to all or any of the above; \nf) To invest the funds of The Society in approved investments under the Trustee Act \nand to appoint Trustees to manage such investments; \ng) To vest the trustees with the fund or funds created under clause 3 (f) and to \nempower the executive committee to utilise the income from the said fund or funds \nin accordance with bye-laws approved by the general meeting of The Society.\n\n\n\nCLAUSE 4 MEMBERSHIP\n\n\n\nMEMBERSHIP\nMembership shall be of three (3) categories.\n\n\n\na) Ordinary Members: \n1. Medical practitioners registered with the Malaysian Medical Council; AND \n\n\n\n2. Possess any of the following recognized postgraduate qualifications in \ndermatology and paediatric dermatology:\n\n\n\n2.1 Advanced Master in Dermatology (UKM) \n2.2 American Specialty Board in Dermatology\n2.3 MACD or FACD (Member or Fellow of the Australian College of Dermatology) \n2.4 Any postgraduate qualification in Dermatology involving 3 years fulltime of \nInternal Medicine and at least 3 years of structured residency of diplomat\nstudy deemed equivalent to Advanced Masters in Dermatology (UKM) by the \nExecutive Committee of the Persatuan Dermatologi Malaysia (PDM) with the \nconcurrence of the Dermatology Specialty Subcommittee of the National \nCredentialing Committee (NCC).\n2.5 Paediatric Dermatology Fellowship under Ministry of Health Malaysia\n2.6 Subspecialty certificate of paediatric dermatology of American Board of \nDermatology\n2.7 Any postgraduate qualification in Paediatric Dermatology involving 3 years \nfulltime of Paediatrics and at least 3 years of structured residency of diplomat study \ndeemed equivalent to fellowship in Paediatric Dermatology Fellowship by the \nExecutive Committee of the Persatuan Dermatologi Malaysia (PDM) with the \nconcurrence of the Paediatric Dermatology Specialty Subcommittee of the National \nCredentialing Committee for the National Specialist Register\n\n\n\nOR\n\n\n\n3. Possess a recognized post graduate qualification in medicine including:\n3.1 MRCP (UK)\n3.2 MRACP or FRACP (Australia)\n3.3 M. Med Internal Medicine (UM, UKM, USM)\n3.4 Any postgraduate qualification in internal medicine deemed equivalent to 3.1, \n3.2 or 3.3 by the Executive Committee of the Persatuan Dermatologi Malaysia \n(PDM) with the concurrence of the Dermatology Specialty Subcommittee of the \nNational Credentialing Committee (NCC)\nAnd in addition have\n\n\n\n2\n\n\n\n\n\n\n\n\n3.5 Three years of experience in internal medicine.\n3.6 Three years of full time training under a *Senior Dermatologist in an organized \nSkin Unit.\n- Training should include clinical dermatology (with inpatient and outpatient care), \nVenereology (sexually transmitted diseases) and Leprosy.\n- The centre should have supportive facilities in histopathology, immunology, \nmicrobiology and mycology, and library facilities. \n*Senior Dermatologist refers to a Consultant Dermatologist with at least 5 years \nexperience of Dermatology \n3.6.1 Of the three years training, at least 1 year is to be done after obtaining the \npostgraduate qualification. \n3.6.2 Those having in addition, the Diploma in Dermatology, can consider the \ncourse at the St. John\u2019s Institute of Dermatology, University of London, as 1 year of \ntraining. \n3.6.3 Training done overseas may be considered on a case to case basis as \ndefined in 3.6 and 3.6.1 above.\n\n\n\nOR \n\n\n\n4. A medical practitioner who does not hold any of the recognized postgraduate \nqualifications stated in 2 and 3 above, may be considered a Dermatologist if all the \nfollowing requirements are fulfilled up to 1st January, 1983: \n4.1 Possesses a Diploma in Dermatology\n4.2 Has at least 5 years of experience in Dermatology (Diploma in Dermatology \nfrom St. John Institute of Dermatology shall be considered as 1 year of experience \nin dermatology \n(This Clause 4 will be valid for 3 years from the inception of the National Specialist \nRegister on 23rd August, 2006) \n\n\n\nOR\n\n\n\n5. For a grace period of 3 years from the inception of the National Specialist \nRegister (NSR) on 23rd August, 2006, a doctor working full-time in the Ministry of \nHealth Malaysia (MOH) hospitals or public (Government funded) Universities who is \ngazetted or officially recognized as a Dermatologist by the MOH or the Public \nUniversities may be considered as a Dermatologist for the registration with the \nNSR. \n\n\n\nTo maintain membership of the Persatuan Dermatologi Malaysia, each member \nmust within that year, either: \ni) Publish a paper on dermatology in any one medical journal, or \nii) Present a paper at any one scientific meeting or\niii) Attend at least one Dermatological Scientific Meeting \n\n\n\nb) Honorary Members:\n\n\n\nHonorary Members shall be distinguished persons who have rendered notable \nservice to The Society or to the advancement of Dermatology in Malaysia and \nrecommended by the Executive Committee and elected by majority at a General \n\n\n\n3\n\n\n\n\n\n\n\n\nMeeting.\n\n\n\nApplication for Ordinary Membership shall be made in to the Honorary Secretary on \nthe approved form for approval by the Executive Committee. \n\n\n\nc) Life Members:\n\n\n\nOrdinary members in good standing with more than 10 years of continuous \nmembership. \n\n\n\nRIGHT AND PRIVILEGES OF MEMBERSHIP:\n\n\n\na) a) Members are entitled to attend meeting of the Society. Guests may be invited \nto attend the scientific meeting only by invitation of the Executive Committee. \nGuests shall not attend business meetings of the Society. \n\n\n\nb) Only Ordinary Members and Life Members shall be entitled to hold office in the \nExecutive Committee, and to vote thereat.\n\n\n\nc) Ordinary Members who have been suspended for non-payment can be restored \nto membership upon payment of all unpaid dues. \n\n\n\nd) No appeal shall lie from any decision of The Society to any court of Law.\n\n\n\nCLAUSE 5 RESIGNATION AND TERMINATION\n\n\n\n1. Any member may terminate his membership by written notice to the Honorary \nSecretary. Membership shall be automatically suspended if a member subscription \nhas not been paid up within 3 months of the beginning of the financial year.\n\n\n\n2. Members whose professional or personal conduct has been detrimental to the \ninterests of the Society may, at the Executive Committee\u2019s decision, be removed \nfrom the membership of the Society either temporarily or permanently. Such \nmembers may appeal at the Annual Meeting or Extra-Ordinary General Meeting, \nwhich shall be final and binding.\n\n\n\nCLAUSE 6 SOURCE OF INCOME\n\n\n\nSubscriptions\n\n\n\na) The Annual Subscription for Ordinary Members shall be Malaysian Ringgit Fifty \nonly (RM50) payable at the beginning of each financial year or a lump sum of \nMalaysian Ringgit Five Hundred only (MYR500) ie a total of ten years subscription \npayable on registration of membership. \n\n\n\nb) Honorary Members - Free. \nc) Life Members - Free\n\n\n\n4\n\n\n\n\n\n\n\n\nd) Funds collected from organising CME activities\ne) Contribution from recognised and relevant authorities /companies for any specific \ncause\n\n\n\nCLAUSE 7 GENERAL MEETING\n\n\n\nA) The Annual General Meeting shall be held as soon as possible after the close of \neach financial year but not later than the month of September. The Annual General \nMeeting will preferably be face-to-face except for exceptional \nunavoidable circumstances in which it will be a hybrid or completely virtual meeting. \nThe business of each Annual General Meeting shall include: \n\n\n\n(i) The Annual Report of the activities of The Society. \n(ii)Presentation of the Balance Sheet and the Receipt and Payments of The society. \n(iii) Election of Office Bearers. \n(iv) Election of Honorary Auditor. \n(v) Any other business of which seven (7) days notice in writing has been \ngiven to the Honorary Secretary \n\n\n\nb) Extraordinary General Meeting: The Executive Committee may convene an \nExtraordinary General Meeting at any time for any special reason on receipt of a \nwritten requisition signed by Ten (10) or more Ordinary Members. The \nExtraordinary General Meeting may be face-to-face and/or through virtual online \n(electronic) media as decided by the Executive Committee. . \n\n\n\nc) Notice of all General Meeting shall be given to members in writing at least two \nweeks in advance. The annual report for the current term and the audited statement \nof accounts of the Society for the previous year shall be sent to all members \ntogether with the notice of the General Meeting via electronic communications \n\n\n\nd) The quorum for all General Meeting shall be twice the total number of executive \ncommittee members. \n\n\n\ne) In the event of the lack of quorum, the Chairman shall postpone the General \nMeeting to a day not later than fourteen (14) days. Should the members present at \nthe postponed meeting be insufficient to form a quorum, those present shall be \nconsidered a quorum, but they shall have no power to make amendments to the \nConstitution or make decision affecting the whole membership. \n\n\n\nf) The President shall chair all meetings. In his absence the Vice-President shall be \nchairman. In the absence of both President and Vice-President, the members \npresent shall elect a chairman for the meeting.\n\n\n\nCLAUSE 8 COMMITTEE\n\n\n\nManagement of the Society\n\n\n\n5\n\n\n\n\n\n\n\n\n(i) The Society shall be managed by an Executive Committee consisting of:\nPresident \nVice President\nImmediate Past President\nHonorary Secretary \nHonorary Treasurer\nFour Committee Members\n\n\n\n(ii) All Members of the executive committee and every officer performing executive \nfunctions in The Society shall be Malaysian citizens.\n\n\n\nElection of Office bearers\n\n\n\nAll members of the Executive Committee shall be elected by a majority vote at the \nAnnual General Meeting, to hold office for a period of two years. Vacancies in the \nExecutive Committee occurring during the year shall be filled by a majority vote of \nthe Executive Committee. \n\n\n\nCLAUSE 9 DUTIES OF OFFICE BEARERS\n\n\n\nPowers and Duties of Office Bearers\n\n\n\na) The Executive Committee shall meet at least four times a year. Notice of such \nmeetings will be seven days in advance and may be face-to-face and/or through \nvirtual online (electronic) media \n\n\n\nb) The quorum for Executive Committee Meetings shall be not less than one-half of \nmembers of the Executive Committee. \n\n\n\nc) The Executive Committee shall have the power to form Sub-Committees to deal \nwith special matters. \n\n\n\nd) The Executive Committee shall be responsible for the management of The \nSociety in all matters. \n\n\n\ne) Minutes shall be kept by the Honorary Secretary of all meetings of the Executive \nCommittee. He shall also keep membership register containing the following \nparticulars:\n\n\n\nName \nDate of Admission \nDate of Birth \nIdentity Card Number\nOccupation and Address of each member \n\n\n\nf) The Honorary Treasurer shall be responsible for the collection and accounting of \nall funds of the Society, and shall issue receipts for all payments made to the \n\n\n\n6\n\n\n\n\n\n\n\n\nSociety. He may hold a petty cash advance not exceeding Malaysian Ringgit Two \nThousand (MYR2,000.00) at any time. All money in excess of this sum shall within \nseven days of receipt be deposited in a bank approved by the Executive \nCommittee. The Bank Account shall be in the name of the Society. All bank \naccounts of the Society shall be operated by the Honorary Treasurer and by the \nPresident or the President-Elect. The Honorary Treasurer shall be responsible for \nthe preparation and submission of the Audited Statement of Accounts at the Annual \nMeeting.\n\n\n\nCLAUSE 10 FINANCIAL PROVISION\n\n\n\nThe financial year shall start on 1st January and end on 31st December. \n\n\n\n1. The General Meeting as proposed by the Executive Committee are empowered \nfrom time to time to make, alter and revoke bye-laws for the utilization of income \nderived from Research Funds by the Trustees and for the internal management of \nthe Society. All such bye-laws until revoked shall be binding on all members of the \nSociety and the Society and the appointed Trustees as if they were contained in this \nConstitution.\n\n\n\n2. The Executive Committee can authorise the expenditure of not more than \nMalaysian Ringgit Ten Thousand only (MYR10,000) per transaction from the \nSociety\u2019s funds for the Society\u2019s purposes unless such payment is to establish a \nResearch Fund or add to a Research Fund under the management and control of \nthe Trustees or to disburse payments pursuant to Article 8a (iv). \n\n\n\nCLAUSE 11 AUDITORS\n\n\n\nElections of Auditor\n\n\n\nAt the Annual General Meeting of The Society, one member of The Society shall \nbe elected as Auditor to hold office for one year, and he shall not be re-elected the \nfollowing year. \n\n\n\nCLAUSE 12 PROPERTY ADMINISTRATOR\n\n\n\nThe Society may acquire by purchase, hire, lease, grant or sell any moveable or \nimmoveable properties in furtherance of the objects of The Society. The Society \nmay receive, borrow or invest monies for any of the objects of The Society. All \nproperty and income of The Society shall be applied solely towards the promotion of \nthe objects of the Society. \n\n\n\nThe Trustees shall be charged with the management of any surplus funds not \nrequired for the use of The Society and once so vested shall not be utilised by\nthe Executive Committee without prior approval of two thirds of the members\n\n\n\n7\n\n\n\n\n\n\n\n\npresent and voting at a General Meeting. The Trustees may make available to\nthe executive committee to utilise the interest or dividends of such surplus\nfunds invested in accordance with the Trustees Act or any Statutory\nmodification thereon solely for the advancement of Dermatological Research,\nResearch in Venereal Diseases or Leprosy; provide scholarships or grants, give\nawards and sponsorships and make loans to students approved by the Executive\nCommittee, undertaking research in Dermatology, Leprosy or Venereal\nDiseases and comply with the Bye-Laws prescribed by the General Meeting for\nthe utilisation of Research Funds. These funds are only to be made available for \nMalaysians. \n\n\n\nCLAUSE 13 INTERPRETATION\n\n\n\nThe General Meeting and Extraordinary General Meeting as proposed by the \nExecutive Committee are empowered from time to time to make, alter and revoke \nbye-laws for the utilization of income derived from Research Funds by the Trustees \nand for the internal management of the Society. All such bye-laws until revoked \nshall be binding on all members of the Society and the Society and the appointed \nTrustees as if they were contained in this Constitution.\n\n\n\nCLAUSE 14 ADVISOR / PATRON\n\n\n\nNil\n\n\n\nCLAUSE 15 PROHIBITION\n\n\n\nA) The funds of The Society shall not be used to pay the fines of members who \nhave been convicted in court.\n\n\n\nb) The Society shall not indulge in any political activity or allow its funds and /or \npremises to be used for political purposes or illegal activities. \n\n\n\nc) The Society shall not have any affiliation or connection outside Malaysia without \nthe prior approval from the Minister concerned. \n\n\n\nd) Neither the Society nor its members shall attempt to restrict or in any other \nmanner interferes with the trade or prices or engages in any Trade Union activities \nas defined in The Trade Union Ordinance, 1959.\n\n\n\ne) All moneys and profits accruing to The Society from participation in any business \nshall be applied solely towards the furtherance, promotion and execution of the \nobjects of The Society and no portion thereof shall be paid by way of dividend, \nbonus or profit to any member of The Society, provided that nothing herein \nexpressed or contained shall prevent the payment in good faith of remuneration or \nexpenses or both to any officer or servant of The Society, or to any member of The \n\n\n\n8\n\n\n\n\n\n\n\n\nSociety, or other person or persons for services actually rendered by him or them to \nThe Society.\n\n\n\nCLAUSE 16 AMENDMENT OF CONSTITUTION\n\n\n\nThese rules may not be altered or amended except by resolution of a General \nMeeting. Any proposals for Amendment shall be given in writing at least 2 weeks \nbefore the Annual General Meeting of the Society.\n\n\n\nAny amendments proposed after the Annual General Meeting shall be given in \nwriting to the Committee who shall submit to the extraordinary General Meeting duly \nsummoned to consider them or at the next Annual General Meeting.\n\n\n\nSuch amendments to these Rules must be proposed and seconded by ordinary \nmembers and must be passed by a majority of at least two-thirds of the voting \nmembers present at the meeting. \n\n\n\nSuch alterations or amendments shall take effect from the date of their approval by \nthe Registrar of Societies.\n\n\n\nCLAUSE 17 DISSOLUTION\n\n\n\n(1) The Society may be voluntarily dissolved by a resolution of not less than three-\nfifths of the membership present in a general meeting.\n\n\n\n(2) In the event of the Society being dissolved as provided above, all debts and \nliabilities legally incurred on its behalf shall be fully discharged, and the remaining \nfunds shall be disposed of in such manner as may be decided upon by a general \nmeeting.\n\n\n\n(3) Notice of dissolution shall be forwarded to the Registrar of Societies within 14 \ndays of its dissolution\n\n\n\nCLAUSE 18 FLAG, LOGO AND BADGE\n\n\n\n1. Flag\n- \nDescription \n-\n\n\n\n2. Logo \n- \nDescription\n-\n\n\n\n3. Badge \n- \n\n\n\n9\n\n\n\n\n\n\n\n\nDescription\n-\n\n\n\n10\n\n\n\n\n\n"
"\n\n101\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nPrevalence of Chlamydia trachomatis in Genito-urinary \nMedicine Clinic, Hospital Kuala Lumpur: A 5-year\nRetrospective Analysis\n\n\n\nS Norashikin, MBBS, MRCP1, HB Gangaram, MBBS, FRCP2 and Suraiya H. Hussein, MBBS, FRCP2\n\n\n\n1 Department of Internal Medicine\nFaculty of Medicine and Health Sciences\nUniversity Putra Malaysia, Serdang\n2 Department of Dermatology, Hospital Kuala Lumpur\nKuala Lumpur\n\n\n\nCorrespondence\n\n\n\nS Norashikin, MBBS MRCP,\nDepartment of Dermatology, Hospital Kuala Lumpur\n53000 Jalan Pahang, Kuala Lumpur\nEmail : aliffarhan@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Chlamydia trachomatis is the most common bacterial\nsexually transmitted infection worldwide. It is the commonest cause of\nnon-gonococcal urethritis in men and can cause serious complications\nin the female reproductive tract if left untreated.\n\n\n\nObjective The aim of this study is to establish the prevalence of\nChlamydia trachomatis infection in symptomatic patients attending the\nGUM Clinic in HKL.\n\n\n\nMethod A retrospective study involving 596 patients seen from\nJanuary 2001 to December 2005 was performed. Relevant\ndemographics and test results were obtained from the case notes and\nthe Chlamydia test log books.\n\n\n\nResults A total of 549 patients were tested for C. trachomatis during\nthis period and had the test results available for analysis. 366 were\nmales and 183 were females with a ratio of 2:1. The prevalence of C.\ntrachomatis infection was 23.5% (n=86) for male patients and 17.5%\n(n=32) for female patients with the highest prevalence in the group\naged 15-19 years in both sexes. The highest prevalence was found in\nMalays in both sexes, probably reflecting the racial composition of the\nGUM Clinic attendees rather than a true peak prevalence in this\npopulation.\n\n\n\nConclusion The high prevalence rates in this study were expected as\nwe were only screening symptomatic patients. The need for routine\nscreening in the sexually active population aged less than 30 years\nshould also be considered to assess the prevalence of C. trachomatis\ninfection in the general population in this country.\n\n\n\nKeywords chlamydia; prevalence; non-gonococcal urethritis\n\n\n\nIntroduction\nChlamydia trachomatis is the most common bacterial\nsexually transmitted infection in many parts of the world,\n\n\n\nwith estimated new cases of  more than 90 million people\nworldwide1. In women, infection most commonly presents\nas cervicitis. Left untreated, it may cause serious sequelae in\nthe female reproductive tract such as  pelvic inflammatory\ndisease, ectopic pregnancy, chronic pelvic pain and tubal\ninfertility. Chlamydial infection in men may cause\nurethritis, epididymitis and prostatitis and may be\nassociated with infertility but rarely cause complications. In\nthe majority of patients however, infection remains\nasymptomatic. Chlamydial infection has been shown to\nincrease both the transmission and acquisition rates for\nHIV infection2. Early effective treatment is therefore of\nparamount importance.\n\n\n\nEstimates of prevalence vary enormously among different\npopulations in countries across the world depending on the\npopulations studied. Overall, healthcare settings have\nhigher prevalence estimates than population-based studies3.\nIn general, chlamydial prevalence is higher in sexually active\nadolescent women and those attending sexually transmitted\ndisease centres, ranging from 10% to 40%4. A systematic\nreview of estimates in various populations in the UK\nrevealed that in female patients, the highest estimates were\nin those under 20 year old from the GUM clinics3.\nAlthough prevalence data in men are limited, the growing\nnumbers of research in this area have shown that the\nprevalence of infection in men is also considerable3, 5-6.\n\n\n\nDespite the importance of chlamydial genital infection, data\non its prevalence in Malaysia is still scarce. A few prevalence\nsurveys conducted in selected female populations showed\nvariable rates with the highest prevalence in those with\npelvic inflammatory disease7-8. Little information is available\nregarding the prevalence of C. trachomatis infection among\npatients attending a GUM clinic. The only previous\npublished data on GUM clinic attendees showed that\nC. trachomatis caused urethritis in approximately 8% of\nsymptomatic\n\n\n\n\n\n\n\n\n102\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nsymptomatic heterosexual male patients9. In this study, we\nsought to estimate the prevalence of Chlamydia trachomatis\ninfection in symptomatic male and female patients\nattending the GUM clinic at Hospital Kuala Lumpur.\n\n\n\nMethod\nA retrospective study involving 596 patients who were\ntested for C. trachomatis from January 2001 to December\n2005 was carried out. These patients presented with either\na urethral or vaginal discharge and microscopy showed at\nleast 5 pus cells per high power field with a negative culture\nfor Gonorrhoea. 47 patients had to be excluded from the\nstudy as the Chlamydia test results were not available.\nPatients\u2019 demographic details and test results were obtained\nfrom the case notes and the Chlamydia test logbooks. All\nmale and female patients had their respective urethral and\nendocervical swabs sent for direct fluorescent antibody\n(DFA) test (MicroTrak Chlamydia trachomatis Direct\nSpecimen Test, Trinity Biotech, Ireland) for Chlamydia\nantigen detection.\n\n\n\nResults\nA total of 549 patients were available for analysis in this\nstudy. 366(67%) patients were males and 183 (33%) females.\nMore than half of the patients were Malays (58%) followed\n\n\n\nby Indians (25%), Chinese (13%) and others (4%) who were\neither Bangladeshi or Indonesian immigrant workers. More\nthan 70% of patients were in the 20-40 age group.\n\n\n\n86(23.5%) of male patients tested positive for Chlamydia as\ncompared to 32(17.5%) female patients. In the male\npatients, the prevalence of Chlamydia infection was highest\nin two age groups, the 15-19 (30.6%) and 30-39 (30.8%)\nyears. The prevalence also did not seem to decline with age,\nremaining high even in the oldest age group (Figure 1).\n\n\n\nIn contrast, the highest prevalence in the female patients\nwas in the youngest age group of 15-19 years (38.9%).\nThere appears to be a declining trend in prevalence with\nincreasing  age (Figure 2).\n\n\n\nThe annual trend of chlamydial prevalence shows a rising\ntrend towards the end of the five year study period for both\nsexes (Figure 3).\n\n\n\nIn both male and female patients, the prevalence of\nChlamydia infection was highest in Malays at 24.7% and\n20% respectively (Figure 4). However female patients from\nthe minority ethnic group (all Indonesians) had an equally\nhigh prevalence as the Malays (Figure 4).\n\n\n\nFigure 1.   C. trachomatis prevalence by age group in male patients\n\n\n\nP\nre\n\n\n\nva\nle\n\n\n\nn\nce\n\n\n\n (\n%\n\n\n\n)\n\n\n\nFigure 2.   C. trachomatis prevalence by age group in female patients\n\n\n\nP\nre\n\n\n\nva\nle\n\n\n\nn\nce\n\n\n\n (\n%\n\n\n\n)\n\n\n\n\n\n\n\n\n103\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nThe prevalence of Chlamydia trachomatis in both male and\nfemale attendees at the GUM clinic was very high. This was\nexpected as we were only screening symptomatic patients\nfrom a sexually transmitted disease clinic population.\nTable 1 shows a comparison of Chlamydia prevalence\nbetween different female populations previously studied in\nthis country.\n\n\n\nIt is interesting to note that male patients had a higher\nprevalence as opposed to female patients, in contrast to\n\n\n\nprevious studies. However, this gender difference may not\nnecessarily reflect a true difference in the epidemiology of\nC.trachomatis infection in this country. This is probably\ndue to a higher attendance rates of male patients in the\nGUM clinic as compared to the female patients. Female\npatients are more likely to present themselves to a\ngynaecological clinic when faced with symptoms. This\nfinding is consistent with studies conducted in STD clinic\npatients in European countries like Sweden and Slovenia\nwhere a relatively larger proportion of male as opposed to\nfemale cases has been reported10-11.\n\n\n\nFigure 3.   Annual prevalence of C. trachomatis infection, GUM clinic HKL\n\n\n\nP\nre\n\n\n\nva\nle\n\n\n\nn\nce\n\n\n\n (\n%\n\n\n\n)\n\n\n\nFigure 4.   Racial distribution of C. trachomatis infection, GUM clinic HKL\n\n\n\nP\nre\n\n\n\nva\nle\n\n\n\nn\nce\n\n\n\n (\n%\n\n\n\n)\n\n\n\nTable 1. Sungai Buluh Augmented Regime\n\n\n\nGUM clinic HKL\n\n\n\nFemales with PID8\n\n\n\nSex workers8\n\n\n\nANC attendees7\n\n\n\nPrevalence (%)\n\n\n\n17.5\n\n\n\n22.7\n\n\n\n6.3\n\n\n\n1.6\n\n\n\nn\n\n\n\n549\n\n\n\n88\n\n\n\n208\n\n\n\n1070\n\n\n\nTest method\n\n\n\nDFA\n\n\n\nPCR\n\n\n\nPCR\n\n\n\nPCR\n\n\n\n\n\n\n\n\n104\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe prevalence pattern in female patients in this study\nappears to conform to what is already well known about\nChlamydia genital infection where it is commonest in those\nbelow 20 years of age and declines with increasing age.\nSexually active young adults are more susceptible to genital\nchlamydial infections because of greater exposure to high-\nrisk social behaviour. Male patients however do not seem to\nfollow the same pattern. The prevalence peaked at two age\ngroups, the youngest (less than 20 years old) and those in\ntheir thirties and did not decrease with increasing age.\nWhether this could reflect differences in sexual behaviour\npattern between the two sexes in this country as they get\nolder is a contention and should be studied further.\n\n\n\nAmong the various ethnic groups in this country,\nChlamydia seems to be most prevalent in Malays in both\nsexes. This does not necessarily mean that the Malays were\nmore afflicted with the infection compared to other races as\nthe Malays form the largest racial group attending the\nGUM clinic. The differences in prevalences among the\nraces appear to reflect the racial composition of patients\nattending the GUM clinic rather than a true racial\ndifference.\n\n\n\nAs this is a retrospective study, inherent limitations such as\nmissing test results (n=47) and missing data are\nunavoidable. Nevertheless this could skew the data and\nhence some degree of caution should be exercised in\ninterpreting the findings in this study.\n\n\n\nDespite these limitations, our findings are comparable to\nother studies in C. trachomatis infection in the South East\nAsia region (Table 2).\n\n\n\nConclusion\nThe results of this study strongly support the\nimplementation of testing for C. trachomatis infection\namong symptomatic men and women who attend GUM\nclinics in Malaysia. More resources should be allocated to\nenable implementation of routine screening in all patients as\nmore than 70% of both male and female patients are\nasymptomatic at the time of infection. Effective screening,\ncontact tracing and treatment of patients and the sexual\npartners are imperative to reduce the prevalence of\nC. trachomatis genital infection and the burden of untreated\ndisease. The need for routine screening in the sexually active\npopulation aged less than 30 years should also be considered\nto assess the prevalence of C. trachomatis infection in the\ngeneral population in this country.\n\n\n\nReferences\n\n\n\n1. Global Prevalence and Incidence of Selected Curable Sexually \nTransmitted Infections Overview and Estimates 2001. World \nHealth Organization. \n\n\n\n2. D Mabey. Interactions between HIV infection and other sexually \ntransmitted diseases. Tropical Med Int Health 2000; 5(7):\nA32-A36\n\n\n\n3. E J Adams, A Charlett, W J Edmunds and G Hughes. Chlamydia \ntrachomatis in the United Kingdom: a systematic review and \nanalysis of prevalence studies. Sex Transm  Inf 2004; 80: 354-362\n\n\n\n4. C M Black. Current methods of laboratory diagnosis of \nChlamydia trachomatis infections. Clinl Microb Rev 1997; 10(1): \n160-184\n\n\n\n5. D S LaMontagne, DN Fine, JM Marrazzo. Chlamydia trachomatis \ninfection in asymptomatic men. Am J Prev Med 2003; 24(1):\n36-42\n\n\n\n6. D S LaMotagne, K A Fenton, S Randall et al. Establishing the \nnational Screening Programme in England: results from the first \nfull year of screening. Sex Transm Infect 2004; 80: 335-341.\n\n\n\n7. J Ravindran, Y I Tan, Y F Ngeow. The Prevalence of Chlamydia\nTrachomatis in Patients with Pelvic Inflammatory Disease. Med \nJ Mal 1998; 53(1): 16-21\n\n\n\n8. Consensus Report on STI, HIV and AIDS Epidemiology Malaysia \n2001. WHO Regional Office for the Western Pacific. Department \nof Public Health, Ministry of Health Malaysia.\n\n\n\n9. HB Gangaram, A Kaur, AT Gan et al. Urethritis in Men, Genito-\nUrinary Medicine Clinic in Hospital Kuala Lumpur. Mal J \nDermatol  2003; 16: 8-12\n\n\n\n10. D Kese, M Maticic, M Potocnik. Chlamydia trachomatis \ninfections in heterosexuals attending sexually transmitted \ndisease clinics in Slovenia. Clin Microb Infect 2005; 11(3):\n240-242\n\n\n\n11. Gotz H, Lindback J, Ripa T et al. Is the increase in notifications \nof Chlamydia trachomatis infections in Sweden the result of \nchanges in prevalence, sampling frequency or diagnostic \nmethods? Scand J Infect Dis 2002; 34: 28-34\n\n\n\n12. Lim KB, Thirumoorthy T, Nadarajah M et al. Endocervical \nchlamydial infection in women attending a sexually transmitted \ndisease clinic in Singapore. Singapore Med J 1989; 30(2): 167-9\n\n\n\n13. Kuvanont K, Chitwarakorn A, Rochananond C et al . Etiology of \nurethritis in Thai men. Sex Transm Dis 1989; 16(3): 137-140\n\n\n\nTable 2. Sungai Buluh Augmented Regime\n\n\n\nCountry\n\n\n\nMalaysia (this study)\n\n\n\nSingapore12\n\n\n\nThailand13\n\n\n\nPrevalence (%)\n\n\n\nMale \n\n\n\n23.5\n\n\n\nNA \n\n\n\n16.1\n\n\n\nFemale \n\n\n\n17.5\n\n\n\n17.0\n\n\n\nNA\n\n\n\n* 1 BP patient and 3 pemphigus patients defaulted follow-up\nbefore treatment was instituted.\n\n\n\n\n\n\n\n\n105\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nA Case of acne scarring treated with Fractional \nPhotothermolysis \n\n\n\nKo Chung Beng, MBChB, MRCP, Chua Sak Eng, MBBS, MRCP, Seah Keh Seng, MBBS MMed, Chu Kooi Yen, MBBS\n\n\n\nand Ko Chung Yee, MD, MS\n\n\n\nKo Skin Specialist Centre, Klang, Malaysia\n\n\n\nCorrespondence\n\n\n\nDr Koh Chung Beng\nKo Skin Specialist Centre, 10A-22A, Jalan Temoh\nOff Jalan Goh Hock Huat, 41400 Klang\nSelangor Darul Ehsan, Malaysia\nEmail : skin.specialist@hotmail.com \n\n\n\nAcne is a disorder of the pilosebaceous follicle that affects\nup to 80% of people in their teens and twenties and up to\n10% of the older adults. While many are left without any\npermanent sequelae, some result in disfiguring acne scars.\nWe report a case of depressed acne scars which improved\nwith fractional resurfacing erbium glass 1550nm laser\n(Fraxel laser).\n\n\n\nCase Report\nThis is a 35-year-old Chinese man who presented with\nmultiple acne scars. He has no known medical illness and is\nnot taking any medication (including isotretinoin) currently.\nHe has not undergone any laser procedure prior to this.\n\n\n\nThere were multiple ice-picked and saucer-shaped\n(depressed fibrotic) acne scars over his face, predominantly\nover his bilateral cheeks and temporal region.\n\n\n\nThe treatment plan consisted of a few sessions of full face\nFraxel laser resurfacing, with an interval of 1 month\nbetween each session. The laser settings were stepped up\naccording to the patient\u2019s response. Initial treatment level\nwas:\n\n\n\n8mJ / 1000 MTZ\n10 mJ / 1000 MTZ\nTotal energy: 3.0 kJ\n\n\n\nThe subsequent treatment level was stepped up to:\n8 mJ / 500 MTZ\n15 mJ / 500 MTZ\n20 mJ / 500 MTZ\n25 mJ / 250 MTZ (spot treatment to ice-pick scars)\nTotal energy: 5.0 kJ \n\n\n\nBoth treatments were tolerated well, with minimal\ndowntime. After the 2 sessions of Fraxel laser, his acne scars\nbecame less prominent and shallower. Please refer to the\nbefore-and-after photographs attached.\n\n\n\nFigure 1.   (A) Before treatment (B) Marked\nimprovement after 2 sessions of Fraxel laser\n\n\n\nFigure 2.   (A) Before treatment B) Marked\nimprovement after 2 sessions of Fraxel laser\n\n\n\n\n\n\n\n\n106\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nAcne scarring affects 30% of patients with moderate to\nsevere acne vulgaris. It is particularly common in acne\nconglobata and acne fulminans. To reduce the incidence of\nscarring, acne is best treated early. There are various\ntreatments available for acne scars, such as chemical peel,\ndermabrasion, laser (resurfacing), dermal fillers, punch\ngrafting and subcision therapy.\n\n\n\nFractional photothermolysis is a novel technology designed\nto create a network of microscopic intradermal zones of\nthermal injury in the dermis and overlying epidermis with\nislands of spared, normal tissue, using focused beams\nof infrared laser energy (1550nm). Fractional\nphotothermolysis (Fraxel laser treatment; Reliant\nTechnologies; Palo Alto; California) is currently approved\nby the US Food and Drug Administration for the treatment\nof periorbital rhytids and dyspigmentation. The Fraxel laser\nis a 30watt, diode pumped, 1,550nm erbium fiber laser that\ntargets water as its chromophore. It is a safe and gradual\nlaser procedure that stimulates the body to replace aged and\nphoto-damaged skin, even on delicate skin areas, such as the\nneck, chest and hands.\n\n\n\nUtilizing the concept of fractional treatment, 70-100um\nwide and 250-800um deep, microthermal zones of tissue\ncoagulation are produced. Tissue is not vaporized and the\nstratum corneum remains intact. The epidermal coagulated\ntissue is expelled and replaced by keratinocyte migration.\n\n\n\nWhen there is a significant damage to the basement\nmembrane zone, the dermal contents are also expelled as\nmicroscopic epidermal and dermal necrotic debris. Zone of\ncollagen denaturation in the dermis cause upregulation of\nthe inflammatory cascade, which leads to collagen\nremodeling and new collagen formation.\n\n\n\nThe mid-infrared wavelength of the Fraxel laser allows\ndeeper penetration into the tissue without the injury\nobserved with traditional ablative laser (such as lengthy\ndowntime, severe pain and prolonged edema). The reported\ncomplications are post-inflammatory hyperpigmentation\n(up to 20%), hypopigmentation, infection and scarring.\n\n\n\nReferences\n\n\n\n1. Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. \nFractional photothermolysis: a new concept for cutaneous \nremodeling using microscopic patterns of thermal injury. Lasers \nSurg Med 34(5):426-38 (2004). \n\n\n\n2. Fisher GH, Kim KH, Bernstein LJ, Geronemus RG. Concurrent \nuse of a handheld forced cold air device minimizes patient \ndiscomfort during fractional photothermolysis. Dermatol Surg \n31(9 Pt 2): 1242-4 (2005 Sep). \n\n\n\n3. Rahman Z, Rokhsar CK, Tse Y, Lee S, Fitzpatrick R. The treatment \nof photodamage and facial rhytides with fractional \nphotothermolysis. Lasers Surg Med 36(suppl 17):32 (2005). \n\n\n\n4. Rahman Z, Tanner H, Jiang K. Treatment of atrophic scars with \nthe 1550nm erbium-fiber fractional laser. Lasers Surg Med \n38(suppl 18):24 (2006).\n\n\n\n\n\n\n\n\n107\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nSweet\u2019s Syndrome with extracutaneous involvement\n\n\n\nLee YY, MD, MRCP, MMED1, Loh LC, MBChB, MRCP1 and Wong KT, MBBS, M Path, FRCPath2\n\n\n\n1 Dermatology Unit, Department of Medicine\nUniversity Malaya Medical Centre, Kuala Lumpur.\n2 Department of Pathology, Faculty of Medicine\nUniversity Malaya, Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nDr YY Lee, MD, MRCP, MMED,\nDermatology Unit, Department of Medicine\nUniversity Malaya Medical Centre, Kuala Lumpur\nEmail : yleemd@yahoo.com\n\n\n\nSweet\u2019s syndrome was first described by Dr. Robert Douglas\nSweet in 19641. It was originally described as an \u2018acute\nfebrile neutrophilic dermatosis\u20191. There are primarily three\nsubtypes of Sweet\u2019s syndrome, ie. classical Sweet\u2019s\nsyndrome, malignancy-associated Sweet\u2019s syndrome and\ndrug-induced Sweet\u2019s syndrome. We are reporting a case of\nclassical Sweet\u2019s syndrome in a 47-year-old man.\n\n\n\nCase Report\nA 47-year-old Chinese man was presented to University\nMalaya Medical Centre in March 2003 with a 2-month\nhistory of fever, headache, swelling of the left side of his\nneck together with skin lesions on both hands. He did not\nhave any symptoms suggestive of an underlying systemic or\nregional infection and denied any ingestion of drugs,\nsupplements or traditional medication. There was no\nsignificant past medical history and a  systemic review was\nnormal. Physical examination revealed that he was febrile\nwith a temperature of 38\u02daC. There was a tender, firm\nlymphadenopathy measuring 4 to 5cm at the left cervical\nregion together with painful plaques and pustules on both\nhands. The rest of the systemic examinations were normal.\nOur differential diagnoses for his skin lesions included\npyoderma gangrenosum, Sweet\u2019s syndrome or\ngranulomatous vasculitis with pyrexia of unknown origin.\n\n\n\nInvestigations showed leukocytosis (32.5*109 /L) with\nneutrophilia (85%) and thrombocytosis (554*109 /L) in the\nfull blood count. C-reactive protein (CRP) and erythrocyte\nsedimentation rate (ESR) were raised [CRP-15.2mg/dl,\nESR-121 mm/hour], but renal function test, liver function\ntest, hormonal studies, tumour markers, connective tissue\nscreening (ANF, ANCA, C3, C4) and retroviral screening\nwere normal.\n\n\n\nCultures of blood, urine, sputum and skin swab and biopsy\nfor bacteria, fungus and mycobacteria cultures were all\nnegative.\n\n\n\nChest x-ray was normal. Computer tomography (CT) of his\nneck, thorax, abdomen and pelvis showed multiple left\ncervical lymphadenopathy, most likely due to an infective or\ninflammatory process. Cervical lymph node biopsies\nperformed at three different occasions were consistent with\nreactive hyperplasia. Skin biopsy histopathology showed\nmarked edema of papillary dermis. The upper dermis was\ninfiltrated with neutrophils and a few eosinophils.\nHistiocytes containing nuclear debris were present. There\nwere no granuloma and no evidence of malignancy. The\nfindings were consistent with a diagnosis of \u2018acute febrile\nneutrophilic dermatitis\u2019. Bone marrow aspiration and\ntrephine biopsy showed a reactive marrow with no evidence\nof infiltration by malignancy.\n\n\n\nThe patient was diagnosed to have classical / idiopathic\nSweet\u2019s syndrome without any underlying malignancy. He\nwas treated with oral indomethacin 50mg three times a day,\nbut this was discontinued due to angioedema.\nCommencement of oral prednisolone 30mg daily led to a\ngradual resolution of fever, skin lesions and\nlymphadenopathy. As the prednisolone was tapered to a\ndose of 7.5mg daily, he had a relapse with fever and\nlymphadenopathy. A repeat of the investigations showed\nsimilar findings as previously. The dose of oral prednisolone\nwas increased to 30mg daily and oral azathioprine 50mg\ndaily was supplemented as a steroid sparing\nimmunosuppressant. He remained relatively well for 2 years\non a low dose of prednisolone and azathioprine. In mid\n2005, both his medications were stopped as he was in\nremission.\n\n\n\nHowever, less than a year later, in March 2006, he presented\nto UMMC with fever, right neck swelling and painful\nplaques on his neck and extremities. Physical examination\nrevealed that he was febrile with tender right cervical\nlymphadenopathy and multiple erythematous plaques and\npustules on the neck and extremities (Figure 1).\n\n\n\n\n\n\n\n\n108\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nInvestigations showed leukocytosis (29.8*109/L) with\nneutrophilia (89%), elevated CRP of 13.3 mg/dl and ESR\nof 66 mm/hour. Repeat of all blood investigations and\ncultures of urine, sputum and skin swabs were negative.\nHowever, computer tomography (CT) of thorax and pelvis\nwere normal. An abdominal CT however showed multiple\nhypodense lesions in the spleen, and a biopsy showed the\nsplenic tissues extensively infiltrated with small clusters of\nneutrophils. No organisms were cultured from the tissue. A\nrepeat skin biopsy showed evidence of focal spongiosis with\nperivascular infiltrates composed of a mixture of neutrophils\nand chronic inflammatory cells which was compatible with\na \u2018febrile neutrophilic dermatitis\u2019 histopathology.\n\n\n\nOral prednisolone was recommenced at 30mg daily with\ngradual tapering and discontinued in January 2007. On his\nrecent follow-up in April 2007, he was in remission and did\nnot require any medication.\n\n\n\nDiscussion\nSweet\u2019s syndrome was first described by Dr. Robert Douglas\nSweet in 1964 as an \u2018acute febrile neutrophilic dermatosis\u2019.\nThe syndrome is characterized by pyrexia, elevated\nneutrophil count, painful red papules, nodules and plaques\nand an infiltrate consisting predominantly of mature\nneutrophils diffusely distributed in the upper dermis1.\nEpidemiological studies of Sweet\u2019s syndrome did not reveal\nany racial predilection and it affects primarily the adult\npopulation. The peak incidence of Sweet\u2019s syndrome is\nbetween the fourth to seventh decade2. There are primarily\n\n\n\nthree subtypes of Sweet\u2019s syndrome3 : classical Sweet\u2019s\nsyndrome, malignancy-associated Sweet\u2019s syndrome and\ndrug-induced Sweet\u2019s syndrome5. The classical / idiopathic\nSweet\u2019s syndrome has a greater female predominance\nespecially those in the third to fifth decade4. This form of\nSweet\u2019s syndrome     can be preceded by an upper respiratory\ntract or gastrointestinal infection or associated with\ninflammatory bowel disease4.\n\n\n\nThe specific pathogenesis of Sweet\u2019s syndrome is unknown.\nChromosomal anomalies have been reported in a few\npatients with hematological malignancy-associated Sweet\u2019s\nsyndrome. Abnormality of chromosome 3q has been\ndescribed in three Sweet\u2019s syndrome patients with\nhematological malignancy. Sweet\u2019s syndrome has also been\nlinked to a form of hypersensitivity reaction to bacterial,\nviral or tumour antigen as evident by the characteristics of\nskin lesions and also excellent response of signs and\nsymptoms to systemic corticosteroids1. It has been\npostulated that the hypersensitivity reaction in turn leads to\ncytokine stimulation with subsequent neutrophilic\nactivation2. Cytokines which may potentially play a role in\nthe pathogenesis of Sweet\u2019s syndrome include granulocyte\ncolony stimulating factor (GCSF), granulocyte macrophage\ncolony stimulating factor (GMCSF), interferon-gamma,\ninterleukin-1, interleukin-3, interleukin-6 and interleukin-\n84. These are supported by the significant elevation of serum\ninterleukin-1-alpha, interleukin-1-beta, interleukin-2 and\ninterferon-gamma in patients with Sweet\u2019s syndrome.\n\n\n\nFigure 1. Figure 2\n\n\n\n\n\n\n\n\n109\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nSu and Liu proposed a diagnostic criteria for Sweet\u2019s\nsyndrome in 1986 shown in the diagram above.\n\n\n\nOur patient has fulfilled both the major and three out of\nfour of the minor criteria: pyrexia >38\u02daC, excellent response\nto systemic corticosteroids, raised ESR, positive CRP,\nleukocytosis and neutrophilia.\n\n\n\nIn addition, this patient also presented with extracutaneous\nmanifestation as evidenced by the aseptic splenic abscess.\nThese hypodense lesions in the spleen resolved completely\nwithin 3 months of treatment initiation with\ncorticosteroids, which is in keeping with the natural history\nof this disease (Figure 2). So far in the literature search,\nextracutaneous involvement of bone, lungs, liver, kidneys\n\n\n\nheart, eyes and joints have been described. Nevertheless,\nthere is only one case of Sweet\u2019s syndrome with aseptic\nsplenic lesions reported in a case of Sneddon-Wilkinson\u2019s\ndisease7 .\n\n\n\nSystemic corticosteroids remain the gold standard for the\ntreatment of classical Sweet\u2019s syndrome. Systemic steroids\nprovide prompt relief of cutaneous and systemic symptoms.\nThe dosage of prednisolone used is usually 1mg/kg/day\nwith gradual tapering within 4 - 6 weeks. Nevertheless,\nsome patients may require a longer duration of treatment or\neven daily pulse intravenous treatment during acute\npresentation, followed by tapering of oral dose of\ncorticosteroid or another immunosuppressant agent to\nachieve optimal disease control4.\n\n\n\nMajor criteria\n\n\n\nMinor criteria\n\n\n\n\u2022 Abrupt onset of painful erythematous plaques or nodules\n\n\n\n\u2022 Histopathologic evidence of a dense neutrophilic infiltrate without evidence of \nleukocytoclastic vasculitis\n\n\n\n\u2022 Pyrexia > 38\u2019C\n\n\n\n\u2022 Association with an underlying haematologic or visceral malignancy,\ninflammatory disease, or pregnancy, or preceded by an upper respiratory or \ngastrointestinal infection or vaccination\n\n\n\n\u2022 Excellent response to treatment with systemic corticosteroids or potassium \niodide\n\n\n\n\u2022 Abnormal laboratory values at presentation (3 of 4): ESR >20mm/hour,\npositive CRP, >8,000 leukocytes >70% neutrophils\n\n\n\n* Both major criteria and 2 of the 4 minor criteria are required to establish a diagnosis of classical Sweet\u2019s syndrome.\n\n\n\nMultiple hypodense splenic lesions. Hypodense lesions completely resolved after initiation of\nsteroids therapy\n\n\n\n\n\n\n\n\n110\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOther pharmacotherapeutic agents which have been found\nto have therapeutic efficacy include potassium iodide,\ncolchicine, indomethacin, dapsone, clofazimine,\ncyclosphosphamide and cyclosporine4, 6, 7.\n\n\n\nReferences\n\n\n\n1. Cohen PR, Kurzock R. Sweet\u2019s syndrome: a review of current \ntreatment options. Am J Clin Dermatol 2002; 3(2):117-31.\n\n\n\n2. Edwin K Joe. Sweet syndrome. Dermatology Online Journal 9(4): \n27.  ???year\n\n\n\n3. Cohen PR, Kurzrock R. Sweet\u2019s syndrome: A Neutrophilic \nDermatosis Clasically Associated with Acute Onset and Fever. \nClinics in Dermatology 2000;18:265-282.\n\n\n\n4. Cohen PR. Sweet\u2019s syndrome. Orphanet Encyclopedia. October \n2003. http://www.orpha.net/data/patho/GB/uk-Sweet.pdf\n\n\n\n5. Walker DC, Cohen PR: Trimethoprim-silfamethoxazole-\nassociated acute febrile neutrophilic dermatosis: Case report \nand review of drug-induced Sweet\u2019s syndrome. J Am Acad \nDermatol 1996; 34:918-23.\n\n\n\n6. Jeanfils et al. Indomethacin treatment of eighteen patients with \nSweet\u2019s syndrome. J Am Acad Dermatol 1997; 36:436-9.\n\n\n\n7. R Quilichini, F Mazzerbo et al. Syndrome de Sweet et Abces \naseptiques de la rate. Rev Med Interne 1996;17:1029-1031.\n\n\n\n8. Maillard H, Leclech C, Peria P, Avenel-Audan M, Verret JL. \nColchicine for Sweet\u2019s syndrome. A study of 20 cases. Br J  \nDermatol 1999; 140(3):565-566.\n\n\n\nSplenic tissues extensively infiltrated with small clusters of\nneutrophils.\n\n\n\n\n\n\n\n\n111\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nCutis Marmorata Telangiectatica Congenita in a\n3-month-old infant\n\n\n\nSM Wong, MBChB, MRCP and LC Loh, MBChB, MRCP\n\n\n\nDermatology Unit, Department of Medicine\nUniversity Malaya, Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nDr Loh LC, MBChB, MRCP,\nDermatology Unit, Department of Medicine\nUniversity Malaya, Kuala Lumpur\nEmail : LCLOH@ummc.edu.my  \n\n\n\nCutis marmorata telangiectatica congenita (CMCT) is an\nuncommonly reported, sporadic, congenital cutaneous\ndisorder with persistent cutis marmorata, telangiectasia, and\nphlebectasia. It may be associated with a variety of other\ncongenital anomalies, including but not limited to\nundergrowth or overgrowth of an involved extremity. We\nreport a case of a baby with CMCT.\n\n\n\nCase Report \nA 3-month-old male baby presented with an erythematous\nrash on the right thigh and leg since birth and had gradually\nfaded over the months. He was the only child in the family\nand had been otherwise well and healthy. Antenatal and\npostnatal histories were normal. There was no maternal\nfamily history of similar problem and the mother is a single\nparent with no past medical history. An ultrasound scan of\nthe abdomen by a private pediatrician showed normal\nkidneys.\n\n\n\nOn examination, there was a reticulate erythema on the\nright thigh and leg (Figure. 1). A lighter similar rash was\nseen on the right side of the abdomen. The right leg was\nslightly smaller than the left. Other physical examination\nand the developmental assessment for his age were normal.\nA diagnosis of cutis marmorata telangiectatica congenita\nwascongenita was made based on the clinical findings. His\nmother was not keen on further evaluation of the associated\nlimb asymmetry. On follow up he showed further\nimprovement of his condition.\n\n\n\nDiscussion\nCutis marmorata telangiectatica congenital (CMTC) is a\ncongenital cutaneous vascular phenomenon presenting with\nreticulate, mottled blue-violet discoloration at birth or early\ninfancy. It was first described in 1922 by the Dutch\npediatrician, Van Lohuizen. It has been known less\ncommonly as congenital generalised phleblectasia, naevus\nvascularis reticularis, congenital livedo reticularis and Van\nLohuizens Syndrome.\n\n\n\nFigure 1. Reticulate erythema on the right thigh and leg\n\n\n\n\n\n\n\n\n112\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe pathophysiology of CMTC remains unclear, and the\ncause may be multifactorial. Various theories have been\nsuggested including an unknown environmental factor1,\nautosomal dominant inheritance and elevated maternal\nserum human chorionic gonadotrophin hormone levels\nduring pregnancy2. Most cases occur sporadically, although\nrare cases occur in families. There have been only two\nreports in the literature describing autosomal dominant\ninheritance of CMCT within a family3. Several case reports\nshow a female preponderance or equal sex incidence.\n\n\n\nThe distribution can be localized (often unilateral) as in this\ncase, or generalised, although never involving the whole\nbody. There is a full spectrum of severity ranging from faint\nreticular, patchy skin changes to ulceration and scarring.\nCapillary malformations (ie, nevus flammeus), capillary and\ncavernous hemangioma, atrophy or hypertrophy of the\naffected extremity, macrocephaly4 (macrocephaly cutis\nmarmorata telangiectatica congenita syndrome), and\nglaucoma5 may also be associated with CMCT.\n\n\n\nDiagnosis is clinical. Biopsies are not necessary as histology\nfindings are non-specific and non-diagnostic. Microscopic\nfindings include dilated veins and capillaries, or increased\nnumber of vessels.\n\n\n\nIt is important to differentiate CMTC from other skin\nconditions presenting with a reticulate dermatosis. These\ninclude:\na) Physiological cutis marmorata with a symmetrical \n\n\n\npattern, which is transient in nature, appearing with \ncold and disappearing with re-warming. It is common in \nyoung infants.\n\n\n\nb) Portwine stain with a reticulate pattern may create \nconfusion. It may co-exist with CMTC.\n\n\n\nc) Neonatal lupus erythematosus. A serology test should \nbe done if there is neonatal heart block and/ or a \nmaternal history of lupus.\n\n\n\nd) Brockenheimer's diseases: a rare progressive deep \nvenous malformation that begins in childhood and \ncarries a poor prognosis.\n\n\n\nd) Klippel-Trenaunay Syndrome with vascular lesions \nassociated with asymmetrical hypertrophy of soft tissue \nor bones.\n\n\n\ne) Bluish mottled skin may also be seen in Down's \nSyndrome, homocystinuria, and Lange Syndrome but \nthe other co-existing clinical features of these conditions \nwill differentiate them from CMTC.\n\n\n\nThe prognosis of CMTC is good. Skin lesions usually\nimprove, especially during the patient's first 2 years of life\nwith spontaneous resolution by adolescence or early\nadulthood. This phenomenon is attributed to skin\nmaturation. No treatment is needed unless associated\nanomalies (eg, glaucoma, hypospadias, syndactyly, cranial\nabnormalities, limb asymmetry) require treatment. In these\ncases, consultation with an orthopaedic surgeon and/or\nneurosurgeon may be necessary for evaluation of associated\nanomalies. Consultation with an ophthalmologist may be\nnecessary because glaucoma has been reported in\nassociation with CMTC. However, all patients with\nglaucoma have periocular skin changes around the affected\neye. Therefore, ophthalmologic evaluation is less indicated\nin this setting.\n\n\n\nCTMC is a rare benign congenital vascular abnormality\npresenting with reticulate discoloration involving varying\nextent of the body. Diagnosis is clinical and made by\nexclusion of other differential diagnoses. A careful\nexamination should be made for associated abnormalities.\nCMTC has a favorable prognosis with partial or complete\nresolution during adolescence and therefore needs no\nspecific therapy.\n\n\n\nReferences\n\n\n\n1. Rogers M, Poyzer KG. Cutis marmorata telangiectatica \ncongenita. Arch Dermatol 1982; 118:895-899. \n\n\n\n2. Chen CP, Chen HC, Liu FE et al. Cutis marmorata telangiectatica \nassociated with an elevated maternal serum human chorionic \ngonadotrophin level and transitory fetal ascites. Br J Dermatol \n1997; 136:267-271. \n\n\n\n3. Kurczynski TW Hereditary cutis marmorata telangiectatica \ncongenita. Pediatric 1982; 70:52-53. \n\n\n\n4. Moore C, Toriello H, Abuelo D et al. Macrocephaly/CMTC:a \ndistinctive disorder with development delay and connective \ntissue abnormalities. Am J Med Genet 1997; 70:67-73.\n\n\n\n5. Weilepp AE, Eichenfield LE. Association of glaucoma with cutis \nmarmorata telangiectatica congenita: a localized anatomic \nmalformation. J Am Acad Dermatol 1996; 35:276-8. \n\n\n\n\n\n\n\n\n113\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nUveitis: A presenting sign of both secondary syphilis \nand HIV Infection\n\n\n\nChoon SE, MBBS FRCP1, Lee CK, MBBS1, Loh SS, MBBS, FRCS2 and Tey KE, MD, MRCP, MMed1\n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah\nJohor Bahru, Johor\n2Department of Ophthalmology, Hospital Sultanah Aminah\nJohor Bahru, Johor\n\n\n\nCorrespondence\n\n\n\nDr SE Choon, MBBS FRCP,\nDepartment of Dermatology, Hospital Sultanah Aminah\nJohor Bahru 80100, Johor, Malaysia\nEmail : choonse@yahoo.co.uk\n\n\n\nIntroduction\nUveitis is a well-documented presentation of syphilis with\nor without concomitant HIV infection1,2. Syphilitic uveitis\noccurs most frequently during secondary and tertiary phases\nof the infection and its prevalence has declined in tandem\nwith the decline in syphilis prevalence during the early\nphase of the HIV epidemic. However, during the past 5\nyears, there has been a resurgence of syphilis and an\nincreased number of patients with ocular syphilis has been\nreported3,4. Early diagnosis of ocular syphilis which is highly\namenable to simple antibiotic treatment can prevent\nblindness. Unfortunately, the ocular manifestations of\nsyphilis are indistinguishable from that of other causes.\nHence, a high index of suspicion is necessary to diagnose\nsyphilitic uveitis. Awareness and recognition of concurrent\nsyphilitic skin involvement, often mistaken for psoriasis, can\naid in the diagnosis. We describe a patient whose ocular\nsyphilis was diagnosed and treated promptly because of the\npresence of a palmoplantar rash.\n\n\n\nCase Report\nA 69-year-old Chinese gentleman presented with a 2- week\nhistory of left eye pain and photophobia. He was diagnosed\n\n\n\nto have bilateral panuveitis for which he was admitted to\nour hospital for further management. A palmoplantar rash\nwas noted and he was referred to us for possible\npalmoplantar psoriasis. He gave a 1-month history of scaly\nskin lesions that affected both his palms and soles but\ndenied any previous skin problem including genital rash and\nulcer. He had intermittent arthralgia affecting his knees and\nankles. He has been separated from his wife for the past 20\nyears but had a regular sexual partner for 10 years when he\nwas younger. He is retired but used to work as a general\nworker in the logging industry. His last sexual exposure was\n3 years ago when he had unprotected genital sex with a\ncommercial sex worker.\n\n\n\nPhysical examination revealed multiple erythematous scaly\nplaques on his palms and soles (Figure 1, 2, 3). Ocular\nexamination revealed bilateral injected eyes with a best-\ncorrected visual acuity of perception to light for his left eye\nand 6/60 for his right eye. Right eye had dense vitritis with\nfocal retinochoroiditis and hyperaemic disc. Left eye had\ncataractous lens with seclusio pupillae and poor fundal\nview. Intraocular pressures of both eyes were normal.\nNeurological examination was unremarkable.\nCardiovascular\n\n\n\nFigure 1: Erythematous scaly plaques on right palm Figure 2: Erythematous scaly plaques on left palm\n\n\n\n\n\n\n\n\n114\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCardiovascular examination revealed a pansystolic murmur,\ngrade 3/6 over the left sternal edge radiating to the whole\nchest wall with no evidence of heart failure. There was no\nhepatosplenomegaly or palpable lymph nodes.\n\n\n\nBoth serum Treponema pallidum particle agglutination test\n(TPPA) and Rapid plasma reagin test (RPR ) were positive.\nSerum RPR titer was 1:64. Lumbar puncture revealed a\nclear and colourless cerebrospinal fluid (CSF) with positive\nCSF-VDRL, a pleocytosis of predominantly neutrophils\n(>10 cells per high power field with 70% polymorph) and a\nraised CSF protein of 64 g/L with normal glucose level. He\nwas also found to be HIV positive with a CD 4 count of 433\ncells/\u03bcL. His CD4 to CD8 ratio was 0.34.\n\n\n\nChest radiography showed cardiomegaly with enlarged\nright ventricle and atrium. Echocardiography showed\nminimal pericardial effusion with severe tricuspid\nregurgitation and tricuspid valve prolapse. Right atrium and\nventricle were dilated with paradoxical septal motion.\nEjection fraction was 70%.\n\n\n\nThe patient was given intravenous crystalline penicillin 4\nmega units 4 hourly (24 mega units daily) for 2 weeks. He\nwas referred to our infectious disease specialist and\ncardiologist for further management of his retroviral\ninfection and heart problem. He responded well to\ntreatment.\n\n\n\nOn his last follow-up, 6 months post-treatment, his skin\nwas clear with a RPR titer  of 1:8. The best corrected vision\nfor his right and left eye improved to 6/12 and 6/36\nrespectively. The panuveitis resolved leaving behind\nextensive posterior synechiae of the left pupil. He rejected a\nrequest for a repeat CSF analysis.\n\n\n\nDiscussion\nUveitis is a well-documented although rare clinical\npresentation of syphilis. It is however, the commonest\nocular presentation of this ever-present sexually transmitted\nspirochaetal infection, accounting for 2.5% to 4.3% of\n\n\n\ncases1. Common ocular manifestations of syphilitic uveitis\ninclude granulomatous iridocyclitis, non-granulomatous\niridocyclitis, panuveitis and keratouveitis. Several reports on\nocular syphilis in HIV patients suggest that ocular\ninvolvement may be more common in this group of\npatients1,2,5.\n\n\n\nSeveral studies have linked syphilis with HIV\nseroconversion 6,7. The majority of the studies showed an\nincreased likelihood of HIV seroprevalence in persons with\nsyphilis compared to similar populations without syphilis.\nIn a review of several studies done in the  United States, the\nmedian HIV seroprevalence in patients with syphilis  was\n27.5% for men and 12.4% for women whereas the median\nHIV seroprevalence in persons without syphilis was 4.5 and\n2.7 for men and women, respectively.\n\n\n\nSecondary syphilis is a systemic disease and patients can\npresent with signs and symptoms referable to any system.\nThese include hepatitis, nephrotic syndrome, uveitis or\nneurosyphilis but the commonest presentation of secondary\nsyphilis is a non-irritating generalized maculopapular\neruption involving the palms and soles8. In our patient, the\npresence of a palmoplantar rash helped us to clinch the\ndiagnosis of syphilis which led to the detection of a\nconcomitant HIV infection. We routinely screen all our\npatients with STDs for retroviral infection because of the\nhigh prevalence of HIV infection in these patients. Syphilis\ndoes not appear to be a more common cause of uveitis in\nHIV-infected patients as compared to cytomegalovirus,\nherpes simplex virus and toxoplasmosis which still remain\nimportant culprits1. However, early treatment of ocular\nsyphilis can prevent blindness, making it a worthwhile\neffort to screen all patients with uveitis for syphilis.\n\n\n\nOcular syphilis is more common in HIV-infected patients,\nand, it may be more severe and associated with a higher\nprevalence of neurosyphilis making HIV screening\nparticularly important in syphilitic uveitis1,2,5. Our patient\nhad severe panuveitis with dense vitritis similar to that\ndescribed by Kuo et al probably because of the concomitant\nHIV infection5. The positive CSF-VDRL with CSF\npleocytosis and a raised CSF protein satisfy the criteria for\nthe diagnosis of neurosyphilis but HIV patients often have\npleocytosis and raised proteins in their CSF making these\ndiagnostic parameters less helpful9. It is important to rule\nout neurosyphilis in HIV patients because of reports of\nmore severe disease, treatment failure and reactivation.\nCentre for Disease Control, Atlanta recommends lumbar\npuncture for all HIV-infected patients with late latent\nsyphilis or syphilis of unknown duration. A recent study\nshowed that neurosyphilis is commoner in patients with a\nserum RPR titer of 1:32 and suggested performing a lumbar\npuncture only for those with signs and symptoms suggestive\nof neurosyphilis or those with a  serum RPR titer of 1:329.\nWe routinely perform lumbar puncture for all patients with\nocular syphilis but treat all ocular syphilis with intravenous\ncrystalline penicillin regardless of CSF findings and use\nabnorma\n\n\n\nFigure 3: Erythematous scaly plaques on right sole\n\n\n\n\n\n\n\n\n115\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nabnormal CSF findings to monitor treatment of associated\nneurosyphilis. Our patient responded very well to crystalline\npenicillin with marked improvement in his vision. The best\ncorrected visual acuity improved from only perception to\nlight to 6/36 for his left eye and from 6/60 to 6/12 for his\nright eye.\n\n\n\nConclusion\nDuring the past 5 years, there has been a resurgence of\nsyphilis with an increasing number of ocular syphilis being\nreported as an initial presentation. Diagnosis of ocular\nsyphilis requires a high index of suspicion since the ocular\nmanifestations are non-specific. The presence of a\npalmoplantar rash with uveitis is highly suggestive of\nsyphilis but even without skin manifestation, it is prudent to\nscreen all patients with uveitis for syphilis which can lead to\nblindness if left untreated or treated late. All patients with\nSTDs particularly syphilis should be screened for HIV\ninfection and all patients with ocular syphilis should be\nassessed for neurosyphilis and treated as neurosyphilis\nregardless of CSF findings.\n\n\n\nReferences\n\n\n\n1. Aldave AJ, King JA, Cunningham ET. Ocular sypphilis. Current \nOpin Opthalmol 2001;12:433-441\n\n\n\n2. Guadio PA. Update on Ocular Syphilis. Curr Opin Ophthalmol \n2006;17:562-566\n\n\n\n3. Primary and secondary syphilis: United States, 2003-2004. \nMMWR Morb Mortal Wkly Rep 2006; 55: 269-273\n\n\n\n4. Simms I, Fenton KA, Ashton M, et al The Re-Emergence of \nSyphilis in the United Kingdom: The New Epidemic Phases. \nSexually Transmitted Diseases 2005; 32(4):220-226\n\n\n\n5. Kuo IC, Kapusta MA, Rao NA: Vitritis as the primary \nmanifestation of ocular syphilis in patients with HIV infection. \nAm J Ophthalmol 1998, 125: 306-311\n\n\n\n6. Weintrob AC, Crum-Cianflone N, Michael NL. Syphilis and \nHuman Immunodeficiency Virus Coinfection: More Than the \nSum of Its Parts. Infect Dis Clin Pract 2006;14:197-203 \n\n\n\n7. Blocker ME, Levine WC, St Louis ME. Prevalence of HIV in \npatients with syphilis, United States. Sex Transm Dis 2000;27:\n53-59\n\n\n\n8. French P. Syphilis: Clinical Review. BMJ 2007;334:143-147\n9. Libois A, De Wit S, Pol B, et al. HIV and Syphilis: \n\n\n\nWhen to Perform a Lumbar Puncture Sexually Transmit Dis 2007; \n34:141-144\n\n\n\n\n\n\n\n\n116\n\n\n\n\n\n\n\n\n117\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nKaposi\u2019s Sarcoma in a 35-year-old homosexual \n\n\n\nTan WC, MD1, Lo Kang SC, MD, MRCP, MMed1, Ong CK, MD, MRCP2, Leong KN, MBBS, MRCP2\n\n\n\nand Subathra S, MBBS, MPath3\n\n\n\n1 Department of Dermatology, Penang Hospital\n2 Department of Medicine, Penang Hospital\n3 Department of Pathology, Penang Hospital\n\n\n\nCorrespondence\n\n\n\nTan Wooi Chaing, MD,\nDepartment of Dermatology\nHospital Pulau Pinang, Jalan Residensi, 10450 Penang\n\n\n\nKaposi\u2019s sarcoma (KS) is strongly associated with Human\nHerpes Virus 8 (HHV8) and Human Immunodeficiency\nVirus infection (HIV). It was the first malignancy to be\nlinked with Acquired Immunodeficiency Syndrome\n(AIDS) and it is still the most commonly encountered\nmalignancy associated with HIV. We report a case of\nKaposi\u2019s sarcoma in a homosexual man.\n\n\n\nCase Report\nA 35-year-old Chinese homosexual first presented in\nNovember 2004 with prolonged fever for 2 months, which\nwas associated with shortness of breath and significant\nweight loss. He was noted to have multiple painless, non\npruritic, purplish plaque-like lesion, involving the face and\ntrunk for past 4 months.\n\n\n\nOn examination, he had multiple firm discrete violaceous\nplaques and nodules scattered over the hard palate, trunk\nand face (Figure 1). Systemic examination revealed oral\nthrush, hepatosplenomegaly, multiple cervical and inguinal\nlymph nodes.\n\n\n\nLaboratory investigations showed normochromic anaemia,\nhigh erythrocyte sedimentation rate (ESR) and deranged\nliver function test. Serological tests for syphilis, hepatitis B\nand C were non reactive. Sputum culture, acid fast bacilli\n(AFB) smear and AFB culture were negative.\n\n\n\nChest x-ray and Computed Tomography of the thorax\nshowed mediastinal and abdominal lymphadenopathy,\nascites and pleural effusion. The Enzyme-Linked\nImmunosorbent Assay (ELISA) screening test was positive\nfor HIV-1 and the Western blot confirmed the diagnosis.\nThe CD4 count was 60 cells/\u03bcL. Punch biopsy from a skin\nnodule and lymph node biopsy confirmed Kaposi\u2019s sarcoma\n(Figure 2).\n\n\n\nHe was started on PCP prophylaxis and Highly Active\nAntiretroviral Therapy (HAART - Indinavir / Ritonavir /\nEfavirenz). The skin lesions responded well to HAART.\nUnfortunately, patient defaulted treatment and succumbed\nto disease after 12 months of the diagnosis.\n\n\n\nFigure 1.   Multiple dark red plaque and nodules over\nface, scalp and hard palate\n\n\n\nFigure 2.   (skin histopathology slide of x10) : Skin slide\nshowed underlying dermis showing angiosarcomatous\ncomponent which composed of numerous slit like congested\nvascular channels. Extravasation of red blood cells are noted.\nImmunohistochemical stains for Factor VIII antigen is positive.\n\n\n\n\n\n\n\n\n118\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nHIV disease presentation has dramatically changed since\nthe introduction of antiretroviral therapy (ART). ART has\nreduced both the morbidity and the mortality associated\nwith HIV1. However, HIV-infected individuals still have an\nincreased risk of developing a malignancy compared with\nthe general population2. Kaposi\u2019s sarcoma is the most\ncommon HIV-related malignancy.\n\n\n\nKaposi\u2019s sarcoma is first described by Dr Moritz Kaposi in\n1872. HIV-associated or Epidemic Kaposi\u2019s sarcoma is an\naggressive form of the disease. Kaposi\u2019s sarcoma is one of\nthe AIDS defining skin diseases. It is strongly linked to\nHHV 8 and male homosexual behavior. It is characterized\nby few or widespread multifocal brown violaceous or dark\nred colour patches, papules, plaques and/or deep skin\nnodules. Typically, the lesions are bilateral, symmetrically\ndistributed along the lines of skin cleavage, involving the\nextremities. These lesions may involve the skin, mucosal\nmembranes, lymph nodes and visceral organs such as the\ngastrointestinal tract, lungs, liver and spleen.\n\n\n\nThe mucocutaneous Kaposi\u2019s sarcoma lesions are usually\nasymptomatic, it may be single or multiple and sometimes\nappear simultaneously or sequentially. The skin lesions can\nappear over the face, trunk or extremities, particularly\nbehind the ears and the earlobes. Oropharyngeal lesions are\nseen over the hard and soft palate, gingival and buccal\nmembrane.\n\n\n\nIf left untreated, the median survival is 18 months. But with\nthe introduction of ART, there is a marked decline in the\nincidence (30-50%), morbidity, and mortality (81%)3.\nCurrently, ART is the first-line therapy for Kaposi\u2019s\nsarcoma in patients with low CD4 counts and/or high viral\nloads. First-line treatment for Kaposi\u2019s sarcoma in patients\nwith CD4 counts greater than 350 cells / \u03bcL is unclear4.\n\n\n\nIn aggressive disease, liposomal doxorubicin or\ndaunorubicin are the first-line chemotherapeutic agents.\nPaclitaxel is a safe and effective alternative monotherapy,\nwith response rates ranging from 59% to 71%. Other agents\nused alone or in combination include vinca alkaloids5,\nbleomycin6 and Granulocyte Macrophage Colony\nStimulating Factor (GM-CSF). Less commonly used\nsystemic approaches include interferon alpha, thalidomide,\nsystemic retinoids, and human chorionic gonadotrophin.\n\n\n\nThere are many options for local treatment which include\nradiotherapy, electron beam therapy, photodynamic therapy,\nliquid nitrogen, intralesional vinca alkaloids, intralesional\ninterferon alpha and the others.\n\n\n\nPrognosis of Kaposi\u2019s sarcoma depends on the extent of the\ndisease (tumour burden), the presence or absence of\nsystemic B symptoms (fever, weight loss >10%) and the\npresence of opportunistic infections7.\n\n\n\nDespite the marked reduction in morbidity and mortality\nfrom HIV with the introduction of ART, the excess\nmalignancy in this population has not reduced. New\nchallenges like drug resistance, treatment complications and\nincreased incidence of malignancies have been noted in this\ngroup of patients who are now living longer.\n\n\n\nAcknowledgement\nWe are most grateful to the infectious disease team, surgical\nteam and pathologist from Penang Hospital for co\nmanaging Mr. L.\n\n\n\nReferences\n\n\n\n1. Porter K, Babiker A, Bhaskaran K, Darbyshire J, Pezzotti P, \nWalker AS. Determinants of survival following HIV-1 \nseroconversion after the introduction of HAART. Lancet \n2003:362: 1267-1274.\n\n\n\n2. Giordano GG, Sigalotti L, Maio M. New dimensions in cancer \nbiology and therapy. J Cell Physiol 2000: 183: 284-287.\n\n\n\n3. Jones JL, Hanson DL, Dworkin MS, Jaffe HW. Incidence and \ntrends in Kaposi\u2019s sarcoma in the era of effective antiretroviral \ntherapy. J AIDS 2000: 24: 270-274.\n\n\n\n4. Chan J, Kravcik S, Angel JB. Development of Kaposis\u2019s sarcoma \ndespite sustained suppression of HIV plasma viremia. J AIDS \n1999: 22: 209-210.\n\n\n\n5. Tulpule A, Groopman J, Saville MW et al. Multicenter trial of \nlow-dose paclitaxel in patients with advanced AIDS related \nKaposi\u2019s sarcoma. Cancer 2002: 95: 147-154.\n\n\n\n6. Hernandez DE, Perez JR. Advanced epidemic Kaposi\u2019s sarcoma: \nTreatment with bleomycin or combination of doxorubicin, \nbleomycin, and vincristine. Int J Dermatol 1996: 35: 831-833.\n\n\n\n7. Krigel RL, Friedman-Kien AE. Kaposi\u2019s sarcoma in AIDS. In: De \nVita VTJ, Hellman S, Rosenberg SA, editors. AIDS Etiology, \nDiagnosis, Treatment and Prevention. JB Lippincott,\nPhiladelphia, 1985; 7: 185-209.\n\n\n\n\n\n\n\n\n119\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nExtramammary Paget\u2019s Disease in an elderly man\n\n\n\nKE Tey, MD, MRCP, MMed, AM1, SE Choon, MBBS, FRCP, AM1 and Noraida K, MBBS, MPath2\n\n\n\n1 Department Of Dermatology\n2 Department of Pathology\nHospital Sultanah Aminah, Johor Bahru\n\n\n\nCorrespondence\n\n\n\nDr KE Tey, MD, MRCP, MMed, AM,\nDepartment Of Dermatology, Hospital Sultanah Aminah\nJohor Bahru, 80100 Johor\nEmail : ketey08@yahoo.com\n\n\n\nIntroduction\nExtramammary Paget\u2019s disease (EMPD) is a rare form of\nadenocarcinoma observed in areas with numerous apocrine\nor eccrine glands. It is presumed to be a variant of epithelial\ncarcinoma, with potential to develop from or to be the cause\nof an underlying adenocarcinoma. The clinical\nmanifestation of EMPD is varied. The lesions appear as a\nsolitary patch with an eczematous surface and well-defined\nborders. Differential diagnoses include Bowen\u2019s disease,\npsoriasis, leukoplakia, superficial fungal infection and\neczematous dermatoses. Definitive diagnosis requires\nbiopsy of the lesion and immunohistochemical staining. In\nmost cases of non invasive or minimally invasive EMPD,\nsurgical resection with clear margins and careful follow up is\nrecommended, since the recurrence rates is high.\n\n\n\nCase report\nA 66-year-old male Chinese retired timber worker\npresented with reddish skin lesions on his left groin of 3\nyears duration. The skin lesions initially started as a small\n\n\n\nreddish patch, which gradually increased in size. They were\noccasionally itchy. He experienced no bowel or urinary\ndisturbances. He consulted general practitioners and was\ntreated for eczema and fungal infection, without\nimprovement.\n\n\n\nExamination revealed a large erythematous plaque with a\nwarty surface, with some areas of atrophy and telangiectasia\nover the left groin and scrotal skin measuring 8 x 7 cm in\nsize (Figure 1). His regional lymph nodes were not enlarged\nand he had no organomegaly.\n\n\n\nOur clinical diagnosis was Bowen\u2019s Disease with a\ndifferential diagnosis of Extramammary Paget\u2019s Disease.\nThe skin histology showed clusters of intraepithelial large\ntumour cells displaying ovoid, pleomorphic nucleoli and\nvacuolated cytoplasm. Mitoses are visible (Figure 2 & 3).\nThere were chronic inflammatory cells in the dermis. The\ntumour cells were stained positive with Carcinoembryonic\nAntigen  (CEA) (Figure 4) and Periodic Acid Schiff (PAS.)\n\n\n\nFigure 1.   Erythematous plaque with a\nwarty surface, some areas of atrophy and\ntelangiectasia over the left groin and scrotal\nskin\n\n\n\nFigure 2.   Clusters of Paget\u2019s cells with abundant\ncytoplasm and prominent nucleolus\n\n\n\n\n\n\n\n\n120\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe tumour cells showed diastase resistant cytoplasm with\nprominent hyperchromatic nucleus.\n\n\n\nImmunohistochemical stains for cytokeratin 20 (CK 20)\nand Human Melanoma, Black 45 (HMB 45) were negative.\nColonoscopy and cystoscopy examination were normal.\nThis was performed to exclude adenocarcinoma of\ngastrointestinal tract and urethra respectively.\n\n\n\nHe was referred to the urologist and plastic surgeon for wide\nexcisionwide excision of the lesion. The histology of the\nexcised lesion was consistent with EMPD, with excision\nmargin free of tumour.\n\n\n\nDiscussion\nExtramammary Paget\u2019s disease (EMPD) is a rare form of\nadenocarcinoma observed in areas with numerous apocrine\nor eccrine glands. This tumour was first described by\nCrocker in 1889. The clinical lesions and histological\nchanges are similar to Paget\u2019s disease of the Breast.\n\n\n\nThree patterns of EMPD have been described:\n\n\n\n1. An in situ epithelial form without associated carcinoma\n2. An epithelial form with associated adnexal carcinoma\n3. A form associated with visceral malignancy of either \n\n\n\ngenitourinary or the gastrointestinal tract.\n\n\n\nSeventy seven percent of patients with EMPD are women.\nIt is most common in postmonopausal Caucasian women,\nespecially in the 6th and 7th decades1. The common sites are\nthe vulva, perianal, scrotal and penile regions. Rarely, lesions\naffecting the thighs, buttocks, axillae, eyelids and external\near canal have been reported2.\n\n\n\nClinically, EMPD presents as an erythematous plaque with\na velvety surface, sometimes with exudation and crusting, or\nscaling. Pruritus is common. Occasionally the skin lesions\nshow hyperpigmentation, hypopigmentation, ulceration and\nleukoplakia.\n\n\n\nLong-standing lesions may be modified by repeated trauma,\nexcoriation or superimposed infection.\n\n\n\nOur patient presented with itchy skin lesion on the left\ngroin for 3 years and was treated as eczema and fungal\ninfection by various general practitioner with no\nimprovement. The clinical lesions of extramammary Paget\u2019s\ndisease can mimic other dermatoses such as eczema, tinea\ncruris, candida intertrigo, Bowen\u2019s disease, flexural psoriasis,\nerythrasma, lichen sclerosis, and superficial spreading\namelanotic melanoma. The diagnosis could be easily missed\nif diagnosis was not considered and biopsy not performed.\nHence, any eczematous or thickened lesions where apocrine\nglands are encountered, and which does not resolve with\nappropriate therapy should arouse the suspicion of Paget\u2019s\ndisease.\n\n\n\nEMPD is often associated with underlying malignancy. We\nhad investigated our patient for associated malignancy and\nhe did not have other associated malignancy. Various reports\nhave shown different percentages of associated malignancy\nover different durations of follow up. One case series\nreported a prevalence rate of 59%3 and two others found a\nvisceral malignancy prevalence rates of 86%4 and 50%5\n\n\n\nrespectively. Twenty five percent of EMPD is associated\nwith adnexal adenocarcinoma of the dermis. Twenty nine\npercent of the patients had concurrent or subsequent\ninternal malignancy1. Penile and scrotal Paget\u2019s is associated\nwith adenocarcinoma of the male genitourinary tract.\nPerianal Paget\u2019s disease has an association with colorectal\ncarcinoma. Vulval Paget\u2019s is associated with endometrial,\nendocervical, vaginal, urethral and bladder carcinoma.\n\n\n\nPaget\u2019s cells are large, with abundant pale cytoplasm with\nlarge nuclei and absent intercellular bridges. The cells are\ndispersed between keratinocytes. They form clusters,\nglandular structures or solid nests, and extrude into adnexal\nstructures. Chronic inflammatory cells are found in the\ndermis.\n\n\n\nFigure 3.   Multiple Paget\u2019s cells with vacuolated\ncytoplasm\n\n\n\nFigure 4.   The Paget\u2019s cells were stained positive\nwith CEA\n\n\n\n\n\n\n\n\n121\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nPaget\u2019s cell cytoplasm is positive with PAS and diastase\nresistant which suggest the cells are glandular in origin.\nMost cases of EMPD are strongly positive for CEA,\nespecially those without an associated cancer. Cytokeratin\n20 is found in cases of EMPD with an underlying\ncarcinoma. HMB45 does not react with Paget\u2019s cells in\nmammary or extramammary PD (to differentiate Paget\u2019s\ndisease from melanoma)\n\n\n\nThe differential histological diagnosis includes\npagetoidincludes pagetoid Bowen\u2019s disease and pagetoid\nsuperficial spreading melanoma. Bowen\u2019s disease can show a\npagetoid pattern of epidermal involvement but the\ninfiltrating atypical cells are squamous in origin.\nIntracellular mucin, signet cells and glandular structures are\npresent in Paget\u2019s disease but absent in Bowen\u2019s disease. In\ncases where morphological features of glandular\ndifferentiation are absent, immunohistochemical staining\n(Cam5.2, Epithelial Membrane Antigen (EMA), CEA\npositive in Paget\u2019s disease) will usually resolve the problem7.\n\n\n\nThe cells of Paget\u2019s and melanoma both contain melanin\ngranules. Reactive epidermal atypia is common in Paget\u2019s\nbut rare in melanoma. S100 and HMB45 are positive in\nmelanoma. HMB45 does not label Paget\u2019s cells. However,\nS100 is positive in 25% of mammary Paget\u2019s and\noccasionally positive in EMPD7.\n\n\n\nTreatment of EMPD includes wide surgical excision and\nsplit skin graft, Moh\u2019s micrographic surgery, radiation,\ncurettage, laser, cryosurgery, and topical 5 florouracil\n(5-FU)5,6.\n\n\n\nLocal recurrence is high (33%)8 and usually requires a wider\nlocal excision. With no underlying malignancy, EMPD has\na high local recurrence despite adequate excision. Multifocal\ninvolvement and difficulty in clinical delineation of\ncutaneous margins are major factors in relapse. With\nunderlying malignancy, the prognosis is poor. Helwig and\nGraham reported a mortality rate of 83%3. Therefore, close\nlong term follow up of all patents with EMPD is important\nto look for recurrence and development of associated\nmalignancy.\n\n\n\nConclusions\nEMPD is a rare, slow growing adenocarcinoma. The clinical\npresentation resembles eczema, psoriasis, fungal infection,\nand Bowen\u2019s disease. This tumour is often misdiagnosed\nand topical steroids or antifungal medication prescribed.\nAny eczematous or thickened lesions where apocrine glands\nare encountered, and which does not resolve with\nappropriate therapy should arouse the suspicion of Paget\u2019s\ndisease. Long term follow-up is required to detect\nrecurrence and the development of an associated cancer.\n\n\n\nAcknowledgement\nI would like to thank the Director General, Ministry of\nHealth, Malaysia, for his permission to publish this paper.\n\n\n\nReferences\n\n\n\n1. Chanda JJ : Extramammary Paget\u2019s disease. Prognosis and \nrelationship to internal malignancy. J Am Acad Dermatol \n1985;13:1009-1014  \n\n\n\n2. Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute \nexperiment with extramammary Paget\u2019s disease. Br. J. \nDermatol. 2000 Jan; 142(1):59-65 \n\n\n\n3. Helwig EB,Graham JH : Anogenital extramzammary Paget\u2019s \ndisease, a clinicopathological review. Cancer 1963; 16:387-403\n\n\n\n4. Nirav J.Metha et al : Extramammary Paget\u2019s disease South Med \nJ 2000 93(7):713-715.\n\n\n\n5. Beck DE, Fazio VW: Perianal Paget\u2019s disease. Dis Colon Rectum \n1987; 30 : 263-266\n\n\n\n6. Jensen SL et al : Paget\u2019s disease of anal margin. Br J Surg \n1988; 75:1089-1092\n\n\n\n7. J Lloyd, A M Flanagan; Mammary and extramammary Paget\u2019s \ndisease. J Clin Patholo 2000;53(10):742-749\n\n\n\n8. Banerjee Santanu et al : Case Reports-Extramammary Paget\u2019s \ndisease. Ind J of Dermatol 2005; 71(6) 417-420\n\n\n\n\n\n\n\n\n122\n\n\n\n\n\n\n\n\n123\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nChronic Arsenicism - a forgotten entity?\n\n\n\nVitharana K, MBBS, MD1, Janthorn Pakdeethai, MBBS2, Yong-Kwang Tay, MBBS, FRCP, FAMS2,\nLiu TT, MBBS, Dip Derm (London), FAMS2 and Poh WT, MBBS, FRCPA, FAMS2\n\n\n\n1 Department of Laboratory Medicine,\nChangi General Hospital, Singapore\n2 Division of Dermatology, Changi General Hospital, Singapore\n\n\n\nCorrespondence\n\n\n\nDr Janthorn Pakdeethai, MBBS,\nDivision of Dermatology, Changi General Hospital\n2 Simei Street 3, Singapore 529889\nEmail : janthorn@hotmail.com\n\n\n\nIntroduction\nArsenicism is now rare but is still a relevant disease as\narsenic is present in the environment and occupational\nsetting. Moreover, it is preventable and warrants long-term\nfollow-up for cutaneous and internal carcinoma.\n\n\n\nCase Report\nA 66-year-old Chinese man was referred to us with\nhyperkeratotic papules on palms and soles, on the\nbackground of cryptogenic cirrhosis Child\u2019s B, complicated\nby several episodes of hepatic encephalopathy. Cirrhosis\nwork-up was negative, including hepatitis A IgM, hepatitis\nB surface antigen, hepatitis C IgG, caeruloplasmin, copper\nand iron levels, smooth muscle antibody, anti-nuclear\nantibody, anti-neutrophil cytoplasmic antibody, anti-\ndouble-stranded DNA antibody, rheumatoid factor and\nalphafeto protein. Computerised tomography of the\nabdomen showed decompensated liver cirrhosis with portal\nhypertension and no hepatoma.\n\n\n\nHe had pancytopaenia (Hb 9.8 g/dL, WBC 1.3x103/\u03bcL,\nplatelet 83x103/\u03bcL). Bone marrow aspirate features were\nsuggestive of early myelodysplastic syndrome. The rest of\nthe investigations were negative (vitamin B12, folate, acute\nleukaemia, T cell CD4 and T cell CD8 panels). He was\n\n\n\nimmobile from peripheral neuropathy and declined any\nfurther tests.\n\n\n\nHe had a significant history of drinking well-water during\nhis teenage years but did not consume traditional Chinese\nmedicine (TCM) or arsenic-containing medications. He\nworked as a plumber and a contractor. He had no history of\nasthma or skin problems.\n\n\n\nClinically, he had signs of chronic arsenic poisoning, viz\nhypopigmented macules on the background of generalised\nhyperpigmentation, diffuse alopecia, palmoplantar punctate\nhyperkeratosis (Figure 1), Mee\u2019s lines (Figure 2) and\nbilateral ankle oedema. Skin biopsy showed features\nconsistent with arsenic keratosis. (Figure 3)\n\n\n\nDiscussion\nOur patient has chronic arsenicism, complicated by\ncirrhosis, pancytopaenia and peripheral neuropathy.\n\n\n\nArsenic is a ubiquitous metal found in naturally\ncontaminated drinking water and landfill in some areas of\nthe world1, 2, Chinese proprietary medicines3 and in\noccupational settings, including agricultural chemicals,\nmining, carpentry and manufacture of gallium arsenide\ncomputer microchips4.\n\n\n\nFigure 1.   Photograph shows\nhyperkeratotic papules on the index\nfinger, middle and ring fingers -\n\u2018arsenical keratosis\u2019\n\n\n\nFigure 2. Photograph shows transverse\nwhite lines on nails - \u2018Mee\u2019s lines\u2019\n\n\n\n\n\n\n\n\n124\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nIn acute exposure (medicinal, homicidal, suicidal), the\npatients present with nausea, vomiting, diarrhoea, fatigue,\nfacial oedema and acute renal failure. If survived, they often\ndevelop peripheral polyneuropathy, shedding of hair and\nnails and cutaneous signs of chronic arsenic poisoning.\n\n\n\nChronic arsenicism, in our local context, is due primarily to\ninorganic arsenic in traditional chinese medicine (TCM)5.\nThere is symmetrical mottled hyperpigmentation on the\nupper chest, axillae, nipples, groin, arms, legs, palms, soles\nand pressure points, which may become generalised, with\nsuperimposed hypopigmented macules, described as\n\u2018raindrops on a dusty road\u2019. Alopecia, nasal perforation,\nperipheral neuropathy, encephalopathy, haematologic\nabnormalities, hypertension, chronic lung disease,\ncirrhosis, diabetes mellitus, oedema of legs, digital cyanosis\nand necrosis of the legs (black foot disease) may occur6.\n\n\n\nThere is a risk of developing cutaneous malignancy (basal\ncell carcinoma (BCC), Bowen\u2019s disease (squamous cell\ncarcinoma in situ), squamous cell carcinoma (SCC)) from\narsenical ketasoses (ArKs) and internal cancers (lung,\nstomach, colon, liver, kidney, bladder and hematopoietic\nsystem)1, 2. The current WHO and US Environmental\nProtection Agency sets a maximum arsenic contaminant\nlimit at 0.05mg/L7, although at this level, some carcinoma\nmay still develop.\n\n\n\nArKs are precancerous6,8 punctate, yellow, corn-like, easier-\nfelt-than-seen papules (2-5 mm), which may become large,\ndiscrete confluent elevations (>5 mm) with a nodular, wart-\nlike or horny appearance. They typically appear several years\nafter the first exposure, symmetrically distributed on palms\n(thenar and hypothenar eminences, lateral aspects of\nfingers, dorsal aspects of interphalangeal joints) and weight-\n\n\n\nbearing plantar surface, and occasionally on the trunk,\nproximal extremities, eyelids, penis and scrotum.\n\n\n\nArsenic-induced BCC are multiple, randomly scattered,\nprimarily on the trunk and in hair-bearing regions.\nArsenical Bowen\u2019s disease appear initially as skin-coloured\nto red papules. The papules may enlarge and become\nkeratotic. The crust, when removed, reveals a red, oozing\nand papillomatous base. Arsenic-related SCC can arise de\nnovo or from malignant transformation of ArKs and\nBowen\u2019s disease3. A diagnosis of ArKs and chronic\narsenicism should be considered when numerous\ncharacteristic keratoses are seen on the palms and soles or\nwhen multiple lesions of BCC, Bowen\u2019s disease or SCC are\nfound on an individual, especially in sun-protected areas of\nthe body.\n\n\n\nChelation therapy with Dimercaprol (British anti-lewisite;\nBAL) is the mainstay in acute arsenicism. ArKs can be\ntreated by cryotherapy, curettage, topical chemotherapy\n(5FU9), topical immunomodulator (5% imiquimod10), oral\nacitretin11 and photodynamic therapy. Vitamin E and\nselenium, which works by impeding the carcinogenic effects\nof DNA damage, shows promise as potential treatments for\nthese skin lesions12, 13.\n\n\n\nReferences\n\n\n\n1. Piamphongsant T. Chronic environmental arsenic poisoning. Int \nJ Dermatol 1999; 38: 401-410.\n\n\n\n2. Schwartz RA. Arsenic and the skin. Int J Dermatol 1997; 36: 241-\n250.\n\n\n\n3. Wong SS, Tan KC, Goh CL. Cutaneous manifestations of chronic \narsenicism: review of seventeen cases. J Am Acad Dermatol \n1998; 38: 179-185.\n\n\n\n4. Schwartz, RA. Premalignant keratinocytic neoplasms. J Am \nAcad Dermatol 1996; 35: 223-242.\n\n\n\n5. Tay CH, Seah CS. Arsenic poisoning from anti-asthmatic herbal \npreparations. Med J Aust 1975; 2: 424-428.\n\n\n\n6. National Research Council (U.S.) Subcommittee on Arsenic in \nDrinking Water. Arsenic in Drinking Water. Washington, DC: \nNational Academy Press 1999.\n\n\n\n7. Col M et al. Arsenic-related Bowen\u2019s disease, palmar keratosis, \nand skin cancer. Environ Health Perspect 1999; 107: 687.\n\n\n\n8. Alain G, Tousignant J, Rozenfarb E. Chronic arsenic toxicity. Int \nJ Dermatol 1993; 32: 899-901.\n\n\n\n9. Khandpur S, Sharma VK. Successful treatment of multiple \npremalignant and malignant lesions in arsenical keratosis with a \ncombination of acitretin and intralesional 5-fluorouracil. J \nDermatol 2003; 30: 730-734.\n\n\n\n10. Boonchai W. Treatment of precancerous and cancerous lesions \nof chronic arsenicism with 5% imiquimod cream. Arch Dermatol \n2006; 142: 531-532. \n\n\n\n11. Yerebakan O, Ermis O, Yilmaz E, et al. Treatment of arsenical \nkeratosis and Bowen\u2019s disease with acitretin. Int J Dermatol \n2002; 41: 84-87.\n\n\n\n12. Liu SX, Athar M, Lippai I, et al. Induction of oxyradicals by \narsenic: implication for mechanism of genotoxicity. Proc Natl \nAcad Sci USA 2001; 98: 1643-1648.\n\n\n\n13. Hsueh YM, Ko YF, Huang YK, et al. Determinants of inorganic \narsenic methylation capability among residents of the Lanyang \nBasin, Taiwan: arsenic and selenium exposure and alcohol \nconsumption. Toxicol Lett 2003; 137: 49-63.\n\n\n\nFigure 3. H&E stain of a section of skin.\n10x magnification. Epidermis shows marked\nhyperkeratosis with focal parakeratosis and\nmild spongiosis. Mild parabasal and basal\ncell dysplasia. Superficial dermis shows\nmoderate superficial perivascular infiltrates\nof lymphocytes, eosinophils and plasma\ncells. No elastotic changes.\n\n\n\n\n\n\n\n\n127\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nAtypical Presentation of Genital Herpes in an\nHIV Infected Man\n\n\n\nTang JJ, MBBS, Tang MM, MD, MRCP, Chan LC, MD, MMed and Heng A, MBBS,MRCP\n\n\n\nDepartment of Dermatology, Ipoh Hospital, Perak, Malaysia\n\n\n\nCorrespondence\n\n\n\nAgnes Heng, MRCP,\nDepartment of Dermatology, Ipoh Hospital\n30990 Ipoh, Malaysia\nEmail : agnesheng@gmail.com\n\n\n\nHerpes simplex virus (HSV) infection is one of the\ncommon opportunistic viral infections that may occur in\nhuman immunodeficiency virus (HIV) - infected patients.\nThe natural history of HSV infection is often altered in this\ngroup of patients. Characteristically, genital herpes presents\nwith multiple painful vesicles and erosions in\nimmunocompetent patients. However, clinical\npresentations in immunocompromised patients are\nfrequently severe and atypical which may lead to a delay in\ndiagnosis and treatment. Genital herpes enhances\ntransmission of HIV infection and hence early detection of\nthis condition is important to reduce transmission of HIV\nand HSV.\n\n\n\nCase Report\nA 50-year-old, single, heterosexual Chinese man, diagnosed\nwith HIV infection since 2006 was referred for evaluation\nof non-healing ulcerated perianal nodules & plaques of 6\nmonths duration. The lesions started as vesicles which\nslowly evolved over months. They were not painful but\nassociated with mild pruritus. There was a persistent foul\nsmelling serous discharge from the lesions. He had no fever,\nurinary symptoms or urethral discharge. He was started on\n\n\n\nHAART since March 2006 with zidovudine, lamivudine\nand nevirapine and at the time of evaluation, his CD4+ T-\ncell count was 15/mm3. He was also on co-trimoxazole for\nprophylaxis against pneumocystis carinii pneumonia. He\nadmitted to a history of unprotected casual sex but denied\nabusing any illicit drug. He had been treated with several\ncourses of antibiotics from various doctors prior to\npresentation without any improvement. Incision and\ndrainage was also done but the lesions persisted.\n\n\n\nOn examination, there were ulcerated nodules on his\nsuprapubic region and a verrucous nodular lesion at the\nperianal region with surrounding vesicles (Figure 1a).\nSwabs for Gram stain demonstrated a few Gram positive\ncocci but bacterial culture was negative. Screening for\ngonorrhea and syphilis were negative. Tzanck smear\nexamination revealed multinucleated giant cells. A\nskin biopsy for histopathological examination showed\npseudoepitheliomatous hyperplasia of the epidermis with\nintraepithelial vesicles (Figure 2) and the presence of\nmultinucleated cells with viral inclusion bodies (Figure 3).\nSkin biopsy specimen for fungal culture was negative. He\nwas diagnosed to have verrucous genital herpes.\n\n\n\nFigure 1. (a) Initial verrucous ulcerated nodules at perianal region with surrounding\nvesicles. (b) All lesions resolved with post-inflammatory dyspigmentation after 6 months\nof therapy\n\n\n\n\n\n\n\n\n128\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nHe was started on oral acyclovir 200mg 5 times per day for\n5 days initially but without much improvement. Acyclovir\nwas then increased to 400mg 5 times per day for another 2\nweeks. There was significant improvement of the lesion\nafter 2 weeks of treatment. The drug was subsequently\ntapered to 400mg 4 times per day for the next 3 months\nwith almost complete resolution of his lesions. This was\nfollowed by suppressive therapy at a dose of 400mg 3 times\nper day and he remained clear of any lesions 6 months later\n(Figure 1b).\n\n\n\nDiscussion\nImmunocompromised persons such as HIV-infected\npatients often experience a severe, chronic and atypical form\nof lesion in both primary and reactivated HSV infections as\ncompared to immunocompetent patients. This can result in\na delay in diagnosis and treatment among these patients. As\nin our case, the patient\u2019s condition was undiagnosed for 6\nmonths, causing him much distress. Although HSV\ninfection is typically painful, the relatively painless nature of\nhis lesions added to more confusion. Verrucous genital\nlesions are usually caused by infection with human\npapillomavirus (HPV) although concomitant infection with\nmore than one organism can result in verrucous lesions in\npatients with acquired immunodeficiency syndrome\n(AIDS)1. There have been several case reports of genital\nherpes presenting as verrucous lesions in HIV-infected\npatients. Carrasco et al reported a 28-year-old HIV-positive\nman who presented with hyperkeratotic, verrucous or\nexophytic plaques on his scrotum that were due to herpes\nsimplex infection2. Tong et al described a 32-year-old HIV-\npositive man who presented with a verrucous lesion of the\nintergluteal cleft that clinically resembled condyloma\nacuminata or verrucous carcinoma1. Type 2 HSV was\nisolated when lesional tissue was cultured and cultures for\nother viruses, fungi and acid-fast bacilli were all negative..,\nIt is postulated that immune dysfunction secondary to HIV,\nmediated by T-helper type 2 cytokines results in epidermal\nhyperplasia2. Furthermore, the chronicity of the lesion also\npredispose to the atypical presentation.\n\n\n\nNodules are another atypical presentation of genital herpes\nas reported in the literature. Emanuela et al reported a case\nof a man with AIDS who presented with perianal nodules,\nwhich clinically resembled squamous cell carcinoma3. The\ndiagnosis of herpes was confirmed by histopathology of the\nbiopsy specimen and nested PCR analysis. Besides\nverrucous and nodular lesions, there have also been reports\nof atypical presentation of genital herpes in the form of an\nindolent penile ulcer as reported by Tayal el al4. The case was\natypical in that the lesion was large, single, painless and not\nassociated with lymphadenopathy. The diagnosis was\nconfirmed by histopathology and immunochemistry using\npolyclonal antibodies directed against both HSV types 1\nand 2.\n\n\n\nAcyclovir, valaciclovir and famciclovir are all recognized as\nappropriate treatment for primary or recurrent genital\nherpes in HIV-infected patients. Antiviral therapy should\nbe continued until all mucocutaneous lesions have dried and\ncrusted. Increased dosages of acyclovir, valaciclovir and\nfamciclovir, above those recommended for\nimmunocompetent individuals, may be required5. Acyclovir\nat a dose of 400 mg given five times daily has been used to\ntreat HSV in immunocompromised patients2. As in our\ncase, the patient responded to treatment only after doubling\nthe dose of acyclovir. It has been reported that\nhyperkeratotic herpes infection is associated with acyclovir\nresistance1. Fortunately, our patient proved to be sensitive to\nacyclovir although the duration of therapy was longer for\ndisease resolution. In general, long term suppressive therapy\nis recommended in a HIV-infected patient with a CD4+ T-\ncell count of < 100/mm3 and who suffer severe and\nprotracted HSV outbreaks. It is also indicated in a HIV-\ninfected patient with a CD4+ T-cell count in any range but\nexperiences frequent recurrences (more than 6 episodes per\nyear). Acyclovir, valaciclovir and famciclovir all appear\nuseful for the treatment and suppression of HSV in\nimmunocompromised persons. In cases that do not respond\nto increased doses of these antiviral therapies, susceptibility\ntesting of HSV cultures should be performed if the test is\navailable.\n\n\n\nFigure 3.Figure 2.\n\n\n\n\n\n\n\n\n129\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nIn cases with confirmed or presumed acyclovir resistance,\nintravenous foscarnet or topical cidofovir have been\nsuccessfully used2.\n\n\n\nThere is a close relationship between HSV and HIV\ninfection. In HIV-seropositive individuals, genital herpes\nlesions may not only be the source of transmission of HSV,\nbut may also be a focus of shedding of HIV due to the\ninfected CD4+ cells infiltrating the herpetic lesions.\nFurthermore genital ulceration during HSV infection\nprovides increased available surface area for the exchange of\ninfected fluids which facilitates HIV transmission5. In\naddition, the plasma HIV load increases to a median of 3.4\ntimes during an acute outbreak of HSV infection and this\nwill accelerate progression of HIV5. Studies have shown that\nby reducing or attenuating the occurrences of HSV\noutbreaks, acyclovir therapy may help reduce the deleterious\neffects of these infections. These studies suggest that\nchronic suppressive acyclovir therapy prolongs survival in\nAIDS patients with a prolonged history of HSV infection2.\nResistance does not appear to be increased or induced by\nchronic suppressive therapy with these antiviral agents2.\n\n\n\nIn summary, genital herpes can present in an atypical\nmanner among immunocompromised patients. HSV\ninfection should be considered in the differential diagnosis\n\n\n\nof chronic verrucous genital papules, nodules or plaques in\nHIV-seropositive persons. When in doubt, a biopsy and\nculture for all potential organisms should be performed.\nAntiviral therapy with acyclovir, famciclovir or valaciclovir\nare all useful but dose requirement and treatment duration\nmay be higher and more prolonged than in\nimmunocompetent patients to ensure successful therapy.\nEarly detection and treatment of genital herpes among\nHIV-infected patient will not only reduce transmission of\nHSV but also HIV infection.\n\n\n\nReferences\n\n\n\n1. Tong P, Mutasim DF. Herpes simplex virus infection \nmasquerading as condyloma acuminata in a patient with HIV \ndisease. Br J Dermatol 1996; 134: 797-800.\n\n\n\n2. Carrasco DA, Trizna Z, Colome-Grimmer M, Tyring SK. Verrucous \nherpes of the scrotum in a human immunodeficiency virus-\npositive man: case report and review of the literature. J Eur \nAcad Dermatol Venereol 2002; 16: 511\u2013515.\n\n\n\n3. Gubinelli E, Coccurocia B, Lazzarotto T, Olomoni G.  Nodular \nperianal herpes simplex with prominent plasma cell infiltration. \nSex Transm Dis 2003; 30(2): 157-159.\n\n\n\n4. Tayal SC, Pattman RS, Clelland JM, Sviland L, Snow MH. An \nIndolent penile herpetic ulcer in a patient with previously \nundiagnosed HIV infection. Br J Dermatol 1998; 138: 334-336.\n\n\n\n5. Sardana K, Sehgal VN. Genital ulcer disease and human \nimmunodeficiency virus: a focus. Int J Dermatol 2004; 44:\n391-405.\n\n\n\n\n\n\n\n\n130\n\n\n\n\n\n\n\n\n131\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Report\n\n\n\nPurpura Fulminans in an army trainee\n\n\n\nPrakash B, MBBS and Najeeb A Safdar, MBBS MRCP\n\n\n\nDepartment of Dermatology, Hospital Tuanku Ja\u2019afar, \nSeremban, Negeri Sembilan\n\n\n\nCorrespondence\n\n\n\nNajeeb A Safdar, MBBS MRCP,\nDepartment of Dermatology, Hospital Tuanku Ja\u2019afar\nSeremban, Negeri Sembilan\nEmail : najeebkishwar@yahoo.com\n\n\n\nPurpura fulminans is a condition characterized by\nhaemorrhagic tendencies and usually associated with\nsepticaemia or a previous history of infection. It was first\ndescribed by Guelliot in 1884 as an acute disease with\nfeatures of hypotension, disseminated intravascular\ncoagulation and purpura leading to necrosis.\n\n\n\nCase Report\nA 20-year-old female army trainee presented with a 2-day\nhistory of spiking fever, chills, rigors, vomiting, diarrhea,\nabdominal pain and numbness of all limbs. She was\nadmitted to Hospital Tuanku Ja\u2019afar with a Glasgow Coma\nScale (GCS) of 11/15. She was subsequently intubated and\nventilated and admitted to ICU for respiratory distress and\na low GCS.\n\n\n\nShe was treated for septicaemic shock as well as\ndisseminated intravascular coagulation with our DIVC\nregime consisting of 6 units of cryoprecipitate, 6 units of\nfresh frozen plasma and 2 units of platelet. She was treated\n\n\n\nwith IV antibiotics and was supplemented with intravenous\nfluid support and ionotropes. Within the next 24 hours she\nwas noted to have well demarcated purplish red macular\npatches on an erythematous base over the trunk, limbs and\nface which later transformed into gangrenous lesions over\nthe right lower limb especially on the 2nd to 5th toes up to\nthe shin (Figure 1). A referral was made to our department\nfor her acute skin changes. A provisional diagnosis of\ngeneralized purpura secondary to DIVC was made initially\nand subsequently changed to purpura fulminans. The\npatient was referred to the orthopaedic team in view of her\ngangrenous wound and underwent two wound\ndebridements under general anaesthesia. She was put on\nmultiple antibiotics for various different organisms from the\nculture and sensitivity report.\n\n\n\nHer creatinine on admission was 180umol/L. The clotting\nprofile was also found to be deranged but normalized after\nthe DIVC regime. X-ray of both ankles did not reveal any\nosteomyelitic changes.\n\n\n\nFigure 1. Hemorrhagic and ecchymosed purplish well\ndemarcated lesions with signs of necrosis over the\npatellar region bilaterally on the lower limbs\n\n\n\n\n\n\n\n\n132\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nA skin biopsy performed revealed the presence of a scanty\nand unremarkable epidermis. The main changes involved\nthe vessels in the subcutaneous tissue and adnexae.\nInflammation, necrosis and fibrinoid deposits were seen\ninvolving these structures consistant with disseminated\nintravascular coagulation. Immunofluorescense studies and\nconnective tissue screen were negative. The final diagnosis\nwas purpura fulminans based on clinical & histological\nfeatures (Figure 2).\n\n\n\nHer coagulation profile normalized and her general\ncondition improved with the prompt and aggressive\nmanagement. However her limbs were gangrenous and she\nhad lost most of her sensation over her lower limbs\nespecially her right lower limb. She was referred to\nUniversity Hospital for fasciotomy and reconstruction\nunder the orthopedic team.\n\n\n\nDiscussion\nPurpura fulminans is an acute onset haemorrhagic\ncondition with a high morbidity and mortality rate. It\npresents with extensive multiple ecchymotic (purplish,\nviolaceous) purpuric lesions throughout the body. It is\nassociated with fever, hypotension as well as disseminated\nintravascular coagulation.\n\n\n\nThere are 3 different categories of classification2,4.\n(1) Inherited or acquired abnormalities of protein C or\nother coagulation systems. (2) Acute infectious Purpura\nFulminans (commonest cause is Gram negative\nmicroorganism) and (3) Idiopathic.\n\n\n\nPurpura fulminans is commonly associated with\nmeningococcal sepsis which usually has a poor prognosis1.\nIt usually presents with an acute onset of cutaneous\nhaemorrhage and necrosis secondary to vascular thrombosis\nand DIVC.\n\n\n\nThere is often pain followed by petechiae. Ecchymosis\ndevelops and evolves into painful indurated, well\ndemarcated purple papules with erythematous borders.\n\n\n\nThese lesions then progress into necrosis with formation of\nbullae and vesicles. Gangrenous necrosis follows with\nextension into the subcutaneous tissue and occasionally\ninvolves the muscle and bone as in our patient.\n\n\n\nManagement of purpura fulminans should be prompt and\naggressive with treatment of the underlying cause, which is\nmore commonly due to meningococcal septicaemia3 as in\nour patient. Prompt resuscitation with fluids, broad\nspectrum antibiotic therapy bearing in mind gram negative\norganisms in particular and inotropic support if the patient\nis haemodynamically compromised5. The triggered DIVC\nmust be corrected appropriately and ventilatory support\nwith a team of efficient intensive care unit staff is important.\n\n\n\nIt must be mentioned here that purpura fulminans due to\nStaphylococcus .aureus infection has symptoms identical to\nthose of fulminant meningococcemia but requires\nadditional treatment against methicillin resistant\nStaphylococcal aureus.\n\n\n\nAcknowledgements\nI would like to thank the Director General of Health,\nMinistry of Health, Malaysia, for allowing me to publish\nthis article.\n\n\n\nReferences\n\n\n\n1. Karina J Kennedy, Sarah Walker, Paul Pavli, Lavinia Hallam and \nChris Hemmings What may underlie recurrent purpura \nfulminans? Med J Aust 2007; 186 (7): 373-375.\n\n\n\n2. Smith OP, White B. Infectious purpura fulminans: diagnosis and \ntreatment. Br J Haematol 1999; 104: 202-207\n\n\n\n3. Nolan and R. Sinclair. Review of management of purpura \nfulminans and two case reports; Br J  Anaes 2001;86 (No. 4):\n581-586.\n\n\n\n4. Adcock DM, Brozna J, Marlar RA. Proposed classification and \npathologic mechanisms of purpura fulminans and skin necrosis. \nSemin Thromb Hemostat 1990; 16: 333-40.\n\n\n\n5. Darmstadt GL. Acute infectious purpura fulminans: \npathogenesis and medical management. Ped Dermatol \n1998;15:169-83.\n\n\n\nFigure 2. Thrombosis of venules and capillaries are visible in both superficial and\ndeep dermis (arrows)\n\n\n\n\n\n\n\n\n133\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCommentary\n\n\n\nTherapeutic advances in reducing risk of genital herpes \ntransmission\n\n\n\nHB Gangaram, MBBS, FRCP\n\n\n\nGenito-Urinary Medicine Clinic, Department of Dermatology\nHospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nCorrespondence\n\n\n\nHB Gangaram, MBBS, FRCP,\nGenito-Urinary Medicine Clinic, Department of Dermatology\nHospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAnogenital herpes is the commonest cause of sexually\ntransmitted genital ulcers worldwide, including Malaysia1,\nand is mainly caused by HSV type 2 although the incidence\nof HSV type 1 is increasing2. The disease may have an\noverall negative impact on the individual, the community\nand the nation. This consists of not only the physical impact\nof the disease on the individual and the life-threatening\nencephalopathy if transmitted to an infant around birth3,\nbut also the psychosocial and financial implications. More\nimportantly, it has been shown to enhance the transmission\nand acquisition of HIV infection4. Studies of adolescent\nsexual culture have shown a trend towards a younger age at\nfirst intercourse, but age at first marriage is unchanged\nresulting in an expanded \u201crisk window\u201d during which young\npeople may have many sexual partners, which may further\ncompound the negative impact.\n\n\n\nIn order to treat and prevent the transmission of the disease\nand prevent any outbreak of HIV infection, numerous\nadvances have been made although the ultimate strategy is\nstill far from sight. Over the last 20 years, we have had\nspecific antiviral agents (acyclovir, valacyclovir, famciclovir)\nto treat the acute episode as well as reduce the frequency of\nrelapse. Recently, antiviral therapy was shown to reduce the\nfrequency and degree of viral shedding from the genital\nmucosal surfaces5-6. This prompted a study to determine\nwhether a reduction in viral shedding would result in a\nreduction in transmission of the disease. In this landmark\nstudy7, a randomized, double-blind, placebo-controlled of\n1484 immunocompetent, monogamous, HSV-2 discordant\ncouples, partners with HSV-2 received either 500mg of\nvalacyclovir once daily or placebo for 8 months. The\nincidence of clinically symptomatic HSV-2 infection\n(genital herpes) in susceptible partners was reduced by 75%\nwith the use of valacyclovir. Overall, the acquisition of\nHSV-2 infection (defined via laboratory-confirmed\nsymptoms or seroconversion) by susceptible, HSV-2\nseronegative heterosexual partners was reduced by 48%.\n\n\n\nAmong the source partners, valacyclovir significantly\nreduced the frequency at which HSV DNA was detected in\nsamples of genital secretions (2.9% compared with 10.8%\ndays in the placebo group; p<0.001). However, transmission\ncan still occur in people prescribed antiviral therapy.\nTherefore, infected individuals and their partners should be\ncounseled to use safer sex practices, including the use of\ncondoms.\n\n\n\nThese encouraging data have raised more questions as to\nwhether the clinical effects would be similar for other\nantiviral drugs in the same class and for the management of\ngenital HSV infection, particularly with regards to\nprevention of transmission, in different patient populations.\nMore research is required to provide answers to these\nimportant questions.\n\n\n\nReferences\n\n\n\n1. S Zainah, M Sinniah, Y M Cheong et al. A microbiological study \nof genital ulcers in Kuala Lumpur. Med J Malaysia 1991;\n46:274-282.\n\n\n\n2. L J Haddow, B Dave, A Mindel et al. Increase in rates of herpes \nsimplex virus type 1 as a cause of anogenital herpes in Western \nSydney, Australia, between 1979 and 2003. Sex Transm Infect \n2006;82:255-259.\n\n\n\n3. Whitley R. Neonatal herpes simplex virus infections. J Med Virol \n1993;41(Suppl1):13-21.\n\n\n\n4. Freeman EE, Weiss HA, Glynn JR, et al. Herpes simplex virus 2 \ninfection increases HIV acquisition in men and women: \nsystematic review and meta-analysis of longitudinal studies. \nAIDS 2006;20:73-83.\n\n\n\n5. Wald A, Zeh J, Barnum G. et al. Suppression of subclinical \nshedding of herpes simplex virus type 2 with acyclovir. Ann \nIntern Med 1996;124:8-15.\n\n\n\n6. Wald A, Corey L, Cone R, et al. Frequent genital herpes simplex \nvirus type 2 shedding in immunocompetent women: effect of \nacyclovir treatment. J Clin Invest 1997;99:1092-1097.  \n\n\n\n7. Corey L, Wald A, Patel R, et al. Once-daily valaciclovir to reduce \nthe risk of  transmission of genital herpes. N Eng J Med \n2004;350(1):11-20.\n\n\n\n\n\n\n\n\n134\n\n\n\n\n\n\n\n\n135\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCorrespondence\n\n\n\nUnderstanding towards leprosy: a ground level \nsurvey among public & medical personnel in Penang Hospital\n\n\n\nAlthough leprosy is one of the oldest diseases of mankind,\nmany people remain unaware of the significance of the early\nsymptoms of leprosy and the importance of early diagnosis\nand treatment1. When people do recognize the possibility of\nleprosy, they are subjected to the traditional fears and stigma\nassociated with the disease2.\n\n\n\nAlthough multi-drug therapy (MDT) is well established as\nthe effective cure and is widely available, an important\nminority of patients continue to delay in presentation.\nThose who delay have an increased risk of nerve\nimpairment3 or disability4,5.\n\n\n\nThe aim of the study was to determine the level of\nawareness of leprosy among the public and medical\npersonnel in Penang Hospital and to gather data and\nexplore individual\u2019s treatment preference and the beliefs and\nattitudes towards leprosy.\n\n\n\nA survey was carried out over a 2-month period (May - June\n2006) in the Dermatology Clinic, Penang Hospital where\nrandomly selected individuals were interviewed and\nanswered a survey questionnaire in 3 languages (Malay,\nEnglish and Mandarin) . Public is defined as patients who\nvisited the skin clinic during May - June 2006 (excluding\nthe diagnosed leprosy cases, age < 12 years old, illiterate or\nill patients).\n\n\n\nMedical personnel is defined as staff nurses and medical\nassistants working in Penang Hospital excluding skin clinic\nstaff. A total of 800 respondents (400 public; 400 medical\npersonnel) were interviewed. 20.5% of public and 10.3% of\nmedical personnel never heard of the disease leprosy or\n\u201ckusta\u201d. 19.2% of public and 10.2% of medical personnel\nthought that leprosy did not exist in Malaysia. Only 58.8%\nof public and 78.0% of medical personnel recognized the\nsigns and symptoms of leprosy Majority of respondents\nequate deformities to leprosy. Most of the respondents\nfailed to recognize the subtle signs of leprosy. Majority of\nrespondents still thought that leprosy was an incurable\ndisease Only 41.8% of public and 68.0% of medical\npersonnel chose to consult a doctor as their first priority\n(Figure 1). The medical personnel\u2019s knowledge on leprosy,\nalthough inadequate was better than the public (P<0.0001).\n\n\n\nSince the introduction of Multiple Drug Therapy (MDT)\nin 1982 by WHO, the prevalence of leprosy has declined\nsteadily. MDT was started in Malaysia since 1985. Malaysia\nhas achieved elimination status with prevalence < 1 per\n10,000 & incidence rate of < 1 per 100,000 populations in\n1994. Thus, Malaysia has achieved WHO\u2019s target for\ncontrol earlier than expected.\n\n\n\nHowever, recently for the past 3 years, there has been  an\nincrease in incidence rate. It may be partly contributed by\npoor awareness among the health care provider and the\npublic (In our series, 19.2% of public and 10.2% of medical\npersonnel thought that leprosy did not exist in Malaysia)\nand an increase of immigrants into our country.\n\n\n\nThe clinical diagnosis of leprosy is frequently missed or\nmisdiagnosed. As shown in our series, only 58.8% of public\nand 78.0% of medical personnel recognized the signs and\nsymptoms of leprosy. Being a great imitator, leprosy has a\nwide spectrum of clinical manifestations ranging from\nsimple dermatological and neurological to that of\nophthalmological, orthopaedic, rhinological or dental\npresentations4-6. In our series, 84.5% of respondents equated\ndeformities to leprosy. They failed to recognize the subtle\nsign of leprosy. Only 63.1% and 57.0% of respondents knew\nthat patients may present with skin lesions and neuropathy.\nIt is often considered too formidable or difficult to diagnose\nand treat as most doctors have scanty knowledge of the\ndisease. They often have misperception that leprosy is\nincurable. In our series, only 43.0% of respondents knew\nthat leprosy was a curable disease\n\n\n\nA high index of suspicion is needed to make a correct\ndiagnosis. Medical personnel should always consider leprosy\nas a possible cause of peripheral neuropathy or neuropathic\nulcers6.\n\n\n\nIt was very interesting to note that, 50.2% of public and\n32.0% medical personnel preferred to seek alternative\ntreatment before they choose to consult the doctors.\nMisbeliefs about leprosy, low level of awareness to modern\ntreatment, stigma2,7 and the influence of traditional healers\nare important factors associated with this issue8.\n\n\n\nFigure 1. What would you do, if you suspect yourself\nhaving leprosy?\n\n\n\nPUBLIC\n\n\n\nMEDICAL\n\n\n\nPERSONEL\n\n\n\n\n\n\n\n\n136\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTo achieve  the aim of \u201cMalaysia without leprosy\u201d, the level\nof awareness towards the disease need to be improved.\nThere are 2 guiding principles to achieve the mission: (1)\nHigh index of suspicion to diagnose and (2) to treat leprosy\nearly & promptly5.\n\n\n\nTan WC, MD\n\n\n\nLo Kang SC, MRCP\n\n\n\nKalaikumar N, MD\n\n\n\nCheah CM, MBBS\n\n\n\nOng CK, MBBS, MRCP\n\n\n\nOng KP, MBBS\n\n\n\nSiti R\n\n\n\nLam YC\n\n\n\nDepartment of Dermatology\nPenang General Hospital, Penang\n\n\n\nAcknowledgements\nWe are most grateful to all the staff of dermatology clinic,\nPenang General Hospital for their help in collecting and\nrecording  data on leprosy.\n\n\n\nReferences\n\n\n\n1. Rao S, Garole V, Walawalkar S, Khot S, Karandikar N. Gender \ndifferentials in the social impact of leprosy. Lepr  Rev \n1996;67:190-99.\n\n\n\n2. Bainson K.A, Van Den Borne B. Dimensions and process of \nstigmatization in leprosy. Lepr Rev1998; 69:341-50.\n\n\n\n3. Saunderson P. The epidemiology of reactions and nerve \ndamage. Lepr Rev 2000;71(suppl.): S106-110.\n\n\n\n4. Schreuder P A. The occurrence of reactions and impairments in \nleprosy: experience in the leprosy control program of three \nprovinces in northeastern Thailand, 1987-1995 Overview of the \nstudy. Int  J  Lepr Other Mycobact. Dis. 1998;66:149-58.\n\n\n\n5. WHO Expert Committee on Leprosy. World Health Orgainzation. \nTech. Rep. Ser. No. 1998;874:1-43.\n\n\n\n6. Brilton W J, Lockwood D N J. Leprosy. Lancet 2004; 363:\n1209-19.\n\n\n\n7. Scambler G. Stigma and disease: changing paradigms. Lancet, \n1998; 352: 1054-1055.\n\n\n\n8. Bekri W, Gebre S, Mengiste A et al. Delay in presentation and \nstart of treatment in leprosy patients: a case-control study of \ndisabled and non-disables patients in three different settings in \nEthiopia. Int J Lepr 1998; 66: 1-9.\n\n\n\n\n\n"
"\n\n69\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nDefaulter rate of follow-up of patients with gonorrhoea \nat the Genitourinary Medicine Clinic\n\n\n\nCC Chang, MBBS, MRCP, K Akbal, MBBS, HB Gangaram, MBBS, FRCP and Suraiya H Hussein MBBS, FRCP\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Malaysia\n\n\n\nCorrespondence\n\n\n\nChang Choong Chor MRCP,\nDepartment of Dermatology\nHospital Kuala Lumpur, Jalan Pahang, 50586 Kuala Lumpur\nEmail : ccchor@streamyx.com\n\n\n\nAbstract\n\n\n\nBackround Gonorrhoea is the third most common sexually\ntransmitted infection (STI) in the Genitourinary Medicine Clinic.\nDespite high cure rates achieved with the use of intramuscular\nceftriaxone, all patients with gonorrhoea are followed up with one test\nof cure (gonococcal culture) after treatment. This is essential to ensure\nsuccess of cure hence preventing complications, to screen for and treat\nconcomitant STIs, and to reduce the possibility of re-infection through\nrepeated patient education. A defaulter is defined as a patient who fails\nto attend follow-up and undergo test of cure within a period of 2 weeks\nafter completion of treatment. Previous studies showed high defaulter\nrates of 41.1% and 43.8% in 1996 and 1997 respectively. This study\naims to determine the defaulter rate of follow-up of patients with\ngonorrhoea, and to formulate remedial measures to reduce defaulter\nrate and thereby improve the management of gonorrhoea specifically\nand all sexually transmitted infections in general.\n\n\n\nMaterials and Methods An audit of defaulter rate of patients\ndiagnosed as gonorrhoea was performed from January 1998 to\nDecember 2005 in the Genitourinary Medicine Clinic, Department of\nDermatology, Kuala Lumpur Hospital. All patients who failed to\nattend follow-up visit within 2 weeks after treatment were recorded as\ndefaulters. An analysis was performed on all defaulters from January to\nDecember 2005.\n\n\n\nResults Defaulter rates for patients with gonorrhoea were generally\nhigh throughout the years studied, ranging from 35.0% to 48.2%, the\nhighest being in year 2001. Despite continuous and relentless efforts in\npatient education and counseling, there has been no decreasing trend.\nIn the year 2005, all defaulters were males. Majority (72.1%) of the\ndefaulters were young adults aged between 21 and 40 years. 67.4% of\nthe defaulters were Malay, followed by Indian 14.0%, Chinese 7.0%\nand other ethnic groups 11.6%. Among the defaulters, 30.2% had\nrepeated gonococcal infection and 38.5% had concomitant STIs.\n\n\n\nConclusions More effort is necessary in educating patients to attend\nfollow-up visit after treatment of gonorrhoea. Emphasis has to be made\non the importance of confirming cure and thereby preventing\ncomplications and transmission to sexual partners. Counseling should\n\n\n\nalso be given to all patients regarding practice of safe sex to prevent\ngonococcal re-infection and other STIs.\n\n\n\nKeywords gonorrhoea, defaulter, defaulter rate\n\n\n\nIntroduction\nGonorrhoea is the third most common sexually transmitted\ninfection (STI), after syphilis and non-gonococcal\nurethritis, in the Genitourinary Medicine (GUM) Clinic,\nHospital Kuala Lumpur. In our clinic, high cure rates\n(100%) have been achieved with the use of directly observed\ntherapy using single dose of intramuscular ceftriaxone.\nDespite this, all patients are followed up after treatment. A\ntest of cure i.e. gonococcal culture from urethral swab is\nperformed after 72 hours post-treatment in all patients\n(Figure 1). Follow up is essential to ensure success of cure,\nthereby preventing complications. It also provides us with\nan  opportunity to screen for and treat concomitant STIs,\ndetect development of resistant gonococcal strains, evaluate\nrisk of re-infection, pursue partner screening and treatment,\nas well as reinforce patient education and counseling.\n\n\n\nIn view of the importance of follow-up in the management\nof gonorrhoea, rate of defaulting follow up visits has thus\nbeen used as a negative marker of success in the\nmanagement. This has been one of the quality indicators\nmonitored annually in the Continuous Quality\nImprovement activities of the Department of Dermatology,\nHospital Kuala Lumpur, since 1998. It is hoped that efforts\ntaken to reduce defaulter rates may improve the overall\nmanagement of gonorrhoea as well as other STIs.\n\n\n\nThe aims of the study was to improve the management of\nall sexually transmitted infections, using gonorrhoea as the\nmain proxy indicator. It aims to determine the defaulter rate\nof follow up of patients with gonorrhea, to formulate\nremedial measures to reduce defaulter rate and to ensure\ncontinuous improvement by re-evaluating the defaulter rate\nannually.\n\n\n\n\n\n\n\n\n70\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nMaterials and Methods\nAnnual audit of defaulter rates of all patients diagnosed as\ngonorrhoea was performed throughout an 8-year period\nfrom January 1998 to December 2005 in the GUM Clinic,\nDepartment of Dermatology, Hospital Kuala Lumpur. All\npatients who did not attend pre-scheduled follow-up visits\nwithin one week post-treatment were identified. Attempts\nwere made to contact them via telephone and urge them to\nattend the clinic at an earliest possible date. Patients who\nfailed to attend follow-up visit and undergo one test of cure\nwithin 2 weeks post-treatment were recorded as defaulters.\nA defaulter rate of less than 20% was adopted as an arbitrary\nstandard of good care.\n\n\n\nA retrospective review of all gonorrhoea defaulters from\nJanuary to December 2005 was performed. The study\nfocused on their demographic pattern, reasons of default,\nwhether it was the first or repeated gonococcal infection,\nand concomitant STIs, if any, detected by screening at the\nfirst visit.\n\n\n\nResults\nThe number of new cases of gonorrhoea seen in the GUM\nClinic ranged from 83 to 123 per year (median 92.5) during\nthe study period. This had markedly reduced from more\nthan 400 new cases per year in the early 1990\u2019s (Figure 2).\n\n\n\nFigure 1.   Management algorithm of gonorrhoea in the GUM Clinic,\nHospital Kuala Lumpur\n\n\n\nFigure 2.   New cases of gonorrhoea from 1998 to 2005\n\n\n\n\n\n\n\n\n71\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDefaulter rates remained high throughout the years studied,\nranging from 35.0% to 48.2%. Overall mean defaulter rate\nwas 41.3%, much higher than the arbitrary standard of <\n20%. Defaulter rates for the later period from 2001 to 2005\nwere higher than that of the earlier years from 1998 to 2000\n(mean 44.6% vs 35.7%) (Figure 3).\n\n\n\nFrom January to December 2005, all defaulters were males.\nAll female gonorrhoea patients, who constituted only 6% of\nall gonorrhoea cases, attended follow-up within two weeks\npost-treatment. Majority (72.1%) of the defaulters were\nyoung adults aged between 21 and 40. Patients aged\nbetween 31 to 40 had the highest defaulter rate of 73.3%\n(Figure 4).\n\n\n\nThe ethnic distribution of the defaulters was similar to that\nof all gonorrhoea cases. 67.4% of the defaulters were Malay,\nfollowed by Indian 14.0%, Chinese 7.0% and other ethnic\ngroups 11.6%. Although about half of all patients who\nattended the GUM clinic were Malays, more than two-\nthirds of gonorrhoea cases were Malay patients (Figure 5).\n\n\n\nFigure 3.   Gonorrhoea defaulter rates\n\n\n\nFigure 4.   Age distribution of gonorrhoea patients\n\n\n\nFigure 5.   Ethnic distribution of gonorrhoea defaulters compared to all gonorrhoea cases and total\nclinic attendance in year 2005\n\n\n\n\n\n\n\n\n72\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCommon reasons for defaulting given by the gonorrhoea\ndefaulters included feeling cured after treatment, unable to\nspare time to come for follow up, and refusal of a repeat test\n(Table 1).\n\n\n\nAmong the defaulters, 30.2% had repeated gonococcal\ninfection. From the screening of STIs during the first visit,\n38.5% of the defaulters had concomitant STIs detected.\nThese included chlamydial urethritis (23.1%), syphilis\n(5.1%), HIV (2.6%), hepatitis B (2.6%), hepatitis C (2.6%),\nand a combination of HIV, hepatitis B and hepatitis C\n(2.6%) (Figure 6).\n\n\n\nAll patients were  educated and counseled  during their first\nvisit, particularly emphasizing the importance of confirming\ncure during follow-up visits. Practice of safe sex was actively\npromoted in preventing spread and re-infection. Education\npamphlets printed in different languages were distributed to\nall patients during their first visit.\n\n\n\nFollow-up appointments were made to patients\u2019\nconvenience. Moreover, unscheduled walk-in follow-up\nvisits, though not encouraged, were all attended and seen at\nthe same clinic session. Patients who did not attend follow-\nup one week after treatment were reminded by phone calls\nfrom the clinic staff. Time-off slips or medical certificates\nwere given for follow-up visits to all working patients.\n\n\n\nClinic environment was improved, with spacious patient\nwaiting area and tinted window glasses. Patients\u2019 privacy has\nalways been maintained, with spouses or partners\ninterviewed, managed and counseled individually. Clinic\nwaiting time was shortened by streamlining the process of\nregistration, consultation, laboratory tests, treatment and\ncounseling to minimise patient waiting time for each\nsection. Clinic parking spaces were increased. Friendly and\nnon-judgmental approach to patients has been a policy and\npractised by all doctors and clinic staff.\n\n\n\nDiscussion\nAlthough antibiotic treatment is usually simple and\nstraight-forward, the widespread occurrence of gonococcal\nstrains resistant to commonly used antibiotics in recent\nyears demands vigilance in ensuring treatment success.\nAbsence or resolution of symptoms following treatment\nmay not indicate cure of infection. Almost half of treatment\nfailures in gonococcal urethritis are asymptomatic8.\nTreatment inadequacy may lead to complications such as\nepididymitis and prostatitis in males, and pelvic\ninflammatory disease, ectopic pregnancy and infertility in\nfemales. It also perpetuates the silent spread of gonorrhoea\nto sexual partners and enhances the transmission of human\nimmunodeficiency virus (HIV) and other STIs.\n\n\n\nAccording to current international guidelines2,3,4, routine\nfollow up of gonorrhoea cases after treatment is\nrecommended. Test of cure may not be routinely necessary\nif treated with recommended antibiotic and sensitivity of\norganism to the antibiotic is confirmed. However, test of\ncure is routinely performed in our centre due to its value in\nensuring eradication of infection thus preventing\ncomplications, prevention of spread to community, and\ndetection of emerging resistant strains. Gonococcal culture\nfrom direct plating of the urethral swab in males and\nendocervical swab in females is used as a test of cure in our\nclinic. Alternative tests which have been used in other\ncentres\n\n\n\nTable 1.\n\n\n\nReasons for defaulting follow-up\n\n\n\nFelt cured after treatment\nUnable to get time off work\nToo busy\nClinic too far to come for follow up\nWas out-station\nDo not want repeat test\n\n\n\nFigure 5.   Concomitant STI in gonorrhoea defaulters in 2005\n\n\n\n\n\n\n\n\n73\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ncentres include nucleic acid amplification tests (NAATs)\nwhich may be more sensitive (>90%) for genital as well as\nextragenital sites, and results are less affected by the\nadequacy of specimens. However, specificity of NAATs is\nnot 100%, and hence confirmation of positive results by\nculture is recommended4.\n\n\n\nA previous study in the same centre showed defaulter rates\nof 41.1% and 43.8% in 1996 and 1997 respectively1. Several\ncentres in UK reported defaulter rates ranging from 24% to\n53%5,6,7. Defaulter rates of 35.0% to 48.2% in our centre are\nhigh, and should be a cause for alarm. Majority of the\ndefaulters are young men. Almost one-third of them had\nrepeated gonococcal infection and hence had been given\ncounseling repeatedly. The lack of awareness and\nlackadaisical attitude of this group is worrying. More than a\nthird of the defaulters carry concomitant STIs, for which\npotential opportunity of treatment may be missed. The\nefforts put into partner tracing and screening are often\nhindered.\n\n\n\nTo reduce the alarmingly high defaulter rates in our GUM\nClinic, additional remedial measures should be\nimplemented. Patient education and counseling should be\nfurther consolidated with additional training given to\nprofessional counselors, and emphasis put on creating\nawareness at the importance of follow-up. Clinic\nenvironment will be further improved by a proposed plan of\nmoving to a new building with more consultation rooms,\nand a more comfortable fully air-conditioned patient\nwaiting area with television. With consent given at the first\nvisit, patients can be reminded of their follow-up\nappointments via mobile phone short-message services\n(SMS) delivered through an automated system. Use of non-\ninvasive and more sensitive tests such as NAATs for test of\ncure should be considered. These tests enable the use of\nfirst-pass urine sample, obviating the need for\n\n\n\nuncomfortable urethral swab and exposure of genitals. Only\npositive test results require confirmation and sensitivity\ntesting by culture methods.\n\n\n\nConclusion\nMuch more effort is needed in improving the rate of follow\nup of gonorrhoea patients after treatment. Emphasis has to\nbe made on the importance of confirming cure thereby\npreventing complications and transmission to sexual\npartners, as well as the detection and treatment of\nconcomitant STIs. Counseling should also be given to all\npatients regarding practice of safe sex to prevent gonococcal\nre-infection and other STIs.\n\n\n\nReferences\n\n\n\n1. K Akbal, HB Gangaram, AT Gan, SH Hussein, T Ganesapillai. \nDefaulter rate of follow-up of patients with gonorrhoea at \ngenitourinary medicine clinic. Jurnal Dermatologi Malaysia \n2001;14: 37-42\n\n\n\n2. Centers for Disease Control: 2002 Sexually transmitted diseases \nguidelines. MMWR 2002;51RR-6:1-78\n\n\n\n3. Bignell C. European guideline for the management of \ngonorrhoea. Int J STD AIDS 2001;12(Suppl 3):27-9\n\n\n\n4. National guideline on the diagnosis and treatment of \ngonorrhoea in adults, revised Aug 2005. Clinical Effectiveness \nGroup, British Association for Sexual Health and HIV\n\n\n\n5. Holland TM, Hussey J, Pattman RS, et al. Audit of gonorrhoea \ntest of cure at the genitourinary medicine department in \nNewcastle upon Tyne, UK. Int J STD AIDS Sept 2003; 14(9):\n630-631\n\n\n\n6. Harry TC. The management of uncomplicated adult gonococcal \ninfection: should test of cure still be routine in patients \nattending genitourinary medicine clinics? Int J STD AIDS July \n2004;15(7): 453\u2013458\n\n\n\n7. Singh G, Thomas PD, Blackwell AL. An audit of the problems in \nmanagement of patients with gonorrhoea. Int J STD AIDS 1997; \n8: 208-209\n\n\n\n8. Carne CA. Epidemiological treatment and tests of cure in \ngonococcal infection: evidence for value. Genitourin Med 1997; \n73(1):12-15\n\n\n\n\n\n\n\n\n74\n\n\n\n\n\n\n\n\n75\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nHIV infection among patients attending the \nGenitourinary Medicine Clinic, Hospital Kuala Lumpur \n(2000-2005)\n\n\n\nNoorlaily Mohd Noor, MBBS, MRCP, Gangaram H. Belani, MBBS, FRCP, Akbal Kaur, MBBS, Dip. Derm and\nSuraiya H. Hussein, MBBS, FRCP\n\n\n\nGenito-Urinary Medicine Clinic (GUM)\nDepartment of Dermatology, Hospital Kuala Lumpur\n50586 Kuala Lumpur, Malaysia\n\n\n\nCorrespondence\n\n\n\nNoorlaily Mohd Noor MBBS, MRCP,\nDepartment of Dermatology\nHospital Kuala Lumpur, 50586 Kuala Lumpur, Malaysia\nEmail : laily124@tm.net.my\n\n\n\nAbstract\n\n\n\nBackground According to the Department of Public Health\nMalaysia, the total number of HIV patients up to December 2006 was\n76,389. More than 90% were males with Malays being the majority.\nIVDU was the main mode of transmission followed by heterosexual\ncontact.\n\n\n\nObjectives To determine the sociodemography, associated risk factors\nand clinical presentation of patients with HIV attending the\nGenitourinary Medicine (GUM) clinic.\n\n\n\nMethod A retrospective study analyzing the data using a standard\nquestionnaire. All HIV patients seen in the GUM clinic between\n1/1/2000-31/12/2005 were recruited\n\n\n\nResults A total of 191 patients with HIV were seen, with 84% being\nmales and 16% females. This constituted 4.2% of the total number of\npatients seen in the clinic. 64% were Chinese, 18% Malays, 15%\nIndians and 2% other races. 90% were between 21-50 years of age. The\nmajor risk factors for males were sexual promiscuity (61%) and IVDU\n(14%). 41% frequented commercial sex workers. 74% were\nheterosexuals, 18% homosexuals and 8% bisexuals.\n\n\n\nThe major risk factors for females were being sexual partners of HIV\ninfected males (48%), IVDU (16%) and sex workers (6%). Majority\nreported no usage of condom.\n\n\n\nThe main diagnoses at presentation were herpes genitalis (24%),\ngenital warts (22%), gonorrhoea (10%) and syphilis (10%). Non\nvenereal disease accounted for 23%.\n\n\n\nConclusions The major risk factor for HIV transmission in patients\nattending the GUM clinic was exposure to sex workers, and the\npredominant race was Chinese. According to the national figure the\nmain mode of HIV transmission was IVDU with Malays being the\n\n\n\nmajority. The main diagnoses at presentation were herpes genitalis,\ngenital warts, gonorrhoes and syphilis.\n\n\n\nKeywords HIV, Sexually Transmitted Infection, risk factors\n\n\n\nBackground\nAccording to the Department of Public Health Malaysia,\nthe total number of HIV patients up to December 2006 was\n76,389. More than 90% were males with Malays being the\nmajority. IVDU was the main mode of transmission\nfollowed by heterosexual contact. The proportion of\nreported HIV infections transmitted through heterosexual\nand homosexual/bisexual contacts has increased from 7.4%\nin 1995 to 17.4% in 2002.\n\n\n\nThe presence of sexually transmitted infection (STI)\nparticularly genital ulcer disease and also genital discharge\ncan enhance both acquisition and transmission of HIV. The\nincreased susceptibility to HIV is related to the STI causing\ndamaged mucosa or skin and the increased presence of HIV\nsusceptible macrophages. The increased transmission of\nHIV is related to increased shedding of the virus when STI\nis present1,2.\n\n\n\nObjectives\nThe main objective of this study is to determine the\nsociodemography, associated risk factors and diagnoses at\npresentation of patients with HIV attending the\nGenitourinary Medicine Clinic, Department of\nDermatology, Hospital Kuala Lumpur.\n\n\n\nMethod\nThis is a retrospective study analyzing the patients\u2019 data\nobtained using a standard questionnaire. The questionnaire\ncontains the patients\u2019 basic demographic information, risk\nfactors for HIV, presenting complaint and diagnosis. The\nquestionnaire was filled in by the attending doctor on the\npatients\n\n\n\n\n\n\n\n\n76\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\npatients\u2019 first visit to the GUM clinic. All HIV patients seen\nin the GUM clinic, Department of Dermatology, HKL\nbetween 1/1/2000 and 31/12/2005 were recruited in the\nstudy. The National Statistics figures were obtained from\nthe Department of Public Health, Malaysia.\n\n\n\nResults\nA total of 191 patients with HIV were seen in the GUM\nclinic during the study period of six years. This constituted\n4.2% of the total number of 4521 patients seen in the clinic.\nOut of these 191 patients, 65% were Chinese, 18% were\nMalays, 15% were Indians and the remaining 2% were of\nother races (Figure 1). There were more males (84%) than\n\n\n\nfemales (16%) infected with HIV in the GUM clinic\n(Figure 2).\n\n\n\nNinety percent of HIV patients were between 21-50 years\nof age (Figure 3). The major risk factors for males were\nsexual promiscuity (56%), combination of IVDU and\npromiscuity (12%) and IVDU (2.5%). Out of these male\npatients 74% were heterosexuals, 18% homosexuals and 8%\nbisexuals. Forty six percent of males frequented sex workers.\nInformation regarding precaution during sexual intercourse\nin the questionnaire did not specify the use of condoms.\nHowever from the data available it appears that the usage of\ncondom is low.\n\n\n\nFigure 1.   Racial distribution of patients with HIV (n=191)\n\n\n\nFigure 3.   Distribution of patients with HIV by age and sex (n=191)\n\n\n\nFigure 2.   Gender distribution of patients with HIV (n=191)\n\n\n\n\n\n\n\n\n77\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe major risk factors for females were being sexual\npartners of HIV infected males (48%), IVDU (16%) and\nbeing sex workers (6%). The main diagnoses at presentation\nwere herpes genitalis, genital warts, gonorrhoea and syphilis\n(Table 1).\n\n\n\nDiscussion\nThe racial distribution of patients with HIV in GUM clinic\ndiffers from the National Statistics. Chinese made up the\nmajority of patients with HIV in GUM clinic (64%) as\nopposed to the national figures which showed Malays\n(72.6%) as the majority with HIV in the country.\n\n\n\nMost of the male patients with HIV attending the GUM\nclinic acquired the infection through heterosexual contacts\nand 46% had exposure to sex workers. Most of the HIV\ninfected females in the clinic had sexual partners who were\nHIV positive and only a smaller number were sex workers.\nIVDUs form a much smaller group for both sexes. These\nfindings differ from the National Statistics where the main\nmode of HIV transmission in the country was IVDU\n(76.2%) followed by heterosexual contact (17.5%). This is\nbecause HIV patients attending the GUM clinic represents\na biased group where sexual exposure is a high risk\nbehaviour with predisposition to HIV infection.\n\n\n\nRecent studies have shown that heterosexual transmission is\nbecoming more important in the country, with rates\nincreasing from 20% to 38.9%.3 The percentage of females\ninfected with HIV in the country has risen from 1.4% in\n1990 to 7% in 2003 concomitant with the rise in percentage\nof infections classified as heterosexual. Most of the women\nwere infected by their sex partners. The socioeconomic\nsituation in Asian women makes them more vulnerable and\nsubmissive to their partners4. Thus they should be educated\nto create awareness so that they are able to protect\nthemselves.\n\n\n\nBoth the national and figures from GUM clinic indicate\nmales being predominantly infected with HIV, the majority\nin the 20-39 years age group which is also the productive\nyears of an individual. This has important repercussions to\nthe economy and workforce of the country in the future.\n\n\n\nMost patients presented in the GUM clinic with ulcerative\nSTIs which have been shown to increase susceptibility to\nHIV infection5. In fact both ulcerative STIs such as genital\nulcer disease and syphilis, as well as non-ulcerative STIs\nsuch as gonorrhoea, chlamydia and non-gonococcal\nurethritis may be associated with increased risk of HIV\ntransmission1,6. HIV patients with STI are more likely to\ntransmit HIV through sexual contact than those without\nSTI. Thus early STI treatment should be part of the HIV\nprevention strategy. Patients should also be advised to use\ncondoms and practice safe sex as most of the GUM clinic\nattendees do not use condoms.\n\n\n\nThere are several limitations in this study. As it is a\nretrospective study, the accuracy of the data depends on\ngood case documentation. The number of patients with\nHIV infection may not be representative of the actual figure\nas the HIV test is voluntary, thus some patients may refuse\nto be tested.\n\n\n\nConclusions\nThe sociodemography and risk factors of patients with HIV\nattending the GUM clinic are different from those of the\ncountry. This could be explained by the fact that HIV\npatients attending the GUM clinic belong to a high risk\ngroup where sexual exposure is a potential risk of HIV\ntransmission. Thus they should be educated, counseled,\nscreened and treated for STIs to reduce the risk of HIV\ntransmission.\n\n\n\nReferences\n\n\n\n1. Fleming DT, Wasserheit JN. From epidemiological synergy to \npublic health policy and practice; the contribution of other \nsexually transmitted diseases to sexual transmission of HIV \ninfection. Sex Trans Infect 1999; 75: 3-17 \n\n\n\n2. Adler MW, Meheust AZ. Epidemiology of Sexually Transmitted \nInfections and Human Immunodeficiency Virus In Europe. \nJEADV 2000; 14: 370-377\n\n\n\n3. Rokiah I. HIV infection in Malaysia. A report of cases seen at \nUniversity Hospital Kuala Lumpur. Med J Malaysia 1995; 50:\n298-301\n\n\n\n4. Rokiah I. Sexually Transmitted Disease (STD) and Acquired \nImmunodeficiency Syndrome (AIDS) in Southeast Asia. Clinics \nin Derm 1999; 17: 127-135\n\n\n\n5. Simonsen JN, Cameron DW, Gakinya MN  et al. Human \nimmunodeficiency virus infection among men with sexually \ntransmitted diseases. Experience from a center in Africa.\nNEJM 1988;319:274-278 \n\n\n\n6. Hanson J, Posner S, Hassig S et al. Assessment of sexually \ntransmitted diseases as risk factors for HIV seroconversion in a \nNew Orleans sexually transmitted disease clinic, 1990-1998. Ann \nEpidemiol 2005;15:13-20\n\n\n\n7. Section of AIDS/STD, Division of Disease Control, Dept of Public \nHealth, Malaysia\n\n\n\nTable 1.   Diagnosis of HIV patients at\npresentation\n\n\n\nDiagnosis at presentation   Percentage\n\n\n\nHerpes genitalis 24\n\n\n\nGenital wart 22\n\n\n\nGonorrhoea 10\n\n\n\nSyphilis 10\n\n\n\nNon venereal disease 23\n\n\n\n\n\n\n\n\n78\n\n\n\n\n\n\n\n\n79\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nCutaneous Adverse Drug Reactions in a General Hospital \nin Singapore: A One-Year Retrospective Analysis\n\n\n\nRachael YL Teo, MBBS, MRCP, MMed1, Yong Kwang Tay, MBBS, FRCP, FAMS1 and Kwong Ming Fock, MBBS, FRACP, MMed2\n\n\n\n1Division of Dermatology, Changi General Hospital, Singapore\n2Department of Medicine, Changi General Hospital, Singapore\n\n\n\nCorrespondence\n\n\n\nRachael Yu Lin Teo, MBBS, MRCP, MMed,\nDivision of Dermatology, Changi General Hospital\n2 Simei Street 3, Singapore 529889\nEmail : rachael_teo@cgh.com.sg\n\n\n\nAbstract\n\n\n\nBackground Rashes are the most common adverse reaction to drugs.\nOur aim is to describe  (i) the prevalence of cutaneous adverse drug\nreactions in hospitalised patients over a 1-year period in our hospital;\n(ii) the variety of cutaneous drug reactions; (iii) the characteristics of\npatients with cutaneous drug reactions and (iv)the drugs implicated.\n\n\n\nMethods A retrospective analysis of all adverse drug reactions from\nthe pharmacists\u2019 database from January to December 2003 was\nconducted. Patients\u2019 records were reviewed to extract demographic\ndata, drug implicated, route of administration, drug allergy history, type\nof cutaneous reaction, severity and presence of underlying chronic\ndisease.\n\n\n\nResults Sixty-five patients met our inclusion criteria, giving an\nestimated prevalence of 1.8/1000 among hospitalised patients. The\ncases were mostly from the general medicine department (64.6%), with\na slight male predominance (males, 53.8%; females 46.2%). Cutaneous\nadverse drug reactions were more common in the Malay population\n(32.3%). The mean age was 41.6 years (range, 13 to 85 years). The main\ndrugs implicated were antibiotics (49.2%), mainly penicillins and\ncephalosporins, and non-steroidal anti-inflammatory agents (16.9%).\nUrticarial (46.1%) and generalised maculopapular eruptions (40.0%)\nwere the most common patterns encountered. Others included\nStevens-Johnson syndrome/toxic epidermal necrolysis (7.7%), drug\nreaction with eosinophilia and systemic symptoms (1.5%) and\nerythroderma (1.5%). 29.2% of cases were considered to be severe.\nThere were no deaths. 44.6% had an associated chronic disease and\n24.6% had a previous documented drug allergy.\n\n\n\nConclusion Antibiotics and NSAIDs were the major drugs involved.\nThe commonest cutaneous manifestations were urticarial and\nmaculopapular eruptions. A high proportion of reactions were\nconsidered severe and almost one-quarter had a previous drug allergy.\n\n\n\nKeywords exanthema, hypersensitivity, skin\n\n\n\nIntroduction\nCutaneous adverse drug reactions (ADRs) are a common\noccurrence in hospitalised patients, causing significant\nmorbidity and mortality. However, there is a lack of local\ndata on this subject. We therefore conducted a retrospective\ndescriptive study over a 12-month period in a local general\nhospital with the aims of (i) describing the prevalence of\ncutaneous ADRs in this population, (ii) the types of drugs\nimplicated, (iii) the clinical spectrum of cutaneous ADRs\nseen and (iv) the characteristics of patients with cutaneous\nADRs. This information will help to update the spectrum\nof cutaneous drug reactions seen locally.\n\n\n\nMaterials and Methods\nThis was a retrospective hospital-based descriptive study\ncarried out in Changi General Hospital, Singapore. All\nADRs from the pharmacists\u2019 database were reviewed over a\n12-month period from January to December 2003.\nInformation from the database had been mainly gathered\nthrough healthcare staff, including doctors and nurses, who\nhad reported these adverse events to the central database.\n\n\n\nInclusion criteria included all inpatients with a reported\nADR with a cutaneous component. Outpatients and\npatients whose adverse reactions were non-cutaneous were\nexcluded from the study. Patients\u2019 records were reviewed for\ndemographic data, including age, gender, race and\nadmitting department. In addition, we determined the drug\nimplicated and route of administration.\n\n\n\nThe patterns of cutaneous reaction were classified into\nthe following groups: (i) maculopapular, (ii)\nurticaria/angioedema, (iii) Stevens-Johnson syndrome (SJS)\nor toxic epidermal necrolysis (TEN), (iv) drug reaction with\neosinophilia and systemic symptoms (DRESS) syndrome,\n(v) erythroderma (vi) fixed drug eruption, (vii) acute\ngeneralised exanthematous pustulosis (AGEP) and (viii)\nvasculitis.\n\n\n\n\n\n\n\n\n80\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe ADR was considered severe if it was the reason for\nhospitalisation or prolonged the stay; if it caused\nhypotension, fever or blisters; if it was life-threatening or\ncaused death; or if there were systemic abnormalities such as\nliver or renal dysfunction.\n\n\n\nThe patients\u2019 medical histories were reviewed to determine\nif they had a documented previous drug allergy and any\nassociated chronic diseases. These included cancer, chronic\nrenal failure, asthma and other respiratory diseases,\nconnective tissue disease, chronic liver disease, diabetes\nmellitus, hypertension, ischaemic heart disease and human\nimmunodeficiency virus infection.\n\n\n\nData were tabulated on Microsoft Excel spreadsheets and\nprevalence rates were calculated based on data collected by\nthe operations department of our hospital. Data were\nanalysed using goodness of fit test.\n\n\n\nResults\nA total of 65 patients met our inclusion criteria. A\nprevalence of 1.8/1000 among hospitalised patients was\nestimated. The mean age was 41.6 years (range, 13 to 85\nyears). There was a male predominance (males 53.8%,\nfemales 46.2%). The ethnic distribution is shown in Table\n1. Compared to the ethnic distribution of hospitalised\npatients in 2003, cutaneous ADRs were more common in\nthe Malay population (P = 0.007). There was no specific\ndrug that was implicated more commonly in the Malay\npopulation, with the antibiotics (penicillins, cephalosporins\nand quinolones) and NSAIDs accounting for the majority\n(57.1%) of reactions. The majority of patients who\nexperienced cutaneous ADRs were from the general\nmedicine department (64.6%). The rest were from the\ndepartments of general surgery (13.8%), orthopaedics\n(12.3%), and cardiology (4.6%), and equal numbers (1.5%)\nwere from the departments of psychiatry, ophthalmology\nand geriatric medicine\n\n\n\nFive patterns of cutaneous drug reactions were seen in our\npopulation. In order of decreasing incidence, these were\n\n\n\nurticaria/angioedema, maculopapular, SJS/TEN, DRESS,\nand erythroderma (Table 2). Fixed drug eruption, acute\ngeneralised exanthematous pustulosis, and vasculitis were\nnot observed. In 2 patients, the cutaneous reaction was not\nspecified.\n\n\n\nNineteen patients (29.2%) had severe reactions, but there\nwere no reported deaths. Of these 19 patients, hypotension\nor anaphylaxis occurred in 10.5% and biological\nabnormalities such as renal or liver dysfunction were\nobserved in 15.8%. The ADR was responsible for\nhospitalisation or prolonged stay in 73.7%.\n\n\n\nThe list of causative drugs and their frequency are shown in\nTable 3. Antibiotics, particularly penicillins and\ncephalosporins, and non-steroidal anti-inflammatory agents\n(NSAIDs) accounted for the majority (66.1%) of cases.\nTogether with anti-convulsants, they were also responsible\nfor the more serious reaction patterns of erythroderma,\nTEN or SJS. Of these drugs, 55.4% were administered via\nthe intravenous route, 43.1% orally and 1.5% by\nintramuscular injection.\n\n\n\nThere were 44.6% of patients that had at least 1 concurrent\nchronic disease. These include hypertension (44.8%),\nischaemic heart disease (27.6%), diabetes mellitus (24.1%),\nasthma (17.2%), chronic liver disease (17.2%), other\nrespiratory diseases (10.3%), cancer (6.9%), chronic renal\nfailure (6.9%), connective tissue disease (3.4%) or human\nimmunodeficiency virus (HIV) infection (3.4%).\n\n\n\nDiscussion\nCutaneous drug eruptions are the most common drug-\ninduced adverse reaction, and have been reported in 2% of\nhospitalised patients1. The estimated prevalence rate of\n1.8/1000 hospitalised patients in our study is lower than\nthat of most reports2, and this may be due to an\nunderreporting of ADRs to the database on the part of\nhealthcare workers. Our study showed that the commonest\ndrugs causing cutaneous ADRs were antibiotics. When\ncompared to previous local studies,3,4 a higher number of\ncutaneous \n\n\n\nTable 1.   Ethnic Group Distribution of Hospital Admissions and Those Inpatients with Reported Cutaneous ADR\n\n\n\nADR: adverse drug reaction\n\n\n\nEthnic group\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nTotal\n\n\n\nNumber of hospital admissions\nin 2003 (%)\n\n\n\n22,795 (62.2)\n\n\n\n6548 (17.8)\n\n\n\n3469 (9.5)\n\n\n\n3851 (10.5)\n\n\n\n36,663 (100.0)\n\n\n\nNumber of patients who\nreported cutaneous ADR (%)\n\n\n\n38 (58.5)\n\n\n\n21 (32.3)\n\n\n\n4 (6.2)\n\n\n\n2 (3.0)\n\n\n\n65 (100.0)\n\n\n\nP value\n\n\n\n0.007\n\n\n\n\n\n\n\n\n81\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ncutaneous ADRs were found to be due to newer drugs like\ncephalosporins and quinolones. This is probably due to an\nincreased usage of such drugs in the hospital setting today.\n\n\n\nFrom previous studies, the incidence of ADR varied greatly\namongst departments2. We found this to be true in our\nstudy, with the largest proportion of patients coming from\nthe general medicine department. There was also a slight\nmale predominance in our study, which is consistent with\nprevious data2,5.\n\n\n\nMaculopapular exanthems and urticaria/angioedema were\nthe most common manifestations of cutaneous ADRs\nwhatever the suspected drug, accounting for 86.1% of the\ncutaneous reactions seen. This is consistent with previous\nretrospective studies3,5,6, but our study demonstrated an\nunusually higher proportion of urticarial eruptions. More\nsevere reactions like SJS/TEN, DRESS and erythroderma\nwere\n\n\n\nTable 3.   Table 3. Drugs Implicated in Adverse Cutaneous Reactions in a Hospital Setting\n\n\n\nACE: angiotensin-converting enzyme, AE: angioedema, DRESS: drug reaction with eosinophilia and systemic symptoms,\nERY: erythroderma, MP: maculopapular, NAC: N-acetylcysteine, SJS/TEN: Stevens-Johnson Syndrome/toxic epidermal necrolysis,\nURT: urticaria\n\n\n\nCephalosporin\n\n\n\nPenicillin\n\n\n\nQuinolone\n\n\n\nOther antibiotics\n\n\n\nVancomycin\n\n\n\nBactrim\n\n\n\nNSAIDs\n\n\n\nNAC\n\n\n\nAnti-convulsant\n\n\n\nAnalgesics excluding \nNSAIDs\n\n\n\nAnti-coagulant\n\n\n\nAnti-hypertensive\n(ACE-inhibitor)\n\n\n\nAnti-depressant\n\n\n\nAnti-malarial\n\n\n\nRadiographic contrast\nmedia\n\n\n\nTotal\n\n\n\nURT/AE\n\n\n\n9\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n10\n\n\n\n2\n\n\n\n0\n\n\n\n4\n\n\n\n1\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n30\n\n\n\nMP\n\n\n\n3\n\n\n\n7\n\n\n\n4\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n7\n\n\n\n2\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n26\n\n\n\nSJS/TEN\n\n\n\n1\n\n\n\n2\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n5\n\n\n\nDRESS\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\nERY\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n1\n\n\n\nNot\nspecified\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n1\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n2\n\n\n\nTotal\n\n\n\n13\n\n\n\n11\n\n\n\n5\n\n\n\n2\n\n\n\n1\n\n\n\n11\n\n\n\n9\n\n\n\n3\n\n\n\n4\n\n\n\n2\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n1\n\n\n\n65\n\n\n\nTable 2.   Patterns of Cutaneous Adverse Drug\nReactions and Its Occurrence in a Hospital Setting \n\n\n\nSJS/TEN: Stevens-Johnson Syndrome/toxic epidermal necrolysis\nDRESS: Drug reaction with eosinophilia and systemic symptoms \n\n\n\nReaction pattern\n\n\n\nUrticaria/angioedema\n\n\n\nMaculopapular\n\n\n\nSJS/TEN \n\n\n\nDRESS\n\n\n\nErythroderma\n\n\n\nNot specified\n\n\n\nTotal\n\n\n\nNumber (%)\n\n\n\n30 (46.2)\n\n\n\n26 (40.0)\n\n\n\n5 (7.7)\n\n\n\n1 (1.5)\n\n\n\n1 (1.5)\n\n\n\n2 (3.1)\n\n\n\n65 (100.0)\n\n\n\n\n\n\n\n\n82\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nwere associated mainly with anti-microbials, NSAIDs and\naniticonvulsants. The single patient who developed DRESS\nhad, in addition to the usual features of fever, malaise,\ndermatitis and lymphadenopathy, rare manifestations of\nreversible hypersensitivity myocarditis and thyrotoxicosis7.\nThe culprit drug was maloprim (comprising dapsone 100\nmg and pyrimethamine 12.5 mg), which was administered\nfor anti-malarial prophylaxis. Our study also emphasises the\nhigh proportion of severe cutaneous ADRs (29.2%).\n\n\n\nIn addition, a large proportion of the patients (44.6%) had\nan associated chronic disease. The commonest associated\ndiseases were hypertension, ischaemic heart disease and\ndiabetes mellitus. This may be an additional risk factor for\nthe development of cutaneous ADR due to the increased\nuse of medication, polypharmacy, and drug interactions,\nleading to decreased clearance of drug metabolites. Almost\none-quarter of the patients had a documented previous\ncutaneous ADR. Although the exact mechanism is not\nknown, some authors have suggested that a genetic\nsusceptibility to drug-induced cutaneous ADR may play a\nrole2. For example, N-acetyltransferase activity may vary\nbetween individuals due to genetic polymorphism8.\n\n\n\nUnderreporting of cutaneous ADRs by ward doctors is\nlikely to be a limitation in our study. In addition, we took\nthe reported data at face value, and did not attempt to take\ninto account the causal association of the drug implicated.\nHowever, we feel that this study provides insight into local\ndata on this topic and helps to update the spectrum of\ncutaneous ADRs seen in hospital practice. This is important\nas new drugs are constantly being introduced into the\nmarket.\n\n\n\nOur study highlights several important findings: antibiotics\nand NSAIDs were the major drugs involved, a high\nproportion of patients had severe reactions, the proportion\nof patients with urticaria/angioedema was higher than in\nmost previous studies, and the Malay population may be at\na higher risk for cutaneous ADRs. We recommend a\nprospective investigation of ADRs in the hospital setting in\nSingapore.\n\n\n\nAcknowledgements\nThe authors thank Ms Liew Siew Huey for her help in\ngenerating the patient database and the NUH-NUS\nMedical Publications Support Unit, Singapore, for its\nassistance in the preparation of this manuscript.\n\n\n\nReferences\n\n\n\n1. Baune B, Kessler V, Patris S, et al. Medicinal iatrogenics in \nhospitals. A survey on a given day. Presse Med 2003;32:683-8.\n\n\n\n2. Fiszenson-Albala F, Auzerie V, Mahe E, et al. A 6-month \nprospective survey of cutaneous drug reactions in a hospital \nsetting. Br J Dermatol 2003;149:1018-22.\n\n\n\n3. Tan SF, Oon CH, Yeoh TS. Adverse drug reaction reporting in the \nSingapore General Hospital. Ann Acad Med Singapore \n1979;8:141-3.\n\n\n\n4. Fong PH, Chan HL. Current cutaneous drug reaction patterns in \nSingapore. Singapore Med J 1984;25:336-9.\n\n\n\n5. Kidon MI, See Y. Adverse drug reactions in Singaporean \nchildren. Singapore Med J 2004,45:574-7.\n\n\n\n6. Sushma M, Noel MV, Ritika MC, et al. Cutaneous adverse drug \nreactions: a 9-year study from a South Indian hospital. \nPharmacoepidemiol Drug Saf 2005;14:567-70.\n\n\n\n7. Teo RYL, Tay YK, Tan CH, et al. Presumed dapsone-induced drug \nhypersensitivity syndrome causing reversible myocarditis and \nthyrotoxicosis. Ann Acad Med Singapore 2006;35(11):833-6.\n\n\n\n8. Shapiro LE, Shear NH. Mechanisms of drug reactions: the \nmetabolic track. Semin Cutan Med Surg 1996;15:217-27.\n\n\n\n\n\n\n\n\n83\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nCutaneous Adverse Drug Reactions observed in a \nDermatology Clinic, Penang General Hospital\n\n\n\nTan WC, MD, Lo Kang SC, MD, MRCP, MMed, Ong CK, MD, MRCP, Kalaikumar N, MD and Cheah CM, MBBS\n\n\n\nDepartment of Dermatology, Penang General Hospital\nPenang, Malaysia\n\n\n\nCorrespondence\n\n\n\nTan Wooi Chiang, MD,\nDepartment of Dermatology\nHospital Pulau Pinang, Jalan Residensi, 10450 Penang\nEmail : tanwooichiang@yahoo.com\n\n\n\nAbstract \n\n\n\nBackground Cutaneous Adverse Drug Reaction (CADR) is\ncommonly encountered in our daily clinical practice1. Knowledge of\nthe various patterns of CADR and the common offending agents will\ncertainly help the physician in assessing the likelihood of the drug\ninduced eruption as opposed to another dermatological diagnosis.\n\n\n\nObjectives To improve the understanding of CADRs in Penang\nGeneral Hospital, To evaluate the incidence of CADR in Dermatology\nclinic Penang Hospital, to identify the common offending drugs and to\ndescribe the characteristics of CADR and to identify the associated risk\nfactors of developing CADR.\n\n\n\nMaterials and Methods This prospective study covers a 12-month\nperiod from April 2005 to March 2006. Demographic characteristics,\ncausative drugs, management and treatment outcome were analysed.\n\n\n\nResults A total of 174 cases were referred to the Dermatology Clinic\nover 1-year period (Incidence of 4.9% of Dermatology Clinic new case\nattendees). Chinese comprises of 51.4%, followed by Malay 32.4%,\nIndian 10.8% and others 5.4%. Male to female ratio was 1.2:1. 74.1 %\nof CADR occurred between 13 - 59 year age group. The offending\ndrugs included antimicrobials 28.6%, antituberculous 19.7%, analgesics\n17.7%, allopurinol 8.4%, anticonvulsants 5.4%, HAART 1.0%,\ntraditional medicines 2.0% and others 17.2%. High proportion of\nerythema multiforme syndrome cases was observed (23.5%). Toxic\nepidermal necrolysis has a high mortality rate. It was caused by\namoxycillin, sulphonamide and phenytoin. 80.5% of CADR occurred\nwithin 2 weeks of drug introduction. Overall mortality rate secondary\nto CADR was 2.3%. Risk factors identified included poly-pharmacy\n(37.9%), renal insufficiency (31.0%), personal history of previous drug\nallergy (19.0%), liver disorder (18.4%), tuberculosis (16.7%), HIV\ninfection (10.3%), autoimmune disorders (6.3%) and hematological\nmalignancy (4.0%).\n\n\n\nConclusions Diagnosis of CADR requires a high index of suspicion\nespecially in those having symmetrical eruption within 2 months in\nrelation to initial dose of medication, particularly the high risk groups.\n\n\n\nKeywords Cutaneous adverse drug reaction, toxic epidermal\nnecrolysis, drug rash\n\n\n\nIntroduction\nCutaneous Adverse Drug Reactions (CADR) is commonly\nencountered in our daily clinical practice. Cutaneous\nadverse drug reactions to drugs are common, affecting 2 to\n3 percents of hospitalized patients1.\n\n\n\nKnowledge of the various patterns of cutaneous adverse\ndrug reactions and the common offending agents will\ncertainly help the physician in assessing the likelihood of\nthe drug induced eruption as opposed to another\ndermatological diagnosis. The true incidence and prevalence\nin any community is probably difficult to determine as it\ndepends on the prescribing pattern, availability of\nmedication and surveillance system of the specific medical\ncommunity.\n\n\n\nThe aim of this study is to to improve the understanding of\nCADRs in Penang General Hospital, to evaluate the\nincidence of CADR in Dermatology clinic Penang General\nHospital, to identify the common offending drugs and to\ndescribe the characteristics of CADR, including the type\nand severity and to identify the associated risk factors of\ndeveloping Cutaneous ADR.\n\n\n\nMaterials and Methods\nThe Penang General Hospital is a tertiary centre and\nteaching hospital in the state of Penang, Malaysia. It is a\n1090 bedded hospital that serves a population of 1.4 million\n(47% Chinese, 40% Malay, 10% Indian and others).\n\n\n\nThis prospective study covered a 12-month period from\nApril 2005 to March 2006. Reporting forms were filled up\nby the doctor in-charge. Demographic characteristics,\ncausative drug, management and treatment outcomes were\nnoted and analysed.\n\n\n\n\n\n\n\n\n84\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAll patients including inpatient and outpatient in the\nDepartment of Dermatology Penang General Hospital,\nwith diagnosis of CADR seen within the study period were\nincluded. Diagnosis of CADR was based on clinical\nimpression and relevant investigations including a skin\nbiopsy.\n\n\n\nThe drug responsible for the condition was determined\nfrom the history based on the timing of the drug reaction\nand the attending dermatologist\u2019s impression with the best\navailable information.\n\n\n\n\u2022 Inclusion criteria:\n- Clear history of drug induced reaction.\n- De-challenge improved the skin condition.\n\n\n\n\u2022 Exclusion criteria:\n- Absence of a causative drug according to our \n\n\n\ndefinition\n- Lack of recorded date when the causative drug \n\n\n\nwas started / stopped or disease evolution.\n- Allergic contact dermatitis\n- Skin disorder attributable to infection\n\n\n\n\u2022 Data analysis:\nAll analyses were performed using SPSS 13.0 version.\n\n\n\nResults\nA total of 174 cases were  referred to the Dermatology\nClinic from April 2005 to March 2006, over a 1 year period.\nThis represents 4.9% of Dermatology Clinic new case\nattendees (Total of 3539 new cases during the study period).\nThis was a conservative figure and only reflected perhaps\nthe cases which needed referral for diagnosis or\nmanagement.\n\n\n\nThere were 82 Chinese (51.4%); 73 Malay (32.4%); 12\nIndian (10.8%); 7 others (5.4%). Male to female ratio was\n1.2:1. 74.1 % of CADR occurred in 13 - 59 year age group\n(ranged from day 7 of life to 83 years).\n\n\n\nThe offending drugs included antimicrobials 28.6%,\nantituberculous 19.7%, analgesics 17.7%, allopurinol 8.4%,\nanticonvulsants 5.4%, Highly Active Antiretroviral Therapy\n(HAART) 1.0%, traditional medicines 2.0% and others\n17.2% (Figure 1 & 2).\n\n\n\nAmong the antimicrobials, the penicillin group was the\ncommonest offending agent (31.0%), followed by sulphur\nbased drugs (27.6%), cephalosporin (20.0%), tetracycline\n(8.6%), and quinolones (5.2%).\n\n\n\nFor antituberculous drugs, pyrazinamide and rifampicin\neach contributed to 27.5% of reactions, ethambutol (20.0%)\nand isoniazid (20.0%). Among the analgesics, the NSAIDS\ngroup was the commonest identified agents 88.9%.\n\n\n\nIn the anticonvulsants, phenytoin was the commonest\nculprit, causing 54.5% of reactions, carbamazipine 36.4%\nand sodium valproate 9.1%. Interestingly to note that, all\nthe CADR cases in patiens taking HAART  were due to\nNNRTI.\n\n\n\nAllopurinol caused significant numbers of CADR (8.4%).\nThe frequency of the various morphological types seen were\nmorbiliform 23.6%, SJS 23.6%, erythroderma 17.6%,\nphotodermatitis 17.6% and EM minor 17.6%.\n\n\n\nFigure 1.   Offending agents that identified among CADR patients in dermatology\nClinic Penang Hospital\n\n\n\n\n\n\n\n\n85\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe commonest drug implicated for morbiliform rashes\nwas NSAIDS and antituberculous drugs (25.0%),\nallopurinol for SJS (28.6%), NSAIDS for EM (38.5%),\nNSAIDS for FDE (38.5%) and NSAIDS for urticaria\n(28.6%).\n\n\n\nVarious types of CADR were observed in our series (Figure\n3). A high proportion was due to erythema multiforme\nsyndrome  23.5% (the second commonest type of CADR\nobserved). Toxic epidermal necrolysis was the most serious\nCADR among all with a high mortality rate. It was mainly\ncaused by amoxycillin, sulphonamide, phenytoin,\ncarbamazepine and cephalosporin.\n\n\n\nAs for  the onset of CADR in relation to the initial dose of\nmedication taken, 80.5% of CADR occurred within the first\n2 weeks and none was observed after 2 months (Figure 4).\n\n\n\nAmong the patients with CADR, 53.4% were managed as\nout-patient, 43.7% required hospitalization and 2.9%\nneeded ICU admission. Intravenous Immunoglobulin (IV\nIG) was given to 11 patients (10 TEN; 1 SJS). In our series,\nmortality rate of TEN was 15.4% and SJS was 0.0%.\nOverall mortality rate of CADR was 2.3%. 10.3% of\npatients recovered but with sequelae including pigmentary\nproblems.\n\n\n\nIn our study population, risk factors for CADR identified\nincluded poly-pharmacy (37.9%), renal insufficiency\n(31.0%), personal history of previous drug allergy (19.0%),\nliver disorder (18.4%), TB (16.7%), HIV infection (10.3%),\nautoimmune disorders (6.3%) and hematological\nmalignancy (4.0%) (Figure 5).\n\n\n\nFigure 2.   Offending agents identified among\nCADR patients in dermatology clinic, Penang\nHospital, April 2005 to March 2006\n\n\n\nDRUG GROUP\n\n\n\nANTIBIOTIC\n\u2022 PENICILLIN\n\u2022 CEPHALOSPORIN\n\u2022 SULPHA GROUP\n\u2022 OTHERS\nANTI-TB\n\u2022 RIF\n\u2022 INH\n\u2022 PZA\n\u2022 ETH\n\u2022 SM\n\u2022 OTHERS\nANALGESIA\n\u2022 NSAIDS\n\u2022 OPIOIDS\n\u2022 OTHERS\nANTICONVULSANT\n\u2022 CABARMAZEPINE\n\u2022 PHENYTOIN\n\u2022 SOD. VALPROATE\nALLOPURINOL\nHAART\n\u2022 NNRTI (NVP)\n\u2022 NRTI\n\u2022 PI\nTRADITIONAL \nMEDICATION\nOTHERS\n\n\n\nTOTAL\n\n\n\n58 (28.6%)\n18\n11\n16\n13\n\n\n\n40 (19.7%)\n11\n8\n11\n8\n1\n1\n\n\n\n36 (17.7%)\n32\n2\n2\n\n\n\n11 (5.4%)\n4\n6\n1\n\n\n\n17 (8.4%)\n2 (1.0%)\n\n\n\n2\n0\n0\n\n\n\n4 (2.0%)\n\n\n\n35 (17.2%)\n\n\n\nFigure 3.   Type of CADR observed in dermatology Clinic Penang Hospital,\nApril 2005 to Mar 2006\n\n\n\n\n\n\n\n\n86\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nThe increasing use of new drugs especially growth factors,\nhormones and chemotherapeutic agents have resulted in\nincreasing number of cutaneous adverse drug reactions\n(CADR). Besides western medicine, traditional and\nalternative medications can also cause CADR2.\n\n\n\nCADR is defined as unwanted skin reaction in response to\na systemic administration (oral / subcutaneous /\nintramuscular / intravenous / inhalation) drug, which is\n\n\n\nnoxious and unintended, which occurs at doses used in\nhuman for prophylaxis, diagnosis or therapy. CADR can\nmimic all the morphologic expressions in dermatology3.\n\n\n\nThe types of CADR observed in our series were similar to\nthose reported worldwide. But we observed a high\nproportion of erythema multiforme syndrome cases 23.5%\n(the second commonest type of CADR observed). This may\nbe due to the fact that Penang Hospital is a tertiary referral\ncentre. Common CADR like morbilliform and urticaria\nusually do not get referred.\n\n\n\nFigure 4.   Onset of CADR in relation to the initial dose\n\n\n\nN\nU\n\n\n\nM\nB\n\n\n\nE\nR\n\n\n\n O\nF\n\n\n\nC\nA\n\n\n\nS\nE\n\n\n\nS\n\n\n\nFigure 5.   Risk factors that observed among CADR patient\n\n\n\nN\nU\n\n\n\nM\nB\n\n\n\nE\nR\n\n\n\n O\nF\n\n\n\nC\nA\n\n\n\nS\nE\n\n\n\nS\n\n\n\n\n\n\n\n\n87\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCADR should be considered as one of the differential\ndiagnoses of a suddenly appearing symmetrical skin\neruption The diagnosis of cutaneous ADR is heavily\ndependent on history & physical examination. Previous\ndrug allergy history, morphology & distribution of rashes\nand chronology of drug intake  are the key factors in\ndiagnosis. CADR usually occurs within 2 months of\ninitiation of drug therapy3-5. This was also observed in our\nseries.\n\n\n\nIt is important to be familiar with the various morphology\nof cutaneous eruption to drugs. Recognizing them will help\nto pinpoint the most likely offending agent especially in the\ncase of poly-pharmacy.\n\n\n\nIt is equally important to recognize those at high risk of\ndeveloping a CADR. The at risk groups  include those\nwith underlying multi organ failure3, elderly3,5, poly-\npharmacy3,6-7, malignancy especially hematological3,\nunderlying infection like HIV / Epstein-Barr Virus (EBV)\n/ tuberculosis3,7-8, certain autoimmune diseases (Rheumatoid\narthritis, Sjogren\u2019s disease or Systemic Lupus\nErythematosus)3,9 and genetic susceptibility10-11. Similar\npicture also observed in our series. Interestingly it was\nobserved that, 19.0% of CADR (33 cases) were preventable.\nThese involved  patients with a personal history of previous\ndrug allergy who have been given same group of\nmedication.\n\n\n\nManagement of CADR involves a multi-disciplinary\napproach12. Early diagnosis and prompt withdrawal of the\nmost likely offending medication is crucial13. The patient\nshould be informed and given in writing, the name of the\noffending medication and the type of reaction seen in\nallergy notification card. Medic alert bracelet is encouraged\nin those with severe CADR.\n\n\n\nAll cases should be notified14-15 to the Malaysian Adverse\nDrug Reaction Advisory Committee (MADRAC). This\nhelps to create awareness by sharing information and\ndeveloping a database, in the hope of reducing the incidence\nof CADR.\n\n\n\nConclusion\nThe diagnosis of CADR requires a high index of suspicion\nespecially in those with symmetrical cutaneous eruption\nwithin 2 months after a new medication, particularly the\nhigh risk groups.\n\n\n\nAcknowledges\nWe are most grateful to all the staff of Department of\nDermatology, Penang General Hospital for their help in\ncollecting and compounding data.\n\n\n\nReferences\n\n\n\n1. Bigby M and Stern R  Cutaneous reactions to non-steroidal anti-\ninflammatory drugs. J Am Acad Dermatol 1985;12:866\u2013876.\n\n\n\n2. John Koo, Sumaira Arain. Traditional chinese medicine for the \ntreatment of dermatological disorders. Arch Dermatol 1998; \n134:1388-1393.\n\n\n\n3. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to \ndrugs. N Engl J Med. 1994;331:1272-1285.\n\n\n\n4. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk \nof Stevens-Johnson syndrome or toxic epidermal necrolysis. N \nEngl J Med 1995;333:1600-1607.\n\n\n\n5. Daphne Yee,  et al. Incidence of Serious Side Effects from 1st \nLine Anti-tuberculosis Drugs among Patients Treated for Active \nTuberculosis. AJRCCM 2003; 167: 1472-77.\n\n\n\n6. Saiag P, Caumes E, Chosidow O, Revuz J, Roujeau JC. Drug-\ninduced toxic epidermal necrolysis (Lyell syndrome) in patients \ninfected with the human immunodeficiency virus. J Am Acad \nDermatol 1992;26:567-574.\n\n\n\n7. Rzany B, Mockenhaupt M, Stocker U, Hamouda O, Schopf E. \nIncidence of Stevens-Johnson syndrome and toxic epidermal \nnecrolysis in patients with the acquired immunodeficiency \nsyndrome in Germany. Arch Dermatol 1993;129:1059-1059.\n\n\n\n8. Dover JS, Johnson RA. Cutaneous Manifestations of HIV in \nInfection. Arch Dermatol 1991; 127: 1383-91.\n\n\n\n9. Burge SM, Dawber RPR. Stevens-Johnson syndrome and toxic \nepidermal necrolysis in a patient with systemic lupus \nerythematosus. J Am Acad Dermatol 1985;13:665-666.\n\n\n\n10. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, \nTouraine R. Genetic Susceptibility to Toxic Epidermal Necrolysis. \nArch Dermatol 1987; 123: 1171-1173.\n\n\n\n11. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, \nTouraine R. Genetic susceptibility to toxic epidermal necrolysis. \nArch Dermatol 1987;123:1171-1173.\n\n\n\n12. Taylor JA, et al. Toxic epidermal necrolysis. A comprehensive \napproach. Multi-disciplinary management in a burn center. Clin \nPediatr (Phila) 1989;28:404-407.\n\n\n\n13. Ignacio Garcia-Doral, et al. Toxic epidermal necrolysis and \nStevens-Johnson syndrome: Does early withdrawal of causative \ndrug decrease the risk of death? Arch Dermatol 2000;136:323-\n327.\n\n\n\n14. Kessler DA. Introducing MEDWatch: a new approach to \nreporting medication and device adverse effects and product \nproblems. JAMA 1993;269:2765-2768.\n\n\n\n15. Moore N, Biour M, Paux G, et al. Adverse drug reaction \nmonitoring: doing it the French way. Lancet 1985;2:1056-1058.\n\n\n\n\n\n\n\n\n88\n\n\n\n\n\n\n\n\n89\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nHansen\u2019s Disease in Penang: A 10-year Retrospective \nAnalysis\n\n\n\nTan WC, MD, Lo Kang SC, MD, MRCP, MMed and Ong CK, MD, MRCP\n\n\n\nDepartment of Dermatology, Penang General Hospital\nPenang, Malaysia\n\n\n\nCorrespondence\n\n\n\nTan Wooi Chiang, MD,\nDepartment of Dermatology\nHospital Pulau Pinang, Jalan Residensi, 10450 Penang\nEmail :  tanwooichiang@yahoo.com\n\n\n\nAbstract \n\n\n\nBackground Leprosy is a chronic granulomatous infection caused by\nMycobacterium leprae. The principal manifestations are skin lesions and\nperipheral neuropathy. The aims of the study is to improve the\nunderstanding of  leprosy cases managed in Penang General Hospital\nand to analyse the demographics, clinical patterns, treatment regimen\nand outcome of leprosy in Penang Hospital.\n\n\n\nMaterials and Methods This retrospective study covered a 10-year\nperiod from 1997 to 2006. Demographic characteristics, clinical\npatterns, treatment regimen of leprosy and outcome were analysed.\n\n\n\nResults A total of 95 patients were diagnosed to have leprosy\n(prevalence rate of 0.68 per 100,000). The mean age at presentation\nwas 40.4 years \u00b1 17.9 (range from 3 to 91 years old). There were 35\nMalays (36.8%), 34 Chinese (35.8%), 5 Indians (5.2%) and 21 others.\nPatients experienced symptoms for a mean of 21.4 months before being\nreferred to our clinic. Only 29 patients (30.5%) had a family history of\nleprosy. 34 patients (35.8%) presented with lepromatous leprosy. 95\npatients (100%) presented with skin lesions, 61 patients (61.2%) with\nnerve lesions, 17 patients (17.9%) with deformities and 12 (12.6%)\nwith reactions. The skin lesions occurred predominantly over the lower\nlimbs, face and trunk. 95.8% of skin lesions were hypo/anaesthetic.\nCommon thickened nerves observed were ulnar nerve (40.0%), great\nauricular nerve (38.9%) and posterior tibialis nerve (25.3%). The lepra\nreaction rate was 51.6%. Type 1 reaction commonly involved those\nwith borderline spectrum but type 2 reaction commonly involved those\nwith lepromatous spectrum. Common side effects observed with MDT\nwere dapsone induced hemolytic anaemia (10.5%), cutaneous adverse\ndrug reaction (8.4%) and drug induced hepatitis (2.1%). None of them\nexperienced severe drug toxicity. In terms of treatment for leprosy,\n71.6% of patients had completed their treatment and 18.9% were still\non treatment. 24.1% of patients had their regimen changed because of\nside effects and drug resistance. 6 patients died (due to unrelated cause)\nand another 3 patients defaulted treatment.\n\n\n\nConclusions Our study showed similar epidemiological findings as\nother studies except for a higher reaction rate. There was a significant\n\n\n\ndelay in diagnosis in our cohort. Identification of the reasons of delay\nin diagnosis, and the risk factors of lepra reaction are important in the\nmanagement of leprosy. Anti-leprotic treatment is relatively safe and\neffective in treating leprosy.\n\n\n\nKeywords Epidemiology, leprosy, lepra reactions\n\n\n\nIntroduction\nLeprosy is a chronic granulomatous infection caused by\nMycobacterium leprae. The principal manifestations are skin\nlesions and peripheral neuropathy. Complications are\ncaused by nerve damage, immunological reactions and\nbacillary infiltra-tion. Drug treatment is effective in killing\nthe bacilli, but does not prevent nerve damage and reaction.\nThe aim of the study was to improve the understanding of\nleprosy cases managed in Penang General Hospital and to\nanalyse the demographics, clinical patterns, treatment\nregimen and outcome of leprosy in Penang Hospital.\n\n\n\nMaterials and Methods\nThe Penang General Hospital is a tertiary centre and\nteaching hospital in the state of Penang, Malaysia. It is a\n1090 bedded hospital that serves a 1.4 million population\n(Chinese 47%, Malay 40%, Indian 10% and others 3%).\n\n\n\nThis retrospective study covered a 10-year period from 1997\nto 2006. Reporting forms were filled up by the doctor in-\ncharge. Demographic characteristics, clinical patterns,\ntreatment regimen of leprosy and outcomes were noted and\nanalysed.\n\n\n\nAll patients (inpatient and outpatient) in the Department of\nDermatology Penang General Hospital, with a diagnosis of\nleprosy within this period were included.\n\n\n\nDue to paucity of cases and difficulty in doing a skin biopsy\nin young children, some cases were diagnosed clinically\nwithout a biopsy. Slit skin smears were taken from the site\nof the lesion and stained with Ziehl-Neelsen's staining\nmethod. Skin biopsy was done after obtaining an informed\nconsent.\n\n\n\n\n\n\n\n\n90\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nconsent. The tissue specimens were processed for routine\nhistopathological examination (i.e. staining with\nHematoxylin-Eosin and Fite-Faraco stains). A definite\nhistological diagnosis of leprosy requires: a) presence of\ninfiltration within dermal nerves and b) the presence of\nAcid Fast Bacilli (AFB).\n\n\n\nThe diagnosis of leprosy is primarily clinical. Anaesthetic or\nhypoesthetic skin lesions with or without thickened\nperipheral nerves are virtually pathognomonic of leprosy. A\nfull thickness skin biopsy from an anesthetic lesion showing\ngranuloma and lymphocytic infiltration of nerves essentially\nconfirms the diagnosis.\n\n\n\nLeprosy is categorized as TT (Tuberculoid Leprosy), BT\n(Borderline Tuberculoid), BB (Borderline Borderline), BL\n(Borderline Lepromatous) and LL (Lepromatous Leprosy)\ntypes according to the Ridley Jopling classification.\n\n\n\n\"Lepra reaction\" is the term given to a violent but often\nineffective tissue response presenting as an acute\ndeterioration in the clinical lesions of the patient\nundergoing treatment for leprosy.\n\n\n\nInclusion Criteria:\n\u2022 Patients with Leprosy\n\n\n\n(With one or more of the following symptoms)\n1. Hypopigmented or erythematous skin lesion(s) with \n\n\n\ndefinite loss of sensation.\n2. Damage to the peripheral nerves as demonstrated by \n\n\n\npalpable thickening with or without impairment of \nsensation and/or weakness of the muscles of hands,\nfeet or face \n\n\n\n3. Presence of acid-fast bacilli in slit skin smears \n4. Histological changes diagnostic of leprosy in skin \n\n\n\nbiopsy\n\n\n\n\u2022 Receiving standard MDT treatment for leprosy or \ncompleted treatment for leprosy\n\n\n\nExclusion Criteria:\n\u2022 Presence of other skin or neurological disorders that \n\n\n\nmay be confused with the clinical picture of leprosy.\n\u2022 On oral corticosteroid or other immunosuppressive \n\n\n\ntreatment for other disorder, not for the purpose of the \ntreatment of lepra reaction.\n\n\n\n\u2022 Concurrent participation in another clinical trial.\n\n\n\nAll analyses were performed using SPSS 13.0 version.\n\n\n\nResults\nA total of 95 patients were diagnosed to have leprosy during\nthis period in the Dermatology Clinic, Penang Hospital.\nThe mean age at presentation was 40.4 \u00b1 17.9 years (ranged\nfrom 3 to 91 years old). The patients were predominantly\nmale (70.5%). There were 35 Malays (36.8%), 34 Chinese\n(35.8%), and 5 Indians (5.2%) (Refer figure 1). The rest of\nthe 21 patients (22.2%) were immigrants from\n\n\n\nneighbouring countries like Indonesia, Nepal, Bangladesh\nand Philippines.\n\n\n\nPatients experienced symptoms for a mean of 21.4 months\nbefore being referred to our clinic. At presentation, patients\nhad a mean Bacteriological Index (BI) of 1.38 and mean\nMorphological Index (MI) of 1.00. 66 patients (69.5%) had\nno family history of leprosy.\n\n\n\nFigure 1.   Characteristic features of patients with\nleprosy seen at dermatology clinic, Penang General\nHospital (1997 to 2006)\n\n\n\nSex\nMale \nFemale\n\n\n\nEthnic\nMalay\nChinese\nIndians\nForeign\n\n\n\nAge\n1-10\n11-20\n21-30\n31-40\n41-50\n51-60\n> 60\n\n\n\nFamily history of leprosy\nYES\nNO\n\n\n\nAverage BI\n0\nUp to & including 1\nUp to & including 2\nUp to & including 3\nUp to & including 4\nUp to & including 5\nUp to & including 6\n\n\n\nDelay in presentation\nUp to 6 month\n7-12\n13-24\n25-36\n37-60\n> 60 months\n\n\n\nNo (%) of patients\n\n\n\n67 (70.5%)\n28 (29.5%)\n\n\n\n35 (36.8%)\n34 (35.8%)\n5 (5.2%)\n21 (22.2%)\n\n\n\n4 (4.2%)\n7 (7.4%)\n23 (24.3%)\n17 (17.9%)\n14 (14.7%)\n14 (14.7%)\n16 (16.8%)\n\n\n\n29 (30.5%)\n66 (69.5%)\n\n\n\n43 (45.3%)\n10 (10.5%)\n15 (15.8%)\n18 (18.9%)\n8 (8.4%)\n1 (1.1%)\n0 (0%)\n\n\n\n48 (50.5%)\n18 (18.9%)\n15 15.8%)\n4 (4.2%)\n2 (2.1%)\n\n\n\n8 (8.5%)\n\n\n\n\n\n\n\n\n91\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n34 (35.8%) of the patients presented as LL, 13 (13.7%) as\nBL, 13 as BB (13.7%), 18 (18.9%) as BT, and 17 (17.9%) as\nTT (Refer figure 2).\n\n\n\n95 patients (100%) presented with skin lesions, 61 patients\n(61.2%) with nerve lesions, 17 patients (17.9%) with\ndeformities and 12 (12.6%) with reactions. 2.1% of patients\nwere detected to have leprosy during the contact tracing\n(Figure 3).\n\n\n\nMajority of patients (55.8%) presented with > 5 skin lesions\nat presentation. The skin lesions occurred predominantly\nover the lower limbs, face, trunk, upper limbs, back and\ngenital region. 95.8% of skin lesions were hypo/anaesthetic\n(Figure 4).\n\n\n\nAs for nerve dysfunction, 56 patients (58.9%) were noted to\nhave thickened nerves, 32 patients (33.7%) had sensory loss\n\n\n\nand 11 patients (11.6%) had motor dysfunction. Common\nthickened nerves observed were ulnar nerve (40.0%), great\nauricular nerve (38.9%), posterior tibialis nerve (25.3%),\nperoneal nerve (9.5%) and radial nerve (2.1%).\n\n\n\nIn our series, the lepra reaction rate was 51.6%. Type 1\nreaction commonly involved those with borderline\nspectrum but type 2 reaction commonly involved those with\nlepromatous spectrum. Lepra reaction can occur before,\nduring or after completing treatment. At presentation, 12\npatients (12.6%) had ongoing lepra reaction and majority of\nthem had type 2 reaction. During treatment, 35 patients\nexperienced a reaction, and following cessation of treatment\nan additional 2 patients experienced a reaction. Lepra\nreactions seen during treatment were mainly type 1\nreaction. The majority of the reactions occurred within 6\nmonths on MDT. They were rarely seen among those\nalready on MDT for more than 12 months (Figure 5).\n\n\n\nFigure 2.   Classification of leprosy (Ridley Jopling classification)\n\n\n\nFigure 3.   Initial presentation among subjects in the cohort\n\n\n\n\n\n\n\n\n92\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCommon side effects observed with MDT were dapsone\ninduced hemolytic anaemia (10.5%), cutaneous adverse\ndrug reaction (8.4%) and drug induced hepatitis (2.1%).\nNone of them experienced severe drug toxicity\n\n\n\nIn terms of treatment for leprosy, 71.6% of patients had\ncompleted treatment and 18.9% were still on treatment.\n24.1% of patients had their regimen changed because of side\neffects and drug resistance. 6 patients died (due to unrelated\ncause) and another 3 patients (foreigner) defaulted\ntreatment (Figure 6).\n\n\n\nDiscussion\nWHO introduced Multiple Drug Therapy (MDT) in 1982.\nThe prevalence of leprosy has declined steadily. MDT was\nstarted in Malaysia since 1985. Malaysia achieved\nelimination with a prevalence < 1 per 10,000 & incidence\nrate of < 1 per 100,000 population in 1994. Malaysia\nachieved WHO\u2019s target for control earlier than expected1.\nBut leprosy is still considered a public health problem in\nMalaysia. Leprosy is regarded as a public health problem\nbecause of its capacity to cause permanent disabilities and\ntheir social consequences of discrimination and stigma.\n\n\n\nThe incidence of leprosy in Penang Hospital for the year\n2006 was 15 patients. The incidence rate of Penang in 2006\nwas 0.11 per 10,000 and prevalence rate of 0.68 per\n100,000.\n\n\n\nLeprosy is a chronic granulomatous infection caused by\nMycobacterium leprae, a non-cultivable, extremely slow-\ngrowing, acid-fast bacillus. M. leprae grows best in humans\nat\n\n\n\nFigure 4.   Signs and symptoms at presentation\namong subjects in the cohort\n\n\n\nSkin lesions\n\n\n\nNumber\n1\n2-5\n> 5\n\n\n\nSite\nFace\nTrunk\nBack\nUl\nLl\nGenital\n\n\n\nSensation\nAbsent / reduced\nNormal\n\n\n\nNerve involvement\n\n\n\nThickened nerve\nGreat auricular n.\nUlnar n.\nMedian n.\nRadial n.\nPosterior tibialis n.\nPeroneal n.\n\n\n\nSensory\n\n\n\nMotor\n\n\n\nNo (%) of patients\n\n\n\n95 (100%)\n\n\n\n11 (11.6%)\n31 (32.6%)\n53 (55.8%)\n\n\n\n60 (63.2%)\n59 (62.1%)\n50 (52.6%)\n57 (60.0%)\n66 (69.5%)\n10 (10.5%)\n\n\n\n91 (95.8%)\n4 (4.2%)\n\n\n\n56 (58.9%)\n\n\n\n37 (68.5%)\n38 (70.4%)\n0 (0%)\n2 (3.7%)\n24 (25.3%)\n9 (9.5%)\n\n\n\n32 (33.7%)\n\n\n\n11 (11.6%)\n\n\n\nFigure 6.   Treatment outcome among the subjects in\nthe cohort study\n\n\n\nCompleted treatment / cure\n\n\n\nChange of regimen\n\n\n\nSide effect\nCADR\nAnaemia\nDIH\n\n\n\nDrug resistance\n\n\n\nDefaulted treatment\n\n\n\nDied\n\n\n\nStill on treatment\n\n\n\nNo (%) of patients\n\n\n\n68 (71.6%)\n\n\n\n23 (24.1%)\n\n\n\n8 (8.4%)\n10 (10.5%)\n2 (2.1%)\n\n\n\n3 (3.1%)\n\n\n\n3 (3.2%)\n\n\n\n6 (6.3%)\n\n\n\n18 (18.9%)\n\n\n\nFigure 5.   Lepra reaction observed among the\nsubjects in the cohort study\n\n\n\nType 1\nBefore treatment\nDuring treatment\nAfter treatment\n\n\n\nType 2\nBefore treatment\nDuring treatment\nAfter treatment\n\n\n\nLucio phenomenan\n\n\n\nNo reaction\n\n\n\nNo of patients\n\n\n\n26\n4\n21\n1\n\n\n\n22\n7\n14\n1\n\n\n\n1\n\n\n\n46\n\n\n\n\n\n\n\n\n93\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nat temperatures below 37\u00b0C. It therefore grows well in\ncooler areas of the body and is viable in the armadillo and\nrodents. The long incubation period of M. leprae is unique\namong bacterial diseases. The minimum and average\nincubation times are 2-3 and 5-7 years and can be as long as\n40 or more years.\n\n\n\nLeprosy demonstrates a wide spectrum of immunological,\nmicrobiological, histological and clinical sequelae as\nclassified by Ridley and Jopling in 19622-4. Clinical\nmanifestations are largely confined to the skin, upper\nrespiratory system, eyes, testes and peripheral nerves, with\nsubsequent physical deformities and nerve damage.\n\n\n\nAt one polar is tuberculoid leprosy, which is characterized\nby a strong cell-mediated immunity towards M. leprae,\ngiving rise to localized disease. This is clinically manifested\nby up to three small elevated erythematous cutaneous\nplaques with a well-defined border. The plaque has a\nhealing center with anaesthesia with or without the\npresence of an enlarged peripheral nerve and associated\nsensory or motor dysfunction. It also contains an\nundemonstrable number of bacilli2-4.\n\n\n\nAt the other end of the spectrum is lepromatous leprosy,\nwhich is characterized by numerous disseminated macules /\nnodules / papules having ill defined borders and no healing\ncenter. There is sensory nerve damage with significant\npresence of the bacilli in Schwann cells. Deformities of the\nhands and feet are common. If untreated, lepromatous\nleprosy progresses slowly with continuous bacteremia and\nsubsequent death from renal failure or acute infections2-4.\n\n\n\nLeprosy is also classified according to the degree of skin-\nsmear positivity based on the Ridley-Jopling classification\nsystem. This classification served as a basis for\nchemotherapy. Multibacillary leprosy consists of the polar\nto borderline lepromatous leprosy, while paucibillary leprosy\nconsists of tuberculoid and borderline tuberculoid leprosy.\nMost leprosy cases fall between the two polar forms under\nborderline categories and can transform along this\nspectrum. They are stable at the two polar extremes and\nmost labile at the mid-point of the spectrum2-3. The polar\nforms of leprosy vary widely in different populations. In\nIndia and Africa, 90% of patients are tuberculoid, while in\nMexico 90% are lepromatous. In our cohort, about 50% of\nleprosy patients are in lepromatous spectrum.\n\n\n\nMycobacterium leprae has the affinity for peripheral nerves\nand neuropathy is a cardinal manifestation of the disease.\nThe nerve damage affects sensory, motor and autonomic\nfibers resulting in physical impairment and limitation of\nphysical activities and social participation5.\n\n\n\nType 1 lepra reaction is the most common type of reaction.\nIt is mediated by delayed-type hypersensitivity (Type 4)\n\n\n\ndirected against M. leprae antigens which usually localized\nto the skin and nerve and result in mycobacterial\nelimination. These reactions typically occur in\n\u2018immunologically unstable BT, BB and BL leprosy\npatients4-5. A similar pattern was observed in our cohort\n(76.9% of type 1 reaction occurred among these groups).\nThey manifest clinically as acutely inflamed skin lesions and\nacute neuritis. Type 1 reactions may not be associated with\nsystemic symptoms such as fever or arthralgias. Systemic\ncorticosteroid remains the treatment of choice for type 1\nreaction.\n\n\n\nType 2 (erythema nodosum leprosum, ENL) reactions\noccur as a result of immune-complex deposition in the\nvascular endothelium and tissues and mediated by type 3\nimmune reactions (immune-complex mediated). ENL is an\nepisodic reaction which occurs in about half of borderline\nlepromatous and lepromatous leprosy patients and mostly\ndevelops within the first 1 years of drug treatment4-5. 90.9%\nof type 2 reaction cases in our cohort belonged to BL and\nLL leprosy. Precipitating factors include pyrogenic\ninfection, pregnancy and parturition. ENL is usually a\nsystemic disorder associated with fever, malaise, anorexia,\nleukocytosis and anemia. Classic clinical manifestations\ninclude crops of erythematous painful nodules in the skin\nand subcutaneous tissue anywhere in the body but mainly in\nthe face, forearms, torso and medial thighs. There may be\naccompanying nerve, ocular, hepatic, splenic, joint,\nmusculoskeletal, reticuloendothelial, testicular (in males),\ncardiac and renal involvement.\n\n\n\nMost of the ENL reactions are mild in nature and do not\nrequire any specific treatment except with some analgesics\nor antipyretics. In those suffering ENL-associated neuritis,\nthe drug of choice is prednisolone. For chronic recurrent\nreactions the drug of choice is clofazimine (Pannikar 2003)6.\n\n\n\nLucio phenomenon is a rare occurrence reported mainly in\nLatin Americans, especially Mexicans. Patients have a form\nof lepromatous leprosy described as diffuse lepromatosis,\nresulting in necrotic lesions that ulcerate, especially below\nthe knees. Lesions are the result of dermal ischemic\ninfarction resulting in turn from endothelial proliferation\nand/or thrombosis in small vessels. Bacilli are often present\nalong with endothelial cells. Unlike ENL, Lucio is present\nat the time of initial diagnosis. The only case of Lucio\u2019s\nphenomenon in our series was a previously undiagnosed\nlepromatous leprosy patient and Lucio\u2019s phenomenon was\nhis initial presentation.\n\n\n\nThe lepra bacillus has not been successfully cultured in\nartificial media. But genetically susceptible armadillos,\nmouse foot pad and thymectomized irradiated rats can be\nused to grow bacilli. Diagnosis of leprosy is essentially\nclinical but there are several laboratory and clinical tests that\nprovide bacteriologic, histopathologic, and immunologic\nevidence to support the clinical diagnosis7-8.\n\n\n\n\n\n\n\n\n94\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe World Health Organization (WHO) recommends\nmultiple-drug therapy (MDT) to prevent drug resistance9.\nThree main drugs are used: dapsone, rifampin and\nclofazimine. Standard MDT for multibacillary leprosy\nconsists of 600 mg rifampin once a month, 100 mg dapsone\ndaily and 300 mg clofazimine once a month and 50 mg\ndaily for 12 months. Paucibillary leprosy is treated with 600\nmg rifampin once a month and 100 mg dapsone daily for 6\nmonths. Ofloxacin and minocycline have also been used in\npatients who developed side-effects. In contrast, the MDT\nregimen used in Malaysia is based on the Sungai Buloh\nAugmented Regimen. Sungai Buloh Augmented Regimen\nis an intensified regimen. Treatment duration for\npaucibacillary leprosy is 1 year. For multibacillary leprosy,\nthe maintenance treatment duration is 3 years and intensive\nphase of daily Rifampicin, Clofazimine and Dapsone is for\nat least 3 weeks or until MI = 0. In our cohort study, 100%\nof leprosy patients received MDT as scheduled.\n\n\n\nMulti-drug therapy (MDT) is well established. It is safe,\neffective and widely available. Those who presented late\nhave an increased risk of nerve impairment or disability.\nLeprosy is a curable disease and treatment provided in the\nearly stages will prevent the disability.\n\n\n\nConclusions\nOur study showed similar epidemiological findings as other\nstudies except for a higher reaction rate observed. There was\na significant delay in diagnosis observed in our cohort.\nIdentification of the reasons of delay in diagnosis, and the\nrisk factors of lepra reaction are important in the\nmanagement of leprosy. Anti-leprotic treatment is relatively\nsafe and effective in treating leprosy.\n\n\n\nReferences\n\n\n\n1. WHO. Overview and epidemiology review of Leprosy in the \nWHO Western Pacific Region 1991-2001, pp42.\n\n\n\n2. D. Ridley, W. Jopling, A classification of leprosy for research \npurposes, Lepr Rev 1962;33:119-129.\n\n\n\n3. R. Hastings, S. Franzblau, Chemotherapy of leprosy, Ann Rev \nPharmacol Toxicol 1988;28:231-245.\n\n\n\n4. D. Jolliffe, Leprosy reactional states and their treatment, Br J  \nDermatol1977; 97:345\u2013352.\n\n\n\n5. Amit Agrawal, Lekha Pandit, Monica Dalal, J.P. Shetty. \nNeurological manifestations of Hansen\u2019s disease and their \nmanagement. Clinical Neurology and Neurosurgery \n2005;107:445-454. \n\n\n\n6. Pannikar V. The return of thalidomide: new uses and renewed \nconcerns. Lepr Rev 2003;74: 286-288.\n\n\n\n7. Sehgal VN, Koranne RV, Sehgal S, et al. Correlation of \nmorphological bacteriological and histopathological features of \nleprosy: double blind study. J Dermatol 1985; 12: 243-50.\n\n\n\n8. Sehgal VN, Srivastava G. Status of histoid leprosy. A clinical, \nbacteriological, histopathological and immunological appraisal. \nJ Dermatol 1987; 14: 38-42. \n\n\n\n9. WHO expert committee on leprosy, WHO technical report series \n#874 7th report, World Health Organization, Switzerland, \nGeneva, 1998.\n\n\n\n\n\n\n\n\n95\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nManagement of leprosy in the Department of \nDermatology, Hospital Sultanah Aminah, Johor Bahru\n\n\n\nTey KE, MD, MRCP, MMed, AM, Choon SE, MBBS, FRCP, AM, Zainah M, MD and Zabedah I\n\n\n\nCorrespondence\n\n\n\nDr KE Tey, MD, MRCP, MMed, AM,\nDepartment Of Dermatology\nHospital Sultanah Aminah, Johor Bahru 80100 Johor\nEmail : ketey08@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Malaysia has achieved control of leprosy with an\nincidence rate of 1.1 case per 100,000 population, and a prevalence rate\nof 0.5 per 10,000 population since 19941. However, recently the\nincidence has increased with the influx of foreign workers, especially\nfrom Indonesia, Nepal and Bangladesh. In order to eliminate leprosy,\ncertain issues of need to be addressed namely, imported cases, default\nfrom treatment and drug-resistant cases.\n\n\n\nObjectives\n\n\n\n1. To determine the demography of leprosy patients who \nattended the Skin Department at Hospital Sultanah \nAminah Johor Bahru (HSAJB) for treatment.\n\n\n\n2. To determine  the clinical subtypes of Hansen\u2019s Disease,\nthe incidence of erythema nodosum leprosum (ENL) \nand reversal reactions.\n\n\n\n3. To review the management, side effects of treatment,\nand disease surveillance Materials and Methods A 15-\nyear retrospective study of all new cases of Hansen\u2019s \ndisease attending the Skin Clinic from 1992 to 2006 \nwas undertaken.\n\n\n\nResults A total of 166 patients were treated in the study period, of\nwhom 74.4% were male. The median age at presentation was 37 years\n(range 4 to 85 years). 33% of the patients were immigrants, 34% local\nMalays, 27% local Chinese and 6% local Indians. Of the 166 patients,\n59% had lepromatous leprosy (LL), 22% tuberculoid leprosy (TT), 9%\nborderline tuberculoid leprosy (BT), 8% borderline lepromatous\nleprosy (BL), 1% indeterminate leprosy and 1% neural leprosy.\n\n\n\nThe mean bacteriological index (BI) was 1.63 \u00b1 1.63 std deviations, and\nthe mean morphological index (MI) was 0.77 \u00b1 1.24 std deviations at\nthe time of diagnosis.\n\n\n\nAll patients achieved an MI of zero after three weeks of intensive\ntherapy. 84.6 % of the patients received multiple drug therapy\n(MBCOMBI) in the blister pack distributed by WHO. The remainder\nwas put on modified regimens, because of side effects or drug\nresistance. 43% of patients developed reactions. Of these, 21.1% had\n\n\n\ntype I reaction and 22.9% had erythematous nodosum leprosum\n(ENL). 2 patients developed Lucio\u2019s phenomenon at initial\npresentation. 53% of these developed reaction at  presentation while\n47% had reaction after a few months\u2019 treatment. 9.6% of the patients\ndeveloped side effects secondary to multidrug therapy which\nnecessitated withdrawal of the drugs. The defaulter rate was 15 %.\n\n\n\nLimitations Retrospective analysis with inadequate documentation is\na limitation of this study. In addition, the population studied was\nlimited to referrals being made to the Skin Clinic, which is a tertiary\nreferral center.\n\n\n\nConclusions Control and elimination of leprosy still posed a problem\nas the majority of the foreign patients had lepromatous leprosy, and a\nhigh defaulter rate. Although leprosy in Malaysia has reached the\nelimination target set by the WHO, new cases will continue to be\nobserved in small numbers due to the long incubation period of this\ndisease.\n\n\n\nBackground\nIn 1991, the World  Health Organization formed a\ncampaign to eliminate leprosy as a public health problem by\nthe year 20002. Elimination was defined as a prevalence rate\nof less than 1 per 10,000 population3. Although this goal\nwas achieved at the global level by the end of the year 2000,\nextra effort is still needed to achieve such rates at the\nnational level in some countries.\n\n\n\nMalaysia has achieved control of leprosy with an incidence\nrate of 1.1 case per 100,000 population and a prevalence rate\nof 0.5 case per 10,000 population since 19941. With the\ninflux of foreign workers, especially from Indonesia, Nepal\nand Bangladesh, the incidence of leprosy is again increasing.\n\n\n\nIn order to eliminate leprosy, issues like imported cases,\ndefault from treatment and drug-resistant cases have to be\naddressed.\n\n\n\n\n\n\n\n\n96\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe objectives of the study are:\n1. To determine the demography of leprosy patients who \n\n\n\nattended the Skin Department HSAJB for treatment\n2. To determine  the clinical subtypes of Hansen\u2019s \n\n\n\nDisease, the incidence of erythema nodosum leprosum \n(ENL) and reversal reactions\n\n\n\n3. To review the management , side effects of treatment \nand surveillance\n\n\n\nMaterials and Methods\nThis is a cross-sectional retrospective study of all the\nregistered patients with leprosy referred to the Skin Clinic\nover the past 15 years ( January 1992 - December 2006).\nThis study is based on patient records of the Dermatology\nClinic, Hospital Sultanah Aminah, Johor Bahru. A database\nof the main parameters was created from information\nextracted from the case records. Statistical analysis was done\nusing Microsoft Excel.\n\n\n\nWe used the following terminology and definitions in our\nstudy.\n1. Multiple Drug Therapy (MDT) consists of  a \n\n\n\ncombination of Rifampicin, Dapsone and Clofazimine \nwhich is given for 3 years in patients with multibacillary \nleprosy and 1 year for patients with paucibacillary \nleprosy.\n\n\n\n2. Monotherapy refers to single-drug treatment with \nDapsone.\n\n\n\n3. For monotherapy, a defaulter is one who has absconded \nfrom treatment for 2 years or more. For MDT, a \ndefaulter is one who has not presented for treatment for \nat least 3 consecutive months.\n\n\n\n4. MDT Relapse refers to patients who have completed an \nadequate course of MDT, but who subsequently develop \nnew signs and symptoms of the disease either during the \nsurveillance period or thereafter.\n\n\n\n5. Monotherapy Relapse refers to patients who have \ncompleted an adequate course of monotherapy  \n(Dapsone) and who subsequently develop new signs and \nsymptoms of the disease after the surveillance period \n(Release from Control (RFC)\n\n\n\n6. Reactivation refers to patients who have completed an \nadequate course of monotherapy but who subsequently \ndevelop new signs and symptoms of the disease during \nthe surveillance period.\n\n\n\nResults\n\n\n\nDemographic data\n\n\n\nThe number of new cases from 1992 till 2006 is depicted in\n(Figure. 1). A total of 166 cases were included in the study\nof which 74.4% were male. (Figure. 2)\n\n\n\nThe median age at presentation was 37 years (range 4 to 85\nyears old). 33% of the patients were immigrants; 34% local\nMalays, 27% local Chinese and 6% local Indians (Figure. 3)\n\n\n\nClinical subtypes of Hansen\u2019s disease\n\n\n\nOut of the 166 patients, 59% had lepromatous leprosy (LL),\n22%  tuberculoid leprosy (TT), 9 %  borderline tuberculoid\n(BT), 8 %  borderline lepromatous (BL), 1 %  indeterminate\nleprosy and 1 %  neural leprosy. (Figure 4)\n\n\n\nFigure 1.   Incidence of Leprosy in Hospital Sultanah\nAminah, Johor Bahru\n\n\n\nC\nA\n\n\n\nS\nE\n\n\n\nS\nFigure 2.   Sex distribution\n\n\n\nFigure 3.   Race distribution\n\n\n\n\n\n\n\n\n97\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAccording to the WHO classification, 111 patients (67%)\nwere classified as having multibacillary leprosy (MB) and 55\npatients (33%) paucibacillary leprosy (PB). Of the 111 MB\ncases, 99 patients (89%)) were found to be skin smear\npositive, and 12 patients (11%) were skin smear negative.\nAll patients had a skin biopsy consistent with Hansen\u2019s\ndisease. As for the remaining 17 patients currently under\ntreatment, 10 had MB leprosy while 7 PB leprosy.\n\n\n\nReactional states and treatment of reactions\n\n\n\nA total of 72 patients (43%) developed reactions. 34 patients\n(21.1%) had type I reaction while 38 patients ( 22.9%) had\nerythematous nodosum leprosum (ENL). 2 patients\ndeveloped Lucio\u2019s phenomenon at initial presentation. 53%\nof the patients developed reaction at time of presentation\nwhile 47% had a reaction after a few months of treatment.\nDrugs that were used to treat reactions are depicted in the\npie chart below (Figure 5)\n\n\n\nFigure 4.   Clinical subtypes of leprosy Figure 4.   Drugs used to treat reversal reaction\n\n\n\nTable 1.   Types of MDT Treatment Regimes\n\n\n\nTREATMENT\n\n\n\nMB COMBI\nROM\nROD\n\n\n\nROC, RCM\nMB COMBI RCM\n\n\n\nROC\nMB COMBI ROD\nMB COMBI ROM\n\n\n\nRMD\nRC\nMC\n\n\n\nRC  ETHIONAMIDE\nRD ETHIONAMIDE\n\n\n\nRCD\nCMD\n\n\n\nRD\nROD ROM\n\n\n\nMB COMBI RC\n\n\n\nFREQUENCY\n\n\n\n138\n6\n3\n3\n2\n2\n1\n1\n1\n1\n1\n1\n1\n1\n1\n1\n1\n1\n\n\n\nPERCENTAGE\n\n\n\n84.60%\n3.61%\n1.80%\n1.80%\n1.20%\n1.20%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n0.60%\n\n\n\nMB COMBI - Blister pack distributed by WHO\nROM - Rifampicin, ofloxacin, minocycline\nROD - Rifampicin, ofloxacin, dapsone\nROC, RCM - Rifampicin, ofloxacin, clofazimine\nfollows by Rifampicin, clofazimine,Minocycline\nMB COMBI RCM - MB COMBI follows by\nRifampicin, clofazimine, minocycline\nROC - Rifampicin, ofloxacin, clofazimine\nMB COMBI ROD - MB COMBI follows by\nRifampicin, ofloxacin, dapsone\nMB COMBI ROM - MB COMBI follows by\nRifampicin, ofloxacin, minocycline\nRMD - Rifampicin, minocycline, dapsone\nRC - Rifampicin, clofazimine\nMC - Minocycline, clofazimine\nRC  Ethionamide - Rifampicin, clofazimine,\nEthionamide \nRD  Ethionamide - Rifampicin, dapsone,\nEthionamide \nRCD - Rifampicin, clofazimine, dapsone  \nCMD - Clarithromycin, minocycline, dapsone\nRD - Rifampicin, dapsone\nROD ROM - Rifampicin, ofloxacin, dapsone follow\nby Rifampicin , ofloxacin, minocycline\nMB COMBI RC - MB COMBI follow by Rifampicin,\nclofazimine\n\n\n\n\n\n\n\n\n98\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTreatment, side effects of treatment\n\n\n\nand surveillance\n\n\n\nA total of 138 patients (84.6%) received multiple drug\ntherapy (MBCOMBI) in a blister pack provided by WHO.\nThe remainder were put on modified regimens because of\nside effects of drugs or drug resistance. (Table 1) As for the\n17 patients still under treatment, 10 patients had MB\nleprosy while 7 patients had PB leprosy. 9.6% of the patients\ndeveloped side effects secondary to multidrug therapy\nwhich necessitated withdrawal of the drugs.\n\n\n\nFive patients developed a greyish pigmentation due to\nminocycline, 3 had hepatitis from rifampicin, and 5 had\nhemolytic anaemia with dapsone. A single patient had toxic\nepidermal necrolysis due to ofloxacin. One patient had\nurticaria due to ofloxacin, while another developed severe\nneutropenia following azathioprine.\n\n\n\nFour patients had concurrent pulmonary tuberculosis\n(PTB) and were referred to the chest physician for\ntreatment. 2 patients had preexisting renal failure prior to\ndiagnosis of leprosy. For all patients with a positive skin\nsmear, a skin biopsy was taken and sent to Sungai Buloh\nLeprosy Centre for mouse foot pad inoculation, and MDT\nsensitivity testing. Ten of our patients proved resistant to\ndapsone, and 1 patient had partial resistance to clofazimine.\n(Table 2) The treatment regimes were modified accordingly.\n\n\n\nTwelve patients relapsed after completing treatment. 7 out\nof these had been treated with monotherapy with dapsone\nin 1948-1979. Twenty two patients (13.3 %) developed\ndeformities. Table 3 showed the breakdown of the\ndeformities seen among the cases  over the past 15 years. A\ntotal of 25 patients defaulted follow-up. The defaulter rate\nwas 15 % despite rigorous surveillance.\n\n\n\nDiscussion\nMalaysia has achieved control of leprosy with an incidence\nrate of 1.1 cases per 100,000 population and a prevalence\nrate of 0.5 case per 10,000 population since 1994. With the\ninflux of foreign workers, especially from Indonesia, Nepal\nand Bangladesh, the incidence is again increasing. Over the\npast 15 years, a total of 166 new cases were seen in our skin\nclinic. The majority of these cases were referred to our clinic\neither by the district hospitals, out-patient departments or\nprivate clinics. The number of new cases has declined\nsignificantly from 1992 (21 cases) till 2003 (5 cases), with a\nsmall increase between 2004 and 2006. One third of the\npatients were foreign nationals from Indonesia, Myanmar,\nNepal and India.\n\n\n\nLeprosy affects all age groups, ranging from early infancy to\nthe very old. Prevalence rates usually peak between the age\nof 30 and 50 years. The youngest patient reported in the\nmedical literature is 3 week old child in Martinique by\nMontestruc and Berdonneau in 1954.\n\n\n\nIn our case series, the peak incidence occurred between the\nages of 30 to 40 years. Our youngest patient was 4 years old\nand oldest 85 years old at presentation. In our series, leprosy\naffected the most productive age group and this poses an\neconomic loss to the family and country. A delay in\ntreatment may result in complications and the necessary\nrehabilitation would be even costlier.\n\n\n\nIn most parts of the world, males are affected more\nfrequently than female in the ratio of 2 to 1. In our study,\n74.4% of cases were males while 23.6 % were females.\nHowever, the male preponderance in leprosy is not\nuniversal. In Africa, leprosy affects both sexes equally. A\nhigher prevalence of leprosy among females is observed in\nUganda, Nigeria, Malawi, Gambia, Burkino Faso, Zambia,\nThailand & Japan.\n\n\n\nThe epidemiology of the disease itself is still a problem\nbecause there is still no effective way to measure the level of\ninfection and the incidence of the disease in the community.\nThis is complicated by very long incubation period of the\ndisease and the process of self-healing of many single\nlesions. There is also a tendency for patients to conceal  their\ndisease because of social stigma4.\n\n\n\nTable 2.   Drug resistance\n\n\n\nDRUG TYPE\n\n\n\nCLOFAZIMINE\n\n\n\nDAPSONE\n\n\n\nFREQUENCY\n\n\n\n1\n\n\n\n10\n\n\n\nPERCENTAGE\n\n\n\n0.61%\n\n\n\n6.10%\n\n\n\nTable 3.   Deformities\n\n\n\nDeformities\n\n\n\nLeonine\n\n\n\nCollapse of Nose + Exposure keratitis\n\n\n\nUlnar Claw Hand\n\n\n\nFoot Drop\n\n\n\nPeripheral Neuropathy\n\n\n\nPartial Absorption of Hands & Feet\n\n\n\nFrequency\n\n\n\n4\n\n\n\n1\n\n\n\n3\n\n\n\n2\n\n\n\n7\n\n\n\n2\n\n\n\n\n\n\n\n\n99\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThirty three percent of the patients were foreigners. More\nnew cases were detected among immigrants since 2000. As\nmajority of the immigrants do not come forward for\ntreatment and do not possess a fixed abode, contact tracing,\nfollow-up and surveillance is difficult. High defaulter rates\nwere seen among this group of patients. This may well serve\nas a source of infection to the local population.\n\n\n\nIn 1960, Ridley and Jopling classified leprosy into 5 groups\nbased on immunological and histological evidence namely\ntuberculoid leprosy (TT), borderline tuberculoid (BT)\nborderline borderline (BB), borderline lepromatous (BL)\nand lepromatous leprosy (LL)7,8.\n\n\n\nOut of the 166 patients, 59% had lepromatous leprosy (LL),\n22% tuberculoid leprosy (TT), and 9% borderline\ntuberculoid (BT), 8% borderline lepromatous (BL), 1%\nindeterminate leprosy and 1% neural leprosy.\n\n\n\nAccording to the WHO classification, 111 patients (67%)\nwere classified as multibacillary leprosy (MB) while 55\npatients (33%) were classified as paucibacillary (PB) cases.\nOf the 111 MB cases, 99 patients (89%)) were found to be\nskin smear positive, 12 patients (11%) were skin smear\nnegative. All diagnoses were confirmed by skin biopsy. As\nfor the 17 patients currently under treatment, 10 patients\nhad MB leprosy while 7 patients had PB leprosy.\nComparing both classifications, most of the patients were\ndiagnosed late.\n\n\n\nDapsone was first used to treat leprosy in 1943. Clofazimine\nwas introduced in 1963 and Rifampicin in 1966.\nMonotherapy with Dapsone had resulted in resistant strains\nof Mycobacterium leprae. In 1981, the World Health\nOrganisation (WHO) introduced Multiple Drug Therapy\n(MDT) comprising of Rifampicin, Clofazimine and\nDapsone. MDT was introduced in Malaysia in 1985, and\nby 1994, almost all cases nationwide were on MDT. The\nprogram was reviewed in 1995 and integrated into the\npublic health service. The WHO MDT regime is\nsummarised in Table 4.\n\n\n\nIn our clinic, we have adopted the Sungai Buloh\nAugmented Regime as showed in (Table 5) where PB cases\nwere treated for a year and, MB leprosy patients were\ntreated for 3 years.\n\n\n\n43% of the patients developed reactions, 21.1% type I\nreaction and 22.9% erythematous nodosum leprosum\n(ENL), 2 patients developed Lucio\u2019s phenomenon at initial\npresentation and were successfully treated with\nprednisolone and MDT. 53% of the patients developed\nreaction at time of presentation while 47% had reaction a\nfew months\u2019 after initiation of therapy. Single-agent\nprednisolone is the the drug of choice for treatment of\nreactions (66%), follow by combinations of prednisolone\nand aspirin (23%), prednisolone and azathioprine (9%), and\naspirin alone (2%)\n\n\n\nA total of 138 patients  (84.6%) o received multiple drug\ntherapy (MBCOMBI ) in the blister pack distributed by\nWHO. The blister pack is easy to understand and\nadminister by most patients, regardless of their education\nlevel. The patients were requested to return the empty pack\neach month during follow-up. This allows a check on the\ncompliance to treatment. The remainder were put on\nmodified regimens because of side effects of drugs and drug\nresistance. As for the 17 patients currently under treatment,\n10 patients had MB leprosy while 7 patients had PB leprosy.\nNine point six percent of the patients had side effects\nsecondary to multidrug therapy which necessitated\nwithdrawal of the drugs.\n\n\n\nThe National Leprosy Elimination programme was\nlaunched in Malaysia in July 1992. The aim is to increase\nearly detection of cases and early treatment with adequate\nfollow- up to prevent transmission, as well as to reduce\ndeformity rate. The national target for deformities was set\nbelow 10%. In our study, 22 patients (13.3 %) developed\ndeformities which is higher than the national target. This\nproblem should be addressed seriously. Health education to\nfamiliarize the public with the early signs and symptoms of\nleprosy should be carried out, as well as campaigns\nencouraging\n\n\n\nTable 4.   WHO recommended MDT\n\n\n\nPaucibacillary (PB)\n\n\n\nWHO recommends 6\nmonths of :\n\n\n\nRifampicin 600mg monthly \n\n\n\nDapsone  100mg daily\n\n\n\nMultibacillary (MB)\n\n\n\nWHO recommends 12\nmonths of :\n\n\n\nRifampicin 600mg monthly\nClofazimine 300mg\nmonthly\n\n\n\nCofazimine 50mg daily \nDapsone 100mg daily\n\n\n\nTable 5.   Sungai Buluh Augmented Regime\n\n\n\nPaucibacillary (PB)\n\n\n\n12 months of:\n\n\n\nRifampicin 600mg monthly\nClofazimine 300mg monthly\n\n\n\nClofazimine 100mg daily\nDapsone 100mg daily\n\n\n\nMultibacillary (MB)\n\n\n\nIntensive Therapy\nRifampicin 600mg daily\nClofazimine 100mg daily\nDapsone 100mg daily\n(3 weeks or until MI=0)\nRifampicin 600mg monthly\nClofazimine 300mg monthly\nClofazimine 100mg daily\nDapsone 100mg daily\n\n\n\n3 years or until smear\nnegative\n\n\n\n\n\n\n\n\n100\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nencouraging the public to seek treatment early. Training of\nhealthcare professionals to have a high index of suspicion\nand recognize leprosy at an early stage is equally important.\n\n\n\nFor all patients with positive skin smears, skin biopsies were\nsent to Sungai Buluh Leprosy Centre for mouse foot pad\ninoculation and MDT sensitivity testing. Ten of our\npatients were resistant to dapsone, and 1 patient had partial\nresistance to clofazimine. The treatment regimes were\nmodified accordingly.\n\n\n\nDapsone was used to treat leprosy since 1943, and was used\nas monotherapy for over 30 years. Emergence of drug\nresistant strains of Mycobacterium leprae was reported soon\nafter the introduction of dapsone. Dapsone resistance was\nfirst reported in 19649. By 1982, secondary dapsone\nresistance was reported in more than 25 countries according\nto a report by WHO.\n\n\n\nClofazimine was found to be effective in the treatment of\nleprosy since  1962. The first case of clofazimine resistance\nwas reported in 1982 by Warndoff and Van die pen.\n\n\n\nRifampicin was used as anti-leprosy drug since 1966.\nSecondary rifampicin resistance was first reported in 197610.\n\n\n\nIn 1989, 22 more strains of M. leprae resistant to rifampicin\nwas detected in 39 multibacillary patients who relapsed11.\nAll cases reported were due to rifampicin monotherapy.\n\n\n\nThe first report of secondary resistance to rifampicin\nfollowing 26 doses of MDT (Rifampicin 600mg and\nClofazimine 600mg for 2 days, Inj Acedapsone 225mg IM\nevery 8 wwks and dapsone 100mg daily) was reprted in\n2003 from India12. Rifampicin resistant cases following\nMDT may have gone undetected. It is necessary to monitor\nand gather the information on it\u2019s magnitude. In order to\nprevent multiple drug resistant strains of M. leprae from\ndeveloping, current leprosy control strategies are based on\nearly detection of cases and treatment with multidrug\ntherapy (MDT) as recommended by the WHO.\n\n\n\nTwelve patients relapsed after completion of therapy. Seven\nout of them had been treated with monotherapy with\ndapsone from 1948-1979. Education on compliance to\nmedication is important to prevent relapse and emergence\nof resistance strains. Early detection of drug-resistant bacilli\namong patients not improving clinically will need treatment\nwith combinations of effective drugs to prevent resistance to\ncurrent and new drugs for leprosy. Twenty-five patients\ndefaulted follow-up and the patient defaulter rate was 15 %\ndespite rigorous surveillance. High defaulter rates were seen\namong foreign nationals, who pose a great challenge to our\nleprosy elimination programme.\n\n\n\nConclusions\nLeprosy affects predominantly males (74.4%). Majority of\nthe patients were in the economically active age group. One\nthird of the patients were immigrants, and this serves as a\nsource of infection to the local population. Sixty seven\npercent of study cohort had MB leprosy at initial\npresentation. The majority of the multibacillary Hansen\u2019s\npatients were immigrants. Despite a rigorous surveillance\npolicy, the defaulter rate was 15%.\n\n\n\nControl and elimination of leprosy still poses a problem in\nview of the fact that the majority of immigrants had MB\nleprosy and a high default rate. Although leprosy in\nMalaysia has reached the elimination target set by the\nWHO, new cases will continue to be seen in small numbers\ndue to the long incubation period of this disease \n\n\n\nEarly diagnosis and prompt referral for treatment is crucial\nto prevent deformities and permanent disability. Public\nhealth education is important to increase public knowledge,\ndispel false beliefs and reduce stigma of this dreaded disease.\n\n\n\nAcknowledgement\nI would like to thank the Director-General of Ministry of\nHealth, Malaysia for permission to publish this paper.\n\n\n\nReferences\n\n\n\n1. Fazilah K. Report on the workshop of Leprosy Elimination in the \nWestern Pacific Region, Manila, Phillippines. 4TH -7TH March \n1996.\n\n\n\n2. Meima A, Gupte MD, Van Oortmarseen GJ, Habblema JD. The \nfuture incidence of Leprosy: A scenario Analysis. Bull. World \nHealth Organisation 2004;82:373-80.\n\n\n\n3. WHO. The final push strategy to eliminate leprosy as a public \nhealth problem, Questions and Answers.  2nd Edition 2003.\n\n\n\n4. WHO. Epidemiological review of leprosy in the WHO Western \nPacific Region 2004 \n\n\n\n5. WHO. Overview and Epidemiological review of leprosy in the \nWHO Western Pacific Region 1991-2001 p42.\n\n\n\n6. A. Joshua Raghavar, K. Rajagopalan .Leprosy in Malaysia. Past, \nPresent and Future. \n\n\n\n7. Ridley DS Jopling WH. Classification of leprosy according to \nimmunity. A five group system. Int  J. Lepr & other \nMycobacterial Diseases 1996; 34(3): 255-73\n\n\n\n8. Ridley DS Jopling WH. A Classification of leprosy for research \npurposes.  Lepr. Rev:  Vol 33 April 1962 p 119-128\n\n\n\n9. Pettit, J. H. S. and Rees, R. J. W. Sulphone resistance in leprosy. \nAn experimental and clinical study. Lancet  1964;2:673-674.\n\n\n\n10. Jacobson, R. R., and Hastings, R. C. Rifampin-resistant leprosy. \n(Letter) Lancet 1976;2:1304-1305.\n\n\n\n11. Grosset JH et al, Study of 39 documented relapses of MB \nleprosy after treatment with rifampicin.   Int  J. Lepr & other \nMycobacterial Diseases . 1989;57:607-614.\n\n\n\n12. Norman et al.  Secondary resistance to rifampicin Following \nMDT. A case report. Int  J. Lepr & other Mycobacterial Diseases \n2003;71(1):18\n\n\n\n\n\n"
"\n\nEditorial Board\n\n\n\nEditor-in-Chief\nHenry Foong Boon Bee, MBBS, FRCP \n\n\n\nEditorial Office\nFoong Skin Specialist Clinic\n33A Persiaran Pearl\nIpoh 31400 Malaysia\nEmail : bbfoong@pc.jaring.my \n\n\n\nAssociate Editors\nChoon Siew Eng, MBBS, FRCP\n\n\n\nGangaram Hemandas, MBBS, FRCP\n\n\n\nAgnes Heng Yoke Hui, MBBS, MRCP\n\n\n\nTing Hoon Chin, MBBS, MRCP\n\n\n\nFounding Editor\nSteven Chow Kim Weng, MBBS, FRCPI (1987-1993)\n\n\n\nEditors Emeritus\nRoshida Baba, MBBS, FRCP (1994-1998)\n\n\n\nMadziah Alias, MD, MMed (1999-2002)\n\n\n\nKoh Chuan Keng, MBBS, MRCP (2003-2004)\n\n\n\nNajeeb Ahmad Mohd Safdar, MBBS, MRCP (2005-2006)\n\n\n\nPresident\nAllan Yee Kim Chye, MBBS FRCP\n\n\n\nVice President\nMadziah Alias, MD MMed\n\n\n\nSecretary\nKoh Chuan Keng, MBBS MRCP\n\n\n\nTreasurer\nNajeeb Ahmad Mohd Safdar, MBBS MRCP\n\n\n\nImmediate Past President\nGangaram Hemandas, MBBS FRCP\n\n\n\nCommittee Members\nHenry Foong Boon Bee, MBBS FRCP\nAgnes Heng Yoke Hui, MBBS MRCP\nOng Cheng Leng, MBBS MRCP\n\n\n\nPersatuan Dermatologi Malaysia\n\n\n\nMalaysian Journal of Dermatology\nJurnal Dermatologi Malaysia\n\n\n\nThe Official Publication for Persatuan Dermatologi Malaysia\n\n\n\nPublished by PERSATUAN Dermatologi Malaysia - Dermatological, Society of Malaysia\n\n\n\nPrinted by Cetak Sri Jaya, 11, Jalan Ambong Kanan 3, Kepong Baru, 52100 Kuala Lumpur, Malaysia\nTel / Fax : 603-6275 9514   Email : cetak_s_j@yahoo.com.my\n\n\n\n\u00ae 2007 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without written permission from the editorial board\n\n\n\n\n\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcomes manuscripts on all\naspects of cutaneous medicine and surgery in the form of original articles,\nresearch papers, case reports and correspondence. Contributions are\naccepted for publication on condition that they are submitted exclusively\nto the Malaysian Journal of Dermatology. The Publisher and Editors\ncannot be held responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and opinions\nexpressed do not necessarily reflect those of the publisher and Editors,\nneither does the publication of advertisements constitute any\nendorsement by the publisher.\n\n\n\nManuscripts should be submitted via email: bbfoong@pc.jaring.my\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology can be sent\nto:\n\n\n\nHenry Foong Boon Bee, MBBS, FRCP\nEditor-in-Chief\nFoong Skin Specialist Clinic\n33A Persiaran Pearl, Fair Park, Ipoh 31400, Malaysia\nTel: +60 5 5487416    Fax: +60 5 5487416\nEmail: bbfoong@pc.jaring.my\n\n\n\nContributions should be written for one of the following categories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than three illustrations.\nThis category offers a means for rapid communication about a single\nsubject.\n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation.This category\nprovides rapid publications and is meant to be a succinct presentation with\na minimum of graphs and tables.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five references.\nThe author may express his or her opinion without complete\ndocumentation.\n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and pathological\nphotographs in color. The diagnosis and legends for the photographs\nshould be listed after the references in the article. The article should be no\nmore than 2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not exceed\n600 words, two figures, and 10 references.\n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article types may\ninclude Review, Report or Case Report Format.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an Introduction,\nMaterials and Methods, Results, Comment, and References. A\nStructured Abstract of not more than 240 words must be included. It\nshould consist of four paragraphs, labeled Background, Methods, Results,\nand Conclusions. It should describe the problem studies, how the study\nwas performed, the main results, and what the author(s) concluded from\nthe results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and summarizes\nthe existing knowledge in a particular field. It should not be an exhaustive\nreview of the literature, and references should not exceed 100 in number.\n\n\n\nTables, diagrams, and selected figures are often helpful. The length is left\nto the judgment of the author, although it generally should not exceed\n5000 words.Topics may include updates in clinically relevant basic science\nand cutaneous biology.\n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the paper, the\nauthor(s)' name(s), degrees, and affiliation(s), the category of the article,\nthe number of figures and tables, and three key words for indexing\npurposes. The name and full postal address (including a street address),\nphone and fax numbers and an email address of the corresponding author\nwho will be responsible for reading the proofs must also be given on the\ntitle page. The author(s) must also declare any affiliation or significant\nfinancial involvement in any organizations or entity with a direct financial\ninterest in the subject matter or materials discussed in the manuscript on\nthis page.\n\n\n\nAll measurements should be according to the metric system. If confusion\ncould result, please include other measurement systems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials should not be\nused.\n\n\n\nReferences must be listed in the order in which they appear in the\nmanuscript. References from journals should include: (1) name(s)\nfollowed by the initials of the author(s), up to four authors: if more than\nfour authors, include the first three authors followed by et al.; (2) title of\npaper; (3) title of the journal as abbreviated in the Index Medicus; (4) year\nof publication; (5) volume number; (6) first and final page numbers of the\narticle.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A Hospital\nKuala Lumpur experience. M J Dermatol 2006;19:52-55\n\n\n\nReferences to books should include: (1) author(s) or editor(s); (2) chapter\n(if any) book titles; (3) edition, volume, etc.; (4) place of publication; (5)\npublisher; (6) year; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual Grand Rounds. In:\nWootton R and Oakley A, editors. Teledermatology. London. Royal\nSociety of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of all\nreferences; incomplete references may result in a delay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, each on a separate\nsheet, and should only include essential information. Drawings, graphs,\nand formulas should be submitted on separate pages.\nSend illustrations as tiff or jpeg files. In the case of photomicrographs, the\nstain type and original magnification should be stated. Each figure should\nbear a reference number corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is important that\nall electronic artwork is supplied to the Editorial Office in the correct\nformat and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for errors or any\nconsequences arising from the use of information contained in this\njournal; the views and opinions expressed do not necessarily reflect those\nof the publisher and Editors, neither does the publication of\nadvertisements constitute any endorsement by the publisher and Editors\nof the products advertised.\n\n\n\n\n\n\n\n\ni\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nVOLUME 19  |  AUGUST 2007  |  ISSN: 1511-5356\n\n\n\nContents\nEditorial\n\n\n\n1 Online Medical Education and \nConsultation for the Dermatologist\nHenry BB Foong, MBBS, FRCP Edin\n\n\n\nReview\n5 The Role of Dermatopathology in the \n\n\n\nPractice of Dermatology\nRyan Olson, MD, David M Jones, MD and \nJ Andrew Carlson, MD, FRCPC\n\n\n\n19 Cutaneous Spirochetal Disease\nM Mahalingam, MD, FRCPath and\nJ Bhawan, MD\n\n\n\nOriginal Articles\n35 Antibiotic Resistance Pattern of Neisseria\n\n\n\ngonorrhoeae in Hospital Kuala Lumpur,\nMalaysia (2001-2005)\nAzura Mohd Affandi, MBBS, MRCP\nHB Gangaram, MBBS FRCP and\nSuraiya H Hussein, MBBS FRCP\n\n\n\n41 A 10-year Retrospective Study on Changing \nPattern of Sexually Transmitted Infections in \nHospitall Kuala Lumpur, Malaysia\nPenny Lim, MBBS, MRCP,\nHB Gangaram, MBBS, FRCP, and\nSuraiya H Hussein, MBBS, FRCP\n\n\n\n47 Allergic Contact Dermatitis in a private \npractice Dermatology Clinic in Ipoh:\nA Seven-Year Retrosspective Study \nHenry BB Foong, MBBS, FRCP,\nEM Taylor, MBBS and N Ibrahim\n\n\n\n51 Prevalence of Herpes Simplex Virus Infection \nin Patients with Herpes Genitalis Using the \nImmunofluorescent Antibody Test\nHB Gangaram, MBBS, FRCP,\nAkbal Kaur, MBBS,\nS Mangalam, MBBS, FRCPath, and\nSuraiya H Hussein, MBBS, FRCP\n\n\n\n57 Autoimmune Bullous Diseases in Ipoh,\nMalaysia: A 5-Year Retrospective Study\nTang MM, MD, MRCP,\nChan LC, MD, MMed and\nHeng A, MBBS, MRCP\n\n\n\n63 The Effect of Explanation and \nDemonstration of Topical Therapy on the \nClinical Response of Atopiic Eczema\nTang MM, MD, MRCP,\nChan LC, MD, MMed and\nHeng A, MBBS, MRCP\n\n\n\n69 Defaulter Rate of Follow-up of Patients\nwith Gonorrhoea at the Genitourinary \nMedicine Clinic\nCC Chang, MBBS, MRCP, K. Akbal, MBBS,\nHB Gangaram, MBBS, FRCP and\nSuraiya H Hussein MBBS, FRCP\n\n\n\n75 HIV infection among patients attending \nthe Genitourinary Medicine Clinic, Hospital\nKuala Lumpur (22000-2005)\nNoorlaily Mohd Noor, MBBS, MRCP,\nGangaram H Belani, MBBS, FRCP,\nAkbal Kaur MBBS, Dip. Derm and\nSuraiya H Hussein, MBBS, FRCP\n\n\n\n79 Cutaneous adverse drug reactions in a \nGeneral Hospital in Singapore: A One-Year \nRetrospective Anaalysis\nRachael YL Teo, MBBS, MRCP, MMed,\nYong Kwang Tay, MBBS, FRCP, FAMS and \nKwong Ming Fock, MBBS, FRACP, MMed\n\n\n\n83 Cutaneous adverse drug reactions \nobserved in a Dermatology Clinic,\nPenang General Hospital\nTan WC, MD,\nLo Kang SC, MD, MRCP, MMed,\nOng CK, MD, MRCP,\nKalaikumar N, MD and Cheah CM, MBBS\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nii\n\n\n\n89 Hansen\u2019s Disease in Penang: A 10-year \nRetrospective Analysis\nTan WC, MD,\nLo Kang SC, MD, MRCP, MMed and\nOng CK, MD, MRCP\n\n\n\n96 Management of leprosy in the Department of \nDermatology, Hospital Sultanah Aminah,\nJohor Bahru\nTey KE, MD, MRCP, MMed, AM,\nChoon SE, MBBS, FRCP, AM, Zainah M, MD \nand Zabedah I\n\n\n\n101 Prevalence of Chlamydia trachomatis in\nGenito-urinary Medicine Clinic, Hospital \nKuala Lumpur: A 5-year Retrospective \nAnalysis\nS Norashikin MBBS MRCP,\nHB Gangaram MBBS FRCP, and\nSuraiya H Hussein, MBBS FRCP\n\n\n\nCase Reports\n106 A Case of Acne Scarring treated with \n\n\n\nFractional Photothermolysis \nKo Chung Beng, MBChB, MRCP,\nChua Sak Eng, MBBS, MRCP,\nSeah Keh Seng, MBBS MMed,\nChu Kooi Yen, MBBS and\nKo Chung Yee MD, MS\n\n\n\n107 Sweet\u2019s Syndrome with Extracutaneous \nInvolvement\nLee YY, MD, MRCP, MMED,\nLoh LC, MBChB, MRCP and\nWong KT, MBBS, M Path, FRCPath\n\n\n\n111 Cutis Marmorata Telangiectatica Congenita \nin a 3-month-old Infant\nSM Wong MBChB, MRCP and\nLC Loh MBChB, MRCP\n\n\n\n113 Uveitis: A Presenting Sign of Both Secondary \nSyphilis and HIV Infection\nChoon SE, MBBS FRCP, Lee CK, MBBS,\nLoh SS, MBBS, FRCS and\nTey KE MD, MRCP MMed\n\n\n\n117 Kaposi\u2019s Sarcoma in a 35-year-old \nhomosexual \nTan WC, MD,\nLo Kang SC, MD, MRCP, MMed,\nOng CK, MD, MRCP,\nLeong KN, MBBS, MRCP, and\nSubathra S, MBBS, MPath\n\n\n\n119 Extramammary Paget\u2019s Disease in an\nelderly man\nKE Tey, MD, MRCP, MMed, AM,\nSE Choon, MBBS, FRCP, AM, and\nNoraida K, MBBS, MPath\n\n\n\n123 Chronic Arsenicism - a forgotten entity?\nVitharana K, MBBS, MD,\nJanthorn Pakdeethai, MBBS,\nYong-Kwang Tay, MBBS, FRCP, FAMS,\nLiu TT, MBBS, Dip Derm (London), FAMS \nand Poh WT, MBBS, FRCPA, FAMS\n\n\n\n127 Atypical Presentation of Genital Herpes in\nan HIV Infected Man\nTang JJ, MBBS, Tang MM, MD, MRCP,\nChan LC, MD, MMed and\nHeng A, MBBS, MRCP\n\n\n\n131 Purpura Fulminans in an army trainee\nPrakash B, MBBS and\nNajeeb A Safdar, MBBS MRCP          \n\n\n\nCommentary\n133 Therapeutic advances in reducing risk of \n\n\n\ngenital herpes transmission\nHB Gangaram, MBBS, FRCP\n\n\n\nCorrespondence\n135 Understanding towards leprosy: A ground \n\n\n\nlevel survey among public & medical \npersonnel Penang Hoospital 2006\nTan WC, MD,\nLo Kang SC, MD, MRCP, MMed,\nKalaikumar N, MD, Cheah CM MBBS,\nOng CK, MD, MRCP, Siti R, Lam YC, and \nOng KP, MBBS\n\n\n\n\n\n\n\n\n1\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nEditorial\n\n\n\nOnline Medical Education and Consultation for the \nDermatologist\n\n\n\nIt is amazing how much we have changed over the last\ndecade. Digital technology has changed the world in\nprofound and exciting ways. Today we can communicate\ninstantly with our colleagues without worrying about\ntraditional limitations of time and location. Ten years ago,\nthe PC was just beginning to achieve broad acceptance.\nToday, the PC and the Internet have all reached critical\nmass, creating opportunities and connections for hundreds\nof millions of people around the globe.\n\n\n\nBut these changes are just the beginning. As more and more\nof the world\u2019s information and communication moves to\ndigital form, it will open to a new world of connected\nexperiences that link our interests and our communities1.\nThis has created the unprecedented opportunities that the\nprovider and the recipient need no longer be physically\npresent in the same place. A remote dermatologist can\nutilize the digital technology and the internet for his own\ncontinuing medical education.\n\n\n\nThe WHO Telematics Policy has stated that with regard to\nits health-for-all strategy it recommends \u201c\u2026.integrate the\nappropriate use of health telematics in the overall policy and\nstrategy for attainment of health for all in the 21st century,\nthus fulfilling the vision of the world in which the benefits\nof science, technology and public health development are\nmade equitably available to all people everywhere.\u201d2\n\n\n\nThe word \u201ctele\u201d derives from a Greek word meaning \u201cat a\ndistance\u201d. Hence telemedicine is the delivery of health care\nand the exchange of health care information across\ndistances.3 It includes rapid access to shared and remote\nmedical expertise by means of telecommunication and\ninformation technologies no matter where the patient or the\nrelevant information is located. It is not a new branch of\nmedicine. In fact telemedicine has existed centuries years\nago when information about Bubonic plague transmitted\nacross Europe by such means as bonfires.\n\n\n\nThe recent advent of low cost high megapixel digital\ncameras combined with improved high speed broadband\ninternet access has allowed teledermatology to become a\nreality. In clinical trials, store-and-forward teledermatology\nconsultations produce similar clinical outcomes when\ncompared with conventional clinic-based consultations.4 In\nthis study, the authors compared the clinical outcomes of\nstore-and-forward teledermatology with those following\nconventional clinic-based consultation. In the usual care\ngroup, 65% were rated as 'improved', 32% as 'no change' and\n3% as 'worse'. For teledermatology group, 64% were rated as\n'improved', 33% as 'no change' and 4% as 'worse'. One can\ncommunicate with colleagues over the face of the globe and\n\n\n\nbenefit in many ways. This has open up avenues for\ncommunication across the continents at the speed of a click.\nThe ability to share cases electronically is a great teaching\nand learning experiences. We can now consult our peers\naround the world.5\n\n\n\nWhile the traditional method of learning still holds true,\nadvances in global mass communication allow one to keep\nin touch with far-flung colleagues and interactively share\nour patient\u2019s problems and occasionally allowing one to\nsolve difficult diagnostic and therapeutic cases through a\nvirtual grand rounds in dermatology (VGRD)6. These\ncolleagues could be as far north as Canada to as far south as\nNew Zealand. They could be experts in areas of\ndermatologic subspecialty such as dermatopathology,\npediatric dermatology, immunodermatology, infectious\ndermatology, intensive care dermatology, and dermatologic\nsurgery. This was conceived of as a collegial meeting ground\nfor dermatologists who might not have the luxury of being\nassociated with a medical center or for those academics who\nare willing to share their expertise with far-flung cyber-\ncolleagues. It is a place where difficult patients can be\npresented for help with diagnosis and treatment. VGRD\n(and the more recently created Anak-VGRD) are vehicles\nto help the orphan patient. The Shelleys in their 1988 letter\nto the NEJM define the orphan patient as an individual\n\u201cwith a unique, inchoate, baffling and often disabling\ndisease and yet clearly not discernable in the medical\nliterature.\u201d7 Their case histories can be presented on either\nof these sites and they may benefit from the opinions of\nmany seasoned dermatologists from around the world.8\n\n\n\nThere are a small but increasing number of publications on\nthe subject of teledermatology. A Pubmed search on the\nkeyword \u201cteledermatology\u201d at the title field listed 203\npapers. The first paper was published in 1995. There are 61\npapers published since January 2005. There are many\ndermatological internet resources. Among the most popular\nones are Pubmed (http://www.ncbi.nlm.nih.gov/sites/\nentrez), Google (www.google.com), New Zealand\nDermnet (www.dermnetnz.org), Cochrane Skin Group\n(http://www.nottingham.ac.uk/~muzd/), ebDerm.org\n(http://www.ebderm.org/), Dermatology Online Journal\n(http://dermatology.cdlib.org/) and International Journal\nof Dermatology (http://www.blackwellpublishing.com/\njournal.asp?ref=0011-9059).\n\n\n\nMany useful atlases are also available such as Global Skin\nAtlas (http://www.globalskinatlas.com), Dermatologic\nImage Online Atlas (http://www.dermis.net/index_e.html)\nand Dermatology Image Atlas (http://dermatlas.\nmed.jhmi.edu/derm/)\n\n\n\n\n\n\n\n\n2\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nCase Histories can be assessed online at virtual grand\nrounds in dermatology (www.vgrd.org), New York\nUniversity Department of Dermatology Tuesday\nEvening Clinical Conference (http://www.med.nyu.edu/\ndermatology/sem_conf/tuesdaynight.html) and Australian\u2019s\nDermconsult (http://www.dermconsult.com.au/index.cfm).\n\n\n\nThere is indeed a need for world-wide consultation for\nproblem patients who have been told repeatedly \"There is\nnothing more that can be done for you.\" In the past when\nwe began practice such difficult patients were sent to\nuniversity centers where the teaching staff would pool their\nexperiences and medical officers would scan the Index\nMedicus and text books for help. Today, the difficult orphan\npatient can have many wonderful adoptive dermatologist\nparents. One can go to one\u2019s computer and adopt one of\nthese orphan patients from the virtual grand rounds in\ndermatology (www.vgrd.org)9. This will make both the\ndermatologist and the patient happier.\n\n\n\nHenry B.B. Foong, MBBS, FRCP Edin\n\n\n\nEditor-in-Chief\nMalaysian Journal of Dermatology\nIpoh, Malaysia\n\n\n\nReferences\n\n\n\n1. Bill Gates.  Enabling Secure Anywhere Access in a Connected \nWorld.  Microsoft Executive Email. Feb 2007.\n\n\n\n2. World Health Organisation.  A Health Telematics Policy \n(document DGO/98.1) Geneva: WHO. 1998\n\n\n\n3. Wootton R. Craig J. eds.  Introduction to Telemedicine. London. \nRoyal Society of Medicine press.1990\n\n\n\n4. Pak H et al.  Store-and-forward teledermatology results in \nsimilar clinical outcomes to conventional clinic-based care. J \nTelemed Telecare 2007;13(1):26-30\n\n\n\n5. Foong. HBB.  Chapter editor:  Teledermatology edited by Richard \nWootton and Amanda Oakley. Transcontinental Dermatology:  \nVirtual Grand Rounds in Dermatology.  Royal Society of \nMedicine 2002.\n\n\n\n6. Laochamroonvorapongse D, Johnson E, Foong HBB, Elpern DJ. \nA Brave New World: Virtual Grand Rounds in Dermatology. \nSemin Cutan Med Surg. 2002 Sep;21(3):232-6.\n\n\n\n7. Shelley WB, Shelley ED. The Orphan Patient. NEJM 1988; \n318:646\n\n\n\n8. Elpern D. The orphan patient.  Virtual Grand Rounds in \nDermatology. Apr 2006\n\n\n\n9. Shelley W.  Comments in The orphan patient. Virtual Grand \nRounds in Dermatology.  Apr 2006.\n\n\n\n\n\n\n\n\n5\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReview\n\n\n\nThe Role of Dermatopathology in the Practice of\nDermatology\n\n\n\nRyan Olson, MD, David M. Jones, MD, and J. Andrew Carlson, MD, FRCPC\n\n\n\nDivisions of Dermatopathology and Dermatology\nDepartment of Pathology, Albany Medical College\nAlbany, NY, USA\n\n\n\nCorrespondence\n\n\n\nJ. Andrew Carlson, MD, FRCPC\n\n\n\nDivision of Dermatopathology and Dermatology\nAlbany Medical College MC-81, 47 New Scotland Ave\nAlbany, NY 12208, USA\nEmail : Carlsoa@mail.amc.edu\n\n\n\nAbstract\n\n\n\nDermatopathology is one of the most powerful diagnostic tools in\nclinical dermatology. In this diagnostic process, the dermatologist and\nthe dermatopathologist are a team in patient care, where the\ndermatologist must know when biopsies are indicated; be able to select\nlesions to biopsy those that are likely to yield diagnostic results;\nskillfully procure the biopsy samples; and provide the\ndermatopathologist with an accurate history, clinical description, and\nclinical differential diagnosis. On the other side, the\ndermatopathologist should be readily accessible to the clinician, and be\ndogged in the pursuit of an accurate histological description and\nclinically relevant diagnosis. In this article, we will discuss the finer\npoints of skin biopsy, benefits and limitations of biopsy interpretation,\nand the future potential of skin biopsy in the selection of targeted\ntherapy and individualized patient care.\n\n\n\nKeywords\n\n\n\nBiopsy; shave; punch; excision; diagnosis; accuracy; targeted\ntherapy\n\n\n\nIntroduction\nDermatopathology, a sub-specialty of anatomic pathology\nand dermatology, is the study of skin disease, which\nencompasses both the diagnosis of individual patients via\nevaluation of skin biopsies, and the study of the etiology and\npathogenesis of skin diseases at the tissue, cellular and\nmolecular levels1-6. Dermatopathologists work in close\nassociation with dermatologists (some dermatologists are\nboth, and read their own slides).\n\n\n\nIn the United States of America, certification in\nDermatopathology requires the completion of 4 years\nresidency training in either dermatology (internship plus 3\nyears of dermatology) or anatomic pathology. Following\nthat, an additional one to two years of dermatopathology\nfellowship training is completed. For pathology trainees,\nthis training includes 6 months of clinical dermatology, and\nfor dermatology trainees, 6 months of anatomic pathology\ntraining. The final step for qualification is to obtain board\n\n\n\ncertification in Dermatopathology, which is jointly\nsponsored by the American Boards of Pathology and\nDermatology. Outside of the USA since 2003, the\nInternational Board of Dermatopathology has certified\nqualified candidates from countries other than the United\nStates by a test given in Europe7. The International Board\nof Dermatopathology seeks to improve the standards of\ndermatopathology as well as the quality and number of\ndermatopathologists around the world.\n\n\n\nIn dermatology, clinical diagnosis is based on gross\nmorphologic findings-type of individual lesion (e.g. macule\nvs. papule), the configuration of these lesions (e.g., grouped,\nlinear, annular), their distribution (e.g., localized,\ndermatomal, generalized), and duration of disease. The\naccuracy of clinical dermatologic diagnosis varies greatly\nand is dependent of expertise and experience, varying from\n26%-34% for family physicians to 71-75% for\ndermatologists assessing neoplastic and inflammatory skin\ndisease respectively8. This may be in part due to lack of\nlogical and reliable systematic method for clinical\ndermatologic diagnosis9. In contrast, dermatopathologic\ndiagnoses can be arrived at by application of a logical\nalgorithmic method that utilizes precise, repeatable\ncriteria1, 10. Therefore, skin biopsy enhances clinical\nevaluation allowing for definitive diagnosis and the ruling\nout of other specific diagnoses or categories of skin disease.\nFurthermore, accurate diagnosis is the first step in effective\ntreatment, thus, integral to the process of disease\nmanagement.\n\n\n\nAs advances in immunopathology and molecular pathology\nincrease the understanding of causes, mechanisms, and\nconsequences of skin disease, there is the expectation that\nthese advances will allow for more precise management and\npotentially, personalized (targeted) therapy of skin disease11.\nDermatopathology plays, and will play, a crucial role in\nthese endeavors.\n\n\n\n\n\n\n\n\n6\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nIn this article, we will review the finer points of skin biopsy,\nbenefits and limitations of biopsy interpretation, and the\nfuture potential of skin biopsy in the selection of targeted\ntherapy and individualized patient care.\n\n\n\nThe biopsy\nAs clinical diagnosis is not 100% accurate8, other diagnostic\ntests are employed in dermatology, including skin scrapings,\ndermatophyte culture, trichograms, serologic tests, and skin\nbiopsy to aid in accurate diagnosis. Skin biopsy is one of the\nmost powerful diagnostic tools in the armature of\ndermatology. Although mostly used for routine light\nmicroscopy, skin biopsy specimens can be utilized for\nmicrobiologic, immunopathologic, cytogenetic, and\nmolecular analysis, often utilizing the same formalin fixed,\nparaffin embedded specimen as for light microscopy. The\nindications for skin biopsy are many, but not absolute12. The\nfollowing are some helpful guidelines for when to biopsy:\n\n\n\n\u2022 Suspected skin cancer\n\u2022 Dermatoses not responding to rational therapy\n\u2022 Cutaneous manifestations of systemic disease\n\u2022 Persistent ulcers (to rule out neoplasia or infection)\n\u2022 For diagnosis confirmation, when potential therapy has \n\n\n\nserious adverse affects, is expensive, and/or is labour \n(time) intensive\n\n\n\n\u2022 When dermatopathology is the only definitive way to \nrender a specific diagnosis (e.g. bullous dermatoses)\n\n\n\n\u2022 When specific infectious agents are suspected that are \nslow growing or difficult to culture \n\n\n\n\u2022 Unusual or atypical dermatologic presentations \n\n\n\nThere also exist scenarios in which biopsy will not be\nhelpful such as in chronic pruritic dermatoses like atopic\ndermatitis where the dominant pathology will be the\nconsequence of \u2018human finger nail disease\u2019: lichen simplex\nchronicus, excoriations, scars and ulcerations. Lastly, skin\nbiopsy should never replace clinical acumen. The clinical\npresentation and diagnostic impression should be the guide\nto biopsy selection; moreover, this clinical data is requisite\nfor accurate dermatopathologic diagnosis, particularly\ninflammatory skin disease13.\n\n\n\nSite and lesion selection\n\n\n\nCutaneous biopsy is not simply removal a sample of skin\nand/or subcutis, but a sequential process of essential steps\nthat if performed correctly can lead to specific diagnosis or\nat least, assignment to a categorical group of diseases,\nnarrowing the differential diagnosis and excluding other,\nspecific disorders1, 14, 15. See table 1.\n\n\n\nThe age of the lesion and location of the biopsy are critical\nfor maximizing diagnostic yield1, 14, 15. Clinical judgment\ncomes to the forefront because different pathologic\nprocesses are best identified at different stages of their\ndevelopment and at different locations. In general, active\nlesions are ideal for diagnosing inflammatory disease.\nEarly-mature lesions, which have not been manipulated or\n\n\n\nsecondarily infected, are to be sought foremost. These\ntypically take the form of macules, papules or vesicles.\nPruritic primary lesions will almost invariably be scratched\nproducing erosions, ulceration and crusts. Breakdown of the\nskin barrier also results in secondary bacterial and fungal\ninfection, which also obscures the primary disease process,\nconfounding the dermatopathologist. In the diagnosis of\nvesiculobullous disorders, early evolving lesions (i.e. an\nedematous papule rather than a fully developed blister\nwhose roof will be lost during biopsy, are preferred). Old\nlesions of subepidermal bullous disorders can appear to be\nintradermal vesicles following regeneration of a new\nepidermis. In cases where there is no evidence of a primary\nlesion, biopsy can be helpful in verifying that there is not an\nauthentic primary process, particularly if dermatitis artifacta\nis suspected. For ulcerative and blistering diseases, sampling\nshould be focused at the edge, to include both the margin of\nthe blister or ulcer and the surrounding \u201cnormal\u201d skin. This\ntransition area holds the greatest potential of leading to the\ncorrect diagnosis. Another important technique is to sample\nmultiple sites, and especially lesions at different stages in\ndevelopment. This may be crucial as some diseases mirror\none another during the early phases (e.g., pityriasis\nlichenoides et varioliformis acuta and erythema\nmultiforme16) whereas many others may all come to\nresemble \u201cburned out\u201d lesions. In short, a biopsy is a\nsnapshot in time that records a truth only in part, that is one\ntime interval of an evolutionary process. Multiple biopsies\nfrom different stages of lesional tissue in effect produces\n\u2018time lapse footage\u2019 allowing for more accurate diagnosis1.\n\n\n\nVarying anatomic locations also play an important role for\nthe clinician\u2019s approach to biopsy1, 14, 15. For example, when a\nrash is present on the legs above and below the knees, more\nproximal lesions should be sampled preferentially due to the\nmorphologic distorting effects of stasis and the resultant\nincreased difficulty of healing. Biopsy of inflammatory\ndisorders affecting elbow and knee should also be avoided\ndue the co-existence of lichen simplex chronicus at these\nsites. Shave biopsies are preferred over punch and excision\nwhen sampling superficial lesions from the back and shin\ndue to the thickness of the back dermis (may exceed 1cm)\nand taught nature of shin, respectively. These characteristics\nincrease the risk of hematoma, dehiscence, infection and\nhypertrophic scarring/keloid formation in these regions\nfrom deep punch or excisional biopsy. When approaching\nlesions on the hands and feet, punch biopsies are best\navoided when possible due to the proximity of myriad\ncrucial structures (large vessels, tendons, nerves and bones).\nLarge and deep shave biopsies should arouse concern when\nsampling lesions from the chest and buttocks due to the risk\nof hypertrophic scarring/keloid formation in these\npotentially cosmetically important areas. Shave biopsies are\npreferred over punch biopsies, however, for lesions on the\nscalp due to its tight, thick and vascular nature. In addition,\nthere is little or no risk of resulting alopecia because of the\nsuperficial nature of shaves. However, if the cause of\nalopecia is being sought, a 4mm punch biopsy(s) extending\nto the \n\n\n\n\n\n\n\n\n7\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.   Essential steps in skin biopsy before dermatopathologic evaluation\n\n\n\nPractical Points\n\n\n\n\u2022 Well-formed, mature lesion is optimal\n\u2022 Early lesion is preferable in bullous disorders\n\n\n\nOlder subepidermal blisters often may appear to be intraepidermal \ndue to reepithelization\n\n\n\n\u2022 Excoriated, scarred, and/or traumatized lesions should be avoided\n\u2022 Multiple biopsies may be necessary in generalized eruptions as lesions \n\n\n\nmay be at different stages of evolution\n\u2022 For immunofluorescent studies for bullous dermatoses, peri-lesional \n\n\n\ntissue will give optimal results\n\u2022 Adjacent normal tissue are helpful in disorders of pigmentation,\n\n\n\nsclerosing disorders/atrophoderma, anetoderma, and connective tissue \nnevi\n\n\n\nPunch biopsy:\n\u2022 Inflammatory disorders\n\u2022 Alopecia\n\u2022 Dermal lesions\n\n\n\nShave biopsy:\n\u2022 Lesions confined to the epidermis\n\n\n\nExcisional biopsy\n\u2022 Ideal for melanoma and other smaller lesions of suspected skin \n\n\n\ncancer\nIncisional biopsy\n\n\n\n\u2022 In case of large lesions where primary closure is difficult\n\u2022 To confirm diagnosis and avoid unnecessary surgery\n\u2022 Panniculitis\n\n\n\n\u2022 Avoid crush artifact by avoiding forceps and using needle to lift punch \nbiopsy specimen\n\n\n\n\u2022 Avoid specimen dry-out by placing immediately in fixative or covering \nwith saline-soaked guaze\n\n\n\nBuffered Formalin (fixative should be at least 10x volume of lesion):\n\u2022 Light microscopy\n\u2022 Immunohistochemistry, in situ hybridization, PCR\n\n\n\nMichel\u2019s or Zeus\u2019 transport medium\n\u2022 Direct immunofluorescent studies\n\n\n\nGlutaraldehyde or modified Millonig\u2019s fixative:\n\u2022 Electron microscopy\n\n\n\nThe importance of answering every question of laboratory requisition\ncannot be over emphasized\n\u2022 Demographics: name, age, sex, race, address, pertinent medications \n\n\n\nand medical history\n\u2022 Description: morphology of individual lesions and their, configuration \n\n\n\nand number\n\u2022 Duration of lesions\n\u2022 Diameter, site of biopsy, and/or distribution of lesions\n\u2022 Diagnosis: report most likely clinical diagnosis and differential \n\n\n\ndiagnoses\n\u2022 Report use of topical and/or systemic therapy\n\u2022 Any relevant previous biopsies must noted\n\n\n\nSteps\n\n\n\nSelection of one or more lesions to be\nsampled\n\n\n\nRemoval of the sample by the biopsy\nmethod that is optimal for diagnosis\n\n\n\nDelicate handling of the specimen\n\n\n\nProper fixation of the specimen\n\n\n\nReporting of clinical information\n\n\n\n\n\n\n\n\n8\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nto the subcutis is preferred, and is to be sectioned\ntransversely/horizontally by the pathology lab for optimal\nhistologic assessment of hair growth17, 18. Shave biopsies (or\nsmaller punches, <3mm) are also preferred over punches\nnear the eyelids, ears, nose and lips. This is due to the\ncosmetic concerns of dog ears. In particular, eyelid biopsies\nshould avoid the conjunctival margin, and attention must be\ngiven to insure that the vermilion border is aligned after lip\nbiopsy.\n\n\n\nChoice of biopsy procedure\n\n\n\nSkin biopsies may be generally categorized into 3 types:\nshave, punch, or excisional15. Incisional, curettage and snip\nbiopsies are other techniques. Selection of biopsy procedure\nis paramount in its influence on diagnostic yield, cosmetic\nresult and procedural time requirement. Each of the three\noffers their respective advantages and limitations, which\nvary based upon the clinically suspected nature of the lesion\nto be sampled. (See table 1). Therefore, it is the clinical\nsuspicion of the pathologic process, based upon the gross\nmorphology of the lesion and its location, which determines\nthe best technique for sampling lesional tissue.\n\n\n\nShave biopsies are often optimal for evaluating lesions\nrestricted to the epidermis (superficial benign & malignant\ntumors - e.g., seborrheic keratoses, dome shaped nevi, &\nnon-melanoma malignancies like superficial basal cell\ncarcinoma). Advantages include minimal bleeding, rapid\nhealing (because only a superficial wound is created),\nminimal scarring and therefore desirable cosmetic results,\nability to remove wider lesions, and the relative speed and\nease of the procedure. These advantages may become\nparticularly desirable when evaluating difficult anatomic\nsites to suture such as the shin and back. The primary\nlimitation of a shave biopsy, similar to its advantages, arises\nfrom its implicitly superficial nature. Dermis and subcutis\nare rarely included, and pathologic processes therein may be\nmissed. In addition, future punch and excisional biopsies at\nthe same site may be confounded by a preceding deep shave,\ndue to indentation and subsequent scar formation1, 14, 15.\n\n\n\nPunch biopsies are typically ideal for inflammatory or\ninfiltrative diseases in which the predominant pathology lies\nin the dermis (most superficial inflammatory and bullous\ndiseases; diffuse and nodular infiltrates; benign & malignant\ntumors, except melanoma). Advantages over shave biopsies\nlie primarily in the increased depth. When properly\nperformed, punch biopsies include the epidermis, dermis\nand subcutaneous fat. The standard punch biopsy is 4mm\nin diameter, but their size can vary from 1mm diameter up\nto 8mm, which can sometimes be substituted for elliptical,\nexcisional biopsies of larger lesions. Although similarly\nsimple to perform as a shave, they require a bit more time\nand equipment, and typically result in increased scarring.\nHowever, small punches (~2mm) may have excellent\ncosmetic results when care is taken to produce a defect\nfalling within skin tension lines, making them surprisingly\nideal for facial biopsies1, 14, 15.\n\n\n\nExcisional biopsies are the technique of choice for lesions\nwith a high index of suspicion for cancer, and those that\nrequire removal. The former refers primarily to potential\nmelanomas, and the latter may include subcutaneous cysts,\nlipomas and those too large for punch biopsies (i.e. >8mm).\nIn addition, deep inflammatory processes such as nodules of\nerythema nodosum may benefit from this technique. The\nadvantage lies in increased depth and area, however at the\ncost of increased scarring, and increased time and skill to\nclose the wider defects. Excisional and incisional biopsies\nare also employed to acquire specimens, which include both\nlesional and adjacent normal skin, to evaluate subtle\nconnective tissue changes1, 14, 15. Incisional biopsies are also\nused in the case of large lesions where primary closure is\ndifficult, to confirm diagnosis, and to avoid unnecessary\nsurgery, and for sampling subcutaneous disorders like\npanniculitis.\n\n\n\nCurettage specimens from the skin are the least desirable,\nand some feel that it is best to never send them to pathology\nat all14. This is due to the high likelihood of losing fragments\nand the difficulty of reconstructing anatomic orientation on\nhistologic sections. In cases clinically requiring curettage, it\nis best to send an intact shave biopsy prior to curettage and\ndesiccation of the lesion site. Snip (scissor) biopsy is a useful\nprocedure for sampling and excising polypoid and\nfilamentous lesions with a small base.\n\n\n\nBiopsy to confirm diagnosis of suspected vasculitis provides a\nuseful model for how to approach the type, timing and site of skin\nbiopsy19, 20. Firstly, the optimal time for skin biopsy is 24-\n48hrs after the appearance of a vasculitic lesion. If the\nbiopsy is poorly timed, the pathologic features of vasculitis\nmay be absent- a fact that clinicians must bear in mind\nwhen interpreting a negative biopsy from a patient whose\nclinical findings suggest vasculitis. See figure 1. A punch\nbiopsy of a lesion at the appropriate stage (\u201clesions have life-\nspans\u201d and therapy affects the histopathologic findings) will\nenable histologic confirmation of most small-vessel\nvasculitides. Purpuric lesions obtained in the first 24hours\nare characterized by fibrin deposits within the vessel wall\naccompanied by neutrophilic infiltration and surrounding\nhemorrhage and nuclear debris. After 24 hours, neutrophils\nare replaced by lymphocytes and macrophages. Biopsy of\nlesions greater than 48hrs old, regardless of the underlying\nform of vasculitis, may show lymphocyte-rich infiltrates.\nSecondly, choice of a shave biopsy, punch biopsy or\nexcisional biopsy will affect which vessels are examined as\nthe type of vessel is dependent on location within the skin\nand subcutis- i.e. the deeper the location, the larger the\nvessel. Thus, if a medium vessel vasculitis such as\npolyarteritis nodosa (PAN) is suspected, the biopsy must\ninclude the subcutaneous fat where medium sized vessels\nare situated. Incisional biopsy is required for cases affecting\nlarger vessels (nodular vasculitis and giant cell arteritis). In\nthe case of livedo reticularis/racemosa, a deep biopsy\nextending to the subcutis should be taken from the center of\nthe circular livedo segment (the \u2018white\u2019 center, not the \u2018red\u2019\nperiphery)\n\n\n\n\n\n\n\n\n9\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 1.   Biopsy is required to confirm the clinical suspicion of cutaneous\nvasculitis when a patient presents with palapable purpura of the lower\nextremeties. Choosing an early lesion, less than 48hours, is crucial in\nidentifying the diagnostic histologic changes of vasculitis- neutrophilic\ninfiltrate disrupting a small vessel associated with nuclear debris\n(leukocytoclastia) and fibrin depositis (top right).  After 48hours, fibrin is\nlost and lymphocytes and macrophages replace the neutrophilic infiltrate\n(bottom right).\n\n\n\nFig 2.   Crush artifact-a mild example. Squeezing the specimen with\nnon-toothed forceps causes crush artifact. In this punch biopsy of\ncutaneous lymphoid hyperplasia, note the dark, smeared appearance of\nthe infiltrate in lower dermis (top panel) due to compression and\ndistortion of the inflammatory infiltrate (bottom panel). If crush artifact is\nsevere, the biopsy specimen will be unreadable. Inserting a needle into\nthe dermis or gently using a toothed forceps to lift the tissue out of the\npunch defect helps avoid crush artifact.  \n\n\n\nFig 4.   Vitiligo (bottom right panel) is one condition that can resemble\nnormal skin under the microscope (top left and right panels).  Unless the\nconsulting physician informs the dermatopathologist that he suspects\nand wishes to confirm the diagnosis of vitiligo, the dermatopathologist\ncould interpret this biopsy specimen as normal, \u201cunremarkable\u201d skin.\nFontana-Masson stain demonstrates the absence of melanin vitiligo skin\n(bottom left panels).\n\n\n\nFig 3.   Laboratory processing of the biopsy specimen for histologic\nassessment- from fixed tissue to hematoxylan and eosin (HE) stained\ntissue section.  1) All specimens are signed a unique accession number,\nand are \u201cgrossed\u201d or \u201ccut in\u201d.  This process entails describing the type of\nspecimen, its dimensions, and any other distinguishing characteristics (in\nthis case, a small, orientated ellipse of skin).  The tissue is then sectioned\nand submitted in tissue processing cassettes labeled with the accession\nnumber and block number.  2).  The tissue cassettes then undergo\nautomatic processing to further fixate the tissue, dehydrate the specimen,\nand impregnate with paraffin wax.  3) Processed tissue sections are then\nembedded in wax.  4) Paraffin block with embedded tissue.  5) Paraffin\nblocks are then trimmed and 5\u03bc sections are cut from them.  6) These 5\u03bc\ntissue sections are floated in water bath and then placed on slide with the\nspecimen\u2019s unique accession number and block numbers from which\nthey were cut from.  7-8) Unstained sections are then stained with HE (in\nthis case by an automatic stainer (8)).  9) The HE stained slides are then\ncover-slipped and placed in slide trays with the submitting requisition for\nmicroscopic assessment.  The histologic description and diagnosis are\nthen transcribed onto a report with the patients demographic data, its\npathologic accession number, and the gross description.  \u201cSign out\u201d,\nsigning the pathology report is the last step of the process before the\nreport is distributed to the referring clinician.\n\n\n\n\n\n\n\n\n10\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nperiphery) because this where the stenosed vessel\nresponsible for the cyanotic periphery is located. Thirdly,\nbiopsies should be obtained from non-ulcerated sites, or if\nnot possible, from the edge of an ulcer. Lastly, omission of a\nbiopsy for direct immunofluorescence (DIF) studies wastes\nan opportunity to collect potentially valuable information\nand often leads to misdiagnosis. For example, DIF provides\nthe only way of diagnosing Henoch-Schonlein purpura\n(IgA vasculitis). It is best to take 2 biopsies, one for light\nmicroscopy and one for DIF examination, rather than split\none specimen. Procuring multiple biopsies and extending\nthe biopsy depth to the subcutis and fascia can significantly\nincrease the diagnostic yield for vasculitis19. If multiple\nbiopsies do not reveal evidence of vasculitis, then a\npseudovasculitis (hemorrhagic or vaso-occlusive) disorder\nshould be strongly considered20.\n\n\n\nProper fixation and optimal preparation \n\n\n\n(Laboratory handling)\n\n\n\nProper fixation of biopsy specimens is a crucial part of the\nbiopsy procedure and requires at least a superficial\nunderstanding of the various available pathologic studies.\nFor standard hematoxylin and eosin histology, specimens\nshould be placed immediately in a container of 10% neutral\nbuffered formalin, and the volume of fixative should be at\nleast 10 times the volume of the specimen. Be sure the\nspecimen is completely submerged, and avoid \u201cdrying out\u201d\nbetween the biopsy procedure and being placed into\nfixative. If the specimen is to be transported through cold\nweather, check with the laboratory to ensure that the\nfixative contains antifreeze. Also, when handling specimens,\ntake special care to avoid excessive squeezing and physical\ntrauma (e.g., pressure from forceps or a dull surgical blade).\nFreezing, drying and crushing may cause significant\nmorphologic artifacts, thus limiting histologic\ninterpretation, and possibly precluding definitive diagnosis.\nSee figure 2. Histochemical, immunohistochemical, and\nchromogenic or fluorescent in situ hybridization studies\nmay also be performed on standard formalin fixed, paraffin-\nembedded tissue cassettes. In addition, DNA can be readily\nextracted from these samples for molecular testing for\ninfectious agents, or genetic aberrations such as mutations,\nmonoclonal gene rearrangements, promoter methylation,\nand gene amplifications. For specimens requiring direct\nimmunofluorescence (DIF), formalin must be strictly\navoided; instead the tissue should be transported in saline\n(to avoid drying) or fixed in Michel\u2019s transport medium.\nSpecimens for microbiology (culture and sensitivity) should\nbe kept fresh and as sterile as possible. For cytogenetic\nanalysis/karyotyping, the tissue should be submitted fresh\nor in normal saline. Electron microscopy requires tissue to\nbe transported in glutaraldehyde or Millagong\u2019s fixative.\n\n\n\nAt the pathology laboratory, the patient\u2019s name is verified\nand the specimen is assigned a unique accession number,\nwhich is noted on the requisition form and on the specimen\ncontainer. Specimens are routed to a \u2018grossing\u2019 area, where a\ntechnician is responsible for orienting and properly\n\n\n\ndissecting specimens. Most routine punch and shave\nbiopsies are bisected vertically (epidermis to subcutis) and\nthe halves submitted for processing (fixation, dehydration,\nand wax impregnation) and embedding in paraffin wax\nblocks. Larger specimens are serially sectioned, and if\nperformed for cancer, the margins are inked to aid in\nhistologic assessment of margin involvement. If the\nspecimen is oriented (specific margins are identified), its\nmargins are differentially inked and sections are submitted\nwith orientation defined for each section embedded. In the\ncase of alopecia assessment, the punch biopsy is transversely\nrather than vertically sectioned; this method yields sections\nwith numerous follicles, allowing evaluation of follicular\ndensity, follicular unit morphology, and follicular growth\ndynamics, i.e., anagen-telogen ratio17. Once embedded,\ndepending on the tissue size, one to several profiles (5\u03bc\nthick tissue sections) are cut from the paraffin tissue blocks,\nplaced on a glass slide, and routinely stained with\nhematoxylan and eosin. In certain circumstances, such as\nclinical impression or pathologic suspicion of scabies,\nGrover\u2019s disease, dermatitis herpetiformis, or folliculitis,\nlevel or serial sections (typically 3 glass slides with tissue\nsections from deeper levels of the biopsy) are performed to\nincrease the yield of identifying diagnostic findings of focal\npathologic processes. In addition, other histochemical stains\ncan be applied to the tissue for identification of specific\norganisms or tissue components. Some commonly used\nhistochemical stains include periodic acid Schiff with or\nwithout diastase (fungus, basement membrane), Grocott\u2019s\nmethamine silver (fungus), Fite\u2019s acid fast bacillus\n(mycobacteria), alcian blue or colloid iron (mucin), Prussian\nblue (iron-hemosiderin), trichrome (collagen and smooth\nmuscle), and Fontana Masson stain (melanin). See figure 3.\n\n\n\nReporting clinical information\n\n\n\nSuccessful diagnosis of skin pathology requires, perhaps\nabove all else, effective cooperation, and teamwork, between\nthe clinician and the dermatopathologist. Not only\nproviding a diagnostic tissue sample by the best possible\nprocedure, but also by conveying relevant clinical\ninformation does this. See figure 4. Clinical information is\ninvariably helpful and often absolutely essential to the\nhistologic diagnosis of skin disease, especially inflammatory\ndermatoses. Many lesions may appear identical under the\nmicroscope and therefore require the background\ninformation for proper discrimination. See figure 5. In\ngeneral, increased and effective communication between\nclinician and pathologist results in more accurate diagnosis\nand treatment for the patient, and this begins with\nthe relatively brief yet informative specimen\nsubmission/requisition form. At the bare minimum, five\npieces of information should accompany every dermatologic\nspecimen for pathologic evaluation: \u201cDescription,\nDemogrpahics, Duration, Diameter, and Diagnosis\u201d15. The\ndescription may include scarcely more than a word or two\nregarding the general appearance of the lesion as seen\ngrossly on the patient (e.g., erythematous, scaly, pearly,\nraised, ulcerative etc\u2026). Demographics must include at\nleast\n\n\n\n\n\n\n\n\n11\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 5.   The skin reacts in a limited number of ways, distinguishable by\nlight microscopy, so for any given pathologic change, several possible\ncauses exist.  By clinical correlation, the differential diagnosis may be\nlimited to one or two entities.  Illustrated here are two examples of\nlichenoid dermatitis: on the left is a biopsy from lichen planus-like\nkeratosis (LPLK or benign lichenoid keratosis) and on the right is biopsy\nof from lichen planus.  If the dermatopathologist is informed that the\nbiopsy was done for suspected skin cancer, then this lichenod dermatitis\nwould be interpreted as a \u201cLPLK\u201d.  In contrast, if the clinical information\nprovided was generalized pruritic eruption of polygonal, erythematous,\nslightly violaceous papules, the diagnosis of lichen planus would be\nrendered.\n\n\n\nFig 6.   Cutaneous malignant spindle cell neoplasms.  Depending the\ndegree of differentiation and co-existence of precursor lesions (solar\nkeratosis, melanoma in situ), it may be impossible to reliably distinguish\natypical fibroxanthoma ((AFX) a.k.a. superficial malignant fibrous\nhistiocytoma)(bottom panels) from spindle cell counterparts of melanoma\n(top right panel) and squamous cell carcinoma (top left panel).  In\nsituations such as this, immunohistochemistry is used to distinguish\nspecific tumors fro\u00dfm one another.\n\n\n\nFig 7.   Immunohistochemistry for cutaneous malignant spindle cell tumors.  Atypical\nfibroxanthoma ((AFX) (bottom panels) is distinguished from spindle cell variants of melanoma\n(top right panel) and squamous cell carcinoma (top left panel) by the absence of cytokeratin\n(CK) and S100 protein (sensitive melanoma marker) expression.\n\n\n\n\n\n\n\n\n12\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nleast the age and sex of the patient, however in certain\ncircumstances the race, medications and known medical\nhistory can also prove invaluable. Duration is often crucial\nin distinguishing subacute from more chronic or acute\nprocesses. The diameter of the lesion is particularly helpful\nwhen the lesion has been only partially excised. For\neruptions, one may substitute \u201cdistribution\u201d over the body\nfor diameter. Finally, the clinically suspected diagnosis and\ndifferential should be included for it is the\ndermatopathologist\u2019s ultimate goal to bring in line the\nhistologic morphology with the clinical impression.\nAlthough some clinicians purposefully withhold this last\n\u201cD\u201d (diagnosis), in an effort to avoid biasing the pathologist,\nit is the burden of the pathologist to avoid this pitfall, and\nto maximize the utility of the clinical information. In order\nto avoid bias, dermatopathologists do not read the clinical\ninformation until after review of the histologic sections. In\nthis fashion, the dermatopathologist generates a histologic\ndifferential diagnosis that can be reconciled with the\nsubmitted clinical differential diagnosis.\n\n\n\nSpecial attention is warranted to a few specific vagaries\ncommonly encountered on pathology requisition forms. As\nreferred to above, many clinicians unfortunately fall into the\npattern of either leaving the clinical impression lines blank,\nor else employing vague and essentially meaningless terms\nsuch as \u201clesion\u201d or \u201cskin anomaly.\u201d Whether such practice\nindicates a dearth of clinical acumen, laziness, or mere\noversight remains debatable; however, it undeniably results\nin limited clinicopathologic correlation and the potential to\nrender an erroneous diagnosis that could lead to therapeutic\nmisadventure. Indicative of the significance of including\ninformative clinical information, are the results of a recent\nstudy from the Cleveland Clinic8, 21. Dermatologists, whose\nresidency training includes extensive exposure to\ndermatopathology, were more than 20x less likely to omit\npertinent clinical information when submitting specimens\nfor dermatopathologic evaluation, as compared to family\npracticioners. Another unfortunately common practice to be\navoided is use of the term \u201crule out\u201d on a requisition form.\nThe ambiguity of the phrase is easily appreciated when one\nconsiders its typical meaning as indicative of the suspected\nlesion (i.e., \u201cplease rule out basal cell carcinoma because that\nis what I think it is\u201d) or the exact opposite (i.e., \u201cI do not\nthink it is basal cell carcinoma however please rule it out to\nbe sure\u201d)21. Although seemingly obvious, in the fast paced\nand high-pressure practice of modern clinical medicine, the\ntask of filling out the clinical suspicion is often relegated to\nclinical staff in place of the submitting physician (e.g.\nnurses, technical staff, etc. \u2026). This practice should be\navidly avoided due to the complexity and importance of\nsuch information to the dermatopathologist. Lastly, the use\nof obscure or even made-up abbreviations is also to be\navoided due to the resulting obligatory phone calls and\nunnecessary communiqu\u00e9, which slow down the diagnostic\nprocess21. In essence, biopsy is a physician-to-physician\nconsultation; therefore the dermatologist should be\ncommunicating to the dermatopathologist the most\n\n\n\nrelevant clinical information to assist in arriving at correct\ndiagnosis.\n\n\n\nOn a final note, there is the question of submitting digital\nimaging of the gross lesion along with the specimen for\nhistologic analysis. Rapid advancement in digital imaging\nhas drastically reduced the time and cost associated with\nsubmission of photographs of the lesion on the patient.\nFurthermore, increasing resolution continues to improve,\nwhich only serves to raise future expectations for\nclinicopathologic correlation. A recent study from Hershey\nMedical Center22 showed that inclusion of clinical photos\nhelped confirm initial diagnoses and narrowed differential\ndiagnoses with statistical significance, and of note, inclusion\nof digital images with specimens did not change diagnoses\nor decrease the number of additional studies. The diagnostic\ncontribution for digital images had the most impact on the\ndiagnosis of inflammatory dermatoses: these images were\n\u201cgood help\u201d in 43% of biopsies and narrowed the differential\nin diagnosis in 31%. Therefore, although not absolutely\nnecessary, the submission of digital images with\ndermatologic specimens is strongly encouraged, particularly\nas the cost of digital images decreases while their quality\nincreases.\n\n\n\nAccurate biopsy interpretation\n\n\n\nThe dermatopathologist\u2019s role in dermatologic care is to\nidentify the microscopic skin abnormalities and translate\nthis information into a meaningful, clinically useful\npathology report. Before histologic assessment, the\ndermatopatholigist must ensure that specimen number on\nthe paperwork matches that on the glass slide and that the\nmicroscopic sections are reflective of the gross description\n(e.g. bisected punch biopsy will have 2 punch silhouettes on\nthe slide). In general, when one views histopathologic\nsections, one should: 1) Be able to imagine how the lesion\nlooked clinically. 2) Apply reliable and reproducible criteria\nfor diagnosis. 3) Use clear and concise language that is\nclinically relevant in the report. 4) Keep an open mind as\ncriteria evolve and new concepts arise. 5) Learn from errors\nas mistakes are inevitable (mistakes and malpractice are not\nequivalent)1, 6. All of the above entails a familiarity with\nnormal skin and its variants (e.g., age-related changes,\nanatomic variations, the effects of exposure to the\nelements), familiarity with artifacts produced by processing\nand specimen handling/transport to avoid false-positive and\nnegative results, an understanding of the natural chronology\nof various dermatologic diseases, being cognizant of the\nlimitations of one\u2019s own skill and seeking outside\nconsultation when appropriate, and keeping up to date with\nthe constantly evolving knowledge of disease, criteria for\ndiagnosis, and the elucidation of new dermatologic entities.\n\n\n\nAn approach as described above for histologic interpretation\nwill manifest itself in a predictable algorithmic method1, 6.\nDermatopathologic \u201csign-out\u201d should be performed in a\nquiet place, free from distraction. Prior to using the\nmicroscope, the slide should be observed with the naked\neye,\n\n\n\n\n\n\n\n\n13\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\neye, taking note of the number of pieces of tissue and\ncorrelating this with how the specimen was grossed, and\nwhat type of biopsy is being examined (e.g., punch vs. shave\nbiopsy). Importantly, as stated above, knowledge of the\nclinical history should be avoided prior to histologic\nexamination, in order to avoid a biased approach. When the\nslide is placed under the scope, low magnification should be\nemployed first for pattern recognition. First confirm the\nmethod of biopsy. The primary question then becomes\nwhether the process involves an inflammatory or neoplastic\ninfiltrate? Higher power should be used only later to\nevaluate cytology. While at low power, the anatomic site\nshould be determined when possible (e.g., abundant\ncompact orthokeratosis and absence of follicles is\n\n\n\ncharacteristic of volar skin) because certain disease favor\nsome locales over others and some locales may predictably\nalter the appearance of the pathology (e.g., stasis changes\nco-existing with lower leg dermatoses and skin tumors).\nClues to the age of the patient (e.g., solar elastosis from\nchronic sun exposure) should also be sought in order to alter\nthe differential as some diseases favor pediatric patients and\nothers more geriatric populations. At this point the\ndermatopathologist should apply their own personal\nsystematic approach to examining all skin sections on the\nslide such as from top to bottom (stratum corneum to the\nbasal layer of the epidermis to the dermis ending at the\nsubcutis then examine for the pathologic pattern). The\norder is not important, but individual consistency is\nessential\n\n\n\nTable 2.   Skin inflammatory patterns and tissue reaction patterns\n\n\n\nExamples\n\n\n\nDrug reactions, viral exanthema\nLght reactions, lupus erythematosus\nUrticarial vasculitis, polyarteritis nodosa\nLepromatous leprosy, xanthoma\nPustular psoriasis, candidiasis\nDermatitis herpetiformis,\nSuppurative folliculitis, rosacea\nScar, dermatofibromas\nErythema nodosum, nodular vasculitis\n\n\n\nLichen planus, erythema multiforme\nAllergic contact dermatitis, pityriasis rosea\nPsoriasis, pityriasis rubra pilaris\nPemphigus, bullous pemphigoid\nWarfarin necrosis, hypersensitivity vasculitis\nSarcoidosis, granuloma annulare\n\n\n\nEpidermal nevi, keratoderma\n\n\n\nGrover's disease, Darier's disease\n\n\n\nPorokeratosis, incidental finding\nVerruca vulgaris, solar keratosis\n\n\n\nFbrous papules (adenoma sebaceum)\n\n\n\nEosinophilic cellulitis\n\n\n\nPerforating folliculitis\n\n\n\n9 Basic Patterns of  Inflammation\n\n\n\n1) Superficial Perivascular\n2) Superficial & deep perivascular\n3) Vasculitis\n4) Nodular & diffuse dermatitis\n5) Intraepidermal pustular dermatitis\n6) Subepidermal vesicular dermatitis\n7) Folliculitis & perifolliculitis\n8) Fibrosing dermatitis\n9) Panniculitis\n\n\n\nMajor Tissue Reaction Patterns\n\n\n\n\u2022 Lichenoid/interface (basal cell damage)\n\u2022 Spongiotic (intercellular epidermal edema)\n\u2022 Psoriasiform (regular epidermal hyperplasia)\n\u2022 Vesiculobullous (blisters within or beneath epidermis)\n\u2022 Vasculopathic (vessel damage or occlusion)\n\u2022 Granulomatous (granulomatous infiltrates)\n\n\n\nMinor Tissue Reaction Patterns\n\n\n\n\u2022 Epidermolytic hyperkeratosis (hyperkeratosis with \ngranular & vacuolar degeneration)\n\n\n\n\u2022 Acantholytic dyskeratosis (suprabasilar clefts with \nacantholysis and necrotic keratinocytes)\n\n\n\n\u2022 Cornoid lamellation (column of parakeratotic cells)\n\u2022 Papillomatosis (undulations & digitations of the \n\n\n\nepidermis)\n\u2022 Acral angiofibromas (increase of dermal vessels with \n\n\n\nsurrounding fibrosis)\n\u2022 Flame figures (dermal eosinophils & eosinophilic \n\n\n\nmaterial adherent to collagen bundles)\n\u2022 Transepidermal elimination (release of material via the \n\n\n\nepidermis or hair follicles)\n\n\n\nAdapted from Weedon2 and Ackerman' et al1\n\n\n\n\n\n\n\n\n14\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nessential to determine whether the lesion is due to\ninflammation, malformation, deposition or neoplasm. The\nmajor distinction is most often between an inflammatory or\nneoplastic process, which can often overlap as in the case of\nlichenoid host response to tumor such as melanoma.\n\n\n\nInterpretation of inflammatory skin biopsies requires the\nidentification and integration of 2 different morphologic\nfeatures- the pattern of inflammation and the tissue reaction\npattern1, 2. Some dermatopathologists base their diagnostic\napproach on the inflammatory pattern while others\ncategorize biopsies into one of the major tissue reactions. In\npractice, an experienced dermatopathologists uses both\nmethods simultaneously. See table 2.\n\n\n\nIn the case of neoplastic skin disease, benign neoplasms are\neasy to recognize and have super-imposable features,\nallowing for accurate and precise diagnosis. However, each\nmalignancy has one or many features that are unique to it.\nThus, particularly in the case for melanomas, widespread\nagreement on criteria for reliable and reproducible\ndiagnosis, or concordance amongst experts does not exist\n[23]. Nonetheless, there is a constellation of morphologic\nfeatures that one can commonly find in malignancies that\nleads to their diagnosis and/or a high degree of suspicion for\ntheir presence. See table 3. One key point to remember is\nthat there is no single feature that reliably and reproducibly\ndetects cancer. The diagnosis of malignancy is the\nsummation of morphologic, clinical and molecular\nevidence. Immunophenotypic analysis of skin tumors also\nplays an important role in the distinction between poorly\ndifferentiated malignancies and spindle cell tumors. See\ntable 4 for the results of common antibodies employed in\nthe skin, and figures 6 and 7 for an illustration of their use\nfor diagnosis.\n\n\n\nCommunication and clinicopathological \n\n\n\ncorrelation\n\n\n\nIt is always advantageous to examine histopathologic\nsections from the outset without reference to any clinical\ninformation, including the clinician's diagnosis. In this\nfashion, a pathologist is forced to make an analysis based on\nthe powers of observation alone without the being biased by\nclinical impressions. Usually, a skilled dermatopathologist\ncan formulate a meaningful diagnosis without assistance\nfrom the clinician, but when this is not possible, reference to\nthe clinical data can aid in the evaluation of the biopsy. This\nmethod allows for accurate observations to be made and\nrational conclusions to be formulated without prejudice. If a\nclinical diagnosis differs strikingly from a histologic\ndiagnosis, a pathologist should request additional sections,\ndetermine whether the specimens have been mixed up,\nconsult with the clinician, or rethink the matter over the\nfollowing day. In short, all attempts should be made to\nreconcile the findings on the slide with those on the patient.\n\n\n\nOn the other hand, once the dermatologist receives the\ndermatopathology report, the task of correlating the clinical\n\n\n\nfindings with pathologic findings begins. If the pathologic\nfindings are supportive of the clinical findings, the\ndermatopathology consult was immediately rewarding.\nHowever, if the pathologic findings cannot be reconciled\nwith clinical findings, then a dialogue with the\ndermatopathologist should begin and all efforts to reconcile\nthe gross with the microscopic be made.\n\n\n\nThe future of skin biopsy\n\n\n\nElucidation of the human genome, the burgeoning field of\nproteomics, the new science of bioinformatics and\ndevelopment of highly sensitive and accurate, and high\nthroughput technologies such as laser capture\nmicrodissection, mass spectroscopy, DNA and tissue\nmicroarrays are leading a revolution towards the molecular\nscreening, diagnosis, and management of cancer11, 24, 25.\nMolecular diagnosis is the detection of pathogenic\nmutations in DNA or RNA, or the associated protein in\norder to aid in the detection, diagnosis, subclassification,\nprognosis, selection of therapy, and monitoring of response\nto that therapy11, 24, 26. These techniques have only become\npossible due to the abundance of knowledge that has been\ncreated over the last 50 years concerning the molecular\nevents occurring in human cancers27. For instance, by\noutlining the signaling pathways that regulate cell growth,\nthe cell-cycle, and apoptosis (programmed cell death),\ntargets for anticancer drugs have been developed and have\nbeen shown to be effective for selected groups of affected\npatients. Three examples of targeted therapeutics include 1)\ntrastuzumab (Herceptin, Genentech) for the treatment of\nHER-2/neu overexpressing breast cancer28; and 2) imatinib\n(Gleevec, Novartis Pharmaceuticals) for the treatment of\nchronic myelogenous leukemia featuring a bcr/abl\ntranslocation29, gastrointestinal stromal tumors with\nselective c-kit oncogene\u2013activating mutations30,\nunresectable or metastatic dermatofibrosarcoma\nprotruberans [31], and potentially a subset of melanomas\n[32]; and 3) epidermal growth factor receptor (EGFR)\ninhibitors such as cetuximab (Erbitux, ImClone),\npanitumumab (Vectibix, Amgen), and erlotinib (Tarceva;\nOSI Pharmaceuticals) for non-small cell lung cancers . (It\u2019s\ninteresting to note that the EGFR inhibitor induced skin\nrash is significantly linked to overall and progression-free\nsurvival33). Introduction of these treatments into clinical\npractice has shown how the basic science of molecular\npathogenesis of cancer can be translated into diagnostic,\ntissue based tests for the selection of patients for targeted\ntherapy. For dermatology, the development of small\nmolecule inhibitors targeting skin cancer-related protein\nkinases will likely make an impact on cancer management in\nthe next decade11, 34. Protein kinases mediate most signal\ntransduction pathways in malignant cells and result in\nincreased proliferation, evasion of apoptosis, invasion, and\nmetastasis and are one of the largest groups of drug targets\naccounting for 20% to 30% of the drug discovery programs\nat some biotechnology and pharmaceutical companies.\nProtein kinase inhibitors (e.g. imatinib) have the potential\nto be effective in the treatment of nonmelanoma skin\ncancer,\n\n\n\n\n\n\n\n\n15\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 8.   Pathologic assessment for aberrant expression of c-kit/CD117, a receptor tyrosine kinase RTK, labeled 3 in right panel), is frequently found mutated\nin melanoma arising in sun-damaged skin (lentigo maligna melanoma) [32].  Lentigo maligna melanoma arising on sun-damaged skin (top left panel) shows\nCD117/c-kit expression in both the in situ and invasive components, most melanomas lose c-kit expression with development of invasive/vertical growth\nphase, which has a potential to metastasize directionally related to its thickness (bottom left panel).  Right panel shows an outline of the major molecular\npathways in the pathogenesis of melanoma and potential targets (tagged by light blue hexagons) for small molecule inhibitors.  Activating mutations of RAS\nare found in approximately 10-20% of melanomas; loss of PTEN in ~30-50%; activating mutations of BRAF in ~50%; Akt3 gene amplification and or activation\nin ~60% and ERK activation in a subset of melanomas.  Arrows represent activation.  Barred lines indicate inhibition.  Numbered hexagons represent new\nsmall molecule inhibitors targeting cell-cycle specific steps that regulate melanoma cell growth: 1) antisense oligonucleotides to Bcl-2 (oblimerson); 2) CDK\ninhibitors (flavopiridol); 3) receptor tyrosine kinase inhibitors (Imatinib, gefinitib, erlotinib); 4) farnesyl transferase inhibitors; 5) RAF inhibitors (BAY 43-9006\n(sorafenib); and 6) mTOR inhibitors (CCI-779).  Akt: murine v-akt oncogene homologue.  ARF: alternate reading frame.  Bcl-2: B cell lymphoma derived\nprotein.  BRAF: v-raf murine sarcoma viral oncogene.  cAMP: cyclic adenosine monophospate.  CDK2NA\u201d cyclin dependent kinase inhibitor-2A.  CDK: cyclin\ndependent kinase.  E2F: E2F cell cycle regulated transcription factor.  ERK: extracellular signal-regulated kinase.  Hdm2: human double minute-2.  MC1R:\nmelanocortin-receptor.  MEK: (MAPK) mitogen activated protein kinase.  MITF: microphthalmia transcription factor.  MSH: melanocyte stimulating hormone\n(melanocortin).  mTOR: mammalian target of rapamycin.  PI3K: phosphatidynlinositol-3 kinase.  PTEN: phosophatase and tensin homolog.  RAS: rous avian\nsarcoma homologue.  Rb: retinoblastoma protein\n\n\n\nTable 3.   Histologic features that differentiate benign versus malignant neoplasms\n\n\n\nMalignant\nLarge\nAsymmetric\nPoorly circumscribed\nIrregular, jagged margins\nNo wedge-shaped profile\nDeeply situated\nUlcerated\nNeoplastic cells in sheets\nAggregates vary in size & shape\nCells poorly differentiated\nLoss of adnexal structures\nNo maturation\n\n\n\nNecrosis en masse\nPerineural invasion\nVascular invasion\nSingle files of neoplastic cells between collagen bundles\nPoorly formed or absent capsule\nClefts between neoplastic cells and tumor stroma\n\n\n\nBenign\nSmall\nSymmetric\nWell circumscribed\nSmooth margins\nV-(wedge)-shaped; vertically oriented\nSuperficially situated\nNon-ulcerated\nNeoplastic cells discretely arranged\nAggregates small, uniform\nCells well differentiated\nAdnexal structures usually preserved\nMaturation: nuclei of cells at base of lesion smaller than\nthose at the surface\nNo necrosis, or lonely, solitary cell necrosis\nNo perineural invasion\nNo vascular invasion\nNo single filing of neoplastic cells\nThick fibrous capsule at periphery\nClefts between tumor stroma & normal stroma\n\n\n\nAdapted from Ackerman10\n\n\n\n\n\n\n\n\n16\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ncancer, melanoma, dermatofibrosarcoma protuberans,\nMerkel cell carcinoma, Kaposi's sarcoma, and systemic\nmastocytosis.\n\n\n\nPersonalized medicine includes the concepts that for a given\ndisease, the rate of progression of the disease for each person\nis unique and each person responds in a unique way to\ndrugs24, 35. With respect to melanoma as a dermatologic\nexample, a personalized medical approach would include\nthe detection of disease predisposition, screening and early\ndisease diagnosis, assessment of prognosis, detection of\nminimal residual disease, pharmacogenomic measurements\nof drug efficacy and risk of toxic effects for treatment of\nmetastatic disease, and the monitoring for melanoma\nrecurrence11. Precise identification of melanoma patients at\nrisk for death is the first step in developing efficacious\nmelanoma therapies as the prognosis for individuals with\nmetastatic melanoma is poor with a 5-year survival rate of\n5-10%, due, in part, to the lack of effective treatment for\nmetastatic melanoma which is chemoresistant. Melanoma is\na good model for targeted therapy as its lesions (and\nprecursors) are often available for sampling, which will be\nnecessary to assess the presence or absence of therapeutic\ntargets. Figure 8 outlines the melanoma cell-cycle pathway\nand the proteins specifically targeted by these small\nmolecule inhibitors.\n\n\n\nConclusion\nRoutine histologic examination of skin biopsy is a powerful,\ncost-effective (inexpensive) and widely available technique\nthat is not readily replaced by other modalities for the\ndiagnosis of skin disease. However, skin biopsy is not an\nanalytic (black box) test like complete blood count (CBC)\nor serum cholesterol test that require little more than a\nblood sample and calibrated analyzer. Rather, procurement\nof a skin biopsy is a physician-to-physician consultation\nwhere the histopathologic findings are correlated with the\nclinical morphology and disease course to arrive at a\nrelevant and accurate dermatologic diagnosis. This process\ncannot work without proper biopsy site and procedure\nselection, delicate and appropriate handling of the tissue,\ncommunication of pertinent clinical details, and discourse\n\n\n\nbetween the dermatologist and dermatopathologist. With\nthe advent of new pathology based tests and delineation of\nthe molecular and immunologic defects of dermatologic\ndisorders, skin biopsy will likely play an increasingly greater\nrole in the evaluation and management of individual\npatients.\n\n\n\nReferences\n\n\n\n1. Ackerman AB, B\u00f6er A, Bennin B, Gottlieb GJ. Histologic \nDiagnosis of Inflammatory Skin Diseases: An Algorithmic \nMethod Based on Pattern Analysis. second edition ed. New \nYork City: Ardor Scribendi 2005.\n\n\n\n2. Weedon D. Skin Pathology. Edinburgh: Churchill Livingstone \n2002.\n\n\n\n3. Barnhill R, Crowson A. Textbook of Dermatopathlogy. 2nd ed. \nNew York: McGraw-Hill Professional Publishing 2004.\n\n\n\n4. Rapini RP. Practical dermatopathology. Philadelphia: Elsevier \nMosby 2005.\n\n\n\n5. Elder DE. Lever's histopathology of the skin. 9th ed. \nPhiladelphia: Lippincott Williams & Wilkins 2005.\n\n\n\n6. Grant-Kels JM. Color Atlas of Dermatopathology. New York: \nInforma Healthcare USA, Inc. 2007.\n\n\n\n7 Kerl H, Cerroni L, Burg G, Cerio R, Gollnick H, Kutzner H, et al. \nInternational Board Certification in Dermatopathology: a \nworldwide effort to raise standards in dermatopathology. J \nCutan Pathol. 2006 Feb;33(2):156-9.\n\n\n\n8. Sellheyer K, Bergfeld WF. A retrospective biopsy study of the \nclinical diagnostic accuracy of common skin diseases by \ndifferent specialties compared with dermatology. J Am Acad \nDermatol. 2005 May;52(5):823-30.\n\n\n\n9. Weyers W. The 21st century--time for a reliable method for \ndiagnosis in clinical dermatology. Arch Dermatol. 2000 \nJan;136(1):103-5.\n\n\n\n10 Ackerman AB. Differentiation of benign from malignant \nneoplasms by silhouette. Am J Dermatopathol. 1989\nAug;11(4):297-300.\n\n\n\n11. Carlson JA, Ross JS, Slominski A, Linette G, Mysliborski J, Hill J, \net al. Molecular diagnostics in melanoma. J Am Acad Dermatol. \n2005 May;52(5):743-75; quiz 75-8.\n\n\n\n12. Campbell GA, Sauber L. Getting the most from \ndermatopathology. The Veterinary clinics of North America. 2007 \nMar;37(2):393-402, viii.\n\n\n\n13. Massone C, Peter Soyer H, Lozzi GP, Di Stefani A, Leinweber B, \nGabler G, et al. Feasibility and diagnostic agreement in \nteledermatopathology using a virtual slide system. Hum Pathol. \n2007 Apr;38(4):546-54.\n\n\n\n14. Rapini RP. Obtaining a skin biopsy specimen and interpreting the \nresults. Dermatol Clin. 1994 Jan;12(1):83-91.\n\n\n\nTable 4.  Immunohistochemical evaluation of poorly differentiated skin tumors\n\n\n\nMelanoma\n\n\n\n+\n+\n+\n-\n+\n-\n-\n-\n\n\n\nDesmoplastic\nmelanoma\n\n\n\n+\n-\n-\n-\n+\n-\n\u00b1\n\u00b1\n\n\n\nCarcinoma\n\n\n\n-\n-\n-\n+\n\u00b1\n-\n-\n+\n\n\n\nSarcoma\n\n\n\n\u00b1\n-\n-\n-\n+\n-\n\u00b1\n\u00b1\n\n\n\nLymphoma\n\n\n\n-\n-\n-\n-\n\u00b1\n+\n-\n-\n\n\n\nAntibody\n\n\n\nS100 protein\nHMB-45\nMart-1\nCytokeratins\nVimentin\nLeukocyte common antigen (LCA)\nActin\nEpithelial membrane antigen (EMA)\n\n\n\n\n\n\n\n\n17\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n15 Tobinick EL, Usatine RP. Choosing the type of biopsy. In: Usatine \nRP, Moy RL, eds. Skin Surgery: A Practical Guide. St. Louis: \nMosby 1998.\n\n\n\n16. LeBoit PE. Interface dermatitis. How specific are its \nhistopathologic features? Arch Dermatol. 1993;129(10):1324-8.\n\n\n\n17. Templeton SF, Santa Cruz DJ, Solomon AR. Alopecia: histologic \ndiagnosis by transverse sections. Semin Diagn Pathol. 1996 \nFeb;13(1):2-18.\n\n\n\n18. Whiting DA. Diagnostic and predictive value of horizontal \nsections of scalp biopsy specimens in male pattern \nandrogenetic alopecia. J Am Acad Dermatol. 1993 May;28\n(5 Pt 1):755-63.\n\n\n\n19. Carlson JA, Ng BT, Chen KR. Cutaneous Vasculitis Update: \nDiagnostic Criteria, Classification, Epidemiology, Etiology, \nPathogenesis, Evaluation and Prognosis. Am J Dermatopathol. \n2005 Dec;27(6):504-28.\n\n\n\n20. Carlson JA, Chen KR. Cutaneous pseudovasculitis. Am J \nDermatopathol. 2007 Feb;29(1):44-55.\n\n\n\n21. Sellheyer K, Bergfeld WF. \"Lesion,\" \"rule out...,\" and other \nvagaries of filling out pathology requisition forms. J Am Acad \nDermatol. 2005 May;52(5):914-5.\n\n\n\n22. Fogelberg A, Ioffreda M, Helm KF. The utility of digital clinical \nphotographs in dermatopathology. Journal of cutaneous \nmedicine and surgery. 2004 Mar-Apr;8(2):116-21.\n\n\n\n23. Cerroni L, Kerl H. Tutorial on melanocytic lesions. Am J \nDermatopathol. 2001 Jun;23(3):237-41.\n\n\n\n24. Ross JS, Ginsburg GS. The integration of molecular diagnostics \nwith therapeutics. Implications for drug development and \npathology practice. Am J Clin Pathol. 2003 Jan;119(1):26-36.\n\n\n\n25. Keesee SK. Molecular diagnostics: impact upon cancer \ndetection. Expert Rev Mol Diagn. 2002 Mar;2(2):91-2.\n\n\n\n26. Amos J, Patnaik M. Commercial molecular diagnostics in the \nU.S.: The Human Genome Project to the clinical laboratory. Hum \nMutat. 2002 Apr;19(4):324-33.\n\n\n\n27. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 \nJan 7;100(1):57-70.\n\n\n\n28. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, \nFehrenbacher L, et al. Efficacy and safety of trastuzumab as a \nsingle agent in first-line treatment of HER2-overexpressing \nmetastatic breast cancer. J Clin Oncol. 2002 Feb 1;20(3):719-26.\n\n\n\n29 Mauro MJ, O'Dwyer M, Heinrich MC, Druker BJ. STI571: a \nparadigm of new agents for cancer therapeutics. J Clin Oncol. \n2002 Jan 1;20(1):325-34.\n\n\n\n30. Bumming P, Andersson J, Meis-Kindblom JM, Klingenstierna H, \nEngstrom K, Stierner U, et al. Neoadjuvant, adjuvant and \npalliative treatment of gastrointestinal stromal tumours (GIST) \nwith imatinib: a centre-based study of 17 patients. Br J Cancer. \n2003 Aug 4;89(3):460-4.\n\n\n\n31. McArthur GA. Molecular targeting of dermatofibrosarcoma \nprotuberans: a new approach to a surgical disease. J Natl \nCompr Canc Netw. 2007 May;5(5):557-62.\n\n\n\n32. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic Activation of \nKIT in Distinct Subtypes of Melanoma. J Clin Oncol. 2006 Aug 14.\n\n\n\n33. Wacker B, Nagrani T, Weinberg J, Witt K, Clark G, Cagnoni PJ. \nCorrelation between Development of Rash and Efficacy in \nPatients Treated with the Epidermal Growth Factor Receptor \nTyrosine Kinase Inhibitor Erlotinib in Two Large Phase III \nStudies. Clin Cancer Res. 2007 Jul 1;13(13):3913-21.\n\n\n\n34. Kondapalli L, Soltani K, Lacouture ME. The promise of molecular \ntargeted therapies: protein kinase inhibitors in the treatment of \ncutaneous malignancies. J Am Acad Dermatol. 2005 \nAug;53(2):291-302.\n\n\n\n35. Ginsburg GS, McCarthy JJ. Personalized medicine:\nrevolutionizing drug discovery and patient care. Trends \nBiotechnol. 2001 Dec;19(12):491-6.\n\n\n\n\n\n\n\n\n18\n\n\n\n\n\n\n\n\n19\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReview\n\n\n\nCutaneous Spirochetal Disease\n\n\n\nM Mahalingam, MD, FRCPath1 and J Bhawan, MD2\n\n\n\n1Dept of Pathology, UMASS Medical School, 3 Biotech, One\nInnovation, Drive, Worcester, MA 01605, USA\n2Dermatopathology Section, Department of Dermatology,\nBoston University School of Medicine, J-609 Albany Street,\nBoston, MA, USA\n\n\n\nCorrespondence\n\n\n\nM Mahalingam, MD, PhD, FRCPath\n\n\n\nemail : mahalinm@ummhc.org\n\n\n\nIntroduction\n\n\n\nCutaneous Spirochetal Diseases -\nUnifying Features\n\n\n\n\u2022 Portal of entry - skin or mucous membrane \n\u2022 Systemic dissemination of spirochetes results in \n\n\n\nmultiorgan involvement \n\u2022 Multiple clinical disease stages interspersed with \n\n\n\nlong latency periods (months to years) \n\u2022 Histology varies with biopsy site and age of the \n\n\n\nlesion\n\u2022 Causative organism - detected by special stains/\n\n\n\nculture months to even years after primary \ninnoculation\n\n\n\nAlthough involvement of the skin in the more common\nspirochetal-induced diseases is clinically distinctive, making\nthe correct diagnosis continues to remain an on-going\nchallenge. Contributory factors include lack of systematic\nprogression from one stage of the disease to the next, co-\nexistence of manifestations of more than one stage in a\npatient at a given time and, initial presentation with\nsymptoms of late stage disease. Other confounding variables\ninclude atypical clinical presentations and absence of\nserologic evidence of disease in patients with co-existing\nimmunodeficiency disease such as human\nimmunodeficiency disease (HIV)1.\n\n\n\nA. Borrelial Infection\n\n\n\nThese include Lyme disease and relapsing fever or febrile\nrecurrens.\n\n\n\n1. Lyme disease\n\n\n\nEarly manifestations - Erythema migrans\n\n\n\nInitially called \u201cerythema chronicum migrans Afzelius\u201d\nbecause of its migratory nature, the name is now known to\nbe a misnomer as the rash manifests within 3-30 days of the\ntick bite2, 3, 4. Erythema migrans (EM) may be seen anywhere\non the body but is most common on the lower extremities,\ninguinal/axillary regions of adults (Figure 1) and, on the\n\n\n\nface in children (\u2018\u2018slapped cheek\u201d appearance)5. Women are\nreported to be more commonly affected in European\nstudies2. Typically described as \u201cround\u201d, the rash in reality is\nmore oval with the \u201clong line of the oval parallel to the lines\nof least skin tension\u201d (Langer lines) (Figure 2)6, 7, 8. As\nmigration of the rash proceeds, distortion of this\nconfiguration occurs (Figure 3)9. The center fades after a\nfew weeks leaving only the annular border erythematous.\nThe rash in itself is usually asymptomatic but 50% of\npatients complain of mild tingling, or itching10. Systemic\nmanifestations reported in approximately 50% of patients,\nmay appear8 before, during or, after the classic rash6, 9.\n\n\n\nMultiple erythema migrans-like lesions occur in between\n1-17% of patients6. The reported prevalence of multiple\nlesions is believed to be higher in the United States than in\nEurope11. Secondary EM lesions number from 2 to more\nthan 80, usually occur away from the original lesion and, are\nusually smaller and non-migratory (occur in \u201ccrops\u201d of\nsimilar size, color and shape) in comparison to classic EM6.\nConstitutional symptoms are usually more severe than those\nassociated with classic erythema migrans12. A rare event,\nreminiscent of a Koebner-like phenomenon, is the\ndevelopment of chicken pox in an area previously the site of\nEM (Figure 4, personal communication S O\u2019Connell, MD,\nUK).\n\n\n\nPrimary and secondary EM have an excellent prognosis\nattributable in part to the activation of pro-inflammatory\ncytokines such as interferon-\u03b313. The rash usually heals\nspontaneously but may persist for as long as 6-12 months\n(median duration of the rash in the United States is shorter\nthan that in Europe)2 14 10.\n\n\n\nHistopathologic findings vary with the biopsy site9 and age\nof the lesion. Biopsies of early lesions show papillary dermal\nedema and a mixed infiltrate of lymphocytes, neutrophils,\nfew plasma cells and few eosinophils (Figure 5). Biopsies of\nolder lesions display a variably dense perivascular and\ninterstitial infiltrate of lymphocytes and plasma cells\n(Figure 6). Helpful, albeit non-specific, clues include the\npresence of plasma cells and mast cells in the infiltrate15.\n\n\n\n\n\n\n\n\n20\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 1.   Erythema migrans in the groin with expanding\nmargin at the site of the tick bite of a week\u2019s duration\n(reprinted with permission from Dermatopathology\nInteractive Atlas, edited by Bhawan J, Sau P, Byers HR, 2001)\n\n\n\nFig 2.   Erythema migrans. Oval configuration of rash\n(courtesy of S Luger, MD, CT)\n\n\n\nFig 3.   Erythema migrans. Distortion of oval\nconfiguration with migration of the rash (courtesy of S\nLuger, MD, CT)\n\n\n\nFig 4.   Development of chicken pox in an area\npreviously the site of erythema migrans (\u201cKoebner-\nlike\u201d phenomenon, courtesy S O\u2019Connell, MD,\nSouthampton, UK)\n\n\n\nFig 5.   Histopathology of early erythema migrans.\nPapillary dermal edema and a mixed inflammatory\ninfiltrate. (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\nFig 6.   Histopathology of late erythema migrans.\nDense perivascular lymphoid cell infiltrate with many\nplasma cell (hematoxylin and eosin stain, 40X)\n(reprinted with permission from Dermatopathology\nInteractive Atlas, edited by Bhawan J, Sau P, Byers HR,\n2001)\n\n\n\n\n\n\n\n\n21\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe presence of both plasma cells and eosinophils in the\nsame specimen is reported to be much less common than\nthe presence of either9. From biopsy specimens, spirochetes\nare best located in the papillary dermis and may be short or\nelongate at this stage of the disease (Figure 5 inset)9. Direct\ndetection of the spirochete from biopsy specimens by\nculture or by PCR typically has good sensitivity but is\nusually unnecessary16.\n\n\n\nEM - Histopathologic Highlights\n\n\n\n\u2022 Histology - varies with biopsy site and age of \nlesion\n\n\n\n\u2022 Early lesions - papillary dermal edema and a \nmixed inflammatory infiltrate\n\n\n\n\u2022 Older lesions - variably dense perivascular and \ninterstitial infiltrate of lymphocytes and plasma \ncells\n\n\n\n\u2022 Clues - presence of both plasma cells and mast \ncells in the infiltrate\n\n\n\n\u2022 Spirochetes - best located in the papillary dermis\n\n\n\nImmunohistochemical studies indicate the infiltrate to be\ncomposed of CD4+ T lymphocytes with the exception of\nthose seen in association with HIV infection in which the\ninfiltrate is mainly CD8+ T lymphocytes (reflective of the\nCD4 lymphopenia of HIV infection)17. Histopathologic\nfeatures of multiple lesions of EM are identical to primary\nEM.\n\n\n\nLate Manifestations -\nAcrodermatitis Chronica Atrophicans (ACA)\n\n\n\nObserved mainly in elderly patients in Europe, ACA has an\ninsidious onset and appears to have predilection for\nfemales18. An inflammatory phase presenting as a bluish-red\ndiscoloration on the extensor aspect of joints and lower\nextremity characterizes the early clinical stages of this\nbiphasic disease (Figure 7)19. Lesions typically extend from\ndistal to the proximal portion of the extremity involved.\nAlthough the erythema and swelling initially vary in\nintensity (\u2018waxes and wanes\u2019), swelling of the posterior\naspect of the lower extremities is believed by some to be\nparticularly indicative of Lyme disease (Figure 8)10.\n\n\n\nCutaneous atrophy characterized by lesions with a\n\u201ccigarette-paper-like\u201d appearance (Figure 9) a feature of the\nlater clinical stage is not an obligatory sequel to the\ninflammatory phase of ACA19.\n\n\n\nCentral and peripheral nervous system involvement has also\nbeen documented in approximately 45% of patients with\nACA11. Chronic joint and bone involvement is attributed to\npersistence of spirochetes in cutaneous lesions. The\ncharacteristic symptom, exhibited in about a third of the\npatients in one study, was a swollen or painful foot and\nheel11. Solitary or multiple fibrotic lesions near joints,\nparticularly in the olecranon area, may develop in some\npatients (Figure 10)19.\n\n\n\nHistopathologic findings vary with the clinical phase of\nACA. In inflammatory lesions, three layers are typically\ndescribed: an atrophic epidermis, a zone of uninvolved\npapillary dermis and a layer of inflammatory cells composed\nof lymphocytes and plasma cells20. The presence of plasma\ncells in the infiltrate is documented mainly from studies\nfrom Europe as American reports indicate that few or no\nplasma cells are found19, 21. The infiltrate may be deep with\nextension into the subcutis10. Occasionally, interface\ndermatitis has been reported.\n\n\n\nACA - Histopathologic Highlights\n\n\n\n\u2022 Two distinct clinical phases - early inflammatory phase \nand late atrophic phase\n\n\n\n\u2022 Histopathology varies with clinical phase of the disease  \n\u2022 Inflammatory phase characterized by three layers \n\n\n\nLayer 1 - atrophic epidermis\nLayer 2 - zone of uninvolved papillary dermis \nLayer 3 - inflammatory infiltrate of lymphocytes and \nplasma cells\n\n\n\n\u2022 Causative organism - detected by special stains/culture \nmonths to even years after primary innoculation\n\n\n\nUnusual findings include the presence of vacuoles, either\nsingly or in groups, at different levels of the dermis22. While\nsome believe these represent mature adipocytes, others\nbelieve them to be an expression of lymphedema, given that\nthey are mainly observed from biopsies of markedly\nedematous sites. In favor of the latter hypothesis is the\nabsence of such vacuoles from the same site post-treatment.\n\n\n\nAll three species of B. burgdorferi that infect humans have\nbeen found in ACA lesions23. Phenotypic studies indicate\nthe lymphocytes in the infiltrate are mainly of the CD4\nphenotype, favoring the concept that ACA is a T-cell\nmediated immune response24. Further in support of this\ntheory is the expression of adhesion molecules such as\nICAM-1 on endothelial cells, lymphocytes and basal\nkeratinocytes in the inflammatory infiltrate25. Chronicity of\nthe lesions may be partially explained by downregulation of\nMHC class II molecules on Langerhans cells26. An\nineffective anti-B. burgdorferi immune response essentially\ntranslates to ineffective elimination of the spirochete.\n\n\n\nCutaneous Scleroborrelioses\n\n\n\nSclerotic skin lesions clinically indistinguishable from\nprimary lichen sclerosus et atrophicus (LSEA), morphea,\nprogressive facial hemiatrophy/Parry-Romberg syndrome\n(PRS) or eosinophilic fasciitis/Schulman\u2019s disease (\u201cborrelial\nfasciitis\u201d) develop in association with or in the absence of\nother dermatoborrelioses27, 28, 12, 29, 30. Periarticular (\u201culnar\u201d)\nfibrous nodules, presenting as hard nodules on the lateral\naspect of the digits near joints and described in association\nACA, may also occur in the absence of it or any other\ndermatoborrelioses31.\n\n\n\n\n\n\n\n\n22\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 7.   Acrodermatitis chronica atrophicans - early\nclinical stage. Bluish-red discoloration on the dorsum\nof the foot (courtesy of the late J White, MD, UK) \n\n\n\nFig 8.   Acrodermatitis chronica atrophicans.\nCharacteristic swelling on the posterior aspect of the\nlower extremities (courtesy S O\u2019Connell, MD,\nSouthampton, UK)\n\n\n\nFig 9.   Acrodermatitis chronica atrophicans - late\nclinical stage. Typical end-stage cutaneous atrophy\nwith prominence of superficial veins (courtesy\nS O\u2019Connell, MD, Southampton, UK)\n\n\n\nFig 10.   Acrodermatitis chronica atrophicans.\nErythematous, fibrotic lesion in the olecranon area\n(courtesy S O\u2019Connell, MD, Southampton, UK)\n\n\n\nFig 11.   Borrelial lymphocytoma of ear lobe, three\nmonths duration (courtesy of the late J White, MD, UK)\n\n\n\nFig 12.   Cutaneous borrelial lymphocytoma with\ndefinitive history of tick bite. Nodular and dense\nlymphohistiocytic infiltrate with prominent germinal\ncenter (hematoxylin and eosin stain, 40X)\n\n\n\n\n\n\n\n\n23\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nLesions clinically resembling LSEA/scleroderma present\nwith histologic features of the same. A unifying feature of\nLSEA- and morphea-like scleroborrelioses is the\nabundance of plasma cells in the inflammatory infiltrate19.\nUnusual histologic findings include a scleromyxedema-like\npicture with increased dermal mucin and fibroblast\nproliferation31.\n\n\n\nHistopathologic examination of a periarticular fibrous\nnodule reveals a relatively well-circumscribed nodules of\nbroad hyalinized bundles of collagen with macrophages and\nplasma cells32, 33. Adjacent capillaries may be occluded by\nsimilar deposits.\n\n\n\nProgressive facial hemiatrophy and eosinophilic fasciitis\nshow variable dermal sclerosis, loss of appendages and a\nperivascular infiltrate composed predominantly of\nlymphocytes and plasma cells with scattered histiocytes10.\nFeatures specific to borrelial fasciitis are that eosinophilic\ninfiltration of the fascial planes is not as impressive as in\n\u201cidiopathic\u201d Schulman\u2019s disease29.\n\n\n\nCutaneous Atrophoborrelioses\n\n\n\nAtrophic lesions indistinguishable from primary\nanetoderma may also occur in the absence of other\ndermatoborrelioses34 19. When associated with ACA, these\nlesions are usually seen at the periphery of an extensive\nlesion35.\n\n\n\nBiopsy specimens from atrophic/anetoderma-like skin\nlesions show absence of elastic tissue fibers in association\nwith a perivascular infiltrate of lymphocytes with occasional\nhistiocytes, neutrophils or eosinophils19. Spirochetes are\nfound with difficulty in histologic sections.\n\n\n\nCutaneous lymphoborrelioses\n(B- and T-cell lymphoid hyperplasias)\n\n\n\nThe least common of the cutaneous hallmarks of Lyme\ndisease (1%), lymphocytic infiltrates associated with borrelia\nmay present either as single (lymphadenosis benigna cutis\nsolitaria, LABC solitaria, borrelial lymphocytoma) or, as\nmultiple lesions (LABC dispersa)10. More common in\nchildren than in adults, LABC clinically presents as a\nnodulo-papular lesion in the ear lobes (Figure 11) in\nchildren and the nipple-areolar area in adults12. The precise\nreason for this predilection is not known but may be tissue\ntemperature-related10. The incubation period varies\nanywhere from a few weeks to 10 months. The duration of\nan untreated solitary lesion can vary anywhere from months\nto years (average 5 years)36. Spontaneous resolution may\noccur in months or years but typically, lesions resolve more\nrapidly with antibiotic therapy11. Lesions of LABC-dispersa\ncan be entirely subcutaneous, may last for decades, and\ntypically have no specific site predilection or associations\nwith other dermatoborrelioses. LABC has been reported\n\n\n\nsolely in Europe. However, all three species of\nB. burgdorferi sensu lato have been associated with LABC so\nit is unclear whether the lack of U.S. cases is related to strain\ndifferences23.\n\n\n\nSeveral reports suggest an association of low-grade\ncutaneous B-cell lymphoma with B. burgdorferi infection37,\n\n\n\n38. Clinical presentation of borrelia-associated B-cell\nlymphoproliferative disease is varied and consists of\nmultiple ill-defined, slowly progressive, plaques and nodules\npresenting on the trunk and/or extremities of usually older\npatients.\n\n\n\nHistologic features in both benign B- and T-cell dominant\nlesions are essentially similar to benign lymphoid\nhyperplasias (Figure 12) secondary to an arthropod bite,\nvaccination or other causes. Briefly, these include a dense,\ndeep dermal, predominantly lymphocytic infiltrate with\nadmixed plasma cells and eosinophils. The presence of\nscattered follicles with tingible body macrophages, mitoses\nand a polymorphous infiltrate (\u201creactive germinal centers\u201d)\nare helpful clues to the reactive nature of the infiltrate10. In\ncases where germinal centers are absent,\nimmunohistochemical studies definitively prove the\npolyclonal nature of the infiltrate. In order of frequency of\nBorrelial infection marginal zone lymphoma (20-52%) is\nfollowed by follicular center lymphoma (15-26%) and\ndiffuse large B-cell lymphoma (16-15%)37, 39.\n\n\n\nThat antigenic drive by borrelia may be a pathogenic factor\nin more than one subtype, is supported by the association of\nB. burgdorferi with multiple subtypes of cutaneous B-cell\nlymphoma. Demonstration of the organism in the skin\nprior to development of overt cutaneous B-cell lymphoma\nserves to confirm the temporal progression of\nB. burgdorferi - associated B-cell lymphoproliferative\ndisease. Clinical regression of marginal zone lymphoma\nafter eradication of B. burgdorferi argues in favor of a benign\nprocess40, 41, 38.\n\n\n\nDefinitive classification of borrelia-associated B-cell\nlymphoma is confounded by the immunohistochemical\nprofile. Expression of CD5 and CD10 (CALLA), antigens\ntypically associated with centrocytic lymphoma, are absent\nin borrelia-associated B-cell lymphoma37.\n\n\n\nCutaneous lesions other than those reported above have\nbeen reported in patients with documented Lyme disease\n(Table 1)8. These include panniculitis, vasculitis, granuloma\nannulare, erythema multiforme and a syphilis-like papulo-\nsquamous eruption. The association of these lesions with\nB. burgdorferi infection is at the level of case reports and\nB. burgdorferi has not been directly recovered from the\ninfected areas of any of these lesions. As such, systemic\nB. burgdorferi infection may be a precipitant of pathways\nleading to the development of these lesions in rare\ninstances.\n\n\n\n\n\n\n\n\n24\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 13.   Primary syphilis. Penile chancre (reprinted\nwith permission from Dermatopathology Interactive\nAtlas, edited by Bhawan J, Sau P, Byers HR, 2001)\n\n\n\nFig 14.   Secondary syphilis. Macular rash involving\npalms (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\nFig 15.   Secondary syphilis. Macular rash involving\nsoles (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\nFig 16.   Secondary syphilis. Condyloma lata involving\ngenitals (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\nFig 17.   Secondary syphilis. Irregular epidermal hyperplasia\n(lichen planus-like) and dense underlying perivascular and\ninterstitial lymphoid cell infiltrate  (hematoxylin and eosin\nstain, 10X) (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan J, Sau\nP, Byers HR, 2001)\n\n\n\nFig 18.   Secondary syphilis Plasma-cell rich\ninflammatory infiltrate (hematoxylin and eosin stain,\n40X) (courtesy of R Rapini, MD, TX)\n\n\n\n\n\n\n\n\n25\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nUncommon Cutaneous\nManifestations of Lyme Disease\n\n\n\n\u2022 Cutaneous scleroborrelioses \n- Morphea\n- Lichen sclerosus et atrophicus\n- Periarticular fibrous nodules\n- Progressive facial hemiatrophy\n- Eosinophilic fasciitis\n\n\n\n\u2022 Cutaneous atrophoborrelioses\n- Anetoderma\n\n\n\n\u2022 Cutaneous lymphoborrelioses\n- B-cell dominant (including B-cell lymphoma)\n- T-cell dominant\n\n\n\n\u2022 Others\n- Panniculitis\n- Granuloma annulare\n- Erythema multiforme\n- syphilis-like papulo-squamous eruption \n\n\n\n2. Febrile Recurrens\n\n\n\nFar less common than Lyme disease, febrile recurrens is also\ncharacterized by an initial erythema migrans-like bite\nreaction (\u201ccentral nodule with a distinctive brownish ring\u201d)\nand initial viremia, typically does not have as long a clinical\ncourse42. Typically, there may be anywhere from 3 to 10\nrecurring febrile attacks which means a disease lasting from\nas few as 21 days to as many as 140 days (5 months) but\nessentially no longer. The variability in clinical course of\nfebrile recurrens is believed to be due to antigenic phase\nvariations undergone by relapsing fever borreliae42.\n\n\n\nB. Treponemal Infections\n\n\n\nThese include syphilis, pinta, yaws and endemic syphilis.\nSyphilis, the best known of these four, is a venereal disease\nand thus presents with initial manifestations in the genital\narea, while the other three, collectively known as the non-\nvenereal treponematoses, are not spread by sexual activity\nand thus do not initially manifest in the genital area. Since\nessential morphologic and serologic differences are not fully\nrecognized between the different treponematoses, clinical\nhistory including geographic differences is crucial to\ndifferentiating and recognition of each of these entities.\n\n\n\nPrimary Syphilis -\nHistopathologic Hightlights \n\n\n\n\u2022 Erosion or ulceration\n\u2022 Dense, predominantly perivascular, inflammatory \n\n\n\ninfiltrate of lymphocytes and plasma cells \n\u2022 Spirochetes - located in almost all cases \n\n\n\nSyphils \nWhile Lyme disease is the most recently recognized of the\nspirochetal diseases that affect humans, syphilis historically\nremains the better known. Parallels are often drawn\n\n\n\nbetween these two entities and justifiably so, given that both\ndiseases are caused by spirochetes, start with a primary\nlesion, affect multiple organ systems including the skin and\nrun a chronic course43. Also, while spontaneous healing of\nthe primary lesion may occur in either, in both years without\nsymptoms may be followed by new manifestations.\n\n\n\nPerhaps a consequence of the reduced morbidity associated\nwith HIV infection, recent epidemiological reports have\nshown a resurgence of syphilis both in the United States and\nEurope44.\n\n\n\nEarly Manifestations (primary syphilis)\nThe chancre, the characteristic initial lesion of primary\nsyphilis, occurs about three weeks after the initial\ninoculation, is highly infectious, and usually presents as a\nsmall painless ulcer on the genitals (Figure 13)45. The classic\nHunterian chancre ulcer, fully developed in about two\nweeks and typically persisting for 2-6, is a sharply\ndemarcated round or oval papule, measuring about 2 mm in\ndiameter, with rolled edges and a clean eroded surface. In\nmen it is predominantly located on the penis (glans, the\ncoronal sulcus and prepuce) and women, the labia majora\nand minora, cervix, fourchette and perineum are involved in\ndecreasing order of frequency. \u201cKissing chancres\u201d may\ndevelop in areas of skin-to-skin contact. Extragenital\nchancres (on the lips and oral mucosa) are increasingly\nbeing reported44. The presence of a palpable, unilateral\nsatellite lymph node is a helpful clue to the etiology of the\nlesion. Spirochetemia is believed to precede onset of\ndevelopment of the ulcer.\n\n\n\nThe primary lesion is histologically characterized by an\nerosion or ulceration with a fibrinopurulent exudate\ncovering the surface 46. Hyperplasia of the adjacent\nepidermis with or without spongiosis may be seen. A\npredominantly perivascular, dense, inflammatory\ninfiltrate of lymphocytes and plasma cells and reactive\nendothelial cell atypia are believed to be integral features.\nRare cases with fibrinoid necrosis of vessel walls have\nbeen noted.\n\n\n\nFluorescent antibody staining using immunohistochemistry\nis believed to be more useful than special stains in detecting\nthe causative organisms in early lesions47, 48, 47. In the absence\nof identification of the spirochete, serologic testing is\nessential. Reaginic tests may however be negative (20% of\ncases) or reactive at low titers in patients with primary\nsyphilis.\n\n\n\nSecondary Syphilis\nThe eruption of secondary syphilis typically develops\n3-12 weeks after the primary chancre and is bilateral,\nsymmetric, more prominent on the upper extremities and\ninvolves the palms (Figure 14) and soles (Figure 15)49, 50.\nThe rash may be macular, papular or papulo-squamous\npruritic or non-pruritic eruption, and usually involves\nskin \n\n\n\n\n\n\n\n\n26\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nskin and mucous membranes51. Condyloma lata are moist\npapular lesions that coalesce to form plaques and are\ntypically located on the genitals (Figure 16), perianal area\nand axilla52. Nodular lesions are not entirely uncommon and\ncontinue to be reported despite the overall decreasing\nprevalence of secondary lesions53. Pustular secondary\nsyphilitic exanthemata have also been known to occur and\nbased on clinical morphology may be miliary, large\nacneiform, flat pustular, or pustoloulcerative 54, 55. Alopecia\nsyphilitica, referring to the moth-eaten, irregular pattern of\npatchy hair-loss sometimes seen in secondary syphilis, is\nrarely seen now-a-days56.\n\n\n\nUncommon secondary cutaneous manifestations include\ncondyloma lata involving the toe webs, \u201chorny syphilid\u201d\n(characterized by discrete, hyperkeratotic lesions on the\nvolar aspect of palms and soles), papulo-nodular lesions\nclinically mimicking histioid leprosy, targetoid or erythema\nmultiforme-like lesions, pseudo-lymphomatous,\npapulonodular lesions and follicular lesions52, 57-61. Vegetating\nsyphilid, refers to a variant that appears during the late\nstages of secondary syphilis and includes extensive, annular\nplaque-like lesions that may be verrucous44. \u201cMalignant\nsyphilis\u201d, a rare, ulcerative variant of secondary syphilis also\nknown as lues maligna, is believed to be a result of an\nimpaired cell-mediated immune system, is clinically\ncharacterized by verrucous, ulcerative, infiltrative\ngranulomatous pigmented lesions primarily involving the\nface62-64. In the largest series reported from a single center,\nfive of the six patients with lues maligna were HIV\npositive65.\n\n\n\nThe old adage that syphilis is a great mimic is perhaps as\ntrue for its histopathologic features as it is for its clinical\npresentation66, 67, 67. The variation in histology of lesions of\nsecondary syphilis is believed to be dependant on clinical\nmorphology and spatial relationship of the eruption to\ninfection68.\n\n\n\nThe histopathologic features of papular lesions, both early\nand late, are believed to the most diagnostic and that of\nmacular lesions non-specific69. Overall epidermal change is\nminimal in macular lesions51. Epidermal change is varied\nand may be spongiotic, irregular (lichen planus-like, figure\n17) or psoriasiform (with neutrophilic parakeratosis and\nepidermal pallor) with or without exocytosis70, 51. In one\nstudy, keratinocytes necrosis (63%) and exocytosis (84%),\nfound in a large proportion of biopsies studied, were\ndefined as \u201cconstant\u201d histologic features70.\n\n\n\nAlthough dermal changes are varied, unifying, albeit not\nentirely specific, histologic features include endothelial cell-\nlined vascular proliferation, reactive atypia and the presence\nof a plasma cell-rich inflammatory infiltrate (Figure 18).\nThe composition and depth of the infiltrate can vary from\narea to area within a single biopsy. Erythema multiforme-\nlike lesions are characterized by vacuolar interface\ndermatitis with necrotic keratinocytes59. While plasma cells\n\n\n\nare typically found in the peripheral portion of the infiltrate,\ntheir presence in the inflammatory infiltrate is not\ninvariable. While one study documents their presence in\n23/27 cases (85%), yet another found them to be minimal or\nabsent in 15/64 cases (approximately 25%)66, 70. Numerous\nplasma cells have been noted in the perivascular infiltrate of\nnodular seronegative lesions of syphilis in patients with\nHIV infection71, 72. An unusual, but useful, finding is the\npresence of intra/peri-neurial plasma cells found in 12% of\ncases in one study51.\n\n\n\nSecondary Syphilis -\nHistopathologic Hightlights\n\n\n\n\u2022 Varied histologic patterns\n- Epidermal change\n\n\n\n-  Lichen-planus like \n-  Psoriasiform\n-  Spongiform\n\n\n\n- Dermal change\n-  Lichenoid \n-  Diffuse dermatitis\n-  Granulomatous\n\n\n\n\u2022 Unifying features\n-  Keratinocyte necrosis\n-  Exocytosis\n-  Endothelial cell\u2013lined vascular proliferation\n-  Reactive endothelial cell atypia\n-  Plasma cell-rich, predominantly perivascular,\n\n\n\ninfiltrate\n\u2022 Spirochetes - best located within epidermis and in \n\n\n\nblood vessels of the superficial plexus\n\n\n\nOther reported changes include the presence of a\ngranulomatous infiltrate that may be epithelioid (with or\nwithout giant cells) (Figures 19, 20) and papillary dermal\nedema51, 70. Cases of secondary syphilis with histologic\nfeatures essentially similar to benign lymphoid hyperplasias\nsecondary to an arthropod bite, vaccination or other causes\nhave been known to occur (Figure 21)60, 73. Uncommon\nfindings include a perineural infiltrate (Figure 22)\nmimicking histioid leprosy61, Sweet\u2019s like neutrophilic\ndermatosis51, obliterative vasculitis of medium-sized vessels\nat the dermal-subcutaneous junction with prominent\nkaryorrhexis, noted in lesions of malignant syphilis62 and\ncases with histologic features that \u201cfit\u201d the criteria for the\ndiagnosis of a malignant cutaneous neoplasm (cytologic\natypia, mitoses and dense infiltrate)73.\n\n\n\nThe presence of spirochetes is typically seen in the\nsuperficial dermis and around blood vessels and has been\nreported in both typical and atypical lesions with the use\nof special stains such as the Warthin-Starry and Steiner\nin upto 70% of cases of secondary syphilis74-76.\nUltrastructural studies showing scant treponemes\nsubstantiate the difficulties encountered in visualizing\nthe organism by special stains77. Immunohistochemistry\nis a diagnostically useful ancillary aid in cases in which\nsdsf\n\n\n\n\n\n\n\n\n27\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ntreponemes are not visible with special stains78, 79. In support\nof this is a recent study demonstrating the presence of the\ncausative organism in 12/19 cases (63%)80. An interesting\nfinding in the same study was that the organism was found\nin the dermis and not the dermo-epidermal junction, a\nfinding contrary to accepted teaching. Ultrastructural\nstudies indicate the presence of treponemes not only in\nendothelial cells but also in the perineurium and\nendoneurium of peripheral nerves77.\n\n\n\nCutaneous lesions of secondary syphilis are believed to be\nthe result of immune response accompanied by the presence\nof antigen presenting cells and the influx of  T. pallidum\nsensitized T lymphocytes produced during the primary\nstage of infection81. More recently, in vitro evidence\nsupports the in vivo hypothesis that dendritic cells activated\nby T. pallidum play a key role in the TH1 response in\nsecondary syphilis82. Mechanisms for increased angiogenesis\nin lesions of secondary syphilis have been attributed to\nelaboration of angiogenic cytokines such as vascular\nendothelial growth factor (VEGF) and epidermal growth\nfactor (EGF)83.\n\n\n\nUncommon Cutaneous\nManifestation of Secondary Syphilis\n\n\n\n\u2022 Condyloma lata involving web spaces of toe\n\u2022 Horny syphilids\n\u2022 Histioid leprosy - like lesion\n\u2022 Targetoid (erythema-multiforme-like) lesions\n\u2022 Papulo-nodular lesions\n\n\n\n-  Sweet\u2019s-like\n-  Pseudolymphoma-like\n\n\n\n\u2022 Vegetating syphilids\n\u2022 Malignant syphilids\n\n\n\nTertiary syphilis\nA variety of names (transitional, intermediate or precocious\ntertiary syphilis) have been historically used for\nmanifestations of late-stage infection with overlapping\nfeatures of secondary and tertiary disease71. Given that the\nclinical presentation and histopathology of secondary and\ntertiary syphilis are quite similar, distinguishing the two\nstages is often impossible. Further compounding is the fact\nthat late lesions may occur anywhere from three to 35 years\nafter the original infection84.\n\n\n\nAlthough late lesions are overall rare, the most common\n(75%) manifestations of tertiary syphilis (\u201csyphilid\u201d) are\ngummatous (gummatous syphilid) lesions of the skin85, 86.\nMucosal lesions may also occur but are relatively\nuncommon. Clinically, gummas are painless, firm\nsubcutaneous nodules that occur almost anywhere on the\nbody. Secondary ulceration is not an uncommon\nphenomenon85, 86. Gummatous syphilis may become nodulo-\nulcerative (nodulo-ulcerative syphilid) lesions87, 88. The latter\nbegin as asymmetric reddish-brown nodules with a\n\n\n\npredilection for the face, trunk and extensor aspects of\nextremities and progress peripherally to form serpiginous\n(arciform or polycyclic lesions) lesions. Papulo-squamous\nlesions have also been noted in tertiary syphilis as have\ngranuloma annulare-like lesions85, 89. Syphilids typically\nresolve to form non-contracting scars with\nhyperpigmentation87. Grouped violaceous papulo-nodular\nlesions have also been reported71.\n\n\n\nThe histopathology of a gumma is that of a granulomatous\ndermatosis with foci of caseation necrosis, an associated\ninflammatory infiltrate of lymphocytes and plasma cells and\nthickened vessel walls with reactive endothelial cell atypia.\nWhile granulomas may also be seen in nodulo-ulcerative\nsyphilid, these are typically smaller than those observed in\ngummas, lack caseation necrosis, a prominent feature of\ngummatous lesions and, may even appear \u201csarcoidal\u201d85.\nLesions that resemble granuloma annulare clinically, have\nhistologic features of the same89. Cases in which plasma cells\nare not present have been reported86. Definitive diagnoses\ncan only be made by identification of the spirochete in\ntissue sections, positive cultures or positive serology.\n\n\n\nLike secondary lesions, late lesions are believed to be\nthe consequence of an immune-complex mediated\nphenomenon81.\n\n\n\nNon-Venereal Treponematoses\nIn addition to having a non-sexual mode of transmission,\nunifying features of the non-venereal treponematoses\ninclude similarities in the histologic features of lesions at\ndifferent clinical stages of the disease. Given this, the\nhistologic features of these three entities are addressed\ntogether with salient differences highlighted.\n\n\n\n1. Pinta\n\n\n\nThe causative agent of pinta, Treponema carateum is closely\nrelated to the causative agent of the other treponematoses90.\nDespite this, features unique to pinta include the fact that\nclinically it only has cutaneous manifestations, are the least\ncontagious of all the treponematoses and affects individuals\nof all ages91. Pinta is found only in the Western hemisphere\nincluding Southern and central America and Mexico.\n\n\n\nThe first clinical manifestation is a primary papule or\nplaque which typically appears 2-3 weeks after inoculation.\nSecondary skin lesions or \u201cpintids\u201d appear after three to nine\nmonths anywhere on the body and enlarge by local\nextension. Repetitive crops occur and are the reason pinta\ncan remain infectious for years - far longer than any of the\nother treponemal diseases90. Both the primary and the\nsecondary lesions are remarkable for the pigmentary\nchanges they undergo which often persist lifelong. In\ncontrast, the atrophic tertiary lesions, occurring after 1 to 3\nyears, are usually depigmented.\n\n\n\n\n\n\n\n\n28\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFig 19.   Secondary syphilis. Granulomatous lympho-\nhistiocytic  infiltrate with giant cells (hematoxylin and\neosin stain, 40X) (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\nFig 20.   Spirochetes in the same biopsy stained with\nWarthin-Starry (oil immersion) (reprinted with\npermission from Dermatopathology Interactive Atlas,\nedited by Bhawan J, Sau P, Byers HR, 2001)\n\n\n\nFig 21.   Secondary syphilis.  Nodular\nlymphohistiocytic infiltrate (hematoxylin and eosin\nstain, 40X) (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\nFig 22.   Secondary syphilis. Perineural lympho-\nhistiocytic infiltrate mimicking leprosy (hematoxylin\nand eosin stain, 40X) (reprinted with permission from\nDermatopathology Interactive Atlas, edited by Bhawan\nJ, Sau P, Byers HR, 2001)\n\n\n\n2. Yaws\n\n\n\nYaws, caused by Treponema pallidum subspecies pertenue\nprimarily affects children, spreads by skin-skin contact and,\noccurs primarily in the tropics although rare cases from the\nUnited Kingdom have also been reported90-92. The initial\nlesion, teeming with treponemes, is a non-tender papule\ncalled the \u201cmother yaw\u201d that is often pruritic. It typically\noccurs in the lower extremity, develops about three weeks\nafter the primary inoculation and persists for about three\nmonths. Clinically similar secondary lesions may follow and\noften involve the palms and soles (crab yaws)92. Late or\ntertiary lesions, developing in only a small proportion of\npatients (<10%), are nodular or ulcerated with occasional\ninvolvement of the underlying bone (\u201cperiosteitis\u201d).\n\n\n\n3. Endemic Syphilis\n\n\n\nThe causative organism is Treponema pallidum subspecies\nendemicum. Like yaws, endemic syphilis more commonly\noccurs in children but, unlike yaws, is prevalent in dry, arid\nclimactic conditions90.\n\n\n\nClinically, endemic syphilis can be divided into an early and\na late stage. The early stage comprises both the initial and\nsecondary lesions as initial apthous ulcer-like mucosal\nlesions are usually not clinically discernable93. Disseminated\n\u201csecondary\u201d lesions involving the intertriginous areas are\nthus often the \u201cfirst\u201d manifestation of the disease. Tertiary\ndisease is rare and typically does not involve the skin.\n\n\n\n\n\n\n\n\n29\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nHistopathologic Features\nof the Non-Venereal Treponematoses\nEarly histopathologic changes of all of the non-venereal\ntreponematoses are characterized predominantly by\nepidermal change in the form of mild acanthosis. Interface\nchange with pigment incontinence is characteristic of the\nhyperpigmented lesions of pinta91. While endothelial cell\natypia may be seen in pinta and endemic syphilis, it is not\nusually apparent in yaws. Intra-epidermal neutrophilic\nmicroabscesses, on the other hand, are a feature unique to\nyaws46. Late changes in all of the non-venereal\ntreponematoses may be either acanthotic or atrophic90.\nUltrastructural studies on achromic lesions of late pinta\nindicate hyperplasia of Langerhans cells94. In both early and\nlate lesions treponemes may be visualized in the epidermis\nwith the use of special or immunofluorescent stains,\nalthough achromic late lesions of pinta typically do not\ncontain treponemes46. Given the overall lack of specificity of\n\n\n\nthe histology of early and late lesions, definitive diagnoses\nof the non-venereal treponematoses can only be made by\nidentification of the spirochete in tissue sections, positive\ncultures or positive serology.\n\n\n\nNon-Venereal Treponematoses -\nHistopathologic Highlights\n\n\n\n\u2022 Histology - varies with biopsy site and age of\nlesion\n\n\n\n\u2022 Early lesions - epidermal change (mild \nacanthosis), papillary dermal edema and a mixed \ninflammatory infiltrate\n\n\n\n\u2022 Older lesions - acanthotic or atrophic \n\u2022 Helpful clues \n\n\n\n-  Endothelial cell atypia - Pinta and endemic syphilis\n-  Intra-epidermal neutrophilic microabscesses - Yaws\n\n\n\n\u2022 Spirochetes - best visualized in the epidermis\n\n\n\nONSET\nweeks-months (early)\n\n\n\nmonths-years (late)\n\n\n\nD/DX\narthropod bite, erythema multiforme\ngranuloma annulare, urticaria,\nbrown recluse spider bite\n\n\n\nvenous insufficiency,\nlichen sclerosus, scleroderma,\nphysiologic age-related changes\n\n\n\nErythema multiforme\n\n\n\nAcrodermatitis chronica atrophicans\n\n\n\nmonths-years (late)\n\n\n\nmonths-years (late)\n\n\n\nmonths-years (late)\n\n\n\nweeks-months-years (early or late)\n\n\n\nprimary morphea, primary LSEA,\nrheumatoid nodule, gouty tophi\nprimary progressive facial\nhemiatrophy/Parry-Romberg syndrome\n(PRS), primary eosinophilic\nfasciitis/Schulman\u2019s disease\n\n\n\nprimary anetoderma\n\n\n\narthropod bite reaction, response to\nvaccination, granulomas, neoplasm\npityriasis lichenoides, polymorphous\nlight eruption  \n\n\n\nerythema nodosum,\ninsect bite reaction\ndrug eruption\nprimary syphilis\n\n\n\nCutaneous scleroborrelioses \n\u2022 Morphea\n\u2022 Lichen sclerosus et atrophicus\n\u2022 Periarticular fibrous nodules\n\u2022 Progressive facial hemiatrophy\n\u2022 Eosinophilic fasciitis\n\u2022 Cutaneous atrophoborrelioses\n\u2022 Anetoderma\n\n\n\nCutaneous lymphoborrelioses\n\u2022 B-cell dominant (including B-cell \n\n\n\nlymphoma)\n\u2022 T-cell dominant\n\n\n\nOthers\n\u2022 Panniculitis\n\u2022 Granuloma annulare\n\u2022 Erythema multiforme\n\u2022 Syphilis-like papulo-squamous \n\n\n\neruption\n\n\n\nTable 1.   Cutaneous Manifestations of Lyme Disease\n\n\n\nC O M M O N  M A N I F E S T A T I O N S\n\n\n\nU N C O M M O N  M A N I F E S T A T I O N S\n\n\n\n\n\n\n\n\n30\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nConclusion\nGiven their common mode of entry and clinical course, it\nappears as if the pathogenic organisms of cutaneous\nspirochetal-induced disease share relatively unique virulent\ncharacteristics, a feature particularly striking in view of the\ndiverse epidemiology of the different diseases detailed\nabove. We appear to have made considerable progress in\nidentification of the causative organisms and clinical\nfeatures of most spirochetal diseases that involve the skin.\nWhile serologic testing is the diagnostic gold standard, the\nuse of adjunct ancillary aids such as immunohistochemistry\nis strengthening the role of histopathology in\ndiscrimination of the various cutaneous spirochetal-induced\ndiseases.\n\n\n\nReferences\n\n\n\n1. Johns DR, Tierney M, Felsenstein D. Alteration in the natural \nhistory of neurosyphilis by concurrent infection with the human \nimmunodeficiency virus. N Engl J Med 1987;316(25):1569-72.\n\n\n\n2. Asbrink E. Erythema chronicum migrans Afzelius and \nacrodermatitis chronica atrophicans. Early and late \nmanifestations of Ixodes ricinus- borne Borrelia spirochetes. \nActa Dermato-Venereologica Supplementum 1985;118:1-63.\n\n\n\n3. Afzelius A. Erythema chronicum migrans. Acta Derm Venereol \n(Stockh) 1921;2:120-125.\n\n\n\n4. Dammin GJ. Erythema migrans: a chronicle. Rev Infect Dis\n1989; 11(1):142-51.\n\n\n\n5. Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, \nAndiman WA. Erythema chronicum migrans and Lyme arthritis: \nthe enlarging clinical spectrum. Annals of Internal Medicine \n1977;86:685-98.\n\n\n\n6. Berger BW. Cutaneous manifestations of Lyme borreliosis. \nRheum Dis Clin North Am 1989;15(4):627-34.\n\n\n\n7. Melski JW. Language, logic, and Lyme disease. [see comment]\n[comment]. Arch Dermatol 1999;135(11):1398-400.\n\n\n\n8. Mahalingam M. Fitzpatrick's Dermatology in General Medicine.\n7th ed: McGraw-Hill; 2007.\n\n\n\n9. Berger BW, Clemmensen OJ, Ackerman AB. Lyme disease is a \nspirochetosis. A review of the disease and evidence for its \ncause. Am J Dermatopathol 1983;5(2):111-24.\n\n\n\n10. Duray PH, Asbrink E, Weber K. The cutaneous manifestations \nof human Lyme disease: a widening spectrum. Adv Dermatol \n1989; 4:255-75; discussion 276.\n\n\n\n11. Asbrink E, Hovmark A. Early and late cutaneous manifestations \nin Ixodes-borne borreliosis (erythema migrans borreliosis,\nLyme borreliosis). Annals of the New York Academy of \nSciences 1988;539:4-15.\n\n\n\n12. Malane MS, Grant-Kels JM, Feder HM, Jr., Luger SW.\nDiagnosis of Lyme disease based on dermatologic \nmanifestations. Annals of Internal Medicine 1991;114(6):490-8.\n\n\n\n13. Mullegger RR, McHugh G, Ruthazer R, Binder B, Kerl H, Steere \nAC. Differential expression of cytokine mRNA in skin \nspecimens from patients with erythema migrans or \nacrodermatitis chronica atrophicans. J Invest Dermatol \n2000;115(6):1115-23.\n\n\n\n14. van Dam AP, Kuiper H, Vos K, Widjojokusumo A, de Jongh BM, \nSpanjaard L, et al. Different genospecies of Borrelia\nburgdorferi are associated with distinct clinical manifestations \nof Lyme borreliosis. Clinical Infectious Diseases 1993;17(4):\n708-17.\n\n\n\n15. Duray PH. Clinical pathologic correlations of lyme disease. Rev \nInf Dis 1989;11(S6):S1487-S1493.\n\n\n\n16. Berger BW, Johnson RC, Kodner C, Coleman L. Cultivation of \nBorrelia burgdorferi from erythema migrans lesions and \nperilesional skin. J Clin Microbiol 1992;30(2):359-61.\n\n\n\n17. Cordoliani F, Vignon-Pennamen MD, Assous MV, Vabres P, \nDronne P, Rybojad M, et al. Atypical Lyme borreliosis in an HIV-\ninfected man. British Journal of Dermatology 1997;137(3):437-9.\n\n\n\n18. Kaufman LD, Gruber BL, Phillips ME, Benach JL. Late \ncutaneous Lyme disease: acrodermatitis chronica atrophicans. \nAmerican Journal of Medicine 1989;86(6 Pt 2):828-30.\n\n\n\n19. Burgdorf WH, Worret WI, Schultka O. Acrodermatitis chronica \natrophicans. Int J Dermatol 1979;18(8):595-601.\n\n\n\n20. Duray PH. The surgical pathology of human Lyme disease. An \nenlarging picture. American Journal of Surgical Pathology \n1987;11(Suppl 1):47-60.\n\n\n\n21. DiCaudo DJ, Su WP, Marshall WF, Malawista SE, Barthold S, \nPersing DH. Acrodermatitis chronica atrophicans in the United \nStates: clinical and histopathologic features of six cases. Cutis \n1994;54(2):81-4.\n\n\n\n22. Asbrink E, Brehmer-Andersson E, Hovmark A. Acrodermatitis \nchronica atrophicans-a spirochetosis. Clinical and \nhistopathological picture based on 32 patients; course and \nrelationship to erythema chronicum migrans Afzelius. Am J \nDermatopathol 1986;8(3):209-19.\n\n\n\n23. Picken RN, Strle F, Ruzic-Sabljic E, Maraspin V, Lotric-Furlan S, \nCimperman J, et al. Molecular subtyping of Borrelia burgdorferi \nsensu lato isolates from five patients with solitary \nlymphocytoma. Journal of Investigative Dermatology\n1997;108(1):92-7.\n\n\n\n24. Buechner SA, Rufli T, Erb P. Acrodermatitis chronic \natrophicans: a chronic T-cell-mediated immune reaction \nagainst Borrelia burgdorferi? Clinical, histologic, and \nimmunohistochemical study of five cases. Journal of the \nAmerican Academy of Dermatology 1993;28(3):399-405.\n\n\n\n25. Ilowite NT. Muscle, reticuloendothelial, and late skin \nmanifestations of Lyme disease. American Journal of Medicine \n1995;98(4A):63S-68S.\n\n\n\n26. Silberer M, Koszik F, Stingl G, Aberer E. Downregulation of \nclass II molecules on epidermal Langerhans cells in Lyme \nborreliosis. Br J Dermatol 2000;143(4):786-94.\n\n\n\n27. Kaya G, Berset M, Prins C, Chavaz P, Saurat JH. Chronic \nborreliosis presenting with morphea- and lichen sclerosus et \natrophicus-like cutaneous lesions. a case report. Dermatology \n2001;202(4):373-5.\n\n\n\n28. Tuffaneli D. Do some patients with morphea and lichen \nsclerosus et atrophicans have a borrelia infection? Am J \nDermtopathol 1987;9:371-373.\n\n\n\n29. Granter SR, Barnhill RL, Duray PH. Borrelial fasciitis: diffuse f\nasciitis and peripheral eosinophilia associated with Borrelia \ninfection. Am J Dermatopathol 1996;18(5):465-73.\n\n\n\n30. Aberer E, Stanek G, Ertl M, Neumann R. Evidence for \nspirochetal origin of circumscribed scleroderma (morphea). \nActa Derm Venereol 1987;67(3):225-31.\n\n\n\n31. Espana A, Torrelo A, Guerrero A, Suarez J, Rocamora A, Ledo \nA. Periarticular fibrous nodules in Lyme borreliosis. British \nJournal of Dermatology 1991;125(1):68-70.\n\n\n\n32. Marsch WC, Mayet A, Wolter M. Cutaneous fibroses induced \nby Borrelia burgdorferi. British Journal of Dermatology 1993;\n128(6):674-8.\n\n\n\n33. Marsch WC, Wolter M, Mayet A. Juxta-articular fibrotic \nnodules in Borrelia infection--ultrastructural details of therapy-\ninduced regression. Clinical & Experimental Dermatology \n1994;19(5):394-8.\n\n\n\n34. Hofer T, Goldenberger D, Itin PH. Anetoderma and borreliosis: \nis there a pathogenetic relationship? European Journal of \nDermatology 2003;13(4):399-401.\n\n\n\n35. Hauser W. Dermatitis atrophicans maculosa. Dermatologie und \nVenerologi 1958;2:867.\n\n\n\n36. Abele DC, Bedingfield RB, Chandler FW, Given KS. Progressive \nfacial hemiatrophy (Parry-Romberg syndrome) and \nborreliosis.[see comment]. J Am Acad Dermatol\n1990;22(3):531-3.\n\n\n\n37. Garbe C, Stein H, Dienemann D, Orfanos CE. Borrelia \nburgdorferi-associated cutaneous B cell lymphoma: clinical \nand immunohistologic characterization of four cases. Journal \nof the American Academy of Dermatology 1991;24(4):584-90.\n\n\n\n\n\n\n\n\n31\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\n37. Garbe C, Stein H, Dienemann D, Orfanos CE. Borrelia \nburgdorferi-associated cutaneous B cell lymphoma: clinical \nand immunohistologic characterization of four cases. Journal \nof the American Academy of Dermatology 1991;24(4):584-90.\n\n\n\n38. Goodlad JR, Davidson MM, Hollowood K, Batstone P, Ho-Yen \nDO. Borrelia burgdorferi-associated cutaneous marginal zone \nlymphoma: a clinicopathological study of two cases illustrating \nthe temporal progression of B. burgdorferi-associated B-cell \nproliferation in the skin.[see comment]. Histopathology \n2000;37(6):501-8.\n\n\n\n39. Slater DN. Borrelia burgdorferi-associated primary cutaneous\nB-cell lymphoma. Histopathology 2001;38(1):73-7.\n\n\n\n40. Roggero E, Zucca E, Mainetti C, Bertoni F, Valsangiacomo C, \nPedrinis E, et al. Eradication of Borrelia burgdorferi infection in \nprimary marginal zone B-cell lymphoma of the skin. Human \nPathology 2000;31(2):263-8.\n\n\n\n41. Kutting B, Bonsmann G, Metze D, Luger TA, Cerroni L. Borrelia \nburgdorferi-associated primary cutaneous B cell lymphoma: \ncomplete clearing of skin lesions after antibiotic pulse therapy \nor intralesional injection of interferon alfa-2a. Journal of the \nAmerican Academy of Dermatology 1997;36(2 Pt 2):311-4.\n\n\n\n42. Schmid GP. Epidemiology and clinical similarities of human \nspirochetal diseases. Rev Infect Dis 1989;11 Suppl 6:S1460-9.\n\n\n\n43. Lane KL, Parker JC, Jr. Lyme disease: a confusing multisystem \nborreliosis. South Med J 1989;82(9):1147-52.\n\n\n\n44. Pournaras CC, Masouye I, Piletta P, Piguet V, Saurat JH, French \nLE. Extensive annular verrucous late secondary syphilis. Br J\nDermatol 2005;152(6):1343-5.\n\n\n\n45. Sanchez MR. Infectious syphilis. Semin Dermatol 1994;13(4):\n234-42.\n\n\n\n46. Engelkens HJ, Judanarso J, Oranje AP, Vuzevski VD, Niemel PL, \nvan der Sluis JJ, et al. Endemic treponematoses. Part I. Yaws. \nInt J Dermatol 1991;30(2):77-83.\n\n\n\n47. Al-Samarrai HT, Henderson WG. Immunofluorescent staining of \nTreponema pallidum and Treponema pertenue in tissues fixed \nby formalin and embedded in paraffin wax. Br J Vener Dis \n1977;53(1):1-11.\n\n\n\n48. Deacon WE, Freeman EM, Harris A. Fluorescent treponemal \nantibody test. Modification based on quantitation (FTA-200). \nProceedings of the Society for Experimental Biology & \nMedicine 1960;103:827-9.\n\n\n\n49. Sapra S, Weatherhead L. Extensive nodular secondary syphilis. \nArch Dermatol 1989;125(12):1666-9.\n\n\n\n50. Baughn RE, Musher DM. Secondary syphilitic lesions. Clin \nMicrobiol Rev 2005;18(1):205-16.\n\n\n\n51. Jordaan HF. Secondary syphilis. A clinicopathological study. \nAm J Dermatopathol 1988;10(5):399-409.\n\n\n\n52. Templeton SF. Condyloma latum of the toe webs: an unusual \nmanifestation of secondary syphilis. A report of two cases. \nCutis 1996;57(1):38-40.\n\n\n\n53. Papini M, Bettacchi A, Guiducci A. Nodular secondary syphilis. \nBr J Dermatol 1998;138(4):704-5.\n\n\n\n54. Waldman GD, Wise RD. Miliary pustular syphilid. Cutis \n1984;34(6):556-8.\n\n\n\n55. Aggarwal K, Gupta S, Jain VK. Pustulocrustaceous secondary \nsyphilis. Acta Derm Venereol 2005;85(4):378-9.\n\n\n\n56. Friedli A, Chavaz P, Harms M. Alopecia syphilitica: report of two \ncases in Geneva. Dermatology 2001;202(4):376-7.\n\n\n\n57. Chapel TA, Blum D. Horny syphilid. Cutis 1978;22(1):55-9.\n58. Winchell SA, Tschen JA, McGavran MH. Follicular secondary \n\n\n\nsyphilis. Cutis 1985;35(3):259-61.\n59. Lee JY, Lee ES. Erythema multiforme-like lesions in syphilis. Br \n\n\n\nJ Dermatol 2003;149(3):658-60.\n60. McComb ME, Telang GH, Vonderheid EC. Secondary syphilis \n\n\n\npresenting as pseudolymphoma of the skin. J Am Acad \nDermatol 2003;49(2 Suppl Case Reports):S174-6.\n\n\n\n61. Pandhi D, Reddy BSN, Khurana N, Agarwal S. Nodular syphilis \nmimicking histoid leprosy. Journal of the European Academy of \nDermatology & Venereology 2005;19(2):256-7.\n\n\n\n62. Petrozzi JW, Lockshin NA, Berger BJ. Malignant syphilis. \nSevere variant of secondary syphilis. Arch Dermatol \n1974;109(3):387-9.\n\n\n\n63. Pariser H. Precocious noduloulcerative cutaneous syphilis. \nArch Dermatol 1975;111(1):76-7.\n\n\n\n\n\n\n\n\n34\n\n\n\n\n\n"
"\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more than \n2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Comment \nand References. A Structured Abstract of not more than 240 \nwords must be included. It should consist of five paragraphs, \nlabelled Background, Methods, Results, Discussion and \nConclusion. It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and \nfax numbers and an email address of the corresponding \nauthor who will be responsible for reading the proofs must \nalso be given on the title page. The author(s) must also \ndeclare any affiliation or significant financial involvement \nin any organizations or entity with a direct financial \ninterest in the subject matter or materials discussed in the \nmanuscript on this page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: \nA Hospital Kuala Lumpur experience. M J Dermatol \n2006;19:52-55.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and \nopinions expressed do not necessarily reflect those of \nthe publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher \nand Editors of the products advertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38\n\n\n\nContents\n\n\n\nREVIEW ARTICLES\n\n\n\n2 MOHS Micrographic Surgery: The Malaysian \nExperience and a Review of the Evidence\n\n\n\n Yong ASW, Kwan Z, Tan LL, Ch\u2019ng CC, Pailoor J\n\n\n\nORIGINAL ARTICLES\n\n\n\n13\t Microbiological\tProfile\tand\tAntibiotic\tSusceptibility\t\nPatterns of Isolates of Skin Specimens from the \nDepartment of Dermatology, Hospital Kuala \nLumpur: A 3-year Audit\n\n\n\n Tee SH, Tang MM, Suganthi T \n\n\n\n19 Prevalence of Skin Diseases in Dermatology \nOutpatient Clinic, Hospital Kuala Lumpur\n\n\n\n Heah SK, Noorlaily MN, Asmah J\n\n\n\n25 Cardiac Abnormalities in Psoriasis\n\t P\tGill,\tTang\tMM,\tA\tJamil,\tSZ\tZulkifli,\tNZ\tAzizan\n\n\n\n43 Liquid Nitrogen Cryotherapy versus 20% Salicylic \nAcid Ointment for the Treatment of Plantar Warts: A \nRandomized Trial\n\n\n\n S\tRosniza,\tNZ\tAzizan\n\n\n\n52 An Epidemiological Study of Stevens-Johnson \nSyndrome (SJS), Toxic Epidermal Necrolysis (TEN) \nand Stevens-Johnson Syndrome/Toxic Epidermal \nNecrolysis (SJS/TEN) overlap in University Malaya \nMedical Centre (UMMC)\n\n\n\n Tan LL, Ooi ST, Wong SM, Ch\u2019ng CC, Kwan Z, \n Yong ASW\n\n\n\n57 Drug Reaction with Eosinophilia and Systemic \nSymptoms (DRESS): A Review of 21 Cases over 7 \nyears Period from Selayang Hospital\n\n\n\n\t Voo\tSYM,\tWong\tLC,\tNg\tHW,\tR\tRidzwan,\tTan\tSS\n\n\n\n65 Low Dermatitis Potential of a Powder-Free, \n\u201cAccelerator-Free\u201d Non Natural Rubber Latex \nGloves\tUsing\tModified\tDraize\tStudy\n\n\n\n Maryam Sakinah J, Wan Muhamad Aiman WM, Iman \nJ,\tHanisah\tJ,\tMardhiah\tJ,\tMuhammad\tSyafiq\tMI,\tSaid\t\nAG, Emad Ibrahim HS, Doaa kamal IS, Sharifah I, Nor \nWajihan M, Siti Maryam AJ, Saadiah S\n\n\n\nCASE REPORT \n\n\n\n72 Beh\u00e7et\u2019s Disease: a case series of 5 patients in \nthe Department of Dermatology, Hospital Kuala \nLumpur, Malaysia\n\n\n\n Wan Ahmad Kamal WSA, Tang MM, S Thevarajah\n\n\n\n79 Acitretin an Additional Treatment Option for \nElephantiasis Nostras Verrucosa: A Case Report\n\n\n\n Low DW, Jamil A, Md Nor N\n\n\n\n83 Toxic Epidermal Necrolysis as the First Presentation \nof Systemic Lupus Erythematosus\n\n\n\n A Bhullar, WW Kamal, K Rahim\n\n\n\n87 A Case Report of Acne Agminata\n Goh WS, Tey KE, Choon SE, Yabitha V\n\n\n\n91 Pseudolymphoma due to Hair Dye on Background \nof Chronic Actinic Dermatitis Responding to Intra-\nlesional Triamcinolone\n\n\n\n Kwong HL, Pan JY\n\n\n\nCORRESPONDENCE \n\n\n\n94 Malaysia Urticaria Expert Group (MARTEG) \nmeeting outcomes\n\n\n\n Yong ASW, Chang CC, Ch\u2019ng CC, Lee CK, Woo CK,  \nLee YY, Johar A, Gill P, Muniandy P, Heng AYH, Md \nNor\tN,\tAbdul\tLatiff\tAH\n\n\n\n97 A Rare Case of Cutaneous Infection of \nMycobacterium fortuitum\n\n\n\n Xu CR, Laura Hui, Pan JY\n\n\n\n100 A Case of Senescent Actinic Depigmentation\n Wu XT, Pan JY\n\n\n\n102 The Night is Darkest Just Before the Dawn\n Wang RSH, Yang SSY \n\n\n\nORBITUARY NOTICE\n\n\n\nERRATUM\n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 1\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office \nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nExecutive Committee\nDr Agnes Heng Yoke Hui - President \nDr Rohna Ridzwan - Vice President \nDato Dr Noor Zalmy Azizan - Secretary \nDr Chan Lee Chin - Treasurer \nDr Henry Foong Boon Bee - Past President \nDr Sabeera Begum - Committee Member \nDr Tan Wooi Chiang - Committee Member\nDr Azura Mohd Affandi - Committee Member \nDr Ruban Nathan - Committee Member\n\n\n\nDermatological Society of Malaysia \n(Rumah Dermatology)\nG1, Medical Academics of Malaysia, 210, \nJalan Tun Razak, 50400 Kuala Lumpur, \nMalaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise \n723E 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang.\nTel : 04-658 4515 / 04-657 8515    Fax : 04-658 4505\n\n\n\n\u00ae2017 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 382\n\n\n\nREVIEW\n\n\n\nMOHS Micrographic Surgery: The Malaysian Experience and a \nReview of the Evidence\n\n\n\nAdrian Sze Wai Yong1, MRCP, CCT, Zhenli Kwan1, Adv M Derm, Leng Leng Tan1, Adv M Derm, Chin Chwen Ch\u2019ng1, \nAdv M Derm, Jayalakshmi Pailoor2, FRCPath\n\n\n\n1Dermatology Unit, Department of Medicine, University Malaya, Kuala Lumpur, Malaysia\n2Department of Pathology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia\n\n\n\nSummary:\nMOHs micrographic surgery is a technique of microscopic margin control in the surgical management \nof skin cancers particularly at cosmetically sensitive sites. This review article is aimed at sharing our \ninitial experience of performing MOHs surgery for skin cancers in Malaysia since 2015.\n\n\n\nKey words: MOHs\tmicrographic\tsurgery,\tSkin\tcancer,\tBasal\tcell\tcarcinoma,\tSquamous\tcell\tcarcinoma\n\n\n\nIntroduction\nMohs micrographic surgery (MMS) was first \ndiscovered in the early 1930s by Frederic E. Mohs \nas a medical student in Madison, Wisconsin, United \nStates of America (US). In 1976, Dr. Mohs reported \na 99.8% five-year cure rate (3450 of 3466 patients) \nusing the fresh tissue technique, resulting in \nreplacement of the fixed tissue technique (originally \ndescribed and performed by Frederic Mohs himself \ninitially).1 \n\n\n\nThe fresh tissue technique considerably shortened \ntissue diagnosis by making MMS an efficient \ntechnique to complete within a working day. MMS \nhas been practised in office-based setting in the US \nsince the 1970s. The technique was then taught \nto any physician who was interested and attended \nattachments with Frederic Mohs. Eventually a keen \ninterest was taken by dermatologist in training \nand eventually led to the increasing use across \nEurope and Australasia where skin cancer rates are \nhigh. MMS has always been the gold standard in \nthe management of skin cancers even in the Asia \nPacific region, hence the development of Mohs in \nSingapore and Thailand within the last 10 years. \n\n\n\nMMS was pioneered in University Malaya Medical \nCentre (UMMC) since July 2015.\n\n\n\nMMS is indicated where there are skin cancers \narising in cosmetically sensitive sites or when \nthe tumour is of \u201chigh-risk\u201d histological subtype \nand especially for cancers recurring after initial \ntreatment with either surgery or radiotherapy. It is \nmost suitable for cancers that exhibit contiguous \ngrowth pattern.2 Skin cancers commonly excised \nusing MMS include basal cell carcinoma (BCC) and \nsquamous cell carcinoma (SCC).\n\n\n\nMMS should be characterised by having peripheral \nmargins cut at an angle of 45o; frozen section \nlaboratory is near the operating theatre and the surgeon \nshould be the one reading the slides. Unifying the \nduties of surgeon and pathologist minimises errors \nwhen performing clinic-pathological correlation for \npatients. Quality assurance through interaction with \na dermato-pathologist is strongly encouraged.2 \n\n\n\nThe aim of this review article is to share the \ndemographic data on MOHs surgery in Malaysia \nand comparing it with updated international \npublications. \n\n\n\nMaterials and Methods\nThis review summarises all cases of MOHs \nmicrographic surgery performed in University \nMalaya Medical Centre for the period of July 2015 \nuntil May 2017. The following describes how MMS \nis performed in UMMC.\n\n\n\nCorresponding Author\nAssociate Professor Dr. Adrian Yong Sze Wai\nDermatology Unit, Department of Medicine, Faculty of \nMedicine, University of Malaya, Lembah Pantai 50603 \nKuala Lumpur, Malaysia\nEmail: adrian.yong@ummc.edu.my\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 3\n\n\n\nInitial biopsy of skin is taken to define the \nhistological subtype of skin cancer. Curettage is \npreferred over a punch biopsy in order to avoid \npushing tumour into deeper histological planes.  \nSubsequent steps of MMS performed in our setting \nare as described below and shown in Figures 1 (a-\ne). Clinically visible tumour margins drawn around \nwith a marker pen with additional 1-2 mm lateral \nmargin and clock face positions 12,3,6,9 o\u2019clock \nmargins are drawn. (Figure 1a) Double nick is made \nat 12 o\u2019clock and single nicks are made at 3, 6 and \n9 o\u2019clock positions respectively. The nicks made \nshould be from peripheral to central, cleaning the \nblade carefully after each nick to avoid dragging \ntumour into a different histological plane. (Figure \n1b) \n\n\n\nLocal anaesthetic is injected around the skin site at \nleast 4-5 mm lateral to the visible peripheral margin \nof the tumour to avoid seeding tumour from lateral \nmargins into deep margins in case needle used for \ninjecting passes through the tumour. After scoring \nthe surface with a scalpel gently, the scalpel is \nthen angled at a 45 degree angle with blade facing \nmedially and cut is made down to desired plane. \nThe tissue plane should be down to mid fat for BCC \nand superficial fascia or muscle for SCC.\n\n\n\nSpecimen is then brought to lab for preparation of \nfrozen section using Tissue-Tek\u00ae optimum cutting \ntemperature compound. The lateral edges of the \ntissue are flattened against the glass slide such that \nthe central deep margin is on the same histological \nplane as the lateral ones. The specimen is then left in \nan aluminum foil molded to a maximum size of 2cm \nacross to match the size of a standard glass slide, \nand left in a cryostat to freeze at -18oC (Figure 1d).\n\n\n\nOnce specimen is completely frozen, the specimen \nis separated from the aluminum foil and mounted \nwith the deep margin exposed first to the cryostat \nblade. Cryostat slices were set at 8 microns each \nturn and standard practice is to ensure in excess of \n200 microns clearance (Figure 1d).\n\n\n\nA hand-drawn MMS map is used to map out location \nof tumour. Nicks on the specimen corresponds \nto intersecting lines drawn on the Mohs map to \ndenote 12 o\u2019clock, 3 o\u2019clock, 6 o\u2019clock and 9 \no\u2019clock positions. The latter is also colour-coded to \nsecure orientation. Our experience is that of using \nhistology slides analysed (Figure 1e) and coloured, \nthen used to superimpose onto Mohs map, similar \n\n\n\nto that described by Tiger et al. The latter method \nhas been shown to increase accuracy and specificity \ncompared to conventional Mohs map drawing on \nits own. Tiger describes using histopathological \nphotographs as the Mohs map.3\n\n\n\nDefect repair options depend on the site involved. \nSide to side primary closure is ideal when possible. \nThis is then followed by local flap (Figure 1c), \nfull thickness skin graft, partial thickness skin \ngraft and secondary intention. Secondary intention \nhealing maybe more appropriate than previously \nunderstood. Concave surfaces including temporal, \nperiocular, perinasal, periauricular, scalp and \nanterior lower extremity, deep wounds and large \nwounds. Many surgeons elect secondary intention \nhealing in patients with current or previous wound \ndehiscence, flap necrosis or infection, or when \ntreating high-risk large, recurrent or aggressive \ntumours.4  \n\n\n\nKey personnel involved with MOHs surgery \nset up include lab technician experienced in \nthe preparation of good quality frozen sections; \npathologist to confirm and sign off specimen reports; \ndermatological surgeon performing and mapping \ncancer pre-intra and post-operatively; assistant \nsurgeon who is familiar with haemostasis and is able \nto react in the event of a patient becoming unwell \nin minor operating theatre; and last but not least \ntheatre nurses who can assist with patient handling.\n\n\n\nA literature review was performed online using \nPubMed, Google Scholar and Medline using the \nterms \u201cMohs micrographic surgery\u201d and \u201cSkin \ncancer\u201d from 1970 to 2017. Search was performed in \nApril 2017. Best available evidence was shortlisted \nand presented in this review article aimed to \nproduce a concise up to date guide on appropriate \nindications for MMS. \n\n\n\nResults\nThe University Malaya Medical Centre\u2019s performed \n16 MMS over the last 22-month period. The \ncharacteristics of our cohort of patients who have \nundergone MMS are shown in Table 1. The mean \nage of patients was 70 years old (range 48-84 \nyears). The Karnofsky performance status scale5 of \nour patients was > 70 in 88% of our patients. The \nlatter confirms that majority of patients undergoing \nMMS are highly functioning.5 There was a male \npreponderance for MMS in our cohort with a male \nto female ratio of 7:1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 384\n\n\n\nAll cases had the tumour located on the face \nincluding nose, periocular, cheek, forehead and \nears. Four cases (25%) were histologically cleared \nwithin one stage, nine (56%) completed in two \nstages and three (19%) of cases went on to three \nstages. Histological clearance was double-checked \nby further sectioning of remaining \u201cclear\u201d tissue \nspecimens and embedding in paraffin sections. All \nour 16 cases were finally confirmed histologically \nclear. \n  \nComplications observed included one case of post-\nop local infection overlying the ear abutting the \nexternal auditory meatus and the preauricular site, \nwhich resolved with oral antibiotics over 2 weeks \nleading to an uncomplicated recovery. \n\n\n\nDiscussion\n\n\n\nInitial experience of MMS in Malaysia \nMMS was performed for skin tumours in our setting \nto areas close to cosmetically sensitive sites, when \ninitial histology is more likely to exhibit higher risk \nof incomplete excision. These include infiltrative \nBCC, poorly differentiated SCC, SCC in high risk \nindividuals such as in post-transplant patients on \nimmunosuppressive agents, and recurrent skin \ncancers following previous radiotherapy or surgery. \n\n\n\nThe number of MMS cases performed in Malaysia \nis still low due to two main factors. Firstly, MMS \nis more time consuming than standard excision \n(SE). There is a limited number of Dermatologists \nin the country performing MMS. Both experienced \nDermato-pathologists and Dermatological surgeons \nare in short supply in Malaysia. As a result, time \npressures from MMS that requires a longer duration \nthan other \u201croutine\u201d cases put pressure on involved \nparties to have a higher threshold to enlist patients \nfor MMS in our centre.  \n\n\n\nSecondly, high cost involved with the procedure. \nOur experience is that of having offered MMS as \nthe gold standard to our patients but eventually \ncompromising with SE due to patients\u2019 decision to \nprioritize affordability despite being aware of the \nlower recurrence rates with MMS versus SE. As our \nnation\u2019s average income rises with time, in line with \ntransformation into a developed nation, our patients \nwill be able to afford gold standard treatment of skin \ncancers such as MMS.   \n  \n\n\n\nDue to the listed factors, there is a selection bias \ntowards a more challenging caseload in our centre. \nThe latter is confirmed by the demographics of our \nMMS cases; 60% of referrals to us for MMS had \nat least one previous excision (recurrent tumour) \nand 20% of referrals to us had two previous \nunsuccessful excisions. All of the patients with \nrecurrent tumours had an initial histopathology \nreport stating clear (complete excision) lateral and \ndeep margins through conventional bread-loafing or \ncross-sectioning technique. The latter confirms that \nconventional histological analysis is substandard in \nthe complete assessment of histological clearance \nof skin tumour. The follow up period for patients \nwho have undergone MMS in our centre is \nnow between 3-23 months with no evidence of \nrecurrence. Our initial follow up post MMS is 6 \nweekly for the first three months to include scar \nmanagement if necessary and monitoring for local \nrecurrence. Beyond that, patients are then followed \nup 6 monthly for up to 5 years.\n\n\n\nOur mean number of stages was 1.94, consistent \nwith the published literature where cases selected \nwere appropriate for MMS and our figures were \ncomparable to the site (head and neck area) operated \non.6 Our data confirms that MMS performed at our \ncentre produced similar results to existing published \nliterature despite our suspicions that selection bias \nwould have increased the mean number of stages \ncloser to three due to the more complex cases \nselected for MMS in our centre. \n\n\n\nHow\tis\tMMS\tdifferent\tfrom\tconventional\tsurgery\t\nand histological analysis?\nSkin specimen containing suspected cancer can \nbe sliced in several ways. Firstly, bread-loafing or \ncross-sectioning whereby slices of tissue are cut \nthrough the centre (where the tumour is located) \nand laterally (to confirm tumour absence at the \nperipheral margin (figure 2a). Secondly, peripheral \nsectioning method whereby lateral and deep edges \nof tumour are cut to rule out any residual tumour \n(figure 2b). Thirdly MMS sectioning method \nsuch that 100% of the tissue can be analysed \n(both lateral and deep margins) on the same plane \nconcurrently, making it the only technique with \ncomplete histological margin control (figure 2c). It \nis important to note that the first two methods of \nsectioning only allow examination of less than 0.1% \nof the entire specimen, hence the risk of missed \ntumour of unsectioned areas account for a higher \n5-year recurrence rate for conventional histological \nanalysis compared to MMS.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 5\n\n\n\nIn a multi-centre published case series involving \n20,821 cases in 23 centers, there were 149 adverse \nevents, 4 serious events and no deaths. Common \nadverse events reported were infections (61.1%), \nwound dehiscence, partial or full necrosis (20.1%), \nand bleeding and haematoma (15.4%). The latter was \npredominantly associated with patients receiving \nanticoagulation therapy.7\n\n\n\nMosterd et al in 2008 performed a prospective \nrandomised controlled trial to compare the cost-\neffectiveness of MMS compared to SE for the \ntreatment of primary and recurrent facial BCC.8 The \ndifference in the number of recurrences between \ntreatments was in favour of MMS for recurrent \nfacial BCC but was not significant for primary \nBCC. In primary BCC the total treatment costs were \n\u20ac1248 for MMS and \u20ac990 for surgical excision. For \nrecurrent BCC, the total treatment costs were \u20ac1284 \nfor MMS and \u20ac1043 for SE. \n\n\n\nThe estimated cost of MMS in our setting is \nRM3625 (\u20ac754). The cost includes procedural cost \n(RM500) for the use of minor operating theatre, \ndermatological surgeon\u2019s time, supporting staff \nincluding theatre nurses, and physician assistants. \nThe laboratory and histo-pathologist fees are \nsubsidized by the University Malaya Medical Centre \nup to an approximate value of 50% for MMS (mean \nof 2 stages). The cost for a SE including pathology \ncharges (excluding indirect financial, time and \npsychosocial costs to patient associated with re-\nattendance to hospital for further surgical procedure \nand medication) is RM 500 (\u20ac106.70). \n\n\n\nDue to the significant cost difference, SE is still \nthe first choice for most patients. MMS should be \nstrongly recommended to patients by doctors and \ndermatologists when there are \u201chigh risk\u201d patient or \ntumour characteristics present. The characteristics \ninclude locally recurrent skin cancers following \neither SE or radiotherapy, immunocompromised \nindividuals on long term immune-supressives, \naggressive histological subtypes such as perineural \nand/or perivascular invasion and micronodular/\ninfiltrative histological subtype. Secondary factors \ninclude occurrence at cosmetically sensitive sites \nwhere tissue sparing is crucial to optimize the final \ncosmetic outcome post-surgery. \n \nWhen discussing cost of MMS versus SE, one should \nconsider extra hospital visits for close monitoring \nand the potential need for subsequent MMS if SE \ndoes not successfully clear the skin tumour the first \ntime round. \n\n\n\nEvidence favouring Mohs Micrographic Surgery \n(MMS) over Standard Excision (SE) for Basal \nCell Carcinoma (BCC)\nIt is well established in numerous publications that \nthe 5-year recurrence rates of BCC using MMS is \nsuperior to that of standard excision (SE). Five year \nrecurrence rates of BCC when SE was performed \nranges from 5-40% whilst the equivalent for MMS \nranges from 3-8%.9,10,11,12  \n\n\n\nMMS is strongly recommended for recurrent facial \nBCC, especially with poor prognostic factors. \nSmeets and colleagues specifically studied MMS \nin the setting of facial BCC. The study comprised \na retrospective study of 720 BCCs reporting an \nestimated 5-year recurrence rate of 3.2% for \nprimary BCC and 6.7% for recurrent BCC13. \nPredictive factors for recurrence include aggressive \nhistopathological subtype, greater than four MMS \nstages, a large defect size and a recurrent BCC.\n\n\n\nSmeets et al in a randomised controlled trial in \n2004 concluded that the recurrence rates over a \nfollow-up period of 5 years for facial primary basal \ncell carcinoma (BCC) were lower when excised \nby MMS (2.5%) compared to surgical excision \n(4.1%) albeit not statistically significant.14 Due to \nthe limitations of the study, no recommendation \ncould be made for the management of primary \nfacial BCCs. The limitations of this above include \n3mm lateral margins of excision taken in both SE \nand MMS groups. In addition, there was reluctance \nfor a significant number of patients to participate, \npotentially introducing population and selection \nbias. Furthermore, there were a large number of \nsubjects lost to follow up. Even with the intention-\nto-treat analysis, attrition bias might lead to \nunderestimation of recurrence rates. With a cross-\nover design of the trial, there were patients crossing \nover from one treatment arm to the other, namely \n3.7% in the primary BCC group and 17% in the \nrecurrent BCC group. Therefore, carry-over effect \ncould lead to bias tending to favour lower recurrence \nrates in the recurrent BCC group.\n\n\n\nInterestingly, the 10-year follow-up data from the \nsame cohort, 5 years later, published recently in the \nEuropean Journal of Cancer strongly favoured MMS \nagainst SE with fewer recurrences; 4.4% vs 12.2% \nfor primary BCC, and 3.9% vs 13.5% for recurrent \nBCC15. A substantial proportion of recurrences \noccurred after more than 5 years post-treatment: \n56% for primary BCC and 14% for recurrent BCC. \nThis is important as we can now better decide on \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 386\n\n\n\nwhat age group of patients we should be offering \nMMS to. The authors suggest that patients expected \nto live beyond 5 years after MMS would be deemed \nas having the benefits of MMS outweigh the time \nand expertise cost. \n\n\n\nA large prospective multicentre case series by \nLeibovitch and colleagues in 2005 reported on the \nclinical findings of all patients with BCC treated \nwith MMS9. A total of 11,127 patients were included \nin the study (47% females and 53% males) with a \nmean age of 62 years (range, 15-98 years). Most of \nthe BCCs (98.3%) were on the head and neck area. \nSites on the head and neck in decreasing frequency \ninclude the nose, cheek and maxilla, periocular area, \nand auricular region. The most common histological \nsubtypes were infiltrating (30.7%) and nodulocystic \n(24.2%). Recurrent BCC accounted for 43.8% of \ncases suggesting that standard excision of basal \ncell carcinomas on the head and neck area should \nbe planned with caution. However, in reality it \nis difficult due to the fact that a generous margin \nwould consistently result in lower recurrence rates \nbut would be offset against a larger defect and \nlikely an inferior cosmetic outcome. Conversely an \ninadequate margin around the skin cancer would \nlead to higher recurrence rates.   \n\n\n\nFurther details from Leibovitch were that recurrent \ntumours were larger than primary tumors (p <0.001), \nhad a larger post-excision defect and a more \nsubclinical extension, and required more levels of \nexcision (P <0.001). High-risk tumours dominated \nthe case load for MMS in this series. Most tumours \nwere located in the mid-facial area and the histologic \nsubtype was mainly infiltrating or nodulocystic. \nRecurrent tumours were larger and demonstrated \na more extensive subclinical extension compared \nwith primary tumours, emphasising the importance \nof initial tumour eradication with margin control.9\n\n\n\nA Cochrane review performed in 2014 comparing \nMMS versus SE for periocular basal cell carcinoma \nby Narayanan et al16 concluded that there was \ninsufficient randomised controlled trials (RCTs) \nto make a comparison on the recurrence rates, \ncomplications, cost effectiveness and acceptability \nof either technique. Good quality RCTs are \ndesperately needed in this field. However, we are \naware that randomised controlled trials for surgery \ncan be challenging as there are numerous variables \nto control for, with differences such as surgical \ntechniques and different levels of experience \nin reading the MMS histopathology slides. It is \n\n\n\ntherefore premature to make any conclusions \nthat MMS is not useful for periocular BCC in the \nabsence of RCTs. \n\n\n\nOur experience of performing MMS on two \nperiocular cases between 2015 and 2017 involved \nan average of 2.5 stages (excising 2 mm lateral to the \nmacroscopically visible margins of BCC each time). \nWe also observed that infiltrative BCCs were likely \nto invade into orbicularis oculi. Unlike SE, MMS \nis essential prior to a complex closure of the eyelid \nto avoid difficulties with tracking a future cancer \nrecurrence. Recurrent cancers within complex \nclosure sites pose two major challenges. Firstly, \nthey tend to be aggressive histological subtypes that \nare more difficult to interpret. Secondly, residual \ntumour recurrence tends to proliferate along the \nwound-closure scar lines during the healing process \nfrom the initial surgery. We therefore strongly \nrecommend MMS for infiltrative or recurrent skin \ncancers in the periocular region.\n\n\n\nEvidence supporting MMS for squamous cell \ncarcinoma\nEvidence for MMS in the management of squamous \ncell carcinoma (SCC) has been reported in a large \nretrospective review by Pugliano et al in 2010 \ninvolving 260 high risk squamous cell carcinoma \n(SCC) in 215 patients. A recurrence rate of 1% \nwas detected following MMS for squamous cell \ncarcinoma over a mean follow up period of 3.9 \nyears.18 The latter suggests that MMS is an effective \ntreatment for high risk SCC as the comparable rates \nfor SE in current literature is much higher, closer to \n10%, as previously reported by Rowe et al.19\n\n\n\nWe would recommend that in Malaysia, any SCC \nthat has been reported as being close to the excision \nmargin or with aggressive histological features \nincluding perineural/perivascular invasion or with \nequal to or greater than 6mm Breslow thickness \nshould have the histology slides reviewed. MMS \nshould be considered to ensure a complete local \ndisease control is achieved in addition to further \nappropriate imaging to obtain accurate staging of \nthe disease.\n\n\n\nEvidence supporting MMS for rarer skin \ntumours\nA systematic review of 23 non-randomised trials (4 \ncomparative, 19 non-comparative) as per Cochrane \nHandbook for Systematic Reviews of Interventions \nwas performed on MMS for the treatment of \nDermatofibrosarcoma Protuberans.20 MMS was \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 7\n\n\n\ngiven a weak recommendation based on the \nfollowing recurrence rates. MMS (1.11%; 95% CI: \n0.02%-6.03%) versus wide local excision (6.32%, \n95% CI: 3.19%-11.02%).\n\n\n\nThomas and colleagues (2007) conducted a \nretrospective review to evaluate the effectiveness \nof MMS in the treatment of six rare aggressive \ncutaneous malignancies as seen by Mohs surgeons \nworking at a referral centre. Retrospective chart \nreview of 26,000 cases treated with MMS at \nthe Geisinger Medical Center Department of \nDermatology during a 16-year period with the \nfollowing diagnoses: poorly differentiated squamous \ncell carcinoma (PDSCC), dermatofibrosarcoma \nprotuberans (DFSP), microcystic adnexal carcinoma \n(MAC), extramammary Paget\u2019s disease (EMPD), \nMerkel cell carcinoma (MCC), and sebaceous \ncarcinoma (SEB CA). Patient demographic data, \ntumour measurements, treatment characteristics, \nand marginal recurrence rates were compiled and \nevaluated. The mean numbers of cases identified per \nyear for each tumor type were as follows: PDSCC, \n6.19; DFSP, 2.44; MAC, 1.63; and EMPD, 0.63. For \nPDSCC, 85 cases were available for follow-up with \na local recurrence rate of 6% at a mean follow-up \ntime of 45 months. For DFSP, there were 35 cases \nwith no local recurrence at a mean follow-up of \n39 months. For MAC, there were 25 cases with a \nlocal recurrence rate of 12% at a mean follow-up \nof 39 months. For EMPD, there were 10 cases \nwith no local recurrences at a mean follow-up of \n34 months. The authors concluded that the data on \nPDSCC, DFSP, MAC, and EMPD, combined with \nother studies in the literature, showed that MMS is \nthe most effective therapy for these rare aggressive \ncutaneous malignancies.21\n\n\n\nA further large case series recently published adds \nsupport to MMS as an appropriate treatment for rare \ncutaneous tumours with a recurrence rate of less \nthan 3%. This case series comprised 27 DFSP, 22 \nAFX, 8 MCC, 9 MAC, 6 Sebaceous carcinoma, 2 \nEMPD.22\n\n\n\nMMS can be considered for rarer skin tumours in \nMalaysia provided MMS continues to advance \nfurther to a subspecialty with good support of \nresources and sufficient workforce.\n\n\n\nSlow MOHs for melanoma\nBene and colleagues published the results of a \nprospective study in 2008, evaluating if margins \n\n\n\ndetermined to be cleared by MMS were confirmed \nby subsequent paraffin-embedded sections (gold \nstandard for determining margins) and to compare \nthe cure rate with available data for MMS versus \nSE. A total of 167 patients with melanoma in-situ \nparticipated in the study and were treated by MMS \nwith subsequent evaluation over a period of 12 \nyears. Overall, the authors reported of 167 cases of \nmelanoma in-situ, eight cases had a positive margin \non paraffin-embedded sections after margins on \nMMS frozen sections were called \u201cclear\u201d, resulting \nin a 95.1% clearance rate. However, after one re-\nexcision, all eight tumors had clear margins on \nparaffin-embedded sections. Cure rates reported \nfor mean follow-up of 50 months and of 63 months \nwere 98.6% and 98.2%, respectively.23\n\n\n\nBricca and colleagues conducted a prospective \ncase series in 2005, consisting of 625 patients \nwith primary cutaneous melanoma or melanoma \nin situ of the head and neck treated with MMS \ntechnique. Follow-up was conducted biannually for \nthe majority of cases with invasive melanoma, and \nannually for patients with melanoma in situ. The \nmean follow-up for the group was 58 months. The \nresults of their study suggest that MMS achieved \na five-year local recurrence rates, metastasis rates, \nand disease-specific survival rates comparable \nto or better than historical controls after Breslow \nthickness stratification. The size of the surgical \nmargin required for a complete excision was \nsignificantly related to the tumour thickness but not \nthe tumour size or the specific location.24\n\n\n\nMcKenna and colleagues in 2006 conducted a review \nevaluating the clinical features, histopathology and \nvarious treatments for lentigo maligna, a subtype \nof melanoma in situ that develops on sun-damaged \nskin. In the authors\u2019 opinion, standard excision using \na 5 mm margins is insufficient in many cases, and \nthe recurrence rates with standard excision ranges \nfrom 8 to 20%. MMS and staged excision may \noffer improved margin control and lower recurrence \nrates.25 \n\n\n\nWe would recommend that melanoma in situ can \nbe managed with slow Mohs. However, invasive \nmelanoma extending deeper than the epidermis \nshould be managed with wide excision and \nconsideration of sentinel lymph node biopsy, as \nwell as appropriate staging through computed \ntomography (CT) or positron emission tomography \nCT (PET-CT) scans. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 388\n\n\n\nMMS is a tissue sparing treatment\nMuller et al17 in a blinded assessor observational \nstudy in 2009, reported that the median area of \nMMS defect size is significantly lower than the \nSE group for small nodular BCCs. Therefore, \nthere is an additional tissue sparing role for MMS, \nbeyond achieving lower recurrence rates. The \nabove observation is not comparable to our dataset \nbecause our current criteria for MMS are stringent \nwith recurrent tumour, clinically ill-defined tumour \nor aggressive histological subtypes. The size of \nsuch defects are certainly larger than excising small \nnodular BCCs based on our observation that out of \nour total of 16 cases, 25% were closed side-to-side \nwith the majority (75%) needing a complex closure.\n\n\n\nMMS improves quality of life\nOne would wonder about whether there is a \ndifference between different surgical treatment \noptions for non-melanoma skin cancer. Chren and \ncolleagues in 2007 reported an improvement in \nquality of life Skindex Symptom scores by 9.7 (95% \nCI: 6.9,12.5) after SE, 10.2 (95% CI: 7.4,12.9) after \nMMS, and 3.4 (CI: -0.9,7.6) after electrodessication \nand cautery. Quality of life improvements were \nnot statistically different comparing SE and MMS. \nHowever, it is notable that the latter two approaches \nwere better than electrodessication and cautery.26\n\n\n\nMMS have been criticized as a lengthy procedure, \ntolerated poorly by elderly patients. Both our \nexperience and that in the United Kingdom is \nthat almost all patients had their MMS procedure \ncompleted within 4 hours after arriving.27 Secondly, \nthere have been concerns about overall safety \nof MMS and reconstruction. These were mainly \nreported in the United States where such surgery \noccurs in office-based setting. However, recent \nwork has demonstrated that MMS is very safe in \nthis context27. In our centre, we have a set up as a \nday-case or outpatient operating rooms rather than \nan aseptic, main theatre environment just like in the \nUnited Kingdom, with an acceptable complication \nrate.\n\n\n\nThere are, however, notable risk factors for types \nof surgical repairs associated with higher risk of \ncomplications such as infection, wound dehiscence, \nflap or graft failure. The risk factors are firstly, \ncomposite location of defects, secondly, interpolated \nflaps with cartilage grafting and thirdly, delayed \nreconstruction of more than two days.28 \n\n\n\nRecurrence rate in MMS\nThe 5-year recurrence rate is reported to be 1%. \nHisto-pathological pitfalls of MMS could result in \ninaccuracies and hence higher recurrence rates.29 Our \nrecurrence rate so far at 23 months is nil, however, \nwe would of course have to continue monitoring \nand resubmit further data in due course.\n\n\n\nThe future of MMS in Malaysia\nAs our caseload increases, we will be keen to report \non the recurrence rate after 5 years. The authors\u2019 \nrecommendation is that frozen section MMS should \nbe performed in the following situations in Malaysia \nfor primary skin cancers. This includes commonly \nBCC and SCC, in cosmetically sensitive sites, with \nhistological features that portend poorer prognosis, \nwith patient being financially able to enjoy the \nlower recurrence rates offset against any potential \nfinancial hardship that may arise and finally in an \nage category where the likelihood of enjoying a \nrecurrence-free five-year is highly relevant to the \npatient\u2019s quality of life. The latter would ultimately \ndiffer from one patient to another and would have to \nbe decided on a case-to-case basis.\n\n\n\nFor rarer skin cancers such as dermatofibrosarcoma \nprotuberans (DFSP), microcystic adnexal carcinoma \n(MAC), extramammary Paget\u2019s disease (EMPD), \nMerkel cell carcinoma (MCC), and sebaceous \ncarcinoma (SEB CA), it is not possible for us to \ncomment as there is no local data or experience \navailable yet. \n\n\n\nThe same is true for malignant melanoma. \nHowever, based on current literature, slow MOHs \nshould be considered for better histological margin \nevaluation in cases where wider excisions are \nnecessary following histological confirmation \nof malignant melanoma. Frozen section MMS is \nnot recommended due to a significant number of \ncases reported as clear on frozen Mohs sectioning, \nsubsequently found to be positive for melanoma on \nparaffin-embedded specimens. As a 5mm lateral \nmargin is associated with a 20% local recurrence \nrate25, the first slow MOHs stage should be taken with \na 5mm lateral margin around the first scar, followed \nby smaller 2-3 mm lateral margins for subsequent \nstages. Due to the fatal nature of melanoma, it is \neven more challenging to design an ethical trial that \nanswers our many unanswered questions on MMS \nfor melanoma.\n\n\n\nMohs surgical reconstruction education would spur \ninterest in Dermatological surgery in Malaysia \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 9\n\n\n\nand develop this subspecialty within Dermatology \nfurther. Hands-on courses and reconstruction \neducational activity can be utilised to increase \nDermatology trainee\u2019s confidence in complex \nrepairs32.\n\n\n\nConclusion\nBased on the current observations of MMS cases \nat our centre, we are pleased to report that despite \nthe higher threshold (hence selection bias towards \ncomplicated cases) at which MMS is considered and \nsubsequently performed, we have comparable mean \nnumber of stages compared to existing publication. \n\n\n\nThis review summarises the current up-to-date \nexperience in the first centre in Malaysia performing \nMMS. It is hoped that this technique can be adopted \nby other centres in Malaysia to cover the entire \ngeography of Malaysia. As MMS training is offered \nto future Dermatology trainees, it is hoped that this \ntechnique will be more widely available and hence \nthere would be sufficient manpower to conduct \ncollaborative data collection and clinical studies on \nMMS to enhance this technique further in Malaysia.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe authors would like to thank the lab technicians \nin University Malaya Medical Centre for their \npatience and perseverance with perfecting the \ntechnique of Mohs tissue preparation. The authors \nare also thankful to the Board of Directors of \nUniversity Malaya Medical Centre for approving \nand supporting the procedure in the hospital ethics \ncommittee in 2015.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3810\n\n\n\nFigure 1. The steps of MMS done in UMMC.\n\n\n\nFigure 2. The method of histological sectioning in MMS as compared to conventional methods.\n                                              \n\n\n\na. Patient with Mohs map drawn on site of excision; b. \nFinal defect after 3 stages; c. Process of reconstruction \nwith an O-to-T bilateral advancement flap by \ndermatological surgeon d. Skin with tumour flattened \nand submerged in optimum cutting temperature gel in \naluminium foil prior to freezing in cryostat; e. Multi-\nheaded microscope discussion between dermatologist, \npathologist and lab technician.\n\n\n\na. d.\n\n\n\ne.\nb.\n\n\n\nc.\n\n\n\nCross-sectioning MOHs sectioning\n\n\n\na) 8-10 micron slices\n\n\n\nAnalysed once\n\n\n\nb) 8-10 micron slices\n\n\n\nAnalysed once\n\n\n\nc) 8 micron slices\n\n\n\nAnalysed progressively \nuntil >200 microns clear\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nPeripheral sectioning\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 11\n\n\n\nTable 1. Characteristics of patients who underwent MOHs micrographic surgery in UMMC between July 2015-May 2017\n\n\n\nNo Sex Age Fitzpatrick\nskin type\n\n\n\nKarnofsky \nperformance \nscale (%)\n\n\n\nIndication\nfor MMS\n\n\n\nSite No of \nstages\n\n\n\nFinal\nhistological\ndiagnosis\n\n\n\nMargin \nclearance\n(microns)\n\n\n\nComplications Closure Total \ncost \n(RM)\n\n\n\n1 F 72 III 100 Ill-defined BCC Right ala \nnasi\n\n\n\n2 Infiltrative \nBCC\n\n\n\n246 Nil Local \nFlap\n\n\n\n3600\n\n\n\n2 F 77 III 90 Incompletely excised \nBCC\n\n\n\nBridge of \nnose\n\n\n\n2 Infiltrative \nBCC\n\n\n\n250 Nil Side to \nside\n\n\n\n4000\n\n\n\n3 M 84 IV 70 Deep margin close and \nperineural invasion \n\n\n\nRight \ntemple\n\n\n\n1 SCC 292 Nil Side to \nside\n\n\n\n2500\n\n\n\n4 M 72 IV 90 Cosmetically sensitive \nsite \n\n\n\nLeft lower \neyelid\n\n\n\n2 Infiltrative \nBCC\n\n\n\n240 Nil Local \nflap\n\n\n\n3500\n\n\n\n5 M 62 IV 90 Incompletely excised  \nBCC\n\n\n\nLeft side \nof nose\n\n\n\n1 Nodular \nBCC - local \ntissue \nreaction\n\n\n\n288 Nil Local \nflap\n\n\n\n1500\n\n\n\n6 M 87 IV 70 Poorly defined BCC Right ear 3 Infiltrative \nBCC\n\n\n\n388 Post-op \ninfection under \nflap\n\n\n\nFlap \nand full \nthickness \nskin graft\n\n\n\n5000\n\n\n\n7 M 64 II 90 Poorly defined BCC Left \nnasolabial \nfold\n\n\n\n2 Infiltrative \nBCC\n\n\n\n292 Nil Local \nflap\n\n\n\n4500\n\n\n\n8 M 67 IV 80 Incompletely excised \nnodular BCC\n\n\n\nLeft upper \ncutaneous \nlip\n\n\n\n1 No residual \ntumour \nseen\n\n\n\n292 Nil Side to \nside\n\n\n\n1500\n\n\n\n9 M 75 IV 80 Cosmetically sensitive \nsite\n\n\n\nLeft upper \neyelid\n\n\n\n2 Infiltrative \nBCC\n\n\n\n280 Nil Local \nflap\n\n\n\n5800\n\n\n\n10 M 48 V 100 Ill defined margins Right \nnasolabial \nfold\n\n\n\n2 Infiltrative \nBCC\n\n\n\n242 Nil Local \nflap\n\n\n\n3800\n\n\n\n11 M 67 III 90 Immunocompromised- \nrenal transplant patient\n\n\n\nLeft cheek 3 Infiltrative \nBCC\n\n\n\n242 Nil Local \nflap\n\n\n\n4800\n\n\n\n12 M 72 II 90 Cosmetically sensitive \nsite\n\n\n\nTip of \nnose\n\n\n\n3 Infiltrative \nBCC\n\n\n\n242 Nil Full \nthickness \nskin graft\n\n\n\n5000\n\n\n\n13 M 74 II 90 Incompletely excised \nBCC\n\n\n\nRight \ncheek\n\n\n\n1 No residual \ntumour\n\n\n\n240 Nil Side to \nside\n\n\n\n1000\n\n\n\n14 M 77 III 90 Ill defined BCC Forehead 2 Infiltrative \nBCC\n\n\n\n242 Nil Local \nflap\n\n\n\n3500\n\n\n\n15 M 74 IV 90 Cosmetically sensitive \nsite\n\n\n\nRight ala \nnasi\n\n\n\n2 Nodular \nBCC\n\n\n\n292 Nil Local \nflap\n\n\n\n3000\n\n\n\n16 M 51 II 100 Ill defined tumour Right ala \nnasi \n\n\n\n2 Infiltrative \nBCC\n\n\n\n288 Nil Local \nflap\n\n\n\n5000\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3812\n\n\n\nReferences\n\n\n\n1. Mohs FE. The chemosurgical method for the \nmicroscopically controlled excision of cutaneous cancer. \nIn: Epstein E, editor: Skin Surgery. Philadelphia. Lea & \nFebiger 1956.\n\n\n\n2. Swanson NA. Mohs surgery. Technique, indications, \napplications, and the future. Arch Dermatol 1983;119:761\u2013\n73.\n\n\n\n3. Tiger JB, Ganesh Z, Mouzakis J, Iwamoto S. Histological \nMohs Maps improve the accuracy of Dermatology \nResidents\u2019 Interpretations of Mohs Slides: A Pilot \nStudy. Dermatol Surg. 2017 Mar 23. doi: 10.1097/\nDSS.0000000000001126.\n\n\n\n4. Vedvyas C, Cummings PL, Geronemus RG, Brauer JA. \nBroader practice indications for Mohs surgical defect \nhealing by secondary intention: A survey study. Dermatol \nSurg 2017;43:415-423.\n\n\n\n5. Regula CG, Alam M, Bershad R, Glashofer M, Hanke CW, \nHarmon C et al. Functionality of patients 75 years and older \nundergoing Mohs Micrographic Surgery: A multicenter \nstudy. Dermatol Surg. 2017;4:904-910.\n\n\n\n6. Alam M, Berg D, Bhatia A, Cohen JL, Hale EK, Herman \nAR et al. Association between number of stages in Mohs \nmicrographic surgery and surgeon-, patient-, and tumor-\nspecific features: a cross-sectional study of practice patterns \nof 20 early- and mid-career Mohs surgeons. Dermatol Surg \n2010;36:1915-20.\n\n\n\n7. Alam M, Ibrahim O, Nodzenski M, Strasswimmer JM, \nJiang SI, Cohen JL et al. Adverse events associated with \nMohs Micrographic Surgery Multicenter Prospective \nCohort Study of 20821 cases at 23 centers. JAMA Dermatol \n2013;149:1378-85.\n\n\n\n8. Mosterd K, Krekels GA, Nieman FH, Ostertag JU, Essers \nBA, Dirksen CD et al. Surgical excision versus Mohs\u2019 \nmicrographic surgery for primary and recurrent basal cell \ncarcinoma of the face: a prospective randomised controlled \ntrial with 5 years\u2019 follow-up. Lancet Oncol 2008;9:1149-\n56.\n\n\n\n9. Leibovitch I, Huilgol SC, Selva D, Richards S, Paver \nR. Basal cell carcinoma treated with Mohs surgery in \nAustralia I. Experience over 10 years. J Am Acad Dermatol \n2005;53:445-51.\n\n\n\n10. Robins P. Chemosurgery: My 15 years of experience. J \nDermatol Surg Oncol 1981;7:779-89.\n\n\n\n11. Menn H, Robins P, Kopf AW, Bart RS.. The recurrent \nbasal cell epithelioma. A study of 100 cases of recurrent, \nre-treated basal cell epitheliomas. Arch Dermatol \n1971;103:628-31.\n\n\n\n12. Rowe DE, Carroll RJ, Day CL Jr. Mohs surgery is the \ntreatment of choice for recurrent (previously treated) basal \ncell carcinoma. J Dermatol Surg Oncol 1989;15:424-31.\n\n\n\n13. Smeets NW, Kuijpers DI, Nelemans P, Ostertag JU, \nVerhaegh ME, Krekels GA et al. Mohs\u2019 micrographic \nsurgery for treatment of basal cell carcinoma of the face - \nresults of a retrospective study and review of the literature. \nBr J Dermatol 2004;151:141\u20137.\n\n\n\n14. Smeets NW, Krekels GA, Ostertag JU, Essers BA, \nDirksen CD, Nieman FH et al. Surgical excision vs Mohs\u2019 \nmicrographic surgery for basal cell carcinoma of the face: \nrandomised controlled trial. Lancet 2004;364:1766-72.\n\n\n\n15. Van Loo E, Mosterd K, Krekels GA, Roozeboom MH, \nOstertag JU, Dirksen CD et al. Surgical excision versus \nMohs\u2019 micrographic surgery for basal cell carcinoma of the \nface: A randomised clinical trial with 10-year follow-up. \nEur J Cancer 2014;50:3011-20.\n\n\n\n16. Narayanan K, Hadid OH, Barnes EA. Mohs micrographic \nsurgery versus surgical excision for periocular basal \ncell carcinoma. Cochrane Database Syst Rev 2014 Dec \n12;(12):CD007041. doi: 10.1002/14651858.CD007041.\npub4.\n\n\n\n17. Muller FM, Dawe RS, Moseley H, Fleming CJ. Randomized \ncomparison of Mohs micrographic surgery and surgical \nexcision for small nodular basal cell carcinoma: tissue-\nsparing outcome. Dermatol Surg 2009;35:1349-54.\n\n\n\n18. Pugliano-Mauro M, Goldman G. Mohs surgery is effective \nfor high risk cutaneous squamous cell carcinoma. Dermatol \nSurg 2010;36:1544-53.\n\n\n\n19. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for \nlocal recurrence, metastasis, and survival rates in squamous \ncell carcinoma of the skin, ear, and lip. Implications \nfor treatment modality selection. J Am Acad Dermatol \n1992;26:976-90.\n\n\n\n20. Foroozan M, Sei JF, Amini M, Beauchet A, Saiag P. \nEfficacy of Mohs Micrographic Surgery for the Treatment \nof Dermatofibrosarcoma Protuberans: Systematic Review. \nArch Dermatol 2012;148:1055-63.\n\n\n\n21. Thomas CJ, Wood GC, Marks VJ. Mohs micrographic \nsurgery in the treatment of rare aggressive cutaneous \ntumors: the Geisinger experience. Dermatol Surg \n2007;33:333-9.\n\n\n\n22. Flohil SC, van Lee CB, Beisenherz J Mureau MA, \nOverbeek LI, Nijsten T et al. Mohs micrographic surgery \nof rare cutaneous tumours. J Eur Acad Dermatol Venereol \n2016 Dec 15. doi:10.1111/jdv.14079.\n\n\n\n23. Bene NI, Healy C, Coldiron BM. Mohs micrographic \nsurgery is accurate 95.1% of the time for melanoma in \nsitu: a prospective study of 167 cases. Dermatol Surg \n2008;34:660-4.\n\n\n\n24. Bricca GM, Brodland DG, Ren D, Zitelli JA. Cutaneous \nhead and neck melanoma treated with Mohs micrographic \nsurgery. J Am Acad Dermatol 2005;52:92-100.\n\n\n\n25. McKenna JK, Florell SR, Goldman GD, Bowen GM. \nLentigo maligna/lentigo maligna melanoma: current state \nof diagnosis and treatment. Dermatol Surg 2006;32:493-\n504.\n\n\n\n26. Chren MM, Sahay AP, Bertenthal DS, Sen S, Landefeld \nCS. Quality-of-life outcomes of treatments for cutaneous \nbasal cell carcinoma and squamous cell carcinoma. J Invest \nDermatol 2007;127:1351-7.\n\n\n\n27. Hussain W, Affleck A, Al-Niaimi F, Cooper A, Craythorne \nE, Fleming C et al. Safety, complications and patients\u2019 \nacceptance of Mohs micrographic surgery under local \nanaesthesia: results from the U.K. MAPS (Mohs \nAcceptance and Patient Safety) Collaboration Group. Br J \nDermatol 2017;176:806-8.\n\n\n\n28. Patel SA, Liu JJ, Murukami CS, Berg D, Akkina SR, \nBhrany AD. Complication rates in delayed reconstruction \nof the head and neck after Mohs Micrographic Surgery. \nJAMA Facial Plast Surg 2016;18:340-6.\n\n\n\n29. Fran\u00e7a K, Alqubaisy Y, Hassanein A, Nouri K, Lotti T. \nHistopathologic Pitfalls of Mohs Micrographic Surgery \nand a Review of Tumor Histology. Wiener Medizinische \nWochenschrift. 2016 Nov 2016 Nov 10. doi.10.1007/\ns10354-016-0528-0.\n\n\n\n30. Croley JA, Malone CH, Goodwin BP, Phillips LG, Cole \nEL, Wagner RF. Mohs surgical reconstruction educational \nactivity: a resident education tool. Adv Med Educ Pract \n2017;8:143-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 13\n\n\n\nORIGINAL ARTICLE\n\n\n\nMicrobiological Profile and Antibiotic Susceptibility Patterns of \nIsolates of Skin Specimens from the Department of Dermatology, \nHospital Kuala Lumpur: A 3-Year Audit\n\n\n\nShwu Hoon Tee1, Adv M Derm, Min Moon Tang2, Adv M Derm, Suganthi Thevarajah2, MMed\n\n\n\n1Department of Dermatology, Hospital Serdang, Selangor, Malaysia\n2Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nDue to the emergence of antibiotic resistance worldwide, the bacterial pathogens and susceptibility \npatterns causing skin infections should be monitored periodically to alert early intervention. This study \naimed to analyse the bacterial profile and their antibiotic susceptibility patterns among the patients \nwith cutaneous infections at Department of Dermatology, Hospital Kuala Lumpur (HKL).\n\n\n\nMethods:\nThis retrospective analysis analysed the bacterial profile and the antibiotic susceptibility patterns of \n1221 positive cultures obtained from skin swabs and biopsy specimens sent from the Department of \nDermatology Hospital Kuala Lumpur (HKL) from 2013-2015.\n\n\n\nResults: \nStaphylococcus aureus (2/3 methicillin-sensitive, 1/3 methicillin-resistant) was the most frequent \nisolate (44%), followed by Pseudomonas aeruginosa (17.4%); Acinetobacter sp. (6.7%); Proteus sp. \n(6.1%); Klebsiella sp. (5.7%), Enterobacter sp. (3.0%), Escherichia coli (2.8%) and others. About \n45% and 10% of MRSA was resistant to fucidic acid and mupirocin respectively.  About 15% of \nPseudomonas aeruginosa was resistant to ciprofloxacin. Majority of Acinetobacter sp. were resistant \nto most of the common antibiotics used.\n\n\n\nConclusion:\nStaphylococcus aureus remained the main microorganisms isolated from patients with cutaneous \nbacterial infections. Empirical use of antibiotics prior to availability of culture sensitivity should be \navoided for prevention of multi-resistant micro-organisms. We advocate judicious use of antibiotics \nbased on results of the culture sensitivity and strict adherence to infection control measures to prevent \ndevelopment of antibiotic resistance. \n\n\n\nKey words: Microbiological\tprofile,\tantibiotic\tsusceptibility,\tStaphylococcus\taureus,\tPseudomonas\taeruginosa\n\n\n\nIntroduction\nDue to the emergence of antibiotic resistance \nworldwide, the bacterial pathogens and \nsusceptibility patterns causing skin infections \nshould be monitored periodically to alert early \nintervention. This retrospective analysis aimed to \nanalyse the bacterial profile that cause cutaneous \n\n\n\nCorresponding Author\nDr Tee Shwu Hoon\nDepartment of Dermatology, Hospital Serdang, Jalan \nPuchong, 43000 Kajang, Selangor, Malaysia.\nEmail: shwuhoontee@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3814\n\n\n\ninfections and the antibiotic susceptibility patterns \namong the patients presented to the Department of \nDermatology, Hospital Kuala Lumpur (HKL).\n\n\n\nMaterials and Methods \nThis is a retrospective analysis conducted in the \nDepartment of Dermatology, HKL from January \n2013 to December 2015. All positive cultures \nobtained from skin swabs and biopsy specimens \nsent from the dermatology clinic and ward were \nanalysed.\n\n\n\nResults \nThere were a total of 1221 positive cultures \nisolated from skin specimens with predominantly \ngram positive organisms (54%). Nearly 99% \nof the microorganisms were aerobic bacteria. \nStaphylococcus aureus (537, 44.0%) was the \nmost frequent isolate; followed by Pseudomonas \naeruginosa (213, 17.4%); Acinetobacter sp. (82, \n6.7%); Proteus sp. (75, 6.1%); Klebsiella sp. (69, \n5.7%), Enterobacter sp. (37, 3.0%), Escherichia \ncoli (34, 2.8%), Group B Streptococcus (30, 2.5%), \nStreptococcal pyogenes (28, 2.3%), Pseudomonas \n\n\n\nsp. (28, 2.3%), Enterococcus sp. (13, 1.1%), \nStaphylococcus coagulase negative (12, 1.0%) \nand others. About 80% of methicillin-sensitive \nStaphylococcus aureus (MSSA) was resistant to \npenicillin G (Figure 1).\n\n\n\nA third of Staphylococcus aureus (34.3%) was \nmethicillin-resistant (MRSA). 62.5% of MRSA \nwere resistant to clindamycin while 47.8% were \nresistant to co-trimoxazole. About 45% and 10% of \nMRSA were resistant to fucidic acid and mupirocin \nrespectively. About 14% of Pseudomonas \naeruginosa was resistant to ciprofloxacin. Figure \n2 demonstrated the antibiotic sensitivity pattern of \nPseudomonas aeruginosa. Majority of Acinetobacter \nsp. were resistant to most of the antibiotics tested \nincluding piperacillin/tazobactam, carbapenem \nand tigecycline (52.4-64.6%). About 67 to 100% \nof gram negative organisms such as Proteus sp., \nKlebsiella sp., Enterobacter sp. and Escherichia \ncoli were resistant to ampicillin. The susceptibility \nrates of Proteus sp., Klebsiella sp., Enterobacter sp. \nand Escherichia coli to ciprofloxacin were 73.3%, \n49.3%, 86.5% and 67.6% respectively.\n\n\n\nFigure 1. Antibiotic resistance pattern of Staphylococcus aureus cultured from skin specimens sent from the Department of Dermatology, \nHKL from January 2013 to December 2015.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 15\n\n\n\nDiscussion\nAbout 44% of the isolates in this study cohort was \nStaphylococcus aureus. It was much higher than \nprevious local studies as shown in Table 1. Previous \nreports studied on patients with diabetic foot \ninfections mainly. Different types of infections and \nthe patients\u2019 underlying immune status could have \ncontributed to different types of microorganisms \nisolated as shown in various studies. We propose \nproper prospective studies in the future addressing \nbacteriological pattern of cutaneous infections \nwith important factors such as comorbidities; \nsites of specimens obtained; types of specimens \n(swab versus biopsy samples) together with proper \nsampling methodology.\n\n\n\nWhen compared to the results being reported by a \nrecent study conducted in UMMC on patients on \nnon-infected atopic dermatitis, we reported a higher \nresistance rate of Staphylococcal aureus to various \nantibiotics; i.e. penicillin (86.6% versus 82.1%), \nfucidic acid (37.2% versus 17.9%), erythromycin \n(35.4% versus 7.7%), clindamycin (24.6% versus \n7.7%) and co-trimoxazole (17.3% versus 2.6%).1\n\n\n\nAbout a third (34.3%) of Staphylococcus aureus \nisolated was MRSA; which was comparable to \n\n\n\nFigure 2. Antibiotic sensitivity pattern of Pseudomonas aeruginosa cultured from skin specimens sent from the Department of \nDermatology, HKL from January 2013 to December 2015.\n\n\n\na report1 published in 1994 in HKL where 35.4% \nof Staphylococcus aureus was MRSA. In that \nreport, Staphylococcus aureus were cultured from \nskin, blood, cerebral spinal fluid, peritoneal fluid \nand throat swabs; but the highest yield was from \nwounds, ulcers and skin swabs.2 However, the \nresistance rate to rifampicin and fucidic acid had \nincreased from 4.5% and 2% in 1994 to 32.6% and \n45.7% respectively in our audit.  Interestingly, the \nresistance rate to co-trimoxazole; erythromycin and \ngentamicin had reduced from 71.0%; 97.0%; and \n98.7% to 47.8%; 85.3% and 56.0% respectively. \nIn another study published in 20003, the rate of \nmupirocin resistant MRSA was 2.8% in HKL but it \nhas increased to 10.3% in this audit. \n\n\n\nThe resistance rate of Staphylococcus aureus to \nfusidic acid was 37% generally and 45% among \nMRSA in present study. This is far higher than the \npreviously reported local data which showed 3.6% \nresistance generally and 3.2% among MRSA.3 \nWhen compared with other countries, the resistance \nrate to fusidic acid in our study is much higher than \nEuropean countries such as 0.4-1.0% in Denmark \nfrom 1967 to 19874, 1.2-1.7% in England between \n1969 and 19835 and 0.7% in Germany in 1970.6 \nThe widely availability of topical fusidic acid is a \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3816\n\n\n\ncontributing factor for its increasing resistance rate.  \nWe therefore advocate topical fusidic acid to be \nused selectively in indicated cases of skin infections \nsuch as localised impetigo in outpatient setting. \n\n\n\nDifferent amino acid alterations were shown to \nbe responsible for rifampicin and fucidic acid \nresistance among Malaysian MRSA strains.7 Both \nrifampicin and fusidic resistance were associated \nwith mutation at\t rpo\u03b2 and fusA respectively.7 The \nhigh rifampicin and fusidic acid resistance rates \nagainst MRSA in our cohort indicate that the use of \ncombination of oral fusidic acid and rifampicin in \nthe management of MRSA infection in skin may not \nbe as effective as previously thought. \n\n\n\nThe fact that the development of rifampicin \nresistance is prevented by combination with other \nantibiotic such as fusidic acid is disputed by a \nsystematic review that concluded that in vitro \nresults of interactions between rifampicin and \nother antibiotics are method dependent and do not \ncorrelate with in vivo findings.8 Combination of \noral fusidic acid and rifampicin may be considered \nonly if the strain is susceptible in cases of recurrent \nactive MRSA skin and soft tissue infections despite \noptimisation of wound care and hygiene measures, \nnasal and topical decolonization.9 A retrospective \ncohort study showed that early initiation of \nrifampicin combination treatment within 7 days \nof positive blood culture for at least 14 days in \nStaphylococcus aureus bacteraemia patients with a \ndeep infection focus improved survival.10\n\n\n\nThe use of mupirocin should be reserved for \nculture-proven MRSA. Appropriate infection \ncontrol measures and use of antiseptics such as \nchlorhexidine and potassium permanganate should \nbe practised.\n\n\n\nOur analysis reported an important finding of high \nresistance rate of MRSA towards co-trimaxazole \n(47.8%) and clindamycin (62.5%) which are \ncommon antibiotics employed to treat MRSA. This \nshould serve as a warning sign to call for a strict \npolicy on the usage of these antibiotics in Malaysian \nhospitals. Judicious and controlled use of these \nantibiotics in indicated cases of culture-proven \nMRSA infections is essential. \n\n\n\nPseudomonas aeruginosa exhibited the lowest \nsusceptibility to piperacillin/tazobactam and \nciprofloxacin in this audit. The resistant rate to \nciprofloxacin of 14% was slightly reduced from the \nprevious study done in HKL i.e. 16.5% in 2009.11 \nNevertheless, the susceptibility rate to piperacillin/\ntazobactam had reduced from 92.8% to 83.6%. The \nsusceptibility rate to amikacin was the highest in \nthis audit i.e. 97.2% followed by cefepime (96.2%). \nJudicious use of ciprofloxacin in outpatient and \npiperacillin/tazobactam in inpatient setting is \nimportant to reduce their resistance rate. \n\n\n\nIt is attention-grabbing to the findings that most \nimportant gram-negative bacteria cultivated \nwere resistant to ampicillin. The widely use of \nampicillin, ampicillin/sulbactam and amoxicillin/\nclavulanic acid at primary care level due to the \neasy availability and convenient dosing frequencies \nmay not be very effective in treating gram-\nnegative bacteria cutaneous infections, which \ncontributed 46% of cutaneous infections in this \naudit. Similarly, ciprofloxacin which is available \nin oral form and widely prescribed at primary care \nsetting demonstrated significant reduction in the \neffectiveness towards many gram-negative bacteria \ncutaneous infection especially Klebsiella sp.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 17\n\n\n\nConclusion \nStaphylococcus aureus remained the main \nmicroorganisms isolated from patients with \ncutaneous bacterial infections. Gram negative \nbacteria demonstrated lower sensitivity rate to \nmost of the common oral antibiotics used in the \nclinical setting. This analysis served as an important \nreference for the construction of local antibiotic \nusage guideline specifically on cutaneous infections. \nEmpirical use of antibiotics prior to availability of \nculture sensitivity should be avoided for prevention \nof multi-resistant micro-organisms. We advocate \njudicious use of antibiotics based on results of the \nculture sensitivity and strict adherence to infection \ncontrol measures to prevent development of \nantibiotic resistance.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nWe would like to extend our gratitude to the \nDepartment of Microbiology HKL who provided us \nthe data. We would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npresent this report.\n\n\n\nReferences\n\n\n\n1. Lee CK, Yusof MY, Lee YY, Tan ESS, Wong SM, Ch\u2019ng \nCC et al; Staphylococcal aureus antibiotic resistance in \natopic eczema. MJD 2016;36:5-10.\n\n\n\n2. Cheong I, Tan SC, Wong YH, Zainudin BMZ, Rahman \nMZA. Methicillin-resistant Staphylococcus aureus \n(MRSA) in a Malaysian hospital. Med J Malaysia. 1994; \n49:24-8.\n\n\n\n3. Rohani MY, Raudzah A, Lau MG, Zaidatul AA, \nSalbiah MN, Keah KC et al. Susceptibility pattern of \nStaphylococcus aureus isolated in Malaysian hospitals. Int \nJ Antimicrob Agents. 2000;13:209-13.\n\n\n\n4. Mette F, Rosdahl VT. Susceptibility of fusidic acid among \nDanish S. aureus strains and fusidic acid consumption. J \nAntimicrob Chemother 1990;25:7-14\n\n\n\n5. Gransden WR, Eykyn SJ, Phillips I. S. aureus bacteraemia: \n400 episodes in St. Thomas\u2019s Hospital. Br Med J \n1984;288:300-3.\n\n\n\nTable 1. Comparison of top 5 microorganisms isolated among present and other local studies.\n\n\n\nAuthor, year n Type of patients Top 5 microorganisms (%)\n\n\n\nNadeem Sajjad Raja, 2007 194 Diabetic foot infections 1. Staphylococcus aureus (17%)\n2. Proteus sp. (15%)\n3. Pseudomonas aeruginosa (13%)\n4. Group B Streptococcus (11%)\n5. Bacteroides sp. (1%)\n\n\n\nSD Balakrishnan et al 2014 96 Diabetic foot infections 1. Staphylococcus aureus (27.0%)\n2. Klebsiella pneumoniae (22.0%)\n3. Streptococcus sp. (15.0%)\n4. Pseudomonas sp. (12.0%)\n5. Enterobacter sp. (10.0%),\n\n\n\nProteus mirabilis (10.0%)\n\n\n\nNur Hilda Hanina Abd Wahab et \nal 2015\n\n\n\n77 Diabetic foot ulcers 1. Proteus mirabilis (20.5%)\n2. Pseudomonas aeruginosa (19.3%)\n3. Staphylococcus aureus (13.3%)\n\n\n\nKlebsiella pneumoniae (13.3%)\n4. Group B Streptococcus (8.4%)\n5. Escherichia coli (7.2%)\n\n\n\nSL. Vijaya Kumar et al 2016 122 Diabetic foot infections 1. Klebsiella sp. (14.7%)\n2. Pseudomonas sp. (13.2%)\n3. Staphylococcus sp. (12.1%)\n4. Bacter group (Citrobacter, Enterobacter, Acinetobacter, etc) \n\n\n\n(11.7%)\n5. Escherichia coli (11.3%)\n\n\n\nPresent study, 2016 1221 All cutaneous infections 1. Staphylococcus aureus (44.0%)\n2. Pseudomonas aeruginosa (17.4%)\n3. Acinetobacter sp. (6.7%)\n4. Proteus sp. (6.1%)\n5. Klebsiella sp. (5.7%)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3818\n\n\n\n6. Roser H. Die resistenzver haltnisse von S. aureus gegen \nfucidine seit 1970 im Vergleich zu anderen wirksamen \nantibakteriellen substanzen. Munch Med Wochenschr \n1974;116:1849\u201352.\n\n\n\n7. Lim KT, Teh CS, Yusof MY, Thong KL. Mutations of rpo\u03b2 \nand fusA cause resistance to rifampicin and fusidic acid in \nmethicillin-resistant Staphylococcus aureus strains from a \ntertiary hospital in Malaysia. Trans R Soc Trop Med Hyg \n2014;108:112-8.\n\n\n\n8. Perlroth J, Kuo M, Tan J, Bayer AS, Miller LG. \nAdjunctive use of rifampin for the treatment of \nStaphylococcus aureus infections: a systematic review of \nthe literature. Arch Intern Med. 2008;168:805-19.\n\n\n\n9. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin \nSK, Gorwitz RJ et al. Clinical practice guidelines by \nthe infectious diseases society of America for the treatment \nof methicillin-resistant Staphylococcus aureus infections \nin adults and children: executive summary. Clin Infect \nDis. 2011;52:285-92. \n\n\n\n10. Forsblom E, Ruotsalainen E, J\u00e4rvinen A. Improved \nOutcome with Early Rifampicin Combination Treatment in \nMethicillin-Sensitive Staphylococcus aureus Bacteraemia \nwith a Deep Infection Focus \u2013 A Retrospective Cohort \nStudy. PLoS ONE 2015;10:e0122824. doi:10.1371/\njournal.pone.0122824.\n\n\n\n11.  Pathmanathan SG, Samat NA, Mohamed R. Antimicrobial \nsusceptibility of clinical isolates of Pseudomonas \naeruginosa from a Malaysian Hospital. The Malaysian \nJournal of Medical Sciences: MJMS 2009;16:27-32.\n\n\n\n12. Nadeem Sajjad Raja. Microbiology of diabetic \nfoot infections in a teaching hospital in Malaysia: a \nretrospective study of 194 cases. J Microbiol Immunol \nInfect. 2007;40:39-44.\n\n\n\n13. SD Balakrishnan, NJ Shahid, TM Fairuz, IMA Ramdhan. \nDoes the National Antibiotic Guideline- 2008 remain \napplicable for treating diabetic foot infection? A new \nevidence-based regional study on culture and sensitivity \npatterns in Terengganu population. Malaysian Orthopaedic \nJournal.2014;8:42-5.\n\n\n\n14. Nur Hilda Hanina AW, Intan NS, Syafinaz AN, Zalinah \nA, Lailatul Akmar MN, Anand Sobhraj Devnani. \nClinical presentation and microorganisms sensitivity \nprofile for diabetic foot ulcers: a pilot study. Med J \nMalaysia. 2015;70:182-7.\n\n\n\n15. SL Vijaya Kumar, Ashutosh SR, Gokulshankar S, Ranjith \nMS, Mohanty BK, LIM MY. Is bacteriology a contributing \nfactor in unsalvageable nature of diabetic foot infections? \nA study in a district hospital in Malaysia. Int J Pharm \nPharm Sci. 2016;8:262-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 19\n\n\n\nORIGINAL ARTICLE\n\n\n\nPrevalence of Skin Diseases in Dermatology Outpatient Clinic, \nHospital Kuala Lumpur\n\n\n\nSwee Kuan Heah, MD, Noorlaily Mohd Noor, AdvMDerm, Asmah Johar, MMed\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nCases referred to a tertiary hospital tend to be more difficult to manage. Therefore, the demographic \npattern may differ and changes with time. To determine the prevalence and changing trend of skin \ndiseases according to age, gender and ethnicity in Hospital Kuala Lumpur.\n\n\n\nMethods:\nThis retrospective, cross sectional study was conducted in the Department of Dermatology, Hospital \nKuala Lumpur from 1st January 2008 to 31st December 2014.\n\n\n\nResults: \nThe top five skin diseases in descending order of frequency were eczema, infection, acne and acneiform \ndisorders, psoriasis and urticaria/angioedema. Eczema is now the most common skin disease as \ncompared to an earlier study from 1995 to 1999 where infection was the most common. A total of \n58,252 clinic attendees consist of Malays (61.0%), followed by Indians (20.1%) and Chinese (18.9%). \nOut of these, 51.6% were females and 48.4% were males. Majority of patients were 20-29 years old (n \n= 11546, 24.6%) followed by 30-39 (n= 6621, 14.1%) and 10-19 years old (n= 6335, 13.5%).\n\n\n\nConclusion: \nAs eczema is now the most common skin disease encountered, the management of each patient need \nto be tailored according to the different type of eczema. Training for eczema and other skin diseases \ncan be provided by primary care health providers as treatment for these cases are available at primary \ncare level. \n\n\n\nKey words: Prevalence, skin diseases, Malaysia\n\n\n\nIntroduction\nSkin diseases are common in the community and \nthe more difficult patients will be referred to a \nhospital for further investigation and treatment. \nThe most common skin diseases encountered in \nthe Department of Dermatology Hospital Kuala \nLumpur for the year 1995 to 1999 in descending \norder of frequency were infection, eczema, acne, \npsoriasis and tumours.1\n\n\n\nThe pattern of skin diseases may be influenced \nby external factors such as personal lifestyle, \neducational background and socioeconomic status \n\n\n\nCorresponding Author\nDr Heah Swee Kuan\nDepartment of Dermatology, Hospital Kuala Lumpur,\nJalan Pahang, 50586 Kuala Lumpur, Malaysia.\nEmail: alexanderskheah@yahoo.com \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3820\n\n\n\nas well as internal factors such as age, gender, and \nethnicity.2 Malaysia is a developing country with \nthree major ethnicities namely Malay, Chinese \nand Indian. However, there is no recent study to \ndetermine the prevalence and changing trend of skin \ndiseases in our centre.\n\n\n\nThe aim of this study was to determine the \nprevalence of skin diseases among patients \nattending the dermatology clinic HKL, which is a \ntertiary referral centre. We were also interested to \nlook at the distribution of skin diseases according to \nage, gender and ethnicity.\n\n\n\nMaterials and Methods\nThis retrospective, cross sectional study was \nconducted in the Department of Dermatology, \nHospital Kuala Lumpur. Data was collected and \nretrieved from electronic database for all patients \nseen in the dermatology outpatient clinic from 1st \nJanuary 2008 to 31st December 2014. Most of the \ndiagnoses were made based on clinical history and \nphysical examination. In some cases, the diagnoses \nwere supported by laboratory tests and histo-\npathological examination. Diagnoses were captured \nin accordance to the International Classification of \nDiseases, version 10 (ICD -10). Data were analyzed \nusing Microsoft Office Excel (version 2013).\n\n\n\nPatients with Sexually Transmitted Infections under \nthe care of Genitourinary Medicine Clinic were not \nincluded in the study as they are not captured in the \ndatabase. Benign tumours were excluded in this \nstudy as the scope was too wide to be analysed from \nthe database.\n\n\n\nResults \nThe top 5 skin diseases were eczema, infection, acne \nand acneiform disorders, psoriasis and urticaria and \nangioedema as shown in table 1.\n\n\n\nA total of 58,252 patients in the 3 main ethnic groups \nattended the skin clinic over a period of seven years \nfor which the majority were Malays (n=35509, \n61.0%), followed by Indians (n=11728, 20.1%) \nand Chinese (n=10652, 18.9%). Out of these 51.6% \nwere females and 48.4% were males. The majority \nwere 20-29 years old, (n = 11546, 24.6%) followed \nby 30-39 (n= 6621, 14.1%) and 10-19 age groups \n(n= 6335, 13.5%).\n\n\n\nThe Malaysian main ethnic group, gender and age \ngroup are shown in figure 1. The top 10 skin disease \ngroups by ethnicity are shown in table 2. Almost \ntwo third of the cases were eczema and infections.\n\n\n\nTable 1. Prevalence of common skin diseases among clinic \nattendees.\n\n\n\nDiseases Number, n Percentage, %\n1  Eczema 23429 39.07\n2  Infection 13957 23.27\n3  Acne and acneiform disorders 6241 10.41\n4  Psoriasis 5719 9.54\n5  Urticaria and angioedema 2478 4.13\n6  Pigmentary disorders 2365 3.94\n7  Alopecia 1080 1.8\n8  Drug allergy 591 0.99\n9  Melanoma & Non melanoma skin \n    cancer\n\n\n\n328 0.55\n\n\n\n10  Autoimmune bullous diseases 286 0.48\nOthers 3493 5.82\nTotal 59967 100\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 21\n\n\n\nFi\ngu\n\n\n\nre\n 1\n\n\n\n. T\nhe\n\n\n\n d\nis\n\n\n\ntri\nbu\n\n\n\ntio\nn \n\n\n\nof\n c\n\n\n\nlin\nic\n\n\n\n a\ntte\n\n\n\nnd\nan\n\n\n\nce\n a\n\n\n\ncc\nor\n\n\n\ndi\nng\n\n\n\n to\n a\n\n\n\nge\n, g\n\n\n\nen\nde\n\n\n\nr a\nnd\n\n\n\n e\nth\n\n\n\nni\nci\n\n\n\nty\n.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3822\n\n\n\nDiseases Malay Chinese Indian Others Total number of patients Percentage, %\n1) Eczema 13234 5234 4529 432 23429 39.07\nContact dermatitis 3526 1339 992 173 6030 10.06\nAtopic eczema 2617 789 643 54 4103 6.84\nHand & feet eczema 1619 671 607 52 2949 4.92\nSeborrheic dermatitis 1465 690 553 59 2767 4.61\nDiscoid eczema 1452 421 322 28 2223 3.7\nPhototoxic dermatitis 743 559 264 25 1591 2.65\nStasis eczema 498 268 511 14 1291 2.15\nLichen simplex chronicus 670 188 364 10 1232 2.05\nOthers 644 309 273 17 1243 2.07\n       \n2) Infectious diseases 8256 2232 3055 414 13957 23.27\ni) Viral infection       \nViral wart 1055 330 342 57 1784 2.97\nHerpes zoster 875 195 110 41 1221 2.04\nHerpes simplex 149 69 32 27 285 0.43\nii) Bacterial infection       \nImpetigo 272 29 42 8 351 0.59\nCellulitis 130 50 68 4 252 0.42\nFolliculitis 121 56 52 5 234 0.39\nLeprosy 53 32 7 75 167 0.28\nCutaneous TB 17 10 2 1 30 0.05\niii) Fungal infection       \nTinea corporis 1483 307 449 26 2265 3.78\nTinea cruris 656 198 310 11 1175 1.96\nTinea pedis 475 138 263 15 891 1.49\nTinea capitis 276 33 67 10 386 0.64\nPityriasis versicolor 301 59 134 16 510 0.85\nOnychomycosis 613 287 490 33 1423 2.37\nSporotrichosis, lymphocutaneous 40 7 2 1 50 0.08\nIntertrigo 593 136 400 7 1126 1.88\nOthers 1147 296 285 77 1807 3.05\n       \n3) Acne and acneiform disorders 4214 928 977 122 6241 10.41\nAcne vulgaris 3900 841 903 102 5746 9.58\nAcne cystic 179 28 27 4 238 0.4\nRosacea 54 38 24 10 126 0.21\nHidradenitis suppurativa 24 10 18 3 55 0.09\nOthers 57 9 5 3 76 0.13\n       \n4) Psoriasis 3084 908 1569 158 5719 9.54\nPsoriasis vulgaris 2910 848 1504 145 5407 9.02\nErythrodermic psoriasis 53 29 13 4 99 0.17\nGuttate psoriasis 49 9 14 3 75 0.13\nGeneralised pustular psoriasis 7 4 1 1 50 0.08\nOthers 65 18 37 5 88 0.15\n       \n5) Urticaria and angioedema 1473 531 417 57 2478 4.13\n       \n6) Pigmentary disorder 1191 366 695 113 2365 3.94\nVitiligo 711 199 412 76 1398 2.33\nMelasma 234 91 152 20 497 0.83\nPost inflammatory hypermelanosis 185 42 126 13 366 0.61\nNaevus of Ota 30 20 2 2 54 0.09\nHori \u2018s spot 31 14 3 2 50 0.08\n       \n\n\n\nTable 2. Prevalence of top ten skin disease groups according to ethnicity and specific diagnoses.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 23\n\n\n\n7) Alopecia 634 134 285 27 1080 1.8\nAlopecia areata 469 80 222 21 792 1.32\nAndrogenic alopecia 33 9 16 0 58 0.1\nAlopecia totalis 10 7 3 1 21 0.04\nAlopecia universalis 12 6 2 0 20 0.03\nTelogen effluvium 103 32 41 5 181 0.3\nOthers 7 0 1 0 8 0.01\n       \n8) Drug allergy 380 102 83 26 591 0.99\nFixed drug eruption 96 19 31 6 152 0.25\nSJS, SJS-TEN overlap, TEN 68 15 13 13 109 0.18\nMaculopapular drug reaction 61 32 9 0 102 0.17\nAGEP 52 5 9 2 68 0.11\nDRESS 43 11 9 4 67 0.11\nOthers 60 20 12 1 93 0.16\n       \n9) Melanoma & Non Melanoma Skin \n    Cancer\n\n\n\n127 143 45 13 328 0.55\n\n\n\nMelanoma 15 12 5 1 33 0.06\nNon melanoma 112 131 40 12 295 0.49\n\n\n\n- BCC 75 97 24 9  205  0.34\n- SCC 37 34 16 3 90 0.15\n\n\n\n10) Autoimmune bullous disease 134 74 65 13 286 0.48\nPemphigus vulgaris 64 37 41 4 146 0.24\nPemphigus foliaceous 39 18 14 4 75 0.13\nOthers 31 19 10 5 65 0.11\n\n\n\n11) Others     3493 5.82\n\n\n\nSJS - Stevens Johnson Syndrome; TEN - Toxic Epidermal necrolysis; AGEP - Acute Generalized Exanthematous Pustulosis; DRESS \u2013 Drug Reaction, \neosinophilia with systemic symptoms; BCC \u2013 basal cell carcinoma; SCC - Squamous cell carcinoma.\n\n\n\nDiscussion\nThe top five skin diseases in the Department of \nDermatology from 1st January 2008 to 31st December \n2014 in descending order of frequency were eczema, \ninfection, acne and acneiform disorders, psoriasis \nand urticaria/angioedema. This was almost similar \nto an earlier study in the department for the year \n1995 to 1999 which showed that the top five skin \ndiseases were infection (30.9%), eczema (29.5%), \nacne (6.1%), psoriasis (5.2%) and tumours (4.1%). \nThere is a changing trend as eczema appeared to be \nthe most common skin disease.\n\n\n\nLooking into more specific diagnosis, contact \ndermatitis (10.06%) was the commonest followed \nby acne vulgaris (9.58%), psoriasis vulgaris \n(9.02%), atopic eczema (6.84), hands & feet eczema \n(4.92), seborrheic dermatitis 4.61% and urticaria/ \nangioedema (4.13%).  Allergy related diseases such \nas contact dermatitis, atopic eczema and urticaria/\nangioedema were on the rise, as compared to \nprevious study for the year 1995-1999, as the data \nshowed the following: contact dermatitis (6.19%), \natopic eczema (4.01%) and urticaria (4.0%).1 This \nmight be due to various environmental and genetic \nfactors causing the population at risk to be more \n\n\n\nsusceptible to allergy related diseases.\n\n\n\nAmongst the infections, fungal was the commonest, \nfollowed by viral and bacterial infections. This may \nnot represent the actual figure as skin infections \nare also managed by primary care doctors. Only \nthose with more serious infections are referred to \ndermatologists. \n\n\n\nAlthough leprosy has reached elimination phase \nin Malaysia (0.7:100,000 population: data from \nMinistry of Health 2015), new cases are still being \ndetected mainly among the foreigners, Sabahan, \nSarawakian and indigenous groups. Malaysia has \na large influx of foreign workers from countries, \nwhich are still endemic with leprosy. The public \nhealth still needs to continue addressing this issue to \nprevent the spread of disease.\n\n\n\nAcne still contributed to the bulk of consultation. \nLyn DD et al3 noted that acne was the top three most \nprevalent skin conditions in the general population \nas found in large studies within UK, France, and \nUSA. Throughout the world, similar numbers were \nfound among young adults in various countries.4 \nThis prevalence of about 10% in our center was not \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3824\n\n\n\nreflective of the actual burden in the community \nas many tried over the counter or on-line products \nand sought treatment in primary care and private \ndermatologist.\n\n\n\nWe were also seeing a large number of patients with \npsoriasis. According to the Malaysian Psoriasis \nRegistry from March 2007 to December 2014, \n12462 new patients were registered.5 In our study \nthere were more Indians (27.4%) with psoriasis as \ncompared to Chinese (15.9%) despite the clinic \nbeing attended by almost similar numbers of Indians \nand Chinese. \n\n\n\nThere were more Indian patients with pigmentary \ndisorders as compared to Chinese and Malays with \na ratio of 2:1:1. The pigmentary problems seen were \nmainly vitiligo, melasma and post inflammatory \nhypermelanosis. Due to the significant contrast in \nskin colour among Indians with vitiligo, they sought \nfurther treatment in hospitals with phototherapy \nservices. \n\n\n\nAs expected, both melanoma and non-melanoma \nskin cancers (NMSC) were not very common. \nThey only constituted 0.55% and majority was \nChinese (0.24%, n=143). Chinese were at higher \nrisk of getting skin cancers, probably due to the fair \nskin phototype. Basal cell carcinoma (n=205) was \ncommoner than squamous cell carcinoma (n=90). \nHowever, there may be cases that are being treated \nby surgeons. Melanoma appeared to be uncommon.\n\n\n\nAs this is a retrospective study, there may be \nerrors in data entry and missing data in the system. \nThere may be recall or misclassification bias, as \nthe diagnosis may change in the subsequent visits \nbut the latest diagnosis may not be updated in the \nsystem.\n\n\n\nBased on these data, we plan to train and educate \nthe general practitioners and family medicine \nspecialists to manage the more prevalent diseases \nin the community. We may further assess the factors \nwhich may be specific to a certain ethnic group that \nput them at higher risk for certain skin diseases.\n\n\n\nHowever, we do acknowledge that this study was \nconducted in a tertiary centre in the heart of Kuala \nLumpur. Thus, it may not be representative of the \nactual epidemiology of the whole country. Similar \nstudies should be done in the rural areas as well \nas Sabah and Sarawak to look at the prevalence of \ncommon skin diseases. \n\n\n\nConclusion \nFrom this study, as eczema was now the most \ncommon skin disease encountered, the management \nof each patient needs to be tailored according to the \ndifferent types of eczema. Training for eczema and \nother skin diseases can be provided by primary care \nhealth providers as treatment for these cases are \navailable at primary care level. It is also important \nfor us to train health care providers to recognize \ncertain diseases such as leprosy and skin cancers so \nthat treatment can be instituted earlier.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nWe would like to thank our officers, Zaina Mohd \nYusof and Norhayati Hatim for the data entry. We \nwould also like to thank Dr Wan Syameen for her \nassistance in obtaining references for this paper. \nThe authors would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nReferences\n\n\n\n1.  NAK Jailani, A Johar, SH Hussein. Pattern of Skin \nDiseases in A Tertiary Dermatology Centre in Malaysia. \nMJD 2001;14:23-30.\n\n\n\n2.  Ogunbiyi AO, Daramola OO, Alese OO. Prevalence of skin \ndiseases in Ibadan, Nigeria. Int J Dermatol 2004;43:31\u20136.\n\n\n\n3.  Darren D Lynn, Tamara Umari, Cory A Dunnick, Robert \nP Dellavalle. The epidemiology of acne vulgaris in late \nadolescence. Adolesc  Health  Med Ther 2016;7:13\u201325.\n\n\n\n4.  Bhate K, Williams HC. Epidemiology of acne vulgaris. Br \nJ Dermatol. 2013;168:474\u201385.\n\n\n\n5.  A Mohd Affandi, FA Alias, N Baharum, A Johar. Summary \nof the Malaysian Psoriasis Registry Result (2007-2014). \nPersatuan Dermatologi Malaysia News 2015;11:11-2.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 25\n\n\n\nORIGINAL ARTICLE\n\n\n\nCardiac Abnormalities in Psoriasis\n\n\n\nPriya Gill1, Adv M Derm, Min Moon Tang2, Adv M Derm, Adawiyah Jamil3, Adv M Derm, Siti Zulfa Zulkifli, MRCP, \nNoor Zalmy Azizan2, Adv M Derm\n\n\n\n1Manipal Hospitals, Klang, Selangor, Malaysia \n2Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n3Dermatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Malaysia\n4Department of Medicine, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nPsoriasis is considered an independent cardiovascular risk factor. This study aims to determine and \ndescribe the cardiac abnormalities using echocardiography and electrocardiography in patients with \nplaque psoriasis. \n\n\n\nMethods: \nThis is a case control study of psoriasis patients with no previous history of cardiac disease. One \nhundred and thirty-five patients attending the Dermatology Clinic, Hospital Kuala Lumpur were \nrecruited over one year. A full history, physical examination, echocardiogram and electrocardiogram \nwere done. The controls were 135 age and sex matched healthy individuals.\n\n\n\nResults: \nThe psoriasis group had a significantly higher body mass index and blood pressure. The echocardiogram \nshowed that the mean left ventricular wall diastolic thickness, aortic annulus diameter and isovolumetric \nrelaxation time of the left ventricle was significantly prolonged, and a higher prevalence of tricuspid \nregurgitation in psoriasis. On the electrocardiogram, more psoriasis patients had left ventricular \nhypertrophy, ischaemia and right bundle branch block. The QRS interval was significantly shorter \nin these patients. The tricuspid valve E/A ratio was significantly lower in patients with psoriatic \narthropathy. The mitral valve early filling velocity deceleration time, tricuspid valve E/A ratio and \nQRS interval were significantly higher among systemic therapy na\u00efve patients. The mean mitral and \ntricuspid valve E/A ratio were significantly lower; and the mean ascending aorta diameter larger, in \nthose with psoriasis for more than ten years. \n\n\n\nConclusion: \nPsoriasis may be associated with an increased risk of cardiac abnormalities suggesting diastolic \ndysfunction and tricuspid regurgitation. These abnormalities appear to be related to disease duration. \nFurther studies employing newer echocardiographic and cardiac imaging techniques are needed to \nvalidate this.\n\n\n\nKey words: Psoriasis, cardiovascular disease, cardiac abnormalities, echocardiogram, electrocardiogram\n\n\n\nIntroduction\nPsoriasis is one of the commonest chronic skin \ndiseases worldwide. It is an immune mediated \ninflammatory, papulo-squamous, immune disease \nwith cutaneous and skeletal manifestations,1 \n\n\n\nCorresponding Author\nDr Priya Gill\nManipal Hospitals Sdn Bhd, Lot 83211, Persiaran Batu \nNilam/KS 6, Bandar Bukit Tinggi 1, 41200 Klang, \nSelangor, Malaysia\nEmail: drpriya74@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3826\n\n\n\nwhich is characterized by cycles of remission and \nexacerbations.2 Before the 1980s, psoriasis was \ndefined as an inflammatory cutaneous disorder.3 \nIn recent years; substantial advances have been \nmade in elucidating the molecular mechanisms \nof psoriasis. The concept of an inflammatory \nautoimmune component has recently emerged \nbased on the observation of psoriasis association \nwith diseases like Crohn\u2018s, ulcerative colitis and \ngiant cell arthritis.3\n\n\n\nThe association of psoriasis with cardiovascular \ndisease has been well established and received much \nattention over the last 40 years or so. Possible risk \nfactors and relative mechanisms responsible for the \nepidemiological associations between CV disease \nand psoriasis include the concomitant traditional \nCV risk factors e.g. hypertension, diabetes mellitus, \nobesity and dyslipidaemia, which are part of the \nmetabolic syndromes that place the patient at a \nhigher risk for CV disease.4 Interestingly, there is \nan increased prevalence of metabolic syndrome in \npsoriasis patients that is independent of psoriasis \nseverity. Epidemiological data from large population \nbased studies found an increase in the prevalence \nof both conventional and non conventional \ncardiovascular risk factors in patients with psoriasis.\n\n\n\nIn addition, the treatment of psoriasis, especially \nsevere psoriasis, may cause side effects that increase \ncardiovascular risks. Retinoids have been shown to \nincrease serum triglycerides, and to reduce insulin \nsensitivity and high-density lipoprotein cholesterol. \nCyclosporine may induce or worsen arterial \nhypertension and alter lipid metabolism.5\n\n\n\nHowever, in a patient with psoriasis and no \nknown cardiovascular disease, are other cardiac \nabnormalities and cardiac conduction defects \npresent? To date, very scant data is found regarding \nmyocardial, valvular and conduction pathologies in \npsoriasis with no available data in Asian patients. \nThis study hopes to shed some light in this aspect. \nThus, we aim to study the cardiac abnormalities in \npatients with psoriasis using electrocardiography \nand echocardiography compared to healthy controls.\n\n\n\nMaterials and Methods\nThis is a case control study conducted in Hospital \nKuala Lumpur that compares cardiac abnormalities \nin patients with plaque psoriasis versus healthy \ncontrols from August 2010 to August 2011. We \nrecruited patients aged 18 years and above with \nplaque psoriasis diagnosed by dermatologists. \n\n\n\nPregnant patients, smokers and patients with any \nform of pre-existing diagnosed cardiac diseases, \ndiabetes mellitus, thyroid disorders, obesity, \nconnective tissue disease, hepatic disorders, renal \nfailure and dyslipidaemia were excluded. Controls \nwere age-and-sex matched subjects with no \npersonal or family history (in a 1st degree relative) \nof psoriasis. After obtaining consent, recruited \npatients and controls were interviewed; followed by \nphysical examination. The severity of psoriasis was \nassessed using body surface area (BSA) affected by \npsoriasis; Psoriasis area and severity index (PASI) \nand Physician Global Assessment (PGA). The \ncapillary blood sugar was measured, and 12-lead \nelectrocardiogram and an echocardiogram were \ndone.\n\n\n\nAll data was analyzed using SPSS version 16.0. \nNormality was tested using the Kolmogorov-\nSmirnov test. Parametric data are expressed as mean \n\u00b1 SD. Non-parametric data are expressed as median \n+ tertiles. Precision of measurement is calculated \nas 1.96 times the standard deviation of repeated \nmeasurements (expressed as percentage of the sample \nmean value). Descriptive statistics are provided for \nthe numerical and categorical variables using mean \n\u00b1 SD and percentage distribution where appropriate. \nSub-group analyses used the Mann-Whitney U-test; \nfor normal distribution, the Student\u2019s t-test were \nused to compare numerical variables across groups. \nThe chi-squared test and Fisher\u2019s test were used \nto compare percentage distributions across levels \nof nominal variables. The Pearson correlation was \nused to assess the relationship between numerical \nvariables, and the Spearman correlation was used \nto measure the relationship between categorical \nvariables. Comparison of the accuracy and precision \nof each method is calculated using the Student\u2019s t \ntest. A p value < 0.05 is considered as significant.\n\n\n\nResults\nThe study population consisted of 135 patients with \npsoriasis and 135 control subjects with no     known \nmedical problems. The control subjects who fulfilled \nthe inclusion and exclusion criteria were invited to \nparticipate in the study after they were matched for \nage and gender with the enrolled psoriasis patients. \nThe demographic data and clinical characteristics \nof both groups are shown in Table 1. The majority \nof the subjects were males (55.5%). The mean age \nwas 40.24 \u00b1 12.9, range 20-80 years in the psoriasis \ngroup and 40.55 \u00b1 12.7, with range 20-79 years in the \ncontrol group. The highest number of subjects was \nin the younger age group of less than 40 (56.3%), \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 27\n\n\n\nfollowed by the middle age group of between 41-60 \nyears old (36.3%) and the least number of patients \n(7.4%) were more than 61 years old. The majority \nethnic groups in both the psoriasis and control groups \nwere Malays. There was no significant difference \nin the random capillary blood sugar between the \npsoriasis patients and the control group. However, \nthe psoriasis group had a significantly higher body \nmass index, systolic blood pressure and diastolic \nblood pressure compared to controls (p = 0.01, 0.02 \nand 0.00 respectively).\n\n\n\nTable 2 summarizes the management of the 135 \npatients with psoriasis. At the time of recruitment, \n108 (80%) of patients were on topical treatment alone \nand the other 27 patients were on the combination \nof topical treatment with either phototherapy or a \nsystemic agent. One patient was on a combination of \ntwo systemic agents (Leflunomide and Etanercept) \nand one patient was on Ustekinumab. In the past, \n37% of patients (50 patients) had been on systemic \ntreatment. Of these 50 patients, 13 patients had been \non more than one systemic treatment. The systemic \nagents used in these patients included methotrexate, \ncyclosporine, sulphasalazine, adalimumab, \netanercept and acitretin.\n\n\n\nThe electrocardiogram and echocardiogram findings \nof the study populations are shown in Table 3 and 4. \nThere were no abnormalities in terms of rhythm in \neither group. All patients were in sinus rhythm with \nno statistically significant difference noted between \nthe two groups in term of the prevalence of atrial \nor ventricular premature beats. The QRS interval \nwas significantly shorter in the patient group. \nThe prevalence of left ventricular hypertrophy, \nischemic changes and right bundle branch block \nwas significantly higher in the psoriasis group. In \nthis study, ischemic changes on ECG were defined \nas ST elevation, ST depression or T wave inversion \nin contiguous leads with or without the presence of \nQ waves.\n\n\n\nThe mean left ventricular posterior wall diastolic \nthickness was significantly longer in the psoriasis \ngroup as was the aortic annulus diameter. The \nisovolumetric relaxation time of the left ventricle \nwas also significantly prolonged in the psoriasis \ngroup compared to controls. There was no \nstatistically significant difference in the prevalence \nof right or left ventricular diastolic dysfunction \nbetween the two groups. Similarly, there was no \nstatistically difference in the E/A ratio of both \nthe mitral and tricuspid valves between the two \n\n\n\ngroups. There was no pulmonary valve pathology \nnoted in either group. The prevalence of tricuspid \nvalve regurgitation was significantly higher in the \npsoriasis group. Otherwise, no other statistically \nsignificant differences were noted in terms of \nvalvular pathology between the psoriasis and \ncontrol group.\n\n\n\nThe study population was then divided into three \ngroups based on age (\u2264 40, 41-60 and \u2265 61) and \nthe above analysis of the electrocardiogram and \nechocardiogram modalities was carried out. This \nwas to ascertain if a particular age group of psoriasis \npatients was more at risk for cardiac abnormalities. \nAs age is an independent risk factor for cardiac \ndisease especially ischemic heart disease, the cases \nand controls are matched in terms of age. In the \nstudy population aged \u2264 40, there is a statistically \nsignificant higher prevalence of tricuspid \nregurgitation in the psoriasis group. The prevalence \nof mitral regurgitation and aortic regurgitation was \nnot significantly different between the two groups. \nThe only ECG parameter to note is the QRS interval. \nThis was significantly higher in the control group.\n\n\n\nIn the study population aged 41-60, diastolic \ndysfunction of the right ventricle was significantly \nmore prevalent in the psoriasis group compared \nto controls. The aortic annulus diameter was \nsignificantly larger in the psoriasis group as well. The \nprevalence of all other echocardiogram parameters \nwas not significantly different between psoriasis \npatients and the control population in this age \ngroup. No significance difference in the prevalence \nof valvular pathologies was found between patients \nand controls too. The only statistically significant \nparameter on the ECG of this age group was the \nprevalence of ischaemic changes. The prevalence of \nischemic changes was higher in the patient group.\n\n\n\nIn the study population aged 60 years and above, \nthere was no difference in term of the ECG findings. \nHowever, it was noted that patients with psoriasis \nhad significant higher posterior wall diastolic \nthickness, longer mitral valve early filling velocity \ndeceleration time, longer mitral valve isovolumetric \nrelaxation time and a larger aortic annulus diameter. \nThe other echocardiographic parameters were not \nsignificantly different from the controls.\n\n\n\nWith regards to disease severity, there was no \nstatistically significant difference between the BSA \n(affected by psoriasis) and PASI of patients with any \nECG and echocardiographic abnormalities as shown \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3828\n\n\n\nin Table 5. Nevertheless, there was a weak positive \ncorrelation between the BSA (affected by psoriasis) \nand the left atrial diameter and the posterior wall \nthickness on echocardiogram. The coefficients of \ndeterminations (R2) were 0.039 (Pearson product-\nmoment correlation test) and 0.040 respectively. \nThere was a weak positive correlation between \nthe PASI score and the left atrial diameter together \nwith left ventricular posterior wall thickness on \nechocardiogram (R2=0.067 and 0.037 respectively). \nThere was also a weak negative correlation between \nthe PASI score and the ejection fraction (R2=0.029).\n\n\n\nThere was a weak positive correlation between \nthe disease duration and PR interval on the ECG \n(R2=0.03); isovolumetric relaxation time of the left \nventricle (R2=0.031); and ascending aorta diameter \n(R2=0.044) on echocardiogram. Nevertheless, \nthere was a weak negative correlation between the \ndisease duration and mitral E/A ratio (R2=0.053). \nThe mean mitral valve early filling velocity (E); \nmean mitral E/A ration; and mean tricuspid E/A \nratio were significantly longer in patients with a \ndisease duration of \u2264 10 years [0.72 (SD 0.16) \ncm/s vs 0.65(SD 0.18) cm/s, p = 0.01; 1.51(0.46) \nvs 1.29(0.45, p=0.01; and 1.54(0.43) vs 1.37(0.44), \np=0.02 respectively]. However, the ascending aorta \ndiameter was significantly longer in the group with \na disease duration > 10 years [25.5(3.3) mm vs \n24.1(3.1) mm, p=0.01] (Table 6).\n\n\n\nThere were 50 patients (37%) who had received \noral systemic therapy for psoriasis in the current \ncohort.  The only statistically significant finding \non the ECG was the mean QRS interval which \nwas longer in the patients who had never received \nsystemic therapy (76.2ms vs 68.0ms; p=0.04). \nThe mean mitral valve early filling velocity \ndeceleration time was significantly higher (193.9ms \nvs 167.0ms; p=0.03) and the tricuspid valve E/A \nratio was significantly lower (1.4 vs 1.5; p=0.03) \nin group that never received systemic therapy.  The \nother echocardiogram parameters did not show a \nsignificant difference between the two groups.\n\n\n\nOf the 135 patients with psoriasis, 40 patients \nhad some form of psoriatic arthropathy. No \nstatistically significant difference was seen between \npatients with and without arthropathy in terms \nof electrocardiogram parameters. The tricuspid \nvalve E/A was significantly lower in the patients \nwith arthropathy (1.3 vs 1.5; p=0.05). No other \nechocardiogram parameters significantly differed \nbetween the two groups of psoriasis patients.\n\n\n\nDiscussion\nPsoriasis is now viewed as a systemic inflammatory \nprocess that may increase the prevalence of \nother co-morbidities in this patient population. \nA considerable body of evidence supports the \nassociation between psoriasis and cardiovascular \ndisease. However, the data on cardiac abnormalities \nis limited. The studies that have been done so far \nhave been in Western and Far Eastern populations \nlike the Jewish, Turkish and Europeans. This study \naims to explore the association between psoriasis \nand cardiac abnormalities in a multi ethnic Asian \npopulation. Limitations of the studies so far have \nbeen in terms of; patient number whereby most \nstudies have less than 100 patients with psoriasis,6-15 \n\n\n\nor no control group.16 One study was retrospective.17 \nSome of the studies only included patients less than \n60 years old6,8,10,18 whereas our study includes those \nfrom age 18 to 80. To minimize bias, our patient \npopulation was matched in terms of age and sex.\n\n\n\nInterestingly, although obese patients were excluded, \nthe mean BMI of the psoriasis group is significantly \nhigher than the control group in this study. This is \nconsistent with many other studies that have shown \nthat, compared to the general population; patients \nwith psoriasis are more frequently overweight and \nobese.19-22\n\n\n\nBoth the systolic and diastolic blood pressure \nwas noted to be significantly higher in the \npsoriasis group. This was in keeping with several \nepidemiologic studies that have shown hypertension \nto be a common co-morbidity in patients with \npsoriasis.19,23-25 The higher the blood pressure, the \ngreater is the risk of stroke, myocardial infarction, \nheart failure and kidney failure.26 Cohen et al27 in \ntheir large scale study that looked at more than \n12,000 patients; attributed the association between \npsoriasis and hypertension  to angiotensin II, a \nproduct of angiotensin-converting enzyme (ACE) \nthat regulates vascular tone and stimulates the \nrelease of pro-inflammatory cytokines. They also \ndiscussed the possible role of oxidative stress, \nwhich is present in all acute and inflammatory \nstates including psoriasis. Oxidative stress may \nplay a role in hypertension by destructive effects of \nreactive oxygen species, damaging endothelium-\ndependent vasodilatation. The association between \npsoriasis and hypertension may also be attributed to \nthe production of endothelin-1, which is produced \nby keratinocytes as an autocrine growth factor. \nEndothelin-1 is a potent vasoconstrictor and may \ncontribute to hypertension in psoriasis patients. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 29\n\n\n\nBonifati et al,28 reported that endothelin-1 was \nincreased in both sera and lesional skin of patients \nwith psoriasis, compared with controls. \n\n\n\nThe left ventricular posterior wall diastolic thickness \nrefers to the thickness of the left posterior wall at \nthe end of diastole and it normally ranges from \n7-11mm. This parameter positively correlates to left \nventricular mass and left ventricular hypertrophy \n(LVH).29 Although the value of this parameter was \nwithin normal range for both groups in our study, \nit was significantly higher in the psoriasis group. \nThis differs from the study by Biyik et al18 that \nshowed no significant difference between their \npsoriasis patient and control groups. This could \nbe due to the fact that all the patients in Biyik\u2019s \nstudy18 were younger with the oldest patient being \n55 years old. In our study, we further analyzed this \nparameter based on age groups and found that more \nspecifically, in the \u2265 61 age group, the mean left \nventricular posterior wall diastolic thickness was \nsignificantly higher in the psoriasis group compared \nto controls. Grossman et al30 demonstrated that the \nleft posterior wall diastolic thickness is an important \ndeterminant of left ventricular diastolic stiffness and \npressure, and that wall thickness appears to predict \ndiastolic stiffness independent of the presence or \nabsence of LVH. Hence, this suggests that psoriasis \npatients have increased diastolic stiffness of the left \nventricle compared to controls. This may possibly \nbe explained the higher incidence of myocardial \nfibrosis (due to systemic inflammation) or higher \nblood pressure amongst patients with psoriasis (as \ndemonstrated in our study and also by Biyik et al;18 \nin keeping with Akkoc et al.31 who demonstrated that \nleft posterior wall diastolic thickness is increased \nin hypertensives compared to controls. Therefore, \nthe author postulates that the positive correlation \nbetween the left ventricular wall diastolic thickness \n& the severity of disease study may be related \nto inflammation. In our current study, a weakly \npositive correlation between the PASI/BSA and \nthe left ventricular wall diastolic thickness was \ndemonstrated. A higher PASI score and a higher \npercentage of BSA affected by psoriasis suggest \nmore extensive disease that possibly translates to \nmore inflammation; hence the presence of larger \namounts of inflammatory mediators that contribute \nto diastolic stiffness of the left ventricle.\n\n\n\nThe principal method to diagnose LVH is \nechocardiography, where the thickness of the \nheart muscle can be measured. The ECG often \nshows signs of increased voltage from the heart in \n\n\n\nindividuals with LVH, but has high sensitivity and \nlow specificity. This is because the ECG criteria \nfor LVH, particularly those that are heavily reliant \non voltage criteria may result from abnormal \nthickening of the LV free wall or ventricular \nseptum, LV chamber dilatation or increased LV wall \ntension.32 Feld et al15 noted a higher prevalence of \nLVH on the ECG among patients with psoriatic \narthritis compared to controls in their study but \nthis difference was not statistically significant. The \nlarge scales study by Biyik et al18 also showed a \nstatistically significant higher prevalence of LVH \namong psoriasis patients compared to controls. \nThe prevalence of left ventricular hypertrophy \ndemonstrated by ECG in this study was significantly \nhigher in the psoriasis group compared to control \ngroup. One may argue that these could be false \npositive findings. Nevertheless, this ECG finding \nmay reflect early LVH that is not yet visible on \nthe echocardiogram. Moreover, the fact that left \nventricular posterior wall diastolic thickness as \nmentioned above positively correlates to left \nventricular mass and left ventricular hypertrophy \n(LVH) supports our theory that the ECG finding of \na higher prevalence of left ventricular hypertrophy \nin psoriasis patients was not merely a false positive. \nThis may be associated with the higher blood \npressures found in psoriasis patients than in controls. \nWhether high blood pressure levels in patients with \npsoriasis predisposes them to develop hypertension \nand left ventricular hypertrophy requires further \ninvestigation. The Framingham study, published \nin 1991, states that hypertension predisposes to \nsudden death caused by left ventricular hypertrophy. \nThe presence of left ventricular hypertrophy was \nassociated with a 5-year mortality rate of 33% in \nmen and 21% in women.33 The risk of sudden death \nin the presence of left ventricular hypertrophy was \ncomparable to that of coronary artery disease or heart \nfailure.34 Left ventricular hypertrophy identified by \nechocardiography (or features suggestive of early \nleft ventricular hypertrophy) may increase the risk \nof sudden cardiac death and pose an additional risk \nfor patients with psoriasis.18\n\n\n\nDiastolic heart failure is defined as a condition \ncaused by increased resistance to the filling of one or \nboth ventricles; this leads to symptoms of congestion \nfrom the inappropriate upward shift of the diastolic \npressure volume relation. Diastolic dysfunction \nresults in a decline in the performance of one or \nboth ventricles during the time phase of diastole. \nIt is characterized by elevated diastolic pressure \nin the left or right ventricle despite essentially \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3830\n\n\n\nnormal systolic function and ejection fraction.35 \nOn echocardiography, the peak velocity of blood \nflow across the mitral valve during early diastolic \nfilling corresponds to the E wave. Similarly, atrial \ncontraction corresponds to the A wave. From these \nfindings, the E/A ratio is calculated. Under normal \nconditions, E is greater than A and the E/A ratio is \napproximately 1.5. In early diastolic dysfunction, the \nventricular relaxation is impaired and, with vigorous \natrial contraction; the E/A ratio decreases to less \nthan 1.0. As the disease progresses, left ventricular \ncompliance is reduced, which increases left atrial \npressure and, in turn, increases early left ventricular \nfilling despite impaired relaxation. This paradoxical \nnormalization of the E/A ratio is called pseudo-\nnormalization. In patients with severe diastolic \ndysfunction, left ventricular filling occurs primarily \nin early diastole, creating an E/A ratio greater than \n2.30,36 The isovolumetric relaxation (IVRT) time is \nmeasured as the time between the closure of the aortic \nvalve and the opening of the mitral valve. Normally \nin adults, it is less than 100ms. The left ventricular \nearly filling velocity deceleration time (DT) is the \ntime taken from the maximum E point to baseline \nand is normally less than 200ms in adults.36,37 In \nearly diastolic dysfunction, a lengthening of the \ndeceleration time and isovolumetric time may be \nseen, without changes in early and late ventricular \nfilling velocities.38 This is an extremely important \npoint to guide prognostic stratification and treatment \nin these groups of patients.\n\n\n\nBiyik et al18 revealed that left ventricular diastolic \ndysfunction was significantly more common in \npatients with psoriasis than control subjects. In \na smaller study, Guven et al10 showed that the \nincidences of left ventricular diastolic dysfunction \nand was higher in 62 psoriasis cases compared with \nhealthy controls. Gunes et al8 also found a higher \nprevalence of diastolic dysfunction among psoriasis \npatients compared to controls.  In 1991, Rowe \nand coworkers reported the presence of diastolic \ndysfunction in 7 of 11 patients with psoriatic \narthropathy13. Saricaoglu et al12 have suggested that \nmild left ventricular diastolic dysfunction may be \nseen in patients with psoriatic arthropathy. \n\n\n\nIn our study, the overall prevalence of left \nventricular diastolic dysfunction was higher among \nthe psoriasis group compared to controls although \nnot statistically significant. However, our results do \nsuggest the presence of possible early left ventricular \ndiastolic dysfunction which has a statistically \nsignificant higher prevalence in the psoriasis group. \n\n\n\nThis is supported by a few of our results. Firstly, \nin our cohort of patients as a whole, the mean \nisovolumetric relaxation time is significantly longer \nin the psoriasis group. Secondly, in the older age \ngroup of \u2265 61 years old, the mean IVRT was  not \nonly significantly longer in the psoriasis group, but \nabnormal as well (>100ms).This suggests Grade 1 \nleft ventricular  diastolic dysfunction.36 A similar \nresult in the DT was noted in this age group as well. \nThe mean DT was not only significantly longer in \nthe psoriasis group, but abnormal as well (>200ms), \nagain suggesting Grade 1 left ventricular diastolic \ndysfunction.36\n\n\n\nHypertension and cardiac ischaemia are known to be \nthe most common causes of left ventricular diastolic \nheart failure.35 As mentioned previously, the mean \nblood pressure among the psoriasis patients in \nour study was higher than the controls. This may \nexplain the higher prevalence of left ventricular \ndiastolic dysfunction in our psoriasis patients, \nconcurring with Biyik et al.18 They suggested that \nthe significantly higher blood pressure levels in \ntheir group of psoriasis patients might partly explain \nthe significantly higher incidence of left ventricular \ndiastolic dysfunction detected. The other significant \nfactor in our cohort that may be contributing to left \nventricular diastolic dysfunction is ischaemia. We \nfound a significantly higher prevalence of ischemic \nchanges on the ECGs of our psoriasis patients \ncompared to controls. This is not surprising as it is \na well-established fact that psoriasis is associated \nwith both macrovascular and microvascular \ndisease, both of which contribute to myocardial \nischaemia.4,5,20,21,23,39-41 This was seen looking at the \npatient cohort as a whole and more specifically, in \nthe 41-60 age group. In our study subjects of \u2265 61 \nyears of age, although 4 out of 10 individuals in each \ngroup had left ventricular diastolic dysfunction, none \nhad ischemic changes on the electrocardiograms. \nThis could be due to the fairly small number of \nsubjects (only 20) aged \u2265 61 in our study .The other \npossibility is that hypertension or other factors may \ncontribute more to diastolic dysfunction in this age \ngroup rather than ischaemia. However, more studies \nthat look at this age group specifically are needed to \nsupport or refute this theory.\n\n\n\nThere have been reports of secondary amyloid \ndepositions in the myocardial interstitium, intra-\nmyocardial small vessels, cardiac conduction \nsystem and other heart structures in patients with \npsoriasis.42-45 These changes might also partly \nexplain the frequently observed echocardiographic \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 31\n\n\n\nabnormalities in patients with psoriasis, such as left \nventricular hypertrophy and left ventricular diastolic \ndysfunction. This aspect was not studied by us but \nmay be a contributing factor to bear in mind. Further \nstudies looking at this aspect will be helpful.\n\n\n\nIn terms of valvular disturbances, we found that \npatients with psoriasis had a higher prevalence \nof mitral valve prolapse, tricuspid regurgitation \nand aortic regurgitation compared to controls. \nThe only statistically significant result was that of \ntricuspid regurgitation; the prevalence of which \nwas significantly higher among psoriasis patients \ncompared to controls. This was noted more \nspecifically in patients\u2264 40 years old. However, the \nprevalence of tricuspid regurgitation was higher \nin all age groups of the psoriasis group compared \nto controls. Gunes et al. noted that 31.9% of \npatients with psoriasis in their study had tricuspid \nregurgitation as well but this was not statistically \nsignificant compared to controls.8 This is most \nlikely due to the fact that the number of controls \nin the study was less than half of the subjects. In \n2005, Gonzalez-Juanetey and colleagues also \nnoted a higher prevalence of tricuspid regurgitation \namong patients with psoriatic arthritis compared to \ncontrols.9\n\n\n\nWe postulate that the higher prevalence of tricuspid \nregurgitation in this study may be a surrogate to \nhigher pulmonary artery pressure among psoriasis \npatients. The Bernoulli equation applied to tricuspid \nregurgitation suggests that tricuspid regurgitation \nis a reflection of increased pulmonary artery \npressure.46 Nevertheless no patient in our study \nhad pulmonary hypertension (PH) based on the \nDoppler echocardiogram. On the echocardiogram, \nthe presence of pulmonary valve regurgitation in \ncombination with a tricuspid valve regurgitation \nflow of less than 25 mmHg/ sec indicates PH. \nThe actual pulmonary artery systolic pressure is \nmeasured by an invasive procedure using a Swan-\nGanz catheter that is beyond the scope of this \nstudy. Gunes et al found an increased frequency \nof mild pulmonary hypertension in otherwise \nhealthy, asymptomatic psoriasis patients to controls, \nsuggesting that patients with psoriasis may have a \nmean pulmonary artery pressure that is higher than \ncontrols, albeit not reaching the stage of pulmonary \nhypertension yet.8 However, further studies that \nmeasure the actual pulmonary artery pressure are \nneeded to confirm this hypothesis. This is further \nsupported by the finding in our study of a statistically \nsignificant higher prevalence of right ventricular \n\n\n\ndiastolic dysfunction among psoriasis patients \naged 41-60 compared to controls. Faludi et al \ndemonstrated that diastolic dysfunction of the right \nventricle may be a sign of stress-induced (or latent) \npulmonary hypertension.47 This means that patients \nwith psoriasis may have this form of pulmonary \nhypertension that was not detected at rest on routine \nechocardiography but may account for the findings \nof tricuspid regurgitation and right ventricular \ndiastolic dysfunction as mentioned. This may also \nexplain in part why the prevalence of tricuspid \nregurgitation was statistically significant compared \nto controls among the youngest group of patients \nstudied (\u2264 40 years old) whereas right ventricular \ndiastolic dysfunction showed up as statistically \nsignificant later on; in the middle aged patient group \nstudied, suggesting that tricuspid regurgitation may \nbe an early sign preceding right ventricular diastolic \ndysfunction and pulmonary hypertension.\n\n\n\nIt has been proposed that inflammatory mechanisms \ncould play a part in the genesis or progression \nof pulmonary hypertension (PH). Pulmonary \nhypertension is an increasingly recognized \ncomplication of rheumatic diseases, including \nrheumatoid arthritis and an inflammatory/\nautoimmune pathogenesis has been suggested. \nSimilar mechanisms may be responsible for the \nfinding of increased frequency of pulmonary \nhypertension in psoriasis patients.  The systemic \nnature of the inflammatory processes underlying \nthe pathogenesis of psoriasis may potentially \nresult in systemic involvement. Increased antigen \npresentation, increased cutaneous T lymphocyte \nactivity, interleukins and tumor necrosis factor-\u03b1 \nin the pathophysiology of psoriasis also cause \nendothelial dysfunction, an important mechanism \nin pathophysiology of PH. Increased procoagulant \nactivity and platelet activation in psoriasis are also \npotential mechanisms for PH Gunes et al.8\n\n\n\n \nThe valvular disturbances found in other studies \ndiffered from our slightly. Biyik et al found a \nstatistically significant more common prevalence of \nmitral valve prolapse and tricuspid valve prolapse \nin their study.18 These findings may be due to the \nhigher number of patients in their study i.e. 216 in \neach arm, allowing for perhaps a higher pick up \nrate of these anomalies; and the phenotype of their \npopulation compared to ours. There is a possibility \nthat valvular anomalies associated with psoriasis \nmay differ among different populations.  Guven \net al noted a higher prevalence of mitral valve \nregurgitation among psoriasis patients in their \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3832\n\n\n\nstudy but this was not statistically significant.10 \nMore studies looking at various populations and \nphenotype are needed to confirm this postulation.\n\n\n\nThe aortic annulus is a complex fibrous ring in the \nwall of the root of the aorta. The normal absolute \ndiameter of the aortic annulus is 17-25cm.48 \nEnlargement of the aortic root (due to any cause) will \nresult in enlargement of the aortic annulus, and in \nsevere cases, lead to aortic regurgitation. We found \nthat although still within normal limits, the aortic \nannulus diameter was significantly larger in the \npsoriasis group compared to controls. This was noted \nlooking at the study population as a whole; and in the \n41-60-year-old age group as well as those more than \n61 years old i.e. in patients those above 41 years old. \nThis may be due to the significantly higher blood \npressure found in the psoriasis patients compared to \ncontrols or it may be a common non specific finding \nof psoriasis as chronic inflammatory disease; or a \ncombination of both factors. It is interesting to note \nthe prevalence of aortic regurgitation was higher in \nthe psoriasis group (9 patients) compared to only 3 \ncontrol subjects. Aortic regurgitation is related to \nabnormalities in the ascending aorta which in our \nstudy is reflected by the higher mean aortic annulus \ndiameter among psoriasis patients. To the best of \nthe author\u2019s knowledge, no other studies regarding \npsoriasis and cardiac abnormalities have commented \non the aortic annulus diameter. There is a need for \nfurther studies involving larger case series to clarify \nthe results of our study.\n\n\n\nThere is scarcity of data on heart rate abnormalities \nand conduction disturbances in psoriatic patients, \ndespite quite a clear connection between these \nparameters and chronic inflammatory processes.49,50 \nMarkuszeski et al found a mean faster heart rate \nof 73 \u00b1 6 beats /min in their psoriasis patients \ncompared to 63 \u00b1 4 beats per minute in the control \ngroup7. This difference was statistically significant. \nThe sample size of only 64 patients in total was \nprobably a limiting factor in their study. All patients \nin our study, however, were in sinus rhythm and \nmean heart rate was similar in both the groups. Feld \net al15 noted similar findings in their cohort of 92 \npatients with psoriatic arthritis and 92 controls as \ndid Gunes et al in their study.8 \n\n\n\nThere were twice as many patients with right bundle \nbranch block (RBBB) compared to controls in the \nstudy by Feld et al15 but this difference was not \nstatistically significant. This was perhaps due to \ntheir smaller sample size of 184 compared to 270 \n\n\n\nsubjects in our study. One can argue that RBBB \ncould be considered a normal variant based on \n12-lead ECG when there were no other significant \ndifferences in conduction abnormalities between \nthe groups in our study. RBBB occurs when the \nelectrical impulse from the bundle of His does \nnot conduct along the right bundle branch. The \nright bundle branch is vulnerable to disturbance \nfor two thirds of its course when it is near the sub-\nendocardial surface and can be compromised by \nmyocardial ischaemia, myocardial inflammation, \nhigh blood pressure and increased right ventricular \npressure. In the author\u2019s opinion, these contributing \nfactors could account for the significantly higher \nprevalence of RBBB among the psoriasis group \nin our study. In the group of 22 patients with \npsoriatic arthritis, Carvalho et al reported a higher \nincidence of premature atrial beats; however, this \ngroup observed both atrial tachy- and bradycardia \nin the examined group of patients.6 Markuszeski et \nal did not note a higher prevalence of conduction \ndisturbances in their 32 psoriasis patients compared \nto controls.7 Ozturkan et al noted an unspecified \nintra-ventriculary conduction disorder on the ECG \nof one of their 36 psoriasis patients compared to \nnone in the control group.11 \n\n\n\nThe QRS complex corresponds to the depolarization \nof the right and left ventricles. Shortening of the QRS \ncomplex occurs either in tachycardia or presence of \nan accessory conduction pathway in the ventricles.51 \nAlthough within normal range, the QRS complex \nduration was significantly shorter in the psoriasis \ngroup compared to controls in the current study, \nparticularly those younger than 40 years old. This \nfinding could be explained easily by a higher mean \npulse rate among the psoriasis patients, especially \nthose less than 40 years of age. The mean pulse rate \nof patients aged 41-60 was similar in both groups \ni.e. around 72 and hence no difference was seen \nin the QRS complex duration. In the oldest cohort \nof patients (\u2265 61 years old), the mean pulse rate \nwas higher in the psoriasis group but there was no \nstatistical difference noted in the QRS complex \nduration between groups. Further research that \nencompasses 24 hour ambulatory electrocardiogram \nholter monitoring and electrophysiological studies \nmay shed more light on this matter and would \ncertainly be very interesting. To the best of the \nauthor\u2019s knowledge, no other similar study to date \nhas noted a shorter QRS duration among psoriasis \npatients. Feld et al found no statistically significant \ndifference with respect to the QRS interval among \ntheir cohort of 92 psoriatic arthritis patients \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 33\n\n\n\ncompared to controls.15 However the major finding \nof their study was a statistically significant longer \nPR interval in the patients with psoriatic arthropathy \n(PsA) compared to controls. The PsA patients mean \nPR interval was found to be 5.5% longer compared \nto controls. They postulated that there was subtle AV \nnode pathology in psoriatic arthritis, most likely due \nto inflammation. In our study, the mean PR interval \nwas longer in the psoriasis group (149.2 \u00b1 22.2 ms) \nbut this was not statistically significant compared to \ncontrols. \n\n\n\nThe inflammatory character of psoriatic \nabnormalities leads to excessive Th-1 type \ncytokines that exert systemic effects and thus could \ninduce arrhythmias, conduction disturbances and \ntachycardia, which are regarded as non-specific \nresponse to inflammatory processes. Laboratory \ndata revealed pro-arrhythmic effect of some \ncytokines (IL-1, IL-2, and IL-3) and TNF-\u03b17. It \nshould be stressed that the innate inflammatory \ncytokine TNF-\u03b1 is of prime importance as an inducer \nof psoriasis.52 TNF-\u03b1 and its receptors exert toxic \neffects on cardiomyocytes. Up regulation of TNF-\u03b1 \ntogether with down regulation of its receptors is \nobserved in cardiac insufficiency. Patients with \ncardiac disease have increased TNF-\u03b1 levels in \nthe circulation. Animal studies have confirmed a \nrelationship between TNF-\u03b1 and supraventricular \narrhythmias. Some researchers demonstrated a \ncorrelation between C-reactive protein level, IL-1 \nand TNF-\u03b1 and atrial fibrillation incidence.53,54 \nIt could be speculated that our observation of \nincreased incidence of atrial premature beats \nin psoriatic patients could predispose to further \natrial fibrillation development. An inflammatory \nbackground of ventricular arrhythmias was reported \nby Kowalewski et al.55 This group demonstrated \na positive correlation between TNF-\u03b1 levels and \nventricular arrhythmias. This may explain the \nincreased prevalence of ventricular premature beats \nin our psoriasis population compared to controls.\n\n\n\nThe authors are not surprised to find no complex \nforms of arrhythmia in psoriasis patients in our \nstudy. This is because a special group of patients \nwas selected i.e. relatively young (mean age \n40 years) and with negative personal history of \ncardiovascular diseases. Based on the obtained \nresults, it seems important to include in further \nstudies a higher number of the older population \nof psoriatic patients and carrying out a 24-hours \nambulatory electrocardiogram holter monitoring or \na rhythm card monitoring.\n\n\n\nThe electrocardiogram results noted in our study \ndo strongly suggest that the active inflammatory \nprocesses observed in psoriasis seem to exert \ntheir influence on increased heart rate and cardiac \nconduction abnormality development in psoriatic \npatients. However, to confirm the above findings, \nfurther studies on larger groups of psoriatic \npatients presenting different types of the disease are \nmandatory.\n\n\n\nBiyik et al18 found no associations between the \nclinical and echocardiographic abnormalities and \nthe PASI scores of the patients.18 On the other \nhand, Marcuszeski et al found a positive correlation \nbetween the PASI and heart rate in their small cohort \nof 32 patients.7 Unlike their study, there was no \ncorrelation noted between the heart rate and PASI \nscores or BSA affected in our study. This is probably \ndue to the much higher number of patients (more \nthan four times) in the current study. Our study \nfound a weakly positive correlation between the \nPASI scores with the left atrial diameter and the left \nventricular posterior wall diastolic thickness on the \nechocardiogram. A similar correlation was noted for \nthe affected BSA as well. Thus, it could be regarded \nas a useful measure of the systemic inflammatory \nprocess intensity. So, the positive correlations \ndescribed above could result from the above \nextrapolation. There was a negative correlation of \nPASI with the ejection fraction, suggesting that a \nhigher severity of inflammation may result in the \ncompromise of both the structural and functional \ncomponents of the left side of the heart. The author \npostulates that the reason for this may be due to the \nthicker muscle layer of the left heart, rendering it \nmore susceptible to insult. The other contributing \nfactor could be that increased inflammation may \nlead an increase afterload and increased systemic \nvascular resistance, resulting in increased diastolic \nventricular stiffness and a compromised ejection \nfraction. To overcome the increased diastolic \nstiffness, there is compensatory dilatation of the \nleft atrium. However, further studies should be \nencouraged to confirm that. The correlation between \nthe PASI/BSA and the above discussed abnormalities \nis weak. Therefore, clinicians must not rely on the \nPASI or BSA alone as a tool to identify the psoriasis \npatient group at a higher risk of developing cardiac \nabnormalities.\n\n\n\nAbout a third of our patients (37%) had received \nsystemic therapy over the course of their disease. \nThe prescription of systemic therapy in psoriasis is \nusually reserved for more severe disease. Hence, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3834\n\n\n\nwe would extrapolate that the patients who received \nsystemic therapy had more severe disease and more \nsystemic inflammation; resulting in a worse cardiac \nabnormality profile compared to those who have \nnever been on systemic therapy. Surprisingly, our \nresults revealed otherwise. The mitral valve early \nfilling velocity deceleration time was significantly \nlonger in the subgroup that had never been on \nsystemic therapy, suggesting possible very early \ndiastolic dysfunction among these patients. \nMoreover, there was not a single case of diastolic \ndysfunction reported on the echocardiogram of \npatients who had been on systemic therapy. In the \ngroup that had never been on systemic therapy, \ndiastolic dysfunction was seen in 5 patients. We \ncould not explain this result; perhaps another \nstudy with higher number of psoriasis patients on \nsystemic therapy will answer better. Further studies \nare also needed to ascertain if perhaps, commencing \nsystemic therapy reverts cardiac abnormalities. \n\n\n\nSimilarly, the results suggest that patients who \nhave never been on systemic treatment may also \nhave a higher risk of right ventricular diastolic \ndysfunction. The mean tricuspid valve E/A ratio \nin this group of patients was significantly lower at \n1.4 compared to 1.5 in the other group. Although \nthe clinical relevance of this finding is questionable \nsince the absolute difference was small, the \nimportance of the observation is the implication \nof possible right ventricular dysfunction should \nthe E/A ratio become less than 1 in the future. \nTherefore, long term follow up is very important \nin these patients. Interestingly, the percentage of \npatients with right ventricular dysfunction detected \non echocardiography is the same for both groups. \nLastly, the QRS interval was significantly longer in \nthe systemic treatment na\u00efve group although in both \ngroups, it was within normal range. The simplest \nexplanation for this finding would be the mean \nlower pulse rate in the treatment na\u00efve group. Our \nresults suggest that diastolic dysfunction (both left \nand right sided) may have a higher prevalence in \nsystemic treatment na\u00efve patients. This is probably \nbecause of the anti-inflammatory property of the \nsystemic agents to the pericardium, myocardium, \ncardiac conducting system and both the macro and \nmicro vasculature of the cardiovascular system as \nwell. The most common systemic treatment used in \nour setting is methotrexate which is known to be a \npotent anti inflammatory agent.56 Methotrexate has \nbeen associated with reduced risk of cardiovascular \ndisease events in patients with rheumatoid arthritis \nby reducing disease specific outcomes and collateral \n\n\n\ndamage such as atherosclerosis.57 Prodanowich \net al showed that methotrexate therapy reduced \nthe incidence of vascular disease in veterans with \npsoriasis or rheumatoid arthritis, most likely due \nto its anti inflammatory effect.58 The resultant of \nother therapies as protection against cardiac disease \nhas not been fully investigated yet, but the author \nassumes that side effects like hypertension (seen \nwith cyclosporine) or dyslipidaemia (seen with \nacitretin) will be negatively influencing the anti-\ninflammatory effects. \n\n\n\nOnly about 30% of patients with psoriasis in our \ncohort had psoriatic arthropathy (PsA). The only \nparameter with a statistically significant difference \nbetween those with arthropathy and without was the \ntricuspid valve E/A ratio. The mean tricuspid valve \nE/A ratio in patients with arthritis is significantly \nlower i.e. 1.3 compared to 1.5 in the other group. \nThis may not be clinically significant as the absolute \nvalue is very small, but it may also represent very \nearly right ventricular dysfunction in this group of \npatients. An E/A ratio of less than 1 is consistent with \ngrade 1 diastolic dysfunction. Whether or not these \npatients will progress to grade 1 diastolic dysfunction \ncannot be predicted at this stage. Interestingly, 10% \nof patients with PsA had right ventricular diastolic \ndysfunction noted on the echocardiogram compared \nto 5% of patients without PsA, but this difference \nwas not statistically significant. To the best of the \nauthor\u2019s knowledge, there have been no previous \nstudies that have compared the tricuspid valve \nE/A ratio between patients with and without joint \nmanifestations of psoriasis. However, clinicians \nmanaging PsA patients should be aware of the \nabove results. Symptoms suggestive of \u201cpre\u201d right \nheart failure warrant an early cardiology referral.\n\n\n\nThe small study by Saricaoglu et al consisting of 21 \npatients with psoriatic arthropathy found that mild \nleft ventricular diastolic dysfunction may accompany \nPsA and was related to the duration of psoriasis.12 No \nmention was made about right ventricular diastolic \ndysfunction. Rowe et al also reported lower mitral \nE/A ratios consistent with diastolic dysfunction in 11 \nPsA subjects compared to controls.13 They postulated \nthat the most likely cause of these abnormalities \nwas an increased connective tissue deposition in \nthe myocardium. Gonzalez-Juanetey et al assessed \nthe prevalence of echocardiographic and Doppler \nabnormalities in 50 PsA patients without clinically \nevident cardiovascular manifestations or classic \natherosclerosis risk factors and compared them \nto controls.9 There were no significant differences \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 35\n\n\n\nbetween both groups.\n\n\n\nAs mentioned above, in our study, the overall \nprevalence of left ventricular diastolic dysfunction \nwas higher among the psoriasis group, with or \nwithout PsA; compared to controls. Our results also \nsuggest the presence of possible early left ventricular \ndiastolic dysfunction which has a statistically \nsignificant higher prevalence in the psoriasis group \ncompared to controls. Hence, indirectly perhaps, \nour results do somewhat concur with previous \nstudies by Saricaoglu et al12 and Rowe et al.13 The \npatient selection by Gonzalez-Juanetey et al might \nhave contributed to their results.9 They selected \npatients with PsA who were actively being treated \nby the rheumatology team in their hospital for the \ndisease. As we know, most DMARDS and NSAIDs \nresult in reduced inflammation which is believed to \nbe the main culprit in the pathogenesis of cardiac \nabnormalities in psoriasis. The active management \nof the arthritis most likely led to reduced systemic \nas well as cardiac inflammation which then resulted \nin no significant findings on the echocardiogram \nbetween the two groups.\n\n\n\nAnother study with a similar design to the current \nstudy i.e. looking at a small cohort of patients with \npsoriasis and comparing those with and without \narthropathy was done by Pines et al.14 Most of \ntheir 25 PsA patients had peripheral joint disease, \nsimilar to our cohort. Axial disease was present in \n12% of their cohort and 10% of ours. They found \nthat 56% of their patients with PsA had mitral valve \nprolapse (MVP). In our study however, no PsA \npatient had mitral valve prolapse compared to 2.1% \nof patients without PsA. MVP was present in 6.4% \nof their psoriatic patients without arthritis. These \nfindings suggest that in their population as a whole, \nthe prevalence of mitral prolapse is higher. Some \nstudies have estimated the prevalence of MVP in the \ngeneral population at 5-15% or even higher59,60 but \nmost of these studies have been done in Caucasian \npopulations with a different geno-phenotype \ncompared to our population. In addition, no aortic \nvalve lesion were detected in their cohort of patients \nwhere as we found aortic regurgitation in 10% of \nPsA patients and 5.3% of patients without PsA. This \nfurther leads the author to postulate that there may \nbe a geno-phenotypic element that influences the \ndevelopment of valvular problems; in addition to \nthe chronic inflammatory state of psoriasis.\n\n\n\nPatients with PsA have increased HLA-B locus \nantigens, including B27. The presence of HLA-B27 \n\n\n\ncorrelates best with axial arthritis involvement. \nThe cardiac manifestations of the prototypical B27 \narthropathy include aortitis and conduction system \ndisorders.15 Bergfeldt et al61 postulated that the \nHLA-B27 antigen itself may be pathogenic to the \ndevelopment of conduction system abnormalities. \nFeld et al, in their study of cardiac conduction \ndisturbances of psoriasis arthritis patients; noted \na significantly longer PR interval in patients with \nPsA compared to controls15. The study has identified \nthe possible subtle AV node involvement in PsA as \nobserved by the prolonged PR interval. The mean PR \ninterval of the PsA patients in our study was noted to \nbe longer than the patients without PsA but this was \nnot statistically significant. Biyik et al18 noted that \nlonger disease duration was significantly associated \nwith (i) a higher incidence of left ventricular diastolic \ndysfunction; (ii) a higher systolic blood pressure and \n(iii) a higher diastolic blood pressure. There were \nno other significant associations between psoriasis \ndisease duration and other echocardiographic or \nclinical abnormalities in their study. Saricaoglu et \nal also showed that the incidence of left ventricular \ndiastolic dysfunction was significantly related to the \nduration of the disease.12 Gunes et al on the other \nhand did not observe any significant correlations \nbetween the disease duration and abnormalities \nnoted on the echocardiogram or 24 hour ambulatory \nholter monitoring in their study.8 Gonzalez-Juanetey \net al found no correlation between disease duration \nand diastolic dysfunction in their study either.9 \nAgain, the findings were limited by the small patient \nnumbers. Markuszeski et al commented that there \nwas no correlation between psoriasis duration and \narrhythmia incidence in their study.7 Feld et al found \nno correlation between the PR intervals on the ECG \nwith disease duration in their cohort of 92 patients \nwith psoriatic arthritis.15 Our study identified a \nweak positive correlation between the duration of \ndisease and the PR interval on the ECG, the left \nventricular IVRT and the ascending aorta diameter. \nThe weak correlation suggests that the etiology \nof the prolonged PR interval is multifactorial and \nheterogeneous. Disease duration is most likely is \nminor contributing factor only.\n\n\n\nThe positive correlation between the ascending \naorta diameter and disease duration can most likely \nbe explained by the chronic inflammatory state as \nwell. Aortic dilatation, seen in aortitis is a known \ncomplication of chronic inflammation. However, \nother causes of aortic dilatation in patients with \npsoriasis include atherosclerotic disease and \ndegenerative dilatation.51 Degenerative dilatation \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3836\n\n\n\noccurs with age and it is a well-established fact \nthat psoriasis is associated with accelerated \natherosclerosis as well as macrovascular and \nmicrovascular endothelial dysfunction.5 The \npresence of this other factors may be the reason \nthat the correlation between disease duration and \nascending aorta diameter is weak.\n\n\n\nLeft ventricular IVRT and mitral valve E/A are \nmarkers of left ventricular diastolic dysfunction. \nThe increase of left ventricular IVRT and decrease \nof the mitral valve E/A as the duration of psoriasis \nincreases in our study is in keeping with the studies \ndone by Biyik et al18 and Saricaoglu et al.12 Both \nnoted that disease duration significantly correlates \nwith left ventricular diastolic dysfunction. \nHowever, the weak correlation found in our study \nagain suggests a multifactorial etiology of diastolic \ndysfunction in patients with psoriasis that includes \nhigh blood pressure, ischaemia and atherosclerosis.\n\n\n\nLooking at the actual duration of the disease, we \nfound a statistically significant difference of a few \nechocardiogram parameters between patients who \nhad psoriasis for duration of > 10 years compared \nto patients who had the disease for \u2264 10 years. \nOur results suggest that after >10 years of disease, \nthe risk of left and right diastolic dysfunction \nand aortic abnormalities is higher. Therefore, the \nauthor strongly recommends that the attending \ndermatologists or clinicians screen their patients \nwho have had psoriasis for more than ten years for \ncardiac abnormalities, even if symptoms are absent.\n\n\n\nWe acknowledge a few limitations in our study. \nAlthough the power of the study was achieved, this \nstudy still had a relatively small number of subjects, \nparticularly in the > 60-year-old age group. There is \nno assessment of cardiac abnormalities in patients \nless than 18 years old.\n\n\n\nInflammation indices were not measured and thus no \ndirect correlation based with disease activity could \nbe imputed. Regrettably the QT intervals were not \nstudied in this study. QT intervals represent global \nventricular electrical repolarization. Any slightest \nchange in QT interval signifies subtle subclinical \ncardiac manifestation in various conditions. A \n24-hours holter measurement or a rhythm card \nwould be a preferred method of assessing conduction \nabnormalities rather that an electrocardiogram. The \nuse of E and A wave measurement in echocardiogram \nis one of many techniques in determining diastolic \n\n\n\nfunction. Newer techniques such as Tissue Doppler \nImaging (TDI) or Strain and Strain rate are shown \nto be more accurate, either used on its own or in \ncombination.62-63 However, due to logistic reasons \nand limited resources, these could not be done for \nthis study but are excellent starting points for similar \nfuture research. \n\n\n\nConclusion\nOur study supports that the view psoriasis affects \nthe heart not only from an increased cardiovascular \nrisk point of view, but also in terms of structural \nand conduction abnormalities. Psoriasis may be \nassociated with high blood pressure, increased \nrisk of cardiac abnormalities suggesting diastolic \ndysfunction and tricuspid regurgitation. These \nabnormalities appear to be related to disease duration. \nThere may an association between the PASI and \nBSA scores with the left atrial diameter and the left \nventricular posterior wall diastolic thickness on the \nechocardiogram, perhaps suggesting that the higher \ndegree of inflammation in more severe disease may \ncontribute to the development of early diastolic \ndysfunction. Further studies employing newer \nechocardiographic and cardiac imaging techniques \nare needed to validate this. \n\n\n\nThe findings of this study regarding cardiac \nabnormalities in psoriasis and previous studies that \nhave established that psoriasis is an independent risk \nfactor for cardiovascular disease suggest to us that \ncardiac disease is a source of mortality and morbidity \nin patients with psoriasis. Therefore, dermatologists \nand physicians must be aware of the cardiac and \ncardiovascular manifestations of psoriasis. History \ntaking and a physical examination related to the \ncardiovascular system must be incorporated into \nconsultations and follow up appointments with \npsoriasis patients including a simple ECG. In \naddition, the authors recommend that the attending \ndermatologists or clinicians screen their patients \nwho have had psoriasis for more than ten years for \ncardiac abnormalities, even if symptoms are absent.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors hereby certify that, to the best of our \nknowledge, the work which is reported on in said \nmanuscript has not received financial support from \nany pharmaceutical company or other commercial \nsource and neither us nor any first degree relatives \nhave any special financial interest in the subject \nmatter discussed in said manuscript.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 37\n\n\n\nAcknowledgement\nThe author would like to thank the Deputy Director \nGeneral of Health, Malaysia (Datuk Dr Jeyaindran \nTan Sri Sinnadurai) for all his guidance and support. \n\n\n\nThe author would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nTable 1. Demographic data and clinical characteristics of the study population.\n\n\n\nTable 2. Management of the psoriasis patients (n=135).\n\n\n\nParameter Patients\nn=135\n\n\n\nControls\nn=135\n\n\n\np-value\n\n\n\nAge \n \n\n\n\nMean age in years (SD) 40.24\u00b1 12.9 40.55 \u00b1 12.7 0.52\nAge group \u226440 76 (56.3%) 76(56.3%) 1.0\n\n\n\n41-60 49 (36.3%) 49(36.3%)\n> 61 10 (7.4%) 10(7.4%)\n\n\n\nGender, \nn (%)\n\n\n\nMale 75(55.5%) 75(55.5%) 1.00\nFemale 60(44.5%) 60(44.5%)\n\n\n\nBody Mass Index, (kg/m2) 25.7(3.5) 24.5(3.6) 0.01\nRandom capillary blood sugar,(mmol/dl) 5.8(1.9) 5.6(1.6) 0.51\nMean blood pressure in mmHg (SD) Systolic 128.8(16.5) 124.2(15.7) 0.02\n\n\n\nDiastolic 80.4(10.9) 74.6(9.5) 0.00\nMean heart rate in beats per minute (SD) 76(13.0) 73(10.0) 0.07\nMean duration of disease in years (SD) 12.1(8.0) N/A N/A\nMean body surface area involvement in % (SD) 12.3(18.4) N/A N/A\nMean PASI (SD) 7.6(7.2) N/A N/A\nPresence of nail psoriasis,n (%) 105 (77.7%) N/A N/A\nPresence of psoriatic arthropathy, n(%) 40 (29.6%) N/A N/A\n\n\n\nN/A: not applicable \nMean values between psoriasis and controls were compared using independent samples t-test. Comparison of categorical variables was performed \nusing Chi-square test for independence. p value <0.05.\n\n\n\nParameter Current therapy n (%) Previous therapy n (%)\nTopical only 108(80.0) 85(63.0)\nSystemic/Phototherapy & topical 27 (20.0) 50(37.0)\nSystemic Methotrexate 18(13.3) 19 (14.0)\n\n\n\nAcitretin 5 (3.7) 1(0.7)\nSulphasalazine 0 1(0.7)\nCyclosporine 0 0\nBiologics 2 (1.5) 0\n\n\n\nPhototherapy 2 (1.5) 16 (11.9)\nVarious (patients who have received more than one systemic agent in the \npast, with and without phototherapy)\n\n\n\n13(9.7)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3838\n\n\n\nTable 3. Electrocardiogram findings in patients with psoriasis and control subjects.\n\n\n\nTable 4. Two Dimensional and Doppler echocardiogram measurements of patients with psoriasis and control subjects.\n\n\n\nParameter Psoriasis\nn=135\n\n\n\nControls\nn=135\n\n\n\np-value\n\n\n\nRhythm:\nSinus, n(%)  \n                             \n\n\n\n135 135 1.00\n\n\n\nAtrial conduction:\nAtrial premature beats, n(%)   2 (1.5) 0 0.25\n\n\n\nLeft ventricular hypertrophy, n(%)                                           \nRight ventricular hypertrophy, n(%)                                         \nLeft atrial enlargement, n(%)                                                  \nRight atrial enlargement, n(%)\nRBBB, n(%)                                                                             \nLBBB, n(%)                                                                              \nLeft anterior hemiblock, n(%)                                                   \nLeft posterior hemiblock, n(%)     \n\n\n\nVentricular Conduction:                                      \nVentricular premature beats, n(%)   \n\n\n\nIschaemic changes, n(%)   \n  \nPulse Rate, (Mean, SD)\n                                   \n\n\n\n5(3.7)\n0\n0\n0\n9(6.7)\n0\n1(0.7)\n0\n\n\n\n2(1.5)\n\n\n\n10(7.4)\n\n\n\n76(13.0)\n\n\n\n0(0)\n0\n0\n0\n2(1.5)\n0\n0\n0\n\n\n\n0\n\n\n\n1(0.7)\n\n\n\n73(10.0)\n\n\n\n0.02\n-\n-\n-\n0.03\n-\n0.32\n0.16\n\n\n\n1.56\n\n\n\n0.01\n\n\n\n0.07\n\n\n\nAV conduction:\nPR interval, ms (Mean, SD)   \n                                                                         \n\n\n\n149.2(22.2) 148.4(22.1) 0.78\n\n\n\nVentricular Conduction:\nQRS interval, ms (Mean.SD) 73.2(16.8) 78.0(14.3) 0.01\n\n\n\n \nMean values between groups were compared using independent samples t-test. Comparison of categorical variables was performed using Chi-square test \nfor independence. p value <0.05 is significant\n\n\n\nParameter Psoriasis\nn=135\n\n\n\nControls\nn=135\n\n\n\np-value\n\n\n\nLeft atrial measurements \nLeft atrial diameter, mm (SD) 30.3(5.1) 29.6(4.7) 0.19\n\n\n\nLeft ventricular measurements\nEnd systolic diameter, mm (SD) \nEnd diastolic diameter, mm (SD)\nInterventricular septum diastolic thickness, mm (SD)\nPosterior wall diastolic thickness, mm (SD)\nEjection fraction, (%)\nHypertrophy (n, %)                                                            \nWall motion abnormalities (n, %)                                                                                                       \n\n\n\n27.1(3.8)\n43.2(5.8)\n8.7(1.6)\n8.6(1.7)\n66.8(5.8)\n3(2.2)\n0(0)\n\n\n\n27.2(3.3)\n44.3(5.2)\n8.6(1.4)\n8.1(1.5)\n67.4(5.0)\n5(3.7)\n0(0)\n\n\n\n0.79\n0.11\n0.81\n0.01\n0.37\n0.47\n-\n\n\n\nMitral\tvalve\tinflow\tmeasurements\nEarly filling velocity (E), cm/s (SD)\nLate filling velocity (A), cm/s (SD)\nE/A ratio\nEarly filling velocity deceleration time, ms (SD)\nIsovolumetric relaxation time, ms (SD)\n\n\n\n0.7(0.2)\n0.5(0.2)\n1.4(0.5)\n187.9(44.2)\n93.2(20.8)\n\n\n\n0.7(0.2)\n0.5(0.2)\n1.5(0.5)\n185.2(41.8)\n87.9(18.9)\n\n\n\n0.54\n0.19\n0.30\n0.60\n0.03\n\n\n\nDiastolic dysfunction of the left ventricle (n, %) 7(5.2) 5(3.7) 0.56\n\n\n\nTricuspid\tvalve\tinflow\tmeasurements\nEarly filling velocity (E), cm/s (SD)\nLate filling velocity (A), cm/s (SD)\nE/A ratio\nPressure half time, ms (SD)\n\n\n\n0.5(0.5)\n0.4(0.1)\n1.5(0.4)\n63.7(22.8)\n\n\n\n0.5(0.1)\n0.4(0.1)\n1.5(0.5)\n57.6(13.8)\n\n\n\n0.57\n0.73\n0.39\n0.20\n\n\n\nDiastolic dysfunction of the right ventricle (n, %) 7(5.2) 3(2.2) 0.19\n\n\n\nAortic measurements\nAnnulus, mm (SD)\nAscending aorta, mm (SD)\n\n\n\n19.2(2.3)\n24.8(3.2)\n\n\n\n18.5(2.1)\n24.3(3.0)\n\n\n\n0.01\n0.27\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 39\n\n\n\nMitral valve, n(%)\nStenosis\nProlapse\nRegurgitation\n\n\n\n0\n2(1.5)\n8(5.9)\n\n\n\n0\n0(1.5)\n8(5.9)\n\n\n\n-\n1.00\n1.00\n\n\n\nTricuspid valve, n(%)\nStenosis\nProlapse\nRegurgitation\n\n\n\n0\n0\n9(6.7)\n\n\n\n0\n1(0.7)\n1(0.7)\n\n\n\n-\n0.32\n0.01\n\n\n\nAortic valve, n(%)\nStenosis\nProlapse\nRegurgitation\n\n\n\n0\n0\n9(6.7)\n\n\n\n0\n0\n3(2.2)\n\n\n\n-\n-\n0.08\n\n\n\nMean values between groups were compared using independent samples t-test. Comparison of categorical variables was performed using Chi-square test \nfor independence. p value <0.05 is significant.\n\n\n\nTable 5. The association of electrocardiographic and echocardiogram parameters with BSA and PASI in psoriasis patients, n=135.\n\n\n\nParameters BSA PASI\n(Mean, SD) p-value (Mean, SD) p-value\n\n\n\nElectrocardiographic\tfindings\nIschaemia  \n\n\n\nYes\n  No\n\n\n\n11.6(8.1)\n12.4(19.0)\n\n\n\n0.89 8.8(5.7)\n7.5(7.3)\n\n\n\n0.53\n\n\n\nVentricular premature beats                                             \n  Yes\n  No                                                                                      \n\n\n\n12.0(11.3)\n12.3(18.5)\n\n\n\n0.90 9.5(7.7)\n7.6(7.2)\n\n\n\n0.79\n\n\n\nAtrial premature beats  \n  Yes\n  No                           \n\n\n\n41.5(54.4)\n11.9(17.5)\n\n\n\n0.58 14.0(15.6)\n7.5(7.1)\n\n\n\n0.66\n\n\n\nLeft ventricular hypertrophy                                        \n  Yes\n  No\n\n\n\n10.2(7.5)\n12.4(18.7)\n\n\n\n0.79 8.1(3.4)\n7.7(7.3)\n\n\n\n0.78\n\n\n\nRight bundle branch block\nYes\n No\n\n\n\n17.7(26.3)\n11.9(17.8)\n\n\n\n0.37 9.5(7.8)\n7.5(7.1)\n\n\n\n0.41\n\n\n\nLeft anterior hemiblock                                                \n  Yes\n  No\n\n\n\n6\n12(18.4)\n\n\n\n0.73 4.8\n7.6(7.2)\n\n\n\n0.69\n\n\n\nEchocardiographic\tfindings\nLeft ventricular hypertrophy\n\n\n\n  Yes\n  No\n\n\n\n4.2(2.1)\n12.5(18.6)\n\n\n\n0.45 4.1(0.7)\n7.7(7.2)\n\n\n\n0.39\n\n\n\nDiastolic dysfunction of the left ventricle                                               \n  Yes\n  No                                                                                                                                       \n\n\n\n3.5(4.4)\n1\n\n\n\n0.93 3.2(0.5)\n7.8(7.3)\n\n\n\n0.17\n\n\n\n Diastolic dysfunction of the right ventricle                                               \n Yes\n  No                                      \n\n\n\n4.9(2.9)\n12.8(18.8)\n\n\n\n0.27 4.4(1.7)\n7.8(7.3)\n\n\n\n0.23\n\n\n\nMitral valve prolapse                                        \n  Yes\n  No\n\n\n\n2.5(0.7)\n12.5(18.5)\n\n\n\n0.44 4.8(1.6)\n7.6(7.2)\n\n\n\n0.57\n\n\n\nMitral valve regurgitation                                       \n  Yes\n  No\n\n\n\n18.9(23.2)\n11.9(18.1)\n\n\n\n0.30 12.2(11.9)\n7.3(6.7)\n\n\n\n0.06\n\n\n\nTricuspid regurgitation                                \nYes\n No\n\n\n\n14.0(28.6)\n12.2(17.6)\n\n\n\n0.78 7.6(6.8)\n7.6(6.9)\n\n\n\n0.88\n\n\n\nAortic regurgitation   \n  Yes\n  No\n\n\n\n6(5.6)\n12.8(18.9)\n\n\n\n0.29 5.5(3.8)\n7.7(7.3)\n\n\n\n0.36\n\n\n\nMean values between groups were compared using independent samples t-test.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3840\n\n\n\nReferences\n\n\n\n1. Griffiths CE, Barker JN. Pathogenesis and clinical features \nof psoriasis. Lancet 2007;370:263\u201371.\n\n\n\n2. De Korte J, Sprangers MAG, Mombers FMC, Bos JD. \nQuality of life in patients with psoriasis: a systematic \nliterature review. J Investig Dermatol Symp Proc \n2004;9:140-7.\n\n\n\n3. Makredes M, Robinson JR D, Bala M, Kimball AB. \nThe burden of autoimmune disease: A   comparison of \nprevalence ratios in patients with psoriatic arthritis and \npsoriasis. J Am Acad Dermatol 2009;61:405-10.\n\n\n\n4. Shelling ML, Federman DG, Prodanovich S, Kirsner RS. \nPsoriasis and Vascular Disease: An Unsolved Mystery. Am \nJ Med 2008;121:360-5.\n\n\n\n5. Vena GA, Vestita M, Cassano N. Psoriasis and \ncardiovascular disease. Dermatol Ther 2010;28:141-51.\n\n\n\n6. Carvalho M, Soares R, Ribeiro F, Gaiao L, Rosa M, \nRodrigues M et al. Rhythm profile in patients in psoriatic \narthritis. Rev Post Cardiol. 1990;9:311-7.\n\n\n\n7. Markuszeski L, Bissinger A, Janusz I, Narbut J, \nJedrzejowska AS, Zalewska A. Heart rate and arrhythmia \nin patients with psoriasis vulgaris. Arch Med Res \n2007;38:64-9.\n\n\n\n8. Gunes Y, Tuncer M, Calka O, Guntekin U Aknedin \nN, Simsek H et al. Increased frequency of pulmonary \nhypertension in psoriasis patients. Arch Dermatol Res \n2008;300:435-40.\n\n\n\n9. Gonzalez-Juanatey C, Amigo-Diaz E, Jose A, \nTesta A, Revuelta J, Garcia-Porrua C et al. Lack of \nechocardiographic and Doppler abnormalities in psoriatic \narthritis patients without clinically evident cardiovascular \ndisease or classic atherosclerosis risk factors. Semin \nArthritis Rheum 2005;35:333-9.\n\n\n\n10. Guven A, Sasmaz S, Aksu E, Emre C. Echocardiographic \nevaluation in patients with psoriasis.T Klin J Cardiol \n2003;16:77-81.\n\n\n\n11. Ozturkan S, Ermertcan AT, Sekuri C, Kllyccyoolu B. \nCardiovascular findings in patients with psoriasis. Ann \nSaudi Med 2006;26:159-61.\n\n\n\n12. Saricaoglu H, Gullullu S, Bulbul Baskan E, Cordan J, \nTunali S. Echocardiographic findings in subjects with \npsoriatic arthropathy. J Eur Acad Dermatol Venereol \n2003;17:414-7.\n\n\n\n13. Rowe IF, Gibson DG, Keat ACS, Brewerton DA. \nEchocardiographic diastolic abnormalities in the left \nventricle in inflammatory joint disease. Annals of \nRheumatic Disease 1991;50:227-30.\n\n\n\n14. Pines A, Ehrenfield M, Fisman EZ, Kaplinsky N, Samra Y, \nRonnen M et al. Mitral valve prolapse in psoriatic arthritis. \nArch Intern Med 1986;146:1371-3.\n\n\n\n15. Feld J, Weiss G, Rosner I, Rozenbaum M, Laor A, Rimar D \net al. Electrocardiographic findings in psoriatic arthritis: a \ncase-controlled study. J Rheumatol 2008;35:2379-82.\n\n\n\n16. Badokin VV, Kotel\u2019nikova GP. The heart damage in \npatients with psoriatic arthritis. Ter Arkh 2004;76:56-61.\n\n\n\nTable 6. Two Dimensional and Doppler echocardiogram measurements of psoriasis patients based on disease duration of \u2264 10 years and \n> 10 years\n\n\n\nParameter Duration\u226410 years, \nN=69\n(Mean, SD)\n\n\n\nDuration>10 years,\nN=66\n(Mean, SD)\n\n\n\np-value\n\n\n\nLeft atrial measurements:\nLeft atrial diameter, mm 29.9(4.7) 30.7(5.4) 0.38\n\n\n\nLeft ventricular measurements:\nEnd systolic diameter, mm \nEnd diastolic diameter, mm\nInterventricular septum diastolic thickness, mm\nPosterior wall diastolic thickness, mm\nEjection fraction, %\nHypertrophy (n, %)                                                            \nWall motion abnormalities (n, %)          \n                                                                                             \n\n\n\n27.2(2)\n43.5(6.3)\n8.7(1.6)\n8.6(1.8)\n67.2(6.0)\n2(2.9)\n0\n\n\n\n26.9(3.8)\n42.9(5.3)\n8.7(1.6)\n8.7(1.6)\n66.5(5.7)\n1(1.5)\n0\n\n\n\n0.76\n0.59\n0.93\n0.72\n0.48\n1.00\n-\n\n\n\nMitral\tvalve\tinflow\tmeasurements:\nEarly filling velocity (E), cm/s\nLate filling velocity (A), cm/s\nE/A ratio\nEarly filling velocity deceleration time, ms\nIsovolumetric relaxation time, ms\n\n\n\n0.7(0.2)\n0.5(0.1)\n1.5(0.5)\n190.6(47.8)\n91.2(21.7)\n\n\n\n0.6(0.2)\n0.5(0.2)\n1.3(0.4)\n185.2(40.2)\n95.4(19.4)\n\n\n\n0.01\n0.25\n0.01\n0.49\n0.24\n\n\n\nDiastolic dysfunction of the left ventricle (n, %) 4(5.8) 1(1.5) 0.37\n\n\n\nTricuspid\tvalve\tinflow\tmeasurements:\nEarly filling velocity (E), cm/s\nLate filling velocity (A), cm/s\nE/A ratio\nPressure half time, ms\n\n\n\n0.5(0.1)\n0.3(0.1)\n1.5(0.4)\n62.2(23.6)\n\n\n\n0.6(0.7)\n0.3(0.1)\n1.490.4)\n63.1(22.1)\n\n\n\n0.52\n0.11\n0.02\n0.82\n\n\n\nDiastolic dysfunction of the right ventricle (n, %) 3(4.3) 4(6.1) 0.71\n\n\n\nAortic measurements:\nAnnulus, mm\nAscending aorta, mm\n\n\n\n18.9(2.3)\n24.1(3.1)\n\n\n\n19.5(2.3)\n25.5(3.3)\n\n\n\n0.15\n0.01\n\n\n\nMean values between groups were compared using independent samples t-test. 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Hameed W, Razi MH, Khan MA, Hussain MM, Habib S, \nAslam M. Electrocardiographic diagnosis of left ventricular \nhypertrophy: comparison with echocardiography. Pak J \nPhysiol 2005;1:1-2.\n\n\n\n33. Kannel WB. Left ventricular hypertrophy as a risk factor: \nthe Framingham experience. J Hypertens Suppl 1991;9:S3 \n\u2013 S8.\n\n\n\n34. Haider AW, Larson MG, Benjamin EJ, Levy D. Increased \nleft ventricular mass and hypertrophy are associated with \nrisk for sudden death. J Am Coll Cardiol 1998;32:1452-9.\n\n\n\n35. Satpathy C, Mishra TK, Satpathy R, Satpathy KS, Barone \nE. Diagnosis and management of diastolic dysfunction and \nheart failure.  Am Fam Physician 2006;73:841-6.\n\n\n\n36. Quinones MA, Otto CM, Stoddard M, Waggoner A, \nZoghbi WA. 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Lin HW, Wang KH, Lin HC. Increased risk of acute \nmyocardial infection in patients with psoriasis: A 5-year \npopulation-based study in Taiwan. J Am Acad Dermatol \n2011;64:495-501.\n\n\n\n41. Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn \nEJ, Korman NJ et al. National Psoriasis Foundation \nclinical consensus on psoriasis comorbidities and \nrecommendations for screening. J Am Acad Dermatol \n2008;58:1031-42.\n\n\n\n42. Maeyama S, Yamamoto, Sasai Y, Yoshida K. Secondary \namyloidosis complicating arthropathic psoriasis. Clin Exp \nDermato 1996;21:141-4.\n\n\n\n43. Wittenberg GP, Oursler JR, Peters MS. Secondary \namyloidosis complicating psoriasis. J Am Acad Dermatol \n1995;32:465-8.\n\n\n\n44. Ahmed Q, Chung-Park M, Mustafa K, Khan MA. Psoriatic \nspondyloarthropathy with secondary amyloidosis. J \nRheumatol 1996;23:1107\u201310.\n\n\n\n45. Tsuda S, Maeyama Y, Yamamoto N, Sasai Y, Yoshida \nK. Secondary amyloidosis complicating arthropathic \npsoriasis. Clin Exp Dermatol 1996;21:141\u20134.\n\n\n\n46. Kaddoura S. Echo Made Easy. Second Edition. Churchill \nLivingstone Elsevier 2009; 54-7.\n\n\n\n47. Faludi R, Komocsi A, Bozo J, Kumanovics G, Czirjak \nL, Papp L et al. Isolated diastolic dysfunction of right \nventricle: stress-induced pulmonary hypertension. Eur \nRespir J 2008;3:475-6.\n\n\n\n48. Messika-Zouton D, Serfaty JM, Brochet B, Ducrocq G, \nlampage L, Detaint D et al. Multimodal assessment of \nthe aortic annulus diameter-implications for transcatheter \naortic valve implantation. J Am Coll Cardiol 2010;55:186-\n194.\n\n\n\n49. Klein RM, Vester EG, Brehm MU, Dees H, Picard F, \nNiederacher D.  Inflammation of the myocardium as an \narrhythmia trigger. Z Kardiol 2000;89:24-35.\n\n\n\n50. Sajadieh A, NielsenOW, RasmussenV, Hein HO, Abedini \nS, Hansen JF. Increased heart rate and reduced heart-rate \nvariability are associated with subclinical inflammation in \nmiddle-aged and elderly subjects with no apparent heart \ndisease. Eur Heart J 2004;25:363-70.\n\n\n\n51. Longmore M, Wilkinson IB, Rajagopalan SR. Oxford \nHandbook of Clinical Medicine. 6th Edition. Oxford. \nOxford University Press. 2004.\n\n\n\n52. Nestle FO, Kaplan DH, Barker J. Mechanisms of disease \u2013 \nPsoriasis. N Engl J Med 2009;361:496-509.\n\n\n\n53. Acevedo M, Corbalan R, Braun S, Pereira J, Navarrete \nC, Gonzalez I. C-reactive protein and atrial fibrillation: \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3842\n\n\n\nevidence for the presence of inflammation in the \nperpetuation of the arrhythmia. Int J Cardiol 2005;108:326-\n31.\n\n\n\n54. Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos \nG, Kremastinos DT. Relation of elevated C-reactive protein \nand interleukin-6 levels to left atrial size and duration of \nepisodes in patients with atrial fibrillation. Am J Cardiol \n2005;95:764-7.\n\n\n\n55. Kowalewski M, Urban M, Mrocko B, Szmitowski M. \nPro-inflammatory cytokines in serum of young people \nwith ventricular arrhythmias. Pol Arch Med Wewn \n2002;108:647-51. \n\n\n\n56. Cronstein BN, Naime D, Ostad E. The anti-inflammatory \nmechanism of methotrexate. J Clin Invest 1993;92:2675-\n82.\n\n\n\n57. Westlake SL, Colebatch AN, Baird J, Kiely P, Quinn M, \nChoy E et al. The effect of methotrexate on cardiovascular \ndisease in patients with rheumatoid arthritis: a systematic \nliterature review. Rheumatology 2010;49:295-307.\n\n\n\n58. Prodanovich S, Ma F, Pezon C, Fasihi T, Kirsner S. \nMethotrexate reduces incidence of vascular disease in \nveterans with psoriasis or rheumatoid arthritis. J Am Acad \nDermatol 2005;52:262-7.\n\n\n\n59. Freed LA, Levy D. Levine R, Larson MG, Evans JC, Fuller \nDL et al. Prevalence and Clinical Outcome of Mitral-Valve \nProlapse. N Engl J Med 1999;341:1-7.\n\n\n\n60. Hepner AD, Ahmadi-Kashani M, Movahed MR. The \nprevalence of mitral valve prolapse in patients undergoing \nechocardiography for clinical reason. Int J Cardiol \n2007;123:55-7.\n\n\n\n61. Bergfeldt L, Insulader P, Lindbolm D, Moller E, Edhag O. \nHLA-B27: an important genetic risk factor for lone aortic \nregurgitation and severe cardiac conduction abnormalities. \nAm J Med 1998;85:12-8. \n\n\n\n62. Choudhury A, Magoon R, Malik V, Kapoor PM, \nRamakrishnan S. Studying diastology with speckle \ntracking echocardiography: The essentials. Ann Card \nAnaesth 2017;20(Supp):S57-S60.\n\n\n\n63. Suran D, Sinkovic A, Naji F. Tissue Doppler imaging is a \nsensitive echocardiographic technique to detect subclinical \nsystolic and diastolic dysfunction of both ventricles in type \n1 diabetes mellitus. BMC Cardiovasc Disord 2016;16:72-\n81. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 43\n\n\n\nORIGINAL ARTICLE\n\n\n\nLiquid Nitrogen Cryotherapy Versus 20% Salicylic Acid Ointment \nfor the Treatment of Plantar Warts \u2013 A Randomized Trial \n\n\n\nSharifah Rosniza, Adv M Derm, Noor Zalmy Azizan, Adv M Derm\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\nCryotherapy and salicylic acid ointment are the two most common treatments used for treating plantar \nwarts. The aim of this study is to compare the clearance rate of plantar warts at 12 weeks between \nliquid nitrogen cryotherapy and 20% salicylic acid ointment.\n\n\n\nMethods: \nPatients with plantar warts were randomized into cryotherapy and 20% salicylic acid groups.  Patients \nassigned into cryotherapy group received a maximum of four treatments given two weeks apart.  \nPatients recruited into 20% salicylic acid group were instructed to apply the salicylic acid ointment \nonto the wart nightly and to cover the treated area with a hypoallergenic plaster.  Both groups were \nalso provided with a personal foot file to thin out the surrounding callus daily at home.  Digital pictures \nwere taken at first visit and 12 weeks after enrolment to assess the resolution of plantar wart.\n\n\n\nResults: \nEighty patients with plantar warts were included. Thirty-nine patients were randomized into cryotherapy \ngroup and forty-one patients were randomized into 20% salicylic acid ointment group.  Thirteen \n(33.3%) patients had a complete clearance of the warts with cryotherapy whereas eleven (26.8%) \npatients had a complete clearance of the warts with topical 20% salicylic acid ointment (p=0.526). \nNine patients were lost to follow-up. With cryotherapy, two patients reported blister formation and one \npatient developed hyperpigmentation. No side effects were reported with 20% salicylic acid ointment.  \n\n\n\nConclusion: \nThere is no difference in effectiveness between cryotherapy and 20% salicylic acid ointment in the \ntreatment of plantar wart.\n\n\n\nKey words: Plantar wart, Cryotherapy, salicylic acid \n\n\n\nIntroduction\nCutaneous warts are caused by human papilloma\nvirus (HPV). Over 200 types of papillomaviruses \nhave been identified and have been completely \nsequenced, including more than 150 types of HPV.1  \nAn incubation period of 3 weeks to 8 months can \noccur before lesions become apparent, depending \non inoculation.2  Inoculations are more common if \nthere is a break in the skin barrier such as in atopic \ndermatitis3 and also at sites where there is regular \n\n\n\nCorresponding Author\nDr. Sharifah Rosniza Binti Syed Nong Chek\nDepartment of Dermatology, Hospital Kuala Lumpur, \n50586 Jalan Pahang, Kuala Lumpur, Malaysia.\nEmail: srsyed@doctors.net.uk\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3844\n\n\n\nfrictions and traumas such as on the palms and \nsoles.4 \n\n\n\nA plantar wart has the typical appearance of a \nsharply demarcated, rounded lesion, with a rough, \nkeratotic surface surrounded by a smooth collar of \nthickened horn.  The small tortuous capillary loops \nin the most superficial layer of papillary dermis \ncan also become damaged and thrombosed in the \npresence of cutaneous HPV infection and paring of \nthe surface will reveal small bleeding points.  This \nfeature distinguishes warts from calluses, which \nmay present with hyperkeratotic stratum corneum \nbut lacks the appearance of these small bleeding \npoints.  With localized spread of the infection, there \nmay be satellite lesions, which are lesions erupting \nnear the site of a longstanding wart.  Multiple \nlesions may also coalesce to form a single mosaic \nwart, which is often resistant to treatment.\n\n\n\nHPV1 and 4 are frequently the cause of plantar \nwarts, although HPV57, 60, 63, 65, and 66 can also \nbe involved.5 HPV1 is more commonly associated \nwith a painful lesion that manifests as a keratotic \nplug surrounded by a hyperkeratotic rim.5 HPV4 \non the other hand causes mosaic warts, which are \nmore superficial lesions that occur in a confluent \ncobblestone pattern and are usually painless.6\n\n\n\nSalicylic acid and cryotherapy have been used to \ntreat plantar warts for more than 20 years and these \nare the two most commonly prescribed treatments \nfor plantar warts.7 This study aims to determine \nwhether 20% salicylic acid would have the same \nefficacy as cryotherapy in treating plantar warts.\n\n\n\nMaterials and Methods\nThis is an open label, prospective, two-arm, \nrandomized study. This study was conducted at the \nDermatology Day Care Unit, Hospital Selayang \nand Dermatology Clinic, Hospital Kuala Lumpur \nfrom February 2014 to August 2015. The target \npopulation was patients aged 12 years and above \nwith plantar warts attending the Dermatology Day \nCare Unit, Hospital Selayang and the Dermatology \nClinic, Hospital Kuala Lumpur during the study \nperiod.  \n\n\n\nInclusion criteria are patients above 12 years of age, \nplantar warts must have been present for at least 2 \nmonths and patients must be able to read and sign the \ninformed consent.  Exclusion criteria are patients with \ndiabetes mellitus and peripheral vascular disease, \npatients who are immunosuppressed, patients with \n\n\n\nprevious history of salicylate sensitivity and patients \nwho are unable to give informed consent.  Patients \nwho were already undergoing treatment were given \na 1month wash-out period before being included in \nthe study. \n\n\n\nThis study was funded by Department of \nDermatology, Hospital Selayang and Department \nof Dermatology, Hospital Kuala Lumpur.  \nRandomization was performed by assessing \nan online randomization programme (www.\nrandomizer.org)  \n\n\n\nFor cryotherapy, topical anaesthetic EMLA \n(lidocaine 2.5% and prilocaine 2.5% cream) was \nfirst applied onto the warts and left for 60 minutes.  \nParing was then performed with a No.10 curved \nblade before cryotherapy. The liquid nitrogen was \napplied with a cryospray (Brymill) and the size of \nthe plantar wart determined the size of probe tip to \nbe used.  Specifically, size A probe tip was used for \nlarge lesion more than 1.0cm, size B probe tip for \nlesions between 0.5 and 1.0cm, and size C probe tip \nwas used for small lesion measuring less than 0.5cm.  \nThe cryospray was directed from a 90-degree angle \nat a distance of 1 to 2cm from the wart and liquid \nnitrogen was applied to the wart until there was a \n2mm halo around the wart.  Two freeze-thaw cycles \nwere used.  \n\n\n\nPatients randomized into cryotherapy group \nwith liquid nitrogen received a maximum of four \ntreatments given two weeks apart by the same \nhealth care professional.  Patients in the cryotherapy \ngroup were also given a foot file so that they could \nfile down the callosity surrounding the plantar wart \nafter soaking the plantar wart in water for about 5 \nminutes. Filing of the callosity surrounding the warts \nwas performed daily at home during the intervals \nbetween the cryotherapy sessions.  Patients were \nseen during the two weekly cryotherapy sessions \nand at 12 weeks.  \n\n\n\nPatients randomized into self-treatment with 20% \nsalicylic acid ointment (Xorlyx 20, manufacturer: \nXorix Sdn Bhd) were taught on how to apply the \ntreatment by a designated health care professional. \nThe wart was soaked in water for about 5 minutes \nto soften the skin.  A foot file was supplied to each \npatient and the patient was instructed to file down \nany callus surrounding the plantar wart every night \nafter soaking.  20% salicylic acid ointment was \nthen applied with their finger directly onto the wart \nuntil it covered the entire wart.  After application \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 45\n\n\n\nof the salicylic acid ointment, the treated area was \ncompletely covered with a non-medicated, water-\nproof and hypoallergenic plaster (Tegaderm). \nTreatment was left overnight for 8 hours before \npatient was allowed to remove the plaster and \nsalicylic acid the next morning.  The treatment \nregime was repeated every night for 12 weeks. \nPatients were seen at the beginning of the study and \nat 12 weeks.  \n\n\n\nPrimary end point of this study was to determine \nthe complete clearance of all plantar warts at 12 \nweeks after randomization.  Clearance of plantar \nwarts was defined as the restoration of normal \nskin on close inspection.  Digital photographs of \nthe plantar warts were taken at baseline and at the \noutcome assessment at week 12.  The photographs \ntaken at baseline and at week 12 were compared and \nassessed by two independent dermatology clinical \nspecialists who were blinded to treatment allocation \nin order to determine whether the plantar wart has \ncleared.  Should any discrepancies occur, the digital \nphotographs were referred to a third assessor.  The \nsecondary end-point is to determine complete \nclearance of all plantar warts after controlling for \nage, duration of warts, type of warts, and whether \nthe plantar wart had been treated before.  We also \nsought to determine any adverse events for each of \nthe intervention groups and to compare the number \nof plantar warts at 12 weeks between the two \ntreatment groups with adjustment for the number of \nplantar warts at baseline.  \n\n\n\nAll analyses were conducted on an intention-to-\ntreat basis. Analyses were conducted using the \nSPSS version 22, using two-sided significance tests \nat 5% significance level.  Independent T-test was \nused to compare the mean age between cryotherapy \nand salicylic acid ointment groups.  Chi-square test \nwas used to compare the clearance rate between \ncryotherapy and salicylic acid ointment groups.  \nFisher\u2019s exact test was used when the frequency of \none or more of the cells were less than five.  Mann-\nWhitney U test was used to compare the number \nof plantar warts at baseline between cryotherapy \nand salicylic acid ointment groups.  Cohen\u2019s kappa \nwas used to assess the agreement between the two \nassessors of the photographs, to indicate whether \npatient had complete or incomplete response.  \nLogistic regression analysis was used to look for \nassociated factors that could influence the rate of \nclearance between the cryotherapy and salicylic \nacid ointment groups. \n\n\n\nComparison between the mean number of warts at \n12 weeks between the two treatment groups before \nand after adjusting for the mean number of warts \nat baseline was performed.  Analysis of covariance \n(ANCOVA) was used to allow comparison between \nthe mean numbers of warts at 12 weeks after taking \ninto account of the number of warts at baseline.\n\n\n\nResults\nThis study was conducted from February 2014 to \nAugust 2015.  Eighty five patients were diagnosed \nwith plantar warts; with 80 patients fulfilling \nthe inclusion and the exclusion criteria defined \nby the study.  These 80 patients were randomly \nallocated to cryotherapy (n=39) and 20% salicylic \nacid ointment (n=41).  Five patients with plantar \nwarts were excluded from the study.  One of the \npatients excluded had underlying systemic lupus \nerythematosus and was taking oral prednisolone, 3 \nof the patients have diabetes mellitus and 1 patient \nrefused to join the study.\n\n\n\nDemographic and baseline characteristics of \nthe patients are shown in Table 1.  There was no \nstatistically significant difference between the two \ntreatment groups in terms of their mean age, gender \nand ethnicity.  Overall, 46% of patients had sought \ntreatment prior to participating in this study.  More \npatients in the cryotherapy group had previous \ntreatment for their plantar warts (59%) compared \nto those in the salicylic acid group (34.1%) and \nthis difference is statistically significant (p=0.026).  \nPrior treatments consisted of topical salicylic \nacid of various concentrations (2% to 20%) and \ncryotherapy.  \n\n\n\nFor the topical salicylic acid, treatments were \nobtained from retail pharmacy, primary care clinic \nand from hospital setting and they were in the form \nof wart paint, ointment and plaster impregnated \nwith salicylic acid.  Previous cryotherapy sessions \nwere performed in hospital setting and the intervals \nbetween cryotherapy sessions varied between 2 \nweeks interval to 8 weeks interval.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3846\n\n\n\nFigure 1. Response to treatments at 12-weeks\n\n\n\nTable 1. Demographic and baseline characteristics between patients presented with plantar warts randomized to either cryotherapy or \nsalicylic acid treatment\n\n\n\nCharacteristics Overall\n(n=80)\n\n\n\nSalicylic acid\n(n=41)\n\n\n\nCryotherapy\n(n=39)\n\n\n\np-value\n\n\n\nMean age (SD) 36.11 (17.39) 34.44 (17.13) 37.87 (17.72) 0.381a\n\n\n\nGender, n (%)\n0.978b   Male 35 (43.8%) 18 (43.9%) 17 (43.6%)\n\n\n\n   Female 45 (56.2%) 23 (56.1%) 22 (56.4%)\nEthnicity, n (%)\n\n\n\n0.822b\n   Malay 57 (71.2%) 28 (68.3%) 29 (74.4%)\n   Chinese 11 (13.8%) 6 (14.6%) 5 (12.8%)\n   Indian 12 (15.0%) 7 (17.1%) 5 (12.8%)\nNumber of plantar warts per warts per participants\n\n\n\n0.657c\n\n\n\n   Mean (SD) 3.63 (4.36) 3.95 (5.16) 3.28 (3.36)\n   Median (Range) 2 (1-24) 2 (1-24) 2 (1-17)\n\n\n\nDuration of warts \n\n\n\n0.372b\n   <1 year 33 (41.2%) 20 (48.8%) 13 (33.3%)\n   1-2 years 31 (38.8%) 14 (34.1%) 17 (43.6%)\n   >2years 16 (20%) 7 (17.1%) 9 (23.1%)\nPredominant types of plantar warts, n (%)\n\n\n\n0.124b\n    Mosaic 15 (18.8%) 5 (12.2%) 10 (25.6%)\n    Non mosaic 65 (81.2%) 36 (87.8%) 29 (74.4%)\nPrevious treatment, n (%)\n\n\n\n0.026b\n    Yes 37 (46.2%) 14 (34.1%) 23 (59.0%)\n    No 43 (53.8%) 27 (65.9%) 16 (41.0%)\nReason for seeking plantar warts treatment, n (%)\n\n\n\n 0.941d\n   Pain 72 (90%) 37 (90.2%) 35 (89.7%)\n   Cosmetic & others 8 (10%) 4 (9.8%) 4   (10.3%)\n\n\n\naIndependent T-test   b Chi Square test c Mann Whitney U test d Fisher\u2019s exact test SD standard deviation.\n\n\n\nThe unit of analysis for clearance is taken as the \npatient rather than the individual wart.  A participant \nwas considered cured when all warts present at \nbaseline were gone at follow-up.  This outcome is \nshown in Figure 1.  Overall, 24 of the 80 (30.0%) \npatients had complete clearance of their plantar warts \n\n\n\nat 12-weeks. There were 13 (33.3%) patients with \ncompletely cleared plantar warts in the cryotherapy \ngroup as compared to 11 (26.8%) patients from the \ntopical 20% salicylic acid ointment.  This difference \nwas not statistically significant (P = 0.526).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 47\n\n\n\nCohen\u2019s kappa is an index that measures inter-\nrater agreement for categorical items. In this study, \nit was used to assess the agreement between the two \nassessors of the photographs, to indicate whether \npatient had complete or incomplete response.  The \nagreement was estimated to be 0.76 (95% confidence \ninterval 0.61 to 0.91; p<0.001), which indicates a \ngood level of agreement.  \n\n\n\nA logistic regression model was used to adjust the \nprimary analysis for important prognostic variables \n(Table 2). These variables include age, duration of \nwarts, whether the plantar warts had been previously \ntreated (yes or no) and the type of plantar warts \n(mosaic or non-mosaic).  For secondary analysis, \npatients were divided into 2 categories; age of 12 \nyears to 19 years, and age of 20 years or more.  This \nstudy found no difference in the rate of clearance \nof plantar warts between the two age categories, \nduration of warts, type of warts, and whether patients \nhad received prior treatment for their plantar warts.\n\n\n\nFactors Simple Logistic Regression Multiple Logistic Regression\nCrude ORa 95% CIb p-value Adjusted ORa 95% CIb p-value\n\n\n\nAge (years)\n   12-19 1 - - 1 - -\n   >20 1.04 0.32,3.35 0.952 0.86 0.23,3.17 0.820\nDuration of warts\n   <1 year 1 - - 1 - -\n   1-2 years 0.51 0.17,1.54 0.297 0.53 0.16,1.72 0.288\n   >2years 0.80 0.22,2.84 0.537 0.95 0.24,3.75 0.941\nPredominant types of warts\n   Non mosaic 1 - - 1 - -\n   Mosaic 0.13 0.02,1.06 0.056 0.12 0.01,1.01 0.051\nPrevious treatment\n   Yes 1 - - 1 - -\n   No 0.64 0.24,1.66 0.354 0.64 0.22,1.89 0.417\nTreatment\n   Cryotherapy 1 - - 1 - -\n   Salicylic acid 0.73 0.28,1.91 0.526 0.65 0.22,1.92 0.434\n\n\n\nBoth treatments were well-tolerated with only 3 \npatients developing adverse events while having \ntreatment with cryotherapy. Two patients had \nblisters after cryotherapy. The blisters were already \nruptured by the time patient came back for a \nreview.  One patient developed post inflammatory \nhyperpigmentation after cryotherapy.  The adverse \nevents were not categorized as serious and did not \nwarrant withdrawal from the study.  There was no \nreported severe adverse event with cryotherapy. \nThere was no reported adverse event with salicylic \nacid such as maceration.\n\n\n\nWhen the comparison of the number of warts at \nweek 12 was made without controlling for number \nof warts at baseline, there was no significance \ndifference in the mean number of warts at week \n12 between the two treatment groups (p=0.751).  \nSimilar finding was reported after controlling for \nthe number of warts at baseline (p=0.550). \n\n\n\naOdd Ratio bConfidence Interval Constant=0.223.\n\n\n\nTable 2. Factors associated with complete clearance of plantar warts between the two treatment groups\n\n\n\nOverall, 9 patients were lost to follow-up in this \nstudy and efforts were made to contact these patients \nvia the telephone. 2 (4.9%) patients from the \nsalicylic acid group were lost to follow-up.  One of \nthe patients complained about difficulty in adhering \nto the treatment regime whereas the other one was \nnot contactable. 7 (17.9%) patients did not come \nfor their follow-up from the cryotherapy group. 4 \nof these patients cited inability to come for the two-\nweekly follow-up because of their work schedule; \nwith one of them already relocated to another state. \n1 patient cited difficulty in paying the treatment \n\n\n\nfee.  2 of the other patients were not contactable.  \nThe difference between the drop-out rates is not \nstatistically significant (p=0.084).\n\n\n\nDiscussion\nThere are numerous treatments for plantar warts \nand they can be divided into destructive, virucidal, \nantiproliferative agents and immunotherapy.8 \nDestructive therapy include the usage of salicylic \nacid, cryotherapy, laser and photodynamic therapy.  \nVirucidal therapy includes usage of formaldehyde \nand glutaryldehyde.  Antiproliferative agents include \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3848\n\n\n\ndithranol, podophyllotoxin and 5-fluorouracil.  \nImmunotherapy includes imiquimod and contact \nimmunotherapy with diphenylcyclopropenone/\ndiphenocyprone (DPC) or squaric acid dibutyl ester \n(SADBE).  The cure rates for these treatments are \nshown in the table below:\n\n\n\nTable 3. Different treatment modalities for cutaneous warts and \ntheir cure rates\n\n\n\nTreatment modalities Cure rates\nSalicylic acid (all preparations)8 0-69%\nCryotherapy8 0-69%\nPulsed dye laser9 74%\nNd YAG laser10 70%\nPhotodynamic therapy11 75%\nFormaldehyde12 80%\nGlutaryldehyde13 72%\nDithranol14 71%\nPodophyllotoxin15 67%\n5-fluorouracil16 95%\nDiphenylcyclopropenone/diphenocyprone (DPC)17 88%\nSquaric acid dibutyl ester (SADBE)18 58%\n\n\n\nOur study found cryotherapy and 20% salicylic acid \nointment were equally effective in treating plantar \nwarts.  Our results confirm the findings of three \nother published studies comparing cryotherapy and \nsalicylic acid for the treatment of plantar warts.19-21\n\n\n\nOur cure rate was 33.3% (13/39) for cryotherapy and \n26.8% (11/41) for 20% salicylic acid ointment and \nthis was found to be almost similar to Bruggink et \nal,20 which found that cure rates for all patients with \nplantar warts were 30% and 33% for cryotherapy \nand salicylic acid respectively.20  However, our \nstudy differed from the two other previous studies \nin terms of the cure rate.19, 21  Our overall cure rate \nis less when compared to an earlier study showing \nclearance rate of 58% and 41% for cryotherapy and \nsalicylic acid, respectively.19 This difference could \nbe attributed to the different populations recruited \nto the study. This previous study excluded patients \nwith mosaic warts, patients with more than five \nwarts and lesions outside an average diameter of \n3-9mm.  There were 18.8% of patients in our study \npatients with mosaic warts and 21.2% had more than \nfive warts; and mosaic warts are generally regarded \nas more resistant to treatment.  However, when \ncompared to Cockayne et al,21 which showed 14% \nclearance for both cryotherapy and salicylic acid, \nwe found our cure rate was higher.  This difference \ncould be due to the cryotherapy regime employed \nby our study.  \n\n\n\nOur study used two freeze-thaw cycles for each \n\n\n\ntreatment, whereas cryotherapy in the study by \nCockayne et al21 was not standardized.  In the study \nby Cockayne et al,21 each centre was allowed to \ndeliver the cryotherapy according to the site\u2019s usual \npractice and the median number of cryotherapy \napplied was 1.5, which is lower compared to the two \nfreeze-thaw cycles used in our study.  Plantar wart \nis typically surrounded by callus and this callus can \nact as a good thermal insulator and may prevent the \ncellular destruction from cryotherapy.  Two freeze-\nthaw cycles may help to alleviate this.22  \n\n\n\nOur study found that there is no difference in the \ncomplete clearance rate between the two treatments \nafter taking into consideration their age, duration \nof warts, type of warts, and previous therapy.  Our \nstudy recruited patients who were adolescents and \nadults whereby adolescent was taken as 19 and \nbelow and adults were taken as the age of 20 and \nabove.  Using World Health Organization definition, \nadolescence age is defined as between the ages of \n10 to 19 years.  We did not include patients below \nthe age of 12 as previous study had shown that \neven without treatment, patients who are less than \n12 years old have a 43% chance of clearing their \nplantar wart without treatment.20 Cockayne21 et al \nonly included patients aged 12 years or older but \nthis study however did not delineate further whether \nthere is a difference in the rate of clearance between \nadolescent and adult patients.21 \n\n\n\nOur study found that there is no difference in the \nclearance rate of plantar wart between adolescent \nand adult patients when they were treated with \n20% salicylic acid ointment and cryotherapy.  Most \nadolescents are in the school-going age and choosing \nsalicylic acid ointment over cryotherapy for these \npatients would allow for administration of treatment \nat home and therefore avoid disruption of their \neducation because of the need to come to hospital \nfor cryotherapy sessions at regular intervals.  \n\n\n\nOverall, the rate of clearance for both treatments \nwere about 30%, which means that majority of \npatients (about 70%) were still not cleared of their \nplantar warts at 12 weeks.  The response to treatment \nmay be related to the types of warts.  HPV types \nhave been shown to influence the natural course \nand treatment response.  Warts containing HPV 1 \nhave shown the most distinct clinical profile, being \nrelated to children aged <12 years, plantar location, \nduration <6 months and to patients with < 4 warts.23 \nHPV 27 and HPV 57 were related to patients aged \nmore than 12 years old, and especially to patients \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 49\n\n\n\naged more than 21 years old.23 For plantar warts, \nthe subgroup with HPV 1 had a favourable natural \ncourse compared to those with HPV 2, 27 and 57; \nwith 58% spontaneously cured in patients with \nHPV 1 versus 7% in patients with HPV 2, 27 and \n57.24 The higher prevalence of HPV 1 in younger \npatients might explain why younger patients have \na higher rate of spontaneous clearance compared to \nadolescents and adults.  This study was conducted \nin the Netherlands so the application of these \nfindings to Malaysian population is still unknown.  \nOur study only involves patient above the age of \n12 years and the higher percentage of incomplete \nresponse compared to complete response (70% vs \n30%) could be caused by the predominance of HPV \n2, 27 and 57 in the plantar warts of our patients.  \nHowever, further study is needed to confirm this.\n  \nSeventy percent of patients in our study did not \nhave complete clearance at 12 weeks and it is \nimportant to identify which of these patients are \nclassified as having recalcitrant warts.  Recalcitrant \nwarts can be defined as warts of more than 2 years \nduration and had persisted despite treatment with \nat least 2 different treatment modalities.25 In terms \nof availability of treatment at our local setting a \nmore aggressive approach of cryotherapy may be \nemployed for treating recalcitrant warts and mosaic \nplantar warts.  Cryotherapy techniques can vary \nin application mode, freeze times and intervals \nbetween treatments.  Freeze times for warts are \ndefined as traditional or aggressive.26 Traditionally, \ncryotherapy is applied until the wart has a 2mm \nwhite halo around it.  An aggressive or longer \nfreeze maintains a white halo for 5-20 seconds.  In \na comparison between traditional freeze versus 10 \nseconds freeze, the longer freeze was more effective \nthan the traditional method, although the incidence \nof pain and blistering is significantly greater.27 After \nthawing, a second freeze cycle has been shown to \nimprove the cure rate in plantar warts.22 Paring can \nalso improve the efficacy of cryotherapy in treating \nplantar warts.28 Standard practice is to repeat the \ntreatment every 2-3 weeks until clearance of the \nwarts.8  \n\n\n\nOur study uses the traditional method of cryotherapy, \nwhereby the application of cryotherapy is stopped \nonce there is a 2mm halo around the wart.  Efficacy \nmight be improved if we adopt a more aggressive \nmethod of cryotherapy by applying the cryotherapy \nfor 10 seconds for each cycle, as evidenced by the \nstudy done by Connolly et al.27 Apart from this, \na combination of cryotherapy and salicylic acid \n\n\n\nmay also be considered for patients presenting \nwith recalcitrant or mosaic plantar warts and a \ncombination of cryotherapy and 70% salicylic acid \nhave been tried before, with a clearance rate of \n86%.29    \n\n\n\nProphylactic quadrivalent HPV vaccine (types \n6, 11, 16 and 18) has been proven to be effective \nin preventing HPV-associated precancerous and \ncancerous lesions.30 Specifically for plantar wart, \nthere was a reported case of complete regression \nof recalcitrant plantar wart after treatment with a \nrecombinant quadrivalent human papillomavirus \nvaccine,31 and in this case the patient had already \nreceived treatment with cryotherapy, 40% \nsalicylic acid, topical imiquimod 5%, intralesional \nbleomycin, pulsed dye laser, and oral cimetidine; \nwith no success.  HPV vaccines have been proven to \nshow cross-protection against other strains,32 and it \nis postulated that this may have caused the complete \nclearance of wart in this patient. Malaysia started \nits national HPV vaccination programme in 2010 \nand it is interesting to see whether this has affected \nthe epidemiology of cutaneous HPV infection in \nMalaysia. \n\n\n\nCryotherapy and 20% salicylic acid ointment were \ngenerally well tolerated by the patients and there \nwere only 3 patients who reported side effects to \ncryotherapy.  Two of these patients developed blisters \nand 1 patient developed hyperpigmentation.  There \nwas no reported adverse event with 20% salicylic \nacid ointment such as maceration.    These findings \nare similar to two previous studies, which also found \nthat more side effects were related to cryotherapy.20, \n\n\n\n21 20% salicylic acid ointment has been shown to be \npainless and maybe more cosmetically acceptable \ncompared to cryotherapy as it does not cause side \neffects such as hyperpigmentation. Cryotherapy is \nassociated with a higher cost.33 For the hospital, \nthere is a higher cost associated with the healthcare \nprofessional\u2019s time for treatment administration \nand the cost of the treatment itself, which included \nthe cost of equipment and liquid nitrogen.  For the \npatient, the cost of travelling to the hospital, parking \nfees and registration fees also need to be taken into \nconsideration.  Since both treatments were shown \nto be equally effective, the safety profile of salicylic \nacid and the fact that cryotherapy is more expensive \nmakes salicylic acid a more attractive treatment for \nplantar warts.\n\n\n\nThere are several limitations in this study. This study \ndid not have an arm for placebo so natural resolution \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3850\n\n\n\nof the warts cannot be elucidated.  A better designed \nstudy would include a wait-and-see treatment arm \nas this would allow for a control group for the study.  \nThere is also no blinding for the patients and the \nhealth care provider who administered the treatment \nas the two treatments used different modalities and \nrealistic blinding cannot be achieved.  Salicyclic \nacid ointment were applied by the patients \nthemselves so there is bound to be some variations \nbetween each individual including compliant issue \nwith this self-applied topical treatment.   We did not \nevaluate the effectiveness of salicylic acid treatment \nif it is delivered by a health care professional as this \nwould mean a daily visit to hospital by the patient \nand therefore would be impractical.  \n\n\n\nConclusion\nThis study showed that cryotherapy is as effective \nas 20% salicylic acid ointment in the treatment \nof plantar warts.  Cryotherapy is associated with \nmore side effects including pain, blisters and \nhyperpigmentation. The cost of treatment for \ncryotherapy is also higher for the hospital and the \npatient. Salicylic acid ointment on the other hand \ndid not have any reported side effects in this study \nand can be applied at home.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Bernard HU,  Burk RD, Chen Z, van Doorslaer K, zur Hausen \nH, De Villiers EM. Classification of papillomaviruses \n(PVs) based on 189 PV types and proposal of taxonomic \namendments. Virology 2010;401:70-9.\n\n\n\n2. Harwood CA, Surentheran T, McGregor JM, Spink PJ, \nLeigh IM, Breuer J et al.  Human papillomavirus infection \nand non-melanoma skin cancer in immunosuppressed and \nimmunocompetent individuals. J Med Virol 2000;61:289-\n97.\n\n\n\n3. Rubben A, Kalka K, Spelten B, Grussendorf-Conen EI. \nClinical features and age distribution of patients with \nHPV 2/27/57-induced common warts. Arch Dermatol Res \n1997;289:337-40.\n\n\n\n4. Elston DM, Bergfeld WF. Skin diseases of the hands and \nfeet. Phys Sportsmed 1994;22:40-50.\n\n\n\n5. Grayson W. In McKee\u2019s Skin Pathology with Clinical \nCorrelations. L. A. Calonje BTE, Mckee P (eds). Toronto, \nElsevier; 2012:760\u2013895.\n\n\n\n6. Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. \nHuman papillomavirus molecular biology and disease \nassociation.  Rev Med Virol 2015;25:2-23.\n\n\n\n7. Lipke MM. An armamentarium of wart treatments. Clin \nMed Res 2006;4:273-93.\n\n\n\n8. Sterling JC, Gibbs S, Haque Hussain SS, Mohd \nMustapa MF, Handfield-Jones SE.  British Association \nof Dermatologists\u2019 guidelines for the management of \ncutaneous warts 2014. Br J Dermatol 2014;171:696-712.\n\n\n\n9. El-Mohamady Ael S, Mearag I, El-Khalawany M, \nElshahed A, Shokeir H, Mahmoud A.  Pulsed dye laser \nversus Nd:YAG laser in the treatment of plantar warts: a \ncomparative study. Lasers Med Sci 2014;29:1111-6.\n\n\n\n10. Smith EA, Patel SB and Whiteley MS.  Evaluating the \nsuccess of Nd: YAG laser ablation in the treatment of \nrecalcitrant verruca plantaris and a cautionary note about \nlocal anaesthesia on the plantar aspect of the foot. J Eur \nAcad Dermatol Venereol 2015;29:463\u20137.\n\n\n\n11. Fabbrocini G, Di Costanzo MP, Riccardo AM, Quarto M, \nColasanti A, Roberti G et al.  Photodynamic therapy with \ntopical delta \u2013aminolaevulinic acid for the treatment of \nplantar warts.  J Photoceh Photobio B 2001;61:30-4.\n\n\n\n12. Vickers CF. Treatment of plantar warts in children. BMJ \n1961;2:743-5.\n\n\n\n13. Bunney MH, Nolan MW, Williams DA.  An assessment \nof methods of treating viral warts by comparative \ntreatment trials based on a standard design.  Br J Dermatol \n1976;94:667-79.\n\n\n\n14. Hjorth N, Madsen K, Norgaard M. Anthralin stick \n(Anthraderm) in the treatment of mosaic warts.  Acta Derm \nVenereol 1986;66:181-2.\n\n\n\n15. Duthie DA, McCallum DI. Treatment of plantar warts with \nelastoplast and podophyllin.  BMJ 1951;2:216-8.\n\n\n\n16. Salk RS, Grogan KA, Chang TJ.  Topical 5% 5-fluorouracil \ncream in the treatment of plantar warts: a prospective, \nrandomized, and controlled clinical study. J Drugs \nDermatol 2006;5:418-24. \n\n\n\n17. Armour K, Orchard D. Treatment of palmoplantar \nwarts with a diphencyprone and salicylic acid ointment. \nAustralas J Dermatol 2006;47:182\u20135.\n\n\n\n18. Micali G, Nasca MR, Tedeschi A, Dall\u00d3glio F, Pulvirenti \nN. Use of squaric acid dibutylester (SADBE) for cutaneous \nwarts in children. Paedr Dermatol 2000;17:315-8.\n\n\n\n19. Steele K; Irwin WG. Liquid nitrogen and salicylic/lactic \nacid paint in the treatment of cutaneous warts in general \npractice. J R Coll Gen Pract 1988;38:256-8.\n\n\n\n20. Bruggink SC, Gussekloo J, Berger MY, Zaailer K, \nAssendelft WJ, de Waal MW et al. Cryotherapy with \nliquid nitrogen versus topical salicylic acid application for \ncutaneous warts in primary care: randomized controlled \ntrial. CMAJ 2010;182:1624-30.\n\n\n\n21. Cockayne S, Hewitt C, Hicks K, Shalmini Jayakody, \nArthur Ricky Kang\u2019ombe, Eugena Stamuli et al. \nCryotherapy versus salicylic acid for the treatment of \nplantar warts (verrucae): a randomised controlled trial. \nBMJ 2011;342:d3271.\n\n\n\n22. Berth-Jones, J, Bourke J, Eglitis H, Harper C, Kirk  P,  Pavord \nS et al. Value of a second freeze-thaw cycle in cryotherapy \nof common warts. Br J Dermatol 1994;131:883-6.\n\n\n\n23. Bruggink SC, de Koning MN, Gussekloo J, Egberts PF, \nTer Schegget J, Feltkamp MC et al. Cutaneous wart-\nassociated HPV types: prevalence and relation with patient \ncharacteristics. J Clin Virol 2012;55:250-5.\n\n\n\n24. Bruggink SC, Gussekloo J, de Koning MN, Feltkamp \nMC, Bavinck JN, Quint WG et al. HPV type in plantar \nwarts influences natural course and treatment response: \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 51\n\n\n\nsecondary analysis of a randomised controlled trial. J Clin \nVirol 2013;57:227-32.\n\n\n\n25. Rogers CJ, Gibney MD, Siegfried EC, Harrison BR, \nGlaser DA. Cimetidine therapy for recalcitrant warts in \nadults: is it any better than placebo? J Am Acad Dermatol \n1999;41:123-7.\n\n\n\n26. Leman JA, Benton EC. Verrucas. Guidelines for \nmanagement. Am J Clin Dermatol 2000;1:143-149.\n\n\n\n27. Connolly MK, Bazmi, O\u2019Connell M, Lyons JF, Bourke \nJF. Cryotherapy of viral warts: a sustained 10-s freeze is \nmore effective than the traditional method. Br J Dermatol \n2001;145:554-7.\n\n\n\n28. Berth-Jones J, Hutchinson PE. Modern treatment of warts: \ncure rates at 3 and 6 months. Br J Dermatol 1992;127:262-\n5.\n\n\n\n29. van Brederode RL, Engel ED. Combined cryotherapy/70% \nsalicylic acid treatment for plantar verrucae. J Foot Ankle \nSurg 2001;40:36-41.\n\n\n\n30. Markowitz LE, Dunne EF, Saraiya M, Herschel W. \nLawson, Harrell Chesson, Elizabeth R. Unger. Centers \nfor Disease, Prevention and P. Advisory Committee on \nImmunization. Quadrivalent Human Papillomavirus \nVaccine: Recommendations of the Advisory Committee \non Immunization Practices (ACIP). MMWR Recomm Rep \n2007;56:1-24.\n\n\n\n31. Landis MN, Lookingbill DP, Sluzevich JC. Recalcitrant \nplantar warts treated with recombinant quadrivalent \nhuman papillomavirus vaccine. J Am Acad Dermatol \n2012;67:e73-74.\n\n\n\n32. Ault KA. Human papillomavirus vaccines and the potential \nfor cross-protection between related HPV types. Gynecol \nOncol 2007;107:S31-3.\n\n\n\n33. Le Cleach L, Trinquart L, Penso-Assathiany D, Chosidow \nO. Comparative effectiveness of cryotherapy and salicylic \nacid for plantar warts. Arch Dermatol 2012;148:1311-3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3852\n\n\n\nORIGINAL ARTICLE\n\n\n\nAn Epidemiological Study of Stevens-Johnson Syndrome (SJS), \nToxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome/\nToxic Epidermal Necrolysis (SJS/TEN) overlap in University Malaya \nMedical Centre \n\n\n\nLeng Leng Tan1, Adv M Derm, Sze Ting Ooi2, Su Ming Wong3, Adv M Derm, Chin Chwen Ch\u2019ng1, Adv M Derm, \nZhenli Kwan1, Adv M Derm, Adrian Sze Wai Yong1, MRCP, CCT \n\n\n\n1Dermatology Unit, Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia\n2Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia\n3Koh and Wong Skin Specialist Clinic, Selangor, Malaysia\n\n\n\nAbstract\nIntroduction:\nSteven-Johnson syndrome and Toxic Epidermal Necrolysis are rare but life threatening severe \ncutaneous adverse reactions to drugs. To determine the epidemiology of SJS, TEN and SJS/TEN \noverlap in University Malaya Medical Centre (UMMC).\n\n\n\nMethods: \nAll patients admitted to UMMC from year 2013-2015 for SJS, SJS/TEN, TEN were recruited. The \nclassification of SJS, SJS/TEN overlap and TEN was made based on the criteria laid down by Bastuji \net al.2\n\n\n\nResults: \nA total of 32 patients were recorded to have SJS, SJS/TEN overlap and TEN from 2013 to 2015. Drugs \n(n=32, 86.49%) remained the most common aetiology of SJS and TEN. The top three commonest \ndrugs are allopurinol (n=6), followed by carbamazepine (n=5) and bactrim (n=3).  \n\n\n\nConclusion: \nThis study demonstrates that drugs were the most common cause of SJS/TEN. Antibiotics were the \nmost common drug group that caused SJS/TEN. Awareness of the common etiology such as drug \nis important and high index of suspicion of SJS and TEN is needed if patients were on the above \nmedications.\n\n\n\nKey words: Severe Cutaneous Adverse Reactions (SCAR), Stevens-Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN) \n\n\n\nCorresponding Author\nDr Tan Leng Leng\nDivision of Dermatology, Department of Medicine, \nFaculty of Medicine, University of Malaya, 50603 \nLembah Pantai, Kuala Lumpur, Malaysia\nEmail: tllktc@hotmail.com\n\n\n\nIntroduction\nStevens-Johnson syndrome (SJS) and Toxic \nEpidermal Necrolysis (TEN) are severe cutaneous \nadverse reactions (SCAR) to drugs. Previous \nconceptions on the SJS and TEN as two individual \nreactions with differing pathogenesis had been \nreplaced by SJS and TEN being a continuum that \ndiffers by the extent of skin detachment.1 The \nclassification depends on the extent of body surface \narea affected by epidermal detachment and the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 53\n\n\n\nextent of mucosal involvement (at least 2 mucosal \nsurface comprising ocular, oral and genital). SJS is \ncharacterized by the presence of flat, atypical target \nlesions with epidermal detachment of less than 10% \nof the total body surface area. As for TEN, TEN with \nspots involves detachment above 30% of the body \nsurface area plus widespread purpuric macules or \nflat atypical targets while toxic epidermal necrolysis \nwithout spots involves detachment above 10% of \nthe body surface area with large epidermal sheets \nand without any purpuric macule or target.  In the \nSJS/TEN overlap, epidermal detachment of 10-30% \nof the total body surface area is observed.1 The study \nis to determine the epidemiology of SJS, TEN and \nSJS/TEN overlap in University Malaya Medical \nCentre (UMMC).\n\n\n\nMaterials and Methods\nThis is a single centre study of SJS, SJS/TEN \noverlap and TEN cases done on patients admitted to \nUMMC from year 2013-2015. Patients who refused \nto participate in the study were excluded. \n\n\n\nThe classification of SJS, SJS/TEN overlap and \nTEN was made based on the criteria laid down \nby Bastuji et al.2 No skin biopsies were done. The \ndiagnoses were achieved by dermatologists on \nclinical grounds. Drug(s) taken within and up to \neight weeks preceding the onset of symptoms were \nconsidered as the causative drugs. If more than \none drug were taken, they were all considered as \ncausative drugs. Blood investigations were taken to \nassess for organ involvement and to exclude other \n\n\n\nsevere cutaneous adverse drug reactions like Drug \nHypersensitivity Syndrome.\n\n\n\nPatients who had not taken any drugs regularly or \nprior to the onset of symptoms and did not have any \nnoticeable cause of their symptoms were categorized \nas unknown.\n\n\n\nThe data collected were all compiled on a Microsoft \nExcel spreadsheet. Descriptive statistical analysis \nwas performed.\n\n\n\nResults\nA total of 32 patients were recorded to have SJS, \nSJS/TEN overlap and TEN from 2013 to 2015. \nDrugs (n=32, 86.49%) remained the most common \naetiology of SJS and TEN. In the other 5 patients (n=5, \n13.51%) the aetiology was not identified. Antibiotics \n(n=15, 46.88%) turned out to be the most common \ntype of drug that led to SJS and TEN followed by \nanti-gout medication (n=6, 18.75%), antiepileptics \n(n=5, 15.63%) and then NSAIDS (n=3, 9.38%) and \nothers (n=3, 9.38%). Penicillins group accounted for \nmost of the cases caused by antibiotics with 7 cases \n(n=7, 21.88%) followed by sulphonamides with a \ntotal of 3 cases (n=3, 9.38%). The only antiepileptic \nthat was recorded to cause SJS was carbamazepine. \nThe drug most frequently associated with the cases \nin this study was allopurinol (6 cases, 18.75%) \nfollowed by carbamazepine (5 cases, 15.63%) and \nSulfamethoxazole and trimethoprim (Bactrim) (3 \ncases, 9.38%). \n\n\n\nSJS, n TEN, n SJS/TEN, n No. of cases, n (%)\nDrugs 30 2 0 32 (86.49)\nUnknown 1 1 3 5 (13.51)\n\n\n\nTable 1. Causes of SJS, SJS/TEN overlap and TEN\n\n\n\nOut of the 32 patients, 4 patients (12.5%) had more \nthan one drug being the suspected aetiological \nagents. The initial age of presentation ranges \nfrom15 to 85 years old with the mean age of 50. Out \n\n\n\nof 32 patients, the majority affected is male (n=22, \n68.75%). 21.4% (6 out of 28 patients) has renal \nimpairment and only 7% (2 out of 28 patients) has \nliver impairment. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3854\n\n\n\nTable 2. Drugs implicated in SJS, SJS/TEN overlap and TEN\n\n\n\nSJS, n TEN, n SJS/TEN, n No. of cases, n (%)\nAntibiotics 15(46.88%)\n  Sulphonamides\n\n\n\nSulfamethoxazole+trimethoprim \n(Bactrim)\n\n\n\n3 0 0 3 (9.38)\n\n\n\n  Penicillins\nAmoxicillin 2 0 0 2 (6.25)\nAmoxicillin+Clavulanic acid \n(Augmentin)\n\n\n\n2 0 0 2 (6.25)\n\n\n\nCloxacillin 1 0 0 1 (3.13)\nPenicillin 1 0 0 1 (3.13)\nBacampicillin 1 0 0 1 (3.13)\n\n\n\nTotal: 7 (21.88)\n  Tetracycline\n\n\n\nDoxycycline 1 0 0 1 (3.13)\n  Macrolides\n\n\n\nAzithromycin 1 0 0 1 (3.13)\n  Cephalosporins\n\n\n\nCefuroxime (Zinnat) 1 0 0 1 (3.13)\n  Others\n\n\n\nVancomycin 1 0 0 1 (3.13)\nRifampicin+Isoniazid (Akurit) 1 0 0 1 (3.13)\n\n\n\nAnti-epileptics 5 (15.63)\n  Carbamazepine 5 0 0 5 (15.63)\nNSAIDS 3 (9.38)\n  Etoricoxib (Arcoxia) 0 1 0 1 (3.13)\n  Mefenamic acid(Ponstan) 2 0 0 2 (6.25)\nAnti-gout 6 (18.75)\n  Allopurinol 5 1 0 6 (18.75)\nOthers 3 (9.38)\n  Fluconazole 1 0 0 1 (3.13)\n  Telmisartan(Micardis) 1 0 0 1 (3.13)\n  Thalidomide 1 0 0 1 (3.13)\n\n\n\nTable 3. Demographic of SJS, SJS/TEN overlap and TEN\n\n\n\nCharacteristics Mean age of initial presentation (years) No. of cases, n (%)\nMean age 50.00\nMale 47.95 22 (68.75)\nFemale 55.12 10 (31.25)\nRenal impairment 63.83 6 (21.40)\nLiver impairment 65.50 2 (7.00)\n\n\n\nDiscussion\nThe most commonly implicated drugs were \nallopurinol (6 cases, 18.75%) followed by \ncarbamazepine (5 cases, 15.63%), possibly due \nto common usage of both drugs and the genetic \nsusceptibility to SJS, SJS/TEN and TEN in this \nregion. No previous epidemiological studies on SJS, \nSJS/TEN and TEN had been done in University \nMalaya and surrounding regions. However, there \nhad been studies on SJS, SJS/TEN and TEN done \non other regions in Malaysia that showed drugs, \nmainly antibiotics and antiepileptics as the most \ncommon culprit.3-5 These results are also consistent \nwith other studies done in Thailand, Singapore and \nKorea.6-8 \n\n\n\nA study done by Ding et al. in Johor showed \nthat allopurinol, carbamazepine, phenytoin and \ncotrimoxazole were the main culprit for adverse \ndrug reactions with allopurinol 39 (13.9%), \ncarbamazepine in 29 (10.3%), phenytoin in 27 \n(9.6%) and cotrimoxazole in 26 (9.3%) cases.5 \nChoon et al also has done a study in Johor, out of 362 \ncases of cutaneous adverse drug reactions, 144 cases \nwere severe cutaneous adverse reaction to drugs. \nCarbamazepine, allopurinol and cotrimoxazole \nwere the top three etiology of SJS/TEN.4 In 2015, \nSasidharanpillai et al had conducted a study \non drug eruption and severe cutaneous adverse \nreaction which included 14 patients. The culprit \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 55\n\n\n\ndrugs identified were anticonvulsants, antibiotics \nand NSAIDs.15 This is consistent with our study. \nHowever, phenytoin is not the causative drug in \nour study. This finding is surprising and was not \nconsistent with other countries. Phenytoin has been \na common causative agent for SJS, SJS/TEN and \nTEN up to 13% in a study involving 127 patients.14 \nOur study showed that carbamazepine was second \ncommonest agent associated with SJS and TEN in \nour population. \n\n\n\nThis is difficult to explain as phenytoin is still one \nof the first line antiepileptics used in this region \nespecially for status epilepticus. On top of that, \nHLA1502 testing is available in University Malaya \nMolecular laboratory and is routinely carried out \nbefore initiating treatment of carbamazepine but not \nfor phenytoin and allopurinol. This explained the \nhigh incidence of allopurinol induced SJS but not \nfor the lack of phenytoin induced SJS. Phenytoin \nis not the preferred 1st line for maintenance therapy \nfor epilepsy in University Malaya may be because \nchronic phenytoin user is associated with high \nincidence of side effects such as sedation, gum \nhypertrophy, lymphadenopathy, chorea and ataxia. \nAmong those, there are a few reports on cerebellar \natrophy and degeneration. However, the usage \nof phenytoin is still high in this university due to \ncompliance and financial issues.\n\n\n\nThe correlation between human leukocyte antigen \n(HLA) genotype and SJS/TEN had been observed \nin many studies. An association between the \nHLA-B*5801 allele and allopurinol-induced SJS/\nTEN can be found in some studies, including one \ndone in Europe.9-10 There are currently no studies \npublished in Malaysia regarding this.\n\n\n\nStudies have also suggested that Han Chinese and \nother Asian populations, including Malaysia are \nmore susceptible to carbamazepine-induced SJS/\nTEN due to the HLA-B*1502 gene.11-12 However, \nstudies done in Europe have so far failed to prove \nthis correlation.13\n\n\n\nConclusion\nThis study demonstrates that drugs were the most \ncommon cause of SJS/TEN. Antibiotics were the \nmost common drug group that caused SJS/TEN. \nOther common drug groups that caused SJS/TEN \nincludes anti-gout medication, antiepileptics and \nnon-steroidal anti-inflammatory drugs (NSAIDS). \nThe most commonly implicated individual drug \nwas allopurinol, followed by carbamazepine. Our \n\n\n\nstudy showed that drugs that were implicated in \nthe aetiology of SJS and TEN in our population \nare commonly used drugs in the clinical setting. \nWe support the need for HLA testing prior to the \ncommencement of carbamazepine. Obtaining an \nallergy history prior to prescribing antibiotics and \nNSAIDs may be useful to reduce the incidence of \nSCARs as prescribers can then avoid using possibly \nimplicated drugs for patients with known allergies \nwhile maintaining a high index of clinical suspicion \nfor any patients who report adverse reactions in \norder to commence necessary treatment at an early \nstage.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. T Harr, LE French. Toxic epidermal necrolysis and Stevens-\nJohnsons syndrome. Orphanet J Rare Dis 2010;5:1\u201311.\n\n\n\n2. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi \nL, Roujeau JC. Clinical Classification of Cases of Toxic \nEpidermal Necrolysis, Stevens-Johnson Syndrome, and \nErythema Multiforme. Arch Dermatol 1993;129:92-6.\n\n\n\n3. Kamaliah MD, Zainal D, Mokhtar N, Nazmi N. Erythema \nmultiforme, Stevens-Johnson syndrome and toxic \nepidermal necrolysis in northeastern Malaysia. Int J \nDermatol 1998;7:520-3.\n\n\n\n4. Choon SE, Lai NM. An epidemiological and clinical \nanalysis of cutaneous adverse drug reactions seen in a \ntertiary hospital in Johor, Malaysia. Indian J Dermatol \nVenereol Leprol 2012;78:734.\n\n\n\n5. Ding WY, Lee CK, Choon SE. Cutaneous adverse drug \nreactions seen in a tertiary hospital in Johor, Malaysia. Int \nJ Dermatol 2010;49:834-41. \n\n\n\n6. Kim HI, Kim SW, Park GY, KwonEG, Kim HH, Jeong JY \net al. Causes and Treatment Outcomes of Stevens-Johnson \nSyndrome and Toxic Epidermal Necrolysis in 82 Adult \nPatients. Korean J Intern Med 2012;27:203-10. \n\n\n\n7. Tan SK, Tay YK. Profile and Pattern of Stevens-Johnson \nSyndrome and Toxic Epidermal Necrolysis in a General \nHospital in Singapore: Treatment Outcomes. Acta Derm \nVenerol 2012;92:62-6.\n\n\n\n8. Su P, Aw CW. Severe cutaneous adverse reactions in a \nlocal hospital setting: A 5-year retrospective study. Int J \nDermatol 2014;53:1339-45.\n\n\n\n9. Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, \nHalevy S et al. A European study of HLA-B in Stevens \nJohnson syndrome and toxic epidermal necrolysis related \nto five high-risk drugs. Pharmacogenetics and Genomics \n2008;18:99-107.\n\n\n\n10. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang \nHP et al. HLA-B*5801 allele as a genetic marker for \nsevere cutaneous adverse reactions caused by allopurinol. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3856\n\n\n\nProceedings of the National Academy of Sciences \n2005;102:4134-9. \n\n\n\n11. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho \nHC et al. Medical genetics: A marker for Stevens\u2013Johnson \nsyndrome. Nature 2004;428:486. \n\n\n\n12. Chang CC, Too CL, Murad S, Hussein SH. Association \nof HLA-B*1502 allele with carbamazepine-induced toxic \nepidermal necrolysis and Stevens-Johnson syndrome in \nthe multi-ethnic Malaysian population. Int J Dermatol \n2011;50:221-4.\n\n\n\n13. Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, \nLeLouet H et al. A marker for Stevens-Johnson syndrome: \nEthnicity matters. Pharmacogenomics J 2006;6:265-8.\n\n\n\n14. Sanmarkan AD, Sori T, Thappa DM, Jaisankar TJ. \nRetrospective analysis of stevens-johnson syndrome and \ntoxic epidermal necrolysis over a period of 10 years. \nIndian J Dermatol 2011;56:25\u20139.  \n\n\n\n15. Sasidharanpillai S, Riyaz N, Khader A, Rajan U, \nBinitha MP, Sureshan DN. Severe cutaneous adverse \ndrug reactions: a clinicoepidemiological study. Indian J \nDermatol 2015;60(1):102.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 57\n\n\n\nORIGINAL ARTICLE\n\n\n\nDrug Reaction with Eosinophilia and Systemic Symptoms (DRESS): \nA Review of 21 Cases over 7 years Period from Selayang Hospital \n\n\n\nSook Yee Michelle Voo1, Adv M Derm, Luk Chin Wong2, MBBS, Hui Wen Ng3, B Pharm, Rohna Ridzwan4, MRCP, \nSeok Siam Tan5, MRCP\n\n\n\n1Department of Dermatology, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia\n2Department of Medicine, Hospital Selayang, Selangor, Malaysia\n3Department of Pharmacy, Hospital Selayang, Selangor, Malaysia\n4Department of Dermatology, Hospital Selayang, Selangor, Malaysia\n5Department of Hepatology, Hospital Selayang, Selangor, Malaysia\n\n\n\nAbstract\nIntroduction:\nDRESS is an uncommon severe cutaneous adverse drug reaction, which is under recognized. In this \nreview, we aim to study the clinical characteristics of patients with DRESS that presented to our \nhospital.\n\n\n\nMethods: \nWe conducted a retrospective analysis on the data of all the patients with DRESS from January 2006 \nto December 2012 in Selayang Hospital.\n\n\n\nResults: \nTwenty-one patients were included with median age of 33 and male to female ratio of 1:1. Allopurinol \nwas the most frequent causative drug followed by anti-tuberculous drugs. The mean latency period \nwas 28.6 days. All patients had macula-papular rash of which 6 progressed to erythroderma. Liver was \nthe most frequent extra cutaneous organ involvement with median peak alanine transaminase of 746 \niu/l, (range 45-3677) and median peak aspartate transaminase of 632 iu/l (range 30-3136). Six patients \n(28.5%) had acute liver failure.  The mainstay of treatment was systemic corticosteroid. Mortality rate \nwas 23.8%.\n\n\n\nConclusion:\nDRESS is a severe cutaneous adverse drug reaction with a myriad of clinical presentation and is \nassociated with mortality. Our series has higher mortality compared to most other reported studies, \nmost probably due to referral bias. Early recognition is crucial. \n\n\n\nKey words: severe cutaneous adverse drug reaction, maculo-papular rash, acute liver failure, eosinophilia\n\n\n\nCorresponding Author\nDr Voo Sook Yee @ Michelle\nDepartment of Dermatology, Hospital Queen Elizabeth, \nKota Kinabalu, Malaysia\nEmail: miyee03@yahoo.com\n\n\n\nIntroduction\nDRESS (Drug reaction with eosinophilia and \nsystemic symptoms) or otherwise also known as \nDrug induced hypersensitivity syndrome (DIHS) is \nan uncommon but severe idiosyncratic cutaneous \nadverse drug reaction, which carries a mortality \nrate of up to 10%.1 It is characterized by fever, \nskin rash, lymphadenopathy and multi-organ \ninvolvement. The incidence of this adverse drug \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3858\n\n\n\nreaction ranges between 1:1000 to 1:10,000.2 The \nonset of symptoms usually occurs 2-8 weeks after \ndrug ingestion, which is delayed when compared to \nother types of cutaneous drug reactions.3,4 There is \nalso possible persistence or worsening of DRESS \ndespite withdrawal of the offending drug.5 The \ndiagnosis is a challenge as it mimics other clinical \ndiseases such as sepsis and connective tissue \ndisease. Currently, There is no specific markers for \nthe diagnosis of DRESS and the clinical features \nare not pathognomonic therefore it is a diagnosis of \nexclusion, however awareness of the condition will \nhelp. \n\n\n\nRecently with the increasing awareness about this \nsevere cutaneous adverse drug reaction, there is \nan increased in the number of published reports \nfrom overseas on DRESS. Some studied the clinic-\npathogical features6,11,12,13,14,15 while others attempted \nto look for prognostic factors11,16 or long term \noutcome.17 However local data is scarce. Hence the \nobjective of this study is to report on the clinical \nfeatures, disease course and outcome in patients \nwith DRESS. \n\n\n\nMaterials and Methods \nA retrospective medical records review was \nconducted on Adverse Drug Reaction Registry \nin Selayang Hospital, Malaysia from January \n2006 to December 2012. Patients recruited were \neither diagnosed to have DRESS by a consultant \ndermatologist or had drug rash and eosinophilia. All \ncases also had to fulfill the criteria proposed by the \nEuropean Registry of Severe Cutaneous Adverse \nDrug Reaction (RegiSCAR).6 (Table 1) \n\n\n\nThe definitions of extra cutaneous involvement \nwere as from previous studies.1,14 Liver involvement \nwas defined as increased in transaminases of more \nthan two times upper limit of normal (Upper limit \nnormal of aminotransferase for male = 43iu/l, \nfemale = 30iu/l) or patient\u2019s baseline and other \ncommon causes of hepatitis were excluded. Acute \nliver failure was defined as evidence of coagulation \nabnormality with International Normalized Ratio \n(INR) >1.5 and any degree of mental alteration \n(encephalopathy) in a patient without preexisting \ncirrhosis of less than 26 weeks\u2019 duration.7\n\n\n\nTable 1. RegiSCAR6 criteria for DRESS \n\n\n\nHospitalization\nReaction suspected to be drug related\nAcute skin rash*\nFever 38\u00b0C or more*\nEnlarged lymph node in at least 2 sites*\nInvolvement of at least one internal organ*\nBlood count abnormalities\nLymphocytes 1.8 > or < 4.0 x 103 \u03bcL\nAbsolute eosinophil count > 700/\u03bcL\nPlatelet < 150 x 103 \u03bcL\n\n\n\n*3 or more required\n\n\n\nRenal involvement was defined as unexplained \nincreased in creatinine level of more than twice \nfrom baseline or new onset proteinuria or hematuria. \nPulmonary involvement was defined as unexplained \nabnormal chest radiograph findings. Cardiac \ninvolvement was defined by unexplained elevation \nof cardiac enzymes. Blood culture and sensitivity, \nHepatitis surface antigen, anti\u2013Hepatitis C antibody \nand anti-nuclear antibodies were performed to \nexclude septicemia, connective tissue diseases and \nother common liver diseases. In cases of acute liver \nfailure, ultrasound liver was also done.\n\n\n\nPatients whom fulfill the inclusion criteria were \nfurther divided into possible, probable or definite \nbased on RegiSCAR\u2019s scoring system.3 A final \nscore of 4-5 is probable case whereas final score of \nmore than 5 is definite case. Only the probable and \ndefinite cases were analyzed.\n\n\n\nAny drug(s), including prescribed medications, \nover the counter self medications, supplements \nand herbal products consumed within the 2-months \nperiod before the onset of symptoms were recorded. \nA criteria set by Naranjo et al8 was used to assign \ncausality of each potential agent. The offending \nagent(s) was categorized as uncertain if more than \none drug were implicated. \n\n\n\nStatistical analysis\nSPSS version 20 was used to analyze the data \ncollected. Chi square test was adopted for 2-sample \ncomparison for allopurinol or anti-tuberculosis \ninduced DRESS with other drug induced DRESS \nfor categorical variables. The results were expressed \nas means or medians. P value of less than 0.05 is \nconsidered to be statistically significant.\n\n\n\nResults\nThere were 21 patients with equal proportion of \nmales and females whom were diagnosed with \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 59\n\n\n\nDRESS and fulfilled the inclusion criteria during \nthe study period, yielding a frequency of 0.024% \namong the reported adverse drug reactions in our \nhospital. The median age of the patients in years \nwas 33 (IQR 27; range 20-73). There were 9 Malay \npatients, 6 Chinese patients, 2 Indian patients and 4 \nforeigners (3 from Indonesia and 1 from Pakistan). \nThe clinical data of the patients are summarized in \nTable 2. \n\n\n\nCulprit Drugs\nThe offending agents in order of decreasing \nfrequencies were: allopurinol (n=6, 28.5%), anti-\ntuberculous drugs (n=5, 23.8%), anti-infectives \nnamely minocycline, ceftriaxone, doxycycline and \ndapsone (n=4, 19.0%), anti-epileptics (n=3, 14.3%), \nherbal medications (n=2, 9.5%) and anti-rheumatics \n(n=1, 4.7%) (Figure 1).\n\n\n\nFigure 1. Pie chart showing drug groups causing DRESS.\n\n\n\nClinical Features \nThe mean latency period from ingestion of drug to \nonset of rash was 29 days with median of 28 days \n(range 12\u201360). The anti-tuberculous groups had \nthe longest latency period of 33.8 days compared \nto all the other groups but this was not statistically \nsignificant (p =0.431). Fever was reported in 13 out \nof 21 patients (61.9%). \n\n\n\nAll of our patients had maculo-papular rash, of these \n6 patients (28.5%) progressed to erythroderma. \nEight patients had facial oedema, two of these had \nallopurinol as the culprit agent who also developed \nconcomitant pustules. One patient had Steven \nJohnson Syndrome like presentation with mucosal \ninvolvement. \n\n\n\nFigure 2. A DRESS patient with macula-papular rash and facial \nedema.\n\n\n\nLaboratory Investigations and other organ \ninvolvements\nTwenty of our patients (95.2%) had liver involvement \nwith peak median alanine transaminase of 746 iu/l, \n(IQR 1236; range 45-3677), peak median aspartate \ntransaminase of 632 iu/l (IQR1099; range 30-3136), \nmedian bilirubin of 74 umol/l (range 10-803) and \nmedian INR of 1.5 (IQR 4.6; range 1.09-30.7). Six \npatients had acute liver failure. All of these acute \nliver failure patients had poor prognostic criteria \nas defined by the King\u2019s College Criteria7. Renal \nimpairment was present in 23.8% of our patients. No \nrenal impairment was detected in the antiepileptic \ngroup.\n\n\n\nIn 12 patients with peripheral blood film performed, \n54.5% had atypical lymphocytes. Eosinophilia was \npresent in 85.7% of the study group (18 out of 21) \nand the highest median eosinophil count was 2.4 \n(range 0.0 -16.6).\n\n\n\nLiver Histopathological Findings\nPatients 12 and 15 had liver biopsy performed \nduring liver transplant and post mortem respectively. \nThe liver tissue of patient 15 showed widespread \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3860\n\n\n\ndegeneration and necrosis of hepatocytes with \nextensive intra-acinar fibrosis and inflammation. \nPortal tracts were expanded and infiltrated by \nlymphocytes, plasma cells and also significant \nnumber of eosinophils. There was also evidence of \ncholestasis.\n \nTreatment/Management\nThe causative drug(s) was discontinued in all \npatients. Sixteen patients (76.2%) received systemic \ncorticosteroids (intravenous hydrocortisone or oral \nprednisolone) and the remaining 5 patients received \ntopical corticosteroids and other supportive \ntherapies, which included oral antihistamines and \nemollients. Of the patients whom did not receive \nsystemic steroids, one patient (patient 18) had mild \nDRESS while 4 patients were not recognized to \nhave DRESS (patients 11, 12, 15, 19). Out of the \n16 patients who received systemic corticosteroid \nof an average duration of one month, 4 patients \n(25%) experienced cutaneous flare during tapering \nof prednisolone.\n\n\n\nOutcome\nSixteen of the 21 patients recovered. One patient \nwith acute liver failure and poor prognostic criteria \nreceived cadaveric organ liver transplantation \nand remained well at 5 years post transplant. Five \npatients died within median of 7 days of admission \n(range 4 -12) to our hospital. The causes of death \nwere acute liver failure and sepsis (n=3) and \nmulti-organ failure (n=2). The offending agents in \nthose who died were allopurinol (n=2), traditional \nmedications (n=1), carbamazepine (n=1) and anti-\ntuberculous therapy (n=1).\n\n\n\nDiscussion\nIn this cohort of patients with DRESS, we found \nthat the common presentations were macula-papular \nrash, liver involvement, peripheral eosinophilia \nand fever.  The in-hospital mortality rate was \nhigh at 23.8% which was much higher than the \n5.9 -10% reported in other published literature. \nThe Taiwanese1,11 and European9 studies report a \nmortality rate of 10% (Table 3) whereas an earlier \nMalaysian study reported a lower mortality rate \nof 5.9%.10 The higher mortality rate in the present \nstudy could be due to referral bias as our hospital \nis a tertiary referral center for hepatology services. \nAll of the cases that died had preceding acute liver \nfailure. Five out of the 6 patients with acute liver \nfailure were referred from other government or \nprivate hospitals for further management of drug \ninduced liver injury. The period between the onset \n\n\n\nof rash and diagnosis of DRESS were almost similar \nbetween those that died (mean 16.4 days) and those \nthat recovered (15.8 days). \n\n\n\nThe most frequent causative drug in our study was \nallopurinol. This finding is consistent with findings \nfrom the Taiwanese studies.1,11 However, studies from \nEurope,12 Brazil,13 Thailand14,18 and Korea15 reported \nanticonvulsant as the most frequent causative drug. \nThis could be due to the difference in the prevalence \nof genetic susceptibility such as HLA-B*5801 \nin different populations.19,20 While prescribing \nallopurinol for asymptomatic hyperuricemia is \nprobably more common in Taiwan,1 only one of the \nsix patients in our cohort was prescribed allopurinol \nfor this reason. It is worth noting that the Malaysian \nAdverse Drug Reaction Advisory Committee has \ntaken several risk minimization measures to ensure \nproper allopurinol prescription among health care \nproviders, including restricting the prescription of \nthis drug to specialist only.21\n\n\n\nIn the present study, patients\u2019 median age was 39, \nwhich is similar to other studies.1, 12, 13 The anti-\ntuberculosis medications had higher mean latency \ntime of 33.8 days (range 28 \u2013 60 days) compared \nto the overall mean of 28 days. It is important for \nthe health care providers to take note of the delayed \npresentation of this adverse drug reaction related \nto anti-tuberculosis drugs. On a further note, it is \ncommendable that the Malaysia Clinical Practice \nGuidelines 201222 has recommended an earlier \nfollow-up with liver function test monitoring \nwithin one month (2-4 weeks) after starting anti-\ntuberculosis medications instead of 2 months as in \nthe 2002 version. \n\n\n\nThe most common skin presentation was macula-\npapular rash. 38.1% of the patients had facial edema \n(Fig 2). This finding is lower compared to other \nstudies probably because of incomplete physical \nexamination. Walsh et al12 and Wongkitisophon \net al14 found 85.1% and 74.1% of their DRESS \npatients respectively had facial edema. Patient that \npresents with facial edema along with macula-\npapular or exanthematous rash should alert the \nhealthcare provider the possibility of DRESS. In \naddition, DRESS is known to be associated with \nvesicles, bullae, atypical targetoid plaque, purpura \nand pustules.17 Hence it is prudent for clinicians to \nbe aware of the various manifestations in order not \nto miss the diagnosis of DRESS.\n\n\n\nIn this study, liver is the most common extra \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 61\n\n\n\ncutaneous involvement, as with findings from \nmost other studies.1,11,12,13,14 Lin et al23 who studied \npattern of liver injury in patients with DRESS found \nmost of their patients had cholestatic type of liver \ninjury followed by mixed and hepatocellular type. \nHowever, we did not study this. One third of our \npatients with hepatic involvement had acute liver \nfailure. One had liver transplant, whereas the others \ndied. Walsh S et al12 reported in their cohort of 27 \ncases of DRESS, one out of the three patients with \nsevere hepatic impairment died following rejection \nof a liver transplant. In a case report,24 a patient with \nsulphasalazine induced DRESS had fatal recurrence \nafter given vancomycin post liver transplant. \n\n\n\nAbout one fifth of our patients had renal involvement. \nAs with the previous Taiwanese studies1,11 our cohort \nof patients had higher rate of renal involvement \ncompared to European studies.8,11 Chen YC et al1 \npostulated that the high rate of renal involvement \nof 40% in their study might be related to the large \nproportion of allopurinol induced DRESS as they \nfound statistical significance in renal involvement \nrate compared with other drugs. In the present study \namong those with renal involvement, half was due \nto allopurinol induced DRESS whereas the other \nhalf was due to anti-tuberculosis therapies.\n\n\n\nEarly recognition of this cutaneous adverse drug \nreaction and withdrawal of the causative agent are \ncrucial in the management of DRESS.5,25 Systemic \ncorticosteroid is the mainstay of treatment. However \nit may not be required in the management of mild \nforms of DRESS.26 Near to a third of our patients \nwho received systemic steroid had relapse of the rash \ndemonstrating the importance of gradual tapering \nof systemic corticosteroids and careful frequent \nassessment during that process. Prospective studies \n\n\n\nare needed to evaluate optimal pharmacological \nmanagement.\n\n\n\nThe limitation of this study is the small number \nof patients and its retrospective nature. Wei \nCH et al16 in their cohort of 91 patients found \ntachycardia, leukocytosis, tachypnea, coagulopathy, \ngastrointestinal bleed and systemic inflammatory \nresponse syndrome (SIRS) were associated with \npoor outcome in DRESS patients, which we did \nnot study. It would be utmost useful to study the \nprognostic factors as we have higher mortality \nhowever we are unable to do so in this study due \nto its small sample size. We also did not look at \nthe long-term outcome of these patients. Another \ninteresting area to be studied is human herpes virus \n6 reactivation, which is considered to be part of a \ndiagnostic marker of DRESS.27\n\n\n\nConclusion\nDRESS presents with a variety of cutaneous as well \nas extra cutaneous manifestations and is associated \nwith mortality. Our series had higher mortality, \nwhich is contributed by referral bias. Awareness and \nrecognition of this adverse drug reaction by front-\nline clinicians is pertinent especially when patient is \non allopurinol, anti-tuberculosis therapies and even \ntraditional medication.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3862\n\n\n\nN\no\n\n\n\nA\nge\n\n\n\n \n(y\n\n\n\nea\nrs\n\n\n\n) \nSe\n\n\n\nx\n\n\n\nR\nac\n\n\n\ne\nC\n\n\n\no-\nm\n\n\n\nor\nbi\n\n\n\nd(\ns)\n\n\n\nO\nffe\nnd\nin\ng\t\ndr\nug\n(s\n)\n\n\n\nL\nat\n\n\n\nen\ncy\n\n\n\n(d\nay\n\n\n\ns)\nLy\n\n\n\nm\nph\n\n\n\nad\nen\n\n\n\nop\nat\n\n\n\nhy\nL\n\n\n\niv\ner\n\n\n\nin\nvo\n\n\n\nlv\nem\n\n\n\nen\nt\n\n\n\nR\nen\n\n\n\nal\nin\n\n\n\nvo\nlv\n\n\n\nem\nen\n\n\n\nt\nO\n\n\n\nut\nco\n\n\n\nm\ne\n\n\n\nR\neg\n\n\n\niS\nC\n\n\n\nA\nR\n\n\n\n*\nTr\n\n\n\nea\ntm\n\n\n\nen\nt \n\n\n\n(S\nys\n\n\n\nte\nm\n\n\n\nic\n c\n\n\n\nor\ntic\n\n\n\nos\nte\n\n\n\nri\nod\n\n\n\ns)\n\n\n\n1\n20\n\n\n\n M\nM\n\n\n\nEp\nile\n\n\n\nps\ny\n\n\n\nC\nar\n\n\n\nba\nm\n\n\n\naz\nep\n\n\n\nin\ne\n\n\n\n21\n \n\n\n\nN\no\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n6\n\n\n\nYe\ns\n\n\n\n2\n24\n\n\n\n M\nM\n\n\n\nTB\n ly\n\n\n\nm\nph\n\n\n\nad\nen\n\n\n\niti\ns\n\n\n\nA\nnt\n\n\n\ni-T\nB\n\n\n\n m\ned\n\n\n\nic\nat\n\n\n\nio\nn\n\n\n\n60\n \n\n\n\nU\nnk\n\n\n\nno\nw\n\n\n\nn\nYe\n\n\n\ns\nYe\n\n\n\ns\nR\n\n\n\nec\nov\n\n\n\ner\ned\n\n\n\n9\nYe\n\n\n\ns\n3\n\n\n\n28\n M\n\n\n\nC\nG\n\n\n\nou\nty\n\n\n\n a\nrth\n\n\n\nrit\nis\n\n\n\nA\nllo\n\n\n\npu\nrin\n\n\n\nol\n14\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nN\n\n\n\no\nR\n\n\n\nec\nov\n\n\n\ner\ned\n\n\n\n7\nYe\n\n\n\ns\n4\n\n\n\n25\n M\n\n\n\nM\nR\n\n\n\nen\nal\n\n\n\n c\nal\n\n\n\ncu\nli\n\n\n\nA\nllo\n\n\n\npu\nrin\n\n\n\nol\n60\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nYe\n\n\n\ns\nD\n\n\n\nea\nth\n\n\n\n7\nYe\n\n\n\ns\n5\n\n\n\n47\n M\n\n\n\nIn\ndo\n\n\n\nne\nsi\n\n\n\nan\nH\n\n\n\nyp\ner\n\n\n\nte\nns\n\n\n\nio\nn,\n\n\n\n \nLe\n\n\n\npr\nos\n\n\n\ny\nD\n\n\n\nap\nso\n\n\n\nne\n21\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nN\n\n\n\no\nR\n\n\n\nec\nov\n\n\n\ner\ned\n\n\n\n8\nYe\n\n\n\ns\n\n\n\n6\n49\n\n\n\n M\nM\n\n\n\n \nH\n\n\n\nyp\ner\n\n\n\nte\nns\n\n\n\nio\nn\n\n\n\nC\nef\n\n\n\ntri\nax\n\n\n\non\ne\n\n\n\n12\n \n\n\n\nN\no\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n7\n\n\n\nYe\ns\n\n\n\n7\n52\n\n\n\n M\nM\n\n\n\nH\nyp\n\n\n\ner\nte\n\n\n\nns\nio\n\n\n\nn,\n C\n\n\n\nK\nD\n\n\n\nD\nox\n\n\n\nyc\nyc\n\n\n\nlin\ne\n\n\n\n2\nU\n\n\n\nnk\nno\n\n\n\nw\nn\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n5\n\n\n\nYe\ns\n\n\n\n8\n58\n\n\n\n M\nC\n\n\n\n-\nTr\n\n\n\nad\niti\n\n\n\non\nal\n\n\n\n m\ned\n\n\n\nic\nat\n\n\n\nio\nns\n\n\n\n14\nN\n\n\n\no\nYe\n\n\n\ns\nYe\n\n\n\ns\nD\n\n\n\nea\nth\n\n\n\n5\nYe\n\n\n\ns\n9\n\n\n\n69\n M\n\n\n\nC\nG\n\n\n\nou\nty\n\n\n\n a\nrth\n\n\n\nrit\nis\n\n\n\nA\nllo\n\n\n\npu\nrin\n\n\n\nol\n21\n\n\n\n \nU\n\n\n\nnk\nno\n\n\n\nw\nn\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n4\n\n\n\nYe\ns\n\n\n\n10\n73\n\n\n\n M\nC\n\n\n\nH\nyp\n\n\n\ner\nte\n\n\n\nns\nio\n\n\n\nn,\n R\n\n\n\nen\nal\n\n\n\n \nca\n\n\n\nlc\nul\n\n\n\ni\nA\n\n\n\nllo\npu\n\n\n\nrin\nol\n\n\n\n41\n \n\n\n\nN\no\n\n\n\nYe\ns\n\n\n\nYe\ns\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n5\n\n\n\nYe\ns\n\n\n\n11\n22\n\n\n\n F\nI\n\n\n\nEp\nile\n\n\n\nps\ny\n\n\n\nPh\nen\n\n\n\nyt\noi\n\n\n\nn\n29\n\n\n\n \nU\n\n\n\nnk\nno\n\n\n\nw\nn\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n5\n\n\n\nN\no\n\n\n\n12\n26\n\n\n\n F\nM\n\n\n\nSm\nea\n\n\n\nr n\neg\n\n\n\nat\niv\n\n\n\ne \nPT\n\n\n\nB\nA\n\n\n\nnt\ni-T\n\n\n\nB\n m\n\n\n\ned\nic\n\n\n\nat\nio\n\n\n\nn\n35\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nN\n\n\n\no\nR\n\n\n\nec\nov\n\n\n\ner\ned\n\n\n\n4\nN\n\n\n\no\n13\n\n\n\n26\n F\n\n\n\nM\nA\n\n\n\ncn\ne\n\n\n\nM\nin\n\n\n\noc\nyc\n\n\n\nlin\ne\n\n\n\n42\n \n\n\n\nYe\ns\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n7\n\n\n\nYe\ns\n\n\n\n14\n29\n\n\n\n F\nPa\n\n\n\nki\nns\n\n\n\nta\nni\n\n\n\nR\nhe\n\n\n\num\nat\n\n\n\noi\nd \n\n\n\nA\nrth\n\n\n\nrit\nis\n\n\n\nSu\nlfa\n\n\n\nsa\nla\n\n\n\nzi\nne\n\n\n\n36\n \n\n\n\nYe\ns\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n8\n\n\n\nYe\ns\n\n\n\n15\n31\n\n\n\n F\nIn\n\n\n\ndo\nne\n\n\n\nsi\nan\n\n\n\n-\nTr\n\n\n\nad\niti\n\n\n\non\nal\n\n\n\n m\ned\n\n\n\nic\nat\n\n\n\nio\nns\n\n\n\n30\n \n\n\n\nU\nnk\n\n\n\nno\nw\n\n\n\nn\nYe\n\n\n\ns\nN\n\n\n\no\nD\n\n\n\nea\nth\n\n\n\n5\nN\n\n\n\no\n16\n\n\n\n32\n F\n\n\n\nC\nD\n\n\n\nia\nbe\n\n\n\nte\ns\n\n\n\nA\nllo\n\n\n\npu\nrin\n\n\n\nol\n20\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nN\n\n\n\no\nR\n\n\n\nec\nov\n\n\n\ner\ned\n\n\n\n5\nYe\n\n\n\ns\n17\n\n\n\n33\n F\n\n\n\nM\nPT\n\n\n\nB\nA\n\n\n\nnt\ni-T\n\n\n\nb \nm\n\n\n\ned\nic\n\n\n\nat\nio\n\n\n\nns\n28\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nN\n\n\n\no\nD\n\n\n\nea\nth\n\n\n\n5\nYe\n\n\n\ns\n18\n\n\n\n36\n F\n\n\n\n \nIn\n\n\n\ndo\nne\n\n\n\nsi\nan\n\n\n\nG\nut\n\n\n\n T\nB\n\n\n\nPy\nra\n\n\n\nzi\nna\n\n\n\nm\nid\n\n\n\ne\n16\n\n\n\n \nYe\n\n\n\ns\nN\n\n\n\no\nN\n\n\n\no\nR\n\n\n\nec\nov\n\n\n\ner\ned\n\n\n\n7\nN\n\n\n\no\n19\n\n\n\n37\n F\n\n\n\nI\nEp\n\n\n\nile\nps\n\n\n\ny\nC\n\n\n\nar\nba\n\n\n\nm\naz\n\n\n\nep\nin\n\n\n\ne\n35\n\n\n\n \nN\n\n\n\no\nYe\n\n\n\ns\nN\n\n\n\no\nD\n\n\n\nea\nth\n\n\n\n6\nN\n\n\n\no\n20\n\n\n\n54\n F\n\n\n\nM\nH\n\n\n\nyp\ner\n\n\n\nte\nns\n\n\n\nio\nn,\n\n\n\n \nA\n\n\n\nsy\nm\n\n\n\npt\nom\n\n\n\nat\nic\n\n\n\n \nhy\n\n\n\npe\nru\n\n\n\nric\nem\n\n\n\nia\n\n\n\nA\nllo\n\n\n\npu\nrin\n\n\n\nol\n14\n\n\n\n \nU\n\n\n\nnk\nno\n\n\n\nw\nn\n\n\n\nYe\ns\n\n\n\nN\no\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n6\n\n\n\nYe\ns\n\n\n\n21\n61\n\n\n\n F\nC\n\n\n\nD\nia\n\n\n\nbe\nte\n\n\n\ns, \nPT\n\n\n\nB\n, \n\n\n\nH\nyp\n\n\n\ner\nte\n\n\n\nns\nio\n\n\n\nn,\n \n\n\n\nG\nen\n\n\n\ner\nal\n\n\n\nis\ned\n\n\n\n a\nnx\n\n\n\nie\nty\n\n\n\n \ndi\n\n\n\nso\nrd\n\n\n\ner\n\n\n\nA\nnt\n\n\n\ni-T\nB\n\n\n\n m\ned\n\n\n\nic\nat\n\n\n\nio\nns\n\n\n\n30\n \n\n\n\nN\no\n\n\n\nN\no\n\n\n\nYe\ns\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n5\n\n\n\nYe\ns\n\n\n\n M\n- M\n\n\n\nal\nay\n\n\n\n, C\n- C\n\n\n\nhi\nne\n\n\n\nse\n, I\n\n\n\n- I\nnd\n\n\n\nia\nn\n\n\n\nR\neg\n\n\n\niS\nC\n\n\n\nA\nR\n\n\n\n*:\n F\n\n\n\nin\nal\n\n\n\n sc\nor\n\n\n\ne<\n2:\n\n\n\n n\no \n\n\n\nca\nse\n\n\n\n; fi\nna\n\n\n\nl s\nco\n\n\n\nre\n 2\n\n\n\n-3\n: p\n\n\n\nos\nsi\n\n\n\nbl\ne \n\n\n\nca\nse\n\n\n\n; fi\nna\n\n\n\nl s\nco\n\n\n\nre\n 4\n\n\n\n-5\n: p\n\n\n\nro\nba\n\n\n\nbl\ne \n\n\n\nca\nse\n\n\n\n; fi\nna\n\n\n\nl s\nco\n\n\n\nre\n> \n\n\n\n5:\n d\n\n\n\nefi\nni\n\n\n\nte\n c\n\n\n\nas\ne\n\n\n\nTa\nbl\n\n\n\ne \n2.\n\n\n\n C\nlin\n\n\n\nic\nal\n\n\n\n d\nat\n\n\n\na \nof\n\n\n\n th\ne \n\n\n\npa\ntie\n\n\n\nnt\ns.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 63\n\n\n\nReferences\n\n\n\n1. 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Am J Transplant \n2009;9:2197-202.\n\n\n\nTable 3. Comparison with other studies\n\n\n\nRoujeau & Stern9 Walsh S et al12 Chen YC et al1 Wongkitisophon et al14                  Present study\nNumber of patients - 27 60 27 21\nMost frequent drug Anticonvulsant - Allopurinol Phenytoin Allopurinol\nFever (%) 87 100 87 88.9 61.9\nMost frequent rash Exanthem Urticated papular \n\n\n\nexanthem\nExanthem Macula-papular Macula-papular\n\n\n\nLymphadenopathy (%) 75 88 31 22.2 20\nEosinophilia (%) 30 93 52 70.4 85.7\nHepatic involvement (%) 51 100 80 96.3 95.2\nLiver Failure (%) - - - -                                                             28.5\nRenal involvement (%) 11 7 40 7.4 23.8\nMortality (%) 10 11 10 3.7 23.8\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3864\n\n\n\n25. Hussain Z, Reddy BY, Schwartz RA. DRESS syndrome. \nPart II. Management and therapeutics. J Am Acad \nDermatol 2013;68:709 e1-e9\n\n\n\n26. Funck-Brentano E, Duong TA, Bouvresse S, Bagot M, \nWolkenstein P, Roujeau JC et al. Therapeutic management \nof DRESS: a retrospective study of 38 cases. J Am Acad \nDermatol 2015;72:246-52.\n\n\n\n27. Shiohara T, Inaoka M, KanoY. Drug induced \nhypersensitivity syndrome (DIHS): a reaction induced by \na complex interplay among herpes viruses and antiviral \nand antidrug immune responses. Allergol Int 2006;55:1-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 65\n\n\n\nORIGINAL ARTICLE\n\n\n\nLow Dermatitis Potential of a Powder-Free, \u201cAccelerator-Free\u201d Non \nNatural Rubber Latex Gloves Using Modified Draize Study\n\n\n\nMaryam Sakinah Jeffrey1, MBBS, Wan Muhamad Aiman Wan Muhamad2, MBBS, Iman Jeffrey3, MBBS, Hanisah Jeffrey4, \nMBBS, Mardhiah Jeffrey5, MBBS, Muhammad Syafiq Muhammad Isa4, Said AlGhora6, PhD FOM, Emad Ibrahim Husein \nShaqoura6, MBBS, Master of anatomy, Doaa kamal Ibrahim Shaqoura6, MBBS, Master of Physiology, Sharifah Ismail7, \nMD, Nor Wajihan Muda7, Msc.Chem, Siti Maryam Abdul Jabar7, Bsc. Biotech, Saadiah Sulaiman7, MMed\n\n\n\n1Hospital Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia \n2Hospital Selayang, Batu Caves, Selangor, Malaysia \n3Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n4Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n5Hospital Duchess of Kent, Sandakan, Sabah, Malaysia \n6Islamic University of Gaza, Gaza, Palestine \n7Healthmedic Research Sdn Bhd, Cheras, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction: \nThe escalated demand for protective rubber glove in the healthcare industries has resulted in increased \nprevalence of glove related skin problem, irritant and allergic contact dermatitis and latex sensitivity. \nThe industry has recently introduced a new nitrile glove product using a novel patented non-sulphur \nsystem to effect co-valent bond crosslinking to provide the desired elasticity of the gloves. This glove \nalso has ionic crosslinking provided by the zinc oxide used in the formulation and the carboxylic \ngroup of the nitrile latex. The main objective of this study is to prove that residual chemical additives \nat a level that may induce Type IV allergy in the unsensitized general user population are not present \nin this rubber glove and to compare it with a powder free latex examination glove.\n\n\n\nMethods:\nIn collaboration with the Islamic University of Gaza, we conduct modified test on a specially formulated \nand powder free, accelerator free LOW DERMA\u2122 enhanced   nitrile rubber glove that has physical \nproperties and barrier integrity similar to that of NRL gloves. This glove does not contain sulphur or \nsulphur related compound. Two sets of Powder free, accelerator free LOW DERMA\u2122 Nitrile Patient \nExamination Gloves*, white and blue colour were tested using the modified draize-95\u2019 test. Filter \npaper soaked in normal saline and powder free latex examination glove were used as control.   \n\n\n\nResults:\nA total of 209 subjects, 149 subjects, Caucasian (71.29%), 30 subjects, Afro Caribbean (14.35%) and \n30 subjects, Asiatic (14.35%) were recruited. All 209 subjects had a final patch testing scoring of not \nmore than 1.5 during both the induction phase and the challenge phase for both types of Powder Free \nNitrile Patient Examination Gloves (white and blue) and to the negative control, normal filter paper \nand the powder free NRL control glove. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3866\n\n\n\nCorresponding Author\nDr Saadiah Sulaiman\nHealthmedic Research Sdn Bhd, Lot B-G-34, \nPangsapuri Sri Penara, Jalan Sri Permaisuri 1, Bandar \nSri Permaisuri, 56000 Cheras Kuala Lumpur. \nEmail: saadiahazim@yahoo.co.uk\n\n\n\nConclusion:\nThe skin sensitization test (\u2018Modified Draize-95\u2019 Test) of Powder Free Nitrile Patient Examination \nGloves (white and blue) and the powder free NRL examination glove were negative. There was no \nclinical evidence on the presence of residual chemical additives at the level that may induce Type \nIV allergy in unsensitized general user population for both Powder Free Nitrile Patient Examination \nGloves, blue and white colored, non-sterile. Both gloves qualify for \u201cLow dermatitis Claim\u201d.\n\n\n\nKey words: Latex, Allergy, Nitrile, Glove\n\n\n\nIntroduction\nWith the practice of universal precaution in response \nto the AIDS epidemic and the worldwide emergence \nof fatal influenza A(H1N1), A(H5N1), MERS-CoV, \nthe sporadic  epidermic of the deadly ebola virus \nand many other fatal transmissible diseases, the \nuse of protective glove has become  an absolute \nnecessity not only  among healthcare professionals \nbut also caregivers.\n\n\n\nConsequent to this, there is an exponential increase \nin the demand and usage of protective rubber \ngloves, both natural and synthetic. This inevitably \nresulted in the increased prevalence of rubber glove \nrelated skin  problem mostly  contributed by three  \nconstituents of rubber gloves, namely the latex \nprotein, chemical accelerators and the powder that \nis used to ease donning of these gloves.  \n\n\n\nThree major cutaneous effect of rubber gloves are \nirritant contact dermatitis, type I allergic reactions \nand type IV allergic reactions namely allergic \ncontact dermatitis.1 Irritant contact dermatitis which \nis non allergenic in nature is most common, affecting  \nany individual and can occur with gloves made from \nany form of materials. \n\n\n\nType I allergy is an IgE immune-mediated response \ntriggered by exposure to  allergenic proteins or \npolypeptides that occur in latex products. The \nreaction is immediate and presents typically as direct \ncontact urticaria, less commonly rhinoconjunctivitis \nand asthma or rarely, systemic in nature, most \nsevere of which is anaphylactic reaction.2 Chronic \noccupational exposure to latex results in higher \nincidence of latex allergy  (type I hypersensitivity)3 \n\n\n\naffecting 4.32% to 12% of healthcare workers3-4 \nand even higher,  among atopics with chronic \noccupational exposure, 43% when compared a \nprevalence is only 1.4%  in the general population.5\n\n\n\n    \nType IV reaction is a delayed type hypersensitivity \nreaction that occurs in response to rubber \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 67\n\n\n\nchemicals, manifesting also as contact dermatitis \nwhich is illicited following usage of rubber \nglove (24 to 48 hours) in an already sensitised \nindividual. Common causes are residual \nchemical additives, rubber as accelerators such as \ndithiocarbamate, tetramethylthiuram disulphide or \nmercaptobenzothiazoles and antioxidant that was \nadded during the manufacturing of NRL gloves \nto facilitate cross linking, which is a fundamental \nprocess that provide the excellent elastic nature of \nNRL glove with effective barrier property which \ncan hardly be challenged by synthetic rubber.\n \nStarch powder used to ease donning of rubber glove, \nincreases the allergenic nature of rubber glove as it \nhas the capacity to bind with protein antigens (NRL) \nand released into the air when the gloves are donned \nor removed which through inhalation or ingestion \ncan lead to the sensitisation and allergic reactions \nto NRL.8-9 Most powdered gloves,   powdered \nsurgeon\u2019s gloves, powdered patient examination \ngloves in Germany (1990\u2019s)  and the United States.10\n\n\n\nLatex sensitisation which heightened in the 1980s \nand 1990s has declined dramatically with the \ncombination of safety regulation imposed on latex \nproducts, improved education and awareness \nand with the shift from the use of NRL powdered \nexamination and surgical gloves to the use of \npowder-free NRL gloves with reduced protein \nlevels and synthetic gloves.11-17\n\n\n\nSeveral types of latex-free gloves such as vinyl and \nnitrile have since been invented to overcome the \nsituation as the demand for glove wearing increased \nand to provide suitable alternative to individuals \nwith latex allergy.  Compared to vinyl, nitrile glove \nserves greater protective barrier, almost comparable \nto that offered by latex gloves.19 However, these \nsynthetic gloves also use the similar cross-linking \nagent and vulcanisation accelerator with that of \nNRL glove. Hence, the shift from NRL to synthetic \nrubber glove did not solve rubber glove related \nproblem. Reports of allergic contact dermatitis to \nnon-latex gloves like nitrile gloves, that used to be \nfar less prevalent than those to NRL gloves, have \nbecome more common in recent years.18\n\n\n\n \nIn order to avoid type IV allergy, it is crucial that \nsynthetic gloves adopt a different formulation \nor using a different cross-linking system that \neliminates the use of chemicals that may cause \nallergic reactions. The industry has recently \nintroduced a new nitrile glove product using a novel \n\n\n\npatented non-sulphur system to effect co-valent \nbond cross linking to provide the desired elasticity \nof the gloves. This glove also has ionic cross linking \nprovided by the zinc oxide used in the formulation \nand the carboxylic group of the nitrile latex.\n\n\n\nThe main objective of this study is to prove that \nresidual chemical additives at a level that may \ninduce Type IV allergy in the unsensitized general \nuser population are not present in this rubber \nglove and to compare it with a powder free latex \nexamination glove. This study is also designed \nto meet the requirements for claim, \u201cwhere this \nproduct must demonstrate reduced potential for \nsensitizing users to chemical additives as described \nin \u201cGuidance for Industry and FDA Staff - Medical \nGlove Guidance Manual. Supporting Test Data: A \nnegative skin sensitization test (Modified Draize-95 \nTest)\u201d on a minimum of 200 non-sensitized human \nsubjects.\n\n\n\nMaterials and Methods\nIn collaboration with Islamic University of Gaza, we \nconducted a modified test on a specially formulated \nand powder free, accelerator free LOW DERMA\u2122 \nenhanced   nitrile rubber glove that has physical \nproperties and barrier integrity similar to that of \nNRL gloves, made from acryclonitrile-butadiene. \nThis glove does not contain sulphur or sulphur \nrelated compound.\n\n\n\nEthical Consideration \nThis study was conducted in compliance with the \nHelsinki Declaration and a written informed consent \nfrom the subject was obtained prior to recruitment \nand filed with the subject\u2019s records. The ethical \napproval were obtained from Islamic University of \nGaza (Ethics approval number: PHRC/HC/46/14) \nand Healthmedic Research Ethics Committee \n(HMREC) (Ethics approval number: HMREC-\nHMR-12-2016-B).\n\n\n\nMaterials\nTwo sets of Powder free, accelerator free LOW \nDERMA\u2122 Nitrile Patient Examination Gloves, \nwhite and blue colored that have undergone primary \nskin irritation test and guinea pig sensitisation \nstudies and have been tested negative for rubber \nchemical accelerators using chemical analytical \ntechnique were tested. Filter paper soaked in normal \nsaline were used as negative control and powder \nfree latex examination glove were used as control. \nThe nitrile gloves are produced from a patented \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3868\n\n\n\nmanufacturing process No. US 2013/0198933 A1 \nand are provided provided by the sponsor (Kossan \nInternational Sdn. Bhd.).  \n\n\n\nSelection and recruitment of study \nsubjects\nA total of 209 non-sensitized healthy adult human \nsubjects with no skin problem or previous type 1 or \ntype IV allergy, aged between 18 to 65 years were \nrecruited into the study. \n\n\n\nThe study comprised of 3 weeks induction phase, \n2 weeks rest period followed by challenge phase. \nDuring the induction phase, a total of 10 test \npatches that consists of 2cm by 2cm of tests and \ncontrol materials were patched onto the skin on \neach working day. The test patches were removed \nand replaced with a new one at the same site every \n48 hours, for a total of 10 changes. Patches applied \n\n\n\nbefore the weekend were removed the next working \nday, ie 72 hours later.  \n\n\n\nDuring the challenge phase, two samples of the \nsame test material were applied consecutively to \na virgin site for 48 hours each. The test sites are \nevaluated for cutaneous reaction at the time of each \npatch removal and for the challenge patch, the test \nsites are again evaluated 2 to 4 days after removal of \nthe second patch.\n\n\n\nScoring Criteria\nPatch Testing Scoring criteria are based on standard \nscoring of the North American Contact Dermatitis \nResearch Group (NACDRG).19 The intensity of \nreactions were scored as basic and supplemental \nscore according to the criteria listed in table 1a and \n1b.\n\n\n\nTable 1a. Scoring Criteria (Basic Score)\n\n\n\nTable 1b. Scoring Criteria (Supplemental Score)\n\n\n\nSkin reaction during the patch testing were observed \nand labelled using the scoring criteria provided. For \nskin reactions (basic score) that occur together with \nthe described signs (supplemental score), both of \nthe scores were added to produce the final score as \nthe final result.\n\n\n\nIn order to qualify for the claim of a reduced \nsensitization potential, all the subjects completing \nthe study should exhibit score value of no more than \n1.5 based on the scoring criteria describe above.\n\n\n\nBasic Score Description\n0 No visible reaction\n0.5 Doubtful or negligible erythema reaction\n1.0 Mild or just perceptible macular erythema reaction in a speckled/follicular, patchy or confluent pattern (slight pinking)\n2.0 Moderate erythema reaction in a confluent pattern (definite redness)\n3.0 Strong or brisk erythema reaction that may spread beyond the test site\n\n\n\nSupplemental scores Description Label\n0.5 Edema E\n0.5 Papules P\n0.5 Vesicles V\n0.5 Bullae B\n\n\n\nResults\nA total of 209 subjects, 149 Caucasian subjects \n(71.29%), 30 Afro Caribbean subjects (14.35%) \nand 30 Asiatic subjects (14.35%) were recruited and \ncompleted the study. Age range of the study subjects \nwere between 18 \u2013 58 years (25.29\u00b1 9.13). One \nhundred and five subjects were females (50.24%) \nand 104 subjects were males (49.76%).\n\n\n\nAll 209 subjects had a final score of not more than \n1.5 during both the induction phase and the challenge \nphase for both types of Powder Free Nitrile Patient \nExamination Gloves (white and blue) and to the \nnegative control, normal filter paper and the powder \nfree NRL glove. The results of the final score are \nsummarized in the table 2 while table 3 summarizes \nthe percentage of positive reaction in the duration of \ninduction and challenge test.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 69\n\n\n\nTable 2. Final Score of the skin reaction induced by the test patches during the challenge phase for non-sensitized subjects for inner \nsurface of both types of Powder Free Nitrile Patient Examination Gloves (white and blue).\n\n\n\nSample Total Score Number of Subject\nPowder Free Nitrile Patient Examination Gloves, White Colored, Non-\nsterile, Low Dermatitis Potential Claim (inner surface).\n\n\n\nScore less than 1.5 209\nScore more than 1.5 0\n\n\n\nPowder Free Nitrile Patient Examination Gloves, Blue Colored, Non-sterile, \nLow Dermatitis Potential Claim (inner surface).\n\n\n\nScore less than 1.5 209\nScore more than 1.5 0\n\n\n\nTable 3. Summary of percentage of positive reaction during the induction phase and the challenge phase for the test material and the \ncontrol sample.\n\n\n\nDescription Number of \nsubject\n\n\n\nPercentage of positive reaction in non sensitized subjects\nInduction Challenge\n\n\n\nTest material: \n\n\n\nPowder Free Nitrile Patient Examination Gloves, White Colored, \nNon-sterile, Low Dermatitis Potential Claim (inner surface).\n\n\n\n209 0% 0%\n\n\n\nPowder Free Nitrile Patient Examination Gloves, Blue Colored, \nNon-sterile, Low Dermatitis Potential Claim (inner surface).\n\n\n\n209 0% 0%\n\n\n\nNegative control:\n\n\n\nFilter paper 209 0% 0%\n\n\n\nControl glove:\n\n\n\nNRL glove 209 0% 0%\n\n\n\nDiscussion\nThese nitrile gloves are manufactured from a co-\npolymer of acrylonitrile and butadiene synthetic \nlatex, (carboxilic nitrile rubber latex) instead of NRL, \nusing a patented method. It is the best alternative and \nto a certain extent almost equal to latex glove, in terms \nof performance.18 The patented method eliminates \nthe usage of sulfur as crosslinking agent and sulfur \ncontaining compound as crosslinking accelerator, \nspecifically, dithiocarbamate, tetramethyltiuram-\ndisulfide (TMTD) or mercaptobenzothiazole \n(MBT)19 which are among the commonest sensitizers \ndetected in patients with contact dermatitis (Type \nIV) and suspected glove allergy21-22. It serves as one \nof the best option for synthetic rubber latex and does \nnot contain latex protein, which is a known cause of \nType 1 allergy.\n\n\n\nPatch testing, chosen for this study to evaluate the \npresence of and the potential effects of the sensitizers \nis universally regarded as the best method to identify \nthese allergens. It is used to simulate and exaggerate \nthe everyday situations of product application on \nthe skin. None of the volunteers showed positive \nreaction towards the gloves sample. The results \ncan be interpreted as the non-existence of allergen \ncausative agent or perhaps it exists in a very low \n\n\n\namount that has no clinical effects on the skin of \nthe study subjects, thus, provides more than 95% \nconfidence that the chemical sensitization potential \nin the user population is expected to be less than \n1.5%.\n\n\n\nNRL glove which uses the chemical accelerators that \nwas used as control in this study also gave similar \nresult. In this case the chemical accelerators in this \nNRL gloves maybe present in very small quantity \nthat is lower than the threshold for sensitisation \nhence also qualify for claim of low dermatitis \npotential. \n\n\n\nChanges in glove technology and a dramatic \ndecrease in the prevalence of NRL allergies after \ninterventions, technological advances and education \njustify the revisit of glove restriction policies of the \nuse of devices made of NRL in healthcare that has \nbeen practised as precautionary measures against \nthe perceived risk of NRL allergy.\n\n\n\nThe introduction of powder-free gloves has been \nassociated with reductions in protein content and \nassociated allergies. The use of low-protein, low-\nallergenic, powder-free gloves is associated with \na significant decrease in the prevalence of type I \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3870\n\n\n\nallergic reactions to NRL among healthcare workers. \nGiven the excellent barrier properties and physical \ncharacteristics, dramatically reduced incidences of \nallergic reactions, competitive costs, biodegradable \nin nature23-25 and naturally derived environmental \nfriendly material, the restriction of usage of NRL \ngloves within the hospital environment warrants \nreappraisal.  Nevertheless, low-protein, low-\nallergenic, powder-free gloves does totally eliminate \nproblem relating to NRL allergy, hence there is still \na need for non NRL glove especially among high \nrisk individuals.\n\n\n\nAlthough most patients can be treated effectively \nfor type IV and type I reactions without clinical \nsequelae, major allergy may prevent them from \npursuing certain careers, using many household \nand workplace objects, and seeking timely medical \ncare. Moreover, those with underlying atopy and \nsensitive skin may well be sensitised with prolonged \nexposure. Type 1 allergy eg contact urticaria26 can \ndirectly impair barrier function through swelling of \nthe skin surface or indirectly, through scratching, \npredispose to type IV allergy even with very small \nquantity rubber chemical.\n  \nThis powder free, accelerator free LOW DERMA\u2122 \nrubber glove provides reasonable alternative to NRL \nrubber glove and further advantage over NRL rubber \nglove among atopic individuals, high risk group \nand latex sensitised individuals and elimination of \npossible future latex sensitisation even though both \nmeets the criteria of low dermatitis potential.\n\n\n\nConclusion\nThe skin sensitization test (\u2018Modified Draize-95\u2019 \nTest) of Powder Free Nitrile Patient Examination \nGloves (white and blue) and the powder free NRL \nexamination glove is negative. There was no clinical \nevidence of the presence of residual chemical \nadditives at the level that may induce Type IV \nallergy in the unsensitized general user population \nin the Powder Free Nitrile Patient Examination \nGloves, Blue and white Colored, Non-sterile, Low \nDermatitis Potential Claim. Powder free, accelerator \nfree LOW DERMA\u2122   provides for the continuing \nrequirement for synthetic gloves with low dermatitis \npotential for known latex-allergic patients and staff \nand those who are high risk of latex sensitisation.\n\n\n\nConflict\tof\tInterest\tDeclaration\nAuthors declare no affiliation or significant financial \ninvolvement in any organizations or entity with a \n\n\n\ndirect financial interest in the subject matter or \nmaterials discussed in the manuscript on this page. \nKossan International Sdn. Bhd sponsored the study \nmaterial - nitrile gloves (US 2013/0198933 A1).\n\n\n\nAcknowledgement\nThe authors would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nReferences\n\n\n\n1. Cohen DE, Scheman A, Stewart L, Taylor J, Pratt M, Trotter \nK, Prawer S et al. American Academy of Dermatology\u2019s \nposition paper on latex allergy. J Am Acad Dermatol \n1998;39:98\u2013106.\n\n\n\n2. Ownby DR, Tomlanovich M, Sammons N, McCullough \nJ: Anaphylaxis associated with latex allergy during \nbarium enema examinations. AJR Am J Roentgenol \n1991;156:903\u20138.\n\n\n\n3. Bousquet J, Flahault A, Vandenplas O, Ameille J, Duron \nJJ, Pecquet C et aI. Natural rubber latex allergy among \nhealth care workers: a systematic review of the evidence. J \nAllerg Clin Immunol 2006;118:447\u201354.\n\n\n\n4. Occupational Safety and Health Administration. Latex \nAllergy. US Department of Labor. 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A preliminary report \non the incidence of pre-existing pinhole defects in nitrile \ndental gloves. British dental journal 2003;195:509-12.\n\n\n\n19. North American Contact Dermatitis Research Group \n(NACDRG). Am. J. Contact Dermatitis 1991;2:122-9.\n\n\n\n20. Khoo SH, Lim LST, Lee SP, Enomoto M (2013). United \nStates Patent Application Publication. US20130198933A1.\n\n\n\n21. Nettis E, Assennato G, Ferrannini A, Tursi A. Type I \nallergy to natural rubber latex and type IV allergy to rubber \nchemicals in health care workers with glove-related skin \nsymptoms. Clin Exp Allergy. 2002;32:441-7.\n\n\n\n22. Geier J, Lessmann H, Uter W, Schnuch A. Occupational \nrubber glove allergy: results of the Information Network of \nDepartments of Dermatology (IVDK), 1995\u20132001. Contact \nDermatitis 2003;48:39-44.\n\n\n\n23. Yip E, Cacioli P. The manufacture of gloves from natural \nrubber latex. J Allergy Clin Immunol 2002;110:S3\u2013S14.\n\n\n\n24. Berekaa MM, Linos A, Reichelt R, Keller U,Steinb\u00fcchel \nA: Effect of pretreatment ofrubber material on its \nbiodegradability by various rubber degrading bacteria. \nFEMSMicrobiol Lett 2000;184:199\u2013206. \n\n\n\n25. Yikmis M, Arensk\u00f6tter M, Rose K, Lange N, Wernsmann \nH, Wiefel L et al. Secretion and transcriptional regulation \nofthe latex-clearing protein, lcp, by the rubber-degrading \nbacterium Streptomyces sp.Strain K30. App Environ \nMicrobiol 2008;74:5373\u201382.  \n\n\n\n26. Turjanmaa K, Laurila K, M\u00e4kinen-Kiljunen S, Reunala \nT.  Rubber contact urticaria: allergenic properties of 19 \nbrands of latex gloves. Contact Dermatitis. 1988;19:362\u2013\n7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3872\n\n\n\nCASE REPORT\n\n\n\nBeh\u00e7et\u2019s Disease: A Case Series of 5 Patients in the Department of \nDermatology, Hospital Kuala Lumpur, Malaysia \n\n\n\nWan Ahmad Kamal Wan Syameen Afira, AdvMDerm1; Min Moon Tang, AdvMDerm2, Suganthi Thevarajah, MMed2\n\n\n\n1Department of Dermatology, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia\n2Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nBehcet\u2019s disease (BD) is a variant of systemic vasculitides characterized by recurrent oral aphthous \nulcers, recurrent genital ulcers with eyes, cutaneous, gastrointestinal, joints, neurological and others \norgan involvement. Here we aim to describe the demography, clinical patterns and the treatment of 5 \ncases of BD presented to the Department of Dermatology Hospital Kuala Lumpur between 2002 and \n2016. All the patients had a delay in their diagnosis.  The clinical characteristics and the choices of \ntreatment in our patients did not differ greatly compared to the reports from other countries. BD could \nbe under-diagnosed in Malaysia as the presenting symptoms are non-specific. Therefore, a high index \nof suspicion is needed. \n\n\n\nKey words: Beh\u00e7et\u2019s disease, systemic vasculitides, neurological manifestation\n\n\n\nCorresponding Author\nDr Wan Syameen Afira Wan Ahmad Kamal\nUniversiti Teknologi MARA\nDepartment of Dermatology, Faculty of Medicine, \nUniversiti Teknologi MARA, Jalan Hospital, Selangor, \nMalaysia\nEmail: syameen.afira@gmail.com\n\n\n\nIntroduction\nOriginally described in 1937, Beh\u00e7et\u2019s disease \nwas defined as a disease with a triad of recurrent \noral aphthous ulcer, genital ulcer and uveitis by \nProfessor Hulusi Beh\u00e7et, a Turkish Dermatologist.1 \nIn 2012, BD was classified under the Variable \nVessel Vasculitis group in the Revised International \nChapel Hill Consensus Conference Nomenclature \nof Vasculitides.2 Unlike other forms of autoimmune \ndiseases, BD has a distinctive clinical progress. \nIt affects vessels of variable sizes at one or more \ndifferent organs with unpredictable duration of \nactive diseases and remissions.3\n\n\n\nIn Malaysia, scarce reports of BD had been \ndescribed by vascular surgeons, ophthalmologists \nand neurologists.4-6 Here we aim to describe the \ndemography, clinical patterns and the treatment of \nBD managed in the Department of Dermatology, \nHospital Kuala Lumpur between 2002 and 2016. \n\n\n\nCase Reports\nThere were a total of five cases diagnosed to have \nBD during this period, involving three male and two \nfemale patients. The characteristics of these patients \nwere shown in Table 1. All were Malay patients \nexcept one with mixed ethnicity (Bajau, Philippine \nand Chinese). The median age of these patients at \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 73\n\n\n\nlatest clinic review was 36 years old (range: 27-\n57). The median age when their first symptoms \ndeveloped was 24 years old (range: 15 - 40). All \npatients presented with recurrent oral aphthous \nulcers while four patients had recurrent genital \nulcers. Four patients had eye involvement which \nincluded uveitis, scleritis, chorioretinitis and optic \nneuritis. Both female patients had history of unusual \npapulopustular eruptions and ulcerated papules or \nplaques over the face (Figure 1a). Presence of \npathergy reactions (Figure 1b) were documented in \nthree patients. Erythema nodosum (Figure 1c) was \npresent in 4 patients. Severe ulceration in small and \nlarge intestines was reported in one patient whom \nsubsequently underwent right hemicolectomy. \nTransient acute arthritis was observed in three \npatients. \n\n\n\nOne patient presented with neurological \nmanifestations. This Malay gentleman who \nwas positive for HLA-B51 first presented with \nrecurrent oral and genital ulcers associated with \nerythema nodosum at the age of 15 years old. He \nsubsequently had blurring of vision of the right \neye at 20 years old. Two years later, he presented \nwith bilateral optic neuritis and superior sagittal \nsinus thrombosis.  He was treated with warfarin \nfor 6 months duration for the superior sagittal sinus \nthrombosis. Unfortunately, he became completely \nblind. Since the age of 26 years old he started to \nexperience recurrent epilepsy with intermittent \nstatus epilepticus. His electroencephalography \nshowed cerebral dysfunction with focal pathology \nover the left fronto-temporal lobe. The diagnosis \nof BD was only made after 11 years of the first \npresentation of oral ulcers. His magnetic resonance \nimaging of brain at the age of 29 years old revealed \npatchy, nodular and linear contrast enhanced \nchanges in the parenchymal of both frontal lobes \nwith ongoing cerebral atrophy. At the age of 31 \nyears old, this unfortunate gentleman succumbed to \nstatus epilepticus. \n\n\n\nDue to the non-specific presentation, all the patients \nhad a delay in diagnosis, with a mean duration \nfrom initial presentation to diagnosis of 5.9 years \n(range: 1.5 to 12 years). They were misdiagnosed \nas having a recurrent genital herpes in two patients, \nrecurrent simple oral aphthosis in one, systemic \nlupus erythematosus in another and demyelinating \ndisease prior to the final diagnosis of Behcet\u2019s \ndisease. Histopathology examination of the \nerythema nodosum-like lesions revealed nodular \nvasculitis (Figure 1d) in one patient and septal \n\n\n\npanniculitis with vasculitis in another. Laboratory \ninvestigations during initial presentations revealed \nhypochromic microcytic anaemia in one patient \nand raised erythrocyte sedimentation rate (less than \n80mm/hr) in four patients. Anti-nuclear antibodies \n(ANA) and anti-neutrophil cytoplasmic antibodies \n(ANCA) were negative in the three patients tested. \n\n\n\nAll the patients received systemic corticosteroids \ninitially and during disease exacerbations \n(intravenous methylprednisolone, intravenous \nhydrocortisone and oral prednisolone). The steroid \nsparing immunosuppressive agents used included \nmethotrexate, cyclosporine, colchicine, dapsone \nand azathioprine. The longest disease free duration \nranged from five to eight months while on treatment. \n\n\n\nDiscussion\nBeh\u00e7et\u2019s disease is a multi-system vasculitis of \nvariable vessel sizes with the disease most active at \nyoung adulthood3. It was classically described to be \nmost frequently seen in countries along the historical \nSilk Road such as Turkey, Iran, Saudi Arabia, Iraq, \nItaly, Israel, China, Japan etc.7 In South East Asia, \ncase series of BD has been reported in Singapore8 \nand Thailand;9 while a few case reports had been \npublished in Malaysia.4-6\n\n\n\nTill date, the aetio-pathogenesis of the disease \nremains unidentified; however patients\u2019 genetic \nmake-up, infectious agents and immunological \nabnormalities have been implicated.10 The major \nhistocompatibility complex (MHC)-related human \nleukocyte antigens (HLA)-B51 or HLA-B5 is found \nto be carried by a third to two third of patients with BD. \nThe presence of these HLA significantly increases \nthe risk of BD development11. More predominant \nin males, these HLA carriers are associated with \na higher prevalence of genital ulcer, ocular and \nskin manifestations but with  lower prevalence of \ngastrointestinal involvement.12 Interestingly the \nmale patient with neuro-BD in our cohort was \nidentified to carry this HLA-B51 and he had the \nworst prognosis among the 5 patients. Regrettably \nHLA-typing was not able to be arranged for the \nother four patients. More recently, the imbalances in \nthe expression of innate immunity together with T \nhelper1 (Th1) and Th17-related cytokines have been \nshown to play an important role in the pathogenesis \nand the disease severity of BD.13\n\n\n\nLacking of a universally recognized pathognomonic \ntest, BD diagnosis is primarily based on clinical \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3874\n\n\n\ncriteria. The diagnosis of BD is often delayed \nas it imposes great challenges to clinicians to \nrecognize the non-specific disease pattern. We had \na mean duration of 5.9 years prior to the diagnosis, \ncomparable to East Africa14 which was 5.5 years. \nInterestingly, even in Turkey, a country with one \nof the highest prevalence rate of BD in the world, \nAlpsoy et al15 reported that the duration taken \nto fulfill the diagnostic criteria was 2.83 years. \nThere are many diagnostic criteria available for \nBD of which the most important ones include the \nInternational Study Group criteria (ISG) 1990 and \nthe International Criteria for Behcet\u2019s Disease \n(ICBD) 2014.16-18 The original ICBD was created in \n2006, with the collaboration of 27 countries. It was \nthen revised and then published in 201418 as shown \nin Table 2. As compared to the ISG 1990, the ICBD \n2014 has been shown to have a higher sensitivity \nand equivalent specificity.3 Therefore the accuracy \nof BD diagnosis is expected to be better with the use \nof ICBD 2014.3\n\n\n\n \nThe disease presentations may vary in different \nethnic groups and countries19-22 as shown in \nTable 3. Our patients had a high prevalence of \noral ulcers, skin lesions, and eye manifestations. \nAside from Korea,20 cutaneous manifestations \nare not very common in the other countries and \npathergy test particularly has a low prevalence. \nAlthough relatively rare, the central nervous system \ninvolvement which frequently develops late is \nassociated with significant morbidity and mortality.\n \nIn our cohort of patients, pathergy reactions were \ndemonstrated in 3 patients when papules on an \nerythematous base were noted at branula insertion \nsites and venipuncture sites during disease flares. \nHowever in another 2 patients, pathergy tests were \nperformed when the patients were on high dose \nprednisolone and as a result they were negative. \nPathergy is the term used to describe hyper-reactivity \nof the skin or development of new skin lesions or \naggravation of existing skin lesions in response \nto trauma.23 It has been reported positive not only \nin BD but in pyoderma gangrenosum, erythema \nelevatum diutinum and Sweet\u2019s syndrome.23 The \nmethod to perform a pathergy test is not standardized \nglobally. Different techniques have been reported.3 \nAs a result, the rates of positive pathergy tests in BD \nare inconsistently reported in different countries.3 \nLiterature reviews have shown that patients with \nBD duration of less than 5 years24 and  patients who \ndid not take the medications for the BD at the time \n\n\n\nof testing25 had a higher rate of positive pathergy \nreactions. \n\n\n\nNeurological manifestation of BD (Neuro-BD) is \namong the most aggressive forms of BD with high \nmortality.26 According to the 2014 International \nConsensus Recommendation of diagnosis and \nmanagement of Neuro-BD, there are two main \nsubtypes of Neuro-BD i.e. parenchymal and non-\nparenchymal.27 Our only neuro-BD patient suffered \nfrom both the subtypes at different occasions. Being \na potentially treatable disease, clinicians need to \nconsider Neuro-BD as a differential diagnosis of \nother central nervous system disorders. Correlation \nof variable neurological manifestations with other \nclinical presentations through a thorough history \ntaking is vital to reach the diagnosis of Neuro-BD. \n\n\n\nThe main goal of therapy in patients with BD is to \ninduce and maintain remission and improve patients\u2019 \nquality of life. There were similarities in terms \nof the types of immunosuppressive agents used \nbetween our centre and a rheumatology centre in \nSingapore.8 Systemic corticosteroids, azathioprine \nand methotrexate were commonly used in these \nregions. We have used dapsone, pentoxiphylline \nand colchicine in our cohort of patients. The \nuse of other immune-modulating agents such as \ncyclophosphamide and sulphasalazine had been \nreported as well.8 \n\n\n\nOver the last decade, a considerable amount of \nliterature has been published regarding the use \nof tumor necrosis factor (TNF) inhibitors in BD \nwith beneficial effects noted with infliximab, \netanercept and adalimumab.28 As Interleukin-1\u03b2 \n(IL-1\u03b2) is intimately involved in the pathogenesis \nof BD,29 biologics that inhibit this cytokine are \nalso being evaluated. Gevokizumab, a recombinant \nhumanized anti-IL-1\u03b2 antibody, was associated \nwith rapid and durable clinical response in seven \npatients with acute posterior or panuveitis, or retinal \nvasculitis who failed to respond to azathioprine \nor cyclosporine A.30 Meanwhile canakinumab, a \nfully human anti-IL-1\u03b2 antibody, was efficacious in \nachieving a prompt and complete disease response \nin one patient  with resistant fevers, oral and genital \naphthosis, arthritis and ileocolic ulcers,  who was \nunresponsive other agents.31 In addition, anti-CD52 \nantibody (alemtuzumab) has been described to be \nable to induce remission in majority of patients with \ndifficult-to-treat BD. Nevertheless, relapses were \ncommon and it may cause new autoimmunity.32\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 75\n\n\n\nConclusion\nIn conclusion, we reported 5 cases of Behcet\u2019s \ndisease managed in Hospital Kuala Lumpur \nMalaysia. All of the patients had recurrent oral \nulcers and 4 of them had recurrent genital ulcers, \nocular involvement and cutaneous manifestations. \nAlthough it is a rare disease, Beh\u00e7et\u2019s disease is \nlikely to be under-diagnosed in Malaysia. Perhaps it \nis more commonly managed by the rheumatologists \nthan the dermatologists. In addition, patients may \nbe evaluated by ophthalmologists, neurologists, \ngastroenterologist or other medical specialties. Early \ndiagnosis which enables prompt and appropriate \ntreatment is vital to prevent morbidity in BD. A high \ndegree of awareness among physicians is important \nto diagnose BD especially in the context of recurrent \naphthous ulcerations that present with other organs \ninvolvement. \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nAcknowledgement\nThe authors would like to thank the Department \nof Neurology, Hospital Kuala Lumpur for the \ncontribution of part of the data of this paper. The \nauthors would like to acknowledge the Department \nof Pathology, Hospital Kuala Lumpur who had \ncontributed the slide of skin biopsy in one of the \npatients. The authors would also like to thank the \nDirector General of Health, Malaysia for permission \nto publish this paper.\n\n\n\nFigure 1. (a) Papulopustular  eruptions with ulcers around the nose, nasal ala, philtrum, above the left eyebrow;  (b) Positive pathergy \nreactions with papulopustular eruptions at the branula insertion side; (c) erythema nosodum  at right anterior shin; (d) lobular panniculitis \nwith vasculitis (H&E x400)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3876\n\n\n\nTa\nbl\n\n\n\ne \n1.\n\n\n\n C\nha\n\n\n\nra\nct\n\n\n\ner\nis\n\n\n\ntic\ns o\n\n\n\nf fi\nve\n\n\n\n p\nat\n\n\n\nie\nnt\n\n\n\ns w\nith\n\n\n\n B\neh\n\n\n\n\u00e7e\nt\u2019s\n\n\n\n d\nis\n\n\n\nea\nse\n\n\n\n (B\nD\n\n\n\n).\n\n\n\nPa\ntie\n\n\n\nnt\n N\n\n\n\no\nA\n\n\n\nge\n a\n\n\n\nt l\nat\n\n\n\nes\nt r\n\n\n\nev\nie\n\n\n\nw\n in\n\n\n\n \nye\n\n\n\nar\ns/\n\n\n\n E\nth\n\n\n\nni\nci\n\n\n\nty\n/G\n\n\n\nen\nde\n\n\n\nr\nA\nge\n\to\nf\tfi\nrs\nt\t\n\n\n\nsy\nm\n\n\n\npt\nom\n\n\n\ns i\nn \n\n\n\nye\nar\n\n\n\ns\n\n\n\nD\nur\nat\nio\nn\t\nfr\nom\n\n\n\n\tfi\nrs\nt\t\n\n\n\nsy\nm\n\n\n\npt\nom\n\n\n\ns t\no \n\n\n\nth\ne \n\n\n\ndi\nag\n\n\n\nno\nsi\n\n\n\ns o\nf B\n\n\n\nD\n (y\n\n\n\nea\nrs\n\n\n\n)\n\n\n\nC\nlin\n\n\n\nic\nal\n\n\n\n p\nre\n\n\n\nse\nnt\n\n\n\nat\nio\n\n\n\nns\nM\n\n\n\ned\nic\n\n\n\nat\nio\n\n\n\nns\n g\n\n\n\niv\nen\n\n\n\nC\nom\n\n\n\npl\nic\n\n\n\nat\nio\n\n\n\nns\n d\n\n\n\nue\n \n\n\n\nto\n B\n\n\n\nD\nO\n\n\n\nut\nco\n\n\n\nm\ne\n\n\n\n1\n36\n\n\n\n/M\nul\n\n\n\ntir\nac\n\n\n\nia\nl \n\n\n\n(B\naj\n\n\n\nau\n,P\n\n\n\nhi\nlip\n\n\n\nin\ne,\n\n\n\n C\nhi\n\n\n\nne\nse\n\n\n\n)/\nM\n\n\n\nal\ne\n\n\n\n18\n12\n\n\n\nR\nec\n\n\n\nur\nre\n\n\n\nnt\n o\n\n\n\nra\nl u\n\n\n\nlc\ner\n\n\n\ns, \nul\n\n\n\nce\nrs\n\n\n\n a\nt l\n\n\n\nar\nge\n\n\n\n &\n sm\n\n\n\nal\nl \n\n\n\nin\nte\n\n\n\nst\nin\n\n\n\nes\n, p\n\n\n\nan\nga\n\n\n\nst\nrit\n\n\n\nis\n, g\n\n\n\nen\nita\n\n\n\nl u\nlc\n\n\n\ner\ns, \n\n\n\ner\nyt\n\n\n\nhe\nm\n\n\n\na \nno\n\n\n\ndo\nsu\n\n\n\nm\n, p\n\n\n\nos\niti\n\n\n\nve\n p\n\n\n\nat\nhe\n\n\n\nrg\ny \n\n\n\nre\nac\n\n\n\ntio\nn,\n\n\n\n u\nve\n\n\n\niti\ns\n\n\n\nPr\ned\n\n\n\nni\nso\n\n\n\nlo\nne\n\n\n\n, m\net\n\n\n\nho\ntre\n\n\n\nxa\nte\n\n\n\n, \ncy\n\n\n\ncl\nos\n\n\n\npo\nrin\n\n\n\ne,\n c\n\n\n\nol\nch\n\n\n\nic\nin\n\n\n\ne\nR\n\n\n\nig\nht\n\n\n\n h\nem\n\n\n\nic\nol\n\n\n\nec\nto\n\n\n\nm\ny\n\n\n\nA\nliv\n\n\n\ne \n\n\n\n2\n57\n\n\n\n/M\nal\n\n\n\nay\n/M\n\n\n\nal\ne\n\n\n\n40\n3\n\n\n\nR\nec\n\n\n\nur\nre\n\n\n\nnt\n o\n\n\n\nra\nl u\n\n\n\nlc\ner\n\n\n\ns, \nge\n\n\n\nni\nta\n\n\n\nl u\nlc\n\n\n\ner\ns, \n\n\n\nch\nor\n\n\n\nio\nre\n\n\n\ntin\niti\n\n\n\ns\nPr\n\n\n\ned\nni\n\n\n\nso\nlo\n\n\n\nne\n, c\n\n\n\nol\nch\n\n\n\nic\nin\n\n\n\ne,\n \n\n\n\npe\nnt\n\n\n\nox\nify\n\n\n\nlli\nne\n\n\n\n, a\nza\n\n\n\nth\nio\n\n\n\npr\nin\n\n\n\ne\n-\n\n\n\nA\nliv\n\n\n\ne\n\n\n\n3\n46\n\n\n\n/M\nal\n\n\n\nay\n/F\n\n\n\nem\nal\n\n\n\ne\n30\n\n\n\n2\nR\n\n\n\nec\nur\n\n\n\nre\nnt\n\n\n\n g\nen\n\n\n\nita\nl u\n\n\n\nlc\ner\n\n\n\ns, \nre\n\n\n\ncu\nrr\n\n\n\nen\nt o\n\n\n\nra\nl u\n\n\n\nlc\ner\n\n\n\ns, \ner\n\n\n\nyt\nhe\n\n\n\nm\na \n\n\n\nno\ndo\n\n\n\nsu\nm\n\n\n\n, p\nap\n\n\n\nul\nop\n\n\n\nus\ntu\n\n\n\nla\nr l\n\n\n\nes\nio\n\n\n\nns\n, \n\n\n\npo\nsi\n\n\n\ntiv\ne \n\n\n\npa\nth\n\n\n\ner\ngy\n\n\n\n re\nac\n\n\n\ntio\nn,\n\n\n\n a\nrth\n\n\n\nrit\nis\n\n\n\n\n\n\n\nPr\ned\n\n\n\nni\nso\n\n\n\nlo\nne\n\n\n\n, c\nol\n\n\n\nch\nic\n\n\n\nin\ne,\n\n\n\n d\nap\n\n\n\nso\nne\n\n\n\n-\nA\n\n\n\nliv\ne\n\n\n\n4\n27\n\n\n\n/M\nal\n\n\n\nay\n/F\n\n\n\nem\nal\n\n\n\ne\n24\n\n\n\n1.\n5\n\n\n\nR\nec\n\n\n\nur\nre\n\n\n\nnt\n o\n\n\n\nra\nl u\n\n\n\nlc\ner\n\n\n\ns, \ner\n\n\n\nyt\nhe\n\n\n\nm\na \n\n\n\nno\ndo\n\n\n\nsu\nm\n\n\n\n, \nar\n\n\n\nth\nrit\n\n\n\nis\n, u\n\n\n\nlc\ner\n\n\n\nat\ned\n\n\n\n p\nap\n\n\n\nul\nes\n\n\n\n a\nnd\n\n\n\n p\nla\n\n\n\nqu\nes\n\n\n\n, \nsc\n\n\n\nle\nrit\n\n\n\nis\n, p\n\n\n\nos\niti\n\n\n\nve\n p\n\n\n\nat\nhe\n\n\n\nrg\ny \n\n\n\nre\nac\n\n\n\ntio\nn\n\n\n\nPr\ned\n\n\n\nni\nso\n\n\n\nlo\nne\n\n\n\nA\nbo\n\n\n\nrti\non\n\n\n\n d\nur\n\n\n\nin\ng \n\n\n\na \nfla\n\n\n\nre\nA\n\n\n\nliv\ne\n\n\n\n5\n31\n\n\n\n* /M\nal\n\n\n\nay\n/M\n\n\n\nal\ne\n\n\n\n15\n11\n\n\n\nR\nec\n\n\n\nur\nre\n\n\n\nnt\n o\n\n\n\nra\nl u\n\n\n\nlc\ner\n\n\n\ns, \nge\n\n\n\nni\nta\n\n\n\nl u\nlc\n\n\n\ner\ns, \n\n\n\ner\nyt\n\n\n\nhe\nm\n\n\n\na \nno\n\n\n\ndo\nsu\n\n\n\nm\n, o\n\n\n\npt\nic\n\n\n\n n\neu\n\n\n\nrit\nis\n\n\n\n, c\nen\n\n\n\ntra\nl r\n\n\n\net\nin\n\n\n\nal\n v\n\n\n\nei\nn \n\n\n\nob\nst\n\n\n\nru\nct\n\n\n\nio\nn,\n\n\n\n su\npe\n\n\n\nrio\nr s\n\n\n\nag\ngi\n\n\n\nta\nl s\n\n\n\nin\nus\n\n\n\n th\nro\n\n\n\nm\nbo\n\n\n\nsi\ns, \n\n\n\nre\ncu\n\n\n\nrr\nen\n\n\n\nt h\nea\n\n\n\nda\nch\n\n\n\ne,\n e\n\n\n\npi\nle\n\n\n\nps\ny\n\n\n\nPr\ned\n\n\n\nni\nso\n\n\n\nlo\nne\n\n\n\n,\nm\n\n\n\net\nhy\n\n\n\nlp\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne,\n m\n\n\n\net\nho\n\n\n\ntre\nxa\n\n\n\nte\nB\n\n\n\nlin\ndn\n\n\n\nes\ns, \n\n\n\nep\nile\n\n\n\nps\ny\n\n\n\nD\nie\n\n\n\nd \nat\n\n\n\n 3\n1 \n\n\n\nye\nar\n\n\n\ns \nol\n\n\n\nd\n\n\n\n*a\nge\n\n\n\n w\nhe\n\n\n\nn \npa\n\n\n\ntie\nnt\n\n\n\n d\nie\n\n\n\nd\n\n\n\nSi\ngn\n\n\n\n / \nSy\n\n\n\nm\npt\n\n\n\nom\nD\n\n\n\nes\ncr\n\n\n\nip\ntio\n\n\n\nn\nPo\n\n\n\nin\nts\n\n\n\nO\ncu\n\n\n\nla\nr l\n\n\n\nes\nio\n\n\n\nns\nA\n\n\n\nnt\ner\n\n\n\nio\nr u\n\n\n\nve\niti\n\n\n\ns, \npo\n\n\n\nst\ner\n\n\n\nio\nr u\n\n\n\nve\niti\n\n\n\ns, \nre\n\n\n\ntin\nal\n\n\n\n v\nas\n\n\n\ncu\nlit\n\n\n\nis\n2\n\n\n\nG\nen\n\n\n\nita\nl A\n\n\n\nph\nth\n\n\n\nos\nis\n\n\n\nU\nlc\n\n\n\ner\ns a\n\n\n\nre\n u\n\n\n\nsu\nal\n\n\n\nly\n la\n\n\n\nrg\ner\n\n\n\n, d\nee\n\n\n\npe\nr t\n\n\n\nha\nn \n\n\n\nth\ne \n\n\n\nor\nal\n\n\n\n a\nph\n\n\n\nth\nos\n\n\n\nis\n. I\n\n\n\nn \nfe\n\n\n\nm\nal\n\n\n\ne \nth\n\n\n\ney\n a\n\n\n\nre\n m\n\n\n\nai\nnl\n\n\n\ny \nlo\n\n\n\nca\nliz\n\n\n\ned\n o\n\n\n\nn \nth\n\n\n\ne \nvu\n\n\n\nlv\na,\n\n\n\n ra\nre\n\n\n\nly\n in\n\n\n\n th\ne \n\n\n\nva\ngi\n\n\n\nna\n a\n\n\n\nnd\n e\n\n\n\nxc\nep\n\n\n\ntio\nna\n\n\n\nlly\n o\n\n\n\nn \nth\n\n\n\ne \nce\n\n\n\nrv\nix\n\n\n\n. I\nn \n\n\n\nm\nal\n\n\n\nes\n, u\n\n\n\nlc\ner\n\n\n\ns a\nre\n\n\n\n m\nai\n\n\n\nnl\ny \n\n\n\nse\nen\n\n\n\n o\nn \n\n\n\nth\ne \n\n\n\nsc\nro\n\n\n\ntu\nm\n\n\n\n b\nut\n\n\n\n c\nan\n\n\n\n b\ne \n\n\n\nse\nen\n\n\n\n o\nn \n\n\n\nth\ne \n\n\n\nsh\naf\n\n\n\nt o\nf t\n\n\n\nhe\n p\n\n\n\nen\nis\n\n\n\n a\nnd\n\n\n\n o\nn \n\n\n\nth\ne \n\n\n\nm\nea\n\n\n\ntu\ns\n\n\n\n2\n\n\n\nO\nra\n\n\n\nl A\nph\n\n\n\nth\nos\n\n\n\nis\nA\n\n\n\nph\nth\n\n\n\nou\ns o\n\n\n\nra\nl u\n\n\n\nlc\ner\n\n\n\nat\nio\n\n\n\nn \nat\n\n\n\n le\nas\n\n\n\nt 3\n ti\n\n\n\nm\nes\n\n\n\n in\n a\n\n\n\n 1\n2-\n\n\n\nm\non\n\n\n\nth\n p\n\n\n\ner\nio\n\n\n\nd\n2\n\n\n\nSk\nin\n\n\n\n m\nan\n\n\n\nife\nst\n\n\n\nat\nio\n\n\n\nns\nPs\n\n\n\neu\ndo\n\n\n\nfo\nlli\n\n\n\ncu\nlit\n\n\n\nis\n, e\n\n\n\nry\nth\n\n\n\nem\na \n\n\n\nno\ndo\n\n\n\nsu\nm\n\n\n\n, s\nki\n\n\n\nn \nap\n\n\n\nht\nho\n\n\n\nsi\ns\n\n\n\n1\nN\n\n\n\neu\nro\n\n\n\nlo\ngi\n\n\n\nca\nl M\n\n\n\nan\nife\n\n\n\nst\nat\n\n\n\nio\nns\n\n\n\nC\nen\n\n\n\ntra\nl (\n\n\n\nPa\nre\n\n\n\nnc\nhy\n\n\n\nm\nal\n\n\n\n a\nnd\n\n\n\n n\non\n\n\n\n-p\nar\n\n\n\nen\nch\n\n\n\nym\nal\n\n\n\n24\n) a\n\n\n\nnd\n p\n\n\n\ner\nip\n\n\n\nhe\nra\n\n\n\nl\n1\n\n\n\nVa\nsc\n\n\n\nul\nar\n\n\n\n M\nan\n\n\n\nife\nst\n\n\n\nat\nio\n\n\n\nns\nA\n\n\n\nrte\nria\n\n\n\nl t\nhr\n\n\n\nom\nbo\n\n\n\nsi\ns, \n\n\n\nla\nrg\n\n\n\ne \nve\n\n\n\nin\n th\n\n\n\nro\nm\n\n\n\nbo\nsi\n\n\n\ns, \nph\n\n\n\nle\nbi\n\n\n\ntis\n, s\n\n\n\nup\ner\n\n\n\nfic\nia\n\n\n\nl p\nhl\n\n\n\neb\niti\n\n\n\ns\n1\n\n\n\nPo\nsi\n\n\n\ntiv\ne \n\n\n\nPa\nth\n\n\n\ner\ngy\n\n\n\n T\nes\n\n\n\nt*\n*\n\n\n\nPa\nth\n\n\n\ner\ngy\n\n\n\n te\nst\n\n\n\n w\nas\n\n\n\n d\non\n\n\n\ne \nby\n\n\n\n 3\n n\n\n\n\nee\ndl\n\n\n\ne \npr\n\n\n\nic\nks\n\n\n\n. O\nne\n\n\n\n w\nith\n\n\n\n a\n 2\n\n\n\n1 \nga\n\n\n\nug\ne \n\n\n\nne\ned\n\n\n\nle\n, t\n\n\n\nhe\n se\n\n\n\nco\nnd\n\n\n\n w\nith\n\n\n\n a\n 2\n\n\n\n5 \nga\n\n\n\nug\ne \n\n\n\nne\ned\n\n\n\nle\n, a\n\n\n\nnd\n th\n\n\n\ne \nth\n\n\n\nird\n w\n\n\n\nith\n a\n\n\n\n 2\n5 \n\n\n\nga\nug\n\n\n\ne \nne\n\n\n\ned\nle\n\n\n\n a\nnd\n\n\n\n th\ne \n\n\n\nin\nje\n\n\n\nct\nio\n\n\n\nn \nof\n\n\n\n d\nro\n\n\n\nps\n o\n\n\n\nf a\n n\n\n\n\nor\nm\n\n\n\nal\n sa\n\n\n\nlin\ne \n\n\n\nso\nlu\n\n\n\ntio\nn.\n\n\n\n T\nhe\n\n\n\n re\nsu\n\n\n\nlts\n w\n\n\n\ner\ne \n\n\n\nre\nad\n\n\n\n 2\n4 \n\n\n\nho\nur\n\n\n\ns l\nat\n\n\n\ner\n. A\n\n\n\n te\nst\n\n\n\n w\nas\n\n\n\n c\non\n\n\n\nsi\nde\n\n\n\nre\nd \n\n\n\npo\nsi\n\n\n\ntiv\ne,\n\n\n\n if\n a\n\n\n\nt t\nhe\n\n\n\n si\nte\n\n\n\n o\nf t\n\n\n\nhe\n n\n\n\n\nee\ndl\n\n\n\ne \npu\n\n\n\nnc\ntu\n\n\n\nre\n a\n\n\n\n \npa\n\n\n\npu\nle\n\n\n\n o\nr a\n\n\n\n p\nus\n\n\n\ntu\nle\n\n\n\n w\nas\n\n\n\n fo\nrm\n\n\n\ned\n, a\n\n\n\nnd\n it\n\n\n\n w\nas\n\n\n\n su\nrr\n\n\n\nou\nnd\n\n\n\ned\n b\n\n\n\ny \nan\n\n\n\n e\nry\n\n\n\nth\nem\n\n\n\na.\n\n\n\n1\n\n\n\n*P\noi\n\n\n\nnt\n sc\n\n\n\nor\ne \n\n\n\nsy\nst\n\n\n\nem\n: s\n\n\n\nco\nrin\n\n\n\ng \n\u2265 \n\n\n\n4 \nin\n\n\n\ndi\nca\n\n\n\nte\ns B\n\n\n\neh\n\u00e7e\n\n\n\nt\u2019s\n d\n\n\n\nis\nea\n\n\n\nse\n d\n\n\n\nia\ngn\n\n\n\nos\nis\n\n\n\n.\n**\n\n\n\nPa\nth\n\n\n\ner\ngy\n\n\n\n te\nst\n\n\n\n is\n o\n\n\n\npt\nio\n\n\n\nna\nl. \n\n\n\nH\now\n\n\n\nev\ner\n\n\n\n, w\nhe\n\n\n\nre\n p\n\n\n\nat\nhe\n\n\n\nrg\ny \n\n\n\nte\nst\n\n\n\nin\ng \n\n\n\nis\n c\n\n\n\non\ndu\n\n\n\nct\ned\n\n\n\n o\nne\n\n\n\n e\nxt\n\n\n\nra\n p\n\n\n\noi\nnt\n\n\n\n m\nay\n\n\n\n b\ne \n\n\n\nas\nsi\n\n\n\ngn\ned\n\n\n\n fo\nr a\n\n\n\n p\nos\n\n\n\niti\nve\n\n\n\n re\nsu\n\n\n\nlt\n\n\n\nTa\nbl\n\n\n\ne \n2.\n\n\n\n R\nev\n\n\n\nis\ned\n\n\n\n In\nte\n\n\n\nrn\nat\n\n\n\nio\nna\n\n\n\nl C\nrit\n\n\n\ner\nia\n\n\n\n fo\nr B\n\n\n\neh\n\u00e7e\n\n\n\nt\u2019s\n d\n\n\n\nis\nea\n\n\n\nse\n (a\n\n\n\nda\npt\n\n\n\ned\n fr\n\n\n\nom\n D\n\n\n\nav\nat\n\n\n\nch\ni e\n\n\n\nt a\nl 2\n\n\n\n01\n418\n\n\n\n)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 77\n\n\n\nJa\npa\n\n\n\nn19\n\n\n\n19\n93\n\n\n\n(n\n=3\n\n\n\n31\n6)\n\n\n\nK\nor\n\n\n\nea\n20\n\n\n\n20\n01\n\n\n\n(n\n=1\n\n\n\n52\n7)\n\n\n\nTu\nrk\n\n\n\ney\n21\n\n\n\n20\n03\n\n\n\n(n\n=2\n\n\n\n31\n3)\n\n\n\nSi\nng\n\n\n\nap\nor\n\n\n\ne8\n\n\n\n20\n04\n\n\n\n(n\n=3\n\n\n\n7)\n\n\n\nT\nha\n\n\n\nila\nnd\n\n\n\n9\n\n\n\n20\n06\n\n\n\n(n\n=2\n\n\n\n3)\n\n\n\nIr\nan\n\n\n\n22\n\n\n\n20\n10\n\n\n\n(n\n=6\n\n\n\n50\n0)\n\n\n\nC\nur\n\n\n\nre\nnt\n\n\n\n st\nud\n\n\n\ny\n20\n\n\n\n16\n(n\n\n\n\n=5\n)\n\n\n\nM\nea\n\n\n\nn \nag\n\n\n\ne \nof\n\n\n\n o\nns\n\n\n\net\n (y\n\n\n\nea\nrs\n\n\n\n)\n35\n\n\n\n.7\n33\n\n\n\nN\n/A\n\n\n\n32\n.7\n\n\n\nN\nA\n\n\n\n26\n24\n\n\n\nM\nal\n\n\n\ne:\nFe\n\n\n\nm\nal\n\n\n\ne \nra\n\n\n\ntio\n0.\n\n\n\n98\n:1\n\n\n\n1:\n1.\n\n\n\n75\n1.\n\n\n\n03\n:1\n\n\n\n1:\n1.\n\n\n\n1\n1.\n\n\n\n56\n:1\n\n\n\n1.\n2:\n\n\n\n1\n1.\n\n\n\n5:\n1\n\n\n\nO\nra\n\n\n\nl u\nlc\n\n\n\ner\ns\n\n\n\n98\n%\n\n\n\n98\n.8\n\n\n\n%\n10\n\n\n\n0.\n0%\n\n\n\n10\n0%\n\n\n\n10\n0%\n\n\n\n97\n.3\n\n\n\n%\n10\n\n\n\n0%\nG\n\n\n\nen\nita\n\n\n\nl u\nlc\n\n\n\ner\ns\n\n\n\n65\n%\n\n\n\n83\n.2\n\n\n\n%\n85\n\n\n\n.6\n%\n\n\n\n64\n.9\n\n\n\n%\n69\n\n\n\n.6\n%\n\n\n\n64\n.6\n\n\n\n%\n10\n\n\n\n0%\nSk\n\n\n\nin\n le\n\n\n\nsi\non\n\n\n\ns\n65\n\n\n\n%\n84\n\n\n\n.3\n%\n\n\n\n38\n.0\n\n\n\n%\n48\n\n\n\n.6\n%\n\n\n\n60\n.9\n\n\n\n%\n64\n\n\n\n.9\n%\n\n\n\n80\n%\n\n\n\nO\ncu\n\n\n\nla\nr l\n\n\n\nes\nio\n\n\n\nns\n57\n\n\n\n%\n50\n\n\n\n.9\n%\n\n\n\n45\n.5\n\n\n\n%\n35\n\n\n\n.1\n%\n\n\n\n52\n.2\n\n\n\n%\n56\n\n\n\n.8\n%\n\n\n\n80\n%\n\n\n\nA\nrti\n\n\n\ncu\nla\n\n\n\nr l\nes\n\n\n\nio\nns\n\n\n\n37\n%\n\n\n\n38\n.4\n\n\n\n%\n11\n\n\n\n.3\n%\n\n\n\n43\n.2\n\n\n\n%\n34\n\n\n\n.8\n%\n\n\n\n37\n.4\n\n\n\n%\n60\n\n\n\n%\nG\n\n\n\nI l\nes\n\n\n\nio\nns\n\n\n\n16\n%\n\n\n\n7.\n3%\n\n\n\n1.\n4%\n\n\n\n40\n.5\n\n\n\n%\n8.\n\n\n\n7%\n7.\n\n\n\n4%\n20\n\n\n\n%\nEp\n\n\n\nid\nid\n\n\n\nim\nyt\n\n\n\nis\n6%\n\n\n\n0.\n6%\n\n\n\nN\n/A\n\n\n\n0%\n4.\n\n\n\n3%\n4.\n\n\n\n7%\n0\n\n\n\nVa\nsc\n\n\n\nul\nar\n\n\n\n le\nsi\n\n\n\non\ns\n\n\n\n9%\n1.\n\n\n\n8%\n11\n\n\n\n.7\n%\n\n\n\n5.\n4%\n\n\n\n8.\n7%\n\n\n\n8.\n3%\n\n\n\n0\nN\n\n\n\neu\nro\n\n\n\nlo\ngi\n\n\n\nc \nle\n\n\n\nsi\non\n\n\n\ns\n3.\n\n\n\n8%\n4.\n\n\n\n6%\n3.\n\n\n\n3%\n5.\n\n\n\n4%\n8.\n\n\n\n7%\n3.\n\n\n\n8%\n20\n\n\n\n%\nPa\n\n\n\nth\ner\n\n\n\ngy\n44\n\n\n\n%\nN\n\n\n\n/A\nN\n\n\n\n/A\nN\n\n\n\n/A\n33\n\n\n\n.3\n%\n\n\n\n52\n.5\n\n\n\n%\n60\n\n\n\n%\nC\n\n\n\nar\ndi\n\n\n\nac\n \n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\n0.\n6%\n\n\n\nN\n/A\n\n\n\nPu\nlm\n\n\n\non\nar\n\n\n\ny\nN\n\n\n\n/A\nN\n\n\n\n/A\nN\n\n\n\n/A\nN\n\n\n\n/A\nN\n\n\n\n/A\n0.\n\n\n\n9%\nN\n\n\n\n/A\nTr\n\n\n\nea\ntm\n\n\n\nen\nt m\n\n\n\nod\nal\n\n\n\niti\nes\n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\nC\nor\n\n\n\ntic\nos\n\n\n\nte\nro\n\n\n\nid\ns\n\n\n\nA\nza\n\n\n\nth\nio\n\n\n\npr\nin\n\n\n\ne\nM\n\n\n\net\nho\n\n\n\ntre\nxa\n\n\n\nte\nC\n\n\n\nyc\nlo\n\n\n\nph\nos\n\n\n\nph\nam\n\n\n\nid\ne\n\n\n\nSu\nlfa\n\n\n\nsa\nla\n\n\n\nzi\nne\n\n\n\nN\n/A\n\n\n\nN\n/A\n\n\n\nC\nor\n\n\n\ntic\nos\n\n\n\nte\nro\n\n\n\nid\ns\n\n\n\nA\nza\n\n\n\nth\nio\n\n\n\npr\nin\n\n\n\ne\nM\n\n\n\net\nho\n\n\n\ntre\nxa\n\n\n\nte\nD\n\n\n\nap\nso\n\n\n\nne\nC\n\n\n\nol\nch\n\n\n\nic\nin\n\n\n\ne \npe\n\n\n\nnt\nox\n\n\n\nip\nhy\n\n\n\nlli\nne\n\n\n\nN\n/A\n\n\n\n \u2013\n n\n\n\n\not\n a\n\n\n\nva\nila\n\n\n\nbl\ne;\n\n\n\n G\nI-\n\n\n\n g\nas\n\n\n\ntro\nin\n\n\n\nte\nst\n\n\n\nin\nal\n\n\n\nTa\nbl\n\n\n\ne \n3.\n\n\n\n C\nom\n\n\n\npa\nris\n\n\n\non\n o\n\n\n\nf b\nas\n\n\n\nel\nin\n\n\n\ne \ncl\n\n\n\nin\nic\n\n\n\nal\n c\n\n\n\nha\nra\n\n\n\nct\ner\n\n\n\nis\ntic\n\n\n\ns a\nnd\n\n\n\n tr\nea\n\n\n\ntm\nen\n\n\n\nt m\nod\n\n\n\nal\niti\n\n\n\nes\n o\n\n\n\nf v\nar\n\n\n\nio\nus\n\n\n\n c\nou\n\n\n\nnt\nrie\n\n\n\ns\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3878\n\n\n\nReferences\n \n1. Beh\u00e7et H. Uber rezidivierende aphthouse durch ein \n\n\n\nvirus verursachte Geschwuere am Mund, am Auge und \nan den Genitalien. Dermatol Monatsschr Wochenschr \n1937;105:1152\u20137.\n\n\n\n2. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario \nF et al. 2012 revised International Chapel Hill Consensus \nConference Nomenclature of Vasculitides. Arthritis Rheum \n2013;65:1-11.\n\n\n\n3. Davatchi F, Chams-Davatchi C, Shams H, Shahram F, \nNadji A, Akhlaghi M et al. Behcet\u2019s disease: epidemiology, \nclinical manifestations and diagnosis. Expert Rev Clin \nImmunol 2017;13:57-65.\n\n\n\n4. Segasothy M. Beh\u00e7et\u2019s syndrome with sagittal sinus and \ninferior vena caval thrombophlebitis. Med J Malaysia \n1982;37:132-3.\n\n\n\n5. Normayah K, Mazri YM, Suib I, Zainal AA. Beh\u00e7et\u2019s \ndisease with vascular complications. Med J Malaysia \n2004;59:547-9.\n\n\n\n6. Othman K, Liza-Sharmini AT, Ibrahim M, Tharakan J, \nYanai R, Zunaina E. Int. Med Case Rep J 2017;10:35-40.\n\n\n\n7. Davatchi F, Shahram F, Chams-Davatchi C, Shams H, \nNadji A, Akhlaghi M et al. Clin Rheumatol 2010;29:823-\n33.\n\n\n\n8. YK Cheng, BY Thong, HH Chng. Beh\u00e7et\u2019s disease: \nExperience in a Tertiary Rheumatology Centre in \nSingapore and a Review of the Literature. Ann Acad Med \nSingapore 2004;33:510-4.\n\n\n\n9. Arromdee E, Tanakitivirul M. Epidemiology of Behcet\u2019s \ndisease in Thai patients. J Med Assoc Thai 2006;89:S182-\n6.\n\n\n\n10. Direskeneli H, Behcet\u2019s disease: infectious aetiology, \nnew autoantigens, and HLA-B51, Ann. Rheum. Dis. \n2001;60:996\u20131002. \n\n\n\n11. de Menthon M, Lavalley MP, Maldini C, Guillevin L, \nMahr A. HLA-B51/B5 and the risk of Behcet\u2019s disease: a \nsystematic review and meta-analysis of case control genetic \nassociation studies. Arthritis Rheum 2009;61:1287-96.\n\n\n\n12. Maldini C, LaValley MP, Cheminant M, de Menthon M, \nMahr A. Relationship of HLA-B51 or B5 genotype with \nBehcet\u2019s disease clinical characteristics: systematic review \nand meta-analyses of observational studies. Rheumatology \n2012;51:887-900.\n\n\n\n13. Gholijani N, Ataollahi MR, Samiei A, Aflaki E, \nShenavandeh S, Kamali-Sarvestani E. An elevated pro-\ninflammatory cytokines profile in Behcet\u2019s disease: a \nmultiplex analysis. Immunology Letters 2017;186:46-51.\n\n\n\n14. Liozon \u00c9, Roussin C, Pu\u00e9chal X, Garou A, Valadier P, \nP\u00e9rinet I et al. Beh\u00e7et\u2019s disease in East African patients \nmay not be unusual and is an HLA-B51 negative condition: \nA case series from Mayotte (Comoros). Joint Bone Spine \n2011;78:166\u201370.\n\n\n\n15. Alpsoy E, Donmez L, Bacanli A, Apaydin C, Butun B. \nReview of the Chronology of Clinical Manifestations \nin 60 Patients with Beh\u00e7et\u2019s Disease. Dermatology \n2003;207:354-6.\n\n\n\n16. Davatchi F, Sadeghi Abdollahi B, Chams-Davatchi C, \nShahram F, Shams H, Nadji A et al. The saga of diagnostic/\nclassification criteria in Behcet\u2019s disease. Int J Rheum Dis \n2015;18:594-605.\n\n\n\n17. International Study Group for Behcet\u2019s Disease. Criteria \nfor diagnosis of Behcet\u2019s disease. Lancet 1990;335:1078\u2013\n80.\n\n\n\n18. Davatchi F, Assaad-Khalil S, Calamia KT, Crook JE, \nSadeghi-Abdollahi B, Schirmer M et al. The International \nCriteria for Beh\u00e7et\u2019s Disease (ICBD): A collaborative \nstudy of 27 countries on the sensitivity and specificity of \nthe new criteria. JEADV 2014;28:338\u201347.\n\n\n\n19. Nakae K, Masaki F, Hashimoto T, Inaba G, Mochizuki \nM, Sakane T. Recent epidemiological features of Behcet\u2019s \ndisease in Japan. In: Godeau P, Wechsler B (eds) 1993, \nBehcet\u2019s Disease, pp. 145\u201351. \n\n\n\n20. Bang D, Lee JH, Lee ES, Lee S, Choi JS, Kim YK et al. \nEpidemiologic and clinical survey of Beh\u00e7et\u2019s disease \nin Korea: the first multicenter study. J Korean Med Sci \n2001;16:615-8.\n\n\n\n21. Tursen U, Gurler A, Boyvat A. Evaluation of clinical \nfindings according to sex in 2313 Turkish patients with \nBeh\u00e7et\u2019s disease. Int J Dermatol 2003;42:346-51.\n\n\n\n22. Davatchi F, Shahram F, Chams-Davatchi C, Shams H, \nNadji A, Akhlaghi M. Beh\u00e7et\u2019s disease in Iran: analysis of \n6500 cases. Int J Rheum Dis 2010;13:367\u201373.\n\n\n\n23. Varol A, Seifert O, Anderson CD. The skin pathergy test: \ninnately useful? Arch Dermatol Res 2010;302:155-68.\n\n\n\n24. Dilsen N, Konice M, Aral O, Aykut S. Standardization and \nevaluation of the   pathergy test in Behcet\u2019s disease and \ncontrols. In:Lehner T, Barnes C (eds). Recent advances \nin Behcet\u2019s disease. Royal Society of Medicine Services, \nLondon 1986:pp 177\u201380.\n\n\n\n25. Askari A, Al-Aboosi M, Sawalha A. Evaluation of pathergy \ntest in North Jordan. Clin Rheumatol 2000;19:249\u201351.\n\n\n\n26. Borhani Haghighi A, Pourmand R, Nikseresht AR. Neuro-\nBehcet disease. A review. Neurologist 2005;11:80-9.\n\n\n\n27. Kalra S, Silman A, Akman-Demir G, Bohlega S, Borhani-\nHaghighi A, Constantinescu CS et al. Diagnosis and \nmanagement of Neuro-Behcet\u2019s disease: international \nconsensus recommendations. J Neurol 2014;261:1662-76.\n\n\n\n28. Saleh Z, Arayssi T. Update on the therapy of Behcet\u2019s \ndisease. Ther Adv Chronic Dis 2014;5:112-34.\n\n\n\n29. Zhou Z, Chen S, Shen N, Lu Y. Cytokines and Behcet\u2019s \ndisease. Autoimmun Rev 2012;11:699\u2013704.\n\n\n\n30. Gul A, Tugal-Tutkun I, Dinarello, C, Reznikov L, Esen \nB, Mirza A et al. Interleukin-1beta- regulating antibody \nXOMA 052 (gevokizumab) in the treatment of acute \nexacerbations of resistant uveitis of Behcet\u2019s disease: an \nopen-label pilot study. Ann Rheum Dis 2012;71:563\u20136.\n\n\n\n31. Cantarini L, Vitale A, Borri M, Galeazzi M. Franceschini \nR. Successful use of canakinumab in a patient with resistant \nBehcet\u2019s disease. Clin Exp Rheumatol 2012;30:S115. \n\n\n\n32. Mohammad AJ, Smith RM, Chow YW, Chaudhry AN, \nJayne DR. Alemtuzumab as remission induction therapy \nin Behcet\u2019s disease: A 20-year Experience. J Rheumatol \n2015;42:1906-13\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 79\n\n\n\nCASE REPORT\n\n\n\nAcitretin an Additional Treatment Option for Elephantiasis Nostras \nVerrucosa: A Case Report \n\n\n\nDy Win Low, MRCP, Adawiyah Jamil, Adv M Derm, Norazirah Md Nor, Adv M Derm\n\n\n\nDepartment of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia \n\n\n\nSummary\nElephantiasis nostras verrucosa occurs due to chronic lymphedema, characterized by cutaneous \nchanges consisting of papillomatous, verrucous, and hyperkerototic lesions. Treatment of \nelephantiasis nostras verrucosa is challenging and results are often disappointing. We report our \nexperience with a patient who was successfully treated with oral acitretin. \n\n\n\nKey words: Elephantiasis nostras verrucosa, elephantiasis, acitretin\n\n\n\nCorresponding Author\nDr Low Dy-Win\nDepartment of Medicine, Universiti Kebangsaan \nMalaysia Medical Center, Bandar Tun Razak, Cheras, \n56000 Kuala Lumpur, Malaysia \n\n\n\nE-mail address: dywinlow@gmail.com\n\n\n\nIntroduction\nElephantiasis nostras verrucosa occurs due to \nchronic non filarial lymphedema.1 It is characterized \nby cutaneous changes consisting of papillomatous, \nverrucous, and hyperkerototic lesions.1 This \ncondition has been reported under a variety of \nother names, including elephantiasis nostras, \nelephantiasis verrucosa, elephantiasis crurum \npapillaris et verrucosa, lymphostatic papillomatosis \ncutis, pachydermia vegetans, lymphostatic \nverrucosa, papillomatosis cutis verrucosa and \nmossy foot.2 Treatment of elephantiasis nostras \nverrucosa is challenging and results are often \ndisappointing. Conservative therapies aim to reduce \nedema and infection using manual or mechanical \nmassages, elastic bandages, pneumatic stockings, \ndiuretics, topical agents, antibiotics and surgical \ndebridement.3-5 The beneficial effects of systemic \nretinoid for elephantiasis nostras verrucosa have \nbeen described.6 We report our experience with \na patient who was successfully treated with oral \nacitretin. \n\n\n\nCase report\nA 67-year-old man with hypertension presented \nwith fever and right leg pain of 4 days duration. In \naddition, he has chronic right lower limb swelling for \npast 15-years and diagnosed as elephantiasis nostras \nverrucosa secondary to recurrent cellulitis. He was \ntreated conservatively with elastic bandages and \nhydrocolloid dressings with not much improvement. \n\n\n\nOn examination, the right leg was enlarged \nfrom the foot up to the knee. There were mossy, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3880\n\n\n\ncobblestone-like verrucous papules, nodules and \nplaques noted on the skin surface. These lesions \nwere also malodorous, macerated and covered with \nslough in few areas (Figure 1a & b). The leg was \nwarm and tender on palpation. He was diagnosed as \nchronic lymphedema with cellulitis and treated with \n\n\n\nintravenous ampicillin/sulbactam and potassium \npermanganate wet dressing. Once the cellulitis \nresolved, oral acitretin (0.6 mg/kg/day) was \nintroduced and the dose was increased to 0.9 mg/\nkg/day after 6 weeks of therapy. \n\n\n\nFigure 1. Clinical presentations of patient with elephantiasis verrucosa nostra; (a&b) Enlarged left lower limb with mossy and \ncobblestone-like verrucous palques and nodules affecting the foot, ankle and lower leg; (c&d). The left lower limb after 16 weeks \nof acitretin therapy. Calf circumference was reduced by 10cm while ankle circumference was reduced by 2 cm. There was marked \nimprovement of the skin with disappearance of the cobblestoned verrucous plaques.\n\n\n\nAcitretin treatment resulted in disappearance of \nthe verrucous masses and remarkable flattening \nof hyperkeratotic lesions (Figure 1c & d). Clinical \nresponse was measured by the reduction in \ncalf and ankle circumferences. Calf and ankle \ncircumference were 40 cm and 32 cm pre-treatment \nand following 16 weeks of therapy were 30 cm and \n\n\n\n31 cm respectively. There were no more episode \nof cellulitis during the course of oral Acitretin \ntherapy. Liver function tests and serum cholesterol \nremained normal. Treatment was discontinued after \n12 months due to minor side effects of dry skin with \neczema craquele, sticky skin and brittle nails. And \nunfortunately, he developed recurrent cellulitis.\n\n\n\na b\n\n\n\nc d\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 81\n\n\n\nDiscussion \nLymphatic vessels are the main drainage channel \nfor interstitial proteins and fluid that regulates \ncell hydration and osmosis.11 In elephantiasis \nnostras verrucosa, lymphatic obstruction causes \naccumulation of protein rich fluid which stimulates \nproliferation of keratinocytes, fibroblasts and \nadipocytes.11,12 The epidermal, dermal layers \nand subcutaneous tissue became hardened due \nto excessive fibroblast activity.12 Lymph stasis \nresults in a localised immune deficiency as immune \ncells fail to circulate through the affected tissue \npredisposing it to bacterial infection. Lymph leaks \non the skin surface and fissures in the skin increase \nthe susceptibility of the area to infection.1,7 Chronic \nperipheral oedema due to lymph stasis produce \nthickened skin with hyperkeratotic, verrucous and \npapillomatous lesions.12 Mixed venous/lymphatic \noedema caused by recurrent infection further \ninduces or promotes elephantiasis13 as seen in this \npatient. \n\n\n\nManagement of elephantiasis nostras verrucosa is \nchallenging. Strategies to reduce of lymph stasis \ninclude lymphatic massages, elevation of the \naffected limb, compressive stockings or dressings \nand pneumatic compression devices. Results of \nthese conservative therapies are often inadequate. \nInfections should be aggressively treated to prevent \nprogression of fibrosis and lymphatic obstruction. \nSurgical debridement may be considered in cases \nwhere there is no improvement with medical \ntreatment.9\n\n\n\nOral and topical retinoid should be considered \nas treatment for elephantiasis nostras verrucosa. \nAcitretin induces loosening and thinning of \nhyperkeratotic stratum corneum. In addition, it may \nalso induce collagen degradation and thus beneficial \nin reducing fibrosis. The efficacy of oral retinoid \nhave been demonstrated by a few case reports. \nZouboulis et al reported three cases successfully \ntreated with oral etretinate at a dose of 0.6\u20130.75 mg/\nkg/day for 4 to 6 weeks.8 Block et al achieved very \ngood response in 2 patients treated with acitretin \n0.3mg/kg and 0.6mg/kg.6 Another patient showed \nmarked improvement with acitretin 0.3mg.kg for \n7 weeks.10 However, the disease relapsed upon \ndiscontinuation of treatment. Therapeutic response \nwas preserved when acitretin was reintroduced \nfollowing a relapse in one patient.8 Other than the \noccurrence of hypertrigliceridaemia, acitretin was \nwell tolerated.\n\n\n\nAcitretin had markedly improved the papillomatous \nnodules, verrucous lesions, hyperkeratosis, and \nlymphedema in our patient and he has no further \nepisodes of cellulitis. However, treatment was \nwithheld due to mucocutaneous side-effects. Despite \nbeing a good treatment option for this condition, \nthe optimal dose and duration of treatment is still \nunclear. Improvement has been shown with doses \nas low as 0.3mg/kg and eight weeks of therapy \nseemed adequate to achieve satisfactory response \nnevertheless, there is a high probability for \nrelapse upon its discontinuation. Hence, long term \nmaintenance therapy at a lower dose is required to \nminimalize relapses and side effects. \n\n\n\nConclusion\nAcitretin is a useful alternative treatment for \nelephantiasis nostras verrucosa. But the optimal \ndose and duration of treatment is still unclear. Long \nterm maintenance therapy at a lower dose is needed.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nAcknowledgement\nThe authors would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nReferences\n\n\n\n1. Schissel DJ, Hivnor C, Elston DM. Elephantiasis nostras \nverrucosa. Cutis 1998;62:77-80.\n\n\n\n2. Castellani A. Researches on elephantiasis nostras and \nelephantiasis tropica with regard to their initial stage \nof recurring lymphangitis (lymphangitis recurrens \nelephantogenica). J Trop Med Hyg 1969;72:89-96. \n\n\n\n3. Rowley MJ, Rapini RP. Elephantiasis nostras. Cutis \n1992;49:91-6.\n\n\n\n4. Mortimer PS. Therapy approaches for lymphedema. \nAngiology 1997;48:87-91.\n\n\n\n5. Lee B, Andrade M, Bergan J, Boccardo F, Campisi C, \nDamstra R et al. Diagnosis and treatment of primary \nlymphedema. Consensus document of the International \nUnion of Phlebology (IUP)-2009. Int Angiol 2010;29:454-\n70.\n\n\n\n6. Bock VL, Lee S. Taming elephantiasis with acitretin. Hong \nKong J. Dermatol. Venereol. 2011;19:125-9.\n\n\n\n7. Lu S, Tran TA, Jones DM, Meyer DR, Ross JS, Fisher HA \net al. Localized lymphedema (elephantiasis): a case series \nand review of the literature. J Cutan Pathol 2009; 36:1-20.\n\n\n\n8. Zouboulis C, Biczo\u00b4 S, Gollnick H, Reupke HJ, Rinck \nG, Szab\u00f3 M et al. Elephantiasis nostras verrucosa: \nbeneficial effect of oral etretinate therapy. Br J Dermatol \n1992;127:411-6\n\n\n\n9. Krisanne S,Amor K, Elephantiasis nostras verrucosa: A \nreview. Am J Clin Dermatol 2008;9:141-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3882\n\n\n\n10. Feind-Koopmans A, van de Kerkhof PC. Successful \ntreatment of papillomatosis cutis lymphostatica with \nacitretin. Acta Derm Venereol 1995;75:411.\n\n\n\n11. Ryan TJ. The lymphatics of the skin. In: The Physiology \nand Pathophysiology of the Skin, 2nd edition. Vol 5. \nLondon: Academic Press. 1978;1755-80.\n\n\n\n12. Casiey-Smith JR. Discussion of the definition, \ndiagnosis and treatment of lymphoedema. In: Progress \n\n\n\nin Lymphology: Proceedings of the Xth International \nCongress of Lymphology. Adelaide: University of \nAdelaide,1985;1-16.\n\n\n\n13. Sanders LJ. Slomsky JM, Burger-Caplan C. Elephantiasis \nnostras: an eight-year observation of progressive non-\nfilarial elephantiasis of the lower extremity. Cutis \n1988;42:406-11.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 83\n\n\n\nCASE REPORT\n\n\n\nToxic Epidermal Necrolysis as the First Presentation of Systemic \nLupus Erythematosus\n\n\n\nAnisha Bhullar1, Adv M Derm, Wan Syazween Iyana Wan Ahmad Kamal2, MRCP, Kartini Rahim1, Adv M Derm\n\n\n\n1Universiti Putra Malaysia, Serdang, Malaysia\n2Department of Medicine, Hospital Tuanku Fauziah, Kangar, Perlis \n\n\n\nSummary\nToxic epidermal necrolysis (TEN) is a severe mucocutaneous disease characterized by extensive \nepidermal detachment with drugs as the most probable cause. We describe a unique case of TEN \nwhere systemic lupus erythematosus (SLE) was found to be the precipitating underlying disease. Our \npatient was managed in ICU, however succumbed one month after her diagnosis due to overwhelming \nsepsis and multiorgan failure. \n\n\n\nKey words: TEN and SLE, TEN-like SLE, Acute cutaneous lupus\n\n\n\nCorresponding Author\nDr Anisha Bhullar\nDepartment of Medicine, Faculty of Medicine and \nHealth Sciences, Universiti Putra Malaysia, 43300 \nSerdang, Malaysia\n\n\n\nE-mail address: anishabhullar@gmail.com\n\n\n\nIntroduction\nToxic epidermal necrolysis is a severe mucocutaneous \ndisease characterized by more than 30% of body \nsurface involvement of epidermal detachment. \nThis disease may also have oral, ocular, pulmonary \nand genitourinary complications. The initial \npresentation of the rash maybe nonspecific, together \nwith prodromal symptoms of fever. However, the \ncutaneous lesions are rapidly progressing and lead \nto desloughing of the epidermis with extensive \nmucosal lesions. The involvement of the\noral and genital mucosa can lead to ulcerations \nand mucositis. Most TEN can be attributed to drug \ningestion.1 Here, our patient presented a case of \nrapid progressing TEN which surprisingly was \nthe rare variant of TEN-like acute cutaneous SLE \nconfirmed by skin biopsy.\n\n\n\nCase Report\nA 33-year-old Chinese female with underlying \nbipolar disorder presented with a history of \ngeneralised maculopapular rash of a rapid onset of \none week. History revealed no drug consumption or \nover the counter medication, including supplements \nand traditional medicines prior to developing \ncutaneous lesions. She had defaulted her psychiatric \nmedications for the past few years. She was spiking \na high temperature of 40 degrees Celsius and her \nother vital signs were within normal range. \n\n\n\nCutaneous examination revealed a generalised \nmaculopapular rash with 6% body surface area (BSA) \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3884\n\n\n\nof epidermal detachment, positive Nikolsky\u2019s sign \nwith severe oral and genital ulcerations. Within days \nshe progressed to full blown TEN with BSA >30% \n(Figure 1) and also required intubation for respiratory \ndistress. Further blood investigations fulfilled the \nSystemic Lupus International Collaborating Clinics \n(SLICC) criteria for Systemic Lupus Erythematosus \n(SLE) consisting of thrombocytopenia, leukopenia, \n\n\n\nlymphopenia, proteinuria (24 hour urine protein \n1273 mg/24 hours, urine protein creatinine index \n=3.8g/mmol), positive ANA titres 1: 160, positive \nSSA antibodies at 1:640 and low c3 levels(0.51mg/\ndL). Also, other pertinent investigations like \nmycoplasma pneumonia, chlamydia psittaci, \nchlamydia trachomatis and chlamydia pneumonia \nserologies were negative.\n\n\n\nFigure 1. The clinical presentation of the patient showing extensive epidermal detachment\n\n\n\nHistology showed an atrophic epidermis, marked \nparakeratosis, presence of civatte bodies and basal \ncell vacoular degeneration (Figure 2 and 3). There \nwas scanty perivascular lymphocytic infiltrates seen \nin the upper dermis with lymphocyte exocytosis. \nAlcian blue stain was positive for copious amounts \nof mucin deposition. However the specimen was \n\n\n\nunsuitable for immunofluorescence study. These \nfindings of interface dermatitis are consistent with \nlupus erythematous. A diagnosis of TEN like SLE \nwas made from her clinical presentation, skin \nhistology findings and laboratory and autoimmune \nmarkers.\n\n\n\nFigure 2. The histopathological examination of the skin biopsy; (a) parakeratosis with vacuolar degeneration of the basement membrane \n(H&E x40); (b) presence of civette bodies within the epidermis (H&E x100).\n\n\n\nba\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 85\n\n\n\nShe was treated with IV hydrocortisone and \nintensive skin nursing with bactigrass dressing for \nthe erosions. Her condition was complicated with \nsevere sepsis and acute kidney failure for which \nactive treatment was instituted comprising of IV \nantibiotics and haemodialysis. She succumbed to \nher disease after one month of admission due to \noverwhelming sepsis and multiorgan failure. \n\n\n\nDiscussion\nTEN is considered to be a T cell mediated disease \nwhich causes extensive keratinocyte apoptosis \nin the epidermis which further leads to the blister \nand bullae formation with epidermal detachment \nbeing the end result. Increased levels of soluble Fas \nligand detected in the serum of TEN and granulysin \ndetected in blister fluid have both been implicated \nin the pathogenesis of TEN as the cause of massive \nkeratinocyte cell death.2, 3 \n\n\n\nDrugs are believed to be the most common \nprecipitant while there have been other suggested \naetiologies like mycoplasma pneumonia and herpes \nsimples virus infections. As this disease carries a \nhigh mortality rate of 25%-30%, it is pertinent to \nconsider other underlying aetiologies. This clinical \nscenario previously referred to as acute syndrome \nof apoptotic pan-epidermolysis (ASAP) by Ting \net al covers the spectrum of TEN to include the \ndrug induced TEN (drugs as the cause) and other \ndiseases such as graft versus host disease (GVHD) \nand pseudoporphyria which may present similarly.4 \nThe association between SLE and TEN has been \nwell documented in the literature. In most reported \ncases, the diagnosis of SLE had been established \nwell before the onset of TEN. The classical TEN and \nSLE induced TEN is a difficult one to distinguish.\n\n\n\nIn our case, the cutaneous lesions were the presenting \nmanifestation of florid SLE. Prior to this, she had \nnot displayed any systemic symptoms suggestive \nof lupus. The progression of the rash in this patient \nfrom a generalised maculopapular rash to extensive \nepidermal detachment of >30% occurred in a \nvery short span of time, is similarly seen in drug \n-induced TEN. Despite detailed history taking, we \nwere unable to demonstrate any drug ingestion that \nmay have led to TEN, thus making the possibility \nof other aetiologies plausible. We had also excluded \nunderlying infections like mycoplasma and \nchlamydia in our search of underlying aetiology. \nAlbeit rare, there should be a high index of suspicion \n\n\n\nfor SLE in cases where the treating physician has \ndifficulty establishing a causal drug. \n\n\n\nThe fact that our patient presented with \u201cfulminant \nTEN\u201d contradicts previous case reports of SLE-\nassociated TEN which have a very gradual slow \nprogression. The histopathology findings from the \nskin biopsy help strengthen our diagnosis of SLE as \nthe probable underlying cause.\n\n\n\nTEN being a potentially fatal disease is a medical \nemergency necessitating ICU admission. Severity \nof Illness Score for Toxic Epidermal Necrolysis \n(SCORTEN) should be used in the initial assessment \nof TEN as it assists in prognosis.5 Treatment instituted \nis centred on supportive care to the skin and other \nvital organs. As large areas of skin are denuded, \nwound care is critical for the prevention of acute \nskin failure and the complications that may arise \nsuch as electrolyte imbalance, hypoalbuminemia, \nhypo/hyperthermia and fulminating sepsis. \n\n\n\nTherapeutic trends with IVIG and systemic \ncorticosteroids although used extensively, has \nnot been consistently beneficial for TEN.6 In a \nreview by Kirchhof et al there was benefit shown \nwith the administration of cyclosporine when \ncompared to the use of IVIG.7 In this case, short \ncourse of Methylprednisolone followed by IV \nHydrocortisone was prescribed, and showed \nsome initial improvements. Single dose of \netanercept has also induced re-epithelisation with \nsuccess in patients where SLE was the cause.8 In \nour patient, the development of TEN and SLE \nsynchronously contributed to her being severely \nimmunocompromised, which led to her demise.\n\n\n\nConclusion\nSLE-associated TEN is a potentially fatal disease, \na dermatological emergency. A multidisciplinary \nteam comprising of dermatologist, rheumatologist, \nintensivist and infectious disease specialist should \nbe managing the patient for better clinical outcomes.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nAcknowledgement\nThe authors would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3886\n\n\n\nReferences\n\n\n\n1. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal \nnecrolysis: Part I. Introduction, history, classification, \nclinical features, systemic manifestations, etiology, and \nimmunopathogenesis. J Am Acad Dermatol 2013;69:173-\ne1.\n\n\n\n2. Chung WH, Hung SI,Yang JY, Su SC, Huang SP, Wei \nCY et al. Granulysin is a key mediator for disseminated \nkeratinocyte death in Stevens-Johnson syndrome and toxic \nepidermal necrolysis. Nature medicine 2008;14:1343-50.\n\n\n\n3. Abe R. Toxic epidermal necrolysis and Stevens\u2013\nJohnson syndrome: soluble Fas ligand involvement in \nthe pathomechanisms of these diseases. J Dermatol Sci \n2008;52:151-9. \n\n\n\n4. Ting W, Stone MS, Racila D, Scofield RH, Sontheimer \nRD. Toxic epidermal necrolysis-like acute cutaneous lupus \nerythematosus and the spectrum of the acute syndrome \nof apoptotic panepidermolysis (ASAP): a case report, \nconcept review and proposal for new classification of \nlupus erythematosus vesiculobullous skin lesions. Lupus \n2004;13:941-50.\n\n\n\n5. Roujeau JC and Bastuji-Garin S. Systematic review \nof treatments for Stevens Johnson syndrome and toxic \nepidermal necrolysis using the SCORTEN score as a tool \nfor evaluating mortality. Ther Adv Drug Saf 2011;2:87-94.\n\n\n\n6. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal \nnecrolysis: Part II. Prognosis, sequelae, diagnosis, \ndifferential diagnosis, prevention, and treatment. J Am \nAcad Dermatol 2013; 69:187.e1-16.\n\n\n\n7. Kirchhof MG, Miliszewski MA, Sikora S, Papp A, Dutz JP. \nRetrospective review of Stevens-Johnson syndrome/toxic \nepidermal necrolysis treatment comparing intravenous \nimmunoglobulin with cyclosporine. J Am Acad Dermatol \n2014;71: 941-7.\n\n\n\n8. Napolitano M, Giampetruzzi AR, Didona D, Papi M, \nDidona B. Toxic epidermal necrolysis-like acute cutaneous \nlupus erythematosus successfully treated with a single dose \nof etanercept: Report of three cases. J Am Acad Dermatol \n2013;69:e303-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 87\n\n\n\nCASE REPORT\n\n\n\nA Case Report of Acne Agminata \n\n\n\nWei Siong Goh1, MBBS, Kwee Eng Tey1, MRCP, Siew Eng Choon1, FRCP, Yabitha Vasavam2, MPath\n         \n1Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia\n2Department of Pathology, Hospital Sultanah Aminah, Johor Bahru, Malaysia \n\n\n\nSummary\nGranulomatous facial skin lesions are a rare and challenging clinical problem. Differential diagnoses \ninclude cutaneous tuberculosis, sarcoidosis, granulomatous rosacea and acne agnimata. We reported a \ncase of acne agminata presented with granulamatous facial papules. \n\n\n\nKey words: Acne agminata, granulomatous facial papules\n\n\n\nCorresponding Author\nDr Tey Kwee Eng\nDepartment of Dermatology, Hospital Sultanah Aminah, \nJohor Bahru, Malaysia.\n\n\n\nEmail: ketey08@yahoo.com\n\n\n\nIntroduction\nGranulomatous facial skin lesions are a rare and \nchallenging clinical problem. Differential diagnoses \ninclude cutaneous tuberculosis, sarcoidosis, \ngranulomatous rosacea and acne agnimata. We \nreported a case of acne agminata presented with \ngranulamatous facial papules.\n\n\n\nCase Report\nA 51 years old Indian lady presented with multiple \nbrown-coloured, non-pruritic painless papules over \nher face and neck since June 2015. The skin lesions \ninitially started on the lateral side of nose and \nperioral region, which later spread to the periorbital \nregion. No history of facial flushing or worsening \nupon sun exposure. She had no constitutional \nsymptoms and no history of steroid consumption. \nExamination revealed multiple discrete brownish \ncoloured papules on the forehead, periorbital and \nperioral region. (Figure 1a, 1b)\n\n\n\nSystemic examination was normal. Laboratory \nindices were normal except for a positive antinuclear \nantibody (ANA) with a titre of 1:256. Mantoux test \nwas negative. Her chest x-ray and CT brain revealed \nno abnormal findings.\n\n\n\nSkin histology revealed numerous epitheloid \ngranulomas (Langerhan\u2019s type giant cell) within \nthe dermis and peri-appendageal areas. These \ngranulomas are formed by collection of epitheloid \nhistiocytes, with some showing evidence of necrosis \n(Fig 2a, 2b, 2c). Patchy infiltrates of lymphocytes \nand plasma cells were seen in peri-vascular and \nperi-appendageal areas. There was no evidence of \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3888\n\n\n\nmalignancy. No fungal bodies were seen on PAS \nand GMS stains. No acid fast bacilli were detected \non Ziehl-Neelsen (ZN) and Wade Fite stains.\n\n\n\nThe clinical presentation and histological findings \nwere consistent with acne agminata.  She was treated \nwith dapsone but showed minimal improvement. \nShe was then started on prednisolone which resulted \nin significant improvement of her skin lesions. \nHowever upon tapering down the prednisolone \ndosage to 15mg OD, her condition worsened.  She \nwas then commenced on oral isotretinoin 20mg OD \nand her lesions improved greatly. Her prednisolone \nwas tapered off after one month. \n\n\n\nDiscussion\nAcne agminata or lupus miliaris disseminates faciei \n(LMDF) was first described by Fox in 1878 as \n\u201cdisseminated follicular lupus\u201d.2 Its pathogenesis is \nstill much unclear. It is a rare condition which was \ninitially thought to be associated with tuberculosis.1 \n\n\n\nIt is seen often in young adults of both sexes though \nit can affect at any age groups.3-4 In 2000, Skowron et \nal proposed a name change from LMDF to FIGURE \n(facial idiopathic granulomas with regressive \nevolution).\u2075\n\n\n\nIn our patient, her presentation is similar to those \ndescribed in previous reports of acne agminata. The \nskin lesions are characterised by multiple, 1 \u2013 3 mm, \ndiscrete, smooth, brown/red to yellowish dome-\nshaped papules. Typically, the lesions appeared on \ncentral and lateral side of the face, particularly on \nand around eyelids and often extend onto the neck \nand chin5-9. Diascopy examination may reveal apple-\njelly nodules like those seen in lupus vulgaris1.\n\n\n\nHistologically, there are typical changes seen in the \nskin biopsy of our patient. This includes epithelioid \ngranulomas within the dermis, which may be \ncaseating even in the absence of tubercle bacilli.8 \nThere were no acid fast bacilli detected on ZN and \nWade Fite stains in the histology of our patient. \nThese changes are conforming to those seen in acne \nagminata.\n\n\n\nAcne agminata is classified into 3 stages based on \nage of the lesions, which are early (developing), fully \ndeveloped and late lesions. In the early (developing) \nstage, the lesions developed within 1 month and \nusually less than 2 mm diameter. The histology will \nshow superficial peri-vascular and peri-appendegeal \ncellular infiltrate composed of lymphocytes, a few \n\n\n\nhistiocytes and occasional neutrophils.10 In the fully \ndeveloped stage (which usually occurs 3 \u2013 6 months \nlater), the lesions will enlarged to 3 - 4 mm in size. \nHistologically it will show ruptured follicular wall \ninvolving one or more hair follicles with peri-\nfollicular epithelioid cell granuloma.10 Late stage \nusually appears after 8 months and biopsy will \nshow extensive fibrosis at peri-follicular areas with \nscattered lymphocytes, histiocytes and neutrophils \nwithin fibrotic area.10 In this case, our patient\u2019s \nhistology is likely to be in the fully developed stage. \n\n\n\nOur initial differential diagnosis include cutaneous \ntuberculosis, nodular sarcoidosis, granulomatous-\nrosacea, steroid dermatitis-resembling rosacea, \nacne vulgaris, eruptive syringomas and multiple \ntrichoepithelioma.  However, there was no \nsignificant lymphadenopathy or other systemic \ninvolvement suggestive of tuberculosis or \nsarcoidosis. Chest radiograph and CT scans were \nnormal. Our patient also did not have any history \nsuggestive of rosacea such as flushing of the face \nor lesions being aggravated by sun exposure. \nHistologically the lesions were not suggestive of \nmultiple trichoepithelioma or eruptive syringoma.\n\n\n\nThe management of acne agminata is often difficult. \nThe disease itself is self-limiting with spontaneous \nresolution seen within 2 years. However, it often \nheals with scarring.5,11 Several modalities have been \ntried and found to be effective which include dapsone, \ndoxycycline, minocycline, isotretinoin, clofazimine, \nisoniazid and even oral corticosteroids.12  Topical \nsteroids and psoralen-UVA, erythromycin, and \nmetronidazole have also been used.\n\n\n\nOur patient showed no response to dapsone. However \nshe responded well to a course of oral prednisolone. \nGood response to prednisolone was also seen in a \nstudy done by Uesugiet al\u00b9\u00b3, whereby 3 out of 4 of \nhis patients showed dramatic improvement with \nprednisolone.\n \nOur patient developed new lesions while on \ntapering dose of prednisolone. Hence, we decided \nto start her on isotretinoin. She responded very well \nand we were able to taper off her prednisolone after \none month. Isotretinoin is known to have effects \non the pilosebaceous apparatus and inflammatory \nprocesses. Maryam et al reported good response in \n2 patients treated with isotretinoin on doses as low \nas 0.5mg/kg/day.14 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 89\n\n\n\nConclusion\nAcne agminata is a rare condition whereby its \npathogenesis is still unclear. Typically, it presented \nwith brown / red to yellowish papules over the facial \nregion. Diagnosis is via clinical and histological \nexamination. We should always bear in mind of the \npossibility of cutaneous tuberculosis or sarcoidosis \nupon encountering similar skin lesions. Current \nmodalities of treatment showed variable results. A \nnumber of case studies have been reported on the \nefficacy of different treatments for acne agminata, \nbut no control studies have been done to establish \nstandard-of-care treatment. \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nAcknowledgement\nThe authors would also like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nFigure 1 (a&b). The clinical presentation of the patient showing multiple discrete brownish papules over the forehead, periorbital, along \nthe nasolabial fold, nose and perioral region.\n\n\n\nFigure 2. The histopathological examination of the skin biopsy; (a) Numerous epitheloid granuloma with areas of necrosis (H&E x 40); \n(b) Numerous epitheloid granuloma with areas of necrosis (H&E x 100); (c) Epitheloid granuloma (H&E x 400)\n\n\n\nba\n\n\n\na b c\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3890\n\n\n\nReferences\n\n\n\n1. Hodak E, Trattner A, Feuerman H, Feinmesser M, Tsvieli \nR, Mitrani-Rosenbaum S et al. Lupus miliaris disseminatus \nfaciei - the DNA of Mycobacterium tuberculosis is not \ndetectable in active lesions by polymerase chain reaction. \nBr J Dermatol 1997;137;614\u20139. \n\n\n\n2. Al-Mutairi N. Nosology and Therapeutic Options for Lupus \nMiliaris Disseminatus Faciei. Journal of Dermatology \n2011;38:864-73.\n\n\n\n3. Sehgal VN, Srivastava G, Aggarwal AK, Belum VR, \nSharma S. Lupus Miliaris Disseminatus Faciei Part I: \nSignificance of Histopathologic Undertones in Diagnosis. \nSkinmed 2005;4:151-6.\n\n\n\n4. Dawson GW. Acne agminata. Proc R Soc Med 1909;2:45-\n8.\n\n\n\n5. Skowron F, Causeret AS, Pabion C, Viallard AM, Balme \nB, Thomas L. F.I.GU.R.E.: facial idiopathic granulomas \nwith regressive evolution is \u2018lupus miliaris disseminates \nfaciei\u2019 still an acceptable diagnosis in the third millennium. \nDermatology 2000;201:287-9.\n\n\n\n6. Sehgal VN, Srivastava G, Aggarwal AK, Belum VR, \nSharma S. Lupus Miliaris Disseminatus Faciei Part II: An \nOverview. Skinmed 2005;4:234-8.\n\n\n\n7. Warren CM. Acne agminata. Proc R Soc Med 1938;31:1178.\n8. O\u2019Driscoll T, Morgan G. Acne agminata of the eyelid. Proc \n\n\n\nR Soc Med 1974; 67:869-70.\n9. Bedlow AJ, Otter M, Marsden RA. Axillary acne agminata \n\n\n\n(lupus miliaris disseminates faciei). Clin Exp Dermatol \n1998;23:125-8.\n\n\n\n10. Darouti M. El, Zaher H. Lupus Miliaris Disseminatus \nFaciei - Pathologic Study Of Early, Fully Developed And \nLate Lesions. Int J Dermatology 1993;32:508-11.\n\n\n\n11. Van de Scheur MR, van der Waal RIF, Starink TM. \nLupus miliaris disseminates faciei: a distinctive rosacea-\nlike syndrome and not a granulomatous form of rosacea. \nDermatology 2003;206:120\u20133.\n\n\n\n12. E. Mullan, P. Green, S. Pasternak. Lupus miliaris \ndisseminates faciei with extrafacial involvement in a \n17-year-old white girl. J Cutan Med Surg 15 (2011), \npp. 340-343 Acne agminate - Pathology of the skin, PH \nMcKee, 3rd Ed. Elsevier-Mosby.\n\n\n\n13. Uesugi Y, Aiba S, Usuba M, Tagami H. Oral prednisolone \nin the treatment of acne agminata. Br J Dermatol \n1996;134:1098-100.\n\n\n\n14. Daneshpazhooh M, Ehsani A, Toosi S, Robati RM. \nIsotretinoin in Acne agminate. Saudi Med Journal \n2007;28:1600-2.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 91\n\n\n\nCASE REPORT\n\n\n\nPseudolymphoma due to Hair Dye on Background of Chronic \nActinic Dermatitis Responding to Intra-lesional Triamcinolone \n\n\n\nHui Li Kwong, MBBS, Joyce Siong See Lee, MRCP, FAMS, Jiun Yit Pan, FRCP, FAMS\n\n\n\nNational Skin Centre, Singapore \n\n\n\nSummary\nCutaneous pseudolymphoma refers to a heterogenous group of benign T-cell or B-cell \nlymphoproliferative  processes  that  mimic cutaneous lymphoma clinically and sometimes  \nhistologically. The causes of cutaneous pseudolymphoma are diverse, including lymphomatoid drug \neruptions, lymphomatoid contact dermatitis, arthropod-bite reactions, chronic actinic dermatitis \n(CAD). Here we describe a case of pseudolymphoma due to hair dye on background of CAD.\n \n\n\n\nKey words: Pseudolymphoma; hair dye, chronic actinic dermatitis\n\n\n\nCorresponding Author\nDr Kwong Hui Li\nNational Skin Centre, 1 Mandalay Road, Singapore \n308205\n\n\n\nEmail: huili.kwong@mohh.com.sg\n\n\n\nIntroduction\nCutaneous pseudolymphoma refers to a \nheterogenous group of benign T-cell or B-cell \nlymphoproliferative processes that mimic cutaneous \nlymphoma clinically and sometimes histologically.1 \nThe causes of cutaneous pseudolymphoma are \ndiverse. It can occur in patients with chronic actinic \ndermatitis (CAD). Here we describe a case of \npseudolymphoma due to hair dye on background of \nCAD.\n\n\n\nCase Report\nA 76-year-old first was diagnosed with CAD \nfollowing a year of photo-distributed erythematous, \nscaly plaques affecting the face, V- neck, extensor \naspects of his forearms. His MED to UVB was \n30mJ/cm2 on phototests. Workup for his photo-\ndistributed rash included showed undetectable \nlevels of plasma porphyrins, creatine kinase levels \nof 228u/L (normal range 30-350u/L), negative anti-\nnuclear antibody and extractable nuclear antigen \nantibody (ENA), with marginally raised aldolase \nlevels (6.60u/L; normal range 1.3-6.3u/L). His \nretroviral, hepatitis B and C screens were negative. \nSkin biopsy demonstrated superficial and deep \nperivascular dermatitis with eosinophils.\n\n\n\nThe dermatitis was well-controlled with methotrexate \n(cumulative dose: 835mg) and topical steroids. \nHowever, he had a persistent facial plaque despite \nmultiple changes to his topical therapy. He denied \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3892\n\n\n\nany preceding insect bites, trauma, or contactants, \nthough he had used hair dye regularly for many \nyears. He claims to be compliant to photoprotection. \nA one-month trial of oral doxycycline 100mg twice \ndaily was unhelpful. \n\n\n\nThe facial lesions were only responsive to intra-\nlesional triamcinolone and oral prednisolone, \nthough recurrence occurred upon cessation of \ntherapy. Clinically, the patient has an indurated, \nerythematous plaque on the forehead (Figure 1). \nThere was no palpable cervical lymphadenopathy. \nHe declined to undergo patch-tests. Skin biopsy from \nthe forehead lesion showed a superficial and deep \nlymphocytic infiltrate admixed with eosinophils and \nplasma cells. A lymphoid follicle was present in the \nupper reticular dermis with reactive germinal centre \ncontaining tingible-body macrophages (Figure \n2). Direct immunofluorescence was negative. No \nlight chain restriction was detected on kappa and \nlambda immune-histochemical stains. The clinical \npicture and presence of lymphoid follicle on skin \nbiopsy was suggestive of B-cell pseudolymphoma \non background of CAD. \n\n\n\nThe patient currently remains on follow-up and is on \na tapering dose of prednisolone for his facial lesion.\n\n\n\nDiscussion\nCutaneous pseudolymphoma refers to a group of \nbenign T-cell or B-cell lymphoproliferative processes \nthat clinically or histologically mimic cutaneous \nlymphoma1. Cutaneous T-cell pseudolymphoma \n(CTPL) may be classified into distinct entities such \nas lymphomatoid drug eruptions, lymphomatoid \ncontact dermatitis, arthropod-bite reactions, \nand actinic reticuloid1. Cutaneous B-cell \npseudolymphoma (CBPL) may be idiopathic, or \ntriggered by Borrelia Burgdoferi tick bite, trauma, \ntattoos1. Clinically CBCL usually present as red or \nskin-coloured dermal and subcutaneous nodules and \nplaques, mimicking cutaneous B-cell lymphomas.\n\n\n\nA constellation of histological findings may help \ndistinguish CBPL from cutaneous B-cell lymphoma. \nCBPL typically shows a predominantly nodular \nor diffuse infiltrate of lymphocytes, admixed with \nhistiocytes, eosinophils and plasma cells, which \ntend to favour the papillary dermis (\u201ctop-heavy\u201d). \nThis is contrast to cutaneous B-cell lymphoma \nwhere the infiltrate is more intense in the deep \ndermis (\u201cbottom-heavy\u201d).  Germinal centres in \nCBPL can be divided in to small-cell nodular forms \nthat show typical germinal centre formation with \n\n\n\nno cellular pleomorphism; and large-cell nodular \nforms which show large pleomorphic lymphocytes \nwith mitotic figures. Immunohistochemical studies \nmay then be employed to help distinguish between \nCBPL from cutaneous lymphoma. CBPL typically \ndemonstrate a mixture of \u03ba and \u03bb light chains in \nB cells, in contrast to cutaneous B-cell lymphoma \nwhich usually expresses either \u03ba or \u03bb light chains.2 \nHowever, the expression of monotypic light-chains \nis only useful diagnostically when there is clear-\ncut restriction of light chains with \u03ba/\u03bb ratio of more \nthan 10:1 or less than 0.5:1.3 Other useful markers \ninclude MT2/CD45RA which stains very intensely \nin B-cell lymphoma compared to CBPL, and anti-\nbcl-2 protein monoclonal antibodies, which stain \npositive in cutaneous B-cell lymphoma within \ngerminal centres4. In general, histological features \nthat favour CBPL over cutaneous B-cell lymphoma \ninclude acanthosis, top-heavy infiltrate, mixed \ncellular infiltrate, presence of germinal centres, \npresence of tangible bodies, vascular proliferation, \npreservation of adnexal structures.1\n\n\n\nThe mainstay of treatment of cutaneous \npseudolymphoma is removal of the causative agent. \nHowever, cutaneous pseudolymphoma can have a \nchronic and indolent course. Localized persistent \nlesions may be treated with topical or intralesional \ncorticosteroids, cryosurgery and surgical excision, \nwith varying success.5 There have been reports \nof CBPL transforming to cutaneous lymphoma, \nand therefore long-term follow-up may be \nrequired.2 However, whether these cases represent \na misdiagnosis of lymphoma or true malignant \ntransformation remains to be seen.\n\n\n\nWe believe our patient had B-cell pseudolymphoma, \nand not actinic reticuloid given the histological \nfindings of a lymphoid follicle with a reactive \ngerminal centre, which is suggestive of a B-cell \nlymphocytic infiltrate. In contrast, actinic reticuloid \nis characterized by a predominantly T-cell infiltrate. \nHistological features that point to cutaneous \npseudolymphoma rather than cutaneous lymphoma \nin this patient include a mixed cellular infiltrate, \npresence of germinal centres, and tingible bodies, \nwith negative light-chain restriction studies. Contact \nallergy is frequently reported in CAD.  A more recent \nstudy of 50 patients with CAD reported a significant \nincrease in contact allergy to p-phenylenediamine, a \nmarker of hair dye sensitivity, reflecting the increased \npopularity of hair-dyeing practices in recent years.6 \nHis ongoing use of hair dye and possible underlying \ncontact allergy to P-paraphenylenediamine may \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 93\n\n\n\ncontribute to the persistence of the lesion despite \nphotoprotection, topical and systemic therapy. \nUnfortunately, he declined patch-tests and wishes to \nmaintain his hair-dyeing practices.\n\n\n\nFigure 1. An indurated, erythematous plaque on patient\u2019s \nforehead (arrow)\n\n\n\nFigure 2. Photomicrograph showing reactive lymphoid \nhyperplasia in the (arrow) and superficial and deep lymphocytic \ninfiltrate admixed with eosinophils and plasma cells (H&E, \nx200)\n\n\n\nReferences\n\n\n\n1. Ploysangam T, Breneman DL, Mutasim DF. Cutaneous \npseudolymphomas. J Am Acad Dermatol 1998;38:877-95.\n\n\n\n2. Halevy S, Sandbank M. Transformation of lymphocytoma \ncutis into a malignant lymphoma in association with sign \nof Leser Trelat. Acta Derm Venereol 1987;67:172-5.\n\n\n\n3. LeBoit PE, McNutt NS, Reed JA, Jacobson M, Weiss LM. \nPrimary cutaneous immunocytoma: a B-cell lymphoma \nthat can easily be mistaken for cutaneous lymphoid \nhyperplasia. Am J Surg Pathol 1994;18:969-78.\n\n\n\n4. Chimenti S, Cerroni L, Zenahlik P, Peris K, Kerl H. \nThe role of MT2 and anti-bcl-2 protein antibodies in \nthe differentiation of benign from malignant cutaneous \ninfiltrates of B lymphocytes with germinal center \nformation. J Cutan Pathol 1996;23:319-22.\n\n\n\n5. Rijlaarsdam JU, Willemze R. Cutaneous pseudolymphomas: \nclassification and differential diagnosis. Semin Dermatol \n1994;13:187-96.\n\n\n\n6. Chew AL, Bashir SJ, Hawk JL, Palmer R, White IR, \nMcFadden JP. Contact and photocontact sensitization in \nchronic actinic dermatitis: a changing picture. Contact \nDermatitis. 2010;62:42-6.\n\n\n\nConclusion\nCutaneous pseudolymphoma can mimic cutaneous \nB-cell lymphoma. A constellation of histological \nfindings may help to distinguish CBPL from \ncutaneous B-cell lymphoma. The mainstay of \ntreatment of CBPL is removal of the causative agent.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3894\n\n\n\nCORRESPONDENCE\n\n\n\nMalaysia Urticaria Expert Group (MARTEG) Meeting Outcomes \n\n\n\nAdrian Sze Wai Yong1, MRCP, CCT, Choong Chor Chang2, MRCP, Adv M Derm, Chin Chwen Ch\u2019ng1, MRCP, Adv M \nDerm, Chew Kek Lee3, MRCP, Adv M Derm, Chee Keen Woo2, MD, Yin Yin Lee4, MRCP, Adv M Derm, Asmah Johar5, \n\n\n\nMMed, Priya Gill6, MRCP, Adv M Derm, Pubalan Muniandy7, MRCP, Dip AUM/HIV, Yek Huan Khor8, MRCP, Adv M \nDerm, Agnes Yoke Hui Heng9, MRCP, Norazirah Md Nor10, MRCP, Adv M Derm, Amir Hamzah Abdul Latiff11, FACAAI, \nFAAAAI \n\n\n\n1Dermatology Unit, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia\n2Gleneagles Hospital, Kuala Lumpur, Malaysia\n3Pantai Hospital Cheras, Kuala Lumpur, Malaysia\n4Sunway Medical Centre, Selangor, Malaysia\n5Department of Dermatology, Hospital Kuala Lumpur, Wilayah Persekutuan, Malaysia\n6Manipal Hospital Klang, Klang, Selangor, Malaysia\n7Department of Dermatology, Hospital Umum Sarawak, Kuching, Sarawak, Malaysia\n8Department of Dermatology, Hospital Pulau Pinang, Georgetown, Pulau Pinang, Malaysia\n9Pantai Hospital Ipoh, Ipoh, Perak, Malaysia\n10Dermatology Unit, Medical Department, Universiti Kebangsaan Malaysia Medical Centre\n11Allergy & Immunology Centre, Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n\n\n\nKey words: Chronic urticaria, Chronic spontaneous urticaria, antihistamines\n\n\n\nCorresponding Author\nAssociate Professor Dr. Adrian Yong Sze Wai\nDermatology Unit, Department of Medicine, Faculty of \nMedicine, University of Malaya, Lembah Pantai 50603 \nKuala Lumpur, Malaysia\nEmail: adrian.yong@ummc.edu.my\n\n\n\nDear Editor,\n\n\n\nMalaysia Urticaria Expert Group (MARTEG) met \non the 7th May 2017. The meeting was jointly held \nby the Dermatological Society of Malaysia and the \nMalaysian Society of Allergy and Immunology. \nMARTEG comprised twelve dermatologists and \nthree allergists. It has four main objectives:\n\n\n\n1)  To optimise efficacy and safety of management \nof urticaria in Malaysia\n\n\n\n2)  To promote awareness of urticaria among \nhealthcare professionals and patients\n\n\n\n3)  To adapt management of urticaria to the local \nsetting\n\n\n\n4)  To identify knowledge gaps that impact the \nmanagement of urticaria in Malaysia.\n\n\n\nDuring this meeting, key international urticaria \nguidelines, including the European (EAACI)1, \nBritish (BSACI)2, American (AAAAI)3 and Asian \n(AADV)4, were discussed. MARTEG achieved \nconsensus on treatment recommendations \nfor Malaysian primary care practitioners and \npharmacists managing acute and chronic urticaria. \nOverall, the EAACI 2013 was the most referenced. \nUrticaria is defined as wheals with or without \nangioedema. Acute urticaria is defined as urticaria \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 95\n\n\n\nlasting shorter than 6 weeks and chronic urticaria \nis defined as urticaria lasting longer than 6 weeks.1 \nChronic urticaria is an umbrella term to include \nchronic spontaneous urticaria, physical/inducible \nurticaria and autoimmune urticaria. Refractory \nchronic spontaneous urticaria is defined as cases \nwho fail to achieve urticaria activity scores of less \nthan 3 despite second generation non-sedating \nantihistamines (nsAH) at four-fold licensed dose.\nThe first-line treatment for chronic urticaria is \nnsAH at licensed once daily dosing. If symptoms \nremain after 2 weeks,5 nsAHs dose maybe \nincreased up to four-fold. If symptoms are still \nnot adequately controlled after another 2 weeks, \nreferral to an urticaria specialist (adult and pediatric \ndermatologists, and allergists/immunologists) \nshould be made. In the absence of a prescription, \npharmacists should dispense antihistamines at \nlicensed doses. Only doctors, not pharmacists, \nshould be permitted to up-dose nsAHs by four-fold \nto ensure proper safety monitoring. \n\n\n\nFirst generation, sedating antihistamines should be \navoided in the treatment of urticaria due to their \nsedating and anticholinergic side effects.5 MARTEG \nrecognises that montelukast may be useful as a \nthird line add-on therapy for some patients, hence \nfurther research is required to identify this subset \nof patients in Malaysia. Ciclosporin is an effective \ntreatment for urticaria but patients should be closely \nmonitored by an urticaria specialist for side effects.1 \nOmalizumab is effective and useful in patients who \ndo not respond adequately to high-dose nsAHs1. \nShort-course oral prednisolone 0.5mg/kg/day for 3-7 \ndays can be useful in the management of urticaria \nexacerbations in addition to nsAHs.1 MARTEG \nstrongly discourages frequent or prolonged courses \nof oral, intramuscular or intravenous steroids in \nany form due to potential serious systemic side \neffects. MARTEG recommends that updosing of \n\n\n\nantihistamines in paediatric patients should only be \ndone under supervision of an urticaria specialist. \nMARTEG recommends using standard doses only \nin children due to the lack of evidence in terms of \nlong term safety.   \n\n\n\nMARTEG proposes the following research questions \nin decreasing order of importance:\n\n\n\n1. Epidemiology of chronic urticaria in the \nMalaysian adult and paediatric populations.\n\n\n\n2. Efficacy and safety of montelukast as an add-on \ntherapy to nsAHs in the treatment of refractory \nchronic spontaneous urticaria. (Refractory \nchronic spontaneous urticaria is defined as \nUrticaria Activity Score (UAS) of greater than \n3 despite four-fold dosing of nsAHs.) \n\n\n\n3. The efficacy and safety of dual combination \nnsAHs at doses up to four-fold in patients who \nare not controlled on a single nsAHs at increase \ndosage up to four-fold.\n\n\n\n4. A comparison of efficacy and safety of bilastine \nand desloratadine for the treatment of refractory \nchronic spontaneous urticaria. \n\n\n\nThe second MARTEG meeting will take place \nduring the 42nd Annual Dermatology Conference \nin August 2017.\n\n\n\nConflict\tof\tInterest\tDeclaration\nMARTEG has received support to hold the meeting \nfrom Menarini Asia Pacific Pte Ltd. This manuscript \nhas been written by MARTEG members with no \ninvolvement of MENARINI employees. \n\n\n\nAcknowledgement\nMARTEG would like to thank A/Prof Mokhtar Nor \nfrom Hospital University Sains Malaysia, Kelantan \nfor his contribution during this meeting.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3896\n\n\n\nReferences\n\n\n\n1. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, \nBrzoza Z, Canonica GW et al. The EAACI/GA(2) LEN/\nEDF/WAO Guideline for the definition, classification, \ndiagnosis, and management of urticaria: the 2013 revision \nand update. Allergy 2014;69:868-87.\n\n\n\n2. Powell RJ, Leech SC, Till S, Huber PA, Nasser SM, Clark \nAT et al. BSACI guideline for the management of chronic \nurticaria and angioedema. Clin Exp Allergy 2015;45:547-\n65.\n\n\n\nNo Recommendations\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n*nsAHs is the first-line treatment of urticaria and up to four-fold licensed dose may be used.\n\n\n\nUse of #sAHs are not recommended due to sedation and anti-cholinergic side effects.\n\n\n\nGeneral practitioners are advised to refer to specialists for further management if four-fold updosing of antihistamines fails to adequately \ncontrol urticaria.\n\n\n\nPharmacists should advise the use of nsAHs at standard licensed doses and refer to general practitioners or specialists if standard doses fail to \ncontrol urticaria.\n\n\n\nMontelukast remains a potential add-on for resistant urticaria after four-fold updosing of nsAHs.\n\n\n\nCiclosporin and Omalizumab are effective third-line treatment options for urticaria, which should be used under specialist supervision.\n\n\n\nShort courses of oral prednisolone 0.5mg/kg/day for 3-7 days can be used for acute urticaria and exacerbation of chronic urticaria. However, \nfrequent or prolonged courses of oral, intramuscular or intravenous steroids in any form are strongly discouraged due to potential serious \nsystemic side effects.    \n\n\n\nUpdosing of nsAHs in children should be done under close supervision and caution by specialist due to the lack of available evidence on safety.\n\n\n\n#sAHs: first generation sedating antihistamines, *nsAHs: second generation non-sedating antihistamines\n\n\n\nFigure 1. Key MARTEG recommendations for the treatment of acute and chronic urticaria\n\n\n\n3. Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, \nHsieh F et al. The diagnosis and management of acute and \nchronic urticaria: 2014 update. J Allergy Clin Immunol. \n2014;133:1270\u20137.\n\n\n\n4. Chow SK. Management of chronic urticaria in Asia: \n2010 AADV consensus guidelines. Asia Pac Allergy \n2012;2:149\u201360.\n\n\n\n5. Church MK, Church DS. Pharmacology of Antihistamines. \nIndian J Dermal 201;58: 219\u201324.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 97\n\n\n\nCORRESPONDENCE\n\n\n\nA Rare Case of Cutaneous Infection of Mycobacterium fortuitum \n\n\n\nXu Cong Ruan1,2, B.Sc, Laura Hui2, MBBS, Jiun Yit Pan2, FRCP, FAMS\n\n\n\n1Duke-NUS Medical School, Singapore \n2Department of Dermatology, National Skin Centre, Singapore \n\n\n\nKey words: Mycobacterium fortuitum; non-tuberculous mycobacteria, cutaneous infections\n\n\n\nCorresponding Author\nMiss Xu Cong Ruan\nDuke-NUS Medical School, 8 College Road, Singapore \n169857. \nEmail: ruanxucong@gmail.com\n\n\n\nDear Sir,\n\n\n\nCutaneous infections caused by non-tuberculous \nmycobacteria (NTM) are rare, though there has been \nan increasing trend noted over the past decade.1 It \nis usually suspected in the immunocompromised, \nand diagnosis can be delayed in immunocompetent \npatients. A high degree of clinical suspicion is often \nrequired. We present an unusual case of cutaneous \nM. fortuitum infection in an adult male. \n\n\n\nA 77-year-old Chinese gentleman presented with a \nfour-month history of occasional pruritic papular rash \nover his right forearm (Fig. 1). He had a background \nhistory of metabolic syndrome, coronary artery \ndisease, type two diabetes mellitus (HbA1c 6.4%), \ngout and benign prostatic hyperplasia. He did not \nhave any prior gardening or soil exposure nor was \nhe on any immunosuppressants. Initial impression \nwas that of a granulomatous rash secondary to \natypical infection. Skin biopsies were performed. \nHistology revealed mild compact hyperkeratosis, \nacanthosis with marked elastotic background with \nperivascular aggregates of lymphocytes. There were \nno granulomas detected. Fungal spores were noted \non direct microscopy in 10% potassium hydroxide. \nHe was treated for possible pityrosporum folliculitis \nwith miconazole cream 2 times per day, without \nmuch improvement.\n\n\n\nThe patient subsequently defaulted follow up. Five-\nmonths later, he was hospitalized for worsening \nright forearm cellulitis, with expansion of his \nverrucous plaques. Clinical impression was deep \nfungal infection or NTM infection, and repeat \nhistology and cultures were performed. Initial gram \nstain, fungal and acid-fast bacilli (AFB) smears were \nnegative. Fungal culture later revealed incidental \nscanty growth of M. fortuitum, which was confirmed \non mycobacteria culture. The histology findings \nwere consistent with granulomatous infection, with \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 3898\n\n\n\ncompact hyperkeratosis, focal parakeratosis, lower \ndermal fibrosis, and infiltrates of predominantly \nneutrophils forming an abscess, admixed with \ncollections of histiocytes, lymphocytes and plasma \ncells (Fig. 2). He was treated with ciprofloxacin and \nclarithromycin, with good response.\nM. fortuitum is usually found in immunocompromised \nindividuals, such as those with diabetes, and in \nassociation with trauma or clinical procedures.2 \nDiabetes may predispose patients to M. fortuitum \ninfection due to the impairment of the anti-\nmycobacterial function of their macrophages, \nleading to poorer outcomes.3,4 Therefore, in addition \nto appropriate antibiotic treatment, tighter control \nof diabetes is necessary to achieve treatment \nobjectives.4 \n\n\n\nOur patient\u2019s diagnosis was delayed due to a \nnon-representative biopsy with positive fungal \nscrape presenting as a red herring. Cutaneous M. \nfortuitum was only confirmed after repeat biopsy \nand cultures. Histological findings for rapidly-\ngrowing mycobacteria may be non-representative, \ndepending on the immune status of the patient \nas well as the disease duration.5 Therefore, the \nchance of false-negative investigations can be \nhigh, especially in immunocompetent individuals. \nIf there is a high degree of clinical suspicion and \nwhen lesions are unresolved despite prior treatment, \nrepeat microbiological investigations with histology \nare warranted to allow for timely and effective \ntreatment of patients.  \n\n\n\nThe diagnosis of NTM is often made on clinical, \nmicrobiological and pathological grounds. \nConfirmatory microbiology testing with isolation of \nthe causative species on tissue cultures remain as the \ngold standard6. Polymerase chain reaction with the \ndetection of mycobacterial deoxyribonucleic acid, \nwhen available, may provide a faster alternative. \nHistopathology of skin biopsies demonstrate \ninflammatory granulomatous infiltrate with \ngranuloma formation, abscesses or histiocytic \ninfiltration to the dermis and subcutaneous tissue.7 \n\n\n\nEmpirical treatment with antibiotics such as \nmacrolides or quinolones may be initiated while \nresults from susceptibility testing are pending.8 \nConventional anti-tuberculosis treatment is \nineffective for M. fortuitum. The antibiotic treatment \nof choice include ciprofloxacin, sulfonamides, \nclarithromycin, amikacin, doxycycline and \nimipenem for three to six months.5,6 Dual-drug \ntherapies are recommended to reduce the risk for \n\n\n\nantimicrobial resistance, and success rate varies \ndepending on patient and microbial factors.9 If \nantibiotics are given timely, surgical debridement \nor drainage can be avoided.1 Surgical excision is \nan option for patients who are recalcitrant to dual \nantibiotic therapy.1 \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nAcknowledgement\nWe thank the National Skin Centre, Singapore, for \nproviding us with the support and resources for this \ncase report.\n\n\n\nFigure 1. Right forearm verrucous plaques \n\n\n\nFigure 2. Higher power revealed an infiltrate of histiocytes \nadmixed with Langhans-type giant cells and surrounded by \nnumerous lymphocytes, plasma cells and neutrophils (H&E, \noriginal magnification 100x)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 99\n\n\n\nReferences\n\n\n\n1. Winthrop KL, Albridge K, South D, Albrecht P, Abrams M, \nSamuel MC et al. The Clinical Management and Outcome \nof Nail Salon\u2014Acquired Mycobacterium fortuitum Skin \nInfection. Clinical Infectious Diseases. 2004;38:38-44.\n\n\n\n2. Kwan K, Ho ST. Mycobacterium chelonae and \nMycobacterium fortuitum infection following open \nfracture: a case report and review of the literature. Indian \njournal of medical microbiology. 2010;28:248-50.\n\n\n\n3. Alim MA, Sikder S, Bridson TL, Rush CM, Govan BL, \nKetheesan N. Anti-mycobacterial function of macrophages \nis impaired in a diet induced model of type 2 diabetes. \nTuberculosis. 2017;102:47-54.\n\n\n\n4. Yew WW, Leung CC, Zhang Y. Oxidative stress and TB \noutcomes in patients with diabetes mellitus? The Journal \nof antimicrobial chemotherapy. 2017;72:1552-5.\n\n\n\n5. Sethi S, Arora S, Gupta V, Kumar S. Cutaneous \nMycobacterium fortuitum Infection: Successfully Treated \nwith Amikacin and Ofloxacin Combination. Indian Journal \nof Dermatology. 2014;59:383-4.\n\n\n\n6. Khan FA, Khakoo R. Nontuberculous mycobacterial \ncutaneous infections: an updated review. Cutis. \n2011;88:194-200.\n\n\n\n7. Silvestre Salvador JF, Betlloch MI, Alfonso R, Ramon RL, \nMorell AM, Navas J. Disseminated skin infection due to \nMycobacterium fortuitum in an immunocompetent patient. \nJournal of the European Academy of Dermatology and \nVenereology : JEADV. 1998;11:158-61.\n\n\n\n8. Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. \nElsevier Health Sciences UK; 2012.\n\n\n\n9. Atkins BL, Gottlieb T. Skin and soft tissue infections \ncaused by nontuberculous mycobacteria. Current opinion \nin infectious diseases. 2014;27:137-45.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38100\n\n\n\nCORRESPONDENCE\n\n\n\nA Case of Senescent Actinic Depigmentation \n\n\n\nXiao Tian Wu1, MBBS, Jiun Yit Pan2, FRCP FAMS\n\n\n\n1Department of Medicine, Khoo Teck Puat Hospital, Singapore\n2National Skin Centre, Singapore \n\n\n\nKey words: leukoderma, hypopigmentation, senescent actinic depigmentation, pigmentary disorders\n\n\n\nCorresponding Author\nDr Xiaotian Wu\n90, Yishun Central, Singapore 768828\nEmail: Xiaotian.wu@mohh.com.sg\n\n\n\nDear Sir,\n\n\n\nA 68 years old diabetic Sri Lankan man with \nextensive androgenic alopecia and seborrheic \ndermatitis presented to the National Skin Centre \nin Singapore with hypopigmented patches on the \nscalp of a few months\u2019 duration. The patches are \nnot pruritic nor painful. He reports occasional sun \nexposure with no protection. There is no history \nof application of cosmetic products or medication \non the scalp. On examination, there is extensive \nalopecia with multiple patches and macules of \nhypo-pigmentation involving the entire scalp (Fig. \n1). There are no other areas of hypopigmentation. \nThere were solar lentigines and ephelides on his \nface and other sun exposed areas. Skin scraping \nand microscopy revealed no fungus. A skin biopsy \nwas offered, but the patient declined. A diagnosis of \nsenescent actinic depigmentation was made.\n\n\n\nSenescent actinic depigmentation is a relatively \nnew pigmentary disorder of the scalp introduced by \nVerma et. al.1 The condition was first described in \na case series of 10 dark skinned patients who had \nandrogenic alopecia and subsequently developed \nasymptomatic hypo-pigmented macules which were \nlimited to areas affected by androgenic alopecia. It \nis uncommon in light skinned individuals, which \npresent with hypermelanosis.1 No association of this \ncondition with other forms of alopecia was found in \nEnglish literature.\n\n\n\nSenescent actinic depigmentation occurs in older \npatients with androgenic alopecia.2 It is postulated \nthat an excess of pro-oxidants, formed due to the \nloss of UV protection caused by alopecia, induce \nmelanocyte apoptosis in the pigmentary unit of \nthe aging hair follicles.3 It usually presents as \nasymptomatic, well defined patches and macules \nof hypo-pigmentation which are limited within the \nhair margins. An important differential diagnosis \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 101\n\n\n\nto consider is vitiligo \u2013 however, unlike vitiligo, \nsenescent actinic depigmentation is limited only to \nthe scalp area.  There is also no personal or family \nhistory of vitiligo or other autoimmune disorders. \nOther differential diagnoses, such as drug induced \npigmentary disorders, chemical induced leukoderma \nor post-inflammatory hypopigmentation can be \nexcluded based on the history. A skin scraping for \nmicroscopy should be done to look for Malassezia.\n\n\n\nSenescent actinic depigmentation is thought to \nbe a benign condition. However, it is important \nfor clinicians to recognize this condition to avoid \nunnecessary investigations and inappropriate \ntreatment. Reassurance should be given to patients, \nespecially in patient populations where pigmentary \ndisorders have sociocultural implications.4 \nAlthough this condition is not thought to be pre-\nmalignant, it must be noted that oxidative stress has \nbeen implicated in cutaneous carcinogenesis5 and \nhence patients with actinic depigmentation should \nbe checked and followed up for the development of \nany suspicious skin lesions.\n\n\n\nThe management of senescent actinic \ndepigmentation is not well established. As it is a \nbenign and asymptomatic condition, our patient was \neducated on the importance of sun avoidance and \nprotection. 3 years since presentation, he has not \nreturned with any issues.\n\n\n\nIn summary, senescent actinic depigmentation of \nthe scalp can occur in dark skinned individuals with \na history of androgenic alopecia and should not be \nconfused with other conditions. \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nFigure 1. A 68 years old Sri Lankan man with extensive \nandrogenic alopecia presents with asymptomatic hypopigmented \nmacules and patches on his scalp.\n\n\n\nReferences\n\n\n\n1. Verma SB, Wollina U. Ultraviolet Light\u2013Induced \nLeukoderma of the Scalp Associated with Androgenetic \nAlopecia: Senescent Actinic Depigmentation of the \nScalp. J Cutan Med Surg 2009;13:262\u20135.\n\n\n\n2. Verma S. Dermatology for the elderly: An Indian \nperspective. Clin Dermatol 2011;29:91-6.\n\n\n\n3. Arck PC, Overall R, Spatz K, Liezman C, Handjiski B, \nKalpp BF et al. Towards a \u201cfree radical theory of graying\u201d: \nmelanocyte apoptosis in the aging human hair follicle is \nan indicator of oxidative stress induced tissue damage. \nFASEB J. 2006;20:1567-9.\n\n\n\n4. Parsad D, Dogra S, Kanwar AJ. Quality of Life in Patients \nwith Vitiligo. Health Qual Life Outcomes 2003;1:58\n\n\n\n5. Sander CS, Chang H, Hamm F, Elsner P, Thiele JJ. Role of \noxidative stress and the antioxidant network in cutaneous \ncarcinogenesis. Int J Dermatol. 2004;43:326-35. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38102\n\n\n\nCORRESPONDENCE\n\n\n\nThe Night is Darkest Just Before the Dawn \n\n\n\nRene Sui Horng Wang, Sam Shi Yao Yang, MRCP\n\n\n\n1Monash University, Clinical School Johor Bahru, Malaysia\n2National Skin Centre, Singapore \n\n\n\nSummary \nThis short essay comments on three inflammatory skin reactions that present following the treatment \nof infectious diseases.\n\n\n\nKey words: IRIS,\tJarisch-Herxheimer,\tMazzotti\n\n\n\nCorresponding Author\nRene Wang Sui Horng\nMonash University, Clinical School Johor Bahru, 8, Jln \nMasjid Abu Bakar, 80100 Johor Bahru, Malaysia.\nEmail: rswan3@student.monash.edu\n\n\n\nDear Editor,\n\n\n\n\u201cThe night is darkest just before the dawn,\u201d Harvey \nDent declares in the 2008 cult classic The Dark \nKnight. It is a proclamation that resonates with the \nhuman condition, and is a sentiment oft-expressed \nby doctors to their patients; to persevere, and that all \nhope is not lost. Here, we discuss three conditions \nwhere the initiation of treatment results in a \nworsening before a turn for the better. \n\n\n\nThe immune reconstitution inflammatory syndrome \n(IRIS) is the first condition that mirrors the spirit \nof the quote. It occurs in HIV patients who have \njust been diagnosed and initiated on treatment. \nThis is characterized by the paradoxical worsening \nof pre-existing infections [1], as the previously \nsuppressed immune system reactivates and starts \nan inflammatory reaction against the infection. \nGenerally, this happens within one to three months \nof starting HAART. An example includes CMV \nretinitis resulting in visual impairment. Many \ndermatoses that are exacerbated by HIV such as \nseborrheic dermatitis, psoriasis and eosinophilic \nfolliculitis can also worsen in the initial stage of \ntreatment. \n\n\n\nThe second condition is the Jarisch-Herxheimer \nreaction- a sequelae of treating syphilis, particularly \nin the acute phase occurring in patients with high \nrapid plasma reagin (RPR) titres [2]. While this \nis generally self-limiting, patients should be \nforewarned about the systemic symptoms that \ncome on soon after the first dose of penicillin. This \nmost commonly manifests as oedema or pain in \nthe primary ulcer and a macular eruption. Severe \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 103\n\n\n\ncases may require admission to be monitored for \ncomplications such as shock. \n\n\n\nThe third condition, the Mazzotti reaction, is less \nwell-known. It is a response to the treatment of \nonchocerciasis using diethylcarbamazine (DEC). \nAs with the J-H reaction, the severity of the \nMazzotti response correlates with the severity of \nthe infection, with the corresponding symptoms \nof fever, hypotension, pruritus and adenitis [3]. \nInterestingly, this reaction is so common that it can \nbe used to confirm the diagnosis of river blindness \nby using DEC in a patch test of patients.\n\n\n\nThe effect of these syndromes has only served to \ncomplicate treatment outcomes for these patients as \nit can be difficult to demand patients place their faith \nin something that will eventually make them better. \n\u201cYou\u2019ll get more sick at first,\u201d does not inspire \nconfidence. It was not very long ago that being \nHIV+ meant a death sentence; today, advances in \nour understanding of the disease has added years \nto the prognosis.  To those patients who waited \n\n\n\nand suffered, mostly in silence, the quality of life \nexperienced by HIV+ patients now would have \nseemed like a pipe dream. I hope someone was there \nto express the second half of the quote, in sentiment \nif not in exact wording, \u201c\u2013 and I promise you, the \ndawn is coming.\u201d\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare \n\n\n\nReferences\n\n\n\n1. Sexton DJ, Pien BC; Immune reconstitution inflammatory \nsyndrome; UpToDate; last updated 2014; [http://\nwww.uptodate.com/contents/immune-reconstitution-\ninflammatory-syndrome]. \n\n\n\n2. Yang CJ, Lee NY, Lin YH, Lee HC, Ko WC, Liao CH et \nal.; Jarisch-Herxheimer Reaction after Penicillin Therapy \namong Patients with Syphilis in the Era of the HIV \nInfection Epidemic: Incidence and Risk Factors. Clin \nInfect Dis 2010;51:976-9. \n\n\n\n3. Francis H, Awadzi K, Ottesen EA. The Mazzotti \nreaction following treatment of onchocerciasis with \ndiethylcarbamazine: clinical severity as a function of \ninfection intensity. Am J Trop Med Hyg 1985;34:529-36.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38104\n\n\n\nOBITUARY NOTICES \n\n\n\nDr Noorlaily binti Mohd Noor\nConsultant Dermatologist\nHospital Kuala Lumpur\n2nd April 1974 \u2013 3rd March 2017\n\n\n\nHow do you say goodbye to someone so young and full of life? That\u2019s our Laily, the sweet and gentle \nperson with a smiling face. Laily succumbed to multiple myeloma the Friday evening of March 3rd \n2017 when the sun was setting and the sky was a glorious array of all the colours that she would \nhave liked. She was in the comforts of her own home, in her own room and surrounded by her close \nfamily and friends. It feels like only yesterday that as we discussed our cases along the corridors of \nthe hospital that she started facing one adversity after another. Though her illness was non-forgiving \nand raging on, she faced it with such grace and strong will, that she actually won the battle in her soul \nthough not in her body. Laily was also a person who found comfort in God\u2019s grace and was always \nsurrounded by people she loved. Her family especially her sisters were her pillars of strength.\n\n\n\nLaily served as a dermatologist in Hospital Kuala Lumpur from July 2009. She obtained her MRCP \nin 2005 and worked as a physician in Hospital Kuala Lumpur from 2005-2006. She went on to pursue \nher degree in Advanced Masters in Dermatology and graduated as a dermatologist in July 2009. She \nthen did her fellowship in infectious dermatology at the St John\u2019s Institute of Dermatology in 2010. \nHer contribution in the field of dermatology especially in Hansen\u2019s disease will be remembered. She \nwanted to continue her work and contributed as much as she could and did so with dedication and \npassion until the end. Laily contributed to the nation through her involvements in the society and the \nfield of dermatology. It was through her lectures and presentations that most of the dermatologists in \nthe country came to know her better.\n\n\n\nWe remember her for her quietness, her gentleness, her grace and her soft-spoken ways. We have lost \nnot only a dermatologist but a friend and comrade. Memories of the good times will carry us on.\n\n\n\nRest sweet Laily, rest in peace. Your journey has ended and your pain and struggles have ceased. We \nwill miss you always. May Allah bless your soul and place you among the pious.\n\n\n\nAlfatihah.\n\n\n\nDawn Ambrose\nNoor Zalmy Azizan\nAzura Mohd Affandi\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38 105\n\n\n\nErratum for Malaysian Journal of Dermatology                 \nVolume 37, Issue December 2016\n\n\n\nIn the Contents, there are errors in authorship of 2 Case Reports:  \n\u2022 \u201cThe wrath of the Rengas: A Report of Severe Contact Dermatitis and Implications for Public \n\n\n\nHealth in Rural Areas\u201d\nThe authors should be \u2013 Xavier G, Yong KY, Pubalan M\n\n\n\n\u2022 Maxillary Oral Cutanous Fistula in Diabetes Mellitus Patient: A Case Report\nThe authors should be \u2013 Tan ST, Gunawan L, Reginata G\n\n\n\nIn the original article \u201cCorrelation Between Cumulative Dose of Methotrexate and Methotrexate \nInduced Hepatotoxicity in Psoriasis Patients Undergoing Liver Biopsy \u2013 A 15 Years Retrospective \nStudy\u201d\nA printing error for the first sentence under the Results in the abstract: \u201cSkin areas treated with \nAEBritening\tComplex-01\tshowed\tsignificant\tdegree\tof\tlightening\teffect\t(+1\u201d. This sentence does not \nbelong to the abstract but was mistakenly printed there.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2017 June Vol 38106\n\n\n\nACKNOWLEDGEMENT\nJune Issue 2017\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Assoc Professor Dr Adrian Yong Sze Wai\n3. Dr Agnes Heng Yoke Hui\n4. Datin Dr Asmah Johar\n5. Dr Azura bt Mohd Affandi\n6. Dr Ch\u2019ng Chin Chwen\n7. Dr Chan Lee Chin\n8. Dr Chang Choong Chor\n9. Dr Chong Yew Thong\n10. Dr Dawn Ambrose\n11. Assoc Professor Dr Felix Yap Boon Bin\n12. Dr Henry Foong Boon Bee\n13. Dr Khor Yek Huan\n14. Dr Kwan Zhenli\n15. Mr. Lim Yang Kwang\n16. Dr Leong Weng San\n17. Dr Lo Kang Shang Chit\n18. Dr Ma Soot Keng\n19. Dr Ng Ting Guan\n20. Dato\u2019 Dr Noor Zalmy Azizan\n21. Assoc Professor Dr Norashikin bt Shamsudin\n22. Dr Norazirah Md Nor\n23. Dr Priya Gill\n24. Mr Regunathan A/L Villanayer\n25. Dr Rohna Ridzwan\n26. Dr Sabeera Begum\n27. Dr Tan Wee Ping\n28. Dr Tang Jyh Jong\n29. Dr Tang Min Moon\n30. Dr Tarita bt Taib\n31. Dr Tey Kwee Eng\n\n\n\n\n\n"
"\n\nVolume 47  |  Dec 2021  |  ISSN: 1511-5356\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 i\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence. Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: tanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in \nthe article. The article should be no more than 2-3 pages in \nlength.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Discussion, \nConclusion and References. A Structured Abstract of not \nmore than 250 words must be included. It should consist of \nfour paragraphs, labelled Background, Methods, Results and \nConclusion. It should describe the problem studies, how the \nstudy was performed, the main results, and what the author(s) \nconcluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to six \nauthors: if more than six authors, include the first six authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; \n(5) volume number; (6) first and final page numbers of the \narticle.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) \nreferred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine 2002. \np.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a delay \nto publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47ii\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\nREVIEW ARTICLE\n\n\n\nA Randomised Study Comparing the Efficacy of \nLow-Dose Oral Azithromycin versus Doxycycline in \nCombination with Topical Benzoyl Peroxide in the \nTreatment of Moderate to Severe Acne Vulgaris\nChandrasakaranpillay D, Ng TG\n\n\n\nPrevalence of Sexually Transmitted Infections \n(STIs) among Adolescents Attending Genitourinary \nMedicine Clinic Hospital Kuala Lumpur between \n2014 and 2018\nKrishnasamy V, Thevarajah S, Tang MM\n\n\n\nCharacteristics of Sexually Transmitted Infections in \nGenito-Urinary Medicine Clinic, Sarawak General \nHospital between 2018 and 2020\nTeo HG, Kiing JW, Lim TH, Lee SE, Foo SY, Badaruddin \nNSF, Muniandy P\n\n\n\nOral Lichenoid Reactions and Contact Sensitization: \nA 5-year Review in the Department of Dermatology, \nHospital Kuala Lumpur, Malaysia\nSyed Nong Chek SR, Tang MM \n\n\n\nA Prospective Case Control Study Comparing \nSerum Vitamin D Levels in Patients with and \nwithout Alopecia Areata\nLeong WC, Muhamad Sarkan M, Tang JJ\n\n\n\nA Study Assessing the Practices and Motivation for \nSeeking Tattoo Removal\nAllaranda Somaiah S, Basavapura Madegowda S\n\n\n\nA Comparative Study of Licochalcone A Moisturiser \nVersus Topical Hydrocortisone in Treating Mild-to-\nModerate Atopic Dermatitis\nTan LL, Faheem NAA, Han WH, Shanmugam T, Wong \nSM\n\n\n\nThe Clinical Characteristics of Inpatients: An audit \nin the Department of Dermatology Hospital Kuala \nLumpur between 2016 and 2020\nChan GP, Thevarajah S, Tang MM\n\n\n\nThe  Effect  of  Narrowband  Ultraviolet  B  \nPhototherapy  on  Vitamin  D  Status  in  Psoriasis \nPatients with Skin Phototype III, IV and V\nKuppusamy RM, Jamil A, Shima N\n\n\n\n2\n\n\n\n12\n\n\n\n21\n\n\n\n28\n\n\n\n35\n\n\n\n43\n\n\n\n48\n\n\n\n56\n\n\n\n63\n\n\n\n70\n\n\n\n77\n\n\n\n81\n\n\n\n86\n\n\n\n91\n\n\n\n95\n\n\n\n100\n\n\n\nCASE REPORT \n\n\n\nRituximab as First-line Therapy for Severe \nPemphigus: A Case Series and Review of Current \nLiterature\nLim MW, Ramalingam R\n\n\n\nIatrogenic Phaeohyphomycosis: A Rare and \nUnderrecognized Disease\nLim MW, Che Abdul Rahim AR, Ramalingam R \n\n\n\nCutaneous Tuberculosis in HIV Patient: A Case \nReport\nMd Isa NA, Low DW, Ab Rahman KS \n\n\n\nCase Series of Akurit-4 Associated DRESS\nChe Abdul Rahim AR, Sabri NZ, Ramalingam R \n\n\n\nPyoderma Gangrenosum Arising De Novo Over an \nUnusual Site: A Case Report\nBelgaumkar VA, Chavan RB, Bhatt N, Agrawal K\n\n\n\nSubcutaneous Sarcoidosis (Darier Roussy Sarcoid): \nA Rare Entity of Cutaneous Sarcoidosis\nLeong WC, Sulaiman W, Tan LT, Tang Jyh Jong\n\n\n\nA Case of Isolated Trichorrhexis Nodosa and \nTrichoscopic Images    \nSomaiah Savitha AS, Sankey Sana M, Raghunatha R\n\n\n\nACKNOWLEDGEMENT\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 iii\n\n\n\nEditor-in-Chief\n\n\n\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm     \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm Wilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm Wilayah Persekutuan Kuala Lumpur   \n    \nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDermatological Society of Malaysia | Persatuan Dermatologi Malaysia\n\n\n\nExecutive Committee\nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPresident\nDr Sabeera Begum, MMed - Vice President\nDr Tan Wooi Chiang, Adv M Derm - Secretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDr Chan Lee Chin, MMed - Past President\nDr Tang Jyh Jong, Adv M Derm - Committee \nMember\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2021 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - Committee \nMember\nDr Nazirin Ariffin, MRCP - Committee Member\n\n\n\nDermatological Society of Malaysia \nMedical Academics of Malaysia, Unit 1.6, \nLevel 1, Enterprise 3B, Technology Park Ma-\nlaysia, Jalan Innovasi 1, Lebuhraya Puchong- \nSg Besi, Bukit Jalil, 57000 Kuala Lumpur, \nMalaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 472\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Randomised Study Comparing the Efficacy of Low-Dose Oral \nAzithromycin versus Doxycycline in Combination with Topical Benzoyl \nPeroxide in the Treatment of Moderate to Severe Acne Vulgaris\n\n\n\nDarshni Chandrasakaranpillay, MRCP, Ting Guan Ng, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia \n\n\n\nAbstract\nBackground\nAcne vulgaris is a common chronic inflammatory skin disease. Long term therapy involving antibiotics \nwarrants for drug with a long half-life to increase compliance of patients. \n\n\n\nMethods\nA twelve-week prospective randomized study was performed on 40 subjects with moderate to severe \nfacial acne to compare the efficacy of oral azithromycin with oral doxycycline. Thirty-six subjects \ncompleted the study. Subjects in azithromycin group received azithromycin 250mg three times \na week plus topical benzoyl peroxide 5% (BPO), whereas subjects in doxycycline group received \ndoxycycline 100mg daily plus topical BPO 5%. Efficacy evaluation included treatment success rate \n(Comprehensive Acne Severity Score /CASS of 0 or 1 or improvement of two grades from baseline) \nand lesion counts.    \n\n\n\nResults\nTreatment was successful in 94.4% of subjects in azithromycin group, compared to 88.9% in \ndoxycycline group (p=1.000) at week 12.However, percentage of clear or almost clear by CASS was \nhigher in the doxycycline group ( 83.3% vs 66.7%; p= 0.443).Percentage reduction of inflammatory \nlesion counts in azithromycin and doxycycline group following treatment for 12 weeks were 78.3% \nand 85.3% (p=0.133) respectively, whereas for non-inflammatory lesion counts were 77.7% and \n78.8% (p=0.852) respectively. Nausea was reported in 77.8% at week 6 and 66.7% at week 12 in \ndoxycycline group, but none in azithromycin group. There were no significant differences in incidence \nof diarrhoea and abdominal pain.\n\n\n\nConclusion\nAzithromycin 250mg three times a week plus topical BPO 5% is as effective as doxycycline 100mg \ndaily plus topical BPO 5%.\n\n\n\nKey words: Acne vulgaris; Azithromycin; Doxycycline; Efficacy; Adverse effects\n\n\n\nCorresponding Author\nDr Darshni Chandrasakaranpillay\nDepartment of Dermatology, \nHospital Tengku Ampuan Rahimah,\nJalan Langat, Klang, Selangor, Malaysia\nEmail: shni84@hotmail.com\n\n\n\nIntroduction\nAcne is an important disease worldwide and is \nthe eighth most prevalent disease defined by the \nglobal burden of disease.1 Approximately 9.4% \nof the world\u2019s population are affected, with over \n90% of males and 80% of females in all ethnic \ngroup.1,2 The prevalence of acne varies among \nvarious countries.3 In Malaysia, the prevalence of \nacne is around 67.5% -68.1% among adolescents \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 3\n\n\n\n(13 - 18 years old), and among medical students \nfrom year 1 to 5, with males and females almost \nequally affected (1:1.1).4,5 Acne vulgaris affects \nboth genders, but the severity may be greater \nin male patients. In the pathogenesis of acne, \nthere is interplay between follicular epithelial \nhyperproliferation with resultant follicular \nplugging, excessive production of sebum, \ninflammation, and Propionibacterium acnes (P. \nacnes) activity.6 Face is the primary site of acne. \nIt can also affect the back, chest and shoulders. \nAt the trunk, lesions are usually concentrated \nnear the midline.6 \n\n\n\nMild acne can be managed with topical \ntreatments such as benzoyl peroxide, topical \nretinoids or topical combination therapy (e.g.: \nbenzoyl peroxide + antibiotic or  retinoid \n+ benzoyl peroxide or  retinoid + benzoyl \nperoxide + antibiotic).7 Systemic antibiotics \nhave been widely used in the treatment of \nmoderate to severe acne vulgaris. The anti-\nPropionibacterium acnes properties in \nantibiotics inhibit colonization of pilosebaceous \nglands by bacteria and prevent further \ninflammation.7 Doxycycline (tetracycline \ngroup) and erythromycin (macrolide group) \nare among the drugs commonly prescribed in \nthese group of patients.8,9 Doxycycline use is \ncontraindicated in certain populations, such as \npregnant and lactating mothers, and children \nunder 8 years of age.10 Oral erythromycin has \nbeen shown to be as effective as tetracycline \nwith good tolerability.11 However, increasing \nevidence of the development of erythromycin \nresistant strains of P. acnes have prompted \nresearchers to look for an alternative macrolide \nwith a long half-life.11 \n\n\n\nThus, studies on azithromycin as an alternative \ntreatment for acne vulgaris emerged. Successful \nusage of azithromycin in treating acne was first \nreported by Fernandez-Obregon AC in 1997.12\n\n\n\nAzithromycin is a 9-methyl derivative of \nerythromycin. It has a long half-life of 2.3- \n3.2 days. Azithromycin is better absorbed \nand is more vastly distributed into tissues \ncompared to erythromycin. It has the ability \n\n\n\nto achieve high concentrations within cells \n(including phagocytes) compared to serum. \nThese properties improve the safety and \nefficacy of azithromycin, whereas the long \nhalf-life reduces the frequency of drug use. \nBesides that, metabolization of azithromycin \nvia the hepatic pathways other than cytochrome \nP450 reduces the risk of drug interactions as \nwell.13,14 There is also increasing evidence that \nazithromycin exert immunomodulatory effects \nby diminishing  production of Interleukin-\n1alpha and Interleukin 8 cytokines (which are \nobserved to be upregulated in acne patients).15 \nMany studies have reported the efficacy and \nsafety of azithromycin in comparison to other \ndrugs with mixed results -either better than \nthe other drug16,17 or no significant difference \nto the other drug.12,18 Additionally, studies also \nreported monthly pulse dosage of azithromycin, \non 4 consecutive days a month to be as effective \nas daily dosage of doxycycline, which is \nan alternative option for subjects with poor \ncompliance.11,24 In terms of safety, mild to \nmoderate gastrointestinal discomforts were the \nmost commonly reported side effects.11,12,16-18,20 \n\n\n\nIn the Malaysian setting, according to the \nClinical Practice Guideline on Management of \nAcne, the recommended dose of azithromycin is \n500mg three times per week.21 This is the most \ncommonly used regime according to current \navailable evidences. Two studies have shown \nthat azithromycin 250mg three times per week \ncan effectively treat acne.16,18  However, to the \nauthors best knowledge at the time of this study, \nthere has been no randomised study published \nto compare the efficacy of azithromycin 250mg \nthree times per week with doxycycline 100mg \ndaily for the treatment of moderate to severe \nacne vulgaris. Furthermore, there is no resistance \nof  azithromycin towards P. acnes reported in \nMalaysia. On the other hand, erythromycin, \nwhich is a cheaper and commonly preferred  \nmacrolide  in the current clinical setting till \ndate, was already found to have a resistance rate \nof  7.5%  towards P. acnes in 2010 and could be \npredicted to be higher at present time.8,21 \n\n\n\nTherefore, the purpose of this study is to \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 474\n\n\n\ndetermine whether azithromycin 250mg thrice \nweekly is as effective and tolerable in terms of \nits adverse effects as doxycycline 100mg daily \nin the treatment of moderate to severe acne \nvulgaris. \n\n\n\nMaterials and Methods\n\n\n\nStudy Drugs \nIn this study, oral antibiotics-doxycycline or \nazithromycin were combined with topical \nbenzoyl peroxide 5% as recommended by acne \nguidelines to reduce antibiotic resistance.22 \n\n\n\nDisease Severity Assessment\nComprehensive Acne Severity Scale (CASS)\nEvaluation included assessment of subjects using \nComprehensive Acne Severity Scale (CASS),23 \na validated tool for acne severity grading. It has \nreproducibility, inter-rater reliability and intra-\nrater reliability. All the inspection was done at \na distance of 2.5 meters away for acne on face. \n\n\n\nAcne lesion count\nOther than CASS assessment, subjects\u2019 acne \nlesions were also manually counted. The lesions \nwere divided into non-inflammatory (open and \nclosed comedones) and inflammatory (papule, \npustule, nodule, cyst). Only lesions on the face \nwere counted. The lesions were counted before \nthe therapy (baseline), at 6-week and at 12-week \nof treatment by a single assessor. Photographs \nof the affected area were also taken from those \nwho consented. \n\n\n\nFinally, all subjects were evaluated for possible \nside effects by conducting an interview and then \na complete physical examination. Subjects were \nalso informed to contact the dermatology clinic \n/ the principal investigator in the event they \nexperienced undesirable side effects any time \nbefore their follow up assessment scheduled \ndates, once the treatment started.\n\n\n\nAll subjects were thoroughly briefed on the \ntechnique of benzoyl peroxide 5% (BPO 5%) \ngel application, i.e. to wash their face, pat dry \nand allow to dry thoroughly before application \nand to apply enough to cover the affected face \n\n\n\narea (avoiding the eye area) once a day at night. \n\n\n\nStudy Population\nThe study population were patients seen and \ndiagnosed with moderate to severe acne vulgaris \nat the Dermatology Clinic of Hospital Tengku \nAmpuan Rahimah who fulfil the inclusion and \nexclusion criteria during the study period 1st \nOctober 2019 \u2013 31st July 2020. Convenience \nsampling method was used and all subjects who \nmet the eligibility criteria within the study period \nwere randomized to receive either doxycycline \nor azithromycin.\n\n\n\nThe inclusion criteria were subjects aged 18 to \n40, diagnosed with moderate to severe facial \nacne vulgaris as defined by Comprehensive \nAcne Severity Score (CASS: score of 3-4 on \na scale from 0 -5), willing and able to comply \nwith the requirements of study protocol. All \nsubjects should be able to give written informed \nconsent as well.\n\n\n\nThe exclusion criteria were subjects younger \nthan 18 years and aged more than 40 years, \nsubjects with acne conglobata, acne fulminans, \ndrug induced acne, and nodulocystic acne that \nwould require oral isotretinoin; subjects who \nwere pregnant or breastfeeding mothers, subjects \nthat received systemic antiacne antibiotics \nwithin 1 month, history of oral isotretinoin  \nin the last 6 months, use of topical antiacne \npreparations, medicated shampoos or cleansers \nwithin 2 weeks, subjects with symptoms of \nhyperandrogenism, females with irregular \nmenstruation, subjects who had chemical \npeels or physical therapies (e.g. laser) within \n1 month, liver disease, history of arrhythmias, \nheart failure, history of hypersensitivity to \ndoxycycline or azithromycin, subjects with \nconcurrent use of oral contraceptive pills, \nconcurrent dermatological problems that \nwould interfere with the course of treatment or \nevaluation and finally patients who were treated \nwith doxycycline for acne previously.\n\n\n\nSubjects were also given the liberty to withdraw \nfrom the study at any time if the protocol was \nnot followed or the investigator deems that it is \ndetrimental or risky for the subject to continue. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 5\n\n\n\nHowever, all withdrawn/dropout subjects were \nnot replaced.\n\n\n\nRandomization and Blinding\nBlock randomization was carried out by an \nindependent unit- the Hospital Tengku Ampuan \nRahimah (HTAR) Clinical Research Centre to \nensure the number of recipients of azithromycin \ntherapy and doxycycline therapy were similar \nduring all phases of the study. The sizes of \nthe blocks were also randomized to reduce \npossibility of guessing the choice of treatment \nfor the next patient. Randomization was done \nusing the \u201cRANDBETWEEN (0,1)\u201d function \nin Microsoft Excel 2007, whereby \u201c0\u201d was \nassigned to azithromycin group; and \u201c1\u201d was \nassigned to doxycycline group. Concealment \nof allocation was done by placing the printed, \nfolded allocation into sealed opaque envelopes. \nThe sequence of the envelopes was then printed \non a separate piece of paper and pasted on the \nfront of the envelopes.\n\n\n\nStudy Design\nThis was an interventional, prospective, \nrandomized, open label comparative study of \nazithromycin 250mg three times a week with \nBPO 5% and doxycycline 100mg daily with \nBPO 5% in moderate to severe acne vulgaris. \nThe study was conducted at the Dermatology \nClinic of Hospital Tengku Ampuan Rahimah \nover a 12 weeks period. After obtaining consent, \nsubjects were screened and those who met the \ninclusion/exclusion criteria were randomized \nto either azithromycin group  or  doxycycline \ngroup during the baseline visit.\n\n\n\nIn azithromycin group, subjects received oral \nazithromycin 250mg three times per week for \n12 weeks along with topical benzoyl peroxide \ngel 5%. In doxycycline group, subjects received \noral doxycycline 100mg daily with topical \nbenzoyl peroxide gel 5 % for 12 weeks. Each \ngroup consisted of 20 subjects. The subject \nand the investigator were aware of the type of \nmedication allotted after baseline assessment \nwas done by the investigator. Subjects were \nclinically assessed and evaluated at baseline, 6 \nweeks and 12 weeks by the principal investigator, \n\n\n\nwho was the only assessor. Subjects were \nprovided with a diary to record the medication \ntaken, any missed pills, and adverse events. At \neach visit, pills were counted and topical BPO \ntubes were inspected.\n\n\n\nEfficacy Measures\nPrimary efficacy outcome of the study was an \nimprovement in CASS from baseline to week \n12. This outcome was dichotomized to success \nor failure using one of the following two criteria \nto be selected:\na) Clear or almost clear (Grades 0 or 1) as \n\n\n\nsuccess: Success is defined as \u201cClear\u201d \n(Grade 0) or \u201cAlmost clear\u201d (Grade 1) at \nweek 12.\n\n\n\nb) Two grades improvement as success: \nSuccess is defined as improvement of two \ngrades from the baseline score.\n\n\n\nSuccess rate was defined as the percentage of \nsubjects with a CASS of 0 (clear) or 1 (almost \nclear) at each post baseline visit or improvement \nof 2 grades from baseline score to week 6 and \n12.\n\n\n\nSecondary efficacy outcome was the change \nin acne lesion count. Percentage change from \nbaseline to week 6 and week 12 in acne lesion \ncounts (inflammatory, non-inflammatory and \ntotal lesion counts) were determined.\n\n\n\nSafety Assessment\nSafety outcome was assessed by incidence of \nadverse effects self-reported by subjects, and \nby using a checklist for side effects attributable \nto either drug. Adverse events were managed \naccordingly depending on the type and severity.\n\n\n\nEthical Approval\nThis study was conducted in compliance with \nethical principles outlined in the Declaration of \nHelsinki and Malaysian Good Clinical Practice \nGuideline. Ethical approval was obtained from \nthe Medical Research and Ethics Committee \nwith the research code of NMRR-19-2433-\n49831.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 476\n\n\n\nStatistical analysis\nNormality of continuous data was assessed \nusing Shapiro Wilk test. Natural log \ntransformation was performed on acne counts \n(inflammatory lesion, non-inflammatory lesion \nand total lesion), and percentage of change in \nacne counts at 12 weeks prior to comparison \nanalysis, as the data were found to have skewed \ndistribution. Mean and standard deviation were \nused to describe normally distributed data, \nwhile median and interquartile range were used \nto describe skewed distributions. Frequencies \nand percentages were used to describe the \ncategorical data. Independent t-test or Mann \nWhitney U Rank test was used to compare \ncontinuous data between the treatment groups. \nPaired t-test was used to compare continuous \ndata within groups. Fisher\u2019s Exact test or Chi \nSquare test was used to assess the association \nbetween categorical variables and study groups. \n\n\n\nStatistical analyses were performed with IBM \nSPSS Statistics 25.0. All statistical significance \nwas set at p<0.05. \n\n\n\nResults\nA total of 40 subjects were randomized to \ndoxycycline and azithromycin group. Each \ngroup consisted of 20 subjects. Two subjects \nfrom each group were lost to follow up. Thirty-\nsix subjects completed the study.\n\n\n\nDemographic and Clinical Characteristics of \nthe Study Population\nMajority of the subjects were females (82.5%), \nand distribution of subjects according to gender \nand ethnicity were similar in both treatment \ngroups (p=1.000 for age; p=0.737 for ethnicity). \nMedian age of subjects were 21 years (IQR=4.0).  \nMedian duration of acne among subjects was \n2.5 years (IQR=4.0). Median CASS score of \nthe study population was 3.0 (IQR=0.0). Mean \nlesion counts for inflammatory lesions, non-\ninflammatory lesions and total lesions were \n25.5 (SD=13.0) ,41.0 (SD=22.1) and 66.5 \n(SD=40) respectively. There were no significant \ndifferences in demographics and baseline \ncharacteristics between the 2 treatment groups \n(p>0.05). (Table 1)\n\n\n\nEfficacy\nComparison of treatment success at 6 and 12 \nweeks between azithromycin and doxycycline \ntreatment groups are displayed in Table 2. \nTreatment was a success in 11.1% of subjects \nin azithromycin group, as opposed to 22.2% \nin doxycycline group at 6 weeks (p=0.658). \nHowever, at 12 weeks, 94.4% of subjects in \nazithromycin group achieved treatment success, \nas opposed to 88.9% in doxycycline group. The \ntreatment success rates at week 12 were not \nstatistically significant between the treatment \ngroups (p=1.000). \n\n\n\nTable 1. Demographic data and clinical characteristics \n\n\n\nTotal Treatment groups P value\n\n\n\nAzithromycin plus \ntopical BPO\n\n\n\nDoxycycline plus \ntopical BPO\n\n\n\n(n=40) (n=20) (n=20)\n\n\n\nGender Male n (%) 7 (17.5) 4 (20.0) 3 (15.0) 1.000a\n\n\n\nFemale n (%) 33 (82.5) 16 (80.0) 17 (85.0)\n\n\n\nEthnicity Malay n (%) 36 (90.0) 19 (95.0) 17 (85.0) 0.737a\n\n\n\nChinese n (%) 2 (5.0) 1 (5.0) 1 (5.0)\n\n\n\nOthers n (%) 2 (5.0) 0 (0.0) 2 (10.0)\n\n\n\nAge (years) Median (IQR) 21.0 (4.0) 20.5 (4.0) 22.0 (5.0) 0.121b\n\n\n\nAcne duration (years) Median (IQR) 2.5 (4.0) 3.0 (4.0) 2.0 (4.0) 0.883b\n\n\n\nCASS score Median (IQR) 3.0 (0.0) 3.0 (1.0) 3.0 (0.0) 0.183b\n\n\n\nInflammatory lesion count Mean (SD) 25.5 (13.0) 21.7 (13.6) 22.9 (12.2) 0.154c\n\n\n\nNon-inflammatory lesion \ncount\n\n\n\nMean (SD) 41.0 (22.1) 43.5 (25.2) 38.6 (17.5) 0.495c\n\n\n\nTotal lesion count Mean (SD) 66.5 (40.0) 71.5 (32.2) 61.5 (22.0) 0.256c\n\n\n\nData was analysed with aFisher\u2019s Exact test; bMann Whitney U Rank Test; cIndependent t-test.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 7\n\n\n\nTable 2. Comparison of treatment success at 6 and 12 \nweeks between treatment groups (n=36)\n\n\n\n    Treatment groups P value\n\n\n\nAzithromycin \nplus topical \n\n\n\nBPO \n (n=18)\n\n\n\nDoxycycline \nplus topical \n\n\n\nBPO \n(n=18)\n\n\n\nCASS at \n6 weeks\n\n\n\nSuccess \nn (%)\n\n\n\n2 (11.1) 4 (22.2) 0.658\n\n\n\nCASS at \n12 weeks\n\n\n\nSuccess \nn (%)\n\n\n\n17 (94.4) 16 (88.9) 1.000\n\n\n\nData was analysed with Fisher\u2019s Exact test. Only patients with complete \nfollow-up data were included in the analysis. \n Success defined as achieving \u2018 clear \u2018(grade 0) or \u2018almost clear\u2019 (grade \n1), or improvement in 2 grades from baseline to         \n week 6 and 12 \n\n\n\nIn terms of CASS, percentage of clear or almost \nclear was higher in the doxycycline group at \nweek 12 (83.3% vs 66.7%) with no significant \ndifference between the two groups (p=0.443). \n(Table 3)\n\n\n\nTable 3. Percentage of \u2018clear\u2019 or \u2018\u2018almost clear\u2019 according \nto CASS at 12 weeks between treatment groups (n=36)\n\n\n\nTreatment groups P value\n\n\n\nAzithromycin \nplus topical \n\n\n\nBPO \n(n=18)\n\n\n\nDoxycycline \nplus topical \n\n\n\nBPO \n(n=18)\n\n\n\nCASS 0 or 1 at \n12 weeks\n\n\n\n n (%) 12 (66.7) 15(83.3) 0.443\n\n\n\nData was analysed with Fisher\u2019s Exact test. Only patients with complete \nfollow-up data were included in the analysis. \nCASS=Comprehensive Acne Severity Score; CASS \u20180\u2019= clear, CASS \n\u20181\u2019=almost clear\n\n\n\nOur study also found a significant reduction in \nthe mean number of inflammatory lesions from \nbaseline to week 6 within the azithromycin \ngroup (27.4+13.9 vs 12.2+8.5, p<0.001) and \n\n\n\ndoxycycline group (23.9+12.4 vs 10.1+5.4, \np<0.001), and significant reduction in the \nmean number of non-inflammatory lesions \nfrom baseline to week 6 in azithromycin group \n(40.5+23.8 vs 19.1+12.4, p<0.001) and in \ndoxycycline group (40.4+17.5 vs 19.9+11.3, \np<0.001). Finally, total lesion counts also \nshowed significant reduction from baseline to \nweek 6 in azithromycin group (67.9+29.1 vs \n31.3+18.8, p<0.001) and in doxycycline group \n(64.3+21.2 vs 29.9+14.7, p<0.001). (Table 4).\n\n\n\nAn overall reduction of 53.8% (SD=20.0) of \ninflammatory lesions at week 6 was observed \ncompared to baseline. Specifically, there were \nmean reductions of 54.0% (SD=16.6) and \n53.6% (SD=23.3) of inflammatory lesions in \nazithromycin group and doxycycline group, \nrespectively.  However, there was no statistical \ndifference in mean changes of inflammatory \nlesions at week 6 between the treatment groups \n(p=0.948). Similarly, an overall reduction \nof 49.8% (SD=19.9) was observed for non-\ninflammatory lesions at week 6 compared to \nbaseline. Specifically, there were mean reduction \nof 50.1% (SD=19.4) and 49.5% (SD=20.9) of \nnon-inflammatory lesions in azithromycin and \ndoxycycline group respectively. Again, there \nwas no statistical difference in mean changes \nof non-inflammatory lesions at week 6 between \nthe treatment groups (p=0.930). Mean reduction \nof total lesions was 53.2% (SD=17.5), with a \ndecrease of 53.8% (SD=15.6) in azithromycin \ngroup and 52.6% (SD=19.6%) in doxycycline \ngroup. The reduction in total lesions percentage \nwas not significant between the treatment \ngroups (p=0.844) (Table 5).\n\n\n\nTable 4. Comparison of acne lesion count from baseline to week 6 within treatment groups (n=36)\n\n\n\nAcne lesion count Treatment groups\n\n\n\nAzithromycin plus topical BPO \n(n=18)\n\n\n\nDoxycycline plus topical BPO\n(n=18)\n\n\n\nBaseline Week 6 P value Baseline Week 6 P value\n\n\n\nInflammatory lesions Mean (SD) 27.4 (13.9) 12.2 (8.5) <0.001** 23.9 (12.4) 10.1 (5.4) <0.001**\n\n\n\nNon-inflammatory \nlesions\n\n\n\nMean (SD) 40.5 (23.8) 19.1 (12.4) <0.001** 40.4 (17.5) 19.9 (11.3) <0.001**\n\n\n\nTotal lesions Mean (SD) 67.9 (29.1) 31.3 (18.8) <0.001** 64.3 (21.2) 29.9 (14.7) <0.001**\n\n\n\nData was analysed with paired t-test. Only patients with complete follow-up data were included in the analysis. \n**significant at p<0.001Data was analysed with paired t-test. Only patients with complete follow-up data were included in the analysis. \n**significant at p<0.001\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 478\n\n\n\nTable 5. Comparison of percentage change of acne \nlesion count from baseline to Week 6 between \ntreatment groups (n=36) \n\n\n\nChange of acne \nlesions\n\n\n\nTotal Treatment groups P \nvalue\n\n\n\nAzithromycin \nplus topical \n\n\n\nBPO\n\n\n\nDoxycycline \nplus topical \n\n\n\nBPO\n\n\n\n(n=36) (n=18) (n=18)\n\n\n\nInflammatory \nlesions (%)\n\n\n\nMean \n(SD)\n\n\n\n-53.8 \n(20.0)\n\n\n\n-54.0 (16.6) -53.6 (23.3) 0.948\n\n\n\nNon-\ninflammatory \nlesions (%)\n\n\n\nMean \n(SD)\n\n\n\n-49.8 \n(19.9)\n\n\n\n-50.1 (19.4) -49.5 (20.9) 0.930\n\n\n\nTotal lesions \n(%)\n\n\n\nMean \n(SD)\n\n\n\n-53.2 \n(17.5)\n\n\n\n-53.8 (15.6) -52.6 (19.6) 0.844\n\n\n\nData was analysed with independent test. Only patients with complete \nfollow-up data were included in the analysis. \nPercentage of change = [(lesion count at week 6 - lesion count at \nbaseline/lesion count at baseline)\n\n\n\nSignificant reduction in the mean number of \ninflammatory lesions from baseline to week \n12 was observed within the azithromycin \ngroup (27.4+13.9 vs 5.7+4.4, p<0.001) and \n\n\n\ndoxycycline group (23.9+12.4 vs 3.4+3.1, \np<0.001). There was also significant reduction \nin the mean number of non-inflammatory lesions \nfrom baseline to week 12 in azithromycin \ngroup (40.5+23.8 vs 8.3+6.2, p<0.001) and \ndoxycycline group (40.4+17.5 vs 8.3+6.2, \np<0.001). Finally, total lesions count also \nshowed significant reduction from baseline \nto week 12 in azithromycin group (67.9+29.1 \nvs 13.9+9.4, p<0.001) and doxycycline group \n(64.3+21.2 vs 11.7+8.0, p<0.001) (Table 6). \n\n\n\nThere was an overall reduction of 81.8% \n(SD=13.2) of inflammatory lesions at week \n12 compared to baseline. Specifically, there \nwere mean reductions of 78.3% (SD=13.0) \nand 85.3% (SD=12.7) of inflammatory lesions \nin azithromycin and doxycycline group, \nrespectively. However, there was no statistical \ndifferences in mean changes of inflammatory \nlesions, non-inflammatory lesions and total \nlesions at week 12 between the treatment groups \n(p=0.133 vs p=0.852 vs p=0.654) (Table 7).\n\n\n\nTable 6. Comparison of acne lesion count from baseline to week 12 within treatment groups (n=36)\n\n\n\nAcne lesion count Treatment groups\n\n\n\nAzithromycin plus topical BPO \n(n=18)\n\n\n\nDoxycycline plus topical BPO\n(n=18)\n\n\n\nBaseline Week 12 P value Baseline Week 12 P value\n\n\n\nInflammatory lesions Mean (SD) 27.4 (13.9) 5.7 (4.4) <0.001** 23.9 (12.4) 3.4 (3.1) <0.001**\n\n\n\nNon- inflammatory \nlesions\n\n\n\nMean (SD) 40.5 (23.8) 8.3 (6.2) <0.001** 40.4 (17.5) 8.3 (6.2) <0.001**\n\n\n\nTotal lesions Mean (SD) 67.9 (29.1) 13.9 (9.4) <0.001** 64.3 (21.2) 11.7 (8.0) <0.001**\nData was analysed with paired t-test. Only patients with complete follow-up data were included in the analysis. \n**significant at p<0.001\n\n\n\nTable 7. Comparison of percentage change of acne lesion count from baseline to week 12 between treatment \ngroups (n=36)\n\n\n\nChange of acne lesions Total Treatment groups P value\n\n\n\nAzithromycin plus topical BPO Doxycycline plus topical BPO\n\n\n\n(n=36) (n=18) (n=18)\n\n\n\nInflammatory lesions (%) Mean (SD) -81.8 (13.2) -78.3 (13.0) -85.3 (12.7) 0.133\n\n\n\nNon- inflammatory lesions (%) Mean (SD) -78.2 (12.7) -77.7 (12.5) -78.7 (13.3) 0.852\n\n\n\nTotal lesions (%) Mean (SD) -80.2 (11.3) -79.1 (10.3) -81.3 (12.4) 0.654\n\n\n\nData was analysed with independent test. Only patients with complete follow-up data were included in the analysis. \nPercentage of change = ((lesion count at week 12 \u2013 lesion count at baseline) / lesion count at baseline) *100%\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 9\n\n\n\nSafety and tolerability \nAt 6 weeks, none of the subjects receiving \nazithromycin reported nausea while 14 (77.8%) \nfrom doxycycline group developed nausea, and \nthe difference between treatment groups was \nstatistically significant (p<0.001). After 12 \nweeks of treatment, 12 (66.7%) subjects from \ndoxycycline group reported nausea (p<0.001), \nwhich is lesser than the percentage at 6 weeks \n(Table 8).\n\n\n\nDiscussion\nThirty-six subjects managed to complete \nthe study and it was comparable to Kus et al \n(2005) which included 45 patients aged 18 to \n40 suffering from moderate acne vulgaris.20 The \nage group of subjects in this study is comparable \nto Moravvej et al. (2012).12 Most of the previous \nsimilar studies included subjects aged 13-48 \nyears with a sample size of 50 to 80.12,16,18 \n\n\n\nAccording to the current findings, treatment \nwas a success only in 11.1% of subjects in \nazithromycin group, as opposed to 22.2% of \nsubjects in doxycycline group at 6 weeks. At \n12 weeks, treatment was a success in 94.4% \nof subjects in azithromycin group, as opposed \nto 88.9% of subjects in doxycycline group. \nThe difference was however not statistically \nsignificant (p>0.05). Additionally, both \ntreatment groups showed more reductions in \nterms of total lesions, inflammatory lesions \nand non-inflammatory lesions at 12 weeks \ncompared to 6 weeks of treatment with no \n\n\n\nsignificant difference between the treatment \ngroups (p>0.05). There was no significant \ndifference found in terms of percentage of \nlesions reductions following treatment between \ndoxycycline or azithromycin groups at both 6 \nand 12 weeks as well.\n\n\n\nOur current findings were similar to few other \nreported studies.11,12,20,24 In a randomized study \nwith 50 patients (more than 16 years old) for \n12 weeks done by Parsad et al. (2001), monthly \npulse dosing of azithromycin 500mg 4 times \neach month was tested against doxycycline \n100mg daily plus topical tretinoin 0.05%.11 \nBased on their results, pulse azithromycin plus \ntopical tretinoin 0.05% was as effective as \ndoxycycline 100mg daily plus topical tretinoin \n0.05%. This was similar to Kus et al. (2005) \nwhere azithromycin with dosage of 500mg/\nday on 3 consecutive days per week in the first \nmonth, followed by  2 consecutive days per \nweek in the second month and consecutively \none day per week in the third month; were found \nto give significant and similar improvement to \ndoxycycline twice a day for the first month and \nonce a day for the second and third months.20 \nIn another randomized, double-blind clinical \ntrial, Babaeinejad et al. (2011) compared the \nefficacy and safety of oral azithromycin 500mg \ndaily, 4 consecutive days per month for 3 \nconsecutive months and  doxycycline, 100mg \ndaily for 3 consecutive months.24 However, they \ndid set the age as the influencing parameter. It \n\n\n\nTable 8. Comparison of adverse effects at 6 and 12 weeks between treatment groups (n=36)\n\n\n\nAdverse Effects 6 Weeks 12 Weeks\n\n\n\nTreatment groups P value Treatment groups P value\n\n\n\nAzithromycin plus \ntopical BPO\n\n\n\n(n=18)\n\n\n\nDoxycycline plus \ntopical BPO\n\n\n\n(n=18)\n\n\n\nAzithromycin plus \ntopical BPO\n\n\n\n(n=18)\n\n\n\nDoxycycline plus \ntopical BPO\n\n\n\n(n=18)\n\n\n\nNausea 0 (0.0) 14 (77.8) <0.001**a 0 (0.0) 12 (66.7) <0.001**a\n\n\n\nVomiting 0 (0.0) 3 (16.7) 0.229 0 (0.0) 0 (0.0) n/a\n\n\n\nDiarrhoea  3 (16.7) 6 (33.3) 0.443 1 (5.6) 4 (22.2) 0.338\n\n\n\nAbdominal pain  3 (16.7) 4 (22.2) 1.000 1 (5.6) 1 (5.6) 1.000\n\n\n\nGiddiness 1 (5.6) 0 (0.0) 1.000 0 (0.0) 0 (0.0) n/a\n\n\n\nData was analysed with Fisher\u2019s Exact test or aChi square test. Only patients with complete adverse events follow-up data at 6 and 12 weeks were \nincluded in the analysis. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4710\n\n\n\nwas concluded that although azithromycin is \nas effective as doxycycline in the treatment \nof moderate acne vulgaris, doxycycline is a \nbetter treatment option for patients above 18 \nyears old. Another report by Moravvej et al. \n(2012) indicated similar efficacy between the \ntwo drugs in reducing the acne lesions too.12 \nTheir 12 weeks study included 60 subjects with \nmoderate facial acne and comparison was done \nbetween azithromycin 500mg/day, three times a \nweek plus topical tretinoin versus doxycycline \n100mg/day plus topical tretinoin.\n\n\n\nFew studies reported azithromycin to be more \neffective than the other drug too.16,17 In a \nretrospective study by Fernandez-Obregon et al. \n(2000) involving 79 patients (13- 48 years old),16 \nindividuals who were intolerant to tetracycline, \ndoxycycline, minocycline and erythromycin \nwere treated with azithromycin 250mg three \ntimes a week. By 4 weeks, azithromycin was \nfound to be significantly better. There were \nmore than 80% reduction in inflammatory \nacne lesions (85.7%) versus an average of \n77.1% for all other agents.16 In a different non-\nrandomized study done by Singhi et al. (2003), \n62 patients were treated with either daily dose of \nazithromycin 500mg for 3 consecutive days in \na 10 days cycle plus topical erythromycin, with \nseven drug free days each cycle; or doxycycline \n100mg/day with topical erythromycin over \n12 weeks period.17 Azithromycin with topical \nerythromycin combination was found to be \nsignificantly better compared to doxycycline \nwith topical erythromycin.\n\n\n\nKapadia and Talib (2004) treated acne patients \nwith azithromycin 500mg 3 times weekly \nand found that 83% showed at least a 60% \nimprovement in only 4 weeks and that the \nmajority achieved 80% clearance in 12 weeks.25 \nIn a study by Naieni et al. (2006), all 3 different \nazithromycin regimens- 5 consecutive days of \ntreatment each month with 500mg on the first \nday and 250mg/day for another 4 days per \nmonth;  500mg/day for 4 consecutive days per \nmonth; and 250mg/day thrice weekly were \neffective in the treatment of acne vulgaris with \nno significant difference in their efficacies.18 This \nwas a 12 weeks  investigator blind, randomized \n\n\n\nstudy involving 58 moderate to severe acne \npatients. \n\n\n\nOn the other hand, Ullah et al. (2014) found \nthat doxycycline worked better for acne with \na significant difference at 12 weeks.19 It was a \nrandomized study design with 386 patients of \nmoderate acne (14- 30 years old) comparing \nazithromycin 500mg/day, for 4 consecutive \ndays monthly, and doxycycline 100mg/day. In \nthis study however, no topical treatment was \ngiven to study subjects.19 \n\n\n\nA large scale worldwide observational study \nof adherence with acne therapy by Dreno et al. \n(2010) reported that approximately 48% of Asian \npatients from Hong Kong, India, Philippines, \nand Singapore are likely to adhere poorly to \ntheir acne treatment regimen. 53% of Asian \npatients adhered poorly to systemic treatment.26 \nThus, azithromycin could be a rational treatment \nbecause there is a possibility of better compliance \nwith lower frequency dosing regimen. Based on \nour findings, azithromycin 250mg thrice weekly \nis as effective as doxycycline 100mg daily, \nhence suggesting this regimen could be used as \nan alternative for patients who are intolerant or \ncontraindicated to doxycycline. This would also \nbe more cost effective than the current Clinical \nPractice Guidelines on Management of Acne \nrecommendation of 500mg three times per \nweek, with potential lesser gastrointestinal side \neffect. 11,12,17,20 \n\n\n\nIn terms of adverse effects, nausea was reported \nby the majority in the doxycycline group but \nnone in the azithromycin group. However, both \nthe study drugs were found tolerable, safe with \nno subjects withdrawing due to the adverse \neffects of the drugs by 6 and 12 weeks. Other \nreported adverse effects from this study include; \ndiarrhoea, abdominal pain, vomiting, and \ngiddiness. Most commonly reported adverse \neffects in patients receiving azithromycin 500mg \nof various dosing were, slight gastrointestinal \nupset and diarrhoea.11,12,17,20 \n\n\n\nLimitations and recommendations\nThe main limitation of our study is small \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 11\n\n\n\nsample size and single assessor, which may \ncause bias of assessment. Hence, a multi-centre \nstudy involving larger sample size would be \nneeded. Further longer study up to 24 weeks is \nalso helpful to determine the relapse rate of both \ngroup of patients.\n\n\n\nConclusion\nThis study demonstrated that in moderate to \nsevere facial acne vulgaris, both low-dose oral \nazithromycin and doxycycline in combination \nwith topical BPO are equally effective. \nAzithromycin can be considered as an alternative \noral antibiotic for patients who are intolerant/ \nallergic or contraindicated to doxycycline such \nas pregnant and lactating mothers.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nWe would like to express our profound gratitude \nto Dr Muralitharan A/L Perumal and Dr Yap \nSoong Yiing from CRC Department, HTAR \nfor their guidance and support in conducting \nthis study. We would like to thank the Director \nGeneral of Health Malaysia for his permission \nto publish this article. \n\n\n\nReferences\n1. Tan JK, Bhate K. A global perspective on the epidemiology \n\n\n\nof acne. Br J Dermatol 2015;172 Suppl 1:3-12. \n2. Yosipovitch G, Tang M, Dawn AG, Chen M, Goh CL, \n\n\n\nChan YH et al. Study of psychological stress, sebum \nproduction and acne vulgaris in adolescents. Acta Derm \nVenereol 2007;87:135-9. \n\n\n\n3. Shen Y, Wang T, Zhou C, Wang X, Ding X, Tian S et al. \nPrevalence of acne vulgaris in Chinese adolescents and \nadults: A community-based study of 17,345 subjects in six \ncities. Acta Derm Venereol 2012;92:40-4. \n\n\n\n4. Hanisah A, Omar K, Shah SA. Prevalence of acne and its \nimpact on the quality of life in school-aged adolescents in \nMalaysia. J Prim Health Care 2009;1:20\u20135.\n\n\n\n5. Muthupalaniappen L, Tan HC, Puah JW, Apipi M, Sohaimi \nAE, Mahat NF et al. Acne prevalence, severity and risk \nfactors among medical students in Malaysia. Clin Ter \n2014;165:187-92. \n\n\n\n6. Kang S, Amagai M, Bruckner AL, Enk AH, Margolis DJ, \nMcMichael AJ et al. Fitzpatrick\u2019s Dermatology, 9th ed. \nNew York.  McGraw-Hill Education. 2019; p.1391-5.\n\n\n\n7. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, \nBaldwin HE, Berson DS et al. Guidelines of care for \nthe management of acne vulgaris. J Am Acad Dermatol \n\n\n\n2016;74:945-73.\n8. Adawiyah J, Priya G, Roshidah B. Oral antibiotics in acne \n\n\n\nvulgaris: Therapeutic response over 5 years. Malays Fam \nPhysician 2010;5:130-3.\n\n\n\n9. Leyden JJ, Del Rosso JQ. Oral antibiotic therapy for \nacne vulgaris: pharmacokinetic and pharmacodynamic \nperspectives. J Clin Aesthet Dermatol 2011;4:40-7.\n\n\n\n10. MIMS Malaysia. Doxycycline: Indication, Dosage, Side \nEffect, Precaution. Available at https://www.mims.com/\nmalaysia/drug/info/doxycycline?mtype=generic. Accessed \non 9th June 2019.\n\n\n\n11. Parsad D, Pandhi R, Nagpal R, Negi KS. Azithromycin \nmonthly pulse vs daily doxycycline in the treatment of \nacne vulgaris. J Dermatol 2001;28:1-4. \n\n\n\n12. Moravvej H, Halim AM, Yousefi M, Givrad S. Efficacy \nof doxycycline versus azithromycin in the treatment of \nmoderate facial acne vulgaris. Iran J dermatol 2012;15:7-\n10. \n\n\n\n13. Foolds G, Shepard RM, Johnson IB. The pharmacokinetics \nof azithromycin in human serum and tissues. J Antimicrob \nChemother 1990;25 Suppl A:73-82. \n\n\n\n14. Rapp RP. Pharmacokinetics and pharmacodynamics \nof intravenous and oral azithromycin: Enhanced tissue \nactivity and minimal drug interactions. Ann Pharmacother \n1998;32:785-93. \n\n\n\n15. Kardeh S, Saki N, Jowkar F, Kardeh B, Moein SA, \nKhorraminejad-Shirazi MH. Efficacy of Azithromycin in \nTreatment of Acne Vulgaris: A Mini Review. World J Plast \nSurg 2018;8:127-34.\n\n\n\n16. Fernandez-Obregon AC. Azithromycin for the treatment of \nacne. Int J Dermatol 2000;39:45-50. \n\n\n\n17. Singhi MK, Ghiya BC, Dhabhai RK. Comparison of oral \nazithromycin pulse with daily doxycycline in the treatment \nof acne vulgaris. Indian J Dermatol Venereol Leprol \n2003;69:274-6. \n\n\n\n18. Naieni FF, Akrami H. Comparison of three different \nregimens of oral azithromycin in the treatment of acne \nvulgaris. Indian J Dermatol 2006;51:255-7. \n\n\n\n19. Ullah G, Noor SM, Bhatti Z, Ahmad M, Bangash AR. \nComparison of oral azithromycin with oral doxycycline in \nthe treatment of acne vulgaris. J Ayub Med Coll Abbottabad \n2014;26:64-7. \n\n\n\n20. Kus S, Yucelten D, Aytug A. Comparison of efficacy of \nazithromycin vs. doxycycline in the treatment of acne \nvulgaris. Clin Exp Dermatol 2005;30:215-20. \n\n\n\n21. Clinical Practice Guidelines Management of Acne. \nMinistry of Health Malaysia. Available at https://www.\nmoh.gov.my/attachments/7190.pdf. Accessed on 9th June \n2019.\n\n\n\n22. Goh CL, Abad-Casintahan F, Aw DC, Baba R, Chan LC, \nHung NT et al. South-East Asia study alliance guidelines \non the management of acne vulgaris in South-East Asian \npatients. J Dermatol 2015;42:945-53. \n\n\n\n23. Tan JK, Tang J, Fung K, Gupta AK, Thomas DR, Sapra \nS et al. Development and Validation of a Comprehensive \nAcne Severity Scale. J Cutan Med Surg 2007;11:211-6. \n\n\n\n24. Babaeinejad S, Khodaeiani E, Fouladi RF. Comparison of \ntherapeutic effects of oral doxycycline and azithromycin \nin patients with moderate acne vulgaris: what is the role of \nage? J Dermatolog Treat 2011;22: 206-10.\n\n\n\n25. Kapadia N, Talib A. Acne treated successfully with \nazithromycin. Int J Dermatol 2004; 43:766-7.\n\n\n\n26. Dr\u00e9no B, Thiboutot D, Gollnick H, Finlay AY, Layton \nA, Leyden JJ et al. Large-scale worldwide observational \nstudy of adherence with acne therapy. Int J Dermatol \n2010;49:448-56.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4712\n\n\n\nORIGINAL ARTICLE\n\n\n\nPrevalence of Sexually Transmitted Infections (STIs) among Adolescents \nAttending Genitourinary Medicine Clinic Hospital Kuala Lumpur between \n2014 and 2018\n\n\n\nVijayaletchumi Krishnasamy, Dip. STD/AIDS, Suganthi Thevarajah, MMed, Min Moon Tang, \nAdvMDerm \n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur Kuala Lumpur, Malaysia\n \nAbstract \nBackground\nAdolescents, who aged between 10 and 19 years old, comprise about 20% of the world\u2019s population.  \nThey are vulnerable to acquisition of sexually transmitted infections (STIs). Here, we aim to determine \nthe demography and pattern of STIs among adolescents attending Genito-Urinary Medicine (GUM) \nClinic, Hospital Kuala Lumpur (HKL).\n\n\n\nMethods \nThis is a retrospective study on all adolescents attending GUM clinic between 2014 and 2018. Data \nwas obtained from case notes and further analysed.\n\n\n\nResults\nA total of 111 adolescents attended GUM clinic between 2014 and 2018.  The mean age was 18 years \n(range 12-19). The male to female ratio was 2.26:1. All patients were Malaysian. Only 2 were foreign \nnationals.  The majority were Malays (85.3%) followed by Indians (11%) and Chinese (3.7%). About \n46.8% were still schooling, 28.8% were employed and 23.4% were unemployed. About 8.3% had a \nhistory of substance abuse. The majority (67.6%) were heterosexual, about 17.1% were homosexual \nand 3.6% were bisexual. Nearly 95% engaged in unprotected sex.  Majority (46%) had casual sex. The \nmost frequent presenting symptoms for male and female adolescents were discharge (43.2%) followed \nby swelling/growth (23.4%). About 83% had confirmed STIs.  The most common STIs among the \nmale were gonorrhoea (44.1%), genital warts (23.4%) and non-gonococcal urethritis (14.7%). The \nmost common STIs among the female were herpes genitalis (50%), genital warts (33.3%) and syphilis \n(8.3%). Six patients were infected with the human immunodeficiency virus (HIV). \n\n\n\nConclusion\nThe most common STI among adolescents between 2014 and 2018 was gonorrhoea for male and \nherpes genitalis for female. \n\n\n\nKey words: Adolescent, Sexually transmitted infections, Gonorrhoea, Herpes genitalis, Genital warts, Syphilis\n\n\n\nCorresponding Author\nDr Vijayaletchumi Krishnasamy \nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur, Malaysia\nEmail: vkrishnasamy44@gmail.com\n\n\n\nIntroduction  \nAdolescents, defined as persons between 10 and \n19 years old by WHO, are among of the most \nfrequent group reported with STIs. Those who \nare sexually active account for approximately \nhalf of reported STI cases annually.1,2 It is \nestimated that about 333 million new cases of \ncurable sexually transmitted infections occur \nworldwide each year, with the highest rates \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 13\n\n\n\namong 20-24 year-old followed by 15-19 \nyear-old age group.1 In Malaysia, adolescents \ncomprise of 18% of the total population.3 The \nimproved surveillance system in Malaysia has \nreported an increasing trend of syphilis and \ngonorrhoea. The incidence rate of syphilis was \nreported at 3.46 per 100,000 population in 2011 \nbut had tripled to 10.75 per 100,000 population \nin 2019.4,5 On the other hand, the incidence \nof gonorrhoea has doubled from 4.71 per \n100,000 population in 2011 to 9.25 per 100,000 \npopulation in 2019.4,5 In 2018, about 3% of \nnew HIV cases were reported among people \nage those aged between 13 and 19 years old in \nMalaysia.6 \n\n\n\nAdolescents are more likely to engage in high-\nrisk sexual behaviour such as multiple partners or \nengaging in sexual activities without a condom. \nThis is due in part to the fact that the prefrontal \ncortex, responsible for executive function, \nis still developing throughout adolescence.7 \nFurthermore, adolescents are less likely than \nadults to access to sexual health services due to \nconfidentiality issues.2 These factors lead to a \nhigher chance of exposure and a lower chance \nof diagnosis and treatment. From a biological \nperspective, adolescent females are particularly \nsusceptible to STIs like Chlamydia trachomatis \nand human papilloma viruses due to lower \nproduction of cervical mucus and increased \ncervical ectopy.7,8 Therefore, if exposed to an \nSTI, adolescent females are more likely than \nadults to get infected.7,8\n\n\n\nSTI guidelines from the CDC United States \nhighlight that youth who are at highest risk of \nsexually transmitted infections include those \nin detention facilities, injection drug users, and \nteens with history of sexual molestation and \nmales who have had anal sex with other males.2, \n\n\n\n9 Female victims of childhood sexual abuse \nare at increased risk for STIs possibly due to \nyounger age at sexual initiation and unsafe \nsex practices.9 Sexually transmitted infections \namong adolescents in Malaysia is largely \nunderreported. Thus there is limited data and \nstudies on STIs in adolescents.   \n\n\n\nThe aim of this study is to describe the \n\n\n\ndemography and pattern of STIs among \nadolescents attending Genito-Urinary Medicine \n(GUM) Clinic, Hospital Kuala Lumpur (HKL).\n\n\n\nMaterials and Methods \nThis is a retrospective study on all adolescents \nattending GUM clinic between 2014 and 2018. \nData was obtained from case notes and further \nanalyzed.\n\n\n\nResults\nThere were 111 adolescents who has attended \nGenitourinary Medicine clinic from the year \n2014 till 2018 (Table 1). Majority were referred \nfrom the outpatient and emergency department. \nFive cases were from the Suspected Child Abuse \nand Neglect (SCAN) team.  There were more \nmales (69.3%) than females (30.6%). The mean \nage of these patients was 18 years and most \nof the adolescent were in the age group of 15 \nto 19 years (89%). The youngest male was 13 \nyears while the youngest female was 14 years. \nMajority were Malaysian of which (85.3%) \nwere Malays followed by Indians (11.1%) and \nChinese (3.7%).  Only one was married. There \nwere 2 adolescents, unmarried presented to us \nduring pregnancy. There were 2 single mothers.\n\n\n\nLess than half were still school going (46.5%), \n28.8% were employed and 23.4% were \nunemployed.  Eleven (1.3%) of them had \nhistory of substance abuse. These substances \nincluded marijuana, glue, amphetamines/\nmethamphetamines, smoking and alcohol.  \nMajority (67.6%) were heterosexual. About \n17.1% and 3.6% were homosexuals and \nbisexuals respectively.  About a tenth of the \nadolescents denied having any kind of sexual \nactivity.   Majority (95%) had engaged in \nunprotected sex. Those who used condom \nclaimed to use them inconsistently. \n\n\n\nThe most common presentation to the GUM \nclinic was genital discharge (43.2%) followed \nby genital growths (23.4%). Following clinical \nassessment and laboratory investigations, 83% \nof adolescents were confirmed to have sexually \ntransmitted infections.  The most common STIs \namong the males were gonorrhoea (45.6%), \ngenital warts (17.6%) and non-gonococcal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4714\n\n\n\nurethritis (17.6%), as shown in Table 2. The most \ncommon STIs among female adolescents were \nherpes genitalis (50%), genital warts (33.3%) \nand syphilis (8.3%). Non-STI causes that were \ndiagnosed in this study included bacterial \nvaginosis, candidiasis, balanitis and molluscum \ncontagiosum. Six male adolescents were \ndiagnosed to have the human immunodeficiency \nvirus (HIV). \n\n\n\nTable 1. Demographic data and sexual behaviour\n of 111 adolescent attending GUM clinic Hospital\nKuala Lumpur between 2014 and 2018\n\n\n\nCharacteristics Male\nn=76\n\n\n\nFemale\nn=35\n\n\n\nTotal\nn= 111\n\n\n\nMean age in years (range) 18 (13-19)\nAge group in \nyears (%)\n\n\n\n<10 0 0 0\n10-14 6 6 12 (10.8%)\n15-19 70 29 99 (89%)\n\n\n\nEthnicity among \nMalaysian (%)\n\n\n\nMalay 65 28 93 (85.5%)\nChinese 3 1 4 (3.6%)\nIndians 7 5 12 (10.8%)\nOthers 1 1 2(1.8%)\n\n\n\nOccupation Student 34 18 52(46.8%)\nEmployed 26 5 31(28.0)\n\n\n\nUnemployed 16 11 27(24. %)\nSelf employed 1 - 1(0.9%)\n\n\n\nSexual \nOrientation \n\n\n\nHeterosexual 46 29 75(67.5%)\nHomosexual 19 - 19(17.1%)\n\n\n\nBisexual 4 - 4(3.6%)\nDenied 6 7 13(11.7%)\n\n\n\nType of sexual \npartner (%) \n\n\n\nCasual 40 11 51(46%)\nSteady 25 17 42(37.8%)\n\n\n\nSex worker 4 - 4(3.6%)\nNo partner 6 7 13(11.7%)\n\n\n\nNumber of \nsexual partner in \nthe last 6 months \n(%)\n\n\n\n1 45 24 69(62%)\n>1 24 5 29(26%)\n\n\n\nNumbers with documented \nsubstance abuse (%)\n\n\n\n10 1 11 (1.3)\n\n\n\nCondom usage \n(%)\n\n\n\nNever 2(1.8%)\n1(0.9%)\n3(2.7%)\n\n\n\n105(89%)\nOccasional\n\n\n\nAlways \nMissing data\n\n\n\nPresenting \nsymptoms (%)\n\n\n\nGenitalia pain 3 2 5(4.5%)\nDischarge 41 7 48(43.2%)\n\n\n\nGenital ulcers 10 11 21(18.9%)\nSwelling/\n\n\n\ngrowth \n18 8 26(23.4%)\n\n\n\nAsymptomatic 2 3 5(4.5%)\nContact 0 3 3(2.7%)\n\n\n\nGenital itch 2 1 3(2.7%)\nScrotal \n\n\n\nswelling \n4 - 4(3.6%)\n\n\n\nTrue sexually transmitted \ndiseases at final diagnosis (%)\n\n\n\n68 24 92 (82.8%)\n\n\n\nTable 2. Pattern of Sexually Transmitted Infections \n(STI) in 92 adolescents \n\n\n\nTypes of sexually transmitted \ninfections\n\n\n\nMale\nn=68(%)\n\n\n\nFemale\nn=24 (%)\n\n\n\nGenital warts 12 (17.6) 8 (33.3)\n\n\n\nHerpes genitalis 5 (7.4) 12 (50)\n\n\n\nSyphilis 10 (14.7) 2 (8.3)\n\n\n\nUrethral \ndischarge\n\n\n\nNeisseria gonorrhea \n(NG)\n\n\n\n30(44.1)\n\n\n\nNon gonococcal \nurethritis (NGU)  \n\n\n\n10 (14.7)\n\n\n\nNG and Chlamydia \ntrachomatis \ncoinfection\n\n\n\n1 (1.5)\n\n\n\nEpididymo-orchitis 4 (5.9)\n\n\n\nVaginal \ndischarge\n\n\n\nNeisseria gonorrhea 1 (4.2)\n\n\n\nChlamydia trachomatis 1 (4.2)\n\n\n\nDiscussion \nThe increasing trend of sexually transmitted \ninfections (STIs) among the young population \nis a significant public health problem. The \nmagnitude of STI prevalence in those age 10 \nto 19 years is difficult to ascertain in our local \nsetting as data tend to be aggregated with \nadults and rarely analysed as a distinct group. \nNeighbouring countries like Singapore had \nreported an 8% increase in STI among young \npeople aged 10\u201319 years old from the year 2014 \nto 2015, with more than 90% of the cases being \nin the age group of between 15 and 19 years.10 \nYouth with acute STIs are at increased risk of \nHIV because of both non\u2013condom-protected \nsexual behaviour and genital tract inflammation. \nOver one\u2019s life span, each STI episode increases \none\u2019s susceptibility to HIV infection.11\n\n\n\nIn our study there was a male preponderance \namongst adolescents who had attended the \nGUM clinic. This was probably because \nmajority of male adolescent were symptomatic. \nA large proportion of male adolescents in our \ncohort presented with urethral discharge and had \nNGU or gonorrhoea. Local studies showed that \nmore upper secondary male students in Penang \nand Negeri Sembilan had engaged in sexual \nactivities12-14.  In the Prevalence of HIV, STD, \nDrug Use, and Risk Behaviours in Adolescents \nand Young Adults (PHRAYA) study conducted \nin Thailand in 1999, it was shown that \nadolescents and young adults in Chiang Rai are \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 15\n\n\n\nat high risk of unprotected intercourse, being \ncoerced to have sex, unwanted pregnancies, \nsexually transmitted diseases, and drug use.16 \n\n\n\nSexual abuse during childhood or adolescence is \noften associated with the adoption of high-risk \nsexual behaviours including sex with multiple \npartners and prostitution, later in life.1,17, 18\n\n\n\nInterestingly, the male adolescents in our cohort \nhad multiple sexual partners with a preference \nfor casual partners when compared to female \nadolescents. This finding was similar to a study \ndone in Thailand.18 Over the years there was a \ntransition from sex workers to casual partners \namong the youth in Thailand. They tend to use \nless protection with casuals as compared with \nsex workers, probably under the impression \nthat sexual activity with a casual contact may \nnot pose a STI risk as compared to a sex worker. \n\n\n\nBased on previous studies on sexual behaviour \nin Malaysia 15-20 years ago, the mean age at \nfirst sexual intercourse among Malaysia teens \nwas 15 years.12-14 This was comparable to the \nstudies from the Western countries for instance \nin US, where it was found that the majority had \nengaged in sexual activity by age 17.19 Initiation \nof sex at an earlier age would expose teens to \nlonger periods of sexual activity thus exposing \nthem to unintended pregnancies and STIs.12 In \nanother study of urban females in US found that \nthe median interval between first intercourse \nand first STI was 2 years.19 Although nearly \n90% of our cohort were in the age group of 15 \nto 19 years, the youngest patients who presented \nwith a STI were 13 and 14 years of age for \nmale and female respectively. This shows that \nour adolescents may have engaged in sexual \nactivities at much younger age and this should \nbe reinvestigated again in our population.\n\n\n\nAbout 1.3% of our adolescent cohort reported \nthe use of recreational drugs. Adolescent drug \nuse has been significantly associated with \nhigher rate of STIs. The 20-23 National Health \nand Morbidity Survey 2017 done in Malaysia \nreported that 3.4% of adolescents were current \ndrug users. About 1 in 25 school students in \nMalaysia claimed to have used substances \n\n\n\nsuch as amphetamines, methamphetamines \nand marijuana.22 Studies have shown that \nprior substance use increases the probability \nof an adolescent initiating sexual activity, \nhaving more sexual partners, less consistent \nuse of condoms, more sexually transmitted \ndiseases, and greater prevalence of human \nimmunodeficiency virus.24,25   \n\n\n\nThe effectiveness of condom for prevention of \nnon-viral STI has been well studied.26-28 It is \ndisturbing to note that majority of the teens in \nour study did not use condoms during sexual \nintercourse. Inconsistent condom usage has \nbeen a major concern among the adolescents \nand youth in Malaysia and it has given rise to \nunintended adolescent pregnancies and STIs.22 \n\n\n\nThe main reason for unprotected sex, however, \nis that men of all ages, including adolescents, do \nnot like to use condoms.16 Adolescent girls are \ncommonly disengaged from safe-sex practices \nas more often than not, the power dynamics \nwithin a couple are dominated by the male \npartner. This disparity provides for men to \ncontrol or determine the use of protection i.e. \ncondoms, birth control etc, especially with older \npartners.1,16 In addition, adolescent girls may \nhave inadequate knowledge on the risk of STI \nand HIV infection via unprotected sex. Based \non a local study done by Shiely et al, only 2% \nof women in their cohort used contraception to \nprotect against STI or HIV.29\n\n\n\nAccording to a study in US, the lack of \navailability was a frequent cited barrier to \ncondom usage.26 Other reasons given were cost \nof condom and the embarrassment associated \nwith purchasing them.26 Zulkifli et al also \nreported similar findings whereby 72% of teens \nreported not using any kind of contraception \nat first intercourse (76% of boys, 61% of \ngirls), despite the fact that condoms are freely \navailable in convenient stores and pharmacies.14 \nBarriers for Malaysian teen and youth to access \ncontraceptive information and methods include \nsocial or cultural taboos, legal restrictions, \nhealth care provider (HCP) attitudes, and \nhealthcare systems.27 A teenager approaching \na health care professional for contraception \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4716\n\n\n\nmay sometimes get a judgemental or biased \nopinion regarding contraception.27 Long acting \nreversible contraception like intrauterine \ncontraceptive device are normally inserted by \ntrained medical personnel and require consent \nof parents or guardians for those less than 18 \nyears.  The cost of contraception services \nand methods is another potential barrier \nfor adolescents. HCPs should counsel on \navailable contraceptive options without bias \nto adolescents. Counselling must include the \neffectiveness, advantages and disadvantages. \nAdolescents should be informed that failure \nrates are the highest for user dependent methods \n(e.g. natural family planning, withdrawal, \ncondoms, and oral contraceptives).28\n\n\n\nIn view of these barriers and with heavy burden \nof STIs amongst the youth and adolescents, a \ncondom availability program was started in some \nschools in United States for students to have \nfree access to condoms.30 This is in addition to a \ncomprehensive sexual education.30 Critics have \nargued that such programs would \u201cpromote\u201d \nsexual activity but studies have shown the \nreverse. The rates of Chlamydia and gonorrhoea \ninfection in US decreased significantly since \nthe implementation of these programs.25,20 It has \nled to increase condoms usage and improved \nsexual health.25,30 Hence, schools proved to be \nan excellent venue for provision of reproductive \nhealth services to teens.1 It should be considered \nin our local secondary schools. A robust and \ncomprehensive scholastic approach to sex, in \ntandem with practical and discerning educators, \ncan help mitigate risky sexual practices among \nstudents.1,30\n\n\n\nStudies have shown that confidentiality is a \nkey concern among adolescents in seeking STI \ntesting for fear of stigmatization, embarrassment \nin revealing sexual behaviour to medical \nproviders and the fear of parents finding out.9,20,31 \n\n\n\nHomosexuality and bisexuality were only \nreported among the males in our cohort.  A few \nhave denied their sexual orientation or having \nhad any partners despite being diagnosed with \na STI. Fear of disclosure of their behaviour to \nthe parents is one of the reasons for this denial \n\n\n\nespecially in teens younger than 18 years.  This \nbrings us to the question of confidentiality \nwhich is a huge barrier to STI testing. It is \nimportant to for us to address this issue when \nworking with adolescents. Female adolescents \nwho had time alone with a medical provider \nduring consultation were twice more likely \nto receive a STI screening than those whose \nparents were in the consultation room with \nthem. This suggests that private discussions are \nimportant.15 To improve young people\u2019s health, \nadolescent health services in Malaysia were \nintroduced by the Ministry of Health Malaysia \n(MOH) since 1996 and were primarily available \nin health clinics and in schools through school \nhealth units (MOH, 2018c).32 These adolescent \nfriendly clinics could be utilized to provide \nopportunistic STI screening for adolescents.  \n\n\n\nThe comparisons of the STIs among adolescents \nwith other countries are shown in Table 3. In the \nUS,21 the most prevalent reported STI among \nadolescents between 14 and 19 years were \ngenital warts and chlamydia.  In Thailand33 the \nprevalence of STIs was 28% amongst pregnant \nteenagers attending antenatal care and the risk \nof acquiring STIs was significantly related to \nprior sexual contact and multiple partners.20 \nSpain noted a rising trend of STI cases among \nadolescents from 2012 to 2017 especially \nChlamydia trachomatis infection, gonorrhoea \nand syphilis.34 \n\n\n\nMalaysian data in 2007 showed that the \nprevalence of chlamydia was highest in the age \ngroup of 15 to 19 years of age.35 In our setting \nChlamydia infection is detected using Direct \nfluorescent antibody (DFA) test (MicroTrak \nChlamydia trachomatis Direct Specimen Test, \nTrinity Biotech, Ireland). This assay has a \nsensitivity of 50% to 80% if performed on \nvaginal and urethral smear specimens collected \nfrom symptomatic individuals. Only 2 cases of \nChlamydia were detected among the patients in \nour cohort.  This is because DFA for chlamydia \ndetection was no longer available during the \nend of the 2017. Symptomatic adolescents were \ntreated presumptively based on the presence of \nleucocytes in gram stains done on urethral and \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 17\n\n\n\nvaginal smears.   Another reason for the small \nnumber of chlamydia infections detected was \nthe refusal on speculum examination by parents \nand patients. \n\n\n\nOur DFA was later replaced by Xpert CT/\nNG only in end of 2018. This is a qualitative \nin vitro PCR test for the automated detection \nand differentiation of genomic DNA from \nChlamydia trachomatis (CT) and Neisseria \ngonorrhoea. This assay aids in the diagnosis \nof chlamydia and gonorrhoeal obtained from \nurogenital sample like urine, urethral and vagina \nswabs, as well as swabs obtained from extra \ngenital (pharynx and rectum) sites.36 Studies \nhave shown that chlamydia and gonorrhoea \ninfection in females are often asymptomatic \nand the best and non-invasive screening test to \ndetect them would be nucleic acid amplification \ntest.2,9,16,19,21\n\n\n\nThe burden of STIs is higher among HIV-\ninfected young men who have sex with \nmen (YMSM) than among HIV-uninfected \nYMSM.37 They are particularly at higher risk \nof syphilis infection, chlamydia and gonorrhoea \nspecifically antibiotic resistant Neisseria \ngonorrhoea (NG).  We would like to note that \nextra genital examination is very important \nespecially in MSM with HIV and those on \npre-exposure prophylaxis.  Rectal Chlamydia \ntrachomatis (CT) and NG testing, as well as \npharyngeal NG testing, are recommended in \nYMSM.37-39  Studies have shown that  26.4% \nof extra genital CT infections and 63.2% of \nextra genital NG infections would have been \nmissed if only urogenital examination was \nconducted.38 Another study found that patient \nreported exposure was not necessarily a reliable \nindicator for anogenital CT and NG screening in \nyoung black MSM.39 While reported anal sexual \nexposure predicted rectal infection, 19.4% of \nrectal infections would have been missed in \nmen who denied receptive anal sex.38,39\n\n\n\nGenital herpes simplex virus (HSV) is also \ncommon among adolescents shown in our study \nand it is difficult to assess epidemiological \ntrends because it is not a notifiable disease. \n\n\n\nAlthough HSV-2 typically causes genital herpes \nand HSV-1 typically causes orolabial herpes, \nseveral studies have shown that the prevalence \nof genital HSV-1 in adolescents has increased \nsignificantly. In USA, 60% of genital herpes are \ncaused by HSV-1.20\n\n\n\n \nThe increase was postulated \n\n\n\nas result of the decreasing prevalence of orolabial \nHSV-1 in adolescents and thus a lack of HSV-1 \nantibodies upon sexual debut.20 The increase of \nHSV-1 anogenital infection is especially more \nprevalent among women and MSM.20 \n\n\n\nHPV infection is the second most common STI \nreported among male adolescents in our study. \nAgain, there is not much local data of HPV in \nour local adolescents as it is not a notifiable \ndisease. HPV vaccination had been integrated in \nthe national school immunization program since \n2010 and is given to all female students age 13 \nyears. The exclusion of vaccination for male \nadolescents in the program probably accounts \nfor the increasing numbers of anogenital warts \nin males.40 It has been proven that prophylactic \nadministration of quadrivalent HPV vaccine \nis efficacious in preventing the development \nof external genital lesions associated with \ninfection with HPV-6, 11, 16, or 18 in boys and \nmen 16 to 26 years of age.24 Therefore, efforts \nshould be made to introduce HPV vaccination \nfor male students. An interesting local study \ndone by Wong et al showed a low perceived \nsusceptibility to HPV infection among boys.41 \nThis is because mass media has selectively \nemphasized cervical cancer prevention in \nwomen without revealing the consequences of \nHPV infection in males. The public should be \nmade aware that HPV infection in men can be \nassociated with penile, oral and anal cancer and \nthe benefits of vaccination should be highlighted \nto boys or men.41\n\n\n\nSexual coercion or non-consensual sexual \nactivity is something that we should bear in \nmind when managing female adolescents as \nwe have SCAN team. A significant minority \nof cases have been pressured or forced into \nnon-consensual sexual activity by their peers \nor adults.  Female victims of childhood sexual \nabuse are at increased risk for STI possibly due \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4718\n\n\n\nto younger age at sexual initiation and unsafe \nsex practices.1, 16 \n\n\n\nWe cannot generalize the findings of this study \nto the entire adolescent population because most \nof the adolescents who had attended the GUM \nclinic were symptomatic. Evidence has shown \nthat most STIs are asymptomatic therefore \nsubstantial number of infections are missed \nespecially in young MSM and females.2,16,20,38 \n\n\n\nSome adolescents may have sought advice or \ntreatment at general practitioners or alternative \nmedicine centers.  Ideally, a rapid, cost-effective \nscreening method which is non-invasive should \nbe used to diagnose STIs in adolescents.8,16,20,42 \nRapid point of care testing is the most ideal \nmethod as patients could be screened and \ntreated in the same day, hence reducing loss to \nfollow up.20,42  \n\n\n\nTable 3. Comparisons of STI among adolescents in different countries\n\n\n\nAuthor, year, country Age in years Sexual behaviour Prevalence of STI\n\n\n\nPresent study, Malaysia 13-19 Homosexual 17.1%\nCasual 51%\n> 1 Partner 26.1% \n\n\n\nMale:  NG 45.6%, HPV 17.6% \nNGU 17.6%, HSV 7.4%\nFemale: HSV 50%, HPV 33.3%\n\n\n\nVives N et al34\n\n\n\n2020, Spain 13 to 19 years\nCT\n\n\n\n(13.4%)\nGonorrhoea (7.0%) Syphilis\n\n\n\n(1.8%)\n\n\n\nMean age 17.7 18.3 18.5\n\n\n\nHeterosexual female 87.8% 39.3% 16.7%\n\n\n\nHeterosexual male 6.7% 23.1% 13.1%\n\n\n\nHomosexual 1.6% 18.8% 60.7%\n\n\n\nUnknown 3.8% 18.8% 9.5%\n\n\n\nHIV 2.0% 2.8% 8.5%\n\n\n\nAyerdi Aguirrebengoa et al43\n\n\n\n2020, Spain\n%(n) MSM\n\n\n\n39.8% (149)\nHeterosexual\n22.7% (85)\n\n\n\nWomen\n37.4% (140)\n\n\n\nGonorrhoea 30.2 (45)) 22.4(19)) 12.2(17)\n\n\n\nChlamydia 10.1 (15)) 25.9 (22) 19.3 (27)\n\n\n\nSyphilis 0.1(15) 1.2(1) 1.4(2)\n\n\n\nHIV 7.4(9) 0 0\n\n\n\nPark JJ, et al42\n\n\n\n2017, Korea\n16.1 \u00b1 1.5 Substance abuse 8.4%\n\n\n\n>1 partner 25%\nCT 13.9% \nNG 1.7%\nTVS 0.8% \nHSV 0.4%\nSyphilis 0.8%\nHIV 0\nUreaplasma urealyticum  (24.7%)\n\n\n\nAsavapiriyanont et al\n33\n\n\n\n, 2016 \nThailand\n\n\n\n17.16 + 1.3(Mean + SD)\n\n\n\n-\n\n\n\nAge of first sexual contact (years) \nMean + SD 15.38+1.81\n>1 partner 48.2%\n\n\n\nPrevalence of STI 28.0% (CT 19.8%. NG \n1.7%, Hep B 3.3%, TVS 1.7%, HSV 0.8%, \nHPV 0.8%)\n\n\n\nForhan et al21, 2009, USA 14-19 NA HPV 18.3%\nCT 3.9%\n\n\n\nBunnel et al19\n\n\n\n1999, USA\n14 -19 >1 partner 72% Females with STI 40%\n\n\n\nCT 27%, HSV 14%, \ngonorrhoea 6% TVS 3%\n\n\n\nUSA \u2013 United States of America; NG- Nesseria gonorrhoea; CT - Chlamydia trachomatis; HPV \u2013 human papilloma virus; NGU \u2013 non gonococcal urethritis; HSV \u2013 herpes \nsimplex virus; HIV- human immunodeficiency virus; MSM \u2013 men who have sex with men; TVS \u2013 Trichomonas vaginalis; STI \u2013 sexually transmitted infections; SD \u2013 standard \ndeviation\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 19\n\n\n\nConclusion \nSexually transmitted infections are an ongoing \nconcern among our adolescents. We have \nmanaged STIs in those as young as 13 years of \nage. The most common STI among adolescents \nin our cohort between 2014 and 2018 was \ngonorrhoea in male and herpes genitalis in \nfemales. STI preventive efforts for adolescents \nshould encompass contributions, cooperation \nand support from all parties including parents, \nschools, health care providers and social media. \n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto disclosed.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director of \nHealth Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Dehne KL, Riedner G. Sexually transmitted infections \namong adolescents: the need for adequate health services. \nReprod Health Matters 2001;9:170-83.\n\n\n\n2. Workowski KA, Bolan GA; Centers for Disease Control \nand Prevention. Sexually transmitted diseases treatment \nguidelines, 2015. MMWR Recomm Rep 2015;64:1-137. \nErratum in: MMWR Recomm Rep 2015;64:924. \n\n\n\n3. Ministry of Health Malaysia. 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Is Patient-Reported Exposure a Reliable Indicator \nfor Anogenital Gonorrhea and Chlamydia Screening in \nYoung Black Men Who Have Sex with Men? Sex Transm \nDis 2017;44:390-2.  \n\n\n\n40. Centers for Disease Control and Prevention. Sexually \nTransmitted Disease Surveillance 2016. Atlanta: U.S. \nDepartment of Health and Human Services; 2017.\n\n\n\n41. Wong LP, Alias H, Yusoff RNARM, Sam IC, Zimet GD. \nAre Boys Ready for Human Papillomavirus Vaccine? \nA National Study of Boys in Malaysia. Sex Transm Dis \n2019;46:617-24. \n\n\n\n42. Park JJ, Seo YB, Jeong S, Lee J. Prevalence of and \nRisk Factors for Sexually Transmitted Infections among \nKorean Adolescents under Probation. J Korean Med Sci \n2017;32:1771-8. \n\n\n\n43. Ayerdi Aguirrebengoa O, Vera Garcia M, Rueda Sanchez \nM, D Elia G, Chavero M\u00e9ndez B, Alvargonzalez \nArrancudiaga M et al. Risk factors associated with sexually \ntransmitted infections and HIV among adolescents in a \nreference clinic in Madrid. PLoS One 2020;15:e0228998.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 21\n\n\n\nORIGINAL ARTICLE\n\n\n\nCharacteristics of Sexually Transmitted Infections in Genito-Urinary \nMedicine Clinic, Sarawak General Hospital between 2018 and 2020\n\n\n\nHock Gin Teo, MRCP, Jiu Wen Kiing, AdvMDerm, Tzyy Huei Lim, MRCP, Sut Enn Lee, MRCP, Sze \nYing Foo, MD, Nur Shairah Fatin Badaruddin, MD, Pubalan Muniandy, FRCP\n\n\n\nDepartment of Dermatology, Hospital Umum Sarawak, Kuching, Sarawak, Malaysia\n\n\n\nAbstract\nBackground\nSexually transmitted infections (STIs) are common worldwide. This study aims to determine the \npatterns of STIs among attendees in the Genito-Urinary Medicine (GUM) clinic of Sarawak General \nHospital (SGH).  \n\n\n\nMethods\nThis is a retrospective study. Medical records of new cases referred to GUM clinic, SGH between the \nyear 2018 and 2020 were reviewed. Demography data, diagnosis, and clinical characteristics of STIs \nwere reviewed and analysed using SPSS software.\n\n\n\nResults\nThere was a total of 225 patients with newly diagnosed STIs. Their mean age was 30.9 years old. \nThere were 124 (55.1%) males and 101 (44.9%) females. Nearly half (46.7%) of the patients were \nMalay, followed by Sarawak indigenous groups (33.3%), and Chinese (18.7%). Most patients (n=119, \n52.9%) were single at the time of diagnosis. Three quarters (73.3%) of the patients were heterosexual, \nwhile 47 (20.9%) patients were homosexual or bisexual, and missing data in the remaining 5.8%. \nAnogenital wart was the commonest STI (49.8%), followed by syphilis (n=91, 40.4%), genital herpes \n(n=24,10.7%) and gonorrhoea (n= 15, 6.7%). The commonest symptoms were genital growth (n= 107, \n47.6%), followed by pelvic discharge (n=22, 9.8%).\n\n\n\nConclusion\nThe most common STIs in our study are anogenital warts, syphilis, genital herpes and gonorrhea. \nEffective national sexuality education in Malaysia is paramount in reducing premarital sex and \nSTIs. Human Papillomavirus (HPV) vaccines are effective to reduce genital warts and HPV related \nmalignancies.\n\n\n\nKey words: Sexual transmitted disease, Syphilis, Anogenital warts\n\n\n\nCorresponding Author \nDr Teo Hock Gin \nDepartment of Dermatology, \nHospital Umum Sarawak, \nJalan Hospital, \n93586 Kuching, Sarawak, Malaysia.\nEmail: hgteo86@hotmail.com\n\n\n\nIntroduction\nSTIs are very common with 1 million new cases \nevery day worldwide in the year 2016.1 Sexual \ntransmitted infections can be caused by viral, \nbacterial or parasites. According to WHO, the \ncommonest STIs are chlamydia, gonorrhoea, \nsyphilis and trichomoniasis which contribute to \n376 million new cases in males and females aged \nbetween 15 and 49 years in 2016.2 On the other \nhand, viral STIs such as Herpes Simplex Virus \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4722\n\n\n\n(HSV) infection and Human Papillomavirus \n(HPV) infections had been reported as high \nas well, with estimated cases of 417 and 291 \nmillion, respectively in the same year.1 STIs can \nincrease the risk of acquisition and transmission \nof the Human Immunodeficiency Virus (HIV).3 \nSTIs can lead to a wide range of complications \nsuch as pelvic inflammatory diseases, cancers, \nectopic pregnancies and infertility.4 Furthermore, \nuntreated STIs can have poor maternal and fetal \noutcomes.5 \n\n\n\nTherefore, STIs should be treated promptly. \nHowever, many symptomatic patients are \nreluctant to seek treatment due to social \nstigmatisation, needless to say for those \nasymptomatic patients. The true incidence \nof STIs is largely unknown, as not all STIs \nneed mandatory reporting including genital \nherpes. Perhaps under-reporting of STIs among \ngeneral practitioner further jeopardy the true \nincidence of STIs. Younger generations tend \nto have earlier sexual exposure with a higher \npercentage of teenage pregnancies in Sabah and \nSarawak compared to Peninsular Malaysia.6 \nThere is also an increasing number of men \nhaving sex with men (MSM) and a change in \nsexual preference such as oral sex as well. As \na result, the presentations and disease patterns \nof STIs have been changed. However, there is \nlimited local data on the STIs among our local \npopulation. This study aims to determine the \npatterns of STIs among attendees in the Genito-\nUrinary Medicine clinic of Sarawak General \nHospital (SGH) from the year 2018-2020.  \n\n\n\nMaterials and Methods\nThis retrospective study was done in Genito-\nUrinary Medicine (GUM) clinic, SGH. SGH is \na tertiary hospital in East Malaysia and received \nreferrals from Kuching and its surrounding cities \nin southern Sarawak. A team of dermatologists, \ndermatology fellows and senior medical officers \nmanage the clinic and provide care for patients \nwith STIs. Patient records will be kept in a \ndesignated area in the clinic to maintain patient \nconfidentiality. \n\n\n\nIn this study, all medical records of new cases \n\n\n\nreferred to the GUM clinic, SGH between \nJanuary 2018 and December 2020 were \nretrieved. Demography data, diagnosis, and \nclinical characteristics of STIs were reviewed \nand analysed using SPSS software version 26.0. \n\n\n\nResults\nThere were 245 new cases referred to GUM \nclinic, Sarawak General Hospital between the \nyear 2018 to 2020. Of these, 225 patients were \ndiagnosed with STIs. The remaining 20 patients \nwere diagnosed with non-STIs such as vaginal \ncandidiasis, screening test and other dermatoses. \nWe analysed the data from all 225 patients \ndiagnosed with STIs during our study periods. \nThe age of the STI patients ranged widely from \n3-88 years old with a mean of 30.94 +/-13.52. \nMost patients were in the age group of 20-29 \nyears old (n=165,73.3%), followed by those \naged <20 (n=21,9.3%) and 40-49 (n=19,8.4%). \nThere were 124 (55.1%) male and 101 (44.9%) \nfemale patients with a ratio of 1.2:1 in our \nstudy population. For the ethnic group, 105 \n(46.7%) of the patients were Malay, followed \nby Sarawak Indigenous groups (n=75, 33.3%), \nand Chinese (n=42, 18.7%). There were only 2 \n(0.9%) and 1 (0.4%) of the study populations \nwere foreigners and Indians respectively. Most \nof the patients (n=119, 52.9%) were single at \nthe time of diagnosis. Ninety-five (42.2%) of \nthem were married with the remaining 9 (4%) \nand 2 (0.9%) of the patients were divorcees and \nwidowed, respectively. \n\n\n\nIn terms of sexual orientation, 165 (73.3%) \nof the patient were heterosexual, while the \nremaining 39 (17.3%) were homosexual and 8 \n(3.6%) of the patients were bisexual. Among \nour study population, 115 (51.1%) of them were \nemployed, 37 (16.4%) were housewives and \n26 (11.6%) of them were students. Another 9 \n(4%) patients were unemployed, 7 (3.1%) were \nretirees and 5 (2.2%) of the remaining were \nself-employed.  Our sources of referral were \nmainly inter-department referral from our centre \n(n=106,47.1%), government clinic and district \nhospital (n=98, 43.6%), blood bank (n=14, \n6.2%) and general practitioner (n=7, 3.1%). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 23\n\n\n\nA total of 172 (76.4%) patients were \nsymptomatic whereas the remaining 53 \n(23.6%) were asymptomatic at the time of \ndiagnosis. Most of the symptomatic patients \npresented with growth at anogenital area (n= \n107, 47.6%), followed by pelvic/urethral \ndischarge (n=22, 9.8%), cutaneous skin lesions \n(n=20, 8.9%), genital ulcer (n=10, 4.4%), \npainful lesion (n=9, 4%) and pruritus (n=4, \n1.8%).  Asymptomatic patients were mainly \ndiagnosed via asymptomatic screening (n=22, \n9.8%), blood donation screening (n=14, 6.2%), \nantenatal screening (n=12, 5.3%), and contact \ntracing (n=5, 2.2%).  \n\n\n\nAmong the 225 patients with STIs, anogenital \nwarts were the commonest reported STI, \ndiagnosed in 112 (49.8%) of the patients. \nAnother 91 (40.4%) patients were diagnosed \nwith syphilis, 24 (10.7%) patients diagnosed \nwith genital herpes, followed by gonorrhoea \n(n=15, 6.7%), and trichomoniasis (n=2, 0.9%). \nA total of 19 (8.4%) patients had concomitant 2 \ndifferent STIs at the time of presentation. Among \nthe patients with STIs, 50 (22.2%) of them had \nconcomitant HIV infection, with another 7 \n(3.1%) had hepatitis B infection and 8 (3.6%) \nhad hepatitis C infection.  Further analysis of \nthe trend of STI cases revealed that a total of \n100 patients with STIs had been reported in our \ncentre in the year 2018. This number had been \nreduced to 77 cases in 2019 and 48 cases in \nthe year 2020. The total number of cases in the \nindividual STI group showed a similar reducing \ntrend except for genital herpes in which 5 cases \nwere reported in 2018 and the reported cases \nincreased significantly to 11 cases in the year \n2019 before it was reduced to 8 cases in 2020 \n(Figure 1). \n\n\n\nFor the treatment of anogenital warts, 74 \n(66.1%) of patients received liquid nitrogen \n(LN) spray alone, whereas 24 (21.4%) of \nthem received LN sprays in combination with \nother treatment modalities like imiquimod and \npodophyllin. Another 5 (4.5%) and 4 (3.6%) \npatients received imiquimod and podophyllin \nlocal application alone, respectively. One \n(0.9%) patient underwent electrocautery, and \nanother patient (0.9%) underwent surgical \n\n\n\nremoval of warts (table 2). There were 3 (2.7%) \npatients with anogenital warts resolved without \nactive treatment. All patients with syphilis \nreceived intramuscular benzathine penicillin as \nthe standard of treatment.\n\n\n\nTable 1. Demographic data and clinical presentation \nof new STI cases in GUM clinic, SGH between the \nyear 2018-2020\n\n\n\nVariables Frequency, \nn=225\n\n\n\nPercent \n(%)\n\n\n\nAge Group <20 21 9.3\n\n\n\n20-29 165 73.3\n\n\n\n30-39 1 0.4\n\n\n\n40-49 19 8.4\n\n\n\n50-59 6 2.7\n\n\n\n>=60 13 5.8\n\n\n\nTotal 225 100.0\n\n\n\nGender Male 124 55.1\n\n\n\nFemale 101 44.9\n\n\n\nEthnicity Malay 105 46.7\n\n\n\nSarawak Indigenous 75 33.3\n\n\n\nChinese 42 18.7\n\n\n\nIndian 1 0.4\n\n\n\nForeigners 2 0.9\n\n\n\nMarital \nStatus\n\n\n\nSingle 119 52.9\n\n\n\nMarried 95 42.2\n\n\n\nDivorcees 9 4.0\n\n\n\nWidowed 2 0.9\n\n\n\nSexual \nOrientation\n\n\n\nHeterosexual 165 73.3\n\n\n\nHomosexual 39 17.3\n\n\n\nBisexual 8 3.6\n\n\n\nMissing Data 13 5.8\n\n\n\nEmployment Employed 115 51.1\n\n\n\nUnemployed 9 4.0\n\n\n\nSelf Employed 5 2.2\n\n\n\nHousewife 37 16.4\n\n\n\nStudents 26 11.6\n\n\n\nRetirees 7 3.1\n\n\n\nMissing data 26 11.6\n\n\n\nPresenting \nsymptoms\n\n\n\nSymptomatic 172 76.4\n\n\n\nGrowth 107 47.6\n\n\n\nDischarge 22 9.8\n\n\n\nSkin Lesions 20 8.9\n\n\n\nGenital Ulcer 10 4.4\n\n\n\nPain 9 4.0\n\n\n\nPruritus 4 1.8\n\n\n\nAsymptmatic 52 23.6\n\n\n\nAsymptomatic Screening 22 9.8\n\n\n\nBlood donation screening 14 6.2\n\n\n\nAntenatal Screening 12 5.3\n\n\n\nContact Screening 5 2.2\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4724\n\n\n\nFigure 1. Number of New STI Cases in GUM Clinic, SGH During 2018-2020\n\n\n\nIntramuscular ceftriaxone in combination \nwith azithromycin or doxycycline was given \nto patients with gonorrhoea infection whereas \nacyclovir was given for all patients with genital \nherpes infection except one who was diagnosed \nwith resolved genital herpes with no evidence \nof recurrence.  \n\n\n\nTable 2. Treatment modalities among patients with \nanogenital wart in GUM Clinic SGH, year 2018-\n2020\n\n\n\nAnogenital Wart Frequency, n Percent/%\nTreatment LN Spray 74 66.1\n\n\n\nCombination Therapy 24 21.4\nImiquimod 5 4.5\nPodophyllin 4 3.6\nElectrocautery 1 0.9\nSurgical Excision 1 0.9\nObservation 3 2.7\nTotal 112 100.0\n\n\n\nDiscussion\nOur study showed that the majority of the STI \npatients are from the age group of 20-29 with \na male to female ratio of 1.2:1. This finding \nis consistent with previous studies on the \nprevalence of STIs.7 This group of patients \nare of reproductive age. Inadequate treatment \nwill lead to deleterious effects among females \nand during their pregnancies.4,5 On the other \nhand, untreated STIs increase the risk of HIV \ninfection. Both AIDS and STDs have a major \ndemographic, economic, social, and political \nimpact.8 Therefore, prompt diagnosis and \ntreatment of these curable STIs and HIV are \nfundamental to minimise their impact on \ncountry developments and health.\n\n\n\nPrevalence of STIs\nThe WHO report in the year 2016 on the \nprevalence of 4 common STIs showed that \ntrichomoniasis had the highest prevalence, \nespecially in females, followed by chlamydia, \ngonorrhoea and syphilis.1,2 A study done in \nChiang Mai, Thailand in 1997 showed the \nprevalence of chlamydial infection (16.9%), \ngonococcal infection (14.4%) and condyloma \nacuminata (4.6%) among commercial sex \nworkers.9 Our study showed that the highest \nnumber of STIs among attendees of our GUM \nclinic were anogenital warts followed by \nsyphilis, genital herpes, and gonorrhoea. This \nfinding is consistent with the other study done \nby Hariyadurai HR et al. in Hospital Kuala \nLumpur (HKL).7 The common STIs along \nthe GUM clinic attendees in HKL were warts \n(30.2%), syphilis (21.7%), gonorrhoea 13.8% \nand primary herpes (11.4%). However, our study \nwill likely underestimate the true prevalence of \ngonorrhoea, chlamydia and trichomoniasis for \na few reasons. Firstly, many patients with STIs \nare reluctant to seek treatment at government \nhospitals due to the social stigmata and lack of \nconfidentiality. They tend to receive treatment \nat private clinics or hospitals. A prevalence \nstudy done in 1998 showed that 77% of the STI \nnotification were done by private clinics and \nhospitals.10 On the other hand, those who seek \ntreatment at government facilities are mostly \ntreated at the health clinics due to easy access. \nBasic investigations and treatments are readily \navailable in these health clinics. \n\n\n\nMoreover, most specialist clinics in tertiary \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 25\n\n\n\nhospitals do not accept walk-in consultation. \nPatients are required to have an initial assessment \nat the health clinics before they are scheduled \nfor an appointment to receive treatment at the \nspecialist clinic if needed. This forms a barrier \nto the treatment of STIs by dermatologists \namong the local population. Thirdly, the lack of \nhigh sensitivity tests such as the Nucleic Acid \nAmplification Test (NAAT) for gonorrhoea, \nchlamydia and trichomoniasis is the other factor \nfor the low prevalence of these diseases in our \ncentre. In our centre, smear for gonococcal and \nculture with chocolate agar are commonly used \nin cases of suspected gonorrhoea. Posterior \nvaginal wet mount microscopies are done for \ncases suggestive of trichomoniasis. These tests \nhad lower sensitivity to diagnose STIs and \nhighly depend on the sampling method as well.11\n\n\n\nThere is no molecular test available to diagnose \nchlamydia infection in our centre. Centers for \nDisease Control and Prevention (CDC) has \nrecommended NAAT in cases of suspected \nNeisseria gonorrhoea, Chlamydia trachomatis \nand Trichomonas vaginalis infection given its \nhigher sensitivity and specificity when compared \nto the other methods12. The high number of \nanogenital warts in our clinic is due to a variety \nof treatment modalities that are available only \nin the GUM clinic such as liquid nitrogen spray, \nimiquimod and podophyllin application. \n\n\n\nTrend of STD Referral in GUM clinic, SGH \nIn our study population, the total number of STIs \ncases were reducing in trend from the year 2018 \nto 2020.  There were 100 STI Patients seen in \nthe GUM clinic in 2018 and the number reduced \nto 77 and 48 patients, respectively, in 2019 and \n2020. The reducing GUM referral is unlikely \ndue to the reducing incidence of STIs in our \nlocal population. According to the Ministry of \n\n\n\nHealth, Malaysia report in the year 2016-2019, \nthe 2 notifiable diseases, namely gonorrhea \nand syphilis, continue to see an increasing \nincidence, especially among male patients.13 \nMalaysia has started STI friendly clinics in \nselected government health clinics since June \n2016.14 These primary healthcare facilities offer \nvarious point-of-care testings and treatments for \nSTIs thus the STIs referral to GUM clinic in the \nhospital is significantly reduced. The cases were \nfurther reduced in the year 2020 largely due to \nthe Covid-19 pandemic announced by WHO \non March 2020.15 With the movement control \norder and strict social activities including the \nclosure of the entertainment centers such as \npubs and karaoke centers, the cases of STIs \nhad been estimated to be reduced. On the other \nhand, patients with STI may not seek treatment \nduring the pandemic in the fear of COVID-19 \ninfection.    \n\n\n\nSTIs among patients with HIV and MSM \nIn our study, 50 (22.2 %) and 47 (20.9%) of the \npatients were HIV positive and homosexual/\nbisexual, respectively. Among this group, 96% \nof the HIV positive patients and 97.4% of the \nnon-heterosexual patients were male (p=0.000) \n(table 3). For the past decades, the HIV cases \nin Malaysia has been commonly transmitted via \nsharing needle but more recently sexual contact \nhad become the main mode of transmission of \nthe HIV according to the local data.16 In the \nMalaysia key population estimation report 2018, \nIt is estimated that there is a total of 220,000 \nMSM in Malaysia. This represents 2.2% of \nthe total adult male population in Malaysia.17 \nThe Integrated Biological and Behavioural \nSurveillance (IBBS) 2014 report revealed that \nHIV prevalence among MSM substantially \nincreased over the years. Increased alcohol \nconsumption prior to sex and reduced condom \nused had been shown to be significantly \nassociated with HIV prevalence among MSM.18 \n\n\n\nTable 3. Distribution of HIV infection and sexual orientation according to gender\n\n\n\nHIV (n=225) Sexual Orientation (n=212*)\n\n\n\nPositive (n=50) Negative (n=175) p-Value Homosexual/ Bisexual (n=47) Heterosexual (n=165) p-Value\n\n\n\nFemale 2  (4%) 99 (56.6%) 0.000 1(2.1%) 98(59.4%) 0.000\n\n\n\nMale 48 (96%) 76 (43.4%) 46(97.9%) 67(40.6%)\n\n\n\nTotal 50 (100%) 175 (100%) 47(100%) 165(100%)\n*13 missing data on sexual orientation\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4726\n\n\n\nThe incidence of STIs among this population \nis expected to be increased as well. Malaysia \nNational Strategic Plan for Ending AIDS \n2016-2030 aimed to end AIDS epidemic by \nthe year 2030. The strategies include prompt \ndetection and treatment of HIV among high-\nrisk populations and decentralize testing and \ntreatment to accredited primary health centres.  \nThe Harm Reduction Programme will be \nintensified among injecting drug users. To \nreduce sexual transmission of HIV and STIs, \nmapping of the geographic and local hotspots \nfor HIV transmission will be conducted. A \nNational Task Force on Mitigation of HIV \nthrough Sexual Transmission will look into \ninnovative and effective ways to reduce sexual \ntransmission and explore innovative ways of \naddressing the changing sexual transmission \nscenarios, particularly the increasing use of \nmobile devices and social media for the sex \ntrade. These strategies will be implemented \nbetween 2016 to 2030 as part of the national \nefforts to reduce HIV and STI cases.   \n\n\n\nPremarital Sex and Sexuality Education\nOur study showed that 52.9% of the patients were \nsingle. This indicates an alarmingly high rate \nof premarital sex among the local population. \nTherefore, innovative, and effective sexuality \neducations are fundamental among teenagers \nin secondary schools to advocate correct sexual \nbehaviours and minimise high-risk sexual \nactivities. Johari Talib et al. reported that 90% \nof the university students agreed that sexuality \neducation has not been taught in Malaysian \nschools. The same study also concluded that \ninformal information given by most of the \nteachers were vague thus not useful in term of \nsexuality education.19 Khalaf ZF et al. reported \nthat Malaysian multicultural society, lack of \ncommunity involvement as some of the barriers \nto national sexuality education. Respondents \nin this study believed that school-based \nsexuality education is not easily accomplished \nin Malaysia. Therefore, campaigning to raise \nthe awareness of families, teachers, community \nleaders, religious authorities and policymakers \nare essential to establish an effective national \nsexuality education in Malaysia.20\n\n\n\nHPV Vaccination\nVaccinations are helpful to prevent Human \n\n\n\nPapillomavirus (HPV) Infections which \ncan potentially lead to anogenital warts and \nmalignancies. HPV 6, 11 contribute up to 90% \nof genital warts. Moreover, 4.5% of all cancer \ncases are attributable to HPV every year and \npresent with vulva, vagina, anus, penis, and \noropharynx cancer.21 HPV 16, 18, 33, and 58 \nwere commonly detected HPV types from the \ncervical samples among females in Malaysia.22 \nThere are three HPV vaccines available at the \nmoment, 2vHPV (HPV 16, 18), 4vHPV (HPV 6, \n11, 16, 18), and 9vHPV (HPV 6, 11, 16, 18, 31, \n33, 45, 52, 58). Only 4vHPV and 9vHPV protect \nagainst HPV type 6 and 11 that are commonly \nassociated with anogenital warts. Both 2vHPV \nand 4vHPV protect against HPV 16 and \nHPV 18 infections which are the commonest \nHPV types implicated in the majority of \ncervical malignancies. 9vHPV provide extra \nprotection towards other HPV types such as \nHPV 31,33,45,52,58 that contribute to cervical \nmalignancies as well. A study in Sweden \nreported a substantially reduced risk of invasive \ncervical cancer at the population level after \nquadrivalent HPV vaccination.25 \n\n\n\nGiuliano AR et al. reported that the 9vHPV \nvaccine did not prevent disease related to \nvaccine HPV types detected at baseline, but \nsignificantly reduced cervical, vulvar, and \nvaginal diseases related to other vaccine HPV \ntypes.26 In the global health sector strategy \non sexually transmitted infections 2016-\n2021 which aim toward ending STIs, WHO \nadvocated the implementation of prophylactic \nHPV vaccination to eliminate cervical cancer \nand genital warts.23  HPV vaccination has been \nincorporated in our national immunization \nprogram in 2010 for all female students who \nare 13 years of age at government schools, with \nthe aim of three doses completion rate of 95%.24 \nHowever, vaccination among boys will be \nrequired to reduce the incidence of HPV related \nwarts and cancers in male patients. To date, \nthe vaccination is not offered for male students \nunder the national immunisation programme. \n\n\n\nConclusion\nThe most common STIs in our study are \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 27\n\n\n\nanogenital warts, syphilis, genital herpes \nand gonorrhea. HIV and MSM are common \nespecially among male patients in our study \ncohort. With the strategies endorsed under \nthe national strategies plan to end AIDS \nepidermic by 2030, the incidences of STIs are \nexpected to be reduced. STI-friendly clinics in \nprimary care settings help to provide quality \nand prompt treatment of STIs in the effort to \nreduce transmission. National Sex education \nprogrammes require collaboration between \ngovernment, private sector and religious \nauthorities to improve the quality and efficacy of \nsex education among school children and young \nadults. HPV vaccination for both adolescent \nmale and female students is recommended to \nreduce HPV related diseases and malignancies.\n\n\n\nConflict of Interest Declaration \nThe authors have no conflict of interest to be \ndeclared.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish \nthis article.\n\n\n\nReferences \n\n\n\n1. WHO. Report on global sexually transmitted infection \nsurveillance 2018. Geneva: World Health Organization \n2018. Available at https://www.who.int/reproductive health/\npublications/stis-surveillance 2018/en. Accessed on 24/9/21\n\n\n\n2. Rowley J, Vander Hoorn S, Korenromp E, Low N, \nUnemo M, Abu-Raddad LJ et al. Chlamydia, gonorrhoea, \ntrichomoniasis and syphilis: global prevalence and incidence \nestimates, 2016. Bull World Health Organ 2019;97:548-62.\n\n\n\n3. Adler MW. Sexually transmitted diseases control in \ndeveloping countries. Genitourin Med 1996;72:83-8. \n\n\n\n4. Holmes KK, Bell TA, Berger RE. Epidemiology of sexually \ntransmitted diseases. Urol Clin North Am 1984;11:3-13. \n\n\n\n5. Mullick S, Watson-Jones D, Beksinska M, Mabey D. \nSexually transmitted infections in pregnancy: prevalence, \nimpact on pregnancy outcomes, and approach to treatment \nin developing countries. Sex Transm Infect 2005;81:294-\n302. \n\n\n\n6. Mohd Azri MS, Adibah HI, Haliza G. A review of \nteenage pregnancy research in Malaysia. Med J Malaysia \n2015;70:214-9. \n\n\n\n7. Hariyadurai HR, Syed Nong Chek SR, Johar \nA,.Prevalence of Sexually Transmitted Infections in Genito-\nUrinary Medicine Clinic, Hospital Kuala Lumpur between \n2015 - 2016. Malaysian J Dermatol 2019;42:8-13.\n\n\n\n8. World Bank. World Development Report 1993: Investing in \nHealth. New York: Oxford University Press 1993. \n\n\n\n9. Rugpao S, Wanapirak C, Sirichotiyakul S, Yutabootr Y, \nPrasertwitayakij W, Suwankiti S et al. Sexually transmitted \ndisease prevalence in brothel-based commercial sex \nworkers in Chiang Mai, Thailand: impact of the condom use \n\n\n\ncampaign. J Med Assoc Thai 1997;80:426-30. \n10. A Rohani, AA Nasir. Sexually Transmitted Infections \n\n\n\n(including HIV infection) Care Management Using the \n\u201cModified Syndromic Approach\u201d in Malaysia. Malaysian J. \nPublic Health Med 2002;2:52-7.\n\n\n\n11. Herbst de Cortina S, Bristow CC, Joseph Davey D, \nKlausner JD. A Systematic Review of Point of Care Testing \nfor Chlamydia trachomatis, Neisseria gonorrhoeae, \nand Trichomonas vaginalis. Infect Dis Obstet Gynecol \n2016;2016:4386127. \n\n\n\n12. Workowski KA, Bolan GA; Centre for disease Control \nand Prevention. Sexually transmitted diseases treatment \nguidelines, 2015. MMWR Recomm Rep 2015;(RR-03:1-\n137.\n\n\n\n13. Ministry of Health Health Facts 2019. Planning Division, \nHealth Informatics Centre 2019. MOH/S/RAN/152.19 \nAvailable at: https://www.moh.gov.my/moh/resources/\nPenerbi.tan/Penerbitan%20Utama/HEALTH%20FACTS/\nHealth%20Facts%202019_Booklet.pdf.\n\n\n\n14. Country Progress Report on HIV/AIDS 2018. HIV/STI \nSection, Disease Control Division, Ministry of Health \nMalaysia 2018. Available at: https://www.moh.gov.my/\nmoh/resources/Penerbitan/Laporan/Umum/Report_ \nGAM_2019_(Final).pdf. Accessed on 24/9/21.\n\n\n\n15. Cucinotta D, Vanelli M. WHO Declares COVID-19 a \nPandemic. Acta Biomed. 2020;91:157-160.\n\n\n\n16. National strategic plan on Ending Aids 2016-2030. HIV/ \nSTI Section, Disease Control Division, Ministry of Health \nMalaysia 2018. Available at: https://www.moh.gov.my/moh/ \nresources/auto%20download% 20images/589d6c1097220. \npdf. Acessed opn 24/9/21.\n\n\n\n17. Sector HIV/STI/Hepatitis C, Disease Control Division. Size \nof Key Populations in Malaysia 2018 Estimates. Ministry of \nHealth Malaysia. 2018.\n\n\n\n18. Sector HIV/STI/Hepatitis C, Disease Control Division. \nIntegrated Biological and Behavioural Surveillance. \nMinistry of Health Malaysia. 2014.\n\n\n\n19. Talib J, Mamat M, Ibrahim M, Mohamad Z. Analysis on sex \neducation in schools across Malaysia. Procedia Soc Behav \nSci 2012;59:340-8.\n\n\n\n20. Khalaf ZF, Low WY, Merghati-Khoei E, Ghorbani B. \nSexuality education in Malaysia: perceived issues and \nbarriers by professionals. Asia Pac J Public Health \n2014;26:358-66. \n\n\n\n21. Serrano B, Brotons M, Bosch FX, Bruni L. Epidemiology \nand burden of HPV-related disease. Best Pract Res Clin \nObstet Gynaecol 2018;47:14-26. \n\n\n\n22. Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R. \nPrevalence and type distribution of human papillomavirus \n(HPV) in Malaysian women with and without cervical \ncancer: an updated estimate. Biosci Rep 2018;29;38: \nBSR20171268. \n\n\n\n23. WHO. Global Health Sector Strategy on Sexually Transmitted \nInfections 2016-2021 Towards Ending STIs. Geneva: World \nHealth Organization 2016;WHO/ RHR/16.09. Available at \nhttp://apps.who.int/iris/bitstream/handle/10665/246296/\nW H O - R H R - 1 6 . 0 9 - e n g . p d f ; j s e s s i o n i d = \n7969FBAA2D6D05775CE274D308569CB2?sequence=1. \nAccessed on 24/9/21.\n\n\n\n24. Ezat SW, Hod R, Mustafa J, Mohd Dali AZ, Sulaiman \nAS, Azman A. National HPV immunisation programme: \nknowledge and acceptance of mothers attending an \nobstetrics clinic at a teaching hospital, Kuala Lumpur. Asian \nPac J Cancer Prev 2013;14:2991-9.\n\n\n\n25. Lei J, Ploner A, Elfstr\u00f6m KM, Wang J, Roth A, Fang F et al. \nHPV Vaccination and the Risk of Invasive Cervical Cancer. \nN Engl J Med 2020;383:1340-8.\n\n\n\n26. Giuliano AR, Joura EA, Garland SM, Huh WK, Iversen OE, \nKjaer SK et al. Nine-valent HPV vaccine efficacy against \nrelated diseases and definitive therapy: comparison with \nhistoric placebo population. Gynecol Oncol 2019;154:110-\n7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4728\n\n\n\nORIGINAL ARTICLE\n\n\n\nOral Lichenoid Reactions and Contact Sensitization: A 5-year Review in \nthe Department of Dermatology, Hospital Kuala Lumpur, Malaysia\n\n\n\nSharifah Rosniza Syed Nong Chek, AdvMDerm, Min Moon Tang, AdvMDerm,\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nBackground\nOral lichen planus is an idiopathic autoimmune inflammatory condition and oral lichenoid reactions \nare lesions that resemble oral lichen planus clinically and histopathologically, but develop secondary \nto various underlying causes.  Oral lichenoid reactions have been reported to be caused by contact \nallergy to dental materials.  This study aims to describe the characteristics of patients with a clinical \nand/or histopathological diagnosis of oral lichen planus who underwent patch testing in Hospital \nKuala Lumpur, Malaysia.    \n\n\n\nMethods\nThis is a 5-year retrospective study of patients who had oral lichen planus and had undergone patch \ntesting at the Department of Dermatology, Hospital Kuala Lumpur, Malaysia between January 2015 \nand Cecember 2019.  Patch tests were performed with European Baseline Series and relevant extended \nseries, which include dental and metal series as well as patients\u2019 own products.  Patch test results were \nrecorded according to the International Contact Dermatitis Research Group recommendation.  \n\n\n\nResults\nThere were 41 patients with oral lichen planus who underwent patch test.  The median age was 56 \n(range 21 to 73) with 70.7% of patients being female.  There were 29 (70.7%) patients who developed \nat least one positive reaction. The most frequent sensitizing allergens were nickel sulfate (34.1%), \ngold(I)sodium thiosulphate dihydrate (22.0%), fragrance mix I (19.5%), cobalt chloride (14.6%), \nPeru balsam (12.2%) and sodium tetrachloropalladate (II) hydrate (12.2%).  Current relevance was \nrecorded in 16 patients (39.0%) and of these patients, 12 of them had positive patch test reactions \nto allergens found in dental materials such as dental fillings, dental implants, orthodontic braces, \ndentures and dental crowns.   \n\n\n\nConclusion\nContact sensitization was detected in about 70% of our patients with oral lichen planus. The most \ncommon sensitizing allergen was nickel sulfate.  Current relevance was found mainly towards dental \nmaterials.\n\n\n\nKey words: Allergic contact dermatitis, Patch test, Oral lichen planus, Oral lichenoid reactions, Oral lichenoid lesions, \nOral lichenoid diseases, Lichen planus-like lesions, Oral lichenoid tissue reactions\n\n\n\nCorresponding Author\nDr Sharifah Rosniza Syed Nong Chek\nDepartment of Dermatology, \nHospital Kuala Lumpur, \nJalan Pahang,\n50586 Kuala Lumpur, Malaysia\nEmail: srsyed@doctors.org.uk\n\n\n\nIntroduction\nLichen planus is an inflammatory disease \nof unknown aetiology that primarily affects \nthe skin and oral mucosa.  Apart from oral \nmucosa, other mucous membranes that can \nbe involved include the genitalia, esophagus \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 29\n\n\n\nand conjunctiva. 1  Cutaneous lichen planus \nis characterized by erythematous-violaceous, \npolygonal, shiny and symmetrical papules with \nthe presence of whitish streaks on the surface \nknown as Wickham striae.   Oral lichen planus \nusually presents in two ways, either as painful \nand erythematous erosions and ulcerations or \nas painless radiating white papules or patches \non the buccal mucosa.  These lesions may also \ninvolve the lips, tongue and palate.2\n\n\n\nOral lichenoid reactions are lesions that \nresemble oral lichen planus clinically and \nhistopathologically but develop secondary to \nvarious underlying causes.  There are several \nsynonyms that have been used to describe \noral lichenoid reactions and these include \noral lichenoid lesions, oral lichenoid diseases, \nlichen planus-like lesions and oral lichenoid \ntissue reactions. 3  These lesions can be caused \nby exogenous factors such dental restoration \nmaterials and systemic medications, whereas \nothers may be due to systemic diseases such as \ngraft-vs-host disease (GVHD), systemic lupus \nerythematosus or malignant tumours.3  Patch \ntest plays an important role in diagnosing oral \nlichenoid reactions related to contact allergy, \nespecially from dental materials.\n\n\n\nThis study aims to describe the characteristics of \npatients with a clinical and/or histopathological \ndiagnosis of oral lichen planus who underwent \npatch testing in Hospital Kuala Lumpur, \nMalaysia.\n\n\n\nMaterials and Methods \nThis is a 5-year retrospective study of patients \nwho had oral lichen planus and had undergone \npatch testing at the Department of Dermatology, \nHospital Kuala Lumpur, Malaysia between \nJanuary 2015 and December 2019.  Patch \ntests were performed with European Baseline \nSeries and relevant extended series from \nChemotechnique Diagnostics using IQ \nchambersTM.  Extended series used include \ndental screening series, metal series, cosmetic \nseries, and plastic and glue series.  Patients \nwere also tested with their own products, which \ninclude toothpaste and mouthwash.  Toothpaste \n\n\n\nwas tested \u201cas is\u201d.  Mouthwash was diluted with \nwater to 10% (w/w).  \n\n\n\nPatches were applied to the patients and removed \nafter 48 hours.  Initial reading was done at 48 \nhours and final reading was recorded at 96 \nhours after patch application.  The parameters \nstudied include positive patch test reactions \nand the source of allergens.  Readings were \nrecorded according to the International Contact \nDermatitis Research Group recommendation. 4\n\n\n\nResults\nThere were 41 patients with oral lichen planus \nwho underwent patch test.  The demographic \ndata is shown in Table 1.  The median age \nwas 56 (range 21 to 73) and the majority of \npatients (70.7%) were female.  In addition to \nthe oral lichen planus, cutaneous involvements \nwere found in 5 patients.  These patients had \ninvolvement of the trunk (3 patients), upper and \nlower limbs (1 patient) and lower limbs only \n(1 patient).  Twenty-four (58.5%) patients had \ndental procedures done which include dental \nfillings, crown, bridges, implant, dentures and \northodontic braces.  The diagnosis of oral lichen \nplanus was confirmed histopathologically in \n31 patients (75.6%), whereas the rest of the \npatients had no biopsy, inconclusive biopsy \nresults or the biopsy results were not available.  \nAll patients were referred to our centre from \ndental departments in hospitals based in Klang \nValley areas.\n\n\n\nMore than half of the patients (53.7%) had \nsymptoms of six months or less, 8 patients \n(19.5%) had symptoms between 6 months \nto 1 year and the rest (26.8%) had symptoms \nlasting more than 1 year.  All patients described \nsymptoms of pain and discomfort, especially \nwhen eating spicy foods.\nThere were 29 (70.7%) patients who developed \nat least one positive reaction. As shown in \nTable 2, the most frequent sensitizing allergens \nwere nickel sulfate (34.1%), gold (I) sodium \nthiosulphate dihydrate (22.0%), fragrance mix \nI (19.5%), cobalt chloride (14.6%), Peru balsam \n(12.2%) and sodium tetrachloropalladate (II) \nhydrate (12.2%).  Current relevance was recorded \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4730\n\n\n\nin 16 patients (39.0%) and of these patients, 12 \n(75%) of them had positive patch test reactions \nto allergens found in dental materials such as \ndental amalgam, dental implants, orthodontic \nbraces and dental crowns. Four (25%) of these \npatients had current relevance attributed to their \nown toothpastes.  \n\n\n\nTable 1. Characteristics of 41 patients who \nunderwent patch test for oral lichen planus\n\n\n\nCharacteristics n=41\n\n\n\nMedian age in years (range) 56 (21-73)\nMale:Female ratio 1:2.4\nEthnicity, n (%) Chinese 19 (46.3)\n\n\n\nIndian 15 (36.6)\n\n\n\nMalay 6 (14.6)\n\n\n\nOthers 1 (2.4)\n\n\n\nPresence of cutaneous involvement, n (%) 5 (12.2)\n\n\n\nOral lichen planus confirmed by \nhistopathological examination, n (%)\n\n\n\n31 (75.6)\n\n\n\nSeries used, \nn (%) \n\n\n\nEuropean Baseline 41 (100.0)\n\n\n\nDental 41 (100.0)\nMetal 15 (36.6)\nCosmetics 3 (7.3)\nPlastic and glue 1 (2.4)\n\n\n\nOwn products 15 (36.6)\n\n\n\nTable 2. Sensitization pattern of current cohort\n\n\n\nPositive Patch Test n (%)\n\n\n\nNickel sulfate 14 (34.1)\nGold(I)sodium thiosulphate dihydrate 9 (22.0)\nFragrance mix I 8 (19.5)\nCobalt chloride 6 (14.6)\nPeru balsam 5 (12.2)\nSodium tetrachloropalladate (II) hydrate 5 (12.2)\nPalladium chloride, formaldehyde, mercury 4 each (9.8)\n\n\n\nColophony, MCI/MI 3 each (7.3)\n\n\n\nThiuram mix, potassium dichromate, textile dye \nmix, butylphenol formaldehyde resin\n\n\n\n2 each (4.9)\n\n\n\nEpoxy resin, neomycin, Quaternium-15, me-\nthylisothiazolinone, fragrance mix II, carvone, \nmercury ammonium chloride, triethylene glycol \ndimethacrylate, amalgam, BIS-GMA, MDB-\nGN, thimerosal, 2-Hydroxyethyl methacrylate\n\n\n\n1 each (2.4)\n\n\n\nMCI/MI - methylcholoroisothiazolinone/methylisothiazolinone; \nBIS-GMA - Bisphenol A glycerolate dimethacrylate; MDBGN- \nmethyldibromoglutaronitrile\n\n\n\nDiscussion \nContact sensitization was detected in about \n70% of our patients with oral lichen planus.  \n\n\n\nThe 3 most common sensitizing allergens were \nnickel sulfate, gold sodium thiosulphate and \nfragrance mix.  These findings were similar to \nstudies conducted in other countries (Table 3).  \nOther metals that were also found as common \nsensitizers in our study include cobalt chloride \nand palladium.\n\n\n\nThe high number of positive reactions to metal \nallergens in our study can be explained by the \npresence of metal in dental restoration materials.  \nMost metals found in dentistry are in the form \nof alloys.  Alloys are mixtures of metals and \nnon-metals. They are preferred as pure metals \ndo not have the appropriate physical properties \nto function as dental restoration materials. 5 \nMetal-ceramic alloy has been used in dental \nrestoration materials since the 1950s.  The \ndurability of these alloys was proven by studies.  \nNearly 90% of metal-ceramic crowns and \n80.2% of metal-ceramic fixed partial dentures \nwere still in function after 10 years. 6  Nickel, \ngold, cobalt and palladium are present in dental \nrestoration materials in variable combinations \nwith ceramic and other metals to optimize their \nclinical performance, aesthetics and physical \nproperties. This possibly explains why these \nmetals were found as top sensitizing allergens \nin our study.\n\n\n\nMetal alloys used in dentistry can be divided \ninto noble and base metal alloys.  Noble metals \nare gold, palladium, iridium, ruthenium, and \nplatinum. 7 Base metals in dentistry are further \ndivided into two main systems, which are nickel \nbased and cobalt based.  Alloys in both systems \ncontain chromium as their second largest \nconstituent. Other base metal used in dentistry \ninclude titanium. 8 Adverse effects due to these \nmetals are chiefly caused by corrosion, which \nresults in release of metal ions and subsequent \nmetal-protein or metal-cell interactions.9 \n\n\n\nThe most common sensitizing allergen found in \nour study was nickel sulfate.  Nickel is widely \nused in dental restoration materials as it is \ncheaper compared to metals such as gold and \npossesses better mechanical properties to gold \nwhen combined with other metals.8  Nickel \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 31\n\n\n\nis found in alloys such nickel-chromium-\nberyllium, nickel-chromium and nickel-high \nchromium alloys. 5 Beryllium was used in the \npast with nickel as it facilitates casting and \nenhanced porcelain bonding but due to the \nincreased corrosion especially at low pH, this \nalloy is no longer recommended. 8,9  As nickel \nis a highly sensitizing metal, there is a need for \nother affordable metal alloys that are free of \nnickel yet confer similar properties as nickel \ncontaining alloys.  An alternative to nickel \ncontaining alloys is chromium-cobalt alloys, \nwhich have a high biocompatibility and since \nthey are nickel-free, they can be used in patients \nwho are known to be allergic to nickel. 5\n\n\n\n \nThe relevance of contact sensitization to nickel \nand oral eruptions is however controversial as \nit is abundant in our environment and sources \nof exposure can be unrelated to the dental \nrestoration materials.  Nickel allergy presenting \nas oral eruption alone is thought to be rare. \nExposure to nickel during treatment of with \northodontics braces is thought to confer tolerance \nin nickel insensitive patients. 10  In nickel \nsensitive patients however, exposure to nickel \nvia orthodontic implants have shown conflicting \nfindings.  Studies have shown exacerbation \nof dermatitis together with lip swelling and \nburning after fixation of orthodontic implants \nin previously nickel sensitized individuals. \n11 On the other hand, there were also patients \nwho were nickel-sensitive but developed lower \nincident of oral contact reactions following \northodontic implants, which is thought to be \ndue to the development of tolerance.12 With this \nin mind, determining the relevance of nickel \nin causing oral lichenoid reactions requires \ncareful consideration and interpretation.  Often \ntimes, current relevance can only be made \nretrospectively when there is improvement of \nlesions upon removal of the suspected dental \nmaterials that contain nickel as a constituent. \n\n\n\nThe second most common allergen in our study \nis gold sodium thiosulphate.  Gold is used in \ndental restorations because it is easily malleable \nand is highly resistant to corrosion.13 It is also \ninert and is fairly nonreactive with other metals. \n\n\n\nGold alloys as dental restoration materials \ncomprised of over 70% of gold predominated \nuntil the price of gold skyrocketed in the mid-\n1970s. Subsequently, the demand for lower \ncost of metal alloys paved the way for the \nuse of cheaper metal alloys such as nickel.5 \nThe gold-platinum-palladium alloys were the \nfirst to be used successfully for metal-ceramic \nrestorations; however their used decreased after \nmore economical alloys were developed with \nsignificantly better mechanical properties.8  \nGold dental alloy that is still used nowadays has \na reduced gold content, typically in the range of \n35 to 50%, which is less costly.5\n\n\n\nThe clinical features of intra-oral contact \nallergy related to gold exposure are not specific, \nalthough lichenoid reactions appear to be the \nmost common manifestation of gold contact \nallergy in the oral mucosa.. 14 Patients with oral \nlichenoid reactions have been found to have \nan increased frequency to patch test positivity \nto gold compared to patients undergoing \nevaluation of other dermatitis not affecting the \noral lesions.15  Other manifestations of gold \nallergy in the oral cavity include non-specific \nstomatitis and burning mouth syndrome. 16  \nAdditionally, studies have also shown that \nthere is a statistically significant and dose-\ndependent relationship between contact allergy \nand the number of dental gold restorations.17 \nMetallic gold (foil) and trivalent auric chloride \nwere previously used for patch testing but \nthey are no longer recommended today.  At \npresent, monovalent gold salts in the form of \ngold sodium thiosulfate in petrolatum is used \nas the gold allergen in patch test. 18 It is also \nrecommended that patch test reading for gold \nallergy is extended to day 7 as the development \nof a positive reaction may be delayed.18  In \ndentistry, gold is mostly alloyed with other \nmetals such as palladium, platinum and silver \nand therefore it is important to patch test these \nmetals as well. \n\n\n\nFragrances are also common allergens in our \nstudy as evidenced by the high sensitization to \nfragrance mix I and Peru Balsam.  Fragrance \nmix I contains eight fragrances, consisting \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4732\n\n\n\nof seven defined chemicals (amyl cinnamal, \ncinnamal, cinnamyl alcohol, eugenol, geraniol, \nhydroxycitronellal and isoeugenol) and \noakmoss absolute (Evernia prunastri extract).19 \nPeru Balsam is the balsam obtained from the \nbark of Myroxylon balsamum (L.) Harms \nvar. pereirae (Royle) Harms tree and contain \nallergenic ingredients such as isoeugenol, \neugenol and cinnamyl alcohol, but there are \nalso other unknown chemicals in Peru Balsam \nthat can cause contact allergy.20  Fragrances \nare used as flavouring agents in food products \nand oral hygiene products such as toothpaste \nand mouthwash.21 Flavourings are added to \ntoothpaste as they make the toothpaste more \npleasant to use and at the same time freshen the \nbreath.  Eugenol is also used in dentistry in the \nform of zinc oxide eugenol cement due to its \nanti-inflammatory and antibacterial properties \nand this has been shown to cause oral lichenoid \nreaction.22 \n\n\n\nApart from containing fragrance allergens \nlisted above, toothpaste can also contain \ncarvone.  Carvone is used as a flavoring agent \nin toothpaste and chewing gum and it is one of \nthe main constituents of spearmint oil.  Carvone \ngives out a mint flavor and hence is an ingredient \nof most toothpastes.23  Carvone is available as \nan allergen in the dental screening series used \nat our centre.  In our study, we only had one \npatient who was found to have positive patch \ntest reaction to carvone.  Interestingly, a study \nin Sweden has found that 57% of patients with \ncarvone allergy had oral lichenoid reactions \nand this over-representation of oral lichenoid \nreactions is not connected with concomitant \ncontact allergy to gold or mercury.24  These \nfindings were also found in few other similar \nstudies.25-27  \n \nAs fragrances and carvone present in toothpaste \nmay be the causative allergens causing oral \nlichenoid reactions, patch testing to patient\u2019s \nown toothpaste should strongly be considered.  \nHowever, there is currently no consensus on \npatch testing to toothpaste.  Irritant reaction \nis deemed to be common when patch testing \nusing undiluted toothpaste due to the presence \n\n\n\nof abrasives and detergents.  Diluting the \ntoothpaste on the other hand will reduce its \nirritant potential but may cause false negative \nreaction.  As a starting point, a semi-open test or \nclosed patch test with the undiluted toothpaste \ncan be performed.  If a positive patch test \nreaction to an undiluted toothpaste developed, \nit should be followed with retesting and/or \ntesting a dilution series (e.g. undiluted, 40% pet \nor water and 20% pet or water) and/or control \ntesting.28\n\n\n\nAll of our patients complained of pain or \ndiscomfort especially after eating spicy foods. \nAround 70% of them sought medical attention \nwithin 1 year of onset of symptoms.  This \nsuggests that oral lichen planus negatively \nimpacts their quality of life, prompting them to \nseek treatment early.  This is especially true in \nMalaysia whereby spicy foods, which form part \nof our normal diet, may exacerbate or perpetuate \nthis condition.  Therefore, it is imperative that \nthe cause of oral lichenoid reactions is assessed \ncarefully. In order to distinguish contact allergy \nfrom other causes of oral lichenoid reactions, \nwe recommend that patch test is performed \nin all patients who presented with oral lichen \nplanus.\n\n\n\nAs with other cases of contact allergy, \navoidance of the causative allergen remains \nthe pivotal part of management.  Treatment \nof oral lichenoid reactions related to contact \nallergy to dental restoration materials includes \nremoval, replacement or recovering of fillings \nin direct contact with the lesions. 29 Upon \nremoval, improvement can be expected within \n1 to 6 months.30  The criteria for replacement \nof restorations vary considerably in different \npractices.  In some studies, the replacement of \nrestorations was undertaken only in cases of \na positive patch test, while others replaced all \nrestoration in contact with the lesion, irrespective \nof the patch test result.30  Despite a negative \npatch test, improvement can still be observed \nafter removal of the dental restoration materials \nin close proximity to the oral lichenoid lesions. \nThis is because these lesions may be due to the \nirritant effect of the dental restoration materials \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 33\n\n\n\nas well.31  However, results from a positive patch \ntest is still useful in providing guidance on the \ntypes of replacement restoration materials.  \n\n\n\nFor contact allergy related to fragrances, \npatient should be advised to avoid foods and \noral hygiene products that contains fragrances \nand flavourings.  Although difficult to achieve, \nstudies have shown that avoidance of fragrance \nallergens in these patients gave better control \nof their lesions than what they had achieved \npreviously.32  Due to the widespread presence of \nthese allergens in our foods, complete avoidance \nmay not be possible and occasional adjunctive \ntherapy (such as topical steroids) may be \nrequired.  Apart from cinnamon derivatives, the \nmost common flavourings used in toothpaste are \nderivatives extracted from the main varieties of \nmint, such as spearmint, peppermint, menthol \nand carvone, as they produce sensation of \nfreshness.33  One study showed a dramatic \nimprovement in a patient with oral lichen planus \nwhen spearmint oil was avoided.34 Therefore, in \npatients with oral lichenoid reactions showing \npositive patch test reaction to fragrance, we may \nempirically recommend alternative-flavoured \ntoothpaste that uses flavourings derived from \nfruit extracts instead such as orange, banana, \nstrawberry and pineapple.35\n\n\n\nThere are several limitations to this study.  \nThis is a single centre study and our findings \nmay not be representative of the Malaysian \npopulation as a whole.  We did not follow up \nthese patients after the patch test is completed. \nWe are not aware of the progress of the patients \nafter the patch test results were revealed and \nthe measures taken for these patients.  We \ndid not perform delayed reading after 5 days \nand patients with late positive patch reactions \nmight have been missed.  We also did not \nrepeat the patch test with 40% or 20% dilution \nin patients who had positive patch test reaction \nto undiluted toothpaste and this could pose a \nrisk of a false positive patch test reaction.  In \nthe future, we will extend our readings to day 7 \nfor patients tested with dental screening series \nand offer a repeat patch test with serial dilutions \nof toothpaste at 20% and 40% for patients who \n\n\n\ndevelop a positive patch test to their toothpaste.  \nFuture studies should also include follow-up \nthese patients after completion of their patch \ntests, in order to evaluate whether avoidance of \ncausative allergens has resulted in improvement \nof their symptoms.  \n\n\n\nTable 3. Oral lichen planus and oral lichenoid \nreactions: a review of the literature\n\n\n\nAuthor Study \nperiod\n\n\n\nNo of \npatients\n\n\n\nPositive \nreaction\n\n\n\nTop 3 allergens\n\n\n\nOur \nstudy,\nMalaysia\n\n\n\n2015 - 2019 41 70.7% Nickel sulfate, \ngold sodium \nthiosulphate, \nfragrance mix\n\n\n\nTorgerson \net al36\n\n\n\nUSA\n\n\n\n2000 - 2004 59 55.9% Potassium \ndicyanoaurate, \nfragrance mix, \ngold sodium \nthiosulphate\n\n\n\nKhamaysi \net al37\n\n\n\nIsrael\n\n\n\n2000 - 2004 17 35.3% Gold sodium \nthiosulphate, \nnickel sulfate, \nmercury\n\n\n\nKim et \nal38\n\n\n\nSouth \nKorea\n\n\n\n2004 - 2011 24 75.0% Nickel sulfate, \ngold sodium \nthiosulphate, \npotassium \ndichromate\n\n\n\nLomaga \net al39,\nCanada\n\n\n\n2006 - 2007 24 66.7% Nickel sulfate, \nfragrance mix, \ncobalt chloride\n\n\n\nConclusion\nContact sensitizations were detected in about \n70% of our patients with oral lichen planus and \nthe most common sensitizing allergen was nickel \nsulfate.  Current relevance was found mainly \ntowards metals in dental restoration materials.  \nApart from metals, other source of exposure to \ncontact allergens included fragrances as part of \nthe ingredients in oral hygiene products.  Patch \ntest should be considered in all cases of oral \nlichen planus.  Studies evaluating the trends of \ncontact allergens in oral lichen planus would \nhelp in determining the appropriate dental \nrestoration materials in our population. \n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto disclosed.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4734\n\n\n\nReferences\n\n\n\n1. Le Cleach L, Chosidow O. Clinical practice. Lichen \nplanus. N Engl J Med 2012;366:723-32.\n\n\n\n2. 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The role of patch testing in \nthe management of oral lichenoid reactions. J Oral Pathol \nMed 2016;45:48-57.\n\n\n\n31. Sharma R, Handa S, De D, Radotra BD, Rattan V. Role \nof dental restoration materials in oral mucosal lichenoid \nlesions. Indian J Dermatol Venereol Leprol 2015;81:478-\n84.\n\n\n\n32. Yiannias JA, el-Azhary RA, Hand JH, Pakzad SY, Rogers \nRS, 3rd. Relevant contact sensitivities in patients with \nthe diagnosis of oral lichen planus. J Am Acad Dermatol \n2000;42:177-82.\n\n\n\n33. Francalanci S, Sertoli A, Giorgini S, Pigatto P, Santucci B, \nValsecchi R. Multicentre study of allergic contact cheilitis \nfrom toothpastes. Contact Dermatitis 2000;43:216-22.\n\n\n\n34. Clayton R, Orton D. Contact allergy to spearmint oil in \na patient with oral lichen planus. Contact Dermatitis \n2004;51:314-5.\n\n\n\n35. Zirwas MJ, Otto S. Toothpaste allergy diagnosis and \nmanagement. J Clin Aesthet Dermatol 2010;3:42-7.\n\n\n\n36. Torgerson RR, Davis MD, Bruce AJ, Farmer SA, Rogers \nRS, 3rd. Contact allergy in oral disease. J Am Acad \nDermatol 2007;57:315-21.\n\n\n\n37. Khamaysi Z, Bergman R, Weltfriend S. Positive patch \ntest reactions to allergens of the dental series and the \nrelation to the clinical presentations. Contact Dermatitis \n2006;55:216-8.\n\n\n\n38. Kim TW, Kim WI, Mun JH, Song M, Kim HS, Kim BS \net al. Patch Testing with Dental Screening Series in Oral \nDisease. Ann Dermatol 2015;27:389-93.\n\n\n\n39. Lomaga MA, Polak S, Grushka M, Walsh S. Results of \npatch testing in patients diagnosed with oral lichen planus. \nJ Cutan Med Surg 2009;13:88-95.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 35\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Prospective Case Control Study Comparing Serum Vitamin D Levels in \nPatients with and without Alopecia Areata\n\n\n\nWei Cheng Leong, MRCP, Madiha Muhamad Sarkan, AdvMDerm, Jyh Jong Tang, AdvMDerm\n\n\n\nDermatology Department, Hospital Raja Permaisuri Bainun Ipoh, Ministry of Health Malaysia\n\n\n\nAbstract\nBackground\nAlopecia areata (AA) is the most common cause of non-scarring alopecia.1 Many studies reported \ndecreased serum vitamin D levels in patients with AA compared to healthy subjects.1-8 This study \naimed to assess the prevalence of vitamin D deficiency in patients with AA compared to patients \nwithout AA. The secondary objective was to determine the correlation between vitamin D deficiency \nwith disease severity and the pattern of AA.\n\n\n\nMethods\nThis research was a case control study involving patients with AA from the dermatology clinic in \nHospital Raja Permaisuri Bainun. All the subjects and controls were age, sex and Fitzpatrick skin type \nmatched. Serum vitamin D (25-hydroxyvitamin D) (25 OHD) levels were obtained and analysed by \nthe chemiluminescence immunoassay method. AA severity was assessed by Severity of Alopecia Tool \n(SALT) score.\n\n\n\nResults\nA total of 50 subjects, out of which 25 patients with AA and 25 controls, were recruited. The median \nserum vitamin D level was 54.15 nmol/L (IQR 139) in the AA group and 53.79 nmol/L (IQR 64.47) in \nthe control group. However, the difference was not statistically significant (p=0.823). The prevalence \nof vitamin D deficiency was higher in the AA group (12%) compared to the control group (4%), but \nit was not statistically significant (p=0.304). There was no statistical significance in serum vitamin D \nlevels with disease severity (SALT score) (p=0.171) and pattern of AA (p=0.657).\n\n\n\nConclusion\nThere was no statistical difference in the prevalence of vitamin D deficiency between patients with \nand without AA. There was no correlation between serum vitamin D levels with disease severity and \npattern of AA. Further studies using a larger sample size is needed to justify measuring serum vitamin \nD levels in patients with AA.\n\n\n\nKey words: Alopecia areata, Vitamin D, SALT score, Malaysia\n\n\n\nCorresponding Author\nDr Leong Wei Cheng\nDepartment of Dermatology,\nHospital Raja Permaisuri Bainun Ipoh,\nJalan Raja Ashman Shah,\n30450 Ipoh, Perak, Malaysia\nEmail: leongweicheng@hotmail.com\n\n\n\nIntroduction\nAlopecia areata (AA) is a common form of \nnon-scarring hair loss.1 AA usually presents \nas patches of hair loss on the scalp, but it \nmay also involve any areas of hair-bearing \nskin.2 AA is an organ-specific autoimmune \ndisease exemplified by T-cell infiltrate and \ncytokine production around anagen-stage hair \nfollicles.3 AA affects about 1-2% of the general \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4736\n\n\n\npopulation, with an estimated lifetime risk of \n1.7%.9 There is a higher prevalence in younger \n(21-40 years old) patients, but no significant \ndifference in incidence exists between males \nand females.10 AA can profoundly affect a \npatient\u2019s quality of life, resembling the degree \nseen in other diseases, such as psoriasis and \natopic dermatitis.11 Vitamin D is a secosteroid \nhormone that is vital for calcium homeostasis \nand bone health.3 Vitamin D is also implicated \nin certain cancers, cardiovascular health and \nimmune system.12,13,14 \n\n\n\nLiterature data suggest that vitamin D may \nbe involved in the pathogenesis of AA due to \nits immunomodulatory effects.3,7 It has been \nshown that Vitamin D Receptors (VDRs) are \nstrongly expressed in hair follicles. The lack \nof VDRs reduced epidermal differentiation \nand the growth of hair follicles.4 Some studies \nreported decreased serum vitamin D levels \nin AA in comparison to healthy subjects.1-8 \n\n\n\nA significant negative correlation between \nSeverity of Alopecia Tool Score (SALT score) \nand serum vitamin D was found in several \nstudies.2,3,5,6,8 However, data concerning the \ncorrelation between vitamin D and clinical \ndisease parameters were inconsistent.2,15 A study \nby Ghafoor R et al.16 showed that serum vitamin \nD levels were significantly lower in patients \nwith AA than healthy controls. Yilmaz et al.17, \nhowever, did not find any correlation between \nserum vitamin D concentrations in 42 patients \nwith AA and the extent of hair loss, number of \npatches, disease duration and nail involvement. \nErpolat et al.18 conducted a case control study \non 41 AA patients and found no statistically \nsignificant difference in the serum vitamin D \nlevels between AA patients and healthy controls. \nTherefore, the vitamin D levels among patients \nin Malaysia with AA is not known. \n\n\n\nThe findings of our study may justify \nincorporating vitamin D supplements as adjunct \ntherapy on top of the standard therapy. Our \nprimary objective was to compare vitamin \nD deficiency in patients with or without \nAA. Secondary objectives were to assess the \nprevalence of vitamin D deficiency in patients \n\n\n\nwith AA and determine the correlation of \nvitamin D deficiency with disease severity in \npatients with AA.\n\n\n\nMaterials and Methods\nStudy design and subject recruitment\nThis was a prospective case control study \nconducted at the dermatology clinic of Hospital \nRaja Permaisuri Bainun Ipoh, Perak, Malaysia, \nbetween the period of May 2020 and November \n2020. AA patients aged 12 years old and above \nwere recruited into the study by a convenient \nsampling method. Exclusion criteria included \npregnancy/lactating females; patients on oral \nvitamin D supplementation/topical vitamin D \nanalogues, patients with other types of alopecia \n(such as tinea capitis, androgenic alopecia, \ntrichotillomania, scarring alopecia, traction \nalopecia, telogen effluvium), patients with \nBMI>25(as vitamin D deficiency was associated \nwith obesity)3 and patients with other systemic \nautoimmune diseases (e.g. vitiligo, rheumatoid \narthritis, diabetes mellitus, thyroid disorder, \nlupus erythematosus etc.). \n\n\n\nAA patients were interviewed to obtain \ndemographic data, which consisted of their age, \ngender, ethnicity, Fitzpatrick skin phototype, \neducation level, family history of AA, duration \nof the disease, presence of comorbidities, \nsmoking and drinking habits, dietary restrictions \nand clothing practices.\n\n\n\nDiagnosis of AA was based on clinical findings \nand dermatoscopy (to look for exclamation mark \nhairs, coudability, yellow dots, black dots, short \nvellus hair). Clinical data and clinical variables \nwere documented. The duration of disease, \nsite of involvement, severity assessment for \nscalp involvement (SALT score) and pattern \nof hair loss was recorded. Patients were asked \nto recall their 3-day diet history, which would \nsubsequently be analysed for its vitamin D \ncontent using Nutritionist Pro\u2122 Software of \nthe United States Department of Agriculture \n(USDA) Standard Reference Database, First \nDataBank, Inc., San Bruno, California. \n\n\n\nThe sun exposure index (SEI) was calculated \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 37\n\n\n\nusing the formula: hours of sun exposure per \nweek multiplied by the fraction of BSA (body \nsurface area involvement using the Wallace \nRule of Nines chart) exposed to sunlight. \nSubjects in the control group were selected \nrandomly among patients and hospital staff \nwithout alopecia. The controls were matched \nto age, sex and Fitzpatrick skin type. Similar \nexclusion criteria were applied to the control \ngroup. Control subjects were assessed clinically \nwith detailed history and thorough examination. \nA total of 50 subjects were recruited with 25 AA \npatients and 25 healthy controls into each arm, \nrespectively.\n\n\n\nSerum vitamin D sampling and analysis\nThree millilitres (ml) of venous blood was \nobtained from all subjects and transferred to a \nLithium Heparin tube. Samples were collected \nand sent to the biochemical pathology laboratory \nin Hospital Raja Permaisuri Bainun Ipoh. The \nsamples were centrifuged and transported to the \nbiochemical pathology laboratory in Hospital \nPutrajaya. The blood samples were analysed \nby chemiluminescence immunoassay method \nthrough Beckham DXI analyser to measure \nserum total Vitamin D (25 -hydroxyvitamin D) \n(25OHD) levels. Clinical decision values were \ndefined as deficient (<25 nmol/L), insufficient \n(25-75 nmol/L), sufficient (76-250 nmol/L) and \npossible intoxication (>250 nmol/L).\n\n\n\nSample size calculations\nThe sample size of this study was calculated \nbased on a systematic review and meta-analysis \nby Lee S et al.15 This sample size was calculated \nusing Power and Sample Size Calculation \nversion 3.1.2 with alpha = 0.05 and power = \n80%. The sample size calculated was 46 (i.e. 23 \nsubjects with AA and 23 subjects in the control \ngroup).\n\n\n\nData analysis \nThe Statistical Package for Social Sciences \nfor Windows version 22.0 (SPSS, Chicago, \nIL, USA) was used to perform the statistical \nanalysis. The data normality was checked by the \nShapiro-Wilk test. The computed significance \nlevels for age, BMI, vitamin D level, vitamin \n\n\n\nD category and vitamin D intake are > 0.05). \nTherefore, normality cannot be assumed, and \na non-parametric test was performed. The \ndescriptive data were expressed as median and \ninter quarter range, or frequency and percentage. \nMann- Whitney test was used for the analysis of \nthe difference between two study group means. \nBecause of the small sample size of SALT 4 and \nSALT 5, and Ophiasis, Totalis and Universalis, \nthey were collapsed into one single group, \nrespectively (Naidu &Baddireddy 2020).19 \nKruskal Wallis H test was used to determine \nthe difference between the three study groups \nmeans; p<0.05 was considered statistically \nsignificant.\n\n\n\nEthical approval\nThis study was registered with the National \nMedical Research Registry (NMRR-20-41-\n52526). Ethical approval for the study was \nobtained from the Medical Research and Ethics \nCommittee, Ministry of Health, Malaysia.\n\n\n\nResults\nTable 1 shows the demographic and clinical \ncharacteristics of subjects with AA and controls. \nA total of 50 subjects were recruited, with 25 \nAA patients and 25 healthy controls in each arm, \nrespectively. There was no significant difference \n(p>0.05) between the two groups regarding \nage, sex, BMI, race, education, comorbidities, \nsmoking habits, alcohol intake, diet, Fitzpatrick \nskin type, medications, family history with AA \nand family history of autoimmune diseases. \n\n\n\nThe median vitamin D level was slightly higher \nin the AA group compared to the control group, \nalthough the difference was not statistically \nsignificant (54.15 nmol/L vs 53.79 nmol/L, \np=0.823). The median vitamin D intake was \nhigher in the control group (7.86 mcg; IQR 34.9) \ncompared to the AA group (6.65 mcg; IQR:44), \nbut the difference was not statistically significant \n(p=0.503). The median SEI was higher in the \nAA group (220.5; IQR: 209.8) compared to the \ncontrol group (146.16; IQR: 863.7) even though \nthe difference was not statistically significant \n(p=0.823). Vitamin D deficiency was higher in \nthe AA group (12%) compared to the control \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4738\n\n\n\ngroup (4%), while vitamin D insufficiency was \nfound in 76% of AA patients and 92% in the \ncontrol group. However, the results were not \nstatistically significant (p=0.304). (Table 2)\n\n\n\nTable 1. Demographic characteristics and clinical \ncharacteristics of subjects with and without alopecia \nareata (n = 50)\n\n\n\nDemographic Subject (AA)\nn = 25\n\n\n\nControl\nn = 25\n\n\n\np value\n\n\n\nMedian (IQR) or n (%)\nAge (in years) 29 (25) 29 (22) 0.938c\n\n\n\nSex\n\n\n\n   Male 11 (44 %) 9 (36 %) 0.773b\n\n\n\n   Female 14 (56 %) 16 (64 %)\n\n\n\nBMI 23 (5.1) 22 (5.1) 0.839c\n\n\n\nRace \n\n\n\n   Malay 7 (28 %) 7 (28 %) 1.000a\n\n\n\n   Chinese 9 (36 %) 9 (36 %)\n\n\n\n   Indian 9 (18 %) 9 (18 %)\n\n\n\nEducation\n\n\n\n   Primary 1 (4 %) 0 (0 %) 0.456a\n\n\n\n   Secondary 15 (60 %) 13 (52 %)\n\n\n\n   Tertiary 9 (36 %) 12 (48 %)\n\n\n\nComorbid\n\n\n\n   Yes 7 (28 %) 3 (12 %) 0.289b\n\n\n\n   No 18 (72 %) 22 (88 %)\n\n\n\nSmoker\n\n\n\n   Yes 4 (16 %) 4 (16 %) 1.000a\n\n\n\n   No 20 (80 %) 20 (80 %)\n\n\n\n   Ex-smoker 1 (4 %) 1 (4 %)\n\n\n\nAlcohol\n\n\n\n   Yes 7 (28 %) 3 (12 %) 0.289b\n\n\n\n   No 18 (72 %) 22 (88 %)\n\n\n\nDiet\n\n\n\n   Vegetarian 2 (8 %) 0 (0 %) 0.490b\n\n\n\n   Non- vegetarian 23 (92 %) 25 (100 %)\n\n\n\nFitzpatrick\n\n\n\n   Type III                    9 (36 %) 9 (36 %) 1.000a\n\n\n\n   Type IV                 7 (28 %) 7 (28 %)\n\n\n\n   Type V                    9 (36 %) 9 (36 %)\n\n\n\nMedications\n\n\n\n   Yes 8 (32 %) 12 (48 %) 0.387b\n\n\n\n   No 17 (68 %) 13 (52 %)\n\n\n\nFamily history AA\n\n\n\n   Yes 1 (4 %) 0 (0 %) 1.000b\n\n\n\n   No 24 (96 %) 25 (100 %)\n\n\n\nFamily history Autoimmune\n\n\n\n   Yes 2 (8 %) 2 (8 %) 1.000b\n\n\n\n   No 23 (92 %) 23 (92 %)\naChi-Square test; bFisher\u2019s exact test; cMann-Whitney test\n\n\n\nTable 2. Vitamin D level and deficiency in case and \ncontrol group\n\n\n\nSubject (AA)\nn =25\nMedian (IQR)\n\n\n\nControl\nn =25\nMedian (IQR)\n\n\n\np value\n\n\n\nVitamin D level \n(nmol/L)\n\n\n\n54.15 (139.0) 53.79 (64.47) 0.823a\n\n\n\nVitamin D intake \n( )\n\n\n\n6.65 (44) 7.86 (34.9) 0.503a\n\n\n\nSun Exposure \nindex (SEI) \n\n\n\n220.50 (209.8) 146.16 (863.7) 0.823a\n\n\n\nVitamin D \ncategories \n\n\n\n  n (%)   n (%)\n\n\n\n Deficient < 25 3 (12 %) 1 (4 %) 0.304b\n\n\n\n Insufficient 25-75 19 (76 %) 23 (92 %)\n\n\n\n Sufficient 76-250 3 (12 %) 1 (4 %)\naMann-Whitney test; bChi-Square test\n\n\n\nThe association of SALT score with vitamin D \nlevel was obtained by Kruskal-Wallis statistic \nand was interpreted as a chi-square value. There \nwas no statistically significant association \nbetween SALT score and vitamin D levels \n(p=0.171). (Table 3)\n\n\n\nTable 3. Association of SALT scores with vitamin \nD level\n\n\n\nSALT subclass (n=25) n (%) Median (IQR) p value\n\n\n\nS1 18 (72 %) 54.56 (32.5) 0.171a\n\n\n\nS2 2 (8 %) 34.42 (0)\n\n\n\nS3-S5 5 (20 %) 42.78 (43.13)\naKruskal-Wallis test\n\n\n\nA similar analysis was performed for the \nassociation of AA patterns with vitamin D \nlevels. The result showed no statistically \nsignificant difference between the pattern of AA \nwith vitamin D levels (p=0.657). (Table 4)\n\n\n\nTable 4. Association of pattern scores with vitamin \nD level\n\n\n\nPattern subclass (n=25) n (%) Median (IQR) p value\n\n\n\nP1 (patchy: single) 6 (24 %) 44.62 (37.29) 0.657 a\n\n\n\nP2 (patchy: multiple) 15 (60 %) 54.16 (30.65)\n\n\n\nP3 (ophiasis, totalis and \nuniversalis)\n\n\n\n4 (16 %) 43.49 (35.66)\n\n\n\naKruskal-Wallis test\n\n\n\nDiscussion\nVitamin D can be obtained from 3 sources: \nendogenous synthesis in the skin induced \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 39\n\n\n\nby ultraviolet B (UVB) radiation, dietary \nintake, and vitamin D supplementation.3,13,14 \n\n\n\n7-dehydrocholesterol is the precursor molecule \nin the skin which absorbs UVB light and converts \nto vitamin D3(cholecalciferol). Vitamin D3 \nbinds to vitamin D3 binding protein and is \ntransported to the liver where it is hydroxylated \nto 25-hydroxyvitamin D (calcidiol) (25(OH)D). \nCalcidiol is then converted to 1,25-dihydroxy-\nvitamin D3 (calcitriol) in the kidney by \n1-\u03b1 hydroxylase.13,14 The optimal level for \n25-hydroxyvitamin D (25OHD), the most stable \nand reliable parameter to evaluate vitamin D \nstatus, starts at 30 ng/ml, although the level of \n25OHD required to maintain optimum immune \nsystem homeostasis has yet to be established.20\n\n\n\nThe active form of vitamin D \n(1,25-hydroxyvitamin D) acts by binding to \nspecific vitamin D receptors found in the nucleus \nof target cells.7 Vitamin D Receptor (VDR) is \nhighly expressed in the key structures of hair \nfollicles, and it is vital for the maintenance of \nthe normal hair cycle. It has been demonstrated \nthat a lack of VDRs reduces the growth of hair \nfollicles. Therefore, with the role of vitamin D \nand VDR in the hair cycle, it is hypothesised \nthat vitamin D deficiency may have a role in \nAA.1,2\n\n\n\nA study conducted in Malaysia on vitamin \nD status in Malaysian men found that the \nprevalence of vitamin D deficiency was 0.5% \nand insufficiency was 22.7%, respectively.21 \n\n\n\nNumerous studies have shown that vitamin D \ninsufficiency was common in tropical countries, \nincluding Vietnam, Malaysia, and Indonesia.21 \n\n\n\nThe prevalence of vitamin D deficiency among \nMalaysian adolescents aged 13 years was \n78.8%.22\n\n\n\nIn our study, there was no significant difference \nin terms of the median vitamin D level between \nthe AA and control group, even though the level \nwas slightly higher in the AA group. A study by \nNassiri et al.24 found no statistically significant \ndifference in serum vitamin D levels between \nAA cases and controls (ordinal odds ratio:0.49 \n(0.18-1.34 and 95%CI, p=0.16). Erpolat et al.18 \n\n\n\nalso reported similar findings with mean serum \n\n\n\nvitamin D levels of 8.1 ng/ml in AA patients \ncompared to 9.8 ng/ml in healthy controls, \nwhich was not statistically significant (p>0.05). \nIn contrast, numerous studies reported high \nstatistically significant lower vitamin D levels \nin cases compared to control. Aksu Cerman et \nal.3 reported significantly lower mean serum \nvitamin D levels in AA patients (11.84\u00b16.18 \nng/ml) than healthy controls (23.57\u00b19.03 ng/\nml) (p<0.001). A study conducted by Bhat et \nal.4 found a statistically significant difference \nin the mean serum vitamin D levels of AA \npatients (16.6\u00b15.9 ng/ml) as compared to the \ncontrol group (40.5\u00b15.7 ng/ml) (p<0.001).4 \n\n\n\nSimilar findings of high statistically significant \nlower vitamin D levels in AA cases compared to \ncontrol was also reported in studies conducted \nby Sidappa et al.5, Mahamid et al.7, Rehman et \nal.8, and Yilmaz et al.17\n\n\n\nOur study revealed that Vitamin D deficiency and \ninsufficiency was high in both AA (12%, 76%) \nand control group (4%, 92%). This finding was \nconsistent with recent studies, which showed \nvitamin D insufficiency was commonly found \nin tropical countries such as Vietnam, Malaysia \nand Indonesia.21 A study conducted by Kok-\nYong Chin et al.21 found that the prevalence of \nvitamin D deficiency (<30 nmol/L) was 0.5% \nand insufficiency (30-50 nmol/L) was 22.7% \namong Malaysian men. The result of higher \nvitamin D deficiency and insufficiency in both \ngroups in our study compared to Kok-Yong \nChin et al.21 The discrepancy might be due to \ndifferent definitions of vitamin D deficiency and \ninsufficiency used in the study. Another study \nconducted in Malaysia by Moy et al.23found that \nvitamin D insufficiency was observed in 67.9% \nof participants among Malay adults in Malaysia. \nAnother study conducted by Rahman et al.24 \nin Malaysia also showed a high prevalence \nof inadequate serum vitamin D levels among \npostmenopausal Malaysian women. A total of \n73.3% of Malay postmenopausal women and \n12.2% of Chinese postmenopausal women \nhad insufficient serum vitamin D levels (<50 \nnmol/L).24\n\n\n\nIn our study, there was no statistical difference in \nthe prevalence of vitamin D deficiency between \nAA and the control group even though vitamin \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4740\n\n\n\nD deficiency was higher in the AA group than \nthe control group (12% vs 4%, p>0.05). This \nobservation could be due to a small sample \nsize leading to insignificant results. Erpolat et \nal.18also reported higher vitamin D deficiency \nin the AA group compared to control (93.8% vs \n85.3%), but the difference was not statistically \nsignificant (p>0.05). Numerous studies reported \na significantly higher prevalence of vitamin D \ndeficiency in AA compared to the control group. \nSuchana et al.1 reported 83.3% of vitamin D \ndeficiency in the AA group compared to the \ncontrol group (53.3%; p=0.01). Bakry et al.2 \n\n\n\nfound that 83.3% in the AA group versus 23.3% \nin the control group had deficient serum vitamin \nD levels (p<0.001). Similar findings were \nreported by Aksu Cerman et al.3 and Naidu et \nal.19\n\n\n\nOur study did not find any statistically \nsignificant correlation between serum vitamin \nD levels and SALT scores. Suchana et al.1 found \nthat patients with more severe SALT scores tend \nto have lower serum vitamin D levels, with an \ninverse correlation (r=-.026, p=0.89); however, \nthe results were not statistically significant. \nNaidu et al.19 also showed slightly lower serum \nvitamin D levels as the SALT score progressed, \nbut the difference was not statistically significant \n(p=0.06). Various studies, as reported by Yilmaz \net al.17, d\u2019Ovidio et al.20, El-Mongy et al.25 and \nDarwish et al.26 found no significant correlation \nbetween serum vitamin D levels with disease \nseverity. However, this contradicts numerous \nother studies that found that serum vitamin D \nlevels showed a significant negative correlation \nwith disease severity.2,3,4,5,6,8 Aksu Cerman et al.3 \n\n\n\nfound a significant inverse correlation between \ndisease severity and serum vitamin D levels in \nAA patients (r =-0.730; p<0.001). Bhat et al.4 \n\n\n\nalso reported a significant negative correlation \nbetween SALT sore and vitamin D levels (r=-\n0.730; p<0.001).4 Similar findings of significant \ninverse correlation between SALT score and \nvitamin D levels were reported by Sidappa et \nal.5, Gade et al.6, and Rehman et al.8\n\n\n\nRegarding the correlation of serum vitamin D \nlevels with the pattern of disease, our study \n\n\n\ndid not find any correlation between different \npatterns of AA with serum vitamin D levels. \nThis finding was similar to a study conducted \nby El-Mongy et al.25, which reported no \nstatistical significance between serum vitamin \nD levels and disease pattern (p=0.14). Similar \nfindings were reported in studies conducted by \nYilmaz et al.17,d\u2019Ovidio et al.20 and Nassiri et \nal.27 In contrast, a study conducted by Bakry et \nal.2 showed a gradual decline of serum vitamin \nD levels from patchy AA to Alopecia totalis/\nuniversalis. Serum vitamin D levels of alopecia \ntotalis/universalis patients were significantly \nlower when compared to patchy AA (p<0.001) \nand ophiasis (p<0.05). Rehman et al.8 also \nreported similar findings where serum vitamin \nD levels negatively correlated with the pattern \nof AA (r=-0.273, p=0.004).\n\n\n\nThe median SEI in the AA group was higher \nthan the control group, although the result was \nnot statistically significant (SEI: 220.50 vs \n146.16, p>0.05). A study conducted by Bingley \net al.28 among 93 adults in Hawaii showed low \nserum vitamin D levels despite adequate sun \nexposure, suggesting variable responsiveness \nto UVB radiation among individuals.28 A study \nconducted on 167 Malaysians by Wong et al.29 \non sun exposure among healthy adults in a health \nfacility showed a mean SEI of 160\u00b1144, lower \nthan the median SEI of 220.5 in the AA group \nfrom our study.29 Although Malaysia is a tropical \ncountry with adequate sunlight throughout \nthe year, a low SEI among Malaysians can be \nattributed to sun avoidance to achieve a fairer \nskin tone, which is deemed more desirable, and \nescape the tropical heat. Other factors include \nthe choice of clothing, with most Asians dresses \nmodestly due to influence by tradition, culture, \nor religion, which limits the amount of sunlight \nthat reaches the skin.29 The primary cause of \nvitamin D deficiency is inadequate exposure to \nsunlight.30\n\n\n\nThe median vitamin D intake was lower in the AA \ngroup compared to the control group, although \nit was not statistically significant. Vitamin D \nintake was low in both groups, which correlates \nto low serum vitamin D levels in both groups. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 41\n\n\n\nThe finding could be attributed by very few foods \nthat naturally contain or are adequately fortified \nwith vitamin D. As examples, food sources that \nare naturally high in vitamin D include cod liver \noil, salmon, sardines, tuna, shitake mushrooms \nand egg yolks. The recommended vitamin D \nintake is 600 IU/day (15 mcg) for adults aged \n19-50 years old, and at least 600-800 IU/day \n(15-20 mcg) for adults aged 50-70 years old \nand above 70 years old, respectively. However, \nfor serum vitamin D level to rise above 30 ng/\nml (75 nmol/L), one may require 1500-2000 IU/\nday (38 mcg-50 mcg) of supplemental vitamin \nD.30\n\n\n\nLimitations\nThe limitations of this study include a relatively \nlimited sample size. As this study was conducted \nfrom a single centre in Malaysia, larger studies \ninvolving multiple centres may be more \nrepresentative of the population in Malaysia. In \naddition, as the patients were not followed up \nwith vitamin D supplementation and repeated \nserum vitamin D levels, it was hard to conclude \nif vitamin D supplementation may be beneficial \nas an adjunctive treatment for patients with AA.\n\n\n\nConclusion\nThere is no significant statistical difference in \nvitamin D levels between patients with AA and \nwithout. However, the prevalence of vitamin D \ninsufficiency was high in both AA and control \ngroups. There is also no correlation between \nserum vitamin D levels with severity and pattern \nof disease. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nThis study was funded with a research grant \nfrom the Dermatological Society of Malaysia. \nWe would like to thank all the staff from the \ndepartments of dermatology and pathology \nof Hospital Raja Permaisuri Bainun, Ipoh \nand Hospital Putrajaya, and Suria Junus, the \nstatistical supervisor. We also wish to thank \nthe Director-General of Health Malaysia for \n\n\n\npermission to publish this article.\n\n\n\nReferences \n\n\n\n1. Marahatta S, Agrawal S, Khan S. Study on Serum Vitamin \nD in Alopecia Areata Patients. J Nepal Health Res Counc \n2019;17:21-5. \n\n\n\n2. Bakry OA, El Farargy SM, El Shafiee MK, Soliman A. \nSerum Vitamin D in patients with alopecia areata. Indian \nDermatol Online J 2016;7:371-7.\n\n\n\n3. Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. \nVitamin D deficiency in alopecia areata. Br J Dermatol \n2014;170:1299-304.\n\n\n\n4. Bhat YJ, Latif I, Malik R, Hassan I, Sheikh G, Lone KS et \nal. Vitamin D Level in Alopecia Areata. Indian J Dermatol \n2017;62:407-10.\n\n\n\n5. Siddappa H, Kumar YHK, Vivekananda N. Evaluation \nof Association of Vitamin D in Alopecia Areata: A Case-\ncontrol Study of 100 Patients in a Tertiary Rural Hospital \nof Southern India. Indian Dermatol Online J 2019;10:45-9.\n\n\n\n6. Gade VKV, Mony A, Munisamy M, Chandrashekar \nL, Rajappa M. An investigation of vitamin D status in \nalopecia areata. Clin Exp Med 2018;18:577-84.\n\n\n\n7. Mahamid M, Abu-Elhija O, Samamra M, Mahamid \nA, Nseir W. Association between vitamin D levels and \nalopecia areata. Isr Med Assoc J 2014;16:367-70. \n\n\n\n8. Rehman F, Dogra N, Wani MA. Serum Vitamin D Levels \nand Alopecia Areata- A Hospital Based Case-Control \nStudy from North-India. Int J Trichology 2019;11:49-57.\n\n\n\n9. Pratt CH, King LE Jr, Messenger AG, Christiano AM, \nSundberg JP. Alopecia areata. Nat Rev Dis Primers \n2017;3:17011.\n\n\n\n10. Thompson JM, Mirza MA, Park MK, Qureshi AA, Cho E. \nThe Role of Micronutrients in Alopecia Areata: A Review. \nAm J Clin Dermatol 2017;18:663-79.\n\n\n\n11. Liu LY, King BA, Craiglow BG. Health-related quality of \nlife (HRQoL) among patients with alopecia areata (AA): A \nsystematic review. J Am Acad Dermatol 2016;75:806-12.\n\n\n\n12. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet \nG. Vitamin D: Metabolism, Molecular Mechanism of \nAction, and Pleiotropic Effects. Physiol Rev 2016;96:365-\n408. \n\n\n\n13. Bikle DD. Vitamin D metabolism, mechanism of action, \nand clinical applications. Chem Biol 2014;21:319-29.\n\n\n\n14. Kechichian E, Ezzedine K. Vitamin D and the Skin: \nAn Update for Dermatologists. Am J Clin Dermatol \n2018;19:223-35.\n\n\n\n15. Lee S, Kim BJ, Lee CH, Lee WS. Increased prevalence \nof vitamin D deficiency in patients with alopecia areata: a \nsystematic review and meta-analysis. J Eur Acad Dermatol \nVenereol 2018;32:1214-21.\n\n\n\n16. Ghafoor R, Anwar MI. Vitamin D Deficiency in Alopecia \nAreata. J Coll Physicians Surg Pak 2017;27:200-2. \n\n\n\n17. Tsai TY, Huang YC. Vitamin D deficiency in patients with \nalopecia areata: A systematic review and meta-analysis. J \nAm Acad Dermatol. 2018;78:207-9.\n\n\n\n18. Erpolat S, Sarifakioglu E, Ayyildiz A. 25-hydroxyvitamin \nD status in patients with alopecia areata. Postepy Dermatol \nAlergol 2017;34:248-52. \n\n\n\n19. Abedini R, Shakiba S, Ghandi N, Yazdaniamjad F, Haddadi \nN, Nasimi M. Study of vitamin D deficiency in patients \nwith alopecia areata attending a dermatology center in \nIran. Iran J Dermatol 2021;24:97-101.\n\n\n\n20. d\u2019Ovidio R, Vessio M, d\u2019Ovidio FD. Reduced level of \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4742\n\n\n\n25-hydroxyvitamin D in chronic/relapsing Alopecia \nAreata. Dermatoendocrinol 2013;5:271-3.\n\n\n\n21. Chin KY, Ima-Nirwana S, Ibrahim S, Mohamed IN, Wan \nNgah WZ. Vitamin D status in Malaysian men and its \nassociated factors. Nutrients 2014;6:5419-33.\n\n\n\n22. Al-Sadat N, Majid HA, Sim PY, Su TT, Dahlui M, Abu \nBakar MF et al. Vitamin D deficiency in Malaysian \nadolescents aged 13 years: findings from the Malaysian \nHealth and Adolescents Longitudinal Research Team study \n(MyHeARTs). BMJ Open. 2016;6:e0106.\n\n\n\n23. Moy FM. Vitamin D status and its associated factors of \nfree living Malay adults in a tropical country, Malaysia. J \nPhotochem Photobiol B. 2011;104:444-8.\n\n\n\n24. Rahman SA, Chee WS, Yassin Z, Chan SP. Vitamin D \nstatus among postmenopausal Malaysian women. Asia Pac \nJ Clin Nutr 2004;13:255-60.\n\n\n\n25. El-Mongy NN, El-Nabarawy E, Hassaan SA, Younis \nER, Shaker O.Serum 25-hydroxy vitamin D3 level in \nEgyptian patients with alopecia areata. J Egypt Women\u2019s \nDermatologic Soc 2013;10:37-41.\n\n\n\n26. Darwish NM, Marzok HF, Gaballah MA, Abdellatif HE. \nSerum level of vitamin D in patients with alopecia areata. \nEgypt J Basic Appl Sci 2017;4:9-14.\n\n\n\n27. Soheila N, Zahra S, Shima Y. Association of Vitamin D \nlevel with alopecia areata. Iran J Dermatol 2013;16:1-5.\n\n\n\n28. Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, \nLensmeyer G et al. Low vitamin D status despite abundant \nsun exposure. J Clin Endocrinol Metab 2007;92:2130-5.\n\n\n\n29. Wong LC, Jamil A, Md Nor N. Sun exposure among \nhealthy adults in a health facility. Mal J Med HealthSci \n2018;114:24-6.\n\n\n\n30. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon \nCM, Hanley DA, Heaney RP et al. Endocrine Society. \nEvaluation, treatment, and prevention of vitamin D \ndeficiency: An Endocrine Society clinical practice \nguideline. J Clin Endocrinol Metab 2011;96:1911-30. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 43\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Study Assessing the Practices and Motivation for Seeking Tattoo \nRemoval\n\n\n\nAllaranda Somaiah Savitha1, MD (DVL), Basavapura Madegowda Shashikumar2, MD (DVL)\n\n\n\n1Sapthagiri Institute of Medical Sciences & Research Centre, Bengaluru, Karnataka, India \n2Sparsha Skin Care Clinic, Mandya, Karnataka, India\n\n\n\nAbstract\nBackground\nAs the number of patients getting tattooed is increasing, so is the number of patients seeking removal of \ntattoos. The primary objective of this study was to assess the reasons as to why patients got tattoos and \nalso seek tattoo removal. The secondary objective was to study the demographics and the knowledge \nthey had regarding tattoo removal.\n\n\n\nMethods\nA cross sectional study was done among 250 consecutive patients who attended the Dermatology \ncentre seeking tattoo removal. A questionnaire was used to fill in the details.\n\n\n\nResults \n167 males and 83 females were included in the study. Majority of patients were in the age group of 21 \nto 30 years (43.8%) followed by 31-40 years (26.7%). 56.6% of patients had got tattoos in the third \ndecade and 35.1% in the second decade. 52.6% of those seeking tattoo removal had got their tattoos \nfrom amateur artists, village fairs or roadside tattoo shops. 45.8% did not have a specific reason for \ngetting a tattoo and were decorative tattoos. 34.7% had names of their beloved or family members. \n29.5% were seeking removal for professional reasons and 23.1% due to changes in relationship status.\n\n\n\nConclusion \nPatients seek tattoo removal mainly for professional reasons, changes in personal relationships when \nthey have name tattoo and due to complications. Most of the patients were in the third decade of life. It \nis important to educate school going children ang youngsters regarding the permanent nature of tattoo \nand its complications.\n\n\n\nKey words: Tattoo, Laser removal, Awareness\n\n\n\nCorresponding Author\nDr Basavapura Madegowda Shashikumar\nSparsha skin Care Clinic, \nMandya, \n571401, Karnataka, India\nEmail: shashikumarbm@gmail.com\n\n\n\nIntroduction\nTattooing is a common and popular form of \nbody decoration especially among younger \nindividuals. Tattoo is a permanent change \nbrought about in the skin by injection of a dye \nmolecule into the dermal layer. Tattoos may be \ndecorative, medical or accidental depending on \nwhether the dye was introduced intentionally \nor by accident.1 Medical tattoos are done for \ncosmetic camouflage in vitiligo, permanent \nhair loss, scars and areola reconstruction after \nsurgery.2 Tattoos are part of the cultural heritage \nof various tribes. It used to be an indicator of \nsocial status or a victory.3 With modernisation, \ntattoo has become more of a fashion statement. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4744\n\n\n\nThere are limited studies regarding the \nmotivation for tattoos and for reasons requesting \nits removal.3, 4 \n\n\n\nThe objective of this study was to evaluate what \nmotivated the participants to get tattoo and why \nthey were seeking the removal. \n\n\n\nMaterials and Methods\nStudy design \nA cross sectional descriptive study was \nconducted between Jan 2019 and Jan 2021. \nA sample of 250 consecutive patients who \nattended the centre seeking removal of tattoos \nwere included in the study. Written informed \nconsent was taken from the participants to use \ntheir data. Patients who did not consent were \nexcluded from the study. \n\n\n\nMethods\nA questionnaire in the language known to the \npatient was used to collect the data regarding \nthe demography, education, age at which tattoo \nwas done, reason for the tattoo, amateur or \nprofessional, site and number of tattoos, if they \nwere aware that the tattoo was permanent, why \nthey were seeking tattoo removal and if they had \ntried other methods of removal. The responses \nwere coded from 1 to 5 according to questions \nand entered in excel sheet. Approval was taken \nfrom institutional ethics committee. \n\n\n\nData was entered in excel sheet and analysed \nusing SPSS software. Results were expressed in \npercentage.\n\n\n\nResults\nOut of 250 participants in the study, 167 were \nmales (66.5%) and 83 were females (33.1%). \nThe analysis of demographic data showed \nthat 110 of participants were in third decade \n(43.8%), 67 in the fourth decade (26.7%), and \nwith almost equal number of participants in \nremaining age groups (Table 1). \n\n\n\nTable 1. Age of the patients seeking tattoo removal\n\n\n\nAge in years Number Percentage %\n\n\n\n<20 24 9.6\n\n\n\n20-30 110 43.8\n30-40 67 26.7\n40-50 25 10\n>50 24 9.6\n\n\n\nThe number of participants from the urban area \nwas slightly higher than the rural. (57.4%). \nAmong the participants, one hundred and seven \nwere graduates, (50.6%), 77 had studied up \nto higher primary level (30.7%) and 46 were \neither illiterates or dropped out of primary \nschool (18.3%). Majority of patients 142 \n(83.7%) patients had got their first tattoo in the \nthird decade (56.6%) and 88 in second decade \n(35.1%). \n\n\n\nProfessional tattoos were seen in one hundred \nand seventeen (46.6%) (Figure 1) and 132 had \namateur tattoos (52.6%) (Figure 2). Majority \nof the participants (71%) from rural areas had \namateur tattoos whereas 61% of those from \nurban areas had professional tattoos. Single \ntattoo was seen among 210 participants (83.7%).  \nA large number of participants (45.8%) did not \nhave a specific motive to get a tattoo, it was \nfor decorative purpose. 74 of them had a tattoo \nto symbolise a romantic relationship and 13 \n(5.2%) for a family member. \n\n\n\nOnly 18 (7.2%) were under the influence of \nalcohol at the time of tattooing.  Decorative \ntattoos (46.6%) were the most common, \nfollowed by names of friends or family \nmembers (34.7%), (Figure 3) and 26 (10.4%) \nhad inspirational and religious quotes. (Figure \n4) Forearm was the most common site for \ntattoo in 113 (45.0%), followed by chest in \n73 (29.1%), shoulder and neck in 38 (15.1%), \nbindi and lower back in 9 each (3.6%). Only 35 \nparticipants (13.9%) were not aware about the \npermanent nature of the tattoo. 74 wanted tattoo \nremoved for professional reasons (29.5%), 58 \ndue to separation from partners (23.1%), 43 due \nto tattoo reactions (17.1%), 31 due to family \npressure (12.4%) and 29 due to regret (11.6%). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 45\n\n\n\nAs high as 85% of those who wanted tattoo \nremoval for professional reasons were educated \nhigher primary and above and 86% were men. \nMost common reason for women seeking \nremoval was separation from partners (38%) \nfollowed by pressure from family members \nin 18%. 69.7% of reactions were in men and \n30.3% in women. (Figure 5) Local measures \nlike application of lime (Figure 6), cuts, burning \nwith candles and incense stick was tried by \n33 participants (13.1%), before consulting \nspecialists.\n\n\n\nTable 2. Reasons for seeking tattoo removal\n\n\n\nReason Number Percentage %\nRegret 29 11.6\nProfessional advancement 74 29.5\nSeparation from partner 58 23.1\nReactions 43 17.1\nFamily pressure 31 12.4\nReligious obligations 15 6.0\n\n\n\nFigure 1. Professional black tattoo\n\n\n\nFigure 2. Amateur tattoo\n\n\n\nFigure 3. Tattoo of beloved\u2019s name\n\n\n\nFigure 4. Types of tattoo\n\n\n\nFigure 5. Granulomatous reaction to tattoo\n\n\n\nFigure 6. Irritant contact dermatitis due to \napplication of lime to remove tattoo\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4746\n\n\n\nDiscussion\nTattooing has become a common form of body \ndecoration. Being sported by supermodels and \npopstars, they provide a lot of appeal to the \nyoungsters.5 \n\n\n\nIn the study by Thakur et al. of the tattoo \npractices in North eastern India, more than 50 \n% patients seeking tattoo removal had got their \ntattoos in school going age which they attributed \nto emotional immaturity and influence of \nfashion. Studies by Varma et al and Ltrielle et al \nalso published that majority of participants got \ntattoos in second decade.5,6 However in our study \nonly 35.1% had got tattoos before the age of 20 \nyears, but majority (56.5%) of patients got their \ntattoos in third decade. Few of the participants \nwere not aware about the permanency of the \ntattoo and majority of them were less than \n20 years of age. Knowledge among students \nregarding the safety, permanency and side effects \nof tattoos in insufficient.7 Preventive education \nin school regarding the permanency of tattoo, \npossible effects on future employment, risks \nand complications may help to reduce underage \ntattooing. Most of them being amateur tattoos, \nthere was obviously no explanation given to \nthe participants about the permanent nature or \npossible side effects by tattoo artists.\n\n\n\nMost of the participants (45.8%) in the study \ndid not have a specific motive for getting a \ntattoo, it was for decorative purpose. Our study \nconforms with similar findings of other studies \nwhere most of the tattoos are often applied \nimpulsively.5,8 34.7% of participants had names \ntattooed for sentimental reasons, out of which \n85% had their partners\u2019 names. More women \nhad tattooed their partners\u2019 names (39.7%) than \nmen which was 24.5%.\n\n\n\n52.6% had amateur tattoos in our study which \nis much lower than the study from Eastern India \nwhere 94.3% of tattoos were amateur which \ncan be explained by the cultural heritage of \ntattooing among tribes in North Eastern India.3 \nNo significant difference was noted in the level \nof education and the place of tattoo.  Higher \nproportion of people from rural areas had \n\n\n\namateur tattoos (70.7%), compared to 60.13 % \nof those from urban areas who had professional \ntattoos. This can be explained by the more \nnumber of tattoo parlours in urban areas with a \nlot of advertisements. Also functions like fairs \nwhere amateur tattoo artists are in plenty, are \nnot common in urban areas.\n\n\n\nThe most common reason for removal of tattoos \nwas for employment prospects (74 patients). \nAccording to the revised tattoo policy by Indian \nArmy, only tattoos on inner aspect of forearm and \ndorsum of the hand are permissible. Candidates \nbelonging to tribal communities/from tribal \nareas, as declared by the Government of India \nScheduled Castes and Scheduled Tribes Orders \nAct/Lists (amended and modified from time to \ntime), are permitted to have permanent body \ntattoos on any part of the body, as per existing \ncustoms and traditions of the said tribe to which \na candidate belongs. 9  Though there are no \nopen policies and guidelines regarding tattoo \nin any other government sector In India, people \napplying for Civil services and railways job \nalso sought tattoo removal. 23% were seeking \nremoval of name tattoos due to changes in \nrelationship status. Couples frequently tattoo the \nnames of their partners to show their affection \nwhich is regretted when the relationship ends.4 \n\n\n\nOther reasons were family pressure and religious \nissues. 17% of patients had tattoo reactions like \nallergic contact dermatitis (commonly to red \ncolour). This is similar to previous reported \nstudies, where allergic reactions are found more \nfrequently to red colour.10 According to study by \nThakur et al to be eligible for armed force jobs \nwas the most common reason for tattoo removal \n(49.5%), followed by regret (21.7%), elder or \nschool pressure (14.2%), personal (12.7%) \nand unsightly appearance such as hypertrophic \nscarring in tattoo (1.9%).3 Similar results were \npublished from a study in Western India. 4 These \nwere quite different from Western studies. \n\n\n\nAccording to Varma et al the reasons for seeking \ntattoo removal were improvement of self-\nesteem (48 patients), followed by social reasons \n(24 patients), family pressure (13 patients), \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 47\n\n\n\nimproving potential for employment (12 \npatients) and a change of partner (4 patients).5 \nThe reasons also varied according to the age of \nthe patients. Teenagers sought removal mainly \ndue to regret and familial pressure. In the third \ndecade professional eligibility was the most \ncommon reason. In those over the age of 30 \nseparation from partners and regret were the \nreason why they sought removal frequently. \nThirty-three patients had tried various methods \nof tattoo removal like application of lime, soda, \nburning with incense sticks, scraping with blade \nwhich had resulted in infection and scars.\n\n\n\nThe limitation of this study is that it is a hospital-\nbased study done only on individuals seeking \ntattoo removal at a single centre. Recall bias \nand selection bias have to be considered before \nprojecting the results to the community.\n\n\n\nConclusion\nPatients seeking tattoo removal which was once \ndone enthusiastically is increasing. Counselling \nabout the permanent nature of tattoo and the \nsignificant cost involved in their removal may \nhinder the impulsive nature in few. Physicians \nshould be aware about the different methods \nof tattooing, tattoo removal and complications \nassociated with tattoos. Education about the \ntattoo regulations especially among those \nseeking to join the armed forces is important. \nThe tattoo artists should also involve in \ncounselling the patients, so potential side effects \nlike regret and seeking removal immediately \nmay be reduced.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nNil\n\n\n\nReferences\n1. Braun-Falco O, Plewig G, Wolff H, Burgdorf W. Braun-\n\n\n\nFalco\u2019s Dermatology. Berlin: Springer; 2009. \n2. Khunger N, Molpariya A, Khunger A. Complications of \n\n\n\ntattoos and tattoo removal: stop and think before you ink. J \nCutan Aesthet Surg 2015;8:30-6. \n\n\n\n3. Thakur BK, Verma S. Tattoo practices in North-East India: \nA hospital-based cross-sectional study. J Cutan Aesthet \nSurg 2016;9:172-6.\n\n\n\n4. Anu Patel, Meet Barbhaya, Krina Patel. Tattoo in Modern \n\n\n\nEra - Tattooing Audit in Indian Context. Int J Sci Res \n2019;12:139-41. \n\n\n\n5. Varma S, Lanigan SW. Reasons for requesting laser removal \nof unwanted tattoos. Br J Dermatol 1999;140:483-5.\n\n\n\n6. Latreille J, Levy JL, Guinot C. Decorative tattoos and \nreasons for their removal: A prospective study in 151 adults \nliving in South of France. J Eur Acad Dermatol Venereol \n2011;25:181-7.\n\n\n\n7. Rogowska P, Szczerkowska\u2010Dobosz A, Kaczorowska R, \nS\u0142omka J, Nowicki R. Tattoos: Evaluation of knowledge \nabout health complications and their prevention among \nstudents of Tricity universities. J Cosmet Dermatol \n2018;17:27-32. \n\n\n\n8. Dupont C. Decorative tattoos: an analysis of 100 cases. \n(Letter.) Acta Derm Venereol 1994;74:236.\n\n\n\n9. Mortimer NJ, Chave TA, Johnston GA. Red tattoo \nreactions. Clin Exp Dermatol 2003;28:508-10.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4748\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Comparative Study of Licochalcone A Moisturiser versus Topical \nHydrocortisone in Treating Mild-to-Moderate Atopic Dermatitis\n\n\n\nLeng Leng Tan, AdvMDerm, Nik Aimee Azizah Faheem, MRCP, Winn Hui Han, MRCP, Tharshne \nShanmugam, MBBS, Su-Ming Wong, AdvMDerm\n\n\n\nDivision of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala \nLumpur, Malaysia\n\n\n\nAbstract\nBackground \nTopical corticosteroids are the mainstay of treatment for patients with atopic dermatitis. However, \nadverse effects associated with long-term steroid use often limit its use. This interventional study \ncompared the efficacy of a proprietary moisturiser containing licochalcone A, omega-6 fatty acids, \nand ceramide 3 against 1% hydrocortisone cream in treating patients with mild-to-moderate atopic \ndermatitis. \n\n\n\nMethods\nPatients with mild-to-moderate atopic dermatitis affecting either the cubital fossa or popliteal fossa \nsymmetrically were given twice-daily applications of the moisturiser and hydrocortisone on opposite \nsides of the body and monitored for a total of three weeks in a non-randomised half body, double-\nblind study. Hydrocortisone was switched to aqueous cream after two weeks, whereas the application \nof the moisturiser continued until study completion. The assessment of SCORing Atopic Dermatitis \n(SCORAD) index and Dermatology Life Quality index was performed at baseline and every subsequent \nfollow-up visit to measure patients\u2019 response to treatment. \n\n\n\nResults\nThe licochalcone A (LA) moisturiser and 1% hydrocortisone (HC) cream both demonstrated significant \nreduction in sign and symptom scores after only 1 week of treatment (percentage of reduction in sign \nand symptom scores: 52.8% [LA] vs 58.5% [HC]). Further reduction in mean sign and symptom \nscores for both treatments was observed at week 2 (61.3% [LA] vs 56.8% [HC]) and also at week 3 \nwhen HC was switched to aqueous cream (70.5% [LA] vs 63.5% [HC\u2192aqueous cream]) (p<0.001 \nvs baseline within the same treatment arm at weeks 1, 2 and 3). When comparing the mean difference \nin SCORAD index for both individual as well as total skin signs and symptoms between LA and HC \n(i.e. inter-arm comparison), there was no significant difference between the two treatments for all the \nassessed parameters. Patients reported improvements in itching, sleeplessness, and overall quality of \nlife over the course of treatment. \n\n\n\nConclusion\nThe licochalcone A moisturiser can be considered as an effective steroid-sparing alternative to topical \ncorticosteroids in managing mild-to-moderate atopic dermatitis.\n\n\n\nKey words: Atopic dermatitis; Eczema; Emollient; Licochalcone A; Omega-6 fatty acids; Ceramide 3\n\n\n\nCorresponding Author\nDr Tan Leng Leng \n11, Jalan Teknologi, \nPJU 5, Kota Damansara, \n47810 Petaling Jaya, Selangor Darul Ehsan, \nMalaysia\nEmail: tllktc@hotmail.com\n\n\n\nIntroduction \nAtopic dermatitis (AD, also known as atopic \neczema) is a chronic, recurring inflammatory \nskin condition. The prevalence of AD is \nmost common in childhood with up to 90% \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 49\n\n\n\nof children developing AD by the age of 5 \nyears.1 Although most children achieve disease \nresolution by adulthood, 10\u201330% of patients do \nnot, and a smaller percentage develop symptoms \nas adults.2 Classic signs and symptoms of AD \ninclude dry skin, itching, erythema, erosions, \nlichenification, oozing and crusting. As AD is \noften associated with elevated immunoglobulin \nE (IgE) levels, patients may also present with \ncomorbid conditions related to IgE sensitisation \nsuch as asthma, allergic rhinitis, and food \nallergy. Therefore, AD imposes a substantial \nphysical and psychological burden that can \nnegatively impact the quality of life (QoL) of \npatients and their family.3, 4\n\n\n\nThe aetiology of AD remains unknown, but it has \nbeen postulated that the disease is caused by a \ncomplex interaction of genetic, immunological, \nand environmental factors that leads to altered \nepidermal barrier function.5 Potential triggering \nfactors that can worsen AD include aeroallergen \n(e.g. dust, pollen, animal dander), physical \nirritants (e.g. soaps, detergents, disinfectants), \nfood, as well as patient and environmental \nfactors (e.g. stress, pollution, heat).6\n\n\n\nThe management of AD relies on efficient \ncontrol of flares by treating acute inflammatory \nsymptoms and restoring skin barrier function. \nCurrently, topical corticosteroids (TCS) and \ntopical calcineurin inhibitors (TCI) are the \nmainstay of treatment for disease flares, along \nwith the use of moisturisers to improve skin \nhydration, maintain barrier integrity, and prevent \nnew flare-ups.6 Although TCS is associated with \nsevere adverse effects (AEs) such as skin atrophy, \ntelangiectasia and hypertrichosis, these AEs \ncan be lessened when the duration and strength \nof TCS is used appropriately.7 However, TCS \nis often underutilised owing to patients and/\nor their carers\u2019 steroid phobia, leading to poor \ntreatment adherence and subsequent treatment \nfailure.8\n\n\n\nThe aforesaid drawbacks have thus driven the \nsearch for effective steroid-sparing agents that \ncould be used in the treatment of AD. This \nstudy compared the efficacy of a moisturiser \n\n\n\ncontaining licochalcone A, omega-6 fatty acids \nand ceramide 3 against 1% hydrocortisone \ncream for the treatment of mild-to-moderate \nAD in a small population of Malaysian patients.\n\n\n\nMaterials and Methods\nStudy design and patient population \nThis three-week, non-randomised half body, \ndouble-blind, interventional study was initiated \nto compare the efficacy of a cortisone-, \nfragrance-, colourant- and paraben-free \nmoisturiser containing licochalcone A, omega-6 \nfatty acids and ceramide 3 (LA; Eucerin\u00ae Acute \nCare Cream) against that of 1% hydrocortisone \n(HC) in the treatment of mild-to-moderate AD. \nThe active ingredients in LA were 0.025% \nlicochalcone A, 12% omega-6 fatty acids, \n0.05% ceramide 3, and 10% glycerin, while \nHC contained 1% cortisol (acetate salt of \nhydrocortisone).\n\n\n\nThe study was carried out at the dermatology \nclinic of University Malaya Medical Centre \n(UMMC), Kuala Lumpur, Malaysia between \nNovember 2018 and March 2019. Thirty \npatients aged between 1 and 80 years, who were \ndiagnosed with mild-to-moderate AD based on \nthe United Kingdom working party diagnostic \ncriteria and the modified Hanifin and Rajka \ncriteria, and not on any systemic or topical \ntreatment, were enrolled in the study9; mild-\nto-moderate AD was defined by the SCOring \nAtopic Dermatitis (SCORAD) index score \nrange of 1\u201350.10 To qualify for study enrolment, \npatients were also required to have symmetrical \ninvolvement of skin lesions on both flexural \narea of the body (left and right cubital or \npopliteal fossa). Patients with skin infection and \nknown allergies to any ingredients of the study \ninterventions were excluded.\n\n\n\nOn recruitment, patients were given two white \ncontainers labelled A and B. The content of \ncontainers A and B was applied, twice-daily, \non affected areas of the right and left sides of \npatients\u2019 bodies, respectively. The containers \ncontaining the topical agents were prepared and \ngiven to the patients by a doctor not involved in \nassessing the patients, while the post treatment \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4750\n\n\n\nclinical outcome was assessed by a different \ndermatologist. Container A was filled with LA \nwhile container B was first filled with HC for \ntwo weeks, and then with a lipid-based topical \nformulation cream (AQ) for the remaining \nweek of the study. The switch from HC to AQ \nwas carried out to assess whether symptom \ncontrol can be maintained by AQ (a non-active \nagent) once disease remission has been induced, \nwithout the knowledge of the patient and the \ninvestigators. Oral antihistamine, systemic \nsteroid or immunosuppressant were not used \nby any of the patients during the study period.  \nPatients were required to provide written \nconsent and were free to withdraw from the \nstudy at any time.\n\n\n\nStudy assessments \nClinical outcome post treatment was \ndocumented by digital photography and \nassessed by a modified form of SCORAD.10 \nThe intensity of the disease (i.e. erythema, \noedema, excoriation, lichenification, oozing/\ncrusting, and dryness) was assessed on the \nright and left sides of patients\u2019 bodies and the \ncorresponding scores were documented. Area \nof involvement and subjective symptoms were \nnot included when assessing the right and left \naffected areas. Subjective symptoms, such as \nitch and sleeplessness, were assessed at each \nfollow-up visit throughout the study duration \n(i.e. weeks 1, 2 and 3). QoL was assessed by \nDermatology Life Quality Index (DLQI),11 \na patient-rated questionnaire comprising 10 \nquestions concerning patients\u2019 perception of \nAD\u2019s impact on different aspects of their health-\nrelated QoL. Adverse events were recorded.\n\n\n\nStatistical analysis\nContinuous variables were presented as mean \n(standard deviation), while categorical variables \nwere presented as frequencies and percentages. \nChanges in the SCORAD index of LA- and HC-\ntreated areas were analysed by paired t-test. A \np-value of <0.05 was considered statistically \nsignificant.\n\n\n\nEthics approval statement\nThis study was approved by the Medical \nResearch Ethics Committee of University \n\n\n\nMalaya Medical Centre (approval number: \n42866; 16 June 2018) and was conducted \naccording to the principles of the Declaration of \nHelsinki.\n\n\n\nResults\nPatient characteristics\nA total of 30 patients were enrolled in the study, \nwith 73.3% being younger than 12 years of age \nand 83.3% have had AD for less than 10 years \n(mean duration: 8.35\u00b19.2 years). Many of these \npatients have a family history of atopic diseases, \nparticularly asthma (30%) and AD (30%), as \nwell as a personal history of asthma (30%) and \nfood allergy (30%) (Table 1).\n\n\n\nTable 1. Patient demographics and characteristics\n\n\n\nCharacteristics n (%)\n\n\n\nAge\n\n\n\n1\u20136 years 12 (40.0)\n\n\n\n7\u201312 years 10 (33.3)\n\n\n\n>12 years 8 (26.7)\n\n\n\nGender\n\n\n\nMale 19 (63.3)\n\n\n\nFemale 11 (36.7)\n\n\n\nEthnicity\n\n\n\nMalay 21 (70.0)\n\n\n\nChinese 9 (30.0)\n\n\n\nFamily history\n\n\n\nAsthma 12 (40.0)\n\n\n\nFood allergy 3 (10.0)\n\n\n\nDrug allergy 2 (6.7)\n\n\n\nConjunctivitis 0 (0.0)\n\n\n\nAD 9 (30.0)\n\n\n\nMedical history\n\n\n\nAsthma 9 (30.0)\n\n\n\nFood allergy 9 (30.0)\n\n\n\nDrug allergy 1 (3.3)\n\n\n\nConjunctivitis 2 (6.7)\n\n\n\nChanges in signs and symptoms associated \nwith AD\nBoth LA and HC resulted in a progressive \nimprovement of patients\u2019 mean SCORAD \nindex for total skin signs and symptoms at each \nfollow-up. Compared with the baseline values \nwithin the same treatment arm, both treatments \nshowed comparable reduction in mean sign and \nsymptom scores after one week of treatment \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 51\n\n\n\ninitiation (LA: 52.8% vs HC: 58.5% [percentage \nof reduction from baseline in mean SCORAD \nindex]). At week 2, however, LA showed a \ngreater reduction in mean sign and symptom \nscores compared with HC (LA: 61.3% vs HC: \n56.8%), an observation that continued into \nweek 3 of the study (LA: 70.5% vs HC\u2192AQ: \n63.5%). The mean differences between the \nbaseline SCORAD index value and that \ncalculated at subsequent follow-up visits were \nall significant (p<0.001 for both treatments) \n(Figure 1). Nonetheless, when comparing the \nmean difference in SCORAD index for total skin \nsigns and symptoms between LA and HC (i.e. \ninter-arm comparison), there was no significant \ndifference between the two treatments (LA vs \nHC at baseline, p=0.972; LA vs HC at week 1, \np=0.669; LA vs HC at week 2, p=0.701; LA vs \nHC at week 3, p=0.442). \n\n\n\nAdditionally, when individual symptoms \n(i.e. erythema, oedema, crusting, excoriation, \nlichenification and dryness) were analysed \nseparately, a comparison between LA and \n\n\n\nHC also showed no significant difference in \nSCORAD score reduction for all the assessed \nparameters (Figure 2). As such, LA was shown \nto be non-inferior to standard topical steroid \ntherapy in resolving AD symptoms, especially \nskin erythema, oedema, crusting, excoriation, \nlichenification and dryness within the first week \nof treatment (Figure 3). Of note, one patient \ndeveloped a flare-up of AD after the application \nof LA. \n\n\n\nFigure 1. Mean SCORAD index for total skin signs \nand symptoms after three weeks of treatment with \nLA and HC\n\n\n\n\n\n\n\n5 \n \n\n\n\ntreatments) (Figure 1). Nonetheless, when comparing the mean difference in SCORAD index \nfor total skin signs and symptoms between LA and HC (i.e. inter-arm comparison), there was \nno significant difference between the two treatments (LA vs HC at baseline, p=0.972; LA vs \nHC at week 1, p=0.669; LA vs HC at week 2, p=0.701; LA vs HC at week 3, p=0.442).  \n \nAdditionally, when individual symptoms (i.e. erythema, oedema, crusting, excoriation, \nlichenification and dryness) were analysed separately, a comparison between LA and HC also \nshowed no significant difference in SCORAD score reduction for all the assessed parameters \n(Figure 2). As such, LA was shown to be non-inferior to standard topical steroid therapy in \nresolving AD symptoms, especially skin erythema, oedema, crusting, excoriation, \nlichenification and dryness within the first week of treatment (Figure 3). Of note, one patient \ndeveloped a flare-up of AD after the application of LA.  \n \nFigure 1. Mean SCORAD index for total skin signs and symptoms after three weeks of \ntreatment with LA and HC \n \n\n\n\n\n\n\n\nFigure 2. Inter-arm comparison of disease intensity, as indicated by individual AD symptoms, after three weeks \nof treatment with LA and HC\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4752\n\n\n\nFigure 3. Clinical response shown by patients with AD following treatment with AC and HC\n\n\n\n\n\n\n\nImprovement in itching and sleeplessness\nPatients reported reduced skin itching \nthroughout the study for both treatments. \nLA afforded a greater mean score reduction \nthroughout the study, with a mean difference \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 53\n\n\n\nof 2.04\u00b11.53 at week 1, 2.48\u00b12.12 at week \n2, and 2.84\u00b12.06 at week 3. Meanwhile, HC \nshowed a mean score reduction of 1.96\u00b11.79, \n2.37\u00b12.02, and 2.64\u00b12.16 at weeks 1, 2 and 3, \nrespectively (p<0.001 vs baseline for all data \npoints). Additionally, both treatments showed \nreduced mean score for sleeplessness over a \nperiod of three weeks. The application of either \nLA or HC resulted in a mean score reduction of \n1.96\u00b11.97 at week 1, 2.62\u00b11.52 at week 2, and \n3.26\u00b12.05 at week 3 (p<0.001 vs baseline for all \ndata points).\n\n\n\nImprovement in overall quality of life\nAt baseline, 60% of patients felt that AD had \na very large effect on their QoL (mean score: \n13.00\u00b14.06). However, after three weeks of \ntreatment with either LA or HC, only 12% of the \nstudy participants reported the same degree of \ndisease impact (mean DLQI score: 6.44\u00b15.86; \nmean difference: -6.64\u00b15.86), with close to \nhalf of the study population expressing small to \nno effect at all (48%). DLQI mean scores and \nthe improvement in QoL throughout the study \nduration are shown in Table 2 and Table 3, \nrespectively.\n\n\n\nTable 2. DLQI scoring of patients receiving either \nLA or HC over a period of 2 weeks\n\n\n\nDLQI Baseline\nn=27\n\n\n\nWeek 1\nn=27\n\n\n\nWeek 2\nn=27\n\n\n\nWeek 3\nn=25\n\n\n\nMean score 13.00\u00b14.06 8.74\u00b15.16 7.00\u00b14.48 6.44\u00b15.86\nDifference in \nmean score - -4.62\u00b13.93 -6.00\u00b14.67 -6.64\u00b15.86\n\n\n\n      (p<0.001 vs baseline)\n\n\n\nTable 3. Impact of AD on QoL as measured by \nDLQI\nImpact on QoL \n(DQLI Score)\n\n\n\nBaseline\nn=30 (%)\n\n\n\nWeek 1\nn=27 (%)\n\n\n\nWeek 2\nn=28 (%)\n\n\n\nWeek 3\nn=25 (%)\n\n\n\nNo effect at all \n(0\u20131) - 2 (7.4) 4 (14.3) 6 (24.0)\n\n\n\nSmall effect \n(2\u20135) - 6 (22.2) 8 (28.6) 6 (24.0)\n\n\n\nModerate effect \n(6\u201310) 10 (33.3) 7 (25.9) 8 (28.6) 9 (36.0)\n\n\n\nVery large effect \n(11\u201320) 19 (63.3) 12 (40.0) 8 (29.6) 3 (12.0)\n\n\n\nExtremely large \neffect (21\u201330) 1 (3.3) - - 1 (4.0)\n\n\n\nDiscussion\nPatients in this study were mostly children of \nMalay ethnicity with atopic background and a \nfamily history of atopic disease, which matched \n\n\n\nthe patient demographic of another cross-\nsectional study that reported the prevalence and \nmanagement of AD in Malaysian children.12 \nIncidentally, the same study also revealed that \nparents generally preferred TCS, specifically \nhydrocortisone, over nonprescription drugs in \nAD management. TCS and TCI, along with \nmoisturisers, are the mainstay of treatment \nfor AD in patients requiring pharmacological \nintervention. However, the side effects associated \nwith the persistent use of corticosteroids limit \nits use. These risks, although mostly unfounded, \nhave spurred efforts to seek alternative steroid-\nsparing anti-inflammatory topical agents for the \nmanagement of AD.\n\n\n\nThis study demonstrated that the topical \napplication of LA, a moisturiser containing \nlicochalcone A, omega-6 fatty acids and \nceramide 3, was an effective and safe therapy \nthat is non-inferior to standard topical steroid \ntherapy for the treatment of mild-to-moderate \nAD. These results were consistent with previous \nstudies that demonstrated the efficacy of \nlicochalcone A-based moisturisers, compared \nwith 1% HC creams, in improving the clinical \nmanifestations of AD.13-16\n\n\n\nLicohalcone A is a flavonoid extracted from \nthe Chinese liquorice root, Glycyrrhiza inflata. \nIn vitro studies showed that licochalcone-A \nextracts exhibited potent antibacterial,17 anti-\ninflammatory,18 and immunomodulatory19 \nactivities. Clinical studies have also confirmed \nthe efficacy of licochalcone A-containing \nformulation in reducing erythema18 and skin \nirritations (i.e. dryness, itching, and burning \nsensation).20 Additionally, LA also contains \nceramide which improves skin barrier function \nand prevents transepidermal water loss in \npatients with AD.21 Taken together, the findings \nfrom this study provide new evidence to support \nthe efficacy of licochalcone A as an anti-\ninflammatory agent in the management of mild-\nto-moderate AD.\n\n\n\nItching is a major criterion of AD and is often \nworse at night, leading to a persistent itch-scratch \ncycle that can affect sleep and QoL. Given the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4754\n\n\n\nconsiderable impact of sleep insufficiency on \nmood, health, and development (particularly in \ngrowing children), achieving lasting itch relief \nwith minimal treatment-related side effects is \nan important goal in the management of AD.22, \n\n\n\n23 The management of AD with either LA or \nHC can lead to considerable improvement in \npatients\u2019 overall QoL, as shown by the gradual \nreduction in mean DLQI scores throughout the \nstudy period.\n\n\n\nStrengths and limitations\nIn this study, the side-by-side comparison of \ntreatment efficacy in the same patient reduces the \nrisk of potential errors that could be attributed \nto individual treatment response differences. \nHowever, we acknowledge that this study has \na relatively small sample size and a short study \nperiod.\n\n\n\nConclusion\nThis study demonstrated that a proprietary \nmoisturiser containing licochalcone A, omega-6 \nfatty acids and ceramide 3 as its active ingredients \nwas non-inferior to 1% hydrocortisone cream in \nresolving symptoms associated with acute AD. \nTherefore, it may serve as a valuable steroid-\nsparing therapeutic alternative in the treatment \nof AD.\n\n\n\nConflict of Interest Declaration\nThe authors declare no conflict of interest.\n\n\n\nAcknowledgement\nMedical writing assistance was provided by \nMIMS Medica Sdn Bhd, and complied with \nGood Publication Practice 3 ethical guidelines \n(Battisti et al. Ann Intern Med. 2015; 163: 461\u2013\n4). Medical writing assistance for this article \nhas been funded by Beiersdorf (Malaysia) Sdn \nBhd.\n\n\n\nReferences\n1. Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in \n\n\n\nchildren: Clinical features, pathophysiology, and treatment. \nImmunol Allergy Clin North Am 2015;35:161-83.\n\n\n\n2. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, \nHanifin JM, Simpson EL et al. Guidelines of care for the \nmanagement of atopic dermatitis: section 1. Diagnosis \nand assessment of atopic dermatitis. J Am Acad Dermatol \n2014;70:338-51.\n\n\n\n3. Lifschitz C. The impact of atopic dermatitis on quality of \nlife. Ann Nutr Metab 2015;66 Suppl 1:34-40.\n\n\n\n4. Na CH, Chung J, Simpson EL. Quality of life and disease \nimpact of atopic dermatitis and psoriasis on children and \ntheir families. Children (Basel) 2019;6:133.\n\n\n\n5. Thomsen SF. Atopic dermatitis: Natural history, diagnosis, \nand treatment. ISRN Allergy 2014;2014:354250.\n\n\n\n6. MahTAS. Clinical Practice Guidelines: Management of \nAtopic Eczema 2018. Available at https://www.moh.gov.\nmy/moh/resources/Penerbitan/CPG/Skin%20Condition/\nCPG%20Management%20of%20Atopic%20Eczema.pdf. \nAccessed on 8/1/2021.\n\n\n\n7. Mooney E, Rademaker M, Dailey R, Daniel BS, Drummond \nC, Fischer G et al. Adverse effects of topical corticosteroids \nin paediatric eczema: Australasian consensus statement. \nAustralas J Dermatol 2015;56:241-51.\n\n\n\n8. Li AW, Yin ES, Antaya RJ. Topical corticosteroid phobia \nin atopic dermatitis: A systematic review. JAMA Dermatol \n2017;153:1036-42.\n\n\n\n9. Hanifin JM, Rajka G. Diagnostic features of atopic \ndermatitis. Acta Derm Venereol (Stockh) 1980, 92(suppl): \n44-7.\n\n\n\n10. Severity scoring of atopic dermatitis: the SCORAD index. \nConsensus Report of the European Task Force on Atopic \nDermatitis. Dermatology. 1993;186:23-3.\n\n\n\n11. Finlay AY, Khan GK. Dermatology Life Quality Index \n(DLQI) - a simple practical measure for routine clinical \nuse. Clin Exp Dermatol 1994;19:210-6.\n\n\n\n12. Goh YY, Keshavarzi F, Chew YL. Prevalence of atopic \ndermatitis and pattern of drug therapy in Malaysian \nchildren. Dermatitis 2018;29:151-61.\n\n\n\n13. Angelova-Fischer I, Neufang G, Jung K, Fischer TW, \nZillikens D. A randomized, investigator-blinded efficacy \nassessment study of stand-alone emollient use in mild \nto moderately severe atopic dermatitis flares. J Eur Acad \nDermatol Venereol 2014;28 Suppl 3:9-15.\n\n\n\n14. Udompataikul M, Srisatwaja W. Comparative trial of \nmoisturizer containing licochalcone A vs. hydrocortisone \nlotion in the treatment of childhood atopic dermatitis: A \npilot study. J Eur Acad Dermatol Venereol 2011;25:660-5.\n\n\n\n15. Wananukul S, Chatproedprai S, Charutragulchai W. \nRandomized, double-blind, split-side comparison study of \nmoisturizer containing licochalcone vs. 1% hydrocortisone \nin the treatment of infantile seborrhoeic dermatitis. J Eur \nAcad Dermatol Venereol 2012;26:894-7.\n\n\n\n16. Wananukul S, Chatproedprai S, Chunharas A, \nLimpongsanuruk W, Singalavanija S, Nitiyarom R et \nal. Randomized, double-blind, split-side, comparison \nstudy of moisturizer containing licochalcone A and 1% \nhydrocortisone in the treatment of childhood atopic \ndermatitis. J Med Assoc Thai 2013;96:1135-42.\n\n\n\n17. Tsukiyama R, Katsura H, Tokuriki N, Kobayashi M. \nAntibacterial activity of licochalcone A against spore-\nforming bacteria. Antimicrob Agents Chemother \n2002;46:1226-30.\n\n\n\n18. Kolbe L, Immeyer J, Batzer J, Wensorra U, tom Dieck K, \nMundt C et al. Anti-inflammatory efficacy of Licochalcone \nA: correlation of clinical potency and in vitro effects. Arch \nDermatol Res 2006;298:23-30.\n\n\n\n19. Fontes LB, Dos Santos Dias D, de Carvalho LS, Mesquita \nHL, da Silva Reis L, Dias AT et al. Immunomodulatory \neffects of licochalcone A on experimental autoimmune \nencephalomyelitis. J Pharm Pharmacol 2014;66:886-94.\n\n\n\n20. Broniarczyk-Dy\u0142a G, Prusi\u0144ska-Brato\u015b M, Kmie\u0107 ML. \nAssessment of the influence of licochalcone on selected \nfunctional skin parameters in patients with impaired \nvasomotor disorders and rosacea. Post Dermatol Alergol \n2011;28:241-47.\n\n\n\n21. Chamlin SL, Kao J, Frieden IJ, Sheu MY, Fowler AJ, Fluhr \nJW et al. Ceramide-dominant barrier repair lipids alleviate \nchildhood atopic dermatitis: Changes in barrier function \nprovide a sensitive indicator of disease activity. J Am Acad \nDermatol 2002;47:198-208.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 55\n\n\n\n22. Jeon C, Yan D, Nakamura M, Sekhon S, Bhutani T, Berger \nT et al. Frequency and management of sleep disturbance \nin adults with atopic dermatitis: A systematic review. \nDermatol Ther (Heidelb) 2017;7:349-64.\n\n\n\n23. Ramirez FD, Chen S, Langan SM, Prather AA, McCulloch \nCE, Kidd SA et al. Association of atopic dermatitis with \nsleep quality in children. JAMA Pediatr 2019;173:e190025.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4756\n\n\n\nORIGINAL ARTICLE\n \nThe Clinical Characteristics of Inpatients: An Audit in the Department of \nDermatology Hospital Kuala Lumpur Between 2016 and 2020\n \nGin Peng Chan, MRCP, Suganthi Thevarajah, MMED, Min Moon Tang, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur\n \nAbstract \nBackground\nAlthough Dermatology is primarily a non-acute, outpatient-centered clinical specialty, some of them \nrequire in-patient care for intensive skin management. We aim to describe the demographic data, \nclinical characteristics, and outcomes of Dermatology inpatients in Hospital Kuala Lumpur (HKL).\n\n\n\nMethods\nThis is a retrospective study on all dermatology inpatients in HKL between 2016 and 2020. Data was \nobtained from admission records and further analyzed.\n\n\n\nResults\nA total of 1567 patients were admitted to the Dermatology ward between 2016 and 2020 accounted \nfor 2292 admissions.  The mean age was 45 years (range 8-93). The male to female ratio was 1.16:1. \nThe majority were Malaysian (99.2%). Most Malaysian were Malays (60%) followed by Chinese \n(19.3%) and Indian (17.1%). About 91% of the admissions were arranged from the dermatology \nclinic. The mean length of stay was 5.06 days (range 0-63). About 20% of the patients required \nmultiple admissions. The main dermatological diagnosis requiring inpatient care were non-infective \ndermatoses (60.4%) which included eczematous dermatoses, autoimmune dermatoses, psoriasis, \ncutaneous adverse drug reactions, inflammatory and non-inflammatory dermatoses. This was followed \nby cutaneous infections (24.5%) and drug allergy testing & drug provocation tests (7.9%). About 3% \nof patients were transferred to other departments for further intensive management, and the rest were \ndischarged home well. No mortality occurred in the Dermatology ward.\n\n\n\nConclusion\nThe Dermatology ward HKL managed 2292 admissions between 2016 and 2020. The three main \ndermatological diagnoses requiring intensive skin management were eczematous conditions, cutaneous \ninfections, and autoimmune dermatoses.\n\n\n\nKey words: Dermatology, Inpatients, Eczema, Cutaneous infection, Autoimmune dermatoses\n\n\n\nCorresponding Author\nDr Chan Gin Peng\nDepartment of Dermatology,\nHospital Kuala Lumpur, \nJalan Pahang,\n50586 Kuala Lumpur, Malaysia\nEmail: gpncamel@gmail.com\n\n\n\nIntroduction\nSkin is the outermost part of the human body \nand is subject to a spectrum of skin disorders.1 \nDespite being the largest organ, dermatology \nis primarily a non-acute, outpatient-centered \nclinical specialty.2 However substantial number \nof patients still require in-patient care for \nintensive skin management, advanced nursing \ncare and multispecialty referral. Hospitalization \nimproved patients\u2019 dermatologic disorders and \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 57\n\n\n\ntheir quality of life.3 The Massachusetts General \nHospital was the first hospital to develop its \nfirst dermatology ward in the United States in \n1870.3 This initiative has led to the development \nof inpatient services at many academic \ninstitutions.3 To date, inpatient dermatology is \navailable in the United States (US), the United \nKingdom (UK), Brazil, South Africa, Eastern \nIndia. \n\n\n\nWith the progression and advancement of \ntherapy, the number of patients requiring \ninpatient treatment has reduced.4 In the US and \nUK, many Dermatology programs have reduced \nor abolished inpatient services, whereby patients \nadmitted with dermatological conditions are \nmanaged by non-dermatologists.4,5 Psoriasis, \ncutaneous drug reactions, immunobullous \ndermatoses, infected ulcers and skin infections \nremains the main cause of hospitalization \nworldwide.2 In Malaysia, only Hospital Kuala \nLumpur and Hospital Raja Permaisuri Bainun \nin Ipoh provide inpatient dermatology services \nwith their designated dermatology wards at \npresent. Being the largest hospital in Malaysia, \nthe Department of Dermatology Hospital Kuala \nLumpur (HKL) is a tertiary referral center for \npatients with complex dermatological disorders \nand sexually transmitted infections. The \ndermatology ward, situated at level 1 of the \nAdministration and Financial Block (Bangunan \nPentadbiran dan Kewangan) of Hospital Kuala \nLumpur, has a maximum capacity of 32 beds. \nAll patients admitted to the ward were seen \nby consultant dermatologists and dermatology \ntrainees daily.\n\n\n\nThis study aims to describe the demographic \ndata, clinical characteristics and outcome of \nDermatology inpatients in Hospital Kuala \nLumpur between 2016 and 2020.\n\n\n\nMaterials and Methods\nThis is a retrospective study on all dermatology \ninpatients in HKL between 2016 and 2020. The \nward admission record books were retrieved \nand reviewed. All patients admitted to the \nDermatology ward were included into statistical \nanalysis. Data collected included demographics, \n\n\n\nsource of admission, types of dermatoses, \nnumber of admissions, length of stays and their \noutcomes. Both quantitative and qualitative \ndata were examined using Microsoft Excel and \nfurther analysed through statistical approach. \n\n\n\nResults\nThere was a total of 1567 patients admitted \nto the Dermatology ward in Hospital Kuala \nLumpur during the study period, involving 2292 \nadmissions and 2661 diagnoses were made \nwith an average of 458 admissions per year \nbetween 2016 and 2020. Although dermatology \nward has a maximum capacity of 32 beds, \nthe bed occupancy by patients with pure \ndermatological diseases were intermittently \naffected by temporary lodging of patients from \nother specialities during the study period of \n2016 to 2020. These includes patients from \nthe Department of Urology and others due to \ntemporary closure of the respective wards for \nrenovation and upgrading works. In addition, \nthe strike of pandemic COVID-19 has led \nto a massive increase of in-patient demand \nfor COVID-19 in Hospital Kuala Lumpur. \nAs a result, the bed number catered purely \nfor dermatological diseases has reduced to a \nmaximum 10 beds since March 2020 to date. \nThe demographic characteristics of in-patients \nwith pure dermatological diseases are illustrated \nin Table 1. The youngest patient admitted to \nthe Dermatology ward was 8 years old and the \noldest was 93 years old. The mean age was 45 \nyears with a male to female ratio of 1.16:1. \nNearly half of the patients (49.4%) were aged \nbetween 20-49 years old, and about a third of \nthem (31.3%) were between 50-69 years. \n\n\n\nAmong the Malaysian inpatients, the Malays \ncontributed to 60.1%, followed by Chinese \n19.3%, Indians 17.1% and others, 1.7%. Forty \n(1.7%) patients were foreigners, most of them \nwere Indonesians, 23 (1.0%). The majority of \npatients admitted were male, 1232 (53.8%). \nMost patients (90.7%) were admitted from \nthe dermatology clinic and 143 (6.2%) were \ntransferred from the department of medicine \nor other hospitals to the dermatology ward. \nOnly 3.1% of patients were admitted from \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4758\n\n\n\nthe Department of Accident and Emergency. \nAbout 19.4% of the patients required multiple \nadmissions, of which 11 (0.7%) of them had \nmore than 10 admissions. The average length of \nstay was 5.06\u00b14.95 days with the longest stay of \n63 days. About 4.3% required an inpatient stay \nof more than 2 weeks.\n\n\n\nTable 1. The demographic data of 1567 patients \nadmitted to Dermatology ward Hospital Kuala \nLumpur between 2016 and 2020\n\n\n\nCharacteristics n=1567 (%)\nMean age 45.04\u00b118.79\n\n\n\nGender  Male 1232 (53.8)\n\n\n\nFemale 1060 (46.2)\n\n\n\nMean length of stay (days) 5.06\u00b14.95\n\n\n\nLength of stay \n(days)\n\n\n\n0-7 1903 (83.0)\n\n\n\n8-14 284 (12.4)\n\n\n\n15-21 63 (2.7)\n\n\n\n22-28 18 (0.8)\n\n\n\nMore than 28 days 18 (0.8)\n\n\n\nNo recurrent admission 1263 (80.6)\n\n\n\nRecurrent admission \n(No)\n\n\n\n2 to 5 271 (17.3)\n\n\n\n6 to 10 22 (1.4)\n\n\n\n11 to 15 5 (0.3)\n\n\n\n16 to 20 6 (0.4)\n\n\n\nNumber of \nadmissions per year\n\n\n\n2016 483 (21.1)\n\n\n\n2017 482 (21.0)\n\n\n\n2018 437 (19.1)\n\n\n\n2019 494 (21.6)\n\n\n\n2020 396 (17.3)\n\n\n\nMalaysian -\nEthnicity\n\n\n\nMalay 1377 (60.1)\n\n\n\nChinese 443 (19.3)\n\n\n\nIndian 392 (17.1)\n\n\n\nOthers 40 (1.7)\n\n\n\nForeigner 40 (1.7)\n\n\n\nSource of admission Dermatology \nclinic\n\n\n\n2079 (90.7)\n\n\n\nDepartment of \nMedicine\n\n\n\n121 (5.28)\n\n\n\nAccident & \nEmergency\n\n\n\n70 (3.1)\n\n\n\nOther hospitals 10 (0.43)\n\n\n\nOutcome Discharge home 2229 (97.3)\n\n\n\nTransfer of care 63 (2.7)\n\n\n\nAs shown in Table 2, the main dermatological \ndiagnosis requiring inpatient care were non-\ninfective dermatoses (60.4%) followed by \ninfective dermatoses (24.5%), drug allergy \ntesting and drug provocation tests (7.9%) and \ncutaneous malignancy (1.1%). A hundred \nand sixty-five (6.1%) patients had other \nnon-dermatological diagnoses. Eczematous \ndermatoses were the most frequent non-\ninfective conditions that required admission \nin our cohort. These included severe atopic \ndermatitis, severe contact dermatitis, infected \ndiscoid eczema, idiopathic photodermatitis etc. \nThe main autoimmune dermatoses managed in \ndermatology ward HKL was pemphigus followed \nby cutaneous vasculitis. Psoriasis, cutaneous \nadverse drug reactions, other inflammatory \nand non-inflammatory dermatoses were other \nnon-infective dermatoses that were managed \nin the ward. The type of psoriasis that required \nhospitalization included extensive plaque \npsoriasis, erythrodermic psoriasis, generalized \nor severe localized pustular psoriasis and \nsevere acute psoriatic arthropathy. There was \na total of twenty-nine patients admitted for \nmanagement of cutaneous malignancies, with \nthe majority being mycosis fungoides, followed \nby extramammary Paget\u2019s disease.\n\n\n\nA hundred and thirty patients were admitted \nfor cutaneous adverse drug reactions, of which \nalmost half (51 patients) were due to drug-\ninduced epidermal necrolysis namely Steven \nJohnson syndrome (SJS) and Toxic Epidermal \nNecrolysis (TEN), as shown in Table 3. This \nwas followed by eighteen patients with acute \ngeneralized exanthematous pustulosis (AGEP), \nfourteen with drug rash with eosinophilia and \nsystemic symptoms (DRESS) and seven with \nfixed drug eruptions (FDE). \n\n\n\nInfective dermatoses accounted for nearly \na quarter of the total admissions, with more \nthan half of them being bacterial infection 378 \n(57.8%) as shown in Table 4. This was followed \nby fungal infections 113 (17.3%) and viral \ninfection 105 (16.1%). About 8% of patients \nwere electively admitted for drug allergy skin \ntests and drug provocation test. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 59\n\n\n\nMost patients 2229 (97.3%) were discharged \nhome after treatment and 63 (2.7%) \nwere transferred to other units for further \nmanagement. There was no mortality occurred \nin the dermatology ward for the past 5 years.\n\n\n\nTable 2. The Main types of dermatoses leading to \nadmission to Dermatology ward Hospital Kuala \nLumpur between 2016-2020\n\n\n\nClinical diagnosis n=2661 (%)\n\n\n\nNon infective dermatoses 1608 (60.4)\n\n\n\n   Eczematous dermatoses 687 (42.7)\n\n\n\n   Autoimmune dermatoses 478 (29.7)\n\n\n\n   Psoriasis 215 (13.4)\n\n\n\n   Cutaenous adverse drug reactions 130 (8.1)\n\n\n\n   Inflammatory 86 (5.3)\n\n\n\n   Non inflammatory 12 (0.7)\n\n\n\nCutaneous infections 654 (24.5)\n\n\n\n   Bacterial infection 378 (57.8)\n\n\n\n   Fungal 113 (17.3)\n\n\n\n   Viral 105 (16.1)\n\n\n\n   Mycobacterium 35 (5.4)\n\n\n\n   Parasites 23 (3.5)\n\n\n\nDrug allergy testing and drug provocation \ntests 209 (7.9)\n\n\n\nCutaneous malignancy 29 (1.1)\n\n\n\nMycosis Fungoides 22\n\n\n\nExtramammary Paget\u2019s Disease 4\n\n\n\nAnaplastic Large Cell Lymphoma 1\n\n\n\nGorlin Syndrome 1\n\n\n\nSezary Syndrome 1\n\n\n\nOther non dermatological diagnosis 161 (6.0)\n\n\n\nTable 3. The detailed diagnosis of Non-Infective \ndermatoses that were managed in Dermatology \nward Hospital Kuala Lumpur between 2016-2020 \n\n\n\nType n=1608\n\n\n\nEczematous dermatoses 687\n\n\n\n Eczema \u2013 non erythrodermic 277\n\n\n\n Erythrodermic eczema 204\n\n\n\n Contact dermatitis 133\n\n\n\n Photodermatitis 36\n\n\n\n Dermatomyositis 18\n\n\n\nSeborrhoeic dermatitis, radiation recall \ndermatitis, pompholyx, nodular prurigo, lichen \nsimplex chronicus etc 19\n\n\n\nAutoimmune dermatoses 478\n\n\n\n Pemphigus 246 \n\n\n\n Bullous pemphigoid 90\n\n\n\n Cutaneous vasculitis 103\n\n\n\n Connective tissue diseases 39 \n\n\n\nActive systemic lupus erythematosus/\ncutaneous lupus erythematosus 25\n\n\n\nLinear morphea 11\n\n\n\nMixed connective tissue disease 1\n\n\n\nLupus panniculitis 1\n\n\n\nSystemic sclerosis 1\n\n\n\nPsoriasis 215\n\n\n\nCutaneous adverse drug reactions 130\n\n\n\nStevens-Johnson Syndrome (SJS) 46\n\n\n\nAcute generalized exanthematous pustulosis \n(AGEP) 18\n\n\n\nErythema Multiforme (EM) 18\n\n\n\nDrug Rash with Eosinophilia and Systemic \nSymptoms (DRESS syndrome) 14\n\n\n\nMaculopapular Eruption (MPE) 13\n\n\n\nFixed Drug Eruption (FDE) 7\n\n\n\nToxic Epidermal Necrolysis (TEN) 5\n\n\n\nAngioedema 4\n\n\n\nToxic Erythema 2\n\n\n\nLichenoid dermatitis 2\n\n\n\nAnaphylaxis 1\n\n\n\nInflammatory dermatoses 86\n\n\n\nUrticaria 15\n\n\n\nHydradenitis suppurativa 13\n\n\n\nPyoderma gangrenosum 7\n\n\n\nAlopecia 7\n\n\n\nErythema nodosum 6\n\n\n\nAcne 6\n\n\n\nPityriasis rosea 5\n\n\n\nNetherton syndrome 5\n\n\n\nDarier disease 4\n\n\n\nSweet syndrome 3\n\n\n\nOthers like subcorneal pustular dermatosis, \ngranulomatous cheilitis, pityriasis lichenoides \net varioliformis acuta, Behcet disease, \nlipodermatosclerosis, erythema induratum of \nBazin, paraneoplastic dermatoses (necrolytic \nmigratory erythema), pityriasis rubra pilaris, \ngranulomatous disease, infective vasculitis etc\n\n\n\n15\n\n\n\nNon Inflammatory/Benign tumour 12\n\n\n\nVenous Insufficiency 3\n\n\n\nOthers (melanonychia, fibrokeratoma, patch test \nfor observation, seborrheic keratosis, melasma, \nneurofibromatosis, sebaceous cyst)\n\n\n\n9\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4760\n\n\n\nTable 4. The detailed diagnosis of Infective \ndermatoses that were managed in Dermatology \nward Hospital Kuala Lumpur between 2016-2020\n\n\n\nType of infective dermatoses n=654\n\n\n\nBacterial infections 378\n\n\n\nCellulitis 215\n\n\n\nInfected ulcer 62\n\n\n\nInfected stasis eczema 41\n\n\n\nAbscess 12\n\n\n\nInfected lymphostasis verrucosa cutis 9\n\n\n\nEcthyma 7\n\n\n\nFurunculosis 5\n\n\n\nFolliculitis 4\n\n\n\nImpetigo 3\n\n\n\nInfected Biopsy Wound 3\n\n\n\nInfected Wound 3\n\n\n\nSyphilis 2\n\n\n\nThrombophlebitis 2\n\n\n\nInfected pressure sore 2\n\n\n\nOthers (actinomycosis, bullous impetigo, paronychia, \ngangrene, infected bursitis, genital ulcer, gonorrhoea, \nerysipelas)\n\n\n\n8\n\n\n\nFungal infections 113\n\n\n\nIntertrigo 41\n\n\n\nTinea 36\n\n\n\nOnychomycosis 17\n\n\n\nCandidiasis 12\n\n\n\nSporotrichosis 3\n\n\n\nChromoblastomycosis 2\n\n\n\nPityriasis versicolor 1\n\n\n\nEumycetoma 1\n\n\n\nViral infections 105\n\n\n\nEczema herpeticum 30\n\n\n\nHerpes Zoster 29\n\n\n\nGenital herpes 27\n\n\n\nHerpes Simplex 11\n\n\n\nViral Wart 4\n\n\n\nVaricella zoster 1\n\n\n\nHand Foot Mouth Disease 1\n\n\n\nViral Exanthem 2\n\n\n\nMycobaterium infections 35\n\n\n\nLeprosy 32\n\n\n\nMycobacterium other than tuberculosis 2\n\n\n\nCutaneous tuberculosis 1\n\n\n\nParasite infections 23\n\n\n\nScabies 21\n\n\n\nHead Lice 1\n\n\n\nElephantiasis 1\n\n\n\nDiscussion\nIn-patient care is crucial for a small cohort of \npatients with severe and extensive skin diseases \n\n\n\nwhen topical treatment is complicated. Inpatient \nadmission allows regular clinical and laboratory \nmonitoring, parenteral therapies, advanced \nnursing care and multispecialty referrals.2 \nThese include those with blistering diseases (eg \ntoxic epidermal necrolysis/ Stevens-Johnson \nSyndrome, pemphigus, bullous pemphigoid), \nthose who are frail and disabled as well as those \nwith systemic involvement (eg connective \ntissue diseases, drug reaction eosinophilia with \nsystemic symptoms, cutaneous vasculitis) who \nrequire close monitoring. \n\n\n\nPatients who are ill with their underlying \ndermatosis complicated with a secondary \ninfection will require intravenous antibiotics, \npain management, intravenous fluids and \nnutritional support which is suboptimal when \nmanaged in an outpatient setting.6 Intensive \ntopical treatment and education in the ward \nwill help to improve the disease severity.7 \nEducational sessions including strategies to \nraise patient motivation are vital to maintaining \nimprovement as shown by Masson Regnault et \nal.7 In addition, drug allergy testing and drug \nprovocation test which are laborious and time \nconsuming could be performed comfortably in \nthe dermatology ward in regions where allergy is \na sub-specialty of interest under dermatology. If \nthese patients do not develop systemic reactions \nduring the tests, they could be discharged after \nclose observation for 6-8 hours in the ward. \nOtherwise, observation could be extended \novernight if reactions occurred during the tests.\n\n\n\nUnderstanding the incidence of skin diseases \nis fundamental in making decisions regarding \nallocating resources for clinical care and \nresearch, especially with the introduction \nof the Malaysian Diagnosis Related Group \n(Malaysian DRG) in the Strategic Framework \nof the Medical Programme by the Ministry \nof Health (MOH) for the year 2021-2025.8 \nPopulation-based studies are essential in this \nrespect as an important platform to prepare \nhealthcare system towards evidence-based \nbudget allocation system. Our inpatient services \nencompass medical Dermatology only at \npresent, not aesthetic or dermato-surgery. Our \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 61\n\n\n\nstudy has a male to female ratio of 1.16:1 which \nis similar to that of Sen et al2 in Eastern India and \nGarc\u00eda-Doval et al9 in  Spain, in contrast to that \nof Bertanha et al1 in Brazil, which has a lower \nmale to female ratio, 1:1.72. Like Sen et al2 and \nBertanha et al1, the mean age in our study of \n45.04\u00b118.79, which is much younger than that \nof Garc\u00eda-Doval et al9 and Krisner et al10 in the \nUnited States. This could be explained by the \npattern of dermatoses that contributed to the \nhospitalization. The prevalence of cutaneous \nmalignancies is more prevalent with advanced \nage. The inpatient dermatology unit in Garc\u00eda-\nDoval et al9 and Krisner et al10 comprises of \ndermato-surgery, photochemotherapy and \nskin grafting which cater more to cutaneous \nmalignancy. Specialized dermatology-related \nprocedures like photopheresis, total skin \nelectron beam therapy, Mohs micrographic \nsurgery, skin grafting surgeries, etc are yet to be \nexpanded in our setting. \n\n\n\nLike other studies shown in Table 5, the main \nreasons for hospitalization in our cohort were \nnon-infective dermatoses followed by infective \ndermatoses. Eczematous dermatosis was the \nmost common indication of admission. This \nwas similar to that in Brazil, Australia and South \nAfrica wherein eczema or dermatitis accounted \nfor 17.5-46.6% of the dermatology in-patient \ncare. This is in contrast with Garc\u00eda-Doval \net al9 where 36% of inpatients were surgical \ndermatology cases. Inpatient management of \natopic dermatitis is effective in improving disease \nseverity and should be considered an important \ntreatment option for patients with severe atopic \ndermatitis.7 Only about 1% of our patients \nwere admitted for cutaneous malignancy, far \nlower than the Spain9 and Brazil1 data. Most of \nthe advanced cutaneous malignancies in HKL \nwere managed at the Department of Plastic and \nReconstruction as well as the Department of \nOncology.\n\n\n\nInfective dermatoses was the second most \ncommon dermatoses in our cohort. This is \nconsistent with other studies i.e. Sen et al2 in \nIndia, Garc\u00eda-Doval et al9 in Spain, Krisner et \nal11 in the US. Drug-induced dermatosis is the \n\n\n\nsecond most common cause of admissions after \neczematous dermatosis and papulosquamous \ndisease for Jessop et al11 in South Africa and \nGarc\u00eda-Doval et al9 in Spain.\n\n\n\nOur cohort has the shortest length of stay of \n4.82\u00b14.60 compared to other cohorts. Most \npatients experienced short-term benefits from \ninpatient care and were discharged well. The \nin-patient care services in medical dermatology \ni.e. the setting up of a designated dermatology \nward could be expanded to other dermatology \ncenters in Malaysia.\n\n\n\nThe limitation of our study was stemmed from \nthe nature of the data source. We could not \nassess the complexity of each admission as well \nas the determining factors of the length of stay. \nOur patients may have suboptimal control of \nco-morbidities or develop complications from \nthe treatment which resulted in a prolonged \nstay in the ward. The treatment modalities and \nprocedures done during admission were also \nnot captured from the admission book. Future \naudits on Dermatology inpatients should focus \non the aspects mentioned above as well as the \ncost of inpatient Dermatology care.\n\n\n\nConclusion\nThe Dermatology ward HKL managed \n2292 admissions between 2016 and 2020. \nThe three main dermatological diagnoses \nrequiring intensive skin management were \neczematous conditions, cutaneous infections \nand autoimmune blistering diseases. Standalone \ndermatology inpatient services may be expanded \nto other Department of Dermatology of major \npublic hospitals in Malaysia. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgment\nWe would like to thank the Director General of \nHealth Malaysia for the permission to publish \nthis article.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4762\n\n\n\nReferences\n\n\n\n1. Bertanha F, Nelumba EJ, Freiberg AK, Samorano LP, Festa \nC Neto. Profile of patients admitted to a triage dermatology \nclinic at a tertiary hospital in S\u00e3o Paulo, Brazil. An Bras \nDermatol 2016;91:318-25.\n\n\n\n2. Sen A, Chowdhury S, Poddar I, Bandyopadhyay D. \nInpatient Dermatology: Characteristics of Patients and \nAdmissions in a Tertiary Level Hospital in Eastern India. \nIndian J Dermatol 2016;61:561-4.\n\n\n\n3. Prodanovich S, Kirsner RS, Kerdel FA. Inpatient \ndermatology. A prescription for survival. Dermatol Clin \n2001;19:593-602. \n\n\n\n4. Kirsner RS, Yang DG, Kerdel FA. The changing status of \ninpatient dermatology at American academic dermatology \nprograms. J Am Acad Dermatol 1999;40:755-7. \n\n\n\n5. Ayyalaraju RS, Finlay AY. Inpatient dermatology. United \nKingdom and United States similarities: moving with the \ntimes or being relegated to the back bench? Dermatol Clin \n2000;18:397-404.\n\n\n\n6. Mart\u00ednez-Mor\u00e1n C, Borbujo J. Hospitalization of \nDermatologic Patients: Why, When, and Where? Actas \nDermosifiliogr 2017;108:395-9.\n\n\n\n7. Masson Regnault M, Hegazy S, Konstantinou MP, \nUthurriague C, Bula\u00ef Livideanu C, Tauber M et al. Efficacy \nof hospital inpatient topical treatment for severe adult \natopic dermatitis: a retrospective study of 56 patients. Eur \nJ Dermatol 2017;27:418-9.\n\n\n\n8. Ministry of Health Malaysia. Strategic Framework of \nthe Medical Programme Ministry of Health Malaysia \n2021-2025. Available at https://www.moh.gov.my/moh/\nresources/Pelan_Strategik_KKM.pdf accessed on 28 \nOctober 2021\n\n\n\n9. Garc\u00eda-Doval I, Feal C, Ros\u00f3n E, de la Torre C, Abalde \nMT, Fl\u00f3rez A et al. Inpatient dermatology: characteristics \nof patients and admissions in a Spanish hospital. J Eur \nAcad Dermatol Venereol 2002;16:334-8. \n\n\n\n10. Kirsner RS, Hannon W, Agarwal A, Kerdel FA. The \neffect of health care delivery systems on admission to and \ntreatment at an inpatient dermatology unit. Dermatol Clin \n2000;18:391-5.\n\n\n\n11. Jessop S, McKenzie R, Milne J, Rapp S, Sobey G. Pattern \nof admissions to a tertiary dermatology unit in South \nAfrica. Int J Dermatol 2002;41:568-70.\n\n\n\n12. de Paula Samorano-Lima L, Quit\u00e9rio LM, Sanches JA Jr, \nNeto CF. Inpatient dermatology: profile of patients and \ncharacteristics of admissions to a tertiary dermatology \ninpatient unit in S\u00e3o Paulo, Brazil. Int J Dermatol \n2014;53:685-91.\n\n\n\n13. Bale J, Chee P. Inpatient dermatology: pattern of \nadmissions and patients\u2019 characteristics in an Australian \nhospital. Australas J Dermatol 2014;55:191-5.\n\n\n\nTable 5. Comparison of international data on Dermaology In-patient\n\n\n\n Study, year, \nCountry\n\n\n\nNo of \npatients\n\n\n\nM:F \nratio\n\n\n\nMean age \n(years)\n\n\n\nDiagnosis requiring admission Average length \nof stay (days)\n\n\n\nOutcome\n\n\n\nCurrent study, \nMalaysia\n\n\n\n1567 1.16:1 45.04\u00b118.79 Eczematous dermatoses 35.8%, autoimmune \ndermatoses 18.0%, psoriasis 8.1%, bacterial \ninfection 14.2%, drug induced dermatoses 4.8%, \nfungal infection 4.1%, viral infection 3.9&, \nmalignancy 1.2%\n\n\n\n4.82\u00b14.60 Discharged 97.3%\nTransfer of care \n(2.7%)\n\n\n\nSen et al1 2016 \nEastern India\n\n\n\n375 1.66:1 45.5\u00b12 Immunobullous disorders 24.3%; Erythroderma/\nDermatitis 26.7%; infective disorders 19.5%; drug \nreaction 10.7%; CTD 3.2%; Malignancy 0.53%\n\n\n\n22.16\u00b115.73 Discharged 83.2%\nTransferred of \ncare 2.13%\n\n\n\nde Paula Samorano-\nLima et al12 2014, \nBrazil\n\n\n\n3308 1:1.14 42.8\u00b123.6 Eczema/dermatitis (17.5%), cutaneous infections \n(15.9%), immunobullous diseases (11.0%), \nconnective tissue diseases (9.6%), psoriasis \n(9.2%).\n\n\n\n13 3.7% transferred \nto ICU, 2.5% died\n\n\n\nBale et al13 2014, \nAustralia\n\n\n\n97 1.27:1 42 Dermatitis or eczema (37%), ulcers (12%) 10 N/A\n\n\n\nBertanha et al1  2016  \nBrazil\n\n\n\n16,399 1:1.72 43.9\u00b122.1 Eczematous dermatoses 18.1%; cutaneous \ninfection 13.1%; erythematous squamous \ndermatosis 6.9%; malignancy 6.1%\n\n\n\nN/A No mortality\n\n\n\nI Garc\u00eda-Doval et al9 \n\n\n\n2002 Spain\n1048 1.05:1 66 neoplasm 36%; infection 15%; psoriasis 10%; \n\n\n\ndermatitis 6%; drug reaction 5%\n7(5-10) 0.76% mortality\n\n\n\nJessop S et al11 2002 \nSouth Africa\n\n\n\n133 N/A 34.1 Atopic dermatitis 33.1%; Other forms of \ndermatitis 13.5%; Psoriasis 15.8%; Severe drug \nreactions 7.5%; Leg ulcer5.3%; Skin infection \n5.3%; Bullous disease 4.5%\n\n\n\nN/A N/A\n\n\n\nKirsner et al10 2000 \nUS\n\n\n\n345 NA 60.7 Psoriasis (25%), chronic wounds (23%), \ndermatitis (11%), infections or infestations (10%), \nconnective tissue diseases (9%), Immunobullous \ndiseases (7%), drug reaction (3%)\n\n\n\n6.1\u00b10.2 NA\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 63\n\n\n\nORIGINAL ARTICLE\n\n\n\nThe Effect of Narrowband Ultraviolet B Phototherapy on Vitamin D Status in \nPsoriasis Patients with Skin Phototype III, IV and V\n\n\n\nRani Manohari Kuppusamy1, MRCP, Adawiyah Jamil2, AdvMDerm, Nazatul Shima1, AdvMDerm\n\n\n\n1Dermatology unit, Department of Medicine, Hospital Putrajaya, Wilayah Persekutuan Putrajaya, \nMalaysia\n2Dermatology unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, \nWilayah Persekutuan Kuala Lumpur, Malaysia\n\n\n\nAbstract\nBackground\nNarrowband ultraviolet-B (NBUVB) is an effective treatment option for psoriasis. Vitamin D \ninsufficiency is common in psoriasis patients. We assessed the effect of NBUVB on vitamin D levels \namongst psoriasis patients with skin phototype III, IV and V.\n\n\n\nMethods\nPsoriasis patients planned for NBUVB phototherapy were enrolled in a prospective cohort study in \nHospital Putrajaya and Hospital Kuala Lumpur from May 2020-December 2020. NBUVB phototherapy \nwas given twice weekly for 12 weeks. Serum 25 (OH)D level was measured at baseline and at week \n12. \n\n\n\nResults\nA total of 21(63.6%) male and 12(36.4%) female patients aged 18-66 years participated. Majority were \nFitzpatrick skin phototype (FSP) IV (66.7%) followed by FSP V (21.2%) and FSP III (12.1%). Serum \n25(OH)D increased significantly (p<0.001) from 52.09\u00b121.43 nmol/L at baseline to 72.80\u00b119.56 \nnmol/L at week 12 with the most increment seen in skin type V. There was also a significant improvement \nseen in Body Surface Area (BSA) involvement after 12 weeks of phototherapy (p<0.001). There was \nno correlation seen between BSA at week 12 with serum 25(OH)D and percentage of serum 25(OH)\nD increment.\n\n\n\nConclusion\nNBUVB phototherapy increases the level of serum 25(OH)D in psoriasis patients with darker skin \ntypes while simultaneously clearing psoriasis.  \n\n\n\nKey words: 25-hydroxyvitamin D; Fitzpatrick skin phototype; Psoriasis; Narrowband Ultraviolet-B; \nPhototherapy\n\n\n\nCorresponding Author\nDr Rani Manohari Kuppusamy\nDepartment of Dermatology, \nHospital Putrajaya,\nJalan P9, Presint 7, \n62250 Putrajaya, \nWilayah Persekutuan Putrajaya, Malaysia.\nEmail: rani.manohari@gmail.com\n\n\n\nIntroduction\nPsoriasis is an immune-mediated inflammatory \nskin disease which occurs worldwide and is \nestimated to affect around 2.0% to 3.0% of the \nworld\u2019s population.1,2 Epidemiological evidence \ndemonstrated variable prevalence of psoriasis \namongst different ethnic groups and population.3 \n\n\n\nThe Malaysian Psoriasis Registry recorded a \ntotal of 21,735 psoriasis patients aged \u226518 years \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4764\n\n\n\nfrom January 2007 through December 2018.4\n\n\n\nNarrowband ultraviolet-B (NBUVB) \nphototherapy is an effective and safe treatment \nfor psoriasis. NBUVB reverses several \npathologic alterations in psoriasis which \nultimately causes reduction in T-lymphocytes \nand dendritic cells.5 Inhibition of maturation, \ndifferentiation and migration of dendritic cells \nare caused by activation of vitamin D. The \nepidermis plays an important role in vitamin D \nsynthesis but is also a target tissue for activated \nvitamin D and its analogues. The active \nform of vitamin D 1,25 dihydroxyvitamin D \n[1,25(OH)2D] produced by hydroxylation in the \nliver and kidney suppresses growth and induces \ndifferentiation of keratinocytes, thus reducing \npsoriasis severity.  The radiation wavelength \nof NBUVB (from 311 to 313 nm), lies within \nthe action spectrum responsible for cutaneous \nvitamin D\u2083 production.5 Psoriatic lesions respond \nwell to narrowband ultraviolet B phototherapy.6 \n\n\n\nNBUVB positively affects vitamin D status7,8,9,10 \n\n\n\nand this could partly account for the beneficial \neffect of phototherapy in psoriasis. \n\n\n\nSkin phototype determines response to UVB \nradiation, with a greater rate of vitamin D3 \nsynthesis in lighter skin tones as melanin \nabsorbs UVB irradiation.11 Therefore, people \nwith naturally darker skin are at greater risk of \nvitamin D deficiency. Increase in serum vitamin \nD\u2083 levels as well as improvement in Psoriasis \nArea and Severity Index (PASI) have been \ndemonstrated after NBUVB therapy.8,9,10\n\n\n\nOur study was conducted to assess the effect of \nNBUVB on vitamin D levels amongst psoriasis \npatients of darker skin types (Fitzpatrick skin \nphototype III, IV and V), its association with \nimprovement in body surface area (BSA) \naffected by psoriasis as well as the correlation \nbetween cumulative NBUVB dose and the \nimprovement in serum 25(OH)D.\n\n\n\nMaterials and Methods\nAn observational cohort study was performed. \nThe study population was psoriasis patients \nplanned for NBUVB phototherapy at the \n\n\n\nDermatology Clinics of Hospital Putrajaya \nand Hospital Kuala Lumpur who fulfilled the \ninclusion and exclusion criteria during the study \nperiod from May 2020 to December 2020. \nInclusion criterion was psoriasis patients aged \n18 and above with Fitzpatrick skin phototype III, \nIV or V. Patients with renal or hepatic disease, \nprevious skin malignancy, on vitamin D or \ncalcium supplements were excluded. Psoriasis \nseverity was defined by percentage of BSA \naffected by psoriasis based on the Malaysian \nClinical Practice Guideline for the Management \nof Psoriasis Vulgaris; mild \u226410%, moderate \n>10%-30% and severe >30%.12 \n\n\n\nSerum 25(OH)D was measured at baseline \nprior to NBUVB therapy and after 12 weeks \nof therapy. NBUVB wasdelivered using either \nDaavlin 3 Series or MEDLight N-LINEpro \ncabins. Irradiation protocol was based on the \npatient\u2019s skin type. The irradiation dose started \nat 0.3J/cm2andwas increased by 20% on each \nsubsequent visit till just perceptible erythema \nappeared on uninvolved skin. If symptomatic \nerythema (burning, pain) developed, \nphototherapy was stopped till the erythema \nsettled. On restarting therapy, the irradiation \ndose was decreased by 20%. The dose delivered \nfor each session was documented in a standard \nform. Phototherapy was given twice weekly \non non-consecutive days for 12 weeks. Each \nphototherapy session was approximately \nbetween 10 to 15 minutes. The genitals were \nshielded and eyes were protected with UV \nsafety glasses. If any patient had a gap in his/\nher phototherapy session of more than a week, \nthe date for serum 25 (OH)D was postponed \nappropriately. \n\n\n\nSerum 25(OH)D levels were obtained using \nUniCelDxI 800 Access Immunoassay System \nwhich is a chemiluminescent based automated \nanalyser, that accurately and precisely measures \n25(OH)D. Levels of 25-OH vitamin D3 were \ngraded as: deficient <25 nmol/L, insufficient \n25\u201374 nmol/L, and normal 75\u2013250 nmol/L.13\n\n\n\nSample size estimation was calculated using \ntwo population means formulae.14 Mean \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 65\n\n\n\ndifference in vitamin D levels pre and post \nNBUVB phototherapy was based on the \nresults of Ryan et al.9 Serum vitamin D prior to \nNBUVB therapy was 23\u00b137 nmol/L, the level \npost treatment increased to 59\u00b1 80.0 nmol/L. A \nminimum sample size of 30 was needed to be \nable to reject the null hypothesis with probability \n(power) 0.8 and 10% drop out rate. The Type I \nerror probability in rejecting the null hypothesis \nis 0.05. Data analysis was performed using IBM \nSPSS Statistics for Windows Version 22.0. \n\n\n\nComparison of the differences between two \nsets of normally distributed numerical data was \nanalysed using paired t-test, while the Wilcoxon \nSignedRank test was used if the data was not \nnormally distributed. Pearson or Spearman \nrank correlations, where appropriate, were \ncalculated. All probability values are two-sided, \nand a level of significance of less than 0.05 \n(p-value < 0.05) was considered as statistically \nsignificant.\n\n\n\nThis study was conducted in compliance with \nethical principles outlined in the Declaration of \nHelsinki and Malaysian Good Clinical Practice \nGuidelines. Data collection was commenced \nafter obtaining Medical Research and Ethics \nCommittee approval (Approval Ref : KKM/\nNIHSEC/P20-798(12). \n\n\n\nResults\nA total of 33 subjects were recruited, 30 patients \ncompleted 12 weeks of NBUVB phototherapy. \nThree patients defaulted treatment and follow \nup due to logistical difficulties caused by the \nCOVID-19 pandemic. There were 12 (36.4%) \nmale patients and 21 (63.6%) female patients \nwith a male to female ratio of 4:7. The patients\u2019 \nmean age was 37.00\u00b112.52, with a range of 18\u2013\n66 years. The majority of patients were Malay \n29 (87.9%) followed by Chinese 3 (9.1%) and \nIndian 1 (3.0%). There were 4 (12.1%) patients \nwith Fitzpatrick skin phototype (FSP) III, \n22(66.7%) with FSP IV, and 7 (21.2%) with \nFSP V. Duration of disease ranged between 2 \nand 34 years with a median of 12 years. The \nmean body surface area (BSA) at baseline \nwas 30.39\u00b122.07%. The majority of patients, \n\n\n\n16 (48.5%) had minimal sun exposure having \nspent less than 1 hour under the sun per week. \nMilk consumption was notably low with only a \nmedian value of 1 cup per week. Table 1 shows \nthe demographic and clinical characteristics of \nthe study population.\n\n\n\nTable 1. Demographic and clinical characteristics of \nthe study population (n=33)\n\n\n\nParameters n(%)\n\n\n\nAge, (years); mean\u00b1SD 37.0\u00b112.5\n\n\n\nAge, (range) 18 - 66\n\n\n\nGender \n\n\n\n  Male 21 (63.6)\n\n\n\n  Female 12 (36.4)\n\n\n\nRace\n\n\n\n  Malay 29 (87.9)\n\n\n\n  Chinese  3 (9.1)\n\n\n\n  Indian 1 (3.0)\n\n\n\nFitzpatrick skin phototype\n\n\n\n  III 4 (12.1)\n\n\n\n  IV 22 (66.7)\n\n\n\n  V 7 (21.2)\n\n\n\nDuration of psoriasis, (years) 8.0 (12.0)*\n\n\n\nDuration of psoriasis (range) 2-34\n\n\n\nTotal body surface area (BSA), (%); mean\u00b1SD 30.4\u00b122.1\n\n\n\nTotal BSA (range) 5-80\n\n\n\nPsoriasis Severity\n\n\n\nMild (<10% BSA) 5 (15.2)\n\n\n\nModerate (10-30 BSA) 16 (48.5)\n\n\n\nSevere ( >30% BSA) 12 (36.4)\n\n\n\nSun exposure, (hours per week)\n\n\n\n< 1 hour 16 (48.5)\n\n\n\n  1-2 hours 11 (33.3)\n\n\n\n> 2 hours 6 (18.2)\n*Median (IQR)\n\n\n\nSerum 25(OH)D and psoriasis severity at \nbaseline and after 12 weeks of NBUVB therapy \nis tabulated in Table 2. At baseline, 2(6.7%) \npatients were 25(OH)D deficient, 23(76.7%) \npatients had insufficient levels and 5(16.7%) \nhad normal 25(OH)D levels. The mean \n25(OH)D level at baseline was 52.09\u00b121.43 \nnmol/L. After 12 weeks of NBUVB therapy, \n16(53.3%) patients achieved normal 25(OH)\nD levels whilst 14(46.7%) had insufficient \nlevels. None of the patients were 25(OH)D \ndeficient. There was a statistically significant \ndifference between baseline and week 12 serum \n25(OH)D values (52.09\u00b121.43 vs 72.80\u00b119.56, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4766\n\n\n\np=<0.001). Psoriasis severity measured as BSA \nsignificantly improved with NBUVB. Median \nvalue for baseline BSA was 20 (30%) vs 15 \n(13%) at week 12 with p value =<0.001.\n\n\n\nTable 2. Serum 25(OH)D and psoriasis severity at \nbaseline and after 12 weeks of NBUVB therapy (n \n= 30)\n\n\n\nParameter Baseline Week 12 p value\n\n\n\nSerum 25 (OH)D, mean\u00b1SD 52.1\u00b121.4 72.8\u00b119.6 <0.001a\n\n\n\nDeficient (<25nmol/L), n (%) 2 (6.7) 0 (0.0)\n\n\n\n<0.001b\nInsufficient (25-74nmol/L), \nn (%) 23 (76.7) 14 (46.7)\n\n\n\nNormal(75- 250nmol/L), n (%) 5 (16.7) 16 (53.3)\n\n\n\nPsoriasis severity\n\n\n\nTotal body surface area, % 20 (30.0) 15 (13.0) <0.001c\n\n\n\nMild, n (%) 5 (16.7) 11 (36.7)\n\n\n\n0.002bModerate, n (%) 16 (53.3) 17 (56.7)\n\n\n\nSevere, n (%) 9 (30.0) 2 (6.7)\n\n\n\nFitzpatrick Skin phototype\n\n\n\nIII  (n =4), median(IQR) 50.9 (25.0) 58.8 (28.3) 0.144 c\n\n\n\nIV  (n =21), mean\u00b1SD 50.5\u00b121.8 72.6\u00b121.8 <0.001a\n\n\n\nV   (n =5), mean\u00b1SD 56.7\u00b127.7 79.9\u00b18.1 0.109 a\n\n\n\nData was analysed with aPaired t test, b Stuart-Maxwell Marginal \nHomogeneity, c Wilcoxon Signed Rank test, *Median (IQR)\n\n\n\nTable 3 presents the effects of Fitzpatrick skin \nphototype (FSP) on 25(OH)D levels following \nNBUVB therapy. The results reveal an increase \nin 25(OH)D levels in all the skin types following \nphototherapy with the most prominent increase \nseen in FSP V. \n\n\n\nThere was no correlation seen between psoriasis \nseverity (week 12 BSA) with week 12 serum \n25(OH)D, cumulative NBUVB dose and \npercentage of 25(OH) D increment. The above \ndata is presented in Table 4. \n\n\n\nTable 3. Effect of Fitzpatrick skin phototype on \n25(OH)D increment following NBUVB therapy\n\n\n\nFitzpatrick Skin \nPhototype\n\n\n\n% Increment of 25(OH)D\nMedian (IQR) p value\n\n\n\nIII 23.9 (36.7)\n\n\n\n0.796aIV 22.9 (101.5)\n\n\n\nV 23.4 (179.3)\n\n\n\nData analysed with aKruskal-Wallis test\n\n\n\nTable 4. Correlations between psoriasis severity \n(week 12 BSA) with serum 25(OH)D and \ncumulative NBUVB dose and percentage of 25(OH)\nD increment\n\n\n\nParameter r value p value\n\n\n\nWeek 12 serum 25(OH)D 0.221 0.241\n\n\n\nCumulative NBUVB dose 0.176 0.353\n\n\n\nPercentage of 25(OH)D increment 0.290 0.120\n\n\n\nData analysed with Spearman\u2019s Rho Correlation test\n\n\n\nThere was also no correlation between \ncumulative NBUVB dose with serum 25(OH)D \nand percentage of 24(OH)D increment. (Table \n5)\n\n\n\nTable 5. Correlations between cumulative NBUVB \ndose with serum 25(OH)D and percentage of \n25(OH)D increment\n\n\n\nParameter r value p value\n\n\n\nWeek 12 serum 25(OH)D 0.069 0.717\n\n\n\nPercentage of 25(OH)D increment -0.102 0.593\n\n\n\nData analysed with Spearman\u2019s rho test\n\n\n\nSpearman\u2019s Rho Correlation test was also used \nto assess the correlation between percentage \nBSA improvement with percentage of 25(OH)\nD increment. We found no correlation with p= \n0.585 and r = -0.104.\n\n\n\nAdverse events such as dry skin 14(46.7%) and \nfolliculitis 1(3.0%) were reported. These were \nmild however, and did not require NBUVB \ndose adjustment or cessation of therapy. \n\n\n\nDiscussion\nVitamin D status of patients with psoriasis\nVitamin D insufficiency is common in patients \nwith psoriasis and there is a correlation between \npsoriasis severity with vitamin D deficiency.15 \nA meta-analysis demonstrated that circulating \n25(OH)D levels are lower in patients with \npsoriasis, and a small but significant negative \ncorrelation exists between 25(OH)D levels \nand psoriasis severity.16 Pitukweerakulet al \nalsofound a significant relationship between low \n25(OH)D levels and psoriasis.17 In agreement to \nthis, the majority (75.8%) of our patients in our \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 67\n\n\n\nstudy also had insufficient levels of 25(OH)D.\nWe observed that serum 25(OH)D level in our \ncohort was lower than that from the northern \nlatitudes.9 This is likely related to darker skin \ntones that function as natural sun protection \nand require at least three to five times longer \nexposure to make the same amount of vitamin \nD as a person with fairer skin tone.18 Another \ncontributing factor could be inadequate sun \nexposure as the majority of our patients reported \nless than 1 hour of sun exposure per week. \n\n\n\nThe effect of NBUVB phototherapy on serum \n25(OH)D in psoriasis patients \nNBVUB phototherapy is a well-recognized \nstandard treatment for psoriasis. The skin \nproduces around 85% of total vitamin D. The \nrest is obtained from dietary sources such as \nfortified foods, eggs and oily fish. Our study \nconfirms the results of several studies showing \nthat NBUVB significantly increases serum \n25(OH)D in patients with psoriasis.9,10,11 NB-\nUVB and UVA/UVB phototherapy significantly \nincreased 25(OH)D serum level in patients \nwith psoriasis and atopic dermatitis in Western \nAustralia.19\n\n\n\nTwelve NBUVB exposures within 4 weeks \nincreased serum 25(OH)D concentration \nsignificantly more than 20\u03bcg of oral \ncholecalciferol daily.20 Significantly greater \nincrease in serum 25(OH)D was seen among \nNBUVB treated individuals compared to those \ntreated with the oral vitamin D3.21 Our study \ndemonstrated improvement in serum 25(OH)D \nfollowing NBUVB therapy in psoriasis patients \nwith FSP III, IV or V living in a tropical country. \n\n\n\nThe effect of skin phototypes on phototherapy \ninduced increment of serum 25(OH)D\nThere is limited and conflicting information \nrelating to the effect of NBUVB therapy on \nvitamin D levels in psoriasis patients with \ndarker skin tones, in particular FSP III, IV and \nV. UV transmission is obstructed by melanin, \nthus dark skinned individuals are thought to be \nless capable of vitamin D synthesis compared \nto fair-skinned subjects. Vitamin D status is also \nknown to differ between geographical latitudes. \n\n\n\nIn our study, the majority of patients with darker \nskin had vitamin D deficiency. Armas et al \nreported similarly low levels of 25-OH-D with \ndarker skin.11 We found an increment in serum \n25(OH)D among all FSP (III, IV and V) after \n12 weeks of NBUVB therapy, the difference in \nserum 25(OH)D increment between all FSP was \nnot significant. The mean value of serum 25(OH)\nD at baseline and after 12 weeks was significant \nfor FSP IV. This could be due to a larger sample \nsize as FSP IV had 21 patients, compared to FSP \nIII (4) and FSP V (5) respectively. \n\n\n\nFSP is most likely not a significant predictor of \nchange in vitamin D level as reported by Ryan \net al in a cohort where the majority of patients \nwere of FSP III.9 This was in contrast to Libon \net al in study comparing serum 25(OH)D levels \nafter a single UVB exposure in fair (FSP II\u2013\nIII) and black skinned (FSP VI) volunteers.22 \n\n\n\nThe study found that on day 6 post single \nUVB exposure, serum 25(OH)D levels of fair \nskinned volunteers increased significantly, but \nnot in black-skinned people suggesting that skin \npigmentation negatively influences vitamin D \nsynthesis.\n\n\n\nRelationship between cumulative NBUVB \ndose with improvement in serum 25(OH)D\nRyan et al. found the number of NBUVB \nexposures was the sole predictor of increase \nin serum 25(OH)D level.9 Those with greater \nnumber of exposures had a significantly higher \nserum 25(OH)D level, most likely produced by \nmore prolonged exposure to NBUVB. We found \nno correlation between cumulative NBUVB \ndose with improvement in serum 25(OH)\nD at week 12. The number of phototherapy \nsessions/ NBUVB exposures rather than the \ncumulative NBUVB dose may be associated \nwith improvement of serum 25(OH)D. Further \nresearch is required to confirm this association.\n\n\n\nRelationship between improvement in serum \n25(OH)D with reduction in psoriasis severity \n(body surface area affected by psoriasis)\nNBUVB increases serum 25(OH)D levels in \ninflammatory skin conditions.8,9,10,17There is \nlittle data on the effect of NBUVB on 25(OH)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4768\n\n\n\nD serum levels alongside severity of psoriasis. \nOur results support previous observations that \nNBUVB increases 25(OH)D levels in psoriasis \npatients and decreases the severity of psoriasis. \nGupta et al showed significant improvement in \nPsoriasis Area and Severity Index (PASI) as well \nas serum 25(OH)D (p < 0.05).10 Ryan et al. also \nfound serum 25(OH)D increased significantly \nwith significant improvement in PASI at the end \nof NBUVB treatment.9As minimal as 2 weeks \nof NBUVB treatment resulted in significant \nincrease of 25(OH)D3 serum concentration.23\n\n\n\nWe found significant improvement of BSA and \nincrease in serum 25(OH)D levels after the \ncompletion of treatment. There was however, no \ncorrelation between psoriasis severity at week \n12 with serum 25(OH)D or percentage of serum \n25(OH)D increment. This is similar to a previous \nstudy, whereby the improvement in PASI as well \nas increase in serum 25(OH)D levels after 12 \nweeks of NBUVB were significant. However, \ncorrelation between PASI and 25(OH)D was \nweak and was statistically insignificant.10 Ryan \net al also found no correlation between change \nin serum 25(OH)D levels and change in PASI \nbut the change in the PASI correlated with \ncumulative dose of phototherapy.9 \n\n\n\nOur study had several limitations. There was no \ncontrol arm for comparison, however baseline \nand end of therapy were obtained to demonstrate \nimprovement in vitamin D. A few factors \ninfluencing 25(OH)D levels such as dietary \nvitamin D intake and body mass index were \nnot recorded or adjusted during the analysis.24 \nBody surface area affected (BSA) was used to \nrepresent psoriasis severity, BSA is routinely \nused in clinical practice however Psoriasis Area \nand Severity Index (PASI) is the validated gold \nstandard.\n\n\n\nConclusion\nNBUVB therapy resulted in a significant rise in \n25(OH)D levels amongst psoriasis patients of \nFSP III, IV and V with significant improvement \nin psoriasis severity. There was no correlation \nbetween cumulative NBUVB dose and \nimprovement in serum 25(OH)D. Vitamin D \n\n\n\nlevel is most likely not an important predictor \nin improvement of psoriasis after NBUVB \ntreatment as there was no correlation between \nBSA improvement and increment of serum \n25(OH)D level.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n\n\n\n1. Hayes J, Koo J. Psoriasis: Depression, anxiety, smoking, \nand drinking habits.       Dermatol Ther 2010;23(2):174-80. \n\n\n\n2. Springate A, Parisi R, Kontopantelis E, Reeves D, Griffiths \nCE, Ashcroft DM.   Incidence, prevalence and mortality \nof patients with psoriasis: a U.K. population-based cohort \nstudy. Br J Dermatol 2017;176:650-8. \n\n\n\n3. Perera GK, Di Meglio P, Nestle FO. Psoriasis. Annu Rev \nPathol 2012;7:385-422.\n\n\n\n4. Robinson S, Tang MM, Ramalingam R, Voo SYM, Kwan \nZ, Thevarajah S. The Tenth Report of the Malaysian \nPsoriasis Registry 2007-2018, Kuala Lumpur, Malaysia. \n\n\n\n5. Walters IB, Ozawa M, Cardinale I, Gilleaudeau P, \nTrepicchio WL, Bliss J et al. Narrowband (312-nm) \nUV-B suppresses interferon gamma and interleukin (IL) \n12 and increases IL-4 transcripts: differential regulation \nof cytokines at the single-cell level. Arch Dermatol \n2003;139(2):155-61.\n\n\n\n6. Parrish JA, Jaenicke KF. Action spectrum for phototherapy \nof psoriasis. J Invest Dermatol 1981;76:359-62.\n\n\n\n7. Czarnecki D. Narrowband ultraviolet B therapy is an \neffective means of raising serum vitamin D levels. Clin \nExp Dermatol 2008 Mar;33:202.\n\n\n\n8. Osmancevic A, Landin-Wilhelmsen K, Larko O, \nWennberg AM, Krogstad AL.    Vitamin D production \nin psoriasis patients increases less with narrowband than  \nwith broadband ultraviolet B phototherapy. Photodermatol \nPhotoimmunol Photomed 2009;25:119-23. \n\n\n\n9. Ryan C, Moran B, McKenna MJ, Murray BF, Brady J, \nCollins Pet al. The effect of narrowband UV-B treatment \nfor psoriasis on vitamin D status during wintertime in \nIreland. Arch Dermatol 2010;146:836-42.\n\n\n\n10. Gupta A, Arora TC, Jindal A, Bhadoria AS. Efficacy of \nnarrowband ultraviolet B phototherapy and levels of \nserum vitamin D3 in psoriasis: A prospective study. Indian \nDermatol Online J 2016;7:87-92. \n\n\n\n11. Armas LA, Dowell S, Akhter M, Duthuluru S, Huerter C, \nHollis BW et al. Ultraviolet-B radiation increases serum \n25-hydroxyvitamin D levels: The effect of UVB dose and \nskin color. J Am Acad Dermatol 2007;57:588-93.\n\n\n\n12. Choon S, Chan L, Choon SE, Jamil A, Chin CL, Cheng \nCH et al. Malaysian Clinical Practice Guideline for \nthe Management of Psoriasis Vulgaris: Summary of \nrecommendations for management in primary healthcare \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 69\n\n\n\nsetting. Malays Fam Physician 2014;9:16-21.\n13. Holick MF. Vitamin D status: measurement, interpretation, \n\n\n\nand clinical application. Ann Epidemiol 2009;19:73-8.\n14. Lemeshow S, Hosmer D, Klar J, Lwanga SK, WHO. \n\n\n\nAdequacy of sample size in health studies. Retrieved from \nhttp://apps.who.int/iris/handle/10665/41607. Accessed\n\n\n\n15. Al-Dhubaibi MS. Association between Vitamin D \ndeficiency and psoriasis: An exploratory study. Int J Health \nSci (Qassim) 2018;12:33-9.\n\n\n\n16. Lee YH, Song GG. Association between circulating \n25-hydroxyvitamin D levels and psoriasis, and correlation \nwith disease severity: a meta-analysis. Clin Exp Dermatol \n2018;43:529-35.\n\n\n\n17. Pitukweerakul S, Thavaraputta S, Prachuapthunyachart S, \nKarnchanasorn R. Hypovitaminosis D is Associated with \nPsoriasis: A Systematic Review and Meta-Analysis. Kans \nJ Med 2019;12:103-8.\n\n\n\n18. Lehmann B, Knuschke P, Meurer M. The UVB-induced \nsynthesis of vitamin D3 and 1alpha,25-dihydroxyvitamin \nD3 (calcitriol) in organotypic cultures of keratinocytes: \neffectiveness of the narrowband Philips TL-01 lamp (311 \nnm). J Steroid Biochem and Mol Biol 2007;103:682-5.\n\n\n\n19. Le P, Tu J, Gebauer K, Brown S. Serum 25-hydroxyvitamin \nD increases with NB-UVB and UVA/UVB phototherapy \nin patients with psoriasis and atopic dermatitis in Western \nAustralia. Australas J Dermatol 2016;57:115-21.\n\n\n\n20. Ala-Houhala MJ, Karppinen T, V\u00e4h\u00e4vihu K, Kautiainen, \nDombrowski Y, Snellman E et al. Narrow-band ultraviolet \nB treatment boosts serum 25-hydroxyvitamin D in patients \nwith psoriasis on oral vitamin D supplementation. Acta \nDermato-Venereologica 2014;94:146-51.\n\n\n\n21. Bogh MK, Gullstrand J, Svensson A, Ljunggren B, Dorkhan \nM. Narrowband ultraviolet B three times per week is more \neffective in treating vitamin D deficiency than 1600 IU \noral vitamin D\u2083 per day: a randomized clinical trial. Br J \nDermatol 2012;167:625-30.\n\n\n\n22. Libon F, Cavalier E, Nikkels AF. Skin color is relevant to \nvitamin D synthesis. Dermatology 2013;227:250-4.\n\n\n\n23. Weinhold A, Obeid R, Vogt T, Reichrath J. Prospective \nInvestigation of 25(OH)D3 Serum Concentration \nFollowing UVB Narrow Band Phototherapy in Patients \nwith Psoriasis and Atopic Dermatitis. Anticancer Res.\n\n\n\n24. Tsiaras WG, Weinstock MA. Factors influencing vitamin \nD status. Acta Derm Venereol 2011;91:115-.4\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4770\n\n\n\nORIGINAL ARTICLE\n\n\n\nRituximab as First-line Therapy for Severe Pemphigus: A Case Series and Review \nof Current Literature\n\n\n\nMong Wayne Lim, MRCP, Rajalingam Ramalingam, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nPemphigus refers to a group of life-threatening, autoimmune blistering disease that presents as \nblisters and erosions involving the skin and mucosa. Systemic corticosteroids and rituximab have \nbeen recommended as mainstay therapy for pemphigus vulgaris and pemphigus foliaceus. Herein, we \nreport three cases of pemphigus vulgaris and a case of pemphigus foliaceus treated with rituximab as \nfirst-line therapy. \n\n\n\nKey words: Pemphigus, First-line, Rituximab\n\n\n\nCorresponding Author\nDr Lim Mong Wayne\nDepartment of Dermatology, \nHospital Tengku Ampuan Afzan, \n25000 Kuantan, Pahang, Malaysia\nEmail: limmongwayne@gmail.com\n\n\n\nIntroduction\nPemphigus is a group of life-threatening, \nautoimmune blistering disease that presents \nas blisters and erosions involving the skin and \nmucosa. Systemic corticosteroids and other \nimmunosuppressive drugs have traditionally \nbeen considered the mainstay of therapy. High \ndoses and long treatment period of systemic \nglucocorticoids to achieve adequate clinical \nresponse may lead to serious and life-threatening \nside effects. We hereby report three cases of \npemphigus vulgaris and a case of pemphigus \nfoliaceus treated with rituximab, we also \nincluded an updated review of the literature. \n\n\n\nCase Series \n\n\n\nCase 1\nSH, a previously healthy 32-year-old indigenous \nwoman, presented with progressively \nworsening blisters and erosions over her body \nand oral mucosa for the past 3 months. Physical \nexamination revealed multiple crusted erosions \nover her face, lips, neck, trunk and limbs \ninvolving 30% of her body surface area (BSA) \n(Figure 1 a &b). Intraoral examination revealed \nirregular ulcers with erythematous bases. She \nalso suffered from physical deconditioning and \nmuscle weakness with grade 2 sacral pressure \nulcer due to prolonged immobilization prior \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 71\n\n\n\nto her hospital admission. Our differential \ndiagnoses were pemphigus vulgaris, drug-\ninduced bullous eruption, and bullous lupus \nerythematosus. \n\n\n\nLaboratory values revealed leucocytosis, \nhypochromic microcytic anemia, \nhypoalbuminemia and hypokalaemia. \nHistopathological examination of a perilesional \nskin biopsy revealed suprabasal clefting \nand acantholysis resembling a tombstone \nappearance. Direct immunofluorescence \nshowed intercellular IgG and C3 deposition in \na fishnet-like pattern. A diagnosis of pemphigus \nvulgaris was thus made. \n\n\n\nFigure 1. (a & b) Clinical presentation of the \npatient showing multiple crusted erosions over her \nface, neck, trunk and limbs and (c & d) after three \nmonths during follow-up\n\n\n\n\n\n\n\n\n\n\n\nTreatment was initiated with methylprednisolone \nintravenously 500mg daily consecutively for \n3 days, continued by hydrocortisone 100mg \n\n\n\nthree times a day. However, her condition did \nnot show significant improvement. Therefore, \nrituximab, a monoclonal antibody was given at \n1gm intravenously for 2 infusions 15 days apart \ntogether with a lower oral prednisolone dose \nof 25mg daily (0.5mg/kg/day). She showed \ngood and rapid clinical improvement and was \nsubsequently discharged. We managed to taper \nher prednisolone dose fairly quickly over the \nnext 3 months while azathioprine 50mg a day \nwas added. After one year, her disease remained \nin remission without any oral or systemic \nmedication. \n\n\n\nCase 2\nMR, a 59-year-old gentleman, diagnosed via \nskin biopsy with pemphigus vulgaris three \nyears ago but who unfortunately with a history \nof poor treatment compliance, presented with \ngeneralized painful blisters and erosions over \nhis skin and oral mucosa. Examination revealed \nmultiple raw erosions with areas of peripheral \ncrusting over his trunk and limbs, involving 20% \nBSA (Figure 2: a & b). There were also multiple \nerosive, desquamative lesions over lips, buccal \nmucosa and palate. Blood investigations were \nunremarkable apart from hypoalbuminemia. A \nrepeat skin biopsy was not performed. \n\n\n\nHe too was treated with IV methylprednisolone \n500 mg daily for three consecutive days. \nSubsequently, rituximab was given, due to poor \nclinical response, in addition to 0.5mg/kg/day \noral prednisolone.  He showed marked and \nrapid improvement over the following three \ndays and was discharged well. He was still \nhaving mild disease activity on follow-up at 3 \nmonths and mycophenolate mofetil was added \nwhile prednisolone was quickly tapered off.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4772\n\n\n\nFigure 2. (a & b) Clinical presentation of the patient \nshowing multiple crusted erosions over his trunk \nand limbs and (c & d) upon discharge at day 15\n\n\n\n\n\n\n\n\n\n\n\nCase 3\nMN, an otherwise healthy 20-year-old \ngentleman, presented with progressively \nworsening blisters and erosions all over his body \nfor the past 3 months. Examination revealed \nthick-crusted erosions over his face, neck, \ntrunk, and limbs. There was also bilateral non-\ncicatrizing conjunctivitis with mucopurulent \ndischarge. Blood investigations revealed \nleucocytosis, normocytic normochromic \nanemia, hypokalaemia and hypoalbuminemia. \nOther laboratory values were unremarkable. \nOur differential diagnoses included pemphigus \nvulgaris, pemphigus foliaceus and drug-induced \nbullous eruption. Histopathological examination \nof an intact blister showed suprabasilar cleaving \nwith acantholysis. Direct immunofluorescence \nshowed intercellular deposition of IgG and \nC3 in a fishnet pattern. Thus, a diagnosis of \npemphigus vulgaris was promptly made. \n\n\n\nDue to the severity of his disease, he was given \nrituximab as first-line therapy, at 1000mg \n\n\n\nintravenously given as 2 infusions 15 days apart. \nHe too, was discharged fairly early with 0.5mg/\nkg/day prednisolone and low-dose azathioprine. \nWe managed to wean off prednisolone within \n6 months and azathioprine within a year. At 18 \nmonths follow up, he remains disease-free and \nwithout any oral or topical treatment. \n\n\n\nCase 4  \nZS, a 59-year-old woman with type II diabetes \nmellitus, hypertension, erythrodermic psoriasis \nwith symptomatic palmoplantar pustulosis \ndespite methotrexate since 2018, presented with \ngeneralized raw erosions and flaccid blisters \nwithout mucosal involvement. Our differential \ndiagnoses were pemphigus vulgaris, pemphigus \nfoliaceus, subcorneal pustular dermatosis and \ngeneralized pustular psoriasis. Skin biopsy \nrevealed subcorneal clefting containing \nacantholytic epidermal cells and occasional \nneutrophils. Immunofluorescence study showed \nintercellular IgG and C3 deposited in a fishnet-\nlike pattern. Thus, a diagnosis of pemphigus \nfoliaceus was made. \n\n\n\nHowever, despite an initial treatment of \nintravenous methylprednisolone pulse of \n500mg daily for three days followed by oral \nprednisolone 1mg/kg/day and azathioprine \n150mg daily, she still suffered a severe relapse \neven with minimal tapering of prednisolone six \nmonths later. Rituximab was thus electively \ngiven, similar to the patients above. This time, \nprednisolone could be tapered off quickly \nwithin six months without azathioprine. At \nthe time of writing 15 months later, she is in \ncomplete remission without any systemic or \ntopical treatment whatsoever. \n\n\n\nDiscussion\nPemphigus is a heterogenous group of \nautoimmune, blistering, and potentially \nlife-threatening cutaneous disorders. It is \ncharacterized by acantholysis, resulting in \nintraepithelial blisters in mucous membrane \nand the skin. Pemphigus vulgaris (PV) and \npemphigus foliaceus (PF) are the two most \ncommon forms of pemphigus. PF is attributed \nto IgG autoantibodies directed desmoglein 1 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 73\n\n\n\n(Dsg1) while autoantibodies against desmoglein \n3 (Dsg3) are characteristic for mucosal PV and \nautoantibodies against Dsg1 and Dsg3 have \nbeen linked to mucocutaneous PV. \n\n\n\nTreatment of pemphigus has historically \nbeen a challenge. Systemic corticosteroid \nis recommended as first-line treatment \noptions for pemphigus. Adjuvant steroid-\nsparing immunosuppressants such as \nazathioprine, mycophenolate mofetil (MMF) \nor cyclophosphamide among others are often \nadded for disease control. However, long-\nterm immunosuppressive therapy especially \ncorticosteroid can lead to serious adverse \nreaction. Moreover, a number of patients are \nalso resistant to conventional therapy. \n\n\n\nRituximab is a monoclonal antibody directed \nagainst the CD20 antigen on the surface \nof B-lymphocytes. Hitherto, rituximab \nwas reserved for pemphigus refractory to \nconventional therapies or patients who develop \nsevere adverse reactions to conventional \nimmunosuppressants.1 Multiple literatures have \nshown that rituximab is a valuable treatment \nfor refractory pemphigus.2-12 Following that, \nEuropean Academy of Dermatology and \nVenereology guideline recommends rituximab \nas a third-line therapy from 2015.13\n\n\n\nLiteratures have also reported successful \nexperience with rituximab and corticosteroids \nas first-line combination therapy for pemphigus, \nhowever most of the previous studies only \nincluded a limited number of patients.14-17 More \nrecently, Pascal Joly et al, through a prospective \nopen-label randomized trial, with a high level \nof evidence, has shown the clinical efficacy of \nrituximab as first-line agent for pemphigus.18  \nPemphigus patients were randomly assigned \nto receive oral prednisolone , 1.0 or 1.5mg/kg/\nday tapered over 12 to 18 months (prednisolone \nalone group) or intravenous rituximab \ncombined with oral prednisolone, 0.5 to 1.0mg/\nkg/day tapered over 3 or 6 months (rituximab \nplus short-term prednisolone group). This is the \nmost robust data regarding the use of rituximab \nas first-line agent as it shows the first-line use \n\n\n\nof rituximab plus short-term prednisolone for \npatients with pemphigus is more effective than \nusing prednisolone alone, with fewer adverse \nevents. Moreover, it shows that rituximab can \nbe regarded as the most important advance \nafter the arrival of corticosteroid in the \ntreatment of pemphigus. All these had led to \nthe recommendation of rituximab as first-line \ntreatment in new onset moderate-to-severe \npemphigus by an international panel of experts \nin the management of pemphigus.19 Rituximab \nwas also shown to be superior to MMF in \nproducing sustained complete remission in \npatients with PV.20 \n\n\n\nThe common dosing of rituximab for pemphigus \nwere based on the lymphoma or the rheumatoid \narthritis (RA) protocol. The RA protocol consists \nof 2 infusions of 1000mg, 2 weeks apart while \nthe lymphoma protocol consists of 4 weekly \ninfusions of 375mg/m2. There are also different \nregimen with low-dose rituximab given as \n2 infusions of 500mg, 2 weeks apart with or \nwithout concomitant use of immunoadsorption \nor intravenous immunoglobulin.21 However, \nthere is still no universally accepted dosing \nprotocol for pemphigus. The recommended \ncourse of rituximab by the international panel of \nexperts consists of either the RA protocol or the \nlymphoma protocol.19 Although some studies \nsuggest a potential benefit of the lymphoma \nprotocol for pemphigus, uncertainties remain \nregarding specific dosing modalities. In \na retrospective cohort study published in \n2019, lymphoma protocol was shown to be \nassociated with higher odds of achieving \ncomplete remission off therapy (CROT) as \ncompared to the RA protocol.22 Another meta-\nanalysis showed no superiority of lymphoma \nprotocol over the RA protocol in all outcomes.21 \nWhile other study showed superiority of the \nRA protocol in achieving a higher response \nrate.23 Modified regimen with half the dose \nof conventional RA protocol has also been \nshown to be effective for pemphigus.24 The RA \nprotocol however has the advantage of lower \ncost compared to the lymphoma protocol.1 \nThe RA protocol was used in our patients with \npemphigus as it was the regimen used by Pascal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4774\n\n\n\nJoly et al in their study (the study with the most \nrobust data), however we did not proceed with \nthe maintenance infusion at month 12 and 18 \ndue to financial limitation. \n\n\n\nBefore initiating rituximab, special attention \nneeds to be paid for possible contraindication \nin all patients. Rituximab is contraindicated \nin patients with hypersensitivity to rituximab \nor other murine proteins, active severe \ninfections and severe heart failure (New \nYork Heart Association class IV).25 Infusion \nrelated reactions (IRR) are adverse events \nassociated with the use of rituximab, occurring \nwithin 24hours after drug infusion. Mild to \nmoderate IRR may include fever, skin rash, \npruritus and nausea among others while \nmore severe reactions include hypotension, \nangioedema, bronchospasm, hypoxia and \ncardiac related disorders.26 Our patients were \nall given prophylaxis comprising paracetamol, \nchlorpheniramine and corticosteroid to \nprevent the occurrence of IRR. Other adverse \nreactions related to rituximab may include \ninfections, hematological abnormalities and \nmucocutaneous reaction among others.27,28                                                                                                                                     \nFortunately, all of our patients did not suffer \nfrom any adverse reactions except for MN \nwho suffered from bacteraemia during his \ncomplicated hospital stay. \n\n\n\nIn regards to the need of maintenance rituximab \ntherapy, patients with high Pemphigus \nDisease Area Index [PDAI] score and low \nchanges in anti-desmoglein antibody values \nhave higher risks of relapse and may benefit \nfrom maintenance rituximab infusion at 6 \nmonths.29 Dosing of maintenance rituximab \ntherapy varied among different literature. An \ninfusion of 500mg-1000mg can be repeated at \n6 months or only at 12 months.18,30,31 Besides \nrituximab as maintenance therapy, the use of \nazathioprine as maintenance therapy was shown \nto be beneficial in prolonging the duration of \nremission in patients who received rituximab as \ninitial therapy.32 Two of our patients with newly \ndiagnosed PV are in remission after being put on \nazathioprine as maintenance therapy following \nrituximab as initial therapy. \n\n\n\nFinally, concerns have been raised regarding \nthe prolonged immunosuppressive effect of \nrituximab, which could last at least 6 months, \nespecially during the ongoing novel coronavirus \ndisease (COVID-19) pandemic.33 Literatures \nhave shown that rituximab therapy is associated \nwith more severe COVID-19.33-36 Therefore, the \nattending physician has to offer individualised \ncare and take into account the severity of \nthe disease and potential benefits or risks of \nprescribing rituximab therapy to patients with \npemphigus. In proven cases of COVID-19, \nglucocorticoids, rituximab and other steroid-\nsparing immunosuppressive agents should be \ndiscontinued. In this setting, the administration \nof intravenous immunoglobulin has been \nproposed as a potential option for pemphigus \npatients with COVID-19 and flare of disease.37 \nDealing with vaccination for COVID-19, \nthe American College of Rheumatology \nrecommends vaccination 4 weeks prior to \nnext scheduled rituximab cycle, and to delay \nrituximab 2-4 weeks after final vaccination dose \nif disease activity allows.38 \n\n\n\nConclusion\nOur local experience has shown that rituximab \nis an effective and safe therapy for both newly \ndiagnosed and refractory severe pemphigus, and \nshould be considered as a first-line treatment \noption.  \n\n\n\nConflicts of Interest Declaration\nThe authors have no conflict of interest.\n\n\n\nAcknowledgement\nWe  thank  the  staff  of  departments  of \nDermatology of Hospital Tengku Ampuan \nAfzan, Kuantan, Pahang, Malaysia for their \nsupport in this article. We would also like to \nthank the Director General of Health, Malaysia, \nfor his permission to publish this article.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 75\n\n\n\nTable 1. Literature review of rituximab as first-line therapy for pemphigus\n\n\n\nAuthor, year, \ncountry\n\n\n\nMethodology n Study \nperiod\n\n\n\nRTX \ndosing \nregimen\n\n\n\nGlucocorticoid CAT Conclusions \n\n\n\nAgarwal A, \net al,14 2018, \nUSA\n\n\n\nRetrospective \ncase control \nstudy\n\n\n\n40 1999-\n2015\n\n\n\n1000mg \nday 0, 14.\nMay repeat \ncycle after \n12 months.\n\n\n\nRTX group\nTotal prednisolone \n- 177.2 mg/mo\n\n\n\nCAT group\nTotal prednisolone\n- 141.3 mg/mo\n\n\n\n+\n\n\n\nRituximab significantly reduces the monthly \nprednisolone requirement among CAT-\nresistant PV patients similar with CAT-\nresponsive patients.\n\n\n\nIngen-Housz-\nOro S,15 et al, \n2015, France\n\n\n\nCase reports 5\n-\n\n\n\n1000mg \nday 0, 14\nor\n375mg/m2.\n\n\n\nTopical high-potency \ncorticosteroids -\n\n\n\nConcomitant use of rituximab and high-\npotency topical corticosteroids could be \nconsidered as treatment for PV in some \npatients with contraindications to use of high \ndoses of systemic corticosteroids.\n\n\n\nVinay K,16 \net al, 2017, \nSwitzerland\n\n\n\nRetrospective \nstudy\n\n\n\n31 2008-\n2016\n\n\n\n1000mg \nday 0, 14.\n\n\n\nPrednisolone 0.5-1.0 \nmg/kg/day +\n\n\n\nComplete remission off therapy was more \nlikely to be achieved by patients receiving \nrituximab earlier in the disease course (<6 \nmonths) and as first-line steroid-sparing \nadjuvant.\n\n\n\nChen DM,17 \net al, 2020, \nFrance\n\n\n\nOpen\u2010label, \nrandomized \ncontrolled trial\n\n\n\n36 2010-\n2012\n\n\n\n1000mg \nday 0, 14.\n\n\n\nPrednisolone group\n-1.0 to 1.5 mg/kg/day\n\n\n\nRTX plus short term \nprednisolone group\n-0.5 to 1.0 mg/kg/day\n\n\n\n-\n\n\n\nIn patients with moderate\u2010to\u2010severe PV, \nrituximab plus short\u2010term prednisolone was \nmore effective than prednisolone alone with \nless corticosteroid exposure. \n\n\n\nJoly P et al,18 \n2017, France\n\n\n\nProspective, \nmulticentre, \nparallel-group, \nopen-label, \nrandomised trial\n\n\n\n90 2010-\n2012\n\n\n\n1000mg \nday 0, 14 \nand 500mg \nat months \n12 and 18.\n\n\n\nPrednisolone group\n-1.0 to 1.5mg/kg/day\n\n\n\nRTX plus short term \nprednisolone group\n- 0.5 to 1.0 mg/kg/day \n\n\n\n-\n\n\n\nFirst-line use of rituximab plus short-term \nprednisolone for patients with \npemphigus is more effective than using \nprednisolone alone, with fewer adverse events.\n\n\n\nRTX, rituximab; CAT, conventional adjuvant therapy; mo, months.\n\n\n\nReferences\n\n\n\n1. Kanwar AJ, Vinay K.  Rituximab in pemphigus. Indian J \nDermatol Venereol Leprol 2012;78(6):671-6.\n\n\n\n2. Marzano AV, Fanoni D, Venegoni L, Berti E, Caputo \nR. Treatment of Refractory Pemphigus with the Anti-\nCD20 Monoclonal Antibody (Rituximab). Dermatology \n2007;214(4):310-8.\n\n\n\n3. Dupuy A, Viguier M, B\u00e9dane C, Cordoliani F, Blaise S, \nAucouturier F et al. Treatment of refractory pemphigus \nvulgaris with rituximab (anti-CD20 monoclonal antibody). \nArch Dermatol 2004;140:91-6.\n\n\n\n4. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. \nTreatment of Pemphigus Vulgaris with Rituximab \nand Intravenous Immune Globulin. N Engl J Med \n2006;355(17):1772-9.\n\n\n\n5. Schmidt E, Goebeler M, Zillikens D. Rituximab in severe \npemphigus. Ann N Y Acad Sci 2009;1173:683-91.\n\n\n\n6. Sorce M, Aric\u00f2 M, Bongiorno MR. Rituximab in refractory \npemphigus vulgaris. Dermatol Ther 2008;21 Suppl 1:S6-9.\n\n\n\n7. Schmidt E, Hunzelmann N, Zillikens D, Br\u00f6cker E-B, \nGoebeler M. Rituximab in refractory autoimmune bullous \ndiseases. Clin Exp Dermatol 2006;31(4):503-8.\n\n\n\n8. Kasperkiewicz M, Shimanovich I, Ludwig RJ, Rose \nC, Zillikens D, Schmidt E.  Rituximab for treatment-\nrefractory pemphigus and pemphigoid: a case series of 17 \npatients. J Am Acad Dermatol 2011;65(3):552-8.\n\n\n\n9. Gangan R. Refractory pemphigus vulgaris: Treatment \noptions. J Skin Sex Transm Dis 2019;1:61-5.\n\n\n\n10. Biot Sdel R, Franco JP, Lima RB, Pereira HN, Marques LP, \nMartins CJ. Refractory pemphigus vulgaris treated with \nrituximab and mycophenolate mofetil. An Bras Dermatol \n2014;89:980-4.\n\n\n\n11. Barrera MV, Mendiola MV, Bosch RJ, Herrera E. Prolonged \ntreatment with rituximab in patients with refractory \npemphigus vulgaris. J Dermatolog Treat 2007;18(5):312-\n4.\n\n\n\n12. Londhe PJ, Kalyanpad Y, Khopkar US. Intermediate \ndoses of rituximab used as adjuvant therapy in refractory \npemphigus. Indian J Dermatol Venereol Leprol \n2014;80(4):300-5.\n\n\n\n13. Hertl M, Jedlickova H, Karpati S, Marinovic B, Uzun \nS, Yayli S et al. Pemphigus. S2 Guideline for diagnosis \nand treatment--guided by the European Dermatology \nForum (EDF) in cooperation with the European Academy \nof Dermatology and Venereology (EADV). J Eur Acad \nDermatol Venereol 2015;29:405-14. \n\n\n\n14. Agarwal A, Hall RP 3rd, Ba\u00f1ez LL, Cardones AR. \nComparison of rituximab and conventional adjuvant \ntherapy for pemphigus vulgaris: A retrospective analysis. \nPLoS One 2018;13:e0198074.\n\n\n\n15. Ingen-Housz-Oro S, Valeyrie-Allanore L, Cosnes A, \nOrtonne N, H\u00fce S, Paul M et al. First-line Treatment of \nPemphigus Vulgaris With a Combination of Rituximab \nand High-Potency Topical Corticosteroids. JAMA \nDermatology 2015;151:200-3.\n\n\n\n16. Vinay K, Cazzaniga S, Amber KT, Feldmeyer L, Naldi L, \nBorradori L. Rituximab as first-line adjuvant therapy for \npemphigus: Retrospective analysis of long-term outcomes \nat a single center. J Am Acad Dermatol 2018;78:806-8.\n\n\n\n17. Chen DM, Odueyungbo A, Csinady E, Gearhart L, Lehane \nP, Cheu M et al. Rituximab is an effective treatment in \npatients with pemphigus vulgaris and demonstrates a \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4776\n\n\n\nsteroid-sparing effect. Br J Dermatol 2020;182:1111-9.\n18. Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, \n\n\n\nHouivet E, Calbo S et al. First-line rituximab combined \nwith short-term prednisone versus prednisone alone for \nthe treatment of pemphigus (Ritux 3): a prospective, \nmulticentre, parallel-group, open-label randomised trial. \nThe Lancet 2017;389:2031-40.\n\n\n\n19. Murrell DF, Pe\u00f1a S, Joly P, Marinovic B, Hashimoto T, \nDiaz LA et al. Diagnosis and management of pemphigus: \nRecommendations of an international panel of experts. J \nAm Acad Dermatol 2020;82:575-85.\n\n\n\n20. Werth VP, Joly P, Mimouni D, Maverakis E, Caux F, \nLehane P et al. Rituximab versus Mycophenolate Mofetil \nin Patients with Pemphigus Vulgaris. N Engl J Med \n2021;384:2295-305.\n\n\n\n21. Wang HH, Liu CW, Li YC, Huang YC. Efficacy of \nrituximab for pemphigus: a systematic review and meta-\nanalysis of different regimens. Acta Derm Venereol \n2015;95:928-32.\n\n\n\n22. Kushner CJ, Wang S, Tovanabutra N, Tsai DE, Werth VP, \nPayne AS. Factors Associated With Complete Remission \nAfter Rituximab Therapy for Pemphigus. JAMA Dermatol \n2019;155:1404-9.\n\n\n\n23. Zakka LR, Shetty SS, Ahmed AR. Rituximab in the \ntreatment of pemphigus vulgaris. Dermatol Ther (Heidelb) \n2012;2:17.\n\n\n\n24. Vaidya TP, Martis J, Bhat RM, Dandekeri S. A modified \nregimen of rituximab in pemphigus: A retrospective study. \nClin Dermatol Rev 2020;4:36-41.\n\n\n\n25. Buch MH, Smolen JS, Betteridge N, Breedveld FC, \nBurmester G, D\u00f6rner T et al. Updated consensus statement \non the use of rituximab in patients with rheumatoid \narthritis. Ann Rheum Dis 2011;70:909-20.\n\n\n\n26. Paul F, Cartron G. Infusion-related reactions to rituximab: \nfrequency, mechanisms and predictors. Expert Rev Clin \nImmunol 2019;15:383-9.\n\n\n\n27. Emer JJ, Claire W. Rituximab: a review of dermatological \napplications. J Clin Aesthet Dermatol 2009;2:29-37.\n\n\n\n28. Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical \nreview: Serious adverse events associated with the \nuse of rituximab - a critical care perspective. Crit Care \n2012;16:231.\n\n\n\n29. Mignard C, Maho-Vaillant M, Golinski ML, Balay\u00e9 P, \nProst-Squarcioni C, Houivet E et al. Factors Associated \nWith Short-term Relapse in Patients With Pemphigus \nWho Receive Rituximab as First-line Therapy: A Post Hoc \nAnalysis of a Randomized Clinical Trial. JAMA Dermatol \n2020;156:545-552.\n\n\n\n30. Rashid H, Lamberts A, van Maanen D, Bolling MC, \nDiercks GFH, Pas HH et al. The effectiveness of rituximab \nin pemphigus and the benefit of additional maintenance \ninfusions: Daily practice data from a retrospective study. J \nAm Acad Dermatol 2020;83:1503-5.\n\n\n\n31. Sanchez J, Ingen-Housz-Oro S, Chosidow O, Antonicelli \nF, Bernard P. Rituximab as Single Long-term Maintenance \nTherapy in Patients With Difficult-to-Treat Pemphigus. \nJAMA Dermatology 2018;154:363-5.\n\n\n\n32. Cho YT, Huang YM, Wang LF, Chu CY. Maintenance \ntherapy with azathioprine prolonged duration of remission \nfor pemphigus patients who received rituximab as first-\nline or add-on therapy. J Formos Med Assoc 2020;119(1 \nPt 2):230-7.\n\n\n\n33. Beyzaee AM, Rahmatpour Rokni G, Patil A, Goldust M. \nRituximab as the treatment of pemphigus vulgaris in the \nCOVID-19 pandemic era: A narrative review. Dermatol \nTher 2021;34:e1\n\n\n\n34. Uzuncakmak TK, \u00d6zkoca D, Askin O, Kutlubay Z. \nCan rituximab be used in the treatment of pemphigus \nvulgaris during the COVID-19 pandemic? Dermatol Ther \n2021;34:e14647.\n\n\n\n35. Avouac J, Drumez E, Hachulla E, Seror R, Georgin-\nLavialle S, El Mahou S et al. COVID-19 outcomes in \npatients with inflammatory rheumatic and musculoskeletal \ndiseases treated with rituximab: a cohort study. Lancet \nRheumatol 2021;3:e419-26.\n\n\n\n36. Avouac J, Drumez E, Hachulla E, Seror R, Georgin-\nLavialle S, Mahou SE et al. COVID-19 outcomes in \npatients with inflammatory rheumatic and musculoskeletal \ndiseases treated with rituximab: a cohort study. Lancet \nRheumatol 2021;80:172-3.\n\n\n\n37. Abdollahimajd F, Shahidi-Dadras M, M Robati R, \nDadkhahfar S. Management of Pemphigus in COVID-19 \nPandemic Era; a Review Article. Arch Acad Emerg Med \n2020;8:e51.\n\n\n\n38. Curtis JR, Johnson SR, Anthony DD, Arasaratnam \nRJ, Baden LR, Bass AR., et al. American College of \nRheumatology Guidance for COVID-19 Vaccination in \nPatients With Rheumatic and Musculoskeletal Diseases: \nVersion 1. Arthritis Rheumatol 2021;73:1093-107.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 77\n\n\n\nCASE REPORT\n\n\n\nIatrogenic Phaeohyphomycosis: A Rare and Underrecognized Disease\n\n\n\nMong Wayne Lim, MRCP, Abdul Rahman Che Abdul Rahim, MRCP, Rajalingam Ramalingam, \nAdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia \n\n\n\nSummary\nPhaeohyphomycosis refers to a heterogenous group of mycotic infections caused by dematiaceous \nfungi where unintentional traumatic inoculation accounts for majority of the cases. Herein, we are \nreporting a rare case of iatrogenic subcutaneous phaeohyphomycosis which is secondary to intravenous \ncannula placement. \n\n\n\nKey Words: Iatrogenic; Phaehyphomycosis; Dematiaceous fungi\n\n\n\nCorresponding Author\nDr Lim Mong Wayne, \nDepartment of Dermatology, \nHospital Tengku Ampuan Afzan, \n25000 Kuantan, Pahang, Malaysia\nEmail: limmongwayne@gmail.com\n\n\n\nIntroduction \nPhaeohyphomycosis is a group of fungal \ninfections caused by dematiaceous fungi in \ntissue.1 More than 150 species have been \ndescribed as causal agents which includes \nExophiala, Wangiella, Phialophora and \nCladosporium among others.2 There is a \nlarge variety of clinical presentations which \nincludes superficial cutaneous, subcutaneous \ndisease, cerebral and disseminated disease.3 \nThe subcutaneous infection typically occurs \nat exposed areas of the body from traumatic \ninoculation. We report this case of iatrogenic \nphaeohyphomycosis for its unusual mode of \ninoculation by intravenous cannula placement \nwhich is perceived to be a clean and sterile \nprocedure.  \n\n\n\nCase Report\nHS, a 70-year-old gentleman with type II \ndiabetes mellitus, hypertension and end stage \nrenal failure on haemodialysis, presented with \nslowly enlarging, asymptomatic nodules over \nthe dorsum of both hands for the past one \nmonth. He reported that they started at previous \nsites of intravenous cannula insertion during his \nhospital stay one month ago. He did not notice \nany prior traumatic injury and was otherwise \nwell. \n\n\n\nPhysical examination revealed an erythematous \nplaque with verrucous surface measuring 1 x \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4778\n\n\n\n1cm, over the dorsum of his right hand. Another \nerythematous plaque with verrucous surface \nand minimal surface erosions, measuring 2.5cm \nx 1.5cm, was located over the dorsum of his left \nhand. There was no regional lymphadenopathy \nand examination of other systems was \nunremarkable.\n\n\n\nWe considered several differential diagnoses, \nincluding iatrogenic fixed cutaneous \nsporotrichosis, chromoblastomycosis, \ntuberculosis verrucosa cutis and non-tuberculous \nmycobacterial infection.\n\n\n\nFigure 1. (a).  Clinical presentation of the patient, \nshowing erythematous nodule with verrucous surface \non the bilateral aspect of both hand with minimal \nerosion; (b) After one month on itracomazole\n\n\n\nBlood investigations were unremarkable apart \nfrom mild hypochromic microcytic anaemia \nand high urea and creatinine, in keeping with \nhis underlying renal disease.  Histopathological \nexamination of the plaques revealed \npseudoepitheliomatous epidermal hyperplasia \nwith moderate lymphoplasmacytic infiltration \nwith foci of neutrophilic microabscesses. No \ngranulomas were appreciated. While Ziehl \nNeelsen and periodic acid Schiff (PAS) stains \ndid not demonstrate any fungus, tissue culture, \n\n\n\nhowever, isolated Exophiala species.\n\n\n\nHence, a diagnosis of iatrogenic subcutaneous \nphaeohyphomycosis caused by Exophiala \nspecies was made and he was promptly treated \nwith oral itraconazole. His lesions improved \ndramatically after one month of treatment \nand subsequently successfully cleared after 4 \nmonths of treatment.\n\n\n\nDiscussion\nThe infections caused by dematiaceous fungi, \nare classified into three groups which include \nphaeohyphomycosis, chromoblastomycosis \nand eumycotic mycetoma.1-3 This variety \nof dematiaceous fungi develops in infected \ntissue as darkly pigmented yeast-like cells, \npseudohyphae-like elements, hyphae, \nor in any combination of these forms.3-4 \nPhaeohyphomycosis should be distinguished \nfrom other infectious syndrome also caused \nby dematiaceous fungi which include \nchromoblastomycosis and eumycetoma.\n\n\n\nThere are many different clinical syndromes \nfor phaeohyphomycosis.1-4 One of the more \nextensive clinical syndrome classifications \ndivides it into nine groups, which includes: \n(1) superficial (including black piedra & tinea \nnigra); (2) onychomycosis; (3) subcutaneous; (4) \ncorneal or mycotic keratitis; (5) allergic fungal \nsinusitis; (6) allergic fungal bronchopulmonary \nmycosis; (7) pneumonia; (8) brain abscess; and \n(9) disseminated disease.4  Phaeohyphomycosis \nis caused by more than 150 species of fungi, \nwhich includes Exophiala, Phialophora, \nAlternaria, Cladosporium, Scytalidium, \nDrechslera, Curvularia and Wangiella species. \nThe most common species are E. jeanselmi and \nE. dermatitidis.1-3 \n\n\n\nSubcutaneous phaeohyphomycosis lesions \nmost commonly occur on exposed area of body \nsuch as hands, arms, feet and legs.1 Traumatic \ninoculation accounts for majority of the cause \nof subcutaneous phaeohyphomycosis, however \ncases are being reported which has no prior \nrecollection of traumatic injury.3 There are \nalso reports on iatrogenic phaeohyphomycosis. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 79\n\n\n\nThis includes report of subcutaneous \nphaeohyphomycosis in association with \nintravenous cannula insertion and report \ndemonstrating osteoarticular infection \nsecondary to contaminated methylprednisolone \ninjections.2,6\n\n\n\nThe immune status of the host plays a major role in \nthe clinical presentation of the patient. Typically, \nmajority of cases of phaeohyphomycosis has \nbeen associated with an immunocompromised \nstate, this includes human immunodeficiency \nvirus patients, malignancies, transplant \nrecipients, systemic lupus, vasculitis, primary \nimmunodeficiency syndromes, debilitating \nchronic diseases and diabetes among others.1,3 \nIn addition to that, immunocompromised \nstates are also at risk of cerebral and systemic \nphaeohyphomycosis.  Despite that, cases in \nimmunocompetent patients are on the rise.3 \nAs for subcutaneous phaeohyphomycosis, this \ntypically presents as papulonodules, verrucous, \nhyperkeratotic or ulcerated plaques, cysts, \nabscesses, pyogranuloma, non-healing ulcers or \nsinuses.1,7\n\n\n\nFor the diagnosis of phaeohyphomycosis, \nhistopathologically, the lesions show brown-\nwalled septate hyphae or yeast-like cells, or \nboth in tissue. In order to help differentiate it \nfrom eumycetoma and chromoblastomycosis \nwhich are also caused by dematiaceous fungi, \neumycetoma is characterized by the presence of \nmycotic granules in draining sinus tract while \nchromoblastomycosis is a typically verrucous \nhyperplastic cutaneous infection characterized \nby the presence of medlar bodies (sclerotic \nbodies).2,3 All dematiaceous fungi are similar \nin morphology and cannot be differentiated in \ntissue. Hence, it can only be differentiated by \ncultures.\n\n\n\nThere is no uniform treatment approach for \nthe treatment of these infections. The length of \ntherapy and choice of treatment are primarily \nbased on clinical presentation, underlying \nimmune status of the host and the initial \nresponse to treatment.8 Literature shows surgical \nexcision of the lesion has been successfully \n\n\n\napplied in some cases.9-13 Adding on antifungal \nmonotherapy or combination therapy is also \npreferred to avoid local spread and to treat \nsubclinical lesions.3 Broad-spectrum azoles \nare currently the mainstay of therapy, with \nitraconazole historically the most commonly \nused agent that demonstrates good activity \nagainst the vast majority of melanized fungi. \nVoriconazole is becoming more popular with \npreferable side effect profile and is available \nin intravenous formulation.3 However, it is not \navailable in our local setting for this patient. \nOther systemic agents used successfully \ninclude amphotericin B, flucytosine & \nposaconazole.3 Fluconazole and ketoconazole \nhave essentially no role in invasive disease \ncause by dematiaceous fungi. Terbinafine was \nalso reported to be less effective, especially in \nserious systemic infection.2\n\n\n\nConclusion\nTo the best of our limited knowledge, this is the \nsecond reported case of iatrogenic subcutaneous \nphaeohyphomycosis secondary to intravenous \ncannula insertion. While it is uncommon for \na clean procedure as a source of inoculation \nto cause subcutaneous phaeohyphomycosis, \nclinicians should have a high index of suspicion \nand be aware of this infection. This is to avoid \nany delay in treatment so as to avoid further \ncomplications. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest.\n\n\n\nAcknowledgement\nWe thank the staff of departments of \nDermatology and Pathology of Hospital Tengku \nAmpuan Afzan, Kuantan, Pahang, Malaysia for \ntheir support in this article. We would also like to \nthank the Director General of Health, Malaysia, \nfor his permission to publish this article. \n\n\n\nReferences \n\n\n\n1. Chintagunta S, Arakkal G, Damarla SV, Vodapalli \nAK. Subcutaneous phaeohyphomycosis in an \nimmunocompetent Individual: A case report. Indian \nDermatol Online J 2017;8:29-31. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4780\n\n\n\n2. Arcobello JT, Revankar SG. Phaeohyphomycosis. Semin \nRespir Crit Care Med 2020;41:131-40. \n\n\n\n3. Ramalingam R. The clinical spectrum of cutaneous \nphaeohyphomycosis in three immunocompetent patients \nand a review of literature. Malaysian J Dermatol \n2019;42:33-8.\n\n\n\n4. Prieto-Granada CN, Lobo AZ, Mihm MC Jr, Kradin \nRL. Skin infections: Diagnostic Pathology of Infectious \nDisease. 2nd edition. Philadelphia: Elsevier;2018. p.542-7.\n\n\n\n5. Espanhol CM, Recuero JK, Pagani DM, Ribeiro \nAC, Vettorato G, Duquia RP et al. Cutaneous \nphaeohyphomycosis caused by Exophiala xenobiotica: A \ncase report. Med Mycol Case Rep 2019;27:39-41. \n\n\n\n6. Abdolrasouli A, Gonzalo X, Jatan A, McArthur \nGJ, Francis N, Azadian BS et al. Subcutaneous \nphaeohyphomycosis cyst associated with Medicopsis \nromeroi in an immunocompromised host. Mycopathologia \n2016;181:717-21. \n\n\n\n7. Shirbur S, Telkar S, Goudar B, Mathew T. Recurrent \nphaeohyphomycosis: a case report. J Clin Diagn Res \n2013;7:2015-6.\n\n\n\n8. Chowdhary A, Meis JF, Guarro J, de Hoog GS, Kathuria \nS, Arendrup MC et al. ESCMID and ECMM joint clinical \nguidelines for the diagnosis and management of systemic \nphaeohyphomycosis: diseases caused by black fungi. Clin \nMicrobiol Infect 2014;20:47-75. \n\n\n\n9. Girard C, Dereure O, Rispail P, Durand L, Guilhou JJ. \nSubcutaneous phaeohyphomycosis due to Pyrenochaeta \nromeroi in a patient with leprosy. Acta Derm Venereol \n2004;84:154-5. \n\n\n\n10. Ferrer C, P\u00e9rez-Santonja JJ, Rodr\u00edguez AE, Colom MF, \nGen\u00e9 J, Alio JL et al. New pyrenochaeta species causing \nkeratitis. J Clin Microbiol 2009;47:1596-8.\n\n\n\n11. Badali H, Najafzadeh MJ, van Esbroeck M, van den \nEnden E, Tarazooie B, Meis JF et al. The clinical spectrum \nof Exophiala jeanselmei, with a case report and in vitro \nantifungal susceptibility of the species. Med Mycol \n2010;48:318-27.\n\n\n\n12. Verkley GJ, Gen\u00e9 J, Guarro J, P\u00e9rez-Santonja JJ, Rodr\u00edguez \nAE, Colom MF et al. Pyrenochaeta keratinophila sp. Nov., \nisolated from an ocular infection in Spain. Rev Iberoam \nMicol. 2010;27:22-4. \n\n\n\n13. Khan Z, Ahmad S, Kapila K, Ramaswamy NV, Alath P, \nJoseph L et al. Pyrenochaeta romeroi: a causative agent of \nphaeohyphomycotic cyst. J Med Microbiol 2011;60:842-6. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 81\n\n\n\nCASE REPORT\n\n\n\nCutaneous Tuberculosis in HIV Patient: A Case Report\nNurul Aini Md Isa1, MBBS, Low Dy-win2, AdvMDerm, Khairul Shakir Ab Rahman3, MPath \n\n\n\n1Department of Dermatology, Hospital Tuanku Fauziah, Kangar, Perlis, Malaysia\n2Department of Dermatology, Hospital Sultanah Bahiyah, Alor Setar, Kedah, Malaysia\n3Department of Pathology, Hospital Tuanku Fauziah, Kangar, Perlis, Malaysia\n\n\n\nSummary\nTuberculosis (TB) is a serious communicable disease of major concern in endemic regions. Cutaneous \ntuberculosis (CTB), which accounts for less than 1% of all cases, can cause severe infection in susceptible \npatients.1 The diagnosis of CTB is challenging as it can present with a multitude of clinical presentations. \nThe diagnosis must be supported by highly sensitive and specific investigations. This paper highlights the \nsusceptibility of immunocompromised patients to the development of CTB and the challenges in making a \ndiagnosis.\n\n\n\nKey words: Cutaneous tuberculosis, CTB, HIV, Tuberculosis-HIV, CTB-HIV, Co-infection\n\n\n\nCorresponding Author\nDr Nurul Aini Md Isa\nDepartment of Dermatology, \nHospital Tuanku Fauziah, \n3, Jalan Tun Abdul Razak, \nPusat Bandar Kangar, \n01000 Kangar, Perlis, Malaysia\nEmail: dr.nurulainiisa@gmail.com\n\n\n\nIntroduction\nMycobacterium tuberculosis (MTB) is the \ncausative agent for TB. TB essentially affects \nthe lungs and can involve extrapulmonary sites \nincluding the skin.2 The occurrence of CTB \nis driven by the human immunodeficiency \nvirus (HIV) epidemic as well as in specific \nsettings such as healthcare facilities, prisons \nand homeless shelters. Increased incidence \nis also noted among intravenous drug users, \nand in those with diabetes mellitus and on \nimmunosuppressive therapy.3 It is estimated \nthat one-third to one-half of people with HIV \ninfection are also co-infected with MTB \nworldwide.4\n\n\n\nCase report\nA 46-year-old gentleman with underlying \nhepatitis C and HIV presented with worsening \noral thrush and dysphagia. He had multiple \npinhead-sized nodulo-pustular lesions initially \nover face (Figure 1-d), which then progressed \nto the ears and then the upper limbs and \nlower limbs over one week. Some of nodules \nappeared to have central necrosis. He was an \nintravenous heroin abuser and diagnosed with \nHIV in October 2009 when he presented with \na prolonged headache and left sided weakness. \nHe was treated for cerebral toxoplasmosis. \nHis baseline viral load was more than 50,000 \ncopies/ml, CD4/CD8 ratio was 0.01 (0.83-6.1) \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4782\n\n\n\nand CD4 count was 64 (355-1213). He was on \nStavudine/Lamivudine/Nevirapine since June \n2010. He managed to achieve a non-detectable \nviral load when he was compliant. This was \nuntil October 2016, after which he defaulted \ntreatment. \n\n\n\nGeneral examination revealed extensive \noral candidiasis. He had a residual left \nsided hemiparesis from previous cerebral \ntoxoplasmosis. Sensory examination and \nlung findings were normal. There was \nno lymphadenopathy found. Clinically \nthe differential diagnosis were atypical \nmycobacterial cutaneous infection and \nsubcutaneous or deep fungal infection. Initial \nblood investigations showed normochromic \nnormocytic anemia with thrombocytosis but \nno leucocytosis. The erythrocyte sedimentation \nrate (ESR) and C-reactive protein (CRP) were \nsignificantly raised. Chest X-ray was normal \ninitially. Tuberculin skin test reading was 0mm \nafter 48 hours. \n\n\n\nThis patient underwent echocardiography which \nshowed a 0.6cm to 1.5cm posterior inferior wall \npericardial effusion and computed tomography \nof thorax, abdomen and pelvis showed a \npericardial effusion on the posterior inferior \nwall with enhancement of the pericardial lining, \nmultiple nodular opacities over the right lung, \nleft lower lobe collapsed consolidation with \nminimal pleural effusion, necrotic mediastinal \nlymph nodes, hepatomegaly with minimal \nascites but no evidence of focal liver lesion.\n\n\n\nA punch biopsy of skin was done over the \nforehead. There was a localised ulceration with \ncollection of neutrophils and histiocytes in the \ndermis forming microabscesses. However, no \nwell-formed granuloma, obvious dysplasia \nor malignancy were seen. Abundant acid-fast \nbacilli (AFB) were demonstrated with Ziehl \nNeelson stain and Wide Fite stains.\n\n\n\nSplit skin smear (SSS) was positive with \nbacterial index 3.3 and morphological index \n1.5. MTB and fungal tissue culture and \nsensitivity were negative. However MTB PCR \n\n\n\n(polymerase chain reaction) was positive and \nnegative for Mycobacterium leprae. Based on \nclinical, radiological and PCR findings, the \npatient was treated for acute cutaneous military \ntuberculosis (ACTMB). He was started on \nintensive regimen of anti-TB drugs consisting \nof Rifampicin, Isoniazid, Pyrazinamide, \nEthambutol and Pyridoxine. After 2 weeks, this \npatient had significant improvement of the skin \nlesions (Figure e-h).\n\n\n\nFigure 1. (a) Localised ulceration with collection of \nneutrophils and histiocytes in the dermis, involving \npilosebaceous units (Haematoxylin & Eosin stain \n(H&E), 4x); (b) The edge of the lesion is composed \nof histiocytes and some scattered within were \nepithelioid looking. No well-formed granuloma \nis seen (H&E, 10x); (c) Acid fast bacilli were \ndemonstrated (Ziehl Neelson stain, 60x)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 83\n\n\n\nFigure 2. (a-d) Nodulo-pustular lesions over face, \near, cheek and dorsum of foot. Baseline photo prior \nto anti-TB. (e-h) Photo after anti-TB\n\n\n\nDiscussion\nThe estimated incidence for TB-HIV cases was \n193000 in 2013. In general, Asian countries \ndemonstrated a lower estimated prevalence of \nTB-HIV co-infection at 17.2% as compared to \nother regions such as Africa (31.2%), Europe \n(20.1%), Latin America (25.1%) and USA \n(14.8%).5-6 This low number may be unreliable \ndue to poor screening as not many countries \nin the Asia-Pacific region tested more than \ntwo-third of patients who had TB for HIV.5 \nMany countries in Asia only demonstrated \na prevalence of TB-HIV coinfection rate of \nless than 10% except for Thailand (15%) and \nPapua New Guinea (14%). This was in contrast \nto the African regions where the majority \nexceeded 50% and had the highest number of \nreported HIV co-infection cases.5,7 Overall, the \nincidence of CTB was only 0.7% with 9.1% \nHIV concurrence from 2007 to 2009 in India.8 \nMale patients demonstrated a higher prevalence \nof TB and TB-HIV co-infection in Malaysia \n(91.1%).9 \n\n\n\nThe lifetime risk to develop active TB in HIV \nindividuals is 5-15% annually as compared to \nimmunocompetent adults which is at 5-10%. \nCo-infection with HIV increases the risk \nof  reactivation of latent TB by 20. On the \nother hand, TB exacerbates HIV infection.10 \nThe depletion of CD4 T-cells due to HIV \ninfection causes impairment of the intracellular \nclearance of MTB and disrupts the integrity \nand architecture of the granuloma which leads \nto TB reactivation.11,12 It has been proposed \nthat TB-HIV co-infection as a \u2018danger-couple\u2019 \nmodel in which dysfunctional HIV-infected \nT cells lead to loss of intracellular killing \nabilities of macrophages harbouring MTB, \nwhile MTB-infected macrophages containing \nlipoarabinomannan (LAM) produce increased \nlevels of TNF- \u03b1, IL-1 and IL-6 leading to \nenhanced viral replication and persistence in the \nmacrophages.13\n\n\n\nClinical variants of CTB mainly depends on \ncell-mediated immunity as the primary response \nto mycobacterial infection. It can be concluded \nthat it is a direct reflection of the host\u2019s cellular \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4784\n\n\n\nimmune status. This is totally different from \nleprosy where the predominant response is \nimmunological.4 It is also important to note \nthat the presentation of CTB depends on the \nbacillary load.4 \n\n\n\nThe clinical morphology of CTB can be \ndifferentiated by the mode of infection, i.e. either \nthrough exogenous or endogenous sources. \nThe former is significantly less common. An \nexogenous source infection is by primary \ninoculation on the traumatic skin or mucous \nmembranes which can lead to tuberculosis \nverrucosa cutis (TVC) and tuberculosis \nchancre.1,7 Endogenous routes may also be via \nhematogenous, lymphatic or contiguous spread \nto the skin which may lead to scrofuloderma, \nlupus vulgaris (LV), tuberculous gumma, \norificial tuberculosis or ACTMB as clinical \npresentations.1,7 As MTB can be found at the \nlesional sites via PCR in this case, it is defined \nas true CTB instead of tuberculids.7 Tuberculids \nare delayed-type hypersensitivity reaction to \nbacterial antigens and can be manifested as \npapulonecrotic tuberculid, lichen scrofulosorum \nor erythema induratum of Bazin.4,7 \n\n\n\nScrofuloderma (80%) is the most common \npresentation of TB-HIV cases in Brazil \nfollowed by tuberculous gumma (20%) from \nsamples collected from 2000 to 2016.10 In India, \nwhere there is a high incidence of TB and HIV, \none study showed that 10.4% of patient with \nscrofuloderma, 7.5% of patient with LV, 11.7% \nwith TVC were HIV positive. Scrofuloderma \nrepresented the most commonly seen variant in \nthe study.8 \n\n\n\nACMTB or tuberculosis cutis miliaris \nacuta generalisata usually occurs in \nimmunocompromised patient such as Acquired \nImmunodeficiency Syndrome (AIDS) via \nhematogenous spread. The lesion can present \nwith scattered erythematous macules and \npapules with central vesicles or pustules, \ncharacteristically from a pinhead size to 6 \nmm in diameter, that may rupture, and then \nform a crust. Ultimately, it heals with a \nhypopigmented scar and brownish halo.4,14,15 \n\n\n\nPulmonary basal involvement, hilar or \nmediastinal lymphadenopathy and military TB \nare most commonly observed.13 Microscopic \nexamination may demonstrate  ill-formed or \nno granulomas, focal or extensive necrosis, \nmicroabscesses, abundant AFB and scattered \nnon inflammatory cells.14,15 The absence of a \ncell mediated response in ACMTB results in \nnon-specific necrosis with high bacillary load \nand negative tuberculin test.4 In this case, the \npatient demonstrated a few characteristics of \nACMTB.\n\n\n\nSSS was taken from the most representative \nlesion and stained by modified Ziehl Neelson \n(ZN) stain to demonstrate AFB.16 ZN stain \nwas developed to show mycobacterial genus \nfastness which has become the cornerstone \nin TB diagnosis.17 Differentiation of MTB \nand Mycobacterium leprae by SSS alone is \nimpossible. It was proven that PCR had higher \nsensitivity and specificity compared to SSS in \ndiagnostic challenges.18 The lack of a positive \ntuberculin test, granulomatous reaction and \nhigh bacillary load would make ACMTB \nanalogous to lepromatous leprosy.4 Even though \nco-infection between tuberculosis and leprosy \nhas occurred since the thirteenth century, the \nprobability is estimated at 0.0006 cases per \n100000 population in Malaysia.19\n\n\n\nRoutine sputum microscopy is inadequate to \nrule out TB and is not an optimal screening tool \nsince 24-61% of TB-HIV patients presents with \nsputum-negative disease.5 WHO has endorsed \nthe Xpert MTB/RIF assay (PCR) as the primary \nTB diagnostic test for symptomatic people \nliving with HIV as it is associated with 35-45% \nimprovement in the diagnostic sensitivity. Urine \nLAM assay can be added to rule out active \nTB in severely immunocompromised patients \n(CD4 count less than 100) to achieve diagnostic \ncertainty.5 \n\n\n\nOne in four deaths among HIV patients is \nattributed to TB even though significant \nreduction of TB-related deaths among HIV \npatients was seen in Asia Pacific region.5,6 The \noutcome for ACMTB is grave. Seventy five \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 85\n\n\n\npercent of cases had multidrug resistance to at \nleast Rifampicin and Isoniazid and these cases \neventually succumbed.4\n\n\n\nFemale patients showed a higher tendency for \ntreatment success according to Jalal et al. This \nstudy also significantly supports that a positive \ntuberculin test leads to a higher chance of \ntreatment success and was assumed to be due to \ndevelopment of immune response to the MTB.9 \nHowever, this patient demonstrates a good \nresponse to treatment despite being a male and \nshowing no reaction on tuberculin test. \n\n\n\nConclusion\nCTB is a rare entity and the outcome is rarely \nreported. This case posed its own diagnostic \nchallenges and high level of suspicion is needed \ndue to the variable clinical manifestations. Early \nand specific diagnostic screening may improve \npatient\u2019s prognosis.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare. \n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth, Malaysia, for his permission to publish \nthis article. \n\n\n\nReferences\n\n\n\n1. Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a \npractical case report and review for the dermatologist. J \nClin Aesthet Dermatol 2009;2:19-27.\n\n\n\n2. Dey B, Gochhait D, Prabhakaran N, Chandrashekar \nL, Behera B. A rare case of coexistence of borderline \nlepromatous leprosy with tuberculosis verrucosa \ncutis. Case Rep Infect Dis 2016;2016:1746896.\n\n\n\n3. Tshisevhe V, Mbelle N, Peters RPH. Cutaneous tuberculosis \nin HIV-infected individuals: Lessons learnt from a case \nseries. S Afr J HIV Med 2019;20:1-3.\n\n\n\n4. Libraty DH, Byrd TF. Cutaneous miliary tuberculosis \nin the AIDS era: Case report and review. Clin Infect Dis \n1996;23:706-10.\n\n\n\n5. Trinh QM, Nguyen HL, Nguyen VN, Nguyen TV, \nSintchenko V, Marais BJ. Tuberculosis and HIV co-\ninfection-focus on the Asia-Pacific region. Int J Infect Dis \n2015;32:170-8.\n\n\n\n6. Gao J, Zheng P, Fu H. Prevalence of TB/HIV co-infection \nin countries except China: a systematic review and meta-\nanalysis. PLoS One 2013;8:e64915.\n\n\n\n7. Chen Q, Chen W, Hao F. Cutaneous tuberculosis: A great \nimitator. Clin Dermatol 2019;37:192-9.\n\n\n\n8. Varshney A, Goyal T. Incidence of various clinico-\nmorphological variants of cutaneous tuberculosis and HIV \nconcurrence: A study from the Indian subcontinent. Ann \nSaudi Med 2011;31:134-9.\n\n\n\n9. Jalal TMT, Abdullah S, Wahab FA, Dir S, Naing NN. \nPrevalence and factors associated with tuberculosis \ntreatment success among TB/HIV co-infection in North-\nEast Malaysia. Malays J Med Sci 2017;24:75-82.\n\n\n\n10. Mann D, Sant\u2019Anna FM, Schmaltz CAS, Freitas DFS, \nRolla VC, Cavalcante SC et al. Cutaneous tuberculosis \nand HIV infection at a referral centre in Rio de Janeiro, \nBrazil. Mem Inst Oswaldo Cruz 2018;113:e180184.\n\n\n\n11. Bell LCK, Noursadeghi M. Pathogenesis of HIV-1 and \nMycobacterium tuberculosis co-infection. Nat Rev \nMicrobiol 2018;16:80-90.\n\n\n\n12. Ahmed A, Rakshit S, Vyakarnam A. HIV-TB co-infection: \nMechanisms that drive reactivation of Mycobacterium \ntuberculosis in HIV infection. Oral Dis 22 Suppl 1:53-60.\n\n\n\n13. Shankar EM, Vignesh R, Ellegard R, Barathan M, Chong \nYK, Bador MK et al. HIV - Mycobacterium tuberculosis \nco-infection: A \u2018danger-couple model\u2019 of disease \npathogenesis. Pathog Dis 2014;70:110-8.\n\n\n\n14. Gunawan H, Achdiat PA, Hindritiani R, Essary ED, \nNingtias LD, Siregar EP et al. Various cutaneous \ntuberculosis with rare clinical manifestations: A case \nseries. Int J Mycobacteriol 2018;7:288-91.\n\n\n\n15. Daikos GL, Uttamchandani RB, Tuda C, Fischl MA, \nMiller N, Cleary T et al. Disseminated miliary tuberculosis \nof the skin in patients with AIDS: report of four cases. Clin \nInfect Dis 1998;27:205-8.\n\n\n\n16. Naveed T, Shaikh Z, Anwar M. Diagnostic accuracy \nof slit skin smears in leprosy. Pak Armed Forces Med J \n2015;65:649-52.\n\n\n\n17. Elizabeth AT, Brittany JR. Chapter 92 Molecular Medical \nMicrobiology. 2nd Ed. Vol 3. London. Elsevier 2015. \np.1637-53.\n\n\n\n18. Banerjee S, Biswas N, Kanti Das N, Sil A, Ghosh P, \nHasanoor Raja AH et al. Diagnosing leprosy: revisiting \nthe role of the slit-skin smear with critical analysis of the \napplicability of polymerase chain reaction in diagnosis. Int \nJ Dermatol 2011;50:1522-7.\n\n\n\n19. Tang MM, Tan SN, Tey KE, Lim YT, Tan WC, Chan LC \net al. Leprosy and Tuberculosis Co-infection: A Review of \nCases in Dermatology Clinics in Malaysia. Malaysian J \nDermatol 2019;42:14-9.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4786\n\n\n\nCASE REPORT\n\n\n\nCase Series of Akurit-4 Associated DRESS\n\n\n\nAbdul Rahman Che Abdul Rahim, MRCP, Nurnadwa Zafirah Sabri, MBBCh, Rajalingam Ramalingam, \nAdvMDerm\n\n\n\nDepartment of Dermatology Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nWe describe nine cases of anti-tuberculosis DRESS (drug reaction with eosinophilia and systemic \nsymptoms) syndrome, a potentially serious complication of treatment that led to interruption of \ntreatment, systemic corticosteroid usage and the resumption of treatment with different regimens. All \npatients had skin rash, six out of nine patients with hepatitis, two out of nine patients had acute kidney \ninjury, five out of nine patients died. All-cause mortality is high in our cohort.\n\n\n\nKey words: Akurit-4; Tuberculosis; DRESS\n\n\n\nCorresponding Author\nDr Abdul Rahman Che Abdul Rahim\nDepartment of Dermatology, \nHospital Tengku Ampuan Afzan, \n25000 Kuantan, Pahang, Malaysia\nEmail: namhara85@gmail.com\n\n\n\nIntroduction\nSaltzstein and Ackerman in 1959 described a \ncutaneous adverse reaction to anticonvulsant \ndrugs that included fever, eosinophilia, \nlymphadenopathy and sometimes \nhepatosplenomegaly.1 It was subsequently \ndefined by Bocquet et al as drug rash with \neosinophilia and systemic symptoms (DRESS).2 \nCurrently, the Registry of Severe Cutanenous \nAdverse Reaction (RegiSCAR) scoring system \nis the diagnostic criteria that is widely used for \ndrug reaction with eosinophilia and systemic \nsymptoms (DRESS).3 DRESS is considered \none of the severe cutaneous adverse drug \nreaction(SCAR) with a case fatality rate of 10\u2013\n20%.4\n\n\n\nDRESS occurs generally between 2 weeks and 3 \nmonths after drug initiation and is characterized \nby fever, rash and visceral involvement. Its \nnot uncommon that antituberculosis drugs are \nimplicated with DRESS.5 \n\n\n\nIn 2012, the Ministry of Health, Malaysia, \nhas launched the third edition of tuberculosis \nclinical practice guideline to make a Grade \nA recommendation that prefers fixed-dose \ncombination (FDC) anti tuberculosis drug as the \nfirst-line regime for intensive phase treatment \nfor newly diagnosed pulmonary tuberculosis \n(TB) patient.6 One of the fixed dose combination \n(FDC) brands that are currently used in Malaysia \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 87\n\n\n\nis Akurit-4, that are proven to be bioequivalent \nto separate-drug regime which consist of EHRZ \n[ethambutol(E), isoniazid (H), rifampicin (R), \nand pyrazinamide (Z)] at the same dose level.7\n\n\n\nWe describe the experience as a dermatology \ndepartment in a tertiary referral hospital in the \nmanagement of DRESS syndrome associated \nwith Akurit-4. A retrospective observational \nstudy of nine patients with DRESS syndrome \nrelated to drugs used in the treatment of TB \nwas conducted at the Hospital Tengku Ampuan \nAfzan, Kuantan Pahang, Malaysia between \n2017 and 2020. The diagnosis of TB was based \non clinical findings and/or smear positivity.\nThe causal relationship between antituberculosis \ntreatment and DRESS was based on history of \nprior treatment, absence of other medications, \nthe disappearance or improvement of symptoms \nwhen treatment was stopped and, in some cases, \nthe recurrence of DRESS when re-administered \nan anti-tuberculosis drug.\n\n\n\nCase Series\nThere were nine patients with predominantly \nmale (seven patients).  \n\n\n\nPatient number 1 is a 24-year-old lady G2P1 at \n22th week period of gestation. She presented \nwith fever associated with maculopapular rash \nafter 35 days treatment with Akurit-4. She \nwas treated with intravenous hydrocortisone, \ntopical corticosteroid and a total course of 14 \nweeks of tapering prednisolone. Skin biopsy \nwas performed in this case. She had an initial \nrechallenged with isoniazid after 8th week of \nSCAR however was withheld due to increment \nof her ALT. Subsequently at 6th week post-\npartum(after 14th week post SCAR) she had \nuneventful desensitization of full regime EHRZ.\n\n\n\nPatient number 2 is a 28-year-old Malay \ngentleman was diagnosed with pulmonary \ntuberculosis by district clinic and was started \nAkurit -4 that develop DRESS at Day 10. After \nthe course of systemic corticosteroid, revision of \nclinical diagnosis was made by respiratory team \nas bacterial pneumonia and no reintroduction of \nanti-tuberculosis drug was made.\n\n\n\nPatient number 3 has underlying retroviral \ndisease with pulmonary TB and tuberculous \nlymphadenitis. She developed DRESS 15 \ndays after starting Akurit-4. After her course \nof prednisolone, she was lost to follow up. \nSubsequent tracing from a different healthcare \ncentre was found that she had died from \npulmonary related complication.\n\n\n\nPatient number 4 has underlying Type 2 \nDiabetes Mellitus (DM) on oral hypoglycaemic \nagent (OHA). He had first admission at day \n15 for DRESS after starting on Akurit-4. He \nwas discharged well with tapering dose of \nprednisolone. Subsequently was readmitted for \nrecurrent DRESS after introduction of EHRZ. \nHe had six weeks of eventful and prolong \nhospitalization, that was complicated with line \nrelated methicillin-sensitive Staphylococcus \naureus bacteraemia with infective endocarditis, \nuncontrolled diabetes that was complicated by \nerythroderma secondary to DPP4-inhibitors, \nand an extended spectrum beta-lactamase \n(ESBL) line related sepsis. He was eventually \nsuccumbed due to multi-organ failure.\n\n\n\nPatient number 5 had underlying DM presented \nwith severe transaminitis (with peak ALT \n2200 U/L and AST 1600 U/L) presented on \nday 35 after Akurit-4. He succumbed to death \ndue to fulminant hepatic failure. However \nno documentation in regard to prior level of \nliver enzymes after the initial course of anti-\ntuberculosis treatment.\n\n\n\nPatient number 6 was a 46-year-old gentleman \nwith underlying retroviral disease and co-\ninfection Hepatitis C. He was admitted for \nsmear positive PTB which complicated with line \nrelated enterococcus bacteraemia. He presented \nwith generalized maculopapular rash at day \n16 of Akurit-4. He was given initial course of \nintravenous hydrocortisone 100 mg three times \ndaily for five days and subsequently 6 weeks of \ntapering course of oral prednisolone. \n\n\n\nPatient number 7 has multiple comorbidities \ni.e.: DM, Hypertension, Ischemic heart disease \n(IHD). His onset of DRESS was Day 14 after \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4788\n\n\n\nstarting Akurit-4. Six weeks after, he \nhad received a desensitization regime \nof HREL with recurrent of DRESS \nsyndrome. Unfortunately, he succumbed \ndue to fulminant hepatic failure. \n\n\n\nPatient number 8 with underlying \nischemic heart disease (IHD) and \nChronic Obstructive Pulmonary Disease \n(COPD) had initial DRESS secondary \nto Akurit-4 at day 13 of starting \ntreatment. Throughout his course of \ndesensitization regime with different \nanti-TB he had multiple admission due \nto various reasons (recurrent DRESS; \nrash; acute exacerbation of COPD; \ngastrointestinal-related side effect}. \nHe eventually was on anti-TB regime \nconsist of Ethionamide 500mg OM, \n250mg ON, Cyclcoserine 250mg BD, \nLinezolid 600mg OD, Levofloxacin \n500mg OD for a period of five \nmonths before died due to anemia and \npulmonary related complication.\n\n\n\nPatient number 9 had an initial DRESS \nsecondary to Akurit-4 at day 21 of \ntreatment. He had received different \ndesensitization regime that has resulted \nin recurring of DRESS. Eventually he \nwas able to tolerate his final regime \nof Isoniazid 200mg OD, Ethambutol \n800mg OD, Cycloserine 260mg BD, \nClofazimine 100mg OD.\n\n\n\nIt was difficult to establish a causal \nrelationship between which one or more \nanti-tuberculosis drugs and DRESS \nsyndrome in these nine cases. As all of \nthese data were collected retrospectively \nby manual method, some of which had \nincomplete information. None of the \npatients undergone laboratory testing of \ncardiovascular marker (such as creatine \nkinase (CK) or troponin) or pancreatic \nenzyme marker (such as amylase or \nlipase). The clinical information and \noutcomes are summarised in Table 1.\n\n\n\nTa\nbl\n\n\n\ne \n1.\n\n\n\n C\nlin\n\n\n\nic\nal\n\n\n\n fe\nat\n\n\n\nur\nes\n\n\n\n, b\nio\n\n\n\nch\nem\n\n\n\nic\nal\n\n\n\n a\nbn\n\n\n\nor\nm\n\n\n\nal\niti\n\n\n\nes\n, t\n\n\n\nre\nat\n\n\n\nm\nen\n\n\n\nt a\nnd\n\n\n\n o\nut\n\n\n\nco\nm\n\n\n\ne \nof\n\n\n\n n\nin\n\n\n\ne \nca\n\n\n\nse\ns w\n\n\n\nith\n A\n\n\n\nku\nrit\n\n\n\n-4\n d\n\n\n\nru\ng-\n\n\n\nre\nla\n\n\n\nte\nd \n\n\n\nD\nR\n\n\n\nES\nS \n\n\n\nsy\nnd\n\n\n\nro\nm\n\n\n\ne\n\n\n\nN\no\n\n\n\nA\nge\n\n\n\n/\nR\n\n\n\nac\ne\n\n\n\nSe\nx\n\n\n\nSm\nok\n\n\n\nin\ng \n\n\n\nst\nat\n\n\n\nus\nL\n\n\n\nat\nen\n\n\n\ncy\n(d\n\n\n\nay\ns)\n\n\n\nFe\nve\n\n\n\nr\u00b9\nSk\n\n\n\nin\n \n\n\n\nR\nas\n\n\n\nh\u00b2\nL\n\n\n\nN\n\u00b3\n\n\n\nT\nW\n\n\n\nB\nC\n\n\n\n(1\n0\u02c6\n\n\n\n9/\nL\n\n\n\n)\u2074\nPl\n\n\n\nat\nel\n\n\n\net\n \n\n\n\n(1\n0\u02c6\n\n\n\n9/\nL\n\n\n\n)\u2075\nE\n\n\n\nos\nin\n\n\n\nop\nhi\n\n\n\nl \nco\n\n\n\nun\nt c\n\n\n\nel\nls\n\n\n\n/\n\u03bcl\n\n\n\nA\nLT\n\n\n\n/ \nA\n\n\n\nST\n \n\n\n\n(U\nni\n\n\n\nt/L\n)\u2076\n\n\n\nC\nre\n\n\n\nat\n\u2077\n\n\n\n(\u03bc\nm\n\n\n\nol\n/L\n\n\n\n)\nO\n\n\n\nth\ner\n\n\n\n D\nru\n\n\n\ngs\nIn\n\n\n\niti\nal\n\n\n\n T\nre\n\n\n\nat\nm\n\n\n\nen\nt G\n\n\n\niv\nen\n\n\n\n; \nSu\n\n\n\nbs\neq\n\n\n\nue\nnt\n\n\n\n T\nhe\n\n\n\nra\npy\n\n\n\nA\nnt\n\n\n\ni- \nT\n\n\n\nB\n \n\n\n\nD\nru\n\n\n\ng\nO\n\n\n\nut\nco\n\n\n\nm\ne\n\n\n\nC\nau\n\n\n\nse\n \n\n\n\nof\n \n\n\n\nD\nea\n\n\n\nth\n\n\n\nSk\nin\n\n\n\n \nB\n\n\n\nio\nps\n\n\n\ny\n\n\n\n1\n24\n\n\n\n/\nM\n\n\n\nal\nay\n\n\n\nF\nN\n\n\n\nev\ner\n\n\n\n \nsm\n\n\n\nok\ned\n\n\n\n35\nY\n\n\n\nY\nN\n\n\n\n8.\n2\n\n\n\n36\n9\n\n\n\n16\n00\n\n\n\n48\n7/\n\n\n\n27\n0\n\n\n\n35\nPy\n\n\n\nrid\nox\n\n\n\nin\ne\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nEH\n\n\n\nR\nZ\n\n\n\nSu\nrv\n\n\n\niv\ned\n\n\n\n-\nY\n\n\n\n2\n28\n\n\n\n/\nM\n\n\n\nal\nay\n\n\n\nM\nN\n\n\n\nev\ner\n\n\n\n \nsm\n\n\n\nok\ned\n\n\n\n10\nY\n\n\n\nY\nY\n\n\n\n6.\n1\n\n\n\n20\n8\n\n\n\n37\n0\n\n\n\n53\n/4\n\n\n\n6\n12\n\n\n\n1\nPy\n\n\n\nrid\nox\n\n\n\nin\ne\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nN\n\n\n\not\n re\n\n\n\n-\nin\n\n\n\ntro\ndu\n\n\n\nce\nd\n\n\n\nSu\nrv\n\n\n\niv\ned\n\n\n\n-\nN\n\n\n\n3\n34\n\n\n\n/\nM\n\n\n\nal\nay\n\n\n\nF\nN\n\n\n\nev\ner\n\n\n\n \nsm\n\n\n\nok\ned\n\n\n\n15\nY\n\n\n\nY\nN\n\n\n\nA\n7.\n\n\n\n0\n27\n\n\n\n6\n13\n\n\n\n70\n34\n\n\n\n6/\n49\n\n\n\n0\n33\n\n\n\nC\no-\n\n\n\ntri\nm\n\n\n\nox\naz\n\n\n\nol\ne\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nN\n\n\n\nA\nD\n\n\n\nea\nth\n\n\n\nTB\nN\n\n\n\n4\n41\n\n\n\n/\nM\n\n\n\nal\nay\n\n\n\nM\nSm\n\n\n\nok\ner\n\n\n\n15\nN\n\n\n\nY\nN\n\n\n\n22\n23\n\n\n\n1\n11\n\n\n\n58\n0\n\n\n\n10\n1/\n\n\n\n24\n9\n\n\n\n74\nPy\n\n\n\nrid\nox\n\n\n\nin\ne\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nEH\n\n\n\nR\nZ\n\n\n\nD\nea\n\n\n\nth\nSe\n\n\n\nps\nis\n\n\n\nN\n\n\n\n5\n46\n\n\n\n/ \nM\n\n\n\nal\nay\n\n\n\nM\nSm\n\n\n\nok\ner\n\n\n\n35\nY\n\n\n\nY\nY\n\n\n\n45\n40\n\n\n\n0\n46\n\n\n\n00\n22\n\n\n\n00\n/\n\n\n\n16\n00\n\n\n\n71\nM\n\n\n\net\nfo\n\n\n\nrm\nin\n\n\n\n, \nPy\n\n\n\nrid\nox\n\n\n\nin\ne\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nN\n\n\n\not\n re\n\n\n\n-\nin\n\n\n\ntro\ndu\n\n\n\nce\nd\n\n\n\nD\nea\n\n\n\nth\nLi\n\n\n\nve\nr \n\n\n\nfa\nilu\n\n\n\nre\nN\n\n\n\n6\n46\n\n\n\n/\nIn\n\n\n\ndi\nan\n\n\n\nM\nEx\n\n\n\n-s\nm\n\n\n\nok\ner\n\n\n\n16\nY\n\n\n\nY\nY\n\n\n\n7.\n2\n\n\n\n25\n2\n\n\n\n25\n00\n\n\n\n19\n/N\n\n\n\nA\n13\n\n\n\n8\nVa\n\n\n\nnc\nom\n\n\n\nyc\nin\n\n\n\n, \nSy\n\n\n\nru\np \n\n\n\nN\nys\n\n\n\nta\ntin\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nSH\n\n\n\nEL\nSu\n\n\n\nrv\niv\n\n\n\ned\n-\n\n\n\nN\n\n\n\n7\n60\n\n\n\n/ \nC\n\n\n\nhi\nne\n\n\n\nse\nM\n\n\n\nN\nA\n\n\n\n14\nY\n\n\n\nY\nN\n\n\n\nA\n11\n\n\n\n.3\n13\n\n\n\n8\n10\n\n\n\n0\n61\n\n\n\n7/\n37\n\n\n\n6\n82\n\n\n\nN\nil\n\n\n\nIV\n H\n\n\n\nyd\nro\n\n\n\nco\nrti\n\n\n\nso\nne\n\n\n\n, T\nC\n\n\n\nS;\n \n\n\n\nor\nal\n\n\n\n p\nre\n\n\n\ndn\nis\n\n\n\nol\non\n\n\n\ne\nH\n\n\n\nR\nEL\n\n\n\nD\nea\n\n\n\nth\n \n\n\n\nLi\nve\n\n\n\nr \nfa\n\n\n\nilu\nre\n\n\n\nN\n\n\n\n8\n63\n\n\n\n/ \nC\n\n\n\nhi\nne\n\n\n\nse\nM\n\n\n\nEx\n-s\n\n\n\nm\nok\n\n\n\ner\n14\n\n\n\nN\nY\n\n\n\nN\n7.\n\n\n\n7\n30\n\n\n\n8\n10\n\n\n\n00\n37\n\n\n\n4/\nN\n\n\n\nA\nN\n\n\n\nA\nN\n\n\n\nil\nIV\n\n\n\n H\nyd\n\n\n\nro\nco\n\n\n\nrti\nso\n\n\n\nne\n, T\n\n\n\nC\nS;\n\n\n\n \nor\n\n\n\nal\n p\n\n\n\nre\ndn\n\n\n\nis\nol\n\n\n\non\ne\n\n\n\nEt\n/C\n\n\n\nyc\nlo\n\n\n\n/L\n/ \n\n\n\nLi\nne\n\n\n\nzo\nlid\n\n\n\nD\nea\n\n\n\nth\nC\n\n\n\nO\nPD\n\n\n\nY\n\n\n\n9\n75\n\n\n\n/\nM\n\n\n\nal\nay\n\n\n\nM\nEx\n\n\n\n-s\nm\n\n\n\nok\ner\n\n\n\n21\nY\n\n\n\nY\nN\n\n\n\nA\n2.\n\n\n\n2\n12\n\n\n\n9\n18\n\n\n\n00\n9/\n\n\n\nN\nA\n\n\n\n79\nN\n\n\n\nil\nIV\n\n\n\n H\nyd\n\n\n\nro\nco\n\n\n\nrti\nso\n\n\n\nne\n; o\n\n\n\nra\nl \n\n\n\npr\ned\n\n\n\nni\nso\n\n\n\nlo\nne\n\n\n\nE/\nH\n\n\n\n/C\nyc\n\n\n\nlo\n/ \n\n\n\nC\nlo\n\n\n\nfa\nzi\n\n\n\nm\nin\n\n\n\ne\nSu\n\n\n\nrv\niv\n\n\n\ned\n-\n\n\n\nN\n\n\n\nF:\n F\n\n\n\nem\nal\n\n\n\ne,\n M\n\n\n\n: M\nal\n\n\n\ne,\n Y\n\n\n\n: Y\nes\n\n\n\n, N\n: N\n\n\n\no,\n  I\n\n\n\nV:\n in\n\n\n\ntr\nav\n\n\n\nen\nou\n\n\n\ns, \nN\n\n\n\nA:\n N\n\n\n\not\n a\n\n\n\nva\nila\n\n\n\nbl\ne,\n\n\n\n T\nW\n\n\n\nBC\n: T\n\n\n\not\nal\n\n\n\n w\nhi\n\n\n\nte\n b\n\n\n\nlo\nod\n\n\n\n c\nel\n\n\n\nls\n, C\n\n\n\nre\nat\n\n\n\n: c\nre\n\n\n\nat\nin\n\n\n\nin\ne,\n\n\n\n C\nO\n\n\n\nPD\n: C\n\n\n\nhr\non\n\n\n\nic\n p\n\n\n\nul\nm\n\n\n\non\nar\n\n\n\ny \nob\n\n\n\nst\nru\n\n\n\nct\niv\n\n\n\ne \ndi\n\n\n\nse\nas\n\n\n\ne,\n T\n\n\n\nC\nS:\n\n\n\n T\nop\n\n\n\nic\nal\n\n\n\n c\nor\n\n\n\ntic\nos\n\n\n\nte\nro\n\n\n\nid\ns, \n\n\n\nTB\n: T\n\n\n\nub\ner\n\n\n\ncu\nlo\n\n\n\nsi\ns, \n\n\n\nE:\n E\n\n\n\nth\nam\n\n\n\nbu\nto\n\n\n\nl, \n H\n\n\n\n:I\nso\n\n\n\nni\naz\n\n\n\nid\n, R\n\n\n\n: r\nifa\n\n\n\nm\npi\n\n\n\nci\nn,\n\n\n\n Z\n: P\n\n\n\nyr\naz\n\n\n\nin\nam\n\n\n\nid\ne,\n\n\n\n S\n: S\n\n\n\ntre\npt\n\n\n\nom\nyc\n\n\n\nin\n, E\n\n\n\nt: \nEt\n\n\n\nhi\non\n\n\n\nam\nid\n\n\n\ne,\n C\n\n\n\nyc\nlo\n\n\n\n: C\nyc\n\n\n\nlo\nse\n\n\n\nri\nne\n\n\n\n.\n\u00b9T\n\n\n\nem\npe\n\n\n\nra\ntu\n\n\n\nre\n m\n\n\n\nor\ne \n\n\n\nth\nan\n\n\n\n 3\n8\u00b0\n\n\n\nC\n a\n\n\n\nt p\nre\n\n\n\nse\nnt\n\n\n\nat\nio\n\n\n\nn;\n \u00b2m\n\n\n\nac\nul\n\n\n\nop\nap\n\n\n\nul\nar\n\n\n\n ra\nsh\n\n\n\n; \u00b3\nly\n\n\n\nm\nph\n\n\n\nad\nen\n\n\n\nop\nat\n\n\n\nhi\nes\n\n\n\n a\nt t\n\n\n\nw\no \n\n\n\nor\n m\n\n\n\nor\ne \n\n\n\nsi\nte\n\n\n\n; \u2074\nN\n\n\n\nor\nm\n\n\n\nal\n ra\n\n\n\nng\ne:\n\n\n\n 4\n.0\n\n\n\n to\n 1\n\n\n\n0.\n0 \n\n\n\n(1\n0\u02c6\n\n\n\n9/\nL)\n\n\n\n; \u2075\nN\n\n\n\nor\nm\n\n\n\nal\n ra\n\n\n\nng\ne:\n\n\n\n 1\n50\n\n\n\n to\n 4\n\n\n\n00\n (1\n\n\n\n0\u02c6\n9/\n\n\n\nL)\n; \u2076\n\n\n\nN\nor\n\n\n\nm\nal\n\n\n\n ra\nng\n\n\n\ne \n<\n\n\n\n50\n U\n\n\n\nni\nt/L\n\n\n\n; \u2077\nN\n\n\n\nor\nm\n\n\n\nal\n \n\n\n\nra\nng\n\n\n\ne:\n 5\n\n\n\n9 \nto\n\n\n\n 1\n04\n\n\n\n \u03bc\nm\n\n\n\nol\n/L\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 89\n\n\n\nDiscussion\nAll antituberculosis drugs pose a risk of DRESS \nsyndrome. In general, rifampicin was the most \ncommonly suspected drug because of its larger \nindications, but in the case of tuberculosis \ninfections, isoniazid was the most commonly \nsuspected drug.8 \nIn our case series, the characteristics of \nantituberculosis drug-associated DRESS \nsyndrome are consistent with literature data9 \nwith a mean time to onset of 19.4 days. Liver \nand kidneys were the most frequently involved \norgans. Skin biopsy were performed in two \ncases. \n\n\n\nA reintroduction of culprit drugs is generally \nconsidered contraindicated after a diagnosis \nof DRESS syndrome. Because of the severity \nof the tuberculosis infection, the lack of \ntherapeutic options and the risk/benefit balance, \na reintroduction could be justified.10 \n\n\n\nTreatment of DRESS syndrome generally \nincludes withdrawal of the offending drugs, \ncorrection of electrolyte imbalance, and \nadministration of corticosteroid. In our clinical \npractice, systemic corticosteroids have become \na mainstay of therapy in the form of intravenous \nhydrocortisone and prednisolone. The \nprednisolone dose will be tapered down slowly \nover course of 8 to 12 weeks as rapid tapering \nmay increase the risk of relapse.9 \n\n\n\nOther options include intravenous \nimmunoglobulin or plasmapheresis have \nbeen reported to show a promising treatment \neffectiveness.11 As none of our patients \nreceived this treatment, further studies are \nrequired to establish the benefits of these \nimmunosuppressants.\n\n\n\nBased on the larger cohort from Taiwan which \ninclude a total of 60 cases, DRESS syndrome \nhas mortality rate of around 10%.4 Among those \ndescribe, only two patients on anti-tuberculosis \ndrug and none of them died. In our cohort, five \nout of nine patients had died due to various \nreasons (55% mortality rate). This include \ntwo patients (22.2%) which attributed directly \n\n\n\nto fulminant hepatic failure due to DRESS, \nwhile the others due do various complication of \nprolonged hospitalization and comorbidities.\n\n\n\nDespite DRESS is a life-threatening syndrome, \ndifficulty in identifying predictive factors for \ndeath remain a challenge. It is worth mentioning \nthat five out of six patients with transaminitis \ndied, however whether its usefulness as a \nmarker remain questionable.11 Apart from that, \ndifferences of other clinical variables were not \nfound between cases resulting in death and \nthose that survived.\n\n\n\nBlood eosinophilia could be a useful marker of \ndisease progression and treatment response and \nrecurrence in patients with DRESS.3 However, \nmore experience and clinical evidence is needed.\n\n\n\nExisting human leucocyte antigen (HLA) \ndata is minimal in relation to anti-TB drugs. \nThere has been an association reported in \nKorean patients with DRESS for the class I \nallele HLA-C*04:01,12 which extends to the \nhaplotype HLA-A* 11:01-B*15:01-C*04:01. \nHowever, these alleles are not reported in the \ncases presented by Ye et al.13\n\n\n\nOur study has several limitations. The \nretrospective review is subject to publication \nbias. The conclusions we were able to draw \nare limited by data gaps in these cases. Some \ndetails on clinical and outcome parameters or \non therapy were often not described. No HHV- \n6 serology was done due to unavailability of the \ntest in our centre.\n\n\n\nConclusion\nOur case series highlights the diagnosis and \nchallenges in clinical management of Akurit-4 \nassociated DRESS and its high all-cause \nmortality.\n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto disclosed.\n\n\n\nAcknowledgement\nWe would like to thank the Director of General \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4790\n\n\n\nof Health Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n\n\n\n1. Saltzstein SL, Ackerman LV. Lymphadenopathy \ninduced by anticonvulsant drugs and mimicking \nclinically pathologically malignant lymphomas. Cancer \n1959;12:164-82.\n\n\n\n2. Bocquet H, Bagot M, Roujeau JC. Drug-induced \npseudolymphoma and drug hypersensitivity syndrome \n(Drug Rash with Eosinophilia and Systemic Symptoms: \nDRESS). Semin Cutan Med Surg. 1996;15:250-7.\n\n\n\n3. Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, \nDavidovici BB, Mockenhaupt M, Roujeau JC. Variability \nin the clinical pattern of cutaneous side-effects of drugs \nwith systemic symptoms: does a DRESS syndrome really \nexist? Br J Dermatol. 2007;156:609-11.\n\n\n\n4. Chen YC, Chiu HC, Chu CY. Drug reaction with \neosinophilia and systemic symptoms: a retrospective study \nof 60 cases. Arch Dermatol 2010;146(12):1373-9.\n\n\n\n5. Kaswala DH. Drug rash with eosinophilia and systemic \nsymptoms syndrome due to anti-TB medication. J Family \nMed Prim Care 2013;2:83-5.\n\n\n\n6. Malaysia Heath Technology Assessment Section \n(MaHTAS). Clinical practice guidelines on management \nof tuberculosis. 3rd edition 2012.\n\n\n\n7. Lai JML, Yang SL, Avoi R. Treating more with less: \neffectiveness and event outcomes of antituberculosis fixed-\ndose combination drug versus separate-drug formulation \n(Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) \nfor pulmonary tuberculosis patients in real-world clinical \npractice. J Glob Infect Dis 2019; 11(1): p. 2-6.\n\n\n\n8. Allouchery M, Logerot S, Cottin J, Pralong P, Villier C, \nBen Sa\u00efd B. French pharmacovigilance centers network \nand the French investigators for skin adverse reactions to \ndrugs. antituberculosis drug-associated DRESS: A case \nseries. J Allergy Clin Immunol Pract 2018;6:1373-80.\n\n\n\n9. Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, \nFinzi L et al. The DRESS syndrome: A literature review. \nAm J Med 2011;124:588-97.\n\n\n\n10. Wang L, Li LF. Difficult clinical management of \nantituberculosis DRESS syndrome complicated by \nMRSA infection: A case report. Medicine (Baltimore) \n2017;96:e6346.\n\n\n\n11. Eshki M, Allanore L, Musette P, Milpied B, Grange A, \nGuillaume JC et al. Twelve-year analysis of severe cases of \ndrug reaction with eosinophilia and systemic symptoms: a \ncause of unpredictable multiorgan failure. Arch Dermatol. \n2009;145:67-72.\n\n\n\n12. Cho YT, Chu CY. Treatments for severe cutaneous adverse \nreactions. J Immunol Res 2017;2017:1503709.\n\n\n\n13. Pavlos R, Redwood A, Phillips E. AdDRESSing T-cell \nresponses to antituberculous drugs. Br J Dermatol \n2017;176:292-3.\n\n\n\n14. Ye YM, Hur GY, Kim SH, Ban GY, Jee YK, Naisbitt \nDJ et al. Drug-specific CD4+ T cell immune responses \nare responsible for antituberculosis drug-induced \nmaculopapular exanthema and drug reaction with \neosinophilia and systemic symptoms syndrome. Br J \nDermatol 2017;176:378-86.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 91\n\n\n\nCASE REPORT\n\n\n\nPyoderma Gangrenosum Arising De Novo Over an Unusual Site: A Case \nReport\n\n\n\nVasudha Abhijit Belgaumkar (MDDVL), Ravindranath Brahmadeo Chavan (MDDVL), Neelam Bhatt \n(MDDVL), Kopal Agrawal (MDDVL)\n\n\n\nDepartment of Dermatology, Venereology and Leprosy, B.J.G.M.C and Sassoon General Hospital, \nMaharashtra, India.\n\n\n\nSummary\nPyoderma gangrenosum (PG) of the breast is a rare rapidly progressive neutrophilic dermatosis, \nwhich usually co-exists with severe underlying systemic conditions. A woman presented with a non-\nhealing ulcer over her right breast with characteristic sparing of nipple-areola complex (Bork-Baykal \nphenomenon). It was diagnosed as pyoderma gangrenosum on the basis of clinico-pathological \ncorrelation and managed successfully with systemic corticosteroids and anti-inflammatory drugs \nalong with wound care. The diagnosis and treatment of PG is challenging particularly at unusual \nsites given the paucity of robust clinical evidence and lack of consensus opinion regarding specific \nmanagement guidelines. It is imperative that PG is considered as a clinical diagnosis in any patient \nwith enlarging, sterile, necrotic lesions unresponsive to appropriate antibiotics. Early recognition of \nPG at rare locations can prevent devastating sequelae such as over-zealous surgical debridement and \ndeep tissue infections associated with a chronic open wound leading to severe cosmetic morbidity.\n\n\n\nKey words: Pyoderma gangrenosum, Neutrophilic dermatosis, Bork-Baykal phenomenon\n\n\n\nCorresponding Author\nDr Ravindranath Brahmadeo Chavan\nDepartment of Dermatology, Leprosy and Venereology, \nB.J. Government Medical College and Sassoon General \nHospital, Pune, \nMaharashtra, 411001, India \nEmail: drravindranathchavan@gmail.com\n\n\n\nIntroduction\nPyoderma gangrenosum (PG), a rare \ninflammatory skin condition of unknown \netiology.1 Annually, three to ten in a million are \nreported as newly diagnosed cases with 50\u201370% \nsuffering from underlying systemic diseases like \nautoimmune (inflammatory bowel disease and \nrheumatoid arthritis) or hematologic disorders \n(leukemia and lymphoma).2 PG generally \npresents as an initial papule, pustule or nodule \nafter minor trauma, progressing to painful deep \nnecrotic ulcers that wax and wane over time \nand may mimic an infection. Common sites \nare lower extremities (pretibial area) followed \nby trunk, head, neck, hands, peristomal skin \nand extracutaneous tissues (lungs, liver, bones) \ninfrequently.3 \n\n\n\nBreast PG is seldom encountered, with only \n43 cases reported worldwide, 70% of which \nemerged after breast surgical intervention.4 PG \nis often erroneously diagnosed as a necrotizing \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4792\n\n\n\ninfection where surgical intervention initiates \npathergic phenomenon and accelerates necrotic \nprocess. Herein, we report mammary PG in the \nabsence of systemic association or antecedent \nsurgical manipulation.   \n\n\n\nCase report\nA 52-year-old female presented with a \nprogressively enlarging painful raw area over \nthe right breast since one month. It had started \nfew months ago as a small pus-filled reddish \nlesion which increased in size and ulcerated. \nShe denied trauma, surgical procedures, fever, \nweight loss, abdominal or joint pain, diarrhea \nor similar lesions elsewhere in the past. She \nhad received multiple antibiotic courses \nwithout improvement. General and systemic \nexamination were within normal limits except \npallor. Local examination showed a single, \ntender, well-defined eight by seven cm ulcer \nover the right breast with violaceous margins, \nundermined edges and healthy pink granulation \ntissue with sparing of areola and nipple (Figure \n1a). \n\n\n\nDifferential diagnoses kept were pyoderma \ngangrenosum, Paget\u2019s disease, pemphigus \nvegetans and atypical mycobacterial ulcer. \nLaboratory investigations (complete hemogram, \nliver and renal function tests, C reactive \nprotein, erythrocyte sedimentation rate), chest \nX ray, ultrasonography of abdomen and pelvis, \nelectrocardiography, 2D Echocardiography and \ngastroenterology evaluation were normal except \nanemia of chronic disease and iron deficiency \n(Hemoglobin-7.8mg/dL, peripheral blood smear \nshowed microcytosis and anisocytosis). Pus \nculture and Ziehl Neelsen stain were negative. \nHistopathology (hematoxylin and eosin stain) \nshowed unremarkable epidermis, perivascular \nmononuclear and dermal neutrophilic infiltration \nwith micro-abscess in subcutaneous (Figure \n1c&d). Special stains for acid fast bacilli and \nfungi were negative. \n\n\n\nA final diagnosis of pyoderma gangrenosum \nwas made. Patient was started on tablet \nprednisolone one mg/kg (tapered off gradually \nover four months) along with antibiotics \n\n\n\n(ciprofloxacin, metronidazole, piperacillin-\ntazobactam and meropenem). Two monthly \npulses of injection methylprednisolone (1000 \nmg for three consecutive days per month) were \nadministered with tablet colchicine 0.5mg twice \ndaily and capsule doxycycline 100mg once \ndaily with wound care. After the first pulse, \nthe ulcer showed marked improvement with \nshrinking margins. Complete resolution with \npost-inflammatory pigmentary changes and \ncribriform scarring was seen after ten months \n(Figure 1b).\n\n\n\nFigure 1 (a) A single, well defined 8cm x 7cm \nulcer over the right breast with violaceous margins, \nundermined edges and healthy pink granulation \ntissue with sparing of areola and nipple; (b) The ulcer \nshowed complete resolution with post inflammatory \ndyspigmentation and scarring after ten months; \n(c) Histopathology (hematoxylin and eosin stain) \nshowing unremarkable epidermis, perivascular \nmononuclear and dermal neutrophilic infiltration \nwith micro-abscess in subcutaneous tissue in \nscanner view; (d) Histopathology (hematoxylin \nand eosin stain) showing neutrophilic infiltration in \nsubcutaneous tissue in 40x.\n\n\n\nDiscussion\nFrench dermatologist Brocq termed pyoderma \ngangrenosum as \u201cgeometric phagedenism\u201d, \nconsidering it a bacterial infectious disease.5 \nToday, it is classified as a neutrophilic \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 93\n\n\n\ndermatosis, as histological examination exhibits \npredominantly neutrophilic infiltrates, without \nevidence of infection.6 Although the underlying \npathogenesis remains unclear, autoimmune \nmechanisms of dysregulated inflammation, \nneutrophilic dysfunction, and genetic factors \nhave been implicated.7 \n\n\n\nPreviously, no criteria consistently or reliably \ndistinguished PG from necrotizing soft tissue \ninfections, particularly in the absence of systemic \ndiseases. Recently, a validated set of criteria \nhave been published [1 major criterion: biopsy of \nulcer edge demonstrating neutrophilic infiltrate-\nand 8 minor criteria: (1) exclusion of infection; \n(2) pathergy; (3) history of inflammatory \nbowel disease or inflammatory arthritis; (4) \nhistory of papule, pustule, or vesicle ulcerating \nwithin 4 days of appearing; (5) peripheral \nerythema, undermining border, and tenderness \nat ulceration site; (6) multiple ulcerations, at \nleast 1 on an anterior lower leg; (7) cribriform \nor \u201cwrinkled paper\u201d scar(s) at healed ulcer sites; \nand (8) decreased ulcer size within 1 month of \ninitiating immunosuppressive medication(s)],8 \n\n\n\nwherein one major criterion (skin biopsy \ndemonstrating neutrophilic infiltration) and \nfour out of eight minor criteria (exclusion of \ninfection, history of papule ulcerating within \nfour days, undermined borders and tenderness \nand decreased size of ulcer within one month \nof initiating immunosuppressive medication) \nare mandatory for diagnosis and were fulfilled \nin our case.\n\n\n\nAnother subtle clinical clue that helped us \nconfirm the diagnosis of PG was the typical \nsparing of nipple-areola complex (Bork-Baykal \nphenomenon).9 This quaint appearance has been \nalso been reported with capillary malformations \nand large melanocytic nevi.10 It is probably \nattributable to the immunologic privilege \nimparted by increased quantum of melanocytes \nin this area. Pathergy (development of skin \nlesions that resist healing after tissue injury) is \nan important feature. \n\n\n\nPrevious cases of PG have been documented \nafter breast surgery and silicon augmentation \n\n\n\nmastopexy. However, the development of de \nnovo ulcers in the absence of any systemic \nassociations is extremely rare. The clinical \ncourse of PG is unpredictable. Skin biopsies \nfor histology and microbiology are critical to \nnarrow the differential diagnosis. Infections that \ncan mimic PG include atypical mycobacterial \nulcers, cutaneous tuberculosis, cutaneous \nleishmaniasis, sporotrichosis, and other deep \nfungal infections. The non-infectious differential \ncomprises vasculitis, thrombophilia, cutaneous \nmalignancies and drug-induced conditions.6 \nInitial wound cultures yielding skin flora such \nas S. aureus are often erroneously considered \nthe culprit. In true PG, targeted antimicrobial \ntherapy eventually fails, and lesions can \nprogressively enlarge with debridement.\n\n\n\nTreatment of PG remains challenging as \nno single effective therapeutic regimen or \nconsensus guideline exists. Initial investigation \nfor associated underlying systemic disease is \ncrucial as treating this can hasten resolution. \nFor mild disease such as single or superficial \nlesions, conventional evidence-based first-line \ntreatments involve topical medications such \nas high-potency corticosteroids or calcineurin \ninhibitors.7 There is a paucity of data to inform \nclinical decision-making when considering \nsecond-line systemic therapies (methotrexate, \nazathioprine, mycophenolate mofetil, \ncyclophosphamide, dapsone, thalidomide, \nand intravenous immunoglobulins) which \nare mainly used as steroid-sparing agents for \nmaintenance or in combination with first-line \nagents for refractory disease. Our case responded \nremarkably to two pulses of methylprednisolone \nwith daily colchicine and doxycycline (used as \nanti-inflammatory agents) for ten months.\n\n\n\nConclusion\nPyoderma gangrenosum of the breast is a \nrare entity, to be considered when rapidly \nprogressing ulcerative lesions are observed. \nThough often correlated to previous surgical \ntreatment or systemic inflammatory and \nhematologic disorders, our patient developed \nit de novo. A vigilant clinical examination \n(particularly for characteristic clues like the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4794\n\n\n\nBork-Baykal phenomenon), histopathological \nevaluation and systemic assessment is \nparamount, while treatment with topical or \nsystemic glucocorticosteroids along with \nadjuvant drugs and wound care is the optimum \nfirst-line therapeutic approach. \n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto disclosed.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences \n\n\n\n1. Pereira N, Brites MM, Gon\u00e7alo M, Tellechea O, Figueiredo \nA. Pyoderma gangrenosum\u2013a review of 24 cases observed \nover 10 years. Int J Dermatol 2013;52:938-45.  \n\n\n\n2. Wollina U. Pyoderma gangrenosum \u2013 a review. Orphanet J \nRare Dis 2007;2:19.\n\n\n\n3. Hayes RC, Curtis A. Pyoderma gangrenosum with a \ncontiguous erosion of the distal ulna. J Cutan Med Surg \n2004;8:162-5. \n\n\n\n4. Marinopoulos S, Theofanakis C, Zacharouli T, Sotiropoulou \nM, Dimitrakakis C. Pyoderma Gangrenosum of the breast: \nA case report study. Int J Surg Case Rep 2017;31:203-5. \n\n\n\n5. Farhi D. The clinical and histopathological description of \ngeometric phagedenism (pyoderma gangrenosum) by Louis \nBrocq one century ago. Arch Dermatol 2008;144:755. \n\n\n\n6. Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. \nPyoderma gangrenosum: clinicopathologic correlation and \nproposed diagnostic criteria. Int J Dermatol 2004;43:790-\n800. \n\n\n\n7. Ahronowitz I, Harp J, Shinkai K. Etiology and management \nof pyoderma gangrenosum: a comprehensive review. Am J \nClin Dermatol 2012;13:191-211. \n\n\n\n8. Maverakis E, Ma C, Shinkai K, Fiorentino D, Callen JP, \nWollina U et al. Diagnostic Criteria of Ulcerative Pyoderma \nGangrenosum: A Delphi Consensus of International \nExperts. JAMA Dermatol 2018;154:461-6. \n\n\n\n9. Aytekin S, S\u00fcel S, G\u00fcne\u015f P. The Bork-Baykal phenomenon \nas sparing of areola and nipple is a clue for the diagnosis \nof breast pyoderma gangrenosum. J Eur Acad Dermatol \nVenereol 2020;34:e608-9. \n\n\n\n10. Happle R. The Bork-Baykal phenomenon: a revised \neponymic designation for the sparing of nipple and areola \nin large melanocytic nevi involving the breast. J Eur Acad \nDermatol Venereol 2017;31:e214. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 95\n\n\n\nCASE REPORT\n\n\n\nSubcutaneous Sarcoidosis (Darier Roussy Sarcoid): A Rare Entity of \nCutaneous Sarcoidosis\n\n\n\nWei Cheng Leong1, MRCP, Wahinuddin Sulaiman2, FRCP, Ling Tze Tan3, MPath, Jyh Jong Tang1, \nAdvMDerm \n\n\n\n1 Dermatology Department, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia\n2 Faculty of Medicine, Universiti Kuala Lumpur, Kuala Lumpur, Malaysia\n3 Pathology Department, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia\n\n\n\nSummary\nSarcoidosis is a multisystem disease characterised by granulomatous inflammation possibly due to \nhyperactivation of the immune system; with unknown etiology. Subcutaneous sarcoidosis (also known \nas Darier Roussy sarcoid) is a rare type of specific cutaneous lesion of sarcoidosis characterised by \nmultiple firm, asymptomatic to mildly tender, mobile, round to oval, and skin coloured nodules. Herein \nwe report a rare case of subcutaneous sarcoidosis.\n\n\n\nKey words: Subcutaneous sarcoidosis, Darier Roussy sarcoid, Non-caseating granulomas\n\n\n\nCorresponding Author \nDr Leong Wei Cheng\nDepartment of Dermatology,\nHospital Raja Permaisuri Bainun,\nJalan Raja Ashman Shah,\n30450 Ipoh, Perak, Malaysia\nEmail: leongweicheng@hotmail.com\n\n\n\nIntroduction\nSarcoidosis is a multisystem disease \ncharacterised by granulomatous inflammation \npossibly due to hyperactivation of the immune \nsystem; with unknown etiology.1 The clinical \nfeatures of sarcoidosis can be cutaneous and \nnon-cutaneous. For cutaneous findings, it can \nbe classified into specific and non-specific \nfindings. Subcutaneous nodules (Darier-Roussy \nsarcoid) is a form of specific cutaneous lesion \nof sarcoidosis.1 Subcutaneous sarcoidosis \naccounts for < 6% of sarcoidosis;2 with fewer \nthan 100 cases reported so far.3 Herein we report \na rare case of subcutaneous sarcoidosis on both \nforearms associated with acute polyarthritis in \nan elderly gentleman.\n\n\n\nCase Report\nA 69-year-old Indian gentleman with \nunderlying hypertension and type 2 diabetes \nmellitus for more than 10 years, presented \nwith multiple asymptomatic skin coloured \nnodules over bilateral forearms for 2 months. \nPrior to the onset of the nodules, he had an \nepisode of multiple joint pain involving both \nankle joints and shoulder girdle of which he \nwas diagnosed with polymyalgia rheumatic \n(PMR) by a rheumatologist. However, he had \nno temporal headache or ophthalmic symptoms. \nThis acute episode of polyarthritis was relieved \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4796\n\n\n\ndrastically with corticosteroid over 24 hours.  \nSubsequently, he noticed multiple soft to firm \nand painless subcutaneous nodules over both \nhis forearms which gradually increased in size \nover 2 months. There were no similar nodules \non his legs or other parts of his body. \n\n\n\nOtherwise he did not experience any cough, \nshortness of breath, eye symptoms or \nneurological symptoms. There was no uveitis or \nperipheral neuropathy. He was diagnosed with \ngouty arthritis for more than 10 years with history \nof obstructive uropathy which had resolved.  He \nhad been taking allopurinol only when eating \nseafood which he claimed would precipitate the \npain. He had no cardiorespiratory symptoms. \nNeither had he contact with tuberculosis patient \nnor contributory family history. He never \nsmoked but drank alcohol on social event. \nOn physical examination, there were multiple \nnon-tender, soft to firm subcutaneous nodules \nmeasuring approximately 3cm x 4cm on both \nforearms with normal overlying and surrounding \nskin (Figure 1a). It was not attached to the \nunderlying structure.  \n\n\n\nRespiratory examination was normal and there \nwere no peripheral lymph nodes palpable. \nThere was no organomegaly and examination of \nother systems were unremarkable. The clinical \ndifferential diagnosis included erythema \nnodosum, nodular vasculitis, rheumatoid \nnodules, subcutaneous sarcoidosis and \nsubcutaneous granuloma annulare.\n\n\n\nFigure 1(a) Multiple subcutaneous nodules on left \nforearm (arrows show the outline of the nodules); (b) \nlow power magnification (4x10) of non-caseating \ngranulomas; (c) Non-caseating granulomatous \ninfiltrate in the dermis extends into subcutaneous \nfat; (d) Non caseating granuloma composed of \nepithelioid histiocytes, multinucleated giant cells and \nsparse lymphocytes at the periphery. Asteroid body \nis seen here (arrow); (d) Non caseating granuloma \ncomposed of epithelioid histocytes, multinucleated \ngiant cells and sparse lymphocytes at the periphery.  \nSchaumann body is seen here (arrow).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 97\n\n\n\nLaboratory investigations revealed raised \nESR 63 mm/hour, C-reactive protein (CRP) \n23, negative rheumatoid factor (RF) and anti-\ncitrullinated cyclic peptide (CCP), serum \ncalcium 2.47 mmol/L, normal complete blood \ncount, renal and liver profiles. Skin biopsy was \nperformed which showed multiple noncaseating \ngranulomatous inflammation in the deep \ndermis and subcutis (Figure 1b&c). The naked \ngranulomas were composed of epithelioid \nhistiocytes with abundant eosinophilic \ncytoplasm and oval nuclei containing a small \ncentral nucleolus, with variable amount of \nmultinucleated giant cells and only sparse \nlymphocytes at the periphery. Asteroid body \nand Schaumann body were seen (Figure 1d&e). \nZiehl Neelsen stain for acid fast bacilli and \nPeriodic acid-Schiff stain for fungal body were \nall negative. Tissue culture for tuberculosis was \nnegative. \n\n\n\nFurther investigation revealed raised serum \nAngiotensin Converting Enzyme (ACE) \nlevels (123 U/L) (Normal level: 16-85 U/L) \nor 2.09 mcKat/L (0.27 \u2013 1.45 mcKat/L).   His \nbiochemical profiles, serum calcium and \nphosphate as well as tumour markers were \nnormal. \n\n\n\nThe quantiferon gold test for tuberculosis was \nnegative. Other blood investigations revealed \nAnti-nuclear Antibody (ANA) 1:160 (speckled), \nErythrocyte Sedimentation Rate (ESR):40 \nand Rheumatoid Factor:<20. Plain chest \nradiography was reported as normal. Computed \ntomography (CT) scan of the thorax revealed \nmultiple hilar, mediastinal and paraaortic \nlymph node enlargement consistent with stage \nI sarcoidosis. \\\n\n\n\nHe was diagnosed as subcutaneous sarcoidosis \nwith sarcoid arthritis. He was eventually started \non topical clobetasol propionate cream with \noral prednisolone 30mg od and tapered off \nwithin 1 month. It was combined with oral \nhydroxychloroquine 200mg od. His skin lesion \nresolved completely after 1 month of therapy.  \n\n\n\nDiscussion\nCutaneous involvement in sarcoidosis occurs \nin 20% to 35% of patients and can present as \na variety of different morphologies.4 Cutaneous \nsarcoidosis can be divided into specific and \nnonspecific lesions depending on the presence of \nnoncaseating granulomas on histologic studies.5 \n\n\n\nSpecific sarcoidosis lesions have granulomas on \nhistologic examination and often show the apple-\njelly coloration characteristic of granulomatous \nskin lesions on diascopy.6 The other differential \ndiagnosis of apple-jelly diascopy include lupus \nvulgaris, pseudolymphoma and lupoid rosacea.7 \n\n\n\nSpecific lesions include maculopapules, \nplaques, subcutaneous nodules, lupus pernio, \nscar infiltration, annular, verrucous, lichenoid, \npsoriasiform angiolupoid and ulcerative \nlesions.5 Nonspecific skin lesions are lack \nof granulomas and caused by inflammatory \nreactions to sarcoidosis.8 The most common \nnonspecific lesions are erythema nodosum, \nerythema multiforme, calcifications, prurigo, \nnail clubbing, and Sweet syndrome.2\n\n\n\nSubcutaneous sarcoidosis (also known as Darier \n-Roussy sarcoidosis) is a rare form of cutaneous \nsarcoidosis. Clinically it is characterized by \nmultiple firm, asymptomatic to mildly tender, \nmobile, round to oval, and skin coloured \nnodules.5 It commonly involves the extremities, \nbut the trunk and face can also be affected.2 It \nis more prevalent in middle aged women, who \ncommonly presents with lymphadenopathy or \npulmonary infiltrates on chest imaging; as well \nas elevated levels of serum ACE.9\n\n\n\nSystemic involvement was noted in 64% and \n60% of patients with specific and nonspecific \nskin lesions respectively in a review of 120 \npatients with cutaneous sarcoidosis.6 Pulmonary \nsarcoidosis is the most common manifestation of \nsystemic involvement with up to 90% of patients \nhaving abnormal chest radiographs.6 Bilateral \nhilar adenopathy (stage I disease) is seen in about \nhalf of patients with intrathoracic sarcoidosis.6 \n\n\n\nOcular sarcoidosis is seen in one-third of patient \nwith sarcoidosis with at least two-thirds of cases \nhave anterior uveitis while posterior uveitis \noccurs in up to 28% of sarcoidosis cases.6 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 4798\n\n\n\nOther important systemic involvement include \ncardiac, hepatic and neurological sarcoidosis. \nHypercalcemia and hypercalciuria can be seen \nin patients with sarcoidosis due to activated \nmacrophages in sarcoidal granulomas which \npromote conversion of 25-hydroxyvitamin \nD to 1,25-dihydroxyvitamin D leading to \nincrease intestinal absorption of calcium, bone \nresorption, and urinary calcium excretion.6\n\n\n\nBeing a great imitator, diagnosis of cutaneous \nsarcoidosis requires a high index of clinical \nsuspicion. Cutaneous sarcoidosis is usually an \nearly manifestation of the disease in up to one \nthird of cases.10 This should prompt the clinician \nto evaluate for systemic involvement.  Moreover, \nthe skin is a convenient source for tissue biopsy \nand therefore the diagnosis of cutaneous \nsarcoidosis can be made more rapid than other \nforms of sarcoidosis. A reasonable diagnosis of \ncutaneous sarcoidosis can be made in most cases \nfrom the appearance of skin lesions supported \nby confirmatory histology after excluding other \nnoncaseating granulomatous diseases.6 \n\n\n\nThe characteristic histologic finding of \nsarcoidosis is presence of noncaseating \nepithelioid granulomas, with minimal or \nabsence of lymphocytes or plasma cells (naked \ngranuloma).11 In subcutaneous sarcoidosis, \nthe non-caseating granulomas is present in the \nsubcutaneous tissue.12 Within the giant cells, \nSchaumann bodies and Asteroid bodies may \nbe found but are not specific for sarcoidosis.6 \nSchaumann bodies are rounded, laminated \nbasophilic inclusions that represent degenerating \nlysosomes and observed in 48%-88% of cases \nin sarcoidosis.13 Schaumann bodies can also \nbe seen in other inflammatory granulomatous \nconditions such as tuberculosis, chronic \nberyllium disease, hypersensitivity pneumonitis \nand Crohn\u2019s disease.14 Asteroid bodies are star-\nshaped spiculated structures that represent \nengulfed collagen seen as eosinophilic stellate \ninclusions and it is observed in 2%-9% of \nsarcoidal granulomas.15 Asteroid bodies are most \ncommonly seen in sarcoidosis, histoplasmosis \nand foreign body granulomas, but can be seen \nin any multinucleated giant cells formation.16\n\n\n\nAngiotensin-converting enzyme (ACE) levels \ncan be increased in up to 60% of cases with \nsarcoidosis but the value as a diagnostic test \nand prognostic marker remains limited.6 It is \nbecause serum ACE levels may also be raised \nin other granulomatous diseases and can \nbe influenced by genetic polymorphisms.16 \n\n\n\nIn view of lack of a specific diagnostic test, \nsarcoidosis is a diagnosis of exclusion and \ndiagnosis requires the following 3 criteria: \nclinicoradiographic findings compatible with \nthe diagnosis, histologic confirmation of \nnoncaseating granuloma and exclusion of other \nknown causes of granulomatous disease.17\n\n\n\nDifferential diagnosis of subcutaneous \nsarcoidosis include erythema nodosum, \nsubcutaneous granuloma annulare, tuberculosis, \nrheumatoid nodules, epidermal cyst, lipoma, \nand deep mycosis.5 Based on the clinical and \nhistopathological findings in our patient, \ndiagnosis of subcutaneous sarcoidosis was \nmade after excluding all the above differential \ndiagnosis.\n\n\n\nCorticosteroid is the mainstay treatment for \nsarcoidosis as it suppresses inflammation and \nhalt the progress of granuloma formation.18 \n\n\n\nUltrapotent corticosteroid (e.g. Clobetasol) is \nthe drug of choice for limited mild cutaneous \nlesions.18 Intralesional corticosteroids are used \nfor small sarcoid plaques and papules, with \ndose of 3-20mg/ml repeated 4 weekly until the \nlesions have flattened.18 Systemic corticosteroid \nis indicated for severe disfiguring or destructive \nlesions, widespread involvement, and lesions \nrefractory to localized treatment.18 Prednisolone \ndose ranges form 0.3-0.5mg/kg/day; with \nresponses noted within 4-8 weeks after initiation \nof treatment.3\n\n\n\nSecond line therapy are reserved for steroid-\nresistant sarcoidosis and for patients who \nare unable to tolerate steroids.18 Examples \nof second-line therapy include antimalarial \ntherapy, cytotoxic agents such as methotrexate, \nazathioprine, leflunomide, and mycophenolate.5 \n\n\n\nAntimalarial agents (e.g. chloroquine and \nhydroxychloroquine) have anti-inflammatory \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 99\n\n\n\nproperties, but relapse of sarcoidosis following \ndiscontinuation of therapy is very common.18 \n\n\n\nThe recommended dose of hydroxychloroquine \nis 200-400mg/day for at least 12 weeks to \ninduce clinical improvement. Methotrexate is \ngiven at 10-25mg/week for at least 6 months to \nbe effective.19 \n\n\n\nBiologics are reserved as third-line therapy, \nof which infliximab can be a good choice.18 \n\n\n\nAlternative treatment modalities for sarcoidosis \ninclude pentoxyfylline, tetracyclines, \nthalidomide, isotretinoin, allopurinol, \ncyclosporin and laser therapy.4,18 Newer \ntreatment that have been proven effective \ninclude repository corticotropin injections and \nrituximab.4 For our patient he was started on \noral prednisolone 30mg od (at 0.5mg/kg/day), \nhydroxychloroquine 200mg od and topical \ncorticosteroids with complete resolution of \nlesion following 1 month of therapy.\n\n\n\nConclusion\nSubcutaneous sarcoidosis is rare, which requires \nclinicopathology correlation for diagnosis. It \nremains a diagnosis of exclusion. Cutaneous \nsarcoidosis remains one of the great imitators \ndue to its varied clinical presentation. The \nhallmark of histopathology examination is a \nnaked or sarcoidal non-caseating granuloma. \nThe mainstay of treatment for sarcoidosis \ninclude corticosteroid, antimalarials and \nmethotrexate.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for permission to publish this \narticle.\n\n\n\nReferences \n1. Sewon Kang. Chapter 35, Fitzpatrick\u2019s Dermatology, 9th \n\n\n\nEdition, Volume 1. United States of America. McGraw- \nHill Education 2019. p.572-86.\n\n\n\n2. Kim KS, Lim DS, Choi JH, Hwang JH, Lee SY. \nSubcutaneous Sarcoidosis Occurring in Both Chin and \nToe. Arch Craniofac Surg 2017;18:207-10.\n\n\n\n3. Dalle Vedone C, Colato C, Girolomoni G. Subcutaneous \nsarcoidosis: report of 2 cases and review of the literature. \nClin Rheumatol 2011;30:1123-8.\n\n\n\n4. Karada\u011f AS, Parish LC. Sarcoidosis: A great imitator. Clin \nDermatol 2019;37(3):240-54.\n\n\n\n5. Fernandez-Faith E, McDonnell J. Cutaneous sarcoidosis: \ndifferential diagnosis. Clin Dermatol 2007;25(3):276-87.\n\n\n\n6. Sanchez M, Haimovic A, Prystowsky S. Sarcoidosis. \nDermatol Clin 2015;33:389-416.\n\n\n\n7. Ravikiran SP,Saiswal AK, Syrti C, Madan Mohan NT, \nAradhya SS. Granuloma faciale: An unusual diascopic \nfinding. Indian Dermatol Online J 2016;7:174-6.\n\n\n\n8. Haimovic A, Sanchez M, Judson MA, Prystowsky S. \nSarcoidosis: a comprehensive review and update for the \ndermatologist: part I. Cutaneous disease. J Am Acad \nDermatol 2012;66:699.e1-18; quiz 717-8.\n\n\n\n9. Mehrzad R, Festa J, Bhatt R. Subcutaneous sarcoidosis of \nthe upper and lower extremities: A case report and review \nof the literature. World J Clin Cases 2019;7:2505-12.\n\n\n\n10. Yanardag H, Tetikkurt C, Bilir M, Demirci S, Iscimen \nA. Diagnosis of cutaneous sarcoidosis; clinical and the \nprognostic significance of skin lesions. Multidiscip Respir \nMed 2013;8:26.\n\n\n\n11. Wanat KA, Rosenbach M. Cutaneous Sarcoidosis. Clin \nChest Med 2015;36:685-702.\n\n\n\n12. Marcoval J, Moreno A, Ma\u00f1\u00e1 J, Peyri J. Subcutaneous \nsarcoidosis. Dermatol Clin 2008;26:553-6.\n\n\n\n13. Ma Y, Gal A, Koss M. Reprint of: The pathology of \npulmonary sarcoidosis: update. Semin Diagn Pathol \n2018;35:324-33. \n\n\n\n14. Wood CA, Canterbury LA. Schaumann body identified \non bronchial brushing in a patient with sarcoidosis. Diagn \nCytopathol 2016;44:311-3.\n\n\n\n15. Kallas SJ, Ganesan S. Asteroid bodies in EBUS-FNA \ncytology. Diagn Cytopathol 2015;43:714-5. \n\n\n\n16. Stokes GS, Monaghan JC, Schrader AP, Glenn CL, Ryan \nM, Morris BJ. Influence of angiotensin converting enzyme \n(ACE) genotype on interpretation of diagnostic tests for \nserum ACE activity. Aust N Z J Med 1999;29:315-8. \n\n\n\n17. Judson MA. The diagnosis of sarcoidosis. Clin Chest Med \n2008;29:415-27.\n\n\n\n18. Doherty CB, Rosen T. Evidence-based therapy for \ncutaneous sarcoidosis. Drugs 2008;68:1361-83.\n\n\n\n19. Ruocco E, Gambardella A, Langella GG, Lo Schiavo A, \nRuocco V. Cutaneous sarcoidosis: an intriguing model of \nimmune dysregulation. Int J Dermatol 2015;54:1-12.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47100\n\n\n\nCASE REPORT\n\n\n\nA Case of Isolated Trichorrhexis Nodosa and Trichoscopic Images    \nSomaiah Savitha AS, FRGUHS, Sankey Sana M, MD, Reddy Raghunatha, FRGUHS\n\n\n\nRoots Institute of Dermatological Sciences \n\n\n\nSummary\nTrichorrhexis nodosa (TN) is a hair shaft disorder characterized by fragile hair with nodes on the hair shaft. \nHere we report a case of aquired localised trichorrhexis nodosa and describe the importance of noninvasive \ntools like trichoscopy and light microscopy in the diagnosis of an isolated TN.\n\n\n\nKey words: Trichorrhexis nodosa, Hair shaft, Nodes, Trichoscopy\n\n\n\nCorresponding Author\nDr Sana Mariam Sankey\n#237, HRBR 2nd Stage, \n5th B Main, Kalyannagar,\nBengaluru \u2013 560043, India\nEmail: sanasankey@gmail.com\n\n\n\nIntroduction\nTN is a hair shaft disorder characterized by \nfragile hair with nodes on the hair shaft. It may be \ncongenital, acquired or occur secondary to physical \nand chemical trauma. Careful history taking and \nsimple examination can avoid unnecessary tests and \ncan diagnose this condition. Here we report a case of \naquired localised trichorrhexis nodosa and describe \nthe importance of noninvasive tools like trichoscopy \nand light microscopy in the diagnosis of an isolated \nTN.\n\n\n\nCase Report\nA 28-year-old man presented with a lock of \nhair on the frontotemporal hairline that was \ndifferent from the rest (Figure 1a). The patient \nhad no systemic medical illnesses and there was \nno family history of similar illness. He denied \nhistory of trauma, itching, use of hair cosmetics, \nhair bleaching, hair dyes, hair perming or \nstraightening. \n\n\n\nOn examination the hair was dry, brittle and \nof varying lengths, there were multiple white \nspots along the hair shafts in the affected area \nand the hair over the rest of the scalp was \nnormal. Differential diagnosis considered was \npediculosis capitis, peripilar keratin casts, \ntrichorrhexis nodosa and white piedra. \n\n\n\nTrichoscopy demonstrated broken hairs shafts \nand white nodes along hair shafts (Figure 1b). \nLight microscopy (40x) showed fraying of \ncortical fibers giving the appearance of two \npaint brushes thrust together (Figure 1c). Based \non Trichoscopy and light microscopy, diagnosis \nof trichorrhexis nodosa was confirmed. As \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 101\n\n\n\nthere was no evident cause for trichorrhexis \nnodosa in this patient we suspected physical \nor chemical trauma as an incriminating factor. \nWe also advised him to use straight combs \nwith elongated bristles. Patient was also given \nmultivitamins (B-complex forte) and asked to \nlook out for any habit tics that may be causing \ncuticle damage.\n\n\n\nDiscussion\nTrichorrhexis nodosa was first described by \nSamuel Wilks in 1856 and it was named by \nM. Kaposi in 1876.1 It may be congenital, \nacquired or associated with some disorders like \nhypothyroidism, Menke\u2019s kinky hair syndrome, \nargininosuccinicaciduria and iron deficiency.2 \nAcquired TN, however, is much more frequent \nand is classified into 3 major groups: proximal \n(predominantly among blacks) or distal (the \nmost common in Spain) according to the area of \nthe hair shaft in which the nodules appear, and \nlocalized.3 \n\n\n\nVery few cases of localized TN have been \nreported in the literature. Its main clinical \n\n\n\ncharacteristic is that it is limited to well defined \nhairy areas generally the scalp, but also the \nbeard, moustache, pubic hair, etc. Several \nfactors including physical traumas that may \ncause sufficient damage to the hair shaft include \nexcessive brushing, back combing, stressed \nhairstyles, the application of heat, and prolonged \nexposure to ultraviolet light. Chemical traumas \ninclude excessive exposure to salt water, \nshampooing, setting, perming, bleaching, and \ndyeing of hair.4\n\n\n\nMacroscopically, hair shafts affected by \nTrichorrhexis nodosa contain small white nodes \nat irregular intervals throughout the length of \nthe shaft. The number of nodes may vary from \none to several, depending on the length of the \nhair. These nodes represent areas of cuticular \ncell disruption, which allows the underlying \ncortical fibers to separate and fray. The cortical \nfibers display outwards and fracture, giving the \nnode the microscopic appearance of two brooms \nor paintbrushes thrust together end to end by \ntheir bristles. Complete breakage often occurs \nat these nodes.5,6 There is no specific treatment \n\n\n\nFigure 1(a) Multiple white spots along the hair shafts in the affected area; (b)Trichoscopy (non polarised light) \ndemonstrated broken hairs shafts and white nodes along hair shafts ; (c) On Light microscopy(40x) - fraying of \ncortical fibers giving the appearance of two paint brushes thrust together.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47102\n\n\n\nfor TN. The only possible effective measure is \nto identify the predisposing factors and to avoid \nrepeated traumas. Certain coadjuvant treatments \n(such as hair repairers or vitamin complexes) \ncan also be helpful.7,8  \n\n\n\nTrichoscopy is a non-invasive diagnostic tool. \nIt allows detailed visualisation of hair and \nprovides clues for inherited and aquired causes \nof hair loss. Hair examination using trichoscopy \nand light microscope in routine clinical practice \nmay provide useful information for the correct \ndiagnosis, ranging from common head and pubic \nlice infestations to rarer shaft abnormalities.9,10 \n\n\n\nConclusion\nTrichorrhexis nodosa is a hair shaft disorder that \ncan be easily diagnosed with a careful history \nand simple examination using dermatoscopy \nand light microscope which can thereby avoid \nunnecessary tests.\n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto disclosed.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Martin AM, Sugathan P. Localised acquired trichorrhexis \nnodosa of the scalp hair induced by a specific comb and \ncombing habit - a report of three cases. Int J Trichology \n2011;3:34-7. \n\n\n\n2. Kambil SM. White spotted beard: A case of acquired \ntrichorrhexis nodosa. Indian J Dermatopathol Diagn \nDermatol 2014;1:96-7.\n\n\n\n3. Whiting DA. Structural abnormalities of the hair shaft. J \nAm Acad Dermatol 1987;16(1 Pt 1):1-25.\n\n\n\n4. Miyamoto M, Tsuboi R, Oh-I T. Case of acquired \ntrichorrhexis nodosa: scanning electron microscopic \nobservation. J Dermatol 2009;36:109-10. \n\n\n\n5. Robert A Schwartz. Trichorrhexis Nodosa. Available \nat https://emedicine.medscape.com/article/1073664-\noverview. Accessed on 31/08/2021.  \n\n\n\n6. Tripathi Devika. An herbal approach to trichorrhexis \nnodosa: bamboo hair. European J Biomed Pharm Sci  \n2018;5:124-9.\n\n\n\n7. Dawber RPR, Ebling FJG, Wojnarowska PT. Trichorrhexis \nnodosa. In: Champion RH, Burton JL, Ebling FJG, editors. \nTextbook of Dermatology. 5th ed. Oxford: Blackwell \nScientific Publications; 1992. p.2612-3.\n\n\n\n8. Mart\u00ednez de Lagr\u00e1n Z, Gonz\u00e1lez-Hermosa MR, D\u00edaz-P\u00e9rez \nJL. Tricorrexis nodosa localizada [Localized trichorrhexis \n\n\n\nnodosa]. Actas Dermosifiliogr. 2009;100:522-4.\n9. Lacarrubba F, Verz\u00ec A, E, Micali G: Trichoscopy in the \n\n\n\ndifferential diagnosis of pseudonits. Skin Appendage \nDisord 2019;5:142-5. \n\n\n\n10. Rudnicka L, Rakowska A, Kerzeja M, Olszewska M. Hair \nshafts in trichoscopy: clues for diagnosis of hair and scalp \ndiseases. Dermatol Clin 2013;31(4):695-708.\n\n\n\n\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2021 Dec Vol 47 103\n\n\n\nACKNOWLEDGEMENT\nDec Issue 2021\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Datin Dr Asmah Johar\n4. Dr Ch\u2019ng Chin Chwen\n5. Dr Chan Lee Chin\n6. Dr Chang Choong Chor\n7. Dr Chong Yew Thong\n8. Dr Dawn Ambrose\n9. Assoc Professor Dr Felix Yap Boon Bin\n10. Dr Henry Foong Boon Bee\n11. Dr Khor Yek Huan\n12. Dr Kwan Zhenli\n13. Dr Irene Lee Chew Kek\n14. Dr Lo Kang Shang Chit\n15. Dr Mazlin bt Mohd Baseri\n16. Dr Nazatul Shima bt Abdul Rahim\n17. Dr Ng Ting Guan\n18. Dato\u2019 Dr Noor Zalmy Azizan\n19. Dr Norashikin Bt Shamsudin\n20. Dr Preamala G Singam\n21. Dr Priya Gill\n22. Dr Rajalingam Ramalingam\n23. Dr Tang Jyh Jong\n24. Dr Tarita Bt Taib\n25. Dr Tey Kwee Eng\n26. Dr Wee Ai Leen\n\n\n\n\n\n\n\n\n\n\n \nBooklet A4_Malaysian Journal of  Dermatology-Dec 2021 COVER\n\n\nBooklet A4_Malaysian Journal of  Dermatology-Dec 2021_F\n\n\nBlank Page\n\n\n\n"
"\n\nVolume 26   |  Jul 2011   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.my\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\nMJD 2011 July Vol 26\n\n\n\nErythroderma -\na retrospective study with\nspecial emphasis on good\nprognostic factors                                                             \n\n\n\nAcne - experiences from\nCan Tho, Vietnam\n\n\n\nSyphilis - atypical\npresentation\n\n\n\nPrimary Cutaneous\nAnaplastic Large Cell\nLymphoma\n\n\n\nDermatology \nAchievements\nin the\n1st decade of\nthe millennium\n\n\n\n1\n\n\n\n7\n\n\n\n1 8\n\n\n\n2 1\n\n\n\n2 9\n\n\n\nH i g h l i g h t s\n\n\n\nBull dog skin\n\n\n\n25 Watch out for this\n\n\n\n27 Test your CPC skill\n\n\n\n\n\n\n\n\nMJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nEditorial\n\n\n\nIn the first decade of 21st Century, under the stewardship of Dr. Stevens Chow Kim\nWing, Asian Academy of Dermatology & Venereology was formed with members\nconsisted of senior dermatologists from Asian countries. \n\n\n\nDr Henry Foong established an I n t e rnational Vi rtual Grand Round in\nDermatology in 2000 which is a web based global dermatology network and\ngathering place for dermatologists. The Malaysian Dermatological Society website\nwas created by Dr Allan Yee in 2006 and is located at www.dermatology.org.my. This\nwebsite has facilitated rapid communication among members.\n\n\n\nIn the century too, Advance Masters course in Dermatology was set up in Universiti\nKebangsaan Malaysia which is the brainchild of Puan Sri Dr Suraiya Hani Hussein.\nThe move towards upgrading of post-graduate training has resulted in trainees\ncoming up with thesis and writing original scientific articles.\n\n\n\nThe training on use of Dermatology terminology to describe skin sign was\ni n t roduced to primary care prov i d e rs to facilitate communication betwe e n\nclinicians and also with the paramedics. The introduction of Dermatology nursing\ncare training to non-dermatology nursing personnel at primary and secondary care\nlevels have enabled patients to receive basic skin nursing at first encounter. Another\nMalaysian First is when 2 nurses wrote their thesis in Dermatology nursing care at\nnursing degree course in the local University.\n\n\n\nOn November 2010, Malaysian Journal of Dermatology which was started in 1987\nhas been accepted in West Pacific Region Index Medicus (WPRIM). This enables\nAsian scientific papers to be viewed in the net and knowledge shared with our\ncounterparts in other countries.\n\n\n\nEditor in Chief\nMalaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nMJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nNotice to Au t h o rs\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts\non all aspects of cutaneous medicine and surg e ry in the form of\noriginal articles, research papers, case reports and\nc o rrespondence.  Contributions are accepted for publication on\ncondition that they are submitted ex c l u s ive ly to the Malay s i a n\nJ o u rnal of Derm a t o l og y. The Publisher and Editors cannot be\nheld responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and\nopinions expressed do not necessarily reflect those of the\np u blisher and Editors, neither does the publication of\na d ve rtisements constitute any endorsement by the publ i s h e r.\n\n\n\nManuscripts should be submitted via email:\nro h n a r i d z wa n @ ya h o o . c o m\n\n\n\nQuestions regarding the Malaysian Journal of Derm a t o l og y\ncan be sent to me at:\nro h n a r i d z wa n @ ya h o o . c o m\n\n\n\nC o n t r i butions should be written for one of the follow i n g\nc a t egories: \n\n\n\nCase Report *\nA report of 400-600 words, illustrated by no more than three\nillustrations. This categ o ry offers a means for rapid\ncommunication about a single subject. \n\n\n\nClinical Tr i a l\nAn article of 700-1200 words concerning a drug eva l u a t i o n .\nThis categ o ry provides rapid publications and is meant to be a\nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nC o m m e n t a r y *\nAn editorial 700-1200 words in length with approx i m a t e ly five\nreferences. The author may express his or her opinion without\ncomplete documentation. \n\n\n\nC l i n i c o p a t h o l ogical Challenge\nA photographic essay that includes both clinical and\np a t h o l ogical photographs in color. The diagnosis and leg e n d s\nfor the photographs should be listed after the references in the\na rticle. The article should be no more than 2-3 pages in length. \n\n\n\nC o r re s p o n d e n c e *\nLetters to the editor and short notes. Contributions should not\nexceed 600 words, two figures, and 10 references. \n\n\n\nD e r m a t o l ogical Surgery \nAn article relating to the surgical aspects of treatment. A rt i c l e\ntypes may include Rev i ew, Report or Case Report Fo rmat. \n\n\n\nOriginal A rt i c l e\nAn original article including, wh e n ever possible, an\nIntroduction, Materials and Methods , Results, Comment, and\nReferences. A Structured Abstract of not more than 240 wo r d s\nmust be included. It should consist of four paragraphs, labelled\nB a c k gr o u n d, Methods, Results, and Conclusions. It should\ndescribe the problem studies, how the study was perform e d, the\nmain results, and what the author(s) concluded from the results. \n\n\n\nR ev i ew\nBy invitation only. A major didactic article that clarifies and\nsummarizes the existing knowledge in a particular field. It\nshould not be an ex h a u s t ive rev i ew of the literature, and\nreferences should not exceed 100 in number. Ta bles, diagr a m s ,\nand selected figures are often helpful. The length is left to the\njudgment of the author, although it generally should not ex c e e d\n5000 words. Topics may include updates in clinically releva n t\nbasic science and cutaneous biolog y. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the\np a p e r, the author(s)' name(s), degrees, and affiliation(s), the\nc a t eg o ry of the article, the number of figures and tables, and\nthree key words for indexing purposes. The name and full postal\naddress (including a street address), phone and fax numbers and\nan email address of the corresponding author who will be\nr e s p o n s i ble for reading the proofs must also be given on the title\npage. The author(s) must also declare any affiliation or\ns i g n i ficant financial invo l vement in any organizations or entity\nwith a direct financial interest in the subject matter or materials\ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. If\nconfusion could result, please include other measurement\nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should\nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in\nthe manuscript. References from journals should include: (1)\nname(s) followed by the initials of the author(s), up to four\nauthors: if more than four authors, include the first three authors\nf o l l owed by et al.; (2) title of paper; (3) title of the journal as\na b b r eviated in the Index Medicus; (4) year of publication; (5)\nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A\nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n5 5 .\n\n\n\nReferences to books should include: (1) author(s) or editor(s);\n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4)\nplace of publication; (5) publisher; (6) year; (7) page(s) referr e d\nto. \n\n\n\nFor example:\nFoong HBB.  Transcontinental Derm a t o l ogy: Vi rtual Grand\nRounds. In: Wootton R and Oakley A, editors. Te l e d e rm a t o l og y.\nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of\nall references; incomplete references may result in a delay to\np u blication. \n\n\n\nTa bles should be typed, double-spaced with a heading, each on\na separate sheet, and should only include essential inform a t i o n .\nD r awings, graphs, and formulas should be submitted on\nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of\np h o t o m i c r ographs, the stain type and original magnifi c a t i o n\nshould be stated. Each figure should bear a reference number\nc o rresponding to a similar number in the tex t .\n\n\n\nTo minimise the publication time of your manuscript it is\ni m p o rtant that all electronic art work is supplied to the Editorial\nO ffice in the correct format and resolution. \n\n\n\nD i s c l a i m e r\nThe Publisher and Editors cannot be held responsible for err o r s\nor any consequences arising from the use of inform a t i o n\ncontained in this journal; the views and opinions expressed do\nnot necessarily reflect those of the publisher and Editors, neither\ndoes the publication of adve rtisements constitute any\nendorsement by the publisher and Editors of the products\na d ve rt i s e d .\n\n\n\n\n\n\n\n\nMJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nEditor-in-Chief (Administrative)\nRohna Ridzwan, MRCP\nEmail : rohnaridzwan@yahoo.com\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nAdvertisement Committee\nIndependent team members\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP\nKuala Lumpur\n\n\n\nHenry Foong Boon Bee, FRCP\nIpoh, Perak\n\n\n\nChan Lee Chin, MMed\nPenang\n\n\n\nAgnes Heng Yoke Hui, MRCP\nIpoh, Perak\n\n\n\nEditor Emeritus\nSuraiya Hani Hussein FRCP\nKuala Lumpur\n\n\n\nFounding Editor\nSteven Chow Kim Wing FRCPI\n\n\n\nExecutive Staff\n\n\n\nKoh Chuan Keng, MRCP - President\nMardziah Alias, MMed - Past President\nNajeeb Ahmad Mohd Safdar, MRCP - Vice President\nHenry Foong Boon Bee, FRCP - Secretary\nAgnes Heng Yoke Hui, MRCP - Treasurer\nMohd Nor, MRCP\nChan Lee Chin, MMed\nNoor Zalmy Azizan, MRCP\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJalan 112, Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Cetak Sri Jaya, Jalan Ambong Kanan 3, Kepong Baru, 52100 Kuala Lumpur, Malaysia.\n\n\n\n\u00ae2011 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nThe inclusion of an advertisement in MJD is not to be construed or publicized as an endorsement or\napproval by the Society of any product, service, or company; nor may the advertiser represent that its\nadvertising claims have been approved or endorsed by the Society.\n\n\n\n\n\n\n\n\ni MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nC o n t e n t s\n\n\n\nGENERAL DERMATOLOGY\n\n\n\nOriginal Article\n1 Erythroderma - a retrospective study\n\n\n\nwith special emphasis on good prognostic\nfactors\nPeter C, MBBS, Adam B, Rohna R, MRCP\n\n\n\n7 Clinical and related factors in acne -\nexperiences from Can Tho, Viet Nam\nTran Thi Hanh\n\n\n\n12 Adequacy of care in patient with psoriasis \n(ADECAP) Study\nTan WC, Chan LC, Ong KP, et al\n\n\n\nCase Reports\n18 Syphilis - the great mimicker   \n\n\n\nSu-ming W, MRCP, Moonyza AAK, MD,\nDawn A, MRCP et al\n\n\n\n21 Primary Cutaneous Anaplastic Large Cell\nLymphoma: Report of 3 cases from\nHospital Kuala Lumpur\nTang MM, Adv M Derm, Chang CC, Adv M Derm, \nAffandi AM et al\n\n\n\nShort Communication\n25 Cutis verticis gyrata secondary to\n\n\n\ncongenital melanocytic naevus -\na case report\nVinitha VP, MD, Dhamramaratnam AD, MD,\nJoel Kuruvilla P, MD.\n\n\n\n27 CLINICOPATHOLOGICAL \nCHALLENGE\nDawn A, Lee BR, Latifah\n\n\n\nSNIPPETS ON MALAYSIAN\nDERMATOLOGY DEVELOPMENT IN\nTHE 1ST DECADE OF THE MILLENIUM\n\n\n\n29 Asian Academy of Dermatology &\nVenereology\nSteven Chow KW\n\n\n\n31 Malaysian Dermatological Society\u2019s\nInternet Milestones\nHenry FBB\n\n\n\n32 Dermatology Training in Malaysia\nSuraiya HH\n\n\n\nCONTINUOUS MEDICAL EDUCATION\n\n\n\n34 Advance Masters in Dermatology\n\n\n\n36 Malaysian Dermatology Congress & AGM\n\n\n\n36 Asia Pacific Environmental &\nOccupational Dermatology Symposium\n\n\n\n37 Malaysia participation in 22nd World \nCongress of Dermatology\n\n\n\n37 Book Review\n\n\n\nOBITUARY\n\n\n\n38 Allan\n\n\n\n39 Adam\n\n\n\n\n\n\n\n\n1MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Original Art i c l e\n\n\n\nE ry t h ro d e rma - A re t rospective study with special\nemphasis on good prognosis                                                        \nPeter Ch\u2019ng WB1, MRCP, Adam B2, Rohna R1, MRCP \n\n\n\nAbstract\n\n\n\nBackground Erythroderma is a serious condition in itself, quite apart from hazards associated with\nthe underlying disease, and is sometimes fatal. Prognostic studies are rare in the literature and to date\nthere are no published studies to identify the factors that can determine good prognosis.\n\n\n\nObjectives The aim of the study is to determine the factors that can prognosticate the good outcome\nof erythroderma.\n\n\n\nMethodology Cross sectional study from patients diagnosed to have erythroderma between 2003\nand 2007 were analyzed with regard to age, sex, race, underlying medical illness, aetiology, duration\nof rash before diagnosis of erythroderma, response to topical therapy and prognosis.\n\n\n\nResults Four variables (aetiology, gender, duration of rash before being diagnosed as erythroderma\nand response to topical therapy) were associated with good prognosis. These variables were\nstatistically significant from univariate analysis. When these variables were included into the binary\nlogistic model, the study did not have enough evidence to proof that \u2018aetiology\u2019 and \u2018gender\u2019 can\ndetermine good prognosis. Response to topical therapy and shorter duration of rash (equal and less\nthan 120 days) were significant with odds ratio (CI) of 4.11 (1.556, 10.885) and 4.608 (1.903,\n11.155) respectively.\n\n\n\nConclusion Shorter duration of rash and response to topical therapy are important factors to\ndetermine a good prognosis.\n\n\n\nKeywords exfoliative dermatitis, generalised erythema, outcome\n\n\n\nCorrespondence\nPeter Ch\u2019ng Wee Beng\nDepartment of Dermatology\nSelayang Hospital, Lebuhraya Selayang-Kepong\nBatu Caves 68100, Selangor, Malaysia\nE-mail : p_chng@yahoo.com\n\n\n\n1 Hospital Selayang, Selangor, Malaysia\n2 Clinical Research Centre Hospital Kuala Lumpur,\nKuala Lumpur, Malaysia\n\n\n\nE ry t h r o d e rma is a serious condition in itself,\nbesides hazards associated with the underly i n g\ndisease, and is sometimes fatal despite skilled\nmanagement. It is particularly dangerous in elderly\npeople. Reported death rates have varied from 18 to\n64%,2-4 but with modern therapy the rate is probably\nlower.\n\n\n\nPrognostic studies are rare in the literature and to\ndate there are no published studies to identify the\nfactors that can determine good prognosis5-10.\n\n\n\nThis is important when informing the patient or\nfamily members regarding the prognosis of the\npatient. Hence the aim of the study is to determine\nthe factors that can prognosticate the good outcome\nof\n\n\n\nIntroduction\nErythroderma also known as generalized exfoliative\ndermatitis is characterized by erythema affecting\nmore than 90% of the body surface area\naccompanied by a variable degree of scaling1.\n\n\n\n\n\n\n\n\n2 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nof erythroderma. Furthermore, we also looked at\nvarious clinical data of these patients to have a\nbetter understanding of the disease.\n\n\n\nMaterials and methods\nA cross sectional study of patients diagnosed with\nerythroderma, in local Hospital between 2003 and\n2007, were analyzed. The information was collected\nfrom the patients' records and included age, sex,\nrace, underlying medical illness, aetiology, duration\nof erythroderma, response to topical therapy and\nprognosis. Idiopathic erythroderma will only be\nconsidered if other aetiology had been ruled out and\na skin biopsy has been done for the patient.\n\n\n\nWe defined poor prognosis as having relapse,\npersistent ery t h r o d e rma or death and good\nprognosis as having complete or partial resolution\nof erythroderma. Partial resolution of erythroderma\nis defined as erythema affecting less than 90% of\nthe body surface area.\n\n\n\nStatistical method\nThe analysis was carried out using PASW 18.0.\nCategorical variable were reported in frequency\nwith percentage and numerical va r i a ble we r e\nreported in median and inter quartile range (IQR).\nAppropriate statistical test was used after\nconsidered statistical assumption to determine the\nassociation between selected risk factors towards\nbad or good prognosis. The statistical tests used\nwere Chi square test, Fisher exact test and Mann\nWhitney U test. Binary logistic regression was used\nto test the risk factors simultaneously using\nstepwise with Backward Likelihood Ratio method\nand removal item procedure used was 0.50. The P-\nvalue and Odds ratio with confidence interval were\nreported to determine the strength of factors that\ncan prognosticate the good outcome of\nerythroderma.\n\n\n\nResults\nPrognosis\n5 out of the 124 patients who had missing data or\ndefaulted follow up, were excluded in the analysis.\n82 out of 119 patients (68.9%), had good prognosis\nwhile 37 (31.1%) had poor prognosis. 13 patients\nhad died and none of the patients, the immediate\ncause of death was directly related to erythroderma.\n4 patients died during hospital admission for\nerythroderma of which 2 died of acute coronary\nsyndrome, 1 sudden death and 1 multi-orga n\nfailure. Of the 9 patients whose death was during\nthe study period but not during the admission for\ne ry t h r o d e rma, one died of advanced stomach\n\n\n\ncarcinoma, another died of orga n o p h o s p h a t e\npoisoning while the cause for the other 7 were\na t t r i buted to sepsis. As for the aetiology of\nerythroderma among those who died, 5 patients\nwere idiopathic, 4 patients were having psoriasis\nand 4 were due to drugs.\n\n\n\nFour variables (gender, duration of rash before\nbeing diagnosed as ery t h r o d e rma, response to\ntopical therapy and aetiology) were associated with\ngood prognosis. These 4 variables were statistically\nsignificant from univariate analysis. (Table 1) When\nthese 4 variables were included into the binary\nl ogistic model, the Nagelke r ke R square wa s\nacceptable (0.322) but the analysis did not have\nenough evidence to prove that \u2018aetiolog y \u2019 a n d\n\u2018gender\u2019 can determine good prognosis. \n\n\n\nThis study has enough evidence to prove that\nresponse to topical therapy and shorter duration of\nrash (equal and less than 120 days) were significant\nwith odds ratio (CI) of 4.116 (1.556, 10.885) and\n4.608 (1.903, 11.155) respectively. The difference\nbetween the median for duration of rash before\nbeing diagnosed as erythroderma in days for bad\nand good prognosis were 120 days and 25.5 days\nrespectively.\n\n\n\nPatients who responded to topical therapy are 4.1\ntimes more likely to have good prognosis compared\nto those patients who did not respond to topical\ntherapy. Those with shorter duration of rash (equal\nand less than 120 days) were 4.6 times more likely\nto have good prognosis compared to those patients\nwith longer duration (more than 120 days) of rash.\n\n\n\nHowever for \u2018aetiology\u2019, the strength of odds ratio\ndoes exist especially for \u2018drug induced\u2019\n(P value = 0.493, OR = 1.665, CI = 0.387, 7.169)\nand \u2018contact derm a t i t i s \u2019 (P value = 0.207,\nOR = 5.262, CI = 0.399, 69.443) as compared to\n\u2018idiopathic ery t h r o d e rma\u2019. Besides that, Fe m a l e\nalso has the impact on good prog n o s i s\n(P value = 0.217, OR = 1.953, CI = 0.675, 5.646)\n\n\n\nClinical data\nMajority (46%, n=57) of the patients were more\nthan 60 years old. 78 (63%) were male and 46\n(37%) were female. More than half of our patients\nwere Malays followed by Chinese, Indian and\nothers. (Table 1) As for the underlying medical\nillness, 26 (21%) had diabetes mellitus, 47 (37.9%)\nhad hypertension and 18 (12.9%) had ischaemic\nheart disease.\n\n\n\n\n\n\n\n\n3MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nTable 1 Profile of patients with guarded and good prognosis\n\n\n\n*P-value derived from Fisher\u2019s exact test      **Reported Median (IQR)      ***P-value derived from Mann Whitney U test\n****The size of sample were different in the overall due to missing data\n\n\n\nProfiles\n\n\n\nAge Group (yrs)\n<1\n1-20 \n21-40\n41-60\n>60\n\n\n\nGender\nMale\nFemale\n\n\n\nRace\nMalay\nChinese\nIndian\nOthers\n\n\n\nStatus of DM\nYes\nNo\n\n\n\nStatus of IHD\nYes\nNo\n\n\n\nStatus of HPT\nYes\nNo\n\n\n\nDuration of rash\n(days)**\nDuration of rash\n(days) in category\n<120 days\n>120 days\n\n\n\nSecondary Infection\nYes\nNo\n\n\n\nResponse to topical\nYes\nNo\n\n\n\nAetiology\nDrugs\nPsoriasis\nIdiopathic\nContact\nOthers\n\n\n\n0 (0.0)\n2 (20.0)\n6 (33.3)\n\n\n\n13 (38.2)\n16 (29.6)\n\n\n\n29 (39.2)\n8 (17.8)\n\n\n\n18 (26.1)\n14 (35.0)\n4 (50.0)\n1 (50.0)\n\n\n\n6 (23.1)\n31 (33.3)\n\n\n\n5 (31.3)\n32 (31.1)\n\n\n\n13 (28.3)\n24 (32.9)\n\n\n\n120(807.3)\n\n\n\n17 (20.5)\n20 (55.6)\n\n\n\n6 (20.0)\n29 (35.4)\n\n\n\n22 (23.7)\n15 (57.7)\n\n\n\n9 (18.4)\n16 (51.6)\n6 (40.0)\n1 (11.1)\n5 (33.3)\n\n\n\nGuarded prognosis\nn(%)\n\n\n\n3(100.0)\n8 (80.0)\n\n\n\n12 (66.7)\n21 (61.8)\n38 (70.4)\n\n\n\n45 (60.8)\n37 (82.2)\n\n\n\n51 (73.9)\n26 (65.0)\n\n\n\n4 (50.0)\n1 (50.0)\n\n\n\n20 (76.9)\n62 (66.7)\n\n\n\n11 (68.8)\n71 (68.9)\n\n\n\n33 (71.7)\n49 (67.1)\n\n\n\n25.5 (83.0)\n\n\n\n66 (79.5)\n16 (44.4)\n\n\n\n24 (80.0)\n53 (64.6)\n\n\n\n71 (76.3)\n11 (42.3)\n\n\n\n40 (81.6)\n15 (48.4)\n\n\n\n9 (60.0)\n8 (88.9)\n\n\n\n10 (66.7)\n\n\n\nGood prognosis\nn(%)\n\n\n\n5 (4.0)\n10 (8.1)\n18 (14.5)\n34 (27.4)\n57 (46.0)\n\n\n\n78 (62.9)\n46 (37.1)\n\n\n\n71 (57.3)\n42 (33.9)\n\n\n\n9 (7.3)\n2 (1.6)\n\n\n\n26 (21.0)\n98 (79.0)\n\n\n\n18 (12.9)\n\n\n\n47 (37.9)\n77 (62.1)\n\n\n\n30(231.5)\n\n\n\n83 (69.7)\n36 (30.3)\n\n\n\n33 (28.2)\n84 (71.8)\n\n\n\n96 (78.0)\n27 (22.0)\n\n\n\n49 (39.5)\n31 (25.0)\n17 (13.7)\n\n\n\n9 (7.3)\n18 (14.5)\n\n\n\nOverall ****\nn(%)\n\n\n\n0.711\n\n\n\n0.014\n\n\n\n0.324\n\n\n\n0.318\n\n\n\n0.988\n\n\n\n0.596\n\n\n\n0.009\n\n\n\n<0.001\n\n\n\n0.120\n\n\n\n0.001\n\n\n\n0.016\n\n\n\n*\n\n\n\n*\n\n\n\n***\n\n\n\n*\n\n\n\np-value\n\n\n\n\n\n\n\n\n4 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\n33 (28.2%) of the patients were complicated with\nsecondary bacteria skin infection. 96 (78%) of the\npatients had resolution of erythroderma with topical\nt h e r a py whereas 27 (22%) required systemic\nsteroids.\n\n\n\nAetiology\nDrugs were the commonest cause of erythroderma,\nfollowed by psoriasis, idiopathic, contact dermatitis\nand others.  Out of the 18 causes for others, 6 were\ndue to atopic dermatitis, 6 photocontact dermatitis,\n2 ichthyosis, 1 seborrhoeic dermatitis, 1 food, 1\ncontrast media and 1 due to Werner Syndrome.\nAmong the drugs, antibiotics were the most\nfrequent followed by allopurinol, phenytoin, beta\nbl o c ke r, supplements and analgesic. T h e\ncommonest cause of contact dermatitis, wa s\nliniment followed by cement (Table 1).\n\n\n\nDiscussion\nThe prognosis for patients with ery t h r o d e rm a\nvaried in different published studies. Nicolis and\nHelwig4 recorded 87 of 108 deaths related to the\ndermatosis and the dermatosis cleared in only a\nsmall number of patients. As for Abrahams et al2, 73\nout of 101 cases reported recovery and 19 deaths as\na complication of erythroderma. Hasan and Jansen3\n\n\n\nreported no death attributed to erythroderma; 17 out\nof 35 patients (49%) had completely recovered,\nwhile another 12 patients (34%) had improved.\n\n\n\nAlthough none of the immediate cause of death in\nour study was directly related to erythroderma, it is\ndifficult to determine whether the death was due to\nthe complication of erythroderma or due to natural\ncause. This is because majority of the death in our\nstudy was due to sepsis or cardiac complication,\nwhich can happen as a complication of\nerythroderma. On the other hand, most of our\npatients were more than 60 years old and a\nproportion of the patients may die of natural cause\nduring the study period.\n\n\n\nIn our study we not only looked at mortality but we\nalso looked at factors that can prognosticate the\ngood outcome of erythroderma. In our patients, the\ngroup associated with the best prognosis was that\nrelated to drugs and such findings have been\nobserved in literature16-18.\n\n\n\nBesides drugs, contact dermatitis causing\nerythroderma was associated with good prognosis\nas compared to idiopathic cause. This is because the\naetiology is known and therefore by removing the\ncause, it will lead to resolution of erythroderma.\nWhere else for idiopathic, it tends to have relapse or\nbeing persistent because the main precipitant has\nyet to be identified. Although none of the patient in\nour study was diagnosed to have erythroderma\ns e c o n d a ry to cutaneous lymphoma or other\nmalignancy during the study period, it is possible\nthat some of them may evolve to malignancy later\non.\n\n\n\nTable 2 Aetiology of erythroderma (N=119)\n\n\n\nAetiology\n\n\n\nDrugs\nAntibiotics\nOthers\nUnsure Exact Drug\nAllopurinol\nPhenytoin\nBeta Blocker\nSupplements\nAnalgesic\n\n\n\nPsoriasis\n\n\n\nIdiopathic\n\n\n\nContact Dermatitis\nLiniments\nCement\n\n\n\nOthers\n\n\n\n11 (22.4%)\n9 (18.4%)\n9 (18.4%)\n8 (16.3%)\n4 (8.2%)\n3 (6.1%)\n3 (6.1%)\n2 (4.1%)\n\n\n\n4 (44.4%)\n3 (33.3%)\n2 (22.2%)\n\n\n\nn (%)\n\n\n\n49 (39.5%)\n\n\n\n31 (25%)\n\n\n\n17 (13.7%)\n\n\n\n9 (7.3%)\n\n\n\n18 (14.5%)\n\n\n\nTotal\n\n\n\n\n\n\n\n\n5MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nShorter duration of rash before being diagnosed to\nhave erythroderma tends to have good prognosis.\nOne possibility is that drugs and contact dermatitis\ncommonly present with a short duration of rash and\ntherefore lead to good prognosis.\n\n\n\nFemales are 21.4% more like ly to have good\nprognosis than males. It is perhaps due to the small\nsample size, the test could not detect the difference.\nA study done by Sigurdsson et al11 suggested that\nthere is a possibility that women with erythroderma\nhave a better prognosis than men.\n\n\n\nPatients who responded to topical therapy were\nmore likely to have a good prognosis compared to\nthose patients who did not respond to topical\ntherapy. This is because patients who have relapses\nor persistent erythroderma tend to be resistant to\ntopical therapy and require oral steroid. \n\n\n\nMajority of our patients were more than 60 years of\nage which is similar to the study performed by\nSigurdsson et al11 in which the average age of their\npatients was 61. \n\n\n\nAs shown in Table 2, aetiologies of erythroderma\nare rather similar as compare to other series2-4, 11-17.\n\n\n\nHowever in our study, there was a significantly\nlarger proportion of erythroderma secondary to\nadverse drug reaction especially due to antibiotics\nand allopurinol. This warrants particular attention\nand may be due to high rate of injudicious\nprescription of these drugs in Malaysia.\n\n\n\nConclusion\nShorter duration of rash and response to topical\ntherapy are important factors that can prognosticate\nthe good outcome of patients with erythroderma.\nGender (female) and aetiology (drugs and contact\nallergen) also have contribution to good prognosis,\nhowever due to small sample size, the results were\nnot significant.\n\n\n\nReferences\n\n\n\n1. Burton JL, Holden CA. Eczema, lichenification and\nprurigo. In: Champion RH, Burton JL, Burns DA,\nBreathnach SM, editor. Text book of Dermatology. 6.\nVol. 1. Oxford: Blackwell Scientific Publ i c a t i o n s ;\n1998. pp. 673-8\n\n\n\n2. Abrahams I, McCarthy JT, Sanders SL. 101 cases\nof exfoliative dermatitis. Arch Dermatol 1963; 87:\n96-101\n\n\n\n3. Hasan T, Jansen CT. Erythroderma: a follow-up of 50\ncases. JAAD 1983; 8: 836-40\n\n\n\n4. Nicolis GD, Helwig WB. Exfoliative dermatitis: a\nclinicopathological study of 135 cases. Arch Dermatol\n1973; 108: 788-97\n\n\n\n5. M\u00f6bs M, Knott M, Fritzen B. et al. Diagnostic tools in\nSezary syndrome. G Ital Dermatol Venereol. 2010\nJun;145(3):385-91\n\n\n\n6. Yuan XY, Guo JY, Dang YP et al. Erythroderma: A\nclinical-etiological study of 82 cases. Eur J Dermatol.\n2010 May-Jun;20(3):373-7. Epub 2010 Apr 19\n\n\n\n7. Kim EJ, Lin J, Junkins-Hopkins JM et al. Mycosis\nfungoides and sezary syndrome: an update. Curr Oncol\nRep. 2006 Sep;8(5):376-86\n\n\n\n8. Rym BM, Mourad M, Bechir Z et al. Erythroderma in\nadults: a report of 80 cases. Int J Dermatol. 2005\nSep;44(9):731-5\n\n\n\n9. Rothe MJ, Bernstein ML, Grant-Kels JM. Life-\nthreatening erythroderma: diagnosing and treating the\n\"red man\". Clin Dermatol. 2005 Mar- A p r ; 2 3 ( 2 ) :\n206-17\n\n\n\n10. Foulc P, N'Guyen JM, Dr\u00e9no B. Prognostic factors in\nS\u00e9zary syndrome: a study of 28 patients. BJD. 2003\nDec;149 (6):1152-8\n\n\n\n11. Sigurdsson V, Toonstra J, Hezemans Boer M et al:\nErythroderma: a clinical and follow-up study of 102\npatients, with special emphasis on survival. JAAD\n1996, 35:53-7\n\n\n\n12. Wilson HTH: Exfoliative dermatitis: its etiology and\nprognosis. Arch Dermatol 1954, 69:577-588\n\n\n\n13. Gentele H, Lodin A, Skog B. Dermatitis exfolliativa.\nActa Derm Venereol (Stockh) 1958;38:296-302\n\n\n\n14. N d i aye B, Sissoko F, Strobel M. et al. Les\nerythrodermies de adulte (a propos de 77 cas a Dakar).\nDakar Med 1979; 24:65-74\n\n\n\n15. King LE, Dufresne RG, Lovett F et al: Erythroderma:\nreview of 82 cases. South Med J 1986, 79:1210-1215\n\n\n\n16. Sehgal VN, Srivastava G: exfoliative dermatitis: A\nprospective study of 80 patients. Dermatologica 1986,\n173:278-284\n\n\n\n17. Botella-Estrada R, Sanmartin O, Oliver V et al:\nErythroderma: A clinicopathological study of 56 cases.\nAma Arch Derm Syphilol 1994, 130:1503-1507\n\n\n\n18. Akhyani M, Ghodsi ZS, Toosi S et al. Erythroderma:\na clinical study of 97 cases. BMC Dermatol. 2005\nMay 9; 5:5\n\n\n\n\n\n\n\n\n6 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Original Art i c l e\n\n\n\nClinical and related factors in Acne - Experiences fro m\nCan Tho, Viet Nam\nTran Thi Hanh\n\n\n\nAbstract\n\n\n\nBackground: Acne is a common disease in teenagers and young adults. This study was conducted\nto provide physicians with a better understanding of the disease and to improve their advice to\npatients.\n\n\n\nObjective: To define the prevalence of acne, it\u2019s related factors and its psychological impact on the\npupils at Chau Van Liem Senior High School.\n\n\n\nMethod: A cross sectional descriptive study including 405 pupils in 10th, 11th, 12th grades was\ncarried out by means of medical examination, and interviews based on questionnaires.\n\n\n\nResults: The prevalence of acne in Chau Van Liem Senior High School pupils is 82.5% overall.\nSeparately, the incidence was slightly higher for boys with 83.9% than girls with 81.7%. Most of\nthese pupils had moderate acne (51.5%), with 46.7% having mild acne. Only 1.8% had the disease\nat severe. Moderate acne was 1.72 times more common in males than females (p = 0.02, OR = 1.72).\nThe essential lesions included oily skin, comedone, and papules, accompanied with pigmentation\nand/ or scar. One risk factor associated with acne was identified as the habit of using cosmetics\n(OR=2.12).The research also identified the differences between boys and girls in their habits related\nto acne. These included: the concern about acne (p=0.003), facial massage (p=0.02), using facial\nmilk (p=0.001), using cosmetics (p=0.001). Acne led to diffident (p=0.01), depression (p=0.05), and\nashamed (p=0.003). Boys with acne were less communicative   than girls (p=0.03).\n\n\n\nConclusion: The prevalence of acne in Chau Van Liem Senior High School pupils is 82.5%.  Pupils\nstill display bad habits like acne squeezing, applying cosmetics, using mixed- cream bought from the\nstore or self concocted mixtures of locally obtainable creams including steroids, aspirin, antibiotics,\nvitamins, carelessly applying corticoid-contained medicine which harm their skin. Acne also affects\ntheir mental health, emotional well being, and performance in school, family relationships, and\nfriendships.\n\n\n\nKeywords Vietnam, adolescence, behaviour, skin lesion\n\n\n\nCorrespondence\nTran Thi Hanh\nCan Tho University of Medicine and Pharmacy\n71A1 (Ho Tung Mau) TTTM\nCai Khe - Ninh Kieu District \nCan Tho - Viet Nam\nE-mail : tthanh@ctump.edu.vn\n\n\n\ndisease, with 85% of all teenagers (18) being\naffected to some degree. Generally, involution of\nthe disease occurs before age 25.\n\n\n\nIn prolonged cases, the sequelae can be life long;\nwith pitted hypertrophy scar formation that can\ncause psychological or emotional harm varies from\npatient to patient. In Viet Nam, acne is a very\ncommon disease, most of the patients here practice\nself treatment by using cosmetics, using mixed\ncream bought from the store or self concocted\nmixtures of locally obtainable creams including\nsteroids,  aspirin, antibiotics and vitamins.\n\n\n\nIntroduction\nAcne vulgaris is a self limited disorder of the\npilosebacious unit that is seen primarily in\nadolescent 9,13,17,18. This is one of the most common\n\n\n\n\n\n\n\n\n7MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nIn addition, they take self prescribed medicine,\nsqueeze the affected area, and have facial massage.\nThese types of behaviour worsen acne and form\nscars. This study was conducted to prov i d e\np hysicians with a better understanding of the\ndisease and to improve their advice to patients.\n\n\n\nMaterials and methods\n\n\n\nResearch Design : Cross-sectional Study\n\n\n\nSubjects/Respondents\n405 pupils in 10th, 11th and 12th grades who were\nstudying from October 2006 to April 2007 and\nsatisfied all the sampling criteria as outline below.\n\n\n\nInclusion Criteria \n- All the pupils above were studying during the time\nof data collection\n- Appropriate age: Grade 10 (15 years old), Grade\n11 (16 years old), Grade 12 (17 years old) \n- Consent to participate and be present at school\n\n\n\nSample\nUntil my research, there had not been any study\ncompleted showing the prevalence of acne among\nthe pupils in the senior high school here in Viet\nNam. Thus, P was defined as 50% to get the\nmaximum sample.\n\n\n\nSampling process\nStep 1 : Select Chau Van Liem Senior High \n\n\n\nSchool.\n\n\n\nStep 2 : Contact the Head Board to arrange a \nconvenient time for data collection.\n\n\n\nStep 3 : Make a list of pupils under stratifications, \nCluster Random Sampling was chosen.\n\n\n\nData collection:\nIndividual interviews were given to complete the\ns u rvey questions after a pilot tested for\ncomprehension in a group of 10 patients. These\ninterviews were conducted individually with one\npupil being interv i ewed by one researcher.\nRespondents who had acne would be examined,\ndiagnosed by a dermatologist (Tran Thi Hanh). \n\n\n\nTypical cases would be illustrated by photograph.\nDetermination of acne severity (mild, moderate,\nsevere) based on the number and type of lesions; a\nstandardized system was outlined below:\n\n\n\nSTATISTICS:\nThe statistical analysis was performed using the\nSPSS software version 15.0 and Excel.\n\n\n\nMEDICAL ETHICS:\nThis research is non-invasive, in compliance with\nthe principles of human research set forth by the\nHelsinki declaration. Students are entitled to attend\nand withdraw at anytime; they are examined and\ntreated if required\n\n\n\nRESULTS:\n405 cases were included, of which 143 were males\nand 262 females. Ages ranged from 15 years old\n(pupils in grade 10) (30.4%), to 16 years (pupils in\ngrade 11) (29.9%) and 17 years (pupils in grade 12)\n(39.8%). \n\n\n\nSeverity\n\n\n\nMild\n\n\n\nModerate\n\n\n\nSevere\n\n\n\nDefinition\n\n\n\n< 20 comedones, or < 15\ninflammatory lesions, or < 30 total\nlesions\n\n\n\n20 to 100 comedones, or 15 to 50\ninflammatory lesions, or 30 to 125\ntotal lesions\n\n\n\n> 5 cysts, or total comedone count\n> 100, or total inflammatory\nlesion count > 50, or > 125 total\nlesions\n\n\n\nGender\n\n\n\nMale\n\n\n\nFemale\n\n\n\nTotal (n=405)\n\n\n\nNo Acne\n\n\n\nn=71 (%)\n\n\n\n23 (16.1)\n\n\n\n48 (18.1)\n\n\n\n71 (17.5)\n\n\n\nAcne\n\n\n\nn=334 (%)\n\n\n\n120 (83.9)\n\n\n\n214 (81.7)\n\n\n\n334 (82.5)\n\n\n\nDiagnosis\n\n\n\nTable 1 The prevalence of acne with respect to gender\n\n\n\nx2 = 0.32; p = 0.57 > 0.05\n\n\n\n\n\n\n\n\n8 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nMost of acne was seen on oily skinned sufferers.\nThe most common lesions encountered we r e\ncomedones, then papules and pustules. Nodules and\ncystic lesions were seen in low proportion.\n\n\n\nDistribution of acne lesions on the body\nAcne lesions were mostly seen on the face 334\n(100%), then on the back 95 (28.4%), the chest 41\n(12.3%), and the arm 16 (4.8%). On the face, the\nmost common lesions were on the cheek 308\n(92.2%), the forehead 281 (84.1%), the nose 279\n(83.5%), the chin 207 (62%), and the temple 113\n(33.8%).\n\n\n\nDistribution of pupils using topical corticoid\nand mixed cream (steroids, aspirin, antibiotics,\nself-concocted vitamins): Among 405 cases\nreported, 76 (18.8%) of the pupils with acne used\nm i xed cream and steroid containing topical\nproducts.\n\n\n\nAlthough no significant association was found  by\nthe Chi Square Test but the OR >1 showed that the\nacne subjects using corticoid had the Odd of\ndermatrophy and telangiectasie 2,14 times more\noften than the non acne users.\n\n\n\nConcern of acne with respect to gender-\nTreatment seeking behaviours\n282 (84.4%) pupils with acne are concern about\ntheir problem. Males appear to be less concern\nabout their acne when compared to females (x2=\n8.6; p = 0.003). There was an association between\nthis concern and gender. Here there was a big\nd i fference with girls wanting to deal with the\nproblem and treat acne through various means such\nas facial massage, cleaning with facial milk, and\nusing cosmetics. Most of the times boys did nothing\nand left the problem untreated.  Despite the high\nrate of pupils (84.4%) concerned with their acne\nthere were still high rates of non - treatment (53%),\nself - treatment (37.4%), treatment at private clinics\n(6%), beauty salons (0.7%), and only 2.7% of\npupils are seen in dermatology clinics.\n\n\n\nLesions \n\n\n\nOily skin\n\n\n\nComedone\n\n\n\nPapules\n\n\n\nPustules\n\n\n\nNodule\n\n\n\nCyst\n\n\n\nHypopigmentation\n\n\n\nHyperpigmentation\n\n\n\nPitted scar\n\n\n\nHypertrophy scar\n\n\n\nDermatrophy and\ntelangiectasie\n\n\n\nFrequency\n\n\n\n291\n\n\n\n334\n\n\n\n164\n\n\n\n146\n\n\n\n62\n\n\n\n17\n\n\n\n3\n\n\n\n136\n\n\n\n111\n\n\n\n3\n\n\n\n26\n\n\n\nPercentage\n\n\n\n87.1%\n\n\n\n100%\n\n\n\n49.1%\n\n\n\n43.7%\n\n\n\n18.6%\n\n\n\n8.1%\n\n\n\n0.9%\n\n\n\n40.7%\n\n\n\n33.2%\n\n\n\n0.9%\n\n\n\n7.8%\n\n\n\nTable 2 The Skin lesions of acne sufferers\n\n\n\nUsing\nstatus\n\n\n\nUsers (n=61)\n\n\n\nNon-Users\n(273)\n\n\n\nTotal (n=334)\n\n\n\nDermatrophy and\ntelangiectasie P\n\n\n\n(Fisher\u2019s\nExact Test)\n\n\n\n0.11\n\n\n\nYes\n\n\n\nn=26 (%)\n\n\n\n8 (13.1)\n\n\n\n18 (6.6)\n\n\n\n26 (7.8)\n\n\n\nNo\n\n\n\nn=308 (%)\n\n\n\n53 (86.9)\n\n\n\n255 (93.4)\n\n\n\n308 (92.2)\n\n\n\nTable 3 Correlation between Dermatrophytelangiectasie\nand using Corticoid containing products (mixed cream,\ntopical drugs)\n\n\n\nOR = 2.14. CI: 95% (0.88 - 5.18)\n\n\n\nGender\n\n\n\nMale\n(124)\n\n\n\nFemale\n(n=210)\n\n\n\nTotal\n(n=334)\n\n\n\nDegree\n\n\n\nP=\n0.02;\n\n\n\nOR=\n1.72\n\n\n\nMild\n\n\n\nn (%)\n\n\n\n46\n(37.1)\n\n\n\n110\n(52.4)\n\n\n\n156\n(46.7)\n\n\n\nModerate\n\n\n\nn (%)\n\n\n\n72\n(58.1)\n\n\n\n100\n(47.6)\n\n\n\n172\n(51.5)\n\n\n\nSevere\n\n\n\nn (%)\n\n\n\n6\n(4.8)\n\n\n\n0\n(0%)\n\n\n\n6\n(1.8)\n\n\n\nTable 4 Correlation between gender and the degree of acne\n\n\n\nFigure 1 Classification of acne degree\n\n\n\n\n\n\n\n\n9MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDaily Diet\n\n\n\nHigh lipids\n(fat, eggs,\nmilk)\n\n\n\nHigh\nglucide\n(bread,\ncereal, cake,\nsugar\n\n\n\nFruit with\nhigh sugar\n\n\n\nFruit with\nlow sugar\n\n\n\nChocolate,\ncacao\n\n\n\nHigh\nprotide\n(meat, fish)\n\n\n\nVegetable\n\n\n\nAcne No Acne\n\n\n\nP\nvalue\n\n\n\n0.12\n\n\n\n0.72\n\n\n\n0.75\n\n\n\n0.34\n\n\n\n0.49\n\n\n\n0.053\n\n\n\n0.7\n\n\n\n(+)\n\n\n\nn (%)\n\n\n\n194\n(85.1)\n\n\n\n149\n(83.2)\n\n\n\n148\n(83.1)\n\n\n\n240\n(83.6)\n\n\n\n72\n(80)\n\n\n\n246\n(80.4)\n\n\n\n297\n(82.7)\n\n\n\n(-)\n\n\n\nn (%)\n\n\n\n140\n(79.1)\n\n\n\n185\n(81.9)\n\n\n\n186\n(81.9)\n\n\n\n94\n(79.7)\n\n\n\n262\n(83.2)\n\n\n\n88\n(88.9)\n\n\n\n37\n(80.4)\n\n\n\n(+)\n\n\n\nn (%)\n\n\n\n34\n(14.9)\n\n\n\n30\n(16.8)\n\n\n\n30\n(16.9)\n\n\n\n47\n(16.4)\n\n\n\n18\n(20)\n\n\n\n60\n(19.6)\n\n\n\n62\n(17.3)\n\n\n\n(-)\n\n\n\nn (%)\n\n\n\n37\n(20.9)\n\n\n\n41\n(18.1)\n\n\n\n41\n(18.1)\n\n\n\n24\n(20.3)\n\n\n\n53\n(16.8)\n\n\n\n11\n(11.1)\n\n\n\n9\n(19.6)\n\n\n\nTable 5 The relationship between diet and acne Impact of acne\nB oys with acne were more diffident (p=0.01),\ndepressed (p=0.05), ashamed (p=0.003) than girls.\n\n\n\nBoys with acne were less communicative than girls\n(p=0.03).\n\n\n\n(+): Eat regularly everyday     (-): Eat irregularly\n\n\n\nAverage number \nof facial\ncleaning/day\n\n\n\nCosmetic use\n\n\n\nAcne\n\n\n\nn=334\n(4.32)\n\n\n\nn=174\n(87.9%)\n\n\n\nNo Acne\n\n\n\nn=71\n(4.54)\n\n\n\nn=24\n(12.1%)\n\n\n\nTest\n\n\n\nT test\np=0.31>0.05\n\n\n\nx2\n\n\n\np=0.01<0.05\nOR=2.12\n\n\n\nTable 6 Association between facial hygiene, cosmetic use\nand acne\n\n\n\nAcne\nsqueezing\n\n\n\nFacial\nMassage\n\n\n\nFacial Milk\n\n\n\nCosmetic\n\n\n\nGender\n\n\n\nTest\n\n\n\nx2\n\n\n\np=0.01\n\n\n\nx2\n\n\n\np=0.41\n\n\n\nx2\n\n\n\np=0.01\n\n\n\nx2\n\n\n\np=0.001\n\n\n\nMale\n\n\n\n78\n(54.5%)\n\n\n\n9\n(6.3%)\n\n\n\n55\n(38.5%)\n\n\n\n50\n(35%)\n\n\n\nFemale\n\n\n\n154\n(58.8%)\n\n\n\n369\n(13.7%)\n\n\n\n163\n(62.2%)\n\n\n\n148\n(56.5%)\n\n\n\nTable 7 Association between behaviors and gender\n\n\n\nFigure 3 Impact of acne on personal friendships\n\n\n\nFigure 4 Impact of acne on family relationships\n\n\n\nFigure 5 Impact of acne on pupil performance\n\n\n\nFigure 2 Impact of acne on pupils emotional well being\n\n\n\n\n\n\n\n\n10 MJD 2011 July Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDiscussion\nThe research has confi rmed that acne was a\ncommon health problem among adolescents from\n15-17 years of age, impacting  83.9% of the males\nand 81.7% of the females (p = 0.57). T h e\nprevalence of acne in both sexes was 82.5%. This\nfigure concur with the results noted by Saurat17 and\nKlaus Degit7,11 who found the rate at 80%, and Julie\nC Harper8,9 who showed it at 85-100%. In this study,\nmild and moderate acne were the most common and\noccurred in almost equal numbers in both genders.\nModerate acne was 1.72 times more common in\nmales than females (p = 0.02, OR = 1.72). This\nfinding was also in line with the literature18, on acne\namong young adults which was more severe in\nmales than in females.\n\n\n\nOily skin was the most common contributing factor\nto the onset of acne. This figure was in line with\nliterature as over excretion of oil usually preceded\nthe acne problem and remained as a factor as the\ndisease progressed unless treated. Comedone was\noften present as it was the most observed lesion in\ncommon acne among young adults in our study.\nPapules, pustules were lesions of the ongoing\ninflammation and were observed in high\nproportions. Other lesions such as nodule, cyst,\nhypertrophy scar were common in severe acne,\np a rticular in adults, or in patients who had\ncomplications due to inappropriate treatment. These\nlesions had low proportions. Specifi c a l ly,\ndermatrophy and telangiectasie was a result of an\ninappropriate treatment, or using steroid containing\ndrugs or cosmetics.\n\n\n\nHistorically, the relationship between diet and acne\nhas been highly controversial. Whitney P. Bowe19,\nhave included several studies that he believes are of\ninferior design in an effort to provide historical\nc o n t ext for more recent developments, and to\naddress several dietary factors that, in his opinion,\nmerit further study. Before the 1960s, certain foods\nwere thought to exacerbate acne. Howeve r,\nsubsequent studies6, dispelled these alleg e d\nassociations as myth for almost half a century.\nS everal studies during the last decade have\nprompted dermatologists to revisit the potential link\nbetween diet and acne. Compelling evidence exists\nthat high glycemic load diets may exacerbate acne5.\nAdebamowo et al1,2,3 may have provided consistent\ndata in support of an epidemiolog i c a l ly we a k\nassociation between dairy and acne. Dairy ingestion\n\n\n\nappears to be weakly associated with acne, and\ndietary fibers remain to be elucidated.  In our study,\nthere were no association between diet and acne.\nLimitation included the number of the controlled\ngroup were much lower than the group with acne\nproblem.\n\n\n\nResearch has continued to yield more information\nc o n c e rning the aggr avating factors of acne.\nRecognition of the bad habits of the pupils with\nacne such as acne squeezing and facial massage that\nwould risk worsening and spreading the\ninflammation, and making acne more serious, and\nmore specifi c a l ly the role of facial milk and\ncosmetics in the development of acne. There was a\ncorrelation between cosmetic use and gender with\nthe girls using at a much higher rate than the boys.\nIn addition, this study also found a significant\nc o rrelation between this habit and acne and\nfrequent cosmetic users who had a higher risk (2.14\ntimes) than non users of acne problems. We should\neducate pupils more about the ingr e d i e n t s\ncontained in facial milks and cosmetics and their\nconnection in producing comedone.\n\n\n\nSome research showed a strong association between\nacne and mental health4,12,14,16. This study also found\nthat acne had a psychological impact to patients\nt h e m s e l ves, to their friendships, to their\nrelationships with families and school performance.\nThe degree of impact is depended on gender where\nfemales were more influenced than males. This\nfinding is also noted by Aktan et al4. The most\ncommon impact was loss of confidence, ashamed,\navoiding communication, avoiding social gathering,\nlacking of focus when studying. According to\nRigopoulos et al15, 48% of high school pupils in\nGreece said that acne harmed their personal\nrelationships. According to Jancin B1 0 39% of\nBritish young adults neglected schools due to their\npersonal shame, 55% said that acne made them\ncould not find girlfriends or boyfriends.\n\n\n\nConclusion\nThe prevalence of acne in Chau Van Liem Senior\nHigh School pupils is 82.5%.  Pupils still display\nbad habits like acne squeezing, applying cosmetics,\nusing mixed- cream bought from the store or self\nconcocted mixtures of locally obtainable creams\nincluding steroids, aspirin, antibiotics, vitamins,\ncarelessly applying corticoid-contained medicine\nwhich harm their skin. Acne also affects their\nmental\n\n\n\n\n\n\n\n\n11MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nmental health, emotional well being, and\nperformance in school, family relationships, and\nfriendships. These conclusions from our study are\nve ry essential for our acne prevention school\nprograms.\n\n\n\nReferences\n\n\n\n1. Adebamowo CA, Spiegelman D, Danby FW, et al.\nHigh school dietary dairy intake and teenage acne,\nJAAD 2005; 52:207-214\n\n\n\n2. Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk\nconsumption and acne in teenage boys. JAAD 2008;\n58:787-793\n\n\n\n3. Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk\nconsumption and acne in teenage boys. JAAD 2008;\n58:787-793\n\n\n\n4. Aktans et al. Anxiety, depression and nature of acne\nvulgaris in adolescents. Int J Dermatol 2000; 39:354-7 \n\n\n\n5. Cordain L. Implications for the role of diet in acne.\nSemin Cutan Med Surg 2005; 24:84-91\n\n\n\n6. Fulton JE, Plewig G, Kligman AM. Effect of chocolate\non acne vulgaris. JAMA 1969; 210:2071-2074\n\n\n\n7. Gollnick HP, Cunliffe WJ. Management of acne. JAAD\n2003, 49: S1-S38\n\n\n\n8. Harper JC. An update on the pathogenesis of acne\nvulgaris. JAAD Online 2004, V 51; 1:1-4\n\n\n\n9. Harper JC et al. Acne vulgaris. e-medicine 2007, S1-11\n\n\n\n10. Jancin B. Teens with acne cite shame, embarrassment\nabout skin. Skin and allergy News, 2004 Jan: 28\n\n\n\n11. Klaus Degit et al. Pathophysiology of acne. J German\nsociety of Derm, 2007April, 5; 4:316-323\n\n\n\n12. Lello J et al. Prevalence of acne vulgaris in Auckland\nSenior high school students. J Med NZ 1995;108:287-\n289\n\n\n\n13. Nguyen Thanh Minh. Incidence of acne vulgaris and\nrealated factors in Bach Dang primary high school\npupils, HCMC. General internal medicine HCMC,\n2008 Jan; 12: 235-240\n\n\n\n14. Purvis D. Acne Anxiety, depression, and suicide in\nteenagers: a cross sectional survey of New-Zealand\nsecondary school students\u201d, 2006; 42(12):793-6 \n\n\n\n15. Rigopoulos D et al. Coping with acne: beliefs and\nperceptions in a sample of secondary school Greek\npupils. JEDV 2007 Jul; 21(6):806-810\n\n\n\n16. Smithard A et al. Acne prevalence, knowledge about\nacne and psychological morbidity in mid-adolescence:\na community-based study. BJD; 2001 A u g ; 1 4 5 ( 2 ) :\n274-9  \n\n\n\n17. Saurat H, Grosshans E. Les maladie des glandes\ns e b a c \u00e9 e s - L\u2019acn\u00e9. Derm a t o l ogie et maladies\nsexuellement transmissibles. 1999 3e \u00e9dition,   Masson:\n732-742\n\n\n\n18. Strauss JS, Thiboutot DM. Diseases of the sebaceous\nglands. Fitzpatrick Dermatology in General Medicine,\nfifth edition 1999;Vi:69-784\n\n\n\n19. Whitney PB, Smita SJ, Alan RS. Diet and acne. JAAD\n2010 July, 63;1:124-141\n\n\n\n\n\n\n\n\n12 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Original Art i c l e\n\n\n\nAdequacy of Care in patient with Psoriasis\n(ADECAP) Study\nTan WC, Chan LC, Ong KP, Tan SS, Kweh MW, Jeffrey L, Kalaikumar N\n\n\n\nAbstract\n\n\n\nIntroduction: Psoriasis is a chronic recurrent inflammatory skin disease and poses a lifelong\nburden. Psoriasis is now considered a systemic inflammatory disease. Increasing epidemiological\nstudies have established the role of psoriasis as an independent risk factor in the development of\nmetabolic syndrome and its components. This has led to changes in standard of care\nrecommendations for patients with psoriasis. We conducted a clinical audit on \u201cadequacy of care in\npatient with psoriasis\u201d.\n\n\n\nObjective: To examine current trend of practice in the treatment of adults with psoriasis in\nDermatology clinic (tertiary referral centre), Penang Hospital. This study also aims to determine the\nadequacy of care in psoriasis patients in general, and those on systemic agents in specific.\n\n\n\nMethod: A retrospective study examined all adult psoriasis patients who visited Dermatology\nClinic, Penang Hospital within 1st July - 31st July 2009. Only those who have been on follow-up for\nat least 1 year were included in the study. Demographic characteristics, disease burden and details\nof psoriasis management were documented and analysed. Standards were derived from\nrecommendations of the British Association of Dermatologists (BAD) and American Academy of\nDermatology (AAD).\n\n\n\nResults: Of the 112 patients, 67 were males (59.8%). The mean age of patients was 48.8 years. Fifty\n(44.6%) were Chinese, 35 Malay (31.3%), 26 Indians (23.2%) and 1 foreigner (0.9%). The mean\nfrequency of clinic visit was 8.2. Forty-seven patients required systemic agents to achieve better\ndisease control. Eighty-three (74.1%) patients were offered \u201cPsoriasis Education Programme\u201d.\nPercentage of patients who had their severity scoring done by using the DLQI, BSA & Pain score\nwere 73.2%, 90.2% and 85.7% respectively. Only less than 50% of our patients were offered\n\u201cMetabolic Syndrome Risk Factors Screening\u201d. Of those on systemic agents, only 87.2% and 46.8%\nof patients, had their baseline and follow up blood investigations done respectively.\n\n\n\nConclusion: The care of psoriasis patients in Dermatology Clinic, Penang Hospital is still not\nadequate. Particular areas of concern include blood monitoring for those on systemic agents and\nscreening for metabolic syndrome risk factors.\n\n\n\nRemedial measures: Guidelines have been designed to create awareness and to educate doctors and\npatients on psoriasis and its association with metabolic syndrome. This includes a flow chart / tables\nto facilitate monitoring and screening of patients. Patients will be given pamphlets on the general\nknowledge on psoriasis, treatments and the risk of co-morbidities.\n\n\n\nKeywords Psoriasis, Standard of Care, Clinical Audit, Metabolic Syndrome\n\n\n\nCorrespondence\nTan Wooi Chiang\nDepartment of Dermatology,\nPenang Hospital, Penang, Malaysia\nE-mail : tanwooichiang@yahoo.com\n\n\n\n\n\n\n\n\n13MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nMethodology\nThis is a retrospective study reviewing the clinic\ncards of all psoriasis patients who visited the\nDermatology Clinic, Penang Hospital within 1st\nJuly - 31st July 2009.\n\n\n\nPatient groups and sample\nThe subjects to be included in this clinical audit are\nall adult psoriatic patients who have been followed\nup in Dermatology Clinic for at least 1 year. The\nnewly diagnosed psoriatic patients, or those follow\nup less than a year are excluded from this study.\n\n\n\nInclusion Criteria\n1. Patient confirmed to have psoriasis\n\n\n\n2. Patient of age > 18 years at the time of study\n\n\n\nExclusion Criteria\n1. Patient whom the diagnosis is in doubt\n\n\n\n2. The newly diagnosed psoriatic patient or those \nfollow up less than a year in skin clinic, Penang \nHospital.\n\n\n\nData sources\nThe audit criteria require data to be collected from\na range of sources, including patient records and\nadmission notes.\n\n\n\nIntroduction\nPsoriasis is a chronic recurrent inflammatory skin\ndisease that affects between 1 - 3% of the\npopulation and it poses a lifelong bu r d e n1.\nA d vances in our understanding of the\npathophysiology of psoriasis in the last decades\nhave changed our insight of psoriasis and its\u2019\nmanagement.\n\n\n\nPsoriasis is now considered a systemic\ni n f l a m m a t o ry disease2. The scientific literature\nlinking psoriasis to metabolic syndrome and its\ncomponents, as well as atherosclerosis and\nmyocardial infarction has rapidly ex p a n d e d .\nIncreasing epidemiological studies are establishing\nthe directionality of these associations and the role\nof psoriasis as an independent risk factor in\ndeveloping this outcomes3-9.\n\n\n\nThis concept has led to changes in standard of care\nrecommendations for patients with psoriasis. Due\nto increased awareness about treatments and\ncomorbidities combined with increase expectations\namong patients, there is an urgent need to improve\nthe quality of care for patients with psoriasis.\n\n\n\nWe conducted a clinical audit on \u201cadequacy of care\nin patient with psoriasis\u201d in July 2009. The primary\nobjective is to examine current trend of practice in\nthe treatment of adults with psoriasis in the\nD e rm a t o l ogy clinic, Penang Hospital. T h e\nsecondary objective is to determine the adequacy of\ncare in psoriatic patients in general, and those on\nsystemic agents in specific.\n\n\n\nCRITERION 1 Percentage of psoriasis patients being offered \u201cPsoriasis Education Programme\u201d\n\n\n\nExceptions None\n\n\n\nSettings All\n\n\n\nStandard 100%\n\n\n\nDefinitions Patients should be offered information to help them make informed decisions \nabout their healthcare. This covers the condition, treatments and the health \nservice providing care.\n\n\n\nAudit criteria and standards\nStandards of good care of Psoriasis patients were derived from recommendations of the British\nAssociation of Dermatologists (BAD) and American Academy of Dermatology (AAD).\n\n\n\n\n\n\n\n\n14 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nCRITERION 2 Percentage of patients who had their severity scoring done by using the\nDermatology Life Quality Index (DLQI)\nBody Surface Area (BSA) / Psoriasis Area & Severity Index (PASI)\nPain score (if arthropathy)\n\n\n\nExceptions If patients do not have arthropathy, omit pain score.\n\n\n\nSettings All\n\n\n\nStandard 100%\n\n\n\nDefinitions Patients should have their severity scoring done.\nDLQI (Every 6 monthly)\nBSA / PASI (Every visit)\nPain score (Every visit)\n\n\n\nCRITERION 3 Percentage of patients offered \u201cMetabolic Syndrome Risk Factors Screening\u201d\nObesity (Body Mass Index - BMI / Waist circumference)\nHypertension (Blood Pressure)\nDiabetes Mellitus (Fasting Blood Sugar)\nLipid (Fasting Lipid Profile)\n\n\n\nExceptions Those < 20 years old and with pre-existing metabolic syndrome\n\n\n\nSettings All\n\n\n\nStandard 100%\n\n\n\nDefinitions Patients should be offered information about psoriasis co-morbidities and screen \nthem annually if  > 20 years old.\n\n\n\nCRITERION 4 Percentage of patients (on systemic agents) had their laboratory investigations done\nBaseline investigations\nFollow up monitoring\n\n\n\nExceptions Those on topical medications alone\n\n\n\nSettings All\n\n\n\nStandard 100%\n\n\n\nDefinitions Patients on systemic agent should be monitored according to JAAD 2008 guideline.\n\n\n\nCRITERION 5 Percentage of patients consented prior to initiation of systemic agents\n\n\n\nExceptions Those on topical medications alone\n\n\n\nSettings All\n\n\n\nStandard 100%\n\n\n\nDefinitions Patients should be offered written information to help them make informed \ndecisions about their healthcare. This should cover the condition, treatments and the \nhealth service providing care. Information should be available in formats appropriate \nto the individual, taking into account language, age and physical, sensory or learning \ndisabilities.\n\n\n\n\n\n\n\n\n15MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPsoriasis Care Pattern (Refer table 1)\nEighty-three (74.1%) patients were off e r e d\n\u201cPsoriasis Education Programme\u201d. Percentage of\npatients who had their severity scoring done by\nusing the DLQI, BSA & Pain score were 73.2%,\n90.2% and 85.7% respectively. Only less than 50%\nof our patients were offered \u201cMetabolic Syndrome\nRisk Factors Screening\u201d. The details of metabolic\nsyndrome and its\u2019 risk factor are shown in table 2.\nOf those on systemic agents, only 87.2% and 46.8%\nof patients, had their baseline and follow up blood\ninvestigations done respectively.\n\n\n\nRe-audit\nIf the first data collection and analysis shows room\nfor improvement, an action plan will be developed\nand the audit re-run once changes to the service\nhave had time to make an impact.\n\n\n\nResults\nStudy Cohort\nOf 112 patients, 67 were males (59.8%). The mean\nage of patients was 48.8 years. Fifty (44.6%) were\nChinese, 35 Malay (31.3%), 26 Indians (23.2%) and\n1 foreigner (0.9%). The mean frequency of clinic\nvisit was 8.2. Fo rt y - s even patients required\nsystemic agents to achieve better disease control.\n\n\n\nTable 1 Results of Psoriasis Care Pattern Observed\n\n\n\nCare Pattern\n\n\n\nPsoriasis Education Programme\n\n\n\nPsoriasis Severity Score\nSkin Examination (BSA / PASI)\nPain score (if arthropathy)\nQoL Questionnaire (DLQI)\n\n\n\nMetabolic Syndrome Risk Factors Screening\nDM Screening\nHyperlipidaemia Screening\nHypertension Screening\nObesity Screening\n\n\n\nLaboratory Monitoring\n(If on systemic agents, N = 47)\n\n\n\nBaseline investigations\nFollow up monitoring\n\n\n\nConsent Prior to Initiation of Systemic Agents\n(N = 47)\nMethotrexate (N = 28)\nAcitretin (N =19)\nCyclosporin (N =0)\n\n\n\nN\n\n\n\n83\n\n\n\n101\n96\n82\n\n\n\n50\n46\n27\n86\n\n\n\n41\n22\n\n\n\n4\n\n\n\n0\n4\n0\n\n\n\n%\n\n\n\n74.1\n\n\n\n90.2\n85.7\n73.2\n\n\n\n44.6\n41.1\n24.1\n76.8\n\n\n\n87.2\n46.8\n\n\n\n8.5\n\n\n\n0\n21.1\n\n\n\n0\n\n\n\nYes\nN\n\n\n\n29\n\n\n\n11\n16\n30\n\n\n\n62\n66\n85\n26\n\n\n\n6\n25\n\n\n\n43\n\n\n\n28\n15\n0\n\n\n\n%\n\n\n\n25.9\n\n\n\n9.8\n14.3\n20.8\n\n\n\n55.4\n58.9\n75.9\n23.2\n\n\n\n12.8\n53.2\n\n\n\n91.5\n\n\n\n100\n78.9\n\n\n\n0\n\n\n\nNo\n\n\n\nTable 2 Co-morbidities observed among the study cohort\n\n\n\nCare Pattern\n\n\n\nDiabetes Mellitus (DM)\nHypertension\n\n\n\nHyperlipidaemia\nIschaemic Heart Disease\nCerebrovascular Disease (CVD)\n\n\n\nObesity\n\n\n\nN\n\n\n\n18\n\n\n\n25\n19\n9\n\n\n\n3\n2\n\n\n\n%\n\n\n\n16.1\n\n\n\n22.3\n17\n8\n\n\n\n2.7\n3.6\n\n\n\nPre-existing\nN\n\n\n\n8\n\n\n\n6\n13\nND\n\n\n\nND\n47\n\n\n\n%\n\n\n\n16\n\n\n\n22.2\n28.2\nND\n\n\n\nND\n57.3\n\n\n\nNewly diagnosed\n\n\n\n\n\n\n\n\n16 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\npatients and less than half of them, had their\nbaseline and follow up blood investigations done\nrespectively. Emphasis should be made for close\nblood monitoring of all the patients, especially who\nare on systemic therapy.\n\n\n\nDespite advances in the management of psoriasis,\nthe cumulative effect of the psychological, social\nand physical burden borne by patients with\npsoriasis is still considerable. Assessment of disease\nseverity which complement measurement of disease\nextent and severity and impact on psychosocial\nfunctioning and quality of life should be used to\nassess the appropriateness of disease modifying\ndrugs as well as response to treatment. The most\nwidely used tool for assessing psoriasis severity is\nthe PASI14 and measures of disease severity and\nquality of life impairment is Dermatology Life\nQuality Index (DLQI)15-16.\n\n\n\nBody surface area (BSA) and PASI, for the grading\nof psoriasis symptoms (scaling, erythema and\ninduration \u2044 infiltration) and extent of lesions are the\nmost commonly use parameters in clinical trials.\nThey are useful and reliable tools for assessing\npsoriasis severity in patients with moderate-to-\nsevere disease14. In order to employ an independent\nmeasure of patient-reported psoriasis seve r i t y,\nassessment of HRQoL like DLQI was chosen as an\nappropriate indicator of HRQoL because of its\nwidespread use, simplicity and reliable grading15-16.\nThe Psoriasis severity score and DLQI we r e\nassessed regularly in our patients as part of the six\nmonthly assessments for the National Psoriasis\nRegistry.\n\n\n\nThe concept of psoriasis is now considered a\nsystemic inflammatory disease. Recent studies have\ndescribed the association of various burdening &\nlife threatening comorbidities with psoriasis in\np a rt i c u l a r ly metabolic syndrome5 - 9. Metabolic\nsyndrome has been demonstrated as a common\nprecursor to the development of type II diabetes and\ncardiovascular disease as well as a risk factor for all\ncauses mort a l i t y. Individuals with metabolic\nsyndrome are associated with approximately 2 & 5-\nfold increased risk for CVD & type 2 DM\nrespectively17. These pose a serious implication on\nour country\u2019s healthcare costs and services. Despite\nof our cohort of patients having a mean age of 48.8\nyears, only about half of them were screened for\ndiabetes mellitus or hyperlipidaemia and only a\nquarter was screened for hypertension. We need to\ndo active\n\n\n\nDiscussion\nE a r ly intervention, targeted treatment, treat-to\ntarget strategies and the use of treatment goals is a\nnew management approach in medicine that have\nbeen increasingly employed in the management of\nchronic diseases, such as diabetes, hypertension and\nrheumatoid arthritis over the last decade10. As in\nother chronic diseases, well-defined treatment goals\nwill be helpful in guiding physicians in their care of\npatients with psoriasis, thereby obviating poor\noutcomes and subsequently improve quality of\npsoriasis care11.\n\n\n\nCentral to goal-oriented strategies are three\nprinciples: establish treatment goals, reg u l a r ly\nevaluate treatment response and modify therapy in\ncases of insufficient response. Clinical audit on care\nof psoriasis is necessary to ensure the success of\ngoal oriented strategies. With the above intentions\nin mind, we proceeded to do the above audit. Patient\neducation is critical in promoting active\np a rticipation of the patient towards his / her\nr e c ove ry. A c t ive participation in the decision\nmaking process through a two-way exchange of\ni n f o rmation and strong phy s i c i a n - p a t i e n t\nrelationships is one potential solution to motivate\nadherence in psoriasis patients12-13. Patients with\nbetter knowledge of their condition and treatment\napplication are more able to cope with their\ncondition and also gain better therapeutic control.\nPatient education can be empowered by special\neducation class, verbal communication during\nconsultation and also with written take - h o m e\nmaterials. Still about a quarter of our patients have\nyet to receive patient\u2019s education programme.\n\n\n\nTopical therapies are effective in the treatment of\nmild to moderate disease. However patients with\nmoderate to severe disease usually require\np h o t o t h e r a py or systemic agents to achieve\nc l e a r a n c e2 - 3. In general, these more aggr e s s ive\ntherapies have proven to be highly effective but they\nare not without side effects. As there is no standard\ntherapeutic approach, the benefits and risks of the\ntherapy must be weighed carefully for each patient\nand the impact of the systemic treatment should be\nm o n i t o r e d2 - 4. Proper monitoring of treatment\nprogress and side effects remain the cornerstone for\nbetter treatment outcome. All patients on systemic\ntherapies should have a baseline and also regular\nblood investigation monitoring during follow-up.\nUnfortunately from our audit, of those on systemic\nagents, only slightly more that three quart e r s\n\n\n\n\n\n\n\n\n17MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\n4. Menter A, Griffiths CEM. Current and future\nmanagement of psoriasis. Lancet 2007; 21; 370:272-\n84\n\n\n\n5. Cohen AD, Sherf M, Vidavsky L et al. Association\nb e t ween psoriasis and the metabolic syndrome.\nDermatol 2008; 216:152-155\n\n\n\n6. Murray ML, Bergstresser PR, Adams-Huet B, Cohen\nJB. Relationship of psoriasis severity to obesity using\nsame-gender siblings as controls for obesity. Clin Exp\nDermatol 2009; 34: 140-144\n\n\n\n7. Gelfand JM, Neimann AL, Shin DB et al. Risk of\nmyocardial infarction in patients with psoriasis. J Am\nMed Assoc 2006; 296:1735-1741\n\n\n\n8. Neimann AL, Shin DB, Wang X, et al. Prevalence of\ncardiovascular risk factors in patients with psoriasis. J\nAm Acad Dermatol 2006; 55:829-835\n\n\n\n9. Gisondi P, Tessari G, Conti A, Piaserico S, Schianchi S,\nPeserico A, et al. Prevalence of metabolic syndrome in\npatients with psoriasis: A hospital-based case-control\nstudy. Br J Dermatol 2007\n\n\n\n10. Smolen JS, Aletaha D, Bijlsma JW et al. Treating\nrheumatoid arthritis to target: recommendations of an\ninternational task force. Ann Rheum Dis 2010; 69:\n631-637\n\n\n\n11. Mrowietz U, Kragballe K, Reich K et al. Definition of\ntreatment goals for moderate to severe psoriasis: a\nEuropean consensus. Arch Dermatol Res 2011; 303:\n1-10\n\n\n\n12. Renzi C, Di Pietro C, Gisondi P et al. Insufficient\nknowledge among psoriasis patients can represent a\nbarrier to participation in decision making. Acta Derm\nVenereol 2006; 86: 528-534\n\n\n\n13. Pagliarello C, Di Pietro C, Paradisi A et al. Measuring\nempowerment in patients with psoriasis: the Psoriasis\nEmpowerment Enquiry in the Routine Practice (PEER)\nquestionnaire. Eur J Dermatol 2010; 20: 200-204\n\n\n\n14. Fredriksson T, Pettersson U. Severe psoriasis--oral\ntherapy with a new retinoid. Dermatologica 1978;\n157(4):238-244\n\n\n\n15. Finlay AY, Khan GK. Dermatology Life Quality Index\n(DLQI) - a simple practical measure for routine clinical\nuse. Clin Exp Dermatol 1994; 19: 210-216\n\n\n\n16. L ewis V, Fi n l ay AY. 10 years experiences of the\nD e rm a t o l ogy Life Quality Index (DLQI). J Inve s t\nDermatol Symp Proc 2004; 9: 169-180\n\n\n\n17. Grundy SM, Cleeman JL, Daniels SR, Donato KA,\nEckel RH et al. Diagnosis and management of the\nmetabolic syndrome: an American Heart Association /\nNational Heart, Lung, and Blood Institute Scientific\nStatement: Exe c u t ive Summary. Circulation. 2005;\n112: 2735-2752\n\n\n\ndo active screening for metabolic syndrome among\nour psoriasis patients. If they can be identified\nearly, efforts can be undertaken to reduce their risk\nfactors.\n\n\n\nConclusion\nThe care of psoriasis patients in Derm a t o l og y\nClinic, Penang Hospital is not yet adequate. Doctors\nwho treat psoriasis patients (especially more\nseverely affected patients) need to approach the\ndisease as a potentially multisystem disorder with\nregular screening and monitoring of the associated\nsequelae of the disease and also the complications\nof the treatment.\n\n\n\nRemedial measures\nFirstly, is to create awareness and to educate doctors\nand patients on psoriasis and its association with\nmetabolic syndrome. This is done by having regular\nCME and psoriasis educational class. Next is to\nformat protocol and schedule in a form of charts /\ntables, to facilitate monitoring and screening of\npatients. Patients will be given pamphlets on the\ngeneral knowledge on psoriasis, treatments and the\nrisk of co-morbidities.\n\n\n\nRemedial measures may improve the awareness and\nknowledge of Psoriasis care. But it is the individual\nd o c t o r \u2019s attitude and willingness to adopt the\nchange that makes the difference.\n\n\n\nReferences\n\n\n\n1. G r i ffiths CEM, Barker J. N. W. N. Pa t h ogenesis and\nclinical features of psoriasis. Lancet 2007; 21; 370:\n263-71\n\n\n\n2. Griffiths, CEM, Clark CM, Chalmers RJG, et al.\nSystematic review of treatments for severe psoriasis.\nHealth Technology Assessment 2000; 4; 40: 1-125\n\n\n\n3. Naldi L, Griffiths CEM. Traditional therapies in the\nmanagement of moderate to severe chronic plaque\npsoriasis: an assessment of the benefits and risks. Br J\nDermatol 2005; 152: 597-615\n\n\n\n\n\n\n\n\n18 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Case Report\n\n\n\nSyphilis - The great mimicker                                                          \nSu-ming Wong1, MRCP, Moonyza AAK2, MD, Dawn A3, MRCP, Roshidah B3, FRCP\n\n\n\nCorrespondence\nWong Su-ming, MRCP\n1Dermatology Unit, Department of Medicine,\nUniversity Malaya,\n2Department of Medicine, Universiti Kebangsaan\nMalaysia,\n3Department of Dermatology, Hospital Kuala Lumpur\nE-mail : smwong@um.edu.my\n\n\n\nI n t ro d u c t i o n\nSyphilis is an ancient sex u a l ly transmitted\ninfection, described since centuries ago, caused by\nthe bacterium Treponema pallidum. Syphilis or\nluetic disease is known as the great imitator as it can\nh ave myriads of clinical presentations, often\nmaking it a diagnostic challenge to clinicians. We\nr e p o rt a patient with secondary syphilis, wh o\npresented with scaly plaques on his trunk and face,\nsparing the palms and soles.\n\n\n\nCase re p o rt\nMr A is a 37-year old lorry driver who presented\nwith a 3-month history of pruritic, well demarcated\ncrusted plaques which started on the lateral side of\nhis left leg. Similar smaller discrete plaques were\nalso noted on the left thigh, trunk, back and face.\nHe was initially treated with antihistamines and\ntopical steroids by a general practitioner without\nany improvement.\n\n\n\nA B\n\n\n\nC D E\n\n\n\nFigure 1 Well demarcated scaly plaques on the back (A), left trunk (B), face (C) and legs (D). Erosions and scaly\nplaques on the scrotum (E).\n\n\n\nKeywords sexually transmitted infection, plaques, Treponema\n\n\n\n\n\n\n\n\n19MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nHe is recently married, with no children. On further\nquestioning, he admitted to having unprotected sex\nwith multiple female partners, his most recent\nencounter being about a year ago. He denied\nintravenous drug abuse or having sex with men. He\nwas otherwise well and had no other complaints.\n\n\n\nOn examination, there were multiple, we l l\nd e m a r c a t e d, discoid, hy p e rp i g m e n t e d, scaly and\nthickened plaques scattered on the trunk, back, legs\nand face (Fig 1A-E). Lesions on the left chin and\nupper lip were slightly yellowish and crusted. There\nwere also two small non-tender erosions and\nscattered scaly plaques on the scrotum (Fig 1F). His\npalms and soles were spared. There was no\nevidence of lymphadenopathy, hepatosplenomegaly,\ncardiac murmurs or neurological deficit.\n\n\n\nOur provisional diagnosis was discoid eczema, with\na differential of plaque psoriasis, hy p e rt r o p h i c\nlichen planus and secondary syphilis. \n\n\n\nWe proceeded with laboratory investigations and a\nskin biopsy. Serology tests for syphilis we r e\nstrongly positive. His rapid plasma reagent (RPR)\ntest was reactive at 1:128 dilution and confirmatory\ntest with treponema pallidum haemagglutination\ntest (TPHA) was detected. Screening for other\n\n\n\ns ex u a l ly transmitted diseases including HIV,\nHepatitis B, Hepatitis C, gonorrhea and Chlamydia\ntrachomatis were negative. Skin biopsy showed\ntypical histopathological features of syphilis\nincluding epidermal hyperplasia with parakeratosis\nand a dense band-like infiltrate in the upper dermis\nwith numerous plasma cells (Fig 2). Collections of\nneutrophils were seen within the dermis and the\nepidermis especially at the stratum corneum.\n\n\n\nA diagnosis of secondary syphilis was confirmed\nand he was treated with we e k ly intramuscular\ninjection of benzathine penicillin 2.4 mega units for\ntwo consecutive weeks. Upon review in the clinic\ntwo weeks later, no new skin lesions were seen and\nthe previous lesions were resolving.\n\n\n\nDiscussion \nSyphilis is an ancient sexually transmitted disease\ncaused by the bacterium Treponema pallidum. It has\nbeen referred to as the \u2018great imitator\u2019 of skin\ndiseases, with a myriad of clinical manifestations,\nvariable in appearance and presentations. It occurs\nworldwide and the incidence varies according to the\ngeographical location.  \n\n\n\nIn Malaysia, syphilis is one of the notifi a bl e\ndiseases by law. The exact extent of the problem is\nunknown due to underreporting, underdiagnosis\nand asymptomatic manifestation of the disease. It\nwas reported that from the 1990s to 2005, there has\nbeen a decline in the number of patients seen at our\nlocal genitourinary medicine clinic (31.2% to\n24.1%). However, the World Health Organization\n(WHO) fact sheet on AIDS and sex u a l ly\ntransmitted infections (2004) reported that the\nestimated prevalence of syphilis among female sex\nworkers has been increasing, from 16.7 between\n1997-1999, to 38.2 between 2000-2001. In\naddition, of late, we have noted an increasing trend\nin sexually transmitted infections (STIs) especially\nof syphilis in our clinic. This could be due to the\nincreasing practice of men having sex with men\n(MSM) and an increase in awareness of this disease.\nIn China, the national surveillance program showed\na re-emergence of syphilis where a total of 74,000\ncases of early syphilis were diagnosed in 2005\nalone, despite the eradication of syphilis in the\n1960s to the 1980s.\n\n\n\nFigure 2 (A) There is a dense lichenoid infiltrate in the\nsuperficial dermis (x4 Haematoxylin-Eosin stain) and (B) the\ninfiltrates are mainly lymphocytes with numerous plasma\ncells (x40 Haematoxylin-Eosin stain).\n\n\n\nA\n\n\n\nB\n\n\n\n\n\n\n\n\n20 MJD 2011 July Vol 26\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nSyphilis can be divided into several stages -\nprimary, secondary, early latent (<1 year), late latent\n(>1 year) and tertiary stages. The primary stage is\ndefined by a chancre which is typically a painless,\nindurated erosion or ulcer at the site of inoculation,\noccurring after an incubation period of between 9 to\n90 days. There have been reported cases of syphilis\nbeing spread by kissing, biting or touching a person\nwho has active lesion on the lips, oral cavity, breast\nor genitals. These early lesions are highly infectious\nand transmission is seen in approximately one third\nof patients exposed to these lesions.\n\n\n\nAfter an incubation period ranging from 6 weeks to\n6 months, lesions of secondary syphilis may appear.\nClinically, secondary syphilis is often diverse, and\nmay be subtle; the cutaneous and mucosal lesions\noften mimicking other skin diseases. Ty p i c a l\nmanifestations of secondary syphilis\ninclude ly m p h a d e n o p a t hy, condylomata lata,\npapulosquamous eruption with palm and sole\ninvolvement, moth-eaten alopecia and snail-track\nmouth ulcers. Other less common cutaneous\nmanifestations which have been described include\na macular eruption (syphilitic roseolas,\nl e u ko m e l a n o d e rma), papular (including\np s o r i a s i f o rm, lichenoid, nummular syphilids),\np u s t u l a r, and malignant syphilids which is a\nnodular-ulcerative variant, has a rapid progression\nand frequently involves the face.\n\n\n\nIn a series of 105 patients with secondary syphilis,\nthe dominant cutaneous manifestation wa s\nmaculopapular eruption (up to 2/3 of patients),\nwhile only one patient presented with a\npsoriasiform-type eruption. Our patient presented\nwith pruritic psoriasiform plaques which we r e\ndiscrete, sparing the palm and soles, illustrating that\nthe disease sometime presents atypically and may\nbe missed if not thought of.\n\n\n\nTreatment guidelines from the World Health\nO rganization (WHO) recommend intramuscular\nbenzathine penicillin 2.4 megaunits either as a\nsingle dose or weekly in two to three doses is the\nm a i n s t ay of treatment in developing countries.\nDespite its clinical use for the past several decades,\nno resistance has been reported so far. In patients\nallergic to penicillin, oral doxycycline 100 mg\ntwice daily for 2 weeks, tetracycline 500 mg four\ntimes daily for 2 weeks or azithromycin 500 mg\ndaily for 1 week may be given. However, there have\nbeen reports of azithromycin/macrolide resistant\nT. pallidum in the United States and Ireland. \n\n\n\nConclusion\nIt is of great importance to be familiar with the\nmany, varied clinical manifestations of syphilis in\norder to institute early appropriate treatment for\nquick recovery of the patient as well as to halt the\nspread of this curable disease. Clinicians should\nhave a high index of suspicion in high risk patients\nalthough the clinical presentations can be protean,\nvarying from one individual to another. Reporting is\nalso important so that the information can be used\nto accurately assess the extent of this disease and to\nformulate policies and procedures in Malaysia, as\nwell as being an important means of sharing\ni n f o rmation with other healthcare professionals\nlocally and worldwide.\n\n\n\nReferences\n\n\n\n1. Lim P, Gangaram HB, Hussein SH. A 10-ye a r\nretrospective study on changing pattern of sexually\ntransmitted infections in Hospital Kuala Lumpur,\nMalaysia. Malaysian J Dermatol 2007;19:41-46\n\n\n\n2. CDC. Summary of provisional cases of selected\nnotifiable disease, United States, cumulative, week\nending December 18, 2004 (50th week). MMWR Morb\nMortal Wkly Rep 2004; 53:1185\n\n\n\n3. Chen ZQ, Zhang GC, Gong XD et al. Syphilis in\nChina: results of a national surveillance progr a m .\nLancet 2007;369:132-138\n\n\n\n4. Oh Y, Ahn SY, Hong SP, Bak H, Ahn SK. A case of\nextragenital chancre on a nipple form a human bite\nduring sexual intercourse. Int J Dermatol 2008; 47:\n978-980\n\n\n\n5. Fuehrer NE, Furukawa BJ, Kowalewski CL, Cadena-\nZuluaga J, Becker LE, Fernandez MP. A 48-year old\nmale with crusted plaque on the left side of the neck.\nAm J Dermatopathol 2010;32:99-100\n\n\n\n6. D o u rm i s h ev LA, Dourm e s h ev AL. Syphilis:\nuncommon presentations in adults. Clinics in Dermatol\n2005;23:555-564\n\n\n\n7. Chapel TA. The signs and symptoms of secondary\nsyphilis. Sex Transm Dis 1980;7:161-164\n\n\n\n8. World Health Organization. Sex u a l ly transmitted\ninfections management guidelines.\n(www.who.int/HIVAIDS) Geneva: WHO 2001\n\n\n\n9. Goh BT. Syphilis in adults. Sex Transm Infect\n2005;81:448-452\n\n\n\n10. L u ke h a rt SA, Godornes CBS, Molini BJ et al.\nMacrolide resistance in Treponema pallidum in the\nUnited States and Ireland. N Engl J Med 2004;351:\n154-158\n\n\n\n\n\n\n\n\n\n"
"\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more than \n2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Comment \nand References. A Structured Abstract of not more than 240 \nwords must be included. It should consist of five paragraphs, \nlabelled Background, Methods, Results, Discussion and \nConclusion. It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nREVIEW ARTICLE\n\n\n\n2 Consensus Guidelines in Usage of Biologics in \nDermatology during COVID-19 Pandemic: \nBiologic Advisory Group Malaysia\n\n\n\n Chow SKW, Choon SE, Chan LC, Azizan NZ, \nMuniandy P, Foong HBB, Heng AYH, Teoh BTY, Yap \nFBB, Tan WC, Ch\u2019ng PWB, Tey KE, Slevarajah L, \nThevarajah S\n\n\n\nORIGINAL ARTICLE\n\n\n\n11 Cutaneous Manifestations in Patients Infected \nwith Human Immunodeficiency Virus: An Audit \nin the Department of Dermatology Hospital Kuala \nLumpur\n\n\n\n Chan GP, Nithianandan M, Thevarajah S, Tang MM\n\n\n\n22 The Value of Adding 1,3-Diphenylguanidine, \nN-cyclohexyl-n-phenyl-4-phenylenediamine, \nN-cyclohexylthiophthalimide and Ylang-ylang oil \nto the European Baseline Series to Improve the \nDetection of Rubber and Fragrance Allergy among \nPatients Suspected with Contact Dermatitis in \nHospital Selayang\n\n\n\n Ng FY, Tang MM, Ridzwan R, Johar A\n\n\n\n29 Contact Cheilitis: A 5-Year Review in The \nDepartment of Dermatology, Hospital Kuala \nLumpur\n\n\n\n Syed Nong Chek SR, Tang MM, Johar A\n\n\n\n35 Impact of Eczema Action Plan (EAP) On Disease \nSeverity for Childhood Atopic Eczema\n\n\n\n Mashor M, Lee YW, Choon SE, Tey KE, Jamil A\n\n\n\n\n\n\n\n43 A Case Control Study: Comparison of Zinc Level in \nAndrogenetic Alopecia Patients with Control Group\n\n\n\n Kwan JW, Tang JJ\n\n\n\n50 Association between Vitiligo and Neutrophil-to-\nLymphocyte Ratio in Dr. Sardjito General Hospital, \nYogyakarta, Indonesia\n\n\n\n Trisnowati N, Lukito AM, Wirohadijojo YW\n\n\n\n54 Cutaneous Manifestations in Patients with End \nStaged Renal Disease Undergoing Hemodialysis\n\n\n\n Harish MR, Sriramanan A, Shashikumar BM, \nDeepadarshan K\n\n\n\n60 Psoriasis and Metabolic Syndrome in Rural India:  \nCase Control Study\n\n\n\n Date P, Jain S\n\n\n\nCASE REPORT \n\n\n\n65 Stevens Johnson Syndrome/Toxic Epidermal \nNecrolysis Overlap as a Presentation of Acute \nCutaneous Lupus Erythematosus\n\n\n\n Tan WF, Sook MYV, Rajaintharan S\n\n\n\n69 Acne Fulminans Sine Fulminans\n Yadav N, Kar S, Bonde P, Manwar P, Ramteke K, Patrick \n\n\n\nS\n\n\n\n72 Concurrent Occurrence of Papulonecrotic Tuberculid \nand Erythema Nodosum: A Case Report\n\n\n\n Patrick S, Kar S, Yadav N, Gangane N, Deshmukh A, \nDate P, Sawant A\n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n1\n\n\n\nEditor-in-Chief\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, M Adv Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2020 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm\nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nExecutive Committee \nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPresident\nDr Sabeera Begum, MMed - Vice President\nDr Tan Wooi Chiang, Adv M Derm - Secretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDr Chan Lee Chin, MMed - Past President\nDr Tang Jyh Jong, Adv M Derm -\nCommittee Member\n\n\n\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\nDr Teoh Tze Yuen, Adv M Derm - \nCommittee Member\nDr Nazirin Ariffin - Committee Member\n\n\n\nDermatological Society of Malaysia\nMedical Academics of Malaysia, Unit 1.6, Level \n1, Enterprise 3B, Technology Park Malaysia, \nJalan Innovasi 1, Lebuhraya Puchong-Sg Besi, \nBukit Jalil, 57000 Kuala Lumpur, Malaysia\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2\n\n\n\nREVIEW\n\n\n\nConsensus Guidelines in Usage of Biologics in Dermatology during \nCOVID-19 Pandemic: Biologic Advisory Group Malaysia          \n\n\n\nSteven Kim Weng Chow1, FRCP, Siew Eng Choon2, FRCP, Chan Lee Chin3, MMED, Noor Zalmy Azizan4, AdvMDerm, \nPubalan Muniandy5, FRCP, Henry Boon Bee Foong6, FRCP, Agnes Yoke Hui Heng7, MRCP, Benji Tze Yuen Teoh8, \nAdvMDerm, Felix Boon Bin Yap9, AdvMDerm, Wooi Chiang Tan10, AdvMDerm, Peter Wee Beng Ch\u2019ng11, AdvMDerm, \nKwee Eng Tey12, MRCP, Latha Selvarajah13, AdvMDerm, Suganthi Thevarajah4, MMed  \n\n\n\n1KL Skin Centre, Kuala Lumpur, Malaysia\n2Jeffrey Cheah School of Medicine & Health Sciences, Johor Bahru, Johor, Malaysia\n3Northern Skin Specialist Clinic, Penang, Malaysia\n4Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n5Department of Dermatology, Hospital Umum Sarawak, Kuching, Sarawak, Malaysia\n6Foong Skin Specialist Clinic, Ipoh, Perak, Malaysia \n7Agnes Heng Dermatology, Ipoh, Perak, Malaysia \n8Department of Dermatology, Selayang Hospital, Selangor, Malaysia \n9Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long Campus, Selangor, Malaysia \n10Department of Dermatology, Hospital Pulau Pinang, Pulau Pinang, Malaysia\n11Gleneagles Kuala Lumpur, Kuala Lumpur, Malaysia \n12Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia \n13Department of Dermatology, Hospital Sultan Ismail, Johor Bahru, Johor, Malaysia\n\n\n\nObjective\nThe aim of this Biologic Advisory Group (BAG) \nMalaysia consensus guideline is to provide \nclinicians managing cutaneous diseases with \nbiologics relevant parameters to consider prior to \ninitiating or stopping or continuing any biologic \ntreatment in the current landscape of the COVID-19 \npandemic. Besides reviewing the medical literatures \non COVID-19 and evidences related to other \nhuman coronavirus or influenza, expert opinions \nand clinical experiences are shared and debated in \nformulation of this biologic consensus guideline.\n\n\n\nPreamble\nThe emergence of the 2019 novel coronavirus \nSARS-CoV-2 in December 2019 in Wuhan, \nChina and subsequently the pandemic outbreak of \nCOVID-19 worldwide; is a great concern for public \nhealth around the world. There is a significant \nglobal concern on this COVID-19 pandemic due \nto its widespread of transmission and its effects in \nsignificant proportion of vulnerable patients. \n\n\n\nPatients on immunomodulators, in particular \nbiologics and small molecules for cutaneous \ndiseases represent one of the vulnerable populations \nwho require special consideration with regard to \ntheir treatment during this COVID-19 pandemic \nperiod. \n\n\n\nCorresponding Author\nDr Steven Chow Kim Weng\nThe KL Skin Centre,\n323, Ground Floor, Jalan Pudu,\n55100 Kuala Lumpur, Malaysia.\nEmail: drstevenchow@gmail.com \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n3\n\n\n\nCurrently, the Centre for Disease Control Prevention \n(CDC) and World Health Organization (WHO) have \nno specific guidelines on the use of biologics during \nthe pandemic. \n\n\n\nTreating patients in this COVID-19 pandemic \nsituation, individual clinicians would need to base \non their knowledge and experience to weigh the \nrisks versus benefits to decide whether biologics \nshould be initiated or continued in their patients. \nThere are some who cautioned the use of biologics \nduring COVID-19 pandemic, while others cautioned \nagainst discontinuation of biologics which can \nresult in loss of response when reinitiated later or \nformation of auto-antibodies upon discontinuation \nof biologics.1-4 \n\n\n\nThere are several guidance documents published \nrecently by the American Academy of Dermatology \n(AAD),5 International League of Dermatological \nSocieties (ILDS)6 and International Psoriasis \nCouncil7 with regard to the use of biologics on \npsoriasis patients during COVID-19 pandemic \noffering some general guidance to clinicians on the \nmanagement of psoriasis patients with biologics \nduring this COVID-19 pandemic. \n\n\n\nIn addition, there are some data on the risk of \nCOVID-19 infection with biologic therapy, with \nrecent publication of 2 studies suggesting the usage \nof biologics in immune-mediated inflammatory \ndiseases is not associated with worse COVID-19 \noutcomes or at higher risk of being infected with \nCOVID-19 virus.8-9 In addition, a paper from China \nanalysed 107 psoriasis patients on IL-17 and anti-\nTNF-\u03b1 in pandemic epicentre Wuhan has found that \npatients receiving biologics do not have an increased \nrisk of contracting COVID-19 or developing \ncomplications to COVID-19.10 Emerging data from \nPsoProtect registries evaluating factors associated \nwith adverse COVID-19 outcomes in patients \nwith psoriasis across 25 countries also found that \nbiologic use in moderate to severe psoriasis patients \nwas associated with lower risk of COVID-19 \nrelated hospitalization than non-biologic systemic \ntherapies.11 \n\n\n\nIn Malaysia, biologic therapies have also gained \nacceptance and is currently playing an important \nrole in psoriasis treatment. According to Malaysian \nPsoriasis Registry 2007-2018 annual report, a total \nof 136 adult patients received biologic treatment. \nThe biologic therapy that are most frequently used \ninclude TNF \u03b1 inhibitor [Adalimumab (36%), \n\n\n\nEtanercept (11%), Infliximab (3.6%), Golimumab \n(0.7%), Certolizumab (0.7%)], followed by Anti IL \n12/23 Ustekinumab (34%) others (2.9%).\n\n\n\nSARS-Cov-2 Virus and COVID-19 \nDisease\nIn late December 2019, a cluster of patients was \nadmitted to hospitals with an initial diagnosis of \npneumonia of an unknown etiology, which were \nsupposedly epidemiologically linked to a seafood \nand wet animal market in Wuhan, China12. This \nunknown virus is initially being termed \u201c2019-\nnCoV\u201d and later changed to \u201cSARS-CoV-2\u201d \n(officially known as COVID-19 disease now), a \nbeta coronavirus closely linked to SARS-CoV \n(2003 SARS disease) and MERS-CoV (2011 MERs \ndisease). On 11 Mar 2020, the WHO declared \nCovid-19 as a global pandemic. As of 2nd Oct 2020, \n34 million confirmed cases and around 1 million \ndeaths (3%) have been reported to WHO.13 \n\n\n\nThe initial animal reservoir for this virus is \nbelieved to be from bats, with the intermediate \nhosts suspected to be pangolins.14 Human to human \ntransmission of COVID-19, via respiratory droplets \nor close contact has been detected.15 COVID-19 has \na probable asymptomatic incubation period of 2-14 \ndays during which the virus can be transmitted.16 \nThe rapid spread of COVID-19 virus has occurred \nwith the basic R0 of 2.2-2.6, meaning that on \naverage, each individual has the potential to spread \nthe infection to 2.2 other people.17 \n\n\n\nBased on the hospitalized patients data, the majority \nof COVID-19 cases (about 80-90%) presented \nwith asymptomatic or with mild symptoms while \nthe remainder are severe or critical.18,19 The most \ncommon symptoms of COVID-19 are fever, fatigue \nand respiratory symptoms including cough, sore \nthroat and shortness of breath, while intestinal \nsymptoms were occasionally reported.15,18 Most \npatients developed lymphopenia and pneumonia \nwith characteristics pulmonary ground glass opacity \nchanges on chest CT.15,18\n\n\n\nImmune Response in COVID-19 Patients\nIn addition, significantly high blood levels of \ncytokines and chemokines (inflammatory mediators) \nwere noted in patients with COVID-19 infection. \nSome of the severe cases that were admitted to \nthe intensive care unit showed high levels of pro-\ninflammatory cytokines including IL2, IL7, IL10, \nGCSF, IP10, MCP1, MIP1\u03b1 and TNF\u03b1 that are \nreasoned to promote disease severity.18 Inflammatory \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4\n\n\n\nmediators can become hyperactivated, resulting in \na \u201ccytokine storm\u201d which is the primary cause of \ndeath in severe disease.20 \n\n\n\nTheoretical data from previous coronavirus \n\n\n\noutbreaks has also suggested a prominent role for \ntype 1 interferon, B-cell released antibodies, tumour \nnecrosis factor-\u03b1 (TNF\u03b1) and other cytokines in the \nviral immune response (Figure 1).21\n\n\n\nFigure 1. COVID-19 viral immune response and target of common dermatologic immunomodulators and immunosuppressants. \n(Adapted from Price KN et al21)\n\n\n\n \n3.3 Based on the hospitalized patients data, the majority of COVID-19 cases (about 80-90%) \npresented with asymptomatic or with mild symptoms while the remainder are severe or \ncritical.18,19 The most common symptoms of COVID-19 are fever, fatigue and respiratory \nsymptoms including cough, sore throat and shortness of breath, while intestinal symptoms \nwere occasionally reported.15,18 Most patients developed lymphopenia and pneumonia with \ncharacteristics pulmonary ground glass opacity changes on chest CT.15,18 \n \n \n4. Immune response in COVID-19 patients  \n4.1 In addition, significantly high blood levels of cytokines and chemokines (inflammatory \nmediators) were noted in patients with COVID-19 infection. Some of the severe cases that \nwere admitted to the intensive care unit showed high levels of pro-inflammatory cytokines \nincluding IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1\u03b1 and TNF\u03b1 that are reasoned to \npromote disease severity.18 Inflammatory mediators can become hyperactivated, resulting in a \n\u201ccytokine storm\u201d which is the primary cause of death in severe disease.20  \n \n4.2 Theoretical data from previous coronavirus outbreaks has also suggested a prominent role \nfor type 1 interferon, B-cell released antibodies, tumour necrosis factor-\u03b1 (TNF\u03b1) and other \ncytokines in the viral immune response (Figure 1).21  \n \nFigure 1. COVID-19 viral immune response and target of common dermatologic \nimmunomodulators and immunosuppressants. (Adapted from Price KN et al21) \n \n\n\n\n\n\n\n\nInterleukin (IL) 1 promotes fever and the \ndifferentiation of T-helper cells to IL-17-producing \nT-cells. Interleukin (IL) 17 cytokines are important \nfor immune cell recruitment to infection sites \nto promote clearance, while also activating \ndownstream cascades of cytokines and chemokines. \nTumour necrosis factor-\u03b1 promotes dendritic cell \ndifferentiation, leukocyte recruitment, and mediates \n\n\n\nfever.22 Antibodies produced by plasma cells help \nto neutralize the virus, limit infection, and prevent \nfuture infections. Disruption of B-cell differentiation \ninto plasma cells could limit antibody production.\n\n\n\nWhile normal immune response is essential to \ncontrol and eliminate coronavirus infections, \nhowever, maladjusted immune responses may result \n\n\n\n(Left) (1) Person-to-person transmission of COVID-19 occurs through direct contact with respiratory secretions of infected individuals. \nThe virus invades host cells by binding to their receptors and fusing with the cell membrane. (2) It is hypothesized that once inside the \nbody, the lung epithelial cells become the primary target, where the receptor binding domain of the virus spikes bind to angiotensin-\nconverting enzyme (ACE2) receptors of ACE2-expressing target cells. (3) Although not confirmed, it is believed the virus dampens the \ninitial type 1 interferon (IFN) responses, which contributes to uncontrolled viral replication. (4) Once the virus is identified, macrophages \npresent viral components to activate and induce (5) differentiation of T cells and B cells. (6) Activated B cells differentiate into plasma \ncells that produce antibodies important for neutralizing viruses. (7) The resulting inflammatory cytokines and antibodies continue to \nstimulate the production of additional cytokines and antibodies, which may contribute to the \u2018\u2018cytokine storm\u2019\u2019 noted in those with severe \ndisease. (8) The inflammatory cytokines and antibodies also promote the influx of neutrophils, monocytes, and macrophages along with \nadditional inflammatory cytokines.\n\n\n\n(Right) The drug targets for common dermatologic immunomodulators and immunosuppressants have also been included in this diagram. \nFGF, Basic fibroblast growth factor; GCSF, granulocyte-colony stimulating factor; GMCSF, granulocyte-macrophage colony stimulating \nfactor; IL, interleukin; IP10, interferon-induced protein 10; IRF, interferon regulatory factor; MCP1, monocyte chemoattractant \nprotein 1; MIP1A, macrophage inflammatory protein 1-A; NFAT, nuclear factor of activated T cells; NF-B, nuclear factor-B; PDE4, \nphosphodiesterase 4; PDGF, platelet-derived growth factor; PKA, protein kinase A; TH, T-helper cell; TNF, tumour necrosis factor; \nVEGFA, vascular endothelial growth factor A.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n5\n\n\n\nin immunopathology and impaired pulmonary gas \nexchange.22\n\n\n\nThus, it is currently being hypothesized that \npossibility of inhibiting these pro-inflammatory \nmediators through targeted therapy may actually \nimprove clinical outcomes and reduce mortality \nin severe COVID-19 patients experiencing \ncytokine storm.23,24,25,26 Two trials on tocilizumab \n(IL-6) in France24 and Italy,25 have shown clinical \nimprovement, reduced number of ICU admissions \nand/or mortality in patients with severe COVID-19 \npneumonia. An open label controlled trial on \nadalimumab (TNF-\u03b1 inhibitor) for the use in \ntreating severe COVID-19 pneumonia has also been \ninitiated in Shanghai, China.26\n\n\n\nParameters for Consideration\nIn this guideline, seven (7) parameters have been \nconsidered when drafting this guideline to assess \nthe suitability of patients to be initiated or continued \nwith biologics during this COVID-19 pandemic. \nTraffic light system has been used to determine \n\u201cGo\u201d (Green); \u201cWait, assess other parameters\u201d \n(Yellow) or \u201cNo Go\u201d (Red) in the decision making \nprocess for this guideline. The parameters are:\n\n\n\n1. COVID-19 Antigen (Ag) viral positivity\n2. COVID-19 Antibody (IgM & IgG) seropositivity\n3. Clinical signs & symptoms suggestive of \n\n\n\nCOVID-19 infection or any acute respiratory \ninfection\n\n\n\n4. Exposure to COVID-19 positive patients\n5. Underlying cutaneous disease severity\n6. Patient\u2019s age\n7. Underlying comorbid diseases\n\n\n\nCOVID-19 Antigen (Ag) Viral Positivity\nThis is the most important parameter to be \nconsidered in potential biologics or continuing \nbiologics patients.\n\n\n\nIn Malaysia, there is currently no existing directive \nor requirement to screen all patients with COVID-19 \nAg test before initiating or continuing biologics. \nHowever, for patients living in or coming from \nhigh-risk area (red zone) or suspected COVID-19 \nsymptomatic patients, a COVID-19 Ag test is \nrecommended.18,19 COVID-19 RT-PCR according \nto the Ministry of Health should be used to establish \nCOVID-19 infection status of the patients.\n\n\n\nCOVID-19 Ag positivity indicates current on-going \ninfection with COVID-19 virus. Inflammatory \n\n\n\nresponse and mediators are needed for viral \nclearance.22 Thus, it is advisable to stop patients from \nbiologic treatment or defer initiation of biologic \ntreatment for at least 30 days, or until patients have \ncompletely recovered and tested COVID-19 Ag \nnegative indicating no viral shedding.5,27\n\n\n\nFor patients where COVID-19 Ag test is unavailable, \nclinicians will need to rule out COVID-19 infection \nin their patients through the clinical evaluation \nof signs & symptoms based on respective local \nCOVID-19 practice guidelines.\n\n\n\nGo\n\n\n\nGo\nConfirm COVID-19 \n\n\n\nAg Negative\n\n\n\nNegative\n\n\n\nNegative\n\n\n\nPositive\n\n\n\nPositive\n\n\n\nCOVID-19 Ag\n\n\n\nCOVID-19 IgM \n& IgG\n\n\n\nNo Go\n\n\n\nGo\nConfirm COVID-19 \n\n\n\nAg Negative\n\n\n\nCOVID-19 Antibody (IgM & IgG) Seropositivity\nCOVID-19 Antibody test may or may not be \ndone on the patients, as its value is limited in \nunderstanding the current infection status of the \npatients. Seropositivity of COVID-19 Antibody \ntest signifies that the patient has been exposed to \nCOVID-19 virus prior, but it does not confirm that \nthe patient is currently still having the COVID-19 \ninfection. Thus, we recommend those patients \nwith either COVID-19 Antibody seropositive or \nseronegative to undergo COVID-19 Ag test to \nconfirm the current status of COVID-19 infection \nprior to biologics initiation or continuation of \ntherapy. If covid-19 seropositive, should WAIT and \ncheck COVID-19 Ag.\n\n\n\nClinical Signs & Symptoms Suggestive of \nCOVID-19 Infection or Any Other Acute \nRespiratory Infection\n\n\n\nCold/flu-like Symptoms or Signs & Symptoms \nSuggestive of Any Other Acute Respiratory Infection\nPatients with more severe skin disorders (e.g \nsevere psoriasis) are inherently at increased risk \nof developing pneumonias of any cause.28 While \na number of clinical trials of newer biologics used \nin dermatology patients indicate a slight increased \nrisk of developing upper respiratory tract infections \n(URTI), there does not appear to be a significant \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6\n\n\n\nincrease risk of developing influenza (flu).\n\n\n\nFor patients with cold/flu-like symptoms, it is \nadvisable to stop or defer biologics treatment and \nrefer patients for COVID-19 Ag test.\n\n\n\nFor patients with cold/flu-like symptoms who are \nCOVID-19 Ag negative, it is also advisable to screen \nfor non-COVID-19 pathogens such as influenza, \nrespiratory syncytial virus (RSV), Streptococcus \npneumoniae so that appropriate treatment can \nbe given. Patients with cold/flu like symptoms \nwill still require their active immune system \nand inflammatory mediators for non-COVID-19 \nbacterial/viral clearance, thus we advised biologics \ntreatment to be restarted after 14 days or after cold/\nflu-like symptoms resolves or completion of a \ncourse of antibiotics/antivirals.29\n\n\n\nDiarrhoea\nAs the COVID-19 virus may directly or indirectly \naffect the enteric mucosa,30 diarrhoea and other \ngastrointestinal findings should raise clinical \nsuspicion for COVID-19 infection, with or without \nthe presence of fever, cough and other respiratory \nand non-respiratory manifestation. The WHO \ndefines diarrhoea as 3 or more loose/liquid stools \nper day or an increase in the number of evacuations \ncompared with the usual.33 A few meta-analysis \nconducted found that pooled prevalence among \npatients reporting diarrhoea ranges from 6.1% to \n10.4%.30, 31, 32\n\n\n\nAlthough the prevalence is rather low, the COVID-19 \npandemic has affected millions of people worldwide, \ntranslating to a few hundred thousands of diarrhoea-\nassociated case worldwide due to COVID-19. Thus, \nwe recommend that patients with diarrhoea of \nunknown origin should have COVID-19 infection \nexcluded before initiating or continuing biologics \ntreatment.\n\n\n\nLoss of Smell (Anosmia)\nThere is an increasing evidence that olfactory \ndysfunction can present in COVID-19 patients. \nAnosmia can occur alone or can be accompanied \nby other symptoms of COVID-19, such as dry \ncough. However, the pathogenic mechanism of \nolfactory dysfunction and its clinical characteristics \nin patients with COVID-19 remains unclear.\n\n\n\nThere is a variability of data on anosmia among \ndifferent population of patients. While it has a high \nincidence rate (47-70%) in COVID-19 patients in \n\n\n\nEurope34,35 and American countries, it rarely occurs \nin Chinese patients (pooled data of 5%).36\n\n\n\nA recent retrospective study investigating 949 \npatients with COVID-19 has found that 20% of \nthe patients reported loss of smell during their \ninitial evaluation of COVID-19. This study also \nfound that smell loss is an independent positive \nprognostic factor of a less severe COVID-19 \ninfection; significantly associated with decreased \nhospitalization, intensive care unit admission, \nintubation and acute respiratory distress syndrome \nrates.37\n\n\n\nWe recommend that also patients with recent onset \nanosmia should also have COVID-19 infection \nexcluded before initiating or continuing biologic \ntreatment.\n\n\n\nGo\nConfirm COVID-19 \n\n\n\nAg Negative\n\n\n\nGo\nConfirm COVID-19 \n\n\n\nAg Negative\n\n\n\nNegative\n\n\n\nNo\n\n\n\nPositive\n\n\n\nYes\n\n\n\nCold/Flu-like \nSymptoms, \nSymptoms \nSuggesting \nAcute \nRespiratory \nInfection, \nDiarrhoea or \nAnosmia\n\n\n\nExposed to \nConfirmed \nCOVID-19 \nPositive Patients\n\n\n\nNo Go\nEstablish if Acute \nInfection Occurs\n\n\n\nWait\nComplete 14 Days \n\n\n\nIsolation First\n\n\n\nExposure to COVID-19 Positive Patients\nThis group of patients with high risk of exposure \nto COVID-19 include patients living in or traveling \nfrequently to endemic areas, healthcare worker, \nnursing home resident, household member or co-\nworker with COVID-19 infection.\n\n\n\nThese patients are of very high risk of contracting \nCOVID-19 virus from others with close contact \nwith them. Due to their high susceptibility in \ncontracting the COVID-19 anytime throughout this \nCOVID-19 pandemic, we recommend for this group \nof patients, a 14 days isolation or quarantine if they \nhave been in contact with a COVID-19 positive \npatient. We recommend COVID-19 infection \nshould be excluded from patients before initiation \nor continuation of biologics.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n7\n\n\n\nWait\nConsider Other \n\n\n\nParameters\n\n\n\nGo\nConfirm \n\n\n\nCOVID-19 \nAg Negative\n\n\n\nWait\nConsider \n\n\n\nOther \nParameters\n\n\n\nNo Go\n\n\n\nGo\nConfirm COVID-19 \n\n\n\nAg Negative & \nConsider Other \n\n\n\nParameters\n\n\n\nWait\nExercise Caution \n& Consider Other \n\n\n\nParameters\n\n\n\nStable\n\n\n\nNo Yes, Controlled          Yes, Non-\ncontrolled\n\n\n\n\u226460 years\n\n\n\nFlare\n\n\n\n>60 years\n\n\n\nUnderlying \nCutaneous \nDisease\n\n\n\nUnderlying \nComorbid \ndiseases \n(Exclude PsA \ncomorbidity)\n\n\n\nAge\n\n\n\nGo\nConfirm COVID-19 \n\n\n\nAg Negative\n\n\n\nUnderlying Cutaneous Disease Severity\nThe severity of underlying cutaneous disease is also \nanother parameter that is needed to consider when \ninitiating or continuing biologic therapy. Disease\u2019s \nflare is one factor that clearly indicates benefits \noutweigh the risk of initiation or continuation of \nbiologic therapy during COVID-19 pandemic. \nWe recommend patients with a flare of underlying \ncutaneous disease to have the COVID-19 infection \nexcluded before initiating or continuing biologics \ntreatment.\n\n\n\nPatient\u2019s Age\nPatients of the older age group (>60 years old) is a \nknown major risk factor contributing to the mortality \nof patients with COVID-19 disease. Death is most \ncommonly reported among patients aged >80 years \n(28.7%), followed by 70-79 years (16.6%) and 60-\n69 years (6.7%).19,38,39,41\n\n\n\nIn view of this, we recommend that in patients over \n60 years of age, caution need to be exercised and to \ntake in consideration of other parameters in making \na decision.\n\n\n\nUnderlying Comorbid Diseases\nData from US and China found that severe outcomes \nwere more commonly reported for patients with \nreported underlying conditions (cardiovascular \ndiseases, respiratory diseases, diabetes, liver, \nkidney diseases or cancer patients or on transplant \npatients).24,40,41 Deaths were 12 times higher among \npatients with underlying conditions compared to \nthose without reported underlying conditions.38 As \nsuch, caution will need to be exercised considering \nother parameters in this group of comorbid patients.\n\n\n\nHowever, for psoriasis patients with co-existing \npsoriatic arthritis disease, the use of biologics in \nthese concomitant diseases are much warranted, \nas both diseases respond well to biologics. Thus, \n\n\n\nexception to the recommendation above for \nunderlying comorbid disease shall be made for co-\nexisting psoriatic arthritis disease\n\n\n\nThe Algorithm for The Parameters Discussed \nAbove is Summarized in Figure 2\nIt is important to remember that COVID-19 is a \nnovel, rapidly changing virus. Thus, when more \ndata is available, this BAG Malaysia consensus \nguideline will need to be updated.\n\n\n\nGeneral Measures\nPatients who have been initiated or continued \nwith biologics treatment need to be monitored \nclosely and advised appropriately, while those \nwere deferred or discontinued biologics treatment \nwill need to be monitored closely on their disease \nseverity. In addition, all patients should be reminded \nto practice good infection prevention measures10 \nsuch as frequent hand washing, wear a face mask in \npublic places and practise social distancing.\n\n\n\nCandidates for Biologics Initiation / Continuation\n(Malaysia Scenario)\n\n\n\nNo signs & symptoms \nsuggestive acute infection\n\n\n\nHigh exposure risk \nto COVID-19\n\n\n\nLow exposure risk \nto COVID-19\n\n\n\nCOVID-19 Ag Test\n\n\n\nNo Go\n\n\n\nNo Go\n\n\n\nGo\n\n\n\nNo GoWait**\n\n\n\nCOVID-19 Ag Test\n\n\n\nSigns & symptoms \nsuggestive acute infection\n\n\n\nComorbid** UncontrolledComorbid* Controlled\n\n\n\nDisease FlareStable Disease\n\n\n\nFigure 2. Algorithm for the initiation/continuation of biologics \ntreatment during COVID-19 Pandemic period (Malaysia \nScenario)\n\n\n\n*Including, but not limited to cardiovascular disease, respiratory \ndisease, diabetes mellitus, liver disease, kidney disease, cancer and \norgan transplant patient.\n**Caution needs to be exercised, considering other parameters before \ninitiation of biologics.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8\n\n\n\nCOVID-19 Vaccination in Patients on \nBiologic Treatment\nAs of 2nd Oct 2020, there are 42 COVID-19 \ncandidate vaccines in the clinical evaluation phase, \nwhile 151 candidate vaccines in the pre-clinical \nevaluation phase.42 With vaccines companies \nall over the world working relentlessly to find a \nsafe and efficacious vaccine to halt the spread of \nthis COVID-19 infection, it is a matter of time \nthat the right candidate vaccine will be available \ncommercially.\n\n\n\nCOVID-19 vaccines under development include \nvirus vaccines (inactivated or weakened), viral \nvector vaccines (replicating or non-replicating), \nnucleic acid vaccine (DNA or RNA) and protein-\nbased vaccine (protein subunit or virus like \nparticles). \n\n\n\nPatients on biologic should not be given a virus \nvaccine. Other vaccines are not contraindicated. It is \nadvisable for those undergoing or planning to have \nbiologic therapy to be recommended a COVID-19 \nvaccination.\n\n\n\nKey Recommendations\n\n\n\nLevel of Evidence\n\n\n\nStrengths of Recommendation\n\n\n\nBAG MY Position Statement Level of Evidence Strength of Recommendation\n8.1 The concurrent use of biologics during the COVID-19 pandemic does not increase \n\n\n\nthe risk of COVID-19 infection\nII-2 B\n\n\n\n8.2 The concurrent use of biologics during the COVID-19 pandemic does not increase \nthe severity of COVID-19 infection\n\n\n\nII-2 B\n\n\n\n8.3 Patients with active COVID-19 infection as proven by positive COVID-19 Ag test \nor with COVID-19 clinical symptoms (without positive virology) should postpone/\ndefer biologic treatment for a period of at least 30 days and until being tested \nnegative at the end of the period of postponement    \n\n\n\nIII C\n\n\n\n8.4 Patients with other active respiratory infection (other than COVID-19 infection) \nor with a history of close contact with a proven active COVID-19 patient should \npostpone/defer biologic treatment for a period of at least 14 days and until being \ntested negative at the end of the period of postponement    \n\n\n\nIII C\n\n\n\n8.5 Patients with positive serology (IgM/IgG) for COVID-19 infection with negative \nantigen status can proceed with biologic treatment\n\n\n\nIII C\n\n\n\n8.6 All patients with increased risk from co-morbid diseases should be assessed on \na case-by-case basis by attending physician before commencing use of biologic \nagents\n\n\n\nIII C\n\n\n\n8.7 All patients on biologics should be recommended vaccination with a COVID-19 \nvaccine, should it be available in the near future\n\n\n\nIII C\n\n\n\nLevel Study Design\nI Evidence from at least one properly randomised controlled trial \n\n\n\nII-1 Evidence obtained from well-designed controlled trials without randomisation \nII-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferable from more than one centre or group \nII-3 Evidence from multiple time series with or without intervention. Dramatic result on uncontrolled experiments (such as the results from the \n\n\n\nintroduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence \nIII Opinions of respected authorities based on clinical experience; descriptive studies and case report; or reports of expert committees \n\n\n\nA At least one meta-analysis, systematic review, or RCT, or evidence rated as good and directly applicable to the target population \nB Evidence from well conducted clinical trials, directly applicable to the target population, and demonstrating overall consistency of results; \n\n\n\nor evidence extrapolated from meta-analysis, systematic review, or RCT \nC Evidence from expert committee reports, or opinions and/or clinical experiences of respected authorities; indicates absence of directly \n\n\n\napplicable clinical studies of good quality \n\n\n\nSource: US/Canada Preventive Services Task Force\n\n\n\nSource: Modified from the Scottish Intercollegiate Guidelines Network (SIGN)\nNote: The strength of recommendations related to the strength of the evidence on which the recommendation is based. It does not reflect \nthe clinical importance of the recommendation.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n9\n\n\n\nDisclaimer\nThe recommendations stated in this guideline are \nbased on the currently available and/or published \ninformation related to the COVID-19 and biologics \nusage in psoriasis disease, as well as acts as a \ngeneral guide only. Individual clinicians will need \nto evaluate each patient based on individualized \nneed and discuss with their patients on their diseases \nand consequences before initiating or continuing \nbiologics treatment.\n\n\n\nMembers of BAG MY Panels\na. Dr Steven Chow Kim Weng, Senior Consultant \n\n\n\nDermatologist, KL Skin Centre, Kuala Lumpur; \nPresident, ALDS; Secretary-General, AADV. \n\n\n\nb. Dr Suganthi Thevarajah, Head of Dermatology \nservice, Ministry of Health, Malaysia.\n\n\n\nc. Dato\u2019 Dr Noor Zalmy Azizan, Current President \nPersatuan Dermatologi Malaysia (PDM); \nSenior Consultant Dermatologist, Hospital \nKuala Lumpur. \n\n\n\nd. Assoc Prof Dr Choon Siew Eng, Senior \nConsultant Dermatologist, Hospital Sultanah \nAminah, Johor Bahru; Associate Professor \n(Clinical), Jeffrey Cheah School of Medicine & \nHealth Sciences, Johor Bahru. \n\n\n\ne. Dr Chan Lee Chin, Past President Persatuan \nDermatologi Malaysia (PDM); Consultant \nDermatologist, Northern Skin Specialist Clinic, \nPenang. \n\n\n\nf. Dr Pubalan Muniandy, Senior Consultant \nDermatologist & Head of Dermatology \nDepartment, Hospital Umum Sarawak.\n\n\n\ng. Dr Henry Foong Boon Bee, Senior Consultant \nDermatologist, Foong Skin Specialist Clinic, \nIpoh, Perak.\n\n\n\nh. Dr Agnes Heng Yoke Hui, Consultant \nDermatologist, Agnes Heng Dermatology, \nIpoh, Perak.\n\n\n\ni. Dr Benji Teoh Tze Yuen, Consultant \nDermatologist & Head of Dermatology \nDepartment, Selayang Hospital, Selangor.\n\n\n\nj. Associate Prof Dr Felix Yap Boon Bin, \nConsultant Dermatologist, Sunway Medical \nCentre, Selangor; Associate Professor, Faculty \nof Medicine and Health Sciences, Universiti \nTunku Abdul Rahman, Sungai Long Campus, \nKajang, Selangor. \n\n\n\nk. Dr Tan Wooi Chiang, Consultant Dermatologist \n& Head of Dermatology Department, Hospital \nPulau Pinang, Pulau Pinang.\n\n\n\nl. Dr Peter Ch\u2019ng Wee Beng, Consultant \nDermatologist, Gleneagles Kuala Lumpur, \nKuala Lumpur. \n\n\n\nm. Dr Tey Kwee Eng, Consultant Dermatologist \n& Head of Dermatology Department, Hospital \nSultanah Aminah, Johor Bahru, Johor.\n\n\n\nn. Dr Latha Selvarajah, Consultant Dermatologist \n& Head of Dermatology Department, Hospital \nSultan Ismail, Johor Bahru, Johor.\n\n\n\nConflict of Interest Declaration\nAll panel members do not have direct conflict of \ninterest.\n\n\n\nAcknowledgement\nThe publication of this guidelines is made possible \nby an educational grant from Abbvie.\n\n\n\nReferences\n\n\n\n1. Conforti C, Giuffrida R, Dianzani C, Di Meo N, Zalaudek \nI. COVID-19 and psoriasis: Is it time to limit treatment \nwith immunosuppressants? A call for action. Dermatol \nTher 2020;33:e13298.\n\n\n\n2. Kansal NK. COVID-19, syphilis, and biologic therapies \nfor psoriasis and psoriatic arthritis: A word of caution. J \nAm Acad Dermatol 2020;82:e213.\n\n\n\n3. Lebwohl M, Rivera-Oyola R, Murrell DF. Should biologics \nfor psoriasis be interrupted in the era of COVID-19? J Am \nAcad Dermatol 2020;82:1217-8. \n\n\n\n4. Amerio P, Prignano F, Giuliani F, Gualdi G. COVID-19 \nand psoriasis: Should we fear for patients treated with \nbiologics? Dermatol Ther 2020 Jul;33:e13434.5. \n\n\n\n5. AAD. Guidance on the use of biologic agents \nduring COVID-19 outbreak. Available at \nh t t p s : / / a s s e t s . c t f a s s e t s . n e t / 1 n y 4 y o i y r q i a /\nP i c g N u D 0 I p Y d 9 M S O w a b 4 7 / 0 7 b 6 1 4 6 5 8 a f f \n5fc6ccc4c0bd910509a3/Biologics_and_COVID_19_\nFINAL_V2.pdf (accessed on 4th Sept 2020)\n\n\n\n6. ILDS. Guidance on the use of immunomodulatory and \nimmunosuppressive drugs in dermatology in the era of \nCOVID-19 (May 2020). Available at: https ://ilds.org/wp-\ncontent/uploads/2020/06/ILDS-Guidance-on-the-useof-\nimmunomodulatory-and-immunosuppressive-drugsin-\ndermatology-in-the-era-of-COVID-19-May-2020.pdf. \n(accessed on 4th Sept 2020).\n\n\n\n7. IPC. IPC statement on COVID-19 and psoriasis. Available \nat: https://www.psoriasiscouncil.org/blog/COVID-19-\nStatement.htm.  (accessed on 4th Sept 2020).\n\n\n\n8. Haberman R, Axelrad J, Chen A, Castillo R, Yan D, Izmirly \nP et al. Covid-19 in Immune-Mediated Inflammatory \nDiseases - Case Series from New York. N Engl J Med \n2020;383:85-8.\n\n\n\n9. Gisondi P, Facheris P, Dapavo P, Piaserico S, Conti A, \nNaldi L et al. The impact of the COVID-19 pandemic on \npatients with chronic plaque psoriasis being treated with \nbiological therapy: The Northern Italy experience. Br J \nDermatol 2020;183:373-4.\n\n\n\n10. Zhao L, Du H, Alamgir M, Yang J, Miao X, Jiang B et \nal. Safety of biologics for psoriasis patients during the \nCOVID-19 pandemic: the experience from Wuhan, China. \nEur J Dermatol 2020;30:738-40.\n\n\n\n11. Mahil SK, Dand N, Mason KJ, Yiu ZZN, Tsakok T, \nMeynell F et al. Factors associated with adverse COVID-19 \noutcomes in patients with psoriasis - insights from a \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10\n\n\n\nglobal cross-sectional study. J Allergy Clin Immunol \n2021;147:60-71.\n\n\n\n12. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of \nunknown etiology in Wuhan, China: The mystery and the \nmiracle. J Med Virol 2020;92:401-2.\n\n\n\n13. WHO Coronavirus Disease (COVID-19) Dashboard. Last \nupdated 2nd Oct 2020, 5.04 p.m. CEST. https ://covid19.\nwho.int (accessed 3rd Oct 2020). \n\n\n\n14. Cyranoski D. Did pangolins spread the China coronavirus \nto people. Heidelberg: Springer Nature, 2020. https://\nwww.nature.com/articles/d41586-020-00364-2. (accessed \n3rd Oct 2020). \n\n\n\n15. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J et \nal. A familial cluster of pneumonia associated with \nthe 2019 novel coronavirus indicating person-to-\nperson transmission: a study of a family cluster. Lancet \n2020;395:514-23.\n\n\n\n16. Backer JA, Klinkerberg D, Wallinga J. Incubation period \nof 2019 novel coronavirus (2019-nCoV) infections among \ntravellers from Wuhan, China, 20-28 January 2020. Euro \nSurveill 2020;25: 2000062.\n\n\n\n17. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y et al. \nEarly transmission dynamics in Wuhan, China, of \nnovel coronavirus-infected pneumonia. N Engl J Med \n2020;382:1199-207.\n\n\n\n18. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical \nfeatures of patients infected with 2019 novel coronavirus \nin Wuhan, China. Lancet 2020;395:497-506.\n\n\n\n19. Wu Z, McGoogan JM. Characteristics of and important \nlessons from the coronavirus disease 2019 (Covid-19) \nOutbreak in China. Summary of a report of 72314 \ncases from the Chinese Center for Disease Control and \nPrevention. JAMA 2020;323:1239-42.\n\n\n\n20. Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH \net al. Plasma inflammatory cytokines and chemokines in \nsevere acute respiratory syndrome. Clin Exp Immunol \n2004;136:95-103.\n\n\n\n21. Price KN, Frew JW, Hsiao JL, Shi VY. COVID-19 \nand immunomodulator/immunesuppressant use in \ndermatology. J Am Acad Dermatol 2020;82:e173-5.\n\n\n\n22. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P et al. Coronavirus \ninfections and immune response. J Med Virol 2020;92:424-\n32.\n\n\n\n23. Pacha O, Sallman MA, Evans SE. COVID-19: a case for \ninhibiting IL-17? Nat Rev Immunol 2020;20:345-6.\n\n\n\n24. Klopfenstein T, Zayet S, Lohse A, Balblanc JC, Badie J, \nRoyer PY et al. Tocilizumab therapy reduced intensive \ncare unit admissions and/or mortality in COVID-19 \npatients. Med Mal Infect 2020;50:397-400. \n\n\n\n25. Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli \nF et al. Tocilizumab for the treatment of severe COVID-19 \npneumonia with hyperinflammatory syndrome and acute \nrespiratory failure: A single center study of 100 patients in \nBrescia, Italy. Autoimmun Rev 2020;19:102568.\n\n\n\n26. CHICTR. A randomized, open-label, controlled trial \nfor the efficacy and safety of adalimumab injection in \nthe treatment of patients with severe novel coronavirus \npneumonia (Covid-19) Shanghai, China: Chinese Clinical \nTrial Registry: ChiCTR2000030089;2020. http://www.\nchictr.org.cn/showprojen.aspx?proj=49889. (accessed on \n3rd Oct 2020)\n\n\n\n27. Wang C, Rademaker M, Baker C, Foley P. COVID-19 \nand the use of immunomodulatory and biologic agents \nfor severe cutaneous disease: An Australia/New Zealand \nconsensus statement. Australas J Dermatol 2020;61:210-6. \n\n\n\n28. Kao LT, Lee CZ, Liu SP, Tsai MC, Lin HC. Psoriasis and \nthe risk of pneumonia: a population-based study. PLoS \n\n\n\nONE 2014;9:e116077.  \n29. Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater \n\n\n\nEF, Stoff B et al. Joint AAD-NPF guidelines of care for the \nmanagement and treatment of psoriasis with biologics. J \nAm Acad Dermatol 2019;80:1029-72.\n\n\n\n30. D\u2019Amico F, Baumgart DC, Danese S, Peyrin-Biroulet \nL. Diarrhea during COVID-19 infection: pathogenesis, \nepidemiology, prevention and management. Clin \nGastroenterol Hepatol 2020;18:1663-72.\n\n\n\n31. Parasa S, Desai M, Thoguluva Chandrasekar V, Patel HK, \nKennedy KF, Roesch T et al. Prevalence of Gastrointestinal \nSymptoms and Fecal Viral Shedding in Patients With \nCoronavirus Disease 2019: A Systematic Review and \nMeta-analysis. JAMA Netw Open 2020;3:e2011335. \n\n\n\n32. Villamizar-Pe\u00d1a R, Guti\u00e9rrez-Ocampo E, Rodr\u00edguez-\nMorales AJ. Pooled Prevalence of Diarrhea Among \nCOVID-19 Patients. Clin Gastroenterol Hepatol \n2020;18:2385-7. \n\n\n\n33. WHO. Diarrhoea. Available at https://www.who.int/topics/\ndiarrhoea/en  (accessed 27th Aug 2020).\n\n\n\n34. Lechien JR, Chiesa-Estomba CM, Place S, Van Laethem \nY, Cabaraux P, Mat Q et al. Clinical and epidemiological \ncharacteristics of 1420 European patients with mild-\nto-moderate coronavirus disease 2019. J Int Med \n2020;288:335-44.\n\n\n\n35. Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer \nPY, Lepiller Q, Gendrin V et al. Features of anosmia in \nCOVID-19. Med Mal Infect 2020;50:436-9.\n\n\n\n36. Lovato A, de Filippis C. Clinical presentation of \nCOVID-19: A Systematic Review Focusing on Upper \nAirway Symptoms. Ear Nose Throat J 2020;99:569-76. \n\n\n\n37. Foster KJ, Jauregui E, Tajudeen B, Bishensari F, \nMahdavinia M. Smell loss is a prognostic factor for lower \nseverity of coronavirus disease 2019. Ann Allergy Asthma \nImmunol 2020;125:481-3.\n\n\n\n38. Stokes EK, Zambrano LD, Anderson KN, Marder EP, \nRaz KM, El Burai Felix S et al. Coronavirus disease \nsurveillance 2019 case surveillance - United States, \nJanuary 22-May 30, 2020. MMWR Morb Mortal Wkly \nRep 2020;69:759-65.\n\n\n\n39. Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker \nC, Imai N et al. Estimates of the severity of coronavirus \ndisease 2019: a model-based analysis. Lancet Infect Dis \n2020;20:669-77.\n\n\n\n40. Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, \nDesai P et al. Comorbidity and its impact on patients with \nCovid-19. SN Compr Clin Med 2020:1-8. \n\n\n\n41. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical \ncourse and risk factors for mortality of adult inpatients \nwith COVID-19 in Wuhan, China: a retrospective cohort \nstudy. Lancet 2020;395:1054-62.\n\n\n\n42. WHO. The COVID-19 candidate vaccine landscape. \nAvailable at: https://www.who.int/publications/m/\nitem/draft-landscape-of-covid-19-candidate-vaccines. \n(accessed 3rd Oct 2020).\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n11\n\n\n\nORIGINAL ARTICLE\n\n\n\nCutaneous Manifestations in Patients Infected with Human \nImmunodeficiency Virus: An Audit in the Department of Dermatology \nHospital Kuala Lumpur          \n\n\n\nGin Peng Chan, MRCP, Meena Nithianandan, MBBS, Suganthi Thevarajah, MMed, Min Moon Tang, AdvMDerm  \n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction\nPatients with human immunodeficiency virus (HIV) may have significant cutaneous morbidities \nwhich can potentially affect their quality of life or be life-threatening. This study aimed to describe the \ndemographic data and the pattern of cutaneous manifestations of patients infected with HIV.\n\n\n\nMethods\nThis is a retrospective study on all HIV-infected patients who were referred to the Department of \nDermatology Hospital Kuala Lumpur between 2016 and 2019. Patients\u2019 medical records were retrieved \nand reviewed. \n\n\n\nResults\nThere were 424 patients infected with HIV referred to us between 2016 and 2019. The mean age \nwas 31.74 years. The majority of them (50.4%) were in the age group of 20-29 years. About 96.0% \n(407 patients) were male. Homosexuality was the most common (52.3%) mode of HIV transmission \nin these patients. Two-hundred-and-ninety-six patients (69.8%) had their CD4 count available for \nanalysis. Of these, about 39.5% of them had a CD4 count less than 200/mm3. Less than half of the \npatients (189, 44.6%) were taking anti-retroviral therapy (ART) upon referral to us. There were a \ntotal of 638 cutaneous diagnoses made in this cohort with 152 patients had more than one cutaneous \ndiagnosis. Ninety-four patients (22.2%) underwent skin biopsy with a total 98 biopsies performed. \nThe most frequently encountered dermatosis was cutaneous infections (74.0%). These include genital \nwarts, syphilis, genital herpes, talaromycosis and molluscum contagiosum. The most frequent non-\ninfective inflammatory dermatoses observed in our cohort was eczematous dermatoses including \npapular eczema, seborrheic dermatitis, photodermatitis, contact dermatitis, nodular prurigo, discoid \neczema and stasis eczema, contributing 8.4%. Cutaneous adverse drug reaction was diagnosed in 31 \npatients (7.3%). Fifteen patients (3.5%) had Kaposi sarcoma.\n\n\n\nConclusion\nOur data showed that individuals with HIV infection may present with wide variety of skin disorders \nwhich included infective dermatoses, non-infective inflammatory dermatoses, cutaneous adverse drug \nreactions and tumours. About 35% of them had more than 1 dermatoses in our cohort. The most \nfrequent dermatoses observed was cutaneous infections.\n\n\n\nKey words: Human immunodeficiency virus, retroviral disease, acquired immunodeficiency syndrome, Kaposi sarcoma, \ntalaromycosis\n\n\n\nIntroduction\nHuman immunodeficiency virus (HIV) is a \nretrovirus that causes immunosuppressive state, \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12\n\n\n\nCorresponding Author\nDr Chan Gin Peng\nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586, Kuala Lumpur, Malaysia.\nEmail: gpncamel@gmail.com\n\n\n\nwhich was first described in 1981 in Los Angeles \nand New York in homosexual men.1 Based on \nWorld Health Organization (WHO) data, since \nthe beginning of the epidemic, 75 million people \nhave been infected with HIV virus and about 37.9 \nmillions of people were living with HIV at the end \nof 2018.2 About 0.8% of adults aged between 15 and \n49 years worldwide were living with HIV.2 In 2016, \nthere were 115,263 cases reported to be infected \nwith HIV in Malaysia3, with an average of 3400 \ncases per year between 2010-2017.\n \nHIV infection carries significant morbidity, \nreduces quality of life and causes mortality. With \nthe development of antiviral therapy (ART) it has \nnow significantly changed the perception of HIV/\nAcquired immunodeficiency syndrome (AIDS) \nfrom a fatal to a chronic potentially manageable \ndisease.4 In 2018, 23.3 million people were receiving \nantiretroviral therapy worldwide.2\n\n\n\nIndividuals infected with HIV may present with \nvarious cutaneous manifestations, which may result \nfrom HIV infection or opportunistic disorders. \nRecognizing HIV-related skin changes may \nenable early diagnosis of HIV, thus allowing early \ninitiation of ART. Since the advancement of ART, \nthe incidence of drug reactions and non-infectious \nskin eruptions has also been enhanced.5\n\n\n\n \nThis study aimed to describe the demographic \ndata and pattern of cutaneous manifestations of \npatients infected with HIV who were referred to \nthe Department of Dermatology, Hospital Kuala \nLumpur between 2016 and 2019.\n\n\n\nMaterials and Methods\nThis is a retrospective study on all newly  \nreferred  HIV-infected patients to the Department \nof Dermatology in Hospital Kuala Lumpur \nbetween 2016 and 2019. Patients\u2019 case notes were \nretrieved and reviewed. Data collected included \ndemographics, types of referrals, CD4 counts, \ntreatment durations, types of mucocutaneous \nmanifestations, numbers of skin biopsies done, co-\nmorbidities and co-infections.\n\n\n\nResults\nThere were a total of 424 patients infected with HIV \nreferred to the department between 2016 and 2019. \nTheir demographic characteristics are showed in \nTable 1. The youngest patient referred to us was 15 \nyears old and the oldest was 74 years old. The mean \nage was 31.74 years old. More than half of the total \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n13\n\n\n\npatients, 214 (50.4%) referred were in the age group \nof 20 to 29 years, and a quarter of them were in the \nage group of 30 and 39 years (115, 27.1%). Among \nthe Malaysian patients, Malays contributed to \n65.7% of the referrals, followed by Chinese, 25.4%, \nIndians 7.2% and others, 1.7%. Seven (1.6%) of were \nforeigners, which includes Indonesians (2, 0.5%), \nMyanmarese (2, 0.5%), followed by Pakistani (1, \n0.2%) and American (1,0.2%). Majority of patients \nreferred were male, 407(96.0%). \n\n\n\nHomosexuality was among the most common mode \nof transmission of HIV in these patients, (222, \n52.3%), followed by heterosexual transmission \n(63,14.9%). As shown in Table 2, a third of the \npatients (143, 33.7%) had other concomitant \nmedical illnesses which include extracutaneous \ntuberculosis (TB) (36.4%), extracutaneous fungal \ninfection (11.2%), both extracutaneous tuberculosis \nand fungal infection occurring concurrently (2.8%), \nHepatitis C infection (12.6%), Hepatitis B infection \n(7.7%), Pneumocystis jiroveci pneumonia (4.9%) \netc. Excluding 128 patients whom their CD4 counts \nwere unavailable upon referral, 39.5% (117 of 296 \npatients) had CD4 count less than 200/mm3. About \na quarter (27.4%) had CD4 counts more than 500/\nmm3. Less than half of our cohort (189, 44.6%) \nwere on ART. Of these, 72 patients (38.1%) received \nART within 12 months before they were referred to \nthe Department of Dermatology and most of them \nhas CD4 counts less than 200/mm3. \n\n\n\nA total of 638 cutaneous diagnoses were made for \nthe 424 patients as shown in Table 4. About 36% \nof the 424 patients had more than one dermatosis \ndiagnosed after dermatology review. Ninety-four \npatients (22.2%) underwent skin biopsy with a total \n98 biopsies performed. As shown in Table 4, the \nmost common dermatoses encountered by our HIV \ninfected patients was cutaneous viral infections, \nreported to occur in 263 of them (62.0%). These \ninclude genital warts, herpes labialis, extra genital \nwart, viral exanthem, oral leukoplakia, and genital \nherpes. About 31% of patients (n=131) had bacterial \ninfection, and syphilis was the most common \nbacterial infection in this cohort (94 patients). This \nwas followed by gonorrhea (15 patients), folliculitis \n(7 patients), and others such as abscess, cellulitis, \nfuruncles, chancroid, carbuncle and rectal ulcers \n(Table 4). Seventy-two patients (17%) presented \nwith cutaneous fungal infection, and talaromycosis \n(formerly known as penicilliosis) was the most \ncommon fungal infection (24 patients) encountered. \nThis was followed by oral mucosal candidiasis (14 \n\n\n\npatients), histoplasmosis (11 patients), tinea corporis \n(10 patients) and onychomycosis. Five patients had \nscabies infestation as their first presentation to the \nclinic. Of these 72 patients (38.1%) received ART \nwithin 12 months before they were referred to the \nDepartment of Dermatology and most of them has \nCD4 counts less than 200/mm3. In the subgroup \nof patients who received ART for a duration of 12 \nmonths or less, infective dermatoses were again the \nmost common dermatoses encountered, occurring \nat 2.3x the number of non-infective dermatoses.\n\n\n\nTable 1. Demographic characteristics of 424 patients infected \nwith human immunodeficiency virus (HIV) referred to the \nDepartment of Dermatology Hospital Kuala Lumpur between \n2016-2019\n\n\n\nCharacteristics n=424(%)\nMean age in years (range) 31.74 \u00b1 9.94 (15-74)\nAge group <20 11 (2.6)\n\n\n\n20-29 214 (50.4)\n30-39  115 (27.1)\n40-49 52 (12.3)\n50-59 28 (6.6)\n60-69 2 (0.5)\n70-79 2 (0.5)\n\n\n\nGender Male 407 (96.0)\nFemale 17 (4.0)\n\n\n\nNationality Malaysian 417 (98.4)\nNon-Malaysian\n  Indonesian\n  Myanmar\n  Pakistan\n  American\n  Not available\n\n\n\n7 (1.6)\n2 (0.5)\n2 (0.5)\n1 (0.2)\n1 (0.2)\n1 (0.2)\n\n\n\nRace (n=417) Malay 274 (65.7)\nChinese 106 (25.4)\nIndian 30 (7.2)\nOthers 7 (1.7)\n\n\n\nPossible mode of \nHIV transmission \n(n=339)\n\n\n\nHeterosexual 63 (18.5)\nHomosexual 222 (65.4)\nIVDU 16 (4.7)\nBlood transfusion 2 (0.59)\nBisexual 33 (9.7)\nHomosexual + IVDU 2 (0.59)\nHeterosexual + IVDU 1 (0.29)\nNot available 85\n\n\n\nHAART treatment \n(n=405)\n\n\n\nYes 189 (46.7)\nNo 216 (53.3)\nNot available 19\n\n\n\nCD4 count (cell/\nmm3) (n=296)\n\n\n\n<200 117 (39.5)\n200-500 98 (33.1)\n>500 81 (27.4)\nNot available 128\n\n\n\nAbout a third of our patient (132 patients, 31.1%) \nwas noted to have non-infective dermatoses. \nThe most common non-infective dermatoses \ndiagnosed among the patients infected with HIV \nwas eczematous dermatoses (including papular \neczema, seborrheic dermatitis, photodermatitis, \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14\n\n\n\ncontact dermatitis, nodular prurigo, discoid eczema \nand stasis eczema; a total of 36 patients or 8.4%). \nPruritic papular eruption and eosinophilic folliculitis \nwhich are commonly described among the HIV \ninfected individuals occurred in 4.0% and 1.2% in \n\n\n\nTable 2. Comorbidities and concomitant illness(s) among 424 patients infected with HIV referred to the Department of Dermatology \nbetween 2016 and 2019\n\n\n\nTable 3. Number of cutaneous diagnosis in 424 individuals with HIV referred to the Department of Dermatology Hospital Kuala \nLumpur between 2016 and 2019\n\n\n\nComorbids/Concommitant illness(s) n (%) \nExtracutaneous tuberculosis 52 (36.4)\nHepatitis C 18 (12.6)\nExtracutaneous fungal infection 16 (11.2)\nHepatitis B 11 (7.7)\nPneumocystis jiroveci pneumonia 7 (4.9)\nAnaemia 6 (4.2)\nBoth extracutaneous tuberculosis and fungal infection occurring concurrently 4 (2.8)\nDiabetes Mellitus 4 (2.8)\nBronchial Asthma 3 (2.1)\nToxoplasmosis 3 (2.1)\nDyslipidemia 3 (2.1)\nMood disorders 2 (1.4)\nNeurosyphilis 2 (1.4)\nHypertension 2 (1.4)\nDeep vein thrombosis 1 (0.7)\nIschaemic Heart Disease 1 (0.7)\nRenal Tubular Acidosis 1 (0.7)\nCytomegalovirus retinitis 1 (0.7)\nUpper gastro-intestinal bleed 1 (0.7)\nAutoimmune encephalitis 1 (0.7)\nCardiomegaly 1 (0.7)\nAdrenal insufficiency 1 (0.7)\nCerebral vascular accident 1 (0.7)\nPost ictal psychosis 1 (0.7)\nTotal 143 (100)\n\n\n\nNumber of Cutaneous Diagnosis\nin One Patient\n\n\n\nNumber of Patients\nTotal\nn=424CD4 <200 cells/m3 CD4 200-500 cells/m3 CD4 >500 cells/m3 CD4 Not Available\n\n\n\nn=117 n=98 n=81 n=128\n1 61 (52.1) 66 (67.3) 58 (71.6) 87 (68.0) 272\n2 40 (34.2) 22 (22.4) 19 (23.5) 25 (19.5) 106\n3 14 (12.0) 8 (8.2) 2 (2.5) 9 (7.0) 33\n4 2 (1.7) 2 (2.0) 2 (2.5) 4 (3.1) 10\n5 0 (0.0) 0 (0.0) 0 (0.0) 3 (2.3) 3\n\n\n\nTotal Dermatoses 191 142 110 195 638\n\n\n\nour cohort respectively. Psoriasis was diagnosed in \n1.6% of our cohort. These patients were not known \nto have psoriasis before the HIV was diagnosed. \nThere were 15 patients (3.5%) diagnosed to have \nKaposi sarcoma in our cohort.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n15\n\n\n\nTable 4. Types of dermatoses detected among individuals with HIV between 2016 and 2019\n\n\n\nType of Dermatoses\n\n\n\nNumber\nCD4 <200 \n\n\n\ncells/m3\nCD4 200-500 \n\n\n\ncells/m3\nCD4 >500 \n\n\n\ncells/m3\nCD4 Not \nAvailable Total\n\n\n\nn=117 n=98 n=81 n=128 n=424\nCutaenous Adverse Drug Reactions 16 3 3 9 31\nNon life-threatening\nMaculopapular eruption 8 0 1 7 16\nErythema multiforme 1 1 1 0 3\nPruritus 0 0 0 1 1\nLife threatening\nStevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) 4 1 1 0 6\nDrug reaction with eosinophilia and systemic symptoms (DRESS) 3 1 0 1 5\nNon Infective Dermatosis 53 23 18 38 132\nInflammatory\nPruritic papular eruption 10 3 0 4 17\nPapular eczema 3 1 4 2 10\nSeborrhoeic dermatitis 3 4 0 3 10\nPsoriasis 3 0 3 1 7\nAcne vulgaris 2 1 2 1 6\nPhotodermatitis 1 3 0 1 5\nEosinophilic folliculitis 1 1 1 2 5\nContact dermatitis 2 1 0 2 5\nXerosis 2 0 1 1 4\nNodular prurigo 2 0 1 1 4\nProctitis 0 0 2 1 3\nChronic spontaneous urticaria 0 0 1 2 3\nPapular urticaria 2 0 0 1 3\nAnal fissure 0 1 0 1 2\nDiscoid eczema 0 1 0 0 1\nVenous ulcer 1 0 0 0 1\nLichen planus 1 0 0 0 1\nIcthyosis vulgaris 1 0 0 0 1\nAlopecia 0 0 1 0 1\nNeurogenic pruritis 0 0 0 1 1\nPityriasis lichenoides chronica 0 0 0 1 1\nPost inflammatory hyperpigmentation 0 0 0 1 1\nStasis eczema 0 0 0 1 1\nViral exanthem 0 0 0 1 1\nMilaria rubra 1 0 0 0 1\nEosinophilic dermatitis 1 0 0 0 1\nVasculitis 1 0 0 0 1\nSarcoidosis 1 0 0 0 1\nHidradenitis suppurativa 0 1 0 0 1\nVitiligo 1 0 0 0 1\nNon inflammatory\nBenign growth\nSkin tag 0 2 2 2 6\nSebaceous cyst 1 2 0 1 4\nPerianal cyst 1 1 0 0 2\nSteatocytoma multiplex 0 0 0 2 2\nSyringoma 0 0 0 1 1\nSeborrhoiec keratosis 0 0 0 1 1\nLipoma 0 0 0 1 1\nMalignant tumour\nKaposi sarcoma 12 1 0 2 15\nInfective Dermatoses/Infestation 122 116 88 147 473\nBacterial 28 28 25 50 131\nSyphilis 16 22 18 38 94\nGonorrhea 4 3 2 6 15\nFolliculitis 3 0 3 1 7\nAbscess 1 1 1 0 3\nCellulitis 1 2 0 0 3\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16\n\n\n\nFuruncle 1 0 1 0 2\nChancroid 1 0 0 1 2\nCarbuncle 0 0 0 1 1\nEcthyema 0 0 0 1 1\nRectal ulcer 0 0 0 1 1\nLymphogranuloma venereum 0 0 0 1 1\nChlamydia 1 0 0 0 1\nMycobacterial infection 0 1 1 0 2\nLeprosy 0 0 1 0 1\nLupus vulgaris 0 1 0 0 1\nViral 59 74 59 71 263\nGenital warts 27 47 48 43 165\nHerpes genitalis 13 17 7 12 49\nMolluscum contagiosum 7 2 1 9 19\nHerpes zoster 4 3 0 1 8\nHerpes labialis 3 1 1 2 7\nCommon warts 1 0 2 3 6\nViral exanthem 1 3 0 0 4\nLeukoplakia 1 1 0 0 2\nHerpes simplex 1 0 0 1 2\nPlane wart 1 0 0 0 1\nFungal 33 11 3 25 72\nTalaromycosis 13 1 0 10 24\nOral mucosal candidiasis 8 1 1 4 14\nHistoplasmosis 7 0 0 4 11\nTinea corporis 3 4 1 2 10\nOnychomycosis 1 2 0 2 5\nCryptococcus 1 0 0 1 2\nCandida cheilitis 0 1 0 0 1\nChromoblastomycosis 0 1 0 0 1\nToe webs intertrigo 0 0 1 0 1\nCandida balanitis 0 0 0 1 1\nSporotrichosis 0 0 0 1 1\nTinea cruris 0 1 0 0 1\nScabies infestation 2 2 0 1 5\nNon Dermatological Diagnosis* 0 0 1 1 2\nTotal 191 142 110 195 638\n\n\n\nThirty-one patients were referred for cutaneous \nadverse drug reactions, of which majority was \nmaculopapular eruption (51.6%) to the antibiotics \nreceived for their opportunistic infections (8 to \nbactrim, 3 to bactrim/anti-tuberculosis therapy, \n1 to dapsone, 1 to efavirenz). Eleven patients \n(35.5%) suffered from severe cutaneous adverse \ndrug reactions (SCARs) namely the Stevens \nJohnson Syndrome/Toxic epidermal necrolysis \n(metamphetamine (1), bactrim (1), Akurit-4 (1), \ncarbamazepine (1)) and drug reaction eosinophilia \nwith systemic symptoms (DRESS) due to fansidar \n(1), bactrim (2), anti-tuberculosis Akurit-4 (1), \nbactrim/pyrimethamine(1). Two patients developed \nerythema multiforme secondary to ART therapy \nand one to bactrim. There were two patients were \nfound to have non dermatological disorders after \nassessment, which were reactive arthritis, and false \n\n\n\npositive rapid plasma reagin (RPR) test.\n\n\n\nBased on the 1993 Centers for Disease Control \nand Prevention (CDC) case definition of AIDS,6 \nwe further analysed the type of dermatoses that \nwere seen among patients with clinical category C \n(patients who have AIDS-defining conditions and/\nor CD4 count of less than 200cells//mm3). As shown \nin Table 5, patients with AIDS were significantly \nmore prevalent to suffer from cutaneous adverse \ndrug reactions, non-infective dermatoses, viral and \nfungal infections. Cutaneous viral infections were \nthe most frequent infections encountered in patients \nwith AIDS and without AIDS. However, the rate \nwas significantly higher among the patients without \nAIDS. The rate of cutaneous bacterial infections \nand scabies infestations were similar in patients \nwith AIDS and without AIDS.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n17\n\n\n\nTable 6. Literature review on the prevalence of skin disorders in HIV infected individuals\n\n\n\nUthayakumar S \net al.39\n\n\n\nCoopman SA et al.40 Spira R et al.18 Spira R et al.18 Spira R et al.18\n\n\n\nBrighton Boston France Dallas Bangkok\nYear 2017 1988-1991 1996 1989 2004\nTotal patients observed 151 684 450 100 120\nTotal patients with skin disorders 138 (91.4%) 540 (79%) 294 (65.2%) 92 (92%) 96 (80%)\n\n\n\nTable 5. Types of dermatoses in patients with and without AIDS\n\n\n\nTypes of Dermatoses Patients with AIDS*\nn=144\n\n\n\nPatients without AIDS\nn=167 p value\n\n\n\nCutaneous adverse drug reactions 21 5 <0.05\nNon infective dermatoses 62 38 <0.05\nInfective dermatoses Bacterial infection 44 47 0.64\n\n\n\nViral infection 72 126 <0.05\nFungal infection 48 9 <0.05\nScabies 2 2 1.00\n\n\n\n*Clinical category C - patients who have AIDS-defining conditions and/or CD4 count of less than 200cells//mm3\n\n\n\nDiscussion\nCutaneous manifestations are very common in \nindividuals infected with human immunodeficiency \nvirus (HIV) and are associated with significant \nmorbidity.7 Our National Strategic Plan for Ending \nAIDS targets to end AIDS by 2030.3 At the end of \nyear 2018, it was estimated that 87,041 people were \nliving with HIV in Malaysia and 41,430 (55%) of \nthem are on antiviral therapy.3 In this audit, only \n46.7% of patients referred were on antiviral therapy, \nwhich is less than the national record. We are yet to \nachieve one of the main Global AIDS Monitoring \nindicators which is to have at least 90% of people \nwho know their HIV-positive status are accessing \nART by 2020.8 More efforts are needed to screen \nand detect HIV infection early so that ART can be \ninitiated early in order to improve the overall health \nof these group of patients and their quality of life.9\n\n\n\nMore than 75% of our patients were in the age \ngroup between 20 and 39 years. This is consistent \nwith our national data3 and another 2 studies, Halder \net al in West Bengal, India10 and Sanjay et al. in \nMaharashtra, India.11 Our national data showed that \n77% of individuals infected with HIV were 20-39 \nyears old.3 The trend of HIV epidemic in Malaysia \nhas now shifted to sexual transmission since 2011. \nMen who have sex with men (MSM) was expected \nto become the main driver for the epidemic in the \nyears to come beginning from 2018.2 In our audit \nmost patients contracted HIV via homosexual \npractice in males. This may also explain the reason \nof high prevalence in of genitourinary infections \nobserved in our cohort.\n\n\n\nThe common denominator of the immunosuppressed \nstate resulting from HIV infection is the destruction \nof T-helper cells that express CD4 receptors12, \ncauses profoundly impaired cellular immune \nresponse. The number of circulating CD4 T cells \npredicts the onset of overt immunodeficiency.13 The \nsuppression of HIV replication with ART improves \nthe CD4 T-cell counts and was found to be able to \nreverse immunodeficiency.14 The progression of \ndisease is indicated by the detection of specifically \ndefined opportunistic infections. CD4 count is a \nprognostic indicator and marker of stage of HIV-\ninduced immunodeficiency and estimation of \nmorbidity and mortality.14 The classification system \nfor HIV infection among adolescents and adults has \nbeen revised to include the CD4 + T-lymphocyte \ncount into 3 categories i.e. CD4 counts <200, \n200-499, >500. These categories reflect HIV-\nrelated immunosuppression, clinical status, risk of \nopportunistic infections and assist the clinicians in \ndiagnostic decision-making.6,15  A typical healthy, \nHIV negative individual has a CD4 count greater \nthan 500cells/mm3.14 Individuals infected with HIV \nwho have CD4 counts >500cells/mm3 are expected \nto present with common non-infective skin \nconditions like normal healthy individuals. Patients \nwith lower CD4 counts (<200cells/mm3) may \npresent with serious or fatal opportunistic infections \nwith cutaneous manifestations.14 \n\n\n\nImmunodeficiency state is associated with a wide \nspectrum of clinical disorders that may range between \nasymptomatic to Acquired Immunodeficiency \nsyndrome (AIDS).12 Mucocutaneous eruptions \nassociated with HIV infection are common and \noccur throughout the course of HIV infection. \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18\n\n\n\nAlthough mucocutaneous eruptions are not the \ndirect result of HIV infection, most of these \neruptions are resulted from immunosuppressive \nstate or related to the HIV treatment.12 These lesions \nmay be the first manifestations of HIV infection. \nPre-existing dermatoses may be aggravated or \nworsened when AIDS develops.7,12 It was shown \nthat greater than 90% of patients developed at least \none skin or mucous membrane manifestation during \nthe course of their infection in a study involving 100 \npatients done in Dallas (Table 6).9,16 Another study \nin Bangkok in 1995 also showed that 95% of 248 \nobserved patients had one or more skin disorders.17 \n\n\n\nA cross sectional survey involving 450 patients in \nFrance done in 1996 observed 65.3% of them had at \nleast one skin manifestation during the course of HIV \ninfection.18 Mucocutaneous eruptions in HIV can be \nclassified according to its underlying aetiologies. \nViral, fungal, and bacterial infections as well as \ninflammatory dermatoses have all been reported \nwith an increased frequency in association with \nHIV infection.7 It has been shown that herpes zoster \ninfection is an early manifestation of HIV infection, \nwhereas Kaposi sarcoma and cryptococcosis reflect \nmore advanced immunosuppression. Hence certain \nskin conditions may guide the clinicians to stage the \nclinical progression of HIV infection.7\n\n\n\nTraditionally lower CD4 counts are reported \nto be associated with infective dermatoses.19-21 \n\n\n\nUnsurprisingly, infective dermatoses encountered \namong those with CD4 <500cells/m3 in our cohort \nwas 2.7x more that those with CD4 >500cells/m3. \nBeing the most common indication of referrals, \nviral infections in HIV infected patients contributed \n41.2% of the total dermatology referrals. Genital \nwarts contributed 62.7% of the total viral related \ndermatoses. This was higher than other studies done \nin South of Iran22 and Maharashtra, India11, whereby \nviral infections contributed about 17.9-27.3% \nof their total diagnosis. Genital warts caused by \nhuman papillomavirus (HPV) is the most common \nsexually transmitted infection in the United States \nof America. Common warts may occur in unusual \nlocations, with unusual severity, and with high \nfrequency in HIV-infected patients.7\n\n\n\nThe rising trend of primary and secondary syphilis \nworldwide has been primarily attributable to \nincreased cases amongst men who have sex with men \n(MSM), highest among persons aged 25-29 years.23 \nThere is a higher rate of HIV coinfection among \nMSM with syphilis and the disease course is more \naggressive.24 Syphilis carries significant morbidities \n\n\n\nif left untreated as the infection can span decades \nand progresses through multiple stages of infection. \nIn this audit, 94 patients presented with cutaneous \nmanifestations of different stages of syphilis. Skin \nlesions in secondary syphilis can mimic many other \ndiseases hence detailed workups are needed to \nexclude other bacterial or fungal infections in order \nto institute the appropriate treatment.\n\n\n\nMalaysia is classified as a country with an \nintermediate TB burden, with less than 100 per \n100,000 populations.25 All patients who are diagnosed \nwith tuberculosis will be screened for HIV. It was \nfound that 1346 (6.3%) patients of a total of 21,296 \nnew TB cases were infected with HIV (1234 pre TB \ndiagnosis and 112 post TB diagnosis).25 Systemic \ninfections with Mycobacterium tuberculosis and \nnon-tuberculous mycobacteria are common in \nHIV disease.7 Despite tuberculosis being the most \ncommonly reported opportunistic infection and the \nleading cause of death among people living with \nHIV, the prevalence remained below 6% since \n2014. In our audit, 56 patients were infected with \ntuberculosis (pulmonary tuberculosis, tuberculosis \nmeningitis and disseminated tuberculosis). We only \nencountered a case of cutaneous tuberculosis i.e. \nlupus vulgaris in our current cohort. \n\n\n\nInterestingly, the number of non-infective \ndermatoses detected among those with CD4 counts \n<500cells/m3 counts in our audit were 4 times \nmore than those with CD4 counts >500cells/m3. \nMost patients with non-inflammatory dermatoses \nwere referred for pruritic papular eruptions (PPE), \n14.9% followed by papular eczema and seborrhoiec \ndermatitis, 10%. However, Sivayathorn et al.17 in \n1993-1994 done in Bangkok involving 248 patients \nshowed that there were 32.7% patients with PPE \nand 21.0% with seborrhoiec dermatitis. Another \nstudy in Shiraz, South Iran by Davarpanah et al.22 \nalso showed that 0.5% of the total 240 patients had \neczema. About 19.6% of patients in that study had \nxerosis and pruritis. In our study only 4 patients \n(0.9%) patients had xerosis and 1 had neurogenic \npruritis. Psoriasis affects 1% to 3% of patients with \nHIV infection in the United States of America, as \ncompared with its prevalence of 1% in the general \npopulation.26 In some studies patients infected with \nHIV had psoriasis as their first presentation to a \nclinician before the diagnosis of HIV, or at the late \nstage of HIV during the progression into AIDS.27 \n\n\n\nA flare of psoriasis or worsening arthropathy can \nbe seen in patients with pre-existing psoriasis \nfollowing HIV infection.28 Our audit showed that 7 \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n19\n\n\n\n(1.65%) patients had psoriasis diagnosed after they \nwere confirmed to have HIV. This was comparable \nto an audit reported Davarpanah et al.22, whereby \n2.9% of the patients had psoriasis. Concomitant \nHIV infection with psoriasis complicates the \nmanagement especially in patients who require \nsystemic therapy owing the possibility of drug-to-\ndrug interactions. Commonly used medications \ni.e. methotrexate or cyclosporin may predispose \nHIV patients to malignancies and opportunistic \ninfections due to their immunocompromised state.\n\n\n\nHuman immunodeficiency virus (HIV)-\ninfected patients have complex immunological \nalterations with higher risk of developing drug \nhypersensitivity to antiretroviral or multiple drugs \nthat usually prescribed for prevention or treatment \nof opportunistic infections.29 About 5% of the \ndermatoses among the HIV infected patients referred \nto us were cutaneous adverse drug reactions. About \n82% of SCARs in our cohort developed in those \nwith CD4 counts <500cells/m3. Cutaneous ADRs \nincreased as the immune system deteriorates with \nthe apparent decreasing in CD4 T-cell count.29 The \npathophysiology of drug hypersensitivity in HIV \nis multifactorial and related to alterations in drug \nmetabolism, dysregulation of the immune systems \n(immune hyperactivation, patient cytokine profile), \noxidative stress, genetic predisposition, and also \nthe viral factors.28 Patients with HIV infections \nare at risk of developing severe adverse drug \nreactions (ADR) towards ART, anti-toxoplasmosis \nas well as co-trimoxazole (bactrim) used in PCP \nprophylaxis. Severe drug hypersensitivity reactions \nsuch as Stevens Johnson syndrome and toxic \nepidermal necrolysis develop more often in HIV-\ninfected patients compared to other populations.29 \nDavarpanah et al.22 also observed that 10.8% of their \npatients had drug reactions. ADR was commonly \nseen with the initiation of ART (regardless of \nthe CD4 counts) as well as with the use of anti-\ntoxoplasmosis/bactrim (in patients with low CD4). \n\n\n\nAs life expectancy of HIV infected individuals \nincreases, cancer has become a predominant cause \nof morbidity and mortality in this group of patients.26 \n\n\n\nPatients with HIV infection are at higher risk of \nacquiring a few types of malignancies. Kaposi \nsarcoma, which is the most commonly reported \nmalignancy in HIV infected patients. It occurs at a \nrate of more than 1000 folds greater than general \npopulation. Most Kaposi sarcoma traditionally \noccurs in individuals with low CD4 (<200cells/\nmm3), however cases have been reported to occur \n\n\n\nat individuals with higher CD4 counts (>350cells/\nmm3).30 In our cohort, 12 (80%) patients with Kaposi \nsarcoma had CD4 counts less than 200. Apart from \nthat, Non-Hodgkin Lymphoma (NHL) is also being \nclassified as AIDS defining malignancy.31 There \nwere however no other malignancies observed in \nour cohort.\n\n\n\nThe introduction of ART has been shown to have a \nhuge impact on the spectrum and severity of skin \ndisease. Studies have shown an overall decrease in \nthe prevalence of mucocutaneous manifestations \nwith ART.9 Advancement in ARTs have led to \nimproved quality of life and life expectancies in HIV \npatients. It significantly changes the perception of \nHIV/AIDS from a fatal to a potentially manageable \nchronic disease.4 Immune reconstitution \ninflammatory syndrome(IRIS) represents wide \nrange of immunopathologic reaction resulting in \nrestoration of immune function in HIV-infected \npatients after receiving ARTs.32 Mucocutaneous \npresentations accounted for 68% of IRIS.30 There \nare large varieties of presenting signs and symptoms \nfor IRIS depending on the underlying infection \nacquired after a rapid decrease in HIV viral load and \nmost IRIS results in mild to moderate symptoms.33,34 \n\n\n\nHowever non dermatological manifestation related \nto IRIS may result in significant morbidity and \nmortality.34 It may occur as early as 2 to 6 weeks \nof initiation of ART, but some may present within \ndays to months.35 It was found that the incidence \nof developing IRIS is particularly higher in patients \nstarting ART at CD4 counts below 50cells/microL.36 \nCutaneous IRIS, may varies from infective, \ninflammatory, neoplastic to autoimmune disorders.37 \nPatients may presents with acne, cutaneous \nulcerations due to Mycobacterium avium, eruptions \nof warts, varicella zoster, herpes viruses, genital \nulcers and folliculitis.31,37,38 In our audit, 38.1% \nreceived ART within 12 months before they were \nreferred to us. The dermatoses presented in these \ngroup of patients could be the manifestations IRIS. \nInfective dermatoses were noted to be the most \ncommon dermatoses in this subgroup of patients. \nDue to the retrospective nature of this audit, we \ncould not ascertain that all the dermatoses described \nin these patients were truly manifestations of IRIS \nas we could not demonstrate presence of rebound of \nCD4 counts in them.\n\n\n\nOur data is limited by the retrospective nature of \nthe audit. Further prospective studies are in need for \nbetter describing the mucocutaneous manifestations \nof the HIV infected individuals based on the CD4 \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20\n\n\n\ncounts categories, as well as to monitor the evolution \nof skin diseases through the different stages of HIV. \nNevertheless, our data illustrated the wide range \nof dermatoses in this group of patients which may \nbe encountered by the clinicians. Clinicians should \nhave a high index of suspicion when we manage \nsuch patients so that their skin conditions could be \nmanaged accordingly.\n\n\n\nConclusion\nOur data showed that individuals with HIV infection \nmay present with wide variety of skin disorders \nwhich included infective dermatoses, non-infective \ninflammatory dermatoses, cutaneous adverse drug \nreactions and tumours. About 35% of them had \nmore than 1 dermatoses in our cohort. The most \nfrequent infective dermatoses encountered were \ngenital warts, syphilis, genital herpes, talaromycosis \nand molluscum contagiosum. The most frequent \nnon-infective inflammatory dermatoses observed \nin our cohort was eczematous dermatoses. Kaposi \nsarcoma was the most frequent malignant tumour \nencountered in our cohort especially in those with \nlow CD4 counts. About 7.3% of them developed \ncutaneous adverse drug reactions to the medications \nused to treat the HIV and co-morbidities.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for the permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. CDC. Pneumocystis pneumonia - Los Angeles. MMWR \n1981;30:250--2.\n\n\n\n2. Web Annex 1. Key data at a glance. In: Progress report \non HIV, viral hepatitis and sexually transmitted infections \n2019. Accountability for the global health sector strategies, \n2016\u20132021. Geneva: World Health Organization; 2019 \n(WHO/CDS/HIV/19.22). Licence: CC BY-NC-SA 3.0 \nIGO. \n\n\n\n3. Ministry of Health, Malaysia. Country Progress Report on \nHIV/AIDS 2019.\n\n\n\n4. Oguntibeju OO. Quality of life of people living with HIV \nand AIDS and antiretroviral therapy. HIV AIDS (Auckl) \n2012;4:117-24. \n\n\n\n5. Garman ME, Tyring SK. The cutaneous manifestations of \nHIV infection. Dermatol Clin 2002;20:193-208.\n\n\n\n6. 1993 revised classification system for HIV infection \nand expanded surveillance case definition for AIDS \namong adolescents and adults. MMWR Recomm Rep \n1992;41(RR-17):1-19.\n\n\n\n7. Tschachler E, Bergstresser PR, Stingl G. HIV-related skin \n\n\n\ndiseases. Lancet 1996;348:659-63.\n8. Joint United Nations Programme on HIV/AIDS. Global \n\n\n\nAIDS Monitoring 2020. Geneva: UNAIDS 2019.\n9. Lowe S, Ferrand RA, Morris-Jones R, Salisbury J, \n\n\n\nMangeya N, Dimairo M et al. Skin disease among \nhuman immunodeficiency virus-infected adolescents in \nZimbabwe: a strong indicator of underlying HIV infection. \nPediatr Infect Dis J 2010;29:346-51. \n\n\n\n10. Halder S, Banerjee S, Halder A, Pal PR. Skin diseases \nin HIV-infected patients: Impact of immune status and \nhistological correlation. Indian J Sex Transm Dis AIDS \n2012;33:65-7.\n\n\n\n11. Chawhan SM, Bhat DM, Solanke SM. Dermatological \nmanifestations in human immunodeficiency virus infected \npatients: Morphological spectrum with CD4 correlation. \nIndian J Sex Transm Dis AIDS 2013;34:89-94.\n\n\n\n12. Herbst JS, Resnick L. Mucocutaneous manifestations of \nHIV infection. Clin Dermatol 1989;7:56-64. \n\n\n\n13. Okoye AA, Picker LJ. CD4 (+) T-cell depletion in HIV \ninfection: mechanisms of immunological failure. Immunol \nRev 2013;254:54-64.\n\n\n\n14. Institute of Medicine (US) Committee on Social Security \nHIV Disability Criteria. HIV and Disability: Updating \nthe Social Security Listings. Washington (DC): National \nAcademies Press (US); 2010.\n\n\n\n15. Ford N, Meintjes G, Vitoria M, Greene G, Chiller T. The \nevolving role of CD4 cell counts in HIV Care. Curr Opin \nHIV AIDS 2017;12:123-8.\n\n\n\n16. Coldiron BM, Bergstresser PR. Prevalence and clinical \nspectrum of disease in patients infected with human \nimmunodeficiency virus. Arch Dermatol 1989;125:357-\n61.\n\n\n\n17. Sivayathorn A, Srihra B, Leesanguankul W. Prevalence \nof skin disease in patients infected with human \nimmunodeficiency virus in Bangkok, Thailand. Ann Acad \nMed Singapore 1995;24:528-33. \n\n\n\n18. Spira R, Mignard M, Doutre MS, Morlat P, Dabis F. \nPrevalence of Cutaneous Disorders in a Population of \nHIV-Infected Patients; Southwestern France, 1996. Arch \nDermatol 1998;134:1208-1212\n\n\n\n19. Huang XJ, Li HY, Chen DX, Wang XC, Li ZC, Wu YS et \nal. Clinical Analysis of Skin Lesions in 796 Chinese HIV- \npositive Patients. Acta Derm Venereol 2011;91:552-6\n\n\n\n20. Chandrakala C, Parimalam K, Wahab AJ, Anand N. \nCorrelating CD4 count with mucocutaneous manifestations \nin HIV-positive patients: A prospective study. Indian J Sex \nTransm Dis AIDS 2017;38:128-35.\n\n\n\n21. Oninla OA. Mucocutaneous M       anifestations of HIV and \nthe Correlation with WHO Clinical Staging in a Tertiary \nHospital in Nigeria. AIDS Res Treat 2014;2014:360970.\n\n\n\n22. Davarpanah MA, Motazedian N, Jowkar F. Dermatological \nManifestations of HIV/AIDS Individuals in Shiraz, South \nof Iran. J Glob Infect Dis 2018;10:80-3. \n\n\n\n23. Workowski KA, Bolan GA. Sexually transmitted diseases \ntreatment guidelines, 2015. MMWR Recomm Rep \n2015;64:1-137\n\n\n\n24. Devkota AR, Ghimire R, Sam M, Aung O. Malignant \nSyphilis as an Initial Presentation of Underlying HIV \nInfection: A Case report. BJMP 2015 8:a816.\n\n\n\n25. Ministry of Health Malaysia. National Strategic Plan \nfor Tuberculosis Control (2016-2020). Accessed: 16th \nNovember 2020. Available from: http://www.moh.gov.my/\nindex.php/pages/view/1917?mid=613.\n\n\n\n26. Dlova NC, Mosam A. Inflammatory non-infectious \ndermatoses of HIV. Dermatol Clin 2006;24:439-8.\n\n\n\n27. W\u00f6lfer  LU, Djemadji-Oudjiel N, Hiletework M, Tebbe B, \nHusak R, Goerdt S et al. HIV-associated Psoriasis. Clinical \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n21\n\n\n\nand Histological Observations in 36 Patients. Hautarzt \n1998;49:197-202.\n\n\n\n28. Nakamura M, Abrouk M, Farahnik B, Zhu TH, Bhutani T. \nPsoriasis Treatment in HIV-Positive Patients: A Systematic \nReview of Systemic Immunosuppressive Therapies. Cutis \n2018;101:38-56.\n\n\n\n29. Yunihastuti E, Widhani A, Karjadi TH. Drug \nhypersensitivity in human immunodeficiency virus-\ninfected patient: challenging diagnosis and management. \nAsia Pac Allergy 2014;4:54-67.\n\n\n\n30. Crum-Cianflone N, Hullsiek KH, Ganesan A, Weintrob A, \nOkulicz JF, Agan BK et al. Is Kaposi\u2019s Sarcoma occuring \nat higher CD4 counts over the course of the HIV epidemic? \nAIDS 2010;24:2881-3.\n\n\n\n31. Crum-Cianflone N, Hullsiek KH, Satter E, Marconi V, \nWeintrob A, Ganesan A et al. Cutaneous malignancies \namong HIV-infected persons. Arch Intern Med \n2009;169:1130-8.\n\n\n\n32. Gopal R, Rapaka RR, Kolls JK. Immune reconstitution \ninflammatory syndrome associated with pulmonary \npathogens. Eur Respir Rev 2017;26:160042.\n\n\n\n33. Sharma SK, Soneja M. HIV & immune reconstitution \ninflammatory syndrome (IRIS). Indian J Med Res \n2011;134:866-77.\n\n\n\n34. Lehloenya R, Meintjes G. Dermatologic manifestations \nof the immune reconstitution inflammatory syndrome. \nDermatol Clin 2006;24:549-70.\n\n\n\n35. Summers NA, Armstrong WS. Management of advanced \nhuman immunodeficienct virus disease. Infect Dis Clin \nNorth Am 2019;33:743-67.\n\n\n\n36. Novak RM, Richardson JT, Bucxhacz K, Chmiel JS, \nDurham MD, Palella FJ et al. Immune reconstitution \ninflammatory syndrome: incidence and implications for \nmortality. AIDS 2012;26:721-30.\n\n\n\n37. Huiras E, Preda V, Maurer T, Whitfeld M. Cutaneous \nmanifestations of immune reconstitution inflammatory \nsyndrome. Curr Opin HIV AIDS 2008;3:453-60.\n\n\n\n38. Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune \nreconstitution inflammatory syndrome (IRIS): review of \ncommon infectious manifestations and treatment options. \nAIDS Res Ther 2007;4:9.\n\n\n\n39. Uthayakumar S, Nandwani R, Drinkwater T, Nayagam \nAT, Darley CR. The Prevalence of Skin Disease in \nHIV Infection and Its Relationship to the Degree of \nImmunosuppression. Br J Dermatol 1997;137:595-8.\n\n\n\n40. Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous \nDisease and Drug Reactions in HIV Infection. N Engl J \nMed 1993;328:1670-4.\n\n\n\n41. Wiwanitkit V. Prevalence of Dermatological Disorders in \nThai HIV-infected Patients Correlated with Different CD4 \nLymphocyte Count Statuses: A Note on 120 Cases. Int J \nDermatol 2004;43:265-8.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22\n\n\n\nORIGINAL ARTICLE\n\n\n\nThe Value of Adding 1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-\n4-Phenylenediamine, N-Cyclohexylthiophthalimide and Ylang-\nylang oil to the European Baseline Series to Improve the Detection \nof Rubber and Fragrance Allergy Among Patients Suspected with \nContact Dermatitis in Hospital Selayang         \n\n\n\nFei Yin Ng1,2, Min Moon Tang2, Rohna Ridzwan1, Asmah Johar2  \n\n\n\n1Department of Dermatology, Hospital Selayang, Selangor, Malaysia\n2Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction\nAllergic contact dermatitis affects 15 to 20% of the population. The pattern of contact allergy varies \nacross nations. Therefore, many countries utilize their unique individual baseline series for patch \ntesting.  In this study, we aimed to assess the outcome of rubber and fragrance allergy detection \nwith the addition of 1,3-Diphenylguanidine. N-Cyclohexyl-N-Phenyl-4-Phenylenediamine, \nN-Cyclohexylthiophthalimide and Ylang ylang oil.\n\n\n\nMethods\nThis a cross-sectional study on 292 patients who underwent patch testing with European Baseline \nSeries, 3 additional rubber allergens namely 1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-4-\nPhenylenediamine, N-Cyclohexylthiophthalimide and Ylang ylang oil between July 2015 to December \n2016. Additional patch test series were also added based on relevant clinical history. The patch test \nreactions were read at 48 and 96 hours after application of the allergens. \n\n\n\nResults\nA total of 292 patients completed the study. There were 118 (40.4%) males and 174 (59.6%) females. \nThe mean age was 43 years old (range 19 to 78 years). Two-third of patients had atopy. The sensitization \nrate increased to 70.5% from 67.1% with the four additional allergens included in the European \nBaseline Series. The rubber allergy detection rate significantly increased by 53.8% (p<0.00001) \nwith the addition of 1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-4-Phenylenediamine, and \nN-Cyclohexylthiophthalimide to the European Baseline Series. The addition of 1,3-Diphenylguanidine \nalone to the baseline series improved the rubber allergy detection rate by 49.2%. The sensitization rate \nof 1,3-Diphenylguanidine was 10.6%, which ranked the third most sensitizing allergen in the cohort. \nThe addition of N-Cyclohexyl-N-Phenyl-4-Phenylenediamine and N-Cyclohexylthiophthalimide \nonly increased the detection rate of rubber allergy by 4.6%, where each had a sensitization rate of \n1.4%. Fragrance allergy detection rate increased by 6.5% with the addition of Ylang ylang oil to the \nEuropean Baseline Series. The sensitization rate of Ylang ylang oil was 3.4% in this cohort..\n\n\n\nConclusion\nThe overall detection rate of sensitization increased by 3.4% with the addition of 1,3-Diphenylguanidine, \nN-Cyclohexyl-N-Phenyl-4-Phenylenediamine, N-Cyclohexylthiophthalimide and Ylang ylang oil. \nThe addition of 1,3-Diphenylguanidine rubber in the baseline series improved the detection of rubber \nsensitization by 49.2% while the addition of Ylang ylang oil increased fragrance sensitization detection \nrate by 6.5%.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n23\n\n\n\nKey words: Allergic contact dermatitis, 1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-4-Phenylenediamine, \nN-Cyclohexylthiophthalimide, Ylang ylang oil\n\n\n\nCorresponding Author\nDr Ng Fei Yin\nDepartment of Dermatology,\nHospital Tengku Ampuan Rahimah,\n41200 Klang, Selangor, Malaysia.\nEmail: willow_fy02@yahoo.com\n\n\n\nIntroduction\nAllergic contact dermatitis affects 15 to 20% of the \npopulation in Europe. In United States, the point \nprevalence of allergic contact dermatitis is 15.2% \nin teenagers and 18.6% in adults.1 The common \ncausative allergens vary between nations due to the \nindustrial policies and cultural practice. Thus many \ncountries constructed their individual baseline \nseries for patch test. \n\n\n\nIn a retrospective analysis of local patch test data2, \nfour emerging allergens were identified from \nthe rubber additives series and fragrance series - \n1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-\n4-Phenylenediamine, N-Cyclohexylthiophthalimide \nand Ylang ylang oil with the sensitization rates of \n11.1%, 3.9%, 3.6% and 14.6%.2 The additional \npatch test series were tested on selected patients \nwhom were clinically suspected with rubber or \nfragrance allergy. \n\n\n\nIn this study, we incorporated these 4 allergens into \nthe European Baseline Series with the aim to assess \nthe outcome of the overall contact sensitization rate \nas well as the detection rate of rubber and fragrance \nallergy.\n\n\n\nMaterials and Methods\nA cross-sectional study was performed on selected \npatients aged 18 and above suspected with allergic \ncontact dermatitis in Selayang Hospital between \nJune 2015 and December 2017. We excluded \npatients with active dermatitis, excessive sun \nexposure, topical corticosteroid application on \nthe test site within one week prior to the study, \ningestion of oral prednisolone (exceeding 20mg \ndaily) or other immunosuppressant agents, pregnant \nor lactating ladies, and those with previous history \nof patch test.  \n\n\n\nAll candidates underwent patch test using \nEuropean Baseline Series with the addition of \n1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-\n4-Phenylenediamine, N-Cyclohexylthiophthalimide \nand Ylang ylang oil. Additional patch test series \nwere also added based on individual presentation as \npart of the daily routine practice.\n\n\n\nThe European Baseline Series from Chemotechnique \nDiagnostics in year 2015 consisted of 30 allergens: \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24\n\n\n\npotassium dichromate, p-phenylenediamine \n(PPD), thiuram mix, neomycin sulfate, cobalt (II) \nchloride hexahydrate, benzocaine, nickel (II) sulfate \nhexahydrate, clioquinol, colophonium, paraben \nmix, N-Isopropyl-N-Phenyl-4-Phenylenediamine \n(IPPD), lanolin alcohol, mercapto mix, epoxy resin, \nbalsam of peru, 4-Tert-Butylphenol formaldehyde \nresin (PTBP), 2-merceptobenzothiazole (MBT), \nformaldehyde, fragrance mix I, sesquiterpene lactone \nmix, quaternium 15, propolis, methylisothiazolinone \n/methylchloroisothiazolinone, budesonide, \ntixocortol-21-pivalate, methyldibromo glutaronitrile, \nfragrance mix II, lyral, methylisothiazolinone and \ntextile dye mix.\n\n\n\nThe patch test reactions were read at 48 and 96 hours \nafter application of the allergens. Interpretation \nof patch test reactions were based on the reading \ncriteria of International Contact Dermatitis Research \nGroup (ICDRG) guidelines.\n\n\n\nData was analyzed using IBM SPSS\u00ae Statistics \nversion 23. \n\n\n\nResults\nA total of 292 patients, comprising of 118 males \n(40.4%) and 174 females (59.6%) aged 18 years and \nabove with the mean age of 43 years, were patch \ntested during the 18-month study period (Table 1). \nAmong the subjects, 157 (53.8%) were Malay, 96 \n(32.9%) were Chinese, 37 (12.7%) were Indian and \n2 (0.7%) of other races. Two-third of the patients \nhad a background history of atopy.\n\n\n\nTable 1. Patient Demographic and Characteristics\n\n\n\nTable 2. Top 10 common allergens in the modified European \nBaseline Series in Hospital Selayang between July 2015 and \nDecember 2016\n\n\n\nTable 3. Sensitization rate of rubber allergens in the European \nBaseline Series\n\n\n\nTable 4. Sensitization rate of fragrance allergens in the \nEuropean Baseline Series\n\n\n\nCharacteristics n=292 (%)\nAge, median (IQR) \nGender\n      Male\n      Female \nEthnicity\n      Malay \n      Chinese \n      Indian \n      Others \nAtopy\n      Presence \n      Absence  \n\n\n\n41 (28, 57)\n\n\n\n118 (40.4)\n174 (59.6)\n\n\n\n157 (53.8)\n96 (32.9)\n37 (12.7)\n2 (0.7)\n\n\n\n200 (68.5)\n92 (31.5)\n\n\n\nAllergen Frequency of Tested Positive,\nn=292 (%)\n\n\n\nNickel Sulfate\nTextile Dye Mix\n1,3 Diphenylguanidine\nFragrance Mix l\nMethylisothiazolinone\nCobalt Chloride\nBalsam of Peru\nParaben Mix\nFormaldehyde\nPotassium Dichromate\n\n\n\n67 (22.9)\n38 (13.0)\n31 (10.6)\n29 (9.9)\n23 (7.9)\n20 (6.8)\n20 (6.8)\n19 (6.5)\n16 (5.5)\n16 (5.5)\n\n\n\nAllergen Frequency of Tested Positive,\nn=292 (%)\n\n\n\nFragrance Mix I\nBalsam of Peru\nFragrance Mix II\nLyral\n\n\n\n29 (9.9)\n20 (6.8)\n 5 (1.7)\n2 (0.7)\n\n\n\nRubber Allergen Frequency of Tested \nPositive, n=292 (%)\n\n\n\nThiuram Mix\n2-Mercaptobenzothiazole\nMercapto Mix\nN-Isopropyl-N-Phenyl-4-Phenylenediamine\n\n\n\n8 (2.7)\n4 (1.4)\n2 (0.7)\n1 (0.3)\n\n\n\nWhen tested with European Baseline Series, 67.1% \nof patients developed at least 1 positive reaction to \nthe patch test allergens. The detected sensitization \nrate increased to 70.5% with the 4 additional \nallergens. The difference was not statistically \nsignificant (p=0.37). The top ten common allergens \nwere nickel sulfate (22.9%), textile dye mix (13%), \n\n\n\n1,3-Diphenylguanidine (10.6%), fragrance mix \nI (9.9%), methylisothiazolinone (7.9%), cobalt \nchloride (6.8%), balsam of Peru (6.8%), paraben \nmix (6.5%), formaldehyde (5.5%), and potassium \ndichromate (5.5%) (Table 2).\n\n\n\nCompared to the original European Baseline Series \n(EBS) with 3 rubber allergens, the modified baseline \nseries detected a significantly higher number rubber \nallergy (p<0.0001). Among the EBS rubber allergens, \nthiuram mix (2.7%) had the highest sensitization \nrate, followed by 2-mercaptobenzothiazole (1.4%), \nmercapto mix (0.7%) and N-Isopropyl-N-Phenyl-\n4-Phenylenediamine (Table 3). The sensitivity \nof the combination of EBS with each individual \nadditional rubber allergen was also analyzed. When \ncompared to using EBS alone, the combination \nwith 1,3-diphenylguanidine significantly raised \nthe sensitivity of detecting rubber allergy by \n49.2% (p<0.00001). Combination with either \nN-Cyclohexyl-N-Phenyl-4-Phenylenediamine or \nN-(Cyclohexylthio) phthalimide, did not contribute \nto significant improvement in the patch test results \n(p=0.545) (Table 5).\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n25\n\n\n\nTable 5. The sensitization rate of European Baseline Series \nrubber allergens and its combination with additional rubber \nallergens\n\n\n\nTest Allergens Detection Rate, \nn (%) p value\n\n\n\nEuropean Baseline Series Rubber \nAllergens Alone 15 (23.1) -\n\n\n\nEuropean Baseline Series Rubber \nAllergens + 3 Additional Rubber \nAllergens\n\n\n\n50 (76.9) <0.00001\n\n\n\nEuropean Baseline Series Rubber \nAllergens + 1,3 Diphenylguanidine 47 (72.3) <0.00001\n\n\n\nEuropean Baseline Series Rubber \nAllergens + N-Cyclohexyl-N-Phe-\nnyl-4-Phenylenediamine\n\n\n\n18 (27.7) 0.545\n\n\n\nEuropean Baseline Series Rubber \nAllergens + N-(Cyclohexylthio) \nphthalimide\n\n\n\n18 (27.7) 0.545\n\n\n\nFragrance mix I (9.9%) was the most common \nfragrance allergen in the EBS (Table 4). The 4 \nfragrance allergens in the EBS (balsam of Peru, \nfragrance mix I, fragrance mix II, lyral) detected \n62.3% of the fragrance allergy cases. A further \ndetection of 6.5% of cases were achieved with the \naddition of Ylang ylang oil though the difference \nwas not significant (p=0.499).\n\n\n\nThere were 5 allergens in the EBS with low \nsensitization rates in our cohort. Lyral, mercapto \nmix and primin were each tested positive in \n0.7% of the subjects. N-Isopropyl-N-Phenyl-4-\nPhenylenediamine and budesonide only showed \n0.3% positive reactions.\n\n\n\nDiscussion\n\n\n\nHistorical Comparison\nA historical comparison was made with a \nretrospective study from the same centre, Hospital \nSelayang. It studied the contact sensitization rate of \n705 subjects between 2011 and 2013 (36 months) \n(Table 6). The overall sensitization rate of EBS in \nthe study was almost similar to the current study \n(66.1% vs 67.1%). There was a reduction in the rate \nof positive reaction to N-Cyclohexyl-N-Phenyl-\n4-Phenylenediamine and Ylang ylang oil. This \ncould be explained by patient selection to undergo \npatch test with extended series. They were strongly \nsuspected to have allergic contact dermatitis to \nrubber or fragrance based on exposure history and \nwere then tested with rubber or fragrance series. \nHence, the subjects were not a random population. \nWhen the allergens were tested on all patients in \nour study, the sensitization rates were significantly \nreduced except for 1,3-diphenylguanidine and \nN-Cyclohexylthiophthalimide. The sensitizing rate \n\n\n\nof 1,3-Diphenylguanidine was hugging around 10%. \nThe sensitizing rate of N-Cyclohexylthiophthalimide \nwas 1.4% (decreased from 3.6%).\n\n\n\nBendewald et al. carried out an 8-year retrospective \nreview on patch test using rubber allergens.3 The \npositive rate of reaction to diphenylguanidine in \nthis study was 7.5%. Bendewald et al also made \na comparison with 3 other similar studies which \nshowed a prevalence of diphenylguanidine allergy \nof 1% to 4.4%.4,5,6 The rates of sensitisation to \nN-(Cyclohexylthio) Phthalimide (5.2%) and  \nN-Cyclohexyl-N-Phenyl-4-Phenylenediamine \n(1.3%) were comparable to our data. The study \nalso demonstrated that carba mix had a low \nsensitivity in detecting diphenylguanidine allergy. \n1,3-Diphenylguanidine is a rubber accelerator \nwhich is also a component within carba mix. The \nprevalence of diphenylguanidine allergy is gradually \nrising. Most cases have been reported with exposure \nto synthetic gloves.7\n\n\n\n \nYlang ylang oil, well known for its fragrant scent, \nis a plant found in South East Asian countries \nsuch as in Malaysia, Indonesia, Vietnam and some \nislands of Indian Ocean. The essential oil extracted \nfrom the flower is widely used in aromatherapy, \nperfume and food industry. The plant is also used \nby traditional healers in many aspects, such as \ntreatment of asthma, malaria, depression, itch, gout \nand headache.8 Ylang ylang oil has been included \nwithin the North American baseline screening \nseries since 2001.9 Prior to that, a multicenter \nstudy on fragrance contact dermatitis involving \ncenters from Japan, Northern Ireland, United \nStates, Sweden, England and Switzerland showed \nthat the addition of Ylang ylang oil, narcissus oil, \nand sandalwood oil to fragrance mix would detect \n94.2% of the cases of fragrance contact dermatitis.10 \nIn this study, the sensitization rate to Ylang ylang \noil was 17.4%, which was the third most common \nfragrance allergen. Ylang ylang oil is also present \nin the China baseline series. Studies which have \nincluded Ylang ylang oil in the routine testing \nof patients with contact dermatitis documented \nprevalence rates between 0.7% and 2.6%.11,12 Our \ncurrent study reported a sensitization rate of 3.4% \nwith Ylang ylang oil was comparable to other parts \nof the world. The previous reported 14.6% in the \nsame center reflected a patient selection bias instead \nof a true increase of Ylang ylang oil allergy. The \naddition of Ylang ylang oil in the EBS in our cohort \nimproved the fragrance allergy detection rate from \n62.3% to 68.8%.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26\n\n\n\nAs seen in the results section (Table 5), incorporating \nall 4 additional allergens in the baseline series did \nimprove the overall contact sensitization rate. The \ndetection of rubber allergy  was significantly  improved \nwith the presence of 1,3-Diphenylguanidine. \nTherefore, 1,3-Diphenylguanidine should be \nconsidered to be included in the baseline screening \nseries in our population. We are yet to formulate \nour very own local baseline series which could \ndetect at least 90% of fragrance and rubber contact \ndermatitis. A multicenter study involving a larger \nlocal population may provide a better reflection of \nthe local pattern of contact sensitization. Based on \nthe current data, there are other allergens which are \nlocally important but yet to be identified to improve \nfurther the contact sensitization detection rate.\n\n\n\nComparison of Data With Other Countries\nStudies published from the local patch test data \nin Singapore13, Thailand14, Hong Kong15, and \nKorea16, United Kingdom12 and North America17 \nwere reviewed (Table 7). Females seemed to have a \nhigher preponderance to develop contact dermatitis \nin all nations. The sensitization rates were as \nfollow: Korea (85.8%), Thailand (73.8%), our \nstudy (70.5%), North America (63.8%), Singapore \n(47.1%) and the United Kingdom (43%).\n\n\n\nNickel sulfate remained the most common \nsensitizing allergen in all listed centres. Its presence \nin jewellery, cosmetics, household products, coins, \nand food explain the high prevalence of nickel sulfate \nallergy.18 The European Union Nickel Directive \nregulation in 1994 had led to a temporary reduction \nin nickel allergy. However the improvement was \nnot sustained in further analysis thereafter. Non-\ncompliance to the legislation was a raised concern.19\n\n\n\nFragrance allergens were the next most common \nallergens across the countries, namely fragrance mix \nI and balsam of Peru. A Swedish study demonstrated \n\n\n\nthat 88% out of 204 products (shampoos, hair \nconditioners, liquid soaps, wet tissues, washing-\nup liquids, and multipurpose cleansers) analysed \ncontained sensitizing fragrance allergens.20   \n\n\n\nFragrance mix II and lyral were included in the EBS \nin 2008. The recommendation was based on the \nreported allergy rates of up to 5% to Fragrance mix \nII and between 1-3% to lyral in various centres in \nthe Europe. The prevalence of lyral allergy in North \nAmerica however was only 0.4%. The difference \nwas attributed to the higher concentrations in the EU \ndeodorants.21 Fragrance mix II was among the top \n10 common allergens in United Kingdom (3.2%), \nSingapore (3.9%) and North America (5.2%).  In \nour study, the sensitization rate of Fragrance mix II \nand lyral were 1.7% and 0.7% respectively. Among \nthe other countries, Ylang ylang oil was only present \nin the North American baseline series, and it was \nnot among the top 20 common allergens list.\n\n\n\nApart from nickel sulfate and fragrance allergens, \ncobalt chloride, formaldehyde, neomycin \nsulfate, thiuram mix, para-phenylenediamne, \nparaben mix, methyl-chloroisothiazolinone and \nmethylisothiazolinone were among the top 10 \nallergens in these studies. Besides textile dye \nmix (which was added to the EBS in 2015) and \n1,3-Diphenylguanidine (which was not routinely \ntested in the other countries except for North \nAmerica), the rest of the common allergens were \ncomparable to the mentioned centres.\n\n\n\nRubber gloves usage among healthcare, industrial \nand domestic workers resulted in the increasing \ntrend of rubber allergy. Latex allergy was a major \nconcern due to the occurrence of immediate \nhypersensitivity reaction. Subsequently, synthetic \nrubber gloves gradually replaced natural rubber \nlatex gloves. However, the rubber accelerators \nused in the vulcanization process such as thiuram \nand carbamates also induced allergic contact \n\n\n\nTable 6. Comparison between 2 study findings in Hospital Selayang \n\n\n\n2011-2013 2015-2016 p\nDuration of study period in months 36 18 -\nTotal number of subjects patch tested 705 292 -\nRate of positive reaction European Baseline Series 466 (66.1%) 196 (67.1%) 0.755\nRate of positive reaction European Baseline Series + Additional Series 546 (77.4%) 229 (78.4%) 0.736\nRate of positive reaction to specific rubber allergen [in \nthe total number of patients tested with rubber series \n(2011-2013) or modified European Baseline Series \n(2015-2016)] \n\n\n\n1,3 Diphenylguanidine 52 (11.1%)\nn=468\n\n\n\n31 (10.6%) \u2193\nn=292 0.824\n\n\n\nN-Cyclohexyl-N-Phenyl-4-Phenylene-\nDiamine\n\n\n\n18 (3.9%)\nn=462\n\n\n\n4 (1.4%) \u2193\nn=292 0.047\n\n\n\nN-Cyclohexylthio phthalimide 17 (3.6%)\nn=472\n\n\n\n4 (1.4%) \u2193\nn=292 0.064\n\n\n\nRate of positive reaction to Ylang ylang oil (in total number of patients tested with Ylang ylang \noil)\n\n\n\n21 (14.6%) \nn=144\n\n\n\n10 (3.4%) \u2193\nn=292 0.00002\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n27\n\n\n\ndermatitis. Thiuram allergy seemed to have declined \nfollowed by a rise in sensitization to carbamates. \n1,3-Diphenylguanidine, also a carbamate, is \nincreasingly identified as a clinically significant \nsensitizing agent.22,23,24 This phenomenon is \nprobably related to the change in manufacturing \ningredients. In a previous local study carried out \nbetween 1994 and 1996, Rohna et al demonstrated \nthat thiuram was the most common sensitizing \nrubber allergen, while 1,3-Diphenylguanidine was \nless common.25 In contrast, the results in our study \nshowed that we have more patients sensitized to \n1,3-Diphenylguanidine.\n\n\n\nAn allergen eligible for inclusion in the screening \nseries should have a sensitization rate of 0.5% \nto 1%, when routinely tested on patients with \nsuspected contact allergy.26 In the current study, \nboth budesonide and IPPD had only 0.3% positive \nreactions. IPPD is one of the components of black \nrubber mix, which functions as an antidegradant in \nthe process of rubber manufacturing.  Lam et al. and \nWaranya et al. reported a prevalence of 0.4% and \n1.6% in Hong Kong and Thailand respectively.26,27 \n\n\n\nOther centers utilized black rubber mix in the \nscreening series instead of IPPD alone. In the \nprevious study in Hospital Selayang performed \nbetween 2011 and 2013, the rate of positive reaction \nto IPPD was 3.8%. Our low detection rate could \npossibly be attributed to the change of ingredients \nin products.\n\n\n\nBudesonide, a class B corticosteroid in the European \nBaseline Series is used as a marker to reflect \ncorticosteroid allergy of the same class. Other class \nB corticosteroids include amcinonide, desonide, \nfluocinolone acetonide, halcinonide, triamcinolone \n(acetonide, diacetate), oral budesonide and oral \ntriamcinolone. Budesonide also cross reacts with \nclass D corticosteroids.28 The studies performed in \ndifferent continents have demonstrated a prevalence \nbetween 0.3% to 2% for budesonide (Ochi 2017, \nDararattanaroj 2016, Yu DS 2016, Toholka \n2015, Warshaw 2015).13,14,16,17,29 Ochi et al. and \nDararattanaroj et al each reported a sensitization rate \nof 0.3% and 0.5% in the single centre study carried \nout in Singapore and Thailand respectively.13,14 We \ndid not differ from our neighbouring countries. The \nlow sensitization rate in our cohort could be due to \nthe lower exposure rate to class B corticosteroids.\n\n\n\nConclusion\nThe overall detection rate of contact sensitization \nincreased by 3.4% with the addition of \n\n\n\n1,3-Diphenylguanidine, N-Cyclohexyl-N-Phenyl-\n4-Phenylenediamine, N-Cyclohexylthiophthalimide \nand Ylang ylang oil. The addition of \n1,3-Diphenylguanidine rubber in the baseline series \nimproved the detection of rubber sensitization \nby 49.2% while the addition of Ylang ylang oil \nincreased fragrance sensitization detection rate \nby 6.5%. A multicentre study with a larger local \npopulation is very much needed to support the \ninclusion of these allergens in the local screening \nbaseline patch test series. Apart from that, more \nstudies are needed to identify other locally relevant \nallergens to improve the detection rate of contact \nallergy in our population.  \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle. \n\n\n\nReferences\n\n\n\n1. Peiser M, Tralau T, Heidler J, Api AM, Arts JH, Basketter \nDA et al. Allergic contact dermatitis: Epidemiology, \nmolecular mechanisms, in vitro methods and regulatory \naspects. Current knowledge assembled at an international \nworkshop at BfR, Germany. Cell Mol Life Sci 2012;69:763-\n81. \n\n\n\n2. Ng FY, WSA Wan Ahmad Kamal, L Sinnaiyah, H Ab \nHalim, R Ridzwan. Retrospective analysis of patch test \nresults between 2011 and 2013 in Hospital Selayang, \nMalaysia.  Malaysian J Dermatol 2018;40:5-9.\n\n\n\n3. Bendewald MJ, Farmer SA, Davis MD. An 8-year \nretrospective review of patch testing with rubber allergens: \nThe Mayo clinic experience. Dermatitis 2010;21:33-40. \n\n\n\n4. Conde-Salazar L, del-Rio E, Guimaraens D, Gonz\u00e1lez \nDomingo A. Type IV allergy to rubber additives: a 10-year \nstudy of 686 cases. J Am Acad Dermatol 1993;29:176-80.\n\n\n\n5. Holness DL, Nethercott JR. Results of patch testing with \na special series of rubber allergens. Contact Dermatitis \n1997;36:207-11.\n\n\n\n6. Nettis E, Assennato G, Ferrannini A, Tursi A. Type I \nallergy to natural rubber latex and type IV allergy to rubber \nchemicals in health care workers with glove-related skin \nsymptoms. Clin Exp Allergy 2002;32:441-7.\n\n\n\n7. Crepy MN. Rubber: new allergens and preventive \nmeasures. Eur J Dermatol 2016;26:523-30. \n\n\n\n8. Tan LT, Lee LH, Yin WF, Chan CK, H Abdul Kadir, \nChan KG et al. Traditional Uses, Phytochemistry, and \nBioactivities of Cananga odorata (Ylang-Ylang). Evid \nBased Complement Alternat Med 2015; 2015:896314. doi: \n10.1155/2015/896314.\n\n\n\n9. De Groot AC, Schmidt E. Essential Oils, Part IV. Dermatitis \n2016;27:170-5. \n\n\n\n10. Larsen W, Nakayama H, Lindberg M, Fischer T, Elsner P, \nBurrows D et al. Fragrance contact dermatitis: a worldwide \nmulticenter investigation (Part I). Am J Contact Dermat \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28\n\n\n\n1996;7:77-83. \n11. Wetter DA, Yiannias JA, Prakash AV, Davis MD, Farmer \n\n\n\nSA, el-Azhary RA. Results of patch testing to personal care \nproduct allergens in a standard series and a supplemental \ncosmetic series: An analysis of 945 patients from the Mayo \nClinic Contact Dermatitis Group, 2000-2007. J Am Acad \nDermatol 2010;63:789-98. \n\n\n\n12. Uter W, Schmidt E, Geier J, Lessmann H, Schnuch A, \nFrosch P. Contact allergy to essential oils: Current patch \ntest results (2000-2008) from the Information Network of \nDepartments of Dermatology (IVDK). Contact Dermatitis \n2010;63:277-83. \n\n\n\n13. Ochi H, Cheng SW, Leow YH, Goon AT. Contact allergy \ntrends in Singapore - a retrospective study of patch test \ndata from 2009 to 2013. Contact Dermatitis 2017;76:49-\n50.\n\n\n\n14. Dararattanaroj W, Pootongkam S, Rojanawatsirivej N, \nWongpiyabovorn J. Patterns and risk factors of causative \ncontact allergens in Thai adult patients with contact \ndermatitis. Asian Pac J Allergy Immunol 2016;35:27-32.\n\n\n\n15. Lam WS, Chan LY, Ho SC, Chong LY, So WH, Wong TW. \nA retrospective study of 2585 patients patch tested with the \nEuropean standard series in Hong Kong (1995-1999). Int J \nDermatol 2008;47:128-133.\n\n\n\n16. Yu DS, Kim HJ, Park YG, Bae JM, Kim JW, Lee YB. \nPatch-test results using Korean standard series: a 5-year \nretrospective review. J Dermatolog Treat 2017;28:258-62. \n\n\n\n17. Warshaw EM, Maibach HI, Taylor JS, Sasseville D, \nDeKoven JG, Zirwas MJ et al. North American Contact \nDermatitis Group Patch Test Results. Dermatitis \n2015;26:49-59.\n\n\n\n18. Ahlstr\u00f6m MG, Thyssen JP, Wennervaldt M, Menn\u00e9 T, \nJohansen JD. Nickel allergy and allergic contact dermatitis: \na clinical review of immunology, epidemiology, exposure \nand treatment. Contact Dermatitis 2019;81(4):227-41. \n\n\n\n19. Schnuch A, Geier J, Lessmann H, Arnold R, Uter W. \nSurveillance of contact allergies: Methods and results of \nthe Information Network of Departments of Dermatology \n(IVDK). Allergy 2012;67:847-57. \n\n\n\n20. Yazar K, Johnsson S, Lind ML, Boman A, Lid\u00e9n C. \nPreservatives and fragrances in selected consumer-\navailable cosmetics and detergents. Contact Dermatitis \n2011;64:265-72.\n\n\n\n21. Bruze M, Andersen KE, Goossens A; ESCD; EECDRG. \nRecommendation to include fragrance mix 2 and \nhydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) in \nthe European baseline patch test series. Contact Dermatitis \n2008;58:129-33.\n\n\n\n22. Cao LY, Taylor JS, Sood A, Murray D, Siegel PD. Allergic \ncontact dermatitis to synthetic rubber gloves: changing \ntrends in patch test reactions to accelerators. Arch Dermatol \n2010;146:1001-7.\n\n\n\n23. Pont\u00e9n A, Hamnerius N, Bruze M, Hansson C, Persson C, \nSvedman C et al. Occupational allergic contact dermatitis \ncaused by sterile non-latex protective gloves: clinical \ninvestigation and chemical analyses. Contact Dermatitis \n2013;68:103-10.\n\n\n\n24. Dejonckheere G, Herman A, Baeck M. Allergic contact \ndermatitis caused by synthetic rubber gloves in healthcare \nworkers: Sensitization to 1,3-diphenylguanidine is \ncommon. Contact Dermatitis 2019;81:167-73.\n\n\n\n25. R Rohna, H Suraiya. Rubber allergy at the Dermatology \nClinic, Hospital Kuala Lumpur. Med J Malaysia \n1998;53:161-4.\n\n\n\n26. Bruze M, Cond\u00e9-Salazar L, Goossens A, Kanerva L, White \nIR. Thoughts on sensitizers in a standard patch test series. \nThe European Society of Contact Dermatitis. Contact \n\n\n\nDermatitis 1999;41:241-50.\n27. Boonchai W, Iamtharachai P. Risk factors for common \n\n\n\ncontact allergens and patch test results using a modified \nEuropean baseline series in patients tested during between \n2000 and 2009 at Siriraj Hospital. Asian Pac J Allergy \nImmunol 2014;32:60-5. \n\n\n\n28. Matura M, Goossens A. Contact allergy to corticosteroids. \nAllergy 2000;55(8):698-704. \n\n\n\n29. Toholka R, Wang YS, Tate B, Tam M, Cahill J, Palmer A et \nal. The first Australian Baseline Series: Recommendations \nfor patch testing in suspected contact dermatitis. Australas \nJ Dermatol 2015;56:107-15.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n29\n\n\n\nORIGINAL ARTICLE\n\n\n\nContact Cheilitis: A 5-Year Review in the Department of Dermatology, \nHospital Kuala Lumpur          \n\n\n\nSharifah Rosniza Syed Nong Chek1, AdvMDerm, Min Moon Tang1, AdvMDerm, Asmah Johar1,2, MMed  \n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Klinik Pakar Kulit Dahlia, Bangi, Selangor, Malaysia\n\n\n\nAbstract\nIntroduction\nContact cheilitis is a common cause of cheilitis. However, identifying the causative factor remains \na challenge. This study aims to describe the characteristics of patients with cheilitis who underwent \npatch testing in Hospital Kuala Lumpur.\n\n\n\nMethods\nThis is a 5-year retrospective study of patients who had cheilitis and had undergone patch testing at the \nDepartment of Dermatology, Hospital Kuala Lumpur, Malaysia between January 2013 and December \n2017. Patch tests were performed with European Baseline Series and relevant extended series which \ninclude cosmetic, dental, metal series as well as patient\u2019s own products. Patch test readings were \nrecorded according to the International Contact Dermatitis Research Group recommendation. \n\n\n\nResults\nThere were 73 patients with cheilitis who underwent patch test. The median age of the patients was 26 \n(range 11 to 76) with 91.8% of patients being female.  There were 52 (71.2%) patients who developed \nat least one positive reaction. The most frequent sensitizing allergens were nickel sulfate (30.1%), \npotassium dichromate (13.7%), thimerosal (12.3%), fragrances (9.6%) and cobalt chloride (8.2%).  \nTen (13.7%) patients developed positive patch test reactions to their own products such as toothpaste \n(n=5), lipstick (n=2), lip balm (n=1), facewash (n=1) and lotion (n=1). Current relevance was recorded \nin 14 patients (26.9%).\n\n\n\nConclusion\nContact sensitization was detected in about 70% of our patients with cheilitis. The most common \nsensitizing allergen was nickel sulfate. Toothpaste is more common than lip cosmetics as the likely \ncause of cheilitis.\n\n\n\nKey words: Cheilitis, allergic contact dermatitis, contact cheilitis, patch test\n\n\n\nCorresponding Author\nDr. Sharifah Rosniza Binti Syed Nong Chek\nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang, \n50586 Kuala Lumpur, Malaysia.\nEmail: srsyed@doctors.net.uk\n\n\n\nIntroduction\nCheilitis refers to superficial inflammation of the \nlips and can occur on its own or is associated with \nperioral dermatitis or other oral lesions such as \nstomatitis.1 It excludes tumours, malformations, \ndystrophies, ulcerations or deep nodular lesions \naffecting this site.2 Specifically, angular chelitis \nrefers to inflammation involving only the angles of \nthe mouth and can be either unilateral or bilateral.\n\n\n\nThere are many causes of cheilitis which include \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30\n\n\n\ncontact cheilitis, atopic cheilitis, actinic cheilitis, \ndrug-induced cheilitis, factitious cheilitis, infectious \ncheilitis and glandular cheilitis.2 Contact cheilitis \ncan be further divided into irritant contact cheilitis \nand allergic contact cheilitis. Irritants and allergens \ncan come into contact with the lips via the use of \npersonal care products such as toothpastes, lipsticks \nand lip balms, dental material such as braces or even \nvia ingestion of food products. As with other cases \nof allergic contact dermatitis, patch testing plays \nan important role in diagnosing allergic contact \ncheilitis.\n\n\n\nThis study aims to describe the characteristics \nof contact cheilitis in Hospital Kuala Lumpur, \nMalaysia.\n\n\n\nMaterials & Methods\nThis is a 5-year retrospective study of patients \nwith cheilitis and had undergone patch testing at \nthe Department of Dermatology, Hospital Kuala \nLumpur, Malaysia between January 2013 and \nDecember 2017.  \n\n\n\nPatch tests were performed with European \nBaseline Series and relevant extended series from \nChemotechnique Diagnostics using IQ chambersTM.  \nExtended series used include cosmetic series, dental \nscreening series, metal series, rubber series, plastic \nand glue series and hairdressing series.  Patients were \nalso tested with their own products, which include \nlipstick, lip balm, toothpaste, face wash and lotion.  \nCosmetics such as eye make-up, lipstick, facial \npowder, facial foundation, moisturizers, perfumes \nand deodorants were tested \u201cas is\u201d.  Toothpaste was \nalso tested \u201cas is\u201d. Cleaning products such as facial \nwash, shampoo and shower gel were diluted with \nwater to 10% (w/w).  \n\n\n\nPatches were applied to the patients and removed \nafter 48 hours. Initial reading was done at 48 \nhours and final reading was recorded at 96 hours \nafter patch application. The parameters studied \ninclude positive patch test reactions and the source \nof allergens. Readings were recorded according \nto the International Contact Dermatitis Research \nGroup recommendation.3 In accordance to their \nrecommendation, a positive patch test reaction \nis defined as a reaction that fulfils at least a 1+ \nreaction (i.e. +, ++ or +++).  Other reactions that \ncan be found during patch tests are irritant reaction \n(IR) and doubtful reaction (?/+), but these are not \nconsidered as a positive patch test reaction.\n\n\n\nResults\nA total of 73 patients with cheilitis underwent patch \ntest. The demographic data is shown in Table 1. The \nmedian age of patients was 26 years old (range 11 \nto 76) and 91.8% of patients were female. There \nwere 52 (71.2%) patients who developed at least \none positive reaction. As shown in Table 2, the most \nfrequent sensitizing allergens were nickel sulfate \n(30.1%), potassium dichromate (13.7%), thimerosal \n(12.3%), fragrances (9.6%) and cobalt chloride \n(8.2%). Ten (13.7%) patients developed positive \npatch test reactions to their own products such as \ntoothpaste (n=5), lipstick (n=2), lip balm (n=1), \nfacewash (n=1) and lotion (n=1).\n\n\n\nTable 1. Characteristics of patients who underwent patch test\n\n\n\nCharacteristics N=73 (%)\nMedian Age in Years (Range) 26 (11-76)\nMale : Female Ratio 1:11.2\nEthnicity, n (%) Chinese 38 (52.1)\n\n\n\nMalay 27 (37.0)\nIndian 7 (9.6)\nOthers 1 (1.4)\n\n\n\nOccupations, n (%) Professional 25 (34.2)\nClerks 7 (9.6)\nManager 2 (2.7)\nTechnician 2 (2.7)\nServices 2 (2.7)\nAgricultural 1 (1.4)\nUnemployed 34 (46.6)\n\n\n\nSeries used, n (%) European Baseline 73 (100.0)\nCosmetic 38 (52.1)\nDental 17 (23.3)\nMetal 6 (8.2)\nRubber 4 (5.5)\nPlastic and glue 2 (2.7)\nHairdressing 1 (1.4)\nOwn products 65 (89.0)\n\n\n\nSeventeen (23%) patients had involvement of other \nsites on their body in addition to the cheilitis, most \ncommonly on the face. Relevance of positive patch \ntest reaction was assessed and 14 patients (26.9%) \nwere found to have current relevance. Their current \nrelevance were likely towards own toothpaste \n(35.7%), followed by their lips cosmetics (21.4%), \nfacial wash (21.4%), facial cosmetic (7.1%), \ndentures (7.1%) and orthodontic braces (7.1%).\n\n\n\nIrritant reaction was detected in 29 (39.7%) patients.  \nIrritant reaction in these patients was caused by \ntheir own toothpastes in 24 (82.8%) patients.  Other \ncauses of irritant reactions are lipstick (10.3%), \nformaldehyde (6.9%), facial wash (6.9%), sorbitan \nsesquioleate (3.4%), cocamidopropyl betaine \n(3.4%), hand wash (3.4%) and facial mask (3.4%).\n \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n31\n\n\n\nTable 2. The sensitization pattern of current cohort\n\n\n\nPositive Patch Test n (%)\nNickel sulfate 22 (30.1)\nPotassium dichromate 10 (13.7)\nThimerosal 9 (12.3)\nFragrances 7 (9.6)\nCobalt chloride 6 (8.2)\n4-phenylenediamine base, formaldehyde and \nmercury 4 each (5.5)\n\n\n\nBalsam of Peru, isothiazolinone and amalgam 3 each (4.1)\nMDBGN, iron oxide and thiuram mix 2 each (2.7)\nWool alcohol, epoxy resin, SQL mix, BHT, BHA, \nchlorocresol, cocomidopropylbetaine, thiuram \nmix, iron chloride, stannous chloride, 2-bromo-\n2-nitro-propane-1,3-diol, benzocaine, palladium \nchloride, goldsodium thiosulphate, mercapto mix, \ndibutylthiourea, paraben mix, palladium chloride, \ncopper oxide, copper sulphate, titanium, mercury, \nmercury ammonium chloride, neomycin, benzoyl \nperoxide, clioquinol, colophony \n\n\n\n1 each (1.4)\n\n\n\nToothpaste causes both irritant and allergic reactions \nin our study. Twenty-nine patients developed \nreaction to toothpaste; with 24 (82.8%) categorized \nas irritant reaction and 5 (17.2%) patients categorized \nas a positive patch test reaction.\n\n\n\nMDBGN-Methyldibromoglutaronitrile; SQL-Sesquiterpine Lactone; \nBHT-Butylated Hydroxytoluene; BHA-BButylated Hydroxyanisole\n\n\n\nDiscussion\nContact sensitization was detected in about 70% of \nour patients with cheilitis. This finding is similar to a \nstudy conducted in Athens.4 However, some studies \nonly reported incidence with relevant sensitization \nand we found that our relevant sensitization of \n26.9% is also comparable to other studies (Table 3).\n\n\n\nThe most common sensitizing allergen found in \nour study was nickel sulfate and this finding is \nsimilar to other studies.4,5,6 Nickel is abundant in \nour environment and can be found in cosmetics, \nparticularly in colour cosmetics. The fact that more \nfemales are wearing cosmetics and jewelleries and \nalso undergo ear piercing may also explain why \n91.8% of the patients that develop positive patch \ntest reaction in our study are females.  The presence \nof nickel in cosmetic products may originate \nfrom various sources such as use of raw materials \nand water contaminated with nickel to cosmetics \nproduction and use of metal coated apparatuses \nduring cosmetics productions.7 According to \nthe Regulation No 1223/2009 of the European \nParliament and the Council, the presence of \ncosmetics products of metals particularly dangerous \nfor human health such as nickel is prohibited in the \nEuropean countries. However, small quantities of \nnickel may be present as technically unavoidable \ncontaminants if the preparations are safe for human \n\n\n\nhealth. The safe levels of these contaminants \nunfortunately, are not described.7\n\n\n\nLipsticks that contain traces of nickel may cause \ncontact cheilitis in a sensitized individuals and \ncertain lipstick that is encased in a metal sheath \nmay also be contaminated with nickel, possibly via \nleaching of nickel from the metal casings. However, \ndetermining the current relevance of nickel in the \ncontext of cheilitis is challenging as the presence \nof nickel in cosmetics as a contaminant will not be \nnoted in the ingredient list. Furthermore, another \nsource of exposure to nickel to the lips may also \nbe related to ingestion of food containing high \nlevel of nickel such as legumes, dark chocolates, \nshellfish, grains and canned food.8 Patients may also \nbe exposed to nickel via the use of stainless steel \ncookware as nickel has been found to leach from \nthis cookware especially when used to cook acidic \nfood.9 Certainly, if cheilitis is accompanied by the \npresence of other signs of such as a more widespread \neczema or systemic contact dermatitis, the relevance \nof nickel may become more established.  \n\n\n\nAnother source of nickel exposure in the case of \ncheilitis is from dental restorative materials. Nickel \nis found in base-metal metal-ceramic alloy as nickel-\nchromium alloy.10 In addition to cheilitis, allergic \ncontact dermatitis to dental restorative materials \nmay also include stomatitis, oral lichen planus, \nglossodynia, burning mouth/tongue, periodontitis \nand recurrent apthosis.11 Although the release of \nnickel from these materials has been shown to be \nlow12, the corrosive effect of the oral environment is \nthought to increase the nickel release over time.13 In \nour study, there was only one patient who developed \ncheilitis after commencing on orthodontic braces.  \nThis patient was found to have nickel allergy, \nhowever she declined to remove the braces.  Cheilitis \nto orthodontic braces has been reported before and \nin such cases, substitution of nickel with vitallium \ncan be suggested in those found to be allergic to the \nmetal.14  \n\n\n\nWe also found cobalt and chromium as common \nsensitizers in our cohort of patients. Patients \nwho are sensitized to nickel are more prone to be \nsensitized to other metals and this may explain the \nhigh sensitization to cobalt chloride and potassium \ndichromate in our patients.15 Cobalt and chromium \ncan also be found in coloured cosmetics as \npigments.7 Dyes and pigments are essential in the \nproduction of coloured products such as lipsticks.  \nMany pigments authorized to be used in cosmetics \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32\n\n\n\ncontain or are made of metal oxides or minerals e.g. \niron oxide, chromium oxide, aluminium silicate, \nand titanium oxide, which by their nature contain \ntraces of heavy metals.16 The law of the European \nUnion (EU) allows the presence of various pigments \nin cosmetics.7 Colours such as green can contain \nchromium (III) oxide, chromium (III) hydroxide \nand cobalt aluminium oxide.7 Another source of \nexposure to the lips from these metals may also be \nfrom dental alloys.  Cobalt and chromium can be \nfound in palladium-cobalt alloys, nickel-chromium \nalloys and cobalt-chromium alloys; which are used \nas dental restoration materials.10 Although dental \nalloys are meant for long-term use and the metal \nleaching from these products are generally thought \nto be low, it is important to enquire about dental \nrestoration work in patients who presented with \ncheilitis, especially if there are other concurrent \noral symptoms such as stomatitis or oral lichenoid \nreactions.\n\n\n\nThimerosal was one of the most common allergens \nin this study.  Thimerosal is a mercuric derivative \nof thiosalicylic acid and is used as a preservative \nin products including otic suspensions, ophthalmic \nsolutions, nasal preparation, vaccinations and \ncosmetics.17 Its use however has been limited in \ndermatologic medications and cosmetics because \nof concerns regarding mercuric absorption or \nsensitization.  The relevance of thimerosal allergy \nis often unclear, so much so that it was named \nAmerican Contact Dermatitis Society\u2019s \u201c(non)\nallergen of the year\u201d in 2002 due to its low clinical \nrelevance.18 Thimerosal has been removed from \nthe North American Contact Dermatitis Group \nscreening series and the last available data is from \n2002.19 However, it is still important to enquire \nabout possible source of exposure to thimerosal \nfrom cosmetics when presented with patients with \ncheilitis.        \n\n\n\nFragrance was one of the top allergens in this study \nand this is not surprising as many cosmetics and \noral hygiene products contain fragrances as part \nof their ingredients.20 Fragrances such as geraniol \nare also used as flavouring agents in sweet foods \nsuch as ice-cream and candy and has been reported \nto cause allergic contact cheilitis.21 Fragrances are \nalso used to mask certain odours and in this case, it \nmight not be labelled as fragrance in the ingredient \nlist.22 Nowadays, there is a tendency to use \u201cnatural\u201d \nproducts and this includes the use of essential oil. \nEssential oils are made by steam distillation of \nplant material and they are used in fragrances, \n\n\n\nfoods, cosmetics and flavourings. Allergic contact \ndermatitis has been described for 80 essential oils.23 \n\n\n\nCertain essential oil such as peppermint oil is often \nused in toothpaste and mouthwash and has been \nreported to cause allergic contact dermatitis.24  This \nalso highlights the fact that natural products are not \nentirely risk-free and allergic contact dermatitis can \ndevelop in patients who are sensitized to them.  \n\n\n\nApart from fragrances found in foods, certain foods \nthemselves have been reported to cause allergic \ncontact cheilitis. This is especially relevant if the \npatient develops cheilitis after a reported change \nin dietary habit or consumption of a new food \nproducts including supplements and herbs. Foods \nthat have been reported to cause allergic contact \ncheilitis include garlic,25 rosemary,26 propolis and \nbeeswax.27 Garlic contains diallyl sufide, which has \nbeen found to cause allergic contact dermatitis and \neven systemic contact dermatitis.25 Propolis is a \nresinous substance manufactured by bees and it used \nfor gluing and sealing cracks in the beehive. It is \nproduced when plant material collected by the bees \nis mixed with \u00df-glycosidase from the bee\u2019s saliva \nand added to beeswax.27 Apart from being consumed \nas food supplement, propolis and beeswax are also \nfound in cosmetic products including lip balm and \nlipstick. Therefore, it is important to enquire about \nhistory of food that may have triggered cheilitis as \navoidance of such food will render improvement or \nresolution of cheilitis.\n\n\n\nWe found current relevance in 26.9% of our patients, \nmainly towards own toothpaste. Toothpastes have \ncomplex formulations with often more than 20 \ningredients and these ingredients can cause both \nallergic and irritant contact dermatitis.28 Our study \nhowever, showed that the majority of the reactions \ntowards toothpaste are classified as irritant reaction \n(82.8%). The main symptoms of allergic reactions \nto toothpastes are cheilitis, and to a lesser extent \nintraoral manifestations such as glossitis, gingivitis, \nand stomatitis. Potential allergens that can be found \nin a toothpaste include fragrances and flavorings \nsuch as cinnamon derivatives, peppermint oil, \nspearment oil and tea tree oil.  \n\n\n\nOther potential allergens include carvone, \ncocamidopropyl betaine, anethole, amine fluoride, \ntriclosan, aluminium and chloroacetamide.28  \nToothpaste also contains abrasives and detergents \nsuch as sodium lauryl sulfate and these ingredients \nwere known to cause irritant contact dermatitis.  \nSodium lauryl sulfate (SLS) is a surfactant and its \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n33\n\n\n\npresence in toothpaste renders the formation of \nbubbles, which gives a favorable sensation to the \nuser.    \n\n\n\nAlthough testing to toothpastes is undoubtedly \nuseful, it has its own drawbacks. There is currently \nno consensus on patch testing to toothpaste. Irritant \nreaction is deemed to be common when patch testing \nusing undiluted toothpaste due to the presence of \nabrasives and detergents. Diluting the toothpaste \non the other hand will reduce its irritant potential \nbut may cause false negative reaction. As a starting \npoint, a semi-open test or closed patch test with the \nundiluted toothpaste can be performed. If a positive \npatch test reaction to an undiluted toothpaste \ndeveloped, it should be followed with retesting and/\nor testing a dilution series (e.g undiluted, 40% pet or \nwater and 20% pet or water) and/or control testing.28  \nIt is also important to obtain a full ingredient list of \na toothpaste as the ingredients listed on the actual \nproduct are usually not complete. For example, a \nconcurrent positive patch test reaction to allergens \nin the commercial series and to the patient\u2019s own \ntoothpaste should not mean that these allergens are \npresent in the toothpaste unless it is ascertained by \nobtaining the manufacturer\u2019s full ingredient list, or \nfrom analytical investigations.  \n\n\n\nIrritant reaction was detected in 29 (39.7%) patients, \nmainly towards toothpastes. Irritant reaction had \nbeen reported in patients investigated for cheilitis \nand the percentage of irritant contact dermatitis \nin these patients ranged from 5% to 37% (Table \n3). Our study used undiluted toothpaste during \npatch test and we also diluted patients own rinse-\noff products to 10%, which is the highest dilution \nrecommended by the European Society of Contact \n\n\n\nDermatitis. This guideline recommended patients\u2019 \nown rinse-off products to be patch tested at 1-10% \ndilution, depending on the formulations.3 However, \nno further explanation is given about the types of \nformulations.  Both of these factors can contribute \nto the irritant reaction seen in our study.  Perhaps \na 1% dilution for rinse-off products and retesting \nthe patients with positive patch test reaction to \ntoothpaste with a serial dilution may reduce the \nchance of irritant reaction in our patients.  \n\n\n\nTesting to patients\u2019 own products is important as \nthis study showed that 13.7% patients with positive \npatch test reaction would have been missed if testing \nto their own products is not performed. Apart from \ntoothpaste, products that have been found to cause \npositive patch test reaction include facial wash, lip \nbalm, lipstick and lotion. Testing can be done \u201cas is\u201d \nif the products are categorized as leave-on products; \nsuch as lipstick, lip balm, moisturizer and sunscreen.  \nProducts categorized as rinse-off products can be \npatch tested at 1-10% w/w dilution and these include \nproducts such as facial wash.3 Apart from enquiring \nproducts that are applied directly to the lips, \noccupational and recreational activities must also \nbe documented in patients with cheilitis.  Although \nnot found in our study, musical instruments such as \ntrumpet and saxophone have also been implicated in \ncausing cheilitis in patients.29.30\n\n\n\nThere are several limitations to this study. This is \na single centre study and our findings may not be \nrepresentative of the Malaysian population as a \nwhole.  We also did not repeat the patch test with \n40% or 20% dilution for patients who had positive \npatch test reaction to undiluted toothpaste and \nthis could pose a risk of a false positive patch test \nreaction.\n\n\n\nTable 3. Contact cheilitis: a review of the literature\n\n\n\nAuthor Country Study Period n Mean Age \n(Years)\n\n\n\nPositive PT \nReaction (%)\n\n\n\nRelevant\nReaction (%) Top Two Allergens Irritant\n\n\n\nReaction (%)\n\n\n\nCurrent Study Malaysia 2013-2017 73 32 71.2 26.9 1) Nickel\n2) Potassium Dichromate 39.7\n\n\n\nZoli et al. Italy5 2001-2005 83 40.3 54.2 18 1) Nickel\n2) Thimerosal 37\n\n\n\nLim SW et al. Singapore6 1996-1999 202 30.9 NA 34 1) Nickel\n2) Own Cosmetics 5\n\n\n\nKatsarous et al. Greece4 1992-2006 106 F-35.1\nM-38.5 71.7 NA 1) Nickel\n\n\n\n2) Cobalt NA\n\n\n\nMilanesi et al. Italy31 2009-2013 38 37.9 52.6 36.8 1) Fragrance Mix\n2) Eugenol 31.5\n\n\n\nO\u2019Gorman et al. USA20 2001-2011 91 51 NA 45 1) Fragrance Mix\n2) Balsam of Peru 11\n\n\n\nPT: patch test; F: female; M: Male; NA: not available\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34\n\n\n\nConclusion\nContact sensitization was found in about 70% of \nour patients with cheilitis. Cheilitis is commonly \nfound in women and the top 3 allergens in our \nstudy are nickel sulfate, potassium dichromate and \nthimerosal. Current relevance of positive patch test \nreaction was found in around 1/3 of the patients and \nthese were mostly towards their own toothpaste and \nlips cosmetics. Testing to patients\u2019 own products is \nimperative to ensure that these relevant reactions \nare not missed.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Minciullo PL, Paolino G, Vacca M, Gangemi S, Nettis E. \nUnmet diagnostic needs in contact oral mucosal allergies. \nClin Mol Allergy 2016;14:10.\n\n\n\n2. Collet E, Jeudy G, Dalac S. Cheilitis, perioral dermatitis \nand contact allergy. Eur J Dermatol 2013;23:303-7.\n\n\n\n3. Johansen JD, Aalto-Korte K, Agner T, Andersen KE, \nBircher A, Bruze M et al. European Society of Contact \nDermatitis guideline for diagnostic patch testing - \nrecommendations on best practice. Contact Dermatitis \n2015;73:195-221.\n\n\n\n4. Katsarou A, Armenaka M, Vosynioti V, Lagogianni E, \nStavropoulos PG, Kalogeromitros D. Allergic contact \ncheilitis in Athens. Contact Dermatitis 2008;59:123-5.\n\n\n\n5. Zoli V, Silvani S, Vincenzi C, Tosti A. Allergic contact \ncheilitis. Contact Dermatitis 2006;54:296-7.\n\n\n\n6. Lim SW, Goh CL. Epidemiology of eczematous cheilitis \nat a tertiary dermatological referral centre in Singapore. \nContact Dermatitis 2000;43:322-6.\n\n\n\n7. Borowska S, Brzoska MM. Metals in cosmetics: \nimplications for human health. J Appl Toxicol 2015;35:551-\n72.\n\n\n\n8. Aquino M, Rosner G. Systemic Contact Dermatitis. Clin \nRev Allergy Immunol 2019;56:9-18.\n\n\n\n9. Mislankar M, Zirwas MJ. Low-nickel diet scoring system \nfor systemic nickel allergy. Dermatitis 2013;24:190-5.\n\n\n\n10. Roberts HW, Berzins DW, Moore BK, Charlton DG. \nMetal-ceramic alloys in dentistry: a review. J Prosthodont \n2009;18:188-94.\n\n\n\n11. Raap U, Stiesch M, Reh H, Kapp A, Werfel T. Investigation \nof contact allergy to dental metals in 206 patients. Contact \nDermatitis 2009;60:339-43.\n\n\n\n12. Kettelarij JA, Liden C, Axen E, Julander A. Cobalt, \nnickel and chromium release from dental tools and alloys. \nContact Dermatitis 2014;70:3-10.\n\n\n\n13. Lu Y, Chen W, Ke W, Wu S. Nickel-based (Ni-Cr and \nNi-Cr-Be) alloys used in dental restorations may be a \npotential cause for immune-mediated hypersensitivity. \nMed Hypotheses 2009;73:716-7.\n\n\n\n14. Yesudian PD, Memon A. Nickel-induced angular \ncheilitis due to orthodontic braces. Contact Dermatitis \n2003;48:287-8.\n\n\n\n15. Hegewald J, Uter W, Pfahlberg A, Geier J, Schnuch A, Ivdk. \nA multifactorial analysis of concurrent patch-test reactions \nto nickel, cobalt and chromate. Allergy 2005;60:372-8.\n\n\n\n16. Bruzzoniti MC, Abollino O, Pazzi M, Rivoira L, Giacomino \nA, Vincenti M. Chromium, nickel, and cobalt in cosmetic \nmatrices: an integrated bioanalytical characterization \nthrough total content, bioaccessibility and Cr(III)/Cr(VI) \nspeciation. Anal Bioanal Chem 2017;409:6831-41.\n\n\n\n17. Suneja T, Belsito DV. Thimerosal in the detection of \nclinically relevant allergic contact reactions. J Am Acad \nDermatol 2001;45:23-7.\n\n\n\n18. Belsito DV. Thimerosal: contact (non)allergen of the year. \nAm J Contact Dermat 2002;13:1-2.\n\n\n\n19. Pratt MD, Belsito DV, DeLeo VA, Fowler JF, Fransway \nAF, Maibach HI et al. North American Contact Dermatitis \nGroup patch-test results, 2001-2002 study period. \nDermatitis 2004;15:176-83.\n\n\n\n20. O\u2019Gorman SM, Torgerson RR. Contact allergy in cheilitis. \nInt J Dermatol 2016;55:e386-91.\n\n\n\n21. Tamagawa-Mineoka R, Katoh N, Kishimoto S. Allergic \ncontact cheilitis due to geraniol in food. Contact Dermatitis \n2007;56:242-3.\n\n\n\n22. Johansen JD. Fragrance contact allergy: a clinical review. \nAm J Clin Dermatol 2003;4:789-98.\n\n\n\n23. De Groot AC, Schmidt E. Essential Oils, Part I: \nIntroduction. Dermatitis 2016;27:39-42.\n\n\n\n24. De Groot A, Schmidt E. Essential Oils, Part V: Peppermint \nOil, Lavender Oil and Lemongrass Oil. Dermatitis \n2016;27:325-32.\n\n\n\n25. Ekeowa-Anderson AL, Shergill B, Goldsmith P. Allergic \ncontact cheilitis to garlic. Contact Dermatitis 2007;56:174-\n5.\n\n\n\n26. Guin JD. Rosemary cheilitis: one to remember. Contact \nDermatitis 2001;45:63.\n\n\n\n27. Nyman GSA, Tang M, Inerot A, Osmancevic A, Malmberg \nP, Hagvall L. Contact allergy to beeswax and propolis \namong patients with cheilitis or facial dermatitis. Contact \nDermatitis 2019;81:110-6.\n\n\n\n28. de Groot A. Contact Allergy to (Ingredients of) Toothpastes. \nDermatitis 2017;28:95-114.\n\n\n\n29. Inoue A, Shoji A, Yashiro K. Saxophonist\u2019s cane reed \ncheilitis. Contact Dermatitis 1998;39:37.\n\n\n\n30. Thomas P, Rueff F, Przybilla B. Cheilitis due to nickel \ncontact allergy in a trumpet player. Contact Dermatitis \n2000;42:351-2.\n\n\n\n31. Milanesi N, Gola M, Verdelli A, Francalanci S. Aspects of \ncontact cheilitis: analysis of 38 cases. J Eur Acad Dermatol \nVenereol 2016;30:1052-3.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n35\n\n\n\nORIGINAL ARTICLE\n\n\n\nImpact of Eczema Action Plan (EAP) on Disease Severity for Childhood \nAtopic Eczema          \n\n\n\nMazliha Mashor1, MRCP, Yoong Wei Lee1, Adv M Derm, Siew Eng Choon1,2, FRCP, Kwee Eng Tey1, MRCP, Adawiyah \nJamil3, Adv M Derm \n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia\n2Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor \nBahru, Johor, Malaysia\n3Department of Dermatology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction\nPoor adherence to topical treatment is common in atopic eczema (AE), which may result in treatment \nfailure. Eczema Action Plan (EAP) is a self-management tool designed to improve adherence. This \nstudy aimed to assess the impact of EAP on disease severity in paediatric patients with AE.\n\n\n\nMethods\nA prospective, randomized controlled investigator-blinded study involving mild to moderate AE \nchildren aged below 18 was performed, comparing intervention group implementing EAP with control \ngroup on standard practice alone. Scoring Atopic Dermatitis (SCORAD) index, Investigator Global \nAssessment (IGA) scoring and adherence to treatment were assessed at baseline, week 4 and week 8. \n\n\n\nResults\nIn total, 64 participants were randomised and 54 patients completed the study. The mean age of \nparticipants was 3.54 \u00b1 3.95 years. Male to female ratio was 1:1.06. Compared to the control group, \nthe intervention group had significantly greater improvement of the mean total SCORAD at week 4 \n(p<0.001) and week 8 (p=0.038), and IGA score at week 4 (p<0.001). Use of moisturisers was higher \nin intervention group at week 4 (p<0.001) and week 8 (p=0.014) in comparison to control group. \nSignificantly smaller amount of high potency topical corticosteroid was used in the intervention group \nat week 4 (p=0.003).\n\n\n\nConclusion\nEczema Action Plan has significantly improved eczema severity. It acts as a simple self-management \ninstrument which may aid in AE treatment. Future studies may be warranted to assess the long-term \nbenefit of EAP.\n\n\n\nKey words: Atopic eczema, children, eczema action plan\n\n\n\nCorresponding Author\nDr Mazliha binti Mashor @ Mansor\nDepartment of Dermatology,\nHospital Sultanah Aminah, \nJalan Persiaran Abu Bakar Sultan, \n80100 Johor Bahru, Johor, Malaysia.\nEmail: ammz83@yahoo.com\n\n\n\nIntroduction\nAtopic eczema (AE) is a chronic, pruritic, \ninflammatory cutaneous disorder that affects one \nquarter of children and 2% to 3% of adults.  More \nthan 50% of patients with AE are diagnosed during \nthe first year of life and 90% within 5 years of \nage. Disease onset  typically occurs around 3 \nand 6 months of age.1 The most commonly used \ndiagnostic tools in local setting is the U.K. Working \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36\n\n\n\nParty\u2019s Diagnostic Criteria which has been validated \nwith sensitivity and specificity of 96% and 93.8%, \nrespectively. There is no specific laboratory test \nrequired for the confirmation of AE diagnosis.2,3 In \n2017, the Malaysian\u2019s clinical practice guidelines \n(CPG) on Management of Atopic Eczema was \npublished with written eczema action plan (EAP) \nintegrated as one of the educational interventions \nfor AE patients.4\n\n\n\nNormal skin barrier function, which offers \nprotection against environmental irritants and \nallergens, is impaired in patients with AE. In \nparticular, alterations in the filaggrin gene have been \nidentified to cause disruption to functional integrity \nof the skin barrier. Moisturisers can be occlusive, by \nproviding a layer of lipid on the skin surface to limit \nthe water loss. Some moisturisers act as humectant \nby increasing its moisture-retaining capacity in \nthe stratum corneum. In addition, moisturisers can \nperform as emollient to lubricate and smoothen the \nskin.5,6 Frequent application of moisturiser is vital \nat any stage of AE regardless of age group. The \nusage of moisturiser is associated with reduction \nin pruritus, erythema and lichenification, aiming \nto achieve the reduction in AE severity. Therefore, \nregular use of moisturiser should be an integral \ncomponent of the AE management.1,4,5\n\n\n\nThe usage of topical corticosteroids (TCS) is \nsupported as anti-inflammatory in addition to the \nuse of moisturisers.4 Various factors are taken into \nconsideration when choosing a specific topical \ncorticosteroid such as patient\u2019s age, location of the \nskin lesion, severity of skin inflammation, patient \npreference, and cost of medication.1,7 The low-\npotency TCS can be considered in children to avoid \nthe possible systemic side effects of corticosteroids \ndue to the higher body surface area to weight ratio.4 \n\n\n\nNevertheless, the practice of short courses of high \npotency TCS can be contemplated during acute \nflares for better eczema control. Special sites such \nas face, flexural and genitalia should warrant the use \nof low potency TCS. Application of high potency \nTCS in those areas may result in greater steroid \nabsorption particularly when they are being used for \nlong term.1,4,8 These few considerations, however, \nmay inadvertently lead to confusion among patients \nand caregivers due to the different practices of TCS \napplication depending on sites and severity.\n\n\n\nAdherence to topical treatment is questionable \nin numerous AE cases.9 Sixty-four (85.3%) \npatients demonstrated poor adherence to treatment \n\n\n\nin a local study published by Mazlin et al.10 \nReasons contributing to poor treatment adherence \ninclude intricacy of treatment regimen, lack of \nunderstanding about the disease, infrequent follow \nup, steroid phobia and use of complementary and \nalternative medicine.7,9 Identifiable measures to \nenhance treatment adherence consist of providing \neducation to patients and caregivers, utilisation \nof education adjuncts and frequent follow up.9,11 \nWritten action plan which has been established \nin paediatric asthma serves as a valuable measure \nto encourage treatment adherence. Both asthma \nand AE are similar in several aspects considering \nthe chronicity of the conditions. They require the \nstep-wise approach in the management guided by \nthe disease severity.8,12 EAP is designed to provide \npatients and caregivers specific instructions on the \ncorrect application of topical medications.8 The \ncontent of EAP should comprise individualised \naction steps during basic maintenance and flares, \nwhen to seek medical attention, recognising flares \nand superimposed infection. Ideally, it is preferred \nthat all the information in EAP is contained in less \nthan two A4 pages.13 The instruction on the treatment \nregimen should be kept simple and clearly written.7\n\n\n\nOur study aims to determine the impact of EAP on \ndisease severity in paediatric patients with AE. At \npresent, the utilisation of EAP in dermatology clinic \nin Malaysia has not been studied.\n\n\n\nMaterials and Methods\n\n\n\nStudy Design\nThis was a single-centre, prospective, randomized, \ntwo-arm, investigator-blinded trial conducted from \nMarch 2019 until June 2019. The study intervention \ngroup used EAP versus standard practice alone in \nthe control arm. Patients were recruited from the \nDermatology Clinic of Hospital Sultanah Aminah \nJohor Bahru, a tertiary care centre for southern region \nof Peninsular Malaysia. Approval from the Medical \nResearch & Ethics Committee (NMRR-18-2728-\n43492) was obtained before the commencement of \nthe study. Written consents were obtained from all \nparents or guardians, whilst assent were obtained \nfrom children aged above 7 years old.\n\n\n\nParticipant Recruitment\nPatients aged below 18 years old, diagnosed with \nAE based on the U.K. Working Party\u2019s Diagnostic \nCriteria for Atopic Dermatitis were recruited. Those \nwith mild to moderate AE according to SCORAD \nscore without modifications in their treatment for the \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n37\n\n\n\npast 3 months were selected. Parents or caregivers \nwho are illiterate and unable to read the EAP and \nthose who were on systemic treatments (including \nsystemic corticosteroid, immunosuppressant and \nlight therapy) in last 6 months were excluded. \n\n\n\nRandomization and Blinding\nRandomization was carried out anonymously \nby an independent research staff using computer \ngenerated Randomization Allocation Software \nversion 2.0. The randomisation code was concealed \nin sealed envelopes arranged in random order. \nEnrolled subjects were randomly assigned to EAP \narm (intervention group) or usual education session \n(control group) in 1:1 ratio. The study researcher \nwho performed the assessment was masked, \nwhereas the attending clinicians and patients/\ncaregivers were unmasked as this was a single-\nblinded study. This blinding of the researcher was \nto ensure that the objective assessment of eczema \nseverity was unbiased. Researcher would not have \naccess to the randomization system and would not \nbe able to identify which group the participants had \nbeen assigned to. During baseline clinic visit, an \nattending clinician would educate the intervention \ngroup on how to use the EAP. The clinician involved \nis a dermatologist working in the dermatology \nclinic who was not involved in patient assessment \nin the study. To maintain the masking process, \nthe clinicians and parents were instructed not to \ndisclose the information about the group allocation \nto the study researcher.\n\n\n\nDue to the nature of the intervention, it was not \npossible to blind the participants. Every participant \nfrom both groups would receive an envelope. Only \nthose from intervention group would receive the \nEAP which was concealed within an envelope. \nCaregivers were also asked to ensure that the content \nof each envelope is hidden from view. Follow-up of \nany non-responders would be made via telephone. \nThe withdrawn subjects would not be replaced.\n\n\n\nDevelopment of EAP\nThe written eczema action plan (EAP) in Malaysia \nfor AE was developed and included in the Clinical \nPractice Guidelines (CPG) on Management of Atopic \nEczema. The EAP is a colour-coded document which \ncomprises a set of written instructions on eczema \ncare regimen in three different circumstances \ndepending on disease severity. The content of EAP \nwould describe instructions about when to apply \nmoisturisers and topical corticosteroids, and when \nto call the clinic during severe flare. EAP is available \n\n\n\nin English and Malay as shown in Figure 1 & 2.\n\n\n\nStandard Management with EAP \nThe participants were randomized into two groups \neither intervention or control group. The allocation \nto each group is 1:1 ratio. During baseline clinic visit, \nparticipants in intervention group were given EAP \nplus the standard eczema practice. The participants \nand caregivers were counselled by a clinician (other \nthan primary investigator) on the use of EAP to \nfacilitate them to use it while at home. The subjects \nin the intervention group would be asked not to \nreveal the content inside the envelope to the primary \ninvestigator. No new topical or systemic treatment \nwas allowed during the study period. Therefore, the \nparticipants would maintain their routine treatment \nregime of moisturisers, topical corticosteroids and \noral antihistamines. \n\n\n\nA clinician would educate on how to use the EAP \nduring baseline clinic visit for the intervention \ngroup. Meanwhile the control group would receive \nverbal information on management of AE only \nwithout EAP. They were provided with the usual \ntreatment including basic education regarding \nthe use of moisturizers and topical corticosteroid \nmedications in accordance to the current standard \npractice. Hence, they were not deprived from \nthe standard care. Upon completion of the trial, \nparticipants in the control group were offered the \nopportunity to use EAP if they were interested.\n\n\n\nOutcome Measures\nThe primary outcome of this study was to determine \nwhether the EAP, when used in addition to standard \neczema care, leads to greater reduction of disease \nseverity compared to standard care alone. Data were \ncollected at baseline, week 4 and week 8.\n\n\n\nData on the assessment of patients\u2019  sociodemographic \ninformation comprised of age, gender, ethnicity, \ncaregivers\u2019 marital status, education level and \nemployment status were recorded on the day of the \nenrolment. \n\n\n\nThe primary outcome was measured by the \ninvestigator using Scoring Atopic Dermatitis \n(SCORAD) index at baseline, 4-week and 8-week \nfollow-up. It combines an objective assessment of the \nextent of disease using the rule of nines, six clinical \nfeatures of disease intensity, including erythema, \noedema/papulation, oozing/crust, excoriation, \nlichenification and dryness. The maximum score for \nSCORAD is 83. The subjective SCORAD score is \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38\n\n\n\nan add-on score to the objective SCORAD, which \nassesses symptoms of pruritus and sleep loss on a \nscale of 0 to 10. The subjective score adds up to \nan additional 20 points to the objective SCORAD \nscore. Disease severity can be categorized as mild \n(<25), moderate (25\u201350) or severe (>50). The \nSCORAD index has undergone testing for validity \nand reliability.13,14\n\n\n\nIn addition, Investigator Global Assessment (IGA) \nis another parameter assessed by investigator at \nbaseline, 4 and 8 weeks.  It is rated as clear, almost \nclear, mild, moderate, severe, or very severe. This \nis a second validated tool to measure eczema \nseverity.15\n\n\n\nDuring each visit, the subjects were asked to bring \nall the remaining topical medications and each \nmedication was weighed separately using the same \ndigital scale. Adherence to treatment was assessed \nby comparing amount of topical treatment used. The \nusage of topical moisturisers, low and high potency \nTCS was recorded in a diary. This caregiver-\ncompleted diary will capture the number of days \neach topical treatment used in a month. Changes in \nadherence to topical treatment was the secondary \nobjective of this study.\n\n\n\nStatistical Analysis \nThe data collected was analysed using the \nStatistical Package for the Social Sciences (SPSS) \nversion 22.0 for Windows. The socio-demographic \ncharacteristics of the intervention and control \ngroups were described using frequency, percentage, \nmean and standard deviation. The comparison at \nbaseline between both groups was made by using the \nappropriate inferential tests such as the Chi-square, \nindependent t-test and Fischer\u2019s Exact test. The \ntwo-way repeated measures ANOVA was used to \nmeasure the changes in the mean score of SCORAD \nand IGA between intervention and control groups at \nvarious time points. P- value <0.05 is considered as \nstatistically significant. \n\n\n\nResults\n\n\n\nBaseline Data\nIn total, 74 patients were assessed for eligibility \nto take part in the study. Of these, 64 participants \nwere randomised into 32 participants for each \ngroup. Fifty-five patients completed the study (28 \nintervention group and 27 control group). Nine \nparticipants dropped out at week 8 as they were no \nlonger interested to continue the study. (Figure 3).\n\n\n\nFigure 3. Flow chart of the study participants in intervention \nand control groups \n\n\n\nAssessed for eligibility (n=74)\n\n\n\nConsent taken from parents/\ncaregivers\n\n\n\nFulfilled the inclusion \nand exclusion criteria\n\n\n\nStandard eczema care\n(control group)\n\n\n\n(n = 32 )\n\n\n\nAvailable for analysis \n(n=27)\n\n\n\nAvailable for analysis \n(n=28)\n\n\n\nStandard eczema care \n(control group)\n\n\n\n(n = 32 )\n\n\n\nLost to follow up (n= 0)\n\n\n\nLost to follow up (n= 5)*\n\n\n\nLost to follow up (n= 0)\n\n\n\nLost to follow up (n=4)*\n\n\n\nBaseline demographics, \nSCORAD, IGA\n\n\n\nRandomized (n= 64)\n\n\n\nAllocation\n\n\n\nEnrolment\n\n\n\nAnalysis\n\n\n\nFollow-up \n(week- 4)\n\n\n\nFollow-up \n(week- 8)\n\n\n\n*4 participants allocated to intervention group and 5 \nparticipants in control group dropped out at week 8 (not \ninterested to continue).\n\n\n\nThe mean age of the study participants upon \ndiagnosis and on recruitment were 2.27 \u00b1 3.37 and \n3.54 \u00b1 3.95 years old, respectively. Male to female \nratio was 1:1.06. The majority of participants were \nMalays (87.5%), whereas 12.5 % were Chinese. \nMore than one-quarter of the participants had other \natopic predispositions including allergic rhinitis or \nbronchial asthma. Three-quarter of the participants \nhad family history of atopy. More than 90% of the \ncaregivers were patients\u2019 own parents, and 3 (4.7%) \nwere grandparents. Thirty-eight (approximately \n60%) of the caregivers had completed tertiary \nlevel education and 29 (45.3%) were employed \nfull-time. Detailed sociodemographic and baseline \ncharacteristics of the study population are shown in \nTable 1.\n \nChanges in Measures of Eczema Severity\nAt the baseline visit, the difference of mean total \nSCORAD and IGA between both groups was \nnot statistically significant (p=0.224 p=0.156, \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n39\n\n\n\nrespectively). Of note, there was a significantly \ngreater improvement of mean total SCORAD \n(p<0.001), subjective and objective SCORAD and \nIGA score (p<0.001) in the intervention group at week \n4 compared to the control group. At week 8, there \nwas also significantly greater improvement in mean \ntotal SCORAD (p=0.038) and objective SCORAD \nin the intervention group, but the differences were \nnot significant in subjective SCORAD (p=0.793) \nand IGA score (p=0.283).  (Refer Table 2)\n\n\n\nChanges in Adherence to Topical Treatment\nNo difference was observed in the amount of the \ninitial moisturisers for both control and intervention \ngroups during baseline visit. The intervention group \nshowed significantly higher amount of moisturisers \nused compared to those in the control group at week \n4 and week 8 (p=<0.001, p=0.014 respectively). \nNo significant difference in the mean weight of low \npotency topical corticosteroid among study groups at \nweek 4 and week 8 (p=0.979, p=0.424 respectively). \nHowever there is a significant reduction in the amount \nof high potency topical corticosteroid observed for \nintervention group during week 4 (p<0.001), but no \nsignificant difference at week 8 (p=0.787) (Table 2). \nWhen comparing the frequency of topical agents \nused in both groups as recorded in the caregiver \ndiary, the difference was not statistically significant \n(p=0.093) (Table 3). \n\n\n\nDiscussion\nEczema Action Plan, which is modelled on the \nasthma action plan, is part of the self-management \nto empower patients and caregivers aiming for \nreduction in AE severity and prevention of flare.4,8 \nOur study has illustrated that the intervention group \ndemonstrated significantly greater improvement in \neczema severity particularly at week 4 indicated \nby lower total SCORAD and IGA score. This \nfinding is consistent with previous studies which \nrevealed improvement in the AE management with \nEAP utilisation.17 One of the benefits of EAP is \nenhancing patients\u2019 and caregivers\u2019 understanding \nof their individualized treatment plan.4,18,19,20 A \nwritten plan acts as a quick reference to patients \nand their families. This encourages them to be more \nconfident and motivated in following the treatment \nregime.12,21 Even though EAP lengthens the initial \nclinic visit by 3 to 5 minutes, it is expected to \nimprove future visit duration, and improve long-\nterm clinical outcomes.17,19,21 \n\n\n\nWhilst the total SCORAD demonstrating significant \n\n\n\nimprovement (p=0.038) at week 8 compared to \nbaseline, the expected reduction in the mean IGA \nscore for the intervention group was not significant \nat week 8 (p=0.283). This finding at week 8 was \ninconsistent and has to be explored further. In the \nrandomised trial on Eczema care plan by Rea et al, \nit has been suggested that a greater impact of the \nEAP can be expected if eczema is observed for a \nlonger duration . This observation may reflect the \nnatural variation in eczema severity with relapsing \nand remitting phases.18 There is a probability that \nchildren might experience flare intermittently \nduring their clinic visits which might improve in the \nsubsequent weeks irrespective of any intervention. \nAnother possible explanation is the lack of use of \nEAP by patients or caregivers beyond 8 weeks. Rea \net al found that only half of the caregivers has been \nusing the action plan more than once or twice since \ninitial visit.18 Thus, a more regular use of written plan \nis desirable to make it more effective in reducing the \neczema severity expectantly in longer period.\n\n\n\nA study by Mason et al has shown there is a \nsubstantial underutilisation of moisturisers in \nchildren with AE as caregivers expressed frustration \nat the irregularity of information provided on \neczema management.23 Common misconception \namong patients is that an ideal moisturiser can be \nused in limited frequency. According to a survey \nin Hong Kong, most of the patients believe that \nideal moisturisers are non-fragrant and non-herbal \ncreams which require only two to three applications \nper day.24 They are often incorrectly advised on the \namount and frequency of moisturisers required to \nmaintain good skin barrier function.5 In comparison \nto oral medication, there are difficulties in applying \ntopical treatment which are contributed by various \nfactors including lack of time to apply medications, \nextent of skin involvement, differing opinion towards \nthe vehicle of the medications and chronicity of the \nillness. From our study, the intervention arm has \nshown significantly greater amount of moisturiser \ncompared to those in control arm during week 4 \nand week 8 (Table 2). Education on moisturiser \nis crucial for AE management as improving the \namount of moisturiser used was associated with \nless pruritus and reduction in sleep disturbance.23 \nIn a study by Moore et al, the mean weekly use of \nmoisturiser increased from 54.5 g at baseline to 426 \ng at the final visit, with a significant reduction in \neczema severity after attending an education session \nwith the nurse indicating that education may result \nin enhanced use of moisturiser.25\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40\n\n\n\n*ANOVA, significant at p<0.05; SD standard deviation; CI confidence interval\n\n\n\nTable 1. Sociodemographic characteristics of the participants\n\n\n\nTable 2. Comparison between control and intervention group on Total SCORAD, Objective SCORAD, Subjective SCORAD, IGA score \nand amount of topical agents used\n\n\n\nCharacteristics Total\n(n=64)\n\n\n\nControl\n(n=32)\n\n\n\nIntervention\n(n=32)\n\n\n\np-value\n\n\n\nAge on recruitment, in year (mean \u00b1 SD) 3.54 (3.95) 3.74 (4.34) 3.33 (3.57) 0.676a\n\n\n\nAge on diagnosis, in year (mean \u00b1 SD) 2.27 (3.37) 2.68 (3.89) 1.86 (2.75) 0.336a\n\n\n\nGender, n (%) \n \n\n\n\nMale 31 (48.4) 15 (46.9) 16 (50.0) 0.802b\n\n\n\nFemale 33 (51.6) 17 (53.1) 16 (50.0)\nEthnicity, n (%) Malay 56 (87.5) 27 (84.4) 29 (90.6) 0.708c\n\n\n\nChinese 8 (12.5) 5 (15.6) 3 (9.4)\nPersonal history of atopy other than AE, n (%) No 47 (73.4) 23 (71.9) 24 (75.0) 0.777b\n\n\n\nYes 17 (26.6) 9 (28.1) 8 (25.0)\nMain caregiver, n (%) Mother/Father 61 (95.3) 31 (96.9) 30 (93.8) 1.00c\n\n\n\nGrandparent 3 (4.7) 1 (3.1) 2 (6.2)\nCaregiver education level, n (%) Secondary school 26 (40.6) 13 (40.6) 13 (40.6) 1.00b\n\n\n\nCollege/ university 38 (59.4) 19 (59.4) 19 (59.4)\nCaregiver employment status, n (%) Non-working 35 (54.7) 21 (65.6) 14 (43.8) 0.079b\n\n\n\nWorking 29 (45.3) 11 (34.4) 18 (56.2)\nFamily history of atopy, n (%) No 16 (25.0) 8 (25.0) 8 (25.0) 1.00b\n\n\n\nYes 48 (75.0) 24 (75.0) 24 (75.0)\nMean (SD) baseline score for eczema severity Objective SCORAD 32.08 (8.18) 30.52 (8.32) 33.65 (7.84) 0.126a\n\n\n\nSubjective SCORAD 10.53 (4.19) 10.44 (4.36) 10.63 (4.07) 0.859a\n\n\n\nIGA score 2.77 (0.43) 2.69 (0.47) 2.84 (0.37) 0.145a\n\n\n\nMean (SD) baseline quantity of medication (g) Topical moisturiser 574.23 (6.46) 574.60 (6.64) 573.85 (6.35) 0.647a\n\n\n\nTopical CS\n(low potency)\n\n\n\n58.17 (2.50) 58.49 (2.46) 57.84 (2.55) 0.303a\n\n\n\nTopical CS \n(high potency)\n\n\n\n19.80 (4.74) 19.18 (0.46) 20.41 (6.68) 0.305a\n\n\n\nParameters Control\nMean (SD)\n\n\n\nIntervention\nMean (SD)\n\n\n\nMean difference\n(95%CI) p-value\n\n\n\nTotal SCORAD  Week 0        39.68 (11.28) 43.95 (11.38) 3.32 (-2.08, 8.73) 0.224\nWeek 4 33.55 (13.95) 27.04 (12.02) -9.29 (-15.60, -2.98) 0.005\n\u0394 week 0-4 5.64 (11.30) 18.26 (10.59) 12.62 (7.14, 18.09) <0.001\nWeek 8 21.08 (15.77) 17.56 (11.92) -3.52 (-11.07, 4.02) 0.353\n\u0394 week 0-8 18.60 (13.76) 26.39 (13.36) 7.80 (0.46, 15.13) 0.038\n\n\n\nObjective SCORAD Week 0        30.52 (8.32) 33.65 (7.84) 3.13 (-0.91, 7.17) 0.126\nWeek 4 26.34 (10.77) 18.98 (9.01) -7.36 (-12.32, -2.39) 0.004\n\u0394 week 0-4 4.18 (9.49) 14.67 (9.14) 10.49 (5.83, 15.15) <0.001\nWeek 8 13.41 (13.19) 10.02 (8.60) -3.39 (-8.96, 2.17) 0.227\n\u0394 week 0-8 17.10 (12.78) 23.63 (10.87) 6.53 (0.60, 12.46) 0.031\n\n\n\nSubjective SCORAD Week 0        9.63 (4.16) 10.82 (4.16) 0.188 (-1.92, 2.30) 0.859\nWeek 4 8.22 (4.28) 7.36 (3.77) -1.94 (-4.01, 0.13) 0.066\n\u0394 week 0-4 1.47 (2.90) 3.59 (2.83 2.13 (0.69, 3.56) 0.004\nWeek 8 5.19 (3.71) 6.11 (4.65) 0.92 (-1.36, 3.20) 0.421\n\u0394 week 0-8 4.44 (3.56) 4.71 (4.00) 0.27 (-1.78, 2.31) 0.793\n\n\n\nIGA score Week 0        2.67 (0.48) 2.82 (0.39) 0.16 (-0.06, 0.37) 0.156\nWeek 4 2.30 (0.61) 1.96 (0.64) -0.38 (-0.67, 0.08) 0.015\n\u0394 week 0-4 0.34 (0.65) 0.88 (0.49) 0.53 (0.24, 0.82) <0.001\nWeek 8 1.59 (0.93) 1.50 (0.88) -0.09 (-0.58, 0.40) 0.706\n\u0394 week 0-8 1.07 (0.87) 1.32 (0.82) 0.25 (-0.21, 0.71) 0.283\n\n\n\nAmount of moisturiser used (g) Week 0 574.25 (6.18) 574.18 (6.54) -0.75 (-4.00, 2.50) 0.647\nWeek 4 176.11 (88.97) 270.78 (123.47) 99.73 (46.80, 152.66) <0.001\nWeek 8 252.97 (125.41) 343.17 (138.20) 90.20 (18.74, 161.66) 0.014\n\n\n\nAmount of low potency topical corticosteroid used (g) Week 0 58.31 (2.62) 58.13 (2.29) -0.65 (-1.90, 0.60) 0.303\nWeek 4 23.63 (15.63) 25.09 (15.18) -0.10 (-7.69, 7.49) 0.979\nWeek 8 23.50 (14.71) 20.41 (13.82) -3.10 (-10.81, 4.62) 0.424\n\n\n\nAmount of high potency topical corticosteroid used (g) Week 0 19.14 (0.43) 20.50 (7.16) 1.23 (-1.14, 3.59) 0.305\nWeek 4 9.27 (6.20) 5.44 (4.63) -4.48 (-7.08, -1.88) <0.001\nWeek 8 8.49 (6.33) 7.85 (10.57) -0.64 (-5.38, 4.09) 0.787\n\n\n\naIndependent t-test; bPearson Chi Square; cFischer\u2019s Exact test; SD standard deviation\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n41\n\n\n\nDifficulties in providing effective treatment for AE \nmay be contributed by misunderstanding about \nthe treatment regime or steroid phobia among \nparents of atopic children.7 A study by Shin et al \nhas demonstrated that a considerable proportion of \npatients believed that the use of corticosteroids is \nunsafe and ineffective, compared to Chinese herbal \ntherapies.26 Numerous studies have attributed steroid \nphobia as a major cause of low compliance leading \nto treatment failure which can exacerbate AE. Fear \nof corticosteroids appears to be closely related \nto preference for alternative and complementary \nmedicines.26 In our study, there is no significant \ndifference reported in the mean weight of low \npotency topical corticosteroid used among study \ngroup. We found that the intervention group had \nused significantly lower amount of high potency \ntopical corticosteroid at week 4, possibly due to \ngreater use of moisturiser which might lead to the \nsteroid-sparing effect and improve the effectiveness \nof the TCS.4\n\n\n\nTargeted education regarding TCS is critical at \nthe time of prescription to overcome the effect of \nsteroid phobia. Poor adherence with therapy is \nusually closely linked to inadequate understanding \nabout the nature of the disease and role of topical \ntreatments prescribed.7 Providing proper counselling \nto patients and caregivers about the frequency and \namount of TCS to be applied, using the TCS with \nappropriate potency, and the duration of treatment, \nmay encourage higher acceptance of TCS and reduce \nfear of steroid use.7,11 Potential side-effects from \nTCS are relatively uncommon and usually caused \nby an incorrect use of the TCS or inappropriate use \nof high potency formulations.11 Whenever TCS is \ncorrectly applied, it is usually well tolerated. \n\n\n\nOur study has a few limitations. Firstly, this study \nwas conducted at a single site; hence it is uncertain \nwhether our findings could be generalized to other \nsettings such as primary care. Highly selected \npatients in tertiary hospital are more likely to \nvolunteer in participating in the study. Larger \n\n\n\nrandomised multi-centre studies in primary care \ncentres are necessary to explore the role of EAP in \nmanaging AE in primary care setting. Secondly, the \nmajority of the participants were Malays, whereas \nsmall proportion were Chinese. This may be \nexplained by sampling bias as our majority of clinic \npatients were Malays. Selecting more participants \nwith diverse ethnicities may reduce the threat of \nselection bias. Thirdly, another limitation was we \ndid not follow these patients beyond 8 weeks due to \nthe time constraint placed on the study. Therefore, \nthe long-term improvement is still unclear. \nFuture work should examine longer-term studies \nand multiple exposure of EAP to evaluate the \nlongstanding benefit of this intervention. Lastly, we \ndid not include EAP presented in languages other \nthan English and Malay due to the restriction in our \nresources. Further development of EAP available in \nvarious languages should be considered to benefit \nmore patients and caregivers in the multi-racial \ncommunity. \n\n\n\nConclusion\nThe use of EAP in AE management has significantly \nimproved eczema severity. Adherence to topical \ntreatment is enhanced by increasing moisturiser \nusage and appropriate utilisation of TCS. This \nstudy highlighted the EAP as a simple and useful \nself-management tool which may aid in the AE \ntreatment.20 Future studies may be warranted to \nassess the long-term benefit of EAP.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle.\n\n\n\nReferences\n\n\n\n1. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, \nHanifin JM, Simpson EL et al. Guidelines of care for the \n\n\n\nTable 3. Comparison of frequency of the topical agents used per month as recorded in caregiver diary\n\n\n\naIndependent T test; SD standard deviation; CI confidence interval\n\n\n\nDiary\n(Number of days / month)\n\n\n\nControl\nMean (SD)\n\n\n\nIntervention\nMean (SD)\n\n\n\nMean difference\n(95%CI)\n\n\n\np-valuea\n\n\n\nMoisturiser Week 4 21.89 (4.73) 25.75 (4.30) 1.77 (-0.31,3.84) 0.093\nWeek 8 25.37 (5.65) 27.46 (4.20)\n\n\n\nLow potency topical corticosteroid Week 4 24.85 (3.26) 23.54 (2.98) -2.19 (-6.03,1.66) 0.259\nWeek 8 17.56 (8.68) 18.43 (7.04)\n\n\n\nHigh potency topical corticosteroid Week 4 14.93 (4.79) 12.46 (5.41) -1.41 (-4.28,1.45) 0.327\nWeek 8 10.33 (7.99) 9.29 (5.66)\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42\n\n\n\nmanagement of atopic dermatitis: Section 1. Diagnosis and \nassessment of atopic dermatitis Work Group. J Am Acad \nDermatol 2014;70:338-51. \n\n\n\n2. Brenninkmeijer EE, Schram ME, Leeflang MM, Bos \nJD, Spuls PI. Diagnostic criteria for atopic dermatitis: a \nsystematic review. Br J Dermatol 2008;158:754-65.\n\n\n\n3. Williams HC, Burney PG, Pembroke AC, Hay RJ. The \nU.K. Working Party\u2019s Diagnostic Criteria for Atopic \nDermatitis. III. Independent hospital validation. Br J \nDermatol 1994;131(3):406-16.\n\n\n\n4. MOH. Clinical Practice Guidelines Management of \natopic eczema. MaHTAS 2018. Available at: https://www.\nmoh.gov.my/moh/resources/Penerbitan/CPG/Skin%20\nCondition/CPG%20Management%20of%20Atopic%20\nEczema.pdf  \n\n\n\n5. Rubel D, Thirumoorthy T, Soebaryo RW, Weng SC, \nGabriel TM, Villafuerte LL et al. Asia-Pacific Consensus \nGroup for Atopic Dermatitis. Consensus guidelines for \nthe management of atopic dermatitis: an Asia-Pacific \nperspective. J Dermatol 2013;40:160-71.\n\n\n\n6. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller \nAS, Schwarzenberger K et al. Guidelines of care for the \nmanagement of atopic dermatitis: Section 2. Management \nand treatment of atopic dermatitis with topical therapies. J \nAm Acad Dermatol 2014;71:116-32.\n\n\n\n7. Beattie PE, Lewis-Jones MS. Parental knowledge of \ntopical therapies in the treatment of childhood atopic \ndermatitis. Clin Exp Dermatol 2003;28:549-53. \n\n\n\n8. Chisolm SS, Taylor SL, Balkrishnan R, Feldman SR. \nWritten action plans: Potential for improving outcomes \nin children with atopic dermatitis. J Am Acad Dermatol \n2008;59:677-83.\n\n\n\n9. Bass AM, Anderson KL, Feldman SR. Interventions \nto Increase Treatment Adherence in Pediatric Atopic \nDermatitis: A Systematic Review. J Clin Med 2015;4:231-\n42.\n\n\n\n10. Mazlin MB, Aniza I, Jong YF, Chia SL, Mohd Ikhwan \nNMS, Noramira A. Adherence to topical medication is \npoor among patients with atopic eczema. Malaysian J \nDermatol 2013;31:1-7.\n\n\n\n11. Sokolova A, Smith SD. Factors contributing to poor \ntreatment outcomes in childhood atopic dermatitis. \nAustralas J Dermatol 2015;56:252-7.\n\n\n\n12. Ntuen E, Taylor SL, Kinney M, O\u2019Neill JL, Krowchuk DP, \nFeldman SR. Physicians\u2019 perceptions of an eczema action \nplan for atopic dermatitis. J Dermatolog Treat 2010;21:28-\n33. \n\n\n\n13. Powell K, Le Roux E, Banks JP, Ridd MJ. Developing a \nwritten action plan for children with eczema: A qualitative \nstudy. Br J Gen Pract 2018;68:e81-9.\n\n\n\n14. Schmitt J, Langan S, Williams HC; European Dermato-\nEpidemiology Network. What are the best outcome \nmeasurements for atopic eczema? A systematic review. J \nAllergy Clin Immunol 2007;120:1389-98.\n\n\n\n15. Charman CR, Venn AJ, Williams H. Measuring atopic \neczema severity visually: Which variables are most \nimportant to patients? Arch Dermatol 2005;141:1146-51. \n\n\n\n16. Rehal B, Armstrong AW. Health outcome measures in \natopic dermatitis: A systematic review of trends in disease \nseverity and quality-of-life instruments 1985-2010. PLoS \nOne. 2011;6:e17520. \n\n\n\n17. Sauder MB, McEvoy A, Sampson M, Kanigsberg N, \nVaillancourt R, Ramien ML et al. The Effectiveness \nof Written Action Plans in Atopic Dermatitis. Pediatr \nDermatol 2016;33:e151-3.  \n\n\n\n18. Rea CJ, Tran KD, Jorina M, Wenren LM, Hawryluk EB, \nToomey SL. A Randomized Controlled Trial of an Eczema \n\n\n\nCare Plan. Acad Pediatr 2018;18:789-96. \n19. Shi VY, Nanda S, Lee K, Armstrong AW, Lio PA. \n\n\n\nImproving patient education with an eczema action \nplan: a randomized controlled trial. JAMA Dermatol \n2013;149:481-3.\n\n\n\n20. Brown J, Weitz NW, Liang A, Stockwell MS, Friedman S. \nDoes an Eczema Action Plan Improve Atopic Dermatitis? \nA Single-Site Randomized Controlled Trial. Clin Pediatr \n(Phila) 2018;57:1624-9. \n\n\n\n21. Gilliam AE, Madden N, Sendowski M, Mioduszewski M, \nDuderstadt KG. Use of Eczema Action Plans (EAPs) to \nimprove parental understanding of treatment regimens in \npediatric atopic dermatitis (AD): A randomized controlled \ntrial. J Am Acad Dermatol 2016;74:375-7.e1-3. \n\n\n\n22. Duhovic C, Mohsin M, Duarte-Williamson E, Baron S. \nWritten treatment plans in atopic eczema management in \nchildren. Br J Dermatol 2016;175:1361-2.\n\n\n\n23. Mason JM, Carr J, Buckley C, Hewitt S, Berry P, Taylor \nJ et al. Improved emollient use reduces atopic eczema \nsymptoms and is cost neutral in infants: Before-and-\nafter evaluation of a multifaceted educational support \nprogramme. BMC Dermatol 2013;13:7.\n\n\n\n24. Hon KL, Wang SS, Pong NH, Leung TF. The ideal \nmoisturizer: A survey of parental expectations and practice \nin childhood-onset eczema. J Dermatolog Treat 2013;24:7-\n12. \n\n\n\n25. Moore EJ, Williams A, Manias E, Varigos G, Donath S. \nEczema workshops reduce severity of childhood atopic \neczema. Australas J Dermatol 2009;50:100-6. \n\n\n\n26. Shin JY, Kim DW, Park CW, Seo SJ, Park YL, Lee JR et \nal. An educational program that contributes to improved \npatient and parental understanding of atopic dermatitis. \nAnn Dermatol 2014;26:66-72.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n43\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Case-control Study: Comparison of Zinc Level in Androgenetic \nAlopecia Patients with Control Group         \n\n\n\nKwan JW, MRCP,Tang JJ, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia\n\n\n\nAbstract\nIntroduction\nZinc is known to be an essential trace element that acts as an enzyme cofactor and has important \nfunctional roles within the hair follicles. Several studies reported that zinc deficiency is associated \nwith Androgenetic Alopecia (AGA). However, there is a lack of information on the prevalence of zinc \ndeficiency among Malaysians with AGA. This study is aimed to evaluate the serum level of zinc in \nmale patients with AGA compared to healthy controls. The relationship of zinc deficiency with the \nseverity and duration of AGA was also determined. \n\n\n\nMethods\nThis is a case-control study involving male AGA patients in the Department of Dermatology, Hospital \nRaja Permaisuri Bainun. Serum zinc level is analyzed using atomic absorption spectroscopy technique. \nThe study group was then compared with age- and sex- matched control group. AGA severity was \nevaluated using the Norwood-Hamilton classification system.\n\n\n\nResults\nA total of 70 subjects were recruited, consisting of 35 subjects in each arm. The median serum zinc was \n74.46 ug/dl (IQR 17.17) and 80.37 ug/dl (IQR 17.70) in AGA group and control group respectively. \nAlthough the median of serum zinc was lower in AGA group, there was no statistically significant \ndifference between both groups (U=596, p=0.846). This study showed no statistically significant \ndifference of zinc level between patients with different disease severity (H=0.927, p=0.629). There \nwas no correlation between AGA disease duration with zinc level (rs=-0.022, p=0.901).\n\n\n\nConclusion\nThere was no significant difference in serum zinc level between AGA group and controls, however, \nthe median serum zinc was lower in the AGA group. There was no correlation between serum zinc \nlevel with AGA disease severity and duration. There is a paucity of evidence for zinc supplementation, \nfurther study is required to determine the role of zinc in AGA.\n\n\n\nKey words: serum zinc, zinc deficiency, AGA, male pattern hair loss, androgenetic alopecia\n\n\n\nIntroduction\nAndrogenetic alopecia (AGA) is a common form \nof non-scarring hair loss among men. In the Asian \npopulation, a prevalence of 46.9-60.0% has been \nreported in males older than 70 years.1,2  In Singapore, \nTang et al. reported 63% prevalence of AGA among \nmen in Bishan east in a community study.3 A variety \nof genetic and environmental factors play a role \nin causing AGA.1,4 It results from the conversion \n\n\n\nCorresponding Author\nDr Kwan Jing Wern\nDepartment of Dermatology,\nHospital Raja Permaisuri Bainun, \nJalan Raja Ashman Shah, \n30450 Ipoh, Perak, Malaysia.\nEmail: kwanjingwern@gmail.com\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44\n\n\n\nof scalp terminal hair into miniaturized vellus \nhair in genetically predisposed individuals.4 The \nunderlying causes of AGA is related to androgens, \nparticularly dihydrotestosterone (DHT).4\n\n\n\nZinc is an essential trace element in the body, skin \n(5%) is the third most zinc abundant tissue after \nskeletal muscle (60%) and bones (30%).5 Zinc is \nessential in various biological functions, including \nDNA synthesis, gene expression, hormone control, \nenzymatic reactions, and cell proliferations.6 In \nanimal experimental models, zinc is an ambivalent \nand potent modulator of murine hair growth. It \naccelerates the regrowth of pigmented hair shafts \nand promotes hair follicles recovery.7 It influences \nthe function of hair follicle metabolism by inhibiting \nfollicle regression and accelerates follicle recovery.5 \nZinc also possesses antioxidant properties and has \nbeen found useful in preventing photodamage and \nreducing the incidence of malignancies. It has \nalso been demonstrated to possess antiandrogenic \nproperties as it causes modulation of 5 alpha-\nreductase type 1 and 2 activity, thus promoting hair \ngrowth.8 Zinc is also required in thyroid hormones \nsynthesis, deficiency can lead to hair loss.9 \n\n\n\nThe prevalence of zinc deficiency worldwide \nis estimated at more than 20%.10 A study of \n14770 individuals aged 3-74 years estimated the \nprevalence of zinc deficiency in the USA at 1-3%.10 \nBased on the composite nutrient composition \ndatabase, International Zinc Nutrition Consultative \nGroup (IZINCG), the estimated country-specific \nprevalence of inadequate zinc intake for Malaysia \nwas 15-25%.11 \n\n\n\nSeveral studies reported that zinc deficiency has \nassociation with alopecia.12 A case-controlled study \ndone by Seong Kil et al showed that serum zinc is \nsignificantly lower in subjects with alopecia than \nthe control group, with the mean of 87.74 \u00b1 21.2 \nug/dl and 97.94 \u00b1 21.05 ug/dl in respective group \n(p=0.002).13 Another study done by Ozturk et al \nfound that the levels of zinc in hair were significantly \nlower in the patients with AGA compared to  the \ncontrol group among Turkish (p<0.05).14\n\n\n\nNutrition affects hair condition, for instance, many \nstudies have shown that the administration of zinc \nsulfate and other multivitamins could improve hair \ngrowth.15 Unfortunately, the inconsistencies among \nthe findings in previous studies preclude definitive \nrecommendations at present. The zinc level among \npatients in Malaysia with androgenic alopecia is not \n\n\n\nknown and hence the findings from our study may \njustify incorporating zinc supplement as adjunct \ntherapy on top of the standard therapy.\n\n\n\nDue to the lack of information regarding serum \nzinc level among AGA and its association with \nthe severity of the disease in Malaysia. Thus, our \nprimary objective of this study was to evaluate the \nserum zinc levels among men in Malaysia with \nandrogenetic alopecia (AGA) and to compare with \ncontrols without AGA. Secondary objective was \nto assess the relationship of zinc deficiency with \ndisease duration and disease severity.\n \nMaterials and Methods\n\n\n\nStudy Design and Subject Recruitment\nThis was a case-control study conducted at \nDermatology Clinic of Hospital Raja Permaisuri \nBainun, Perak, Malaysia from September 2019 to \nDecember 2019. Male subjects aged 18 years old \nand above diagnosed with androgenetic alopecia \n(AGA) were included using convenient sampling. \nThe diagnosis of androgenetic alopecia was based \non the progression of hair loss, family history of \nhair thinning, visual confirmation of a receding \nfrontal hairline, and the presence of thin and short \nhairs in the frontal area and vertex. The assessment \nof the AGA severity was performed by investigators \nusing the Norwood-Hamilton classification.16  \nSubjects were then categorized into mild (I and II), \nmoderate (IIA, III, IIIA and IV), and severe (IVA, \nV, VA, VI and VII) to facilitate analysis.17 Subjects \ntaking supplements which may alter zinc level, \nmalabsorption disorders (e.g.Inflammatory bowel \ndisease, short gut syndrome, bariatric surgery) \nand or previously diagnosed with any disease \nassociated with zinc deficiency (e.g. acrodermatitis \nenteropathica) were excluded. Other causes of \nhair loss were assessed and ruled out (e.g. telogen \neffluvium, anagen effluvium and alopecia areata etc). \nSubjects in the control arm were selected randomly \namong patients and hospital staffs without alopecia. \nControl group subject were assessed clinically \nwith detailed history and thorough examination. \nAny subjects with early signs of AGA e.g.frontal \nrecession were excluded. The controls were age \nand sex matched. Patient\u2019s data collection form \nwas utilized to gather demographic data, significant \nfamily history, duration of the disease, presence of \nautoimmune diseases, if any, smoking, drinking \nhabits and dietary restrictions.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n45\n\n\n\nSerum Zinc Sampling and Analysis\n5 milliliters (mls) of random venous blood were \nobtained using lithium heparin tube from all \nsubjects. The estimation of serum zinc was done by \natomic absorption spectroscopy technique (AAS), \nthe flame conditions were fixed as recommended \nby instrument manufacturer, with wavelength of \n213.9nm using Argon as fuel, lamp current setting \nat 440mA at variable lamp position. The values \nobtained were used as continuous variables with the \nnormal reference range of 70-150 ug/dl.18,19  Serum \nzinc were also categorized into normal \u226570 ug/dl \nand deficient <70 ug/dl. Serum zinc levels of the \nAGA cohort were compared with the controls and \ncorrelated with parameters as shown in the results.\n\n\n\nSample Size Calculations\nThe sample size of this study was calculated \nbased on the case-control study carried out by \nSeong Kil et al on Analysis of Serum Zinc and \nCopper Concentration in Hair Loss.13 Calculation \nwas performed using PS Power and sample size \ncalculations software Version 3.0, January 2009. \nThe sample size calculated was 70 subjects (35 \nsubjects with androgenetic alopecia and 35 subjects \nin the control group).\n\n\n\nData Analysis\nDescriptive statistics was presented as counts and \npercentages for categorical variables. All data was \ntested for normality using the Shapiro-Wilk test. \nNon- parametric data was expressed as median \nwith interquartile range (IQR), parametric data was \nexpressed in mean with standard deviation (SD). A p \nvalue <0.05 is considered as statistically significant. \nMann-Whitney test was used to compare the \ndifference in zinc level between AGA and healthy \ncontrols. The relationship of zinc deficiency with \ndisease severity was analyzed by using Kruskal \nWallis H test. The correlation of disease duration \n(continuous data) and the level of zinc deficiency \n(categorical data) was analyzed by using Spearman\u2019s \nrank order correlation test.\n\n\n\nEthical Approval\nThis study was registered with the National Medical \nResearch Registry (NMRR-19-401-46873). Ethical \napproval for the study was obtained from the \nMedical Research and Ethics Committee, Ministry \nof Health, Malaysia.\n\n\n\nResults\nTable 1 shows the demographic and clinical \n\n\n\ncharacteristics of subjects with AGA and controls. \nA total of 70 subjects were recruited in the study: \n35 subjects in the AGA group and 35 subjects in the \ncontrol group. The mean age of the patients with \nAGA and controls was comparable with 45.71 \u00b1 \n12.78 ug/dl, and 45.69 \u00b1 12.71 ug/dl respectively. \nThere is no significant difference between the \ntwo arms in terms of, body mass index, ethnicity, \neducation levels, smoking and drinking habits and \ndiet. There is a higher incidence of autoimmune \ndiseases in AGA arm, two of the AGA subjects had \nhypothyroidism. (refer table 1)\n\n\n\nThe median serum zinc was lower in AGA group \n(74.46 ug/dl; IQR 17.17) compared to the control \ngroup (80.37 ug/dl; IQR 17.70). Although the \nmedian of serum zinc level is lower in AGA \ngroup than control group, there is no statistically \nsignificant difference of zinc level between both \ngroups (U=596, p=0.846). 42.9% (n=15) of the \nsubjects in AGA group have zinc level less than 70 \nug/dl while 31.4% (n=11) subjects in control group \nhave low serum zinc level, however the difference is \nnot statistically significant (p=1.0). (Table 2)\n\n\n\nThe mean disease duration among AGA patients \nis 14.71 \u00b1 9.63 years. In term of disease severity, \n48.6% have severe disease, 40% have moderate \ndisease and the remaining 11.4% have mild disease. \nThe relationship between serum zinc level and \nAGA severity was examined using Kruskal Wallis \nH test, as the distribution of serum zinc level is not \nnormal. Statistical analysis showed that there is \nno statistically significant difference of zinc level \nbetween patients with different disease severity \n(H=0.927, p=0.629). (refer figure 1) In terms of the \nrelationship between disease duration and serum \nzinc level, Spearman\u2019s rank order correlation test \nwas utilised, it showed no statistically significant \nrelationship between AGA disease duration and \nzinc level (rs=-0.022, p=0.901). (refer figure 2)\n\n\n\nFurther sub-analyses show that serum zinc was \nnot affected by BMI, smoking and drinking habits. \nOlder age is not associated with lower serum zinc \nlevels. Association of zinc deficiency and vegetarian \ndiet was unable to assess in this study due to small \nnumbers of vegetarian in the disease group and none \nwere in the control group. (refer table 3)\n\n\n\nDiscussion\nThe argument that zinc deficiency is a risk factor \nfor hair loss is questionable. Numerous studies \nhave been carried out in the past to evaluate zinc \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46\n\n\n\nand AGA. So far, there is no study done in Malaysia \nto evaluate the role of zinc level and alopecia. The \nexact mechanism of zinc deficiency and alopecia \nis not fully understood. A potential explanation \nwas dysregulation of zinc-related metalloenzymes, \nas zinc is known to accelerate  hair growth and \ninhibiting follicle regression.5 \n\n\n\nIn the present study, we found lower median \nserum zinc among AGA subjects in comparison \nto the controls, with the median zinc of 74.46 \nug/dl (IQR17.17) and 80.37 ug/dl (IQR17.70) \nrespectively. Although the difference was not \nstatistically significant, our finding showed findings \nconsistent with the case-control study done by Kil \net al, recruiting 312 subjects with non-scarring \nalopecia, showing that serum zinc is significantly \nlower than the control group, with the mean of 87.74 \n\u00b1 21.2 ug/dl and 97.94 \u00b1 21.05 ug/dl in respective \ngroup.13 A study in Thailand by Aiempanakit et al \nrevealed significantly lower mean plasma zinc levels \namong both female and male AGA patients than the \ncontrol group, with the mean of 56.63 ug/dl (11.44 \nSD) and 63.47 ug/dl (11.10SD) in the respectively \ngroup (p=0.002).20 Sub-analysis in the same study \nalso showed lower zinc among male AGA patients \ncompared to the controls although it was not \nstatistically significant (p=0.09).20 A recent case \ncontrol study in Egypt involving 60 AGA subjects \nnoted serum zinc was significantly lower compared \nto controls, with the mean of 60.26 \u00b1 10.81 ug/dl) \nand 80.8 \u00b1 6.47 ug/dl respectively (p=0.01).21 A \ncase control study by Dhaher et al in Iran showed \nthat the mean of serum zinc concentration level in \nthe women with AGA was significantly lower than \nthat observed in the control group (65.6 \u00b1 14.2 \u03bcg/\ndl, 128.4 \u00b1 41.4 \u03bcg/dl, respectively) (p<0.05).22 \n\n\n\nIn our study, 42.9% (n=15) subjects in AGA group \nhad zinc level deficiency (<70 ug/dl) while 31.4% \n(n=11) subjects in control group had zinc deficiency. \nHowever, the ratio of patients with low serum \nzinc concentration was not statistically significant \n(p=1.0). Kil et al revealed that serum zinc was \nsignificantly lower in non-scarring alopecia group \nthan in the control group with the mean serum \nzinc of 84.33 \u00b1 22.88 \u03bcg/dl and 97.94 \u00b1 21.05 \u03bcg/\ndl respectively (p<0.03).13 However, patients with \nserum zinc concentration lower than 70 \u03bcg/dl was \nonly significantly in the AA group.13 Our study also \nshowed lower median serum zinc concentration \namong AGA group but the median serum zinc still \nfalls within the normal range (\u226570 ug/dl). \n\n\n\nAlthough we expected that zinc levels correlate \nwith the severity of alopecia, but in the present \nstudy, we were unable to demonstrate significant \ncorrelation of  serum zinc level and the disease \nseverity (p=0.629, H=0.927) and disease duration \n(p=0.901, rs=-0.022). Dhaher et al, a case control \nstudy estimating zinc among women with AGA in \nIraq also showed no significant correlation between \nboth serum zinc level and disease severity.22 \nAnother study by El-Esawy et al also showed a \nnon-significant relation between AGA severity and  \nserum zinc level (p=0.485).21\n\n\n\nOur present study did not attempt to measure zinc \nconcentration in the hair. Hematological analysis \nusing blood sample has been commonly used to \ndetermine status of trace elements in the body.23 The \nserum level shows current or short-term body status \nand it tends to fluctuate.23 Plasma zinc represents \nonly 0.1% of total zinc stores, but its concentration \nis tightly regulated within a range of approximately \n10-15mmol/l. This concentration is often maintained \ndespite fluctuations in zinc intake, unless the changes \nin zinc intake are severe or prolonged or both.10 \nHair zinc level possibly represents a depot for trace \nelements and accumulate in hair and possibly more \nsensitive and more precise.10 For instance, there \nwere studies measuring hair zinc level carried out \nin the past. Ozturk et al found that hair zinc level \nwas significantly lower in AGA group (p<0.05) \neven though they were not able to demonstrate a \nsignificant difference in serum zinc levels among \nTurkish with AGA compared to controls.14\n\n\n\nNumerus studies showed that administration of zinc \nsulfate and other multivitamins could improve hair \ngrowth. A study by Siavash et al in Iran showed that \nconcomitant use of oral zinc sulfate and pantothenic \nacid as pulse therapy is effective to increase hair \ncount and hair thickness in women with alopecia.24  \nIn a randomized-controlled clinical study by \nBerger in AGA, a considerable hair growth was \nobserved with topical zinc pyrithione 1% solution \nin androgenic alopecia.25 In Korea, Hoon et al \nevaluated therapeutic effects of oral zinc gluconate \n50mg/day supplementation for 12 weeks in alopecia \nareata patients with low serum zinc level. It was \nshown that 9 (66.7%) out of 15 subjects had positive \ntherapeutic effects after therapy.26 After the 12-week \ntherapy, the serum zinc levels increased significantly \nfrom 56.9 ug/dl to 84.5 ug/dl (p=0.002).26\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n47\n\n\n\nTable 1. Demographic and clinical characteristics of subjects with AGA and control (n=70)\n\n\n\nTable 2. Comparison of serum zinc levels between AGA cohort and controls.\n\n\n\nFigure 1. Correlation between Serum Zinc and disease severity\n\n\n\nDemographic\nAGA (Case), n=35 Control, n=35\n\n\n\np value\nn (%) n (%)\n\n\n\nAge (in years) 20-34 7 (20.0) 7 (20.0)\n\n\n\n0.986a35-49 16 (47.7) 16 (47.7)\n50-64 10 (28.6) 9 (25.7)\n65 and above 2 (5.71) 7 (20.0)\n\n\n\nEthnicity Malay 15 (42.9) 14 (40.0)\n0.879bChinese 14 (40.0) 16 (45.7)\n\n\n\nIndian   6 (17.1) 5 (14.3)\nBody Mass Index (kg/m2) Normal 9 (25.7) 9 (25.7)\n\n\n\n0.35a\n\n\n\n0.148bOverweight 11 (31.4) 18 (51.4)\nObese 15 (42.9) 8 (22.9)\n\n\n\nEducation Level Primary 1 (2.9) 4 (11.4)\n0.204cSecondary 18 (51.4) 12 (34.3)\n\n\n\nTertiary 16 (45.7) 19 (54.3)\nVegetarian Diet Yes 2 (5.7) 0 (0)\n\n\n\n0.493c\n\n\n\nNo 33 (94.3) 35 (100.0)\nSmoking Yes 13 (37.1) 7 (20.0))\n\n\n\n0.202bNo 15 (42.9) 22 (62.9)\nEx-smoker 7 (20.0) 6 (17.1)\n\n\n\nAlcohol Yes 5 (14.3) 6 (17.1)\n0.743b\n\n\n\nNo 30 (85.7) 29 (82.9)\nAutoimmune Disease Yes 2 (5.7) 0 (0)\n\n\n\n0.054c\n\n\n\nNo 33 (94.3) 35 (100.0)\n\n\n\nSerum Zinc Case \n(n=35)\n\n\n\nControl \n(n=35) p value \n\n\n\nZinc level in ug/dl Median (IQR) 74.46 (17.17) 80.37 (17.70) U=596a\n\n\n\np=0.846\nNormal (\u226570 ug/dl)\nDeficient (<70 ug/dl)\n\n\n\n20 (57.1)\n15 (42.9)\n\n\n\n24 (68.6)\n11 (31.4) p=1.000b\n\n\n\naMann-Whitney U test; bChi-Square test; cFisher\u2019s exact test\n\n\n\naKruskal Wallis H test; bFisher\u2019s exact test\n\n\n\n*Kruskal Wallis H test\n\n\n\nTable 2. Comparison of serum zinc levels between AGA cohort and controls\n\n\n\naKruskal Wallis H test; bFisher\u2019s exact test\n\n\n\nFigure 1. Correlation between Serum Zinc and disease severity \n\n\n\n \n*Kruskal Wallis H test\n\n\n\nSerum Zinc Case \n(n=35)\n\n\n\nControl \n(n=35)\n\n\n\nP value \n\n\n\nZinc level in ug/dl\nMedian (IQR) 74.46 (17.17) 80.37 (17.70) U = 596a\n\n\n\np = 0.846\n\n\n\nNormal (\u2265 70ug/dl)\nDeficient (< 70ug/dl)\n\n\n\n20 (57.1)\n15 (42.9)\n\n\n\n24 (68.6)\n11 (31.4) \n\n\n\np = 1.000b\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48\n\n\n\nFigure 2. Correlation between Serum zinc level and disease duration\n\n\n\n*Spearman\u2019s rank order correlation test\n\n\n\nFigure 2. Correlation between Serum zinc level and disease duration \n\n\n\n*Spearman\u2019s rank order correlation test\n\n\n\nTable 3. Association between socio-demographic factors and levels of serum zinc among AGA \ngroup and control group\n\n\n\nFactors\n\n\n\nLevel of Serum Zinc\nAGA (Case)\n\n\n\nn =35\nControl\nn =35\n\n\n\nn Median \n(IQR) ug/dl\n\n\n\nP value n Median\n(IQR) ug/dl\n\n\n\nP value\n\n\n\nAge in years\n20-34\n35-49\n50-64\n65 and above\n\n\n\n7\n16\n10\n2\n\n\n\n69.93 (17.76)\n81.19 (13.26)\n73.00 (20.28)\n90.29 (2.25)\n\n\n\n0.135a 7\n16\n9\n3\n\n\n\n91.14 (29.44)\n71.30 (9.86)\n74.46 (16.17)\n82.13 (14.30)\n\n\n\n0.149a\n\n\n\nEthnicity\nMalay\nChinese\nIndian   \n\n\n\n15\n14\n6\n\n\n\n72.94 (18.05)\n83.80 (10.68)\n72.71 (19.85)\n\n\n\n0.100a\n\n\n\n14\n16\n5\n\n\n\n74.36 (17.19)\n73.45 (18.04)\n79.78 (47.63)\n\n\n\n0.466a\n\n\n\nTable 3. Association between socio-demographic factors and levels of serum zinc among AGA group and control group\n\n\n\nFactors\n\n\n\nLevel of Serum Zinc\nAGA (Case)\n\n\n\nn =35\nControl\nn =35\n\n\n\nn Median (IQR) ug/dl P value n Median (IQR) ug/dl p value\nAge (in years) 20-34 7 69.93 (17.76)\n\n\n\n0.135a\n\n\n\n7 91.14 (29.44) 0.149a\n\n\n\n35-49 16 81.19 (13.26) 16 71.30 (9.86)\n50-64 10 73.00 (20.28) 9 74.46 (16.17)\n65 and above 2 90.29 (2.25) 3 82.13 (14.30)\n\n\n\nEthnicity Malay 15 72.94 (18.05)\n\n\n\n0.100a\n\n\n\n14 74.36 (17.19)\n\n\n\n0.466a\nChinese 14 83.80 (10.68) 16 73.45 (18.04)\nIndian   6 72.71 (19.85) 5 79.78 (47.63)\nOthers 0 0 (0)\n\n\n\nBody Mass Index (kg/m2) Normal 9 72.94 (21.39)\n0.908a\n\n\n\n9 73.48 (23.94)\n0.980aOverweight 11 78.70 (14.61) 18 74.87 (15.97)\n\n\n\nObese 15 81.05 (21.29) 8 76.39 (20.23)\nVegetarian Diet Yes 2 74.69 (14.78)\n\n\n\n0.670b 0 0 (0)\nNA\n\n\n\nNo 33 80.37 (17.42) 35 74.46 (17.17)\nSmoking Yes 13 75.81 (17.58)\n\n\n\n0.866a\n\n\n\n7 82.13 (25.23)\n0.712aNo 15 81.67 (20.44) 22 75.34 (22.14)\n\n\n\nEx-smoker 7 79.07 (15.52) 6 73.18 (5.78)\nAlcohol Yes 5 87.74 (10.10)\n\n\n\n0.06b 6 69.71 (20.83)\n0.126b\n\n\n\nNo 30 78.88 (17.17) 29 75.28 (19.85)\naKruskal Wallis H test; bMann-Whitney U test\n\n\n\nThe major limitation of this study is a limited \nsample size. It is a single-center and hospital-based \nstudy and may not be truly representative of the \nwhole of Malaysia population. Larger trials are \nnecessary to validate the observation of lower zinc \nlevel among patients with AGA and as well as to \nclarify the advantage of zinc supplementation as \nadjunct treatment.\n\n\n\nConclusion\nIn summary, our study showed that zinc level was \nlower in the AGA group compared to the control \ngroup. However, there was no statistical difference \nbetween the two groups. There was no correlation \nbetween serum zinc level with severity of alopecia \nand disease duration. At present, evidence to \nsupport the use of zinc as supplement in AGA is \nstill lacking. Further studies are required in the \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n49\n\n\n\nfuture to justify the need for serum and hair zinc \nlevels monitoring and zinc supplementation in the \ntreatment of alopecia.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflicts of interest to declare.\n\n\n\nAcknowledgement\nThis study was funded with a research grant from \nthe Dermatological Society of Malaysia. We would \nlike to thank all the staffs from the Department of \nDermatology in Hospital Raja Permaisuri Bainun, \nIpoh and our Director General of Health Malaysia \nfor the permission to publish this study.\n\n\n\nReferences\n\n\n\n1. Blume-Peytavi U, Blumeyer A, Tosti A, Finner A, Marmol \nV, Trakatelli M et al. S1 guideline for diagnostic evaluation \nin androgenetic alopecia in men, women and adolescents. \nBr J Dermatol 2011;164:5-15.\n\n\n\n2. Lee WS, Lee HJ. Characteristics of androgenetic alopecia \nin asian. Ann Dermatol 2012;24:243-52.\n\n\n\n3. Tang PH, Chia HP, Cheong LL, Koh D. A community \nstudy of male androgenetic alopecia in Bishan, Singapore. \nSingapore Med J 2000;41:202-5.\n\n\n\n4. Mysore V, Parthasaradhi A, Kharkar RD, Ghoshal AK, \nGanjoo A, Ravichandran G et al. Expert consensus on \nthe management of Androgenetic Alopecia in India. Int J \nTrichology 2019;11:101-6.\n\n\n\n5. Maywald M, Wessels I, Rink L. Zinc Signals and Immunity. \nInt J Mol Sci 2017;18:2222.\n\n\n\n6. Kambe T, Tsuji T, Hashimoto A, Itsumura N. The \nPhysiological, Biochemical, and Molecular Roles of \nZinc Transporters in Zinc Homeostasis and Metabolism. \nPhysiol Rev 2015;95:749-84.\n\n\n\n7. Plonka PM, Handjiski B, Popik M, Michalczyk D, Paus R. \nZinc as an ambivalent but potent modulator of murine hair \ngrowth in vivo- preliminary observations. Exp Dermatol \n2005;14:844-53.\n\n\n\n8. Bibi Nitzan Y, Cohen AD. Zinc in skin pathology and care. \nJ Dermatolog Treat 2006;17:205-10.\n\n\n\n9. Thompson JM, Mirza MA, Park MK, Qureshi AA, Cho E. \nThe Role of Micronutrients in Alopecia Areata: A Review. \nAm J Clin Dermatol 2017;18:663-79.\n\n\n\n10. Tuerk MJ, Fazel N. Zinc deficiency. Curr Opin \nGastroenterol 2009;25:136-43.\n\n\n\n11. Wessells KR, Brown KH. Estimating the global prevalence \nof zinc deficiency: results based on zinc availability in \nnational food supplies and the prevalence of stunting. PloS \nONE 2012;7:e50568.\n\n\n\n12. Finner AM. Nutrition and hair: deficiencies and \nsupplements. Dermatol Clin 2013;31:167-72.\n\n\n\n13. Kil MS, Kim CW, Kim SS. Analysis of serum zinc \nand copper concentrations in hair loss. Ann dermatol \n2013;25:405-9.\n\n\n\n14. Ozturk P, Kurutas E, Ataseven A, Dokur N, Gumusalan Y, \nGorur A et al. BMI and levels of zinc, copper in hair, serum \nand urine of Turkish male patients with androgenetic \nalopecia. J Trace Elem Med Biol 2014;28:266-70.\n\n\n\n15. Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc \ntherapy in dermatology: a review. Dermatol Res Pract \n\n\n\n2014;2014:709152.\n16. Gupta M, Mysore V. Classifications of Patterned Hair \n\n\n\nLoss: A Review. J Cutan Aesthet Surg 2016;9:3-12.\n17. Roshidah B, Gangaram HB. Consensus statement on the \n\n\n\nmanagement of Androgenetic Alopecia. Clinical Practice \nGuideline, Malaysia 2003.p5\n\n\n\n18. Gibson RS, Hess SY, Hotz C, Brown KH. Indicators of zinc \nstatus at the population level: a review of the evidence. Br \nJ Nutr 2008;99(3):S14-23.\n\n\n\n19. Hotz C, Peerson JM, Brown KH. Suggested lower cutoffs \nof serum zinc concentrations for assessing zinc status: \nreanalysis of the second National Health and Nutrition \nExamination Survey data (1976-1980). Am J Clin Nutr \n2003;78:756-64.\n\n\n\n20. Aiempanakit K, Jandee S, Chiratikarnwong K, \nChuaprapaisilp T, Auepemkiate S. Low plasma zinc levels \nin androgenetic alopecia. Indian J Dermatol Venereol \nLeprol 2017;83:741.\n\n\n\n21. El-Esawy FM, Hussein MS, Ibrahim Mansour A. Serum \nbiotin and zinc in male androgenetic alopecia. J Cosmet \nDermatol 2019. doi: 10.1111/jocd.12865.\n\n\n\n22. Dhaher SA, Yacoub AA, Jacob AA. Estimation of Zinc \nand Iron Levels in the Serum and Hair of Women with \nAndrogenetic Alopecia: Case-control Study. Indian J \nDermatol 2018;63:369-74.\n\n\n\n23. Hess SY, Peerson JM, King JC, Brown KH. Use of serum \nzinc concentration as an indicator of population zinc status. \nFood Nutr Bull 2007;28:S403-29.\n\n\n\n24. Siavash M, Tavakoli F, Mokhtari F. Comparing the Effects \nof Zinc Sulfate, Calcium Pantothenate, Their Combination \nand Minoxidil Solution Regimens on Controlling Hair \nLoss in Women: A Randomized Controlled Trial. J Res \nPharm Pract 2017;6:89-93.\n\n\n\n25. Berger RS, Fu JL, Smiles KA, Turner CB, Schnell BM, \nWerchowski KM et al. The effects of minoxidil, 1 % \npyrithione zinc and a combination of both on hair density: a \nrandomized controlled trial. Br J Dermatol 2003;149:354-\n62.\n\n\n\n26. Park H, Kim CW, Kim SS, Park CW. The therapeutic \neffect and the changed serum zinc level after zinc \nsupplementation in alopecia areata patients who had a low \nserum zinc level. Ann dermatol 2009;21:142-6.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50\n\n\n\nORIGINAL ARTICLE\n\n\n\nAssociation between Vitiligo and Neutrophil-To-Lymphocyte Ratio in \nDr Sardjito General Hospital, Yogyakarta, Indonesia         \n\n\n\nNiken Trisnowati, PhD, Angela Mistralina Lukito, MD, Yohanes Widodo Wirohadidjojo, PhD\n\n\n\nDepartment of Dermatology and Venereology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, \nDr. Sardjito General Hospital, Yogyakarta, Indonesia\n\n\n\nAbstract\nIntroduction\nVitiligo is an acquired depigmenting disorder, characterized by circumscribed hypomelanosis of the \nskin and hair. Vitiligo is presumed to be associated with systemic inflammation implied in the presence \nof metabolic syndrome in vitiligo.  This study aimed to investigate the association between vitiligo \nand neutrophil-to-lymphocyte ratio (NLR) as a biomarker of systemic inflammation and correlations \nbetween vitiligo disease severity and NLR. \n\n\n\nMethods\nThis case-control study involved 24 patients with vitiligo and 24 healthy individuals as control group.  \nInclusion criteria of the vitiligo group were: age 18-40 years-old, having vitiligo for at least 6 months, \nwhereas exclusion criteria were: receiving corticosteroids or other immunosuppressant drugs, having \ndiabetes mellitus or other systemic diseases. In both groups NLR was calculated, whereas in the \nvitiligo group Vitiligo Area Scoring Index (VASI) and disease duration were examined.\n\n\n\nResults\nNLR values were higher in the vitiligo group than those in the control group, however the difference \nwas not statistically significant (p>0.05).  Correlation between VASI and NLR showed a weak \ncorrelation, as well as correlation between duration of disease and NLR, but they were not statistically \nsignificant (p>0.05).\n\n\n\nDiscussion\nThe findings of this study possibly suggest an association between vitiligo and NLR, although it was \nnot statistically significant.  The relatively small sample size may have contributed to the insignificant \nstatistical results. \n\n\n\nConclusion\nVitiligo was possibly associated with systemic inflammation and NLR could be utilized as a biomarker \nof systemic inflammation in vitiligo.\n\n\n\nKey words: Vitiligo, non-segmental vitiligo, neutrophil-to-lymphocyte ratio, systemic inflammation\n\n\n\nIntroduction\nVitiligo is an acquired depigmenting disorder \ncharacterized by circumscribed hypomelanosis \nof the skin and hair, resulting in psychological \nproblems and decreased quality of life particularly \nin racial or ethnic groups with darker skin.1\u20133 \n\n\n\nCorresponding Author\nDr Niken Trisnowati\nDepartment of Dermatology and Venereology, \nFaculty of Medicine, Public Health and Nursing, \nUniversitas Gadjah Mada, \nDr Sardjito General Hospital, \n55281 Yogyakarta, Indonesia.\nEmail: nikentris@ugm.ac.id\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n51\n\n\n\nPrevalence of vitiligo varies among countries, with \n0.05% (claimed-based prevalence) in the United \nStates of America4  and 8.8% in India,5 whereas \nworldwide prevalence is estimated to be 0.5-1%.6 \nThe prevalence of vitiligo in Indonesia countrywide \nis not known, but that in Dr Sardjito General \nHospital, Yogyakarta, Indonesia from 2015-2018, it \nwas around 1%.\n\n\n\nBased on the Vitiligo Global Issues Consensus \nConference (VGICC), vitiligo is classified \ninto vitiligo (formerly non-segmental vitiligo/\nNSV), segmental vitiligo (SV) and unclassified/\nundetermined vitiligo. Vitiligo/NSV is an umbrella \nterm for all forms of generalized vitiligo, where \nlesions are often symmetrical, increasing in size \nprogressively or during flares. In SV, depigmented \nlesions are focal or restricted to a segment of the \nskin, whereas in unclassified/undetermined vitiligo \nskin lesions are focal but do not fit a segmental \ndistribution.6  Vitiligo/NSV is more common than \nSV and has a potential lifelong evolution.7 \n \nPathogenesis of vitiligo/NSV is not completely \nunderstood, however autoimmunity is considered \nthe key mechanism in this subclass of vitiligo.7,8  \nBesides autoimmunity, several hypotheses are \nproposed to explain the pathogenesis of vitiligo/\nNSV, including the adhesion defect theory and the \nbiochemical theory.8 Vitiligo/NSV is thought to be \nassociated with systemic abnormalities implied in \nthe presence of metabolic syndrome in vitiligo.\n \nNeutrophil-to-lymphocyte ratio (NLR) is a recently \nfound systemic inflammatory parameter, which is \ncalculated by dividing the number of neutrophils by \nthe number of lymphocytes.9 It is a simple biomarker \nderived from a patient\u2019s complete blood count. \nSome studies have found that abnormal NLR is \nassociated with autoimmune diseases, for example \npsoriasis and systemic lupus erythematosus.10 \n\n\n\nResearch exploring associations between vitiligo \nand NLR is still limited.  This study aimed to \ninvestigate the association between vitiligo and \nNLR (as a biomarker of systemic inflammation) \nand correlation between vitiligo disease severity, \nrepresented by Vitiligo Area Scoring Index (VASI) \nand disease duration, and NLR.\n\n\n\nMaterials and Methods\nThis case-control study was conducted at the \noutpatient Dermatology clinic of  Dr Sardjito \nGeneral Hospital, Yogyakarta, Indonesia. Twenty-\n\n\n\nfour consecutive patients with vitiligo were recruited \nas the case group with inclusion criteria were: \npatients with age 18-40 years-old, having vitiligo \nfor at least 6 months.  Exclusion criteria of the case \ngroup were: patients receiving corticosteroids or \nother immunosuppressant drugs, having diabetes \nmellitus or other systemic diseases.  Twenty-four \nhealthy individuals with age 18-40 years-old were \nrecruited as the control groups.  The participants \nin both groups were matched according to age and \ngender.  This study was conducted in July-August \n2019.\n\n\n\nDemographic characteristics were recorded from \nall participants, including gender and age.  A total \nof 5 ml of peripheral blood samples was collected \nfrom all participants to examine the complete blood \ncount (including the number of neutrophils and \nlymphocytes). NLR is calculated by dividing the \nnumber of neutrophils by the number of lymphocytes. \nIn the case group, duration of disease and VASI \nwere examined. VASI is a validated assessment \ntool used to measure the degree of depigmentation \nof vitiligo.  VASI was measured as follows: in each \nbody region, VASI was calculated by the product of \nthe area of vitiligo in hand units (1% per unit) and \nthe extent of depigmentation within each hand unit-\nmeasured patch (possible values of 0, 10%, 25%, \n50%, 75%, 90% or 100%).  Subsequently, VASI of \nthe whole body was calculated using the following \nformula (possible range 0-100):11 VASI = \u2211 all body \nsite hand units x residual depigmentation\n\n\n\nNLR values of the vitiligo and the control groups \nwere compared using student\u2019s t test. Correlation \nbetween duration of disease and NLR was analyzed \nusing Pearson correlation coefficient, as well as \ncorrelation between VASI and NLR. P-value of \n<0.05 was considered statistically significant. \nStatistical analyses were performed using SPSS \nstatistics version 26 software (IBM Corp., Armonk, \nNY).\n\n\n\nEthical clearance of this study was obtained from \nthe Institutional Review Board of Faculty of \nMedicine, Public Health and Nursing, Universitas \nGadjah Mada, Yogyakarta, Indonesia.\n\n\n\nResults\nTwenty-four patients with vitiligo and 24 healthy \nparticipants were enrolled in this study.  Distribution \nof demographic, clinical and laboratory results of \nvitiligo and normal participants were presented in \nTable 1.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52\n\n\n\nDiscussion\nThe findings of this study possibly suggest that \nthere is an association between vitiligo and NLR, \nwhich could be seen from the higher NLR values \nin the vitiligo group compared to that of the control \ngroup, even though the difference is not statistically \nsignificant. The results tend to show a correlation \nbetween vitiligo disease severity, represented by \nVASI score or disease duration, and NLR, although \nthey are also not statistically significant.\n \nRecently, there were several studies utilizing NLR \nas biomarker of systemic inflammation in vitiligo.  \nSolak et al. in 2017 showed that NLR values and \nserum C-reactive protein levels were significantly \nhigher in vitiligo/NSV patients who had generalized \nvitiligo compared with those with localized vitiligo \nand controls.9 Similar results were also observed \nby Karagun in 2019 who compared NLR values in \npatients with vitiligo/NSV and controls.12 However, \nanother study comparing NLR values in vitiligo/\n\n\n\nNSV and control groups found no significant \ndifference between them.13 \n\n\n\nNLR is an easy to calculate biomarker of systemic \ninflammation. NLR has been shown to be a potential \npredictor of systemic inflammation in internal \ndiseases.14,15 NLR is also associated with disease \nactivity in some immune disorders, including \npsoriasis,16 systemic lupus erythematosus17 and \nBehcet\u2019s disease.18 There is strong evidence that \nvitiligo is an autoimmune disease, involving both \nhumoral and cellular immunities. Furthermore, \nit has been found that several proinflammatory \ncytokines, including interleukin (IL)-6, IL-8, tumor \nnecrosis factor (TNF)-\u0251 and IL-17 are implicated \nin vitiligo.19-21 IL-8 in particular, is involved in \nattracting cytokines to neutrophils.19 Hence, the \nchronic pro-inflammatory environment in vitiligo \nmight result in increased numbers of neutrophils \nand subsequently cause increased inflammation and \ntissue injury.  \n\n\n\nThere is increasing evidence that vitiligo may \nbe associated with metabolic syndrome which \nis a systemic disturbance. It has been known \nthat proinflammatory cytokines (TNF-\u0251, IL-1, \nIL-6) and other inflammatory factors in vitiligo \ncontribute to insulin resistance and other metabolic \ncomplications.22 One study found that insulin \nresistance and lipid profile disturbance were \npresent in patients with vitiligo.23 Furthermore, it \nwas shown that decreased number of melanocytes \nin adipose tissue in vitiligo caused decreased anti-\ninflammatory reactions and decreased reduction or \nbinding with radical oxygen species.24 These factors \ncontribute to produce systemic inflammation which \nhas the potential to cause metabolic syndrome \ncharacterized by increased insulin resistance, \ndecreased high density lipids (HDL) and increased \nlow density lipids (LDL)/HDL ratio.  The findings of \nour study might support the hypothesis that vitiligo \nmay be associated with systemic inflammation.  \n \nWe have to mention limitations in our study, mainly \nrelatively small sample size, which might explain the \ninsignificant statistical results observed.  In future \nresearch, we might consider dividing the vitiligo/\nNSV participants into those with more generalized \nand localized types to examine whether different \ndistribution of vitiligo lesion may affect the NLR.  It \nis recommended to measure clinical and biochemical \nmanifestations of the metabolic syndrome, such \nas blood pressure, waist circumference, insulin \nresistance, serum lipids, etc., in order to determine \n\n\n\nTable 1. Distribution of demographic, clinical and laboratory \nresults of the vitiligo and normal participants\n\n\n\nTable 2. Correlation between VASI score and disease duration \nand NLR\n\n\n\nIn the vitiligo group, there were slightly more \nfemale participants than male participants (13 and \n11 participants, respectively). Median of VASI \nwas 2.6 \u00b1 2.9, whereas mean of disease duration \nwas 43.3 \u00b1 23.7 months.  Results showed the NLR \nvalues were higher in the vitiligo group than those \nin the control group, however this finding was \nnot statistically significant (p>0.05). Correlation \nbetween VASI and NLR showed a weak correlation, \nas well as correlation between duration of disease \nand NLR, but they were not statistically significant \n(p>0.05), as presented in Table 2. \n\n\n\nVitiligo Controls p-value\nGender, n (%)\nFemale\nMale\nAge, mean (SD)\nNLR, mean (SD)\nVASI score, median (IR)\nDuration (months), mean (SD)\n\n\n\n13 (54.2)\n11 (45.8)\n\n\n\n40.8 (14.1)\n2.4 (1.5)\n2.6 (2.9)\n\n\n\n43.3 (23.7)\n\n\n\n13 (54.2)\n11 (45.8)\n\n\n\n40.2 (14.2)\n2.2 (0.7)\n\n\n\n-\n-\n\n\n\n0.65\n\n\n\nr p-value\nVASI score-NLR -0.02 0.93\ndisease duration-NLR 0.26 0.22\n\n\n\nSD standard of deviation; IR interquartile range; NLR neutrophil-to-\nlymphocyte ratio; VASI Vitiligo Area Scoring Index\n\n\n\nr coefficient correlation; NLR neutrophil-to-lymphocyte ratio; VASI \nVitiligo Area Scoring Index\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n53\n\n\n\nthe existence of metabolic syndrome in the patients \nwith vitiligo.\n\n\n\nConclusion\nNevertheless, our study findings may add to other \nstudies exploring NLR as a biomarker of systemic \ninflammation in vitiligo. The presence of systemic \ninflammation and metabolic syndrome in vitiligo \nrequires more investigation. As the growing evidence \nbecome clear, therapies reducing inflammation are \nimportant in patients with vitiligo particularly to \nprevent metabolic syndrome.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil.\n\n\n\nReferences\n\n\n\n1. Yaghoobi R, Omidian M, Bagherani N. Vitiligo: A review \nof the published work. J Dermatol 2011;38:419-31. \n\n\n\n2. Mattoo SK, Handa S, Kaur I, Gupta N, Malhotra R. \nPsychiatric morbidity in vitiligo: Prevalence and correlates \nin India. J Eur Acad Dermatol Venereol 2002;16:573-8. \n\n\n\n3. Grimes PE, Miller MM. Vitiligo: Patient stories, self-\nesteem, and the psychological burden of disease. Int J \nWomens Dermatol 2018;4:32-7. \n\n\n\n4. Lim HW, Collins SAB, Resneck JS, Bolognia JL, Hodge \nJA, Rohrer TA et al. The burden of skin disease in the \nUnited States. J Am Acad Dermatol 2017;76:958-72.e2. \n\n\n\n5. Vora RV, Patel BB, Chaudhary AH, Mehta MJ, Pilani AP. \nA clinical study of vitiligo in a rural set up of Gujarat. \nIndian J Community Med 2014;39:143-6. \n\n\n\n6. Ezzedine K, Lim HW, Suzuki T, Katayama I, Hamzavi \nI, Lan CC et al. Revised classification/nomenclature of \nvitiligo and related issues: the Vitiligo Global Issues \nConsensus Confrence. Pigment Cell Melanoma Res \n2012;25:E1-13. \n\n\n\n7. Lotti T, Gori A, Zanieri F, Colucci R, Moretti S. Vitiligo: \nnew and emerging treatments. Dermatol Ther 2008;21:110-\n7. \n\n\n\n8. Iannella G, Greco A, Didona D, Didona B, Granata G, \nManno A et al. Vitiligo: Pathogenesis, clinical variants and \ntreatment approaches. Autoimmun Rev 2016;15(4):335-\n43. \n\n\n\n9. Solak B, Dikicier BS, Cosansu NC, Erdem T. Neutrophil \nto lymphocyte ratio in patients with vitiligo. Postepy \nDermatol Alergol 2017;34:468-70. \n\n\n\n10. Hu Z, Sun Y, Guo J, Huang YL, Qin BD, Gao Q et al. Red \nblood cell distribution width and neutrophil/lymphocyte \nratio are positively correlated with disease activity in \nprimary Sj\u00f6gren\u2019s syndrome. Clin Biochem 2014;47:287-\n90.                                                         \n\n\n\n11. Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H. \nParametric modeling of narrowband UV-B phototherapy \nfor vitiligo, using a novel quantitative tool: the Vitiligo \nArea Scoring Index. Arch Dermatol 2004;140:677-83. \n\n\n\n12. Karagun E. An Investigation of the Relationship between \nInvolvement Sites in Vitiligo Patients and Autoimmune \n\n\n\nDiseases and Hematological Parameters. Int J Innov Res \nMed Sci 2019;4:570-3. \n\n\n\n13. Sarac G, Altunisik N, Sener S, Hakverdi G. Evaluation of \nchanges in neutrophil-lymphocyte ratio in patients with \nvitiligo. Ann Med Res 2019;26:1344-6.\n\n\n\n14. Afari ME, Bhat T. Neutrophil to lymphocyte ratio (NLR) \nand cardiovascular diseases: An update. Expert Rev \nCardiovasc Ther 2016;14:573-7. \n\n\n\n15. Furutate R, Ishii T, Motegi T, Hattori K, Kusunoki Y, \nGemma A et al. The neutrophil to lymphocyte ratio is \nrelated to disease severity and exacerbation in patients \nwith chronic obstructive pulmonary disease. Intern Med \n2016;55:223-9. \n\n\n\n16. Erek Toprak A, Ozlu E, Uzuncakmak TK, Yalc\u0131nkaya \nE, Sogut S, Karadag AS. Neutrophil/Lymphocyte Ratio, \nSerum Endocan, and Nesfatin-1 Levels in Patients with \nPsoriasis Vulgaris Undergoing Phototherapy Treatment. \nMed Sci Monit 2016;22:1232-7. \n\n\n\n17. Yu H, Jiang L, Yao L, Gan C, Han X, Liu R et al. \nPredictive value of the neutrophil-to-lymphocyte ratio and \nhemoglobin insystemic lupus erythematosus. Exp Ther \nMed 2018;16:1547-53. \n\n\n\n18. Alan S, Tuna S, T\u00fcrko\u011flu EB. The relation of neutrophil-\nto-lymphocyte ratio, platelet-to-lymphocyte ratio, and \nmean platelet volume with the presence and severity of \nBeh\u00e7et\u2019s syndrome. Kaohsiung J Med Sci 2015;31:626-31. \n\n\n\n19. Yu HS, Chang KL, Yu CL, Li HF, Wu MT, Wu CS et al. \nAlterations in IL-6, IL-8, GM-CSF, TNF-\u03b1, and IFN-\u03b3 \nrelease by peripheral mononuclear cells in patients with \nactive vitiligo. J Invest Dermatol 1997;108:527-9. \n\n\n\n20. Basak PY, Adiloglu AK, Ceyhan AM, Tas T, Akkaya VB. \nThe role of helper and regulatory T cells in the pathogenesis \nof vitiligo. J Am Acad Dermatol 2009;60:256-60. \n\n\n\n21. Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani \nI, Fabiani M et al. New insights into the pathogenesis \nof vitiligo: Imbalance of epidermal cytokines at sites of \nlesions. Pigment Cell Res 2002;15:87-92. \n\n\n\n22. Page S, Chandhoke V, Baranova A. Melanin and \nmelanogenesis in adipose tissue: Possible mechanisms \nfor abating oxidative stress and inflammation? Obes Rev \n2011;12(5):e21-31. \n\n\n\n23. Karadag AS, Tutal E, Ertugrul DT. Insulin resistance is \nincreased in patients with vitiligo. Acta Derm Venereol \n2011;91:541-4. \n\n\n\n24. Pietrzak A, Bartosinska J, Hercogov\u00e1 J, Lotti TM, \nChodorowska G. Metabolic syndrome in vitiligo. Dermatol \nTher 2012;25(1):S41-3.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54\n\n\n\nORIGINAL ARTICLE\n\n\n\nCutaneous Manifestations in Patients with End Stage Renal Disease \nUndergoing Hemodialysis        \n\n\n\nHarish MR, MD (DVL), Sriramanan Anandbabu, MD, Shashikumar BM, MD (DVL), Deepadarshan K, MD (DVL)\n\n\n\nDepartment of Dermatology, Mandya Institute of Medical Sciences, Mandya, Karnataka, India\n\n\n\nAbstract\nIntroduction\nEnd stage renal disease (ESRD) is a decline in the function of the kidneys that usually develops over \nmany years. At least one dermatologic condition is considered to be present in most end stage renal \ndisease patients. \n\n\n\nMethods\nThis is a prospective observational study of 83 patients in dialysis seen in Mandya Institute of \nMedical Sciences, Mandya. Detailed medical history and demographic data was obtained. A thorough \ndermatological examination was performed to note the various cutaneous manifestations seen in our \npatients.\n\n\n\nResults\nOut of 83 patients enrolled, 81 had at least one cutaneous manifestation (97.6%), 40 had at least one \nmucosal manifestation (48.2%), 72 had at least one nail change (86.7%) and 27 had at least one hair \nchange (32.5%). The most common cutaneous manifestation was xerosis with 75 patients (90.4%) \nshowing this finding. Xerostomia was the most common mucosal manifestation, seen in 25 patients \n(64.1%). Nail pallor and absent lunula were the most common nail findings, seen in 60 (83.3%) and \n35 (48.6%) patients respectively. Dry, lustreless hair was the most common hair change seen in 18 \npatients (66.7%).\n\n\n\nConclusion\nXerosis, pruritus, pigmentary changes, nail pallor, absent lunula, xerostomia and dry lustreless hairs \nwere the most common mucocutaneous manifestations in our patients. In order to reduce the morbidity \nfrom end stage renal disease specific dermatoses in dialysis patients, long term and regular follow up \nis required.\n\n\n\nKey words: : End stage renal disease, xerosis, pruritus\n\n\n\nIntroduction\nChronic kidney disease is defined as kidney damage \nor glomerular filtration rate of <60 ml/min/1.73m\u00b2 \nfor 3 months or more regardless of etiology.1 This \nis a global issue with nearly 850,000 deaths every \nyear and 15 million disability adjusted lives.2 This \nchronic kidney disease progresses to end stage renal \ndisease over a period of time. Moreover, end stage \nrenal disease patients have a high prevalence of \ncutaneous manifestations (about 50-100%) during \nthe course of their illness.3,4 It has been reported that \n\n\n\nCorresponding Author\nDr. Shashikumar BM\nOPD Room 13, RDL First Floor,\nDepartment of Dermatology,\nMIMS, Nehrunagar, Mandya, \n571401 India.\nEmail: shashikumarbm@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n55\n\n\n\nthe prevalence of end stage renal disease is around \n17.3% in India.5\n\n\n\n  \nEnd stage renal disease has complex consequences \nbecause it affects the normal functioning of multiple \norgan systems. Skin changes are a late clinical \nmanifestation of end stage renal disease. There are \ntwo groups of cutaneous manifestations of end stage \nrenal disease divided into specific and nonspecific.6 \n\n\n\nNon-specific disorders include pigmentary \ndisorders, pruritus, xerosis, acquired ichthyosis, \nand half-and-half nail. Specific disorders include \nacquired perforating dermatosis, calciphylaxis, \nbullous dermatoses, and fibrosing dermopathy of \nuremia.7\n\n\n\nMaterials and Methods\nThis prospective study was conducted in the \noutpatient Department of Dermatology at Mandya \nInstitute of Medical Sciences, a tertiary care \nhospital in Mandya after obtaining permission \nfrom Institutional Ethics Committee for a period \nof 6 months from 15th March 2020 to 15th August \n2020. During this period, 83 patients who were \nknown cases of end stage renal disease diagnosed \nat nephrology department/medical department \nwere thoroughly screened by dermatologists for \nthe evidence of any cutaneous manifestations. \nAfter taking informed consent, a thorough history \nwas taken and general examination was done. The \nfollowing were the inclusion and exclusion criteria. \nThe inclusion criteria were patients above the age \nof 18 years undergoing hemodialysis and patients \nwho were willing to participate and consent for the \nstudy. The exclusion criteria included pregnant & \nlactating women.\n\n\n\nThe patient\u2019s basic demographic data such as age, \nsex, and a detailed medical history with regard to \nduration of ESRD, duration of dialysis, duration \nof skin ailment, onset of changes with relation \nto diagnosis of ESRD and starting dialysis and \nimprovement noticed following dialysis was \nrecorded. The skin, hair, nails and mucosa were \nexamined in detail for\n\n\n\na. Specific lesions of chronic kidney disease.\nb. Presence of cutaneous infections.\nc. Associated skin lesions. \n\n\n\nThe diagnosis and clinical staging of ESRD was \nas per the National Kidney Foundation severity \nassessment criteria, and the severity of pruritus and \nxerosis was graded as mild, moderate, and severe.1,8,9 \n\n\n\nSpecific investigations like skin biopsy, culture and \nsensitivity for bacterial infections, Gram\u2019s stain, \npotassium hydroxide mount and fungal culture \nwere done where indicated, after informed consent. \nRoutine investigations for monitoring renal \nfunctions were also recorded. Serological testing \nfor HIV, Hepatitis B and C were done in all patients. \n\n\n\nData was entered in MS excel spreadsheet. \nDescriptive analysis like proportion, mean, standard \ndeviation, etc. were used. Tests to detect significant \ndifference or association like chi square test, etc \nwere used.  Data was analysed using SPSS software \nversion 20.\n\n\n\nResults\nThe basic clinic-demographic profile is shown in \nTable 1. Among 83 patients, there were 48 males \nand 35 females (M:F = 1.4:1) aged between 21 and \n83 (mean +/- SD = 52.3 + 14.6) years. The majority \nof the patients were in the 41-60 age group. The \nduration of ESRD ranged from 8 months to 216 \nmonths (18 years) with mean duration 62.1 +/- 47.7. \nMajority of patients had ESRD duration of more \nthan 5 years (43.4%). All patients had undergone \nhemodialysis for a variable period of time. The \nduration of hemodialysis ranged from 5 months to \n180 months (15 years) (mean +/- SD = 40.6 + 30.4). \n\n\n\nThe serum creatinine levels ranged from 4.7 to 20.9 \n(mg/dl) (mean +/- SD = 10.3 + 3.1). The blood urea \nlevels ranged from 39 to 287 (mg/dl) with the Mean \nand Standard deviation 116.2 + 38.9. Hemoglobin \nlevels ranged from 4.7 to 13 (mg/dl) with the Mean \nand Standard deviation of 8.3 + 1.63.\n\n\n\nTable 1. Basic clinico-demographic characteristics\n\n\n\nAge Group (Years) Female Male\n20-40 13 (65%) 7 (35%)\n41-60 13 (36.1%) 23 (63.9%)\n\n\n\n61 & above 9 (33.3%) 18 (66.7%)\nTotal 35 (42.2%) 48 (57.8%)\n\n\n\nDuration of ESRD in Months Number\n1-12 10 (12%)\n13-24 11 (13.3%)\n25-36 12 (14.5%)\n37-48 6 (7.2%)\n49-60 8 (9.6%)\n>60 36 (43.4%)\nTotal 83 (100%)\n\n\n\nDuration of Dialysis Number\n<6 months 2 (2.4%)\n\n\n\n6 months - <2 years 35 (42.2%)\n2 years - <5 years 26 (31.3%)\n\n\n\n>5 years 20 (24.1%)\nTotal 83 (100%)\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56\n\n\n\nA wide variety of etiologies were found in our \npatients (Table 2). Hypertension and Diabetes \nwere the most common causes of ESRD with \n77 (92.8%) and 38 (45.8%) patients affected \nrespectively. None of the patients were positive for \nHuman immunodeficiency virus, Hepatitis B virus \nand Hepatitis C virus. All patients were receiving \natleast one medication including antihypertensives, \nantidiabetics, diuretics, iron, or vitamins etc.\n\n\n\nTable 2. Distribution according to etiology of ESRD\n\n\n\nTable 3. Mucocutaneous manifestations of ESRD patients\n\n\n\nEtiology Female Male Total\nHypertension 34 (44.2%) 43 (55.8%) 77 (92.8%)\nDiabetes Mellitus 10 (26.3%) 28 (73.7%) 38 (45.8%)\nPolycystic Kidney \nDisease 3 (75%) 1 (25%) 4 (4.8%)\n\n\n\nEctopic Kidney 0 (0) 2 (100%) 2 (2.4%)\nObststructive\nNephropathy 0 (0) 2 (100%) 2 (2.4%)\n\n\n\nIgA Nephropathy 1 (100%) 0 (0) 1 (1.2%)\nAnalgesic Nephropathy 0 (0) 1 (100%) 1 (1.2%)\nKidney Infection 0 (0) 1 (100%) 1 (1.2%)\nGlomerulonephritis 1 (100%) 0 (0) 1 (1.2%)\nSystemic Lupus\nErythematosus 1 (100%) 0 (0) 1 (1.2%)\n\n\n\nSingle Kidney 0(0) 1 (100%) 1 (1.2%)\n\n\n\nCutaneous Manifestation Number of Patients\nXerosis 75 (90.4%)\nPruritus 36 (43.4%)\nSun-Exposed Skin Hyperpigmentation 25 (30.1%)\nDiffuse Hyperpigmentation 15 (18.1%)\nIcthyosis 14 (16.9%)\nYellowish Tinge 5 (6%)\nPallor 4 (4.8 %)\nPurpura 3 (3.6%)\nEarly Wrinkling 1 (1.2%)\nMucosal Manifestation\nXerostomia 25 (64.1%)\nFissured Tongue 4 (10.3%)\nPigmented Tongue 4 (10.3%)\n\n\n\nOne or more mucocutaneous manifestations \noccurred in 81 of 83 patients (97.6%), although only \n48 (57.8%) patients complained of skin problem \n(Table 3). Xerosis was the most common cutaneous \nmanifestation seen in 75 out of 83 patients (90.4%) \n(Figure 1a). Among these, 50.7% had mild xerosis, \n44% had moderate xerosis and 5.3% were afflicted \nwith severe xerosis. Pruritus was the second most \ncommon manifestation that was seen in 43.4% of \npatients. Among those patients who had pruritus, \n77.8%, 13.9% and 8.3% had mild moderate and \nsevere pruritus respectively. Pruritus was unaffected \nby cold and heat, exacerbated by dry skin and \nameliorated by dialysis and sleep.\n\n\n\nMacroglossia 2 (5.1%)\nCoated Tongue 2 (5.1%)\nAphthous Stomatitis 2 (5.1%)\nNail Manifestation\nNail Pallor 60 (83.3%)\nAbsent Lunula 35 (48.6%)\nNail Discoloration 21 (29.2%)\nLongitudinal Ridging 20 (27.8%)\nLongitudinal Melanonychia 17 (23.6%)\nBeau\u2019s Lines 17 (23.6%)\nHalf and Half Nails 14 (19.4%)\nKoilonychia 14 (19.4%)\nTerry\u2019s Nails 9 (12.5%)\nPitting 1 (1.3%)\nHair Change\nDry, Lusterless Hair 18 (66.7%)\nDiffuse Alopecia 9 (33.3%)\nLoss of Hair 7 (25.9%)\nSparse Scalp Hair 1 (3.7%)\nSparse Body Hair 1 (3.7%)\n\n\n\nOther skin changes seen were sun-exposed \nskin hyperpigmentation (SH) in 30.1%, diffuse \nhyperpigmentation (DH) in 18.1%, icthyosis in \n16.9% (Figure 1b), yellowish tinge to skin in 6%, \npallor in 4.8%, and purpura in 3.6% patients. One \npatient had early wrinkling. Mucosal abnormalities \noccurred in 46.9% patients and in the order of \nfrequency were xerostomia in 64.1%, fissured \ntongue and pigmented tongue in 10% patients each, \ncoated tongue, macroglossia with teeth markings \n(Figure 1c) and aphthous stomatitis in 5% patients \neach. \n\n\n\nNail changes in 86.7% patients comprised nail pallor \nin 83.3%, absent lunula in 48.6%, nail discoloration \nin 29.2%, Lindsay\u2019s nails (half and half) in 19.4% \n(Figure 4), Terry\u2019s nails in 12.5%, Beau\u2019s lines in \n23.6%, koilonychia in 19.4% patients. Other nail \nchanges included longitudinal ridging in 27.8 %, \nlongitudinal melanonychia in 23.6%, and pitting \nin one patient respectively. Hair abnormalities \nin 32.5% patients included dry, lusterless hair in \n66.7%, diffuse alopecia in 33.3%, loss of hair in \n26%, and sparse scalp hair and sparse body hair in \n3.7% patient each.\n\n\n\nDiscussion\nThe mean age of CRF patients in the present study \nis 52.3 which is close to the studies of Sultan MM \net al10 (49.5) whereas other studies report lower \nmean age, such as Singh G et al.11 (40.5). The \ndifferences in these statistics could be due to varied \ndemographic profile of patients enrolled in the \nrespective studies. In the present study, majority of \npatients (43.4%) belonged to the age group of 41-\n60 years, followed by 32.5% in above 61 years age \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n57\n\n\n\ngroup. Even in the studies of Udaykumar et al.12, the \nmajority of patients belonged to the age groups of \n41-50 and 40-60 respectively. In present study, male \npreponderance (1.4:1) is seen which is consistent \nwith the studies of Singh G et al.12 (1.7:1). The \nmost common etiologies of ESRD in our study was \nhypertension (92.8%) and diabetes (45.8%). The \npercentage of patients with diabetes in our study is \nconsistent with study of Thomas EA et al (42.4%).13\n\n\n\nNunley et al.3 have found that at least one cutaneous \nmanifestation was present in 50-100% of patients. \nCutaneous manifestations in ESRD patients were \nobserved in 97% patients in this study, which \ncorrelates with the findings of studies of Pico et al.,4 \nwho reported skin findings in 100% of his patients. \nXerosis, pruritus and hyperpigmentation were the \nthree most common cutaneous manifestations in \nour patient population, consistent with reports from \nother studies Robinson et al.14 Xerosis of variable \nseverity has been well documented in 23-90% \npatients irrespective of dialysis status.15 The primary \nfactors likely to have played a role in causing xerosis \nin our patients might be reduced sebum/sweat \nexcretion, altered skin barrier, reduced emollient \nusage, and dehydration of the skin.15 Xerosis was \nthe most common cutaneous manifestation (72%) \nreported by Khanna et al.15 We report that 90.4% \nof our patients had xerosis which was also the \nmost frequent cutaneous manifestation seen. This \nfinding is higher than that seen by Amatya et al.16 \n(28%). A possible reason for this discrepancy in \nthe percentage of patients with xerosis might be the \nprolonged duration of ESRD in most of our patient \npopulation. Application of moisturizers can help \nwith the xerosis.\n\n\n\nVarious studies show the prevalence of pruritus \nin the hemodialysis patients to be between 19% \nto 90%.12 A number of different mechanisms have \nbeen proposed to explain the origin of pruritus. One \nimportant reason is that Xerosis itself predisposes \nto pruritus. Other risk factors include male sex, old \nage, high pre-dialysis level of blood urea nitrogen, \nand high levels of \u03b22-microglobulin, calcium, and \nphosphate.17 The number of patients having pruritus \nin our study (43.4%) was lower than that of studies \nby Singh G et al11 where the number of patients \nhaving pruritus were 46.7% and 53% respectively. \nThis may be because most of our patients initiate \ndialysis soon after the diagnosis of ESRD. \n\n\n\nIn our study, a majority of patients, i.e, 28 (80%), \nand 24 (68.6%) reported amelioration of pruritus \n\n\n\nwith sleep and dialysis respectively. While heat and \ncold had no effect on pruritus, dry skin exacerbated \nitching in 32 (91.4%) patients. The pigmentation in \nthe present study is seen in 30.1% which is similar \nto studies of Udaykumar et al.12 (43%). In some \nother studies, the frequency of skin discoloration \nwas reported between 20% and 80%.4 Pico and \ncoworkers studied 102 patients on hemodialysis, \nin whom skin discoloration was the most common \nfinding.4 Melanocyte Stimulating Hormone (MSH) \naccumulates due to failure of kidney function and \nthis may be the reason for pigmentation. The most \nseverely affected areas were the extremities and \nphoto-exposed areas. We did not find any correlation \nbetween the incidence of pigmentation abnormality \nand duration of hemodialysis. However, Pico and \ncolleagues noticed a decrease in pigmentation with \nincreasing duration of dialysis.4 They postulated \nthis to be due to reduced exposure to sunlight and \nthe chronicity of the disease. \n\n\n\nIt is important to acknowledge that assessment of \nskin color is dependent on the subjective factors \nsuch as accuracy of the examiner\u2019s visual ability \nand objective factors like the type and intensity of \nthe environment light. In order to prevent a wrong \ndiagnosis, color meter reflectance can be used for \nthe examination.18 Sun avoidance is important for \nreducing the incidence of pigmentation. In the \npresent study pallor of the skin is evident in only \n4.8% patients which is less when compared to \nstudies of Sultan MM et al.10 (45%). In studies of \nFalodun O et al.19 pallor was seen in 2.5% which is \nnearer to our present study. In present study purpura \nis seen in 3.6% of patients which is lower than that \nin studies of Thomas E A et al. (10%).13 \n\n\n\nXerostomia in 62.5% patients was the most common \nmucosal abnormality. Some studies indicate that \nfissured tongue affects 4-8% ESRD patients and \nup to 20% of the general population, but was seen \nin only 10% of our patients.20 The various triggers \nfor this could be nutritional deficiencies, poor oral \nhygiene, smoking, consumption of alcohol or hot/\nspicy foods.21 Macroglossia with teeth markings \nwas seen in 5% patients and this is usually seen \nin 9-43% cases and is considered characteristic of \nuremia.11 Proper mouth hygiene will help prevent \nsuch mucosal changes.\n\n\n\nNail pallor in 83.3% patients was the most common \nfinding consistent with its reported prevalence \nof 67% in ESRD patients and 96% in patients on \nhemodialysis.22 Absent lunula was observed in \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58\n\n\n\n48.6% patients and reportedly occurs in 17-63% \npatients irrespective of dialysis status.21 Lindsay\u2019s \nnails also known as half and half nails are \ncharacterized by a proximal white part and a distal \nreddish pink part that does not fade on pressure. \nThese two zones show a sharp demarcation between \nthem. Half-and-half nail in our study was observed \nin 19.4% of the patients, while others reported it in \n7% to 39% of the patients.12\n\n\n\nIn the majority of our patients, hairs were normal \n(67.5%). 66.7% of our patients had dry, lusterless \nhairs, 33.3% had diffuse alopecia. Only one patient \neach had sparse scalp and sparse body hair. Dry \nlustreless hair may be attributed to decreased \nsecretion of sebum. The numbers of patients having \nhair changes were more in present study compared \nto that of Falodun et al (2.5%).19 The reason for \nthis may be due to associated anemia in the present \ngroup. Udaykumar P et al.12 found sparse body \nhair (30%), sparse scalp hair (11%) and brittle and \nlusterless hair (16%) in his study. In study of Sultan \nMM et al.10 reported brittle and lusterless hair in \n\n\n\n(47%), sparse scalp hair (46%) and sparse body hair \n(27%). Hajheydari Z et al6 noticed scalp alopecia \nin 9.9%, drying and hair fragility in 2% and hair \ndiscolouration in 2% of patients.\n\n\n\nThere were 8.4% cases of skin infection in our \nstudy. Pico and colleagues reported infections \nin 70% of the patients.4 Sultan et al. reported \nan incidence of 33% for fungal infections10 and \nUdaykumar et al. reported bacterial infections in \n13% of cases.12 Additionally, in this study, no case \nof metastatic calcification, bullous dermatosis, or \nacquired perforating dermatosis was observed. \nIn other studies, 2% to 21% of the patients were \nfound to have acquired perforating dermatosis.12 \nThe complete lack of ESRD specific findings can \npartially explained by the specific etiologies of \nESRD seen in our patients. Most of our patients had \nhypertension as the etiology of ESRD. It is probable \nthat due to this, we did not record any such findings. \n\n\n\nShort duration and the cross-sectional nature of the \nstudy are some of the limitations of this study.\n\n\n\n6 \n \n\n\n\nFigure 3. Macroglossia with teeth markings \n \n\n\n\n \n \nFigure 4. Half and half nails  \n \n\n\n\n \n \n \nDiscussion \nThe mean age of CRF patients in the present study is 52.3 which is close to the studies of \nSultan MM et al10 (49.5) whereas other studies report lower mean age, such as Singh G et al11 \n(40.5). The differences in these statistics could be due to varied demographic profile of \npatients enrolled in the respective studies. In the present study, majority of patients (43.4%) \nbelonged to the age group of 41-60 years, followed by 32.5% in above 61 years age group. \nEven in the studies of Udaykumar et al12, the majority of patients belonged to the age groups \nof 41-50 and 40-60 respectively. In present study, male preponderance (1.4:1) is seen which \nis consistent with the studies of Singh G et al12 (1.7:1). The most common etiologies of ESRD \nin our study was hypertension (92.8%) and diabetes (45.8%). The percentage of patients with \ndiabetes in our study is consistent with study of Thomas EA et al (42.4%).13 \n\n\n\n\n\n\n\n6 \n \n\n\n\nFigure 3. Macroglossia with teeth markings \n \n\n\n\n \n \nFigure 4. Half and half nails  \n \n\n\n\n \n \n \nDiscussion \nThe mean age of CRF patients in the present study is 52.3 which is close to the studies of \nSultan MM et al10 (49.5) whereas other studies report lower mean age, such as Singh G et al11 \n(40.5). The differences in these statistics could be due to varied demographic profile of \npatients enrolled in the respective studies. In the present study, majority of patients (43.4%) \nbelonged to the age group of 41-60 years, followed by 32.5% in above 61 years age group. \nEven in the studies of Udaykumar et al12, the majority of patients belonged to the age groups \nof 41-50 and 40-60 respectively. In present study, male preponderance (1.4:1) is seen which \nis consistent with the studies of Singh G et al12 (1.7:1). The most common etiologies of ESRD \nin our study was hypertension (92.8%) and diabetes (45.8%). The percentage of patients with \ndiabetes in our study is consistent with study of Thomas EA et al (42.4%).13 \n\n\n\n\n\n\n\nFigure 1. (a) Xerosis; (b) Icthyosis; (c) Macroglossia with teeth markings; (d) Half and half nails\n\n\n\n5 \n \n\n\n\nDry, lusterless hair 18 (66.7%) \nDiffuse alopecia 9 (33.3%) \nLoss of hair 7 (25.9%) \nSparse scalp hair 1 (3.7%) \nSparse body hair 1 (3.7%) \n \nOther skin changes seen were sun-exposed skin hyperpigmentation (SH) in 30.1%, diffuse \nhyperpigmentation (DH) in 18.1%, icthyosis in 16.9% (Figure 2), yellowish tinge to skin in \n6%, pallor in 4.8%, and purpura in 3.6% patients. One patient had early wrinkling. Mucosal \nabnormalities occurred in 46.9% patients and in the order of frequency were xerostomia in \n64.1%, fissured tongue and pigmented tongue in 10% patients each, coated tongue, \nmacroglossia with teeth markings (Figure 3) and aphthous stomatitis in 5% patients each.  \n \nNail changes in 86.7% patients comprised nail pallor in 83.3%, absent lunula in 48.6%, nail \ndiscoloration in 29.2%, Lindsay\u2019s nails (half and half) in 19.4% (Figure 4), Terry\u2019s nails in \n12.5%, Beau\u2019s lines in 23.6%, koilonychia in 19.4% patients. Other nail changes included \nlongitudinal ridging in 27.8 %, longitudinal melanonychia in 23.6%, and pitting in one \npatient respectively. Hair abnormalities in 32.5% patients included dry, lusterless hair in \n66.7%, diffuse alopecia in 33.3%, loss of hair in 26%, and sparse scalp hair and sparse body \nhair in 3.7% patient each. \n \nFigure 1. Xerosis  \n \n\n\n\n \n \nFigure 2. Icthyosis \n \n\n\n\n\n\n\n\n5 \n \n\n\n\nDry, lusterless hair 18 (66.7%) \nDiffuse alopecia 9 (33.3%) \nLoss of hair 7 (25.9%) \nSparse scalp hair 1 (3.7%) \nSparse body hair 1 (3.7%) \n \nOther skin changes seen were sun-exposed skin hyperpigmentation (SH) in 30.1%, diffuse \nhyperpigmentation (DH) in 18.1%, icthyosis in 16.9% (Figure 2), yellowish tinge to skin in \n6%, pallor in 4.8%, and purpura in 3.6% patients. One patient had early wrinkling. Mucosal \nabnormalities occurred in 46.9% patients and in the order of frequency were xerostomia in \n64.1%, fissured tongue and pigmented tongue in 10% patients each, coated tongue, \nmacroglossia with teeth markings (Figure 3) and aphthous stomatitis in 5% patients each.  \n \nNail changes in 86.7% patients comprised nail pallor in 83.3%, absent lunula in 48.6%, nail \ndiscoloration in 29.2%, Lindsay\u2019s nails (half and half) in 19.4% (Figure 4), Terry\u2019s nails in \n12.5%, Beau\u2019s lines in 23.6%, koilonychia in 19.4% patients. Other nail changes included \nlongitudinal ridging in 27.8 %, longitudinal melanonychia in 23.6%, and pitting in one \npatient respectively. Hair abnormalities in 32.5% patients included dry, lusterless hair in \n66.7%, diffuse alopecia in 33.3%, loss of hair in 26%, and sparse scalp hair and sparse body \nhair in 3.7% patient each. \n \nFigure 1. Xerosis  \n \n\n\n\n \n \nFigure 2. Icthyosis \n \n\n\n\n\n\n\n\na b\n\n\n\ndc\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n59\n\n\n\nConclusion\nThe number of patients presenting with \nmucocutaneous manifestations in our study far \noutnumbered those that actively complained of \na skin problem. This indicates that cutaneous \nmanifestations can be subtle and not noticeable by the \npatient. By actively looking for skin changes in this \npatient population, we can avoid the progression of \nsuch changes with better management. Hypertension \nwas the commonest etiology noted. Patients with \na severe grade of xerosis were significantly lower \ncompared to mild and moderate grades. This might \nbe attributable to effect of early hemodialysis which \ncould have prevented the progression of xerosis \nseverity. Xerosis, pruritus, pigmentary changes, nail \npallor, absent lunula, nail discoloration, xerostomia \nand dry, lusterless hairs were the most common \nmucocutaneous manifestations in the majority of \nstudied patients. Lifelong follow-up is needed to \nreduce the morbidity from dermatoses considered \nESRD/hemodialysis specific that may appear over \ntime. We observe that future studies are needed for a \nbetter determination of the various mucocutaneous \nmanifestations seen in ESRD patients.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil.\n\n\n\nReferences\n\n\n\n1. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh \nJ, Rossert J et al. Definition and classification of chronic \nkidney disease: A position statement from kidney disease: \nImproving global outcomes (KDIGO). Kidney Int \n2005;67:2089-100.\n\n\n\n2. Prabhakar MR, Chandrasekaran V, Soundarajan P. \nEpidemic of chronic kidney disease in India-what can be \ndone? Saudi J Kidney Dis Transpl 2008;19:847-53. \n\n\n\n3. Nunley JR. Dermatological manifestations of renal \ndisease. Available from: http//emedicine.medscape.com/ \narticle/1094846-overview. (accessed on 10 September \n2020)\n\n\n\n4. Pico MR, Lugo Somolinos A, Sanchez JL, Burgos \nCalderon R. Cutaneous alterations in patients with chronic \nrenal failure. Int J Dermatol 1992;31:860-3.\n\n\n\n5. Singh AK, Farag YM, Mittal BV, Subramanian KK, Reddy \nSR, Acharya VN et al. Epidemiology and risk factors of \nchronic kidney disease in India-Results from the SEEK \n(Screening and Early Evaluation of Kidney Disease) study. \nBMC Nephrol 2013;14:114. \n\n\n\n6. Hajheydari Z, Makhlough A. Cutaneous and mucosal \nmanifestations in patients on maintenance hemodialysis. \nIran J Kidney Dis 2008;2:86-90. \n\n\n\n7. Abdelbaqi-Salhab M, Shalhub S, Morgan MB. A current \nreview of the cutaneous manifestations of renal disease. J \n\n\n\nCutan Pathol 2003;30:527-38.\n8. Cockcroft DW, Gault MH. Prediction of creatinine \n\n\n\nclearance from serum creatinine. Nephron 1976;16:31-41. \n9. Akhyani M, Ganji MR, Samadi N, Khamesan B, \n\n\n\nDaneshpazhooh M. Pruritus in hemodialysis patients. \nBMC Dermatol 2005;5:7.\n\n\n\n10. Sultan MM, Mansour HH, Wahby IM, Houdery AS. \nCutaneous manifestations in Egyptian patients with \nchronic renal failure on regular hemodialysis. J Egypt \nWomen Dermatol Soc 2010;7:49-55. \n\n\n\n11. Singh G, Verma AK, Singh G, Singh SJ. Cutaneous changes \nin chronic renal failure. Indian J Dermatol Venereol and \nLeprol 1992;58:320-2.\n\n\n\n12. Udayakumar P, Balasubramanian S, Ramalingam KS, \nLakshmi C, Srinivas CR, Mathew AC. Cutaneous \nmanifestations in patients with chronic renal failure \non hemodialysis. Indian J Dermatol Venereol Leprol \n2006;72:119-25.   \n\n\n\n13. Thomas EA, Pawar B, Thomas A. A prospective study \nof cutaneous abnormalities with chronic kidney disease. \nIndian J Nephrology 2012;22:116-20.\n\n\n\n14. Robinson-Bostom L, DiGiovanna JJ. Cutaneous \nmanifestations of end-stage renal disease. J Am Acad \nDeramtol 2000;43:975-90.\n\n\n\n15. Khanna D, Singal A, Kalra OP. Comparison of cutaneous \nmanifestations in chronic kidney disease with or without \ndialysis. Postgrad Med J 2010;86:641-7.\n\n\n\n16. Amatya B, Agrawal S, Dhali T, Sharma S, Pandey SS. \nPattern of skin and nail changes in chronic renal failure in \nNepal: A hospital based study. J Dermatol 2008;35:140-5.\n\n\n\n17. Ko CJ, Cowper SE. Dermatologic conditions in kidney \ndisease. In: Taal MW, Chertow GM, Marsden PA, Skorecki \nK, Yu ASL, Brenner BM. Brenner Rector\u2019s the kidney. 9th \ned. Philadelphia, PA: Saunders Elsevier; 2011. p2156-68.\n\n\n\n18. Gupta AK, Gupta MA, Cardella CJ, Haberman HF. \nCutaneous associations of chronic renal failure and \ndialysis. Int J Dermatol 1986;25:498-504.\n\n\n\n19. Falodun O, Ogunbiyi A, Salako B,George AK. Skin \nchanges in patients with Chronic Renal Failure. Saudi J \nKidney Dis Transpl 2011;22:268-72.\n\n\n\n20. Tajbakhsh R, Dehghan M, Azarhoosh R, Haghighi AN, \nSadani S, Zadeh SS et al. Mucocutaneous manifestations \nand nail changes in patients with end stage renal disease on \nhemodialysis. Saudi J Kidney Dis Transpl 2013;24:36-40.\n\n\n\n21. Sanad EM, Sorour NE, Saudi WM, Elmasry AM. \nPrevalence of cutaneous manifestations in chronic renal \nfailure patients on regular hemodialysis: A hospital based \nstudy. Egyptian J Dermatol Venereol 2014;34:27-35.\n\n\n\n22. Levillard DT, Kambil SM. Cutaneous manifestations \nin chronic renal disease-an observational study of skin \nchanges, new findings, their association with hemodialysis, \nand their correlation with severity of CKD. IJSRP \n2015;5:727-36.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n60\n\n\n\nORIGINAL ARTICLE\n\n\n\nPsoriasis and Metabolic Syndrome in Rural India:  Case Control Study         \n\n\n\nPriyanka Date, MD, Sonia Jain, MD\n\n\n\nDepartment of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, \nWardha, Maharashtra, India\n\n\n\nAbstract\nIntroduction\nPsoriasis is a chronic, common, inflammatory disorder of the skin and joints. Globally Metabolic \nSyndrome (MS) is found to be significantly associated with psoriasis but there is a paucity of data \nfrom rural in Indian literature. The aim of this study is to study the association of metabolic syndrome \n(MS) with psoriasis and the relationship between its severity, duration of the disease and presence of \nMS in patients of psoriasis of rural setting.\n\n\n\nMethods \nA prospective, hospital-based case-control study was carried out consisting of 65 psoriasis cases \nand 65 healthy controls within duration from November 2016 to August 2018 started after ethical \nclearance from institute with detailed written consent from both cases and controls. MS was diagnosed \nby the presence of \u22653 criteria of the South Asian Modified National Cholesterol Education Program \nAdult Treatment Panel III Criteria (SAM NCEP ATP III). Statistical analysis was done by descriptive \nand inferential statistics using chi-square test and software SPSS 22.0 version, EPI Info version 7 and \nGraph Pad Prism 6.0 version.\n\n\n\nResults\nMetabolic syndrome was significantly more common in psoriatic patients than controls (35.38% vs \n18.46%, P=0.004). Cases also had significantly higher prevalence of hypertriglyceridemia (32.31% vs \n17.91%), hypertension (43.08% vs 26.57%) and impaired fasting plasma glucose levels (33.85% vs \n14.93%). MS was significantly correlated to the disease severity irrespective of the disease duration. \n\n\n\nConclusion\nMetabolic syndrome is more frequent in patients with psoriasis. This study highlights the need of \nscreening of all psoriatic patients for early diagnosis and treatment of associated MS.\n\n\n\nKey words: Psoriasis, metabolic syndrome, hypertriglyceridemia, hypertension\n\n\n\nIntroduction\nPsoriasis is a chronic inflammatory disorder of the \nskin and joints that affects 2% of the population \nand poses a lifelong burden for those affected.1 \nAssociation of psoriasis and other disorders \nassociated with psoriasis are interlinked by a \ncommon pathway of presence of raised levels of \ninflammatory cytokines such as tumor necrosis \nfactor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6).2 \n\n\n\nMetabolic Syndrome (MS) is defined as a \n\n\n\nCorresponding Author\nPriyanka Date\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences,\nSewagram, Maharashtra, \n442102 India.\nEmail: priyankadate16@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n61\n\n\n\nconstellation of abdominal obesity, increased \ninsulin resistance, elevated fasting glucose level, \ndecreased high-density lipoprotein cholesterol, \nhypertriglyceridemia, and hypertension.3 It is shown \nthat patients with psoriasis have an increased risk \nof developing cardiovascular disease (CVD) and \nmetabolic syndrome in comparison to non-psoriatic \npatients.3 The main hypothesis for an association \nbetween psoriasis and CVD and its risk factors is \nincreased systemic inflammation and is a complex \nof several reasons such as unhealthy lifestyles due \nincreased likelihood of smoking, little physical \nactivity and obesity.4 CVD risk factors like diabetes, \nhypertension and hyperlipidaemia have been \nassociated with psoriasis and remedies of psoriasis \nlike cyclosporine and  methotrexate.5 Thus many \nfactors may confound the association between the \ntwo disorders.\n\n\n\nHowever only few studies have highlighted on this \nassociation, prominent being  Zindanc\u0131 et al6 and few \nIndian studies like the one conducted in South India \nby Madanagobalane in 2012,7 using the National \nCholesterol Education Program Adult Treatment \nPanel III (NCEP ATP III) criteria. There is enigma \nregarding the association of psoriasis and metabolic \nsyndrome and if so, by what magnitude. None of \nthe Indian studies have data from rural population. \nRecent studies have estimated a prevalence of 15% \nto 24% for MS in the general population.8,9 \n\n\n\nBecause the implications of the metabolic syndrome \nover healthcare are substantial and psoriasis being \na common disorder, we have undertaken this study \nto assess the prevalence of the metabolic syndrome \nand its associated components among individuals \nwith psoriasis in a rural hospital in Central India. \nBy doing this we as dermatologists can help in early \ndiagnosis and also contribute in pharmacologic as \nwell as non-pharmacologic management for our \npatients. \n\n\n\nMaterials and Methods\n\n\n\nPatients Selection\nIt was a prospective, case control study, performed in \na rural tertiary care hospital of India from November \n2016 to August 2018. Study was approved by \nInstitutional ethical committee.\n\n\n\nWe included biopsy proven psoriasis patients of more \nthan 18 years of age, with disease duration of at least \n6 months and who had not received any systemic \ntreatment for at least 1 month as cases. Patients less \n\n\n\nthan 18 years of age, disease duration of <6 months \nand patients with systemic treatment within past \n1 month were kept as exclusion criteria for cases. \nTo avoid bias in the study we selected age and sex \nmatched controls from same study population. We \nhave taken healthy relatives accompanying patients \nin outdoor patient department (OPD) as controls.\n\n\n\nStudy Procedures\nInformed written consent from adult research \nparticipants, 65 psoriatic patients and 65 age and \nsex matched controls were taken. We collected \ndata by pre\u2013prepared questionnaire which include \ndemographic details, age of onset, duration and \nprogression of psoriasis, percentage body surface \narea (BSA) of involvement, psoriasis area severity \nindex (PASI) were noted. Composite score of PASI \nhas been calculated as mild = 0-7, moderate = 8-12 \nand severe = \u226512.7\n\n\n\nIn the personal history cases were asked about \nhabits of smoking and alcohol and it\u2019s relation with \npsoriasis (whether the habit started before, after or \nat the same time of the disease onset), the number \nof cigarettes smoked daily as well as duration and \namount of alcohol consumption of the patients who \nhad alcohol consumption habit. Same data is noted \nin control group also.\n\n\n\nBlood pressure (BP) was measured as per standard \nprotocol. Venous blood samples collected after 8 \nhours of fasting were evaluated for fasting blood \nglucose, HDL and triglyceride levels. Metabolic \nsyndrome was diagnosed by South Asian Modified \nNational Cholesterol Education Program Adult \nTreatment Panel III criteria (SAM NCEP ATP III),9,12 \nIf three or more of the following were present, the \npatient was diagnosed as having MS:\n\n\n\n1. Abdominal obesity as waist circumference \n(\u2265102 cm for males and \u226588 cm for females)\n\n\n\n2. Blood pressure >130/85 mmHg\n3. Fasting blood glucose \u2265100 mg/dl\n4. Hypertriglyceridemia >150 mg/dl or\n5. Low HDL cholesterol (<40 mg/dl for males and \n\n\n\n<50 mg/dl for females).\n\n\n\nStatistical Analysis\nSample size of 108 (54 cases and 54 controls), were \ncalculated using Software Open EPI-with 95% \nConfidence Interval, power 80% and alpha-5%.10 \nWe included 130 patients (65 cases and 65 controls) \nas results will be more conclusive as sample size \nincreases.11 Collected data was analysed by using \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n62\n\n\n\nCharacteristics Cases Controls p-value\nSex M*/F\u2020 48/17 46/19 0.69\nAge, Mean \u00b1 SD\u2021 43.89 \u00b1 14.48 42.24 \u00b1 13.13 0.79\nSmokers 12 (18.46%) 10 (15.38%) 0.70\nAlcohol Consumption 23 (35.38%) 12 (18.46%) 0.004\nMetabolic Syndrome 23 (35.38%) 12 (18.46%) 0.004\nWaist Circumference >102 cm(M)* or >88 cm(F)\u2020 26 (40%) 26 (38.81%) 0.88\nTriglyceridemia >1.7 mmol/l (150 mg/dl) 21 (32.31%) 12 (17.91%) 0.006\nHDL <1 mmol/l (40mg/dl)(M)* or <1.3 mmol/l (50 mg/dl)(F)\u2020 25 (38.46%) 10 (14.93%) 0.0002\nBlood Pressure >135/85 mmHg 28 (43.08%) 18 (26.67%) 0.017\nFasting Plasma Glucose >6.1 mmol/l (>100 mg/dl) 22 (33.85%) 10 (14.93%) 0.0018\n\n\n\nMetabolic Syndrome Cases Controls value-2\u05d0 Odds Ratio\nMetabolic Syndrome 23 (35.4%) 12 (18.5%)\n\n\n\n4.73\np=0.029\n\n\n\nOR\u2020=2.41\n95% CI\u00a7=1.07-5.42\n\n\n\nRR\u2021=1.48\n95% CI\u00a7=1.07-2.06\n\n\n\nNon Metabolic Syndrome 42 (64.6%) 53 (81.5%)\n\n\n\nTotal 65 (100%) 65 (100%)\n\n\n\n *M:Male,\u2020F: Female ,\u2021SD-Standard deviation\n\n\n\n\u2020OR: Odds ratio, \u2021 RR: Relative risk, \u00a7CI: Confidence interval\n\n\n\nsyndrome with duration of psoriasis in cases was \nnot statistically significant. (p value 0.72) \n\n\n\nThe mean percentage BSA of cases having psoriasis \nand Metabolic syndrome was 22.9%. PASI of <8 \nwere taken as mild psoriasis and \u22658 was set to define \nboth moderate to severe psoriasis. 20 out of 23 \npatients with metabolic syndrome had PASI of more \nthan 8, thereby making the difference statistically \nsignificant with a P-value of 0.0001. (Refer Table 4)\nOut of 23 cases, 12 (52.17%) were taking 6 drinks \nper week and 11 (47.82%) were taking 4 drinks per \nweek, all the cases were male, and they had been \ndrinking alcohol before the onset of disease. In \ncontrast, out of 12 (18.46%) controls all of them \nwere drinking <4 drinks per week, since 10-15 years \nand all were males. As MS is not significantly seen \nin alcoholic drinker cases as compared to controls, \nin our study we can say that alcohol intake is not a \nconfounding factor for MS. (Refer Table 5)\n\n\n\nBody mass index (BMI) of cases and controls \nshows no significant difference (p=0.86), maximum \ncases as well as controls has BMI <23 and mean \nBMI of 22.62 \u00b1 4.19 among cases (Table 6). Our \nstudy shows no significant association of metabolic \nsyndrome with waist circumference.\n\n\n\ndescriptive and inferential statistics using chi \nsquare test and software SPSS 22.0 version, EPI \nInfo version 7 and Graph Pad Prism 6.0 version and \np<0.05 was considered as level of significance.\n\n\n\nResults\nDemographic and disease characteristic of the \nstudy population is summarized in Table 1. In \npresent study, we found male preponderance. Max-\nimum patients were in the age group of 38-47 years \n(23 patients). Out of 65 cases 12 were smokers, all \nof them were males and started smoking before the \nonset of disease. Of the smokers, 8 (66.6%) males \nsmoked 1-10 cigarettes daily; and 4 (33.3%) males \nsmoked 11-40 cigarettes daily. Among controls 10 \nwere smokers and all of them smoked 1-10 ciga-\nrettes daily. \n\n\n\nThere was no significant association of smoking \nwith metabolic syndrome among cases as well as \ncontrols. The ratio of alcohol use was 23 (35.38%)\nvs 12 (18.46%) among cases and controls. \n\n\n\nThere was a significant association of psoriasis with \nmetabolic syndrome p=0.029, 2\u05d0-value = 4.73, Odds \nratio = 2.41, 95% CI = 1.07-5.42, Relative risk = \n1.48, 95% CI = 1.07-2.06. Correlation of metabolic \n\n\n\nTable 1. Sociodemographic characteristics of the participants\n\n\n\nTable 2. Metabolic syndrome in cases and control groups compared by odds ratio\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n63\n\n\n\nDuration of Disease\nTotal\n\n\n\n<1 year 1-5 years >5 years\nMetabolic Syndrome 7 (30.43%) 7 (30.43%) 9 (39.13%) 23 (35.38%)\nNon Metabolic Syndrome 11 (26.19%) 17 (40.48%) 14 (33.33%) 42 (64.62%)\nTotal 18 (27.69%) 24 (36.92%) 23 (35.38%) 65 (100%)\nvalue-2\u05d0 0.64, p=0.72 \n\n\n\nTable 3. Correlation of metabolic syndrome with duration of psoriasis in cases\n\n\n\n*PASI: Psoriasis area severity index, \u2020M: male, \u2021F: female\n\n\n\nMetabolic Syndrome and Its Components PASI* <8\nMild\n\n\n\nPASI* \u22658\nModerate to Severe p-value\n\n\n\nMetabolic Syndrome 3 (4.62%) 20 (30.77%) 0.0001\nWaist Circumference >102 cm(M)\u2020 or >88 cm(F)\u2021 7 (10.77%) 20 (30.77%) 0.0005\nTriglyceridemia >150 mg/dl 5 (7.69%) 16 (24.62%) 0.0012\nHDL <40 mg/dl(M)\u2020 or <50 mg/dl(F)\u2021 5 (7.69%) 20 (30.77%) 0.0001\nBlood Pressure >135/85 mmHg 6 (9.23%) 22 (33.85%) 0.0001\nFasting Plasma Glucose >100 mg/dl 6 (9.23%) 16 (24.62%) 0.0026\n\n\n\nBody Mass Index (kg/m2) Cases Controls value = \u05d0\n<23 37 (56.92%) 37 (56.92%)\n\n\n\n0.29\np=0.86 \n\n\n\n23-24.9 11 (16.92%) 13 (20%)\n\u226525 17 (26.15%) 15 (23.08%)\nTotal 65 (100%) 65 (100%)\n\n\n\nMean\u00b1 22.62 \u00b1 4.19 22.46 \u00b1 3.82\n\n\n\nTable 4. Correlation of metabolic syndrome and its components with PASI score\n\n\n\nTable 6. Distribution of patients in cases and control group according to Body mass index (BMI-kg/m2)\n\n\n\nTable 5. Metabolic syndrome in alcohol drinkers in two groups\n\n\n\nMetabolic Syndrome Cases Controls value-2\u05d0 Odd\u2019s Ratio\nMetabolic Syndrome 9 (39.1%) 3 (25%)\n\n\n\n0.69\np=0.40\n\n\n\nOR*=1.92\n95% CI\u2021=0.40-9.10\n\n\n\nRR\u2020=1.23\n95% CI\u2021=0.77-1.95\n\n\n\nNon Metabolic Syndrome 14 (60.9%) 9 (75%)\n\n\n\nTotal 23 (35.38%) 12 (18.46%)\n*OR: Odds ratio, \u2020RR: relative risk, \u2021CI: confidence interval\n\n\n\nDiscussion\nMetabolic syndrome as a whole is a strong predictor \nof cardiovascular risk, rather than its individual \ncomponents which includes central obesity, \natherogenicdyslipidemia, hypertension and glucose \nintolerance.13\n\n\n\nMean age of patients in our study was (43.89 \u00b1 14.48 \nyears) in concordance with  Khungar et al.14 and  \nGelfand et al.15 We found male preponderance with \nmale to female ratio of 2.8:1 similar to  Nisa et al.16 \n\n\n\nand Gangaiah N et al.17 We found that not only MS \nbut its individual components are also significantly \ncorrelated with psoriasis. 35.38% of psoriasis \npatients had MS whereas only half of control \npatients i.e. 18.46% suffered from MS which is \nstatistically significant (p=0.004). Madanagobalane \nS et al.7 and Nisa et al.16 also reported statistically \nsignificant results (p value <0.05).\n\n\n\nWe found statistically significant correlation of \ntriglyceride levels (32.31% vs 17.91%; p=0.006) \nsimilar with Madanagobalane et al,7 hypertension \nin psoriatics as 43.08% (p=0.017) consistent with \nNisa et al.16 and diabetes (33.85% vs 14.93%; \np=0.0018) consistent with Gangaiah et al17 and Nisa \net al.16 However, Madanagobalane et al.7 found \nhighly significant prevalence of 81% between \npsoriasis and diabetes. All the parameters of the MS \nwere significantly correlated in our cases except \nwaist circumference. The mean BMI of both cases \nand controls were 22.62 \u00b1 4.19 and 22.46 \u00b1 3.82  \nrespectively.\n\n\n\nThe objectives of our study are fulfilled, showing \nthat the prevalence of MS is more in psoriasis \npatients than general population, as well as to \nestablish a correlation of duration and severity of \n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n64\n\n\n\npsoriasis with MS.  Psoriasis acts as an independent \nrisk factor for MS irrespective of its duration but \nwith increasing severity definitely the chances of \nMS increases. Hence, psoriasis is a definitive risk \nfactor for development of MS.\n\n\n\nOur study was conducted in a rural set up and \ndata from rural source is meagre in literature. We \nincluded all biopsy proven cases and took age and \nsex matched controls from same set up to reduce \nchances of bias are the strengths of our study. We have \nnot taken occupational history into consideration, is \na limitation of our study, as sedentary lifestyle can \nalso be one of the risk factors for MS. Our study \ninterprets that psoriasis has a strong association with \nMS. Although psoriasis increases morbidity but MS \nincreases both morbidity as well as mortality. We \nshould be highly vigilant regarding MS in psoriasis \ncases. Advanced investigations like carotid intima-\nmedia thickness, TNF alpha, IL-6 levels and \nechocardiography should also be done if facilities \nare available. \n\n\n\nConclusion\nThrough our study we want to convey that in future \nscreening for MS should be a compulsory tool for \nall psoriasis patients as they have set up an alarming \nsituation due to strong and definite correlation with \nMS.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowlegdement \nNil.\n\n\n\nReferences\n\n\n\n1. Dogra S, Yadav S. Psoriasis in India: Prevalence and \npattern. Indian J Dermatol Venereol Leprol 2010;76:595-\n601.\n\n\n\n2. Lakshmi S, Nath AK, Udayashankar C. Metabolic \nsyndrome in patients with psoriasis: A comparative study. \nIndian Dermatol Online J 2014;5:132-7.\n\n\n\n3. Ghiasi M, Nouri M, Abbasi A, Hatami P, Abbasi MA, \nNourijelyani K. Psoriasis and increased prevalence of \nhypertension and diabetes mellitus. Indian J Dermatol \n2011;56:533-6.\n\n\n\n4. Nijsten T, Wakkee M. Complexity of the association \nbetween psoriasis and comorbidities. J Invest Dermatol \n2009;129:1601-3.\n\n\n\n5. Westlake SL, Colebatch AN, Baird J, Kiely P, Quinn M, \nChoy E et al. The effect of methotrexate on cardiovascular \ndisease in patients with rheumatoid arthritis: a systematic \nliterature review. Rheumatology (Oxford) 2010;49:295-\n307.\n\n\n\n6. Zindanc\u0131 I, Albayrak O, Kavala M, Kocaturk E, Can \n\n\n\nB, Sudogan S et al . Prevalence of metabolic syndrome \nin patients with psoriasis. Scientific World J 2012; \n2012:312463.\n\n\n\n7. Madanagobalane S, Anandan S. Prevalence of metabolic \nsyndrome in South Indian patients with psoriasis vulgaris \nand the relation between disease severity and metabolic \nsyndrome: a hospital-based case-control study. Indian J \nDermatol 2012;57:353-7.\n\n\n\n8. Chandey M, Kaur S, Kaur H. Prevalence of metabolic \nsyndrome in young adults: a study from North India. Int J \nAdv Med 2017;4:463-6.\n\n\n\n9. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel \nRH, Franklin BA et al. Diagnosis and management of the \nmetabolic syndrome: an American Heart Association/\nNational Heart, Lung and Blood Institute scientific \nstatement. Circulation 2005;112:2735-52.\n\n\n\n10. Kothiwala SK, Khanna N, Tandon N, Naik N, Sharma \nVK, Sharma S et al. Prevalence of metabolic syndrome \nand cardiovascular changes in patients with chronic plaque \npsoriasis and their correlation with disease severity: A \nhospital-based cross-sectional study.  Indian J Dermatol \nVenereol Leprol 2016;82:510-8.\n\n\n\n11. Nayak BK. Understanding the relevance of sample size \ncalculation. Indian J ophthalmol 2010;58:469-70.\n\n\n\n12. Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir \nJS, Chadha D et al. Consensus statement for diagnosis of \nobesity, abdominal obesity and the metabolic syndrome for \nAsian Indians and recommendations for physical activity, \nmedical and surgical management. J Assoc Physicians \nIndia 2009;57:163-70.\n\n\n\n13. Gulliver W. Long-term prognosis in patients with psoriasis. \nBr J Dermatol 2008;159(2):2-9.\n\n\n\n14. Khunger N, Gupta D, Ramesh V. Is psoriasis a new \ncutaneous marker for metabolic syndrome? A study in \nIndian patients. Indian J Dermatol 2013;58:313-4.\n\n\n\n15. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis \nDJ, Troxel AB et al. Risk of myocardial infarction in \npatients with psoriasis. JAMA 2006;296:1735-41.\n\n\n\n16. 1Nisa N, Qazi MA. Prevalence of metabolic syndrome in \npatients with psoriasis. Indian J Dermatol Venereol Lepro \n2010;76:662-5.\n\n\n\n17. Gangaiah N, Roshin NA, Thimmappa V, Shivanna R. \nMetabolic syndrome in patients with psoriasis: A hospital-\nbased case\u2013control study. Clin Dermatol Rev 2018;2:64-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n65\n\n\n\nCASE REPORT\n\n\n\nStevens Johnson Syndrome/Toxic Epidermal Necrolysis Overlap as \na Presentation of Acute Cutaneous Lupus Erythematosus         \n\n\n\nWen Foong Tan1, MRCP, Sook Yee Michelle Voo1, AdvMDerm, Sandhya Rajaintharan2, MPath \n\n\n\n1Department of Dermatology, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia\n2Department of Pathology, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia\n\n\n\nSummary\nStevens Johnson/toxic epidermal necrolysis-like (SJS/TEN-like) acute cutaneous lupus erythematosus \n(ACLE) is a life-threatening condition with similar presentation to SJS/TEN. Herein, we report a case \nof a lady who presented to us with SJS/TEN like ACLE.\n\n\n\nKey words: Stevens Johnson syndrome/toxic epidermal necrolysis overlap, acute cutaneous lupus erythematosus, interface \ndermatitis\n\n\n\nIntroduction\nSJS/TEN-like ACLE is a rare entity that has been \ndescribed in recent years. The main distinguishing \nfeatures include no recent precipitating infection \nor drug ingestion, subacute onset, involvement of \nphoto-distributed area, strongly positive antinuclear \nantibodies (ANA) and suggestive histological and \nimmunological findings. \n\n\n\nCase Report\nWe present a case of a 55-year-old lady with 2 days \nhistory of severe conjunctivitis, oral mucositis and \npainful erythematous patch and bullae over her \npalms and soles associated with fever. Prior to this, \nshe had generalised itchy rash at the trunk and limbs \nfor the past 2 months. There were no preceding \nrespiratory, musculoskeletal, gastrointestinal or \ngenitourinary symptoms. There was no significant \nhistory of recent drug ingestion except for vitamins. \nThere was no previous history of similar episode.\n\n\n\nExamination revealed a frail lady with diffuse mild \nnon-scarring alopecia, purulent conjunctivitis, \nextensive haemorrhagic cheilitis with mucositis and \ngeneralised purpuric patch over her trunk and limbs \n(Figure 1a). She also had purpuric macules over \nher upper and lower limbs with tender bullae over \nher palms and soles. Nikolsky\u2019s sign was negative. \nThere was no genitalia involvement. There was \nno lymphadenopathy and examination of the \nrespiratory, cardiovascular and abdominal systems \nwere unremarkable.\n\n\n\nCorresponding Author\nDr Tan Wen Foong\nDepartment of Dermatology, \nHospital Queen Elizabeth,\n2029, Karung Berkunci, \n88586 Kota Kinabalu, Sabah, Malaysia.\nEmail: wftan85@gmail.com\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n66\n\n\n\nLaboratory investigations revealed bicytopenia \n(haemoglobin 9.5 g/dl, platelet 102x103 /\u03bcL) with \nlymphopenia (0.55x103 /\u03bcL), and raised C-reactive \nprotein 55.3 mg/L. Liver function tests were deranged \n(AST275 U/L,  ALT209 U/L, ALP454 U/L, GGT275 \nU/L) with hyperbilirubinemia, hypoalbuminemia \n(albumin 16 g/L) and coagulopathy (INR1.94). Her \nANA was positive with a titre of >1:1280 and her \ncomplements were low (C3-0.4 g/L, C4-0.09 g/L). \nHowever, dsDNA, anti-smith, anti-Ro and anti-La \nantibodies were negative. Hepatitis B, C, HIV and \nmycoplasma serology were also negative.\n\n\n\nA skin biopsy taken from the left sole and abdomen \nfor histopathological examination showed full \nthickness epidermal necrosis (Figure 1b) and \ndyskeratotic cells in all layers of epidermis, with \nvacuolar interface dermatitis and perivascular \nlymphohistiocytic infiltrate (Figure 1c) respectively. \nDirect immunofluorescence (DIF) study showed \ngranular deposition of IgG, IgM and C3 at the \nbasement membrane zone. \n\n\n\nShe was diagnosed with SJS/TEN-like ACLE in \nview of a blistering rash which progressed to full \n\n\n\nFigure 1. (a) Purpuric patches over trunk and limbs with haemorrhagic crusting on lips; (b) Full thickness epidermal necrosis with \nsubepidermal split (Hematoxylin & Eosin x100); (c) Dyskeratotic cells in all layers of epidermis, basal vacuolar degeneration with mild \nperivascular lymphohistiocytic infiltrate (Hematoxylin & Eosin x100)\n\n\n\nno genitalia involvement. There was no lymphadenopathy and examination of the respiratory, \ncardiovascular and abdominal systems were unremarkable.\n\n\n\nFigure 1. Purpuric patches over trunk and limbs with haemorrhagic crusting on lips\n\n\n\nLaboratory investigations revealed bicytopenia (haemoglobin 9.5 g/dl, platelet 102 x 103/\u03bcL) \nwith lymphopenia (0.55 x 103/\u03bcL), and raised C-reactive protein 55.3 mg/L. Liver function \ntests were deranged (AST 275 U/L, ALT 209 U/L, ALP 454 U/L, GGT 275 U/L) with \nhyperbilirubinemia, hypoalbuminemia (albumin 16 g/L) and coagulopathy (INR 1.94). Her \nANA was positive with a titre of >1:1280 and her complements were low (C3 - 0.4g/L, C4 -\n0.09 g/L). However, dsDNA, anti-smith, anti-Ro and anti-La antibodies were negative. \nHepatitis B, C, HIV and mycoplasma serology were also negative.\n\n\n\nA skin biopsy taken from the left sole and abdomen for histopathological examination \nshowed full thickness epidermal necrosis (Figure 2) and dyskeratotic cells in all layers of \nepidermis, with vacuolar interface dermatitis and perivascular lymphohistiocytic infiltrate \n(Figure 3) respectively. Direct immunofluorescence (DIF) study showed granular deposition \nof IgG, IgM and C3 at the basement membrane zone. \n\n\n\nShe was diagnosed with SJS/TEN-like ACLE in view of a blistering rash which progressed to \nfull epidermal detachment, characteristic histological and DIF findings, no history of recent \ndrug ingestion with cytopenias, hypocomplementemia and positive ANA.\n\n\n\nShe was started on intravenous hydrocortisone 100mg 8 hourly and antibiotics for presumed \ninfection. She was co-managed with rheumatology, gastroenterology, ophthalmology and \ndental team. Oral hydroxychloroquine 200mg was added. Cutaneous involvement progressed \n\n\n\nover the next 5 days with epidermal detachment involving 27% body surface area (BSA) \nwhich subsequently re-epithelialized. \n\n\n\nFigure 2. Full thickness epidermal necrosis with subepidermal split (Hematoxylin & Eosin\nx100)\n\n\n\nFigure 3. Dyskeratotic cells in all layers of epidermis, basal vacuolar degeneration with mild \nperivascular lymphohistiocytic infiltrate (Hematoxylin & Eosin x100)\n\n\n\nover the next 5 days with epidermal detachment involving 27% body surface area (BSA) \nwhich subsequently re-epithelialized. \n\n\n\nFigure 2. Full thickness epidermal necrosis with subepidermal split (Hematoxylin & Eosin\nx100)\n\n\n\nFigure 3. Dyskeratotic cells in all layers of epidermis, basal vacuolar degeneration with mild \nperivascular lymphohistiocytic infiltrate (Hematoxylin & Eosin x100)\n\n\n\nepidermal detachment, characteristic histological \nand DIF findings, no history of recent drug ingestion \nwith cytopenias, hypocomplementemia and positive \nANA.\n\n\n\nShe was started on intravenous hydrocortisone \n100mg 8 hourly and antibiotics for presumed \ninfection. She was co-managed with rheumatology, \ngastroenterology, ophthalmology and dental team. \nOral hydroxychloroquine 200mg was added. \nCutaneous involvement progressed over the next \n5 days with epidermal detachment involving 27% \nbody surface area (BSA) which subsequently re-\nepithelialized.\n\n\n\nDiscussion\nSJS/TEN-like lupus is an uncommon manifestation \nof ACLE. This condition is triggered by exposure \nto ultraviolet (UV) light in an individual with \nSLE predisposition which leads to keratinocyte \napoptosis.1 This condition must be differentiated \nfrom SJS/TEN induced by drugs or infection, which \nalso occurs more commonly in patients with SLE.2 \nOther differentials to consider include bullous LE, \nTEN-like acute graft versus host disease (GVHD) \n\n\n\na b\n\n\n\nc\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n67\n\n\n\nand TEN-like pseudoporphyria.\n\n\n\nThe distinctive feature in both SJS/TEN and \nSLE is keratinocyte apoptosis. In SJS/TEN, the \npathogenesis is postulated to be due to cytotoxic \nT cell damage mediated by granzyme, granulysin, \nperforin and Fas-fas ligands interactions.3 In \ncutaneous lupus, UV exposure leads to keratinocyte \napoptosis, increased chemokine production and \nsubsequent activation of autoreactive T cells.4,5 Fas \nexpression is also upregulated in ACLE.5,6\n\n\n\nMost of the patients with SJS/TEN-like ACLE \nare middle-aged females with the onset of rash \npreceding epidermal detachment for days up to \n2 weeks. Up to half of the patients have no prior \ndiagnosis of SLE.2 The rash may initially be photo-\ndistributed, then become generalised.7 Earlier \n\n\n\nstudies have reported that mucous membranes were \nusually spared,2,8 however a recent case series by \nTankunakorn et al. reported that half of the patients \nhad severe mucositis. In their cohort, palms and \nsoles involvement were also noted.4 Lee HY et \nal. also reported presence of oral mucositis in his \npatients with no genital or perineal involvement.5 \nSimilarly, our patient had blistering rash over her \npalms and soles with haemorrhagic mucositis and \nconjunctivitis. \n\n\n\nSerological markers for SLE such as ANA, anti-Ro, \nanti-La, anti-dsDNA, anti-ribonuclear protein (anti-\nRNP) and anti-smith antibodies were commonly \npresent in patients with SJS/TEN-like ACLE. \nIn addition, high disease activity is denoted by \nhypocomplementemia, elevated ESR and organ \ninvolvement in these patients.2 Histological findings \n\n\n\nTable 1. Differential diagnoses to consider8-12\n\n\n\nCharacteristics SJS/TEN SJS-TEN-like ACLE Bullous LE TEN-like acute \nGvHD\n\n\n\nTEN-like \nPseudoporphyria\n\n\n\nOnset Acute - hours to days Subacute - days to \nweeks\n\n\n\nAcute Subacute - days to \nweeks\n\n\n\nSubacute\n\n\n\nComorbid/\nEtiology\n\n\n\nDrugs (80%), rarely \ninfection\n\n\n\nTriggered by UV, may \nhave underlying lupus\n\n\n\nUnknown Recent history of bone \nmarrow transplant\n\n\n\nHistory of ingestion \nof nonsteroidal anti-\niflammatory drugs or \nphotosensitising drug \nwith UV exposure, in \na patient undergoing \nhemodialysis\n\n\n\nSkin manifestations Painful, purpuric \nmacules and patches \nwith blistering\n\n\n\nPurpuric macules and \npatches with blistering, \nphoto distributed areas\n\n\n\nTense bullae at photo \ndistributed area\n\n\n\nMorbilliform eruption \nwith predilection for \nacral areas and upper \ntrunk, folliculocentric \npattern, pruritus\n\n\n\nExtensive area of \nflaccid bulla, with \nepidermal sloughing\n\n\n\nMucosal Involvement Present May be present May be present Present Present\nSystemic involvement Present May be present May be present May be present \n\n\n\n(gastrointestinal/\nhepatobiliary \ninvolvement)\n\n\n\nMay be present\n\n\n\nAutoimmune serology Negative ANA, dsDNA, \nanti-Ro, rheumatoid \nfactor may be positive\n\n\n\nANA, anti-Ro, anti-La, \nrheumatoid factor may \nbe positive\n\n\n\nNegative Negative\n\n\n\nHistological findings Full thickness \nepidermal necrosis \nwith subepidermal \nseparation, sparse to \nabsent lymphocytic \ninfiltrate\n\n\n\nFull thickness \nepidermal necrosis \nwith subepidermal \nseparation, \nmoderate to dense \nsuperficial dermal \nlymphocytic infiltrate \nat perivascular and \nperiadnexal areas, \ninterface dermatitis \nand mucin deposition\n\n\n\nSubepidermal blister \nwith neutrophils, \nvacuolar interface \ndermatitis with mucin \ndeposition\n\n\n\nKeratinocyte apoptosis, \nbasal layer hydropic \ndegeneration, band-\nlike lymphohistiocytic \ninfiltrate in upper \ndermis\n\n\n\nSubepidermal \nbullae with minimal \nperivascular \nlymphocytic infiltrate, \nfestooning of the \ndermal papilla\n\n\n\nDirect \nImmunofluorescence\n\n\n\nNegative Granular IgG, \nIgM, and/or C3 \nmay be present at \ndermoepidermal \njunction (DEJ)\n\n\n\nLinear or granular \nIgG, IgM, IgA and C3 \nat DEJ\n\n\n\nNegative May have granular \ndeposits of C3 and IgG \nat DEJ\n\n\n\nTreatment Stop the offending \ndrug, IVIg, Systemic \ncorticosteroids, \ncyclosporin\n\n\n\nSystemic \ncorticosteroids, \nimmunosuppressants\n\n\n\nDapsone, systemic \ncorticosteroids\n\n\n\nSystemic \ncorticosteroids, \nimmunosuppressants\n\n\n\nStop the offending \ndrug, sun protection\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n68\n\n\n\nare summarised in Table 1. \n\n\n\nManagement of SJS/TEN-like ACLE involves \nhospitalisation with administration of high dose \ncorticosteroids or pulse therapy. Corticosteroids \nwere used in most cases to control the disease \nactivity of ACLE.5,9 In extensive cases, intravenous \nimmunoglobulin (IVIG) has been successfully \nused. IVIG blocks the interaction of Fas-Fas ligand, \nhalting the process of keratinocyte apoptosis.9 For \nrefractory cases, plasmapheresis which has been \nused to remove circulating autoantibodies and \nimmune reactants, has led to treatment success.2,9\n\n\n\nConclusion \nThis rare condition must be considered in patients \nwho has no clear precipitating drug history with \nmultisystem involvement as prompt recognition \nand early treatment with systemic corticosteroids is \nassociated with good prognosis. \n\n\n\nConflict of Interest Declaration \nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper\n\n\n\nReferences\n\n\n\n1. Kuhn A, Bijl M. Pathogenesis of cutaneous lupus \nerythematosus. Lupus 2008;17:389-93.\n\n\n\n2. Ziemer M, Kardaun SH, Liss Y, Mockenhaupt M. Stevens-\nJohnson syndrome and toxic epidermal necrolysis in \npatients with lupus erythematosus: a descriptive study \nof 17 cases from a national registry and review of the \nliterature. Br J Dermatol 2012;166:575-600.\n\n\n\n3. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. \nCurrent Perspectives on Stevens-Johnson Syndrome and \nToxic Epidermal Necrolysis. Clin Rev Allergy Immunol \n2018;54:147-76.\n\n\n\n4. Tankunakorn J, Sawatwarakul S, Vachiramon V, \nChanprapaph K. Stevens-Johnson Syndrome and Toxic \nEpidermal Necrolysis-Like Lupus Erythematosus. J Clin \nRheumatol 2019;25:224-31.\n\n\n\n5. Lee HY, Tey HL, Pang SM, Thirumoorthy T. Systemic \nlupus erythematosus presenting as Stevens-Johnson \nsyndrome and toxic epidermal necrolysis: a report of three \ncases. Lupus 2011;20:647-52.\n\n\n\n6. Werth VP. Cutaneous lupus: insights into pathogenesis and \ndisease classification. Bull NYU Hosp Jt Dis 2007;65:200-\n4.\n\n\n\n7. Merklen-Djafri C, Bessis D, Frances C, Poulalhon \nN, Debarbieux S, Cordel N et al. Blisters and Loss of \nEpidermis in Patients with Lupus Erythematosus: A \nClinicopathological Study of 22 Patients. Medicine \n(Baltimore) 2015;94:e2102.\n\n\n\n8. Ting W, Stone MS, Racila D, Scofield RH, Sontheimer \nRD. Toxic epidermal necrolysis-like acute cutaneous lupus \nerythematosus and the spectrum of the acute syndrome \nof apoptotic pan-epidermolysis (ASAP): a case report, \nconcept review and proposal for new classification of \nlupus erythematosus vesiculobullous skin lesions. Lupus \n2004;13:941-50.\n\n\n\n9. Baker MG, Cresce ND, Ameri M, Martin AA, Patterson \nJW, Kimpel DL. Systemic lupus erythematosus presenting \nas Stevens-Johnson syndrome/toxic epidermal necrolysis. \nJ Clin Rheumatol 2014;20:167-71.\n\n\n\n10. Romero LS, Bari O, Forbess Smith CJ, Schneider JA, Cohen \nPR. Toxic epidermal necrolysis-like acute cutaneous lupus \nerythematosus: report of a case and review of the literature. \nDermatol Online J 2018;24(5):13030/qt5r79d67k.\n\n\n\n11. Mandelcorn R, Shear NH. Lupus-associated toxic \nepidermal necrolysis: a novel manifestation of lupus? J \nAm Acad Dermatol 2003;48:525-9.\n\n\n\n12. Papadopoulos AJ, Schwartz RA, Fekete Z, Kihiczak G, \nSamady JA, Atkin SH et al. Pseudoporphyria: an atypical \nvariant resembling toxic epidermal necrolysis. J Cutan \nMed Surg 2001;5:479-85.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n69\n\n\n\nIntroduction\nAcne fulminans is uncommon and severe \ncomplication of acne vulgaris. Its onset is rapid \nassociated with painful erosions and haemorrhagic \ncrusts. In most severe cases it manifests as fever, \narthralgia and osteolytic lesions. Pseudo-acne \nfulminans is one entity which does not show these \nfeatures. Isotretinoin is most common cause of acne \nfulminans. For combating this unusual but serious \ncomplication low dose steroids should be started \nalong with isotretinoin.1,5  \n\n\n\nCase Report\nA 17-year-old female patient presented in Skin \nOPD with a clinical picture of macro-comedones \nwhich later progressed to pustule-nodular lesions \non face and chest. History of application of topical \nsteroid was present. We started patient on topical \nclindamycin 1% and adapalene 0.1% for 3 weeks; \ndue to no response to treatment with topical \nmedications, she was prescribed azithromycin 500 \nmg pulse therapy along with topical medications \nfor next 3 weeks but patient did not improve. We \nshifted her to oral isotretinoin 20mg (0.3mg/kg/day) \nfor another 15 days. After 15 days of isotretinoin, \nthe girl returned with severe ulcerative crusting \nacne and nodular acne over face and chest (Figure \n1a & 1b). There was no history of fever, arthralgia \nor other systemic symptom and the laboratory \nparameters remained within normal limits. \n\n\n\nGram stain and pus culture report showed growth \nof MRSA after 48 hours of incubation. Isotretinoin \n\n\n\nCASE REPORT\n\n\n\nAcne Fulminans Sine Fulminans         \n\n\n\nNidhi Yadav, MD, Sumit Kar, MD, Pooja Bonde, DDVL, Pooja Manwar, MBBS, Komal Ramteke, MBBS, Safa Patrick, \nMBBS \n\n\n\nDepartment of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, \nWardha, Maharashtra, India\n\n\n\nSummary\nAcne fulminans is a rare and most serious form of acne. It is characterized by the sudden onset \nof nodular and ulcerative acne lesions with systemic symptoms. It can be triggered by initiation of \nisotretinoin however these patients do not have systemic involvement. Some authors have recognised \nthis entity as \u201cpseudo-acne fulminans\u201d or \u201cacne fulminans sine fulminans,\u201d We report a case with \nthese features of pseudo-acne fulminans.\n\n\n\nKey words: Acne fulminans, acne vulgaris, pustules, nodules, scarring, acne fulminans sine fulminans, pseudo-acne fulminans\n\n\n\nCorresponding Author\nProf Dr Sumit Kar\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences, \nSewagram, Maharashtra, \n442102 India.\nEmail: karmgims@gmail.com\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n70\n\n\n\nwas stopped. Later she was started on tab prednisone \n1mg/kg/day and injectable ceftriaxone for 7 days but \nno improvement was seen after 7 days of injectable \nantibiotic. After 7 days intralesional triamcinolone \nacetonide (2.5mg/ml) was given daily for next 7 days \nwith oral prednisolone following which dramatic \nimprovement was recorded with decreased crusting \nand size of nodulocystic acne. He was maintained \non topical adapalene and clindamycin later. But \nwithin a week, it was followed by eruption of new \npustular and ulcerative crusting acne. As patient was \nnot satisfied with the above treatment she visited \nanother dermatologist and was prescribed with oral \ndoxycycline 100 mg twice daily for 2 weeks but \nno improvement was seen. Again patient visited \nus and was prescribed Tab linezolid 600 mg twice \n\n\n\ndaily for 3 days with prednisolone (1mg/kg/day). \nOral linezolid was stopped after 3 days and she was \nmaintained on low dose oral prednisolone for next \n3 months. \n\n\n\nWe followed up the patient after every 7 days and \ntapered off the steroid dose by 5 mg in each visit. \nOral prednisolone was tapered by 5 mg after every \n7 days. After 3 days of this therapy (Oral linezolid \nwith oral prednisolone) there was significant \nimprovement. Later patient was followed up till \ncompletion of treatment with oral steroid (3 months). \nSince the patient had complete resolution of lesions \nwith antibiotic and steroid we did not consider \nreintroducing oral isotretinoin to the patient. \n\n\n\nFigure 1a & 1b. Multiple nodular lesions and ulcerative lesions with adherent crusting over face\n\n\n\nfever, arthralgia or other systemic symptom and the laboratory parameters remained within \nnormal limits.  \n \nGram stain and pus culture report showed growth of MRSA after 48 hours of incubation. \nIsotretinoin was stopped. Later she was started on tab prednisone 1mg/kg/day and injectable \nceftriaxone for 7 days but no improvement was seen after 7 days of injectable antibiotic. \nAfter 7 days intralesional triamcinolone acetonide (2.5mg/ml) was given daily for next 7 days \nwith oral prednisolone following which dramatic improvement was recorded with decreased \ncrusting and size of nodulocystic acne. He was maintained on topical adapalene and \nclindamycin later. But within a week, it was followed by eruption of new pustular and \nulcerative crusting acne. As patient was not satisfied with the above treatment she visited \nanother dermatologist and was prescribed with oral doxycycline 100 mg twice daily for 2 \nweeks but no improvement was seen. Again patient visited us and was prescribed Tab \nlinezolid 600 mg twice daily for 3 days with prednisolone (1mg/kg/day). Oral linezolid was \nstopped after 3 days and she was maintained on low dose oral prednisolone for next 3 \nmonths.  \n \nWe followed up the patient after every 7 days and tapered off the steroid dose by 5 mg in \neach visit. Oral prednisolone was tapered by 5 mg after every 7 days. After 3 days of this \ntherapy (Oral linezolid with oral prednisolone) there was significant improvement. Later \npatient was followed up till completion of treatment with oral steroid (3 months). Since the \npatient had complete resolution of lesions with antibiotic and steroid we did not consider \nreintroducing oral isotretinoin to the patient. \n \nFigure 1a & 1b. Multiple nodular lesions and ulcerative lesions with adherent crusting over \nface \n \n\n\n\n\n\n\n\nfever, arthralgia or other systemic symptom and the laboratory parameters remained within \nnormal limits.  \n \nGram stain and pus culture report showed growth of MRSA after 48 hours of incubation. \nIsotretinoin was stopped. Later she was started on tab prednisone 1mg/kg/day and injectable \nceftriaxone for 7 days but no improvement was seen after 7 days of injectable antibiotic. \nAfter 7 days intralesional triamcinolone acetonide (2.5mg/ml) was given daily for next 7 days \nwith oral prednisolone following which dramatic improvement was recorded with decreased \ncrusting and size of nodulocystic acne. He was maintained on topical adapalene and \nclindamycin later. But within a week, it was followed by eruption of new pustular and \nulcerative crusting acne. As patient was not satisfied with the above treatment she visited \nanother dermatologist and was prescribed with oral doxycycline 100 mg twice daily for 2 \nweeks but no improvement was seen. Again patient visited us and was prescribed Tab \nlinezolid 600 mg twice daily for 3 days with prednisolone (1mg/kg/day). Oral linezolid was \nstopped after 3 days and she was maintained on low dose oral prednisolone for next 3 \nmonths.  \n \nWe followed up the patient after every 7 days and tapered off the steroid dose by 5 mg in \neach visit. Oral prednisolone was tapered by 5 mg after every 7 days. After 3 days of this \ntherapy (Oral linezolid with oral prednisolone) there was significant improvement. Later \npatient was followed up till completion of treatment with oral steroid (3 months). Since the \npatient had complete resolution of lesions with antibiotic and steroid we did not consider \nreintroducing oral isotretinoin to the patient. \n \nFigure 1a & 1b. Multiple nodular lesions and ulcerative lesions with adherent crusting over \nface \n \n\n\n\n\n\n\n\n1a 1b\n\n\n\nDiscussion\nAcne fulminans (AF) is a rare and severe form of \nacne vulgaris. AF was initially labeled acne maligna \nor acute febrile ulcerative acne conglobota. The \nterm acne fulminans was first coined by Plewig and \nKligman in 1975.1 Young males are affected most \ncommonly.2 It is characterised by abrupt onset of \nnodular and ulcerative crusting acne. It is associated \nwith systemic symptoms like fever, myalgia, \narthralgia and osteolytic lesions. \n\n\n\nMost common site is trunk mainly back, however \nface and chest can be involved, Initial lesions are \nusually sterile may get infected secondarily during \nprogression.2 Acne fulminans presents as abrupt \n\n\n\nonset of nodular and ulcerative crusting acne in a \npatient having mild to moderate acne vulgaris.\n\n\n\nBurns and Colville3 has proposed five criteria for \nthe diagnosis of acne fulminans:\n\n\n\n1. Sudden onset of lesions; \n2. Severe ulcerated acne which determine \n\n\n\ncicatricial lesions; \n3. Systemic symptoms like fever and \n\n\n\npolyarthralgia; \n4. Absence of response to antibiotics; \n5. Favourable response to corticosteroid therapy\n\n\n\nPseudo-acne fulminans, also known as acne \n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n71\n\n\n\nfulminans sine fulminans occurs in patients \nstarted on isotretinoin. These patients usually do \nnot have systemic symtoms. The etiology of acne \nfulminans is not yet clearly elucidated. Risk factor \ninclude, hereditary, bacterial infections, drugs and \nimmunological mechanisms have been proposed as \nits triggering factors.4 \n\n\n\nVarious drugs have also been proposed as a triggering \nfactor for the development of this entity. It includes \nisotretinoin, tetracycline and testosterone1,4. Of \nnote, acne fulminans is a rare complication of oral \nisotretinoin therapy. Isotretinoin causes increased \nfragility of epithelium of pilosebaceous ducts leads \nexposure of Propionobacterium acne to systemic \nenvironments. This leads to exaggerated type III \nand IV hypersensitivity reactions in some patients.5\n\n\n\nA common characteristic to virtually all patients was \nthe presence of macro-comedones and use of oral \nisotretinoin before the onset of the clinical picture. \nUse of topical steroids may further lead to thinning \nof their follicular wall.6 To avoid development of \nthis troublesome condition in patients with macro-\ncomedones, early introduction of prednisone with a \ndose of 0.5 or 1.0 mg/kg/day for 4-6 weeks slowly \ndecreasing later on.4,6 \n\n\n\nAs far as isotretinoin induced acne fulminans is \nconcerned, isotretinoin should be discontinued \nand should be started only when the inflammation \ndecreases. Isotretinoin should be restarted at a \nvery low dose of 0.25-0.5 mg/kg/day; dose of \nisotretinoin can then be increased and corticosteroid \ngradually tapered off. Oral antibiotics are usually \nineffective. But In our case, pus culture sensitivity \nreports showed MRSA and we saw improvement \nwithout restarting low dose isotretinoin, we decided \nto maintain patient on low dose steroids only.\n\n\n\nConclusion\nPseudo-acne fulminans presents with abrupt onset \nof flare of inflammatory acne with ulceration and \ncrusting of nodules or plaques without systemic \nsymptoms triggered by initiation of isotretinoin. \nAwareness of this entity among dermatologists is \nimportant so that appropriate measures can be taken \nin the patients at risk of developing this entity when \nstarting isotretinoin.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nNil.\n\n\n\nReferences\n\n\n\n1.  Greywal T, Zaenglein AL, Baldwin HE, Bhatia N, Chernoff \nKA, Del Rosso JQ et al. Evidence-based recommendations \nfor the management of acne fulminans and its variants. J \nAm Acad Dermatol 2017;77:109-17.\n\n\n\n2. Proen\u00e7a NG. Acne fulminans. An Bras Dermatol \n2017;92(1):8-10.\n\n\n\n3. Isotretinoin. Reactions Weekly 2015;1536:125.  \n4. Grando LR, Leite OG, Cestari TF. Pseudo-acne fulminans \n\n\n\nassociated with oral isotretinoin. An Bras Dermatol \n2014;89:657-9. \n\n\n\n5. Gualtieri B, Tonini A, Panduri S, Chiricozzi A, Romanelli \nM. Acne fulminans associated with lymecycline intake: a \ncase report. Clin Cosmet Investig Dermatol 2018;11:403-\n5. \n\n\n\n6. Meena M, Mittal A, Khare AK, Gupta LK. Pseudo acne \nfulminans: An under recognized entity. Indian Dermatol \nOnline J 2018;9:462-4.\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n72\n\n\n\nCASE REPORT\n\n\n\nConcurrent Occurrence of Papulonecrotic Tuberculid and Erythema \nNodosum: A Case Report          \n\n\n\nSafa Patrick, MBBS, Sumit Kar, MD, Nidhi Yadav, MD, Nitin Gangane, MD, Abhay Deshmukh, MD, Priyanka Date, \nMD, Ajinkya Sawant, MBBS\n\n\n\nDepartment of Dermatology, Venereology & Leprosy, Mahatma Gandhi Institute of Medical Sciences. Sewagram, \nMaharashtra, India\n\n\n\nSummary\nDespite having a large national and international burden of tuberculosis, still only one single case report \nhas been published on papulonecrotic tuberculid with erythema nodosum. Herein we are reporting a \ncase of 40-year-old female who presented with both papulonecrotic tuberculid and erythema nodosum \ntype of lesions.\n\n\n\nKey words: Papulonecrotic tuberculid, erythema nodosum, tuberculosis, panniculitis, lichen scrofulosorum\n\n\n\nIntroduction\nMany types of hypersensitivity reactions to \nMycobacterium tuberculosis antigens have been \ndescribed but few entities such as papulonecrotic \ntuberculid and lichen scrofulosorum are classified \nas true tuberculids. Papulonecrotic tuberculid \n(PNT) generally presents as an asymptomatic \nand chronic disorder. The lesions of  PNT tend to \noccur in crops. An underlying focus of tuberculosis \nis usually present.1 Most commonly the lesions \nof papulonecrotic tuberculoid are distributed \nsymmetrically over the extensor aspect of \nextremities, face and ear.2 A characteristic feature \nof this condition is that the lesion heals with \nvarioliform scarring. Erythema nodosum (EN) is \nclinically the most frequent form of panniculitis \nand is triggered by a wide variety of stimuli. We \nare reporting this case report as only one case report \nhas been published on concurrent papulonecrotic \ntuberculid and erythema nodosum until now.\n\n\n\nCase Report\nA 40-year-old female patient presented with \nrecurrent crops of tender; erythematous nodules \npresent symmetrically over extensor aspect of both \nlower limbs over past six years. After three months, \nshe developed multiple crusted papulo-pustular \nlesions over the extensor aspect of both upper limbs \n(Figure 1a). She also gave a history of fever and \narthralgia. There was no history of any substance \nabuse. \n\n\n\nCorresponding Author\nProf Dr Sumit Kar\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences,\nSewagram, Maharashtra, \n442102 India.\nEmail: Karmgims@gmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n73\n\n\n\nReview of systems revealed no No history of cough \nor dyspnea. There was also no history of past \ntuberculosis. There was hilar lymphadenopathy with \nconsolidation in upper lobe of right lung detected \non Chest X-ray. Erythrocyte sedimentation rate was \nelevated at 110 mm/hr. Sputum examination for \nacid fast bacilli was negative. Slit skin smears for \nacid fast bacilli were negative. \n\n\n\nA skin biopsy was done from both types of lesions \nand it confirmed the lesions histopathologically \nto be consistent with erythema nodosum and \npapulonecrotic tuberculid (Figure 1b & c). \nHistological findings of papulonecrotic tuberculid \nincluded an area of necrosis in dermis surrounded \nby granulomatous infiltrate and giant cells. \nHistological findings of erythema nodosum included \na septal panniculitis with a superficial and deep \nperivascular inflammatory lymphocytic infiltrate. A \nbiopsy sample was also sent for AFB culture, which \nreturned as negative. \n\n\n\nShe was empirically started on category 1 \nantitubercular treatment (ATT) based on her Chest \nX-ray findings and raised ESR levels.  A rapid \nresponse to anti-Tuberculosis treatment as expected \nwith tuberculids was seen after initiating the \ntreatment.\n\n\n\nDiscussion\nThe concept of tuberculids was introduced by \nDarier in the year 1896. Tuberculids traditionally \ninclude Papulonecrotic tuberculid (PNT), lichen \nscrofulosorum and erythema induratum of Bazin.3 It \nis mostly seen in females. Its pathophysiology is still \nnot clear. A hypersensitivity reaction to tuberculosis \nantigens from a distant focus of infection is thought \nto be held responsible for the papulonecrotic \ntuberculid.4,5 \n\n\n\nMain diagnostic criteria for PNT include absence of \nmycobacterial organisms in skin culture and smear, \na positive tuberculin test and rapid resolution of \nlesions with the start of Antitubercular treatment. \nErythema nodosum typically presents as painful, \nerythematous nodules on the anterior aspect of the \nlegs. Sometimes the lesions may be ecchymotic \ntoo. This condition is mostly idiopathic but can \noccur secondary to internal diseases, medication \nor many other conditions. EN is also thought to be \na hypersensitivity reaction to antigens associated \nwith a wide variety infection such as tuberculosis, \nstreptococcal infections, Yersinia enterocolitica, Y. \npseudotuberculosis, cat scratch disease, tularemia \nand acute upper respiratory tract infections.6\n\n\n\nPNT seems to be the least common form of cutaneous \ntuberculosis reported even in area endemic for \ncutaneous tuberculosis. Co-existence of PNT and \nlichen scrofulosorum has been reported previously \nin 4 case reports7,8,9,10 but only one case report \nhas been published on concurrent papulonecrotic \ntuberculoid and erythema nodosum to date.  \n\n\n\nFigure 1. (a) Photograph showing papular lesions with crusting \nover forearm; (b) Section showing an area of necrosis in dermis \n(red arrow) surrounded by granulomatous infiltrate and giant \ncells (green arrow) (H&E, 400x); Section showing septal \npanniculitis (red arrow) with superficial and deep perivascular \ninflammatory lymphocytic infiltrate (green arrow) (H&E, 400x)\n\n\n\nFigure 2. Section showing an area of necrosis in dermis (red arrow) surrounded by \ngranulomatous infiltrate and giant cells (green arrow) (H&E, 400x) \n \n\n\n\n \n \nFigure 3. Section showing septal panniculitis (red arrow) with superficial and deep perivascular \ninflammatory lymphocytic infiltrate (green arrow) (H&E, 400x) \n \n\n\n\n\n\n\n\nFigure 2. Section showing an area of necrosis in dermis (red arrow) surrounded by \ngranulomatous infiltrate and giant cells (green arrow) (H&E, 400x) \n \n\n\n\n \n \nFigure 3. Section showing septal panniculitis (red arrow) with superficial and deep perivascular \ninflammatory lymphocytic infiltrate (green arrow) (H&E, 400x) \n \n\n\n\n\n\n\n\nCase Report \nA 40-year-old female patient presented with recurrent crops of tender; erythematous nodules \npresent symmetrically over extensor aspect of both lower limbs over past six years. After three \nmonths, she developed multiple crusted papulo-pustular lesions over the extensor aspect of both \nupper limbs (Figure 1). She also gave a history of fever and arthralgia. There was no history of \nany substance abuse.  \n \nFigure 1. Photograph showing papular lesions with crusting over forearm. \n \n\n\n\n \n \nReview of systems revealed no No history of cough or dyspnea. There was also no history of \npast tuberculosis. There was hilar lymphadenopathy with consolidation in upper lobe of right \nlung detected on Chest X-ray. Erythrocyte sedimentation rate was elevated at 110 mm/hr. \nSputum examination for acid fast bacilli was negative. Slit skin smears for acid fast bacilli were \nnegative.  \n \nA skin biopsy was done from both types of lesions and it confirmed the lesions \nhistopathologically to be consistent with erythema nodosum and papulonecrotic tuberculid \n(Figure 2 & 3). Histological findings of papulonecrotic tuberculid included an area of necrosis in \ndermis surrounded by granulomatous infiltrate and giant cells. Histological findings of erythema \nnodosum included a septal panniculitis with a superficial and deep perivascular inflammatory \nlymphocytic infiltrate. A biopsy sample was also sent for AFB culture, which returned as \nnegative.  \n \n \n \n \n \n \n\n\n\na\n\n\n\nb\n\n\n\nc\n\n\n\n\n\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n74\n\n\n\nConclusion\nBased on the present case, PNT and EN lesions can \ncoexist with distinct uncommon clinical findings. \nTherefore, a high index of suspicion is needed for \nearly diagnosis. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil.\n\n\n\nReferences\n\n\n\n1. Singh SK, Rai T. Papulonecrotic tuberculid in a patient \nwith pulmonary tuberculosis. Indian Dermatol Online J \n2014;5:72-3.\n\n\n\n2. Kullavanijaya P, Sirimachan S, Suwantaroj S. \nPapulonecrotic tuberculid. Necessity of long-term triple \nregimens. Int J Dermatol 1991;30:487-90.\n\n\n\n3. Hallensleben ND, de Vries HJ, Lettinga KD, Scherpbier \nHJ. Tuberculids: cutaneous indicator diseases of \nMycobacterium tuberculosis infection in young patients. J \nEur Acad Dermatol Venereol 2016;30:1590-3.\n\n\n\n4. Dar NR, Raza N, Zafar O, Awan S. Papulonecrotic \ntuberculids associated with uveitis. J Coll Physicians Surg \nPak 2008;18:236-8.\n\n\n\n5. Joshi HS, Zacharia A, Warrier A. Lichen scrofulosorum. \nBMJ Case Rep 2014;2014:bcr2013200858 \n\n\n\n6. Ayd\u0131n-Teke T, Tan\u0131r G, Bayhan GI, Metin O, Oz N. \nErythema nodosum in children: evaluation of 39 patients. \nTurk J Pediatr 2014;56:144-9.\n\n\n\n7. Yadav P, Mendiratta V, Nikita, Chander R. Concurrent \nlichen scrofulosorum and papulonecrotic tuberculid in a \npatient with tubercular lymphadenitis. Indian J Dermatol \nVenereol Leprol 2014;80:483.\n\n\n\n8. Wechsler HL. Tuberculosis of axillary lymph \nnodes; phlyctenular keratitis; lichen scrofulosorum; \npapulonecrotic tuberculide; erythema induratum. AMA \nArch Derm Syphilol 1951;64:508-9.\n\n\n\n9. Thappa DM, Karthikeyan K, Jayanthi S. Tuberculid in \na child: Transformation from papulonecrotic to lichen \nscrofulosorum. Pediatr Dermatol 2003;20:91-3.\n\n\n\n10. Das JK, Sengupta S, Mitra S, Gangopadhyay AK. \nCoexistence of papulonecrotic tuberculide with lichen \nscrofulosorum. Indian J Dermatol 2010;55:109-12.\n\n\n\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2020 Dec Vol 45\n\n\n\nDermatology\n\n\n\n75\n\n\n\nACKNOWLEDGEMENT\nDec Issue 2020\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Datin Dr Asmah Johar\n4. Dr Ch\u2019ng Chin Chwen\n5. Dr Chan Lee Chin\n6. Dr Chang Choong Chor\n7. Dr Chong Yew Thong\n8. Dr Dawn Ambrose\n9. Assoc Professor Dr Felix Yap Boon Bin\n10. Dr Henry Foong Boon Bee\n11. Dr Irene Lee Chew Kek\n12. Dr Khor Yek Huan\n13. Dr Kwan Zhenli\n14. Dr Lo Kang Shang Chit\n15. Dr Mazlin bt Mohd Baseri\n16. Dr Ng Ting Guan\n17. Dato\u2019 Dr Noor Zalmy Azizan\n18. Dr Norashikin Bt Shamsudin\n19. Dr Rajalingam Ramalingam\n20. Dr Tang Jyh Jong\n21. Dr Tang Min Moon\n\n\n\n\n\n"
"\n\nVolume 31   |  Dec 2013   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.myIndexed in: Western Pacific Research Index Medicus\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2013 Dec Vol 31\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:  rohnaridzwan@\nyahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology can \nbe sent to me at:\nrohnaridzwan@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation. \nThis category provides rapid publications and is meant to be a \nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in the \narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods , Results, Comment and \nReferences. A Structured Abstract of not more than 240 words \nmust be included. It should consist of four paragraphs, labelled \nBackground, Methods, Results, and Conclusions. It should \ndescribe the problem studies, how the study was performed, \nthe main results, and what the author(s) concluded from the \nresults. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and \nsummarizes the existing knowledge in a particular field. \nIt should not be an exhaustive review of the literature, and \nreferences should not exceed 100 in number. Tables, diagrams, \nand selected figures are often helpful. The length is left to the \njudgment of the author, although it generally should not exceed \n5000 words. Topics may include updates in clinically relevant \nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author who \nwill be responsible for reading the proofs must also be given on \nthe title page. The author(s) must also declare any affiliation or \nsignificant financial involvement in any organizations or entity \nwith a direct financial interest in the subject matter or materials \ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in \nthe manuscript. References from journals should include: (1) \nname(s) followed by the initials of the author(s), up to four \nauthors: if more than four authors, include the first three authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; (5) \nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A \nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n55.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) referred \nto. \n\n\n\nFor example: \nFoong HBB.  Transcontinental Dermatology: Virtual Grand \nRounds. In: Wootton R and Oakley A, editors. Teledermatology. \nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on \nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\nNotice to Authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\niMJD 2013 Dec Vol 31\n\n\n\nEditor-in-Chief \nRohna Ridzwan, MRCP\nrohnaridzwan@yahoo.com\n\n\n\nFounding Editor\nSteven Chow Kim Wing, FRCPI\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP \nghbelani@hotmail.com\n\n\n\nHenry Foong Boon Bee, FRCP\nbbfoong@pc.jaring.my\n\n\n\nChan Lee Chin, MMed \nlccjess@yahoo.com\n\n\n\nAgnes Heng Yoke Hui, MRCP\nagnesheng2002@yahoo.com\n   \nChang Chong Chor, AdvMDerm\nccchor@gmail.com\n\n\n\nTan Min Moon, AdvMDerm\nminmoon2005@yahoo.com\n\n\n\nFelix Yap Boon Bin, AdvMDerm \nwoodzlamp@yahoo.com\n\n\n\neditorial\n\n\n\nWORLD SKIN \nHEALTH DAY\n2013\n\n\n\nThe Malaysian Dermatological Society \ncelebrates its World Skin Health Day by \nwelcoming patients to join as partners with \nhealth care providers in promoting patient safety. \nPatients and their family members can improve \npatients\u2019 outcome by learning to recognise skin \nreactions caused by medications and alert their \nhealth care providers promptly. They can play \nan important role in preventing medical errors \nand adverse events. This article is published in \nMalaysian English Daily newspaper.\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nExecutive Staff\nNajeeb Ahmad Safdar, MRCP - President \nKoh Chuan Keng, MRCP - Past President \nHenry Foong Boon Bee, FRCP - Vice President  \nAgnes Heng Yoke Hui, MRCP - Secretary\nNoor Zalmy Azizan, AdvMDerm - Treasurer\nMd Noh Idris, FRCP, FRCPI\nChan Lee Chin, MMed\nKhor Guat Ee, MRCP\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJalan 112, Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2013 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nii MJD 2013 Dec Vol 31\n\n\n\nRECOGNISING SKIN ADVERSE\nDRUG REACTIONS\nMedications have relieved many symptoms, cured \nsome and rarely caused unwanted skin reactions \nand suffering. Although most of these skin side \neffects resolve on stopping the medications, severe \nforms of drug reaction can cause a temporary \ndisfigurement and even death especially in those \nwho present late and have other medical illnesses. \nPatients and their family members should learn \nto recognise the different forms of adverse drug \nreactions and seek medical assistance as soon as \npossible. They also have the social obligation to \ninform and educate their family members and \nfriends to prevent others from suffering from \nadverse drug reactions.\n\n\n\nMeasles-like rash\nInform your doctor if you were started on any \nmedication days or weeks before the occurrence of \nitchy red spots. It may be medication for infection, \npain or traditional complementary medication and \nhealth supplements taken for general well being. \nThe rash usually starts on the face and gradually \nextends to the trunk and limbs. After stopping \nthe offending medication, the rash usually settles \nby turning brown with superficial peeling of the \nskin. This is the commonest and least dangerous \nform of skin adverse drug reaction.\n\n\n\nRed eyes with either mouth or/and genital \nulcers associated with painful skin rash\nThis is one of the severe forms of drug reaction \nwhich necessitates inpatient care and nursing \nin the hospital. If the patient has not taken any \nmedication prior to the illness, this condition may \nbe associated with a herpes viral infection.\n\n\n\nSwollen eyelids or lips \nThis usually occurs within minutes or 1 to 2 days \nafter taking medication. Itchy skin wheals may \nbe present. Danger signs include difficulty in \nswallowing, breathing or fainting. Although these \nsymptoms can rapidly improve with treatment, \nthey may recur between 4 and 16 hours later. If \nyou are staying very far from the health centres \nand have difficulty in reaching the hospital \npromptly, it is best to be observed in the hospital.\n\n\n\nOther signs of drug reaction\n\u2022\t Measles-like\trash\twith\tpustules\n\u2022\t Generalised\tred\titchy\tswollen\tskin\tor\t\n generalised dry scaly skin\n\n\n\n\u2022\t Painful\treddish-blue\tround\tpatches\tthat\theals\t\n with a blue-black stain\n\n\n\nPatient\u2019s role in his/her own safety\n1. Inform the doctor if you have \n a. History of rash after taking medication \n  i. itchy or painful red rash\n  ii. swelling of eyelids and lips\n  iii. painful red eyes with oral and/or \n   genital ulcers\n  iv. round painful reddish-blue patches \n   that heals with a blue-black stain\n b. Your face and forearms becomes \n  itchy and red after being exposed \n  to the sun  (photosensitivity/ \n  photodermatitis)\n c. Developing rash after using gloves, \n  costume jewellery, skin care products etc.                              \n  (Contact dermatitis)\n d. Family members with allergy to penicillin, \n  sulphur drugs or anti-epileptic \n  medications (familial drug reactions)\n\n\n\n2. If you are given a specimen bottle or a wrist \n tag, check whether it has your name on it.\n\n\n\n3. Inform the nurse before any injections or \n transfusion if\n a. Your doctor has not indicated that you are \n  going to receive this therapy.\n b. You are given a medication that you are \n  allergic to (e.g. penicillin group).\n c. You suspect that the medication may cross \n  react with the drug you are allergic to.\n d. The blood group stated on the blood pack \n  is different from your own blood group.\n\n\n\n4. Inform the pharmacist if \n a. You are given medication that you are \n  allergic to.\n b. You suspect that the medication may cross \n  react with the drug you are allergic to.\n c. You are given more than the usual dose of \n  your regular medication but you have not \n  been informed by the doctor.\n d. You are given medication which the \n  doctor does not ask you to take.\n\n\n\n5. Know your medications and their possible \n side effects. Return to the clinic and inform \n the doctor if any side effects occur.\n\n\n\neditorial WORLD SKIN HEALTH DAY 2013\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\niiiMJD 2013 Dec Vol 31\n\n\n\n6. If you are on moisturizing soap and \n ointment, be careful when you are walking \n on tiles especially in the bathroom. Have \n a stool, anti-slip mat and hand railing in the \n bathroom to prevent fall. Otherwise, get your \n family members to assist you in walking in \n and out of the bathroom.\n\n\n\n7. If you are given an ointment to apply on your \n lesions, ask the pharmacist\n a. The correct sites to apply it.\n b. The correct way to apply it.\n c. When to stop applying it. \n  i. Stop if the lesion worsens after \n   application\n  ii. Stop when lesion has resolved.\n  iii. Stop after 2 weeks if lesions does not \n   improve with topical steroid\n\n\n\n8. If you are given a solution to apply on the \n skin lesions, ask\n a. The correct sites to apply it.\n b. The correct way to apply it.\n c. Does the solution need to be diluted \n  before use?\n d. Does the solution need to be washed off \n  after application? If yes, when to wash \n  off.\n\n\n\n9. If you do not understand what your health \n care provider tells you, bring along a family \n member to talk to them.\n\n\n\nFAMILY MEMBER / CARE \nPROVIDER\u2019S ROLE IN PATIENT \nSAFETY \n1. Accompany patient if the patient has\n a. Difficulty in communicating with the \n  health provider.\n b. Hard of hearing or visual difficulty.\n\n\n\n2. Check with patient whether medication is \n taken or applied as instructed.\n\n\n\n3. If patient has difficulty in applying topical \n medication, learn from the health care \n provider \n\n\n\n a. How to apply them properly especially \n  shampoo and solution that require \n  dilution.\n b. The correct site for each cream/ointment/ \n  solution/solution.\n\n\n\n c. When to stop the treatment, prolonged \n  usage of certain medication may cause \n  adverse effect.\n\n\n\n4. Ask the doctor about possible side effects \n that can occur and what family/care taker \n should do \n a. When side effects occur.\n b. To prevent the side effects. E.g.\n  i. Avoid fragrant or scented skin care \n   products if the patient has eczema or \n   psoriasis.\n  ii. Protect patient from direct sunlight \n   if the drug can cause photosensitivity \n   e.g. isotretinoin, neotigason and \n   doxycycline.\n  iii. Protect the patient from direct \n   sunlight and apply sunblock if patient \n   has skin disease that is aggravated \n   by sunlight e.g. lupus erythematosus, \n   photodermatitis etc.\n  iv. Do not allow the patient to drive if he/  \n   she is taking a sedating antihistamine.\n  v. Have a stool and anti-slip mat in the \n   bathroom if the patient is on \n   moisturizing soap or ointment.\n  vi. Bring the patient for investigation as \n   instructed to check for blood / urine \n   abnormality caused by the \n   medication. \n\n\n\n5. Inform doctor if patient/sibling has history \n of allergies to medication or contact to a \n particular substance/object. \n a. If patient has allergy to \n  i. black dye, patient can also react to \n   sulfur drug.\n  ii. penicillin, patient may also react to \n   cephalosporin.\n  b. If patient\u2019s sibling has allergy to anti-\n   epileptic medication, patient may also \n   be allergic to this medication.\n\n\n\n6. Alert the nurse if the patient\u2019s name tag / \n medication slip / appointment card does not \n belong to the patient. This is to prevent \n medical error.\n\n\n\nA little effort made by patient and family as \nillustrated above may evade costly medication \nerror and improve patient safety and health while \non medical treatment. Let\u2019s work together for a \nbetter and safer health care.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1 MJD 2013 Dec Vol 31\n\n\n\nDERMATOLOGY THERAPEUTICS - Original Article\n\n\n\nADHERENCE TO TOPICAL MEDICATION IS POOR AMONG\nPATIENTS WITH ATOPIC ECZEMA\n\n\n\nMazlin MB1, Aniza I2, Jong YF2, Chia SL2, Mohd Ikhwan NMS2, Noramira A2 \n\n\n\nAbstract\n\n\n\nBackground: Non-adherence is a major hindrance to treatment success in any disease. In chronic \ndiseases, adherence to long term treatment is about 50% but existing data on adherence to topical \ntreatment in dermatological diseases are limited. In atopic eczema (AE), adherence to topical therapy \nis essential to control inflammation and maintain adequate moisturization but these treatment aims \nwill not be achieved without optimal adherence.\n\n\n\nObjectives: To assess the frequency of treatment adherence among our patients with AE and to identify \nthe influencing factors.\n\n\n\nMethods: We carried out a questionnaire-based study involving dermatology outpatients with AE. \nDemographic data were collected and patients or carers were interviewed to assess steroid phobia, \nknowledge, perception on treatment and use of alternative treatment. \n\n\n\nResults: Out of 75 patients included in the study, only 14.7% were adherent to treatment. 58.7% of \npatients had steroid phobia but this did not significantly affect adherence. 41% of patients who use \nalternative treatment had poor adherence compared to patients who did not.\n\n\n\nConclusion: Adherence to topical treatment is poor among our AE patients and multi-pronged \nintervention is needed to improve adherence. For clinicians, non-adherence should be considered \nwhen managing patients who appear \u2018resistant\u2019 to optimized treatment.\n\n\n\nKeywords: dermatitis, compliance, alternative therapy\n\n\n\nIntroduction\nAdherence to treatment is defined as \u201cthe extent \nto which a patient\u2019s behaviour - taking medication, \nfollowing a diet and/or executing lifestyle changes \n- corresponds with agreed recommendations from a \nhealth care provider.\u201d1. The term \u2018compliance\u2019 is no \n\n\n\nCorrespondence\nMazlin Mohd Baseri, AdvMDerm(UKM)\n1Department of Medicine, Universiti Kebangsaan \nMalaysia Medical Centre (UKMMC), \nJalan Yaakob Latif, Bandar Tun Razak,\n56000 Cheras, Kuala Lumpur, Malaysia.\nEmail: mazlinbaseri@gmail.com\n\n\n\n2Department of Community Health,\nFaculty of Medicine, UKMMC\n\n\n\nlonger used due to its submissive connotation and \nhas largely been replaced by \u2018adherence\u2019; which \nsuggests that patients are equal partners in decision-\nmaking concerning their health.\n\n\n\nThe adherence rate to long-term therapy for chronic \nillnesses in developed countries is on average 50%2 \nand is even lower in developing countries. Poor \nadherence not only affect treatment efficacy, it also \nleads to wastage, increase in disease-related medical \ncost, additional consultations and delayed disease \ncontrol.\n\n\n\nAdherence to topical therapy poses additional \nchallenge as it is affected by day-to-day issues \nsuch as the time available for application, patient\u2019s \nacceptability to the type of vehicle used i.e. ointment \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2MJD 2013 Dec Vol 31\n\n\n\nor creams, patient\u2019s application habits resulting in \nirregular dosaging, etc. Chronic dermatological \ndisease such as atopic eczema (AE) for instance, \nrequires prolonged and regular use of topical \ntreatment and discipline in applying medications \nis essential to ensure treatment success. In AE, two \nmain aims of topical therapy are:  (i) to maintain \nadequate moisture using emollients3 and (ii) to \ncontrol inflammation with anti-inflammatory \nagents4. Topical corticosteroid (TC) is the main \nanti-inflammatory agent used and treatment is often \nrequired for months or years5.\n\n\n\nProlonged use of TC and its side effects can make \npatients become non-adherent towards treatment. \nSteroid phobia is characterized by irrational fear and \nanxiety of patients about using TC preparations and \nit is a common problem among dermatology patients. \nIn a study which included 200 AE patients, 72.5% \nwere worried about using TC and 24% admitted to \nbe non-adherent towards treatment because of their \nworries. The main concerns were the  side effects \nof the TC such as skin thinning (34.5%), growth \nand development disturbance (9.5%); making them \nnon-adherent towards treatment leading to more \nfrequent  relapses in the future6. \n\n\n\nPatients with AE attending outpatient government \ndermatology clinics are often prescribed various \ntypes of topical medications in generous amounts \nin order to control their disease and patients\u2019 \nadherence to treatment is often taken for granted.  \nIn this study, we aim to determine the frequency of \ntreatment adherence to topical medications among \nAE patients with the hope of understanding the \nmagnitude of this problem among our patients. We \nwould also like to identify the associated factors to \nhelp us formulate some interventions which may \nbe applied in order to improve treatment adherence \namong AE patients.\n\n\n\nMethods\nThis cross-sectional study was conducted in \nthe outpatient dermatology clinic Universiti \nKebangsaan Malaysia Medical Centre (UKMMC). \nThe study was conducted from April to May 2013. \nPatients were identified from the clinic database \nand universal sampling method was applied. The \ninclusion criteria include: patients with confirmed \nAE, able to communicate in Bahasa Malaysia and \nEnglish and consented to the study. Patients who did \nnot complete the questionnaire or did not consent \nto the study were excluded. Ethics approval was \nobtained from the ethics committee of Universiti \nKebangsaan Medical Centre (UKMMC). \n\n\n\nData was collected using guided self-administered \nquestionnaire in both English and Bahasa Malaysia. \nThe questionnaire consist of 33 questions covering 5 \ndomains: adherence (8 questions based on Morisky \nscore), steroid phobia (6 questions), perception on \ntreatment (5 questions), knowledge (9 questions) \nand complimentary/alternative treatment (5 \nquestions). Socio-demographic data include gender, \nage, race, educational level, family income, disease \nduration and severity. Direct questions with yes or \nno responses were used to explore about steroid \nphobia and use of alternative treatments. Patient\u2019s \nknowledge on types of medications used in AE and \nstrengths of the TC were assessed. Statements such \nas \u201cI am using too many creams/ ointment on my \nskin\u201d, \u201ccreams/ointment make my skin sticky and \nshiny\u201d, \u201cdoctors give me too many types of cream\u201d \nare examples of questions used to evaluate patient\u2019s \nperception towards treatment. Patient\u2019s perceptions \ntowards severity of their disease were recorded \nas mild, moderate and severe. Data was analysed \nusing Statistical Package for Social Science (SPSS) \nprogram version 21. Chi-square test and Mann-\nWhitney U test were used to analyse the data.\n\n\n\nResults\nTotal of 95 patients with AE were given          \nquestionnaires but only 75 respondents were \nincluded in the study (83.3%). Forty three (57.3%) \npatients were male. Majority of the patients were \nMalays (72%) followed by Chinese (25%), Indian \nand other races. The mean age was 18.6 years \nwith ages ranging from 1 to 72 years. Thirty four \n(45.3%) respondents studied until secondary \nlevel and the mean family income per month was \nRM3746 (ranging from RM950 to RM50,000). The \nmean disease duration was 8.23 years. Thirty eight \n(50.7%) patients had co-existing atopic diseases  \nsuch as asthma, allergic rhinitis, keratoconjunctivitis, \nhypertension and diabetes mellitus. Patients\u2019 \nperception of disease severity was classified into \nmild (22.7%), moderate (48%) and severe (29.3%). \nDetailed sociodemographic data are shown in        \nTable 1.\n\n\n\nThe overall adherence rate was approximately \n14.7% (Table 2). Sixty four (85.3%) patients had \npoor adherence to treatment. Malay patients had \nthe highest rate of poor adherence (87%) compared \nto patients from other ethnicity but the difference \nwas not statistically significant. This may be \nexplained by sampling bias as our patients were \nmostly Malays. Similar to earlier studies we found \nno significant relationship between genders with \ntreatment adherence6,16. (Table 3)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3 MJD 2013 Dec Vol 31\n\n\n\nVariables \n\n\n\nGender \n\n\n\n   Male \n\n\n\n   Female \n\n\n\nAge (years)\n\n\n\nRace \n\n\n\n   Malay \n\n\n\n   Chinese\n\n\n\n   Indian\n\n\n\n   Others\n\n\n\nEducational Level\n\n\n\n   Primary \n\n\n\n   Secondary \n\n\n\n   Matriculation \n\n\n\n   Diploma \n\n\n\n   Degree \n\n\n\nFamily Income\n\n\n\nDisease duration \n\n\n\nPerceived disease severity\n\n\n\n   Mild \n\n\n\n   Moderate\n\n\n\n   Severe\n\n\n\nAdherence\n\n\n\nGood \n\n\n\nPoor \n\n\n\nFrequency (n)\n\n\n\n11\n\n\n\n64\n\n\n\nPercentage (%)\n\n\n\n14.7\n\n\n\n85.3\n\n\n\nFrequency (n)\n\n\n\n43\n\n\n\n31\n\n\n\n18*\n\n\n\n54\n\n\n\n19\n\n\n\n1\n\n\n\n1\n\n\n\n9\n\n\n\n34\n\n\n\n1\n\n\n\n23\n\n\n\n8\n\n\n\n2500*\n\n\n\n5*\n\n\n\n17\n\n\n\n36\n\n\n\n22\n\n\n\nPercentage (%)\n\n\n\n 57.3\n\n\n\n 41.3\n\n\n\n 18**\n\n\n\n 72\n\n\n\n 25\n\n\n\n 12\n\n\n\n 45.3\n\n\n\n 1.3\n\n\n\n 30.7\n\n\n\n 10.7\n\n\n\n 2000-4000**\n\n\n\n 2-11**\n\n\n\n 22.7\n\n\n\n 48.0\n\n\n\n 29.3\n\n\n\n* median      ** Inter quartile range (IQR:25-75)\n\n\n\nTable 1  Sociodemographic data of study patients.\n\n\n\nTable 2  Summary of results on treatment adherence among AE patients.\n\n\n\nIn contrary to what we postulated, there was no \nsignificant association in adherence between \npatients who felt that they had severe disease to those \nwho did not (p = 0.925); we interpret this lack of \ndifference due to the habits of our patients adjusting \nthe dosages/frequency of the topical treatment \non their own based on the response to treatment, \nsuch as reducing the use of cream once the disease \nimproves - and this data is captured as non-adherence \nbecause it was done outside of prescribed practice.  \nConflicting data exists regarding disease severity \ninfluencing adherence but most studies were on non-\ndermatological diseases7,8. There was no significant \ndifference between the rate of adherence in patients \nwith negative attitude towards therapy and those \nwithout (Table 3). Patients\u2019 perception towards \ntreatment was not demonstrated to affect adherence \nsignificantly. (p = 0.855)\n\n\n\nGood parental knowledge about their children\u2019s \ndisease has been shown to be one of the determining \nfactors for improved adherence towards the treatment \nin AE patients9. Our study did not demonstrate \nsignificant relationship between treatment adherence \nand knowledge (p=0.930) but several studies have \nshown improved adherence among AE patients after \nintervention10,11. Education alone is not enough to \nimprove adherence; patient must also be informed, \nmotivated and skilled in the use of cognitive \napproaches12.\n\n\n\nForty-four patients (58.7%) had steroid phobia \nbut we found no significant association between \nsteroid phobia and treatment adherence (p > 0.005). \nHowever, percentage of poor adherence among our \npatients with steroid phobia (88.6%) was higher \ncompared to those without steroid phobia (80.6%) \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4MJD 2013 Dec Vol 31\n\n\n\nbut the difference was not statistically significant \n(p = 0.527). Reasons for their worry about using \nsteroids include skin thinning, worsening of the \ndisease or exacerbation of itch. Half of the patients \ndid not know or remember why they worry about \nusing steroids. Hon et al reported fear of side \neffects such as skin thinning, effect on growth and  \ndevelopment (poor weight gain) were patients\u2019 main \nconcerns13. Misconceptions and lack of knowledge \nmay be corrected by improving patient education \nand counselling.\n\n\n\nThirty one respondents (41%) admitted to using \nalternative medications/supplements for their skin \ncondition. Most received recommendations from \nrelatives, friends and pharmacists. The mean amount \nof money spent on supplements was RM155 per \n\n\n\nmonth and some of the supplements named include \nGel Gamat, vitamin and spirulina. Out of this group, \n93.5% had poor adherence compared to 79.5% of \npatients who did not use alternative medications. \n(p = 0.175). Even though the difference was not \nstatistically significant, we felt that the small sample \nsize may have influenced this finding. In a study by \nAnderson et al, 42.5% of patients with AE used \nalternative treatment and became non-adherent \nto modern medicine treatment14. This might be \ndue to fears of the side effects, poor knowledge \nand influence from family, friends, television, \ninternet and other sources. Lack of satisfaction \ntowards steroid treatment and improvements of a \nfriend\u2019s condition with alternative treatment are \nalso among the known factors which encourage the \nuse of alternative treatment compared to modern \nmedicine15.\n\n\n\nVariables\n\n\n\nGender \n\n\n\n   Male \n\n\n\n   Female \n\n\n\nRace \n\n\n\n   Malay \n\n\n\n   Non Malay\n\n\n\nPerceived Eczema Severity \n\n\n\n   Mild \n\n\n\n   Moderate \n\n\n\n   Severe\n\n\n\nSteroid Phobia\n\n\n\n   Yes \n\n\n\n   No \n\n\n\nPerception on Treatment\n\n\n\n   Poor \n\n\n\n   Good \n\n\n\nKnowledge \n\n\n\n   Good \n\n\n\n   Poor \n\n\n\nUse of Alternative Treatment\n\n\n\n   Yes\n\n\n\n   No \n\n\n\nFamily Income\n\n\n\nDisease duration \n\n\n\nAdherence   n (%)\n\n\n\n            Good                             Poor\n\n\n\n\n\n\n\n 6 (14.0) 37 (86.0)\n\n\n\n 5 (15.6) 7 (84.4)\n\n\n\n\n\n\n\n 7 (13.0) 47 (87.0)\n\n\n\n 4 (19.0) 17 (81.0)\n\n\n\n 3 (17.6) 14 (82.4)\n\n\n\n 5 (13.9)  31 (86.1)\n\n\n\n  3 (13.6) 19 (86.4)\n\n\n\n\n\n\n\n 5 (11.4) 39 (88.6)\n\n\n\n 6 (19.4) 25 (80.6)\n\n\n\n 5 (13.9) 31 (86.1)\n\n\n\n 6 (15.4) 33 (84.6)\n\n\n\n 6 (15.0) 34 (85.0)\n\n\n\n 5 (14.3) 30 (85.7)\n\n\n\n 2 (6.5)  29 (93.5)\n\n\n\n 9 (20.5)  35 (79.5)\n\n\n\n  3000*       2500*\n\n\n\n(3000-4000)**                 (2000-4000)**\n\n\n\n\n\n\n\n  3.00*  5.00*\n\n\n\n (1.00-10.00)**                 (2.25-11.75)**\n\n\n\nP value\n\n\n\n1.000\n\n\n\n0.760\n\n\n\n0.925\n\n\n\n0.527\n\n\n\n0.855\n\n\n\n0.930\n\n\n\n0.175\n\n\n\n0.307#\n\n\n\n\n\n\n\n0.195#\n\n\n\n* Median        ** Interquartile range (IQR: 25-75)        # Mann Whitney Test = Z\n\n\n\nTable 3  Summarize data on influencing factors on adherence with P Value.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5 MJD 2013 Dec Vol 31\n\n\n\nDiscussion\nAdherence to topical medications is poor among \npatients with AE in our clinic. Keeping in mind \nthis study is based on self-reported questionnaire, \nthe actual adherence rate may be even lower. In a \nstudy by Krencji-Manwaring et al using electronic \nmonitors to determine adherence \u2018stealthily\u2019 among \nchildren with AE, mean adherence of 32% was \nreported16. The prevalence of adherence in our study \nis lower than other studies conducted in the west and \nthis is a real cause for concern.\n\n\n\nTopical treatment poses extra challenges as \ncompared to oral treatment because it is affected \nby various factors. Patients\u2019  or carer\u2019s  personality, \noccupation and hence, time available to apply \nmedications, extent of skin involvement, patients\u2019 \nor carers\u2019 perception/acceptability towards the \nvehicle of the medications, chronicity of the illness, \nadequacy of prescribed medications, are just among \nthe few factors which can influence adherence. \nSerrup et al found that the percentage of adherence \ntoward dermatological treatment varies from 55% to \n66% and the adherence to topical treatment is lower \ncompared to other treatment form16. Popping a pill \non a daily basis is often perceived as easier as and \nmore convenient than to apply medication to a large \nextent of skin surface19. \n\n\n\nThe outcome of this study has been limited by several \nfactors. Measuring adherence to topical medications \naccurately in a research setting is not an easy task. \nIn our study, interviews and questionnaires are \nsubjected to recall and response bias which make \nthem susceptible to over - or under-estimates of \nadherence but it remains the cheapest and most \nconvenient method of assessment. Other methods \ncommonly used in research include treatment logs, \nprescription renewals monitoring, weighing of \nmedications as well as electronic monitoring devices \nwhich enable researchers to monitor both frequency \nand time of bottle opening. Each method has its own \nadvantages and disadvantages.\n\n\n\nAnother important limitation is the lack of \nvalidated questionnaire to measure adherence to \ntopical treatment. There are various validated tools \nmeasuring adherence to oral medications such as Drug \nAttitude Inventory (DAI)20, Medication Adherence \nQuestionnaire (SMAQ)21, Medication Adherence \nRating Scale (MARS)22, etc. but none was designed \nto assess adherence to topical medication. We used \na modified version of SMAQ to suit the objectives \nof our study and found certain issues unique to \n\n\n\ntopical treatment which remained unaddressed. For \ninstance, in managing AE, it is accepted practice to \n\u2018step down\u2019 or reduce the frequency of application \nof TC when the disease improves. Such practice \ncan reduce the side effects without making the \ndisease worse. Reducing the dose or frequency of \ntreatment is considered as non-adherent behaviour \nin the questionnaire and therefore, gives a higher \npercentage of non-adherence. Asking patients the \nreasons they reduce/stop treatment may be able to \nshed more light into this matter and self-regulated \n\u2018step down\u2019 approach to treatment should not be \nconsidered as non-adherence.  \n\n\n\nA standardized, universally acceptable target for \ntreatment adherence is also lacking.  In a clinical \ntrial which assessed adherence among psoriasis \npatients over 8-week period using combination \nof patients\u2019 log, weighing of medications and \nelectronic monitoring devices, despite being aware \nthat their medication use was being monitored, \npatients\u2019 adherence rate was merely 55%23. At what \nlevel is considered acceptable adherence rate to \ntopical medication? For oral treatment, it is defined \nas acceptable when consumption is 80-120% of the \nrecommended doses24 but no similar level exists for \ntopical medication.  Achieving 100% adherence rate \nto topical medications is unrealistic and admittedly, \nnear perfect adherence would be more plausible but \ncurrently there is no specified acceptable level of \nadherence.\n\n\n\nMethods used to measure adherence to topical \ntreatment are still far from perfect. Adherence is \noften assessed by determining the quantity and \nfrequency of medications used, but assessing \nwhether application was performed in the correct \nway at the correct time for the prescribed duration is \nrarely measured in clinical research. This will also \naffect the outcome of adherence studies.\n\n\n\nDespite limitations of this study, there are important \nclinical implications. Since the adherence rate \nin our clinic; which is a university-based tertiary \ncare centre with doctor to patient ratio of about                         \n1: 12.5-15 is poor, the adherence rate of AE patients \nin a busier clinic with lower doctor to patient ratio \nmay be even lower because of shorter consultation \ntime per patient. Patients\u2019 adherence to treatment \nplans is essential for treatment success. Good \ncommunication is key to a good doctor-patient \nrelationship and this will be affected by duration of \nconsultation as well as the communication skills of \nthe health care provider.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6MJD 2013 Dec Vol 31\n\n\n\nCommunication skills of a health care provider \nshould not be underestimated as it has been shown \nthat patients adhere to treatment 2.16 times greater \nif their doctor is a good communicator25. Since \nmajority of AE patients are in the paediatric age \ngroup, parental factors such as time availability, \ndynamics of parent-child relationship, parents\u2019 \nunderstanding about the disease and treatment must \nbe taken into consideration. Steroid phobia should \nbe identified early so any misconceptions can be \ncorrected. Parents\u2019 fears can be allayed by good \ndoctor-patient (parent) relationship and this has \nbeen shown by Ohya et al26.\n\n\n\nPatients and carers should be allowed to actively \nparticipate in formulating their treatment plans and \na clinician-patient alliance should be formed. This \nwill encourage trust between patients and doctor, \nempower the patient/carer and hence, improve \nadherence. Use of individualized AE written action \nplans or instructions tailored to patient\u2019s/carer\u2019s \nlifestyle, for instance, would be easier for patients \nto follow and this will improve adherence. \n\n\n\nAdherence to topical treatment can also be affected \nby complicated treatment regimes. Simplifying the \ndaily regimes by minimizing number and frequency \nof topical medications may lead to improved \ncompliance. \u2018Hit hard\u2019 approach to initial treatment \nwould lead to greater initial efficacy and patients \nmay be encouraged to continue treatment to achieve \nand maintain good disease control. \n\n\n\n\u2018White coat compliance\u2019 is a term used to describe \nthe behaviour pattern when patient\u2019s adherence \nimproves around the time of office visits and it \nhas been demonstrated in studies using electronic \nmonitoring devices16,23,27. We can capitalize on this \nbehaviour pattern by having early follow-up visit \nafter initiating treatment - it may be an effective way \nto boost patient\u2019s use of medication to achieve better \ntreatment outcome27. \n\n\n\nPatient education sessions by doctors and specialized \nnurses can be incorporated as part of management \nstrategy at the clinic. When possible, waiting time \nat the clinics can be utilized for patient education \nto save time. Distribution of informative pamphlets \nwith explanation by health care provider, supervised \nvideo screenings or internet are possible sources \nof information for AE patients and should be \nrecommended.  Memberships and regular meetings \nin AE clubs or associations may be used as another \nplatform to educate patients. \n\n\n\nLastly, it is crucial that clinicians be made aware of \nhow dismal the rate of treatment adherence is among \nAE patients. In our dermatology practice, if a patient \ndoes not improve despite adequate and appropriate \ntreatment, we should consider the findings of this \nstudy. Instead of escalating treatment, non-adherence \nmay be a more likely explanation.\n\n\n\nConclusion\nAdherence towards topical treatment among our \npatients with AE is unsatisfactory and intervention \nis needed to improve this in the clinic setting. \nIndividualized patient education, improved             \nhealth care provider-patient relationship and \ncommunication are essential to ensure good \nadherence and hence, treatment success. \n \nAcknowledgement \nWe would like to thank the Dean and Hospital \nDirector of UKMMC, Dermatology Clinic staff and \nlast but not least, all the patients who took part in \nthe study. The study was funded by UKM under the \nSpecial Study Module project for undergraduate \nmedical studies.\n\n\n\nReferences\n \n1. Sabate E. Adherence to long-term therapies. Evidence      \n\n\n\nforaction. Geneva: World Health Organisation, 2003.\n2. Haynes RB. Interventions for helping patients follow \n\n\n\nprescriptions for medications. Cochrane Database of \nSystematic Reviews 2001: Issue 1.\n\n\n\n3. Knownacki S. The Important of Emollients in Treating \nthe Increasing Incidence of Atopic Eczema. Nurs Times \n2009; 105(28):18-22.\n\n\n\n4. Levy M.L. Atopic dermatitis: Understanding the Disease \nand its Management. Curr Med Res Opin. 2007; 23:3091-\n3103.\n\n\n\n5. Aubert-Wastiaux H, Moret L, Le Rhun A et al. 2011. \nTopical corticosteroid phobia in atopic dermatitis: a study \nof its nature, origins and frequency. Br J Dermatol 2011; \n165: 808-814.\n\n\n\n6. Charman CR, Morris AD, Williams HC. Topical \ncorticosteroid phobia in patients with atopic eczema. Br J \nDermatol 2000; 142(5): 931-936.\n\n\n\n7. Seo MA, Min SK. Development of a structural model \nexplaining medication compliance of persons with \nschizophrenia. Yonsei Med J. 2005; 46:331-40.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7 MJD 2013 Dec Vol 31\n\n\n\n8. Matthews D, Hingson R. Improving patient compliance: a \nguide for physicians. Med Clin North Am 1977; 61(4):879-\n89.\n\n\n\n9. Beattie PE, Lewis-Jones MS. Parental knowledge of topical \ntherapies in the treatment of childhood atopic dermatitis. \nClin Exp Dermatol 2003; 28(5):549-53.\n\n\n\n10. Cork MJ, Britton J, Young S et al. Comparison of Parent \nKnowledge, Therapy Utilization and Severity of Atopic \nEczema Before and After Explanation and Demonstration \nof Topical Therapies by a A Specialist Dermatology Nurse. \nBr J Dermatol 2003; 149(3):582-589.\n\n\n\n11. Agner T. Compliance among patients with Atopic Eczema. \nActa Derm Venereol 2005; 215:33-35\n\n\n\n12. Balakrishnan R. The Importance of Medication Adherence \nin Improving Chronic-Disease Related Outcomes: What \nWe Know and What We Need to Further Know. Med Care \n2005; 43(6):517-520.\n\n\n\n13. Hon KLE, KamWY, Leung TF et al. Steroid fears in \nchildren with eczema. Acta Pediatr 2006; 95(11):1451-5.\n\n\n\n14. Anderson PC, Dinulos JG. Atopic Dermatitis and \nAlternative Management Strategies, Curr Opin Pediatr \n2009; 21 (1):131-8.\n\n\n\n15. Zhang W, Leonard T, Bath-Hextall FJ et al. Chinese Herbal \nMedicine for Atopic Eczema The Cochrane Skin Group \nCochrane Library 2009.\n\n\n\n16. Krejci-Manwaring J, Tusa MG, Carroll C et al. Stealth \nmonitoring of adherence to topical medication: Adherence \nis very poor in children with atopic dermatitis. J Am Acad \nDermatol 2007;56: 211-216\n\n\n\n17. Jing J, Sklar GE, Oh VMS, Li SC. Factors affecting \ntherapeutic compliance: A review from the patient\u2019s \nperspective. Ther Clin Risk Manag 2008; 4(1): 269-286.\n\n\n\n18. Serup J, Lindblad AK, Maroti MI et al. J. 2006. To follow \nor not to follow dermatological treatment. Acta Derm \nVenereol. 56(2): 211-217.\n\n\n\n19. Krejci-Manwaring J, McCarthy MA, Camacho F et al. \nAdherence with topical treatment is poor compared with \nadherence with oral agents: implications for effective \nclinical use of topical agents. J Am Acad Dermatol \n2006;54: S235-36.\n\n\n\n20. Hogan TP, Awad AG, Eastwood R. A self-report scale \npredictive of drug compliance in schizophrenics: reliability \nand discriminative validity. Psychol. Med 1983; 13, 177-\n183.\n\n\n\n21. Morisky DE, Green LW, Levine DM. Concurrent and \npredictive validity of a self-reported measure of medication \nadherence. Medical Care 1986;24:67-74.\n\n\n\n22. Thompson K, Kulkarni J, Sergejew AA.  Reliability and \nvalidity of a new Medication Adherence Rating Scale \n(MARS) for the psychoses. Schiz Res 2000; 42(3):241-\n247.\n\n\n\n23. Carroll CL, Feldman SR, Camacho FT et al. Adherence \nto topical therapy decreases during the course of an \n8-week psoriasis clinical trial: Commonly used methods \nof measuring adherence to topical therapy overestimate \nactual use. J Am Acad Dermatol. 2004;51(2):212-216.\n\n\n\n24. Cramer J. ISPOR Medication Compliance and Persistence \nSpecial Interest Group. www.ispor.org/ signs / medication.\nasp (accessed May 20, 2013).\n\n\n\n25. Zolnierek KB, Dimatteo MR. Physician Communication \nand Patient Adherence to Treatment: A Meta-analysis. \nMedical Care 2009, 47:826-834.\n\n\n\n26. Ohya Y, Williams H, Steptoe A et al. Psychosocial factors \nand adherence to treatment advice in childhood atopic \ndermatitis. J Invest Dermatol. 2001; 117(4):852\n\n\n\n27. Feldman SR, Camacho FT, Krejci-Manwaring J et al. \nAdherence to topical therapy increases around the time of \noffice visits. J Am Acad Dermatol 2007; 57:81-83.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8MJD 2013 Dec Vol 31\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nLICHEN PLANUS AND HEPATITIS C INFECTION:\nEXPLORING THE ASSOCIATION AMONG MALAYSIAN PATIENTS\n\n\n\nNorazirah MN1, AdvMDerm, Mazlin MB1, AdvMDerm, Adawiyah J1, AdvMDerm, Asmah J2, MMed\n\n\n\nAbstract\n\n\n\nBackground: The association between chronic hepatitis C infection with lichen planus (LP) remains \ncontroversial. Geographical and immunogenetic factors may play a role in this association. \n\n\n\nObjectives: We sought to compare the prevalence of hepatitis C in patients with LP with healthy blood \ndonors at our centre.\n\n\n\nMaterials & Methods: We conducted a retrospective study in Hospital Kuala Lumpur, Malaysia. All \npatients with biopsy- proven LP who had undergone hepatitis C serology screening from January 2007 \nto June 2012 were recruited. The prevalence of Hepatitis C seropositivity among healthy blood donors \nin Malaysia was used as comparison. \n\n\n\nResults: Thirty five patients with LP were included in the study. Majority of the patients were Indians \n(71.4%) followed by Malays (14.3%), Chinese (8.6%) and other ethnicity (5.7%). 82.6% of patients \nhad classical cutaneous LP out of which 17% had oral involvement. Anti-HCV was reactive in 2.9% \npatients. Among the healthy blood donors, anti-HCV was positive in 1.5% of patients. There was no \nsignificant difference between the prevalence of hepatitis C seropositivity between the two groups \n(p=0.431). \n\n\n\nConclusion: There is no significant association between chronic hepatitis C infection and LP among \nour patients. We recommend screening for hepatitis C in LP patients should be limited to those with \nrisk factors.\n\n\n\nKeywords: lichen planus, viral hepatitis, Malaysia\n\n\n\nIntroduction\nLichen planus (LP) is an idiopathic mucocutaneous \ndermatosis involving the scalp, skin mucous \nmembranes and nails. Classically, it is characterised \nby markedly pruritic, polygonal, flat- topped papules \nwith Wickham\u2019s striae and it exhibits koebnerization. \nThe association of LP and chronic hepatitis C virus \n\n\n\nCorrespondence\nNorazirah Md Nor, AdvMDerm\n1Dermatology unit, Medical Department,\nUniversiti Kebangsaan Malaysia Medical Centre, \nJalan Yaacob Latiff, 56000 Kuala Lumpur.\nEmail: norazirah78@gmail.com\n\n\n\n2Department of Dermatology, Hospital Kuala Lumpur\n\n\n\n(HCV) infection was firstly described in 1989 by \nMokni et al1. A link between these two diseases \nwas postulated by the fact that LP was frequently \nassociated with chronic liver disease2.\n\n\n\nThis was later supported by studies demonstrating \nthe presence of hepatitis C viral RNA via \npolymerase chain reaction from lesional biopsies \nof oral LP and its absence from biopsy of non-\nlesional area within the same individuals3. Despite \nthese findings, the association seemed to vary with \ndifferent geographical regions4. Whilst studies in \nMediterranean countries had demonstrated such \nassociation, several studies from Europe had refuted \nthis finding.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9 MJD 2013 Dec Vol 31\n\n\n\nIn HCV-related LP, the condition tends to be more \ngeneralised, prolonged and has high incidence of \nmucosal involvement5; suggesting a more severe \npresentation compared to the non HCV-related LP.  \n\n\n\nIn Malaysia, where the prevalence of hepatitis C \nviral (HCV) infection is estimated to be 1.5%6,25 \n\n\n\nsuch association has yet to be established. In our \nheterogenous and multiethnic country, the HCV-\nLP association may vary to other countries where \nthe population is more homogenous. We sought to \ndetermine if the HCV-LP association exist among \nour patients. \n\n\n\nMethods\nThis retrospective observational study was \nconducted at the Dermatology Department Hospital \nKuala Lumpur. All patients with biopsy-proven LP \nwho had undergone hepatitis C serology screening \nat diagnosis from January 2007 to June 2012 \nwere included in the study. Hepatitis C serology \nscreening was performed using Enzyme-Linked \nImmunoSorbent Assay (ELISA).\n\n\n\nThe prevalence of HCV seropositivity in the LP \ngroup was compared to the prevalence among \nhealthy blood donors in Blood Services Centre, \nKuala Lumpur. Patients\u2019 demographical and clinical \ndata were analysed using Statistical Package for \n\n\n\nSocial Sciences (SPSS) version 21. The differences \nin hepatitis C seropositivity between the two groups \nwere analysed using Chi square test. P value of less \nthan 0.05 was considered statistically significant.\n\n\n\nResults\nA total of 69 patients with LP were identified. Thirty \nfour patients were excluded due to unavailability of \nhepatitis C serology results. Thirty five patients were \neligible for analysis; 19 males and 16 females with \nmean age of 46.9 years. Majority of the patients \nwere of Indian ethnicity (71.4%) followed by Malays \n(14.3%), Chinese (8.6%) and other ethnics (5.7%). \nThis finding is in contrast to the ethnic proportions \nof our clinic attendees during this period, which \nwere predominantly Malays. \n\n\n\nTwenty nine (83%) patients had classical LP,                        \n5 (14%) had hypertrophic LP and 1 patient had lichen \nplanopilaris (Figure 1). Only 6 (17%) patients also \nhad oral mucous membrane involvement. Out of 35 \npatients, only 1 (2.9%) patient showed hepatitis C \nseropositivity and the patient had hypertrophic LP \nwithout oral mucosal involvement. In the blood \ndonor group, 53 out of 3540 (1.5%) patients were \nHCV positive19. The difference of hepatitis C \nseropositivity observed between the two groups was \nnot statistically significant (p = 0.431).\n\n\n\nFigure 1  Distribution of clinical subtypes of lichen planus.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10MJD 2013 Dec Vol 31\n\n\n\nDiscussion\nIn our study, we did not find significantly higher \nprevalence of anti-HCV antibodies among patients \nwith LP as compared to the historical control group. \nThe prevalence of hepatitis C seropositivity in LP \npatients ranges from 3.8 % to 65 % worldwide4. Its \nprevalence is lower in our study at 2.9%. Our finding \nis consistent with other studies from Slovenia, India \nand Egypt, where no association between LP and \nHCV infection was found7,8,9. Meta-analyses have \nshown significant association between the two \ndiseases mainly in the Mediterranean, Japan and \nUSA10 but not in South Asia, Africa and North \nAmerica11. These meta-analyses also suggest that \nthe variable findings may be explained by variation \nin HCV prevalence in different regions, differences \nin viral characteristics and genetic susceptibility for \nHCV infected individuals to develop LP10. \n\n\n\nIn a meta-analysis by Shengyuan et al, the authors \nfound important association between Hepatitis C \nand LP but there is a difference when the association \nbetween the two diseases are analysed reciprocally11. \nThe odds ratio (OR) for HCV exposure among \npatients with LP was 5.4 (95% confidence interval \n[CI], 3.5-8.3) when compared to control but OR for \nprevalence of LP among HCV patients was 2.5 (95% \nCI, 2.0-3.1). There was no significant association       \nin isolated cutaneous LP (p = 0.17)11. A summarized \ncomparison between the findings in our study and \nother similar studies worldwide is shown in Table1.\n\n\n\nHigh HCV endemicity does not equate to higher LP \nprevalence.  This is suggested by studies conducted in \nAfrican countries with the highest HCV prevalence \nin the general population which did not show \nsignificant association between the two diseases8,15. \nHepatitis C may not be the primary aetiology of \nLP, but its interaction with the host immune system \nhad resulted in LP. Hence, LP probably represents a \ncell-mediated response to an antigenic trigger from \nHCV infection16,17. This also suggests that other \nfactors such as genetics or immunological factors \nplay a more important role in the pathogenesis of \nHCV-related LP.\n\n\n\nHCV-related LP has also been shown to be associated \nwith certain LP subtypes. The association of HCV \nwas demonstrated to be present in erosive LP and \nnot in other form in certain studies18. Majority of \nour patients were of the classical type, which may \nexplain the lack of HCV-LP association. At present, \nthere is a much stronger association between oral LP \ncompared to cutaneous LP with HCV infection7,10,19. \nCarozzo et al had demonstrated that oral LP may \nbe influenced by genetic allele involving HLA-DR6 \nin Italy20. This could partially explain the peculiar \ngeographic heterogeneity of the association between \nHCV and oral LP.  In our study, only 6 patients had \noral lesions. Such a small number of patients with \noral involvement can be explained by the fact that \nmost of purely oral LP cases is often managed by \nthe maxillofacial specialist and will only be referred \nto dermatologist if there is associated cutaneous \ninvolvement.\n\n\n\nStudy\n\n\n\nCountry\n\n\n\nYear\n\n\n\nNo of patients\n\n\n\nLocal prevalence of HCV \ninfection (%)\n\n\n\nReactive anti-HCV (%)\n\n\n\nOral LP present\n\n\n\nAssociation shown\n\n\n\nCurrent\n\n\n\nMalaysia\n\n\n\n2012\n\n\n\n35\n\n\n\n1.5\n\n\n\n2.9\n\n\n\n6\n\n\n\nno\n\n\n\nStojanovic\net al (12)\n\n\n\nSlovenia\n\n\n\n2008\n\n\n\n173\n\n\n\n<1\n\n\n\n1.2\n\n\n\n71\n\n\n\nno\n\n\n\nLodi\net al (4)\n\n\n\nItaly\n\n\n\n2004\n\n\n\n303\n\n\n\n0.5\n\n\n\n19.1\n\n\n\n303\n\n\n\nyes\n\n\n\nIbrahim\net al (8)\n\n\n\nEgypt\n\n\n\n1999\n\n\n\n43\n\n\n\n18.1\n\n\n\n6.9\n\n\n\nnot stated\n\n\n\nno\n\n\n\nKlantrit\net al (13)\n\n\n\nThailand\n\n\n\n2003\n\n\n\n60\n\n\n\n5.6\n\n\n\n8.3\n\n\n\n60\n\n\n\nYes\n\n\n\nGimenez-Garcia \net al (14)\n\n\n\nSpain\n\n\n\n2003\n\n\n\n101\n\n\n\n0.7\n\n\n\n8.9\n\n\n\n53\n\n\n\nyes\n\n\n\nUdayashankar\net al (9)\n\n\n\nIndia\n\n\n\n2003\n\n\n\n40\n\n\n\n4.8\n\n\n\n0\n\n\n\n7\n\n\n\nno\n\n\n\nTable 1  Comparison to other studies.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11 MJD 2013 Dec Vol 31\n\n\n\nLP appears to be more common among Indian \npatients. In our study, we found a striking \npredominance of Indian patients (71.4%) compared \nto other ethnicity. Similar finding was described by \nVijayasingam et al in Singapore in which 69% of \npatients with LP in his study were Indians21. This \nstrongly suggests some genetic predisposition to \ndevelop LP among certain ethnicity. \n\n\n\nHCV related LP may be associated with certain \nHCV genotypes but data on this postulation is rather \nscarce. HCV possesses high genomic variability and \nvarious genotypes have been reported. Certain HCV \ngenotype may influence its ability to induce LP in \nsusceptible individuals. Different genotypes are \nmore prevalent in different parts of the world. Lodi \net al and Imhof et al compared the geno/subtype \ndistribution of patients with chronic hepatitis C with \nand without LP in Italy and Germany respectively23,24. \nThe HCV genotype isolated in their LP patients were \nmostly of 1b, 2a23 and 1b24. However, no convincing \ncorrelation between geno/subtype and the presence \nof LP were found and the studies were limited by its \nsmall sample size23,24. In Malaysia, the commonest \ngenotype is type 1a and 322, which may explain the \nreason for lack of association shown in our study \npopulation.   \n\n\n\nThere are several limitations in this study. To avoid \nselection bias, only patients with histologically \nconfirmed LP were recruited in the study. This \nlimited the number of patients who fulfilled the \nstudy criteria because biopsy was not performed \nin almost half of patients diagnosed as LP. This \nmay be because of its pathognomonic morphology \nat presentation, unintentional omission by the \nattending doctor and patient refusal. This study is \nalso limited by its retrospective nature. Thus, each \nindividual risk factor for acquiring HCV infection \nwas not completely available for analysis. \n\n\n\nLastly, we recommend a larger, controlled, \nprospective study to confirm our findings and \na comparison between prevalence of HCV in \nMalaysian patients with oral VS cutaneous LP may \nalso be explored. A parallel HCV genotype studies \nwill also be beneficial to investigate whether our \nspecific local HCV genotypes is associated to LP.\n\n\n\nConclusion\nThe association between LP and HCV infection is \nlacking among our patients and currently, there is \nnot enough data to support routine screening for \nHCV infection in every patient with LP without any \nrisk factors. \n\n\n\nReferences\n \n1. Mokni M, Rybojad M, Puppin D Jr et al. Lichen planus \n\n\n\nand hepatitis C virus. J Am Acad Dermatol 1991;24:792.\n2. Carrozzo M. Oral diseases associated with hepatitis C \n\n\n\nvirus infection.Part 2: lichen planus and other diseases. \nOral Dis 2008; 14: 217-228.\n\n\n\n3. Erkek E, Bozdogan OE, Olut AI. Hepatitis C virus infection \nprevalence in lichen planus: examination of lesional and \nnormal skin of hepatitis C virus-infected patients with \nlichen planus for the presence of hepatitis C virus RNA. \nClin Exp Dermatol, 26: 540-44.\n\n\n\n4. Lodi G , Giuliani M, Majorana A et al. Lichen planus and \nhepatitis C virus: a multicentre study of patients with oral \nlesions and a systematic review. Br J Dermatol2004; 151: \n1172-1181.\n\n\n\n5. Stephanos J. Hadziyannis. Skin diseases associated with \nhepatitis C virus infection. JEADV 1998; 10: 12-21.\n\n\n\n6. Lavanchy D. Evolving epidemiology of hepatitis C virus. \nClin Microbiol Infect 2011;17:107-115.\n\n\n\n7. Stojanovi L, Lunder T, Poljak M et al.. Lack of evidence \nfor hepatitis C virus infection in association with lichen \nplanus. Int J Dermatol2008;47: 1250-1256.\n\n\n\n8. Ibrahim HA, Baddour MM, Morsi MG et al. Should we \nroutinely check for hepatitis B and C inpatients with lichen \nplanus or cutaneous vasculitis? East Mediterr Health J \n1999;5: 71-78.\n\n\n\n9. Udayashankar C, Nath A.K, M. D\u2019Souza.Hepatitis C \nVirus serology in patients with lichen planus. The Internet \nJournal of Dermatology. 2009; 7(2).\n\n\n\n10. Lodi G, Pellicano R, Carrozzo M. Hepatitis C virus \ninfection and lichen planus: a systematic review with \nmeta-analysis. Oral Dis 2010; 16:601-612.\n\n\n\n11. Shengyuan L, Songpo Y, Wen W et al. Hepatitis C virus \nand lichen planus: a reciprocal association determined by a \nmeta-analysis. Arch Dermatol. 2009;145(9):1040-7.\n\n\n\n12. Larisa Stojanovic L, Lunder T, Poljak M et al. Lack of \nevidence for hepatitis C virus infection in association with \nlichen planus. Int J of Dermatol 2008; 47, 1250-1256.\n\n\n\n13. Klanrit P, Thongprasom K, Rojanawatsirivej S. Hepatitis \nC virus infection in Thai patients with oral lichen planus. \nOral Dis 2003; 9: 292-7.\n\n\n\n14. Gimenez-Garc\u00eda R, P\u00e9rez-Castrill\u00f3n JL Lichen planus and \nhepatitis C virus infection. JEADV2003; 17: 291-295.\n\n\n\n15. Daramola OOM, George AO, Ogunbiyi AO. Hepatitis \nC and Lp in Nigerians: any relationship? Int J Dermatol \n2002; 41:217-219.\n\n\n\n16. Roy KM, Bagg J. Hepatitis C virus and oral disease: a \ncritical review. Oral Dis 1999; 5 :270-277.\n\n\n\n17. Lodi G, Porter SR. Hepatitis C virus infection and lichen \nplanus: a short review. Oral Dis 1997; 3:77-81.\n\n\n\n18. R Gimenez-Garc\u00eda, JL P\u00e9rez-Castrill\u00f3n. Lichen planus and \nhepatitis C virus infection. JEADV 2003 17(3): 291-295.\n\n\n\n19. Nagao Y, Sata M. Hepatitis C virus and lichen planus. J \nGastro Hepatol 2004;19:1101-1113.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12MJD 2013 Dec Vol 31\n\n\n\n20. Carrozzo M,  Brancatello F, Dametto E t al. Hepatitis C \nvirus-associated oral lichen planus: is the geographical \nheterogeneity related to HLA-DR6?. J Oral Pathol Med \n2005; 34: 204-8.\n\n\n\n21. Vijayasingam SM, Lim KB, Yeoh KH et al. Lichen planus: \na study of 72 cases in Singapore. Ann Acad Med Singapore. \n1988 Oct;17(4):541-4.\n\n\n\n22. Davidson F, Simmonds P, Fergson JC et al. Survey of major \ngenotypes and subtypes of hepatitis C virus using RFLP \nsequences amplified from the 5\u2019 non-coding region. J Gen \nVirology 1995;76:1197-1204.\n\n\n\n23. G. Lodi, M. Carrozzo, R. Hallett et al. HCV genotypes in \nItalian patients with HCV-related oral lichen planus. J Oral \nPathol & Med 1997; 26 (8):381\u2013384.\n\n\n\n24. Imhof M ,Popal H, Lee J.H et al. Prevalence of Hepatitis \nC Virus Antibodies and Evaluation of Hepatitis C Virus \nGenotypes in Patients with Lichen planus. Dermatology \n1997;195:1-5.\n\n\n\n25. G. Duraisamy, Zuridah MY Ariffin.Prevalence of hepatitis \nC antibodies in blood donors in Malaysia. Med J Malaysia \n1993; 48 (3) :313-316.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13 MJD 2013 Dec Vol 31\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nPATTERN OF ALLERGIC CONTACT DERMATITIS IN SCHOOL \nCHILDREN IN SELAYANG HOSPITAL, MALAYSIA\n\n\n\nSharifah Rosniza SNC, MRCP, Rohna R, MRCP, Kasmawati T, BcN, Norhasmie R, BcN, Nor Hayati AJ\n\n\n\nAbstract\n\n\n\nBackground: Allergic contact dermatitis (ACD) was thought to be infrequent in children. However, \nthere was an increasing number of case reports and cross-sectional studies in the past three decades \nindicating that ACD is not as rare as previously thought. Understanding the pattern of allergic contact \ndermatitis in children would help with the diagnosis and prevention of this disease.\n\n\n\nAim: This study explored the spectrum of contact allergens in schoolchildren.\n\n\n\nMethodology: This is a retrospective analysis of all primary and secondary schoolchildren who \nunderwent patch test at the Department of Dermatology, Hospital Selayang, Malaysia between January \n2012 and March 2013. Patch tests were performed with European Baseline Series and other additional \ncommercial series from Chemotechnique Diagnostics in IQ chambers. The parameters studied included \nsites of dermatitis, positive patch test reactions and sources of the allergens. Readings were recorded \naccording to the International Contact Dermatitis Research Group recommendation. Results were \nanalyzed using the SPSS Version 12.0.\n\n\n\nResults: 84 out of 327 (25.7%) patients who underwent patch tests were primary and secondary \nschoolchildren. Of the 84 schoolchildren, 60.7% had at least one positive patch test reaction. The most \ncommon allergens were preservatives found in cosmetic series (51%), rubber chemicals (47.1%), \nnickel sulfate (31.3%), fragrances (19.6%) and topical medicaments (19.6%). The majority (86%) of \npatients with facial dermatitis were positive to allergens in dental series, whereas 41.9% of patients \nwith dermatitis involving the upper limbs and 50% of patients with dermatitis involving the lower \nlimbs had positive patch test to rubber chemicals. Patients with dermatitis involving the trunk mostly \nhad positive patch test to fragrances (50%). Sources of fragrances were mainly found in toiletries, \ntopical medicaments and cosmetics.\n\n\n\nDiscussion: This results of this study were interesting because of the high rate of sensitization to \npreservatives, mainly paraben mix. There were also high sensitization rates to rubber chemicals, which \ncould be due to contact with rubberized shoes, sports equipment and stationery.\n\n\n\nConclusions: Schoolchildren with face, limbs or trunk dermatitis should be patch tested with additional \ndental, rubber and fragrance series respectively.\n\n\n\nKeywords: preservative allergy, rubber chemical allergy, fragrance allergy, nickel allergy\n\n\n\nCorrespondence\nSharifah Rosniza Syed Nong Chek, MRCP\nDepartment of Dermatology, Selayang Hospital\nEmail: srosniza@selayanghospital.gov.my\n\n\n\nIntroduction\nAllergic contact dermatitis (ACD) was thought \nto be infrequent in children and most of the cases \nof dermatitis in children are mainly of atopic \ndermatitis1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14MJD 2013 Dec Vol 31\n\n\n\nIt cannot be determined whether the prevalence of \nallergic contact dermatitis is truly low or whether \nACD is not sufficiently considered in children with \ndermatitis.\n\n\n\nThe incidence and prevalence of ACD in the \npopulation of schoolchildren are largely unknown \nbecause only a few systematic studies in unselected \npopulations have been undertaken. Most of the \nstudies did not provide the relevance of positive \npatch test results, and therefore an accurate estimate  \nof ACD could not be determined2. The most frequent \npatch test reactions were to metals, fragrances, \npreservatives, neomycin, rubber chemicals and \nmore recently also colourings3. Detecting ACD in \nchildren may help these patients in making decisions \nregarding occupation as they enter adulthood.\n\n\n\nIt is thought that sensitization rate increases \nwith cumulative environmental exposures. With \nmodernization, children are increasingly exposed    \nto a variety of allergens including fragrances, \ncosmetics, preservatives and dental braces4. \nHowever, studies also reported that the rate of \nsensitization to different allergens varies over time \nand also according to  geographical distribution3,5.\n\n\n\nThe standard diagnostic procedure for allergic \ncontact dermatitis includes clinical history and \npatch testing. Patch test consists of a screening \nseries, which will pick up approximately 80% of \nallergens6,7. However, considerable variations exist \nbetween centres and the series employed are often \nadapted to include allergens of local importance.  \n\n\n\nAim\nThe aim of this study is to explore the spectrum of \ncontact allergens in schoolchildren.\n\n\n\nMethods\nThis is a retrospective analysis of all primary and \nsecondary schoolchildren who underwent patch \ntest at the Department of Dermatology, Hospital \nSelayang, Malaysia.  Primary schoolchildren were \ndefined as children from the age of six to twelve years \nwhile secondary schoolchildren were from  the age \nof 13 to 19 years. Schoolchildren who underwent \npatch testing for allergic contact dermatitis from \nJanuary 1, 2012 to March 31, 2013 were identified \nfrom medical records. \n\n\n\nPatch tests were performed with European Baseline \nSeries and other additional commercial series from \nChemotechnique Diagnostics (Malmo, Sweden) in \nIQ chambers. Patches were applied to the patients \nand removed after 48 hours. Initial reading was \ndone at 48 hours and final reading was recorded at \n96 hours after patch application. The parameters \nstudied included sites of dermatitis, positive patch \ntest reactions and sources of the allergens.  Readings \nwere recorded according to the International Contact \nDermatitis Research Group recommendation: \nnegative reaction, + (erythema, infiltration, discrete \npapules), 2+ (erythema, papules, infiltration, \ndiscrete vesicles) and 3+ (coalescing vesicles, \nbullous reaction).   \n\n\n\nPatients\u2019 clinical presentation were grouped \naccording to site(s) of involvement, i.e. face, trunk, \nupper limbs and lower limbs.  Positivity was defined \nas a positive reaction to at least one or more of the \nallergens tested.\n\n\n\nFigure 1  Clinical presentations of schoolchildren with suspected allergic contact dermatitis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15 MJD 2013 Dec Vol 31\n\n\n\nTable 1  Frequency of sensitization to preservatives, rubber chemicals, nickel sulfate, fragrances and \ntopical medicaments.\n\n\n\nPreservatives\n Gender\n  Male\n  Female\n Age\n  6 -12 year-old\n  13 -19 year-old\n Race\n  Malay\n  Chinese\n  Indian\n\n\n\nRubber chemicals\n Gender\n  Male   \n  Female\n Age\n  10 6 -12 year-old\n  13 -19 year-old\n Race\n  Malay\n  Chinese\n  Indian\n\n\n\nNickel sulphate\n Gender\n  Male\n  Female\n Age\n  6 -12 year-old\n  13 -19 year-old\n Race\n  Malay\n  Chinese\n  Indian\n\n\n\nFragrances\n Gender\n  Male\n  Female\n Age\n  6 -12 year-old\n  13 -19 year-old\n Race\n  Malay\n  Chinese\n  Indian\n\n\n\nTopical medicaments\n Gender\n  Male\n  Female\n Age\n  6 -12 year-old\n  13 -19 year-old\n Race\n  Malay\n  Chinese\n  Indian\n\n\n\nPositive\nn (%)\n\n\n\n 13 (50.0%)\n 13 (50.0%)\n\n\n\n 7 (26.9%)\n 19 (73.1%)\n\n\n\n 14 (53.8%)\n 11 (42.3%)\n 1 (3.8%)\n\n\n\n 12 (50.0%)\n 12 (50.0%)\n\n\n\n 10  (41.7%)\n 14 (58.3%)\n\n\n\n 10 (41.7%)\n 14 (58.3%)\n 0 (0.0%)\n\n\n\n 7 (43.8%)\n 9 (56.3%)\n\n\n\n 9 (56.3%)\n 7 (53.8%)\n\n\n\n 5 (31.3%)\n 8 (50.0%)\n 3 (18.8%)\n\n\n\n 4 (40.0%)\n 6 (60.0%)\n\n\n\n 3 (30.0%)\n 7 (70.0%)\n\n\n\n 2 (20.0%)\n 8 (80.0%)\n 0 (0.0%)\n\n\n\n 5 (50.0%)\n 5 (50.0%)\n\n\n\n 3  (30.0%)\n 7 (70.0%)\n\n\n\n 2 (20.0%)\n 7 (70.0%)\n 1 (10.0%)\n\n\n\nNegative\nn (%)\n\n\n\n 19 32.8%)\n 39 (67.2%)\n\n\n\n 25 (43.1%)\n 33 (56.9%)\n\n\n\n 33 (56.9%)\n 21 (36.2%)\n 4 (6.9%)\n\n\n\n 20 (33.3%)\n 40 (66.7%)\n\n\n\n 22 (36.7%)\n 38 (63.3%)\n\n\n\n 37 (61.7%)\n 18 (30.0%)\n 5 (8.3%)\n\n\n\n 25 (36.8%)\n 43 (63.2%)\n\n\n\n 23 (33.8%)\n 45 (66.2%)\n\n\n\n 42 (61.8%)\n 24 (36.5%)\n 2 (2.9%)\n\n\n\n 28 (37.8%)\n 46 (62.2%)\n\n\n\n 29 (39.2%)\n 45 (60.8%)\n\n\n\n 45 (60.8%)\n 24 (32.4%)\n 5 (6.8%)\n\n\n\n 27 (36.5%)\n 47 (63.5%)\n\n\n\n 29 (39.2%)\n 45 (60.8%)\n\n\n\n 45 (60.8%)\n 25 (33.8%)\n 4 (5.4%)\n\n\n\np-value\n\n\n\n0.151\n\n\n\n0.225\n\n\n\n0.000\n\n\n\n0.000\n\n\n\n0.000\n\n\n\n0.000\n\n\n\n0.776\n\n\n\n0.151\n\n\n\n0.013\n\n\n\n1.000\n\n\n\n0.735\n\n\n\n0.02\n\n\n\n0.495\n\n\n\n0.735\n\n\n\n0.04\n\n\n\nPatch test\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16MJD 2013 Dec Vol 31\n\n\n\nTable 2  Frequency of sensitization to preservatives, rubber chemicals, nickel sulfate, fragrances and\ntopical medicaments with different presentations.\n\n\n\nFacial\n Preservatives\n Rubber chemicals\n Nickel sulfate\n Fragrances\n Topical medicament\n\n\n\nUpper limbs\n Preservatives\n Rubber chemicals\n Nickel sulfate\n Fragrances\n Topical medicament\n\n\n\nLower limbs\n Preservatives\n Rubber chemicals\n Nickel sulfate\n Fragrances\n Topical medicament\n\n\n\nTrunkal\n Preservatives\n Rubber chemicals\n Nickel sulfate\n Fragrances\n Topical medicament\n\n\n\nPositive\nn (%)\n\n\n\n 4 (40.0%)\n 2 (20.0%)\n 4 (40.0%)\n 1 (10.0%)\n 1 (10.0%)\n\n\n\n 14 (25.0%)\n 15 (26.8%)\n 11 (19.6%)\n 5 (8.9%)\n 5 (8.9%)\n\n\n\n 18 (34.6%)\n 18 (34.6%)\n 10 (19.2%)\n 8 (15.4%)\n 9 (17.3%)\n\n\n\n 1 (16.7%)\n 1 (16.7%)\n 0 (0.0%)\n 3 (50.0%) \n 0 (0.0%)\n\n\n\nNegative\nn (%)\n\n\n\n 6 (60.0%)\n 8 (80.0%)\n 6 (60.0%)\n 9 (90.0%)\n 1  (90.0%)\n\n\n\n 42 (75.0%)\n 41 (73.2%)\n 45 (80.4%)\n 51 (91.1%)\n 51 (91.1%)\n\n\n\n 34 (65.4%)\n 34 (65.4%)\n 42 (80.8%)\n 44 (84.6%)\n 43 (82.7%)\n\n\n\n 5 (83.3%)\n 5 (83.3%)\n 6 (100%)\n 3 (50.0%)\n 6 (100%)\n\n\n\np-value\n\n\n\n0.717\n0.717\n0.091\n1.000\n1.000\n\n\n\n0.133\n0.798\n1.000\n0.200\n0.200\n\n\n\n0.467\n0.141\n1.000\n0.305\n0.081\n\n\n\n0.661\n0.669\n0.349\n0.021\n0.604\n\n\n\nPatch test\n\n\n\nStatistics\nResults were analyzed using the SPSS Version \n12.0. Association between categorical variables \nwas analyzed using the chi-squared test. Statistical \nsignificance was set at p<0.05.\n\n\n\nResults\nA total of 84 out of 327 (25.7%) patients who \nunderwent patch tests were primary and secondary \nschoolchildren. Female to male ratio was 1.6 : 1.  \nThe majority (56%) of the patients were Malay, \nfollowed by Chinese (38%) and Indian (6%).  Of the \n84 schoolchildren, 60.7% had at least one positive \npatch test reaction. The most common allergens \nwere preservatives found in cosmetic series (51%), \nrubber chemicals (47.1%), nickel sulfate (31.3%), \nfragrances (19.6%) and topical medicaments \n(19.6%).  \n\n\n\nThere was no statistically significant difference in \nthe sensitization to these allergens with regards to \ngender and age. Compared to Malay and Indian \npatients; Chinese patients were found to be more \nlikely to develop ACD to rubber (58.3%, p=0.042), \nnickel sulphate (50.0%, p=0.013), fragrances (80%, \np=0.02) and topical medicaments (70%, p=0.04).\n\n\n\nOf the patients who had positive patch test \nreactions; 86% of patients with facial dermatitis \nwere positive to allergens in dental series whereas \n41.9% of patients with dermatitis involving the \nupper limbs and 50% of patients with dermatitis \ninvolving the lower limbs had positive patch test to \nrubber chemicals. 60% of the patients with facial \ndermatitis had dermatitis involving the perioral \nregion. Patients with dermatitis involving the trunk \nmostly had positive patch test to fragrances (50%, \np=0.021).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17 MJD 2013 Dec Vol 31\n\n\n\nDiscussion\nMost of the studies pertaining to allergic contact \ndermatitis in children were based on the population \nof children in the United States and Northern \nEuropean countries8. The results of our study differ \nfrom the majority of these studies in terms of the \nmost common allergens. Preservatives, which are \nincluded in the European Baseline Series and \nCosmetic Series, were found to be the most common \nsensitizers in this study. This finding may be due to \nthe difference in legislation concerning the usage of \npreservatives in cosmetics and household products \nin different countries. Paraben mix is the most \nfrequently positive preservative allergen in this \nstudy.  Currently, there is no specific regulation with \nregards to the maximum concentration of parabens \nthat can be used in consumer products in Malaysia9. \nGeographically closer to our study population, there \nis only one study from India which showed similar \nfindings whereby the most common allergen was \nalso found to be paraben mix10.\n\n\n\nRubber chemicals were found to be the second \nmost common allergen in our study and it is the \nmost common sensitizer for patients presented with \ndermatitis involving the upper and lower limbs.  \nAlthough rubber is ubiquitous in the environment, it \nis likely that this trend is due to contact with rubber \ncontaining products such as sports equipment and \nstationery including rubber erasers. Rubber is used \nin handles of badminton and tennis rackets and also \nin squash balls. Additionally, increased sensitization \nto rubber chemicals in patients presented with lower \nlimb dermatitis may also be due to the increasing trend \nfor sports shoes. In particular, one study showed that \nallergic contact dermatitis due to shin guards were \nmost commonly caused by rubber chemicals i.e. \nthiurams and mercaptobenzothiazole11. Increased \nsweating during sports activities and occlusion \nfrom the sportswear may also alter the skin barrier \nand facilitate the entrance of allergens into the skin \ncausing ACD.  \n\n\n\nNickel sulfate was found to be the third most common \nsensitizer in this study and this is in agreement with \nour knowledge of the epidemiology of ACD in \npaediatric and adult populations1. Sources of nickel \nsensitization include jewelry, belt buckles, metal \nfasteners, spectacle frames and ear rings. Although \nthere is a general opinion that more girls than boys \nare sensitized because girls are more likely to have \ntheir ears pierced at a young age, we found no \nstatistically significant difference in the frequency \n\n\n\nof nickel sensitization between girls and boys in this \nstudy. It is perhaps useful to investigate whether \near piercing was performed in those who showed \npositivity towards nickel sulfate to understand more \nabout the relevance of sensitivity to nickel in this \nstudy. \n\n\n\nFragrances were the fourth most common allergens \nfound in our study and this could be contributed by the \nincreased production of perfumed toiletry products \nmade specifically for children. In younger children, \ntoys are another potentially important source of \nexposure to fragrance and these include cosmetic-\ntoy sets which contain products such as perfumes, \nlipstick and eyeshadow. One study found that levels \nof fragrance in some selected cosmetic-toy sets sold \nin retail outlets were higher than the recommended \nindustrial guidelines12. Fragrances are also found \nin topical medicaments.When these products are \napplied on diseased skin such as wounds, leg ulcers \nor eczema, there is a higher chance for the allergens \nto cross the skin barrier and cause sensitization.\n\n\n\nPatients presented with facial dermatitis were \nmostly found to be positive to allergens contained \nin dental series. This could be explained by the fact \nthat most cases of facial dermatitis in this study were \nspecifically perioral dermatitis. Exposure to metal \nand acrylates used in dental fillings could be the \ncause of sensitization in these patients13. However, \ncontact with metal can also happen through playing \nmusical instruments. Thus it is important to obtain \na thorough history that includes such hobbies and \nactivities.\n\n\n\nIn this study, the subset of Chinese patients were \nfound to be more at risk of developing allergic \ncontact dermatitis to rubber, nickel sulphate, \nfragrance and topical medicaments. There may be \na true risk associated with this if they are more \nfrequently exposed to allergens found in traditional \ntopical Chinese medications14. Fragrance, \ncolophony, rubber mix and nickel have been found \nin these topical preparations15. Alternatively, this \nfinding may only be an apparent risk. Parents \nof Chinese schoolchildren may have different \nperception about the seriousness of skin diseases \nand may seek treatment earlier; making the Chinese \nschoolchildren more likely to be identified earlier \ncompared to the other races. Further studies would \nbe needed to elucidate this difference between the \nthree main racial groups in Malaysia.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18MJD 2013 Dec Vol 31\n\n\n\nFrom our study, we find ita ppropriate to use the \nEuropean Baseline Series supplemented with \nallergens according to the child\u2019s history. Children \nand adults can be tested with equal concentrations of \npatch test allergens16. Adolescents may be exposed \nto occupational allergens from part time jobs and \nthus it is important that history should consider \nexposure in such activities17.\n\n\n\nThe limitations of our study include the retrospective \nnature of the study and that it is conducted only in \na single centre. Selayang Hospital receives referral \nfrom areas surrounding Gombak and the population \nstudied may not be fully representative of the \nMalaysian schoolchildren population.  \n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n \n1. Mortz CG, Andersen KE. Allergic contact dermatitis in \n\n\n\nchildren and adolescents. Contact Dermatitis.  1999: 41(3): \n121-30.\n\n\n\n2. Lee PW, Elsaie ML, Jacob SE. Allergic contact dermatitis \nin children: commonallergens and treatment: areview.  \nCurr Opin Pediatr. 2009 Aug:21(4) :491-8.\n\n\n\n3. Flora B. de Waard-van der Spek, Klaus E. Andersen, Ulf \nDarsow et al. Allergic contact dermatitis in children: which \nfactors are relevant? (review of the literature). Pediatr \nAllergy Immunol 2013: 24: 321-329\n\n\n\n4. Bonitsis NG, Tatsioni A, Bassioukas K et al.  \nAllergensresponsible for allergic contact dermatitis among \nchildren: a systematic review and meta-analysis. Contact \nDermatitis. 2005 May:64(5): 245-257\n\n\n\n5. Seidenari S, Giusti F, Pepe P, Mantovani L. Contact \nsensitization 1094 children undergoing patch testing over a \n7-year period. Pediatr Dermatol 2005: 22: 1-5.\n\n\n\n6. Sheretz E F, Swartz S M. Is the screening patch test tray  \nstill worth using? J Am Acad Dermatol. 1993: 36: 1057-\n1058.\n\n\n\n7. Menn\u00e9 T, Dooms-Goosens A, Wahlberg J E, White I R, \nShaw S. How large a proportion of contact sensitivities \nare diagnosed with the European standard series? Contact \nDermatitis.1992: 26: 201-202.\n\n\n\n8. Goon AT, Goh CL. Patch Testing of Singapore Children \nand Adolescents: Our Experience over 18 Years. Pediatr \nDermatol.  2006: 23(2): 117-20 \n\n\n\n9. Voo SY, Ridzwan R. Patch Testing with Preservative \nSensitizers. A Year Retrospective Study from Selayang \nHospital. Malaysian Journal of Dermatology. 2013: 30: \n1-6.\n\n\n\n10. Sarma N, Ghosh S. Clinico-allergological pattern of \nallergic contact dermatitis among 70 Indian children. \nIndian J Dermatol Venereol Leprol 2010: 76: 38-44.\n\n\n\n11. M T Ventura, MDagnello, M G Matino et al. Contact \ndermatitis in students practicing sports: incidence of \nrubber sensitisation. Br J Sports Med 2001; 35: 100-102.\n\n\n\n12. Rastogi SC, Johansen JD, Menne T et al. Contents of \nfragrance allergens in children\u2019scosmetics and cosmetic-\ntoys. Contact Dermatitis.1999: 41(2): 84-8.\n\n\n\n13. Bakula A, Lugovic-Mihic L, Situm M et al. Contact \nallergy in the mouth: diversity of clinical presentations and \ndiagnosis of common allergens relevant to dental practice.  \nActa Clin Croat. 2011: 50(4): 553-61.\n\n\n\n14. Sen P, Ho MS, Ng SK et al. Contact dermatitis: a common \nadverse reaction to topical traditional medicine. Int J \nDermatol. 2010: 49(11): 1255-60.  \n\n\n\n15. L.-F. Li et al. Patch testing in allergic contact dermatitis \ncaused by topical Chinese herbal medicine. Contact \nDermatitis. 2002 47(3): 166-8.\n\n\n\n16. Zug KA, McGinley-Smith D, Warshaw EM et al. Contact \nallergy in children referred for patch testing: North \nAmerican Contact Dermatitis Group data, 2001-2004.  \nArch Dermatol. 2008: 144(10): 1329-36.\n\n\n\n17. Milingou M, Tagka A, Armenaka M et al. Patch tests in \nchildren : a review of 13 years of experience in comparison \nwith previous data. Pediatr Dermatol. 2010: 27(3): 255-9.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19 MJD 2013 Dec Vol 31\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nTRIGEMINAL TROPHIC SYNDROME.\nA CASE REPORT AND LITERATURE REVIEW \n\n\n\nEsther A1, Tang JJ1, Norain K2\n\n\n\nKeywords: cranial nerve, skin atrophy, trigeminal anaesthesia, facial paraesthesia\n\n\n\nIntroduction\nTrigeminal trophic syndrome is a rare cause of \nchronic ulceration of the face1,2. These chronic \nulceration in the trigeminal pathway was first \ndescribed by Wallenberg in 19011. It is usually \na complication after an injury to the trigeminal \nsensory nuclei, spinal trigeminal tract, ganglion, \nor peripheral nerve branches. It is characterized by \nunilateral trigeminal anaesthesia, facial paraesthesia, \ncrescent-shaped ulceration of the ala nasi1,3. We \nreport a case of Trigeminal trophic syndrome in a \n50 year old gentleman with ulcerative plaque on his \nscalp, left upper eyelid, left inner canthus and left \nala nasi for the past 6 months. It is important to be \naware of this disfiguring condition to ensure prompt \ndiagnosis and further management.  \n\n\n\nCase report\nA 50 year-old man presented to us with ulcerative \nplaque on the scalp and left side of the face for 6 \nmonths. He has diabetes mellitus, hypertension \nand history of cerebral vascular accident with right \nhemiparesis a year ago. CT brain showed cerebral \ninfarct involving the left internal capsule. The \nulcerative lesions started on the left side of scalp \nand then involved the left upper eyelid, left inner \ncanthus and the left ala nasi. These lesions were \npainless and associated with contact bleeding. \nThe old lesion on the scalp and left inner canthus \neventually healed but ulcer on the left ala nasi and \nupper eyelid progressively increased in size. \n\n\n\nHe also complained of numbness over the left side of \nhis face due to previous stroke. There was no history \nof preceding trauma, fever, photosensitivity or joint \npain. There was no burning or crawling sensation \nover these area. He denied scratching or rubbing on \nthe affected area.\n\n\n\nCorrespondence\nTang Jyh Jong, AdvMDerm\nDepartment of Dermatology,\nHospital Raja Permaisuri Bainun Ipoh, Perak, Malaysia. \nEmail: tangjyhjong@yahoo.com \n\n\n\nOn examination, there were new and old ulceration \nconfined to left side of his face (Figure 1, 2, 3). \nThere were two ulcerative plaques on left upper \neyelid and left ala nasi. The ulcer on left ala nasi \nhad eroded the nasal cartilage leaving a triangular \nshape of ulcer with punch out appearance. The \nulcer was clean with healthy granulation tissue. \nThere was also another similar ulcer on left upper \neyelid with clean base and minimal crust. He also \nhad two healed crescentic ulcers with scarring over \nleft side of scalp and left inner canthus. There were \nno lesions elsewhere in the body. He did not have \nany oral, genital or nail involvement. Examinations \nof other systems were all unremarkable. Our initial \ndifferential diagnosis included Erosive Discoid \nLupus Erythematous, Erosive Lichen Planus, Lupus \nVulgaris, Lethal Midline Granuloma, Deep Fungal \nInfection and Wegener\u2019s Granulomatosis.\n\n\n\nHis full blood count, liver and renal function, ESR, \nurine analysis were within normal limits. Syphilis, \nHepatitis B and C serology and HIV screening were \nnegative. The ANA, ENA, pANCA, cANCA were \nnegative too. Mantoux test and Chest radiography \nwere normal. Multiple skin biopsies were done but \nall revealed epidermal ulceration with inflammatory \ninfiltrates without evidence of vasculitis, malignancy \nor granulomas (Figure 4). Special staining for fungi \nand acid fast bacili were all negative. Tissue cultures \nfor mycobacteria tuberculosis and fungi were also \nnegative. Immunofluorescence study was negative. \nThe skin biopsy findings ruled out all of the above \ndifferential diagnosis and the final diagnosis of \nTrigeminal trophic syndrome was made. He was \nstarted on amitriptyline and carbamazepine with \ndaily occlusive dressing for the ulcer on the face. \nThe old lesions slowly dried up but he developed \nnew lesion over scalp and left lower eyelids after \n3 months of treatment. He was also referred to \npsychiatrist for co-management.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20MJD 2013 Dec Vol 31\n\n\n\nFigure 1  Ulcerative plaques with clean base and \nminimal crust over the left upper eye lid and left ala \nnasi with destruction of nasal cartilage.\n\n\n\nFigure 3  Close view of the healed ulcer with \nscarring over scalp.\n\n\n\nFigure 2  Close view of the ulcers over the left \nupper eye lid and left ala nasi with healed ulcer on \nleft inner canthus.\n\n\n\nFigure 4  Skin biopsy showed epidermal ulceration \nwith inflammatory infiltrates without evidence of \nvasculitis, malignancy or granulomas.\n\n\n\nDiscussion \nTrigeminal trophic syndrome is rare cause of \nchronic ulceration of the face1,2. These chronic \nulceration in the trigeminal pathway was first \ndescribed by Wallenberg in 19011. Trigeminal \ntrophic syndrome occurs as a complication after \nan injury to the trigeminal sensory nuclei, tract, \nganglion, or peripheral nerve branches. It is reported \nthat two third of all cases is due to the damage \nfrom trigeminal nerve ablation (33%), or as result \n\n\n\nfrom cerebrovascular accident (33%). Other causes \nmay include trauma, craniotomy, herpes zoster \ninfection, astrocytoma, leprosy and complicated \nbirth neurological deficit2,5. The age of onset ranges \nfrom 14 months to 94 year, with mean of 57 to \n60 year and has a female to male ratio of 2.2-11,2. \nThe duration between the injury and the onset of \nthe ulceration can be from weeks to years, with a \naverage of 1 year1,3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21 MJD 2013 Dec Vol 31\n\n\n\nTrigeminal trophic syndrome manifest as an uni-\nlateral trigeminal anaesthesia, facial paraesthesia, \ncrescent-shaped  ulceration of the ala nasi1,3. Even \nthough the most common location of the ulceration \nis at the ala nasi, lesions has also been reported to \ninvolve scalp, ear, cheek, temple, palate or cornea2,4. \nThe tip of the  nose is typically spared due to its \ninnervation by the ethmoidal branch of the ophthalmic \ndivision of the trigeminal nerve2. These lesions is \nusually self induced due to repeated manipulation \nlike scratching or rubbing of the involved area which \nulcerates and  or rubbing of the involved area which \nulcerates and heals with scarring2. The diagnosis \nof trigeminal trophic syndrome is based on clinical \npresentation of the ulcers, anaesthesia and facial \nparaesthesia in the distribution on trigemal nerve \nwith a history of iatrogenic or non iatrogenic injury \nto the trigeminal nerves1,2. \n\n\n\nSkin biopsy for histopathology is needed to exclude \nother diseases that can mimic similar facial ulceration \nsuch as Erosive Discoid lupus Erythematous, \nWegener\u2019s granulomatosis, Destructive Lethal \nMidline granuloma, Lupus vulgaris, Basal cell \ncarcinoma, Subcutaneous fungal infection, Syphilis \nand other facial dermatitis2,3,4. Histopathology of \ntrigeminal trophic syndrome is nonspecific as it only \nshows chronic ulceration with minimal inflammatory \ninfiltrate and no granuloms or vasculitic lesions1. \nOther investigations may include autoimmune \nscreening, infective screening and cultures.\n\n\n\nTrigeminal trophic syndrome is a very challenging \nproblem to treat. Patient education about self \nmanipulation of the lesions is crucial to prevent \nfurther disfiguring of the ulceration. Wound care \nshould be initiated and secondary bacterial infection \ncan be treated with oral and topical antibiotics2,4. \nPharmacologic medications like carbamazepine, \n\n\n\namitriptyline, diazepam, pimozide, clonazepam, \nvitamin B supplements is believed to reduce \nparaesthesia and patients urge to pick on the lesions1,3. \nUsing a protective barrier to cover the affected area \nhelps to reduce manipulation of the lesion2,4. Cervical \nsympathectomy and transcutaneous electrical nerve \nstimulation have been used to improve blood supply \nand promote wound healing of this condition1,3. \nSurgical reconstruction using innervated cross face \nflaps that included nasal, nasolabial and forehead \nneurovascular flaps has been tried with a good long \nterm prognosis1,2. New options are being explored to \ntreat trigeminal trophic syndrome. In vitro cultured \nepidermal cell has been used recently to induce \ntissue regeneration in the treatment of neurotrophic \nulceration of the face1,6. In a single case report, \nSchwerttner et al  used a transplant of autologous \ncultured epidermal cell taken from retroauricular skin \nwith excellent cosmetic result1. The other treatment \noption includes the use of thermoplastic dressings. \nPreston et al reported using thermoplastic dressing \nto treat two cases of trigeminal trophic syndrome \nwith promising outcome6. Thermoplastic dressing is \nbelieved to interrupt the cycle of perceived irritation \nand secondary compulsive rubbing.\n\n\n\nConclusion\nIn conclusion, Trigeminal trophic syndrome is a \nrare cause of chronic ulceration of the face due to \ninjury to the trigeminal nerves. The report of this \ncase is to increase awareness to recognize this \ndisfiguring condition to ensure prompt diagnosis \nand further management. Skin biopsy is essential to \nexclude other causes of facial ulceration. Treatment \nis very challenging and the aims include controlling \nof the paraesthesia, pain management, behavior \nmodification, medical and surgical management of \nthe wound.\n\n\n\nReferences\n\n\n\n1. Rashid RM, Khachemoune A. Trigeminal Trophic \nSyndrome. Eur Acad Dermatol and Ven 2007;21:725-731 \n\n\n\n2. Parrish S, Francis A, Allison TV. Trigeminal Trophic \nSyndrome: Report of Four Cases and Review of the \nLiterarture. Dermatol Surg 2004;30:807-812  \n\n\n\n3. Anil MK, Diona LD, Fergal JM. Trigeminal Trophic \nSyndrome treated with Thermoplastic Occlusion. \nAustralian J Dermatol 2011; 52:1-4\n\n\n\n4. Seetha UM, Jeffrey ET, David MA. The Trigeminal Trophic \nSyndrome: An Unusual Cause of Nasal Ulceration. J Am \nAcad Dermatol 2004; 50:949-52.\n\n\n\n5. Andrew JR, Anjela M, Stuart B, Anngela R. Reconizing \nTrigeminal Trophic Syndrome. J Am Acad Dermatol,Volume \n55,2: 359-361\n\n\n\n6. Preston PW, Orpin SD, Tucker WFG, Zaki I. Successful \nuse of themoplastic dressing in two cases of the Trigeminal \nTrophic Syndrome. Clin and Exp Dermatol 2006; 31:525-\n527\n\n\n\n\n\n\n\n\n\n"
"\n\nVolume 35   |  Dec 2015   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.myIndexed in: Western Pacific Research Index Medicus\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\nM\nA\n\n\n\nLA\nY\n\n\n\nS\nIA\n\n\n\nN\n J\n\n\n\nO\nU\n\n\n\nR\nN\n\n\n\nA\nL O\n\n\n\nF D\nE\n\n\n\nR\nM\n\n\n\nA\nT\n\n\n\nO\nLO\n\n\n\nG\nY\n\n\n\n     Volum\ne 35   |  D\n\n\n\nec 2015  |  ISSN\n: 1511-5356\n\n\n\n\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2015 Dec Vol 35\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. 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Topics may include updates in clinically relevant \nbasic science and cutaneous biology. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author who \nwill be responsible for reading the proofs must also be given on \nthe title page. The author(s) must also declare any affiliation or \nsignificant financial involvement in any organizations or entity \nwith a direct financial interest in the subject matter or materials \ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should \nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in \nthe manuscript. 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Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of \nall references; incomplete references may result in a delay to \npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on \na separate sheet, and should only include essential information. \nDrawings, graphs, and formulas should be submitted on \nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it is \nimportant that all electronic artwork is supplied to the Editorial \nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\nNotice to Authors\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY \n\n\n\n ORIGINAL ARTICLE\n2 Topical Corticosteroid Phobia among \n Atopic Eczema patients and their \n caregivers: Survey in two dermatology \n outpatient clinics in Malaysia\n Noorlaily MN, Baba R\n\n\n\n6 The effect of oral Clindamycin and \n Rifampicin combination therapy in \n patients with Hidradenitis Suppurativa\n in Singapore\n Ochi H, Tan L X, Oon H\n\n\n\n CASE REPORT\n10 Adult Xanthogranulomatosis: A case report\n Ramalingam Rajalingam, Johar Asmah, Lee Bang Rom\n\n\n\n13 Mycobacterium Chelonae infection in a 19-year-old \n Immunocompetent patient successfully treated with \n oral Clarithromycin and Linezolid\n         Ochi H, Pan JY\n\n\n\n16 Contact Dermatitis to a Turmeric coated wedding \n thali: A case report\n Wan Syamee Afira WAK, Tarita T, Rohna R, Zuraini A\n\n\n\n20 Lupus Tumidus in a chinese male: A case report\n Anisha B, Norashikin S\n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1MJD 2015 Dec Vol 35\n\n\n\nEditor-in-Chief \nAssociate Professor Dr Felix Yap Boon Bin \nMRCP Adv MDerm\nUniversiti Tunku Abdul Rahman\n\n\n\nFounding Editor\nDr Steven Chow Kim Weng\nFRCPI\nKuala Lumpur\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP\nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed, Penang\n\n\n\nDr Ng Ting Guan MRCP AdvMDerm\nKlang, Selangor\n\n\n\nDr Adawiyah Jamil MMed AdvMDerm\nKuala Lumpur\n\n\n\nDr Tang Jyh Jong MRCP AdvMDerm\nIpoh, Perak\n\n\n\nDr Tarita Taib AdvMDerm\nSelayang, Selangor\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nExecutive Staff\nHenry Foong Boon Bee, FRCP - President\nNajeed Ahmad Safdar, MRCP - Past President\nAgnes Heng Yoke Hui, MRCP - Vice President\nRohna Ridzwan, MRCP - Secretary\nNoor Zalmy Azizan, AdvMDerm - Treasurer\nChan Lee Chin, MMed\nKhor Guat Ee, MRCP\nSabeera Begum, MMed\nTan Wooi Chiang, AdvMDerm\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\nG1, Medical Academics of Malaysia\n210, Jalan Tun Razak\n50400 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (July and December issues)\n\n\n\nPrinted by Percetakan Sri Jaya, No.27, Jalan Emas SD 5/1A, Bandar Sri Damansara, 52200 Kuala Lumpur\nTel : 03-6276 4082   Fax : 03-6275 9514\n\n\n\n\u00ae2014 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 MJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nTOPICAL CORTICOSTEROID PHOBIA AMONG ATOPIC \nECZEMA PATIENTS AND THEIR CAREGIVERS: SURVEY IN TWO \nDERMATOLOGY OUTPATIENT CLINICS IN MALAYSIA\nNoorlaily MN1, Baba R2\n\n\n\nAbstract\n\n\n\nIntroduction: Steroid phobia has been recognized as a hindrance to successful treatment in patients \nwith atopic eczema. Data on this phenomenon is lacking in Malaysia. This study investigates the \nprevalence and reasons for topical corticosteroid phobia in patients with atopic eczema and their \ncaregivers.  \n\n\n\nMethods: A questionnaire-based study was conducted in both children and adult patients suffering \nfrom atopic eczema in two government dermatology clinics at Hospital Kuala Lumpur and Hospital \nKota Bharu between May and July 2011.\n\n\n\nResults: Of the 77 respondents, 39% were worried about using topical corticosteroids for their eczema \nwith 13% totally avoiding steroids. The most common reason for this fear was concern about skin \nthinning (27.3%) followed by concern on changes in skin colour (14.3%), scarring (13%) and stretch \nmarks (13%). Steroid phobia was significantly higher in those with tertiary education (p=0.005).\n\n\n\nConclusion: Steroid phobia appears to be a significant problem in Malaysia especially in those \nwith higher educational background. Despite these concerns, the patients\u2019 compliance to topical \ncorticosteroids is still reasonably good.\n\n\n\nKeywords: Steroid, phobia, eczema\n\n\n\nCorresponding Author and Reprint Request \nDr Noorlaily Mohd Noor\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang 50586 Kuala Lumpur\nEmail: laily124@hotmail.com\n\n\n\n1 Department of Dermatology, Hospital Kuala Lumpur\n2 Department of Dermatology, Hospital Melaka\n\n\n\nRecently a phenomenon known as steroid phobia \nhas been recognized as a hindrance to successful \ntreatment in patients with atopic eczema in a few \ndeveloped countries. Steroid phobia is irrational \nfear and anxiety about using corticosteroids.2,3 Some \ncentres reported prevalence of steroid phobia to be \nas high as 80.7%.4 However data on steroid phobia \nis lacking from the developing countries. Thus we \nembarked on this study to investigate the prevalence \nand the reasons for topical corticosteroid phobia in \npatients with atopic eczema and their caregivers.  \nWe also explored whether the level of education and \nfamily income have any effect on this phenomenon. \n\n\n\nIntroduction\nTopical corticosteroid is one of the most commonly \nused treatment modalities in atopic eczema patients. \nIt was first introduced in 1952 and remained the \nmainstay of treatment for atopic eczema because \nof its potent anti-inflammatory and antiproliferative \neffects.1\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2015 Dec Vol 35\n\n\n\nMaterials and methods\nTA questionnaire-based study was conducted in both \nchildren and adult patients suffering from atopic \neczema in two government dermatology clinics at \nHospital Kuala Lumpur and Hospital Kota Bharu \nbetween May and July 2011. This questionnaire was \nprepared with reference to an almost similar study \ndone in Queen\u2019s Medical Centre, Nottingham.2 \nThe diagnosis of atopic eczema was made by \ndermatologists and senior medical officers in all \ncases. The questionnaire was given out to successive \npatients, then completed by patients in those over \n18 years of age or a parent or guardian in those less \nthan 18 years of age.\n\n\n\nThe first section of the questionnaire was intended \nto capture the demographics of the patients. In the \nsecond section, the level of education and family \nincome were determined. The level of education \nwas divided into primary (up till primary six or 12 \nyears old), secondary (up till Form 5 or 17 years old) \nand tertiary (educational level following secondary \neducation). The family income was divided into \ndifferent categories based on the monthly income as \nfollows: low (<RM 1500), lower middle (RM 1501-\n5000), upper middle (RM 5001-10000) and high \nincome group (>RM10000).\n\n\n\nThe next section looked into steroid phobia and the \ncause of the phobia with the following questions:\n  \nDo you apply the steroid creams as advised by your \ndoctor?\nAre you worried about applying steroids on your \nskin/your child\u2019s skin?\nIf the answer is yes, why do you worry?\nHave the worries stopped you from applying the \nsteroid creams (on your child)? \n\n\n\nThe effect of the educational background and family \nincome on steroid phobia was analysed using the \nchi-square test.\n\n\n\nResults\nThere were 77 respondents, 59 from Hospital Kuala \nLumpur and 18 from Hospital Kota Bharu. Table 1 \nshows the demographics of the patients.\n\n\n\nTable 1. Patients\u2019 demographics\n\n\n\nTable 2. The reasons for patients\u2019/caregivers\u2019 concerns \nabout using topical corticosteroids.\n\n\n\nAge \n\n\n\nGender \n\n\n\nRace \n\n\n\nIncome \n\n\n\nCause of topical \ncorticosteroid phobia\n\n\n\nSkin thinning \n\n\n\nChange in skin colour \n\n\n\nScarring \n\n\n\nStretch marks \n\n\n\nMay worsen eczema \n\n\n\nMay become dependent \n\n\n\nIncreased risk of infection \n\n\n\nCancer \n\n\n\nCataract \n\n\n\nGrowth delay \n\n\n\nSkin ageing \n\n\n\nIncreased body hair \n\n\n\nSunburn \n\n\n\nBruising \n\n\n\n< 18\n\u2265 18 \n\n\n\nMale \nFemale \n\n\n\nMalay \nChinese \nIndian \nOthers \n\n\n\n< RM 1500\nRM 1501 - 5000\nRM 5001 - 10000\n> RM 10000\n\n\n\nNumber of patients \n(%), n=77\n\n\n\n 51 (66.2%)\n 26 (33.8%)\n\n\n\n 22 (28.6%)\n 55 (71.4%)\n\n\n\n 61 (79.2%)\n 7 (9.1%)\n 7 (9.1%)\n 2 (2.6%)\n\n\n\n 26 (33.8%)\n 40 (51.9%)\n 7 (9.1%)\n 4 (5.2%)\n\n\n\nNumber of patients (%), \nn=77 \n\n\n\n 21 (27.3%) \n\n\n\n 11 (14.3%) \n\n\n\n 10 (13%) \n\n\n\n 10 (13%) \n\n\n\n 9 (11.7%) \n\n\n\n 8 (10%) \n\n\n\n 7 (9%) \n\n\n\n 5 (6.5%) \n\n\n\n 5 (6.5%) \n\n\n\n 5 (6.5%) \n\n\n\n 5 (6.5%) \n\n\n\n 5 (6.5%) \n\n\n\n 4 (5.2%) \n\n\n\n 3 (3.9%) \n\n\n\nTable 3. The effect of educational level on steroid phobia.\n\n\n\nLevel of \neducation \n\n\n\nPrimary and \nsecondary\n\n\n\n Tertiary\n\n\n\nYes\n\n\n\n12/46 \n(26.1%) \n\n\n\n18/31 \n(58.1%)\n\n\n\nNo\n\n\n\n34/46 \n(73.9%) \n\n\n\n13/31 \n(41.9%)\n\n\n\nP value\n\n\n\n0.005 \n\n\n\n> 0.05\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 MJD 2015 Dec Vol 35\n\n\n\nOut of these, 39% (30/77) were worried about using \ntopical corticosteroids for their eczema. The reasons \nfor these worries are shown in Table 2. A total of \n13% (10/77) avoided using topical corticosteroids \nbecause of these worries. The most common reason  \nfor this fear was their concern about skin thinning \n(27.3%). They were also worried about topical \ncorticosteroids causing changes in skin colour \n(14.3%), scarring (13%) and stretch marks (13%). \nThe number of patients with steroid phobia was \nsignificantly higher in those with tertiary education, \np=0.005 (Table 3). Family income has no effect on \nsteroid phobia.\n\n\n\nDiscussion\nSteroid phobia has become an increasingly difficult \nproblem especially in the developed countries such \nas United Kingdom, Japan and Australia.2,4-6 Our \nstudy showed that 39% of patients with atopic \neczema has steroid phobia. This figure is relatively \nsmall compared with data from developed western \ncountries such as United Kingdom and France \nwhere 72.5% and 80.7%  of atopic eczema patients \nhave steroid phobia respectively.2,4 On the other \nhand a study in Japan indicated that the incidence \nof steroid phobia was 38.3% although a slightly \ndifferent methodology was used.7 More studies \nshould be done in Asian countries to see whether \nfear for steroid is less common among Asian \npatients compared to the west. If this is so, it would \nbe interesting to see whether cultural differences \nand belief play any role in this observation.\n\n\n\nOnly a third of our patients with steroid phobia \navoided steroids which was similar to the study \ndone in the UK.2 Thus the majority of patients were \nstill compliant to their treatment despite this fear. \nHowever without proper counselling the figure \nmay rise and potentially cause treatment failure \nas a result of noncompliance. Thus it is important \nfor doctors and other healthcare workers to spend \nmore time with patients and their caregivers to \nensure dissemination of correct information. One \nof the reasons suggested was the inappropriate \nuse of the words \u2018sparingly\u2019 or \u2018thinly\u2019 to describe \nhow corticosteroid creams should be applied on the \nskin. This misled patients to be extremely cautious \nand anxious of the adverse side effects during \napplication. The more suitable advice would be \n\u2018apply enough to cover affected areas\u2019.8\n\n\n\nSkin thinning is the most common reason for the \nfear of topical corticosteroids in this and other \nstudies.2,6 One of the reasons is that this adverse \neffect is probably emphasized the most by doctors \nor perceived as the worst by patients. Change in \nskin colour is the next most worrisome side effects \nin patients with steroid phobia. As the majority of \npatients were Asians with generally darker skin, \nhypopigmentation especially is not an acceptable \nside effect. The other thing to look into is how the \ninformation on adverse effects is phrased in the \nsteroid information leaflet of the creams.\n\n\n\nSteroid phobia was significantly higher in those with \ntertiary education. However family income has no \neffect on steroid phobia. Patients and caregivers are \nmore well informed nowadays, and this is especially \nso with the availability of vast material on the \nmedia and internet. Those with tertiary education \nwould probably search for more information and do \nnot rely solely on advice from the doctors. Future \nstudies should look into the source of information \nin these patients and their caregivers.\n\n\n\nAmong the limitations of this study was the \nsmall number of patients and their selection from \nsubsidized government hospitals only. Further \nstudies should include more centres and include \npatients in private healthcare settings as well as \nthose from rural areas.\n\n\n\nConclusion\nSteroid phobia appears to be a significant problem \nin Malaysia although its prevalence is not as high as \nthat of other developed countries. Steroid phobia is \nalso more common in those with tertiary or higher \neducational background. Despite these concerns, \nthe patients\u2019 compliance to topical corticosteroids is \nstill reasonably good. \n\n\n\nAcknowledgement\nThe authors would like to thank Dr Zulrusydi Ismail \nand Dr Felix Yap for their contribution.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2015 Dec Vol 35\n\n\n\nReferences\n \n1. Smith EW. Do we need new and different glucocorticoids? \n\n\n\nA re-appraisal of the various congeners and potential \nalternatives. Curr Probl Dermatol 1993; 21: 1-10.\n\n\n\n2. Charman CR, Morris AD, Williams HC. Topical \ncorticosteroid phobia in patients with atopic eczema. Br J \nDermatol 2000; 142: 931\u20136. \n\n\n\n3. Charman C, Williams H. The Use of Corticosteroids and \nCorticosteroid Phobia in Atopic Dermatitis. Clin Dermatol \n2003; 21: 193\u2013200.\n\n\n\n4. Aubert-Wastiaux H, Moret L, Le Rhun A et al. Topical \ncorticosteroid phobia in atopic dermatitis: a study of its \nnature, origins and frequency.  Br J Dermatol 2011; 165: \n808\u2013814.\n\n\n\n5. Kawashima M. Quality of life in patients with atopic \ndermatitis. Int J Dermatol 2006; 45: 731-736.\n\n\n\n6. Smith SD, Hong E, Fearns S et al. Corticosteroid phobia \nand other confounders in the treatment of childhood atopic \ndermatitis explored using parent focus groups. Australas J \nDermatol 2010; 51: 168-174.\n\n\n\n7. Kojima R, Fujiwara T, Matsuda A et al. Factors Associated \nwith Steroid Phobia in Caregivers of Children with Atopic \nDermatitis. Pediatr Dermatol 2013; 30: 29\u201335.\n\n\n\n8. Bewley A. Expert consensus: time for a change in the way \nwe advise our patients to use topical corticosteroids. Br J \nDermatol 2008; 158: 917\u2013920. \n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Steroid phobia is not uncommon in Malaysia. However, the phenomenon is not as common as other \n developed countries. This might be due to the belief, upbringing and treatment seeking behavior of \n Malaysian patients. Most patients seek treatment from doctors without much hassle and do not query \n about the medications given. \n\n\n\n2. Despite the concern about steroid, only a third of patients totally abstain from using steroid. It might \n indicate that they have heard about the side effects of steroid that might raise some concern. Most still \n use steroid as they has trust in their doctors.\n\n\n\n3. Topical steroid if used properly will benefit patients with atopic eczema. Doctors should always \n educate patients with eczema about steroid and how to use them properly. They should allay patients\u2019 \n fear about steroid side effects and offer alternative treatment if necessary. \n\n\n\n4. Information about steroids on the media especially social media will cause widespread phobia and\n thus compromise the care of patients with eczema. Thus, it is important for doctors especially \n dermatologists to properly educate patients regarding proper use and side effects of topical steroids. \n Paramedical personnel and medical students should also be educated about proper judicious use \n of topical steroids.\n\n\n\nYap FBB \nEditor-in-Chief, Malaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 MJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nTHE EFFECT OF ORAL CLINDAMYCIN AND RIFAMPICIN \nCOMBINATION THERAPY IN PATIENTS WITH HIDRADENITIS \nSUPPURATIVA IN SINGAPORE\nOchi H, Tan L X, Oon H\n\n\n\nAbstract\n\n\n\nIntroduction: Staphylococcus spp. Are frequently isolated from lesions of hidradenitis suppurativa \n(HS) although it is not an infectious disease. Here, we review 11 patients with HS treated with \ncombination of oral clindamycin and rifampicin. \n\n\n\nMethods: Retrospective review assessing the efficacy of a 10 week course of oral clindamycin 300 mg \ntwice daily and oral rifampicin 300 mg twice daily in the treatment of HS\n\n\n\nResults: Seven patients (63.6%) reported clinical improvement. Three patients (27.3%) achieved clear, \nminimal or mild scoring from all sites after completion of therapy and 2 patients (18.2%) reported a \n2-grade improvement relative to baseline from at least one site. One patient (9.1%) who reported side \neffects of nausea and vomiting and 1 patient (9.1%) who defaulted follow-up.\n\n\n\nConclusion: Combination of oral clindamycin and rifampicin is safe and efficacious in the treatment \nof HS.\n\n\n\nKeywords: Hidradenitis suppurativa, clindamycin, rifampicin\n\n\n\nCorresponding Author and Reprint Request \nDr Ochi Harumi \nNational Skin Centre, 1 Mandalay Road\nSingapore 308205\nEmail: ochi.harumi@mohh.com.sg\n\n\n\nMethodology\nThis retrospective review assessed the efficacy \nof a 10 week course of oral clindamycin 300 mg \ntwice daily and oral rifampicin 300 mg twice daily \nin the treatment of HS. Patients who received this \ncombination therapy between 1 December 2012 and \n31 July 2013 in a tertiary dermatological center in \nSingapore were included.\n\n\n\nResults\nEleven patients (9 males) had a mean age of 24.5\u00b1 \n8.8. There were 6 Chinese (54.5%), 4 Malays \n(36.3%) and 1 Indian (9.1%). Five were smokers \n(45.5%), 6 were obese (54.5%) and 1 had a family \nhistory of HS (9.1%). The duration of HS prior to \ncommencement of oral clindamycin and rifampicin \nranged from 2 to 20 years. Eight patients (72.7%) \nhad previous treatments, including retinoid and \nantibiotics, with limited effect and persistent \ndisease. \n\n\n\nIntroduction\nHidradenitis suppurativa (HS) is a chronic \ninflammatory disease of follicular occlusion \ncharacterized by abscesses, draining sinuses and \nscarring. It mainly affects apocrine gland-bearing \nareas, including the axilla, groin and anogenital \nregions. Although HS is not primarily an infectious \ndisease, Staphylococcus aureus and Staphylococcus \nepidermidis are pathogens most frequently isolated \nas secondary colonizers.1\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2015 Dec Vol 35\n\n\n\nAt the end of 10 weeks of treatment, 7 of the 11 \npatients (63.6%) reported clinical improvement. \nFour patients had digital photography documenting \nresponse before and after treatment and 2 blinded \nassessors evaluated the improvement using the HS \nphysician\u2019s global assessment (PGA) score. Three \npatients achieved clear, minimal or mild scoring \nfrom all sites after completion of therapy and 2 \npatients reported a 2-grade improvement relative \nto baseline from at least one site. There was only 1 \npatient (9.1%) who reported side effects of nausea \nand vomiting and 1 patient (9.1%) who defaulted \nfollow-up. (Table 1)\n\n\n\nDiscussion\nThe efficacy and tolerability of this combination \ntreatment had previously been assessed in 4 \nstudies. Overall results are promising with reported \nimprovement rates between 71.4 % and 85.7%.1, \n\n\n\n2, 3, 4 Statistically significant improvements in all \ndimensions of the quality of life Skindex-France \nquestionnaire was also described in 1 study.2\n\n\n\nIt is hypothesized that both the antibacterial and \nanti-inflammatory properties of clindamycin and \nrifampicin are responsible for the beneficial effects \nin treating HS. Clindamycin is a lincosamide \n\n\n\nTable 1. Demographics of patients, previous treatments, response and side effects of combination therapy.\n\n\n\nCase\nNo.\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\n7\n\n\n\n8\n\n\n\n9\n\n\n\n10\n\n\n\n11\n\n\n\nAge \n(years)\n\n\n\n18\n\n\n\n18\n\n\n\n19\n\n\n\n20\n\n\n\n21\n\n\n\n21\n\n\n\n21\n\n\n\n22\n\n\n\n48\n\n\n\n27\n\n\n\n35\n\n\n\nGender\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nMale\n\n\n\nFemale\n\n\n\nFemale\n\n\n\nPre-treatment \nPhysician Global \n\n\n\nAssessment \n(PGA)\n\n\n\nNil\n\n\n\nNil\n\n\n\n2.75\n\n\n\nNil\n\n\n\n2.67\n\n\n\n1.83\n\n\n\nNil\n\n\n\nNil\n\n\n\n3.13\n\n\n\nNil\n\n\n\nNil\n\n\n\nPost-treatment \nPhysician Global \n\n\n\nAssessment \n(PGA)\n\n\n\nNil\n\n\n\nNil\n\n\n\n1.50\n\n\n\nNil\n\n\n\n1.00\n\n\n\n1.75\n\n\n\nNil\n\n\n\nNil\n\n\n\n3.00\n\n\n\nNil\n\n\n\nNil\n\n\n\nDuration\nof disease\n\n\n\n(years)\n\n\n\n2\n\n\n\n4\n\n\n\n9\n\n\n\n6\n\n\n\n13\n\n\n\n3\n\n\n\n3\n\n\n\n5\n\n\n\n20\n\n\n\n7\n\n\n\n2\n\n\n\nReported \nSide\n\n\n\nEffects\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNil\n\n\n\nNausea, \nvomiting\n\n\n\nNil\n\n\n\nAffected\nArea (s)\n\n\n\nAxilla, neck\n\n\n\nPerineal\n\n\n\nPerineal\n\n\n\nPerineal, axilla\n\n\n\nPerineal, axilla\n\n\n\nPerineal, \naxilla, Neck\n\n\n\nPerineal, back\n\n\n\nPerineal\n\n\n\nPerineal, axilla\n\n\n\nPerineal, axilla\n\n\n\nPerineal, axilla\n\n\n\nPhysician \nclinical \n\n\n\nassessment\n\n\n\nImproved\n\n\n\nImproved\n\n\n\nImproved\n\n\n\nNon-responder\n\n\n\nImproved\n\n\n\nImproved\n\n\n\nDefaulted\n\n\n\nImproved\n\n\n\nNon-responder\n\n\n\nNon-responder\n\n\n\nImproved\n\n\n\nPrior Therapy\n\n\n\nDoxycycline, topical \nclindamycin\n\n\n\nDoxycycline, \nerythromycin,\nisotretinoin, \nminocycline\n\n\n\nBactrim,\ncephalexin, \n\n\n\ndoxycycline,\nerythromycin, \nisotretinoin,\nminocycline\n\n\n\nAugmentin, topical \nclindamycin\n\n\n\nDoxycycline, topical \nclindamycin\n\n\n\nNil\n\n\n\nDefaulted\n\n\n\nIsotretinoin, \nminocycline, topical \n\n\n\nclindamycin\n\n\n\nAugmentin, acitretin. \nciprofloxacin, \nclindamycin, \nceftriaxone, \nisotretinoin, \ninfliximab\n\n\n\nDoxycycline, \nisotretinoin\n\n\n\nNil\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 MJD 2015 Dec Vol 35\n\n\n\nantibiotic that is active against Gram-positive cocci \nand anaerobic bacteria. It mediates inflammation \nby suppressing complement-derived chemotaxis of \npolymorphonuclear leukocytes. Rifampicin is a lipid \nsoluble, broad-spectrum antibiotic highly effective \nagainst Staphylococcus aureus. Additionally, \nit modifies cell-mediated hypersensitivity by \nsuppressing antigen-induced transformation of \nsensitized lymphocytes.\n\n\n\nRapid emergence of bacterial resistance may result \nwith rifampicin monotherapy.5 Hence, combination \ntherapy is synergistic with reduced resistance \nrates and increased anti- inflammatory properties. \nAlthough a longer duration of treatment appears \nwarranted in chronic diseases like HS, no large \ndifferences in outcome between patients treated for \n10 weeks or more and those treated for a shorter \nperiod have been reported.4\n\n\n\nOther studies have similarly described good \ntolerability with low rates of side effects between \n13.0% and 38.2%. Gastrointestinal complaints were \nmost commonly reported but there were no cases \nof clindamycin associated Clostridium difficile \ncolitis.1, 2, 3, 4 \n\n\n\nIn a recent systematic review of HS treatment, \nonly combination clindamycin-rifampicin regimen, \ninfliximab, Nd:YAG laser and surgical excision were \nconsidered effective treatments. However, some of \nthese modalities have limitations. Infliximab has \nreported adverse events including severe allergic \nreactions, multifocal motor neuropathy and drug- \ninduced lupus reactions. Recurrence rates of up \nto 42.8% after surgical excision have also been \ndescribed.6\n\n\n\nConclusion\nIn conclusion, oral clindamycin and oral rifampicin \ncombination therapy is safe and efficacious in the \ntreatment of HS in groups of Caucasian and Asian \npatients in Singapore.\n\n\n\nAcknowledgments\nSpecial thanks to Dr Heng Yee Kiat for assisting \nwith the PGA scoring.\n\n\n\nConflicts of interest\nThere are none to declare. Dr Hazel Oon has received \nresearch grant from Pfizer, Novartis and acted as a \nspeaker for Novartis, Galderma and Abbvie.\n\n\n\nReferences\n \n1. Bettoli V, Zauli S, Borghi A et al. Oral clindamycin and \n\n\n\nrifampicin in the treatment of hidradenitis suppurativa-\nacne inversa: a prospective study on 23 patients. J Eur \nAcad Dermatol Venereol. 2014; 28(1): 125-6.\n\n\n\n2. Gener G, Canoui-Poitrine F, Revuz JE et al. Combination \ntherapy with clindamycin and rifampicin for hidradenitis \nsuppurativa: a series of 116 consecutive patients. \nDermatology 2009; 219(2): 148-154.\n\n\n\n3. Mendon\u00e7a CO, Griffiths CE. Clindamycin and rifampicin \ncombination therapy for hidradenitis suppurativa. Br J \nDermatol. 2006; 154(5): 977\n\n\n\n4. Van der Zee HH, Boer J, Prens EP, Jemec GB. The effect \nof combined treatment with oral clindamycin and oral \nrifampicin in patients with hidradenitis suppurativa. \nDermatology 2009; 219(2), 143-147.\n\n\n\n5. Van Vlem B, Vanholder R, De Paepe P, Vogelaers D, \nRingoir S. Immunomodulating effects of antibiotics: \nliterature review. Infection. 1996; 24(4): 275-91.\n\n\n\n6. Pranita V. Rambhatla, Henry W. Lim, Iltefat Hamzavi. \nA Systematic Review of Treatments for Hidradenitis \nSuppurativa. Arch Dermatol. 2012; 148(4): 439-44. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9MJD 2015 Dec Vol 35\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Combination of oral rifampicin and clindamycin for 10 weeks seems promising in the treatment of \n HS. However, success of treatment is very dependent on the selection of patients.\n\n\n\n2. Those who do not respond to this treatment cocktail seemed to have longer duration of disease. It is \n likely that they have been on multiple courses of antibiotics and anti-inflammatory agents which \n might cause treatment failure\n\n\n\n3. It will be interesting to know how many courses of this cocktail can be given with good treatment \n outcome for patients with HS. \n\n\n\nYap FBB\nEditor-in-Chief, Malaysian Journal of Dermatology\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10 MJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nADULT XANTHOGRANULOMATOSIS: A CASE REPORT\nRamalingam Rajalingam1, Johar Asmah1, Lee Bang Rom2\n\n\n\nCorresponding Author and Reprint Request \nDr Ramalingam, Rajalingam\nDepartment of Dermatology\nHospital Kuala Lumpur, Malaysia\nEmail: raj.blueheart@gmail.com\n\n\n\n1 Department of Dermatology, Hospital Kuala Lumpur\n2 Department of Pathology, Universiti Putra Malaysia\n\n\n\nCase Report\nA 27-year-old Indian housewife gave a 4-month \nhistory of spontaneous, multiple, discreet, yellowish, \npapular eruption over her left ear lobe, anterior neck, \nanterior abdominal wall, right forearm and left leg. \nThe papules were not pruritic and not painful, but \nwere increasing gradually in number and size. There \nwas no history of trauma.\n\n\n\nOn examination, multiple discreet fleshy and \nyellowish papules and nodules were noted over the \nleft earlobe, left anterior neck (Figure 1a), anterior \nabdominal wall (Figure 1b), right anterior upper \narm (Figure 1c) and left medial calf (Figure 1d).\n\n\n\nIntroduction\nXanthogranulomatosis (XG) is the simultaneous \noccurrence of multiple xanthogranulomas, and \nis usually seen in the pediatric population. Adult \nXG (AXG) has many similarities to the childhood \nvariant, including the association with hematologic \ndisorders.\n\n\n\nHerein, we report a case of xanthogranulomatosis in \nan adult without evidence of hematologic disease.\n\n\n\nFigure 1a. yellowish papules on the left anterior \nneck and left earlobe.\n\n\n\nFigure 1b. brownish nodule on the anterior \nabdominal wall.\n\n\n\nFigure 1c. yellowish papule on the \nright anterior upper arm.\n\n\n\nFigure 1d. brownish nodule on the \nleft medial calf.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11MJD 2015 Dec Vol 35\n\n\n\nHence, we diagnosed her as having cutaneous \nxanthogranulomatosis. We initiated monthly \nintralesional triamcinolone injection for her \npapules. On subsequent follow-up, the lesions had \nshown only minimal flattening, but there were no \nnew eruptions.\n\n\n\nDiscussion\nXanthogranulomatosis (XG) is the commonest \nnon-Langerhans cell histiocytosis whose etiology is \npoorly understood.\n\n\n\nAdult XG (AXG) accounts for 10% of all cases \nof XG, having a peak incidence ranging from 30 - \n40 years. Initially pink to red papules, the lesions \nprogress to yellow-brown firm, dome-shaped \npapules and nodules. They are most common on the \n\n\n\nThere was no lymphadenopathy or \nhepatosplenomegaly noted. Examination of all \nother organ systems were unremarkable.\n\n\n\nWe entertained several possible diagnoses at \nthis point, including Eruptive Xanthomata and \nHypertrophic Scars.\n\n\n\nBlood investigations and imaging studies excluded \nthe presence of malignancy. Glaucoma and retinal \nhaemorrhage were also excluded. Excision biopsies \nshowed dense histiocytic infiltrate admixed with \nTouton cells and foam cells of variable number, \nwith lymphocytes, neutrophils and plasma cells \nseen infiltrating into the lesion. These findings \nare consistent with xanthogranuloma. Special \nimmunohistochemical stains were not done.\n\n\n\nFigure 2a. Touton giant cells, hematoxylin & eosin stain, \n100X magnification (from left earlobe nodule).\n\n\n\nFigure 2c. Touton giant cells, hematoxylin & eosin stain, \n400X magnification (from anterior abdominal wall nodule).\n\n\n\nFigure 2b. Sea of histiocytes in the papillary and reticular \ndermis, hematoxylin & eosin stain, 400X magnification\n(from left anterior neck papule).\n\n\n\nFigure 2d. Touton giant cells, hematoxylin & eosin stain, \n400X magnification.\n\n\n\n\n\n\n\n\nhistiocytes are positive to antibodies against factor \nXIIIa, HAM56, HHF35, KP1 (CD68), Ki-M1P and \nVimentin, but negative to CD1a and S-100.5\n\n\n\nTopical6 and intralesional corticosteroid injection7 \n\n\n\nhave not been shown to have a significant effect. \nHowever, our patient shows some improvement with \nthe latter treatment. Methotrexate on the other hand \nhas shown some benefit, and might be considered \nshould our patient not respond to current treatment.  \n\n\n\nConclusion\nXanthogranulomatosis (XG) is the commonest non-\nLangerhans cell histiocytosis that can rarely occur \nin adults. The disease course remains uncertain with \nsome cases demonstrating spontaneous resolution. \nIn view of its association with hematologic \ndisorders, we recommend screening adult patients \nwith XG for those conditions.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 MJD 2015 Dec Vol 35\n\n\n\nhead, neck, and trunk, as seen in our patient. Ocular \ninvolvement is the most common extra-cutaneous \nmanifestation which can lead to hemorrhage and \nglaucoma. Spontaneous resolution has been noted \nin several cases1.\n\n\n\nAXG is associated with hematologic disorders such \nas essential thrombocytosis, chronic lymphocytic \nleukemia, large B cell lymphoma and monoclonal \ngammopathy.2-4 The development of XG lesions \noccurs before, during or following the hematologic \ndisorder. Thus, it is important for us to follow up our \npatient long-term.\n\n\n\nHistopathology typically shows a dense infiltrate of \nfoam cells and Touton giant cells in the upper and \nmid reticular dermis, with variable extension into \nthe subcutis. With immunohistochemical staining, \n\n\n\nReferences\n \n1. Lin SJ, Chiu HC. Adult multiple xanthogranulomas \n\n\n\nwith spontaneous resolution. Acta Derm Venereol \n2003;83(2):157-158\n\n\n\n2. Larson MJ, Bandel C, Eichhorn PJ, Cruz PD Jr. \nConcurrent development of eruptive xanthogranulomas \nand hematologic malignancy: two case reports. J Am Acad \nDermatol 2004;50: 976-8\n\n\n\n3. Pino GM, Miquel FJ, Velasco M, Vilata JJ, Aliaga A. \nMultiple xanthogranulomas in an adult, associated with \nessential thrombocytosis. Br J Dermatol 1995;132:1018-\n21\n\n\n\n4. Chiou CC, Wang PN, Yang LC, Kuo TT, Hong HS. \nDisseminated xanthogranulomas associated with adult \nT-cell leukaemia/lymphoma: a case report and review the \nassociation of haematologic malignancies. J Eur Acad \nDermatol Venereol 2007;21:532-5\n\n\n\n5. Fassina A, Olivotto A, Cappellesso R, Vendraminelli R, \nFassan M. Fine-needle cytology of cutaneous juvenile \nxanthogranuloma and langerhans cell histiocytosis. Cancer \nCytopathol. 2011 Apr 25. 119(2):134-40\n\n\n\n6. Cadera W, Silver MM, Burt L. Juvenile xanthogranuloma. \nCanadian Journal of Ophthalmology. 1983, 18(4):169-174\n\n\n\n7. Victor M. Elner, Roni Mintz, Hakan Demirci, Adam S. \nHassan. Local Corticosteroid Treatment of  Eyelid and \nOrbital Xanthogranuloma. Trans Am Ophthalmol Soc. \n2005 Dec; 103: 69\u201374\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nMYCOBACTERIUM CHELONAE INFECTION IN A 19-YEAR-OLD \nIMMUNOCOMPETENT PATIENT SUCCESSFULLY TREATED \nWITH ORAL CLARITHROMYCIN AND LINEZOLID\nOchi H, Pan JY\n\n\n\nCorresponding Author and Reprint Request \nDr Ochi Harumi\nNational Skin Centre, 1 Mandalay Road,\nSingapore 308205\nEmail: ochiharumi89@gmail.com\n\n\n\nSerology for human immunodeficiency virus and \ndiabetic screening were negative. Subsequently, \nmycobacterial cultures from needle aspiration grew \nM. Chelonae sensitive to clarithromycin and line-\nzolid. She was treated with combination oral clar-\nithromycin 500mg and linezolid 600mg twice daily \nfor 2 weeks with clinical improvement and healing. \nShe will be reviewed in 3 months to check for any          \nrecurrence.\n\n\n\nIntroduction\nMycobacterium chelonae is a rapidly growing non-\ntuberculous mycobacteria (NTM) predominantly \naffecting immunocompromised hosts. We report \na case of disseminated NTM cutaneous infection \noccurring in a healthy individual successfully \ntreated with combination of oral clarithromycin and \nlinezolid.\n\n\n\nCase Report\nA 19-year-old Chinese female with a past medical \nhistory of allergic rhinitis first presented with \nmultiple abscesses on the sacrum, back and shoulder \nfor 5 months. The abscesses developed when she \nwas working in a microbiology lab preparing media \nand culturing bacteria. She denied any preceding \ntrauma to the affected areas and was not on any \nimmunosuppressive medications.\n\n\n\nOn examination, there were 2 discrete subcutaneous \nindurated nodular lesions over the mid-back. The \nlargest lesion measured 5cm by 4cm with ulceration \nand underlying granulation tissue. There were \nmultiple fleshy nodules over left shoulder, right \ninfra-clavicular region and left iliac fossa. (Figure \n1)\n\n\n\nFirst set of fungal, bacterial and acid-fast bacillus \ncultures obtained from incision and drainage of \nback abscesses were negative. Skin biopsy showed \ngranulomatous dermatitis (Figure 2). She was treat-\ned with multiple courses of oral amoxicillin-clavu-\nlanate, ciprofloxacin, clarithromycin, clindamycin, \nrifampicin and ofloxacin on separate occasions. Her \ndisease was refractory to treatment and suppura-\ntive abscesses continued to develop on her trunk.          \n\n\n\nFigure 1. On examination, there were 2 x discrete \nsubcutaneous indurated nodular lesions over mid-back.\n\n\n\nFigure 1. On examination, there were 2 x discrete \nsubcutaneous indurated nodular lesions over mid-back.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 MJD 2015 Dec Vol 35\n\n\n\nDiscussion\nNon-tuberculous mycobacteria (NTM) are \nslender, non-motile, acid-fast bacilli classified \ninto 4 categories based on growth rates and colony \npigmentation.1,2 Cutaneous presentations of NTM \ninfection include localized non-healing ulcers \nand chronically draining subcutaneous nodules in \nimmunocompetent patients. Disseminated disease \nis more frequently seen in immunocompromised \nhosts.3 Mycobacterium chelonae and abscessus \nare responsible for 95% of disseminated cutaneous \ninfections caused by rapidly growing mycobacteria.4\n\n\n\nClarithromycin 500mg daily monotherapy \nwas previously recommended for treatment of \nM. chelonae. However, in vivo efficacy may \nlack correlation with in vitro sensitivity and \nclarithromycin resistance and therapeutic failure in \npatients with disseminated cutaneous infection have \nbeen reported.5 Hence, more recent studies have \nsuggested the use of oral linezolid combination \ntherapy.6\n\n\n\nLinezolid exhibits in vitro bacteriostatic activity \nagainst Mycobacterium tuberculosis and is \nincreasingly used in the treatment of patients \nwith multidrug-resistant (MDR) and extensively \ndrug-resistant (XDR) strains. It blocks bacterial \nribosomal protein synthesis by a novel mechanism: \nbinding to the 50S bacterial ribosomal subunit and \npreventing formation of the initiation complex for \nprotein synthesis. Linezolid has high bioavailability, \nlow protein binding (31%) and exhibits no cross-\nresistance with other antituberculosis drugs.7 \nKoh et al8 reported that daily 300 mg dose of \nlinezolid was useful in the treatment of patients \nwith intractable multidrug-resistant (MDR) and \n\n\n\nextensively drug-resistant (XDR) tuberculosis with \nreduced neurotoxicity, compared with a daily 600 \nmg dose. In vitro synergy between linezolid and \nclarithromycin against Mycobacterium tuberculosis \nhas been reported.9 \n\n\n\nTo date the position of linezolid in the treatment of \ncutaneous nontuberculous mycobacterial infections \nis still unclear. Chetchotisakd et al10 has reported \ncomplete resolution of symptoms in 50% of patients \nwith disseminated NTM infections on linezolid \ntherapy. However, 31% developed adverse reactions \nto linezolid, 3 of whom received 600mg twice \ndaily. Various adverse drug reactions have been \ndescribed with long-term use of linezolid, primarily \nbone marrow suppression and peripheral and optic \nneuropathy. Hematologic adverse reactions ensuing \nfrom the prolonged use of linezolid are dose \ndependent and reversible secondary to inhibition of \nmitochondrial protein synthesis, while peripheral \nneuropathy might be irreversible depending on \nthe prolonged duration of the therapy rather than \ndosage; however, optic neuropathy appears to \nresolve after stopping linezolid.11,12 In view of \npromising clinical response and growing resistance \nto first line clarithromycin, the role of linezolid \nshould be further evaluated.\n\n\n\nConclusion     \nIn summary, we report a case of disseminated \ncutaneous Mycobacterium chelonae infection in an \nimmunocompetent patient successfully treated with \ncombination oral clarithromycin and linezolid. Data \nconcerning the use of linezolid in nontuberculous \nmycobacterial infections is promising and should be \nfurther investigated.\n\n\n\nReferences\n \n1. Runyon EH. Anonymous mycobacteria in pulmonary \n\n\n\ndisease. Med Clin North Am. 1959; 45: 273-290.\n2. Diagnosis and treatment of diseases caused by \n\n\n\nnontuberculous mycobacteria. Am Rev Respir Dis. 1990; \n142: 940-953.\n\n\n\n3. SIamas K, Khachemoune A. Mycobacteria infection in an \nimmunocompetent patient with no risk factors: evaluation \nand management of non- healing majocchi granuloma type \nnodule. Dermatol Online J. 2013 Aug 15; 19(8):19260.\n\n\n\n4. Khan FA, Khakoo R. Nontuberculous mycobacterial \ncutaneous infections: an updated review. Cutis. 2011 Oct; \n88(4):194-200.\n\n\n\n5. Vemulapalli RK, Cantey JR, Steed LL, Knapp TL, Thielman \nNM. Emergence of resistance to clarithromycin during \ntreatment of disseminated cutaneous Mycobacterium \nchelonae infection: case report and literature review. J \nInfection. 2001; 43:163-168.\n\n\n\n6. Wallace RJ, Brown-Elliott BA, Ward SC, Crist CJ, Mann \nLB, Wilson RW. Activities of linezolid against rapidly \ngrowing mycobacteria. Antimicrob Agents Chemother. \n2001;45:764\u20137.\n\n\n\n7. Sotgiu G, Centis R, D\u2019Ambrosio L, et al. Efficacy, safety \nand tolerability of linezolid containing regimens in treating \nMDR-TB and XDR-TB: systematic review and meta-\nanalysis. Eur Respir J 2012; 40: 1430\u20131442.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2015 Dec Vol 35\n\n\n\n8. Koh WJ, Kwon OJ, Gwak H, et al. Daily 300 mg dose \nof linezolid for the treatment of intractable multidrug-\nresistant and extensively drug-resistant tuberculosis. J \nAntimicrob Chemother 2009; 64:388-391 Bolhuis et al \nEur Respir J 2014;44:808-11.\n\n\n\n9. Lee M, Lee J, Carroll MW, et al. Linezolid for Treatment of \nChronic Extensively Drug-Resistant Tuberculosis. NEJM \n2012; 367(16):10.1056.\n\n\n\n10. Chetchotisakd P, Anunnatsiri S. Linezolid in the treatment \nof disseminated nontuberculous mycobacterial infection \nin anti-interferon-gamma autoantibody-positive patients. \nSoutheast Asian J Trop Med Public Health. 2014; \n45(5):1125-31.\n\n\n\n11. Park IN, Hong SB, Oh YM, et al. Efficacy and \ntolerability of daily-half dose linezolid in patients with \nintractable multidrug-resistant tuberculosis. J Antimicrob \nChemother2006;58:701\u2013704.\n\n\n\n12. G.B. Migliori, B. Eker, M.D. Richardson, et al, A \nretrospective TBNET assessment of linezolid safety, \ntolerability and efficacy in multidrug-resistant tuberculosis, \nEur. Respir. J. 34 (2) (2009) 387\u2013393\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16 MJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nCONTACT DERMATITIS TO A TURMERIC COATED WEDDING \nTHALI: A CASE REPORT\nWan Syamee Afira WAK1, Tarita T1, Rohna R2, Zuraini A3\n\n\n\nCorresponding Author and Reprint Request \nDr Ramalingam, Rajalingam\nDepartment of Dermatology\nHospital Kuala Lumpur, Malaysia\nEmail: raj.blueheart@gmail.com\n\n\n\n1 Department of Dermatology, Hospital Kuala Lumpur\n2 Department of Pathology, Universiti Putra Malaysia\n\n\n\nPatch test was done with the European \nStandard Series, plant and textile series (from \nChemotechnique Diagnostics), turmeric \u2018as is\u2019, \nturmeric extract, patient\u2019s own turmeric powder and \npatient\u2019s thali \u2018as is\u2019 with and without turmeric. The \nturmeric was extracted based on the work process \npracticed in the Department of Occupational and \nEnvironmental Dermatology, Malmo Hospital, \nSweden. The turmeric was first cut into small pieces, \nthen immersed in acetone solution as a solvent. The \nextraction procedure was carried out in an ultrasonic \nbath, whereby the mixture was sonicated for 10 \nminutes continuously. At the end of sonication, the \nsuspension was cooled to room temperature and \nthen transferred to a rotating evaporator for it to be \nevaporated under reduced pressure. This resulted \nin a dry form of turmeric extract. The turmeric \nextract and turmeric powder were then diluted with \npetrolatum to 5%, 1% and 0.1% diluents.\n\n\n\nThe patch test was positive for nickel sulphate, \nturmeric \u2018as is\u2019 and the turmeric extract. This patient \nalso had a flare of her dermatitis on the chest during \npatch test. She however tested negative for the \u2018thali\u2019 \nitself and turmeric powder. Aside from avoiding the \nuse of turmeric and nickel containing products, she \nwas also treated with topical streoids, emmolients \nand antihistamine, after which her symptoms \nimproved.\n\n\n\nTo exclude a false positive reaction, further patch \ntests to the turmeric extract were done on 20 normal \ncontrols. None had any positive reaction to the \nturmeric extract.\n\n\n\nIntroduction\nTurmeric is a spice derived from the rhizome of the \nplant Curcuma longa, which is cultivated in India \nand Southeast Asia. Curcumin is the component of \nturmeric that gives the spice its unique taste and \nyellow colour and is thought to be responsible for \nturmeric\u2019s biologic activities1. Curcumin is used as \na spice in foods, treatment in alternative medicine, \ndye for fur, and for traditional and religious \npurposes especially in the Indian culture. Rare cases \nof allergic contact dermatitis from curcumin have \nbeen reported among workers who dye animal furs, \na worker at a pasta factory, in an Indian spice miller \nand from use of the Chinese herbal cream Chuu-\nou-kou2,3,4,5. We report a case of allergic contact \ndermatitis to turmeric in an Indian lady who applied  \nit on her string necklace for religious purposes \n(wedding thali) . We also describe the way turmeric \nis prepared as an allergen for patch test, as it is not \nreadily available in the standard and extended series \npatch tests.\n\n\n\nCase Report\nWe report a 51-year-old Indian housewife \nwho presented with a three year history of an \nerythematous and pruritic rash on the neck and upper \nchest. For the past 23 years, she has been wearing a \nyellow \u2018thali\u2019 (string necklace) with a gold pendant, \nas a symbol of her being   married. This \u2018thali\u2019 was \ncoated with turmeric powder three monthy. Clinical \nexamination showed a scaly, pruritic, erythematous \ncurvilinear patch around the neck and the upper \nchest, with its distribution following the area of \ncontact with \u2018thali\u2019. There was relative sparing of \nthe surrounding skin unexposed to the necklace. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2015 Dec Vol 35\n\n\n\nFigure 1. Evidence of a curvilieniar dermatitis on the \nupper chest.\n\n\n\nFigure 3. Tumeric immersed in acetone.\n\n\n\nFigure 2. Dermatitis with post inflammatory \nhyperpigmentation at nape and upper back.\n\n\n\nFigure 4. Beaker placed in an ultrasound bath.\n\n\n\nFigure 5. Use of a rotating evaporator to \nremove solvent.\n\n\n\nFigure 6. Patch Test. Figure 7. : Flare of dermatitis during \npatch test.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 MJD 2015 Dec Vol 35\n\n\n\nDiscussion\nTurmeric, which has been used widely for religious \nand traditional purposes especially in the Asian \nculture, is also becoming increasingly popular \nin the modern society, as a health supplement. It \nis thus important for physicians to recognize the \ncomplications of turmeric, including its effect on \nthe skin, in causing allergic contact dermatitis, as \ndemonstrated in this case. \n\n\n\nTurmeric contains up to 5% essential oils and 3% \ncurcumin a polyphenol which is the active substance \nof turmeric. Curcumin is also known as C-175300 \nor natural yellow3. This oleoresin is prepared via \nextraction from the turmeric with an organic solvent. \nThe technique of extracting curcumin in this case \nused ultrasound or sonication to break the cell \nmembranes, which has the advantage of reducing \nthe extraction time considerably and increasing the \nextract yield. The application of ultrasound disrupts \nthe cell wall structure of turmeric and accelerates \ndiffusion through membranes; thus, the cell lyses and \nhence facilitates the release of its active contents. We \nused a rotating evaporator to gently and effectively \nremove the solvents by evaporation. Following the \nevaporation of the solvent, the extracted turmeric \nolioresin may contain 15-40% curcuminoids, of \nwhich curcumin predominates. The other two \ncurcuminoids are demethoxycurcumin, and Bis - \ndimethoxycurcumin. \n\n\n\nThis patient developed a classic delayed-type \nhypersensitivity to turmeric. By definition, as it is \nmediated by immune cells rather than by antibodies, \nthe reaction can be thought of as occurring in \ntwo phases, initially a sensitization and then an \nelicitation response. It is the sensitization phase \nthat is the basis for its classification as an immune \nmediated reaction. The capacity for sensitization \nvarious from person to person, but certain \nindividuals are more prone to developing sensitivity \nto a particular substance as compared to others. On \nthe other hand, some individuals are actually more \nresistant to sensitization due to repeated exposure \nto sub-sensitizing doses of an allergen. Women \nhave stronger cell mediated immunity responses \nthan men. The reason for female preponderance \nin clinical patch test studies is mainly explained \nby the large number of metal sensitive females  \nwhich is largely the result of ear piercing and the \ngreater exposure to fragrances, cosmetics and hair \n\n\n\ndyes6. Number of positive patch-test reactions also \ntend to increase with age due to accumulation of \nallergies acquired over lifetime7. Aside from the \nabove factors, UVB exposure has been shown to \ndiminish the skin\u2019s immune response to contact \nallergens. Indian women were found to become \nsensitized to dyes and adhesives in kumkum and \nbindi. which also contain turmeric8. Sensitization \nand subsequent contact dermatitis may occur due \nto repeated exposure to the allergen after years of \ncontact. This patient developed a dermatitis after \nalmost 20 years of repeated exposure to turmeric. \nShe has been wearing the \u2018thali\u2019 persistently \neven during bathing. When exposed to water, the \n\u2018turmeric\u2019 might have leached out to be in direct \ncontact with skin. During this period sensitization \nhas been accomplished, and the residues of the \nallergens in the skin react with newly formed T \nlymphocytes. If a sensitized person is re-exposed \nto a specific allergen in sufficient concentration, the \nclinical reaction subsequently develops much more \nquickly within 24-48 hours, depending on the degree \nof sensitivity, penetration and other factors. A flare \nof her dermatitis demonstrates this during patch \ntest when she was again exposed to turmeric. It is \nworth to note that the negative patch test to turmeric \npowder was possibly because the allergen was too \ndiluted, as the exact concentration of the turmeric \npowder that the patient used to coat her \u2018thali\u2019 might \nhave been higher than our allergens She also tested \npositive to nickel on patch test. The gold pendant on \nher \u2018thali\u2019 could have contained nickel. This could \nbe confirmed by further analyzing the pendant or \nsimply by doing a dimethylglyoxime (DMG) spot \ntest which would indicate nickel release of >0.5\u03bcg/\ncm2 per week.\n\n\n\nConclusion\nThis is a unique case of allergic contact dermatitis \nwhich could have been dismissed as a simple nickel \nallergy. As demonstrated in this intriguing case of \nturmeric coated wedding \u2018thali\u2019 allergy, a thorough \nclinical evaluation and performing patch tests \nbeyond the readily available commercial series is \nsometimes crucial in obtaining the correct diagnosis. \nThis case report illustrates how the extraction of \nturmeric and its preparation as an allergen for patch \ntest is performed.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2015 Dec Vol 35\n\n\n\nContact allergic dermatitis to turmeric, or rather \ncurcumin, its active ingredient, is likely to be under-\nreported in this country. In view of its wide and \ncommon use, it is thus imperative for physicians \nespecially dermatologists to recognize its possible \neffect in causing allergic contact dermatitis in \n\n\n\nsusceptible individuals. The incorporation of \nturmeric extract in our local plant   or even standard \nseries should be the way forward if a bigger study \nof the prevalence and incidence of this condition \nshowed significant results.\n\n\n\nReferences\n \n1. Babu VA. A clinical study on allergic contact dermatitis to \n\n\n\nturmeric. J Evol Med Dental Sci. 2013; 17: 3000-3018.\n2. Liddle M, Hull C, Liu C, et al. Contact urticaria from \n\n\n\ncurcumin, Dermatitis. 2006; 17(4): 196-197.\n3. Thompson DA, Tan BB. Tetrahydrocurcumin-related \n\n\n\nallergic contact dermatitis.  Contact Dermatitis. 2006; 55: \n254-55.\n\n\n\n4. Meiko H, Eiko S, Makoto O, et al.  Allergic contact \ndermatitis  from curcumin (turmeric). Contact \nDermatitis 1997; 36: 107-8.\n\n\n\n5. Goh CL. Ng SK. Allergic contact dermatitis to Curcumin \nlonga (turmeric). Contact Dermatitis 1987; 17: 180-187.\n\n\n\n6 . Menn\u00e9 T, Holm NV. Nickel allergy in female twin \npopulation. Int J Dermatol 1983; 22: 22-8\n\n\n\n7. Coenraads PJ, Nater JP, VanderLende R. Prevalence of \neczema and other dermatoses  of the hands and arms in the \nNether lands.  Association with age and occupation.  Clin \nExp Dermatol 1983; 8: 495-503.\n\n\n\n8. Dwyer CM, Forsyth A. Allergic contact dermatitis from \nbindi Contact Dermatitis. 1994; 30: 174.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 MJD 2015 Dec Vol 35\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nLUPUS TUMIDUS IN A CHINESE MALE: A CASE REPORT \nAnisha B, Norashikin S\n\n\n\nIntroduction\nLupus erythematosus tumidus (LET) was first \nreported in 1909 by Hoffman, and then again in 1930 \nby Gougerot and Burnier 1, 2. Thought to be a rare \nvariant of chronic cutaneous lupus erythematosus \n(CCLE), it presents as succulent erythematous \nnon-scarring plaques on sun exposed areas.  \nHistology shows perivascular and periappendageal \nlymphocytic infiltrate with large amounts of \ninterstitial mucin deposition. The disease follows a \nbenign course, and the prognosis is favorable. Most \nreports of LET are of Caucasian patients. Herein \nwe describe a case of LET in a Chinese patient and \nreview the relevant literature. \n\n\n\nCase Report\nA 27 year old Chinese with a history of papular \neczema presented with a five month history of mildly \n\n\n\nCorresponding Author and Reprint Request \nDr. Anisha Bhullar \nDepartment of Medicine, Facuty of Medicine and \nHealth Sciences, Universiti Putra Malaysia\n43300 Serdang, Malaysia\nEmail : anishabhullar@gmail.com\n\n\n\npruritic plaques on both cheeks and left upper arm. \nThere were no preceding history of foreign body \ninjections or insect bites nor symptoms of systemic \nlupus erythematosus. Examination revealed \nsymmetrical erythematous, indurated plaques on \nthe mandible and left deltoid (figure 1). There was \nminimal scaling and slight atrophy (figure 2).\n\n\n\nSkin biopsy from the left deltoid revealed patchy \nperivascular and periappendageal lymphocytic \ninfiltrates (figure 3) with copious dermal mucin \ndeposition on Alcian blue (Figure 4) consistent with \nLET. Blood investigations including antinuclear \nantibody (ANA) were unremarkable.\n\n\n\nHe was given topical steroids and oral \nhydroxychloroquine 200mg daily. On follow up \nvisit, the condition improved.\n\n\n\nFigure 1. Symmetrical erythematous, \nindurated ill-defined plaques on \nbilateral mandibular regions.\n\n\n\nFigure 2. Minimal scaling and \nslight surface atrophy overlying the \nerythematous plaques.\n\n\n\nA B\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2015 Dec Vol 35\n\n\n\nDiscussion\nLupus erythematosus tumidus (LET) has recently \nbeen accepted as a separate subtype of CCLE3. It \nis a rare dermatological entity and well documented \nin the Caucasian with sporadic cases in Asia. The \npathogenesis of LET has not been clearly established \nbut there has been a prevailing increase in the CD4+/\nCD8 inflammatory infiltrates and expression of \nendothelial cell adhesion molecules with significant \ndecrease in FOXP3+ immunopositivity and CD39+ \nimmunoreactivity.4, 5\n\n\n\nThe lesions are oedematous, erythematous, non-\nscarring plaques with very minimal surface \natrophy with a predilection for sun exposed areas. \nOccasionally indurated papules and linear tumid \nlesions following Blaschko lines can be seen.6,7 \nThe histological characteristics are distinct from \nother forms of CCLE with well-circumscribed \nlymphocytic dermal infiltrate in a perivascular and \nperiadnexal pattern and abundant interstitial mucin \ndeposition without epidermal atrophy and follicular \nplugging7. Basement membrane vacuolation is \nusually absent 8,9 It is  rarely associated with \nsystemic lupus erythematosus. \n\n\n\nPhotosensitivity has been implicated to play a role \nin LET. In a case series by Alexiades-Armenakas et \nal, 86.6 % of the cases were photo-distributed 10 . In \na series done in Germany of 62 Caucasian patients \nwith LET, 72% developed characteristic tumid \nlesions after UV irradiation. A large proportion of \ntheir cases had positive reactions to either UVA \n(50%), UVB (48%) or both wavelengths.11  In Asia, \nthe role of UV ray is not as pronounced. A small case \nseries in Thailand demonstrated only 50% having \npositive photoreactions 12. Antimalarial is the \nmainstay of treatment. Other treatment modalities \ninclude topical tacrolimus and pulsed dye laser \ntherapy13,14. Sun protection is also vital.\n\n\n\nIn summary, LET is a disease with a favorable \nprognosis with the lesions regressing over time. In \norder to gain a better understanding of the clinical \nand histological features of this disease in the Asian \npopulation, larger scale studies or case series are \nwarranted.\n\n\n\nFigure 3. Patchy  dermal lymphocytic infiltrates around the \nperivascular and periadnexal structures (H&E, X10).\n\n\n\nFigure 4. Extensive dermal mucin deposition seen within \nthe collagen bundles (Alcian blue, X10).\n\n\n\nReferences\n \n1. E. Hoffmann. Demonstrationen: Lupus erythematodes \n\n\n\ntumidus. Derm Zeitschr 1909; 16: 159-60.\n2. Gougerot, H, R. Burnier. Lupus \u00e9ryth\u00e9mateux tumidus. \n\n\n\nBull Soc Fr Dermatol Syphiligr 1930; 37: 1291-2.\n3. Schmitt V, Meuth AM, Amler S, et al. Lupus erythematosus \n\n\n\ntumidus is a separate subtype of cutaneous lupus \nerythematosus Br J Dermatol 2010;162(1): 64-73\n\n\n\n4. Kuhn A, Sonntag M, Lehmann P, et al. Characterization of \nthe inflammatory infiltrate and expression of endothelial \ncell adhesion molecules in lupus erythematosus tumidus. \nArch Dermatol Res 2002; 294: 6-13.\n\n\n\n5. Gambichler T, P\u00e4tzholz J, Schmitz L, et al. FOXP3+ and \nCD39+ regulatory T cells in subtypes of cutaneous lupus \nerythematosus. J Eur Acad Dermatol Venereol 2015; 29: \n1972-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 MJD 2015 Dec Vol 35\n\n\n\n6. Nishiyama M, Kanazawa N, Hiroi A, Furukawa F. Lupus \nerythematosus tumidus in Japan: a case report and a review \nof the literature. Mod Rheumatol. 2009; 19(5): 567-72.\n\n\n\n7. Hinz T, Hornung T, Wenzel J, Bieber T. Lupus tumidus \nfollowing the lines of Blaschko. Int J Dermatol 2013; \n52(12):1615-7.\n\n\n\n8. Kuhn A, Sonntag M, Ruzicka T, et al. Histopathologic \nfindings in lupus erythematosus tumidus: review of 80 \npatients. J Am Acad Dermatol 2003; 48(6): 901-8.\n\n\n\n9. Schmitt V, Meuth AM, Amler S,  et al. Lupus erythematosus \ntumidus is a separate subtype of cutaneous lupus \nerythematosus. Br J Dermatol 2010; 162(1): 64-73. \n\n\n\n10. Alexiades-Armenakas MR, Baldassano M, Bince B, et al. \nTumid lupus erythematosus: criteria for classification with \nimmunohistochemical analysis. Arthritis Rheum 2003; \n49(4): 494-500.\n\n\n\n11. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, et al. \nPhototesting in lupus erythematosus tumidus--review of \n60 patients. Photochem Photobiol 2001; 73(5): 532-6.\n\n\n\n12.  Choonhakarn, C., A. Poonsriaram, and J. Chaivoramukul. \nLupus erythematosus tumidus. Int J Dermatol 2004; \n43(11): 815-8.\n\n\n\n13. Bacman D, Tanbajewa A, Megahed M, et al. Topical \ntreatment with tacrolimus in lupus erythematosus tumidus. \nHautarzt 2003; 54(10): 977-9.\n\n\n\n14. Truchuelo MT, Boixeda P, Alc\u00e1ntara J, et al.  Pulsed dye \nlaser as an excellent choice of treatment for lupus tumidus: \na prospective study. J Eur Acad Dermatol Venereol 2012; \n26(10): 1272-9. \n\n\n\n\n\n"
"\n\n21MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Case Report\n\n\n\nC h u rg Strauss Syndrome in a 40 year old woman                       \nTan SS, Chan LC, MMed, Tan WC, MRCP\n\n\n\nCorrespondence\nTan Sam Siew\nDepartment of Dermatology\nHospital Pulau Pinang\nE-mail : tansamsiew@hotmail.com\n\n\n\nKeywords Churg-Strauss syndrome, vasculitis\n\n\n\nI n t ro d u c t i o n\nCutaneous vasculitis is a common manifestation of\nmany systemic diseases. In the setting of asthma,\neosinophilia and multiple disparate signs and\nsymptoms, more serious cause of vasculitis like\nChurg-Strauss syndrome (CSS) should always be\nconsidered.\n\n\n\nCase re p o rt\nA 40 year-old Malay housewife presented with a\ntwo months history of purpuric rash and non-\nhealing leg ulcers followed by one month history of\nbilateral hand numbness. She was diagnosed to\nhave bronchial asthma about a year ago and was\nstarted on inhalers. She did not have history of\nfever, oral ulcer, photosensitivity rash or alopecia.\n\n\n\nP hysical examination showed va rying sizes of\nulcers on both ankles and anterior abdominal wall\nwith multiple non-blanching purpuric lesions over\n\n\n\nthe both hands and both feet (Figure 1, 2, 5 & 6).\nN e u r o l ogical examination revealed peripheral\nmixed sensory and motor neuropathy with the right\nside more affected then the left side. Other systemic\nexaminations were normal.\n\n\n\nInvestigations showed white blood cell count of\n19,200/mm3 with eosinophilia of 22.3%, ESR of 45\nmm/hour and positive pANCA. Other\ni nve s t i gations like A NA, serum cryog l o bu l i n ,\nhepatitis B, C and HIV were negative. Her chest x-\nray and complements C3/C4 levels were normal.\nLung function test showed obstructive lung disease\npicture. Histopathology of the skin biopsy from her\nleft leg was consistent with leuko cy t o c l a s t i c\nvasculitis with infiltration of eosinophils and\nneutrophils within and around vessels (Figure 3).\nThe direct immunofluorescence showed deposition\nof C3, C4, IgM and fibrin within the dermal vessel\nwalls (Figure 4).\n\n\n\nN e rve conduction study was suggestive of\nmononeuritis multiplex. Churg-Strauss syndrome\nwas subsequently diagnosed. She responded to\ntreatment with prednisolone at 1mg/kg/day (Figure\n5 & 6).\n\n\n\nFigure 1 & 2 Vasculitic lesions and ulcers over both palms & forearms\n\n\n\n\n\n\n\n\n22 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nU n f o rt u n a t e ly, she developed worsening of\nvasculitic lesion, cyanosis of right middle and ring\nfingers and bilateral wrist drop after missing her\nmedication for a week. She was then treated with\nintravenous (IV) methyprednisolone, followed by\noral prednisolone and monthly pulses of IV\ncyclophosphamide. After four pulses of\ncyclophosphamide, all her skin lesions had\nresolved. However, she still had residual peripheral\nmixed sensory and motor neuropathy.\n\n\n\nDiscussions\nCSS is a rare syndrome that affects small- to\nmedium-sized arteries and veins. It was fi r s t\ndescribed in 1951 by Churg and Strauss1. The\nAmerican College of Rheumatology (ACR) has\nproposed 6 criteria for the diagnosis of Churg-\n\n\n\nStrauss syndrome2. The presence of 4 or more\ncriteria yields a sensitivity of 85% and a specificity\nof 99.7%. The 6 criteria are as follow:\n\n\n\n(1) Asthma (wheezing, expiratory rhonchi) \n(2) Eosinophilia of more than 10% in peripheral \n\n\n\nblood \n(3) Paranasal sinusitis\n(4) Pulmonary infiltrates (may be transient) \n(5) Histological proof of vasculitis with \n\n\n\nextravascular eosinophils \n(6) Mononeuritis multiplex or polyneuropathy\n\n\n\nThis patient fulfilled four of the six ACR criteria for\nthe diagnosis of CSS. These include vasculitis,\nadult onset asthma, peripheral neuropathy with\nmononeuritis multiplex and eosinophilia.\n\n\n\nFigure 3 & 4 Histopathology showing endothelial cells swelling, degeneration of the vessel wall,\nfibrinoid depositions, extravasation of erythrocytes with perivascular eosinophils and neutrophils\n\n\n\ninfiltration. DIF showed C3 deposits within the dermal vessel walls.\n\n\n\nFigure 5 & 6 Pre and post-treatment photos of legs ulcers\n\n\n\n\n\n\n\n\n23MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThe incidence of CSS is approximately 2.4 to 3.3\nper 1 million population3. Symptoms usually appear\nbetween 20 and 40 years of age, with a slight\npredominance in men4.\n\n\n\nThe cause of CSS is unknown5. It is possibly an\na l l e rgic or autoimmune reaction to an\nenvironmental agent or drug. \n\n\n\nThe most prominent signs and symptoms of CSS\nare those related to pulmonary, cardiac,\nd e rm a t o l ogic, renal, and peripheral nerve .\nPulmonary involvement may be seen in 96 to 100%\nof patients in the form of asthma, pleural effusions,\nor nonfixed patchy infiltrates on chest films. The\nneurologic findings may be either mononeuritis\nm u l t i p l ex or poly n e u r o p a t hy in 66 to 75% of\npatients3.\n\n\n\nLaboratory findings include anemia, eosinophilia,\ne l evated ESR, CRP & serum IgE leve l ,\nhy p e rga m m a g l o bulinemia, positive rheumatoid\nfactor and abnormal renal function test with\nproteinuria and hematuria if there is renal\ninvolvement. ANCA is present in approximately\n40% of patients with Churg-Strauss syndrome\n(CSS). Most of these patients are perinuclear-\nANCA (p-ANCA)-positive (antimye l o p e r ox i d a s e\nantibodies)6.\n\n\n\nLevels of eosinophil cationic protein (ECP) and\nsoluble interleukin-2 receptor (sIL-2R) in CSS are\ne l evated which indicate an immunoreg u l a t o ry\ndefect associated with vasculitis and eosinophilia.\nBesides, soluble thrombomodulin (sTM), which is a\nm a r ker of endothelial cell damage, are also\nelevated.\n\n\n\nOther inve s t i gations that are done only wh e n\nc l i n i c a l ly indicated include bronchioalve o l a r\nlavage, chest x-ray, computed tomography scan,\nECG, echocardiogram, endoscopy, biopsy,\nelectromyelogram & others. Pulmonary opacities\ncan be found in 26% to 77% of cases of Churg-\nStrauss syndrome, and films demonstrate no\nabnormalities in approximately 25% of patients7.\n\n\n\nCSS is associated with high mortality especially\nwhen major organs like cardiac, pulmonary or renal\nare involved. The principal causes of morbidity and\nm o rtality in Churg-Strauss syndrome are\nmyocarditis and myocardiac infarction secondary to\ncoronary arteritis8. A 5-year survival rate is about\n\n\n\n25% without treatment. However,  if it is treated, the\n1-year survival rate is 90% and the 5-year survival\nrate is 62%9,10.\n\n\n\nGlucocorticoids alone are usually adequate for the\ntreatment of Churg-Strauss syndrome11,12. High dose\nc o rticosteroids and other cy t o t oxic agents like\ncyclophosphamide, oral mycophenolate or\nazathioprine are required if it involved major life-\nthreatening organ11,12. High doses of interferon can\nmaintain remission in patients who have responded\nincompletely to cyclophosphamide13.\n\n\n\nConclusion\nMany systemic diseases can present with vasculitis.\nEarly recognition and prompt treatment of those\nvasculitides associated with major complications\nlike CSS is essential.\n\n\n\nSpecial acknowledgement to Dr. Lee SK,\nDepartment of Pathology, Hospital Pulau Pinang\nfor  histopathology interpretation.\n\n\n\nReferences\n\n\n\n1. Churg J, Strauss L. Allergic granulomatosis, allergic\nangiitis, and periarteritis nodosa. Am J Pathol. Mar-Apr\n1951;27(2):277-301\n\n\n\n2. Masi AT, Hunder GG, Lie JT, et al. The American\nC o l l ege of Rheumatology 1990 criteria for the\nc l a s s i fication of Churg-Strauss syndrome (allerg i c\ngranulomatosis and angiitis). Arthritis Rheum. Aug\n1990; 33(8):1094-100\n\n\n\n3. Cakir B, Cyke rt S et al. Asthma associated with\nworsening leg ulcer: a case of vasculitis in primary\ncare. South Med J. 2003 Jul;96(7):677-80\n\n\n\n4. Wechsler ME, Finn D, Gunawardena D, et al. Churg-\nStrauss syndrome in patients receiving as treatment for\nasthma. Chest 2000;117:708-713\n\n\n\n5. Hellmich B, Ehlers S, Csernok E, Gross WL. Update\non the pathogenesis of Churg-Strauss syndrome. Clin\nExp Rheumatol. Nov-Dec 2003;21(6 Suppl 32):S69-77\n\n\n\n6. S a bl \u00e9 - Fo u rtassou R, Cohen P, Mahr A, et al.\nAntineutrophil cytoplasmic antibodies and the Churg-\nStrauss syndrome. Ann Intern Med. Nov 1\n2005;143(9):632-8\n\n\n\n7. Kim Y, Lee KS, Choi DC, et al. The spectrum of\neosinophilic lung disease: radiologic findings. J\nComput Assist Tomogr. Nov-Dec 1997;21(6):920-30\n\n\n\n8. H a s l ey PB, Follansbee W P, Coulehan JL. Cardiac\nmanifestations of Churg-Strauss syndrome: report of a\ncase and review of the literature. Am Heart J. Oct\n1990;120(4):996-9\n\n\n\n9. Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss\nsyndrome. Clinical study and long-term follow-up of\n96 patients. Medicine (Baltimore). Jan 1999; 78(1):26-\n37\n\n\n\n\n\n\n\n\n24 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\n10. Grau RG. Churg-Strauss syndrome: 2005-2008 update.\nCurr Rheumatol Rep. Dec 2008; 10(6):453-8\n\n\n\n11. Keogh KA, Specks U. Churg-Strauss syndrome: update\non clinical, laboratory and therapeutic aspects.\nSarcoidosis Vasc Diffuse Lung Dis. Mar 2006;23(1):3-\n12.\n\n\n\n12. Mukhtyar C, Flossmann O, Hellmich B, et al.\nOutcomes from studies of antineutrophil cytoplasm\nantibody associated vasculitis: a systematic review by\nthe European League Against Rheumatism systemic\nvasculitis task force. Ann Rheum Dis. Jul\n2008;67(7):1004-10\n\n\n\n13. Solans R, Bosch JA, Perez-Bocanegra C, et al. Churg-\nStrauss syndrome: Outcome and long -term follow-up\nof 32 patients. Rheumatology (Oxford) 2001; 40: 763-\n771\n\n\n\n\n\n\n\n\n25MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Case Report\n\n\n\nChildhood disabling Pansclerotic Morphoea \ncomplicated by leg ulcers, contractures and gangrene                 \nPan JY, FAMS, Ker KJ, MBBS, Tang MBY, FAMS\n\n\n\nCorrespondence\nPan Jiun Yit, MRCP, FAMS\nNational Skin Centre\nE-mail : jypan@nsc.gov.sg\n\n\n\nKeywords morphea, ulcers, contracture, gangrene\n\n\n\nI n t ro d u c t i o n\nDisabling pansclerotic morphoea of childhood is a\nsubset of localized scleroderma. It is a rare disease\nin both the adult and paediatric population.\nE t i o l ogical factors are unknown although\nautoimmune, infectious, genetic and environmental\nfactors have been postulated. Sclerotic plaques\npredominantly affect the scalp, face, trunk and\nextensor surfaces of limbs, leaving fingertips and\ntoes uninvo l ved. The absence of Ray n a u d \u2019s\nphenomenon, dysphagia, visceral involvement and\nc e rtain laboratory derangements diff e r e n t i a t e\nsystemic sclerosis and disabling pansclerotic\nm o rphoea of childhood. Diagnosis can be\ns u p p o rted by histolog y. There are seve r a l\nmanagement options including topical, systemic\nand phototherapy.\n\n\n\nCase re p o rt\nAn 11-ye a r-old Chinese boy presented with\nRaynaud\u2019s phenomenon, progressive skin hardening\nand joint contractures at the age of four (Figure 1\na & b). There were no dysphagia or sicca\nsymptoms. A skin biopsy showed morphoea (Figure\n2). Anti-nuclear antibody, anti-double stranded\nD NA and ex t r a c t a ble nuclear antigen (ENA )\nantibodies were nega t ive. As the cutaneous\nsymptoms were severe and progressive and there\nwere no systemic manifestations of scleroderma, he\nwas diagnosed to have pansclerotic morphoea of\nchildhood. Differential diagnoses of this clinical\npresentation include scleromy xedema and\nnephrogenic fibrosing dermopathy / nephrogenic\nsystemic fibrosis (although not common in this age\ngroup.\n\n\n\nHe was started on prednisolone, followed by\nazathioprine, methotrexate and cy c l o s p o r i n e .\nHowever, he did not show any response and his\nparents opted to discontinue oral therapy after three\nyears of failed treatment. He also deve l o p e d\npersistent transaminitis even after the\ndiscontinuation of methotrexate. Hepatitis markers\nand hepatic imaging were unremarkable, and the\ntransaminitis resolved with empiric treatment with\nprednisolone. He was diagnosed to have probable\nautoimmune hepatitis.\n\n\n\nOver the years, the sclerosis of the skin and tendon\nand joint contractures became progressively more\nsevere. He had difficulty ambulating and had to use\na wheelchair for long distances. His quality of life\nwas severely impaired. In spite of his medical\ncondition, he was able to cope well with his studies. \n\n\n\nThe patient developed bilateral lower leg ulcers\nthree years after the diagnosis of disabl i n g\npansclerotic morphoea. The ulcers were more\nsevere over the left medial malleolus and there was\nalso cellulitis at his right ankle. The family was not\nkeen for a biopsy of the skin. He developed the\ncomplications of S t a p hylococcus aure u s\nbacteraemia and septic arthritis of the left knee and\nwas treated with intravenous cloxacillin. There were\nresultant contractures and flexion deformities of his\nknees due to disuse, and the patient became\nwheelchair-bound.\n\n\n\nThereafter, he developed progressive painful dark\ndiscolouration of his left big toe for a week\u2019s\nduration after his mother accidentally stepped on it.\nOther toes were not involved. On examination, he\nwas afebrile with normal vital signs. Dry gangrene\nwas seen involving the left big toe, extending\nproximally to the first metatarso-phalangeal joint.\n(Figure 3 a & b) There was generalized sclerosis\ninvolving the face, trunk and limbs with fixed\nflexion deformities of both legs. Foul smelling\nexudates with crusted areas were seen on dorsum of\nthe left foot. Multiple excoriated scaly plaques and\nmacerated ulcers were present on the extremities. \n\n\n\n\n\n\n\n\n26 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThe full blood count showed a normal total white\ncell count (9.98 x109/L) and mild anemia\n(hemoglobin 11.3 g/dL). Erythrocyte sedimentation\nrate and C-reactive protein were elevated at\n65mm/min and 15.5 mg/L respective ly. Blood\nbacterial cultures were negative. Bacterial wound\nculture from the left big toe grew Staphylococcus\naureus and Gram-negative bacilli. A radiograph of\n\n\n\nthe left foot did not suggest an abscess or\nosteomyelitis. \n\n\n\nI n t r avenous ampicillin and cloxacillin we r e\ncommenced, which were oralised after four days of\ntherapy. His parents were not keen for surgical\nintervention. A decision was made for conservative\ntreatment and auto-amputation of the affected toe.\n\n\n\nFigure 1 a & b Progressive skin hardening with joint contractures\n\n\n\nFigure 3 a & b Ulceration of the lower limbs progressing to gangrene of the left big toe\n\n\n\na b\n\n\n\na b\n\n\n\nFigure 2 A skin biopsy showing features of morphoea: thickening of \ncollagen, and a decrease in the number of fibroblasts and \nadnexal structures (H&E, 10x)\n\n\n\n\n\n\n\n\n27MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDiscussion\nScleroderma is characterized by skin induration and\nthickening with tissue fibrosis. It is differentiated\ninto systemic sclerosis and localized scleroderma.\nPeterson et al1 f u rther classified localized\nscleroderma into five major categories: plaque,\ngeneralized, bullous, linear, and deep morphea.\nInvolvement of deep dermis, subcutaneous tissue,\nfascia and muscle characterizes deep morphoea.\nD i s a bling pansclerotic morphoea of children\n(DPMC) is a subtype of deep morphoea that can\nextend to the fascia, muscle, tendons and bones2.\n\n\n\nLocalised scleroderma (LS) is a rare disease with an\nincidence of 27 cases per million in the adult\npopulation in an epidemiological review done by\nPeterson et al3, out of which about 11% are cases\nwith deep morphoea. In the paediatric population,\nlocalized scleroderma is far commoner than\nsystemic sclerosis but the actual prevalence has not\nbeen well evaluated. A retrospective analysis by\nUziel et al4 in 30 paediatric patients with LS showed\nfemale predominance of 1.5:1; 7.9 years being the\naverage age of onset with a range of 1 to 14 years\nold. Ko rnreich et al5 r e p o rted a series of 35\npaediatric patients, with age of 6 years being the\naverage age of onset. Our patient presented with\nsclerotic plaques and joint contractures at 3 years\nold. \n\n\n\nIt is unknown what causes LS. Several etiologies\nl i ke autoimmune, infectious, genetic and\nenvironmental factors have been postulated but\nnever proven. Circulating autoantibodies can be\nfound in cases of LS and may point to an\nautoimmune cause. LS may also be genetically\nl i n ked as reported by Kuhnl et al6 wh e r e\ndevelopment of morphoea is related to HLA-A3B7\nand DR2. Borrelia burgdorferi infection has been\nassociated with morphoea. There has been\nconflicting reports of borrelial antibodies being\ndetected in patients with morphoea, with up to 45%\nof patients with morphoea testing positive in a\nScandinavian study and none in a Canadian study4,7.\nInfection by Epstein-Barr virus has also been\nthought to cause LS8. Other factors like trauma,\ns u rg e ry, vaccination, varicella infection, post\nradiotherapy in oncology patients and ischaemic\ninjury have been associated with LS. In our patient\nwith DPMC, no possible causative factors have\nbeen identified.\n\n\n\nThe pathogenesis of morphoea can be divided into\n3 pathways, namely vascular alteration, disrupted\ncollagen metabolism and immunoreg u l a t o ry\ndefects. Endothelial cell damage and perivascular\ninfiltration of macrophages and mast cells feature\nprominently in biopsies. Autologous complement\nalso contributes to vascular damage as levels of\ncomplement regulatory proteins are decreased in\nm o rp h o e a9. Disruption to collagen metabolism\noccurs in morphoea due to increased expression of\npivotal cytokines like transforming growth factor\n\n\n\n(TGF-b) and interleukin-4. They stimulate dermal\nfibroblasts, causing the build-up of extracellular\nmatrix components, in particular types 1 and 3\nfi b r i l l a ry collagen. Immunoreg u l a t o ry defects\ninvolving cellular and humoral abnormalities have\nbeen implicated in the pathogenesis of LS. There is\nabnormal activation of B and T cells. \n\n\n\nIn DPMC, sclerotic plaques predominantly affect\nthe scalp, face, trunk and extensor surfaces of\nlimbs, leaving fi n g e rtips and toes uninvo l ve d .\nMultiple joint contractures result from skin\nsclerosis over the joints1 0 , 1 1. The absence of\nRaynaud\u2019s phenomenon, dysphagia and visceral\ninvolvement differentiate systemic sclerosis and\nd i s a bling pansclerotic morphoea of childhood.\nSclerotic plaques occurred in the typical\nd i s t r i bution in our patient, together with fi xe d\nflexion deformities in both his knees and multiple\ncontractures in other joints. He had Raynaud\u2019s\nphenomenon but no evidence of visceral\ninvolvement, dysphagia or sicca symptoms. \n\n\n\nC e rtain laboratory abnormalities are present in\nchildren with localized scleroderma. A positive\nanti-nuclear antibody (ANA), rheumatoid factor\n(RF), hypergammaglobulinaemia, eosinophilia and\nhigh erythrocyte sedimentation rate (ESR) are the\nmore commonly detected abnorm a l i t i e s1 2 , 1 3. In\nlocalized scleroderma, ANA can be positive in\nbetween 23% to 73% of patients12 and in a study by\nFalanga et al14 ANA positivity was more prevalent in\npatients with severe and ex t e n s ive linear\ns c l e r o d e rma. 39% of patients with localized\nscleroderma show RF positivity11 and similar to\nANA, it was associated with more severe disease in\nthose with linear scleroderma. A n t i - h i s t o n e\nantibodies and anti-single stranded DNA antibodies\ncan also be present14. Hypergammaglobulinaemia\nwith raised IgG and IgM levels occur in between\n13% to 50% of patients15,16 and those with joint\ncontractures have higher IgG levels17.\n\n\n\n\n\n\n\n\n28 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nRaised ESR and blood and tissue eosinophilia\ncharacterize deep morphoea13. An association has\nbeen shown between blood eosinophilia and clinical\ndisease activ i t y1 3 with eosinophilia preceding\nexacerbations and declining levels indicating\ndisease remission17.\n\n\n\nPatients with localized scleroderma do not have\nantibodies to extractable nuclear antigens (ENA)\nlike anti-Scl 70, which differentiates them from\nthose with systemic sclerosis. Our patient with\nDPMC had raised ESR (65mm/50 minutes) and\nnegative ANA, RF and ENA antibodies. \n\n\n\nH i s t o p a t h o l ogical findings are characterized by\nfibrosis and thickened homogenized collagen\nbands. The depth of inflammation and sclerosis is\nused to differentiate between the different subtypes.\nIn the subcutis, there are lymphocytes and plasma\ncells with thickened collagen and hyalinization.\nThickened septa and obliteration of fat lobules are\npresent. Deep dermis hyalinization is common.\nSclerosis of the entire dermis and panniculus\ncharacterize disabling pansclerotic morphoea10. The\nfascia is fibrotic and sclerotic, with vacuolated\nmuscle fibres separated by edematous stroma and\ninflammatory infiltrates18,19. The histology of our\npatient corresponded to that of deep morphoea. \n\n\n\nThe majority of children with localized\nscleroderma do not have systemic manifestations\nbut it has been reported by Uziel et al4 that up to\n40% have arthritis or arthralgia. Diaz et al10 reported\n43% of children with DPMC had pulmonary or\nesophageal abnormalities. Although there have\nbeen reports of morphoea progressing to systemic\nsclerosis, it is extremely rare. Our patient did not\nhave any systemic manifestations. \n\n\n\nAs a result of pansclerotic involvement, painful\nulcers and severe joint contractures can develop.\nThese ulcers often have super-imposed bacterial\ninfections, of which Pseudomonas aeruginosa,\nEnterobacteriacae spp, Streptococci, Enterococci,\nS t e n o t rophomonas maltophilia and S e r ra t i a\nM a rc e n s c e n s h ave been report e d2 0. Systemic\nantibiotics are often necessary and in some patients,\nrepeated wound debridements may be needed. Our\npatient developed disabling joint contractures,\nchronic non-healing lower limb ulcers and dry\ngangrene of his left big toe after minimal trauma.\nThe bacterial culture from his ulcers gr ew\nStaphylococci and Enteric bacilli. There was no\nevidence of underlying osteomyelitis.\n\n\n\nOther complications include soft tissue\ncalcification. There have been reports of squamous\ncell carcinomas arising from long-standing ulcers in\npatients with DPMC. The annual incidence of\npatients with DPMC developing squamous cell\ncarcinoma is 6.7%, far higher than patients who\nwere cancer survivors and those with hereditary\ncancer prone syndromes20. Visceral complications\nl i ke abnormal pulmonary function tests,\nesophageal motility disorders and myo p a t h i c\nelectromyographic disorders in sclerotic areas can\noccur10.\n\n\n\nThe management of a paediatric patient with\nm o rphoea requires a holistic approach. Both\nmedical and psychosocial needs of the patient and\nthe family have to be addressed. Medical therapy\ninclude topical and systemic treatments,\nphototherapy, physical and surgical options. All\ntreatments have to be individualized. \n\n\n\nTopical therapies include topical or intralesional\ncorticosteroids and calcipotriene ointment. These\ntreatment options are the initial choices for mild,\nlocalized plaque morphoea but in our patient with\ngeneralized morphoea, the therapeutic eff e c t s\nwould be minimal.\n\n\n\nSystemic therapy is indicated for severe extensive\ndisease, linear scleroderma across joints wh e r e\ncontractures result and facial involvement like en\ncoup de sabre. Multiple treatment reg i m e s\nand options like D-penicillamine, systemic\ncorticosteroids and antibiotics, phenytoin, retinoids,\ncyclosporin and plasma exchange have been\nreported but there has been none with universal\ngood results. \n\n\n\nUse of systemic corticosteroids in the therapy of LS\nis questionable. Joly et al21 reported an improvement\nin 76% of patients after 6 weeks of 0.5 to 1mg/kg of\noral corticosteroid but relapse rate was high (35%)\nafter discontinuation. In contrast, Rosenwasser et\nal22 reported ineffectiveness of oral corticosteroids.\nMethotrexate has been reported to be useful in the\ntreatment of adults with widespread morphoea and\nanecdotal reports in children have show n\nencouraging results as well. The need for regular\nblood monitoring, systemic toxicity issues and drug\ninteractions have to be considered. Our patient was\ninitially started on oral prednisolone at 1mg/kg/day\nand methotrexate 7.5mg/week. The dose of\nmethotrexate was gradually increased for a steroid-\nsparing effect but the patient deve l o p e d\ntransaminitis and methotrexate had to be eventually\nstopped.\n\n\n\n\n\n\n\n\n29MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nOral calcitriol is also an option in the treatment of\nLS. Humbert et al2 3 r e p o rted the use of oral\ncalcitriol (1,25-dihydroxyvitamin D3) in an adult\nwith severe LS and improvement was noted. In a\nstudy by Elst et al24 in paediatric patients with linear\ns c l e r o d e rma, 5 of 7 patients showed good\nimprovement, 1 had a relapse that responded to a\nsecond course of calcitriol and 1 with severe disease\nshowed no benefit. \n\n\n\nUltraviolet (UV) A irradiation alone, or together\nwith psoralens, a photosensitizing agent, has been\nutilized in the treatment of LS. Encouraging results\nhave been noted with UVA (320-400nm), UVA-1\n(340-400nm) and psoralens with UVA (PUVA).\nThere has been positive results of PUVA and UVA-\n1 in treatment of DPMC25,26, especially for UVA-1,\nwhich has been thought to retard disease\np r ogression, including joint contractures2 7.\nAlthough phototherapy is useful in the therapeutic\narmamentarium of LS, concerns regarding possible\nlong-term carcinogenic risks, especially in children,\nmay restrict its use. However, the benefits to quality\nof life of this patient may outweigh the risks of skin\ncancer, which is by no means certain to occur.\nExtracorporeal photophoresis has also been shown\nto be useful in some patients28.\n\n\n\nPhysiotherapy involving heat, splinting, casting,\nmuscle strengthening exercises and joint\nmobilization are useful in patients with flexion\ncontractures. Surgical procedures are rarely\nconsidered as impaired tissue perfusion leads to\ndifficulties in wound healing.\n\n\n\nRoldan et al29 reported the use of bosentan, a dual\noral endothelin receptor antagonist, for 4 weeks in a\npaediatric patient with DPMC and chronic ulcers.\nAn improvement was noted in the ulcers, degree of\nskin sclerosis and joint mobility. This could be\nutilized in our patient as he had chronic non-healing\nulcers that did not respond well to dressings alone. \n\n\n\nFor non-healing chronic ulcers that are not infected,\ntopical agents like chlorhexidine and betadine can\nbe used as they have a broad antimicrobial spectrum\nwith low tissue toxicity. Antimicrobial products\ncontaining silve r, poly h ex a m e t hylene biguanide,\nCadoxemer Iodine or polyacrylates can be used to\ntreat superficial infections30. Necrotic tissue impairs\nwound healing and encourages bacterial growth\nthus surgical debridement may be considered at\n\n\n\ntimes. However, in patients with DPMC, impaired\ntissue perfusion could also lead to difficulties in\nwound healing post-operative ly. Dressings that\nfacilitate autolytic debridement can be used. These\ninclude hy d r ogels, films and hy d r o c o l l o i d s .\nMoisture balance is essential to wound healing, and\nthe nature of exudates in chronic ulcers in DPMC\nmay impair this31. Thus, the removal of exudates in\nchronic ulcers is necessary to promote wo u n d\nhealing. Dressings that serve this function include\ncalcium alginate, foam, fibre and composite\ndressings. Synthetic skin grafts could also be\nconsidered to aid in tissue healing. Our patient had\nbeen on various dressings including silver dressings\n(mepilex silver), iodosorb, hydrogels and duoderm. \n\n\n\nSystemic antibiotics are required to treat infected\nulcers and these should be tailored according to the\nsensitivities of the organisms. Our patient was\ntreated empirically with intravenous ampicillin and\ncloxacillin and converted to oral cloxacillin and\na m oxicillin when culture results of his ulcers\nshowed Staphylococci and Enteric bacilli sensitive\nto the above antibiotics.\n\n\n\nWollina et al20 reported efficacy on use of sildenafil\ntogether with porcine small intestinal submucosal\nacellular matrix in the treatment of chronic ulcers\nassociated with DPMC. A porcine acellular matrix\nskin substitute was applied on the ulcers and\ntogether with oral sildenafil for 2 weeks, significant\nimprovement in granulation of the ulcers was noted.\nThis combination therapy had a synergistic effect\nthat was far more efficacious than either therapy\nalone. In addition, sildenafil has also been reported\nto improve digital flexibility and dexterity32. The\ncombination therapy could be considered in our\npatient as his ulcers are long-standing and has been\nshowing poor response to conventional therapies of\nantibiotics and wound care.\n\n\n\nD a i ly transcutaneous application of dry carbon\nd i oxide gas can also be utilized to reduce\ncolonization of the ulcers and aid in the granulation\np r o c e s s3 3. A 5-day course of intrave n o u s\nimmunoglobulin, followed by another dose a month\nlater, has been used by Wollina et al34 with good\neffect. The improvement noted in the ulcers lasted\nfor nearly a year. Intravenous pentoxyphillin had\nbeen tried with poor results by the same authors34.\n\n\n\n\n\n\n\n\n30 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nIn conclusion, treatment of patients with disabling\npansclerotic morphoea of childhood is difficult and\nquality of life is often severely impaired. Judicious\nskin care and prompt treatment of complications\nsuch as joint contractures and chronic ulcers is\nessential.\n\n\n\nReferences\n\n\n\n1. Peterson LS, Nelson AM, Su WPD: Classification of\nm o rphea (localized scleroderma). Mayo Clin Proc\n70:1068-1076, 1995\n\n\n\n2. Bielsa I, Ariza A: Deep morphea. Semin Cutan Med\nSurg. 2007 Jun;26(2):90-5\n\n\n\n3. Peterson LS, Nelson AM, Su WE et al: T h e\nepidemiology of morphea (localized scleroderma) in\nolmsted county 1960-1993. J Rheumatol 24:73-80,\n1997\n\n\n\n4. Uziel Y, Krafchik BR, Silverman ED, et al Localized\nscleroderma in childhood: A report of 30 cases. Semin\nArthritis Rheum 23:328-340, 1994\n\n\n\n5. Ko rnreich HK, King KK, Bernstein BH, et al:\nScleroderma in childhood. Arthritis Rheum 20:343-\n350, 1977 (suppl 2)\n\n\n\n6. Kuhnl P, Sibrowsky W, Broehm BO, et al: Association\nof HLA antigens with progressive systemic sclerosis\nand morphoea. Tissue Antigens 34:207-209, 1989\n\n\n\n7. Buechner SA, Winkelmann RK, Lautenschlager S, et\nal: Localized scleroderma associated with Borrelia\nbu rgdorferi infection: Clinical, histologic, and\nimmunohistochemical observations. J Am A c a d\nDermatol 29:190-196, 1993\n\n\n\n8. Longo E Saletta S, Lepore L, et al: Localized\nscleroderma after infection with Epstein-Barr virus.\nClin Exp Rheumatol 11:681-683, 1993\n\n\n\n9. Venneker GT, Das PK, Naafs B, et al: Morphea lesions\nare associated with aberrant expression of membrane\nc o factor protein and decay, accelerating factor in\nvascular endothelium. BJr Dermatol 131:237-242,\n1994\n\n\n\n10. D \u00ed a z - Perez JL, Connolly SM, Wi n kelmann RK :\nDisabling pansclerotic morphoea of children. Arch\nDermatol 116:169-173, 1980\n\n\n\n11. Falanga V, Medsger TA, Reichfin M, et al Linear\nscleroderma. Ann Intern Med 104:849-857, 1986\n\n\n\n12. R o s e n b e rg AM, Uziel Y, Krafchik BR, et al:\nAntinuclear antibodies in children with localized\nscleroderma. J Rhemnatol 22:2337-2343, 1995\n\n\n\n13. Falanga V, Medsger TA Jr: Frequency, levels, and\ns i g n i ficance of blood eosinophilia in systemic\nsclerosis, localized scleroderma, and eosinophilic\nfasciitis. J Am Acad Dermatol 17: 648-656, 1987\n\n\n\n14. Falanga V, Medsger TA Jr, Reichlin M: Antinuclear and\nanti-singlestranded DNA antibodies in morphea and\ngeneralized morphea. Arch Dermatol 123:350-353,\n1987\n\n\n\n15. Tuffanelli DL: Localized scleroderma. Semin Cutan\nMed Surg 17:27-33, 1998\n\n\n\n16. Schacter RK: Localized scleroderma. Curt Opin\nRheumat 2:947-955, 1990\n\n\n\n17. Falanga V: Localized scleroderma. Med Clin North Am\n73:1143-1156, 1989\n\n\n\n18. Jablonska S: Localized scleroderma, in Jablonska S\n(ed): Scleroderma and Pseudoscleroderma (ed 2).\nWarsaw, Poland, Polish Medical Publishers, 1975, p277\n\n\n\n19. Fleischmajer R, Nedwich A: Generalized morphea: I.\nHistology of the dermis and subcutaneous tissue. Arch\nDermato1106:509-514, 1972\n\n\n\n20. Wollina U, Buslau M, Heinig B et al: Disabl i n g\npansclerotic morphea of childhood poses a high risk of\nchronic ulceration of the skin and squamous cell\ncarcinoma. Int J Low Extrem Wounds. 2007\nDec;6(4):291-8\n\n\n\n21. Joly P, Bamberger N, Crickx B, et al: Treatment of\ns evere forms of localized scleroderma with oral\ncorticosteroids: Follow-up study on 17 patients. Arch\nDermatol 130:663-664, 1994\n\n\n\n22. R o s e n wasser TA, Eisen AZ: Scleroderma, in\nFitzpatrick TB, Eisen AZ, Wolff K, (eds): Dermatology\nin General Medicine (ed 5). New York, NY, McGraw-\nHill, 1993, pp 2156-2167\n\n\n\n23. Humbert PG, Dupond JL, Rochefort A, et al: Localized\ns c l e r o d e rma-response to 1,25-dihy d r oxyvitamin D3.\nClin Exp Dermatol 15:396-398, 1990\n\n\n\n24. Elst EF, Van Suijlekom-Smit LW, Oranje AP: Treatment\nof linear scleroderma with oral 1,25-dihydroxyvitamin\nD3 (calcitriol) in seven children. Pediatr Dermatol.\n1999 Jan-Feb; 16(1):53-8\n\n\n\n25. Gruss C, St\u00fccker M, Kobyletzki G et al: Low dose\nU VA1 phototherapy in disabling pansclerotic\nmorphoea of childhood. Br J Dermatol. 1997 Feb;\n136(2):293-4\n\n\n\n26. Scharffetter-Kochanek K, Goldermann R, Lehmann P\net al: PUVA therapy in disabling pansclerotic morphoea\nof children. Br J Dermatol 1995; 132:830 1.\n\n\n\n27. Kroft EB, Berkhof NJ, van de Kerkhof PC et al:\nUltraviolet A phototherapy for sclerotic skin diseases: a\nsystematic rev i ew. J Am Acad Dermatol. 2008\nDec:59(6):1017-39. \n\n\n\n28. Neustadter JH, Samarin F, Carlson KR, Girardi M.\nE x t r a c o rporeal photochemotherapy for generalized\ndeep morphea. Arch Dermatol. Feb 2009;145(2):127-\n30\n\n\n\n29. Sibbald RG, et al. Preparing the wound bed-\ndebridement, bacterial balance, and moisture balance.\nOstomy Wound Manage. 2000;46:14-22\n\n\n\n30. Okan D, et al. The role of moisture balance in wound\nhealing. Adv Skin Wound Care. 2007;20:39-53.\n\n\n\n31. Yung A, Reay N, Goodfield MD: Improvement in\ndigital flexibility and dexterity following ingestion of\nsildenafil citrate (Viagra) in limited systemic sclerosis.\nArch Dermatol 2005;141:8;31-3\n\n\n\n32. Wollina U, Heinig B, Uhlemann C. Transdermal CO2\napplication in chronic wounds. Int J Lower Extremity\nWounds 2004; 3:103-6\n\n\n\n33. Wollina U, Looks A, Uhlemann C et al: Pansclerotic\nmorphea of childhood-follow-up over 6 years. Pediatr\nDermatol. 1999 May-Jun;16(3):245-7\n\n\n\n\n\n\n\n\n31MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGENERAL DERMAT O L O G Y - Case Report\n\n\n\nWe g e n e r \u2019s Granulomatosis:\nA case re p o rt and literature re v i e w\nTang JJ1, Tang MM1, Lee BR2, Ng TG1, Roshidah B1\n\n\n\nCorrespondence\nTang JJ\nDepartment of Dermatology, Hospital Kuala Lumpur\nE-mail : tangjyhjong@yahoo.com\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur\n2Department of Pathology, Universiti Putra Malaysia\n\n\n\nKeywords Wegener\u2019s granulomatosis, systemic\nvasculitis, anti-neutrophil cytoplasmic antibody\n\n\n\nI n t ro d u c t i o n\nWegener\u2019s granulomatosis is a rare multisystem\nnecrotizing granulomatous vasculitis aff e c t i n g\nsmall - and medium-sized vessels. Its clinical\nmanifestations can be nonspecific during the initial\nstages and indistinguishable from a variety of\nneoplastic, infectious, and inflammatory diseases.\nThe disease may run a course from indolence to one\nof rapid progression leading to life-threatening\nmultiorgan failure. We report a rare case of rapidly\nprogressing Wegener\u2019s granulomatosis.\n\n\n\nCase re p o rt\nA 39 year old Malay housewife with no co-\nmorbidity, presented to us with a 2-month history of\n\n\n\nmultiple painful non healing ulcerated  nodules and\nplaques involving the left face, right thigh and both\nshins. The lesions were initially papular and\np r ogr e s s ive ly enlarged to form nodules wh i c h\nruptured with pus discharge and eventually formed\nulcers. Apart from that, she also had non productive\ncough, symptoms of rhinitis, anorexia and loss of\nweight for the past 1 month. This was associated\nwith bilateral reduced hearing but without ear\ndischarge or pain. There was no fever, epistaxis,\nhaemoptysis, dypsnoea or urinary symptoms.\n\n\n\nClinically, she was afebrile and normotensive. She\nhad an ulcerated plaque on left cheek (Figure 1), 3\nulcerated plaques on both shins (Figure 2 and 3) and\nan ulcerated plaque on right thigh. All these ulcers\nwere ex t r e m e ly tender with deep punched-out\nmargins and covered with a haemorrhagic crust.\nThe diameter of these ulcers  ranged from 1 to 2cm.\nThere\n\n\n\nFigure 1\nSingle ulcerative plaque with\nhaemorrhagic crust on left cheek\n\n\n\nFigure 2\nMultiple ulcerative plaque on\nboth shins\n\n\n\nFigure 3\nClose view of a ulcerative plaque with\nhaemorrhagic crust on right shin\n\n\n\n\n\n\n\n\n32 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThere was also a tender nodule with norm a l\noverlying skin on the right cheek measuring 1x1cm.\nExamination of the respiratory, cardiovascular and\nneurologic systems were essentially normal. There\nwas no organomegaly on abdominal examination.\nAn ear, nose and throat assessment revealed the\nnasal septum to be ulcerated and crusted with\nbilateral moderate to profound mixed hearing loss,\notitis media and chronic sinusitis. At this point of\ntime, our differential diagnosis included Wegener\u2019s\ngranulomatosis, poly a rteritis nodosa, pyo d e rm a\ngangrenosum, a deep fungal infection, cutaneous\ntuberculosis or non-tuberculous my c o b a c t e r i u m\ninfection.\n\n\n\nInvestigations revealed that she had normochromic\nnormocytic anaemia (Hb 10.8). Her erythrocyte\nsedimentation rate and c-reactive protein were both\nraised at 108 mm/hour and 35.75 mg/dl\nrespectively. Tumour markers for CA125, CA19-9,\na l fa-fetoprotein and carcinoembryonic A n t i g e n\nwere all normal. There was no haematuria or\nproteinuria. Her chest x-ray, renal profile and liver\nfunction tests were normal. Serology for human\nimmunodeficiency virus, hepatitis B and hepatitis\nC were negative. A swab from the ulcer grew\nStaphyloccocus aureus. However, a swab from the\nears did not grow any organism. CT scan of brain\nand neck showed pansinusitis, bilateral mastoiditis\nwith otitis media and small subcutaneous abscess\ncollection at the angle of the mandible.\n\n\n\nFigure 5\nBiopsy form the nasal mucosa showed granulomas as\nwell as multinucleated giant cells admixed lympho-\nplasmacytic cells surrounding the blood vessel.\n(Haemotoxylin & Eosin x 400)\n\n\n\nFigure 6\nBiopsy from nasal mucosa: Firbrinoid necrosis of the\nsmall arterioles and neutrophilic infiltration of the\nblood vessels were clearly seen at tissue distance from\nthe ulcerated mucosa. (Haemotoxylin and Eosin x 400)\n\n\n\nFigure 4\nBiopsy of the ulcerated skin showed granulation tissue\nwith marked neutrophils infiltration. Evidences of\nvasculitis were absent. However, a few vague\ngranulomas were present. (Haemotoxylin and Eosin \nx400)\n\n\n\n\n\n\n\n\n33MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nA skin biopsy of the ulcer on her left shin showed a\ncluster of granuloma with multinucleated giant\ncells and abundant surrounding neutrophils and\nplasma cells (Figure 4). There were no features to\nsuggest vasculitis from the skin biopsy. Special\nstains for PAS, GMS and Ziehl Neelsen were all\nnegative. Tissue culture for mycobacterium, fungus\nand bacteria were negative. However,  her nasal\nbiopsy showed a chronic necrotizing granulomatous\ninflammation with small vessel vasculitis (Figure 5,\n6). Serology using indirect immunofluorescence for\nanti-neutrophil cytoplasmic antiboby (ANCA) was\np o s i t ive for cytoplasmic pattern antineutrophil\ncytoplasmic antibodies (c-ANCA) but negative for\nperinuclear pattern antineutrophil cy t o p l a s m i c\nantibodies (p-ANCA). These features confirmed\nthe diagnosis of Wegener\u2019s granulomatosis. The\npatient howeve r, insisted on being discharg e d\na gainst medical advice to seek for traditional\ntreatment before any treatment specific treatment\ncould be initiated. She did not improve with\na l t e rn a t ive therapy and presented to another\nhospital 1 month later with acute renal failure.\nUnfortunately,  she succumbed to severe pulmonary\nhaemorrhage eventually.\n\n\n\nDiscussion\nWegener\u2019s granulomatosis (WG) is a multisystem\ndisease characterized by necrotizing granulomatous\ninflammation of the upper , lower respiratory tracts\nand kidneys with  necrotizing vasculitis affecting\nsmall- and medium-sized ve s s e l s1. It is an\nautoimmune inflammatory process with\nantineutrophil cytoplasmic antibodies (c-ANCA)\ndirected at neutrophil proteinase 3 (PR3). It is\nuncommon with a prevalence of approximately 3\nper 100,000 in USA3.  It affects males and females\nequally2. The age group as reported in the literature,\nis between 40 to 55 years4 as in our patient. There is\nincreasing evidence that Staphylococcus aureus\nplays a role in the pathogenesis of WG but the\nmechanism is still unclear5.\n\n\n\nThe clinical course of WG is characterized by an\ninitial localized or limited phase  followed by a\ngeneralized or systemic phase. In the initial limited\nphase, symptoms arise from gr a n u l o m a t o u s\ninflammation of the upper and/or lower respiratory\ntract whereas generalized WG is characterized by\nclinical signs of systemic vasculitis1. Limited WG\naccounts for 25% of cases and it usually spares the\nkidney3. In generalized WG,  patients present with\nlife threatening pulmonary-renal syndrome as a\n\n\n\nresult of necrotizing alveolar vasculitis and rapidly\nprogressive necrotizing glomerulonephritis1.\n\n\n\nIn general, over 90% of patient with WG initially\nseek medical attention for upper and/or lowe r\nairway symptoms2. The most frequently affected\nsites of granulomatous inflammation are the nose\nand paranasal sinuses (60-80%)2. Patients may\ncomplain of nasal congestion, epistaxis, pain of the\nsinus cavities, persistent rhinorrhea, perforation of\nthe nasal septum, hyposmia and saddle nose\ndeformity. Ear disease occurs in 25 to 40% of WG\nand most commonly manifest as otitis media with\neffusion due to eustachian tube obstruction as a\nresult of luminal granuloma or nasopharyngeal\ninflammation2. Hearing loss is also common and it\nmay be sensorineural, conductive  or mixed2. Oral\ncavity and oropharynx involvement are uncommon.\nThe most common oral lesion is straw b e rry\ngingivitis which presents as an exophytic gingival\ngrowth with petechiae6. This may be the first sign\nand is nearly pathognomonic of W G6. Lung\ninvolvement is almost universal in patients with\nWG and it can affect pulmonary parenchy m a ,\nbronchi and pleura2. Typically the patient presents\nwith cough, haemoptysis, dyspnea and pleuritic\npain. Chest radiograph may show pulmonary\nnodules, cavitating lesions, or diffuse alve o l a r\nhaemorrhage1,2. Our patient had evidence to suggest\nupper airway involvement of WG which included\npersistent rhinitis,  chronic sinusitis and otitis media\nwith hearing loss. Howeve r, there was no\nradiological evidence to suggest lung involvement\non her initial presentation even though she\nsuccumbed to pulmonary haemorrhage eventually.\n\n\n\nCutaneous manifestations of WG encompass a\ndiverse spectrum and occur in 40-50% of cases2.\nThe most common skin lesion is palpable purpura\ndue to leucocytoclastic va s c u l i t i s7. Other\npresentations include nodules, papules, vesicular\nlesions, ulcerative pyo d e rma ga n gr e n o s u m - l i ke\nlesions and deep erythema nodosum-like\nsubcutaneous nodules2,7. These lesions commonly\noccur on the distal arms and legs7. Our patient\npresented with multiple ulcerative plaques\nmimicking pyoderma gangrenosum or cutaneous\ninfections. In fact, skin lesions were the main\nproblem that brought her to our hospital. However,\nit can be ve ry challenging to determine the\nu n d e r lying cause at the initial stage as\nhistopathology of skin biopsy can be non specific\nas shown in our patient.\n\n\n\n\n\n\n\n\n34 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nRenal invo l vement is the most serious\nmanifestation of WG and  presents in about 20% of\npatients at diagnosis but develops in 80% of\npatients during the course of their disease2. The\npatient can develop rapidly progressive renal failure\nas a result of necrotizing glomeru l o n e p h r i t i s1 , 2.\nRenal biopsy is not a routine as findings are usually\nn o n s p e c i fic and it most often shows a focal\nand segmenting necrotizing proliferative\nglomerulonephritis8,9. Our patient did not have any\nrenal invo l vement initially. Unfort u n a t e ly her\ndisease progressed rapidly within a month after she\nwas discharged on her own accord. She\nsubsequently presented with acute renal failure in\nanother hospital. WG can also involve other organs\nsuch as the eye (causing proptosis, necrotizing\nkeratoscleritis conjunctivitis, retinal va s c u l i t i s ) ,\ncardiac (causing pericarditis, myo c a r d i t i s ,\nconduction abnormalities) and neurologic system\n(causing mononeuritis multiplex, cerebral\nvasculitis)4. Our patient did not have any of these\nrare presentations.\n\n\n\nDiagnosis of WG is generally based on a\ncombination evidence of clinical findings, biopsy\nof invo l ved tissue showing necrotizing\ngranulomas/vasculitis and laboratory evidence of c\nANCA8. The American College of Rheumatology\nhas proposed that the diagnosis of WG can be made\nif two of the following criteria are included:1)\nulcerative lesions in oral mucosa or nasal bleeding\nor inflammation, 2) nodules, fixed infiltrates or\ncavities in chest radiograph, 3) abnormal urinary\nsediment (red cell cast or 5 red blood cell per high\npower field), and 4) granulomatous inflammation\non biopsy10. Our patient had evidence to suggest\nWG based on clinical presentation, histopathology\nfrom nasal biopsy and a positive cy t o p l a s m i c\npattern antineutrophil cytoplasmic antibodies (c-\nANCA). \n\n\n\nThree major histopathologic findings of Wegener\u2019s\ngranulomatosis include parenchymal necrosis,\nvasculitis, and granulomatous inflammation2. The\nsite of biopsy affects the diagnostic yield with\nparanasal sinus biopsy offering the highest yield2.\nCytoplasmic pattern ANCA (cANCA) positivity is\nfound in more than 90% of generalized WG but\nonly 50% in limited WG2. Levels of c-ANCA also\ncorrelates with disease activity in WG11. The titers\nof these antibodies decline during treatment but\nmay rise again before relapse11. As was the case in\nthis patient, an increase in ery t h r o cy t e\n\n\n\nsedimentation rate and C-reactive protein is\ncommon in WG.\n\n\n\nWG is highly fatal if not treated early with more\nthan 90% mortality in the first two years and renal\nfailure is the most common cause of death1. Delay\nin the diagnosis of WG is mainly due to the\nnonspecific symptoms or signs that are experienced\nby the patient during the initial phase of the\ndisease11. Hence, early diagnosis and treatment is\nimportant as the presence of advanced disease at\ndiagnosis limits the potential benefit of therapy.\nTreatment of WG requires induction of remission\nf o l l owed by maintenance. Current remission\ninduction treatment protocols in systemic W G\nconsist of cyclophosphamide and corticosteroids\nsupported by plasma exchange in case of severe\nrenal vasculitis or pulmonary hemorr h a g e1 , 2 , 1 2.\nCyclophosphamide may be given as continuous low\ndose oral treatment or by intravenous pulses\ninitially at 2-3 week interval12. This treatment is\ncontinued for 3 to 6 months until patient has\nachieved remission12. During maintenance therapy,\ncyclophosphamide should be withdrawn and\nsubstituted with either azathioprine or methotrexate\nto avoid the side-effects of cyclophosphamide12.\nPatients should continue maintenance therapy for at\nleast 24 months following successful disease\nremission12. Optimization of treatment protocols\nhas led to remission rates of 70-90% in the first year\nand 5-year survival rate is now reported to be over\n75%1,2. However, relapse rate is high ranging from\n10% in the first year to 66% during long-term\nfollow-up1. Long term treatment with low dose of\nt r i m e t h r o p r i m / s u l fa m e t h oxazole has show n\nsatisfactory response to control bacterial infection1.\nThis treatment is based on the hypothesis that\ninfection exposes neutrophil proteases to\nautoantibodies and justifies the attempt to control\nthe infection2. In this patient, we were not able to\ninitiate appropriate treatment as she insisted on\nd i s c h a rge against medical advice upon\nconfirmation of her diagnosis. \n\n\n\nConclusion\nThis report has described one case of rapidly\np r ogressing Weg e n e r \u2019s granulomatosis based on\nclinical, histopathology, and laboratory evidence of\ncANCA. Our patient presented initially with an\nupper airway and skin manifestation but her disease\np r ogressed rapidly with subsequent renal and\npulmonary involvement 1 month after she was\ndischarged. Diagnosis of this condition may be very\nchallenging\n\n\n\n\n\n\n\n\n35MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nat the initial stage and requires a high index of\nsuspicion due to non-specific presentation.\nTreatment need to be initiated as early as possible to\nimprove the outcome of this condition as it carries a\nhigh mortality rate.\n\n\n\nReferences\n\n\n\n1. Anna M. Schilder. Wegener's Granulomatosis vasculitis\nand granuloma. Autoimmunity Reviews  2010;9:483-\n487\n\n\n\n2. A. M. Khan, F. Elahi, S.R. Hashmi et al. Wegener\u2019s\ngranulomatosis: A rare, chronic and multisystem\ndisease. Surgeon 2006;1:45-52\n\n\n\n3. Lynn E. Harman, Curtis E. Margo. Weg e n e r \u2019s\nGranulomatosis. Survey of Ophthalmolog y\n1998;42:458-480\n\n\n\n4. Cotch MF, et al. The epidemiology of Weg e n e r ' s\ngranulomatosis. Arthritis Rheum  1996;39:87-92\n\n\n\n5. Kallenberg CG, Tadema H. Vasculitis and infections:\ncontribution to the issue of autoimmunity reviews\nd evoted to \u201cautoimmunity and infection\u201d.\nAutoimmunity Reviews 2008;8:29-32\n\n\n\n6. Hellevi R, Tapani H, Johanna A et al. Strawberry-like\ng i n g ivitis being the first sign of Weg e n e r ' s\ngranulomatosis. European J of Int Med 2009;20:651-\n653\n\n\n\n7. Angelo Valerio Marzano Daniele Fanoni. Oral and\ncutaneous findings are valuable diagnostic aids in\nWegener's granulomatosis. European Journal of\nInternal Medicine 2010;21:49\n\n\n\n8. Bajema IM, Hagen EC, Vander Woude FJ, Brujin JA.\nWegener\u2019s granulomatosis: a meta-analysis of 349 case\nreports. Journal of  Laboratory and Clinical Medicine\n1997; 129:17-22\n\n\n\n9. Dana M. Hartl, Patrick A i \u2019dan, Olivier Bru g i G r e ,\nOlivier Sterkers. Wegener\u2019s Granulomatosis Presenting\nas a Recurrence of Chronic Otitis Media. American\nJournal of Otolaryngology 1998;19:54-60\n\n\n\n10. Leavitt RY, Fauci AS, Bloch DA, et al: The American\nC o l l ege of Rheumatology 1990 criteria for the\nclassification of Wegener\u2019s granulomatosis. Arthritis\nRheum 1990;33:1101-1107\n\n\n\n11. I. Ponniah, Ahmed Shaheen, K. A. Shankar, M. G.\nKumaran. Weg e n e r \u2019s granulomatosis: The curr e n t\nunderstanding. India Oral Surgery Oral Medicine, Oral\nPa t h o l og y, Oral Radiology and Endodontolog y\n2005;100:265-70\n\n\n\n12. CC. Lapraik, R. Watts, P. Bacon et al. BSR and BHPR\nguidelines for the management of adults with\nANCA associated vasculitis. Rheumatolog y\n2007;46:1615-1616\n\n\n\n\n\n\n\n\n36 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nA\nbacterial Infection\nfungal infection \nallergy \nviral exanthem \ndrug exanthem \nskin scalding syndrome\natopic dermatitis \ncandidiasis \nimpetigo \nseborrhoeic dermatitis\n\n\n\nB\nallergy\nADR\ndermatitis\nbacterial infection\nviral infection\nangioedema\nphotodermatitis\nhypereosinophilic sensitivity syndrome\n(HESS/DRESS) \npsoriasis\ncontact dermatitis\n\n\n\nC\nallergy\nskin infection \ndermatitis\nimpetigo \nacne \ndeep fungal infection \nchickenpox\nviral wart\nmolluscum contagiosum \neczema herpeticum\n\n\n\nSlide A\n\n\n\nTick at the provided space [\uf061] against answers that correlate to the slide. \nCheck your answer on page 45. Refer to the given criteria in page 46 to discover your clinical diagnostic skill\nstatus.\n\n\n\nSlide B\n\n\n\nSlide C\n\n\n\nGENERAL DERMAT O L O G Y - Self Assessment\n\n\n\nClinical diagnostic skill test\n\n\n\n\n\n\n\n\n37MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nD\ndeep fungal infection\ncutaneous tuberculosis\natypical mycobacterium infection\ntumour \nlymphadenitis \nabscess \nsquamous cell carcinoma \nsporothricosis \nfish tank granuloma\n\n\n\nE\nallergy\nnon infective inflammation\ndermatitis\ninsect bite reaction \nautoimmune disease\ncontact dermatitis \nbullous impetigo \npemphigoid \npemphigus \neczema herpeticum\n\n\n\nF\nADR\nhormonal disorders\nfungal infection\nviral infection\nappendageal disorders\ncandidiasis\nvaricella zoster\nmilia crystalina\nherpes viral infection\nmolluscum contagiosum\n\n\n\nSlide D\n\n\n\nSlide E\n\n\n\nSlide F\n\n\n\n\n\n\n\n\n38 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPA E D I ATRIC DERMAT O L O G Y - Original Art i c l e\n\n\n\nA study of the cause and prognosis of\nc h ronic Urticaria in Malaysian children                                               \nSabeera B1, MMED(Paeds), Asmah J2, MMED, Mardziah A1, MMED(Paeds)\n\n\n\nAbstract\n\n\n\nThe aetiologies of chronic urticaria (CU) in childhood remains incompletely understood because of\nlimited data in children. The objective of this study was to determine the clinical features,\naetiological factors, and response to treatment of chronic urticaria (CU) in children by focusing on\nthe autoimmune and IgE, urticarial vasculitis, parasitic infestation and food allergy. Children 2\u201316\nyr of age with CU were investigated for complete blood count, erythrocyte sedimentation rate (ESR),\nantinuclear antibody (ANA), complement factors, ASST, Radioallergosorbent test (RAST), urine\ncultures and stool examination for parasites. Twenty five children who met the criteria for CU were\nrecruited. None of these patients had clinical features of urticarial vasculitis. None had raised ESR\nor CRP and all had normal infective screening. Positive ASST was found in 60%. There were no\ndifferences in medication requirement and CU remission between patients with positive and negative\nASST. None had parasites infestation. RAST to foods was positive in 25%. Food avoidance was\nbeneficial to the subgroup of patients with positive history of food allergy. The prognosis for\nspontaneous remission is good in children with chronic urticaria.\n\n\n\nKeywords Chronic urticaria, prognosis, causes\n\n\n\nCorrespondence\nSabeera B, MMED (Paeds)\nInstitute of Paediatrics\nHospital Kuala Lumpur\nE-mail : dr_sabeera@yahoo.com\n\n\n\nMethodology\nA total of 25 children were studied from the age of\n2 to 16 years. The study was undertaken at the\nInstitute of Paediatrics, Hospital Kuala Lumpur\n(HKL) over a 2 year period from July 2002 to July\n2004. The diagnosis was made on clinical grounds.\nChronic and intermittent urticaria were identified\nconventionally5.\n\n\n\nInitial evaluation\nThe history was taken using a questionnaire, which\nincludes demography, relevant history on foods,\ndrugs, infections, infestations, aggravating physical\nfactors, family history, general medical history,\nhistory of immunization, possible insect stings, and\nother supposedly allergic events.\n\n\n\nA full physical examination was carried out and the\nduration and specific features of individual wheals\nwere asessed.\n\n\n\nLaboratory investigations included a full blood\npicture, ESR, LFT, CPK, CRP, serum antibodies to\nEBV, CMV, Hep B & C, Toxoplasma, Enteroviruses\nand Herpes simplex, total IgE, specific IgE to\npenicillin, milk proteins and other foods, ANF,\ncomplement profile and serum protein\nelectrophoresis\n\n\n\nIntroduction\nUrticaria is a distressing skin eruption and may be\nacute, chronic or intermittent, with or without\nangioedema. Around 25% of the population suffer\nfrom urticaria at some time in their lives, causing\nc o n s i d e r a ble discomfort1. Various aetiolog i c a l\nfactors have been identifi e d, howeve r, the\nprevalence of the subtypes in children is essentially\nunknown, and the aetiological factors in paediatric\nurticaria have not been fully investigated. Recently,\na specific autoimmune mechanism has been\nidentified as causative by Greaves MW2,3 and has\nbeen repeatedly confi rmed independently\ne l s ewhere. Autoimmune urticaria has been\ndemonstrated in childhood4,  but its prevalence,\nsignificance and prognosis in this age group has yet\nto be determined.\n\n\n\nThe aim of this study is to determine the clinical\nfeatures, aetiological factors, and response to\ntreatment of chronic urticaria (CU) in children.\n\n\n\n\n\n\n\n\n39MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nelectrophoresis. The specific IgE was analy s e d\nusing Pharmacia CAP-RAST system. The normal\nvalue for total IgE is less than 100 ku/L and less\nthan 0.35 ku/L for specific IgE.\n\n\n\nMicrobiological studies included urine microscopy\nand culture and stool examination for ova and cysts. \n\n\n\nAutologous serum skin test (ASST) to support the\ndiagnosis of autoimmune urticaria was performed\nusing the technique as described by Greaves MW\net al2. The ASST has a sensitivity of approximately\n70% and a specificity of 80%.\n\n\n\nSkin biopsy was carried out in children suspected to\nhave urticarial vasculitis clinically. These children\nwere followed up every 3 months for a year to\ndetermine the treatment response and outcome of\nCU.\n\n\n\nPatients with acute urticaria and with seve r e\nsystemic illness were excluded. The study was\napproved by the local ethics committee.\n\n\n\nDefinition\nUrticaria is defined as pruritic wheals which last for\nless than 24 hours. CU is defined as the presence of\ndaily or almost daily wheals for at least 6 weeks.\nIntermitent urticaria is recurrent bouts of urticaria\nwhich lasts up to 6 weeks or more for each episode.\n\n\n\nAnalysis of data\nStatistical analysis was carried out using SPSS\nprogramme. \n\n\n\nResults\n\n\n\nDemographic data\nThere were fourteen (56%) Malays, 7 (28%)\nChinese and 4 (16%) Indian children. Thirteen\n(52%) were males and 12 (48%) females. The male\nto female ratio was 1.1:1. The children we r e\nbetween 2 to 16 years old with a mean age of 7.5\nyears.\n\n\n\nClinical presentation\nThirty two percent of the children were 3 years old\nat the onset of symptoms. Twenty percent were\nmore than 10 years and the mean age at onset was\n5.6 years. The duration of symptoms ranged\nbetween 2.5 months and 100 months with a mean of\n13 months.\n\n\n\nAll had pruritus and wheals on the limbs, palms and\nsoles. Eighty four percent had wheals on the face\nand perioral region. Only two children had\nangioedema. Most of the children had wh e a l s\nintermittently (72%) rather than on a continuous\n(28%) basis. Ninety six percent of the wheals were\nannular in shape.\n\n\n\nTwenty five percent had a positive family history of\natopy such as asthma, eczema and rhinitis. One out\nof 25 children had wheals lasting more than 24\nhours, but the skin biopsy did not show any features\nof urticarial vasculitis.\n\n\n\nInvestigations\nAll the total white blood cell counts were normal\n(range: 4 to 10 x 109 cells/L) and the mean WBC\nwas 6.7 x 109 cells/L. The mean eosinophil and\nbasophil counts were 3.0% and 0.9% respectively.\nHowever, none of the children had a positive stool\nfor ova and cysts. Urine culture and sensitivity were\nnormal in all children. All the children had a\nnegative blood test for Hepatitis A, B and C. None\nhad a  positive  antinuclear factor.\n\n\n\nThe mean total IgE was 770ku/L (range: 60 to\n3351ku/L). Twenty two children had their total IgE\nanalysed and 72% were positive. The IgE level to\npeanut was positive in two children (8%) but only\none was symptomatic with pruritus and wheals. Six\nchildren were positive to fish (4%) but only two\nwere symptomatic with pruritus and wheals. Three\nchildren were positive to milk (12%) but only two\nwere symptomatic with pruritus and wheals. One\nchild was symptomatic and positive to wh e a t .\nTwenty four percent were positive for egg and 8%\nfor wheat and soy (Figure 1).\n\n\n\nASST was tested in all children, and 60% were\np o s i t ive. The basophil counts were low in 13\nchildren but the eosinophil counts were all normal.\nThere is a statistically significant association\nbetween the basophil count and the ASST with a p\nvalue of 0.001. The ASST correlates inversely to the\nbasophil count (r=- 0 .752).\n\n\n\nSixteen percent of children had a history of taking\nantibiotics prior to the development of urticaria and\nnone took non steroidal anti-inflammatory drugs.\nNone of the children had any associated infection or\ncomplaints of passing out worms. \n\n\n\n\n\n\n\n\n40 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAlthough the mechanisms responsible for CU are\nnot fully understood, it has recently been\ndocumented of a strong association with the\npresence of circulating functional autoantibodies\ndirected against either the high affinity IgE receptor\n(Fc_RI_) and/or against IgE2,6,7. Evidence for an\nassociation between circulating autoantibodies and\nCU in children is larg e ly restricted to thy r o i d\nautoantibodies.8 Other aetiologies for both children\nand adults with CU include viral infection, parasitic\ninfestation, food allergy, food additive reactions\nand aeroallergen allerg y9 , 1 0 , 1 1. None of these\nsatisfactorily account for all patients with CU.\n\n\n\nLow basophil count (55%) is demonstrated in this\nstudy. Basophil paucity was also demonstrated in\nother studies12. The finding that peripheral blood\nbasophils are reduced or absent in patients with CU\nwith histamine-releasing autoantibodies may prove\nto be a helpful clinical marker of autoimmune\nu rticaria once rapid and reliable methods for\nmeasuring small numbers of circulating basophils\nare available13.\n\n\n\nSixty percent of our children were positive to ASST.\nThe ASST is currently the best in vivo clinical test\nfor detection of in vitro basophil histamine-\nreleasing activity14. ASST is correlated inversely to\nthe basophil count15.\n\n\n\nSuspected physical factors which aggravated the\nsymptoms were cold water in one child, thirteen to\nsweating and seven to exercise. The other four did\nnot have any aggravating factors. No children had\ninsect bites, previous history of immunization or\nother allergic events.\n\n\n\nTreatment and outcome\nAlmost all the children received an H1 antagonist\n(either loratidine or ceterizine) for symptomatic\nrelief and none required prednisolone or an H2\nantagonist. Sixty percent went into remission and\n40% were still on treatment. Fourty seven percent of\nchildren with autoimmune urticaria, went into\nremission by one year. Only ten percent of children\nwith cholinergic urticaria went into remission. \n\n\n\nDiscussion\nAlthough urticaria is common in children, the\naetiological factors causing CU among them are\nlimited and only a few reports have been published\non this subject. \n\n\n\nIn our study, associated angioedema was not as\ncommonly reported as in other studies5. Only two\nchildren had angioedema, one to wheat and the\nother child to seafood.\n\n\n\nFigure 1 RAST test for specific food\n\n\n\n\n\n\n\n\n41MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nReferences\n\n\n\n1. O\u2019Donnell BF, Lawlor F, Simpson J, Morgan M,\nGreaves MW. The impact of chronic urticaria on quality\nof life. Br J Dermatol 1997;136: 197-201\n\n\n\n2. Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP,\nGreaves MW. Autoantibodies against the high affinity\nIgE receptor as a cause of histamine release in chronic\nurticaria. N Eng J Med 1993;328(22):1599-1604\n\n\n\n3. G r e aves MW. Chronic Urticaria. N Eng J Med\n1995;332:1767\n\n\n\n4. Greaves MW. Chronic Urticaria in childhood. Allergy\n2000;55(4):309-320\n\n\n\n5. Champion RH, Roberts SOB, Carpenter RG, Roger JH.\nUrticaria and angioedema - a review of 554 patients. Br\nJ Dermatol 1969;81:588-9\n\n\n\n6. Sabroe RA, Francis DM, Greaves MW Chronic\nidiophatic urticaria: comparison of the clinical features\nof patients with and without FcRI or anti-IgE\nautoantibodies. J Am Acad Dermatol. 1999;44:446-\n452\n\n\n\n7. Tong LJ, Balakrishnan G, Kochan JP, Kinet J-P, Kaplan\nA P. Assessment of autoimmunity in patients with\nchronic urticaria. J Allergy Clin Immunol 1997;99:461-\n465\n\n\n\n8. Levy YSN, Weintrob N, Danon YL. Chronic Urticaria:\nassociation with thyroid autoimmunity. Arch Dis Child\n2003; 88:517-519\n\n\n\n9. Dalal I, Levine A, Somekh E, Mizrahi A, Hanukoglu. A\nchronic urticaria in children: expanding the\nautoimmune kaleidoscope.  Pediatrics 2000;106:1074-\n1077\n\n\n\n10. Volonakis M, Stratigos J. Etilogical factors in\nchildhood chronic urticaria. Ann Allergy 1992;69:61-\n65\n\n\n\n11. Harris A, Geha RS. Chronic urticaria in childhood;\nnatural course and aetiology Ann Allergy 1983;51:161-\n165\n\n\n\n12. Rorsman H. Basopenia in urticaria. Acta A l l e rg o l\n1962;17:168-184\n\n\n\n13. Grattan CEH, Walpole D, Francis DM, Niimi N,\nDootson G, Edler S, et al. Flow cytometric analysis of\nbasophils numbers in chronic urticaria: basopenia is\nrelated to serum histamine releasing in chronic urticaria\nClin Exp Allergy 1997;27:1417-1424\n\n\n\n14. Grattan CEH, Sabroe RA, Greaves MW. Chronic\nurticaria. J Am Acad Dermatol 2002;46:645-657\n\n\n\n15. Sabore RA, Grattan CEH, Francis DM, Barr BM,\nKobza Black A, Greaves MW. The Autologous serum\nskin test: a screening test for autoantibodies in chronic\nidiophatic urticaria. Br J Dermatol 1999;140(3):446-\n453\n\n\n\n16. G r e aves MW. Chronic Urticaria. J A l l e rgy Clin\nImmunol 2000;105(4):664-672\n\n\n\n17. Kozel MMA, Mekkes JR, Bossuyt PMM, Bos JD.\nNatural history of physical and chronic urticaria and\nangioedema in 220 patients. J Am Acad Dermatol\n2001;45:387-391\n\n\n\n18. Van Der Valk PGM, Moret G, Kiemeney LALM. The\nnatural history of CU and angioedema in patients\nvisiting a tertiary centre. Br J Dermato 2002;146:110-\n113\n\n\n\nThe normal eosinophil counts and the absence of\nparasites in stool do not support the role of\nhelminthic infestation as the cause of CU in this\nstudy.\n\n\n\nFood allergy was implicated in 25% of children\nwith positive specific IgE to wheat, milk, egg and\npeanuts.\n\n\n\nTwenty percent of children had suspected physical\nurticaria especially, cholinergic urticaria.\n\n\n\nOral antihistamines are the mainstay of treatment\nfor CU. They reduce the itch and wheal. In this\nseries, nearly all children were symptomatically\nrelieved with oral antihistamine except for one child\nrequiring systemic steroid16.\n\n\n\nSixty percent went into complete remission by one\nyear. In other studies, 35% went into remission and\n29% had reduced symptoms17,18.\n\n\n\nConclusion\nThis study demonstrated that nearly 25% of CU\npatients had no laboratory abnorm a l i t y. A n\nautoimmune mechanism may underlie the\npathogenesis of chronic urticaria in a subset of\nchildren and CAU was identified in more than one-\nthird these children. However, a long-term follow-\nup would be important to identify any association of\nCAU and other autoimmune diseases. Urticarial\nvasculitis was not identified in the absence of\ntypical clinical features. Food allergy wa s\nencountered in a small number of patients and\nclinical significance was found in the subgroup of\npatients with positive history of allergy to related\nfoods. Avoidance of specific foods could be of\nb e n e fit in a subgroup of patients. Pa r a s i t i c\ninfestation was not found in our children with CU.\nOverall, our investigation supports the concept that\ndetailed history taking and thorough examination\nwill help to avoid unnecessary investigations. And\nin general, the prognosis for spontaneous remission\nis good in children with chronic urticaria.\n\n\n\n\n\n\n\n\n42 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPA E D I ATRIC DERMAT O L O G Y - Short Communication\n\n\n\nN e t h e rton Syndrome presenting as\nE ry t h ro d e rma in newborn\nRaoul RS1, MBBS, Muzhirah AH2, MRCPCH, Suhaila O2, MRCPCH, Rohna R1, MRCP\n\n\n\nCorrespondence\nRaoul Roger Sibert\nDepartment of Dermatology\nSelayang Hospital \nE-mail : Raoul@selayanghospital.gov.my\n\n\n\n1Department of Dermatology, Selayang Hospital \n2Department of Paediatrics, Selayang Hospital \n\n\n\nDear Editor,\n\n\n\nWe would like to report a new b o rn with\nerythroderma. He was born borderline premature\nvia emergency C-section. He did not have any\nfamily history of atopy or skin disease. He was born\nwith a paper thin erythematous dry scaly skin with\nerythema seen prominently on the scalp, face, neck,\nears, perigenital and gluteal regions. The nails and\nmucous membranes were spared. Staphylococcus\ncoagulase negative bacteria was isolated from blood\nculture during this time and he was treated with the\nappropriate intravenous antibiotics. However, the\nwhole skin gradually became more erythrodermic\nwith extensive scaling. He later developed severe\nhy p e rnatremic dehydration which required\naggressive fluid resuscitation. This was attributed to\nextreme insensible fluid loss.\n\n\n\nDue to the worsening skin condition, a skin biopsy\nwas performed  which revealed features suggestive\nof Congenital Ichthyosis. Histopathology of the\nskin revealed mild hyperkeratosis, parakeratosis\n\n\n\nwith acanthosis and mild spongiosis. The upper\ndermis showed mild lymphocytic infiltrate in the\nsuperficial perivascular region. He was reviewed by\na visiting Paediatric Dermatologist and a diagnosis\nof Netherton Syndrome (NS) was entertained when\nhis scalp hair showed trichorr h exis inva g i n a t a .\nImmunodeficiency work up was also carried out\nr evealing generalized hy p oga m m a g l o bu l i n e m i a .\nThe patient was treated with emollients and mild\ntopical steroids. He was discharged well after\nachieving his birth weight at Day 10 of life.\n\n\n\nHe was closely monitored for infections and weight\ngain during his clinic follow up. His skin condition\ns h owed tremendous improvement with topical\napplications alone. After the first few months of\nlife, the erythroderma slowly resolved  and plaques\ntypical of ichthyosis became evident. Despite being\nable to tolerate well orally, he had chronic diarrhoea\nwith severe failure to thrive and had to be admitted\nat 6 months of age for observation of feeding\npattern and optimization of his calorie intake. He\nd eveloped multiple complications during this\nadmission\n\n\n\nFigure 1 Generalised scaly and paper thin\nskin at birth Figure 2 Erythroderma at 6 weeks of life\n\n\n\n\n\n\n\n\n43MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nadmission including difficulty in setting the\nintravenous line, hypoglycaemia and severe osmotic\nd i a rrhoea. He was discharged against medical\nadvice and was brought in very ill a few days later\nto Casualty where he succumbed despite active\nresuscitation.\n\n\n\nThe early diagnosis of the NS is usually difficult\ndue to erythroderma in the first few months of life,\nwhich later slowly disappears, and lesions typical of\nichthyosis linearis circumflexa become evident as\nin this patient. During the first months of life\ne ry t h r o d e rma predominates with hy p e rn a t r e m i c\ndehydration and failure to thrive. Erythroderma can\nbe caused by multiple factors: immunodeficiency,\nmetabolic disease like acrodermatitis enteropathica,\ni c h t hyosis, atopic dermatitis, psoriasis and\ns e b o rrhoeic dermatitis. Sometimes the origin\nremains unknown. The specificity of clinical and\nhistopathological features is low in neonates and\ntherefore there is usually a delay before the final\ndiagnosis is established. \n\n\n\nUltrastructural analyses of skin in patients with NS,\ncongenital ichthyo s i f o rm ery t h r o d e rma, and\nerythrodermic psoriasis can be of great value in\nestablishing a correct diagnosis1. Ultrastructural\na n a lyses of skin in patients with NS show\nreplacement of stratum corneum with parakeratotic\ncells. Distinctive features include premature\nsecretion of lamellar bodies and foci of electron\ndense material in the intercellular spaces of stratum\nc o rneum, which are not observed in other\nerythrodermic disorders, appear to be frequent and\nrelatively specific markers for NS. Ultrastructural\nanalyses of the skin of patients with NS may\nfacilitate the early diagnosis of NS2.\n\n\n\nE ry t h r o d e rmic neonates are at risk of sepsis,\nhypernatremic dehydration, malnutrition, failure to\nthrive, and other life threatening conditions.  In\nsome patients with NS an interm i t t e n t\naminoaciduria has been observed3. It has been\nproposed that increased caloric demands\nconsequent to increased epidermal metabolism and\nhyper proliferation are the basis for failure to thrive\nin this condition. However, it is unclear whether the\ncaloric and nutrient drain of a hy p e rm e t a b o l i c\nepidermis alone can account for the extra caloric\nrequirements for adequate weight gain in children\nwith this condition.\n\n\n\nSpecific nutritional deficiencies arising from skin\nexfoliation or gastrointestinal malabsorption may\nalso be a problem. Nutritional deficiencies could\nexacerbate the barrier defect in these patients. For\nexample, essential fatty acids may be lost through\nex c e s s ive desquamation, and ga s t r o i n t e s t i n a l\nmalabsorption, if present, could further amplify this\ndeficiency. Linoleic acid is a critical constituent of\nthe stratum corneum lamellar membranes. Essential\nfatty acid defi c i e n cy results in an epiderm a l\nphenotype characterized by ery t h r o d e rm a ,\nhy p e rplasia, and transepidermal water loss\n(TEWL), a phenotype similar to that seen in\npatients with erythrodermic ichthyosis . Thus, a\npotentially vicious cycle could arise in patients with\ni c h t hyosis who also have essential fatty acid\ndeficiency.\n\n\n\nGastrointestinal malabsorption from a primary or\ns e c o n d a ry enteropathy may also contribute to\ngrowth failure in these patients. Two studies have\ndemonstrated jejunal villous atrophy in some\ninfants and children with Netherton syndrome. Our\npatient suffered from gastrointestinal involvement4\n\n\n\nwhich could be the reason for the dystrophy and a\npoor weight gain during his infancy period.\n\n\n\nIn the second year of life, the erythroderma slowly\ndisappears and migr a t o ry gyrate lesions with\ndouble-edged scaling become evident. Hair shaft\nabnormalities on the scalp manifest as trichorrhexis\ninvaginata, pili torti and/or trichorrhexis nodosa5.\nIn our patient, ultra structural analysis of the hair\ndisclosed trichorrhexis invaginata. Some patients\ncan remain severely affected with erythrodermic\nflares or have ery t h r o d e rma with pustules6. In\npatients with NS, atopy is usually manifested as\nangioedema, allergic rhinitis, asthma, urticaria and\nelevated IgE7,8. Our patient was not tested for IgE.\nPatients with NS usually have normal values of\ns e rum immunog l o bulin levels but selective\nantibody defi c i e n cy to bacterial poly s a c c h a r i d e\nantigens can be found, so it is important to evaluate\nthe functional antibody response to both protein and\nbacterial polysaccharide4. In our patient the IgG,\nIgA and IgM were low.\n\n\n\nT h e r a py with topical steroids, tars, emollients,\nP U VA, and oral vitamin A deriva t ives is not\nsatisfactory, and offers temporary effects5,9. Long-\nterm treatment with topical tacalcitol was tried in a\nfew cases with good results and without severe side\neffects, but its effect should be additionally proven\non\n\n\n\n\n\n\n\n\n44 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\non a larger group of patients. Children with\ni c h t hyosis and gr owth failure may have\nuncompensated caloric needs because of an\nimpaired skin barrier (unpublished data).\nGastrointestinal dysfunction and nutritional\ndeficiencies are uncommon and do not appear to be\np r i m a ry causes of the gr owth failure in these\nchildren. Because growth failure is of early onset in\nthese children, we suggest that nutritional\nevaluation and caloric supplementation should be\ninstituted early to maximize growth potential. Close\nmonitoring of patient\u2019s nutritional status as well as\nprompt recognition and treatment of infections are\nfundamental in ensuring patient\u2019s surv ival to\nadulthood. In our patient, even the strict\nhy p o a l l e rgenic diet did not improve the skin\ncondition and dystrophy, characterized by a poor\nweight gain.\n\n\n\nN e t h e rton Syndrome should be excluded in\nn ew b o rns presenting with ery t h r o d e rma. Close\nmonitoring, continuous intensive therapy, repeated\nfamily education and support on how to cope with a\nchild with a chronic disease is necessary for better\noutcome.\n\n\n\nReferences\n\n\n\n1. Williams ML. Ichthyosis and Disorders of\nCornification. In: Schachner LA, Hansen RC eds.\nPaediatric Derm a t o l og y. New York: Churchill\nLivingstone, 1988: 412\n\n\n\n2. Fartasch M, Williams ML, Elias PM. Altered lamellar\nbody secretion and stratum corneum membrane\nstructure in Netherton syndrome: differentiation from\nother infantile ery t h r o d e rmas and pathog e n i c\nimplication. Arch Dermatol 1999; 135: 823-32\n\n\n\n3. Caputo R, Vanutti P, Bertani E. Interm i t t e n t\naminoaciduria have been observed in some patients.\nArch Dermatol 1984; 120: 220-2\n\n\n\n4. S c h wayder T, Bernarjee S. Netherton syndrome\npresenting as congenital psoriasis. Pediatr Dermatol\n1997; 14: 473-6\n\n\n\n5. Blaschke S, M\u00f6ller R, Hauser I, Lamprecht IA, Paul E.\nComel-Netherton-Syndrom. Hautartzt 1998; 49: 499-\n504\n\n\n\n6. Judge MR, Morgan G, Harper JI. A clinical and\nimmunological study of Netherton syndrome. Br J\nDermatol 1994; 131: 615-21\n\n\n\n7. Judge MR, Green SL, M\u00fcller SA. Netherton syndrome.\nReport of a case and review of the literature. J Am Acad\nDermatol 1985; 13: 329-37\n\n\n\n8. Plautin P, Delaire P, Guillet MH, Labouche F, Guillet G.\nNetherton syndrome, current aspects. A propose of 9\ncases. Ann Dermat et Venereol 1991; 118: 525-30\n\n\n\n9. K a n s ky A, Po d rumac B, Prelog I. Hereditary\nichthyosis. Pathogenesis and possibilities of treatment.\nACTA Dermatoven APA 1997; 6: 47-54\n\n\n\n\n\n\n\n\n45MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAnswers to Clinical Diagnositic Skill Te s t\n\n\n\nSlide A bacterial Infection\nfungal infection \nallergy \nviral exanthem \ndrug exanthem \nskin scalding syndrome\natopic dermatitis \ncandidiasis \nimpetigo \nseborrhoeic dermatitis\n\n\n\nSlide B allergy\nADR\ndermatitis\nbacterial infection\nviral infection\nangioedema\nphotodermatitis\nhypereosinophilic sensitivity \nsyndrome (HESS/DRESS) \npsoriasis\ncontact dermatitis\n\n\n\nSlide C allergy\nskin infection \ndermatitis\nimpetigo \nacne \ndeep fungal infection \nchickenpox\nviral wart\nmolluscum contagiosum \neczema herpeticum\n\n\n\nSlide D granuloma\ndeep fungal infection\ncutaneous tuberculosis\natypical mycobacterium infection\ntumour \nlymphadenitis \nabscess \nSquamous cell carcinoma \nsporothricosis \nfish tank granuloma\n\n\n\nSuspect cutaneous deep fungal infection or\natypical mycobacterial infection if there is a\npersistent ulcer with multiple nodules arranging in\na linear fashion (lesion with sporothricoid or\nlymphatic spread).\n\n\n\nSuspect cutaneous deep fungal infection when\npatient with human immunodeficiency virus\npresents with persistent crops of papular lesions\nwith central umbilication or scab on the face.\nFungal spores can be detected by bedside Tzanck\ntest within one day if the facility is available. Thus\nurgent antifungal therapy can be instituted as this\nsign is an AIDS defining disease.\n\n\n\nWhen patient presents with angioedema with\ndermatitis or vasculitis, think of hypereosinopilic\nsensitivity syndrome especially if patient has been\non medication before development of skin lesions.\nThis condition may be associated with fever,\neosinophilia and raised liver enzymes. If the drug\nis not stopped, it can result in prolonged morbidity.\n\n\n\nThis patient has skin scalding syndrome as\nevidence by the golden crust radiating from the\ncorners of the corners of the mouth & eyes. It is\nimportant to recognise this condition because of\nthe risk of toxaemia. Misdiagnosis can result in\nfatality if therapy is delayed.\n\n\n\n1\n-2\n0\n0\n0\n2\n\n\n\n-2\n-1\n\n\n\n-1\n-1\n\n\n\n1\n1\n\n\n\n-2\n-2\n-2\n\n\n\n-2\n-2\n2\n\n\n\n-2\n-2\n\n\n\n-3\n1\n\n\n\n-3\n-3\n-2\n\n\n\n2\n1\n\n\n\n-2\n1\n1\n\n\n\n1\n1\n1\n1\n0\n\n\n\n1\n1\n0\n1\n1\n\n\n\n\n\n\n\n\n46 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nSlide E allergy\nnon infective inflammation\ndermatitis\ninsect bite reaction \nautoimmune disease\ncontact dermatitis \nbullous impetigo \npemphigoid \npemphigus \neczema herpeticum\n\n\n\nSlide F ADR\nhormonal disorders\nfungal infection\nviral infection\nappendageal disorders\ncandidiasis\nvaricella zoster\nmilia crystalina\nherpes viral infection\nmolluscum contagiosum\n\n\n\nFirm pearly papules with central umbilication in\nchildren prompt the diagnosis of molluscum\ncontagiosum.\n\n\n\nSuspect autoimmune bullous disease if an adult\npresent with flaccid blisters that ends in crust.\nIt can be induced by certain drug ingestion.\nMisdiagnosis may result in delayed\ncommencement of immunosuppressant resulting\nin prolonged morbidity and can be fatal if\nuntreated.\n\n\n\n0\n1\n\n\n\n-3\n-2\n1\n\n\n\n-3\n-3\n1\n2\n\n\n\n-3\n\n\n\n-1\n-2\n-2\n1\n\n\n\n-2\n\n\n\n-2\n0\n\n\n\n-2\n0\n2\n\n\n\nH ow did you performed? You should aim for correct diagnosis and minimize delayed diagnosis.\n\n\n\nSum up the number of score 2, 1 , 0 , - 1 , -2 and -3 that you have collected.\n\n\n\nSCORE\n\n\n\n-3\n\n\n\n-2\n\n\n\n-1\n\n\n\n0\n\n\n\n1\n\n\n\n2\n\n\n\nTOTAL NUMBER COLLECTED IMPLICATION\n\n\n\nDelayed diagnosis may result in irreversible outcome / deformity\n\n\n\nDelayed diagnosis may result in prolonged morbidity\n\n\n\nTherapy for wrong diagnosis may worsen the primary skin lesion\n\n\n\nNo effect on outcome of primary skin lesion but cost wastage of \nmedication, investigation kit and money\n\n\n\nTherapy for this diagnosis can have good outcome\n\n\n\nCorrect diagnosis enables appropriate investigations, thearpy and even \nlong term follow-up\n\n\n\n\n\n\n\n\n\n"
"\n\n35\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nAntibiotic Resistance Pattern of Neisseria gonorrhoeae in \nHospital Kuala Lumpur, Malaysia (2001-2005)\n\n\n\nAzura Mohd Affandi, MBBS, MRCP, HB Gangaram, MBBS, FRCP and Suraiya H Hussein, MBBS, FRCP\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur\nKuala Lumpur\n\n\n\nCorrespondence\n\n\n\nAzura Mohd Affandi, MBBS, MRCP\n\n\n\nGenito-urinary (GUM) Medicine Clinic\nDepartment of Dermatology, Hospital Kuala Lumpur \n50580 Kuala Lumpur\nEmail : affandi_azura@yahoo.co.uk\n\n\n\nAbstract\n\n\n\nBackground Gonorrhoea is the third most common sexually\ntransmitted infection (after syphilis and non-gonococcal urethritis)\nseen in patients attending the Genitourinary Medicine (GUM) Clinic\nin Hospital Kuala Lumpur (HKL). Its association with poor\nreproductive health outcomes and the increasing prevalence of\nantimicrobial resistance has made it a major public health concern.\n\n\n\nObjective To determine the antibiotic resistance pattern of Neisseria\nGonorrhoeae in patients attending the GUM Clinic in HKL and its\ncomparison with other countries.\n\n\n\nMethod A retrospective study of all patients with gonorrhoea (new and\nrecurrent) between 2001-2005. Antimicrobial susceptibility testing by\nstandard disc diffusion method was performed to detect sensitivity to\npenicillin, tetracycline, kanamycin, ciprofloxacin, spectinomycin,\nceftriaxone and cefuroxime.\n\n\n\nResults A total of 416 positive culture isolates of N.gonorrhoeae from\n2001-2005 were reviewed. Highest level of resistance was detected to\ntetracycline (86.8% of 296 isolates). Resistance to penicillin was noted\nin 64.4% of all isolates. Penicillinase Producing N.gonorrhoeae (PPNG)\naccounted for 62% of cases. Both penicillin and tetracycline showed an\nincreasing resistance trend from 2001-2005. The third commonest\nantibiotic resistance was to kanamycin (38.3%), followed by\nciprofloxacin (10.4%). The resistance to spectinomycin was 1.7%. No\nresistance was detected to ceftriaxone and cefuroxime. All gonorrhea\npatients in GUM Clinic, HKL were treated with ceftriaxone, and\nsubsequent cultures on follow-up were negative. We compared our\nresults with the data obtained from the Gonococcal Resistance to\nAntimicrobials Surveillance Programme (GRASP)6 and the WHO\nWestern Pacific Gonococcal Antimicrobial Surveillance Programme\n(GASP)7.\n\n\n\nConclusion Penicillin and tetracycline resistance remain high in\nMalaysia and other Western Pacific countries. Resistance to\nciprofloxacin was however lower in Malaysia compared to other\ncountries. There was no resistance to ceftriaxone and cefuroxime. The\ncurrent first line antibiotic for treating gonorrhoea in GUM Clinic,\nHKL is ceftriaxone.\n\n\n\nKeywords Gonorrhoea, Antibiotic Resistance Pattern\n\n\n\nIntroduction\nGonorrhoea is amongst the most common sexually\ntransmitted infections in the world and is caused by gram\nnegative bacterium Neisseria gonorrhoeae. It usually infects\nthe mucosal surfaces, causing sexually transmitted urethritis\nin men and endocervicitis in women. It can also cause\nanorectal and pharyngeal infections and in neonates,\nophthalmic infection is acquired during passage through the\nbirth canal. Complications particularly affect women, and\ninclude salpingitis, pelvic inflammatory disease, first\ntrimester abortion and decreased fertility. In men, extension\nof mucosal infection to contiguous areas may give rise to\nepididymo-orchitis and thus reduced fertility. In a small\nproportion of patients, gonococcaemia may occur and result\nin septic arthritis, endocarditis and meningitis. It is well\nrecognized that gonorrhea, together with genital ulcer\ndisease, are potent amplifiers of the spread of HIV1. Rates\nof HIV transmission in those with gonorrhoea may be as\nmuch as 5 times more than in persons without gonorrhoea1.\nThose with gonorrhoea are also more susceptible to\nacquisition of HIV infection2.\n\n\n\nGonorrhoea remains a major global disease with an\nestimated 60 million cases per year globally, making it a\nmajor public health concern3. About half of these cases\noccur in the Western Pacific and South East Asia regions5.\nIn GUM Clinic, HKL, gonorrhoea accounts for the third\nmost common sexually transmitted infection (after syphilis\nand non-gonococcal urethritis). In the recent years,\nincidence of gonorrhoea has also increased in other\ndeveloped countries, with the highest rates in the socially\nand economically deprived subpopulations, and in\nhomosexual men4.\n\n\n\n\n\n\n\n\n36\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAttempts to treat and control gonorrhoea are compromised\nby the emergence and spread of antibiotic resistant Neisseria\ngonorrhoeae. There are many surveillance programmes on\nantibiotic resistance pattern of N.gonorrhoeae  such as\nGRASP (Gonococcal Resistance to Antimicrobial\nSurveilance Programme), which is based in London, UK\nand WHO WPR GASP (World Health Organization\nWestern Pacific Region Gonococcal Antimicrobial\nSurveilance Programme)5, 6. Tetracycline resistance is\nencountered in many countries. Since penicillin resistance\nemerged in the late 1970\u2019s, it has spread to most parts of the\nworld7. This is either due to Penicillinase Producing\nNeisseria gonorrhoeae (PPNG) or chromosomally mediated\nresistance (CMRNG). South East Asian countries are\nnoted to have high PPNG rates7. Resistance to quinolones\nwas first observed in the South East Asia and the Western\nPacific regions in the 1990\u2019s, and have now spread widely\nwithin and beyond the Western Pacific Regions8. There\nwere also reported cases of altered susceptibility to third\ngeneration cephalosporin in the Western Pacific Region9, 10\n\n\n\nand recently these strains have also appeared in centres\noutside the region. Antibiotic resistance pattern vary\nbetween different geographical areas. Therefore, it is\nimportant to know the local antibiotic resistance pattern, so\nthat appropriate treatment can be instituted. In HKL,\nkanamycin was used during the early 1970\u2019s and 80\u2019s, which\nwas subsequently changed to spectinomycin, followed by\nceftriaxone since the early 1990\u2019s.\n\n\n\nObjectives\nTo determine the antibiotic resistance pattern of\nN.gonorrhoeae in patients attending the GUM Clinic, HKL\nand to compare it with other countries.\n\n\n\nMaterials and methods\nThis is a retrospective study of all patients with gonorrhoea\n(new and recurrent), attending the GUM Clinic, HKL\nbetween 2001-2005. Antimicrobial susceptibility testing by\nstandard disc diffusion method was performed to detect\nresistance to penicillin, tetracycline, kanamycin,\nciprofloxacin, spectinomycin, ceftriaxone and cefuroxime.\nAll information was obtained from patients\u2019 case notes.\n\n\n\nResults\nA total of 416 positive culture isolates of Neisseria\ngonorrhoeae from 2001-2005 were reviewed. The number\nof isolates for each year is shown in Table 1.\n\n\n\nTable 1.   Positive culture isolates of N.gonorrhoeae\n\n\n\nDemographics\nMajority of the patients (51.7%) were between the ages of\n21-30 years old (Figure 1). 96.6% were males and 3.4%\nfemales. The majority of the patients were Malays (63.7%),\nfollowed by Indian (23.6%), Chinese (8.9%) and others\n(3.8%). (Racial distribution of patients attending the GUM\nClinic, HKL from 2001-2005 : Malay-44.7%, Indian-25.3%\nChinese-18.6% and Others-11.4%).\n\n\n\nNumber of isolates\n81\n\n\n\n86\n\n\n\n72\n\n\n\n89\n\n\n\n88\n\n\n\n416\n\n\n\nYEAR\n2001\n\n\n\n2002\n\n\n\n2003\n\n\n\n2004\n\n\n\n2005\n\n\n\nTOTAL\n\n\n\nFigure 1.   Age of patients with gonorrhoea (n=416)\n\n\n\n\n\n\n\n\nYear / Antibiotics\n\n\n\nTetracycline\n\n\n\nPenicillin\n\n\n\nPPNG \n\n\n\nCMRNG\n\n\n\nKanamycin\n\n\n\nCiprofloxacin\n\n\n\nSpectinomycin\n\n\n\nCefuroxime\n\n\n\nCeftriaxone\n\n\n\n37\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 2.   Summary of antibiotic resistance pattern of N.gonorrhoeae (2001-2005)\n\n\n\nFigure 2.   Antibiotic resistance pattern of N.gonorrhoeae (2001-2005)\n\n\n\n2001\n\n\n\nND\n\n\n\n54.3%\n(44/81)\n\n\n\n49.4%\n(40/81)\n\n\n\n4.9%\n(4/81)\n\n\n\n13.6%\n(11/81)\n\n\n\nND\n\n\n\n1.2%\n(1/82)\n\n\n\n0%\n(0/81)\n\n\n\n0%\n(0/81)\n\n\n\n2002\n\n\n\n57.4%\n(27/47)\n\n\n\n65.1%\n(56/86)\n\n\n\n50%\n(43/86)\n\n\n\n15.1%\n(13/86)\n\n\n\n89.7%\n(35/39)\n\n\n\n8.7%\n(4/46)\n\n\n\n2.3%\n(2/86)\n\n\n\n0%\n(0/39)\n\n\n\n0%\n(0/86)\n\n\n\n2003\n\n\n\n76.4%\n(55/72)\n\n\n\n41.7%\n(30/72)\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\n10.5%\n(6/57)\n\n\n\n0%\n(0/9)\n\n\n\nND\n\n\n\n0%\n(0/72)\n\n\n\n2004\n\n\n\n100%\n(89/89)\n\n\n\n70.8%\n(63/89)\n\n\n\nND\n\n\n\nND\n\n\n\nND\n\n\n\n9.0%\n(8/89)\n\n\n\nND\n\n\n\nND\n\n\n\n0%\n(0/89)\n\n\n\n2005\n\n\n\n97.7%\n(86/88)\n\n\n\n85.2%\n(75/88)\n\n\n\n85.2%\n(75/88)\n\n\n\n0%\n(0/88)\n\n\n\nND\n\n\n\n12.5%\n(11/88)\n\n\n\nND\n\n\n\nND\n\n\n\n0%\n(0/88)\n\n\n\nOverall (2001-05)\n\n\n\n86.8%\n(257/296)\n\n\n\n64.4%\n(268/416)\n\n\n\n62%\n(158/255)\n\n\n\n6.7%\n(17/255)\n\n\n\n38.3%\n(46/120)\n\n\n\n10.4%\n(29/280)\n\n\n\n1.7%\n(3/177)\n\n\n\n0%\n(0/120)\n\n\n\n0%\n(0/416)\n\n\n\nND - Not done\n\n\n\n\n\n\n\n\n38\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 3.   Overall antibiotic resistance pattern of N.gonorrhoeae (2001-2005) \n\n\n\nFigure 4.   Resistance of N.gonorrhoeae to Penicillin\n\n\n\n\n\n\n\n\n39\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nAntibiotic resistance pattern of\n\n\n\nNeisseria gonorrhoeae\n\n\n\n1. Tetracycline\nTetracycline has never been used for treating gonorrhoea in\nHKL as the resistance is very high. Nevertheless, the\nresistance pattern is continuously monitored for\nepidemiological purposes. In 2002, 57.4% of the isolates\nwere resistant to tetracycline and the levels have continued\nto rise, reaching 100% in 2004 (Table 2 and Figure 2). The\noverall tetracycline resistance from 2001-2005 is 86.8%\n(Figure 3).\n\n\n\n2. Penicillin\nResistance to penicillin also showed an increasing trend\nfrom 54.3% in 2001 to 85.2% in 2005 (Table 2 and Figure\n2). The overall resistance rate from 2001 to 2005 is 64.4%\n(Figure 3). This can be due to Penicillinase Producing\nN.gonorrhoeae (PPNG) or Chromosomal Mediated\nResistance N.gonorrhoeae (CMRNG) (Figure 4). Of the\nisolates resistant to penicillin, 62% were PPNG and 6.7%\nCMRNG.\n\n\n\n3. Kanamycin\nKanamycin was used for treating gonorrhoea in HKL in the\nearly 1970\u2019s and 80\u2019s. However, because of increasing\nresistance since the early 1990\u2019s, it is not used anymore.\nResistance of N.gonorrhoeae to kanamycin was done in 2001\nand 2002 only. There was a marked increase in the\nresistance pattern from 13.6% in 2001 to 89.7% in 2002\n(Table 2 and Figure 2). The overall resistance to kanamycin\nfrom 2001 to 2005 is 38.3% (Figure 3).\n\n\n\n4. Ciprofloxacin\nCiprofloxacin is not the first line treatment for gonorrhoea\nin our clinic. However, it is used by the primary care doctors\nfor treating gonorrhoea due to its accessibility and ease of\nadministration. Susceptibility testing to ciprofloxacin was\ndone since 2002. There was a gradual increase from 8.7% in\n2002 to 12.5% in 2005 (Table 2 and Figure 2). The overall\nresistance rate from 2001-2005 is 10.4% (Figure 3).\n\n\n\n5. Spectinomycin\nSpectinomycin showed a low resistance rate of 1.2% in 2001\nand 2.3% in 2002 (Table 2 and Figure 2). The susceptibility\ntesting was discontinued in 2003. The overall resistance to\nspectinomycin from 2001-2005 is 1.7% (Figure 3).\n\n\n\n6. Cephalosporins - Cefuroxime and Ceftriaaxone\nSusceptibilty of N.gonorrhoeae to cefuroxime was tested in\n2001 and 2002. None of the isolates were found to be\nresistant to cefuroxime. Similarly, since 2001 to 2005, none\nof the N.gonorrhoeae isolates were found to be resistant to\nceftriaxone (Table 2, Figure 2 and Figure 3). All patients in\nour clinic were treated with ceftriaxone and subsequent\ncultures on follow-up were negative.\n\n\n\n7. Multi-resistant N.gonorrhoeae\n44.3% of the N.gonorrhoeae isolates were found to be\nresistant to both penicillin and tetracycline. 5.1% of the\nisolates were resistant to all 3 antibiotics-penicillin,\ntetracycline and ciprofloxacin.\n\n\n\nCountry / Centre\n\n\n\nHKL (2001-05)\n(n= 416)\n\n\n\nSingapore7\n\n\n\n(n= 160)\n\n\n\nPhilippines7\n\n\n\n(n= 175)\n\n\n\nNew Zealand7\n\n\n\n(n= 773)\n\n\n\nAustralia7\n\n\n\n(n= 3,542)\n\n\n\nChina7\n\n\n\n(n= 1,203)\n\n\n\nEngland and Wales6\n\n\n\n(n= 1,744)\n\n\n\nTable 3.   Comparison of N.gonorrhoeae antibiotic resistance pattern in Hospital Kuala Lumpur (HKL)\nwith other countries\n\n\n\n% Tetracycline\nResistant\n\n\n\n86.8\n\n\n\n71.9\n\n\n\n8.0\n\n\n\n17.9\n\n\n\n13.8\n\n\n\n34.2\n\n\n\n44.5\n\n\n\n% Penicillin  Resistant\nOverall\n\n\n\n64.4\n\n\n\n50.5\n\n\n\n51.4\n\n\n\n5.8\n\n\n\n21.7\n\n\n\n75.2\n\n\n\n11.2\n\n\n\nPPNG\n\n\n\n62\n\n\n\n48.7\n\n\n\n37.1\n\n\n\n3.7\n\n\n\n11.1\n\n\n\n48.8\n\n\n\n5.9\n\n\n\n% Ciprofloxacin\nResistant\n\n\n\n10.4\n\n\n\n56.2\n\n\n\n48.5\n\n\n\n20.9\n\n\n\n23.3\n\n\n\n99.2\n\n\n\n14.1\n\n\n\n7The WHO Western Pacific Gonococcal Antimicrobial Surveilance Programme (GASP) 2004\n6The Gonococcal Resistance to Antimicrobials Surveilance Programme (GRASP) 2004\n\n\n\n\n\n\n\n\n40\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe summary of N.gonorrhoeae antibiotic resistance pattern\nfrom 2001 to 2005 is illustrated in Table 2 and Figure 2.\nThe overall (average) antibiotic resistance pattern from\n2001-2005 is shown in Figure 3.\n\n\n\nConclusion\nAttempts to treat and control gonorrhoea are compromised\nby the emergence and spread of antibiotic-resistant N.\ngonorrhoeae. WHO expert committee has recommended\nthat treatment regimens be altered once resistance to a\nparticular antibiotic reaches 5 percent.11 Penicillin and\ntetracycline resistant N.gonorrhoeae remain high in Malaysia\nand other Western Pacific countries and the resistance rate\ncontinue to increase. Resistance to ciprofloxacin was\nhowever lower in Malaysia compared to other countries.\nHowever, the level is gradually increasing and has to be\nmonitored closely. Current first line antibiotic for treating\ngonorrhoea in GUM Clinic, HKL is ceftriaxone, which has\nno documented resistance so far.\n\n\n\nAcknowledgement\nWe would like to convey our special gratitude to Dr Akbal\nKaur, Encik Othman Thani and other staff from the\nGenitourinary Medicine Clinic, HKL for data collection.\n\n\n\nReferences\n\n\n\n1. Cohen MS. Sexually transmitted diseases enhance HIV \ntransmission: no longer a hypothesis. Lancet 1998;351\n(Suppl III):5-7.\n\n\n\n2. Cohen MS, Hoffman IF, Royce RA et al. Reduction of \nconcentration of HIV-1 in semen after treatment of urethritis: \nimplications for prevention of transmission of HIV-1. Lancet \n1997;349:1868-73.\n\n\n\n3. Gerbase AC, Rowley JT, Heyman DHL, Berkley SFB, Piot P. \nGlobal prevalence and incidence estimates of selected curable \nSTDs. Sex Transm Inf 1998;74 (suppl 1):S12-S16.\n\n\n\n4. Surveillance of antibiotic resistance in Neisseria gonorrhoeae \nin the WHO Western Pacific Region, 1998. Commun Dis Intell \n2000;24:1-4.\n\n\n\n5. Tapsall JW. Antibiotic Reistance in Neisseria gonorrhoeae. Clin \nInfect Dis 2005;41:S263-268.\n\n\n\n6. GRASP Steering Group. The Gonococcal Resistance to \nAntimicrobials Surveillance Programme (GRASP) Year 2004 \nreport. London: Health Protection Agency 2005.\n\n\n\n7. The WHO Western Pacific Gonococcal Antimicrobial \nSurveillance Programme. Surveillance of antibiotic resistance in \nNeisseria gonorrhoeae in the WHO Western Pacific Region, \n2004. Commun Dis Intell 2006;30:129\u2013132.\n\n\n\n8. WHO Western Pacific Region Gonococcal Antimicrobial \nSurveillance Programme. Surveillance of antibiotic \nsusceptibility of Neisseria gonorrhoeae in the WHO Western \nPacific Region 1992\u20134. Genitourin Med 1997;73:355\u2013361. \n\n\n\n9. The WHO Western Pacific Gonococcal Antimicrobial \nSurveillance Programme. Surveillance of antibiotic resistance in \nNeisseria gonorrhoeae in the WHO Western Pacific Region, \n2001. Commun Dis Intell 2002;26:541\u2013545. \n\n\n\n10. The WHO Western Pacific Gonococcal Antimicrobial \nSurveillance Programme. Surveillance of antibiotic resistance in \nNeisseria gonorrhoeae in the WHO Western Pacific Region, \n2000. Commun Dis Intell 2001;25:274-276. \n\n\n\n11. Guidelines for the management of sexually transmitted \ninfections WHO/HIV-AIDS. Geneva: World Health Organization; \n2001. Report No.WHO/RHR/01.10. Available online.  \nURL:http://www.who.int/docstore/hiv/STIManagemntguidelines\n/who_hiv_aids_2001.01/ \n\n\n\n12. Ito M, Deguchi T, Mizutani KS, Yasuda M, Yokoi S, Ito S et al. \nEmergence and spread of Neisseria gonorrhoeae clinical \nisolates harbouring mossaic-like structure of penicillin-binding \nprotein 2 in Japan. Antimicrob Agent Chemother 2005;49:137-\n143. \n\n\n\n13. Tapsall JW. Annual Report of the Australian Gonococcal \nSurveilance Programme, 2004. Commun Dis Intell 2005;29:136-\n141.\n\n\n\n14. Wang SA, Lee MV, O\u2019Connor N, Iverson CJ, Ohye RG, Whiticar \nPM et al. Multidrug-resistant Neisseria gonorrhoeae with \ndecreased susceptibility to cefixime - Hawaii, 2001. Clin Infect \nDis 2003;37:849-852.\n\n\n\n\n\n\n\n\n41\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nA 10-year Retrospective Study on Changing Pattern\nof Sexually Transmitted Infections in\nHospital Kuala Lumpur, Malaysia\n\n\n\nPenny Lim, MBBS, MRCP, HB Gangaram, MBBS, FRCP and Suraiya H Hussein, MBBS, FRCP\n\n\n\nGenito-Urinary Medicine (GUM) Clinic\nDepartment of Dermatology, Hospital Kuala Lumpur \n50580 Kuala Lumpur\n\n\n\nCorrespondence\n\n\n\nDr Penny Lim Poh Lu, MBBS, MRCP\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur \n50580 Kuala Lumpur\nEmail : teoleetam@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Sexually transmitted infections (STIs), and HIV\nespecially, are a major health problem in Malaysia. The emergence of\nHIV infection has increased the importance of early and effective\ntreatment of STIs as any delay may lead to enhance transmission or\nacquisition of HIV infection. A proper understanding of the patterns\nof STIs is necessary for effective planning and control strategies. The\npresent study is designed to determine the changing pattern of STIs in\nthe  Genito-urinary Medicine Clinic (GUM), Hospital Kuala Lumpur\n(HKL).\n\n\n\nObjective To study the sociodemographic characteristics of patients\nwith STIs attending the GUM Clinic in HKL and to analyze any\nchanges in the pattern of STIs seen between the 2 study periods of\n1995-1999 and 2001-2005.\n\n\n\nMethod A retrospective review of case notes of new patients with\nSTIs attending the GUM clinic, HKL was done during two study\nperiods of 1995-1999 (Poster presentation on \u201cPattern of STDs\u201d at\n14th RCD, Asia-Australasia, 26-30 July 2000, KL, Malaysia by HB\nGangaram et al) and 2001-2005.\n\n\n\nResults In 1995-1999, a total of 3150 STI patients were studied.\nAmong them, 2016 (64%) were males and 1134 (36%) were females. In\n2001-2005, a total of 2909 STI patients were examined, of which 1862\n(64%) were males and 1047 (36%) were female. There was a decrease\nof 8.3% in the total number of cases seen in 2001-2005 as compared to\n1995-1999. The decline was more evident with bacterial STIs which\nincluded syphilis, gonorrhoea, NGU and chancroid. Viral STIs which\nconsisted of herpes genitalis, genital warts and HIV showed an\nincreasing  trend.\n\n\n\nA younger age group (20-39 years old) appeared to be infected with\nSTIs in 2001-2005. Males outnumbered females in the ratio of 1.8:1,\n\n\n\nwhich remained unchanged in both the study periods. Based on\nethnicity, there was an increase in the percentage of Malays being\ninfected in STIs in the later study period. Syphilis was the commonest\nSTI seen in both the study periods. The second commonest STI seen\nin 1995-1999 was gonorrhoea and non-gonococcal urethritis (NGU).\nIn 2005, there were 184 patients with syphilis; 64% were heterosexuals;\n39.6% homosexuals and 1.6% bisexuals. Majority (82%) were\nasymptomatic (latent syphilis with positive syphilis serology at\npresentation. Symptomatic patients with early infectious syphilis\nconstituted 15% (Primary 8%; Secondary 7%). Screening for HIV was\npositive in 31 (16.8%) patients. HIV infection was noted to be the\ncommonest STI associated with syphilis.\n\n\n\nConclusion was an overall decline in the number of patients with\nSTIs attending the GUM clinic, HKL. The decline was more evident\nwith bacterial STIs; viral STIs however showed an increasing trend.\nSyphilis was still the commonest STI seen in the two study periods\nalthough the percentage has declined. Non specific urethritis has\nsuperseded gonorrhoea as the second commonest STI. HIV was found\nto be the commonest STI seen in association with syphilis.\n\n\n\nKeywords Changing pattern, Sexually transmitted infections, STI\n\n\n\nIntroduction\nNearly one million new people are infected with sexually\n\n\n\ntransmitted infections (STIs) every day nationwide. World\nHealth Organization (WHO) estimated that approximately\n340 million new cases of the four main curable STIs\ngonorrhoea, NGU, syphilis and trichomoniasis occur every\nyear2,13. STIs are responsible for an enormous burden on\nmorbidity and mortality in many developing countries\nbecause of their effects on reproductive and child health and\ntheir role\n\n\n\n\n\n\n\n\n42\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ntheir role in facilitating the transmission of HIV infection.\nThe emergence of HIV infection has increased the\nimportance of measures aimed at control of STIs. A proper\nunderstanding of the patterns of STIs prevailing in different\ngeographic regions of a country is necessary for proper\nplanning and implementation of STI control strategies4. It\nis with this aim that the present study was undertaken.\n\n\n\nObjectives\nTo study the sociodemographic characteristics of patients\nwith STIs attending the Genitourinary Medicine Clinic\n(GUM), Hospital Kuala Lumpur and to analyze any\nchanges in the pattern of STIs seen between the 2 study\nperiods of 1995-1999 and 2001-2005.\n\n\n\nMaterials and Methods\nThis is a retrospective review of case notes of new patients\nwith STIs attending the GUM Clinic, HKL during two\nstudy periods of 1995-1999 and 2001-2005. The National\nStatistics figures were obtained from the Department of\nPublic Health, Malaysia.\n\n\n\nResults\nThis study included a total of 2909 patients in 2001-2005\nas compared to 3150 patients in 1995-1999 (Table 1).\nThere was a decrease of 8.3% in the total number of cases\nseen in 2001-2005.\n\n\n\nMajority of the patients (51.7%) were between the ages of\n30-49 years old in 1995-1999. In the present study, a\nyounger age group between 20-39 years old appear to be\ninfected with STIs1,2,3,4,9,10 as shown in Figure 2. 64% were\nmales and 34% females in both the study periods. In 1995-\n1999, Malay comprised the majority of the patients (38%),\nfollowed by Indian (22%), Chinese (17%), foreigners (18%)\nand others (5%). In 2001-2005, there is was increase in the\npercentage of Malays (47.8%) being infected with STIs,\nfollowed by Indian (21.4%), Chinese(18.9%), foreigners\n(8.0%) and others (3.9%) (refer Figure 2). (Ethnic\nDistribution of Patients Attending the GUM Clinic, HKL from\n2001-2005 : Malay-44.7%, Indian-25.3% Chinese-18.6%\nand Others-11.4%).\n\n\n\nFigure 1.   Total number of new patients with STI in GUM\nClinic, HKL\n\n\n\nFigure 2.   Age distribution of new patients with STI\n\n\n\nTable 1.   Classification of Syphilis in GUM Clinic 2005 (n=184)\n\n\n\nT\nO\n\n\n\nT\nA\n\n\n\nL\n\n\n\nAge group (Age)\n\n\n\n\n\n\n\n\n43\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nSyphilis was the commonest STI seen in both the study\nperiods although there was a decline from 982 (31.2%) to\n702 (24.1%) (Figure 5). In 2005, there were 184 patients.\n118 (64.1%) were heterosexual, 73 (39.6%) homosexuals\nand 3 (1.6%) and 3 (1.6%) bisexuals (Figure 7). Majority\n(82%) were asymptomatic (latent syphilis with positive\nsyphilis serology at presentation (Table 1). The second\n\n\n\ncommonest STI seen in 1995-1999 was gonorrhoea and\nnon-gonococcal urethritis (NGU) in the present study\n(Figure 5). Generally, there was an overall decrease in\nbacterial STI (syphilis, gonorrhoea, NGU and chancroid)\nwith an increase in viral STI (genital warts, genital herpes\nand HIV)1,4,8,9 Figure 6.\n\n\n\nFigure 3.   Sex distribution of new patients with STI\n\n\n\nFigure 4.   Ethnic distribution of new patients with STI\n\n\n\n\n\n\n\n\n44\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 5.   Types of STIs between 1995-1999 and 2001-2005\n\n\n\nFigure 6.   Comparison between Bacterial STI and Viral STI\n\n\n\nT\ny\np\n\n\n\ne\ns\n o\n\n\n\nf \nS\n\n\n\nT\nIs\n\n\n\n\n\n\n\n\n45\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nHIV seropositivity was 5.3% of all clinic attendes during 2001-2005. Of these 78 % were males and 22% females. 68 %\nwere homosexuals, 24% heterosexuals and 8% bisexuals in HIV male patients. Chinese comprised the majority of patients\n(65%) followed by Malays (18%), Indian (15%) and others (2%). Majority of patients were in the age group 21-40 years\nold which is also the most sexually active age group.\n\n\n\nFigure 7.   Syphilis in GUM Clinic, HKL 2005 (n=184)\n\n\n\nFigure 8.   HIV patients in GUM Clinic, HKL 2001-2005 (n=154)\n\n\n\n\n\n\n\n\n46\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nThis study demonstrated an overall decline in the total\nnumber of STI cases1,4,8.9. The total number of patients with\nbacterial STIs such as syphilis, chancroid and gonorrhoea\nalso showed a declining trend. However there was an\nincrease in viral STIs like HIV, herpes genitalis and genital\nwarts. This is similar to the findings in other studies. This\ndecline in the number of patients with STIs attending the\nGUM clinic could be attributed to either a true decline in\nSTIs with the onset of HIV more commonly patients\nseeking treatment at private general practitioner (GP)\nclinic, expecting more confidentiality in dealing with these\ndiseases. Awareness and fear of contracting HIV have\ninfluenced the risk-taking behaviour of people, thereby\nreducing the likelihood of being infected with STIs.\n\n\n\nIn the present study, males outnumbered females by 1.8:1.\nThis pattern of male preponderance is also seen in other\nstudies1,4,8,9. Of particular interest, the age group with the\nhighest number of cases has shifted to a younger age11,14 (20-\n39 years old ). This is not surprising as the average age for\nsexual debut nowadays occurs earlier. Factors that could\ncontribute to this include increasing exposure to sex\nperiodicals, advertisements, the theater, radio, television and\nthe internet. This group are at a high risk of being\nbehaviourally more vulnerable to STI acquisition, as they\ngenerally have a higher number of sexual partners and more\nconcurrent partnerships and change partners more often\nthan older age groups. Being the economically productive\ngroup, there is great loss of workforce due to STI morbidity,\nmeasured as disability adjusted life years (DALYS)1 lost.\nAlthough the teenagers were not spared, the percentage of\nSTI cases was not high. Nevertheless the young adults and\nadolescents should constitute the priority target group in\nSTI control programme.\n\n\n\nThe disporportionate attendance of Chinese patients could\nbe their preference for seeking treatment from GP clinics as\ncompared to government hospitals/ clinics.\n\n\n\nSyphilis is the commonest STI seen in both the study\nperiods although there is a decline. Of the different types,\nlatent syphilis was the most common. The second\ncommonest STI seen in 1995-1999 was gonorrhoea whilst\nin the present study it was non-gonococcal urethritis\n(NGU). This pattern change was also seen in most\ncountries. HIV was the commonest STI seen in association\nwith syphilis. Syphilis increases the risk of both\ntransmitting and getting infected with HIV and can be\nharder to cure and may progress more quickly and severely\nin people infected with HIV2. However, further studies are\nrequired to confirm this association.\n\n\n\nConclusions\nThere was an overall decline in the total number of patients\nwith STIs attending the GUM Clinic, HKL. The decline\nwas more evident with bacterial STIs; viral STIs however\nshowed an increasing trend. Syphilis was still the\ncommonest STI seen in the two study periods although the\npercentage has declined. NGU has superseded gonorrhoea\nas the second commonest STI. HIV was found to be the\nmost common STI seen in association with syphilis.\n\n\n\nAcknowledgement\nWe would like to convey our special gratitude to Dr Akbal\nKaur, Encik Abdul Manaf B. Yusoff and other staff from\nGenitourinary Medicine Clinic, HKL for data collection.\n\n\n\nReferences\n\n\n\n1. Krishna Ray et al; Changing trends in sexually transmitted \ninfections at a Regional STD Centre in north India; Indian J Med \nRes 2006;124:559-68-.\n\n\n\n2. WHO Europe; Trends in sexually transmitted infections and HIV \nin the European Region, 1980-2005; technical briefing document \n01B/06, Copenhagen, 12 September 2006.\n\n\n\n3. Sevgi O. Aral et al; Sexually Transmitted Infections and HIV in \nthe Southern United States: An Overview; Sexually Transmitted \nDiseases; July (suppl) 2006;33(7):1-5.\n\n\n\n4. Narayanan B; A retrospective study of the pattern of sexually \ntransmitted diseases during a ten-year period; IJDVL \n2005;71(5):333-7.\n\n\n\n5. Kevin A. Fenton et al; Reported Sexually Transmitted Disease \nClinic Attendance and Sexually Transmitted Infections in Britain: \nPrevalence, Risk factors and Proportionate Population Burden; \nThe Journal of Infectious Diseases 2005;191(Suppl 1):127-38.\n\n\n\n6. Christopher J. Smith; Social geography of sexually transmitted \ndiseases in China; Asia Pacific Viewpoint; April 2005;46(1):65-80. \n\n\n\n7. E.N. Nnoruka and A.C.J.Ezeoke; Evaluation of syphilis in patients \nwith HIV infection in Nigeria; Tropical Medicine and \nInternational Health; Jan 2005;10:58-64.\n\n\n\n8. Abdul Wahab Al-Fouzan and Nawaf Al- Mutairi; Overview of \nIncidence of Sexually Transmitted Diseases in Kuwait; Clinics in \nDermatology; 2004; 22:509-512.\n\n\n\n9. Sharma VK, Khandpur S.; Changing patterns of sexually \ntransmitted infections in India, Natl Medical Journal India;\n2004;17(6):310-319.\n\n\n\n10. Jaswal AK et al; Changing trends in Sexually transmitted \ndiseases in North Eastern India; IJDVL2002;68(2):65-66.\n\n\n\n11. Hiok-Hee Tan, Roy Chan; Sexually transmitted infections in \nSingapore Youths; National Skin Centre, Singapore 2005.\n\n\n\n12. William K.Bosu; Syndromic management of sexually transmitted \ndiseases; Tropical Medicine and International Health ; February \n1999:(4);2:114-119.\n\n\n\n13. WHO, Office of Information; Sexually transmitted infections \nincreasing- 250 million new infections annually,1990;(152):1-6. \n\n\n\n14. Donald WH; The changing pattern of sexually transmitted \ndiseases in adolescents; Practitioner;1979; 222(1329):383-5.\n\n\n\n15. Raval RC et al; A study of a changing patterns of sexually \ntransmitted diseases and HIV prevalence during intervals of \ndifferent years; International Conference AIDS July 7-12, \n2002;14: Abstract No. C10895\n\n\n\n\n\n\n\n\n47\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nAllergic Contact Dermatitis in a private practice \nDermatology Clinic in Ipoh: A Seven-Year Retrospective\nStudy \n\n\n\nHenry BB Foong, MBBS, FRCP1, Elizabeth M Taylor, MBBS1 and N Ibrahim2\n\n\n\n1Foong Skin Specialist Clinic\n33A Persiaran Pearl, Fair Park, Ipoh 31400, Malaysia\n2Medical Student (Phase 3A), Universiti Kuala Lumpur Royal\nCollege of Medicine Perak, Ipoh, Malaysia\n\n\n\nCorrespondence\n\n\n\nHBB Foong, FRCP,\nFoong Skin Specialist Clinic\n33A Persiaran Pearl, Fair Park, Ipoh 31400, Malaysia\nEmail : bbfoong@pc.jaring.my\n\n\n\nAbstract\n\n\n\nPatch testing has been accepted as the most important investigative\ntechnique of assessing allergic contact dermatitis (ACD) and\nidentifying the contact allergens. The epidemiology of ACD differs in\ndifferent geographic region as the environmental allergens vary in\ndifferent populations. In this study 59.8% of the patients had a positive\npatch test reaction to one or more allergens. The prevalence of ACD\nwas 64.7% in women and 51.4% in men. The commonest causes of\nACD were nickel (30.4%), fragrance mix (18.16%) and balsam of Peru\n(6.73%).\n\n\n\nKeywords contact dermatitis, prevalence, patch tests\n\n\n\nIntroduction\nPatch testing has been accepted as the most important\ninvestigative technique of assessing allergic contact\ndermatitis (ACD) and identifying the contact allergens1\n\n\n\nThe epidemiology of ACD differs in different geographic\nregion as the environmental allergens vary in different\npopulations. A study done in Hospital Kuala Lumpur using\nthe European standard allergens for the period 1994-1996\nshowed the top three allergens to be nickel (36%), rubber\nchemicals (19%) and fragrance mix (17%) while in\nSingapore nickel (13.9%), fragrance mix (8.4%), flavine\n(6.3%) and potassium dichromate (6.3%)2,3. The prevalence\nof ACD in 2471 patients patch tested in Singapore was\n49.2% in women and 49.8% in men3. The epidemiology of\nACD in a private practice dermatology clinic has not been\nwell documented. This is an epidemiologic study of ACD of\npatients attending a private practice dermatology specialist\nclinic in Ipoh. It also aims to identify the most common\ncontact allergens in this population.\n\n\n\nMaterials and methods\nAll patients seen at the Foong Skin Specialist Clinic\nbetween 1999 and 2006 who have had patch tests done were\nincluded in the study. The age and sex of the patient were\n\n\n\nrecorded. All were patch tested to the NSC standard battery\n(Chemotechnique) and additional allergens where\nindicated. The test allergens were mounted on Scanpore\ntape. The allergens were removed at 48 hours and reaction\nrecorded 15 minutes after removal. The reactions were\nrecorded again at 96 hours.\n\n\n\nReactions were recorded according to the standard scoring\nsystem recommended by International Contact Dermatitis\nResearch Group. NR = nonreactive; +/- = erythema; + =\nerythema with papules; ++ = palpable erythema, papules and\nvesicles; +++ = palpable erythema, vesicles, bullae; IR =\nirritant reactions. Reactions of + and greater were\nconsidered positive. The prevalence of ACD (patients with\none or more positive reactions) was evaluated.\n\n\n\nResults\nDuring the study period, 317 women and 173 men were\npatch tested. The age ranged from 6-86 years with a mean\nof 37.5 years. The prevalence of contact dermatitis was\n64.7% (205/317) in women and 51.4% (89/173) in men.\n\n\n\nTable 1 shows the prevalence of positive reaction according\nto age and sex. Most were in the 20-29 years age group.\nThe rate appeared to increase with age. For those less than\n40 years old it was 58.2% (174/299) and more than 40 years\n62.8% (120/191).\n\n\n\nTable 2 shows the prevalence of contact dermatitis\naccording to the ethnic group. The rate was not significantly\ndifferent from the major ethnic groups but was highest in\nthe Chinese followed by Malays and Indians.\n\n\n\nTable 3 shows the prevalence of contact dermatitis to\nstandard allergens according to sex. Nickel (30.4%),\nfragrance mix (18.16%), Balsam of Peru (6.73%), cobalt\n(5.31%), potassium dichromate (3.47%), neomycin (3.27%),\nwool alcohol (3.27%) and parabens (3.27%). were the\ncommonest\n\n\n\n\n\n\n\n\n48\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.   Prevalence of Allergic Contact Dermatitis according to the age group and sex\n\n\n\nAge Group\n\n\n\n<20 yr\n\n\n\n20-29 yr\n\n\n\n30-39 yr\n\n\n\n40-49 yr\n\n\n\n>49 yr\n\n\n\nTotal\n\n\n\nFemale\n\n\n\n18/35 (51.4%)\n\n\n\n60/91 (65.9%)\n\n\n\n51/85 (60%)\n\n\n\n39/50 (78%)\n\n\n\n37/56 (66.1%)\n\n\n\n205/317 (64.7%)\n\n\n\nMale\n\n\n\n9/19 (47.4%)\n\n\n\n15/29 (51.7%)\n\n\n\n21/40 (52.5%)\n\n\n\n12/31 (38.7%)\n\n\n\n32/54 (59.3%)\n\n\n\n89/173 (51.4%)\n\n\n\nTotal\n\n\n\n27/54 (50%)\n\n\n\n75/120 (62.5%)\n\n\n\n72/125 (57.6%)\n\n\n\n51/81 (63%)\n\n\n\n69/110 (62.7%)\n\n\n\n294/490 (59.8%)\n\n\n\nTable 2.   Prevalence of Allergic Contact Dermatitis according to ethnic group and sex \n\n\n\nEthnic Group\n\n\n\nChinese\n\n\n\nMalays\n\n\n\nIndians\n\n\n\nOthers\n\n\n\nTotal\n\n\n\nFemale\n\n\n\n165/248 (66.5%)\n\n\n\n30/46 (65.2%)\n\n\n\n10/19 (52.6%)\n\n\n\n0/4\n\n\n\n205/317 (64.7%)\n\n\n\nMale\n\n\n\n72/128 (56.25%)\n\n\n\n11/28 (39.3%)\n\n\n\n5/12 (41.7%)\n\n\n\n1/5 (20%)\n\n\n\n89/173 (51.4%)\n\n\n\nTotal\n\n\n\n237/376 (63%)\n\n\n\n41/74 (55.4%)\n\n\n\n15/31 (48.4%)\n\n\n\n1/9 (11.1%)\n\n\n\n294/490 (59.8%)\n\n\n\nTable 3.   Prevalence of Allergic Contact Dermatitis according to standard battery\nallergens and sex.\n\n\n\nAllergens\nMetals\n\n\n\nNickel\n\n\n\nPotassium dichromate\n\n\n\nCobalt chloride\n\n\n\nMedicaments\n\n\n\nFlavine\n\n\n\nNeomycin\n\n\n\nRubber chemicals\n\n\n\nThiuram mix\n\n\n\nMercapto mix\n\n\n\nPreservatives/Fragrances\n\n\n\nFragrance mix\n\n\n\nBalsam of Peru\n\n\n\nWool Alcohol\n\n\n\nEthylenediamine\n\n\n\nChlorocresol\n\n\n\nParabens\n\n\n\nOthers\n\n\n\nColophony\n\n\n\nEpoxy resin\n\n\n\nPPD\n\n\n\nFemale n+317\n\n\n\n115 (36.3%)\n\n\n\n12 (3.79%)\n\n\n\n20 (6.31%)\n\n\n\n3 (0.95%)\n\n\n\n15 (4.73%)\n\n\n\n2 (0.63%)\n\n\n\n1 (0.32%)\n\n\n\n67 (21.14%)\n\n\n\n30 (9.46%)\n\n\n\n12 (3.79%)\n\n\n\n2 (0.63%)\n\n\n\n3 (0.95%)\n\n\n\n9 (2.84%)\n\n\n\n8 (2.52%)\n\n\n\n0\n\n\n\n0\n\n\n\nMale n=173\n\n\n\n34 (19.3%)\n\n\n\n5 (28.9%)\n\n\n\n6 (3.47%)\n\n\n\n3 (1.73%)\n\n\n\n1 (0.58%)\n\n\n\n2 (1.16%)\n\n\n\n2 (1.16%)\n\n\n\n22 (12.72%)\n\n\n\n3 (1.73%)\n\n\n\n4 (2.31%)\n\n\n\n1  (0.58%)\n\n\n\n3 (1.73%)\n\n\n\n7 (4.05%)\n\n\n\n3 (1.73%)\n\n\n\n3 (1.73%)\n\n\n\n1 (0.58%)\n\n\n\nTotal n=490\n\n\n\n149 (30.4%)\n\n\n\n17 (3.47%)\n\n\n\n26 (5.31%)\n\n\n\n6 (1.22%)\n\n\n\n16 (3.27%)\n\n\n\n4 (0.82%)\n\n\n\n3 (0.61%)\n\n\n\n89 (18.16%)\n\n\n\n33 (6.73%)\n\n\n\n16 (3.27%)\n\n\n\n3 (0.61%)\n\n\n\n6 (1.22%)\n\n\n\n16 (3.27%)\n\n\n\n11 (2.24%)\n\n\n\n3 (0.61%)\n\n\n\n1 (0.20%)\n\n\n\n\n\n\n\n\n49\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ncommonest allergens. Nickel allergy was more common in\nwomen. Female patients outnumbered the male patients in\ntheir allergens for the above except potassium dichromate\nand parabens where the reverse is true.\n\n\n\nDiscussion\nAllergic contact dermatitis (ACD) is an important\ndermatologic disease with considerable morbidity and\neconomic impact. It represents delayed type hypersensitivity\nto small molecular weight chemicals which acts as haptens.\nIt is caused when contact with a specific allergen elicits a\nspecific immunologic inflammatory response in the allergic\nindividual 24 to 72 hours after re-exposure. Diagnosis of\nACD is frequently facilitated or confirmed through the use\nof patch test procedure.\n\n\n\nThe prevalence of contact dermatitis to various allergens\ndiffers in different population group. Therefore, it is\nimportant for dermatologists to be aware of the common\nallergens and to monitor them in their place of practice. At\nour dermatology clinic in Ipoh, 59.8% of patients had a\npositive patch test reaction to one or more allergens. The\nprevalence was 49.5% in Singapore3, 55% in Scotland4 and\n60.5% in Spain5. In this study the prevalence of ACD and\nthe causative allergens are not much different from existing\npublished epidemiological studies.\n\n\n\nIt has been found that allergic contact dermatitis was more\nfrequent in women as compared to men6. The\npreponderance in women could be due to the high rate of\nsensitization to certain allergens such as nickel and\nfragrances. In our study the prevalence of allergic contact\ndermatitis was 64.7% (205/317) in women and 51.4%\n(89/173) in men. The prevalence of ACD was significantly\nhigher in women than in men. (test of significance, p value\n<0.05) However, Goh in his study found that men and\nwomen were equally susceptible to epicutaneous\nsensitization. In his study the prevalence was 49.2% in\nwomen and 49.8% in men3.\n\n\n\nACD in different ethnic groups has seldom been studied\nbefore. The prevalence between black and white Americans\nappeared to be the same8. In our study, Chinese had the\nhighest prevalence rate (63%), while Malays had a\nprevalence rate of 55.4% and  Indians 41.7%.\n\n\n\nNickel allergy (30.4%) was the commonest cause of ACD in\nour study. It was more common in women (36.3%) than in\nmen (19.3%). The unique ethnic lifestyle has brought about\npeculiar presentation of nickel allergy as scarf button\n\n\n\ndermatitis under the chin as a result of the pin worn by\nMuslim women. The use of costume jewellery and ear\npiercing are among the common causes of sensitization to\nnickel.\n\n\n\nFragrance mix (18.16%) was the second commonest contact\nallergen in this study. The rate appeared to be higher in\nwomen (21.14%) than in men (12.72%). Fragrance is\npresent in most perfumes, cosmetics, toiletries and many\nhousehold products. They are important in our community\nbecause they are widely used. Balsam of Peru formed the\nthird commonest contact allergen. Balsam of Peru is a plant\nproduct, a balsam derived from the trees of the genus\nMyroxylan found in Central and South America. It\ncontains a mixture of fragrance constituents such as\ncinnamic acid, eugenol, benzyl benzoate, benzyl alcohol,\nvanillin, etc. As such it is a useful marker to detect fragrance\nallergy. Not surprising, it was higher in women (9.74%)\nthan in men (1.73%).\n\n\n\nOther common contact allergens were cobalt (5.31%),\npotassium dichromate (3.47%), neomycin (3.27%), wool\nalcohol (3.27%) and parabens (3.27%). In women, co-\nsensitivity of cobalt and nickel occur commonly due to\nwearing of costume jewellery. In men, cobalt allergy is often\nassociated with chromate allergy due to occupational\ncement exposure.\n\n\n\nReferences\n\n\n\n1. Ang P, Ng SK.  Chapter editor: \u201cThe Principles and Practice of \nContact and Occupational Dermatology in the Asia-Pacific \nRegion.\u201d Edited by Ng SK and Goh CL. Investigative techniques \nin Contact Dermatitis.\u201d World Scientific 2001.\n\n\n\n2. Rohna R.  Pattern of contact and photocontact dermatitis at \nHospital Kuala Lumpur - a two year study (1994-1996).  Paper \npresented at the Update Contact Allergy Occup Dermatoses, \nKuala Lumpur, 6 April 1996.\n\n\n\n3. Goh CL. Epidemiology of Contact Allergy in Singapore. Int J \nDermatol 1998;27:308-311.\n\n\n\n4. Husain SL. Contact Dermatitis in the west of Scotland. Contact \nDermatitis 1977;3:327-332.\n\n\n\n5. Romaguera, C, Grimalt F.  Statistical and comparative study of \n4600 patients tested in Barcelona (1973-1977). Contact \nDermatitis 1980;6:309-315.\n\n\n\n6. Rees JL et al. Sex differences in susceptibility to development \nof contact hypersensitivity to dinitrochlorobenzene (DNCB) Br J \nDermatol 1989; 120:371-374.\n\n\n\n7. Hammershoy O.  Standard patch test results in 3225 consecutive \nDanish patients from 1973-1977.  Contact Dermatitis 1980; 6:263-\n268.\n\n\n\n8. Leyden JJ, Kligman AM.  Allergic contact dermatitis: sex \ndifferences.  Contact Dermatitis 1977; 3:332-336.\n\n\n\n\n\n\n\n\n50\n\n\n\n\n\n\n\n\n51\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nPrevalence of herpes simplex virus infection in patients \nwith genital herpes using the immunofluorescent\nantibody test\n\n\n\nHB Gangaram, MBBS, FRCP1, Akbal Kaur, MBBS1, S Mangalam, MBBS, FRCPath2 and Suraiya H Hussein, MBBS, FRCP1\n\n\n\n1Genito-Urinary Medicine Clinic, Department of Dermatology, \nHospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Department of Pathology, Hospital Kuala Lumpur\nKuala Lumpur, Malaysia\n\n\n\nCorrespondence\n\n\n\nGangaram Hemandas, MBBS, FRCP\n\n\n\nDepartment of Dermatology\nHospital Kuala Lumpur, 50586 Kuala Lumpur\nEmail : ghbelani@hotmail.com\n\n\n\nAbstract\n\n\n\nBackground Herpes genitalis (HG) is the commonest cause of\nsexually transmitted ulcerative disease in the world, including\nMalaysia1. Herpes simplex virus (HSV) type 2 is more frequently\nimplicated than HSV type 1. This pattern has seen some changes in\nmany parts of the world, with increasing HSV type 1 rates2.\n\n\n\nObjective The aim of this study was to determine the type of HSV\nimplicated in patients with herpes genitalis at the Genito-Urinary\nMedicine Clinic, Department of Dermatology, Hospital Kuala\nLumpur.\n\n\n\nMethods A retrospective study was undertaken on 242 patients with\na diagnosis of herpes genitalis at the Genito-Urinary Medicine Clinic\nfrom January 2000 to December 2004. The study included all cases of\ngenital herpes in patients aged over 12 years. The typing was done by a\nimmunofluorescent - labeled monoclonal antibody technique specific\nfor HSV antigens.\n\n\n\nResults Majority (76%) were between the ages of 20-49 years. Males\noutnumbered females by 1.6:1. Younger women (20-29 years old) tend\nto be more frequently affected than their male counterpart. One fourth\n(25.7%) of the patients reported having sex with sex workers and less\nthan 1% (0.4%) were sex workers. A significant percentage (30.5%) of\nmarried men reported extramarital relationship with sex workers or had\na casual or regular partner. Usage of condoms was low at 12%. Clinical\ndiagnosis at presentation was primary herpes genitalis (56%) and\nrecurrent (44%). 162 (67%) out of a total of 242 patients had the herpes\nimmunofluorescent test done. 110 (68%) of those done were negative.\nOnly 34 (21%) of patients with herpes genitalis had a positive\nimmunofluorescent antibody test. Of the 21%, herpes simplex virus\ntype 2 was found in 19 (12%) of patients with herpes genitalis, HSV\ntype 1 in 10 (6%) and HSV types 1 & 2 coinfection in 5 (3%) patients.\n\n\n\nConclusions In our study, HSV-2 was still more common causing\n57% of the cases seen, HSV-1 29% and HSV-1 and HSV-2\ncoinfection in 14%. An increased rate of HSV-1 seen could possibly be\ndue to a change in sexual behavior of the patients especially with\nregards to oro-genital sexual contact.\n\n\n\nKeywords Genital herpes, Immunofluorescent antibody test, HSV\ntypes\n\n\n\nIntroduction\nHerpes genitalis (HG) is the commonest cause of sexually\ntransmitted ulcerative disease in the world, including\nMalaysia1. It is associated with not only physical but also\nimportant psychosocial and economic consequences.\nHerpes simplex virus (HSV) type 2 is more frequently\nimplicated than type 1. This pattern has however seen some\nchanges in many parts of the world, with HSV type 1\nbecoming more common than HSV type 2. This is evident\nin most parts of the world including Australia, Europe and\nthe USA. Some of the reasons postulated included earlier\nonset of sexual debut, change in sexual behavior especially\nwith regards to oro-genital sexual contact and lower rates of\npre-pubertal HSV-12.\n\n\n\nThe aim of this study was to determine the type of HSV\nimplicated in patients with herpes genitalis at the Genito-\nUrinary Medicine Clinic, Department of Dermatology,\nHospital Kuala Lumpur.\n\n\n\nMaterials and Methods\nA retrospective study was undertaken on 242 patients with\na clinical diagnosis of herpes genitalis at the Genito-\nUrinary Medicine Clinic from January 2000 to December\n2004. The study included all clinical cases of genital herpes\nin patients aged over 12 years. Specimens were collected\nfrom\n\n\n\n\n\n\n\n\n52\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nfrom genital lesions with a cotton-tipped swab and smeared\nonto micro-wells of daflon-coated slides, air-dried, fixed\nwith acetone and stained with ImagenTM HSV-1 or HSV-\n2 using specific monoclonal antibodies conjugated to FITC\nin two individual wells, from Dalco Cytomation Co; United\n\n\n\nResults\n\n\n\nKingdom3. This direct immunofluorescent antibody\ntechnique (IFAT) read with a fluorescent microscope was\nutilized for HSV detection as well as typing. This is the\nroutine, cost-effective and rapid detection method for\ngenital HSV in this hospital.\n\n\n\nTable 1.   Total number of new cases of\nherpes genitalis by year (n=242)\n\n\n\nA total of 242 case notes were reviewed Majority of the patients were self-referred or came\nfrom the outpatient department of the hospital\n\n\n\nTable 3.   Occupation of patients with herpes genitalis\n(n=242)\n\n\n\nMajority were office-workers. Only 1% of the patients\nwere commercial sex workers.\n\n\n\nTable 5.   Risk factors and marital status in patients with\nherpes genitalis (n=282)\n\n\n\nA significant percentage (30.5%) of married men reported\nextramarital relationship with sex workers or had a casual or\nregular partner\n\n\n\nTable 6.   Provisional diagnosis at first visit (n=242)\n\n\n\nProvisional diagnosis at first visit was :\nPrimary herpes genitalis 135 (56%) Recurrent herpes\ngenitalis 107 (44%)\n\n\n\nTable 4.   Distribution of herpes genitalis by age & sex\n(n=242)\n\n\n\nYounger women (20-29 years old) tend to suffer more from\nherpes genitalis than men. \n\n\n\nTable 2.   Source of referral of herpes genitalis\n(n=242)\n\n\n\n\n\n\n\n\n53\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 1.   Age distribution of patients with herpes\ngenitalis (n=242)\n\n\n\nMajority (76%) of the patients were between the ages of\n20-49 years\n\n\n\nFigure 3.   Racial distribution of patients with herpes genitalis\n(n=242)\n\n\n\nMalays accounted for 44%, Indians 28% and Chinese 25% of the total\npatients. This probably reflects the normal pattern of clinic attendance\n\n\n\nFigure 2.   Distribution of herpes genitalis by sex (n=242)\n\n\n\nMales outnumbered females by 1.6 :1\n\n\n\nTable 7.   Correlation of clinical presentation and\nimmunoflourescent test (n=162)\n\n\n\nIn primary herpes genitalis, HSV type 2 accounted for 70.6% of\nthe positive cases, HSV type 1, 17.6% and HSV types 1 and 2\ncoinfection in 11.8%. In recurrent herpes genitalis, HSV types 1\nand 2 were found to be equally frequent (41.2%) and HSV types\n1 and 2 coinfection in 17.6%.\n\n\n\n\n\n\n\n\n54\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 6.   Risk factors in patients with herpes genitalis (n=242)\n\n\n\nAbout 1/4 (25.7%) of the patients reported sex with sex workers. Less\nthan 1% (0.4%) of the patients were sex workers\n\n\n\nFigure 7.   Use of condoms by patients with herpes genitalis (n=242)\n\n\n\nCondom usage was low (12%)\n\n\n\nFigure 4.   Sexual orientation of patients with herpes\ngenitalis (n=242)\n\n\n\nMajority (97%) of the patients were heterosexually\norientated\n\n\n\nFigure 5.   Marital status of patients with herpes genitalis\n(n=242)\n\n\n\nAbout two thirds (64.9%) of the patients were married\n\n\n\n\n\n\n\n\n55\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nDiscussion\nGenital herpes is a common lifelong virally transmitted\nsexually transmitted disease which may cause not only\nsignificant physical but also severe psychological and\nemotional impact on the life of a patient. It almost certainly\nfacilitates HIV acquisition4 and can cause a life-threatening\nencephalopathy if transmitted to an infant around birth5. It\nis hence important that we make an accurate diagnosis. It is\nequally important to determine the infecting viral type in\norder to assess the natural history, prognosis and clinical\nmanagement of a patient with genital herpes. The clinical\npresentation of genital primary HSV-1 and HSV-2\ninfections is similar. However, their natural history is\ndifferent. Genital HSV-1 infections are characterized by\nless asymptomatic shedding, a lower transmission frequency\n\n\n\nto new patients6, longer time between recurrences, and\nlower clinical recurrence rates7. Once the primary or non-\nprimary attack has resolved, 88% of untreated patients with\nHSV-2 genital infection suffer episodes of recurrence at a\nmean rate of 0.3 and 0.4 recurrences per month, compared\nto 55% of people infected with HSV-1 with a mean\nrecurrence of 0.09 per month8.\n\n\n\nRecent studies suggest that HSV-1 is becoming more\nfrequent as a cause for genital herpes2. The table below\ncompares the prevalence of HSV-1 and 2 in genital herpes\nin various countries. A striking observation seen in both the\nBangkok and Sydney studies was the increase in rates of\nHSV-1 as a cause of genital herpes. Our HSV-1 rate is\nsimilar to the second study done in Sydney.\n\n\n\nFigure 8.   Herpes immunoflourescent test in patients with herpes genitalis\n(n=162)\n\n\n\n162 (67%) patients had the herpes immunofluorescent antibody test done.\n110 (68%) of those done were negative. Only 34 (21%) patients with herpes\ngenitalis had a positive immunofluorescent antibody test.  Of the 21%,\nherpes simplex virus type 2 was found in 19 (12%) patients with herpes\ngenitalis, HSV type 1 in 10 (6%) and HSV types 1 & 2 coinfection in 5 (3%)\npatients. Therefore, the most frequent type of HSV causing herpes genitalis\nin our study was found to be HSV type 2 (57%), HSV type 1 (29%) and HSV\ntype 1 & 2 coinfection (14%).\n\n\n\n*Used viral culture followed by IFAT       **Used viral culture followed by IFAT\n\n\n\nPrevalence of Herpes simplex virus using immunofluorescence antibody test type (IFAT) \n\n\n\nHSV type\n\n\n\nHSV-1(%)\n\n\n\nHSV-2(%)\n\n\n\nHSV-1 & 2 (%)\n\n\n\nKuala Lumpur,\nMalaysia\n2000-2004\n(n=242)\n\n\n\n29\n\n\n\n57\n\n\n\n14\n\n\n\n1994-1996\n(n=154)9\n\n\n\n18.7\n\n\n\n81.3\n\n\n\n1998-2004\n(n=1125)10\n\n\n\n39.0\n\n\n\n43.1\n\n\n\n17.9\n\n\n\n1979-1988\n(n=17,512)   \n\n\n\n9.8\n\n\n\n78.8\n\n\n\n1989-2003\n(n=4359)\n\n\n\n23.3\n\n\n\n76.7\n\n\n\nBangkok, Thailand* Western Sydney, Australia2 **\n\n\n\n\n\n\n\n\n56\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe sensitivity of the IFAT is about 75%. The specificity\nhowever, is higher at 85%. Viral culture, said to be the \u2018gold\nstandard\u2019, is not routinely available in our hospital.\nAlthough the PCR assay is available in-house, we did not\napply this technique for HSV diagnosis on genital lesions\nmainly because of the prohibitory cost. Moreover, the\ngenital lesion specimens are collected sporadically, not in\nbatches. The IFAT can be applied to even one clinical\nsample at a time, is rapid giving results within an hour, if\nnecessary. The benefits of Imagen IFAT technique over\nviral isolation for reduction of hospitalization and\nreduction of anti-bacterial use, are well established. The\nimmunofluorescence positive rate for herpes simplex virus\nin our study was about 21%. Being a retrospective study,\nsome of the reasons for this would include the stage of the\ndisease when the specimen was taken, possibility of\ninadequate specimen for antigen testing, pretreatment with\nspecific anti-viral agents, and the technique itself.\n\n\n\nIn conclusion, our study showed that HSV-2 was found in\n12% of patients with herpes genitalis, HSV-1 in 6% and\nHSV-1 & 2 co-infection in 3%. Therefore, the most\ncommon type of HSV causing herpes genitalis is HSV-2\n(57%), followed by HSV-1 (29%) and HSV-1 & 2 co-\ninfection (14%). The increased rate of HSV-1 is possibly\ndue to a change in sexual behavior of the patients especially\nwith regards to oro-genital sexual contact.\n\n\n\nReferences\n\n\n\n1. S Zainah, M Sinniah, Y M Cheong et al. A microbiological study \nof genital ulcers in Kuala Lumpur. Med J Malaysia 1991;46:274-\n282.\n\n\n\n2. L J Haddow, B Dave, A Mindel et al. Increase in rates of herpes \nsimplex virus type 1 as a cause of anogenital herpes in western \nSydney, Australia, between 1979 and 2003. Sex Transm Infect \n2006;82:255-259.\n\n\n\n3. Patrick C.Y. Woo, Susan S Chiu, Wing-Wong Seto, Malik Peiris. \nCost-effectiveness of rapid diagnosis of viral respiratory tract \ninfections in pediatric patients. J Clin Mivrobiol 1997;35(6):1579-\n1581.\n\n\n\n4. Freeman EE, Weiss HA, Glynn JR, et al. Herpes simplex virus 2 \ninfection increases HIV acquisition in men and women: \nsystematic review and meta-analysis of longitudinal studies. \nAIDS 2006;20:73-83.\n\n\n\n5. Whitley R. Neonatal herpes simplex virus infections. J Med Virol \n1993;41(Suppl1):13-21.\n\n\n\n6. Kinghorn GR. Limiting the spread of genital herpes. (Review)\n(39 refs). Scand Infect Dis (suppl.) 1996;100:20-5.\n\n\n\n7. Mindel A, Weller IV, Faherty A, Sutherland S, Fiddian AP, Adler \nMW. Acyclovir in first attacks of genital herpes and prevention \nof recurrences. Genitouri Med 1986;62:28-32.\n\n\n\n8. Corey L. The current trend in genital herpes: progress in \nprevention. Sex Trans Dis 1994;21:S38-44.\n\n\n\n9. Puthavathana P, Kanyok R, Horthongkham N, Roongpisuthipong \nA.Prevalence of herpes simplex virus infection in patients \nsuspected of genital herpes; and virus typing by type specific \nfluorescent monoclonal antibodies. J Med Assoc Thai 1998 \nApr;81(4):260-4.\n\n\n\n10. Bhattarakosol P, Visaprom S, Sangdara A, Mungmee V. Increase \nof genital HSV-1 and mixed HSV-1 and HSV-2 infection in\nBangkok, Thailand. J Med Assoc Thai 2005 Sep;88 Suppl\n4:S300-4.\n\n\n\n\n\n\n\n\n57\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nAutoimmune Bullous Diseases in Ipoh, Malaysia: \nA 5-Year Retrospective Study\n\n\n\nTang MM, MD, MRCP, Chan LC, MD, MMed and Heng A, MBBS, MRCP\n\n\n\nDepartment of Dermatology, Ipoh Hospital\nIpoh, Perak, Malaysia\n\n\n\nCorrespondence\n\n\n\nAgnes Heng, MRCP\n\n\n\nDepartment of Dermatology\nIpoh Hospital, 30990 Ipoh, Malaysia\nEmail : agnesheng@gmail.com\n\n\n\nAbstract\n\n\n\nBackground Autoimmune bullous diseases (ABD) represent a group\nof chronic blistering dermatoses in which management is often\nchallenging. Epidemiologic data on these diseases in Malaysia has been\nlimited.\n\n\n\nObjectives Our purpose was to study the spectrum of the various\nABD presented to the Department of Dermatology, Ipoh Hospital,\nand to determine the clinico-epidemiological pattern of the 2 main\nABD, namely pemphigus and bullous pemphigoid.\n\n\n\nMethodology We performed a retrospective review of records for all\npatients who were diagnosed with ABD confirmed by histopathology\nand direct immunofluorescence test in this centre between 2001 and\n2005. The data were analyzed with regard to age, sex, ethnicity,\nsubtypes of ABD, treatment provided and outcome.\n\n\n\nResults There were a total of 79 cases of ABD presented to us during\nthis period. Bullous pemphigoid was observed to be the commonest\n(60.8%) followed by the pemphigus group (36.7%) with the mean\nincidence of 0.45/100,000/year and 0.28/100,000/year respectively.\n44% of patients were of ethnic Chinese origin. There was an overall\nfemale preponderance. The mean age of presentation was 65.5 years for\nbullous pemphigoid and 55 years for pemphigus group. The mean\nduration of disease before presentation was 1.6 months for bullous\npemphigoid and 6.3 months for pemphigus. Various combinations of\nimmunosuppressive agents were used to treat the patients. 48% of\nbullous pemphigoid cases were controlled with prednisolone alone\nwhile 67.9% of pemphigus group required at least 2\nimmunosuppressive agents to achieve disease control.\n\n\n\nConclusion In our study population, bullous pemphigoid was more\nfrequently seen than pemphigus.\n\n\n\nKeywords Autoimmune bullous diseases, bullous pemphigoid,\npemphigus vulgaris\n\n\n\nIntroduction\nAutoimmune bullous diseases (ABD) represent a group of\nchronic blistering dermatoses in which management is\noften challenging. Broadly, it encompasses the pemphigus\ngroup in which 2 major subtypes are recognized, namely,\npemphigus vulgaris (PV) and pemphigus foliaceus (PF);\nand the subepidermal group which includes bullous\npemphigoid (BP), dermatitis herpetiformis (DH), linear\nIgA bullous dermatosis (LABD), lichen planus\npemphigoides (LPP), epidermolysis bullosa aquisita (EBA),\ncicatricial pemphigoid (CP), pemphigoid gestationis (PG)\nand bullous systemic lupus erythematosus (BSLE).\nEpidemiologic data on these conditions in Malaysia has\nbeen limited. In 1992, a study carried out in a university-\nbased hospital in Malaysia on the epidemiology of ABD\nshowed that pemphigus vulgaris was the commonest ABD\nencountered followed by bullous pemphigoid, with an\nincidence of 0.2/100,000/year and 0.12/100,000/year\nrespectively1. The study also showed that Indians were\nmore likely to develop ABD, especially BP, when compared\nto the other ethnic groups in Malaysia.\n\n\n\nWe aim to study the spectrum of various ABD presented to\nthe Dermatology Department, Ipoh Hospital, Malaysia and\nto determine the clinico-epidemiological pattern of the 2\nmain ABD, namely pemphigus and bullous pemphigoid.\n\n\n\nMaterials and Methods\nThe Department of Dermatology, Ipoh Hospital, is the\nmain referral centre for all dermatological diseases in the\nstate of Perak, Malaysia, with a catchment area of about\n2.15 million populations. The ethnic mix of Perak\u2019s\npopulation between 2001 and 2005 comprised 53% Malay,\n31.5% Chinese, 12.8% Indian and 2.7% others. In this\nretrospective study, the case records of all patients diagnosed\nto have ABD in Ipoh Hospital between January 2001 and\nDecember 2005 were analyzed.\n\n\n\nPatients with typical clinical and histopathological findings\nwere included. Diagnosis was further confirmed by direct\nimmunofluorescence (DIF) test from perilesional skin\nbiopsy.\n\n\n\n\n\n\n\n\n58\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nbiopsy. Various clinico-epidemiological characteristics\nincluding age, sex, ethnicity, duration of disease, treatment\nprovided and the outcome were analyzed for all cases.\nDisease was considered controlled when the skin eruptions\nwere minimal while the patients were receiving treatment.\nRemission was defined as no development of new lesions\nand patients were able to taper down the\nimmunomodulators. The data findings were analyzed using\nSPSS statistical analysis for Windows 10.\n\n\n\nResults\nOver the 5 year period, 79 patients were diagnosed to have\nABD in which 48 (60.8%) had bullous pemphigoid (BP);\n29 (36.7%) pemphigus (pemphigus vulgaris (PV) -16,\npemphigus foliaceus (PF) -11, pemphigus vegetans (PVG)\n-1 paraneoplastic pemphigus (PNP) -1); 1 (1.3%) linear\nIgA bullous dermatosis and 1 (1.3%) lichen planus\npemphigoides. The racial distribution for all cases of ABD\nwas as follows: 44% Chinese, 37% Malay and 16% Indian.\nThere was a female preponderance in both BP and\npemphigus group with a male to female ratio of 1:1.53 and\n1:1.8 respectively. The estimated incidence of BP in the\nstate of Perak, Malaysia was 0.45/100,000/year whereas for\nthe pemphigus group was 0.28/100,000/year. The age of\npatients at presentation ranged from 15 to 91 years; the\nmean age of presentation for BP and pemphigus was 65.5\nyears and 55 years respectively. Patients with BP appeared to\npresent earlier with the mean disease duration before first\npresentation of 1.6 months (range 0.3 \u2013 12 months) for BP\ncompared to 6.3 months (range 0.3 \u2013 48 months) for the\npemphigus group (Table 1).\n\n\n\nAmong the pemphigus cases, PV was the predominant\nsubtype seen in 16 patients followed by PF in 11 patients,\npemphigus vegetans (PVG) in 1 patient and paraneoplastic\npemphigus (PNP) in 1 patient. PV appeared to be more\ncommon among the Chinese (50%) while PF was more\nfrequently seen among Malays (54.5%). The mean age of\npresentation was 49.6 years for PV and 65.2 years for PF.\nThe mean duration of disease before presentation was 7.1\nmonths for PV and 6.7 months for PF (Table 2). One\npatient presented with oral erosions for 4 years to various\ndoctors before the diagnosis of mucous membrane PV was\nmade while another patient with PF took 3 years before\npresenting to us. Our only patient with PNP was a 65 year\nold Malay female with non-Hodgkin\u2019s lymphoma stage 3B\nwho succumbed to her disease even before treatment was\ninstituted. Majority of the PV patients had both oral\nerosions and skin lesions while none of the PF patients had\nmucosal involvement.\n\n\n\nPrednisolone was used alone or together with various\ncombinations of immunomodulators to treat the ABD\nwhich included azathioprine, dapsone, cyclophosphamide,\ntetracycline and mycophenolate mofetil (Table 3). Majority\nof the pemphigus cases (67.9%) required at least 2\nimmunomodulators to treat while 47.9% of BP cases were\ncontrolled with prednisolone alone. The mean duration to\n\n\n\nachieve disease control was 3.8 months for BP and 13.6\nmonths for pemphigus.\n\n\n\nAmong the 48 patients with BP, 11 (23%) died but none of\nthe deaths were directly related to their disease. The cause\nof death was due to other medical problems like\ncerebrovascular accidents, ischaemic heart disease,\ncomplications of diabetes and malignancy. Of the 5 out of\n29 patients with pemphigus who died, 1 succumbed to\nsepsis while the others died of unrelated illnesses. None of\nthe BP patients had active disease at the time of death and\nwere on low dose corticosteroids.\n\n\n\nDiscussion\nBullous pemphigoid was the commonest ABD seen at our\ncentre, representing 60.8% of all cases. This is in contrast to\nthe previous study done in Malaysia1 in which pemphigus\nwas more commonly encountered. The incidence rate of\n0.45/100,000/year and 0.28/100,000/year respectively for\nBP and pemphigus is higher than previously thought.\nHowever, the true incidence of ABD in this region may be\nhigher than reported in this study as some cases may have\nbeen treated and followed up by dermatologists in private\npractice and hence, not captured in this study. Mild cases of\nBP with localized disease may have also been treated by\nprimary care physicians and not reaching us. There may also\nbe some referral bias; for example pemphigus confined to\nthe oral mucosa may have been referred to the dentists and\nCP to the ophthalmologists. Furthermore, some cases could\nhave been treated by traditional/complementary medicine\n(TCM) practitioners instead as this is not an uncommon\npractice among Malaysians. This could explain the lower\nincidence for both BP and pemphigus in this region as\ncompared to the incidence rate of other countries (Table 4).\n\n\n\nThere was a predilection of ABD for ethnic Chinese which\ncomprised 44% of all cases although they constitute only\n31.5% of the Perak population during the study period. The\nMalays, on the other hand, were less likely to develop ABD\nwhile the percentage of Indians affected corresponds to the\nethnic distribution of this region. This, again, differed from\nthe result of an earlier study done in this country which\nshowed a predilection of ABD for ethnic Indians1.\nAlthough the incidence of ABD in the Malays was\nrelatively lower, it was observed that they were more\npredisposed to develop PF where they made up of 54.5% of\nall PF cases in this study (Table 2). The Singapore study\nnoted an over-representation of PF in their Malay\npopulation, which constituted 25% of all PF cases studied\nwhen compared to their normal ethnic composition, of\nwhich the Malays constitute 10%4.\n\n\n\nAlthough an equal sex predisposition has been reported in\nthe previous Malaysian study1, we observed a female\npreponderance in both bullous pemphigoid (M:F = 1:1.53)\nand pemphigus (M:F = 1:1.8). A similar observation was\nalso seen in Kuwait2,3. Singapore reported an equal sex\ndistribution\n\n\n\n\n\n\n\n\n59\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.   Comparison of characteristics between bullous pemphigoid and pemphigus\n\n\n\nCharacteristic\n\n\n\nIncidence (per 100,000/year)\n\n\n\nAge (years)\n\n\n\nRace (%)\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nM:F ratio\n\n\n\nDuration to diagnosis (months)\n\n\n\nDuration to disease control (months)\n\n\n\nNo. of deaths over 5 years\n\n\n\nBullous pemphigoid (n=48)\n\n\n\n0.45\n\n\n\n65.5 (15 - 91)\n\n\n\n33.3\n\n\n\n45.8\n\n\n\n18.8\n\n\n\n2.1\n\n\n\n1:1.53\n\n\n\n1.6 (0.3 - 12)\n\n\n\n3.8\n\n\n\n11 (23%)\n\n\n\nPemphigus (n=29)\n\n\n\n0.28\n\n\n\n54.8 (17 - 80)\n\n\n\n39.3\n\n\n\n46.4\n\n\n\n10.7\n\n\n\n3.6\n\n\n\n1:1.8\n\n\n\n6.3 (0.3 - 48)\n\n\n\n13.6\n\n\n\n5 (17.2%)\n\n\n\nTable 2.   Demographic data, treatment and course of disease in patients with pemphigus vulgaris and\npemphigus foliaceus\n\n\n\nPemphigus vulgaris Pemphigus foliaceus\n(n = 16) (n = 11)\n\n\n\nPatient\u2019s characteristics\n\n\n\nAge (years) 49.6 (17 - 74) 65.2 (25 - 80)\n\n\n\nSex (M/F) 6/10              4/7\n\n\n\nRace\n\n\n\nMalay 5 (31.3%)                    6 (54.5%)\n\n\n\nChinese 8 (50%)          4 (36.4%)\n\n\n\nIndian 2 (12.5%)                  1 (9.1%)\n\n\n\nIndonesian 1 (6.3%)                      0\n\n\n\nDuration of disease before diagnosis (months) 7.1 (0.5 - 48)               6.7 (0.3 - 36)                         \n\n\n\nTreatment\n\n\n\nPrednisolone alone 4 (25%)                        2 (18.2%)\n\n\n\nPrednisolone + 1 adjuvant 6 (37.5%)                         5 (45.5)\n\n\n\nPrednisolone + 2 adjuvants 5 (31.3%)                      2 (18.2%)\n\n\n\nNo treatment* 1 (6.3%)                             2 (18.2%)\n\n\n\nCourse of disease\n\n\n\nDuration to disease control (months) 12.4                              11.2\n\n\n\nNo. of patients with disease controlled 5                                 1\n\n\n\nNo. of patients in remission 3                                4\n\n\n\nNo. of patients with active disease 1                                     1\n\n\n\nNo. of patients transferred to other centre 1                                   0   \n\n\n\nNo. of patients  who died of disease/sepsis 0                                     1\n\n\n\nNo. of patients who died of unrelated causes 1                                    2 \n\n\n\nNo. of patients lost to follow-up 5                                     2     \n\n\n\n* lost to follow-up before treatment was instituted\n\n\n\n\n\n\n\n\n60\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\ndistribution in pemphigus4 but a striking female\npreponderance (M:F = 1:2) in their BP patients5. Similar\nfemale predominance was also observed in previous\npemphigus studies from Greece6 (M:F = 1:2.25 ), Turkey7\n\n\n\n(M:F = 1:1.41) and Iran8 (M:F = 1:1.33). The factors\nresponsible for this gender difference have yet to be\nelucidated.\n\n\n\nWhile the Singapore study reported EBA to be their second\ncommonest subepidermal immunobullous disorder3, we had\nnone during our study period. This could be explained by\nthe fact that we did not have facilities for salt-split skin\n\n\n\nindirect immunofluorescence test at the time of the study\nperiod and therefore some of the cases may have been\ngrouped together with BP since they share similar DIF\nfindings. We also did not have any cases of BSLE despite\nSLE being a fairly common disease in this region. This\ncould either be due to the incidence of BSLE being rare in\nthis region or the cases were being treated by\nrheumatologists instead. We have had few cases of CP, PG\nand DH on our follow-up but no new cases during the 5\nyear study period. This finding is similar to the studies done\nin Singapore5 and China11 which reflects the rarity of these\ndiseases in this region.\n\n\n\nTable 3.   Therapy for bullous pemphigoid and pemphigus\n\n\n\nCombinations of Immunomodulators\nPrednisolone  alone\n\n\n\nPrednisolone + Azathioprine\n\n\n\nPrednisolone + Tetracycline\n\n\n\nPrednisolone + Dapsone\n\n\n\nPrednisolone + Cyclophosphamide\n\n\n\nPrednisolone + Methotrexate\n\n\n\nPrednisolone + Azathioprine + Dapsone\n\n\n\nPrednisolone + Cyclophosphamide + Tetracycline\n\n\n\nPrednisolone + Azathioprine + Tetracycline\n\n\n\nPrednisolone + Mycophenolate +Tetracycline\n\n\n\n* 1 BP patient and 3 pemphigus patients defaulted follow-up before treatment was instituted.\n\n\n\nBulIous pemphigoid\n23\n\n\n\n9\n\n\n\n2\n\n\n\n6\n\n\n\n2\n\n\n\n0\n\n\n\n3\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\nPemphigus\n(PV + PF+ PVG)\n\n\n\n23\n\n\n\n9\n\n\n\n2\n\n\n\n6\n\n\n\n2\n\n\n\n0\n\n\n\n3\n\n\n\n0\n\n\n\n2\n\n\n\n0\n\n\n\nTable 4.   Incidence of bullous pemphigoid and pemphigus in studies carried out in different regions of the\nworld\n\n\n\nCountry and year of publication\nMalaysia 19921\n\n\n\nFrance 199512\n\n\n\nGermany 199513\n\n\n\nMali 199614\n\n\n\nBulgaria 200015\n\n\n\nSouthern Saudi Arabia 200116\n\n\n\nSingapore 20025\n\n\n\nKuwait 20042\n\n\n\nScotland 20059\n\n\n\nIran 20068\n\n\n\nGreece 20076\n\n\n\nCurrent study (Perak, Malaysia)\n\n\n\nBulIous pemphigoid\n0.12\n\n\n\n0.74\n\n\n\n0.662\n\n\n\n0.76\n\n\n\n0.205\n\n\n\n1.4\n\n\n\n0.47\n\n\n\nPemphigus\n0.2\n\n\n\n0.29\n\n\n\n0.47\n\n\n\n0.16\n\n\n\n0.457\n\n\n\n0.67\n\n\n\n0.8\n\n\n\n0.28\n\n\n\nIncidence (per 100,000 per year)\n\n\n\n\n\n\n\n\n61\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nThe first line of treatment for all cases of ABD was with\noral prednisolone. Adjuvant therapy with various\nimmunomodulators was added when prednisolone alone\nwas not enough to achieve disease control. The choice for\nadjuvant therapy was azathioprine or dapsone as they are\neffective and relatively inexpensive. In the event of an\nadverse drug reaction or poor response to these 2\nmedications, other drugs like methotrexate,\ncyclophosphamide and mycophenolate mofetil were used\ninstead. Tetracycline was usually added as a third agent\nwhen 2 drugs were not adequate to control the disease. We\nfound mycophenolate mofetil to be an effective adjuvant\ntherapeutic agent in 2 of our pemphigus patients who had\nfailed to respond the other conventional agents. In addition\nto systemic therapy, most of our patients also received\ntreatment with potent topical corticosteroids.\n\n\n\nAs expected, BP was easier to control compared to\npemphigus. About half of the BP patients (47.9%) achieve\ndisease control with prednisolone alone compared to only\n25% of pemphigus patients. The duration to disease control\nwas also shorter in BP compared to pemphigus, with a mean\nduration of 3.8 months and 13.6 months respectively (Table\n1). Although the number of deaths was higher in the BP\ngroup, all deaths were due to unrelated causes as most of the\nBP patients were older and had concomitant illnesses. It is\nnoteworthy that none of them had active disease at the time\nof death. This result is in keeping with a previous study\ndone in Scotland9 which reported the first year mortality\nrate of 25%. Most deaths were related to old age and the\ngeneral condition of the patient and rarely due to BP itself.\nAnother study from Germany10 demonstrated the first year\nmortality rate of 29% and they attributed low serum\nalbumin, high dosage of corticosteroids and old age as risk\nfactors for lethal outcome in BP.\n\n\n\nBetween PV and PF, PV appeared to be more difficult to\ncontrol with about one third of them requiring 2 adjuvant\nagents to achieve disease control. The duration needed to\nachieve control was also longer. It is interesting to note that\nour PF patients present at an older age (mean 65.2 years)\nwhen compared to neighbouring Singapore4 (57 years) and\nTurkey7 (52 years). The reason for this is unclear but it could\nexplain the higher mortality encountered in these patients.\n\n\n\nConclusions\nThe results of our retrospective study demonstrate that BP\nis almost twice as common as pemphigus. This is\ncomparable to reports from Singapore where they found BP\nto be three times more common than pemphigus5. The\n\n\n\nincidence rate is higher for both BP and pemphigus than\npreviously thought. Chinese are more predisposed to ABD,\nespecially BP and PV, while PF is more common in Malays.\nThere is no evidence of a predilection for ethnic Indians as\npreviously reported1. There is a female preponderance\namong BP and pemphigus patients and a low occurrence of\nother subepidermal blistering diseases like EBA, CP, DH,\nPG and BSLE in our patients. These results provide a basis\non which future research activities in this region can be\nbuilt.\n\n\n\nReferences\n\n\n\n1. Adam BA. Bullous diseases in Malaysia: epidemiology and \nnatural history. Int J Dermatol 1992; 31: 42-45.\n\n\n\n2. Nanda A, Dvorak R, Al-Saeed K, Al-Sabah H, Alsaleh QA. \nSpectrum of autoimmune bullous diseases in Kuwait. Int J \nDermatol 2004, 43: 876-881\n\n\n\n3. Alsaleh QA, Nanda A, Al-Baghli NM, Dvorak R. Pemphigus in \nKuwait. Int J Dermatol 1999; 38:351-356\n\n\n\n4. Goon A, Tan SH. Comparative study of pemphigus vulgaris and \npemphigus foliaceus in Singapore. Australasian J Dermatol \n2001;42:172-5\n\n\n\n5. Wong SN, Chua SH. Spectrum of subepidermal immunobullous \ndisorders seen at the National Skin Centre Singapore: a 2-year \nreview. Br J Dermatol 2002; 147: 476-480.\n\n\n\n6. Michailidou EZ, Belazi MA, Markopoulous AK, et al. \nEpidemiologic survey of pemphigus vulgaris with oral \nmanifestation in northern Greece: Retrospective study of 129 \npatients. Int J Dermatol 2007; 46: 356-361\n\n\n\n7. Uzun S, Durdu M, et al. Pemphigus in the Mediterranean region \nof Turkey: A study of 148 cases. Int J Dermatol 2006, 45, 523-528\n\n\n\n8. Salmanpour R, Shahkar H, Namazi MR, Rahman-Shenas MR. \nEpidemiology of pemphigus in South Western Iran: A 10-year \nretrospective study (1991-2000). Int J Dermatol 2006; 45,103-105.\n\n\n\n9. Gudi VS, White MI, Cruickshank N, et al. Annual incidence and \nmortality of bullous pemphigoid in the Grampian Region of \nNorth-east Scotland. Br J Dermatol 2005; 153: 424-427.\n\n\n\n10. Rzany B, Partscht K, Jung M et al. Risk factors for lethal \noutcome in patients with bullous pemphigoid: low serum \nalbumin level, high dosage of glucocorticosteroids, and old age. \nArch Dermatol 2002; 138: 903-8. \n\n\n\n11. Jin P, Shao C, Ye G. Chronic bullous dermotoses in China. Int J \nDermatol 1993; 32: 48-52\n\n\n\n12. Bernard P, Vaillant L, Labeille B, et al. Incidence and distribution \nof subepidermal autoimmune bullous skin diseases in three \nFrench regions. Arch Dermatol 1995; 131: 48-52.\n\n\n\n13. Zillikens D, Wever S, Roth A, et al. Incidence of autoimmune \nsubepidermal blistering dermatoses in a region of central \nGermany. Arch Dermatol 1995; 131: 957-958.\n\n\n\n14. Mah\u00e9 A, Flageul B, Ciss\u00e9 I, et al. Pemphigus in Mali. A study of \n30 cases. Br J Dermatol 1996; 134: 114-119.\n\n\n\n15. Tsankov N, Vassileva S, Kamarashev J, et al. Epidemiology of \npemphigus in Sofia, Bulgaria. A 16-year retrospective study \n(1980-1995). Int J Dermatol 2000; 39: 104\u2013108.\n\n\n\n16. Tallab T, Joharji H, Bahamdan K, et al. The incidence of \npemphigus in Southern region of Saudi Arabia. Int J Dermatol \n2001; 40: 570-572.\n\n\n\n\n\n\n\n\n62\n\n\n\n\n\n\n\n\n63\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nOriginal Article\n\n\n\nThe effect of explanation and demonstration of topical \ntherapy on the clinical response of atopic eczema\n\n\n\nTang MM, MD, MRCP, Chan LC, MD, MMed and Heng A, MBBS, MRCP\n\n\n\nDepartment of Dermatology, Ipoh Hospital, \nIpoh, Perak, Malaysia\n\n\n\nCorrespondence\n\n\n\nTang Min Moon, MRCP (UK)\n\n\n\nDepartment of Dermatology\nIpoh Hospital, 30990 Ipoh, Perak, Malaysia\nEmail : minmoon2005@yahoo.com\n\n\n\nAbstract\n\n\n\nBackground Atopic eczema is a common dermatological condition\nseen in our practice in which the mainstay of treatment is topical\nmedications. One of the main reasons for poor clinical response to\ntherapy in atopic eczema is the lack of understanding of topical\npreparation usage and thus poor adherence to treatment.\n\n\n\nObjectives The aim of this study is to determine the effect of\nexplanation and demonstration of topical medication on the clinical\nresponse of atopic eczema.\n\n\n\nMethodology Twenty newly diagnosed patients with atopic eczema\nwho fulfilled the study criteria were recruited and randomized\nconsecutively into 2 groups - A & B. All patients were assessed on the\nseverity of the eczema using the six area, six sign atopic dermatitis\nseverity score (SASSAD) and patients\u2019 assessment of itch, sleep\ndisturbance and irritability were recorded on 10-cm visual analogue\nscales. They were also assessed on their level of understanding on the\nproper usage of topical medications using a questionnaire. Group A\nthen received explanation and demonstration on how to apply the\ntopical medications while Group B was not educated on these. They\nwere followed up 2 weeks after treatment and were re-evaluated on\ntheir understanding and the severity of their skin condition. This was\nfollowed by education by a dermatology nurse on the proper usage of\ntopical medications for both groups. A third evaluation was done 2\nweeks later.\n\n\n\nResults At baseline, 70% of the patients did not understand the\npotency of topical corticosteroid and between 20-30% of them did not\nknow the correct sites, frequency, time and duration of each topical\napplication prescribed. About two thirds of the patients claimed that\nthey did not receive any explanation or demonstration from either their\ndoctors or the pharmacy dispensers. After education on the proper\nusage of topical medications, the level of understanding improved to\n100% for group A at visit 2 and group B at visit 3. A clinical\nimprovement as measured by SASSAD score reduction was seen in\nboth groups. In group A, a significant SASSAD score reduction of\n49.5% (P=0.003) was seen after 2 weeks and it was sustainable, as\n\n\n\nevidenced by a further reduction to 67% (p=0.001) by week 4. In group\nB, a significant SASSAD score reduction (64.8%; p=0.002) was seen\nonly at week 4 after patient education and demonstration. The\nmagnitude of improvement in patients\u2019 symptoms which included itch,\nsleep disturbance and irritability, measured by the patient using visual\nanalog score, were only significant for group A after 4 weeks.\n\n\n\nConclusions This study reinforces the importance of explanation and\ndemonstration on the proper usage of topical medications in achieving\nbetter clinical response. Failure to explain on the use of topical\nmedications may lead to patient dissatisfaction, poor compliance and\nlack of treatment efficacy.\n\n\n\nIntroduction\nThe cause of failure of response to therapy in many\ndermatological skin conditions including atopic eczema is\npoor adherence, rather than severity of disease. This can\narise from a number of reasons, the most important of\nwhich is a lack of understanding of topical applications.\nOther reasons include failure to renew prescriptions, under-\nprescribing, lack of faith in the treatment, or insufficient\ntime to apply the medication. About 80% of our patients are\nprescribed more than one topical medication at any one\ntime. Confusion with treatment may arise when patients are\nnot educated on the proper usage of the various topical\nmedications. So far there is no published record of any\nstudies carried out in Malaysia to support the fact that\nimproving patients\u2019 knowledge of proper topical application\nby explanation and demonstration will improve the\noutcome of treatment. Atopic eczema is chosen for this\nstudy because it is one of the commonest conditions seen at\nour clinic; the modality of treatment is mainly by topical\nmedications and the availability of a standard scoring\nsystem of severity of disease.\n\n\n\nIn this study, we aim to determine the effect of explanation\nand demonstration of topical medications by a trained\ndermatology nurse on the clinical response of atopic\neczema.\n\n\n\n\n\n\n\n\n64\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nMaterials and Methods\nNew patients who were diagnosed with moderate to severe\natopic eczema using the Hanifin and Rajka Criteria1 at the\nDermatology Clinic Ipoh Hospital between February to\nAugust 2006 were recruited into the study. Patients who\nhave had any previous consultations with a dermatologist or\nat any dermatology department were excluded. Those who\nhave a skin disorder other than atopic eczema in the area to\nbe treated were also excluded from this study.\n\n\n\nOnce the patients were enrolled, they were randomized\nconsecutively into 2 groups, Group A and Group B. The\nseverity of atopic eczema was determined by a global\nphysician assessment using the Six Area, Six Sign Atopic\nDermatitis (SASSAD) severity score2 (Appendix 1). The\npatients\u2019 assessments of itch, sleep disturbances and\nirritability were recorded on 10-cm visual analogue scales.\n\n\n\nAfter consultation, a prescription was given to the patients\nto collect their medications from the out-patient pharmacy.\nThey were instructed to return to the clinic after collecting\ntheir medications to fill up a study questionnaire assessing\ntheir knowledge about the treatment given by their doctors.\nFor patients below 17 years of age, their parents or\nguardians responded to the questionnaire. Patients who did\nnot know how to read or write were interviewed by the\nstudy nurse. Following that, Group A received explanation\nregarding their disease followed by demonstration on how\nto apply the topical treatments by a trained nurse from the\ndermatology clinic. All their topical treatments were labeled\nwith cartoon and multi-languages stickers. Patient\ninformation leaflets regarding the disease and the topical\ntreatments which were available in 3 languages (English,\nMalay, and Mandarin), were handed out to the patients.\nGroup B, on the other hand, did not receive additional\nexplanation or demonstration from the nurse.\n\n\n\nBoth groups of patients were reviewed after 2 weeks (Visit\n2). All patients were re-assessed on their knowledge of the\ncorrect usage of topical treatments. The disease severity was\nagain assessed using SASSAD score and patients\u2019\nassessments using visual analogue scale. They were given the\nsame prescription as the first visit and were instructed to\nreturn to the clinic after collecting their medications from\nthe pharmacy. This time, all patients from both Group A\nand Group B were educated on the methods of application\nof their medications. This was again reinforced using\nwritten instructions. Medications were labeled and\ninformation leaflets on the disease were also given.\n\n\n\nBoth groups were followed up 2 weeks later (Visit 3) and\nwere re-assessed on their knowledge of the correct usage of\ntopical treatments. The disease severity was assessed using\nSASSAD score and patients\u2019 assessments using visual\nanalogue scale. All results were analyzed and interpreted\nusing SPSS program version 10.0.\n\n\n\nResults\nA total of 20 patients participated in the study. At baseline,\n60% of the respondents recalled not receiving any\ndemonstration from the doctors on how to apply the topical\ntreatments and 55% claimed that the dispensers did not give\nany explanation to them. 70% of the respondents did not\nunderstand the potency of the topical corticosteroid\nprescribed and between 20-30% of them did not know the\ncorrect sites, frequency, time and duration of each topical\napplication prescribed.\n\n\n\nOnly 14 patients were followed till the end of the study, 7\neach for group A and B. The 6 patients who did not\ncomplete the study were excluded from further analysis.\nOut of the 6, 2 defaulted scheduled follow-up, 3 were not\nwilling to spend additional time at the clinic for further\nassessment and explanation, and therefore left after\ncollecting their medications from the pharmacy and 1 felt\nthat the skin lesion had improved and did not want further\nconsultation. After education on the proper usage of topical\nmedications, the level of understanding had improved to\n100% for group A at visit 2 and group B at visit 3.\n\n\n\nBoth groups showed a reduction in SASSAD score (clinical\nimprovement) at Visit 2 and Visit 3 (Figure 1). A\nsignificant reduction of 49.5% (p=0.003) in the severity of\neczema was noted after 2 weeks (Visit 2) in Group A and a\nfurther reduction of 67% (p=0.001) was noted after 4 weeks\n(Visit 3). In Group B, a significant reduction of SASSAD\nscore (64.8%; p=0.002) was only noted at week 4 (Table 1).\n\n\n\nFor the improvement of symptoms based on visual analogue\nscores, there was a reduction of score at every visit for both\ngroups (Figure 2, 3, 4). At the end of the study, there was a\nsignificant improvement for itch, sleep disturbance and\nirritability for group A whereas in group B, only the score\nfor sleep disturbance showed significant reduction at Visit 3\n(Table 2).\n\n\n\nDiscussion\nDue to the busy clinics and heavy workload, most doctors\ndo not spend enough time explaining the nature of a disease\nand the proper use of medications prescribed to their\npatients. Moreover, doctors tend to depend very much on\nthe pharmacists or dispensers to teach patients on the usage\nor administration of medications prescribed by them. In\naddition, patient educational materials are also insufficient\nfor patients\u2019 reference after each consultation. Educating the\npatients or parents helps them to take charge of the\nmanagement of their illness. One trial had demonstrated\nthat education and demonstration of treatment for atopic\neczema improved parents\u2019 knowledge and the outcome of\ntheir child\u2019s eczema3. Our current study is the first study\ndone in Malaysia to support this finding.\n\n\n\nFrom the literature review, only 5-20% of parents had\nreceived or recalled receiving any explanation of the causes\nof eczema or demonstration on how to apply topical\ntreatments and the side effects of the topical\ncorticosteroids4, 5, 6. Thirty to 60% of patients who were\nfgfgfg \n\n\n\n\n\n\n\n\n65\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nTable 1.   The Magnitude of SASSAD score reduction for Group A and B\n\n\n\nSASSAD\nscore\n\n\n\nGroup A\n\n\n\nGroup B\n\n\n\nVisit 1\n(Baseline)\n\n\n\n35.43\n\n\n\n44.57\n\n\n\nVisit 2\n\n\n\n17.86\n\n\n\n29.43\n\n\n\n% of reduction\n(p value)\n\n\n\n49.5* (0.003)\n\n\n\n34 (0.043)\n\n\n\nVisit 3\n\n\n\n11.57\n\n\n\n15.71\n\n\n\n% of reduction\nat Visit 3 from\nVisit 2 (p value)\n\n\n\n35.2 (0.054)\n\n\n\n46.6 (0.03)\n\n\n\n% of reduction at\nVisit 3 from\nbaseline (p value)\n\n\n\n67.3* (<0.001)\n\n\n\n64.8* (0.002)\n\n\n\nTable 2.   The Magnitude of Symptom Improvement using Visual Analog Score\n\n\n\nItch\n\n\n\nSleep\n\n\n\nIrritability\n\n\n\nItch\n\n\n\nSleep\n\n\n\nIrritability\n\n\n\nVisit 1\n\n\n\n7.14\n\n\n\n5.00\n\n\n\n5.29\n\n\n\n8.00\n\n\n\n7.86\n\n\n\n6.71\n\n\n\nVisit 2\n\n\n\n4.29\n\n\n\n3.71\n\n\n\n3.43\n\n\n\n6.29\n\n\n\n4.57\n\n\n\n5.14\n\n\n\n%\nof change\n\n\n\n39.9\n\n\n\n25.8\n\n\n\n35.2\n\n\n\n21.4\n\n\n\n41.9\n\n\n\n23.4\n\n\n\nVisit 3\n\n\n\n3.43\n\n\n\n2.71\n\n\n\n3.00\n\n\n\n4.57\n\n\n\n3.29\n\n\n\n4.43\n\n\n\n% of change at\nVisit 3 from\n\n\n\nVisit 2\n\n\n\n20.0\n\n\n\n26.9\n\n\n\n12.5\n\n\n\n25.9\n\n\n\n28.0\n\n\n\n13.8\n\n\n\n% of change at\nVisit 3 from\n\n\n\nbaseline (p value)\n\n\n\n51.9* (0.007)\n\n\n\n45.8* (0.007)\n\n\n\n43.3* (0.009)\n\n\n\n42.8\n\n\n\n58.1* (0.007)\n\n\n\n34.0\n\n\n\nGROUP A\n\n\n\nGROUP B\n\n\n\n* Significant (p<0.01)\n\n\n\nFigure 1.   Global Physician Assessment on the severity of Atopic Eczema using\nSix Area, Six Sign Atopic Dermatitis severity Score (SASSAD)\n\n\n\n\n\n\n\n\n66\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nFigure 2.   Comparison of Mean Reduction of Itch between Group A and B\n\n\n\nFigure 3.   Comparison of Mean Reduction of Sleep Disturbances between Group\nA and B\n\n\n\nFigure 4.   Comparison of Mean Reduction of Irritability between Group A and B\n\n\n\n\n\n\n\n\n67\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nprescribed topical corticosteroid were not aware of the\npotency and resulted in either over or under usage of the\ntopical application5,7. Following repeated education and\ndemonstration of topical therapies by a specialist\ndermatology nurse, there was a 65% reduction in the\nseverity of the eczema (SASSAD severity score) after 3\nweeks4.\n\n\n\nWe had excluded patients from entry into this study if they\nhave had any previous consultation with any dermatology\ncentre, in order to provide a population who had not been\nexposed to a dermatologist or specialist dermatology nurse\nin the past. At the first visit, which reflected the usual\ndermatology clinic consultation, majority of patients\nclaimed they received neither explanation nor\ndemonstration on how to apply topical medications from\nthe doctors or dispensers at the pharmacy. After\nquestioning, not all of them understood completely the\ncorrect use of topical medications. It is not possible to\ndetermine whether the lack of knowledge was due to failure\nof the healthcare providers in educating the patients/parents\nor because they had forgotten what they had been told.\nEither way, one can conclude that at the end of a\nconsultation, appropriate medications were given to the\npatients but the information on the disease and proper\nusage of medications were not delivered to the patients.\n\n\n\nOur intervention included recruitment of a trained\ndermatology nurse to explain regarding the disease and to\ndemonstrate to the patients and/or parents on how to apply\nthe topical medications. The patients were taught on the\ncorrect time, frequency, sites of applications, duration of use\nand the potency of the topical corticosteroid prescribed.\n\n\n\nAs reinforcement, all the topical medications were labeled\nwith multi-languages cartoon labels and patient\ninformation leaflets on atopic eczema available in 3\nlanguages were also given to the patients. We also spent\nsome time answering to any queries from patients/parents.\n\n\n\nThere was an improvement in the disease severity in Group\nA as evidenced by a significant reduction of SASSAD score\nwhen proper education and demonstration on how to apply\ntopical treatments were given during the first visit as\ncompared to Group B, where the consultation was done in\nthe usual manner but without further education or\ndemonstration. This significant reduction was reproducible\nin Group B at the third visit when similar education and\n\n\n\ndemonstration was given to them (Table 1). Besides\nimprovement in the disease severity, we also found that\nthere was improvement in the patients\u2019 symptoms of itch,\nsleep disturbances and irritability.\n\n\n\nThe main limitation of this study is the small sample size.\nThe disease severity of Group A appeared to be milder than\nGroup B at baseline. We felt that this randomization bias\nwas due to the small number of subjects in the study. In\naddition, the magnitude of symptom improvement of itch\nand irritability in Group B after education and\ndemonstration were not statistically significant as compared\nto Group A (Table 2). This, again, could be due to the small\nsample size.\n\n\n\nAt the end of the study, we noted that the key to the\nsuccessful management of atopic eczema is to spend time to\nlisten and to explain the nature of disease and how to use\ntopical therapies and dressings. In addition to explanation,\npractical demonstrations on how to apply topical\nmedications and dressings should be given to the patients or\nparents. Patients or parents should also be given written\ninstructions and information to reinforce the therapies\nwhich have been explained and demonstrated. The quality\nof topical medications\u2019 labels could also be improved with\nthe cooperation of the pharmacy department.\n\n\n\nConclusion\nWe found a positive effect of explanation and\ndemonstration of topical therapy on the clinical response of\natopic eczema as evidenced by a significant reduction of\ndisease severity score (SASSAD) as well as improvement in\nitch, sleep disturbances and irritability. This study reinforces\nthe importance of having a trained dermatology nurse to\nexplain and demonstrate on proper usage of topical\napplications in the management of atopic eczema. We\nsuggest that all dermatology clinics utilize the services of\nthese nurses especially in cases when the doctors themselves\ncannot afford to spend more time with the patients due to\ntheir busy schedule. Failure to explain on how to use topical\napplications may lead to patient dissatisfaction, poor\ncompliance and lack of treatment efficacy.\n\n\n\nAcknowledgements\nWe thank the QAP committee of Ipoh Hospital in\nsupporting this study and all the staff of the Department of\nDermatology, especially staff nurse Kong Siew Hong, for\ntheir cooperation and commitment.\n\n\n\nAppendix 1.   The Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score\n\n\n\n\u2022 Six Signs: Erythema, Exudation, Excoriation, Dryness, Cracking, and Lichenification\n\n\n\n\u2022 Six Sites: Arms; Hands; Legs; Feet; Head & neck; and trunk\n\n\n\n\u2022 Grade of severity (Range of score: 0-108)\n\n\n\n0 Absent The sign cannot be detected with certainty even after careful inspection\n\n\n\n1 Mild The sign is certainly present but requires careful inspection to see it\n\n\n\n2 Moderate The sign is immediately apparent\n\n\n\n3 Severe The sign is very prominent\n\n\n\n\n\n\n\n\n68\n\n\n\nMalaysian Journal Of Dermatology  Jurnal Dermatologi Malaysia\n\n\n\nReferences\n\n\n\n1. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. \nActa Derm Venereol (Stockh) 1980; Suppl 92: 44-47.\n\n\n\n2. Berth-Jones J. Six area, six sign atopic dermatitis (SASSAD) \nseverity score: a simple system for monitoring disease activity \nin atopic dermatitis. Br J Dermatol 1996; 135: 25-30.\n\n\n\n3. Broberg A, Kalimo K, Lindblad B et al. Parental education in the \ntreatment of Childhood atopic eczema. Acta Derm Venereol \n(Stockh) 1990;70: 496-9.\n\n\n\n4. Cork MJ, Britton J, Butler L et al. Comparison of parent \nknowledge, therapy utilization and severity of atopic eczema \nbefore and after explanation and demonstration of topical \ntherapies by a specialist dermatology nurse. Br J Dermatol \n2003;149: 582-589.\n\n\n\n5. Basak PY, Ozturk M, Baysal V. Assessment of information and \neducation about topical corticosteroids in dermatology \noutpatient departments: experience from Turkey. J Eur Acad \nDermatol Venerol  2003;17: 652-658 \n\n\n\n6. Beattie PE, Lewis-Jones MS Parental knowledge of topical \ntherapies in the treatment of childhood atopic dermatitis. Clin  \nExp Dermatol 2003; 28: 549-553.\n\n\n\n7. Charman C.R., Morris A.D., Williams H.C. Topical corticosteroid \nphobia in patients with atopic eczema. Br J Dermatol 2000; 142: \n931-936.\n\n\n\n\n\n"
"\n\nVolume 50  |  June 2023  |  ISSN: 1511-5356\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 i\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence. Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. 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Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for \nerrors or any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute any \nendorsement by the publisher and Editors of the products \nadvertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nii MJD 2023 June Vol 50\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\nORIGINAL ARTICLE CASE REPORT \n\n\n\n2\n\n\n\n11\n\n\n\n20\n\n\n\n29\n\n\n\n40\n\n\n\n49\n\n\n\n60\n\n\n\n69\n\n\n\nACKNOWLEDGEMENT\n\n\n\nRelationship between Staphylococcus aureus \nColonization and Face Mask-associated Adverse \nCutaneous Reactions during the COVID-19 \nPandemic\nLim MW, Ramalingam R, Jamil A\n\n\n\nVitamin D Level among Psoriasis Patients, Healthy \nControls and its Relationship with Sun Exposure and \nDietary Intake - A Case Control Study\nLim AY, Tang JJ \n\n\n\nEvaluation of Topical Corticosteroid Phobia As an \nIndicator of Topical Steroid Non-adherence Among \nAtopic Dermatitis Patients\nTan SL, Lee YL, Mohd Affandi A \n\n\n\nAttitudes, Health Seeking Behaviors, Expectations \nand Psychosocial Impact of Patients with Non- \nScarring Alopecia: Results of Tertiary Out-patient \nSkin Specialist Clinics in Penang\nKhoo VL, Loo CH, Khor YH, Mohd Ali N, Tan WC\n\n\n\nCutaneous Manifestations In Patients With \nLeukaemia: A 6 Months Cross-sectional Study in a \nHaematological Referral Centre\nSubramaniam P, Mohd Affandi A, Jamil A\n\n\n\nCutaneous Manifestations in Obese Patients and \nTheir Risk Factors: A Cross-sectional Study in a \nTertiary Center \nGovindarajoo S, Gunabalasinggam P, Jamil A\n\n\n\nAssociation between Acanthosis Nigricans and \nMetabolic Syndrome at Rural Tertiary Care Hospital \nin Central India: A Case Control Study\nDeshmukh A, Jain S, Harode S\n\n\n\nPerplexing Pigmentation in a Young Child: A Case \nReport of Juvenile Systemic Sclerosis\nGalui S, Sonkusale P, Kar S, Deshmukh A, Ambulkar AR\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 iii\n\n\n\nEditor-in-Chief\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, M Adv Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                             \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                          \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                         \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm              \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm Wilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm  Wilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                                \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm                     \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Kwan Zhenli, MRCP, Adv M \nDerm Wilayah Persekutuan Kuala Lumpur \n\n\n\nDermatological Society of Malaysia | Persatuan Dermatologi Malaysia\n\n\n\nExecutive Committee\nDr Sabeera Begum, MMed - President\nDr Tan Wooi Chiang, Adv M Derm - Vice \nPresident\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nSecretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPast President\n\n\n\nDermatological Society of Malaysia \nMedical Academics of Malaysia, Unit 1.6, Level 1, Enterprise 3B, Technology Park Malaysia, Jalan \nInnovasi 1, Lebuhraya Puchong- Sg Besi, Bukit Jalil, 57000 Kuala Lumpur, Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2023 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - Committee \nMember\nDr Nazirin Ariffin, MRCP  - Committee Member\nDr Kevin How Kang Nien, Adv M Derm - \nCommittee Member\nDr Teeba Raja, Adv M Derm - Committee \nMember\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 MJD 2023 June Vol 50\n\n\n\nORIGINAL ARTICLE\n\n\n\nRelationship between Staphylococcus aureus Colonization and Face \nMask-associated Adverse Cutaneous Reactions during the COVID-19 \nPandemic\n\n\n\nLim Mong Wayne1, MRCP, Rajalingam Ramalingam1, AdvMDerm, Adawiyah Jamil2, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n2Dermatology unit, Department of Medicine, Hospital Canselor Tuanku Muhriz UKM, Kuala Lumpur, Malaysia\n\n\n\nAbstract \nBackground\nAdverse reactions on the skin due to face masks are well documented following the COVID-19 \npandemic. This study aims to investigate Staphylococcus aureus colonization in relation to face mask-\nassociated adverse cutaneous reactions (FMACR). \n\n\n\nMethods\nThis was a case-control study involving adult patients attending dermatology clinic, Hospital Tengku \nAmpuan Afzan, Pahang, Malaysia. FMACR was determined via a structured interview. Subjects and \nhealthy controls were matched for age and gender. Skin swabs from the alar crease and glabella were \nobtained and cultured. The possible risk factors for FMACR including type of mask, frequency of \nchange, average duration of use, and skin care practices were also attained. \n\n\n\nResults\nA total of 114 adult participants, which consisted of 57 case and 57 control were recruited. Itching was \nthe most frequent (32; 32.4%) FMACR noted, followed by acne (31; 31.4%) and rashes (22; 22.2%). \nThe presence of facial dermatoses and oily skin type increased the risk of FAMCR (adjusted OR=5.96, \n95% CI (1.96,18.12), p=0.002 and adjusted OR=1.94, 95% CI (0.28,13.28), p=0.009) respectively. \nCosmetic use was associated with lower risk of FMACR, (adjusted OR=0.16, 95% CI (0.05, 0.56), \np=0.004). No significant association was noted between S. aureus skin colonization and FMACR \n(p=0.409). \n\n\n\nConclusion\nStaphylococcus aureus skin colonization was not associated with FMACR. Risk factors for FMACR \nwere the presence of facial dermatoses and oily skin type while cosmetic use appears to have a \nprotective effect.\n\n\n\nKey words: COVID-19, face mask, Staphylococcus aureus \n\n\n\nCorresponding Author\nDr Lim Mong Wayne\nDepartment of Dermatology, \nHospital Tengku Ampuan Afzan, \n25000 Kuantan, Pahang, Malaysia. \nEmail: limmongwayne@gmail.com\n\n\n\nIntroduction\nSevere acute respiratory syndrome coronavirus \n2 (SARS-Cov-2) is the virus that causes \nCOVID-19. The COVID-19 virus spreads \nprimarily through droplets of saliva or \ndischarge from the nose when an infected \nperson coughs or sneezes. Face masks have \nbeen shown to provide protection from human-\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 3\n\n\n\nto-human respiratory viral transmission.1 In \nMarch 2020, during the initial stage of the \nCOVID-19 outbreak in Malaysia, face masks \nwere only required for frontliners and suspected \ncases with symptoms. Given the rapid rise \nin the incidence of COVID-19 infection, the \nMalaysian government has made the wearing of \nface masks mandatory in public spaces effective \nfrom 1st August 2020. Thus, the wearing of face \nmasks during the COVID-19 pandemic became \na new norm for the Malaysian population.\n\n\n\nDue to the increased use of face masks and \nother personal protective equipment (PPE) \nduring the COVID-19 pandemic, especially \namong health care workers, several studies \nhave reported adverse skin reactions due to the \nwearing of face masks.2-10 The types of face \nmask-associated adverse cutaneous reactions \n(FMACR) reported included itching, rashes \non the face, pressure-related skin injury, and \nacne, among others. There are also reports of \nthe worsening of underlying facial dermatoses \nrelated to face mask usage and some other \nstudies have investigated possible contributing \nfactors for FMACR.2-13 Other studies have also \nlooked into the influence of face mask use on \nskin characteristics, including trans-epidermal \nwater loss, sebum secretion, skin temperature, \nand others, to look for possible relationships \nto FMACR.14-16 Avoidance of all these risk \nfactors could potentially help in decreasing \nFMACR. However, none had studied the role \nof Staphylococcus aureus (S. aureus) in the \ndevelopment of FMACR.\n\n\n\nStudies have shown the role of S. aureus as \na potential mechanism for both primary and \nsecondary inflammation in skin diseases.17 In \natopic dermatitis (AD), patients with the disease \nare more likely to be colonized with S. aureus \nthan healthy controls, and colonization increases \nwith AD severity.18 Studies have also shown \nan increased risk of S. aureus colonization in \npatients with psoriasis.17,19 The same study also \nreported a statistically significant relationship \nbetween a higher psoriasis area and severity \nindex (PASI) score and colonization by \nenterotoxin-positive S. aureus.19 \n\n\n\nConsidering the potential role of S. aureus \nin amplifying symptoms in other chronic \ninflammatory skin diseases, we aim to \ndetermine the role of S. aureus skin colonization \nin FMACR. We also aim to identify various \nother factors which may contribute to FMACR, \nnamely, demographics, mask use practice, and \nskin care practice.\n\n\n\nMaterials and Methods \n\n\n\nStudy Design and Subject Selection\nThis was a single-centre, hospital-based case-\ncontrol study conducted at the Dermatology \nClinic of Hospital Tengku Ampuan Afzan \n(HTAA), Kuantan, Pahang, Malaysia between \n1 July 2021 and 31 December 2021. Written \ninformed consent was obtained from the \nparticipants. Ethical approval was obtained from \nthe Medical Research and Ethical Committee \n(MREC), Malaysia with research code NMRR-\n21-1208-59944.\n\n\n\nThe selection of case and control groups was \nbased on convenience sampling. All participants \nage 18 and older were eligible. The subjects of \nthe case group were patients who attended the \nclinic and subsequently diagnosed with FMACR \nvia a structured interview. The control group \nconsisted of participants who did not suffer from \nFMACR determined via the same structured \ninterview and they matched the patients with \nrespect to age and gender. Exclusion criteria \nincluded those who have been on any antibiotics \nwithin the past 6 weeks that may alter S. aureus \ncolonization in both groups.\n\n\n\nA face-to-face interview was performed to \ndetermine baseline variables including age, sex, \ncomorbidities, and underlying skin diseases. \nBody mass index (BMI; weight (kg)/height \n(m2)) and waist circumference (cm) were \nrecorded. The possible risk factors for FAMCR, \nincluding mask practices such as type of mask, \nfrequency of change, average duration of use, \nand skin care practices such as the use of facial \ncleanser, moisturizer, sunscreen, and cosmetic \nproducts, were also obtained in the interview.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 MJD 2023 June Vol 50\n\n\n\nSkin swab for Staphylococcus aureus \ncolonization\nThe investigators obtained skin swabs from the \nright alar crease (left alar crease swabbed if there \nwas a presence of skin disease at the right alar \ncrease) and glabella with the use of two labelled \nsterile cotton wool swabs (Citoswab regular dry \nswab; Citotest labware manufacturing, Haimen, \nChina). The specimens were placed in the \ntransport medium (Citoswab Stuart gel; Citotest \nlabware manufacturing, Haimen, China) and \ndelivered to the laboratory where they were \ninoculated onto sterilized blood agar plates, \nsubsequently incubated at 370C for 24 hours. All \ncultures were carried out at the microbiology \ndepartment of HTAA.\n\n\n\nSample size\nThis is a pilot study to look for the role of S. \naureus colonization in FMACR. Hence, the \nsample size of this study is calculated based \non a similar case-control study carried out by \nAli, Emad et al: Prevalence of Staphylococcus \naureus in Atopic Dermatitis (Eczema) cases in \nAl- Najaf City/Iraq.20  \n\n\n\nSample size estimation was calculated using \ntwo population proportions formulae. Prior \ndata indicate that the proportion of Ali, Emad \net al. of the (Group I) group was 0.54 and the \n\n\n\nproportion of (Group II) group was 0.2. Thus, \na minimum sample size of 41 samples per \ngroup to be able to reject the null hypothesis \nwith probability (power) 0.8. The Type I error \nprobability associated with this test of this null \nhypothesis is 0.05. With an additional of 20% \ndropout rate, the sample size is 52 samples per \ngroup. \n\n\n\nStatistical analysis\nStatistical analysis was performed using the \nStatistical Package for the Social Sciences \n(SPSS Version 24.0, IBM Corp). Descriptive \nstatistical methods, such as means, standard \ndeviations (SD), medians, and frequencies, \nwere used to describe the characteristics of \nthe study population and data set. Both Simple \nLogistic Regression Analysis (univariable \nanalysis) and Multiple Logistic Regression \nAnalysis (multivariable analysis) were \nperformed to test the associations between the \nproposed factors with FMACR and S. aureus \ncolonization respectively.  Simple Logistic \nRegression analysis identified potential \nsignificant associated factors (p < .25). These \npotential significant associated factors were \nthen included in multiple logistic regression \nto confirm whether these are significant \nindependent associated factors (p < 0.05).\n\n\n\nTable 1. Demographic and clinical characteristics of the study population\n\n\n\nDemographic data\nTotal (N=114)\n\n\n\np\u2013valueCase (n=57)\nMean \u00b1 SD / n (%)\n\n\n\nControl (n=57)\nMean \u00b1 SD / n (%)\n\n\n\nAge, in yearsa 33.37\u00b112.05 31.60\u00b111.15 0.417\n\n\n\nGender\n\n\n\nMale 19 (33.3) 19 (33.3)\n1.000Female 38 (66.7) 38 (66.7)\n\n\n\nRace\n\n\n\nMalay 46 (80.7) 50 (87.7)\n\n\n\n0.442Chinese 10 (17.5) 7 (12.3)\n\n\n\nIndian 1 (1.8) 0 (0.0)\n\n\n\nComorbid 22  (38.6) 18 (31.6) 0.432\n\n\n\nSmoking 4(7.0) 5 (8.8) 1.00\n\n\n\nWeight (kg) 67.86\u00b116.45 68.04\u00b19.83 0.956\n\n\n\nBMI (kg/m2) 26.23\u00b15.66 26.46\u00b16.24 0.834\n\n\n\nAbdominal Girth (cm) 86.68\u00b114.54 87.47\u00b115.79 0.779\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 5\n\n\n\nTable 2. Types of face mask-associated adverse \ncutaneous reactions (FMACR) \n\n\n\n FMACR Cases (N = 57)\nn (%)\n\n\n\nItching                                                      \nAcne                                                        \nDermatitis on face                                    \nRashes behind ears                                     \nHyperpigmentation                                     \nPressure related skin injury                        \n\n\n\n32 (32.4)\n31 (31.4)\n22 (22.2)\n5 (5.0)\n5 (5.0)\n4 (4.0)\n\n\n\nResults \nA total number of 114 participants were \nenrolled, 76 (66.7%) were female and 38 \n(33.3%) were male. The mean age of FMACR \nand the control group was 33.37\u00b112.05 and \n31.60\u00b111.15, respectively, with no statistically \nsignificant age difference (p=0.417). The case \nand control groups had similar mean BMIs \nof 26.23\u00b15.66 and 26.46\u00b16.24, respectively \n\n\n\nTable 3. Factors associated with FMACR\n\n\n\nFactors Simple Logistic Regression Multiple Logistic Regression\n\n\n\nCrude OR (95% CI) p-value Adjusted OR (95%CI) p-value\n\n\n\nComorbid\nNo\nYes\n\n\n\n1\n1.36 (0.63, 2.95) 0.433\n\n\n\n- -\n\n\n\nSmoking\nNo\nYes\n\n\n\n1\n0.79 (0.20, 3.09) 0.729\n\n\n\n- -\n\n\n\nBMI 0.99 (0.93, 1.06) 0.832 - -\n\n\n\nAbd circumference 0.99 (0,97, 1.02) 0.777 - -\n\n\n\nHistory of Skin Disease\nNo\nYes\n\n\n\n1\n1.00 (0.33, 3.06) 1.000\n\n\n\n- -\n\n\n\nHistory of Facial dermatoses\nNo\nYes\n\n\n\n1\n6.81 (2.74, 16.92) <0.001\n\n\n\n1\n5.96 (1.96, 18.12) 0.002\n\n\n\nSkin Type\nNormal\nOily\nDry\nCombination\n\n\n\n1\n5.44 (2.11, 14.01)\n0.75 (0.18, 3.17)\n5.22 (0.97, 28.01)\n\n\n\n<0.001\n0.690\n0.054\n\n\n\n1\n4.50 (1.45, 13.93)\n0.46 (0.07, 2.87)\n1.94 (0.28, 13.28)\n\n\n\n0.009\n0.407\n0.498\n\n\n\nMask type\nSurgical mask\nCloth mask\nDouble mask\nKN94\n\n\n\n1\n0.70 (0.15, 3.32)\n1.64 (0.45, 5.98)\n\n\n\n0 (0, 0)\n\n\n\n0.655\n0.455\n0.999\n\n\n\n- -\n\n\n\nFrequency of change\nA few times a day\nEveryday\nEvery 2-3 days\nEvery week\n\n\n\n1\n0.46 (0.20, 1.07)\n0.14 (0.01, 1.43)\n\n\n\n0 (0, 0)\n\n\n\n0.071\n0.098\n1.000\n\n\n\n1\n0.44 (0.16, 1.25)\n0.30 (0.02, 4.07)\n\n\n\n0 (0, 0)\n\n\n\n0.124\n0.368\n1.000\n\n\n\nAverage time of use per day\n< 4 hours\n4-8 hours\n>8 hours\n\n\n\n1\n1.28 (0.59, 2.78)\n2.93 (0.53, 16.26)\n\n\n\n0.525\n0.219\n\n\n\n1\n1.52 (0.55, 4.18)\n8.21 (0.80, 84.82)\n\n\n\n0.421\n0.077\n\n\n\nMoisturizers\nNo\nYes\n\n\n\n1\n1.95 (0.91, 4.18) 0.086\n\n\n\n1\n2.69 (0.80, 9.11) 0.111\n\n\n\nSunscreen\nNo\nYes\n\n\n\n1\n1.47 (0.68, 3.16) 0.330\n\n\n\n- -\n\n\n\nFacial Cleanser\nNo\nYes\n\n\n\n1\n1.69 (0.74, 3.87) 0.213\n\n\n\n1\n1.31 (0.38, 4.55) 0.668\n\n\n\nCosmetic products\nNo\nYes\n\n\n\n1\n0.44 (0.19, 0.99) 0.046\n\n\n\n1\n0.16 (0.05, 0.56) 0.004\n\n\n\nStaph Aureus Colonisation\nNegative\nPositive\n\n\n\n1\n1.59 (0.53, 4.82) 0.409 - -\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 MJD 2023 June Vol 50\n\n\n\n(p=0.834). There was no significant difference \nin the presence of comorbidities, which include \ntype II diabetes mellitus, hypertension, chronic \nrespiratory disease, and autoimmune diseases, \namong others, between the FMACR and control \ngroups (p=0.432). The demographic and clinical \ncharacteristics of study population are shown in \nmore detail in Table 1 below.\n\n\n\nAmong the types of adverse skin reactions \nfound in the FMACR group, itching was the \nmost frequent adverse skin reaction found \n(32; 32.4%), followed by acne (31; 31.4%), \nand dermatitis on the face (22; 22.2%) (Table \n2). Among the patients who presented with \nFMACR acne, 16 (51.6%) also complained of \nitching.  \n\n\n\nTable 4: Factors associated with S. aureus colonization on the face\n\n\n\nVariables Simple Logistic Regression Multiple Logistic Regression\n\n\n\nCrude OR (95% CI) p-value Adjusted OR (95%CI) p-value\n\n\n\nComorbid\nNo\nYes\n\n\n\n1\n0.91 (0.29, 2.89) 0.879\n\n\n\n- -\n\n\n\nSmoking\nNo\nYes\n\n\n\n1\n0.81 (0.09, 7.00) 0.850\n\n\n\n- -\n\n\n\nBMI 0.96 (0.86, 1.05) 0.298 - -\n\n\n\nAbd circumference 0.99 (0.95, 1.02) 0.456 - -\n\n\n\nHistory of skin Disease\nNo\nYes\n\n\n\n1\n0 0.999\n\n\n\n- -\n\n\n\nHistory of facial dermatoses\nNo\nYes\n\n\n\n1\n1.92 (0.64, 5.76) 0.245\n\n\n\n1\n3.22 (0.79, 13.15)\n\n\n\n0.104\n\n\n\nSkin Type\nNormal\nOily\nDry\nCombination\n\n\n\n1\n1.60 (0.40, 6.41)\n7.73 (1.62, 36.82)\n3.87 (0.61, 24.41)\n\n\n\n0.507\n0.010\n0.150\n\n\n\n1\n1.90 (0.35, 10.35)\n7.19 (1.14, 45.42)\n3.41 (0.36, 32.75)\n\n\n\n0.459\n0.036\n0.287\n\n\n\nMask type\nSurgical mask\nCloth mask\nDouble mask\nKN94\n\n\n\n1\n3.64 (0.62, 21.58)\n2.03 (0.38, 10.86)\n6.07 (0.89, 41.31)\n\n\n\n0.154\n0.410\n0.065\n\n\n\n1\n4.73 (0.61, 36.48)\n3.64 (0.51, 26.18)\n2.89 (0.20, 41.64)\n\n\n\n0.136\n0.199\n0.437\n\n\n\nFrequency of change\nA few times a day\nEveryday\nEvery 2-3 days\nEvery week\n\n\n\n1\n1.00 (0.29, 3.53)\n1.81 (0.16, 20.55)\n\n\n\n0\n\n\n\n0.995\n0.631\n1.000\n\n\n\n- -\n\n\n\nAverage time of use per day\n< 4 hours\n4-8 hours\n>8 hours\n\n\n\n1\n0.53 (0.16, 1.81)\n0.88 (0.10, 8.15)\n\n\n\n0.312\n0.913\n\n\n\n- -\n\n\n\nMoisturizers\nNo\nYes\n\n\n\n1\n0.51 (0.15, 1.73) 0.282\n\n\n\n- -\n\n\n\nSunscreen\nNo\nYes\n\n\n\n1\n0.24 (0.05, 1.11) 0.067\n\n\n\n1\n0.25 (0.04, 1.52) 0.131\n\n\n\nFacial Cleanser\nNo\nYes\n\n\n\n1\n0.28 (0.09, 0.85) 0.025\n\n\n\n1\n0.35 (0.08, 1.55) 0.165\n\n\n\nCosmetic products\nNo\nYes\n\n\n\n1\n0.29 (0.06, 1.38) 0.121\n\n\n\n1\n0.62 (0.10, 3.97) 0.609\n\n\n\nAffected by FMACR\nNo\nYes\n\n\n\n1\n1.59 (0.53, 4.82) 0.409\n\n\n\n- -\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 7\n\n\n\nSimple and multiple logistic regression among \nfactors associated with FMACR are presented \nin Table 3. There was no statistically significant \ncorrelation between mask practices, including \ntypes of masks used, frequency of masks \nchanged, and average duration of face masks \nused, with having an adverse skin reaction on the \nface (p>0.05). In terms of skin care practices, \ncosmetic products used on the face were \nassociated with a 56% lower risk of developing \nFMACR compared to patients who did not \nuse cosmetic products, which was statistically \nsignificant [adjusted OR (95% CI)=0.16 (0.05, \n0.56), p=0.004]. We found no relationship \nbetween other skin care practices, including \nfacial cleansers, sunscreens, and moisturizers \nused, and the risks of developing FMACR \n(p>0.05). Our data also showed that patients \nwith facial dermatoses including acne vulgaris, \npsoriasis and others, were associated with a \n5.96 times higher risk of developing adverse \nskin reactions compared to patients without \n[adjusted OR (95% CI)=5.96 (1.96,18.12), \np=0.002]. When other confounding variables \nwere controlled for, patients with oily skin had \n4.50 times the odds of developing an adverse \nskin reaction as patients with normal skin \n[adjusted OR (95% CI)=1.94 (0.28, 13.28), \np=0.009]. \n\n\n\nAmong 114 participants, 15 (13.1%) were \ncolonized with S. aureus. Although there was a \nhigher proportion of S. aureus colonisation in \nthe FMACR group, the analysis using simple \nlogistic regression did not reach statistical \nsignificance (15.8% in FMACR subjects \nversus 10.9% in controls, p=0.409) (Table \n4). Using the same analysis, without respect \nto other factors, dry skin type and not using \nfacial cleansers increased the risk of S. aureus \ncolonization [crude OR (95% CI)=7.73 (1.62, \n36.82), P=0.01 and crude OR (95% CI)=0.28 \n(0.09,0.85), p=0.025]. However, multivariate \nanalysis showed that only dry skin type was \nindependently associated with a higher risk \nfor S. aureus colonization [adjusted OR (95% \nCI)=7.19 (1.14, 45.42), p=0.036]. Patients \nwith dry skin type had a 7.19 times higher risk \nof being exposed to S. aureus colonization \ncompared to patients with normal skin when \n\n\n\nother confounding variables were adjusted \n(Table 4).\n\n\n\nDiscussion\nS. aureus is a ubiquitous bacterium commonly \nfound in both the hospital and community.21 \nAsymptomatic colonization of S. aureus on \nthe skin is widespread, affecting approximately \n30% of the population.21,22 The primary site \nof colonization of this species is the anterior \nnares.23 The frequency of carriage of S. aureus \non different skin areas of adults varies, such as \nthe anterior nares (44%), axillae (8%), chest/\nback (12%) and perineum (22%).24 This may \nexplain the lower rate of colonization in our \nparticipants (15.8% in FMACR subjects versus \n10.9% in control), as swab samples were taken \nfrom both the alar crease and glabella. The lower \nproportion of male participants may also explain \nthe lower rate of S. aureus colonization in our \nstudy, as previous studies have documented that \nmales are more likely to be S. aureus carriers.25,26 \nGender differences in occupation, participation \nin contact sports, and hygiene practices may \npotentially influence S. aureus colonization in \nmales.25 \n\n\n\nS. aureus has a role in the mechanism of \nboth primary and secondary inflammation \nin skin diseases.17 S. aureus colonization is \nincreased in patients with atopic dermatitis \n(AD), causing more severe disease as well as \nexacerbations.27,28 There is an increased risk \nof S. aureus skin colonization in both non-\nlesional and lesional skin of psoriasis patients \ncompared with controls.29,30 Psoriasis severity \nwas significantly associated with enterotoxin-\npositive S. aureus colonization.19 To the best of \nour knowledge, our study is the first attempt to \ninvestigate the role of S. aureus colonization in \nFMACR. We found no significant association \nbetween S. aureus colonization and FMACR \nand we propose that S. aureus may not play \nan important role in FMACR pathogenesis.  \nHowever, as the pathogenic roles of several \nmicroorganisms have been demonstrated in \nvarious skin diseases, more research is needed \nto investigate the role of other microorganisms \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 MJD 2023 June Vol 50\n\n\n\nin causing FMACR. \n\n\n\nLonger duration of mask use was associated \nwith development of FMACR.2,4,5,7-9,13 There is \nconflicting data on whether the type of mask \nis associated with FMACR.2,8-10 However, \nunderlying facial dermatoses increases the risk \nof FMACR.3,10,31,32 The most common FMACR \nin our patients was itching.  Itch and acne \nare the two most common reported FMACR \nin previous studies.9,33,34 Itch may be due to \nstress-induced histamine release from mast cell \ndegranulation secondary to prolonged mask \nuse. Thermal stimuli, alloknesis, may also \ncontribute to increased itch.35,36 The occurrence \nof acne (mask-induced acne or \u201cmaskne\u201d)  may \nbe related to 3 factors:  friction or local pressure \nfrom the masks, alteration in local temperature \nand high humidity in the mask area leading to \nfollicular occlusion and lastly, disruption of \nthe skin microbiome.10,12,37 Itch is a relatively \ncommon symptom of  acne.38 A Polish study \nin 2020 demonstrated that subjects with pre-\nexisting acne were at significantly higher \nrisk of itching due to the use of face masks.8 \nPresence of facial dermatoses was found to be \nassociated with an increased risk of FMACR \namong our patients. Face mask aggravates \nunderlying seborrheic dermatitis, acne vulgaris, \nand rosacea.10,31,32,34 An epidemiological study \nreported that prior history of acne vulgaris \nwas associated with higher risks of developing \nnew acne lesions or worsening of existing \nacne due to face masks.39 The risk of redness \nin acne rosacea and contact dermatitis was \nfound to be significantly increased after mask \nuse.34 Skin barrier dysfunction and probable \nskin microbiome dysbiosis might contribute to \nFMACR in patients with facial dermatoses.10  \n\n\n\nWe found significant association between oily \nskin type and the risks of FMACR. Yaqoob S et \nal demonstrated a strong relationship between \nmaskne and oily skin type.40 A systematic review \nin 2020 also found a strong relationship between \nmaskne and oily skin type.41 Sebum secretion \nwas shown to be higher after mask-wearing, \nand the consequences of excess sebum may \ncontribute to the development of FMACR.42\n\n\n\nInterestingly, we observed a significant \nFMACR reduction with the use of cosmetics. \nCosmetics improved the hydration and texture \nof the skin.43,44 Daily cosmetic use increases skin \nmicrobial alpha diversity, resulting in improved \nskin microbial health.43 These factors could \nexplain how cosmetics help reduce FMACR.\n\n\n\nDry skin type among our patients had higher \nrates of S. aureus colonization. Correlation \nbetween skin dryness and S. aureus colonization \nhas been shown on non-lesional skin in atopic \ndermatitis patients.45 Reduction of lipids and \nfatty acids in the skin, resulting in increased \ndryness, is one of the main factors predisposing \nto S. aureus colonization. In atopic dermatitis \npatients, ceramides and sphingosine levels in \nthe stratum corneum are reduced, which also \ncontribute to S. aureus colonization.46 Various \nauthors have encouraged the use of moisturizers \nas a preventive measure for FMACR.47,48 Lotion \nand cream-based vehicles, are preferred over \nointments due to their non-occlusive effect.48 \n\n\n\nWe found that the use of common facial \ncleansers was not significantly associated with \nS. aureus colonization. This was consistent with \na report by Aimee et al where the use of common \ncommercial skin cleansers did not cause \nsignificant change in the bacterial community.49 \nThus, we recommend the use of facial cleansers, \nas these have not been shown to alter the normal \nmicrobiome on the skin. Various authors have \nalso recommended the use of a daily facial \ncleanser to protect against FMACR and help \nmaintain a healthy skin microbiome.48,50\n\n\n\nLimitations\nThere are several limitations to this study. The \nmajor limitation is the small sample size, as it is \na single-centre study, which might explain the \ninsignificant statistical results observed.\n\n\n\nFurthermore, our study is limited by the \npossibility of lower detection of S. aureus \nas swabs were taken from the alar crease and \nglabella while the anterior nares is the primary \nsite of colonization. There was also possible \nunder-detection of S. aureus colonisation as \nmore sensitive molecular tests for S. aureus \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 9\n\n\n\nidentification was not performed. \n\n\n\nConclusion\nThere was no significant difference in the \nprevalence of Staphylococcus aureus skin \ncolonization on the face between patients \naffected by FMACR and controls. The two most \nfrequent adverse skin reactions observed were \nitching and acne. The risk factors for FMACR \nwere the presence of facial dermatoses, oily \nskin type, and cosmetic-free facial skin. \n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto be disclosed.\n\n\n\nAcknowledgement\nWe would like to thank the Director of General \nof Health Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n1. Liang M, Gao L, Cheng C, Zhou Q, Uy PJ, Heiner K et \n\n\n\nal. 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Interactions \nBetween Atopic Dermatitis and Staphylococcus aureus \nInfection: Clinical Implications. Allergy Asthma Immunol \nRes 2019;11:593-603. \n\n\n\n28. Byrd AL, Deming C, Cassidy SKB, Harrison OJ, Ng WI, \nConlan S et al. Staphylococcus aureus and Staphylococcus \nepidermidis strain diversity underlying pediatric atopic \ndermatitis. Sci Transl Med 2017;9:eaal4651.\n\n\n\n29. Chang HW, Yan D, Singh R, Liu J, Lu X, Ucmak D et \nal. Alteration of the cutaneous microbiome in psoriasis \nand potential role in Th17 polarization. Microbiome \n2018;6:154. \n\n\n\n30. Tett A, Pasolli E, Farina S, Truong DT, Ascinar F, Zolfo M \net al. Unexplored diversity and strain-level structure of the \nskin microbiome associated with psoriasis. NPJ Biofilms \nMicrobiomes 2017;3:14. \n\n\n\n31. Choi SY, Hong JY, Kim HJ, Lee GY, Cheong SH, Jung \nHJ et al. Mask-induced dermatoses during the COVID-19 \npandemic: a questionnaire-based study in 12 Korean \nhospitals. Clin Exp Dermatol, 2021;46:1504-10. \n\n\n\n32. Yan Y, Chen H, Chen L, Cheng B, Diao P, Dong L et \nal. Consensus of Chinese experts on protection of skin \nand mucous membrane barrier for health-care workers \nfighting against coronavirus disease 2019. Dermatol Ther \n2020;33:e13310. \n\n\n\n33. Foo CC, Good AT, Leow YH, Goh CL. Adverse skin \nreactions to personal protective equipment against \nsevere acute respiratory syndrome--a descriptive study in \nSingapore. Contact Dermatitis 2006;55:291-4.  \n\n\n\n34. \u0130nan Do\u011fan E, Kaya F. Dermatological findings in \npatients admitting to dermatology clinic after using face \nmasks during Covid-19 pandemia: A new health problem. \nDermatol Ther 2021;34:e14934. \n\n\n\n35. Legat FJ. Itch in Atopic Dermatitis - What Is New? Front \nMed (Lausanne)  2021;8:644760. \n\n\n\n36. Berardesca E, Farage M, Maibach H. Sensitive skin: an \noverview. Int J Cosmet Sci 2013;35:2-8.  \n\n\n\n37. Donovan J, Skotnicki-Grant S. Allergic contact dermatitis \nfrom formaldehyde textile resins in surgical uniforms and \nnonwoven textile masks. Dermatitis 2007;18:40-4. \n\n\n\n38. Reich A, Trybucka K, Tracinska A, Samotij D, Jasiuk B, \nSrama M et al. Acne itch: do acne patients suffer from \nitching? Acta Derm Venereol 2008;88:38-42. \n\n\n\n39. Falodun O, Medugu N, Sabir L, Jibril I, Oyahkire \nN, Adekeye A. An epidemiological study on face \nmasks and acne in a Nigerian population. PLoS One \n2022;17:e0268224. \n\n\n\n40. Heng AHS, Chew FT. Systematic review of the \nepidemiology of acne vulgaris. Sci Rep 2020;10:5754. \n\n\n\n41. Yaqoob S, Saleem A, Jarullah FA, Asif A, Essar MY, Emad \nS. Association of Acne with Face Mask in Healthcare \nWorkers Amidst the COVID-19 Outbreak in Karachi, \nPakistan. Clin Cosmet Investig Dermatol 2021;14:1427-\n33. \n\n\n\n42. Park SR, Han J, Yeon YM, Kang NY, Kim E. Effect of \nface mask on skin characteristics changes during the \nCOVID-19 pandemic. Skin Res Technol 2021;27:554-9. \n\n\n\n43. Hwang BK, Lee S, Myoung J, Hwang SJ, Lim JM, Jeong \nET, Park SG et al. Effect of the skincare product on facial \nskin microbial structure and biophysical parameters: A \npilot study. Microbiologyopen 2021;10:e1236. \n\n\n\n44. Lee HJ, Jeong SE, Lee S, Kim S, Han H, Jeon CO. \nEffects of cosmetics on the skin microbiome of facial \ncheeks with different hydration levels. Microbiologyopen \n2018;7:e00557. \n\n\n\n45. Blicharz L, Usarek P, Mlynarczyk G, Skowronski \nK, Rudnicka L, Samochocki Z. Nasal Colonization \nby Staphylococci and Severity of Atopic Dermatitis. \nDermatitis 2020;31:215-22. \n\n\n\n46. Ogonowska P, Gilaberte Y, Bara\u0144ska-Rybak W, \nNakonieczna J. Colonization With Staphylococcus aureus \nin Atopic Dermatitis Patients: Attempts to Reveal the \nUnknown. Front Microbiol 2021;11:567090. \n\n\n\n47. Wilcha RJ. Does Wearing a Face Mask During the \nCOVID-19 Pandemic Increase the Incidence of \nDermatological Conditions in Health Care Workers? \nNarrative Literature Review. JMIR Dermatol \n2021;4:e22789.\n\n\n\n48. Teo WL. Diagnostic and management considerations for \n\u201cmaskne\u201d in the era of COVID-19. J Am Acad Dermatol \n2021;84:520-1. \n\n\n\n49. Two AM, Nakatsuji T, Kotol PF, Arvanitidou E, Du-\nThumm L, Hata TR et al. The Cutaneous Microbiome \nand Aspects of Skin Antimicrobial Defense System Resist \nAcute Treatment with Topical Skin Cleansers. J Invest \nDermatol 2016;136:1950-4. \n\n\n\n50. Teo WL. The \u201cMaskne\u201d microbiome - pathophysiology \nand therapeutics. Int J Dermatol 2021;60:799-809. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 11\n\n\n\nORIGINAL ARTICLE\n\n\n\nVitamin D Level among Psoriasis Patients, Healthy Controls and its \nRelationship with Sun Exposure and Dietary Intake - A Case Control Study\nAi Y\u2019ng Lim1,2, MRCP, Jyh Jong Tang1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh, Malaysia\n2Dermatology unit, Department of Medicine, Hospital Canselor Tuanku Muhriz UKM, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nBackground\nVitamin D deficiency has been implicated in psoriasis pathogenesis. Studies on the association of \n25-hydroxyvitamin D [25(OH)D] with psoriasis have inconsistent results. We aimed to determine \nthe serum 25(OH)D level among psoriasis patients versus healthy controls; to correlate it with sun \nexposure, dietary intake and psoriasis severity.\n\n\n\nMethods\nA case-control study on adults with plaque psoriasis in a Malaysian tertiary hospital. Control subjects \nwere age, gender and race-matched healthy volunteers.\n\n\n\nResults\nThere were 50 cases and 50 controls recruited: majority being males (68%) and Malays (66%). The \nmean serum 25(OH)D level was comparable between psoriasis patients and healthy subjects (51.59 \nnmol/L vs 49.13 nmol/L, p=0.46). Overall, there was a high percentage of subjects with insufficient \n25(OH)D levels (25-75 nmol/L) among both groups (82% vs 94%, p=0.06). There were more psoriasis \npatients with deficient levels (<25 nmol/L) than controls but the difference was not significant (8% \nvs 2%, p=0.36). Sun exposure index (SEI) was significantly associated with serum 25(OH)D: for \nevery unit of SEI increment, 25(OH)D is expected to increase by 4.39 units (p=0.03). There was \nno association between dietary intake with 25(OH)D level. Psoriasis area and severity index (PASI) \nscore had a negative correlation with serum 25(OH)D among psoriasis subjects albeit not statistically \nsignificant [Mean -0.353 \u00b1 SE (0.262), p=0.17].\n\n\n\nConclusion\nVitamin D insufficiency is common among our population. There was no significant difference in \nterms of mean serum 25(OH)D level, percentage of insufficiency or deficiency in between psoriasis \nsubjects and healthy controls. This study showed that higher SEI is associated with higher vitamin D \nlevel. \n\n\n\nKey words: Psoriasis, sun exposure, vitamin D\n\n\n\nCorresponding Author\nDr Lim Ai Y\u2019ng \n13, Jalan Lapangan Akasia 3, \nPanorama Lapangan Akasia, \n31650 Ipoh, Malaysia.\nEmail: jolim911@gmail.com\n\n\n\nIntroduction\nPsoriasis is a chronic inflammatory, immune \nmediated skin condition that is characterized \nby skin inflammation and keratinocytes \nhyperproliferation with increased risk of painful, \ndestructive arthritis. It is often associated with \ncardio-metabolic morbidity and psychosocial \nchallenges.1\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 MJD 2023 June Vol 50\n\n\n\nVitamin D derivative has been one of the \nimportant topical treatments for mild to \nmoderate psoriasis as it acts through the vitamin \nD receptor (VDR) on keratinocytes, hence the \neffect on cellular function. It also possesses \nimmuno-modulatory effects on T lymphocytes, \nmacrophages, monocytes and dendritic cells, \nin which it alters the gene expression involved \nin epidermal proliferation, differentiation, \napoptosis and neovessels formation.2-4 Studies \nhave shown that vitamin D has a role in regulating \nterminal differentiation of basal keratinocytes. \nHence, vitamin D deficiency may be associated \nwith inflammatory and proliferative activities \nthat are related to pathogenesis of psoriasis, in \nwhich abnormal and exaggerated proliferation \nof keratinocytes is present.5 25(OH)D is known \nto be the major circulating metabolite of vitamin \nD in human body and it reflects the input from \ndietary intake and cutaneous synthesis from \nsunlight exposure; it also circulates at levels \n1,000 times higher than 1,25-hydroxyvitamin \nD [1,25(OH)2D], hence serum 25(OH)D is \nconsidered as the standard clinical measure of \nvitamin D status.6\n\n\n\nSeveral studies have demonstrated the \nassociation of low serum vitamin D level in \npsoriasis and that it is inversely correlated with \ndisease severity and body mass index (BMI).7-9 \nRicerri F et al (2013) had reported a significantly \nlower serum level of 25(OH)D among psoriasis \npatients compared to healthy subjects, and \nsimilar findings were also noted from the study \nby Orgaz-Molina J et al (2012).7-8 However, \nstudies which were published in the more recent \nyears, comparing serum 25(OH)D level among \npsoriasis subjects and healthy controls have \nyielded inconsistent results.10-13 Maleki et al \n(2015) and Zuchi MF et al (2015) have reported \nthat there was no statistical significance in \nserum 25(OH)D level among psoriasis subjects \nand healthy controls in their studies.11-12\n\n\n\nTo date, no local data on correlation of vitamin \nD level with psoriasis is available. Besides, \nlimited studies have looked into the effect of \nsun exposure and dietary intake on the serum \nvitamin D level among psoriasis patients and \ntheir disease severity. \n\n\n\nOur primary objective was to determine and \ncompare the serum 25(OH)D level among \npsoriasis patients and healthy controls. The \nsecondary objective was to determine the effect \nof sun exposure and dietary intake of vitamin \nD on the serum 25(OH)D level among the two \ngroups, as well as to determine the correlation \nbetween serum vitamin D level with disease \nseverity in psoriasis patients.\n\n\n\nMaterial & Methods\nStudy design and subject recruitment\nThis was a case control study aimed to \ndetermine the association of serum 25(OH)D \nlevel with psoriasis subjects in comparison to \nhealthy controls. The study was conducted at \nthe Dermatology outpatient clinic of Hospital \nRaja Permaisuri Bainun, Ipoh, Malaysia. It is a \ntertiary hospital and the state referral center for \nDermatology cases. \n\n\n\nAdult psoriasis patients above 18 years old with \nplaque psoriasis of any disease severity who \nattended to the clinic during the period between \n18 August 2021 \u2013 28 February 2022 were \nrecruited. Convenience sampling method was \nused to recruit psoriasis patients who attended \nthe clinic and fulfilled the eligible criteria for \nthe study, primarily because of the limitations \nencountered during the busy outpatient clinic \nand the sampling frame was not readily \navailable. Healthy subjects were made up of \nage (within a 5-year gap), gender and race-\nmatched volunteers who were relatives or staff \nwithout psoriasis or any active skin lesions. The \npsoriasis subjects were matched to a 1:1 ratio \nwith healthy controls.\n\n\n\nWe have excluded individuals who were pregnant \nor lactating, those with preceding history of \nphototherapy in the past 3 months, on current oral \nor topical vitamin D and calcium supplement, \nbisphosphonates and systemic corticosteroid \ntherapy. Subjects who were obese (BMI>25) \nor those with chronic medical illnesses which \nmay alter vitamin D status, e.g. chronic liver \ndisease, chronic kidney disease (eGFR <60mL/\nmin/1.73m2), hyperparathyroidism, bowel \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 13\n\n\n\ndisease with malabsorption and malignancy \nwere also excluded.\n\n\n\nThe data collected included patient\u2019s \ndemographic data, presence of comorbidities, \nsmoking and alcohol consumption habits, \npsoriasis disease information, along with \nthe duration and body surface area (BSA) \nof sun exposure, as well as dietary intake of \nvitamin D based on a validated food frequency \nquestionnaire (FFQ)14. \n\n\n\nSun exposure was quantified as an index \n(SEI), which was calculated by exposed BSA \n(in fraction) multiplied with the duration of \nexposure per week (in hour).15  \n\n\n\nWe used a validated FFQ developed by Zaleha \net al in 2015 to ascertain the estimated vitamin \nD intake of both case and control subjects based \non their dietary intake within 1 month prior to the \nblood sampling.14 The questionnaire consisted \nof various types of local food enriched with \nvitamin D and the participants were required \nto mark the frequency of consumption of each \ntype of food, e.g. once daily/ weekly/ monthly \nwith the estimated amount of intake based on \nstandard portioning. The quantification of \nthe vitamin D value was performed using the \nNutritionistPro software. \n\n\n\nThe disease severity was assessed among the \npsoriasis subjects using PASI score.16 Inter-\nobserver bias was minimized as there was only \na single interviewer involved in collection of \ndata and assessment of PASI scores.\n\n\n\nSerum vitamin D sampling and analysis\n3mL of venous blood was sampled from \nantecubital veins of participating subjects and the \nblood samples were processed in the Biochemical \nLab of Putrajaya Hospital, Malaysia for serum \n25(OH)D assay (using Chemiluminescence \nImmunoassay method). According to the \nreference ranges stated by the laboratory, serum \n25(OH)D level of <25 nmol/L was defined as \ndeficient, 25 - 75 nmol/L as insufficient, 76 - \n250 nmol/L as sufficient and > 250 nmol/L was \ncategorized as possible intoxication.17 \n\n\n\nStudy size calculations\nThe sample size of this study was calculated \nbased on the case-control study carried out \nby Orgaz-Molina J et al in 2012 on serum \nconcentration of 25(OH)D in psoriasis patients \nversus healthy subjects. The mean and standard \ndeviation (SD) of serum 25(OH)D level of the \nstudy group were 24.41 ng/mL (SD 7.80) and the \nhealthy controls were 29.53 ng/mL (SD 9.38). \nWe required a sample size of 45 for the study \ngroup and a sample size of 45 for the control \ngroup in order to reject the null hypothesis \nwith a probability (power) of 0.8 and Sampling \nRatio=1. The Type 1 error probability associated \nwith this test of this null hypothesis is 0.05. To \nallow a 10% dropout rate, the total sample size \nwas calculated to be 50 subjects per group.\n\n\n\nData analysis\nStatistical analysis was performed using IBM \nSPSS version 26. Chi-Square test and Fisher\u2019s \nexact test were used to compare the demographic \ncharacteristics in between the two groups. \nGeneralized Linear Model was used to test the \ncorrelation in between the serum 25(OH)D \nlevel with its predictors (SEI, dietary vitamin D \nintake and PASI score) for both study groups; \nwhereas Mann-Whitney U test was employed to \ncompare the SEI and dietary vitamin D intake in \nbetween the two groups, as well as PASI score \namong the psoriasis subjects. A value of p<0.05 \nwas considered statistically significant. There \nwas no missing data or dropout during data \ncollection and analysis.\n\n\n\nEthical approval\nThis study was registered with the National \nMedical Research Registry (NMRR-21-1277-\n60526). Ethical approval for the study was \nobtained from the Medical Research Ethics \nCommittee, Ministry of Health, Malaysia.\n\n\n\nResults\nThe first 50 psoriasis patients who attended \nthe clinic and fulfilled the eligible criteria \nwere recruited into the study. The 50 control \nsubjects selected were age, gender and race-\nmatched healthy volunteers who were relatives \nor hospital staff.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 MJD 2023 June Vol 50\n\n\n\nThe demographic characteristics among case \nand control subjects were comparable in terms \nof age, gender, ethnicity, body mass index \n(BMI) and co-morbidities, except that smoking \nhistory was significantly higher among psoriasis \nsubjects (p=0.02) as shown in Table 1. Chi-\nSquare test was used for the majority of the \nvariables, except the ones with *, where Fisher\u2019s \nexact test was used.\n\n\n\nThe mean serum 25(OH)D level was comparable \nbetween psoriasis and control subjects (51.59 \nnmol/L vs 49.13 nmol/L, p=0.46).\n \nOverall, we noticed that there was a significant \ndifference in serum 25(OH)D level for male \n(55.81 \u00b1 16.41) and female (38.77 \u00b1 10.90), \np=<0.001. The comparisons among both \ngenders in the two study groups were further \nillustrated in Table 2. Female subjects in both \npsoriasis group and healthy controls were noted \nto have a significantly lower level of serum \n25(OH)D. \n\n\n\nThere was a higher percentage of subjects with \ninsufficient levels (25-75 nmol/L) of serum \n25(OH)D in both psoriasis and control groups \n(82% vs 94%, p=0.06). There were more \npsoriasis subjects with deficient serum 25(OH)\nD level (<25 nmol/L) compared to healthy \ncontrols (8% vs 2%, p=0.36) even though the \n\n\n\ndifference was not significant. Only 5 psoriasis \nsubjects (10%) and 2 healthy controls (4%) were \nnoted to have normal 25(OH)D level (p=0.43)\n\n\n\nBy using Generalised Linear Model to test on \nthe association of SEI, dietary vitamin D intake, \nPASI score and BMI with serum 25(OH)D \nlevel, as shown in Table 3, we noted that the SEI \nwas significantly associated with serum 25(OH)\nD (p=0.03). It was deduced that for every unit \nof increment in SEI, serum 25(OH)D level is \nexpected to increase by 4.39 units.\n\n\n\nThere was no significant association between \ndietary vitamin D intake and BMI with serum \n25(OH)D level. Disease severity of psoriasis \nin terms of PASI score seemed to have a \nnegative correlation with serum 25(OH)D level \n(Mean -0.353 \u00b1 SE 0.262), although it was not \nstatistically significant (p=0.17).\n\n\n\nThe median level of SEI among the subjects were \nillustrated in Table 4. There was no significant \ndifference in terms of SEI among psoriasis and \ncontrol subjects even though SEI is lower in \npsoriasis than the control group (0.6 vs 0.875, \np=0.34). Female subjects in both the groups \nwere noted to have a much lower SEI (0.27 vs \n1.04 among psoriasis subjects, p=0.002; 0.178 \nvs 1.14 among control subjects, p<0.001). \n\n\n\nTable 1. Demographic characteristics among case and control groups\n\n\n\nDemographic Characteristics Case (n = 50) Control (n = 50) p value\n\n\n\nAge, median (IQR) 32.0 (24-46.25) 31.0 (23-46) 0.99\n\n\n\nGender, n (%)\n\n\n\nMale 34 (68.0) 34 (68.0) 0.99\n\n\n\nFemale 16 (32.0) 16 (32.0)\n\n\n\nEthnicity, n (%)\n\n\n\nMalay 33 (66.0) 33 (66.0) 0.99\n\n\n\nChinese 7 (14.0) 7 (14.0)\n\n\n\nIndian 10 (20.0) 10 (20.0)\n\n\n\nBMI, median (IQR) 23.2 (21.14-24.9) 23.1 (20.16-24.26) 0.84\n\n\n\nComorbidities\n\n\n\nHypertension 8 (16.0) 6 (12.0) 0.56\n\n\n\nDiabetes mellitus* 3 (6.0) 0 (0.0) 0.24\n\n\n\nDyslipidaemia* 7 (14.0) 4 (8.0) 0.26\n\n\n\nSmoking 12 (24.0) 4 (8.0) 0.02\n\n\n\nAlcohol* 1 (2.0) 1 (2.0) 0.99\nBMI = Body mass index; IQR = Interquartile range\n  *Fisher\u2019s exact test was used\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 15\n\n\n\nIn general, the dietary intake of vitamin D among \ncontrol group was higher compared to psoriasis \nsubjects but the difference was not significant \n(224.0 iU vs 170.10 iU, p=0.12). (Table 5)\n\n\n\nThe overall median PASI score was 7.0 (IQR \n3.8 - 17.58). Median PASI score was 6.3 \n(IQR 3.8 - 20.85) among the male psoriasis \nsubjects and 7.3 (IQR 3.63 - 15.4) among \ntheir female counterparts. PASI score had a \nnegative correlation with serum 25(OH)D \namong psoriasis subjects but the difference was \n\n\n\nnot statistically significant [Mean -0.353 \u00b1 SE \n(0.262), p=0.17].\n\n\n\nDiscussion\nThere is currently no consensus over the optimal \nvalues of serum 25(OH)D levels. Levels below \n25 nmol/L are defined as severe deficiency \nbased on the recommendations by International \nOsteoporosis Foundation.18 In 2011, the \nEndocrine Society Task Force had established \nrecommendations for serum 25(OH) vitamin \n\n\n\nTable 2. Comparison of serum 25(OH)D level among both genders in two study groups, n = 100\n\n\n\nGender Mean serum 25(OH)D (SE) p value\n\n\n\nOverall Male (n=68) 55.81 (16.41) <0.001\n\n\n\nFemale (n=32) 38.77 (10.90)\n\n\n\nCase Male (n=34) 56.87 (19.28) 0.003\n\n\n\nFemale (n=16) 40.34 (12.42)\n\n\n\nControl Male (n=34) 54.75 (13.15) <0.001\n\n\n\nFemale (n=16) 37.20 (9.26)\n\n\n\nGroup Mean serum 25(OH)D (SE) p value\n\n\n\nMale Case (n=34) 56.87 (19.28) 0.59\n\n\n\nControl (n=34) 54.75 (13.15)\n\n\n\nFemale Case (n=16) 40.34 (12.42) 0.42\n\n\n\nControl (n=16) 37.20 (9.26)\n25(OH)D=25-hydroxyvitamin D; SE=Standard error\n\n\n\nTable 3. Correlation of serum 25(OH)D with the variables tested by Generalised Linear Model, n = 100\n\n\n\nVariables Mean \u00b1 SE* p value\n\n\n\nSEI 4.39 (2.08) 0.03\n\n\n\nDietary vitamin D intake 0.007 (0.0159) 0.64\n\n\n\nPASI score -0.353 (0.262) 0.17\n\n\n\nBMI 1.007 (0.974) 0.30\nBMI = Body mass index; PASI = Psoriasis area & severity index; SEI = Sun exposure index; 25(OH)D = 25-hydroxyvitamin D\n   *Regression coefficient (SE, Standard error)\n\n\n\nTable 4. Median level of SEI among both groups and gender, n = 100\n\n\n\nSEI Case (Median, IQR) Control (Median. IQR) p value\n\n\n\nGender Overall 0.6 (0.22-1.5) 0.875 (0.24-2.99) 0.34\n\n\n\nMale (n = 68) 1.04 (0.32-2.50) 1.14 (0.56-3.65) 0.11\n\n\n\nFemale (n = 32) 0.27 (0.08-0.66) 0.18 (0.09-0.75) 0.77\nSEI = Sun exposure index; IQR = Interquartile range\n\n\n\nTable 5. Median level of dietary vitamin D intake among the two groups and gender, n = 100\n\n\n\nDietary vitamin D intake Case (Median, IQR) Control (Median, IQR) p value\n\n\n\nGender Overall 170.10 (98.45-272.28) 224.9 (143.56-302.26) 0.12\n\n\n\nMale (n = 68) 190.47 (108.19-282.43) 244.47 (179.36-340.07) 0.07\n\n\n\nFemale (n = 32) 136.16 (83.08-262.09) 179.14 (105.81-230.23) 0.67\nIQR = Interquartile range\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16 MJD 2023 June Vol 50\n\n\n\nD levels as followed: < 50 nmol/L as deficient, \n50 - 75 nmol/L as insufficient, 75 - 250 nmol/L \nas sufficient and > 250 nmol/L as upper safety \nlimit.19\n\n\n\nFrom our study, we noticed that there was no \ndifference of the mean serum 25(OH)D level in \nbetween psoriasis subjects with healthy controls, \nalthough the psoriasis group had a slightly \nhigher percentage of vitamin D deficiency (8% \nvs 2%, p=0.36). \n\n\n\nBy using Generalised Linear Model to test on \nthe association of SEI, dietary vitamin D intake \nand PASI score with serum 25(OH)D level, it \nwas noted that SEI was significantly correlated \nwith vitamin D level, of which for every unit \nof SEI increment, serum 25(OH)D is expected \nto increase by 4.39 units (p=0.03). However, \nthere was no significant association in between \ndietary vitamin D intake with serum 25(OH)\nD level. The severity of psoriasis appeared to \nbe negatively correlated with serum 25(OH)D \nlevel [Mean -0.353 \u00b1 SE (0.262), p=0.17].\n\n\n\nThe findings of our study had showed that \nthere was no significant difference in between \nserum 25(OH)D level among psoriasis subjects \nwith healthy controls, and this finding was in \ncontrast with the case control study published by \nGisondi P et al (2011), in which they have found \na significantly lower level of serum 25(OH)D in \npsoriasis patients compared to healthy controls, \nbut no difference was noted in between psoriasis \nsubjects with those with rheumatoid arthritis.9\n\n\n\nHowever, Maleki M et al (2015) had reported \nthat no statistical significance was observed in \nserum 25(OH)D level among psoriasis subjects \nwith the control group, which showed similar \nfindings with our current study.11 Another case \ncontrol study conducted by Zuchi MF et al \n(2015) had also pointed out that no significant \ncorrelation was observed in serum vitamin D \nlevel among psoriasis patients with healthy \nsubjects.12 The possible reason for inconsistent \nresults reported in the literature might be \nbecause vitamin D level may vary according to \nfactors such as geography, seasonal variations, \nage factor, ethnicity, health conditions of study \n\n\n\nsubjects, the use of vitamin D supplement, \ndietary habit, as well as environmental factors \namong the studies across different countries.19\n\n\n\nLocal studies comparing vitamin D level among \npatients with atopic dermatitis (AD) which are \navailable to date have shown differing results \namong the adult and children subjects. A case \ncontrol study conducted by Mohan A et al \n(2020) had demonstrated positive correlation of \nvitamin D in adult patients with AD, in which \nlower levels of vitamin D were noted among \nthese subjects in comparison with controls. \nAD was identified as an independent risk for \nvitamin D deficiency and insufficiency in this \nstudy, however the levels did not correlate with \nAD severity.20 On the other hand, another case \ncontrol study done locally by YW Lee et al \n(2019) which examined serum 25(OH)D levels \nin children with AD and controls did not show \nstatistical differences among the two groups. \nSimilar to the findings of our study, serum \nvitamin D levels were noted to be significantly \nlower among children with severe AD compared \nto the subjects with mild to moderate AD.21 \n\n\n\nA case control study done by Ramalingam R \net al (2018) looking at 25(OH)D level among \nvitiligo patients versus matched controls in \nMalaysia had reported no significant difference \nin the mean vitamin D level among the two \ncohorts. The study had also found out that \ntwo-thirds of subjects in both the groups had \ndeficient and insufficient levels. This had tallied \nwith one of the findings of our study, i.e. a high \npercentage of our study subjects were noted to \nhave abnormal serum vitamin D levels.22 \n\n\n\nComparing our local data on serum 25(OH)\nD level in the Malaysian adult population, we \nnoticed that our local population generally has \na lower-than normal vitamin D level (< 75 \nnmol/L). Shafinaz & Moy have reported in a \ncross sectional study done in Kuala Lumpur in \n2016 which consisted of 858 subjects ranging \nfrom 30 - 49 years old, in which they noticed \nthat as high as 80.9% of Indian subjects had \na deficient level of vitamin D (< 50 nmol/L), \nfollowed by Malays (75.6%) and Chinese \n(25.1%).23 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 17\n\n\n\nChin et al (2014) had reported in a cross \nsectional study done in Kuala Lumpur on 383 \nmale subjects which showed that the mean \nserum 25(OH)D level was 58.7 nmol/L.24 Moy \n& Bulgiba (2011) had also noticed a mean \nserum 25(OH)D level of 56.2 nmol/L among \nthe male subjects and 36.2 nmol/L in their \nfemale counterparts.25 Lieu et al had reported \nin a cross sectional study in 2020 which was \nconducted among postmenopausal women, of \nwhich the mean serum 25(OH)D level of 214 \nsubjects was 37.4 \u00b1 14.3, and up to 82.7% of \nthe study population had an abnormal level of \nvitamin D.26\n\n\n\nOn the other hand, our current study had \ndemonstrated that sun exposure index was \nsignificantly associated with serum 25(OH)\nD level. This finding of positive correlation \nwas further supported by the results reported \nby Sambrook PN et al in their randomized \ncontrolled trial in 2011, in which the vitamin D \nlevel was noted to be increased more among the \nsubjects exposed to ultraviolet source compared \nto the control group.27 Besides, the randomized \ncontrolled trial conducted by Lee YM et al \n(2011) had also shown a significant increment \nof serum 25(OH)D among the sunlight exposure \ngroup in comparison to the control subjects.28\n\n\n\nIn our current study, we have noted that the SEI \namong psoriasis subjects was slightly lower \nthan their healthy counterparts (0.6 vs 0.875, \np=0.34) but the difference was not significant. \nIt could possibly be due to the fact that psoriasis \npatients have the tendency to cover up their \nbody parts with psoriatic lesions during their \noutdoor activities. Besides, another observation \nnoted was that our female subjects in both the \ngroups had a much lower SEI compared to male \nsubjects in general. This could be because the \nmajority of the female subjects were Malay \nMuslims (68.8%) and due to cultural and \nreligious reasons, Muslim women are usually \ndressed in clothing that cover up most of \ntheir body parts. Serum 25(OH)D levels were \ngenerally lower among the female subjects in \nboth the study groups and this is likely related \nto the significantly lower duration or BSA of \n\n\n\nsun exposure. Another reason for lower sun \nexposure among women subjects could be due \nto the sociocultural norms in this region of Asia, \nwhere fair complexion is commonly being \npreferred.29\n\n\n\nOur current study had also noticed a negative \ncorrelation of PASI score with serum 25(OH)D \nlevel among psoriasis subjects albeit statistically \ninsignificant. A significant correlation was \ndemonstrable by the case control study reported \nby Recerri F et al (2013), which showed that \nserum 25(OH)D had a significant negative \ncorrelation with PASI score.7 Maleki M et al \n(2015) had suggested in a case control study that \npsoriasis disease severity does have an impact \non the level of vitamin D in the body, as lower \nlevel of serum 25(OH)D was correlated with a \nhigher PASI score.11\n\n\n\nBesides, we have also noted that the majority \nof our study subjects (92%) were consuming \na lower-than-recommended amount of dietary \nvitamin D as suggested by the National Health \nService in the United Kingdom, i.e. 400iU per \nday.30 This finding was further supported by \nanother local study conducted by Ramalingam \nR et al (2018), in which they have reported that \none of the independent variables which affected \nvitamin D level was dietary vitamin D intake, \nand the dietary intake in both vitiligo patients \nand matched subjects was extremely low.22 \n\n\n\nGeneralisability\nThe results of our current study are generalisable \nfor our local population and likely among the \nAsian population, given our similar background \nand cultural differences. It may however, not be \napplicable for psoriasis patients who are obese \nor those with factors which may alter vitamin D \nmetabolism, e.g. chronic liver or kidney disease, \nother concurrent autoimmune conditions or \nthose with malignancies.\n\n\n\nLimitations\nThe limitations of this study may include \nrecall bias among the participants, in particular \non the recall of food intake or frequency, and \nsun exposure duration or percentage of BSA \nexposed. Besides, convenience sampling of \nsubjects may have limited the representation of \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 MJD 2023 June Vol 50\n\n\n\nthe general psoriasis population being studied.\n\n\n\nConclusion\nVitamin D insufficiency is common among our \npopulation. There was no significant difference \nin terms of mean serum 25(OH)D level, \npercentage of insufficient or deficient level of \nserum 25(OH)D between psoriasis subjects and \ncontrols. This study showed that higher SEI is \nassociated with higher vitamin D level. \n\n\n\nConflict of Interest Declaration\nAll authors have disclosed no conflicts of \ninterest.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish \nthis article. We also thank Suria J, XJ Lim and \nMN Idy Razlan (Clinical Research Center, Raja \nPermaisuri Bainun Hospital) for their support \nin the registration of research, data analysis and \nmanuscript writing for this study. This study \nwas funded by the Malaysian Dermatological \nSociety on the expenses of laboratory assays.\n\n\n\nReferences\n1. Kang S, Masayuki A, Anna LB, Alexander HE, David JM, \n\n\n\nAmy JM et al. Fitzpatrick\u2019s Dermatology. In: Johann EG, \nJames TE. Psoriasiform disorders: psoriasis. 9th ed, vol 1. \nNew York. McGraw-Hill Publication 2019. p.457.\n\n\n\n2. van de Kerkhof PC. The topical treatment of psoriasis. \nClin Exp Dermatol 2005;30:205-8.\n\n\n\n3. Tanghetti EA. The role of topical vitamin D modulators in \npsoriasis therapy. J Drugs Dermatol 2009;(8 Suppl):s4-8.\n\n\n\n4. Cantorna MT. Vitamin D and autoimmunity: Is vitamin \nD status an environmental factor affecting autoimmune \ndisease prevalence? Proc Soc Exp Biol Med 2000;223:230-\n3.\n\n\n\n5. Morimoto S, Yoshikawa K. Psoriasis and Vitamin D3. A \nreview of our experience. Arch Dermatol 1989;125:231-4.\n\n\n\n6. Holick MF. Vitamin D: a millennium perspective. J Cell \nBiochem 2003;88:296-307.\n\n\n\n7. Ricceri F, Pescitelli L, Tripo L, Prignano F. Deficiency of \nserum concentration of 25-hydroxyvitamin D correlates \nwith severity of disease in chronic plaque psoriasis. J Am \nAcad Dermatol 2013;68:511-2. \n\n\n\n8. Orgaz-Molina J, Buend\u00eda-Eisman A, Arrabal-Polo \nMA, Ruiz JC, Arias-Santiago S. Deficiency of serum \nconcentration of 25-hydroxyvitamin D in psoriatic \npatients: a case-control study. J Am Acad Dermatol \n2012;67:931-8. \n\n\n\n9. Gisondi P, Rossini M, Di Cesare A, Idolazzi L, Farina S, \nBeltrami G et al. Vitamin D status in patients with chronic \nplaque psoriasis. Br J Dermatol 2012;166:505-10. \n\n\n\n10. Sa\u011f MS, Sa\u011f S, Tekeo\u011flu \u0130, Solak B, Kamanli A, Nas \nK et al. Comparison of 25-hidroksi Vitamin D serum \nconcentrations in patients with psoriasis and psoriatic \narthritis. J Back Musculoskelet Rehabil 2018;31:37-43. \n\n\n\n11. Maleki M, Nahidi Y, Azizahari S, Meibodi NT, Hadianfar \nA. Serum 25-OH Vitamin D Level in Psoriatic Patients \nand Comparison With Control Subjects. J Cutan Med \nSurg 2016;20:207-10. \n\n\n\n12. Zuchi MF, Azevedo Pde O, Tanaka AA, Schmitt JV, \nMartins LE. Serum levels of 25-hydroxy vitamin D in \npsoriatic patients. An Bras Dermatol 2015;90:430-2. \n\n\n\n13. Wilson PB. Serum 25-hydroxyvitamin D status in \nindividuals with psoriasis in the general population. \nEndocrine 2013;44:537-9. \n\n\n\n14. Zaleha MI, Khadijah S, Bukhary N, Khor GL, Zaleha \nMA, Haslinda H et al. Malaysian J Nutr 2015;21:179-90.\n\n\n\n15. Barger-Lux MJ, Heaney RP. Effects of above average \nsummer sun exposure on serum 25-hydroxyvitamin \nD and calcium absorption. J Clin Endocrinol Metab \n2002;87:4952-6.\n\n\n\n16. Ashcroft DM, Wan Po AL, Williams HC, Griffiths CE. \nClinical measures of disease severity and outcome in \npsoriasis: a critical appraisal of their quality. Br J Dermatol \n1999;141:185-91.\n\n\n\n17. Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, \nBurckhardt P, Fuleihan HGE et al. IOF position statement: \nvitamin D recommendations for older adults. Osteoporos \nInt 2010;21:1151-4.\n\n\n\n18. International Osteoporosis Foundation, Switzerland: \nVitamin D recommendations. Available from: www.\nosteoporosis.foundation/vitamin-d-recommendations. \nAccessed on 17/2/2023.\n\n\n\n19. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon \nCM, Hanley DA, Heaney RP, et al. Evaluation, Treatment, \nand Prevention of Vitamin D Deficiency: An Endocrine \nSociety Clinical Practice Guideline, J Clin Endocrinol \nMetab 2011;96:1911\u201030.\n\n\n\n20. Arumugam M, Jamil A, Md Nor Norazirah, Baseri M, \nThevarajah S, Mustafa N. Sun exposure, dietary vitamin \nD and vitamin D status in adult atopic dermatitis: a case \ncontrol study. Mal J Med Health Sci 2020;16:66-9.\n\n\n\n21. Lee YW, SE Choon, Izham S. Serum 25-Hydroxyvitamin \nD deficiency in Malaysian children with severe atopic \ndermatitis. Med J Malaysia 2019;74:259-65.\n\n\n\n22. Ramalingam R, Tang MM. 25-hydroxyvitamin D Level \namong Vitiligo Patients in Malaysia. J Endocrinol \nDiabetes Obes 2018;6:1112.\n\n\n\n23. Shafinaz IS, Moy FM. Vitamin D level and its association \nwith adiposity among multi-ethnic adults in Kuala \nLumpur, Malaysia: A cross sectional study. BMC Public \nHealth 2016;16:232.\n\n\n\n24. Chin KY, Ima-Nirwana S, Ibrahim S, Mohamed IN, Wan \nNgah WZ. Vitamin D Status in Malaysian Men and Its \nAssociated Factors. Nutrients 2014;6:5419-33.\n\n\n\n25. Moy FM, Bulgiba A. High prevalence of vitamin \nD insufficiency and its association with obesity and \nmetabolic syndrome among Malay adults in Kuala \nLumpur, Malaysia. BMC Public Health 2011;11:735.\n\n\n\n26. Leiu KH, Chin YS, Shariff ZM, Arumugam M, Chan \nYM. High body fat percentage and low consumption \nof dairy products were associated with vitamin D \ninadequacy among older women in Malaysia. PLoS ONE \n2020;15:e0228803.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 19\n\n\n\n27. Sambrook PN, Cameron ID, Chen JS, Cumming RG, \nDurvasula S, Herrmann M et al. Does increased sunlight \nexposure work as a strategy to improve vitamin D status \nin the elderly: a cluster randomized controlled trial. \nOsteoporos Int 2012;23:615-24.\n\n\n\n28. Lee YM, Kim SA, Lee DH. Can Current Recommendations \non Sun Exposure Sufficiently Increase Serum Vitamin D \nLevel?: One-Month Randomised Clinical Trial. J Korean \nMed Sci 2020;35:e50. \n\n\n\n29. Jang H, Koo FK, Ke L, Clemson L, Cant R, Fraser DR \net al. Culture and sun exposure in immigrant East Asian \nwomen living in Australia. Women Health 2013;53:504-\n18.\n\n\n\n30. National Health Service, United Kingdom: Vitamin D. \nAvailable from: www.nhs.uk/conditions/vitamins-and-\nminerals/vitamin-d. Accessed on 21/11/2022.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 MJD 2023 June Vol 50\n\n\n\nORIGINAL ARTICLE\n\n\n\nEvaluation of Topical Corticosteroid Phobia As An Indicator of Topical \nSteroid Non-adherence Among Atopic Dermatitis Patients\n\n\n\nSee Ling Tan1, MRCP,  Yi Lin Lee2, MPharma, Azura Mohd Affandi1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Ampang, Selangor, Malaysia\n2Department of Clinical Research Center, Hospital Ampang, Malaysia\n\n\n\nAbstract\nBackground \nTopical steroid phobia is associated with a higher rate of non-adherence to topical corticosteroid, \nthereby resulting in poor treatment outcome. Detection of topical corticosteroid (TCS) non-adherence \nis a prerequisite to better adherence among atopic dermatitis (AD) patients with topical corticosteroid \nphobia (TCP). The objective of this study was to evaluate whether the intensity of TCP correlates with \nTCS- non-adherence, and if the Visual Analogue Scale (VAS) for TCP and TOPICOP\u00a9 scales can be \nan indirect indicator for topical steroid non-adherence. \n\n\n\nMethods \nA cross-sectional study was conducted at the dermatology clinic and paediatric dermatology clinic, \nHospital Ampang and Hospital Kuala Lumpur. MyMAAT scale, TOPICOP\u00a9scale and VAS for TCP \nwere used for the survey. \n\n\n\nResults \n146 subjects were recruited. The overall good TCs-adherence rate was only 20.55%. The mean global \nscores of TOPICOP\u00a9 scale was 51.45\u00b119.25 and VAS for TCP was 4.53\u00b12.27. TOPICOP\u00a9scale and \nVAS for TCP were identified to have significant correlation with TCs related non-adherence with the \np<0.001, p=0.012 respectively.\n\n\n\nConclusion \nThis study supports the usage of TOPICOP\u00a9 scale and VAS for TCP as clinical tools for measuring \nthe intensity of TCP and potentially detect TCs-non-adherence in a non-judgemental way. Further \nstudies on optimising and assessing the effect of interventions to reduce TCP and improving clinically \nrelevant outcomes such as TCs related adherence and quality of life among AD patients in Malaysia \nare warranted.\n\n\n\nKey words: Topical corticosteroid phobia (TCP), topical corticosteroid (TCS)-non adherence, atopic dermatitis (AD), \nTOPICOP\u00a9 scale, VAS for TCP\n\n\n\nCorresponding Author\nDr Tan See Ling\nHospital Ampang, \nJalan Mewah Utara, \nPandan Indah, \n68000 Selangor, Malaysia.\nEmail: ttseeling@gmail.com\n\n\n\nIntroduction \nAtopic dermatitis (AD) is a chronic \ninflammatory skin disease1, characterised by \nill-defined erythema with vesicles, and weeping \nin the acute stage and lichenification in the \nchronic stage. Majority of cases develop during \nearly childhood1, with a prevalence of 13.4% \nin Malaysian children.2 Topical corticosteroid \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 21\n\n\n\nremains the cornerstone therapy for AD due to its \npotent anti-inflammatory and anti-proliferative \neffects.3\n\n\n\nTopical corticosteroid phobia (TCP) is \ndescribed as irrational concerns, fears, worries, \nor scepticism regarding corticosteroid use in \npatients, their caregivers or health professionals.4 \n\n\n\nTCP may lead to non-adherence and poor \ndisease control, resulting in more hospitalisation \nand increased healthcare socioeconomic \nburden.4 TCP is highly prevalent in dermatology \npatients, especially among patients with AD or \ntheir caregivers.4 A systematic review by Li Aw \net.al 5revealed TCP prevalence across countries \nranged from 21% to 83.7%. In Malaysia, TCP \nwas reported to be 39% in 20156 and the rate \nincreased to 59.6% in 2018.7 This suggests an \nincreasing trend in the prevalence of TCP in \nMalaysia, although the method of assessments \nwas not standardized.\n\n\n\nA study by Mazlin et al8 in 2013 concluded \nthat the adherence to topical treatment was \npoor among AD patients in Malaysia with \nan adherence rate of only 14.7%. There were \nstudies performed in France, Japan and Korea \nthat found TCP is associated with a higher \nrate of non-adherence to topical corticosteroid \n(TCs).4,9,10 TCP related non-adherence has been \nreported in 36-58% of patients prescribed TCs, \nemphasising the importance of these issues.3-4,9  \n\n\n\nDetection of TCs non-adherence is a prerequisite \nto better adherence among AD patients with \nTCP.11 However, no practical clinical tool to \nevaluate TCP related non-adherence is currently \navailable..3 \n\n\n\nIn addition, direct confrontation could affect \nthe relationship between physician and patients \nwhereas self-reporting of TCs non-adherence \nby patients might not be reliable. Alternative \nstrategies to detect TCs non-adherence may \ntherefore be helpful.4,12 Visual analogue scale \n(VAS) for TCP has been been used to quantify \nTCP in many clinical trials.13 On the other hand, \nthe  TOPICOP\u00a9 scale is a 12-item questionnaire \nthat was developed by Moret and colleagues13 \nin 2013 as a standardised assessment tool \nfor TCP. Instead of using a binary yes or no \n\n\n\nanswer choice to establish the presence of TCP, \nTOPICOP\u00a9 scale will not only be able to better \nquantify TCP but also discern the relative effects \nthat these worries and beliefs have on treatment \nadherence.14 Based on this rationale, the aim of \nthis study is to evaluate whether the available \ntools for measuring the intensity of TCP might \nhelp to detect TCs related non-adherence.  \n\n\n\nMaterials and Methods \nThis was a prospective cross-sectional study \nconducted at the paediatric dermatology clinic \nand adult dermatology clinic in Hospital \nAmpang and Hospital Kuala Lumpur, from \n1st August 2021 to 31st December 2021. Our \ntarget population was clinically confirmed AD \npatients or primary caregivers of children with \ndiagnosis of AD. Accompanying adults must \nbe the primary caregivers of the child with AD, \nwho are 12 years of age and below. The patients \nmust be on TCs for the past one month or \nmore. Subjects who were unable to understand \nMalay or English and had other coexisting \ninflammatory skin diseases were excluded from \nthe study.\n\n\n\nThis study involves the use of 3 questionnaires. \nThe study questionnaires were administered \neither in Malay or English language, consisting \nof six sections (Sections A-F). Section A is \nabout the child / patient personal particulars, \nsection B is about parent / caregiver personal \nparticulars, section C about details on atopic \neczema and section D is the information \nabout the questionnaire on intensity of topical \ncorticosteroid phobia by VAS and exploring the \nsource of information with regards to topical \ncorticosteroid and Section E is the questions on \nTOPICOP\u00a9 scale. Section F is the questionnaire \nabout Malaysia Medication Adherence \nAssessment Tool (MyMAAT) which is to assign \nrespondents to an adherence or non-adherence \ngroup. All sections were obtained from the \npatients or caregivers using a self-administered \nquestionnaire. Information on Section C was \nobtained from the dermatologist assessment of \nAD severity  and topical treatment. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 MJD 2023 June Vol 50\n\n\n\nThe TOPICOP\u00a9 scale is a 12-item \nquestionnaire, assessing two domains of TCP, \nnamely worries and beliefs. Responses were \ngraded on a four-point Likert scale (score \nrange 0\u20133: 0=never, 1=sometimes, 2=often \nand 3=always; or 0=totally disagree, 1=do \nnot really agree, 2=almost agree and 3=totally \nagree) to a maximum of 36 points. A higher \nTOPICOP\u00a9 scale reflects a more pronounced \nTCP phenomenon. \n\n\n\nVAS for TCP ranges from 0 to 10. The \nrespondents were asked to identify, based on \nthis scale, where would they place the intensity \nof their worries about TCs? 0 being calm at \nease and 10 being extremely worried. Another \nadditional question was to explore the source \nof information with regards to TCs among the \nrespondents. \n\n\n\nMyMAAT is a validated scale for assessing \nmedication adherence in Malaysia.14 It comprises \n12 items, the scale ranging from 1-5, with the \ncut-off point of  \u226554 deemed as good adherence. \n\n\n\nSample size estimation was calculated based \non a pilot study done by Simon M Muller et al2 \n\n\n\nAssessment of \u201ccorticophobia\u201d as an indicator \nof non-adherence to topical corticosteroids. \nBurderer\u2019s formula was used for this estimated \nsample size calculation at the required absolute \nprecision level for sensitivity and specificity. \nBased on Simon et al2 study, the sensitivity \nand specificity of VAS for TCP with the cut-\noff point of 5 was 0.87 and 0.42 respectively, a \nminimum sample size of 146 was required. The \ndata obtained from this study was analysed both \ndescriptively and analytically. Data analysis was \ndone by using the IBM\u00ae Statistical Package for \nSocial Sciences (SPSS) Desktop version 23. \nDescriptive data was computed by using the \nsame software. All the demographic data was \npresented as mean and standard deviation or \nfrequency and percentages. For categorical data, \ndifferences between groups were analyzed using \nChi-square test for independence or Fisher\u2019s \nexact test. On the other hand, continuous \ndata was analyzed using independent t tests. \nUnivariate and multivariate logistic regression \n\n\n\nFigure 1. Correlation between TOPICOP\u00a9 scale and VAS scores\n\n\n\nPearson correlation, r= 0.58, p=<0.001 (moderate correlation, positively correlated)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 23\n\n\n\ntests were used for the factors of TCP related to \nTCs non-adherence. All statistical analysis was \nperformed on a two-sided confidence level of \n5%. \n\n\n\nThe study was approved by the Medical \nResearch and Ethics Committee (MREC) of \nthe Ministry of Health,  Malaysia with ethical \napproval number NMRR-21-1165-60133.  \n\n\n\nResults\nAll 146 subjects screened between 1st August \n2021-31st December 2021 were  recruited in \nthis study. The patient\u2019s gender was distributed \nevenly, in which 49.3% were male and 50.7% \nwere female. The mean age of the patients was \n8.8\u00b111.51 years. The mean age of AD onset was \n2.31\u00b13.67 years. Patient\u2019s duration of disease \naveraged at 6.48\u00b110.14 years. The majority of \nthe patients were Malay (85.6%), followed by \nChinese (9.6%), and Indian (2.7%). Most of the \nrespondents were the patients\u2019 mother (67.8%). \nApproximately half of the AD subjects with \nmild disease severity (47%) were recruited in \nthis study. Only 24 respondents (16.4%) from \nour study used alternative therapy. Our study \nrevealed that paediatricians (35.6%) were the \nmost common source of information regarding \nTCs, followed by internet/social media (28.1%), \ndermatologists (24.7%), general practitioner \n(5.5%), pharmacists (4.8%) and the least \ncommon was friends & family (1.4%). The \noverall good adherence rate was only 20.6%. \n79.5% of patients or caregivers had poor \nadherence to AD treatment. The total mean \nTOPICOP\u00a9 scale was 51.45\u00b119.25. Among \nthe two domains, belief domain had higher \nmean scores, which was 63.93\u00b122.28. On the \nother hand, the total mean VAS for TCP was \n4.53\u00b12.27. Other demographics and clinical \ncharacteristics are shown in Table 1. \n\n\n\nAn independent-samples t-test was conducted \nto compare TOPICOP\u00a9 scale and VAS for TCP \namong TCs good adherence and poor adherence \ngroups. Those in TCs-poor adherence group \n(M=54.62, SD=17.73) compared to those with \ngood TCs-adherence (M=39.27, SD=20.23) \ndemonstrate significantly higher mean of \n\n\n\nTable 1. Study population demographic and clinical \ncharacteristic, n=146\n\n\n\nCharacteristic n (%) / mean \n(SD)\n\n\n\nAge (years) 8.80 (11.51)\nAge at onset (years) 2.31 (3.67)\nAge of caregivers (years) 35.30 (6.04)\nAge of subjects answered questionnaires (years) 34.25 (9.19)\nDuration of disease (years) 6.48 (10.14)\nGender\n  Female 74 (50.7)\n  Male 72 (49.3)\nEthnicity\n  Chinese 14 (9.6)\n  Indian 4 (2.7)\n  Malay 125 (85.6)\n  Others 3 (2.1)\nSite of Atopic Dermatitis\n  Generalised 52 (35.6)\n  Localised 94 (64.4)\nSeverity of atopic dermatitis by IGA\n  0-clear 1 (0.7)\n  1-almost clear 11 (7.5)\n  2-mild 70 (47.9)\n  3-moderate 37 (25.3)\n  4-severe 27 (18.5)\nPrevious history of hospitalisation\n  Never 99 (67.8)\n  Yes 47 (32.2)\nTopical therapy\n  No 0 (0.0)\n  Yes 146 (100.0)\nSystemic therapy\n  No 113 (77.4)\n  Yes 33 (22.6)\nAlternative treatment\n  No 122 (83.6)\n  Yes 24 (16.4)\nCaregiver occupation\n  NA 24 (16.4)\n  Non-professional 55 (37.7)\n  Professional 36 (24.7)\n  Unemployed 31 (21.2)\n\n\n\nCaregiver relationship with patient\n  Father 23 (15.8)\n  Mother 99 (67.8)\n  NA 24 (16.4)\nInformation source regarding TCS\n  Dermatologists 36 (24.7)\n  Paediatrician 52 (35.6)\n  General Practitioners 8 (5.5)\n  Pharmacists 7 (4.8)\n  Friends & family 2 (1.4)\n  Internet/ social media 41 (28.1)\nMyMAAT adherence\n Good 30 (20.55)\n\n\n\n Poor 116 (79.45)\nTOPICOP\u00a9 scale (total)\n- Worries domain \n- Belief domain \n\n\n\n51.45 (19.25)\n63.93 (22.28)\n38.96 (20.72)\n\n\n\nVAS scale for TCP 4.53 (2.27)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24 MJD 2023 June Vol 50\n\n\n\nTOPICOP\u00a9 scale (p<0.01). Similarly, there \nwas a significant difference (p=0.012) in the \nmean VAS for TCP in the good adherence group \n(M=3.6, SD=2.36) which was lower than the \npoor-adherence group (M=4.77, SD=2.20).  \n\n\n\nModerate correlation was found between \nTOPICOP\u00a9scale and VAS for TCP (r=0.58, p \n<0.001) as shown in Figure 1.  \n\n\n\nSignificant weak negative correlation was \nobserved between TOPICOP\u00a9scale and \nMyMAAT scale (r= -0.37, p<0.001) as shown \nin Figure 2. \n\n\n\nAs shown in Table 3, only severity of \nAD and low TOPICOP\u00a9 scale were \nfound to be statistically significantly \nassociated with good TCs adherence. \nPatients with moderate to severe AD \nand patients who were in the first \nquartile of TOPCOP\u00a9 scale were 4.01 \nand 7.12 times more likely to have good \nTCs adherence.  \n\n\n\nThere were significant differences in \nTOPICOP\u00a9 scale for those seeking \nalternative treatment were significantly \nhigher (M=60.80, SD=18.83) than \n\n\n\nTable 2. Comparing TOPICOP\u00a9 scale and VAS for TCP among good adherence and poor adherence \n(independent t-test)\n\n\n\nCharacteristic n (%)/ mean (SD) p-value \n\n\n\nGood adherence\nn=30\n\n\n\nPoor adherence n=115\n\n\n\nTOPICOP\u00a9 scale (mean (SD) 39.17 (20.23) 54.62 (17.73) <0.001\n\n\n\nTOPICOP\u00a9 scale - Belief domain (mean (SD) 48.33 (24.42) 67.96 (19.89) <0.001\n\n\n\nTOPICOP\u00a9 scale- Worries domain (mean (SD) 30.00 (22.20) 41.28 (19.76) 0.007\n\n\n\nVAS for TCP (mean(SD) 3.60 (2.36) 4.77 (2.20) 0.012\n\n\n\nFigure 2. Correlation between TOPICOP\u00a9 scale and MyMAAT scale \n\n\n\nPearson correlation, r= -0.371, p<0.001 (low correlation, negatively correlated)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 25\n\n\n\nthose without history of alternative treatment \n(M=49.70, SD=18.92), p-value=0.013. \nRegarding sources of information, TOPICOP\u00a9 \nscale for those seeking information from non-\nhealthcare professionals (M=62.02, SD=15.75) \nwere significantly higher than those seeking \ninformation from healthcare professional \ngroups (M=47.03, SD=18.92) with the p value \nof <0.001.\n\n\n\nPrevious study showed that 30% to 40% of all \nmedications taken for chronic conditions are \nnot taken as prescribed.12 Only 20.55% of good \nTCs- adherence rates were observed in our study, \nwhich is relatively low compared to Alyson et al15 \nwhich reported the mean adherence rates ranging \nfrom 32% to 93%. This result highlights the fact \nthat TCs- non-adherence is very prevalent among \nAD patients and their caregivers in Malaysia. \nThis phenomenon could be explained by the fear \n\n\n\nTable 3. Factors associated with good TCs-adherence \n\n\n\nVariables Crude OR  (95% CI) p value Adjusted OR  (95% CI) p value \n\n\n\nGender\n- Female \n- Male\n\n\n\n1.0\n1.45 (0.65, 3.31) 0.366\n\n\n\n- -\n\n\n\nSources of information regarding TCS\n- Non health care professional \n- Health care professional\n\n\n\n1.0\n2.44 (0.93, 7.66) 0.072 - -\n\n\n\nCaregiver\u2019s  occupation\n- Unemployed \n- Non professional \n- Professional\n\n\n\n1.0\n1.16(0.37, 4.05)\n1.73 (0.53, 6.29)\n\n\n\n0.810\n0.376\n\n\n\n- -\n\n\n\nCaregiver\u2019s education \n- Secondary\n- Tertiary \n\n\n\n1.0 \n1.41 ( 0.55, 3.94) 0.482 \n\n\n\n- -\n\n\n\nCaregiver\u2019s relationship \n- Father \n- Mother \n\n\n\n1.0 \n1.20 (0.40, 4.49) 0.757\n\n\n\n- -\n\n\n\nAge (years) 1.02 (0.99, 1.06) 0.157 - -\n\n\n\nAge of onset (years) 1.09 (0.99, 1.21) 0.071 - -\n\n\n\nFamily history of atopy \n- No \n- Yes \n\n\n\n1.0\n2.86 (0.92, 12.62) 0.071\n\n\n\n- -\n\n\n\nDuration of disease (years) 1.02 (0.98, 1.05) 0.333 - -\n\n\n\nEthnicity\n- Malay \n- Chinese \n- Indian \n- Others \n\n\n\n0.83 (0.24, 3.87)\n1.0\n3.67 (0.33, 44.12)\n7.33 (0.53, 195.32)\n\n\n\n0.783\n\n\n\n0.276\n0.151\n\n\n\n- -\n\n\n\nSite of atopic dermatitis\n- Localized \n- Generalized \n\n\n\n1.0\n2.54 (1.12, 5.83) 0.025\n\n\n\n- -\n\n\n\nSeverity of atopic dermatitis by IGA\n- 0,1,2 (clear, almost clear, mild)\n- 3,4    (moderate, severe)\n\n\n\n1.0\n2.73 (1.20, 6.43)\n\n\n\n-\n0.016\n\n\n\n-\n4.01 (1.63, 10.51)\n\n\n\n-\n0.002\n\n\n\nAlternative treatment \n- No \n- Yes\n\n\n\n1.0 \n0.31 (0.05, 1.13)\n\n\n\n-\n0.078\n\n\n\n-\n0.26 (0.04, 1.09)\n\n\n\n-\n0.068\n\n\n\nTOPICOP\u00a9 scale\n- First quartile (0-36.1) \n- Second quartile (36.2-51.4)\n- Third quartile (51.5-63.9) \n- Fourth quartile (64.0-94.4) \n\n\n\n7.12(1.93,34.70)\n3.56 (1.00, 16.78)\n1.72 (0.39, 8.94)\n1.0 \n\n\n\n0.006\n0.068\n0.482\n- \n\n\n\n7.12 (1.80, 36.84) \n3.38 (0.91, 16.51) \n1.36 (0.29, 7.33) \n-\n\n\n\n0.009\n0.089 \n0.700\n1.0\n\n\n\nOR = Odd ratio, a Likelihood Ratio (LR) test, b Z statistics, Z test\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26 MJD 2023 June Vol 50\n\n\n\nof topical corticosteroid side effects.16\n\n\n\nA significant correlation between disease \nseverity with TCs- adherence were observed \nin our study. This finding was in line with \nthe results of Krejci-Manwaring J et al17 \nconsidering that patients with more severe \ndisease may be more adherent to TCs in order \nto halt the disease progression rapidly; whereas \nsubsequent clearing of the disease may lead to a \ndecrease in compliance. Another study in Japan \nalso supports the notion that disease severity as \nperceived by caregivers prove to be an important \npredictor of adherence to topical therapy.18\n\n\n\nA multicentre study conducted in 17 countries \nfound a mean global TOPICOP\u00a9 scale of \n44.7\u00b120.5.19 In our study, the mean global scores \nof TOPICOP\u00a9 scale was 51.45\u00b119.25, which \nwas comparable with a previous study by KC Yap \net al6  (54.94\u00b116.92%) in year 2018. Therefore, \nTCP appears to be more pronounced in Malaysia \n\n\n\nas compared to most countries. Along the same \nvein, the total mean score of VAS for TCP in our \nstudy was 4.53\u00b12.27, which is consistent with \na study by Aubert-Wastiaux H et al4 Numerous \nstudies have concluded that TCP is exceedingly \nprevalent across the countries and results in TCs \nrelated non-adherence.20 \n\n\n\nIn keeping with previous studies4,9,10,16, TCP \nwhich was assessed by both VAS for TCP and \nTOPICOP\u00a9scale was found to be significantly \nhigher in the TCs poor adherence group. This \nfinding contradicts a similar study by Muller \net al3 which found that TOPICOP scales were \nunreliable to detect TCP related TCS non-\nadherence. These differences in findings could \nprobably be attributed to their relatively small \nsample size and response bias that may happen \nbecause they solely grouped their subjects into \nadherence vs non-adherence based on binary \nanswers. By doing so it could result in too low \nor too high non-adherence rates.3 Additionally, \n\n\n\nTable 4. Comparing between TOPICOP\u00a9 scale and clinical characteristic \nCharacteristic n (%) TOPICOP scores, mean (SD) T statistics (df) / F value (df) p-value\n\n\n\nGender\n- Female\n- Male \n\n\n\n \n74 (50.7)\n72 (49.3)\n\n\n\n52.21 (19.55)\n50.66 (19.04)\n\n\n\n0.49 (144) 0.626\n\n\n\nEthnicity\n- Malay \n- Chinese \n- Indian \n- Others \n\n\n\n125 (85.6)\n14 (9.6)\n4 (2.7)\n3 (2.1)\n\n\n\n52.18 (19.49)\n42.66 (15.92)\n56.94 (22.85)\n54.63 (15.30)\n\n\n\n1.17 (3) 0.322b\n\n\n\nSite of Atopic Dermatitis\n- Generalized \n- Localized \n\n\n\n52 (35.6)\n94 (64.4)\n\n\n\n52.94 (18.58)\n50.62 (19.66) \n\n\n\n-0.69 (144) 0.488\n\n\n\nFamily history of Atopy\n- No \n- Yes \n\n\n\n \n31 (21.2)\n115 (78.8)\n\n\n\n54.57 (16.33)\n50.60 (19.94)\n\n\n\n1.02 (144) 0.310\n\n\n\nSeverity of atopic dermatitis by \nIGA scores\n0-clear\n1-almost clear\n2-mild\n3-moderate\n4- severe \n\n\n\n1.0 (0.7)\n11 (7.5) \n70 (47.9)  \n37 (25.3) \n27 (18.5) \n\n\n\n69.44\n56.82 (27.11)\n49.01 (19.26) \n52.48 (17.23) \n53.50(18.48) \n\n\n\n0.81 (4) 0.519 b\n\n\n\nPrevious history of hospitalisation\n- Never \n- Yes \n\n\n\n \n99 (67.8)\n47 (32.2) \n\n\n\n \n52.89 (19.07)\n48.40 (19.47) \n\n\n\n1.32 (144) 0.189\n\n\n\nAlternative treatment\n- No \n- Yes \n\n\n\n122 (83.6)\n24 (16.4) \n\n\n\n49.70 (18.92)\n60.30 (18.83)\n\n\n\n-2.51 (144) 0.013\n\n\n\nInformation source regarding TCs \n- Non healthcare professional\n- Health care professional\n\n\n\n \n43 (29.45)\n103 (70.55) \n\n\n\n \n62.02 (15.75)\n47.03 (18.92) \n\n\n\n4.57 (144) <0.001\n\n\n\naIndependent t-test, bOne-way ANOVA test\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 27\n\n\n\nwe detected higher significant mean scores of \nboth belief  and worries domain of TOPICOP\u00a9 \nscale among TCs poor adherence group, which \nemphasizes the need of targeted therapeutic \neducation and patient-physician\u2019s relationship \nin order to address the false beliefs regarding \nTCs use. This is supported by a previous study, \nwhich observed an improvement in perception \nregarding TCs with therapeutic education on \ncaregivers of AD patients with TCP.9      \n\n\n\nA significant, low and negative correlation \nbetween TOPICOP\u00a9 scale and MyMAAT scale \nwas detected in our study suggesting that TCP \nplays a pivotal role in contributing to  TCs-non \nadherence among AD patients. This is further \nsupported by a separate finding in our study \nwhich showed that subjects in the first quartile \nof  TOPICOP\u00a9 scale were associated with good \nTCs-adherence. However, these findings are in \nconflict with a previous local study by Mazlin \net al8 This could probably be due to different \nmethodologies and the relatively small sample \nsize in that study. \n\n\n\nWe were able to ascertain the factors associated \nwith TCP including non-healthcare professionals \nbeing the primary source of information \nregarding TCs, as well as previous history of \ntaking alternative treatment. The internet has \nbeen identified as the top information source \nleading to steroid phobia by Lee et al9 Despite \nthe questionable efficacy of complementary and \nalternative treatment (CAM)21, the prevalence \nof CAM use among AD patients in Malaysia \nwas remarkably high, at 46.8%.22 CAM is \npreferred to TCs not only by Malaysians but is \nalso rising in popularity globally.23 This suggests \nthat greater attention needs to be paid to clinical \nand social history to address misinformation \nin regard to TCP and CAM use. Interventions \nto direct patients to internet resources with \naccurate medical knowledge may help mitigate \nthe sensationalization of steroid adverse effects \nwhile reassuring and counselling AD patients \nor their caregivers on appropriate TCs use. \nSimilarly, discussions on TCs sparing agents \nsuch as tacrolimus and pimecrolimus earlier in \nthe treatment course would empower patients \nor their caregivers to actively play their part \n\n\n\nin management. All these measures have been \nsupported by a randomised controlled multi-\ncentre study by Heratizadeh et al24. The study \nshowed that AD patients who were educated \nin a multidisciplinary training programme \nhad a significant improvement in their coping \nbehaviour, quality of life and disease severity.\n\n\n\nLimitation\nLimitations in our study include inherent \ninability to avoid selection bias. As the \nquestionnaire was administered only in English \nand Bahasa Malaysia, this may limit the \ngeneralisability of our findings to the overall \nMalaysian population. The Mandarin or Tamil \nonly speaking populations were not adequately \nrepresented in our study population. This group, \nwith perhaps different backgrounds and sources \nof knowledge, would be worth capturing in \nfuture studies. \n\n\n\nAnother major study limitation is the degree of \ncomplexity for TCP assessment. As of the time \nof writing, there are no established gold standard \ncut-off values for defining TCP and its intensity \nby using TOPICOP\u00a9 scale. TCs-related \nadherence is exceedingly difficult to measure \ngiven multiple variables involved. Furthermore, \nas this was a self-administered questionnaire, \nlimitations of potential misinterpretation of \nquestions by participants were present and may \nbe subjected to recall or response bias. \n\n\n\nConclusion  \nWe conclude that there were significant positive \ncorrelations between TOPICOP\u00a9 scale and VAS for \nTCP and TCs related non-adherence. This supports \nTOPICOP\u00a9 scale and VAS for TCP as useful \nclinical tools for measuring the intensity of TCP and \npotentially detect TCs related non-adherence in a \nnon-judgemental way. Further studies on optimising \nand assessing the effect of interventions to reduce \nTCP and improving clinically relevant outcomes \nsuch as TCs related adherence and quality of life \namong AD patients in Malaysia are warranted.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28 MJD 2023 June Vol 50\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper. \n\n\n\nReferences\n1. Snyder A, Farhangian M, Feldman SR. A review of \n\n\n\npatient adherence to topical therapies for treatment of \natopic dermatitis. Cutis 2015;96:397-401.\n\n\n\n2. Goh YY, Keshavarzi F, Chew YL. Prevalence of Atopic \nDermatitis and Pattern of Drug Therapy in Malaysian \nChildren. Dermatitis 2018;29:151-61.\n\n\n\n3. Mueller SM, Itin P, Vogt DR, Walter M, Lang U, Griffin \nL et al. Assessment of \u201ccorticophobia\u201d as an indicator of \nnon-adherence to topical corticosteroids: A pilot study. J \nDermatolog Treat 2016;28:104-11.\n\n\n\n4. Aubert\u2010Wastiaux H, Moret L, Le Rhun A, Fontenoy AM, \nNguyen JM, Leux C et al. Topical corticosteroid phobia \nin atopic dermatitis: a study of its nature, origins and \nfrequency. Br J Dermatol 2011;165:808-14.\n\n\n\n5. Li AW, Yin ES, Antaya RJ. Topical Corticosteroid Phobia \nin Atopic Dermatitis: A Systematic Review. JAMA \nDermatol. 2017;153:1036-42.\n\n\n\n6. Yap KC, Koo K, Begum S, Mohd Ali A, Mohd Shah N. \nEczema Perception and Understanding of Topical Steroid \nUse among Parents or Caregivers of Children with Atopic \nEczema in Malaysia. Lat Am J Pharm 2019;38:73-9.\n\n\n\n7. Mohd Nor N, Baba R. Topical Corticosteroid Phobia \nAmong Atopic Eczema Patients And Their Caregivers: \nSurvey In Two Dermatology Outpatient Clinics In \nMalaysia. Malaysian J Dermatol 2015;34:2-5.\n\n\n\n8. Mohd Baseri M, Aniza I, Jong YF, Chia SL, Mohd Ikhwan \nNMS, Noramira A. Adherence To Topical Medication Is \nPoor Among Patients With Atopic Eczema. Malaysian J \nDermatol 2013;31:1-7.\n\n\n\n9. Lee JY, Her Y, Kim CW, Kim SS. Topical Corticosteroid \nPhobia among Parents of Children with Atopic Eczema in \nKorea. Ann Dermatol 2015;27:499.\n\n\n\n10. Kojima R, Fujiwara T, Matsuda A, Narita M,  Matsubara \nO, Nonoyama S et al. Factors Associated with Steroid \nPhobia in Caregivers of Children with Atopic Dermatitis. \nPediatr Dermatol 2013;30:29-35.\n\n\n\n11. Furue M, Onozuka D, Takeuchi S, Murota H, Sugaya \nM, Masuda K et al. Poor adherence to oral and topical \nmedication in 3096 dermatological patients as assessed \nby the Morisky Medication Adherence Scale\u20108. Br J \nDermatol 2014;172:272-5.\n\n\n\n12. Richmond NA, Lamel SA, Braun LR, Vivas AC, Cucalon \nJ, Block SG et al. Primary nonadherence (failure to obtain \nprescribed medicines) among dermatology patients. J Am \nAcad Dermatol 2014;70:201-3.\n\n\n\n13. Moret L, Anthoine E, Aubert-Wastiaux H, Le Rhun A, \nLeux C, Mazereeuw-Hautier et al. TOPICOP\u00a9: A New \nScale Evaluating Topical Corticosteroid Phobia among \nAtopic Dermatitis Outpatients and Their Parents. PLoS \nOne 2013;8:76493.\n\n\n\n14. Hatah E, Rahim N, Makmor-Bakry M, Mohamed Shah \nN, Mohamad N, Ahmad M et al. Development and \nvalidation of Malaysia Medication Adherence Assessment \nTool (MyMAAT) for diabetic patients. PLoS One \n2020;15:0241909.\n\n\n\n15. Sokolova A, Smith SD. Factors contributing to poor \ntreatment outcomes in childhood atopic dermatitis. Aust \nJ Dermatol 2015;56:252-7.\n\n\n\n16. Charman CR, Morris AD, Williams HC. Topical \ncorticosteroid phobia in patients with atopic eczema. Br J \nDermatol 2000;142:931-6.\n\n\n\n17. Krejci-Manwaring J, Tusa M, Carroll C, Camacho F, Kaur \nM, Carr D et al. Stealth monitoring of adherence to topical \nmedication: Adherence is very poor in children with atopic \ndermatitis. J Am Acad Dermatol 2007;56:211-6.\n\n\n\n18. Ohya Y, Williams H, Steptoe A, Saito H, Iikura Y, \nAnderson R et al. Psychosocial Factors and Adherence \nto Treatment Advice in Childhood Atopic Dermatitis. J \nInvestig Dermatol 2001;117:852-7.\n\n\n\n19. Stalder JF, Aubert H, Anthoine E, Futamura M, Marcoux \nD, Morren MA et al. Topical corticosteroid phobia in \natopic dermatitis: International feasibility study of the \nTOPICOP score. Allergy 2017;72:1713-9.\n\n\n\n20. Choi E, Chandran NS, Tan C. Corticosteroid phobia: a \nquestionnaire study using TOPICOP score. Singapore \nMed J 2020;61:149-53.\n\n\n\n21. Thandar Y, Botha J, Mosam A. Complementary therapy in \natopic eczema: the latest systematic reviews. S Afr Fam \nPract 2014;56:216-20.\n\n\n\n22. Koo K, Nagayah R, Begum S, Tuan Mahmood TM, \nMohamed Shah N. The use of complementary and \nalternative medicine in children with atopic eczema at a \ntertiary care centre in Malaysia. Complement Ther Clin \nPract 2020;49:102355.\n\n\n\n23. Siti ZM, Tahir A, Farah AI, Use of traditional and \ncomplementary medicine in Malaysia: a baseline study. \nComplement Ther Med 2009;17:292-9.\n\n\n\n24. Heratizadeh A, Werfel T, Wollenberg A,  Abraham S, \nPlank-Habibi S, Schnopp C et.al. Effects of structured \npatient education in adults with atopic dermatitis: \nMulticenter randomized controlled trial. J Allergy Clin \nImmunol 2017;140:845-53.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 29\n\n\n\nORIGINAL ARTICLE\n\n\n\nAttitudes, Health Seeking Behaviors, Expectations and Psychosocial \nImpact of Patients with Non- Scarring Alopecia: Results of Tertiary Out-\npatient Skin Specialist Clinics in Penang\n\n\n\nKhoo Voon Ling1,2, MMed, Loo Chai Har1, AdvMDerm, Khor Yek Huan1, AdvMDerm, Norazlima Bt Mohd Ali1, \nAdvMDerm, Tan Wooi Chiang1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Pulau Pinang, Georgetown, Penang, Malaysia. \n2Dermatology unit, Department of Medicine, Hospital Canselor Tuanku Muhriz UKM, Kuala Lumpur, Malaysia\n\n\n\nAbstract \nBackground   \nHair loss can be a highly distressing condition due to the cosmetic value placed upon hair in many \nsocieties. This study is aimed to characterize the concerns, health care seeking behaviors, expectations \nand psychosocial impact of patients with alopecia plus the contributing factors.\n\n\n\nMethods   \nA questionnaire-based cross-sectional study was conducted among patients who self-identified as \nhaving thinning hair, hair loss, and/or balding attending Dermatology Clinic in Hospital Pulau Pinang \nfrom July 2021 to June 2022. \n\n\n\nResults   \nA total of 240 patients with hair loss problem were recruited. Approximately 75.4% of the patients \nhad significant concern about their hair loss. Younger age, unmarried respondents and females showed \nhigher degree of concern about hair loss (p<0.0001, p=0.002 and p<0.0001). The top reason for \nnot consulting physicians were perceptions that hair loss is part of natural aging process (35.7%). \nDissatisfaction among 46.5% of patients mainly stemmed from not receiving any specific treatment \nrecommendation (48.1%) and not having all their questions answered (24.1%). About 43.8% of \npatients\u2019 quality of life (QoL) were at least moderately affected. Median Dermatology Life Quality \nIndex (DLQI) was 4.0. Younger and employed respondents were more anxious, depressed and had \nworse QoL.\n \nConclusions   \nIndividualized consideration of attitudes and concerns is crucial for effective management of patients \nwith alopecia.\n\n\n\nKey words: Alopecia, attitudes, health seeking behaviors, psychosocial impact. \n\n\n\nCorresponding author\nDr Khoo Voon Ling \nDepartment of Dermatology,\nHospital Pulau Pinang,\nJalan Residensi,\n10990 Georgetown,\nPulau Pinang. \nEmail: voonlingmoon@gmail.com\n\n\n\nIntroduction\nHair loss is a common presenting complaint in \noutpatient clinics, with nonscarring alopecia \nbeing the commonest cause.1-5 Common causes \nof nonscarring alopecia include androgenic \nalopecia, alopecia areata, telogen effluvium and \nanagen effluvium.6 In a community study of \nmale androgenic alopecia in Bishan, Singapore, \nthe prevalence of androgenic alopecia was \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30 MJD 2023 June Vol 50\n\n\n\nfound to be 63%.7 However, effective treatment \nmodalities for alopecia are still limited and \nlargely short-lived.8-9\n\n\n\nHair plays an important role in self-image, \nidentity and social perception.10-12 The \npsychological impact of hair loss is often \noverlooked due to the medically benign nature \nof the condition.13 Yet, there are limited studies \nregarding psychological impact of patients with \nhair loss in Malaysia. Malaysia is a multiracial \ncountry with diverse cultures and the results \nfrom other countries might not be representative \nof Malaysia. \n\n\n\nMany people with hair loss turn to non-\nprescription medicines, as evidenced by the fast-\ngrowing industry of non-prescription medicines \nfor hair growth with unproven efficacy and \nsafety.5,14,15 Unmet expectations from hair loss \nconsultation could have driven patients towards \nconfusing panel of products and intervention \nclaiming to be effective for hair loss. According \nto the National Center for Complementary and \nIntegrative Health (NCCIH), a total of USD 30.2 \nbillion dollars was spent annually on alternative \nmedicine.16 \n\n\n\nTo date, no study in Malaysia has attempted \nto evaluate the attitudes, behavior and \nexpectations of people who do seek hair loss \ntreatment from a physician. Studies like this \nare important to help physicians understand and \nmeet patients\u2019 expectations in order to reduce \nthe psychological barriers between patient and \nphysician. Additionally, a better understanding \non patients with alopecia will enable more \neffective management in the future. Hence, the \nobjectives of this research were to study the \nattitudes, health seeking behaviors, expectations \nand psychosocial impact of patients with \nalopecia.\n\n\n\nMaterials and Methods \n\n\n\nStudy type and design\nThis is a questionnaire-based cross-sectional \nstudy conducted at the Dermatology Clinic in \nHospital Pulau Pinang from July 2021 to June \n\n\n\n2022. Hospital Pulau Pinang is the biggest \ntertiary public hospital in Penang receiving \nreferrals from Northern Malaysia. \n\n\n\nThe inclusion criteria were as follows: (a) \nAdult patients ranging in age from 18 to 70 \nyears old. (b) Patients who self-identified as \nhaving thinning of hair or hair loss regardless \nof whether they were referred for hair loss from \nother center or came for other skin diseases but \nincidentally also self-identified as having hair \nloss. (c) Patients who are able to give informed \nconsent. Exclusion criteria: (a) Scarring alopecia \n(b) Foreigner (c) Pregnant ladies\n\n\n\nConvenience sampling was used and direct \ninterview by investigator was done for data \ncollection. It was a face-to-face 30 minutes \ninterview between investigator and patient \nusing structured case report forms (CRF). The \nCRF was designed to include biodata, disease \ninformation, concerns and attitudes about hair \nloss, health seeking behaviors, expectations \nand experiences of hair loss management, and \ndisease impact plus QoL (based on DLQI and \nHospital Anxiety and Depression Scale, HADS). \n\n\n\nDisease information gathered include onset of \nalopecia, anthropometric measurements and \nscalp examination by investigator to determine \nthe type of alopecia. Patients convey their \ndegree of concern on a scale from 1 = not at \nall concerned to 5 = extremely concerned. \nAttitudes and health seeking behaviors were \nassessed with multiple choice close-ended \nquestions. Expectations and experiences of \nhair loss management was assessed with a total \nof 7 multiple choice close-ended questions \nusing ratings on the level of satisfaction on a \n5-point scale from 1 = completely disagree to \n5 = completely agree. The questions were pilot \ntested on 50 patients and validated.  \n\n\n\nBoth DLQI and HADS have been properly \ntranslated to native language for usage in \nMalaysia and validated. The DLQI questionnaire \nwas used to assess the QoL of patients. DLQI \nscores 0-1=no effect at all, 2-5=small effect, \n6-10=moderate effect, 11-20=very large effect \nand 21-30=extremely large effect on patient\u2019s \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 31\n\n\n\nlife. HADS is a 14-item scale with 7 items each \nfor anxiety and depression subscales. HADS \nscore 0-7=normal, 8-10=borderline abnormal \nand 11-21=abnormal. Approval to use HADS \nin English, Malay and Chinese version was \nobtained (ID 058041). License to use DLQI was \nobtained (license ID CUQoL3138). \n\n\n\nEthical approval was also obtained (NMRR-21-\n705-58779). \n\n\n\nStatistical analysis\nSample size was calculated based on Openepi, \nversion 3, open-source calculator. Using two-\nsided confidence level 95%, power 80% and \nodds ratio of 3.99 based on the objective of \nexploring the factors associated with poor \nquality of life.\n\n\n\nDescriptive statistics were used to evaluate the \ncharacteristics of the sample. Mann-Whitney U \ntest was used to compare two independent groups \non an ordinal or continuous but not normally \ndistributed dependent variable. Kruskal-Wallis \ntest was used to determine if there was any \ndifferences between two or more groups of an \nindependent variable on a continuous or ordinal \n\n\n\ndependent variable, followed by Dunn post \nhoc analysis for a significant Kruskal-Wallis \ntest. Spearman rank correlation test (non-\nparametric) was used to establish the correlation \nbetween two variables measured on at least an \nordinal scale. Chi-square test for independence \nwas used to discover if there is a relationship \nbetween two categorical variables. Logistic \nregression was used to predict a dichotomous \ncategorical outcome. Statistical significance \nwas considered if p<0.05. Statistical analyses \nwere performed using SPSS version 26. \n\n\n\nResults\n\n\n\nSociodermographic and clinical features \nTwo hundred and forty patients were included in \nthe study. The median (IQR) age was 38.5 (24) \nyears, mostly female patients (55.4% female \nvs. 44.6% male). Majority was Malay (42.5%) \nfollowed by Chinese (38.3%), Indian (17.1%) \nand others (2.1%). Married patients accounted \nfor 59.6% and unmarried patients 40.4%. Most \npatients were full time employed (54.2%) and \nwhite-collar worker (37.9%). Median age of \nalopecia onset (IQR) was 33.5 (21) years. \n\n\n\nTable 1. Socio-demographic characteristics of surveyed patients (n=240)\n\n\n\n  Socio-demographic characteristics n (%)\n\n\n\n  Age (years), median (range) 38.5 (18-70)\n\n\n\n  Age of onset (years), median (IQR) 33.5 (21)\n\n\n\n  Disease duration in months, median (IQR) 24 (75)\n\n\n\n  Sex, n (%)\n\n\n\n Male 107 (44.6%)\n\n\n\n Female 133 (55.4%)\n\n\n\n  Race, n (%)\n\n\n\n Malay 102 (42.5%) \n\n\n\n Chinese 92 (38.3%)\n\n\n\n Indian 41 (17.1%) \n\n\n\n Others 5 (2.1%)\n\n\n\n  Marital status (%)\n\n\n\n Married 59.6\n\n\n\n Unmarried 40.4\n\n\n\n  Type of alopecia (%)\n\n\n\n Androgenic alopecia 45.0\n\n\n\n Alopecia areata 18.8\n\n\n\n Diffuse non scarring alopecia associated with SLE 12.9\n\n\n\n Telogen effluvium 10.0\n\n\n\n Others 13.3\n*Cell percentages may not sum to 100% due to rounding\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32 MJD 2023 June Vol 50\n\n\n\nAndrogenic alopecia constitutes the main \ndiagnosis (45.0%), followed by alopecia areata \n18.8% (Table 1). A logistic regression analysis \nshowed that patients with metabolic syndrome \nwere more likely to exhibit androgenic alopecia \n(OR=3.33, 95% CI [1.60-6.96], p=0.001).\n\n\n\nConcerns and attitudes about hair loss \nApproximately 75.4% of the patients had \nsignificant concern (rating of 3 to 5) about their \nhair loss (Figure 1). Younger age and unmarried \nrespondents showed higher degree of concern \nabout hair loss (p<0.0001 and p=0.002). \nFemales were significantly more concerned \nthan males (p<0.0001) (Table 2). \n\n\n\nFigure 1. Patients\u2019 degree of concern about hair loss, n = 240\n\n\n\n1 \n \n\n\n\nFigure 1. Patients\u2019 degree of concern about hair loss, n = 240 \n \n\n\n\n\n\n\n\nFigure 2. Information seeking actions, n = 199 \n \n\n\n\n\n\n\n\n7.1%\n\n\n\n17.5%\n\n\n\n28.3%\n27.5%\n\n\n\n19.6%\n\n\n\nnot concerned at all somewhat concerned concerned\n\n\n\nvery concerned extremely concerned\n\n\n\n0.5\n5\n5.5\n\n\n\n8.5\n9\n\n\n\n17.1\n18.1\n\n\n\n29.1\n37.7\n\n\n\n40.2\n61.3\n62.3\n\n\n\n0 10 20 30 40 50 60 70\n\n\n\nConsult aesthetic physician\nDiscuss with beautician\n\n\n\nDiscuss with nutritionist\nDiscuss with traditional healer\n\n\n\nDiscuss with hair therapist\nConsult pharmacist\n\n\n\nResearch treatment on the book/magazine\nDiscuss with hairdresser/hairstylist\n\n\n\nConsult primary care doctor\nConsult dermatologist\n\n\n\nResearch treatments on the internet\nDiscuss with spouse or friends\n\n\n\nPercentage\n\n\n\nTable 2. Degree of concern, DLQI and HADS scores plus their correlation to a single variable\n\n\n\nVariables DLQI Median (IQR)a HADS-A Median (IQR)a HADS-D Median (IQR)a Degree of concern, Median (IQR)a\n\n\n\nAge in ranges (years)\n\n\n\n< 20 11.0 (12.5) 5.0 (7) 2.0 (4.5) 4 (2)\n\n\n\n20 \u2013 39 6.0 (9) 6.0 (6) 3.0 (6) 4 (2)\n\n\n\n40 \u2013 59 4.0 (9.8) 6.0 (6) 3.0 (4) 3 (2)\n\n\n\n>59 1.0 (2.5) 3.0 (3) 1.0 (3) 3 (2.5)\n\n\n\nAge 18 \u2013 70 years 4 (8.75) 5 (6) 3.0 (5) 3 (1)\n\n\n\np value <0.0001b <0.0001b 0.013b <0.0001b\n\n\n\nAge of disease onset\n\n\n\np value 0.001b 0.001b 0.062b 0.003b\n\n\n\nGender \n\n\n\nMale 4 (8) 5 (5) 2 (4) 3 (2)\n\n\n\nFemale 4 (10) 6 (5) 3 (5) 4 (1)\n\n\n\np value 0.130c 0.201c 0.228c <0.0001c\n\n\n\nMarital status\n\n\n\nUnmarried  5 (10) 6 (7) 3 (5) 4 (2)\n\n\n\nMarried 4 (8) 5 (5) 2 (4) 3 (2)\n\n\n\np value 0.308c <0.0001c 0.009c 0.002c\n\n\n\nHADS-A, Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D, Hospital Anxiety and Depression Scale-Depression subscale; DLQI, \nDermatological life quality index; aData presented are the median and interquartile range, bSpearman rank correlation test to measure association \nbetween age/age of disease onset and DLQI/HADS-A/HADS-D/Degree of concern, cMann-Whitney U test to compare between gender/marital status and \nDLQI/HADS-A/HADS-D/Degree of concern. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 33\n\n\n\nTwo additional indicators of concern were \nthe information seeking actions taken and the \nnumber of treatments tried. The most common \naction was discussing their hair loss with spouse \nor friends (62.3%), followed by researching \ntreatments on the internet (61.3%) (Figure 2). \nApproximately 17.1% of the patients did not \nengage in any information seeking actions. In \nfact, 63.3% engaged in multiple information \nseeking actions. \n\n\n\nRegarding treatments tried, patients were \ngiven a list of 13 types of treatments including \n\n\n\nprescription medicines, nonprescription \nmedicines, alternative treatment, diet \nmodification, hair filler, laser treatment, at \nhome devices, tattoo, change hairstyle, wear \nheadscarf, wigs or cap and stopping possible \noffending agent. Patients without prior \ntreatments consist of 22.1%. Patients who had \ntried more than one treatment consist of 47.9%. \nAmong those who tried treatment, 58.3% \nchose non-prescription medicines followed by \nprescription medicine 46.5% (Table 3). Further \nanalysis showed that there was a significantly \nhigher proportion of Malays that tried non-\nprescription and alternative medicine compared \nto other ethnicities (p<0.0001).\n\n\n\nFigure 2. Information seeking actions\n\n\n\n1 \n \n\n\n\nFigure 1. Patients\u2019 degree of concern about hair loss, n = 240 \n \n\n\n\n\n\n\n\nFigure 2. Information seeking actions, n = 199 \n \n\n\n\n\n\n\n\n7.1%\n\n\n\n17.5%\n\n\n\n28.3%\n27.5%\n\n\n\n19.6%\n\n\n\nnot concerned at all somewhat concerned concerned\n\n\n\nvery concerned extremely concerned\n\n\n\n0.5\n5\n5.5\n\n\n\n8.5\n9\n\n\n\n17.1\n18.1\n\n\n\n29.1\n37.7\n\n\n\n40.2\n61.3\n62.3\n\n\n\n0 10 20 30 40 50 60 70\n\n\n\nConsult aesthetic physician\nDiscuss with beautician\n\n\n\nDiscuss with nutritionist\nDiscuss with traditional healer\n\n\n\nDiscuss with hair therapist\nConsult pharmacist\n\n\n\nResearch treatment on the book/magazine\nDiscuss with hairdresser/hairstylist\n\n\n\nConsult primary care doctor\nConsult dermatologist\n\n\n\nResearch treatments on the internet\nDiscuss with spouse or friends\n\n\n\nPercentage\n\n\n\nTable 3. Treatments tried or used before\n\n\n\nTreatments tried or used before, n = 187 Percentage \n\n\n\nNon-prescription medicines (mineral supplement/vitamin supplement/shampoo/hair tonic/others) 58.3\n\n\n\nPrescription medicines (topical minoxidil/oral minoxidil/propecia/spironolactone/topical steroid/oral steroid/\ninjection steroid/methotrexate/azathioprine/cyclosporine/others)\n\n\n\n46.5\n\n\n\nAlternative treatments (herbal supplement/massage/others) 35.5\n\n\n\nChange hairstyle 17.1\n\n\n\nWear cap 16.6\n\n\n\nWear headscarf 12.8\n\n\n\nDiet modification 4.8\n\n\n\nWear wigs 1.1\n\n\n\nTattoo 0.5\n\n\n\nHair filler 0\n\n\n\nLaser treatment 0\n\n\n\nAt home devices (laser comb/laser helmet/others) 0\n\n\n\nStop the offending agent 0\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34 MJD 2023 June Vol 50\n\n\n\nFigure 3. Reasons for not seeking physician consultation\n\n\n\n2 \n \n\n\n\nFigure 3. Reasons for not seeking physician consultation, n = 113 \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n36%\n\n\n\n34%\n\n\n\n30%\n\n\n\n18%\n\n\n\n18%\n\n\n\n14%\n\n\n\n14%\n\n\n\n10%\n\n\n\n10%\n\n\n\n5%\n\n\n\n5%\n\n\n\n5%\n\n\n\n5%\n\n\n\n5%\n\n\n\n4%\n\n\n\n3%\n\n\n\n2%\n\n\n\n0%\n\n\n\n0%\n\n\n\n0% 5% 10% 15% 20% 25% 30% 35% 40%\n\n\n\nHair loss is a natural aging\n\n\n\nUncertainty that hair loss is really a medical condition\n\n\n\nConcerns about cost\n\n\n\nThe hair loss less bothers them\n\n\n\nWant organic and natural treatment\n\n\n\nIt is a genetic problem, reluctance to consult a physician or to be seen as vain\n\n\n\nDesire to try non-prescription treatments first\n\n\n\nConcern about medicine side effect\n\n\n\nUncertainty which specialist to see for hair loss problem\n\n\n\nThe burden of seeing a doctor\n\n\n\nWork commitment (difficult to take leave)\n\n\n\nEmbarrassment about the hair loss issue\n\n\n\nLimited availability of dermatologist/ specialist\n\n\n\nLogistic problem\n\n\n\nPreference for alternative treatment\n\n\n\nLong waiting times to see doctor\n\n\n\nFear to see doctor\n\n\n\nFear of stigmatization\n\n\n\nA belief that seeking help from doctor reflects weakness\n\n\n\nPercentage of patients\n\n\n\nFigure 4. Reasons not satisfied with health care provider\u2019s service\n\n\n\n3 \n \n\n\n\nFigure 4. Reasons not satisfied with health care provider\u2019s service, n = 59 \n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n48.1%\n\n\n\n24.1%\n\n\n\n22.2%\n\n\n\n14.8%\n\n\n\n11.1%\n\n\n\n9.3%\n\n\n\n9.3%\n\n\n\n5.6%\n\n\n\n3.7%\n\n\n\n3.7%\n\n\n\n0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0%\n\n\n\nI did not receive any specific treatment recommendation\n\n\n\nI did not get all my questions answered\n\n\n\nI did not adequately convey how much my hair loss\nbothers me\n\n\n\nDoctor does not seem knowledgeable about hair loss\ntreatments\n\n\n\nDoctor recommended something i have already tried or\ncould have gotten on my own\n\n\n\nDoctor did not reinforce the hair loss prevention measures\n\n\n\nDoctor seemed uncomfortable/uninterested in discussing\nmy hair loss\n\n\n\nI asked for a specific brand of treatment medication but\nthe doctor gave me something different\n\n\n\nDoctor suggested a treatment that was not an option for\nme (eg hair transplant, surgery, etc)\n\n\n\nDoctor talked me out of treatment\n\n\n\nPercentage of patients\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 35\n\n\n\nTable 4. Satisfaction with the medical and non-medical treatments that patient used to control hair loss\n\n\n\nCompletely disagree \nor somewhat disagree \n(rating 1 or 2)\n\n\n\nNeither agree or \ndisagree (rating 3)\n\n\n\nSomewhat agree or \ncompletely agree \n(rating 4 or 5)\n\n\n\nSatisfaction with the medical treatments, n = 87\n\n\n\nI feel my current treatment are effective in relieving my hair loss 18.4% 34.5% 47.1%\n\n\n\nI feel my current treatments are effective in preventing new flares \nof my hair loss problem\n\n\n\n20.7% 35.6% 43.7%\n\n\n\nThe side effects are acceptable 24.1% 28.7% 47.1%\n\n\n\nI think that my current treatments are convenient to use 9.2% 13.8% 77.0%\n\n\n\nSatisfaction with the non-medical treatments, n = 146\n\n\n\nI feel my current treatment are effective in relieving my hair loss 34.9% 40.4% 24.7%\n\n\n\nI feel my current treatments are effective in preventing new flares \nof my hair loss problem\n\n\n\n39.7% 34.2% 26.0%\n\n\n\nThe side effects are acceptable 14.4% 22.6% 63.0%\n\n\n\nI think that my current treatments are convenient to use 13.0% 19.2% 67.8%\n\n\n\nHealth seeking behavior \nPatients seeking care at hospitals or clinics \namounted to 52.9%. Among those who \nhad consulted physicians, 68.5% had tried \nnonprescription medicines or alternative \ntreatment. The top reasons for consulting a \nphysician include concern about worsening \nhair loss (83.3%) and a desire to benefit from \nphysicians\u2019 treatment expertise (58.7%). \nSimilarly, patients who had yet to consult \na physician were asked to specify the top \ntwo reasons from a list of 19 reasons. The \nresult indicated that the top two reasons were \nperceptions that hair loss was part of natural \naging process (35.7%) and uncertainty that \nhair loss is really a medical condition (33.9%) \n(Figure 3).\n\n\n\nExpectations and experiences of hair loss \nmanagement \nNearly half of the patients agreed (ratings 4 \nor 5) that medical treatments were effective in \nrelieving hair loss problem compared to 24.7% \nof patients who sought non-medical treatments \n(Table 4). Regarding effectiveness of medical \ntreatment in preventing new flares of hair loss, \n43.7% agreed (ratings of 4 or 5) while only \n26.0% for non-medical treatments. As for side \neffects, 47.1% (ratings of 4 or 5) thought the side \neffects of medical treatments were acceptable \nbut 24.1% disagreed (ratings of 1 or 2) compared \nto 63.0% agreed and 14.4% disagreed for non-\nmedical treatments. About 77.0% (ratings of \n\n\n\n4 or 5) thought that the medical treatments \nwere convenient to use while 9.2% disagreed \n(ratings of 1 or 2). As for convenience to use \nnon-medical treatments, 67.8% agreed (ratings \nof 4 or 5) and 13.0% disagreed (ratings of 1 or \n2). Despite these, average expenditure of non-\nmedical treatment (RM156/month) was higher \nthan medical treatment (RM64/month). \n\n\n\nEvaluation of patients\u2019 experiences of their \nconsultative visits showed that 64.6% (ratings \n4 or 5) felt confident in managing their hair loss \nproblem and able to select the right treatment by \nthemselves after doctor\u2019s consultation compared \nto 27.9% after non-health care provider\u2019s \nvisit (Table 5). There was higher percentage \nof patients agreed that doctors provide more \nrelevant hair loss advice and treatment than \nnon-health care provider (74.8% versus 35.6%). \nFurthermore, 75.6% (ratings of 4 or 5) of \npatients felt that their doctors understand how \nthey felt about their hair loss problem versus \n39.4% after non health care provider\u2019s visit. \nAdditionally, when given a list of 10 reasons to \nchoose from, the main reason of dissatisfaction \nafter physician consultation was not receiving \nany specific treatment recommendation (48.1%) \nfollowed by not having all their questions \nanswered (24.1%). Other common reasons were \nbecause they did not adequately convey how \nmuch their hair loss bothers them (22.2%) and \ntheir doctor did not seem knowledgeable about \nhair loss treatment (14.8%) (Figure 4).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36 MJD 2023 June Vol 50\n\n\n\nDisease impact and quality of life (based on \nDLQI and HADS)\nAbout 43.3% of patients\u2019 quality of life (QoL) \nwere moderately affected (DLQI \u22656). Median \n(IQR) DLQI was 4.0 (9). The main domain \naffected in DLQI was the symptoms and \nfeelings, followed by daily activities, leisure, \ninterpersonal relationship, work/study and \nlastly treatment. Younger patients and younger \nage of alopecia onset were associated with \nworse DLQI (p<0.0001 and p=0.001). Being \nemployed was also associated with worse DLQI \ncompared to retired patients (p=0.001).\n\n\n\nMedian (IQR) Hospital Anxiety and Depression \nScale-Anxiety subscale (HADS-A) was 5 (6). \nThis is considered normal. However, further \nanalysis comparing HADS-A score according \n\n\n\nto marital status and age showed that younger \nand unmarried patients were more anxious \n(p<0.0001) (Table 2). Similarly, employed \npatients as well as those who were unemployed \ndue to disease were also found to have \nsignificantly worse anxiety score compared to \nretired patients (p=0.002).\n\n\n\nMedian (IQR) Hospital Anxiety and Depression \nScale-Depression subscale (HADS-D) was 3.0 \n(5). This is considered normal. Nevertheless, \nfurther analysis revealed that younger patients \nwere more depressed (p=0.013). Besides, \nunmarried patients with hair loss were also \nmore depressed compared to married patients \n(p=0.009). \n\n\n\nTable 5. Satisfaction with the health care provider or non-health care provider that patient consulted\n\n\n\nCompletely disagree \nor somewhat disagree \n(rating 1 or 2)\n\n\n\nNeither agree or \ndisagree (rating 3)\n\n\n\nSomewhat agree or \ncompletely agree \n(rating 4 or 5)\n\n\n\nSatisfaction with the health care provider, n = 127\n\n\n\nI feel confident in managing my hair loss problem and I am able to select \nthe right treatment by myself after my doctor\u2019s advice\n\n\n\n13.6% 22.8% 64.6%\n\n\n\nThey provide relevant advice and treatment 10.2% 15.0% 74.8%\n\n\n\nThey understand how I feel about my hair loss problem 8.7% 15.7% 75.6%\n\n\n\nSatisfaction with the non-health care provider, n = 104\n\n\n\nI feel confident in managing my hair loss problem and I am able to select \nthe right treatment by myself with my therapist\u2019s advice\n\n\n\n36.5% 35.6% 27.9%\n\n\n\nThey provide relevant advice and treatment 32.7% 31.7% 35.6%\n\n\n\nThey understand how I feel about my hair loss problem 23.1% 37.5% 39.4%\n\n\n\nTable 6. DLQI and HADS scores within groups in status of occupation\n\n\n\nVariables DLQI\nMedian (IQR)a\n\n\n\nHADS-A\nMedian (IQR)a\n\n\n\nHADS-D\nMedian (IQR)a\n\n\n\nStatus of occupation\n\n\n\nEmployed White collar 6 (10.75) 6 (6) 3 (5)\n\n\n\nBlue collar 4 (7) 6 (5) 2 (3)\n\n\n\nPink collar 5 (11.5) 6 (6) 4 (6)\n\n\n\nUnemployed Due to disease 9 (16) 9 (8) 5 (6.5)\n\n\n\nDue to other reason 0 (7) 7 (12.5) 2 (8.5)\n\n\n\nRetired 1 (3) 3 (4) 1.5 (2.25)\n\n\n\nStudent 8 (10.5) 6 (3) 2 (5.5)\n\n\n\nHomemaker 4 (7) 4 (5) 2 (5)\nHADS-A, Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D, Hospital Anxiety and Depression Scale-Depression subscale; DLQI, \nDermatological life quality index; aData presented are the median and interquartile range.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 37\n\n\n\nDiscussion \nIn this study, androgenic alopecia constitutes \nthe main diagnosis (45.0%), comparable to \nWestern studies of 23% to 87%.7 Interestingly, \nwe found that patients with metabolic syndrome \nwere more likely to exhibit androgenic alopecia, \nsimilar to a study by A. M. Hamed et al.17 Further \nstudies will be needed to assess the possible link \nbetween them.\n\n\n\nMost patients with alopecia (75.4%) had \nprofound concern about their hair loss, \ncorroborated by previous studies.18,19 Patients\u2019 \nconcern was reflected in their behavior, with \nmost engaging in multiple information seeking \nbehaviors and trying multiple remedies. \nSadly, most of them chose non-prescription or \nalternative treatments of unproven effectiveness \nand safety profile. Hence, public education \nwith guidance on the appropriate help available \nwould benefit people with hair loss problems. \n\n\n\nBesides, our study showed that more Malays \ntried non-prescription and alternative medicine \ncompared to other ethnicities. On the contrary, \nNoraidatulakma et al reported highest \ncomplementary medicine usage among Chinese \nwith non-communicable diseases compared to \nother ethnicities in Malaysia.20 Further studies \nare needed to look into this aspect among multi-\nethnic population with hair loss in Malaysia.\n\n\n\nMost patients did not seek care at hospitals \nor clinics mainly because of misconceptions \nabout hair loss. Interventions to improve their \nknowledge might reduce the burden of hair loss. \nIn this study, the main factors motivating patients \nto consult physicians were their concern about \nworsening hair loss and a desire to benefit from \nphysicians\u2019 treatment expertise. Failure to meet \nthese expectations resulted in dissatisfaction \nespecially when they left without any specific \ntreatment recommendation and with questions \nunanswered. These findings were similar to the \nstudy by Cash et al where the top two  reasons \nfor dissatisfaction with consultation among \nmen who consulted a physician were the lack \nof specific treatment recommendation (66%) \nand having unanswered questions (54%).18 \n\n\n\nThus, time should be spent to discuss potential \ntherapies and realistic treatment outcomes with \npatients seeking treatment for hair loss.\n\n\n\nExpenditure on non-prescription medicines \nwas high. In addition, Dong et al reported high \nsafety risk for consumers of hair loss prevention \ncosmetics.21 Hence, it is essential for physicians \nto be aware of the non-prescription medicines \nor alternative treatments available in the market \nboasting the ability to cure hair loss and also \ntheir safety profile to ensure effective patient \ncounselling.\n\n\n\nYounger patients showed higher degree of \nconcern causing worse DLQI, anxiety and \ndepression. This is consistent with other \nstudies.22-26 Younger patients were more \npsychologically disturbed by their hair \ncondition because of the impact on their self-\nesteem, resulting in difficulty in looking for \nlife partners.27 Besides, peer pressure and the \nneed for social acceptance makes them more \nvulnerable to depression and anxiety.19  \n\n\n\nUnmarried patients were also found to be more \nconcerned and anxious compared to their married \ncounterparts. This concurs with the study by \nNg KF et al which showed that single patients \nwith androgenic alopecia were more anxious \nand depressed compared to married patients.22 \nSimilarly, Cash TF reported considerable \npreoccupation, moderate stress and copious \ncoping efforts among younger men, single men \nand those with earlier hair loss onset.28 Both \nmen and women believe that hair loss will erode \ntheir chances in romance.29 Employed patients \nwere similarly affected, having worse DLQI \nand anxiety compared to retirees. This could be \nbecause they fear that their appearances after \nhair loss will result in a change in their social \nstatus and job status as demonstrated by Shi et \nal in 2013.25\n\n\n\nOur study shows that females were more \nconcerned than males about their hair loss but \nthere was no difference in DLQI or HADS. \nThese findings are different from previous \nstudies, whereby females felt more depressed \nand anxious compared to men.22,30,31 Hence, the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38 MJD 2023 June Vol 50\n\n\n\npossible explanation for our observation is that \nmen\u2019s attitude towards their hair appearances \nnowadays are comparable to women. Men \nare probably as vulnerable as women to \npsychosocial impact of hair loss, yet less likely \nto admit their concern about hair loss. \n\n\n\nThe identification of these factors mentioned \nearlier as a risk to mental health will help \nphysician to design specific consultations \nand interventions to improve patients\u2019 mental \noutcomes and quality of life. Psychological \ncounselling and social support network can be \nused to address various psychological issues \nfrom hair loss.13,22,32,33 \n\n\n\nThe median DLQI in our study was only 4, \nindicating small effect of hair loss on patients\u2019 \nlife. This could be because DLQI is not designed \nspecifically for alopecia. Therefore, some of \nthe questions regarding itch, pain and physical \nactivities are not suitable to assess the impact \nof hair loss. Arguably, DLQI is inappropriate \nto thoroughly assess quality of life related to \nhair loss because it mainly refers to cutaneous \nsymptoms rather than alopecia. \n\n\n\nOur study did not show any differences in degree \nof concern, DLQI or HADS among patients \nwith different education levels, income levels \nor occupation. This finding is supported by the \nstudy by Ng et al.22 Similarly, Zhang and Zhang \nfound that QoL was not affected by education \nlevel.34  \n\n\n\nConclusion\nAlopecia leads to anxiety, depression and poor \nquality of life especially in younger patients. \nBeing unmarried or employed are also added \nrisks for psychological impact of hair loss. \nAppreciation of these risks and their pattern of \nhealth seeking behavior could help physicians \nand policy makers to improve the healthcare \nsystem and health promotion strategies. \nRecognition of patients\u2019 expectations and \nreasons for their dissatisfaction after physician \nconsultations would help physicians to alter \ntheir communication style so as to improve \n\n\n\ntreatment outcome mentally and physically.   \n\n\n\nConflict of Interest Declaration\nThe authors declare no conflict of interest.  \n\n\n\nAcknowledgement\nThis research received funding from \nDermatological Society of Malaysia. The \nauthors would like to thank the Director General \nof Health Malaysia for the permission to publish \nthis paper.\n\n\n\nReferences \n1. Abdin R, Zhang Y, Jimenez JJ. Treatment of Androgenetic \n\n\n\nAlopecia Using PRP to Target Dysregulated Mechanisms \nand Pathways. Front Med (Lausanne) 2022;9:843127.\n\n\n\n2. Anudeep TC, Jeyaraman M, Muthu S, Rajendran RL, \nGangadaran P, Mishra PC et al. Advancing Regenerative \nCellular Therapies in Non-Scarring Alopecia. \nPharmaceutics 2022;14:612.\n\n\n\n3. Bolognia JL, Schaffer JV, Cerroni L. Dermatology 4th \nEdition, 2018, Elsevier Limited. p. 3047.\n\n\n\n4. Kang S, Amagai M, Bruckner AL, Enk AH, Margolis DJ, \nMcMichael A et al. Fitzpatrick\u2019s Dermatology 9th Edition, \nKang S, Editor. 2019, McGraw-Hill Education. p.4120.\n\n\n\n5. Kanti V, Messenger A, Dobos G, Reygagne P, Finner A, \nBlumeyer A et al. Evidence based (S3) guidelines for the \ntreatment of androgenetic alopecia in women and in men. \nJ Eur Acad Dermatol Venereol 2018;32:11-22.\n\n\n\n6. Davis DS, Callender VD. Review of quality of life \nstudies in women with alopecia. Int J Womens Dermatol \n2018;4:18-22.\n\n\n\n7. Tang PH, Chia HP, Cheong LL, Koh D. A Community \nStudy of Male Androgenic Alopecia in Bishan, Singapore. \nSingapore Med J 2000;41:202-5. \n\n\n\n8. Daruwalla SB, Dhurat RS, Hamid SAT. All that \na Dermatotrichologist needs to know about Hair \nCamouflage: A Comprehensive Review. Int J Trichology \n2022;14:77-83.\n\n\n\n9. Lee WS, Lee HJ, Choi GS, Cheong WK, Chow SK, \nGabriel MT et al. Guidelines for management of \nandrogenetic alopecia based on BASP classification-\nthe Asian consensus committee guideline. J Eur Acad \nDermatol Venereol 2013;27:1026-34.\n\n\n\n10. Hunt N. Identity and psychological distress in alopecia \nareata. Br J Dermatol 2022;187:9-10.\n\n\n\n11. Liamsombut S, Pomsoong C, Kositkuljorn C, Leerunyakul \nK, Tantrakul V, Suchonwanit P. Sleep quality in men with \nandrogenetic alopecia. Sleep Breath 2023;27:371-8. \n\n\n\n12. Alfonso M, Richter-Appelt H, Tosti A, Viera MS, Garc\u00eda \nM. The psychosocial impact of hair loss among men: \na multinational European study. Curr Med Res Opin \n2005;21:1829-36.\n\n\n\n13. Aukerman EL, Jafferany M. The psychological \nconsequences of androgenetic alopecia: A systematic \nreview. J Cosmet Dermatol 2023;22:89-95.\n\n\n\n14. Adelman MJ, Bedford LM, Potts GA. Clinical efficacy \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 39\n\n\n\nof popular oral hair growth supplement ingredients. Int J \nDermatol 2021;60:1199-210. \n\n\n\n15. Ring C, Heitmiller K, Correia E, Gabriel Z, Saedi N. \nNutraceuticals for Androgenetic Alopecia. J Clin Aesthet \nDermatol 2022;15:26-9.\n\n\n\n16. Hosking AM, Juhasz M, Atanaskova Mesinkovska N. \nComplementary and Alternative Treatments for Alopecia: \nA Comprehensive Review. Skin Appendage Disord \n2019;5:72-89.\n\n\n\n17. Hamed AM, Fatah MA, Shams GM. Androgenetic \nAlopecia and Metabolic Syndrome: Is Alarin a Missing \nLink? J Clin Aesthet Dermatol 2022;15:32-7.\n\n\n\n18. Cash TF. Attitudes, behaviors, and expectations of men \nseeking medical treatment for male pattern hair loss: \nresults of a multinational survey. Curr Med Res Opin \n2009;25:1811-20.\n\n\n\n19. Girman CJ, Rhodes T, Lilly FR, Guo SS, Siervogel RM, \nPatrick DL et al. Efffects of self-perceived hair loss in a \ncommunity sample of men. Dermatology 1998;197:223-\n9.\n\n\n\n20. Abdullah N, Borhanuddin B, Patah AEA, Abdullah \nMS, Dauni A, Kamaruddin MA et al. Utilization of \nComplementary and Alternative Medicine in Multiethnic \nPopulation: The Malaysian Cohort Study. J Evid Based \nIntegr Med 2018;23:2515690X18765945. \n\n\n\n21. Dong Y, Niu S, Qiao Y, Huang C, Wang H, Sun L. \nDetermination of 19 illegally added chemical ingredients \nin hair loss prevention cosmetics by ultra-performance \nliquid chromatography-quadrupole-time of flight mass \nspectrometry Se Pu 2022;40:343-53. \n\n\n\n22. Han SH, Byun JW, Lee WS, Hoon Kang, Kye YC, Kim \nKH et al. Quality of life assessment in male patients with \nandrogenic alopecia: result of a prospective, multicenter \nstudy. Ann Dermatol 2012;24(3):311-8.\n\n\n\n23. Cartwright T, Endean N, Porter A. Illness perceptions, \ncoping and quality of life in patients with alopecia. Br J \nDermatol 2009;160:1034-9. \n\n\n\n24. Yu NL, Tan H, Song ZQ, Yang XC. Illness perception in \npatients with androgenetic alopecia and alopecia areata in \nChina. J Psychosom Res 2016;86:1-6.\n\n\n\n25. Shi Q, Duvic M, Osei JS, Hordinsky MK, Norris DA, \nPrice VH et al. Health-Related Quality of Life (HRQoL) \nin alopecia areata patients-a secondary analysis of the \nNational Alopecia Areata Registry Data. J Investig \nDermatol Symp Proc 2013;16:S49-50. \n\n\n\n26. Gutierrez Y, Pourali SP, Jones ME, Rajkumar JR, Kohn \nAH, Compoginis GS et al. Alopecia areata in the United \nStates: a ten-year analysis of patient characteristics, \ncomorbidities, and treatment patterns. Dermatol Online J \n2021;27(10).\n\n\n\n27. Price VH. Androgenetic Alopecia in Adolescents. Cutis \n2003;71:115-21.\n\n\n\n28. Cash TF. The psychological effects of androgenetic \nalopecia in men. J Am Acad Dermatol 1992;26:926-31.\n\n\n\n29. Inui S, Inoue T, Itami S. Psychosocial impact of wigs or \nhairpieces on perceived quality of life level in female \npatients with alopecia areata. J Dermatol 2013;40:225-6.\n\n\n\n30. Cash TF, Price VH, Savin RC. Psychological effects of \nandrogenetic alopecia on women: comparisons with \nbalding men and with female control subjects. J Am Acad \nDermatol 1993;29:568-75.\n\n\n\n31. Zhuang XS, Zheng YY, Xu JJ, Fan WX. Quality of life \nin women with female pattern hair loss and the impact \nof topical minoxidil treatment on quality of life in these \npatients. Exp Ther Med 2013;6:542-6.\n\n\n\n32. Adamowicz R, Za\u0142\u0119cki P, Dukiel A, Nowicka D. Association \n\n\n\nbetween Androgenetic Alopecia and Psychosocial Disease \nBurden: A Cross-Sectional Survey among Polish Men. \nDermatol Res Pract 2022:2022:1845044.\n\n\n\n33. Shakoei S, Torabimirzaee A, Saffarian Z, Abedini R. \nSleep disturbance in alopecia areata: A cross-sectional \nstudy. Health Sci Rep 2022;5:e576.\n\n\n\n34. Zhang M, Zhang N. Quality of life assessment in patients \nwith alopecia areata and androgenetic alopecia in the \nPeople\u2019s Republic of China. Patient Prefer Adherence \n2017;11:151-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40 MJD 2023 June Vol 50\n\n\n\nORIGINAL ARTICLE\n\n\n\nCutaneous Manifestations In Patients With Leukaemia: A 6 Months Cross-\nsectional Study in a Haematological Referral Centre\n\n\n\nPriyya Subramaniam1, MRCP, Azura Mohd Affandi2, AdvMDerm, Adawiyah Jamil3, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Ampang, Selangor, Malaysia\n2Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n3Dermatology unit, Department of Medicine, Hospital Canselor Tuanku Muhriz UKM, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nBackground\nCutaneous disorders in haematological malignancies have become more common due to advancements in \ntreatments which prolonged survival. Leukaemia is associated with a variety of cutaneous manifestations. We \nassessed the frequency and severity of cutaneous manifestations in patients with leukaemia in our population \nand identified patterns of cutaneous manifestations between myeloid and lymphocytic leukaemia.\n\n\n\nMethods\nAll leukaemia patients in the Haematology ward and outpatient\u2019s clinic, Hospital Ampang were enrolled in a \ncross-sectional study. \n\n\n\nResults\nA total of 150 leukaemia patients were enrolled with 76 (50.7%) male and 74 (49.3%) female. Majority were \nMalay (58.7%) and acute myeloid leukaemia was the commonest leukaemia subtype (38.0%). 118 (78.7%) \npatients showed one or more cutaneous manifestations. Eczema was the commonest cutaneous manifestation \n(18.7%) followed by xerosis (14.7%). Cutaneous adverse drug reactions (11.3%) and infectious skin disorders \n(6.7%) primarily of fungal etiology (60.0%) were more frequent in myeloid leukaemia. Skin graft versus host \ndisease (GvHD) was more common in lymphocytic leukaemia (10.3%). Interestingly, leukaemia cutis was only \nseen in myeloid leukaemia. Leukaemia patients with a disease duration of more than two years and previous \nhistory of eczema have significantly higher risk of developing eczema (OR=2.5, p=0.048; OR=3.09, p=0.026).\n\n\n\nConclusion\nCutaneous manifestations were common in leukaemia patients and eczema was the most observed. \nEarly identification and treatment will lead to more effective patient care and may reduce the prevalence \nof cutaneous manifestations in leukaemia patients. \n\n\n\nKey words: Leukaemia, cutaneous, manifestations\n\n\n\nCorresponding Author\nDr Priyya Subramaniam\nHospital Ampang, \nJalan Mewah Utara, \nPandan Mewah, \n68000 Ampang, Selangor, Malaysia.\nEmail: priyya29@yahoo.co.uk\n\n\n\nIntroduction\nCutaneous manifestations in haematological \nmalignancies have become more common over   \nrecent years due to advancements in treatment and \ntransplants which prolonged survival.1 Leukaemia \nis the 6th most common cancer in Malaysia with an \nincidence of 3.7 per 100,000 population.2 Leukaemia \nis a neoplastic systemic proliferation of atypical \nhemopoietic cells primarily in the bone marrow with \na tendency to involve peripheral blood and other \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 41\n\n\n\norgans including the skin.3 According to the WHO \nClassification of Hematopoietic and Lymphoid \nTissues, leukaemia can be broadly divided into 2 \ntypes based on their origin: myeloid (myelogenous) \nor lymphoid (lymphocytic). Overall, there are \nfour main subtypes of leukaemia: acute myeloid \nleukaemia (AML), acute lymphocytic leukaemia \n(ALL), chronic myeloid leukaemia (CML) and \nchronic lymphocytic leukaemia (CLL).4\n\n\n\nLeukaemia is associated with a wide variety of \ncutaneous manifestations, either due to the underlying \ndisease or secondary to their treatment. Diagnosis \nand management of these cutaneous diseases can be \nparticularly challenging in patients with leukaemia \nwho are immunosuppressed and often on multiple \ndrugs and chemotherapeutic agents. The cutaneous \nmanifestations are conventionally divided into \nspecific malignant lesions and non-specific benign \nlesions. Approximately 25 \u2013 50 % of patients with \nleukaemia or lymphoma have specific or non-\nspecific cutaneous signs.3 Cutaneous manifestations \ncan be classified further into specific or primary \nskin disorders (leukaemia cutis) and non-specific \nwhich is either secondary to the disease (infectious \ndermatoses, infestations, inflammatory, neutrophilic \ndermatoses, paraneoplastic and other malignancies) \nor secondary to treatment (drug eruptions and graft \nvs host disease) and others such as pruritis, xerosis, \nacneiform eruptions and ichthyosis.\n\n\n\nLiterature on cutaneous manifestations in leukaemia \nis limited. There is paucity of data regarding the \nprevalence and types of cutaneous manifestations \nseen in patients with leukaemia in the Malaysian \npopulation. Therefore, the type, frequency and \nseverity of cutaneous manifestations is unknown.\n\n\n\nThe findings of our study will allow us to fully \nexplore the frequency and severity of cutaneous \nmanifestations in patients with leukaemia in our \npopulation and identify the patterns of cutaneous \nmanifestations between myeloid and lymphocytic \nleukaemia.\n\n\n\nMaterials and Methods\nThis is a cross-sectional study conducted on \nall leukaemia patients from September 2021 to \nFebruary 2022 (6 months). Patients were recruited \nfrom the Haematology ward and outpatient\u2019s clinic, \nHospital Ampang. Hospital Ampang is the main \nreferral centre for Haematological diseases, which \n\n\n\nincludes leukaemia in Malaysia. The ability to access \na large cohort of leukaemia individuals allows us the \nopportunity to fully explore the prevalence of skin \nmanifestations in patients with leukaemia in our local \npopulation. The inclusion criteria were patients with \nleukaemia confirmed from bone marrow aspiration \naged 18 and above. Critically ill patients who were \nunable to give informed consent and where clinical \nassessment was difficult were excluded from the \nstudy. \n\n\n\nAll patients underwent a thorough interview and \nphysical examination. Information was obtained on \ncurrent and previous skin problems, type and status of \nleukaemia, full blood count and other relevant blood \ntests, previous history of transplant, drug history and \ndemographic data. In cases of skin graft versus host \ndisease (GvHD), information was also collected on \nthe stage, severity and treatment given. Procedures \nsuch as skin scrapings, cultures and biopsy were \nperformed according to clinical indications. \nThe cutaneous manifestations were classified as \neither primary skin disorder (leukaemia cutis) or \nsecondary to the leukaemia or treatment. Cutaneous \nmanifestations secondary to the disease were \nfurther subclassified into infectious or inflammatory \ndermatoses and cutaneous manifestations secondary \nto treatment were subclassified into adverse drug \nreaction or GvHD.\n\n\n\nThe sample size of this study was calculated based \non a cross-sectional study by Aggarwal et al3 using \na formula with finite population correction. Data \nfrom the study above indicated that the prevalence \nof cutaneous manifestations in leukaemia patients \nwere 0.403. Assuming the similar prevalence in \nour population, we needed to recruit 142 patients to \nachieve 5% precision for 95% confidence interval, \ntaking into account our population of 230 leukaemia \npatients from the hospital database. If the Type I \nerror probability and precision are 0.05 and 0.05, \nwe will need to study 142 samples. Considering the \npotential 5% loss of data or ineligible patients due \nto incomplete database, the final sample size for the \nstudy is estimated to be 150 patients. \n\n\n\nData analysis was performed using the IBM SPSS \nStatistics for Windows Version 22.0. Descriptive \nstatistics were employed for selected variables \nand the findings presented based on the types and \ndistribution of the data. Categorical data were \ndescribed as frequencies and percentages, while \nnumerical data were described as means and standard \ndeviations, or as medians and interquartile ranges.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42 MJD 2023 June Vol 50\n\n\n\nTo study the association between two sets of \ncategorical data, Pearson\u2019s chi-square test for \nindependence was used, while Fisher\u2019s exact test \nwas used if the assumptions for the Pearson\u2019s chi-\nsquare test for independence were violated. All \nprobability values were two-sided and statistical \nsignificance was set at p less than 0.05 (p<0.05).\n\n\n\nThis study was conducted in compliance with ethical \nprinciples outlined in the Declaration of Helsinki \nand Malaysian Good Clinical Practice Guidelines. \nEthical approval was obtained from the National \nMedical Research Registry, Malaysia (NMRR-21-\n1579-60940).\n\n\n\nResults\n\n\n\nDemographic Characteristics\nA total of 150 leukaemia patients were enrolled in \nthis study. The number of male patients were 76 \n(50.7%) and 74 (49.3%) were female. There was a \nhigher proportion of patients diagnosed with myeloid \nleukaemia (61.3%) compared to lymphocytic \nleukaemia (38.7%). The mean age of patients with \nmyeloid leukaemia was 49.5\u00b116.55 years (ranging \nfrom 18 to 82 years) and 41.76\u00b119.18 years (ranging \nfrom 18 to 81 years) in lymphocytic leukaemia. \nMajority of patients were Malay (58.7%), followed \nby Chinese (28.0%) and Indians (13.3%). AML \nwas the commonest leukaemia subtype (38.0%), \n\n\n\nTable 1. Baseline demographics and characteristics of study population\n\n\n\nCharacteristics\nMyeloid leukaemia\n\n\n\nn=92\nMean\u00b1SD or n (%)\n\n\n\nLymphocytic leukaemia\nn=58 \n\n\n\nMean\u00b1SD or n (%)\n\n\n\nAge (years) Mean \u00b1 SD\nMin, Max\n\n\n\n49.50\u00b116.55\n18, 82\n\n\n\n41.76\u00b119.18\n18, 81\n\n\n\nGender Male 46 (50.0) 30 (51.7)\n\n\n\nFemale 46 (50.0) 28 (48.3)\n\n\n\nEthnicity Malay 55 (59.8) 33 (56.9)\n\n\n\nChinese 25 (27.2) 17 (29.3)\n\n\n\nIndian 12 (13.0) 8 (13.8)\n\n\n\nDuration of Leukaemia \n(months)\n\n\n\nMean \u00b1 SD\nMin, Max\n\n\n\n40.78\u00b167.90\n1, 504\n\n\n\n44.02\u00b161.50\n1, 252\n\n\n\nCurrent Status:\nAcute Leukaemia\n\n\n\nChronic Leukaemia\n\n\n\nNewly diagnosed 27 (29.3) 15 (25.9)\n\n\n\nRemission 18 (19.6) 22 (37.9)\n\n\n\nRelapse 7 (7.6) 4 (6.9)\n\n\n\nRefractory 5 (5.4)\n\n\n\nChronic Phase 27 (29.3) 2 (3.4)\n\n\n\nRemission 1 (1.1) 12 (20.7)\n\n\n\nRelapse 3 (5.2)\n\n\n\nBlast 7 (7.6)\n\n\n\nCo-morbidities Diabetes 2 (2.2) 4 (6.9)\n\n\n\nChronic Kidney Disease 2 (2.2) 0 (0.0)\n\n\n\nHypertension 5 (5.4) 0 (0.0)\n\n\n\nIschaemic Heart disease 1 (1.1) 1 (1.7)\n\n\n\nHepatitis B 2 (2.2) 1 (1.7)\n\n\n\nPrevious skin disorder Eczema 6 (6.5) 2 (3.4)\n\n\n\nPsoriasis 2 (2.2) 0 (0.0)\n\n\n\nBone marrow \nTransplant 20 (21.7) 19 (32.8)\n\n\n\nType of transplant Autologous 2 (2.2) 0 (0.0)\n\n\n\nAllogeneic 18 (19.6) 18 (31.0)\n\n\n\nCord blood 0 (0.0) 1 (1.7)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 43\n\n\n\nfollowed by ALL (27.3%) and CML (23.3%). \nPatients diagnosed with lymphocytic leukaemia had \na longer duration of disease (44.02 \u00b1 61.50 months) \ncompared to myeloid leukaemia (40.78 \u00b1 67.90 \nmonths). In leukaemia patients with a previous \nhistory of skin disorder, eczema was the commonest \nin myeloid leukaemia (6.5%). In our cohort, 21.7% \npatients with myeloid leukaemia and 32.8% patients \nwith lymphocytic leukaemia had bone marrow \ntransplantation, with majority having allogeneic \ntransplant (92.3%). The baseline demographics and \nclinical characteristics of the study population are \nshown in Table 1.\n\n\n\nCutaneous Manifestations of the Study \nPopulation\nOne hundred and eighteen (78.7%) of the patients \nshowed one or more cutaneous manifestations. \nTable 2 summarises the characteristics of the \ncutaneous manifestations in the myeloid leukaemia \nand lymphocytic leukaemia group.\n\n\n\nPrimary Cutaneous Manifestations\nLeukaemia cutis was the only specific \ncutaneous manifestation noted in 3(3.3%) \npatients with myeloid leukaemia. All 3 patients \nwere diagnosed with AML, of which 2 patients \nwere newly diagnosed. Leukaemic infiltrates \npresented as erythematous to brownish papules \nand nodules over the trunk and limbs. The \ndiagnosis of leukaemia cutis was confirmed by \nskin biopsy in the 2 patients newly diagnosed \nwith AML. Biopsy was refused by the third \npatient, as she had relapsed AML and was in the \npalliative stage of her disease.\n\n\n\nSecondary Cutaneous Manifestations\nOne hundred and fifteen (76.7%) patients had non-\nspecific cutaneous manifestations with 76.1% of \npatients in the myeloid leukaemia group and 77.6 \n% patients in the lymphocytic leukaemia group. \nThe manifestations were inflammatory dermatoses \n(47.3%), infectious dermatoses (6.7%), other \ndermatoses (4.7%) and secondary to treatment \n(18.0%).\n\n\n\nInflammatory dermatoses (47.3%) were the most \ncommon cutaneous manifestation in both the \nmyeloid leukaemia and lymphocytic leukaemia \ngroups. Eczema was the most common (18.7%) \nfollowed by xerosis (14.7%). Of the eczema \npatients, majority had endogenous eczema in both \nthe myeloid leukaemia (15.2%) and lymphocytic \n\n\n\nleukaemia groups (19.0%). The most common \neczematous dermatoses were papular eczema \n(39.3%), followed by discoid eczema (28.6%) and \nseborrheic dermatitis (10.7%). Xerosis was seen in \n12.0% of myeloid leukaemia patients and 19.0% of \nlymphocytic leukaemia patients. Psoriasis (2.0%), \ninsect bite reaction (0.7%) and erythema nodosum \n(0.7%) were seen only in the myeloid leukaemia \ngroup. Acne vulgaris was more common in the \nmyeloid leukaemia group whereas petechia/purpura \nand post inflammatory hyperpigmentation were \nmore common in the lymphocytic leukaemia group.\nInfectious skin disorders were observed more \nfrequently in the myeloid leukaemia group (8.7%) \nthan the lymphocytic leukaemia group (3.4%). In \nthe myeloid leukaemia group, fungal infections \nwere the commonest (5.4%), followed by viral \n(2.2%) and bacterial (1.1%). However, in the \nlymphocytic leukaemia group, only two patients had \nan infectious dermatosis with one patient of bacterial \nand one patient of fungal aetiology respectively. \nThe superficial fungal infections include, in order \nof frequency onychomycosis, tinea pedis, tinea \ncorporis, tinea cruris and oral candidiasis.\nOther dermatoses observed were seborrheic \nkeratoses (two), keloid (one), dermatofibroma \n(one), idiopathic guttate hypomelanosis (one), \ntrichoepithelioma (one) and angiokeratoma of \nFordyce (one).\nCutaneous adverse drug reactions were more \nfrequent in the myeloid leukaemia (14.1%) \nthan the lymphocytic leukaemia group (6.9%). \nAnagen effluvium (5.3%) was the most common \ncutaneous adverse drug reaction, followed by \nmaculopapular eruption (2.0%) and mucositis \n(2.0%). Most of the drug reaction in our study was \ndue to chemotherapeutic agents (82.4%), followed \nby sulfamethoxazole/trimethoprim (11.8%) and \nallopurinol (5.9%).\n\n\n\nSkin GvHD was more frequent in the \nlymphocytic leukaemia group (10.3%) than \nthe myeloid leukaemia group (4.3%). All cases \nof GvHD occurred following allogeneic stem \ncell transplant. There were equal number of \npatients with acute (5.1%) and chronic GvHD \n(5.1%) in the lymphocytic leukaemia group. In \nour population of GvHD, majority of patients \nhad chronic GvHD (60.0%). All chronic GvHD \npatients clinically had lichenoid manifestation. \nSclerodermoid GvHD was not seen in our \nstudy. Of the patients with acute skin GvHD, all \npatients were in stage 1 and 2 of their disease.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44 MJD 2023 June Vol 50\n\n\n\nTable 2. Characteristics of cutaneous manifestations \n\n\n\nCutaneous manifestations All patients\nn=150\nn (%)\n\n\n\nMyeloid leukaemia\nn=92\nn (%)\n\n\n\nLymphocytic leukaemia\nn=58\nn (%)\n\n\n\nAll cutaneous manifestation 118 (78.7) 73 (79.3) 45 (77.6)\n\n\n\nLeukaemia cutis* 3 (2.0) 3 (3.3) 0 (0.0)\n\n\n\nInflammatory dermatoses* \nEczema      \n      Endogenous\n      Exogenous\nPsoriasis\nInsect bite reaction\nErythema nodosum\nAcne vulgaris\nXerosis\nPetechiae/purpura\nPost inflammatory hyperpigmentation\n\n\n\n71 (47.3)\n28 (18.7)\n25 (16.7)\n3 (2.0)\n3 (2.0)\n1 (0.7)\n1 (0.7)\n6 (4.0)\n\n\n\n22 (14.7)\n7 (4.7)\n3 (2.0)\n\n\n\n40 (43.5)\n16 (17.4)\n14 (15.2)\n2 (2.2)\n3 (3.3)\n1 (1.1)\n1 (1.1)\n4 (4.3)\n\n\n\n11 (12.0)\n3 (3.3)\n1 (1.1)\n\n\n\n31 (53.4)\n12 (20.7)\n11 (19.0)\n1 (1.7)\n0 (0.0)\n0 (0.0)\n0 (0.0)\n2 (3.4)\n\n\n\n11 (19.0)\n4 (6.9)\n2 (3.4)\n\n\n\nInfection*\nBacterial     Cellulitis\n                   Paronychia\nViral           Herpes Zoster \nFungal        Candidiasis\n                   Dermatophytes\n\n\n\n10 (6.7)\n1 (0.7)\n1 (0.7)\n2 (1.3)\n1 (0.7)\n5 (3.3)\n\n\n\n8 (8.7)\n0 (0.0)\n1 (1.1)\n2 (2.2)\n1 (1.1)\n4 (4.3)\n\n\n\n2 (3.4)\n1 (1.7)\n0 (0.0)\n0 (0.0)\n0 (0.0)\n1 (1.7)\n\n\n\nOther Dermatoses* 7 (4.7) 5 (5.4) 2 (3.4)\n\n\n\nDermatoses Secondary to Treatment:\nCutaneous Adverse Drug Reaction (cADR)*\n\n\n\nAnagen effluvium\nMaculopapular eruption\nMucositis \nErythema multiforme\nOthers\n\n\n\nGraft versus host disease (GvHD)*\nAcute       Maculopapular \n                 Vesicobullous \nChronic.   Lichenoid\n\n\n\n27 (18.0)\n17 (11.3)\n\n\n\n8 (5.3)\n3 (2.0)\n3 (2.0)\n1 (0.7)\n2 (1.3)\n\n\n\n10 (6.7)\n2 (1.3)\n2 (1.3)\n6 (4.0)\n\n\n\n17 (18.5)\n13 (14.1)\n\n\n\n6 (6.5)\n3 (3.3)\n2 (2.2)\n1 (1.1)\n1 (1.1)\n\n\n\n4 (4.3)\n0 (0.0)\n1 (1.1)\n3 (3.3)\n\n\n\n10 (17.2)\n4 (6.9)\n\n\n\n2 (3.4)\n0 (0.0)\n1 (1.7)\n0 (0.0)\n1 (1.7)\n\n\n\n6 (10.3)\n2 (3.4)\n1 (1.7)\n3 (5.2)\n\n\n\n*One patient may have more than one mucocutaneous manifestations; the percentage reported is based on the total patients in each group \n\n\n\nTable 3. Univariate analysis of risk factors for eczema \n\n\n\nRisk factors for eczema\nCrude Odds Ratio\n\n\n\nLower Limit\n95% Confidence Interval\n\n\n\np value\nUpper Limit\n\n\n\nAge 40 and below 1.00 - -\n\n\n\nAbove 40 1.73 0.73 4.14 0.22\n\n\n\nGender Male 1.99 0.85 4.65 0.11\n\n\n\nFemale 1.00 - -\n\n\n\nEthnicity Malay 1.00 - -\n\n\n\nChinese 1.73 0.71 4.18 0.23\n\n\n\nIndian 0.54 0.11 2.58 0.44\n\n\n\nDiagnosis Myeloid leukaemia 0.81 0.35 1.86 0.61\n\n\n\nLymphoid leukaemia 1.00 - -\n\n\n\nDuration Less than 1 year 1.00 - -\n\n\n\n1 \u2013 2 years 0.76 0.15 3.93 0.75\n\n\n\nMore than 2 years 2.53 1.01 6.32 0.05\n\n\n\nPrevious history of eczema No\nYes\n\n\n\n1.00\n3.09  \n\n\n\n-\n1.15\n\n\n\n-\n8.31\n\n\n\n0.03\n\n\n\nCo-morbidity No 1.00 - -\n\n\n\nYes 1.01 0.34 3.60 0.87\n\n\n\nTransplant No 1.00 - -\n\n\n\nYes 0.94 0.36 2.41 0.89\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 45\n\n\n\nSub analysis was performed to determine risk \nfactors associated with development of eczema. In \nour cohort, patients with disease duration of more \nthan 2 years have 2.53 odds of eczema compared \nto patients less than one year of disease (OR=2.53, \n95% CI 1.01-6.32, p=0.05). Patients with previous \nhistory of eczema have 3.09 odds of eczema \ncompared to patients without any previous history \nof eczema (OR=3.09, 95% CI 1.15-8.31, p=0.03). \nThere was no significant association between age, \ngender, ethnicity, type of leukaemia, co-morbidities, \nand history of bone marrow transplant with the \noccurrence of eczema observed in our study. These \nfindings are shown in Table 3. \n\n\n\nDiscussion\nIn 2020, leukaemia was estimated to be the 15th and \n11th most frequent cause of cancer incidence and \ncancer-related mortality worldwide, accounting for \n474,519 cases and 311,594 deaths respectively.5 \n\n\n\nThe Malaysian National Cancer Registry reported \nleukaemia as the sixth most common cancer in \nMalaysia, 7th in males and 9th in females. Malays \nhad the highest incidence rates followed by Chinese \nand Indians in both sexes.2 Majority of patients in \nthis study were Malay with a male preponderance, \nconsistent with national demographics. This similar \nfinding of male preponderance was seen in previous \nstudies.6-8 The mean age of our patients with myeloid \nleukaemia was 49 years and lymphocytic leukaemia, \n41 years. The National Cancer Registry showed \na much higher age at 65-74 years for myeloid \nleukaemia and lower age in lymphocytic leukaemia \nat 0-14 years.2 However, we recruited only patients \naged 18 years and older, therefore we are unable to \nmake a true comparison of the mean age. \nHospital Ampang is a tertiary referral centre for \nhaematological cancer and serves as the main referral \ncentre for patients with leukaemia in Malaysia. More \nthan two thirds of our study population had acute \nleukaemia, and about a third had chronic leukaemia. \nCLL accounted for only 11.3% of our cases. CLL \nis the most common leukaemia among adults in \nwestern countries.9 Asians and Asian descendants \nreported lower incidences of CLL and this is \nprobably due to differences in genetic makeup.3,7,10\n\n\n\nThe prevalence of cutaneous manifestations in \nleukaemia patients range from 25-50%.3,12 Up to \n88% of patients admitted to a Hemato-Oncology unit \nhad a mucocutaneous disorder.11 The prevalence of \ncutaneous manifestations in our cohort was notably \nhigh (78.7%). Cutaneous manifestations occurred \nirrespective of gender, age, ethnicity, and leukaemia \n\n\n\nsubtype. This high prevalence is likely attributed to \nthe recruitment of patients in a tertiary haematology \nreferral center similar to that observed by Pearson \net al.11\n\n\n\nSpecific Cutaneous Manifestations\nLeukaemia cutis also known as myeloid or \ngranulocytic sarcoma, is the cutaneous infiltration \nby neoplastic leukocytes (myeloid or lymphoid) \nresulting in identifiable cutaneous lesions.13,17  The \nincidence of leukaemia cutis varies based on the \nunderlying type of leukaemia and is reported in \n1-50% in patients with leukaemia.14,15 Leukaemia \ncutis occurs most commonly in AML, where its \nprevalence has been reported to be approximately \n3%\u20138%, up to 50% of cases of acute myelomonocytic \n(M4) and acute monocytic (M5) subtypes and in \nabout 2% of patients with CML.13,15-17 The prevalence \nof leukaemia cutis in our cohort was 2% and all \npatients were diagnosed with AML. \n\n\n\nLeukaemia cutis does not have a characteristic clinical \nappearance. Depending on whether leukaemia cells \ninfiltrate the epidermis, dermis, or subcutaneous \nfat, the clinical presentation is highly variable and \nmay mimic other skin diseases.3 Leukaemia cutis \nhas varied clinical manifestations ranging from \npapules, macules, plaques, nodules, ecchymoses, \npalpable purpura, and ulcerative lesions. Therefore, \na high index of clinical suspicion is required, and \nskin biopsy performed promptly. The most common \nlesions being multiple papules and nodules (60%) \nand infiltrated plaques (26%).18 All our patients \npresented with multiple papules and nodules. The \ndevelopment of leukaemia cutis portends a poor \nprognosis. Presence of leukaemia cutis indicates that \nthe disease will follow an aggressive course with \nshorter survival and predisposed to relapse.17,19\n\n\n\nInflammatory Dermatoses\nInflammatory dermatoses were the most common \ncutaneous manifestation seen in our study in \nboth the myeloid leukaemia and lymphocytic \nleukaemia group. Of these, eczema was the \nmost common followed by xerosis, petechiae/\npurpura and acne vulgaris. In contrast to our \nfindings, Aggarwal et al showed that infectious \ndermatoses were the commonest  manifestations \nseen in haematological and leukaemic patients.3 \nA retrospective review conducted in the \nhaematology unit in a tertiary level hospital in \nSingapore where more than half of the patients \nhad myeloid or lymphoid malignancies, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46 MJD 2023 June Vol 50\n\n\n\nshowed that infectious dermatoses (15%) and \neczematous dermatitis (13.33%) were the most \ncommon diagnoses.20 \n\n\n\nOur study showed that a longer duration of \nleukaemia and a previous history of eczema were \nrisk factors associated with the development \nof eczema. Leukaemic patients are thought to \nhave an increased risk for immune-mediated \n(eczematous) lesions compared to other onco-\nhematologic patients due to immunological \nmechanisms and production of cytokines or \nautoantibodies resulting from the neoplasm \nitself.1\n\n\n\nXerosis which is dryness of the skin was the second \ncommonest cutaneous manifestation in our patients. \nPatients with advanced malignancy commonly \nexhibit non-specific cutaneous signs such as xerosis \nand pruritis which is attributable to many causes \nincluding malnutrition, dehydration, and cachexia.21\n\n\n\nPallor, spontaneous haemorrhage, petechiae and \nulceration occur more frequently in acute than \nchronic leukaemia.22 In our study population, \n7 patients had petechia/purpura secondary to \nthrombocytopenia. All 7 patients had acute \nleukaemia and amongst them, 4 patients had \nALL which is analogous to that reported by \na study in Bangladesh.22 However, a study by \nAgnew et al showed that from clinical experience \necchymoses and purpura were common in CLL \npatients.12\n\n\n\nInfections\nThe immunosuppressed status in patients \nwith leukaemia makes them prone to develop \nuncommon and opportunistic infections.3 \n\n\n\nInfective dermatoses are the most common \ncutaneous disease in leukaemic patients.3,20,22 \n\n\n\nHowever infective dermatoses was the \nsecond most common manifestation in our \nstudy. Superficial fungal infections were the \npredominant cause of infective dermatoses \nand was observed more frequently in patients \nwith AML. Similar findings were also reported \nby Desch et al. and a higher prevalence of \nsuperficial fungal infections (14.69%) was \nreported in a Turkish study.23,24 However, \nAggarwal et al reported that fungal infections \n\n\n\nwere more common in patients with CML.3 \n\n\n\nThere was no deep fungal infection in any of \nour cases. Although, superficial fungal infection \nwas the most frequently observed finding, it\u2019s \nfrequency probably reflects the high incidence in \nour local population independent of the patient\u2019s \nunderlying leukaemia. Fungal infections \nare commonly seen in immunosuppressed \nconditions, but no relationship exists between \nsuperficial dermatophyte infections and internal \nmalignant diseases.24\n\n\n\nThe risk of herpes zoster is generally \nincreased in internal malignancies due to \nimmune suppression. It is most often seen in \nhaematological malignancies especially in \nleukaemia.24 In our study, herpes zoster infection \nwas seen in two patients with AML who were \nnot on antiviral prophylaxis.  Aggarwal et al \nreported that viral infections were more common \nin patients with ALL and oral acyclovir is \nrecommended for prophylaxis against varicella \ninfection in patients with haematological \nmalignancies.3 Interestingly, in our study there \nwas a low prevalence of infective dermatoses, \nand this could possibly be because dermatology \nopinion was not sought as they were likely \ndiagnosed and treated by the haematologist. \n\n\n\nCutaneous Adverse Drug Reactions\nDermatologic adverse events have become \nmore prevalent and is a growing concern in \npatients with cancer with the introduction of \nnovel anticancer agents.25 The skin, mucous \nmembranes and cutaneous appendages are \ntissues with rapid cellular proliferation and \nare thus susceptible to adverse reactions (toxic \nor hypersensitive) resulting from systemic \nchemotherapeutic treatment.26 Haematology \ninpatients are often acutely sick and on multiple \nmedications for treatment of the underlying \ndisease and its complications and unsurprisingly \nthis causes an increased number of cases of \ncutaneous adverse drug reactions (CADRs). \nMany of these drugs, such as beta-lactam, sulfa-\nbased antibiotics, and allopurinol, are frequently \nassociated with CADRs.20\n\n\n\nIn our study, anagen effluvium was the most common \nCADR, followed by mucositis and maculopapular \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 47\n\n\n\neruption. Similar CADRs were reported in an \nEgyptian study on leukaemia and lymphoma \npatients.26 Most of our CADR were secondary to \nchemotherapy, followed by antibiotics such as \nsulfamethoxazole/trimethoprim and allopurinol, \nwhich was also portrayed in other studies.20 \nSulfamethoxazole/trimethoprim is often used in \nleukaemia patients for Pneumocystis jirovecii \npneumonia prophylaxis as they are at increased \nrisk of opportunistic infections. These CADRs can \nimpede effective management of leukaemia patients. \nIn our study, although patients were exposed to \nmany medications, especially chemotherapeutic \nagents and antibiotics, there was a low prevalence of \ncutaneous adverse drug reactions and there was no \nincident of severe or life threatening CADR. \n\n\n\nGraft versus Host Disease (GvHD)\nGvHD is an immune-mediated reaction and \na major complication following allogeneic \nhematopoietic stem cell transplantation (HSCT) \nand can affect between 40 and 60% of patients.27 \n\n\n\nIn our study, 6.7% of patients developed \nGvHD, an incidence which is much lower \nthan that reported by previous studies.27,28,29 \nThis could be due to multiple factors such as \npatient characteristics, GvHD prophylaxis, \ndifferent conditioning regimens,  source of stem \ncells and short follow up duration. Cutaneous \nGvHD has been classified into acute (100 days \npost-transplant) and chronic (\u2265100 days after \ntransplant). However, this classification may \nnow be outdated. With novel therapies, clinical \nmanifestations of acute GvHD can be seen \nafter 100 days. Conversely, signs of chronic \nGvHD may be seen relatively early.29 Chronic \nGvHD accounted for the majority of skin \nGvHD (60.0%) and all patients were clinically \nof the lichenoid type. Punatar et al. reported \nthat ALL was significantly associated with an \nincreased risk of chronic GvHD. However, \nthe exact reason behind this remains unclear.28 \n\n\n\nInterestingly, majority of our study patients had \nALL. Acute mucocutaneous GvHD was seen \nin four patients and all patients were in clinical \nstage 1 and 2. Majority of our chronic GvHD \npatients (83.3%) had de novo chronic GvHD \nwhich is much higher than reported by Punatar \net al.28\n\n\n\nLimitations\nThis study involved only a single centre. Critically \nill patients who were unable to give informed \nconsent were not recruited, this may have an \ninfluence on the percentages of different types of \ncutaneous manifestations recorded in this study. \nFuture prospective studies with a longer follow up \nperiod are needed to better describe the cutaneous \nmanifestations in patients with leukaemia as \ncutaneous involvement in leukaemia patients has \nprognostic implications. These patients are more \nlikely to have an advanced disease stage, poorer \nprognosis, and decreased overall survival.\n\n\n\nConclusion\nOur study showed that leukaemia patients \npresent with a wide variety of cutaneous \nmanifestations which include leukaemia \ncutis, inflammatory and infective dermatoses, \ncutaneous adverse drug reactions and GvHD. \nEczema was the most common dermatoses \nobserved. Leukaemia cutis and GvHD may \nrepresent disease progression and warrant \nreassessment of the patients underlying disease \nstate and treatment strategy. Prompt recognition \nand management of CADRs circumvents dose \ninterruption or discontinuation of treatment. \nHence, early identification and treatment of \nthese patients will lead to more effective patient \ncare.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle.\n\n\n\nReferences\n1. Merlo G, Cozzani E, Canale F, Miglino M, Gambella M, \n\n\n\nBurlando M et al. Cutaneous manifestations of hematologic \nmalignancies the experience of an Italian dermatology \ndepartment. Hematol Oncol 2019;37:285-90.\n\n\n\n2. Azizah AM, Hashimah B, Nirmal K, Siti Zubaidah AR, \nPuteri NA, Nabihah A et al. Malaysian National Cancer \nRegistry Report 2012\u20132016. Malaysia Cancer Statistic, \nData and Figure. Malaysia: National Cancer Institute \n2019:17-51.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48 MJD 2023 June Vol 50\n\n\n\n3. Aggarwal S, Malhotra P, Dogra S, Vinay K, Kanwar AJ, \nSaikia UN. Spectrum of mucocutaneous manifestations in \nan Asian cohort of patients with leukemia. Int J Dermatol \n2016;55:893-7.\n\n\n\n4. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri \nSA, Stein H et al. WHO classification of tumours of \nhaematopoietic and lymphoid tissues. 4th ed. Lyon: \nInternational Agency for Research on Cancer; 2017. p.10-\n1.\n\n\n\n5. Sung H, Ferlay J, Siegel RL, Laversanne M, \nSoerjomataram I, Jemal A et al. Global Cancer Statistics \n2020: GLOBOCAN Estimates of Incidence and Mortality \nWorldwide for 36 Cancers in 185 Countries. CA Cancer J \nClin 2021;71:209-49.\n\n\n\n6. Yamamoto JF, Goodman MT. Patterns of leukemia \nincidence in the United States by subtype and demographic \ncharacteristics, 1997-2002. Cancer Causes Control \n2008;19:379-90.  \n\n\n\n7. D\u2019Costa G, Siddiqui HM, Pradhan RM, Gupte SS. Pattern \nof leukemias: A 10-year incidence study of 242 cases. J \nPostgrad Med 1989;35:191-5. \n\n\n\n8. Rathod KB, Kulkarni DG, Nakate L. Spectrum of leukemia \nat tertiary care hospital. IP J Diagn Pathol Oncol 2020;5:40-\n3.\n\n\n\n9. Yao Y, Lin X, Li F, Jin J, Wang H. The global burden and \nattributable risk factors of chronic lymphocytic leukemia \nin 204 countries and territories from 1990 to 2019: analysis \nbased on the global burden of disease study 2019. Biomed \nEng Online 2022;2:4.\n\n\n\n10. Pan JW, Cook LS, Schwartz SM, Weis NS. Incidence of \nleukemia in Asian migrants to the United States and their \ndescendants. Cancer Causes Control 2002;13:791-5.\n\n\n\n11. Pearson IC, Sirohi B, Powles R, Treleaven J, Mortimer \nPS. The impact on resources of prevalence and nature of \nskin problems in a modern intensive haemato-oncology \npractice. Hematology 2004;9:415-23. \n\n\n\n12. Agnew KL, Ruchlemer R, Catovsky D, Matutes E, Bunker \nCB. Cutaneous findings in chronic lymphocytic leukaemia. \nBr J Dermatol 2004;150:1129-35.\n\n\n\n13. Li AW, Yin ES, Stahl M, Kim TK, Panse G, Zeidan AM \net al. The skin as a window to the blood: Cutaneous \nmanifestations of myeloid malignancies. Blood Rev \n2017;31:370-88.\n\n\n\n14. Payda\u015f S, Zorludemir S. Leukaemia cutis and leukaemic \nvasculitis. Br J Dermatol 2000;143:773-9. \n\n\n\n15. Kaddu S, Zenahlik P, Beham-Schmid C, Kerl H, Cerroni L. \nSpecific cutaneous infiltrates in patients with myelogenous \nleukemia: A clinicopathologic study of 26 patients with \nassessment of diagnostic criteria. J Am Acad Dermatol \n1999;40:966-78.\n\n\n\n16. Agis H, Weltermann A, Fonatsch C, Haas O, Mitterbauer \nG, Mu\u0308llauer L et al. A comparative study on demographic, \nhematological and cytogenetic findings and prognosis in \nacute myeloid leukemia with and without leukemia cutis. \nAnn Hematol 2002;81:90-5. \n\n\n\n17. Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia \ncutis. Am J Clin Pathol 2008;129:130-42. \n\n\n\n18. Su WP, Buechner SA, Li CY. Clinicopathologic correlations \nin leukemia cutis. J Am Acad Dermatol 1984;11:121-8. \n\n\n\n19. Grunwald MR, McDonnell MH, Induru R, Gerber JM. \nCutaneous manifestations in leukemia patients. Semin \nOncol 2016;43:359-65.\n\n\n\n20. Koh H. A retrospective analysis of dermatological \nproblems in a hematology ward. Clin Cosmet Investig \nDermatol 2013;6:145-9.\n\n\n\n21. Kleyn CE, Lai-Cheong JE, Bell HK. Cutaneous \n\n\n\nmanifestations of internal malignancy: diagnosis and \nmanagement. Am J Clin Dermatol 2006;7:71-84.\n\n\n\n22. Haque AR, Zakaria AS, Sultana A, Khan MR. Skin \nmanifestations of hematologic malignancies. Bangladesh \nMed Journal 2014;43:121-4.\n\n\n\n23. Desch JK, Smoller BR. The spectrum of cutaneous disease \nin leukemias. J Cutan Pathol 1993;20:407-10\n\n\n\n24. Kili\u00e7 A, G\u00fcl U, Soylu S. Skin findings in internal malignant \ndiseases. Int J Dermatol 2007;46:1055-60.\n\n\n\n25. Chen AP, Setser A, Anadkat MJ, Cotliar J, Olsen EA, \nGarden BC et al. Grading dermatologic adverse events \nof cancer treatments: the Common Terminology Criteria \nfor Adverse Events Version 4.0. J Am Acad Dermatol \n2012;67:1025-39.\n\n\n\n26. Bassiouny DA, Abdel Raheem HM, Zawam HM, Abdel \nHamid SE. Cutaneous manifestations in patients with \nhaematological malignancy: a single-centre Egyptian \nstudy. J Egypt Women\u2019s Dermatol Soc 2015;12:90-5.\n\n\n\n27. Strong Rodrigues K, Oliveira-Ribeiro C, de Abreu Fiuza \nGomes S, Knobler R. Cutaneous Graft-Versus-Host \nDisease: Diagnosis and Treatment. Am J Clin Dermatol \n2018;19:33-50.\n\n\n\n28. Punatar S, Gupta A, Gawande J, Bagal B, Mathew L, \nKannan S et al. Chronic Graft Versus Host Disease in Acute \nLeukemia Patients Undergoing Allogeneic Hematopoietic \nStem Cell Transplant: Analysis of Risk Factors, Pattern and \nLong Term Outcome. Indian J Hematol Blood Transfus \n2016;32:32-8.\n\n\n\n29. Fogo A, du Vivier A. The cutaneous manifestations of \nhaematological malignancy. Clin Med (Lond) 2009;9:366-\n70.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 49\n\n\n\nORIGINAL ARTICLE\n\n\n\nCutaneous Manifestations in Obese Patients and Their Risk Factors: A \nCross-sectional Study in a Tertiary Center \n\n\n\nSubashini Govindarajoo1, MRCP, Preamala Gunabalasinggam1, AdvMDerm, Adawiyah Jamil2, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Tuanku Jaafar, Negeri Sembilan, Malaysia\n2Dermatology unit, Department of Medicine, Hospital Canselor Tuanku Muhriz UKM, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nBackground\nObesity is increasing globally. Multiple obesity-related diseases and morbidities pose challenges in \nmanagement with high health economic burden. This study investigated the type and prevalence of \ncutaneous diseases in obesity and its risk factors.\n\n\n\nMethods \nA cross-sectional study was conducted among patients with body mass index (BMI) >27.5kg/m2 in \nHospital Tuanku Jaafar, Negeri Sembilan, Malaysia. Data were collected via face-to-face interview. A \nphysical examination was performed to obtain anthropometry and diagnose dermatoses.\n\n\n\nResults\nA total of 350 patients aged 54.0\u00b111.73 years participated. There were 219 (62.6%) males and 131 \n(37.4%) females with 172 (49.1%) Malays, 55 (15.7%) Chinese and 119 (34.0%) Indians. Common \ndermatoses were acrochordon 284 (81.1%), plantar hyperkeratosis 246 (70.3%), and acanthosis \nnigricans 204 (58.3%). Females, grade 2&3 obesity, diabetes, and ischaemic heart disease (IHD) were \nsignificant independent risks for these dermatoses. Bacterial infection was observed in 49 (14.0%) \npatients, 137 (39.1%) had fungal infection. Folliculitis 41 (11.7%) and tinea pedis 55 (15.7%) were the \nprevalent infections. Males, grade 3 obesity, intertrigo, and hypertension were significant independent \ncontributing factors for infections. \n\n\n\nConclusion\nCutaneous manifestations were common among obese patients. Recognizing risk factors and diagnosing \nthese dermatoses will prevent further morbidities.\n\n\n\nKey words: Obesity, skin diseases, risk factors, body mass index, adiposity\n\n\n\nCorresponding Author \nDr Subashini a/p Govindarajoo\nDepartment of Dermatology, \nHospital Tuanku Jaafar,\nJalan Rasah, Bukit Rasah, \n70300 Seremban, Negeri Sembilan.\nEmail: suba_87@live.com\n\n\n\nIntroduction\nObesity is a public health issue in Malaysia, \naffecting approximately 19.7% of the \npopulation.1 In February 2020, the World \nHealth Organization made a declaration \nthat the prevalence of obesity had reached \nepidemic levels on a global scale.2 According \nto the Global Burden of Disease 2019 Risk \nFactors Collaborators study, high body mass \nindex (BMI) is a significant risk factor for \nseveral non-communicable diseases, ultimately \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50 MJD 2023 June Vol 50\n\n\n\ncontributing to 4.7 million premature deaths in \n2019. The primary cause of death was attributed \nto cardiovascular diseases.3 The figures are grim \nin Malaysia too. According to the 2023 World \nPopulation Review, Malaysia leads Southeast \nAsia in obesity rates among adults, with a \n15.6% prevalence. Brunei follows closely at \n14.1%, while Thailand and Indonesia have rates \nof 10.0% and 6.9%, respectively.4\n\n\n\nThe National Health and Morbidity Survey \n(NHMS) 2019 found 50.1% of adults in \nMalaysia were either overweight (30.4%) or \nobese (19.7%).1 Overweight and obesity levels \nwere exceptionally high among women at \n54.7%, ethnic Indians at 63.9%, and those in the \n55-59 age group at 60.9%.5\n\n\n\nThe impact of obesity on the skin has received \nminimal attention. Recent studies have suggested \nstrong associations between obesity and several \nskin conditions, including acanthosis nigricans, \nacrochordons, keratosis pilaris, and striae \ndistensae, as well as the impact of obesity on \nskin homeostasis.\n\n\n\nThe dermatological ramifications of obesity \nstem from two main factors: firstly, the \nmechanical and physiological impacts resulting \nfrom the expansion of adipose tissue; and \nsecondly, the secretion of endocrine, metabolic, \nand inflammatory peptides by enlarged fat \ncells, which essentially function as an auxiliary \nendocrine organ.6\n\n\n\nThis study aimed to describe the spectrum of \ncutaneous manifestation in the obese Malaysian \npopulation and to determine the association \nbetween various factors (demographic, grade \nof obesity, presence of other comorbidities) \nassociated with dermatoses. This knowledge \nwill prepare clinicians to be better at identifying \nand preventing these skin conditions before \nthey become complex issues.\n\n\n\nMaterials and Methods\nA cross-sectional study using a convenience \nsampling method was conducted among \npatients with obesity body mass index (BMI) \n\n\n\n>27.5 kg/m2 between July 2021 and August \n2022 at Hospital Tuanku Jaafar, Seremban, \nNegeri Sembilan. Patients were recruited from \nthe Otolaryngology and General Medicine \noutpatient clinics. Pregnant women, lactating \nmothers, patients on steroid treatment, and \npatients less than 18 years old were excluded. \nWritten consent was obtained. A thorough \ncutaneous examination from head to toe was \nperformed. Demographic details, including age, \nheight, weight, and the cutaneous finding were \nrecorded. \n\n\n\nEach participant\u2019s height was measured using a \nstadiometer (Health o Meter Professional), the \nsubject stands straight with their back against \nthe stadiometer and their feet together without \nshoes. The headpiece of the stadiometer is \nbrought down to the top of the subject\u2019s head, \nand the height is recorded. An electronic scale \n(Health o Meter Professional) recorded their \nweight. Waist circumference was measured at \nthe midpoint between the lower margin of the \nlast rib and the top of the iliac crest using a \nstandard measuring tape.\n\n\n\nBody mass index (BMI) is a person\u2019s weight \nin kilograms divided by the square of height \nin meters. According to the Malaysian Obesity \nClinical Practice Guidelines, obesity is \ncategorized into three grades based on body \nmass index (BMI). Grade 1 obesity is defined as \na BMI between 27.5 and 34.9, grade 2 obesity \nis defined as a BMI between 35.0 and 39.9, and \ngrade 3 obesity is defined as a BMI of 40 or \nhigher.7\n\n\n\nThe prevalence of obesity in Negeri Sembilan, \nMalaysia was estimated at 37%, with a BMI of \nmore than 27.5kg/m2 from the National Health \nMorbidity Survey 2019.1 Sample size of 399 \nwas calculated based on these values with a \n95% confidence level, 5% absolute precision \nand 10% dropout rate using a single proportion \nsample size formula. \n\n\n\nThis research was approved by the Research \nand Ethics Committee of Hospital Tuanku \nJaafar and registered with the National Medical \nResearch Registry. (NMRR-21-1442-60660).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 51\n\n\n\nStatistical analysis\nThe data were examined and evaluated using \nversion 21.0 of the SPSS software. Numerical \nvariables were displayed as mean and standard \ndeviation, while categorical variables were \npresented as frequency and percentage. \nPearson\u2019s chi-square tests or Fisher\u2019s exact \ntests were utilized to assess categorical \n\n\n\nvariable distributions. A p-value below 0.05 \nwas considered statistically significant. Simple \nLogistic Regression and Multiple Logistic \nRegression were used to determine the risk \nfactors linked to skin manifestations in obese \nindividuals, with or without adjusting for \ncovariates. Odds ratios (ORs) are provided with \n95% confidence intervals (CI).\n\n\n\nTable 1. Baseline characteristics \nVariables n=350\n\n\n\nMean (SD) n (%)\nAge (yr.) 54.0 (11.73)\nGender\n\n\n\nMale 219 (62.6)\nFemale 131 (37.4)\n\n\n\nRace\nMalay 172 (49.1)\nChinese 55 (15.7)\nIndian 119 (34.0)\nOthers 4 (1.1)\n\n\n\nEducation\n\n\n\nNo schooling & Primary 54 (15.6)\n\n\n\nSecondary 181 (52.2)\nTertiary 112 (32.3)\n\n\n\nMarital status \nSingle 36 (10.3)\nMarried 314 (89.7)\n\n\n\nSmoking\n     No 287 (82.0)\n     Yes 63 (18.0)\nAlcohol consumption\n     No 334 (95.4)\n\n\n\n     Yes 16 (4.6)\nBlood pressure, mmHg\n     Systolic 135.35 (17.97)\n     Diastolic 76.12 (10.380\nWeight circumference 114.58 (15.40)\nWeight (kg) 93.72 (19.89)\nHeight (cm) 162.93 (7.82)\nBody mass index (kg/m2)\n     Mean BMI 35.28 (6.82)\n     Grade 1 obesity 31.36 (2.06)\n     Grade 2 obesity 36.93 (1.43)\n     Grade 3 obesity 47.71 (6.30)\nOccupations\n\n\n\nRetired 88 (25.1)\nProfessionals 67 (19.1)\nTechnicians and associate professionals 10 (2.9)\nClerical support 10 (2.9)\nServices and sales 46 (13.1)\nElementary 66 (18.9)\nUnemployed 63 (18.0)\n\n\n\nCo-morbidities\n     Diabetes mellitus 189 (54)\n     Hypertension 272 (77.7)\n     Ischemic Heart disease 185 (52.9)\n     Dyslipidaemia 292 (83.4)\n     Metabolic syndrome 4 (1.1)\n\n\n\nThere are 3 missing data in the variable Education.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52 MJD 2023 June Vol 50\n\n\n\nResults\nA total of 350 patients participated in this \nstudy. The mean age of the patients was 54 \n\u00b1 11.73 years old. Most of the patients were \nmale, consisting of two-thirds of the total \nstudy population. Almost half of the patients \nbelonged to the Malay ethnicity 172 (49.1%), \nfollowed by the Indians 119 (34%) and Chinese \n55 (15.7%). Most at least received secondary \neducation. Only a small number were illiterate \nor only received primary education. Up to 90% \nof patients were married, and about 80% did not \nsmoke or consume alcohol. \n\n\n\nThe mean weight and height of the patients \nwere 93.72\u00b119.89kg and 162.93\u00b17.92cm, \nwith a waist circumference of 114\u00b115.40cm. \nThe mean BMI of this study patients was \n35.28\u00b16.82kg/m2. Patients from grade 1 \nobesity predominated, followed by grade 2 and \ngrade 3. There were 220 (62.9%) grade 1 obese \npatients, 70 (20.0%) grade 2, and 60 (17.1%) \ngrade 3. Patients also suffered from multiple \ncomorbidities, dyslipidemia (83.4%) being the \ncommonest, followed by hypertension (77.7%), \ndiabetes (54.0%), and ischaemic heart disease \n(52.9%). The mean HbA1c was 6.85%. Table \n1 summarized the characteristics of the study \npopulation.\n\n\n\nTable 2. Cutaneous manifestation of the study population\n\n\n\nCommon Manifestation\nOverall\nn=350\nn (%)\n\n\n\n% of 300 subjects\n\n\n\nGrade 1 obesity\nn=220\nn (%)\n\n\n\n% of 220 subjects\n\n\n\nGrade 2 & 3 obesity\nn=130\nn (%)\n\n\n\n% of 130 subjects\n\n\n\np-value\n\n\n\nAcanthosis nigricans 204 (58.3) 109 (49.5) 95 (73.1) <0.001\nCellulite 197 (56.3) 90 (40.9) 107 (82.3) <0.001\nAndrogenetic alopecia 74 (21.1) 56 (25.5) 18 (13.8) 0.010\nAcrochordons 284 (81.1) 167 (75.9) 117 (90.0) 0.001\nStriae distensae 167 (47.7) 78 (35.5) 89 (68.5) <0.001\nPlantar hyperkeratosis 246 (70.3) 150 (68.2) 96 (73.8) 0.263\nAcne vulgaris 24 (4.9) 10 (4.5) 14 (10.8) 0.026\nKeratosis pilaris 13 (3.7) 7 (3.2) 6 (4.6) 0.563a\n\n\n\nIntertrigo 41 (11.7) 19 (8.6) 22 (16.9) 0.020\nHirsutism 8 (2.3) 7 (3.2) 1 (0.8) 0.267a\n\n\n\nHidradenitis suppurativa 2 (0.6) 1 (0.5) 1 (0.8) >0.999a\n\n\n\nPsoriasis 16 (4.6) 6 (2.7) 10 (7.7) 0.032\nInfections\nViral infection\nWarts 10 (2.9) 5 (2.3) 5 (3.8) 0.509a\n\n\n\nHerpes labialis 1 (0.3) 1 (0.5) 0 >0.999a\n\n\n\nHerpes Zoster 2 (0.6) 2 (0.9) 0 0.532a\n\n\n\nBacterial infection\nAny type of bacterial infection 49 (14.0) 27 (20.8) 22 (10.0) 0.005\nFurunculosis 2 (0.6) 1 (0.5) 1 (0.8) >0.999a\n\n\n\nFolliculitis 41 (11.7) 19 (8.6) 22 (16.9) 0.020\nErysipelas 0 0 0 NEb\n\n\n\nErythrasma 1 (0.3) 0 1 (0.8) 0.371a\n\n\n\nCellulitis 9 (2.6) 3 (1.4) 6 (4.6) 0.083a\n\n\n\nFungal infection\nAny type of fungal infection 137 (39.1) 74 (33.6) 63 (48.5) 0.006\nTinea Cruris 54 (15.4) 34 (15.5) 20 (15.4) 0.986\nTinea Corporis 18 (5.1) 12 (5.5) 6 (4.6) 0.731\nTinea Unguium 9 (2.6) 3 (1.4) 6 (4.6) 0.083a\n\n\n\nTinea Pedis 55 (15.7) 26 (11.8) 29 (22.3) 0.009\nTinea Mannum 5 (1.4) 4 (1.8) 1 (0.8) 0.655a\n\n\n\nOnychomycosis 39 (11.1) 25 (11.4) 14 910.8) 0.684\nCandidiasis 0 0 0 NEb\n\n\n\nPityriasis Versicolor 9 (2.6) 4 (1.8) 5 (3.8) 0.301a\n\n\n\nEczema Reactions 176 (50.3) 110 (50.0) 66 (50.8) 0.889\n  Miscellaneous 12 (3.4)         9(4.1) 3 (2.3) 0.546 a\n\n\n\nThe results above were performed using Chi-Square unless specified otherwise. \na Fischer Exact Test \nb non-estimable\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 53\n\n\n\nTable 3. Factors associated with bacterial infections and fungal infections\n\n\n\nBacterial Infections a Fungal Infections b\n\n\n\nCrude OR \n(95% CI)\n\n\n\nAdjusted OR \n(95% CI)\n\n\n\np Crude OR \n(95% CI)\n\n\n\nAdjusted OR \n(95% CI)\n\n\n\np\n\n\n\nAge, years 0.96 (0.93, 0.98) 0.95 (0.92, 0.98) 0.001 1.00 (0.99, 1.02)\n\n\n\nGender 1 1\n\n\n\nMale 1 0.76 (049, 1.19) 0.53 (0.32, 0.88) 0.014\n\n\n\nFemale 0.97 (0.52, 1.81)\n\n\n\nRace\n\n\n\nMalay 1 1 1\n\n\n\nChinese 0.69 (0.27, 1.77) 0.35 (0.17, 0.72) 0.36 (0.17, 0.76) 0.008\n\n\n\nIndian 0.94 (0.48, 1.88) 0.88 (0.55, 1.42) 0.92 (0.55, 1.54) 0.760\n\n\n\nOthers NE NE NE NE\n\n\n\nLevel of education\n\n\n\nNo schooling & Primary 1 1\n\n\n\nSecondary 3.24 (0.95, 11.10) 2.06 (1.06, 4.00)\n\n\n\nTertiary 3.04 (0.85, 10.87) 1.56 (0.77, 3.17)\n\n\n\nBody mass index, kg/m2\n\n\n\nGrade 1 (27.5-35) 1 1 1 1\n\n\n\nGrade 2 (35-39.9) 0.69 (0.25, 1.90) 0.59 (0.21, 1.68) 0.323 1.48 (0.85, 2.56) 1.53 (0.85, 2.77) 0.156\n\n\n\nGrade 3 (>40) 5.21 (2.63, 10.34) 3.96 (1.83, 8.55) <0.001 2.41 (1.35, 4.31) 2.32 (1.21, 4.44) 0.011\n\n\n\nPlantar hyperkeratosis\n\n\n\nNo 1 1\n\n\n\nYes 1.77 (0.85, 3.70) 1.32 (0.82, 2.12)\n\n\n\nIntertrigo\n\n\n\nNo 1 1 1 1\n\n\n\nYes 5.36 (2.44, 11.76) 6.69 (2.67, 16.76) <0.001 4.57 (2.05, 10.22) 4.87 (2.02, 11.78) <0.001\n\n\n\nPresence of fungal \ninfections\n\n\n\nNo 1 Not applicable\n\n\n\nYes 2.13 (1.16, 3.92)\n\n\n\nPresence of bacterial \ninfections\n\n\n\nNo Not applicable 1\n\n\n\nYes 2.13 (1.16, 3.92)\n\n\n\nDiabetes mellitus\n\n\n\nNo 1 1\n\n\n\nYes 1.05 (0.57, 1.93) 1.41 (0.91, 2.17)\n\n\n\nHypertension\n\n\n\nNo 1 1 1\n\n\n\nYes 0.87 (0.43, 1.75) 1.73 (1.002, 2.97) 2.15 (1.19, 3.90) 0.011\n\n\n\nIschemic Heart Disease\n\n\n\nNo 1 1 1\n\n\n\nYes 0.84 (0.46, 1.53) 2.27 (1.03, 5.01) 0.042 1.08 (0.70, 1.60)\n\n\n\nDyslipidemia\n\n\n\nNo 1 1\n\n\n\nYes 0.43 (0.21, 0.86) 1.16 (0.65, 2.08)\na Multiple Logistic Regression with Forward LR was applied. Hosmer-Lemshow test (p=0.613), classification table (overall correctly classified \npercentage=86.7%), and Nagelkerke R2 (0.233) were applied to check the model fitness\nb Multiple Logistic Regression with Forward LR was applied. Hosmer-Lemshow test (p=0.976), classification table (overall correctly classified \npercentage=66.6%), and Nagelkerke R2 (0.170) were applied to check the model fitness\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54 MJD 2023 June Vol 50\n\n\n\nTable 4. Factor associated with Acanthosis nigricans, Acrochordons and Plantar hyperkeratosis\n\n\n\nAcanthosis nigricans a Acrochordons b Plantar hyperkeratosis c\n\n\n\nCrude OR \n(95% CI)\n\n\n\nAdjusted \nOR (95% \n\n\n\nCI)\n\n\n\np Crude OR \n(95% CI)\n\n\n\nAdjusted OR \n(95% CI)\n\n\n\np Crude OR \n(95% CI)\n\n\n\nAdjusted \nOR (95% \n\n\n\nCI)\n\n\n\np\n\n\n\nAge, years 0.99 (0.97, 1.005) 1.04 (1.02, 1.06) 1.06 (1.03, 1.09) <0.001 1.01 (0.99, 1.03)\nGender\nMale 1 1\nFemale 0.63 (0.40, 0.97) 0.40 (0.23, \n\n\n\n0.70)\n0.001 0.66 (0.39, 1.14) 0.52 (0.28, 0.96) 0.037 0.71 (0.44, 1.13)\n\n\n\nRace\nMalay 1 1\nChinese 0.20 (0.10, 0.42) 0.17 (0.07, \n\n\n\n0.40)\n<0.001 0.49 (0.25, 0.96) 0.42 (0.19, 0.92) 0.029 0.76 (0.40, 1.13)\n\n\n\nIndian 3.21 (1.87, 5.50) 4.59 (2.49, \n8.40)\n\n\n\n<0.001 1.78 (0.91, 3.50) 1.82 (0.87, 3.80) 0.111 1.29 (0.76, 2.18)\n\n\n\nOthers 2.43 (0.25, 23.85) 2.33 (0.19, \n27.93)\n\n\n\n0.504 0.71 (0.07, 7.07) 0.28 (0.02, 3.25) 0.307 0.43 (0.06, 3.16)\n\n\n\nLevel of \neducation\nNo schooling & \nPrimary\n\n\n\n1 1\n\n\n\nSecondary 1.14 (0.61, 2.13) 0.84 (0.38, \n1.86)\n\n\n\n0.659 0.78 (0.34, 1.81) 0.67 (0.33, 1.38)\n\n\n\nTertiary 0.71 (0.37, 1.38) 0.41 (0.18, \n0.97)\n\n\n\n0.041 0.64 (0.27, 1.53) 0.58 (0.27, 1.23)\n\n\n\nBody mass \nindex, kg/m2\nGrade 1 (27.5-\n35)\n\n\n\n1 1\n\n\n\nGrade 2 (35-\n39.9)\n\n\n\n1.95 (1.12, 3.42) 2.68 (1.36, \n5.27)\n\n\n\n0.004 1.90 (0.91, 3.98) 2.30 (1.02, 5.19) 0.046 0.89 (0.51, 1.58) 0.81 (0.44, \n3.39)\n\n\n\n0.482\n\n\n\nGrade 3 (>40) 4.54 (2.24, 9.18) 6.40 (2.86, \n14.33)\n\n\n\n<0.001 6.03 (1.81, \n20.05)\n\n\n\n10.57 (2.93, \n38.15)\n\n\n\n<0.001 2.33 (1.12, 4.87) 3.14 (1.46, \n6.74)\n\n\n\n0.003\n\n\n\nHbA1c 1.12 (1.01, 1.25) 1.08 (0.95, 1.24) 1.11 (0.99, 1.24)\n\n\n\nPresence \nof fungal \ninfections\nNo 1 1\nYes 2.83 (,./1.78, \n\n\n\n4.50)\n2.32 (1.35, \n\n\n\n4.01)\n0.002 2.84 (1.50, 5.36) 2.07 (1.04, 4.11) 0.038 1.32 (0.82, 2.12)\n\n\n\nPresence of \nbacterial \ninfections\nNo 1\nYes 1.95 (1.01, 3.78) 1.22 (0.54, 2.75) 1.77 (0.85, 3.70)\nDiabetes \nmellitus\nNo 1\nYes 1.67 (1.09, 2.57) 1.53 (0.89, 2.62) 1.48 (0.94, 2.35) 1.62 (1.001, \n\n\n\n2.61)\n0.050\n\n\n\nHypertension\nNo 1\nYes 0.78 (0.47, 1.32) 1.86 (1.03, 3.37) 1.56 (0.91, 2.64)\nIschemic Heart \nDisease\nNo 1\nYes 1.11 (0.72, 1.70) 1.44 (0.84, 2.47) 1.73 (1.09, 2.75) 2.07 (1.26, \n\n\n\n3.39)\n0.004\n\n\n\nDyslipidemia\n     No 1\n     Yes 0.98 (0.56, 1.74) 1.47 (0.75, 2.88) 1.57 (0.87, 2.82)\n\n\n\na Multiple Logistic Regression with Forward LR was applied. Hosmer-Lemshow test (p=0.0.610), classification table (overall correctly classified \npercentage=71.2%), and Nagelkerke R2 (0.389) were applied to check the model fitness\nb Multiple Logistic Regression with Forward LR was applied. Hosmer-Lemshow test (p=0.463), classification table (overall correctly classified \npercentage=82.4%), and Nagelkerke R2 (0.242) were applied to check the model fitness\nc Multiple Logistic Regression with Forward LR was applied. Hosmer-Lemshow test (p=0.797), classification table (overall correctly classified \npercentage=70.3%), and Nagelkerke R2 (0.079) were applied to check the model fitness\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 55\n\n\n\nThe results showed that the most common type \nof cutaneous manifestations encountered in \nthe obese population was acanthosis nigricans \n(58.3%), acrochordons (81.1%), and plantar \nhyperkeratosis (70.3%). Androgenetic alopecia \n(25.5%) was more commonly found in grade 1 \nobesity. On the other hand, the most common \ncutaneous manifestation found in Grade 2 and \n3 Obesity were acanthosis nigricans (73.1%), \nacrochordons (90%), cellulite (82.3%), striae \ndistensae (68.5%) and psoriasis (7.7%).\n\n\n\nFourteen percent of patients suffered from \nbacterial infection and 39.1% had fungal \ninfection. Folliculitis was observed more with \ngrade 2 and 3 obesity (p=0.02). Tinea pedis was \nsignificantly more common in grade 2 and 3 \nobesity (p=0.009). Other types of bacterial and \nfungal infections were not related to the grade \nof obesity.  \n\n\n\nThere were 12 possible associated factors \nidentified for each of these dermatoses. These \nfactors were analysed using simple logistic \nregression with no adjustment for other \ncovariates. Multiple logistic regression was then \nconducted to assess the independent relationship \nof these factors with each dermatosis.\n\n\n\nThe study found that patients with Grade 3 \nobesity and hypertension had significantly \nhigher odds of developing fungal infections, \nwith odds ratios (OR) of 2.32 (95% confidence \ninterval [CI] 1.21-4.44) and 2.15 (95% CI 1.19-\n3.90), respectively. In addition to that, the study \nrevealed significant associations between Grade \n3 obesity and IHD with an increased risk of \nbacterial infections, with odds ratios of 3.96 \n(95% CI 1.83-8.55) and 2.27 (95% CI 1.03-\n5.01), respectively. These results are shown in \nTable 3.\n\n\n\nBMI was a significant independent contributing \nfactor in the occurrence of the three most \ncommon cutaneous manifestations. Grade \n3 obesity was significantly associated with \nacanthosis nigricans (OR=6.4, 95% CI2.86-\n14.33), acrochordons (OR=10.57, 95% CI 2.93-\n38.15), and plantar hyperkeratosis (OR=3.14, \n95% CI 1.46-6.74) compared to Grade 1. \n\n\n\nAge showed a positive relationship with the \noccurrence of acrochordons. Each additional \nincrease of one year in age is associated with a \n6% increase in the odds of having acrochordons \n(adjusted OR=1.06; 95% CI 1.03-1.09; \np<0.001). Chinese patients have lesser odds of \ndeveloping these manifestations than Malays \nand Indians. The odds for female patients having \nacanthosis nigricans, acrochordons, and plantar \nhyperkeratosis were less than 1.  These findings \nare shown in Table 4. \n\n\n\nDiscussion\nWithout a doubt, obesity is a major health concern \nnot only due to its widespread occurrence but also \nits considerable socioeconomic consequences. \nIt leads to alterations in skin physiology, \npredisposing individuals with obesity to a \nvariety of skin manifestations, the prevalence \nof which differs across the globe. These lesions \ntypically have a subtle onset, are asymptomatic, \nand often occur in areas that are inconspicuous \nto the eye. This study identified acrochordons, \nplantar hyperkeratosis, and acanthosis nigricans \nas the three most common skin manifestations \nin individuals with obesity.\n\n\n\nAcanthosis nigricans (AN) is an indicator of \nadult hyperinsulinemia or insulin resistance. Its \nglobal prevalence ranges from 49% to 73%.8-11 \n\n\n\nOver half of the study patients had AN, with \nan equal number having diabetes mellitus or \nmetabolic syndrome. AN is observed mainly \nin the axilla, groin, and neck, although it can \nalso appear under the breasts, on the knuckles, \nelbows, and face.12 The exact pathogenesis \nremains unclear, but insulin is known to have \na strong proliferative effect on keratinocytes \nat high concentrations.13 Obese individuals \ntend to have elevated levels of free Insulin-\nlike growth factor 1 (IGF-1), which can cause \nepidermal hyperplasia and skin thickening by \nbinding to IGF receptors with high affinity.14 \nRecent research has shown that leptin may \nalso play a paracrine role in the skin, affecting \nthe proliferation, differentiation, growth, and \napoptosis of epithelial cells. Leptin is a hormone \nproduced by adipose tissue that regulates energy \nbalance by suppressing appetite and increasing \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56 MJD 2023 June Vol 50\n\n\n\nenergy expenditure. \n\n\n\nFor instance, Yazici et al speculated that \nhigh levels of leptin could be related to the \ndevelopment of acanthosis nigricans in their \npatient.15 Numerous studies have shown a link \nbetween the occurrence of Acanthosis Nigricans \n(AN) and insulin resistance. For example, \nYamazaki and colleagues found a positive \ncorrelation between these factors in obese \nJapanese children.16 Copeland and co-authors \nexamined the relationship between AN and \ninsulin resistance in children and discovered that \nthe severity of the skin condition was linked to \nthe Homeostatic Model Assessment for Insulin \nResistance (HOMA-IR) value. They also found \nAN to be an independent risk factor for insulin \nresistance development.17 \n\n\n\nSadeghian and team studied insulin resistance \nin obese women with and without AN and \nfound that skin lesions served as an indicator for \ninsulin resistance, with no notable differences \nin lipid profile, triglycerides, or hypertension \nprevalence between the two groups.18 Both \nStoddart et al. and Kong et al. identified \nAN as an independent risk factor linked to \nhyperinsulinemia and the onset of diabetes \nmellitus.19, 20 Kong\u2019s study also revealed that \nchildren with a family history of type 2 diabetes \nhad a higher prevalence of AN, and acanthosis \nwas more common in patients with hypertension \nand elevated BMI.20 However, Hirschler et al. \ndisagreed with these findings in their study of \n1,250 Hispanic children, suggesting that AN \nmight be more reflective of obesity than an \nindependent factor for insulin resistance. In their \nresearch, patients with AN had a higher BMI, \nbut insulin resistance and HOMA values did not \nsignificantly differ compared to those without \nacanthosis.21 The unsightly appearance of AN \nmay cause significant psychological distress. \nTreatment focuses on addressing the underlying \ndisease, with weight loss often helping to reduce \ninsulin resistance and fade the lesion over time.\n\n\n\nAcrochordons, also known as skin tags, are \nskin-coloured or brown soft pedunculated \npapules often found on the neck, axillae, and \ngroin. They were present in 81% of patients \n\n\n\nin our study, a higher percentage than the 30% \nreported by Al-Mutairi N et al and 77% by \nGomez AP et al22-23 The higher prevalence in this \nstudy may be attributed to a larger number of \nolder obese patients. Skin tags tend to increase \nin number and size with age and in areas prone \nto skin irritation.24 Skin tags are commonly \nfound in obese individuals and those with \nnon-insulin-dependent diabetes, with insulin \nresistance being a common factor between the \ntwo conditions. Hyperinsulinemia is thought \nto cause fibroblast proliferation in skin tags by \nactivating insulin-like growth factor (IGF-1) \nreceptors on their surfaces.25 \n\n\n\nRecent studies have attempted to demonstrate \na correlation between skin tags, insulin \nresistance, and serum IGF-1 levels. Jowkar \net al reported that patients with skin tags had \nsignificantly higher insulin levels than control \nindividuals, highlighting insulin\u2019s role in skin \ntag development. However, a connection \nwith IGF-1 levels remains unestablished.26 \nSimilar to acanthosis nigricans, insulin may \nnot be the sole factor in skin tag formation \nbut is likely the most crucial.27 Tamega et al \ndiscovered an independent association between \nthe presence of more than five skin tags and \na 1.4-unit increase in the HOMA-IR index \nin dermatological patients. The significant \ncorrelation with BMI and hypertriglyceridemia \nfound in this study supports the idea that skin \ntags could be markers of insulin resistance.28 \nAdditionally, Singh et al. found that both skin \ntags and acanthosis nigricans were significantly \nlinked to insulin resistance and HOMA-IR \ncompared to controls.29 Skin tags are strongly \nrelated to fasting insulin levels.25 While patients \noften overlook these asymptomatic lesions, \nthey hold great importance and should not be \nignored during clinical examinations, as they \ncan indicate the need for further testing to \ndiagnose insulin resistance. \n\n\n\nAlthough large skin tags may cause discomfort, \nthey are not typically associated with increased \ncancer risk. Nonetheless, obese individuals are \nat higher risk of experiencing inflammation \nfrom twisted or irritated skin tags.30 Removing \nthese skin tags can enhance skin appearance and \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 57\n\n\n\nminimize the risk of irritation and inflammation. \nIn our study, we observed that over 50% of the \nparticipants with both acanthosis nigricans and \nacrochordons (skin tags) also had diabetes. \nHowever, this finding did not demonstrate \nstatistical significance.\n\n\n\nPlantar hyperkeratosis was highly prevalent \nin the study patients, with a higher rate than \nthe 40% and 45% reported by Usma et al and \nDivyaShree, respectively.31, 32 The increased \nprevalence could be attributed to a higher \nnumber of diabetic patients in this study \nwhereby diabetes is a known risk factor for this \ncondition. Additionally, 32% of the participants \nhad jobs in sales and services or held elementary \npositions, which may have involved prolonged \nstanding or walking, potentially contributing \nto the higher rate of plantar hyperkeratosis. \nExcess weight changes foot anatomy due to \nincreased pressure on weight-bearing areas and \nbony prominences, causing skin thickening as a \ncompensatory mechanism. A study by Menz et \nal. reported that obesity was associated with a \nhigher prevalence of plantar hyperkeratosis, with \nindividuals having a body mass index (BMI) \nof 30 or higher being at a significantly higher \nrisk.33 The thickened skin can limit mobility and \ncause discomfort, particularly in weight-bearing \nareas such as the heel and ball of the foot. This \ncan make it difficult for individuals to engage \nin physical activity, exacerbating the effects of \nobesity and increasing the risk of other chronic \nhealth conditions.\n\n\n\nObesity heightens the risk of infectious diseases, \nincluding skin infections, and adversely affects \noutcomes.34-35 The link between obesity and a \npro-inflammatory state, as well as reduced cell-\nmediated immune responses, might contribute \nto this increased vulnerability.35, 36 Additionally, \nlimited mobility and challenges in maintaining \nproper hygiene compound the issue. Intertrigo is \nan inflammatory condition affecting skin folds \nwhere the opposing skin surfaces rub against \neach other.37 Macerated erythematous patches or \nplaques form within skin folds of inframammary, \ngenitocrural, axillary, or abdominal regions.  \n\n\n\nEnhanced subcutaneous fat raises skin friction \n\n\n\nand moisture, creating a humid environment that \nintensifies local inflammation and predisposes \nobese individuals to dermatoses like intertrigo, \naccompanied by secondary overgrowth of \nbacteria, Candida species, and dermatophytes.12, \n\n\n\n37-39 The skin is home to various bacterial, \nfungal, and viral communities, together \nforming the skin microbiome.40 Brandwein et al \nfound a correlation between BMI and the skin \nmicrobiome.41 Overweight individuals display a \nless diverse microbiome and a relative increase \nin Corynebacterium, which promotes skin \ninflammation.42 Interestingly, research has also \nshown that skin surface pH was higher in the \ninguinal folds of diabetic women with a BMI of \nmore than 25 kg/m2, further elevating the risk of \nskin infections.12 If left untreated, complications \nfrom these dermatoses can be severe, potentially \nleading to cellulitis and sepsis.\n\n\n\nOver the past three decades, cellulite has \ngarnered significant attention in the cosmetics \nindustry. This study reports a prevalence of \n56.3%, rising with increasing obesity grades \n(40% in Grade 1 and 82% in Grades 2 and 3). \nThese figures are lower than those reported by \nSakral et al., who found a prevalence of 68%.43 \n\n\n\nIn this study, a possible explanation for the \nobserved discrepancy is the disproportionate \ngender distribution of the study sample. \nSpecifically, the male-to-female ratio was \n2:1. The composition of fibrous tissue differs \nbetween men and women, with women\u2019s \nfibrous tissue being more tightly woven, \ncausing a more pronounced dimpling effect.44 \nCellulite formation commences in adolescence \nwhen estrogen triggers fat accumulation in the \nbody, especially in the thighs and hips. Over \ntime, subcutaneous fat cells expand, and lymph \nfluid accumulates in these tissues, compressing \nfat cells, which eventually harden into lumps, \nresulting in cellulite.44 Although various \ntherapeutic approaches have been attempted, \nsuch as topical agents, injectable treatments, \nand energy-based devices, successful long-term \nprocedures have yet to be identified.45\n\n\n\nThis study has several limitations that should \nbe considered. Firstly, the study had a cross-\nsectional design, which means that it could \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58 MJD 2023 June Vol 50\n\n\n\nonly observe the relationship between obesity \nand skin manifestations at a single point in \ntime. Additionally, the study was conducted at \na single healthcare facility, which may limit \nthe generalizability of the findings to other \npopulations. Moreover, the absence of a control \ngroup consisting of non-obese individuals limits \nthe ability to determine the specific effects of \nobesity on skin manifestations. \n\n\n\nThere is also a possibility of selection bias, \nas the study recruited subjects from patients \nwho presented to a healthcare facility with a \nmedical condition. Another limitation is that \nthe sample size was too small to compare the \nprevalence of less common skin conditions such \nas hidradenitis suppurativa, psoriasis, cellulitis, \nand erythrasma. Therefore, further research is \nrequired to better comprehend the relationship \nbetween obesity and skin manifestations and \nto develop more effective treatments for these \nconditions.\n\n\n\nConclusion\nObesity is associated with various skin \nmanifestations. The common manifestations \nare acrochordons, plantar hyperkeratosis, and \nacanthosis nigricans. Individuals with higher \ngrades of obesity, specifically Grade 3 obesity, \nhave higher odds of developing these cutaneous \nmanifestations. Management of obesity-related \ndermatoses and their complications will increase \nthe health economic burden. Understanding the \nskin changes that take place facilitates better \ntreatment and prevents sequelae. \n\n\n\nConflict of Interest Declaration \nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgment \nThe authors would like to thank the Director \nGeneral of Health Malaysia for his permission \nto publish this article.\n\n\n\nReferences\n1. Ministry of Health, Malaysia (MOH). National \n\n\n\nHealth and Morbidity Survey (NHMS) 2019. Non-\nCommunicable Diseases, Healthcare Demand and Health \nLiteracy. Available at http://www.iku.gov.my/images/\nIKU/Document/ REPORT/NHMS2019/ FactSheet_BI_\nAUG2020.pdf.\n\n\n\n2. World Health Organization (WHO). Obesity and \noverweight Fact sheet no. 311. 2021. Available at https://\nwww.who.int/news-room/fact sheets/detail/obesity-and-\noverweight.\n\n\n\n3. GBD 2019 Risk Factors Collaborators. Global burden of \n87 risk factors in 204 countries and territories, 1990-20\n\n\n\n4. World Population Review. Obesity rates by country 2023. \nAvailable at https://worldpopulationreview.com/country-\nrankings/obesity-rates-by-country.\n\n\n\n5. Lim KG. A Review of Adult Obesity Research in \nMalaysia. Med J Malaysia 2016;71(Suppl 1):1-19.\n\n\n\n6. Mirmirani P, Capenter DM. Skin disorders associated \nwith obesity in children and adolescents: a population-\nbased study. Pediatr Dermatol 2014;31:183-90.\n\n\n\n7. Ministry of Health, Malaysia (MOH). Clinical Practice \nGuidelines: Management of Obesity. Kuala Lumpur: \nInstitute for Public Health, 2014. Available at http://\nwww.moh.gov.my/moh/resources/Penerbitan/Garis%20\nPanduan/Obesiti/Management_of_Obesity_CPG_2014.\npdf.\n\n\n\n8. Ahsan U, Jamil A, Rashid S. Cutaneous manifestations in \nobesity. J Pak Assoc Dermatol 2014;24:21-5.\n\n\n\n9. Niaz F, Shams N, Qureshi S, Bashir F, Shaikh Z, Ahmed \nI. Dermatological manifestations of obesity. J Pak Assoc \nDermatol 2016;25:90-5.\n\n\n\n10. Garc\u00eda Hidalgo L. Dermatological complications of \nobesity. Am J Clin Dermatol 2002;3:497-506.\n\n\n\n11. Sivakumar S, Banupriya K.A cross-sectional descriptive \nclinical study of dermatological manifestations in obesity. \nInt J Res Dermatol 2017;3:337-41.\n\n\n\n12. Yosipovitch G, DeVore A, Dawn A. Obesity, and the skin: \nskin physiology and skin manifestations of obesity. J Am \nAcad Dermatol 2007;56:901-16.\n\n\n\n13. Cruz PD Jr, Hud JA Jr. Excess insulin binding to insulin-\nlike growth factor receptors: proposed mechanism for \nacanthosis nigricans. J Invest Dermatol. 1992;98(6 \nSuppl):82S-5S. \n\n\n\n14. Scheinfeld NS. Obesity and dermatology. Clin Dermatol \n2004;22:303-9.\n\n\n\n15. Yazici AC, Tursen U, Ikizoglu G, Akbay E, Tataroglu \nC, Cimen MY. Atypical localization of acanthosis \nnigricans in an obese patient with increased leptin level: \nis there an association? J Am Acad Dermatol. 2006;55(2 \nSuppl):S55-6. \n\n\n\n16. Yamazaki H, Ito S, Yoshida H. Acanthosis nigricans is a \nreliable cutaneous marker of insulin resistance in obese \nJapanese children. Pediatr Int 2003;45:701-5.\n\n\n\n17. Copeland K, Pankratz K, Cathey V, Immohotichey P, \nMaddox J, Felton B et al. Acanthosis Nigricans, insulin \nresistance (HOMA) and dyslipidemia among Native \nAmerican children. J Okla State Med Assoc 2006;99:19-\n24.\n\n\n\n18. Sadeghian G, Ziaie H, Amini M, Ali Nilfroushzadeh M. \nEvaluation of insulin resistance in obese women with and \nwithout acanthosis nigricans. J Dermatol. 2009;36:209-\n12.\n\n\n\n19. Stoddart ML, Blevins KS, Lee ET, Wang W, Blackett \nPR; Cherokee Diabetes Study. Association of acanthosis \nnigricans with hyperinsulinemia compared with other \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 59\n\n\n\nselected risk factors for type 2 diabetes in Cherokee \nIndians: the Cherokee Diabetes Study. Diabetes Care. \n2002;25:1009-14.\n\n\n\n20. Kong AS, Williams RL, Smith M, Sussman AL, Skipper \nB, Hsi AC et al. Acanthosis nigricans and diabetes risk \nfactors: prevalence in young persons seen in southwestern \nUS primary care practices. Ann Fam Med. 2007;5:202-8.\n\n\n\n21. Hirschler V, Aranda C, Oneto A, Gonzalez C, Jadzinsky \nM. Is acanthosis nigricans a marker of insulin resistance \nin obese children? Diabetes Care 2002;25:2353.\n\n\n\n22. Al-Mutairi N. Associated Cutaneous Diseases in Obese \nAdult Patients: A Prospective Study from a Skin Referral \nCare Center. Med Princ Pract 2011;20:248-52.\n\n\n\n23. Plascencia G\u00f3mez A, Vega Memije ME, Torres Tamayo \nM, Rodr\u00edguez Carre\u00f3n AA. Skin disorders in overweight \nand obese patients and their relationship with insulin. \nActas Dermosifiliogr 2014;105:178-85. \n\n\n\n24. Luba MC, Bangs SA, Mohler AM, Stulberg DL. Common \nBenign Skin Tumors. Am Fam Physician 2003;67:729-38.\n\n\n\n25. Mathur SK, Bhargava P. Insulin resistance and skin tags. \nDermatology 1997;195:184.\n\n\n\n26. Jowkar F, Fallahi A, Namazi MR. Is there any relation \nbetween serum insulin and insulin-like growth factor-I in \nnon-diabetic patients with skin tag? J Eur Acad Dermatol \nVenereol. 2010;24:73-4.\n\n\n\n27. Sudy E, Urbina F, Maliqueo M, Sir T. Screening of \nglucose/insulin metabolic alterations in men with multiple \nskin tags on the neck. J Dtsch Dermatol Ges 2008;6:852-\n6.\n\n\n\n28. Tamega Ade A, Aranha AM, Guiotoku MM, Miot LD, \nMiot HA. Association between skin tags and insulin \nresistance. An Bras Dermatol. 2010;85:25-31.\n\n\n\n29. Singh SK, Agrawal NK, Vishwakarma AK. Association \nof Acanthosis Nigricans and Acrochordon with Insulin \nResistance: A Cross-Sectional Hospital-Based Study from \nNorth India. Indian J Dermatol 2020;65:112-7.\n\n\n\n30. Ljubojevic S, Skerlev M. HPV-associated diseases. Clin \nDermatol 2014;32:227-34.\n\n\n\n31. Iftikhar U, Rashid S, Kamal T. Ghazala B.Cutaneous \nmanifestation of obesity and frequency of systemic \nconditions in obesity. Rawal Med J 2021;46:170-3.\n\n\n\n32. Divyashree RA, Naveen KN, Pai VV, Athanikar SB, \nGupta G. Cutaneous manifestations of obesity among \ndermatology patients in a tertiary care centre. Indian J \nDermatol Venereol Leprol 2014;80:278.\n\n\n\n33. Menz HB, Tiedemann A, Kwan MM, Plumb K, Lord \nSR. Foot pain in community-dwelling older people: an \nevaluation of the Manchester Foot Pain and Disability \nIndex. Rheumatology (Oxford). 2006;45:863-7.\n\n\n\n34. Huttunen R, Syrjanen J. Obesity, and the outcome of \ninfection. Lancet Infect Dis 2010;10:442-3.\n\n\n\n35. Huttunen R, Syrjanen J. Obesity and the risk and outcome \nof infection. Int J Obes (Lond) 2013;37:333-40.\n\n\n\n36. Falagas ME, Athanasoulia AP, Peppas G, \nKarageorgopoulos DE. Effect of body mass index on the \noutcome of infections: A systematic review. Obes Rev \n2009;10:280-9.\n\n\n\n37. De Britto LJ, Yuvaraj J, Kamaraj P, Poopathy S, \nVijayalakshmi G. Risk factors for chronic intertrigo of the \nlymphedema leg in southern India: a case-control study. \nInt J Low Extrem Wounds 2015;14:377-83.\n\n\n\n38. Guida B, Nino M, Perrino NR, Laccetti R, Trio R, \nLabella S et al. The impact of obesity on skin disease \nand epidermal permeability barrier status. J Eur Acad \nDermatol Venereol. 2010;24:191-5.\n\n\n\n39. Ndiaye M, Taleb M, Diatta BA, Diop A, Diallo M, Diadie \n\n\n\nS et al. [Etiology of intertrigo in adults: A prospective \nstudy of 103 cases]. J Mycol Med. 2017;27:28-32.\n\n\n\n40. Byrd AL, Belkaid Y, Segre JA. The human skin \nmicrobiome. Nat Rev Microbiol. 2018;16:143-55.\n\n\n\n41. Brandwein M, Katz I, Katz A, Kohen R. Beyond the gut: \nskin microbiome compositional changes are associated \nwith BMI. Hum Microbiome J 2019;13:100063.                 \n\n\n\n42. Ridaura VK, Bouladoux N, Claesen J, Chen YE, Byrd \nAL, Constantinides MG et al. Contextual control of skin \nimmunity and inflammation by Corynebacterium. J Exp \nMed 2018;215:785-99.\n\n\n\n43. Arti S, Gupta V, Dogra D. A hospital-based clinical study \nof cutaneous changes in overweight and obesity. Int J \nHealth Sci Res 2017;7:56-64.\n\n\n\n44. Nurnberger F, Mu\u0308ller G. So-called cellulite: an invented \ndisease. J Dermatol Surg Oncol 1978;4:221-9.\n\n\n\n45. Sadick N. Treatment for cellulite. Int J Womens Dermatol. \n2018;5:68-72.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n60 MJD 2023 June Vol 50\n\n\n\nORIGINAL ARTICLE\n\n\n\nAssociation Between Acanthosis Nigricans and Metabolic Syndrome at \nRural Tertiary Care Hospital in Central India: A Case Control Study\n\n\n\nArtilata Deshmukh, MBBS, Sonia Jain, MD, Shantanu Harode, MBBS\n\n\n\nDepartment of Dermatology, Venereology & Leprosy, Mahatma Gandhi Institute of Medical Sciences Sewagram, \nWardha, Maharashtra, India\n\n\n\nAbstract\nBackground\nAcanthosis nigricans (AN) characterized by papillomatosis and hyperkeratosis of skin symmetrically \ninvolves neck, axilla, face, groins, antecubital, popliteal fossae, face as well as dorsum of hands and \nfingers. Globally Metabolic Syndrome (MS) is found to be significantly associated with AN but there \nis a paucity of data from rural population in Indian literature. The aim of the study is to determine \nassociation of MS with AN and  compare fasting blood sugar level, lipid profile, blood pressure, and \nwaist circumference in patients with AN to healthy controls.\n\n\n\nMethods\nDescriptive case\u2013control study with 80 cases of AN and 80 healthy controls without AN was conducted \nbetween November 2020 and November 2022 to assess association between AN and MS. \n\n\n\nResults\nEighty cases and 80 controls were evaluated. MS was significantly more common in AN cases than \ncontrols (50% vs 27.5%, p=0.003). Cases had significantly increased waist circumference for females \n(72.34% vs 43.48%), hypertriglyceridemia (46.3% vs 16.3%), hypertension(31.25% vs 13.75%), \nelevated fasting blood sugar (45% vs 17.5%) and decreased high density lipoprotein cholesterol \n(63.64% males and 29.79% females vs 35.29% males and 13.04% females).The association of  MS \nwith AN  in our cases was statistically significant in our study population.\n\n\n\nConclusion\nFifty percent of patients with AN suffering from MS showed statistically significant  association with \nindividual parameters of MS. We found positive correlation between neck severity, axilla severity and \nneck texture with MS. All patients of AN should be routinely screened for MS. Early screening and \nintervention for MS can prevent future complications.\n\n\n\nKey words: Acanthosis nigricans, case\u2013control study, metabolic syndrome\n\n\n\nCorresponding Author\nDr Sonia Jain\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences, \nSewagram, Wardha, Maharashtra, 442102 India.\nEmail: soniajain@mgims.ac.in\n\n\n\nIntroduction\nAcanthosis nigricans (AN) is a condition \ncharacterized by papillomatosis and \nhyperkeratosis of the skin1 manifesting as \nasymptomatic and symmetrical darkening \nof intertriginous areas and  associated with \nendocrine disturbances or malignancy. It \nis strongly associated with obesity.2 It is in \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 61\n\n\n\nturn accompanied by hyperinsulinemia with \ndevelopment of insulin resistant diabetes \nmellitus.3-4 There is an increased incidence of \nobesity even in rural areas due to changes in \nlife style and sedentary life pattern secondary \nto increased industrialization as well as \nurbanization of rural areas.5 Hence more \nnumber of cases of AN are  being seen even in \nrural setup. MS consists of a constellation of \nmetabolic abnormalities that increases risk of \ncardiovascular disease and diabetes mellitus \n(DM). Its features include central obesity, \nhypertriglyceridemia, low levels of high-density \nlipoprotein (HDL) cholesterol, hyperglycemia \nand hypertension.6\n\n\n\nWe have conducted this study to assess the \nprevalence of the MS and its associated \ncomponents among individuals with AN in \na rural hospital in Central India. AN may be \none of the complaints of MS presenting to the \ndermatologist for cosmetic purpose. Therefore, \nthese patients should be investigated for MS to \navoid serious consequences.\n\n\n\nMaterials and Methods\nA descriptive case control study with 80 cases \nof AN and 80 healthy controls without AN \nwas conducted between November 2020 to \nNovember 2022 in a rural tertiary care hospital \nlocated in Central India in outpatient department \nof Dermatology, Venereology and Leprosy. \nEthical clearance for the study was taken from \nthe Institutional Ethics Committee.\n\n\n\nA. Inclusion criteria\nCases:\n1. Patients with clinical diagnosis of AN \n\n\n\ncomprising of both sexes\n2. Patients of 13 to 65 years of age\n3. Giving written informed consent for \n\n\n\ninclusion in the study\n\n\n\nControls:\n1. All healthy individuals of age 13-65 years \n\n\n\nnot having AN of same age and sex\n2. Giving written informed consent for \n\n\n\ninclusion in the study\n\n\n\nB. Exclusion criteria\nCases:\n1. Patients less than 13 years and more than 65 \n\n\n\nyears of age\n2. Patients with a drug history of nicotinic \n\n\n\nacid, oral contraceptives, systemic steroids, \ndiethylstilbesterols and anti-retroviral drugs \nwhich can cause AN.\n\n\n\n3. Pregnancy and lactating female patients\n4. AN due to malignancy associated conditions\n5. Autoimmune causes of AN\n6. Inherited causes of AN\n\n\n\nControls:\n1. Pregnancy and lactating female\n2. Refusal of consent\n\n\n\nTable 1. Scale for acanthosis nigricans (Adapted \nfrom Burke JP et al)1\n\n\n\nNeck severity\n\n\n\n0 Absent: not detectable on close inspection.\n\n\n\n1 Present: clearly present on close visual inspection, not visible to \nthe casual observer, extent not measurable \n\n\n\n2 Mild: limited to the base of the skull, does not extend to the \nlateral margins of the neck (usually <3 inches in breadth).\n\n\n\n3 Moderate: extending to the lateral margins of the neck \n(posterior border of the sternocleidomastoid) (usually 3\u20136 \ninches), should not be visible when the participant is viewed \nfrom the front\n\n\n\n4 Severe: extending anteriorly (>6 inches), visible when the \nparticipant is viewed from the front.\n\n\n\nAxilla\n\n\n\n0 Absent: not detectable on close inspection.\n\n\n\n1 Present: clearly present on close visual inspection, not visible to \nthe casual observer, extent not measurable \n\n\n\n2 Mild: localized to the central portion of the axilla, may have \ngone unnoticed by the participant.\n\n\n\n3 Moderate: involving the entire axillary fossa, but not visible \nwhen the arm is against the participant\u2019s side\n\n\n\n4 Severe: visible from front or back in the unclothed participant \nwhen the arm is against the participant\u2019s side.\n\n\n\nNeck texture\n\n\n\n0 Smooth to touch: no differentiation from normal skin to \npalpation.\n\n\n\n1 Rough to touch: clearly differentiated from normal skin.\n\n\n\n2 Coarseness can be observed visually, portions of the skin \nclearly raised above other Areas\n\n\n\n3 Extremely coarse: \u201chills and valleys\u201d observable on visual \nexamination.\n\n\n\nKnuckles \u2013 Present/ Absent\n\n\n\nElbows- Present/ Absent\n\n\n\nKnees- Present/ Absent\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n62 MJD 2023 June Vol 50\n\n\n\nThe Study Design \nSemi-structured questionnaire was used to collect \ninformation regarding sociodemographic profile, \nclinical history and investigative work-up. The \nstudy participants were subjected to thorough \nhistory taking and clinical examination. Age, \nsex, occupation, age of onset of AN, duration \nof AN, progression of AN, history of weight \ngain, history of drug intake for medical illness, \npast history of AN, medical history and family \nhistory of DM, hypertension, obesity, ischemic \nheart disease, family history of AN, history of \nsmoking, alcohol intake, physical activity and \ntreatment history were noted. \n\n\n\nComplete cutaneous and systemic examination \nwas done for each of the study participants. A \ndetailed cutaneous examination for site of AN, \ndistribution of AN (Nape of neck / axilla / Face \n{zygomatic / temporal / forehead / periorbital / \nperioral} / Knuckle / elbow / knee / groin) was \nnoted. The overall severity of AN, neck and \naxilla severity and neck texture severity was \nassessed using the Burke\u2019s quantitative scale for \nacanthosis nigricans [Table 1].\n\n\n\nMeasurement of height, weight, body mass \nindex (BMI), waist circumference (WC) and \nblood pressure was done. BMI was calculated \nusing weight (Kg) and height (meters) of the \npatient in kg/m2. BMI grading was done as per \nthe WHO criteria7 as follows:\n\u2022\t Underweight - BMI under 18.5 kg/ m2\n\n\n\n\u2022\t Normal weight - BMI greater than or equal \nto 18.5 to 24.9 kg/ m2\n\n\n\n\u2022\t Overweight \u2013 BMI greater than or equal to \n25 to 29.9 kg/ m2\n\n\n\n\u2022\t Obesity \u2013 BMI greater than or equal to 30 \nkg/ m2\n\n\n\n      Obesity class I \u2013 BMI 30 to 34.9 kg/ m2\n\n\n\n      Obesity class II \u2013 BMI 35 to 39.9 kg/ m2\n\n\n\n      Obesity class III \u2013 BMI greater than or equal    \n     to 40 kg/ m2\n\n\n\nWC was measured using a non-stretchable \nflexible tape in the horizontal position. It was \nmeasured by placing the measuring tapes snugly \naround the abdomen at the level of the iliac crest \nand measured in cm. \n\n\n\nFasting blood sugar and lipid profile \ninvestigations were done among the study \nparticipants at Clinical Biochemistry Laboratory \nof Hospital after 8 hours of overnight fasting \nand values of the corresponding reports were \nrecorded. Photographic evaluation of the lesions \nwere done with patient\u2019s consent.\n\n\n\nThe diagnosis of MS was based on the National \nCholesterol Education Program (NCEP) Adult \nTreatment Panel III criteria8 by the presence of \nthree or more of the following criteria.\n1. Central obesity: WC of \u2265102 cm in males \n\n\n\nand \u226588 cm in females are the cutoff points \nof abdominal girth.\n\n\n\n2. Hypertriglyceridemia: Triglyceride level \n\u2265150 mg/dl or specific medication.\n\n\n\n3. Low HDL cholesterol: \u226440 mg/dl in males \nand \u226450 mg/dl in females or specific \nmedication.\n\n\n\n4. Hypertension: Blood pressure \u2265130 mmHg \nsystolic or \u226585 mmHg diastolic or specific \nmedication.\n\n\n\n5. Fasting plasma glucose level \u2265100 mg/dl or \nspecific medication or previously diagnosed \ntype 2 diabetes mellitus.\n\n\n\nStatistic Analysis\nThe collected data was encoded and entered \nelectronically in the computer using Excel \nworksheet 2021 version. Statistical analysis \nwas done by using descriptive and inferential \nstatistics using chi-square test and Odd\u2019s Ratio. \nSoftware used in the analysis were SPSS 27.0 \nversion and GraphPad Prism 7.0 version and \np<0.05 is considered as level of significance.\n\n\n\nResults\nMajority number of cases and controls belonged \nto the age group of 26\u201335 years (40% and \n38.75%, respectively). The mean age of AN \ncases studied was 33.95\u00b110.90 years and in \ncontrols was 32.96\u00b111.01. In our study, females \noutnumbered males, about 58.75% of the cases \nwere females and 41.25% were males and, in \ncontrol group 57.5% were females and 42.5% \nwere males. \n\n\n\nWe found that most of cases (88.75%) and \ncontrols (98.75%) were from rural area. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 63\n\n\n\nMajority of the AN patients were students \n(35%). Mean age of onset of AN was found to \nbe 24.13\u00b1 6.18 (12-40 years). Majority cases \n(60%) had onset of AN between 21-30 years of \nage. In our study, the mean duration of AN was \n9.81 \u00b1 7.91 years. More than 50% of patients \nhad age of onset before 10 years. Progressive \nAN was seen in 80% cases. Medical illnesses \nlike hypertension, obesity, ischemic heart \ndisease (IHD) and hypothyroidism were more \nsignificantly found in cases than controls except \nfor diabetes mellitus [Table 2]. Family history \nof AN, IHD and obesity were found significant \nin cases than controls.  Almost 57% of cases \nand 40% of controls lacked physical activity \nimplying that AN was associated with sedentary \nlifestyle.\n\n\n\nIn our study, among the cases, 26.3 % had \nnormal BMI, 41.3% were pre-obese, and 32.5% \nwere obese. Among the controls, 33.8 % had \nnormal BMI, 43.8 % were pre-obese, and 20 % \nwere obese. The difference of BMI among the \ncases and control groups was not statistically \nsignificant (p = 0.15).\n\n\n\nThe predominant sites affected were neck \n\n\n\nin 100% of the cases (Fig.1), axilla in 83.75 \n% (Fig.2), face in 43.75 %. Other sites of \ninvolvement were knuckles (17.50 %), elbow \n(10%) and knee (5%). Commonest site of facial \nacanthosis nigricans (FAN) was frontal area \n(20 %) followed by temporal region (16.25%), \nPeriorbital area (10%) (Fig.3), zygomatic region \n(8.75%) and Perioral area (1.25%). \n\n\n\nIn our study, grade 3 and 4 neck severity were \nseen in 53.8% and 37.5% cases respectively. \nAlmost 50% of patients suffering from MS had \nneck severity of grade 3 and 4. (Fig.4)\n\n\n\nGrade 2, 3 and 4 axilla severity were seen in \n27.5%, 51.2%, 7.5% cases respectively, out of \nthese 30% had MS with grade 3 axilla severity \nfollowed 8.75% and 6.25% had MS with grade \n2 and grade 4 axilla severity respectively. Out of \n55% cases having MS, 35% patients had grade \n3 neck texture changes whereas 11.25% out of \n40% cases had grade 2 neck texture changes.\n\n\n\nAN was significantly associated with MS. \nThe prevalence of MS in cases (50%) was \nstatistically significant when compared to the \ncontrol group (27.5%) (p=0.003) [Table 3].\n\n\n\nFig 1. Acanthosis nigricans over neck\n\n\n\nTable 2. Distribution according to medical illness in two groups\n\n\n\nMedical illness Cases Controls \u03b1\u03d72-value p value\nDiabetes mellitus (DM) 13 (16.3%) 10 (12.5%) 0.36 0.54\nHypertension (HTN) 15 (18.8%) 7 (8.8%) 4.15 0.04\nObesity 20 (25.0%) 7 (8.8%) 9.07 0.002\nIschemic heart disease (IHD) 3 (3.8%) 0 (0.0%) 4.07 0.04\nHypothyroidism 3 (3.8%) 0 (0.0%) 4.07 0.04\nTotal 54 (67.5%) 24 (30.0%)\n\n\n\n\u03b1 \u03d72: Chi square test, p<0.05: Significant\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n64 MJD 2023 June Vol 50\n\n\n\nFig 2. Acanthosis nigricans of the axilla \n\n\n\nFig 3. Periorbital facial acanthosis nigricans\n\n\n\nWe observed that parameters like HTN, FBS, \nHDL levels, serum TG level as well as WC for \nfemales had a positive correlation in cases as \ncompared to the controls. However, WC for \nmales was not statistically significant between \ncases of AN and controls, as summarized in \n[Table 4]. \n\n\n\nThe above results signify that, patients of AN \nhad higher chances of developing metabolic \nsyndrome than normal population, so all of them \nshould be screened meticulously and treated for \nthe same simultaneously.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 65\n\n\n\nFig 4. Patient of AN having grade 4 neck and axilla severity\n\n\n\nTable 3. Metabolic Syndrome (MS) in two groups\n\n\n\nMetabolic Syndrome Cases Controls \u03d72-value\n\n\n\nPresent 40(50%) 22(27.5%)\n\n\n\n8.53\nP=0.003\n*OR=2.63               \n95% CI# - 1.36-5.09\n\n\n\nAbsent 40(50%) 58(72.5%)\n\n\n\nTotal 80(100%) 80(100%)\n\n\n\n*OR: Odds ratio, # CI: Confidence interval\n\n\n\nTable 4. Components of metabolic syndrome in two groups\n\n\n\nMetabolic Syndrome and it\u2019s components Cases Controls \u03d72-value p value\n\n\n\nMS 40(50%) 22(27.5%) 8.53 0.003\n\n\n\nHTN (\u2265130/85mm Hg) 25(31.25%) 11(13.75%) 7.02 0.008\n\n\n\nWC (>102cm for males) 18(54.55%) 11(32.35%) 3.36 0.06\n\n\n\nWC (>88cm for females) 34(72.34%) 20(43.48%) 7.95 0.004\n\n\n\nFBS (\u2265100mg/dl) 36(45%) 14(17.5%) 14.08 0.0002\n\n\n\nHDL for male (<40mg/dl) 21(63.64%) 12(35.29%) 5.38 0.020\n\n\n\nHDL for female (<50mg/dl) 14(29.79%) 6(13.04%) 3.86 0.049\n\n\n\nTG (\u2265150mg/dl) 37(46.3%) 13(16.3%) 16.76 0.0001\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n66 MJD 2023 June Vol 50\n\n\n\nDiscussion\nMean age of AN cases  in our study was of \n33.95\u00b110.90 years which was comparable to \nstudies carried out by  Shah et al10  with  32.4 \u00b1 9.8 \nyears and Prakash et al6 with  29.83\u00b18.44years \nrespectively.\n\n\n\nIn our study, females (58.75%) outnumbered \nmales (41.25 %) comparable to studies carried \nout by Prakash et al6, Shah et al10 and Puri N12 \nshowing female preponderance. Grandhe et al13 \nand Choudhary SV et al14 found no significant \ndifference in the prevalence of AN among \nmales and females. The higher prevalence of \nAN in female population might be attributed to \nthe fact that they are relatively more conscious \ncosmetically.\n\n\n\nIn our study the mean age of onset of AN was \nfound to be 24.13\u00b16.18 years(12-40 years) years. \nStudy done by Puri N12 reported the clustering \nof cases in the age group 11-40 years, which \nis comparable with our study which could \nbe due to the cosmetic disfigurement. In our \nstudy, the mean duration of AN was 9.81 \u00b1 7.91 \nyears, whereas Shah et al10 reported the mean \nduration to be 2.7 years which was less than \nfound in our study.\n\n\n\nIn our study HTN (p=0.04), obesity (p=0.002), \nIHD (p=0.04) and hypothyroidism (p=0.04) was \nfound significant in cases than controls except \nfor the DM (p=0.54). In our study family history \nof AN, IHD, obesity were found significant in \ncases than controls which was in accordance \nwith study conducted by Kamel et al9, Yadav \net al11, Nithun TM et al thus almost confirming \nthese associations.16\n\n\n\nIn our study, HTN was statistically significant \nin cases as compared to controls which was in \naccordance to study by Shah et al10 and Kamel \net al9  again could be due to a more stressful \nlifestyle. In contrast to our study, Prakash et al6 \nand Panda et al17 found  no association between \nAN and HTN. We found significant association \nbetween AN and WC in females but not in males \nwhich was in contrast to study  by Dassanayake \net al18 where WC in both male and female were \n\n\n\nfound statistically significant. In our study we \nfound females had more central obesity than \nmales because of hormonal changes, multiple \ngestations and sedentary lifestyle of the former.\n\n\n\nIn our study significant association was reported \nbetween AN and FBS analogous to study by \nShah et al10, Kamel et al.9\n\n\n\nWe found neck (100 %) was the commonest \nsite of acanthosis nigricans followed by axilla \n(83.8%), face (43.8%), knuckles (17.5%), \nelbows (10.0%), knees (5.0%) which was  \ncomparable to several other studies carried out \nby various authors [Table 5]. Commonest site of \nfacial AN was frontal area (forehead) followed \nby temporal region, periorbital area, zygomatic \nregion, perioral area in our study  similar to \nPanda et al17 and  Verma et al19. Acanthosis \nnigricans neck severity, axilla severity and neck \ntexture showed positive correlation with MS.\n\n\n\nWith respect to dyslipidemia in our study, \nwe found statistically significant association \nbetween AN and HDL, TG, TC but not with LDL \nand VLDL levels [Table 6]. AN was associated \nwith low HDL in both males and females cases. \nSimilar results were obtained by Shah et al10, \nPrakash et al6 and Kamel et al.9 In this study, the \nvalue of triglycerides in cases was statistically \nsignificant (46.3%) when compared to that of \ncontrols (16.3%). Similar results were seen in \nstudies conducted by Shah et al10 and Prakash \net al.6\n\n\n\nOur study showed that AN was associated with \nraised total cholesterol, similar to  study done \nby Kamel et al.9 The prevalence of MS in cases \n(50%) was statistically highly significant ( \nP< 0.01) when compared to the control group \n(27.5%). Similar results were seen in studies \nconducted by Prakash et al6, Shah et al10, Balaji \net al20 and Dassanayake et al.18\n\n\n\nLimitations\nAN cases were not investigated for serum \ninsulin level and hence association of AN with \ninsulin resistance was not studied. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 67\n\n\n\nTable 5. Comparing results of several other studies\n\n\n\nSites of AN\n\n\n\nStudies with number of patients in percentage (%)\n\n\n\nPresent study Kamel et al9 2013 Shah  et al10  2019 Prakash et al6 2020 Yadav et al11  2022\n\n\n\nNeck 100.0% 100.0% 100.0% 56.0% 88.0%\n\n\n\nAxilla 83.8% 76.7% 31.0% 5.0% 46.0%\n\n\n\nFace 43.8% - 21.0% 2.0% -\n\n\n\nKnuckles 17.5% 30.0% 3.0% - 14.0%\n\n\n\nElbows 10.0% 43.4% 5.0% - 7.0%\n\n\n\nKnees 5.0% 26.7% - - -\n\n\n\nTable 6. Dyslipidemia in cases and controls\nDyslipidemia Cases Controls \u03d72-value p value\n\n\n\nHDL<40mg/dl (male) 21 (63.6%) 12 (35.3%) 5.38 0.02\n\n\n\nHDL<50mg/dl (female) 14 (29.8%) 6 (13.0%) 3.86 0.049\n\n\n\nTG \u2265150 mg/dl 37 (46.3%) 13 (16.3%) 16.76 0.0001\n\n\n\nLDL \u2265100mg/dl 18 (22.5%) 11 (13.8%) 2.06 0.15\n\n\n\nVLDL\u226530mg/dl 14 (17.5%) 7 (8.8%) 2.68 0.10\n\n\n\nTC \u2265200mg/dl 19 (23.8%) 7 (8.8%) 6.61 0.010\n\n\n\nConclusion\nWe conclude that Acanthosis nigricans (AN) \nis associated with metabolic syndrome (MS). \nAN is associated with individual parameters \nof MS (HTN, WC, FBS, HDL, TG) We found \nassociation between the neck severity, axilla \nseverity and neck texture with MS. All the \npatients of AN should be routinely screened \nfor parameters of metabolic syndrome. Early \nscreening and intervention for metabolic \nsyndrome and its components will be beneficial, \nas it prevents future complications.\n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto be disclosed.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n1. Burke JP, Hale DE, Hazuda HP, Stern MP. A Quantitative \n\n\n\nScale of Acanthosis Nigricans. Diabetes Care \n1999;22:1655-9. \n\n\n\n2. Kobaissi HA, Weigensberg MJ, Ball GD, Cruz ML, Shaibi \nGQ, Goran MI. Relation between acanthosis nigricans \nand insulin sensitivity in overweight Hispanic children at \nrisk for type 2 diabetes. Diabetes Care 2004;27:1412-6. \n\n\n\n3. Kong AS, Williams RL, Smith M, Sussman AL, Skipper \nB, Hsi AC et al. Acanthosis nigricans and diabetes risk \nfactors: Prevalence in young persons seen in southwestern \nUS primary care practices. Ann Fam Med 2007;5:202-8. \n\n\n\n4. Stuart CA, Gilkison CR, Keenan BS, Nagamani M. \nHyperinsulinemia and Acanthosis Nigricans in African \nAmericans. J Natl Med Assoc 1997;89:523. \n\n\n\n5. Ramachandran A, Snehalatha C, Baskar AD, Mary \nS, Kumar CK, Selvam S et al. Temporal changes in \nprevalence of diabetes and impaired glucose tolerance \nassociated with lifestyle transition occurring in the rural \npopulation in India. Diabetologia 2004;47:860-5. \n\n\n\n6. Prakash N, Kishan K, Yadalla H, Belliappa PR. A \ndescriptive case-Control study of 100 patients of \nacanthosis nigricans and its utility to detect metabolic \nsyndrome. Clin Dermatology Rev 2020;4:17. \n\n\n\n7. WHO Expert Consultation. Appropriate body-mass index \nfor Asian populations and its implications for policy and \nintervention strategies. Lancet. 2004;363:157-63. \n\n\n\n8. Fulop T, Tessier D, Carpentier A. The metabolic syndrome. \nPathol Biol (Paris). 2006;54:375-86. \n\n\n\n9. Kamel AM, Hassan MA, Ibrahim MY. Relation between \nthe severity of acanthosis nigricans and metabolic \nsyndrome components. J Egypt Women\u02bcs Dermatologic \nSoc 2013;10:75-80. \n\n\n\n10. Shah NG, Khatu SS, Gokhale NR, More YE, Khismatrao \nD. Acanthosis nigricans: A cutaneous marker for metabolic \nsyndrome. Med J DY Patil Vidyapeeth 2019;12:16-21. \n\n\n\n11. Yadav PY, Swaroop MR, Mittamedi NR, Obeidullah \nSM, Kalra TK, Devendra SS. Clinicoepidemiological \nstudy of acanthosis nigricans in pre and primary school \nchildren and its association with body mass index, waist \ncircumference and insulin resistance. IP Indian J Clin Exp \nDermatol 2022;8:152-61. \n\n\n\n12. Puri N. A study of pathogenesis of Acanthosis nigricans \nand its clinical implications. Indian J Dermatol \n2011;56:678-83. \n\n\n\n13. Grandhe NP, Bhansali A, Dogra S, Kumar B. Acanthosis \nnigricans: Relation with type 2 diabetes mellitus, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n68 MJD 2023 June Vol 50\n\n\n\nanthropometric variables, and body mass in Indians. \nPostgrad Med J 2005;81:541-4. \n\n\n\n14. Choudhary SV, Saoji V, Singh A, Mane S. Acanthosis \nnigricans: a clinical marker of insulin resistance. Int J Res \nDermatology 2017;3:161-7. \n\n\n\n15. Shah VH, Rambhia KD, Mukhi JI, Singh RP. Clinico-\ninvestigative Study of Facial Acanthosis Nigricans. Indian \nDermatol Online J 2022;13:221-8. \n\n\n\n16. Nithun TM, Ranugha PS, Betkerur JB, Shastry V. \nAssociation Association of Acanthosis Nigricans and \nInsulin Resistance in Indian Children and Youth \u2013 A \nHOMA2-IR Based Cross-Sectional Study. Indian \nDermatol Online J 2019;10:272-8. \n\n\n\n17. Panda S, Das A, Lahiri K, Chatterjee M, Padhi T, Rathi S \net al. Facial acanthosis nigricans: A morphological marker \nof metabolic syndrome. Indian J Dermatol 2017;62:591-7.  \n\n\n\n18. Dassanayake AS, Kasturiratne A, Niriella MA, Kalubovila \nU, Rajindrajith S, De Silva AP et al. Prevalence of \nAcanthosis Nigricans in an urban population in Sri Lanka \nand its utility to detect metabolic syndrome. BMC Res \nNotes 2011;4:25. \n\n\n\n19. Verma S, Vasani R, Joshi R, Phiske M, Punjabi P, Toprani \nT. A descriptive study of facial acanthosis nigricans and \nits association with body mass index, waist circumference \nand insulin resistance using HOMA2 IR. Indian Dermatol \nOnline J 2016;7:498-503. \n\n\n\n20. Balaji C, Vindhya M, Gurukul S. Significance of \nacanthosis nigricans as marker for metabolic syndrome. \nWorld J Med Sci 2014;10:295-8. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 69\n\n\n\nCASE REPORT\n\n\n\nPerplexing Pigmentation in a Young Child: A Case Report of Juvenile \nSystemic Sclerosis\n\n\n\nSangeeta Galui1, MBBS, Pratiksha Sonkusale1, MD, Sumit Kar1, MD, Abhay Deshmukh2, MD (Pathology), \nAditya Ravindra Ambulkar1, MBBS\n\n\n\n1Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, \nSevagram, Wardha, Maharashtra, India\n2Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, \nIndia\n\n\n\nSummary\nJuvenile systemic sclerosis (JSSc) is an uncommon childhood disorder involving multiple systems \nthat leads to significant morbidity and potentially death.  It differs from adult disease in its clinical \npresentation and the limited form is seen in only very few children. The pattern of organ involvement \nis also different from the adult form. In 95% of the JSS patients, prognosis appears to be better with \na 5-yr survival. There is paucity of data in the literature regarding the standardised treatment of JSSc. \nSo, here we report a rare case of 5-yr-old girl who presented with features of JSSc. \n\n\n\nKey words: Juvenile, systemic sclerosis, methotrexate\n\n\n\nCorresponding Author \nDr Pratiksha Sonkusale\nDepartment of Dermatology, Venereology and Leprosy,\nMahatma Gandhi Institute of Medical Sciences, \nSevagram, Wardha, Maharashtra,\n442102 India.\nEmail: pratiksha.sonkusale@gmail.com\n\n\n\nIntroduction\nScleroderma is a group of diseases varying \nin severity that can affect any stage of life, \nalthough the clinical patterns of scleroderma \nin children varies from those in adulthood.1 \n\n\n\nLocalized scleroderma is predominantly \nseen in childhood.2 The juvenile systemic \nsclerosis (JSSc) form of scleroderma is an \nuncommon entity and has more serious, \npotentially life-threatening morbidity than \nthe other sclerotic disorders. The estimated \nratio of linear scleroderma to JSSc is at least \n10:1 in paediatric age group.3-4 A female \npredominance has been found in more than \n75% patients of juvenile systemic sclerosis \nand disease appears to active before \npuberty. 5\n\n\n\nCase Report\nA 5-year-old female child, born out of non-\nconsanguineous marriage, delivered at \nterm normally with an uneventful antenatal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n70 MJD 2023 June Vol 50\n\n\n\nhistory came with complaints of discoloration \nof face, upper limbs, trunk and lower limb \nwith tightness of skin [Figure 1] for 3 years. \nThe symptoms first started with bilateral hands \nand face and gradually progressed to involve \nbilateral arms, neck, upper chest, bilateral \nfeet, legs up to knee joint. [Figure 2] She had \ndyspnoea on exertion, early fatiguability and \ndifficulty in swallowing of both solid and liquid \nfood. She also had history of weight loss. There \nwas no history of dyspepsia, or Raynaud\u2019s \nphenomenon. Past and family histories were \nnon-contributory.\n\n\n\nClinical examination revealed a thin built child \nwho was below 3rd percentile for weight, and \nbelow 3rd percentile for height, with a pulse \nrate of 88 bpm, respiratory rate 20/min and \nblood pressure of 90/60 mm Hg. She was pale. \nGeneral and systemic examination revealed \nnormal chest expansion. Musculoskeletal \nsystem revealed generalized wasting of \nmuscles. Cutaneous examination showed \nhidebound skin in hands, forearms and legs. \nSalt- and-pepper dyspigmentation were noted \n\n\n\nover face, bilateral hands, legs, and feet. Facial \nfolds were normal. Few telangiectasias were \npresent over face. Partial flexion at proximal \nand distal interphalangeal joints of fingers with \nsclerodactyly was present. \n\n\n\nInvestigations revealed normochromic \nnormocytic anaemia. Serum electrolytes, liver \nfunction test, renal function test, urine analysis, \nChest X-ray and ECG were within normal \nlimit. 2-D ECHO revealed no abnormality. \nESR was raised. Serology revealed raised ANA \nlevels, anti-dsDNA levels were within normal \nlimit. Skin biopsy features were consistent \nwith scleroderma. [Figure 3] Due to lack of \nfacility anti-centromere and anti-topoisomerase \nantibodies, lung function test was not done. \n\n\n\nPatient was started on oral Methotrexate at a \ndose of 10 mg/m2 per week,6 oral prednisolone \n1mg/kg and topical tacrolimus 0.1 percent local \napplication in rotation over tightened skin. \nPatient showed improvement of symptoms in \none week and later was lost to follow up. \n\n\n\nFigure 1. Skin pinch test: Inability to pinch skin due to tightness of skin\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 71\n\n\n\nFigure 2. Salt and pepper dyspigmentation present over forehead, neck, upper chest and bilateral arms extending \nup to knee joint bilaterally, flexion deformity at inter-phalangeal joints of both hands showing clawing\n\n\n\nDiscussion\nJSSc is a rare connective tissue disorder of \nunknown etiology. Though, it resembles adult \nprogressive systemic sclerosis (PSS), it still has \na number of distinguishing features.7-8 Similar \nto the adult counterpart, there is Raynaud\u2019s \nphenomenon (90-95%), diffuse involvement of \nskin and micro vasculopathy which can lead to \nprogressive dysfunction of the esophagus, heart, \nlungs and kidney.5 Our patient presented with \ncutaneous features of PSS.\n\n\n\nThe  criteria for diagnosing JSSc in a patient of less \n\n\n\nthan sixteen years of age as given by Paediatric \nRheumatology European Society (PRES), the \nAmerican College of Rheumatology (ACR), \nand the European Alliance of Associations \nfor Rheumatology depending on clinical \nmanifestations and laboratory parameters \nincludes one major criterion [induration of skin/\nsclerosis] and two minor criteria indicating \ninvolvement of various organ systems e.g. \ncardiac (arrythmias, heart failures), pulmonary \n(pulmonary hypertension, pulmonary fibrosis), \ngastrointestinal (dysphagia, gastroesophageal \nreflux), vascular (Raynaud phenomenon, digital \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n72 MJD 2023 June Vol 50\n\n\n\ntip ulcers, nail fold capillary abnormality), renal \n(renal crisis, new onset arterial hypertension), \nneurological (carpal tunnel syndrome, \nneuropathy), musculoskeletal (arthritis, \nmyositis, tendon friction rubs) and serological \n(anti-nuclear antibodies, SSc selective auto \nantibodies).9\n\n\n\nThe pathogenesis of the disease involves an \ninterplay of wide range of factors. Increased \nactivity of Endothelin-1, intercellular adhesion \nmolecule-1 (ICAM-1) along with increased \nproduction of profibrotic cytokine growth \n\n\n\nfactors (IL-4, IL-6,IL-8, IL-8, IL-10, IL-13, IL-\n17, TGF-alpha) lead to increased myofibroblast \nactivity and production of extracellular \nmatrix leading to structurally normal collagen \ndeposition.10-15 Association has also been \nfound with auto-antibodies, which includes \ntopoisomerase I,16 centromere antigens,16 \nfibrillarin, ribonucleic acid (RNA) polymerase, \nPM-Scl, and fibrillin-1,17 as well as RNA I, \nII, and III. A small cohort study found HLA \nDRB1*10, to be associated in 10.5 percent of \npatients with JSSc in contrast to 1.5 percent of \ncontrols.18\n\n\n\nFigure 3. Section showing thickened collagen bundles in the dermis (red arrow) and extension of \nsclerosis into the underlying subcutaneous fat (blue arrow) (H&E, x100). Section showing mild \nperivascular and periadnexal lymphoplasmacytic infiltrate in the dermis (red arrow) (H&E, x400).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 73\n\n\n\nSkin biopsies taken from patients diagnosed \nwith scleroderma portrays various histologic \nchanges in dermal microvasculature which \nincludes, thickened collagen bundles, swelling \nof endothelium, concentric thickening of \nvascular basement membrane.19\n\n\n\nPulmonary involvement, may present with \ndyspnoea and cough or patient may remain \nasymptomatic. Rahman et al5 reported a \nrestrictive pattern of lung disease. Our patient \nhad complaints of dyspnoea on exertion.\n\n\n\nThe most important cause of gastrointestinal \nmorbidity in children with JSSc is esophageal \ndysfunction.20 Only half of the affected patients \nhave complaints of dysphagia, our patient too \nhad dysphagia. Bodemer et al.4 have reported \nthat in systemic sclerosis involving paediatric \npopulation cardiac abnormalities such as left or \nbiventricular failure, pericarditis or arrhythmias \nare common, but no such complaints were there \nin our patient.\n\n\n\nAbout 40-60% patients show renal involvement \nin the form of proteinuria, azotaemia and \nmalignant hypertension. It usually affects \nwithin the first three years of PSS and indicates \na guarded prognosis.20 In a study of 135 children \nby Foeldvari et al.21 mortality related to renal \ncrisis was seen in only one patient.21 Renal \ncrisis prevalence is found to be less (4%) in \nJSSc than in adults.22 Mortality related to renal \ncrisis has markedly reduced with the usage of \nangiotensin converting enzyme inhibitors.23 \nOur patients did not have so far developed any \nclinical or laboratory abnormalities suggestive \nof renal dysfunction. In 70% to 90% of patient, \nantinuclear antibodies have been reported.5 Our \npatient showed a significantly raised titre for \nANA.\n\n\n\nThere is dearth of literature involving \nstandardized treatment for JSSc. Depending \non organ involved, general measures such \nas use of antacids and prokinetic drugs for \ngastroesophageal reflux, vasodilators to \nimpede Raynaud\u2019s phenomenon, for arthritis, \nnon-steroidal anti-inflammatory drugs, \nand physical activity are recommended.24 \n\n\n\nImmunosuppressants like methotrexate, \nmycophenolate mofetil have showed benefit in \nthe treatment of skin manifestations.  Myositis \nand arthritis have benefitted from use of \ncorticosterioids.25\n\n\n\nThe patient\u2019s family were counseled about the \ndisorder and its slow progression. Progressive \nvisceral disease in childhood scleroderma is \ndifficult to predict and prognosis is dependent \non multi-system involvement.26 Most patients \nsuffering from juvenile systemic sclerosis have \nbeen found to have a successful outcome and \na significant improvement in survival rate in \ncontrast to their adult counterparts as reported \nby Foeldvari et al.3\n\n\n\nConclusion\nThe prevalence of JSSc is low. At times, \nincidence of cases is often sporadic, even at \nthe level of tertiary care. The beginning of \nthe disease may be indicated by Raynaud\u2019s \nphenomenon. The major adjuvant in the \ndiagnosis is capillaroscopy, as determination \nof autoantibodies may not offer sensitive and \nspecific markers. The most common clinical \nfeatures are skin and vascular manifestations, \nwhile internal organ involvement is rare to be \nfound. The most frequent visceral involvement \nis cardiopulmonary disease which can lead to \nsignificant morbidity, and potentially death. Due \nto the rare occurrence of systemic scleroderma \nin children, we are reporting our case with the \npossibility of achieving good results with early \ntreatment initiation.\n\n\n\nConflict of Interest Declaration\nAll authors have no financial/conflict of interest \nto be disclosed.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n1. Denton CP, Derrett-Smith EC. Juvenile-onset systemic \n\n\n\nsclerosis: children are not small adults. Rheumatology \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n74 MJD 2023 June Vol 50\n\n\n\n(Oxford) 2009;48:96-7.\n2. Misra R, Singh G, Aggarwal P, Aggarwal A. Juvenile onset \n\n\n\nsystemic sclerosis: a single center experience of 23 cases \nfrom Asia. Clin Rheumatol 2007;26:1259-62.\n\n\n\n3. Foeldvari I. Scleroderma in children. Curr Opin Rheumatol \n2002;14:699-703. \n\n\n\n4. Bodemer C, Belon M, Hamel-Teillac D, Amoric JC, Fraitag \nS, Prieur AM et al. Scleroderma in children: a retrospective \nstudy of 70 cases. Ann Dermatol Venereol 1999;126:691-4.\n\n\n\n5. Rahman AS, Uddin MB. Juvenile Systemic Sclerosis-A \nCase Report. TAJ 2016;29:70-2.\n\n\n\n6. Niehues T, Lankisch P. Recommendations for the use of \nmethotrexate in juvenile idiopathic arthritis. Paediatr \nDrugs 2006;8:347-56.\n\n\n\n7. Vancheeswaran R, Black CM, David J, Hasson N, Harper \nJ, Atherton D et al. Childhood\u2010onset scleroderma: is \nit different from adult\u2010onset disease? Arthritis Rheum \n1996;39:1041-9.\n\n\n\n8. Blaszczyk M, Janniger CK, Jablonska S. Childhood \nscleroderma and its peculiarities. Cutis 1996;58:141-4, \n148-52.\n\n\n\n9. Zulian F, Woo P, Athreya BH, Laxer RM, Medsger TA Jr, \nLehman TJ et al. The Pediatric Rheumatology European \nSociety/American College of Rheumatology/European \nLeague against Rheumatism provisional classification \ncriteria for juvenile systemic sclerosis. Arthritis Rheum \n2007;57:203-12. \n\n\n\n10. Black CM. 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Serum concentrations of the CXC \nchemokines interleukin 8 and growth-regulated oncogene-\nalpha are elevated in patients with systemic sclerosis. J \nRheumatol 2003;30:1524-8. \n\n\n\n15. Kurasawa K, Hirose K, Sano H, Endo H, Shinkai H, Nawata \nY et al. Increased interleukin-17 production in patients \nwith systemic sclerosis. Arthritis Rheum 2000;43:2455-63.\n\n\n\n16. Reveille JD, Solomon DH, American College of \nRheumatology Ad Hoc Committee of Immunologic \nTesting Guidelines. Evidence-based guidelines for the \nuse of immunologic tests: anticentromere, Scl-70, and \nnucleolar antibodies. Arthritis Rheum 2003;49:399-412.\n\n\n\n17. Tan FK, Arnett FC, Antohi S, Saito S, Mirarchi A, Spiera H et \nal. Autoantibodies to the extracellular matrix microfibrillar \nprotein, fibrillin-1, in patients with scleroderma and other \nconnective tissue diseases. J Immunol 1999;163:1066-72.\n\n\n\n18. Stevens AM, Kanaan SB, Torok KS, Medsger TA, Mayes \nMD, Reveille JD et al. Brief Report: HLA-DRB1, DQA1, \nand DQB1 in Juvenile-Onset Systemic Sclerosis. Arthritis \nRheumatol 2016;68:2772-7. \n\n\n\n19. Fleischmajer R, Perlish JS, Reeves JR. Cellular infiltrates \nin scleroderma skin. Arthritis Rheum 1977;20:975-84.\n\n\n\n20. Singsen BH. Scleroderma in childhood. Pediatr Clin North \nAm 1986;33:1119-39.\n\n\n\n21. Foeldvari I, Zhavania M, Birdi N, Cuttica RJ, De Oliveira \nSH, Dent PB et al. Favourable outcome in 135 children \nwith juvenile systemic sclerosis: results of a multi\u2010national \nsurvey. Rheumatology (Oxford) 2000;39:556-9.\n\n\n\n22. Scalapino K, Arkachaisri T, Lucas M, Fertig N, Helfrich \nDJ, Londino AV Jr et al. Childhood onset systemic \nsclerosis: classification, clinical and serologic features, \nand survival in comparison with adult onset disease. J \nRheumatol 2006;33:1004-13.\n\n\n\n23. Steen VD, Medsger Jr TA. Long-term outcomes of \nscleroderma renal crisis. Ann Intern Med 2000;133:600-3.\n\n\n\n24. Torok KS. Pediatric scleroderma: systemic or localized \nforms. Pediatr Clin North Am 2012;59:381-405. \n\n\n\n25. Bagri NK, Raj D, Kaur J, Punia H, Saini I, Lodha R et al. \nJuvenile systemic sclerosis: experience from a tertiary care \ncenter from India. Rheumatol Int 2017;37:1687-91.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2023 June Vol 50 75\n\n\n\nACKNOWLEDGEMENT\nJune Issue 2023\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n\n\n\n2. Dr Agnes Heng Yoke Hui\n\n\n\n3. Dr Ch\u2019ng Chin Chwen\n\n\n\n4. Dr Chan Lee Chin\n\n\n\n5. Dr Chang Choong Chor\n\n\n\n6. Dr Chong Yew Thong\n\n\n\n7. Dr Henry Foong Boon Bee\n\n\n\n8. Dr Irene Lee Chew Kek\n\n\n\n9. Dr Kwan Zhenli\n\n\n\n10. Dr Lo Kang Shang Chit\n\n\n\n11. Dr Ng Ting Guan\n\n\n\n12. Dato\u2019 Dr Noor Zalmy Azizan\n\n\n\n13. Dr Rajalingam Ramalingam\n\n\n\n14. Dr Sharifah Rosniza Syed Nong Chek\n\n\n\n15. Dr Tang Jyh Jong\n\n\n\n\n\n\n\n\n\n"
"\n\n41MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nC L I N I C O PATHOLOGIC CHALLENGE\n\n\n\nA lady with prickly nodules on both lower limbs\nChoon SE, FRCP\n\n\n\nCorrespondence\nChoon Siew Eng FRCP\nDepartment of Dermatology,\nHospital Sultanah Aminah, Johor Bahru\nEmail: choonse@yahoo.co.uk\n\n\n\n49 year-old lady referred by nephrologist for\nincreasing number of skin nodules on both legs\nfor past 2 years. Systemic lupus erythematosus\nwith lupus nephritis was diagnosed 10 years ago\nwhen she presented with Ray n a u l d \u2019s\nphenomenon, hair loss and nephrotic syndrome.\nPatient was treated initially with monthly pulses\nof IV cyclophosphamide and oral prednisolone\nranging between 30-10mg. Her renal function is\n\n\n\np r e s e rved with instituted treatment. On\npresentation, she was still on prednisolone 7.5mg,\nmycophenolate mofetil 500mg bd and telmisartan\nfor hypertension which she developed 5 years\nago.  Physical examination revealed non-tender,\nwoody-hard induration of both legs with\nunderlying firm, sharply angulated papules and\nnodules (Fig 1).\n\n\n\nFigure 1  A & B show induration of both legs with smooth shiny,\nhide-bound skin.\n\n\n\nB\n\n\n\nA\n\n\n\n\n\n\n\n\n42 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nFig. 2 shows epidermal atrophy with loss of rete pegs, atrophic eccrine glands, haphazardly arranged\nthickened collagen, scanty inflammatory infiltrates and calcium deposits in dermis and subcutis. 2A\nshows close-up of calcinosis cutis, 2B shows abnormal thick, homogenous and haphazardly-arranged\ncollagen fibre.\n\n\n\nWhat is your diagnosis?\n\n\n\nHistologic features are shown Fig 2.\n\n\n\nA B\n\n\n\n\n\n\n\n\n43MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nContact and Occupational Derm a t i t i s\nfor Beginners\n\n\n\nContinuous Professional Development - CME\n\n\n\nOrganizers Dermatology, Selayang Hospital\n\n\n\nVenue Auditorium, Selayang Hospital\n\n\n\nDate 10-11 May 2012\n\n\n\nEmail raoulsibert@gmail.com\n\n\n\nPhototherapy Course\n\n\n\nOrganizers Kuala Lumpur Hospital\n\n\n\nVenue Auditorium Kuala Lumpur Hospital\n\n\n\nDate 24-25 May 2012\n\n\n\nEmail tingguanng@hotmail.com\n\n\n\nPaediatrics Dermatology Update 2012\n\n\n\nOrganizers Dermatology, Sarawak General Hospital\n\n\n\nVenue Pullman Hotel, Kuching\n\n\n\nDate 26 May 2012\n\n\n\nEmail mmaswk@gmail.com\n\n\n\nMs Doroty Tan\n\n\n\n\n\n\n\n\n44 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nD e rmatology Update 2012\n\n\n\nContinuous Professional Development - CME\n\n\n\nOrganizers National Skin Centre\n\n\n\nVenue Mandarin Hotel, Singapore\n\n\n\nDate 11-13 May 2012\n\n\n\nProgram website www.nsc.gov.sg/dermupdate2012\n\n\n\n37th Annual General Meeting & \nMalaysian Dermatology Congre s s\n\n\n\nOrganizers Dermatological Society of Malaysia\n\n\n\nTheme Allergy and Occupational Dermatoses\n\n\n\nVenue Holiday Inn, Malacca\n\n\n\nDate 14-17 September 2012\n\n\n\nProgram website www.dermatology.org.my\n\n\n\n\n\n\n\n\n45MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAdvance Masters in Dermatology Graduates and Thesis\n\n\n\nGRADUATES (DR.)\n\n\n\nADAWIYAH BINTI JAMIL\n\n\n\nAZURA AFANDI\n\n\n\nCHANG CHOONG CHOR\n\n\n\nCHONG YEW THONG\n\n\n\nFELIX YAP BOON BIN\n\n\n\nKARTINI FARAH ABD.\nRAHIM\n\n\n\nLEE CHEW KEK\n\n\n\nLEE YIN YIN\n\n\n\nMAZLIN BASERI\n\n\n\nNG TING GUAN\n\n\n\nTHESIS\n\n\n\nThe effect of smoking cessation on severity of psoriasis \n\n\n\nDevelopment of a computerized objective assessment of area\nand erythema for PASI scoring of severity of psoriasis and\ncomparing with the conventional visual assessment of PASI by\ndermatologist\n\n\n\nHuman leukocyte antigen (HLA) in toxic epidermal necrolysis\n(TEN) and Stevens Johnson Syndrome\n\n\n\nComparison of two dosing regimens for administering oral\nmethotraxate in patients with moderate to severe plaque\npsoriasis (the Co-tromp study)\n\n\n\nAcne vulgaris: Quality of life and cost of illness in\ngovernment dermatology clinics in Sarawak\n\n\n\nNarrowband UVB phototherapy: Comparison of two starting\ndoses using 50%MED and skin phototype\n\n\n\nFingerprint biometrics changes in hand dermatitis\n\n\n\nAssessment of skin phototype, skin colour and minimal\nerythema dose (MED) to ultravioliet B (UVB) radiation in the\nmultiethnic Malaysian population\n\n\n\nImpact of systemic glucocorticoids on\nbone mineral density in patients with pemphigus\n\n\n\nThe efficacy and safety of tacrolimus ointment in patients\nwith moderate to severe atopic eczema\n\n\n\n\n\n\n\n\n46 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nGRADUATES (DR.)\n\n\n\nNORASHIKIN SHAMSUDIN\n\n\n\nNOORLAILY MOHD NOOR\n\n\n\nNOOR ZALMY AZIZAN\n\n\n\nPENNY LIM POH LU\n\n\n\nPRIYA GILL\n\n\n\nTANG JYH JONG\n\n\n\nTANG MIN MOON\n\n\n\nTARITA BINTI TAIB\n\n\n\nWONG SU-MING\n\n\n\nTHESIS\n\n\n\nEfficacy anf safety of tacrolimus ointment in vitiligo using\nboth an objective and subjective method for the evaluation of\nrepigmentation progression\n\n\n\nComparison of transepidermal water loss (TEWL) between\nnormal and erythrodermic patients of various aetiology\n\n\n\nSignificance of toe web microbiology in the aetiology of\nrecurrent cellulitis of the lower leg - a pilot study\n\n\n\nComparative study of the efficacy of benzyl benzoate and\npermethrin in the treatment of scabies\n\n\n\nCardiac abnormalities in Psoriasis\n\n\n\nAntibiotic sensitivity of propionibacterium acnes isolated from\npatients with acne vulgaris in Kuala Lumpur Hospital,\nMalaysia\n\n\n\nQuality of life and cost of illness in patients with psoriasis in\nMalaysia: A multicentre study\n\n\n\nAssessment of cutaneous and systemic manifestations of\npatients with lupus erythematosus (LE) using clinical scoring\nindices\n\n\n\nEfficacy and safety of sodium hypochlorite (bleach) baths in\npatients with moderate to severe atopic dermatitis\n\n\n\n\n\n\n\n\n47MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nAesthetic Medical Practice Guidelines \nfor Medical Specialists\n\n\n\n1. PREREQUISITES FOR MEDICAL SPECIALISTS PERFORMING \nAESTHETIC MEDICAL PROCEDURES\n\n\n\n1.1 A medical practitioner who wishes to perform aesthetic/cosmetic medical procedures must be fully\nregistered with the Malaysian Medical Council.\n\n\n\n1.2 He/she must possess a current and valid Annual Practicing Certificate.\n\n\n\n1.3 He/she is required to possess a higher qualification in dermatology with full dermatological training; or\nalternatively, is registered on the National Specialist Register in a medical related field in order to be\nregarded as medical Specialist.\n\n\n\n1.4 He/she must possess experience through recognised practical training courses conducted by bona-\nfide professional bodies specialising in aesthetic medical practice.\n\n\n\n1.5 He/she must exercise strict patient selection criteria, must communicate to the potential client/patient the\nrisks involved, the possible outcome, obtain valid consent for the aesthetic medical procedure planned, and\ngenerally observe all aspects of the Code of Professional Conduct of the Malaysian Medical Council.\n\n\n\n1.6 He/she must place client/patient safety as the primary concern and should provide aesthetic medical\nservices in a healthcare facility licensed or registered  under the Private Healthcare Facilities and Services\nAct 1998 and regulations 2006.\n\n\n\n1.7 He/she is required to obtain a Letter of Credentialing and Privileging (LCP) for the aesthetic/cosmetic\nmedical procedure(s) which he/she intends to perform. The LCP shall be issued by the Cosmetic\nDermatology and Laser Medicine (CDLM) Board under the Dermatological Society, Malaysia, Academy\nof Medicine, Malaysia.\n\n\n\n1.8 With the LCP, he/she is eligible for registration with the Registry of Aesthetic Medical Practice which shall\nbe maintained by the Medical Practice Division, Ministry of Health (MOH), Malaysia.\n\n\n\n2. SCOPE OF PRACTICE\n\n\n\nThe basic considerations for the scope of practice in aesthetic medical practice by medical specialists are\nwhether they are core medical specialists or non-core medical specialists (refer Table 1).\n\n\n\nA. Core Medical Specialists \nThis consists of dermatologists performing aesthetic/cosmetic surgery within their core curriculum and\ncore competency.\n\n\n\nThe core specialist society will submit a list of their specialists to the CDLM Board for inclusion in the\nNational Registry of Aesthetic Medical Practice.\n\n\n\nSpecialists may also apply directly to the CDLM Board.\n\n\n\nB. Non-Core Medical Specialists \nThis refers to medical specialists whose routine areas of practice are completely unrelated to dermatology e.g.\nanaesthetists, pathologists, radiologists etc.  \n\n\n\nThese specialists may be subjected to similar requirements for privileging of a general practitioner practising\naesthetic medical practice.\n\n\n\nIf possible they should be sanctioned by their own professional peers before application to the CDLM Board;\nalternatively they may apply directly to the Board with the necessary documentation. \n\n\n\n\n\n\n\n\n48 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPROCEDURES\n\n\n\nChemical peels\n(superficial)\n\n\n\nMicrodermabrasion\n\n\n\nIntense pulse light\n(IPL)\n\n\n\nChemical peel\n(medium)\n\n\n\nBotulinum toxin\ninjection\n\n\n\nFiller injection \n\n\n\nSclerotherapy\n\n\n\nLaser for treating\nskin pigmentation\n\n\n\nLaser for treating\nskin tumours\n\n\n\nLaser for skin\nrejuvenation\n(incl fractional)\n\n\n\nLaser for hair\nremoval\n(e.g long-pulsed\nNd-YAG, Diode)\n\n\n\nLaser for treating\nvascular lesions\n\n\n\nChemical peels\n(Deep)\n\n\n\nAblative skin\nresurfacing lasers\n\n\n\nHair transplant\n\n\n\nMechanical\ndermabrasion\n\n\n\nB. MINIMALLY INVASIVE\n\n\n\nCORE\nSPECIALISTS\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nNON-CORE\nSPECIALISTS\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nCase by case basis\n\n\n\nNA**\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nAPPROPRIATE\nPREMISES\nNEEDED\n\n\n\nClinic\n\n\n\nClinic\n\n\n\nClinic\n\n\n\nClinic\n\n\n\nClinic\n\n\n\nClinic\n\n\n\nOT/ Clinic\n\n\n\nOT/ Clinic\n\n\n\nOT/ Clinic\n\n\n\nClinic\n\n\n\nClinic\n\n\n\nOT/ Clinic\n\n\n\nOT/Clinic\n\n\n\nOT/ Clinic\n\n\n\nOT\n\n\n\nOT/ Clinic\n\n\n\nPROCEDURES\nPERFORMED FOR \n\n\n\nNON-CORE SPECIALISTS\n\n\n\n25\n\n\n\n20\n\n\n\n40\n\n\n\n25\n\n\n\n25\n\n\n\n25\n\n\n\n20\n\n\n\n20\n\n\n\n20\n\n\n\n20\n\n\n\n20\n\n\n\nA. NON INVASIVE\n\n\n\nC. INVASIVE\n\n\n\nTable 1 Scope of practice for Medical Specialists.\n\n\n\n\n\n\n\n\n49MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nPROCEDURES\n\n\n\nPhlebectomy\n\n\n\nPhotodynamic\ntherapy\n\n\n\nRadiofrequency\n\n\n\nUltrasound device\n\n\n\nTumescent\nliposuction\n\n\n\nCORE\nSPECIALISTS\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nDermatologists\n\n\n\nNON-CORE\nSPECIALISTS\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nNA\n\n\n\nAPPROPRIATE\nPREMISES\nNEEDED\n\n\n\nOT/Clinic\n\n\n\nOT/ Clinic\n\n\n\nOT/ Clinic\n\n\n\nOT/Clinic\n\n\n\nOT/ Clinic\n\n\n\nPROCEDURES\nPERFORMED FOR \n\n\n\nNON-CORE SPECIALISTS\n\n\n\nNote:\nThis list is subjected to be reviewed whenever there is new evidence-based treatment available.\n*OT = Operation theatre, **NA = Not applicable\n\n\n\n3. PROCESS OF REGISTRATION\n\n\n\n3.1 Medical specialists who intend to practise aesthetic medical practice are required to apply to the Cosmetic\nDermatology and Laser Medicine (CDLM) Board of the Dermatological Society Malaysia.\n\n\n\n3.2 The CDLM Board shall assess and/or examine medical specialists who intend to practice\naesthetic/cosmetic procedures. \n\n\n\n3.3 The CDLM Board will issue a Letter of Credentialing and Privileging (LCP) to the successful candidate,\nspecifying the core specialty, aesthetic/cosmetic procedure(s) approved, and duration of validity. The LCP\nis valid for 5 year and renewable upon endorsement by the CDLM Board.\n\n\n\n3.4 With the LCP, the medical specialists\u2019 names are eligible to be included in the National Registry of\nAesthetic Medical Practice. \n\n\n\n\n\n\n\n\n50 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\n4. THE CREDENTIALING AND PRIVILEGING COMMITTEE \n\n\n\nThe Cosmetic Dermatology and Laser Medicine (CDLM) Board of the Dermatological Society Malaysia will be\nthe credentialing and privileging committee for the medical specialists.\n\n\n\n5. THE SECRETARIAT FOR MEDICAL SPECIALISTS\n\n\n\nPersatuan Dermatologi Malaysia (PDM)\nRumah Dermatologi\n2-16-2,  Block 2 (Remis) Pantai Panorama Condominium\nJalan 112 H, off Jalan Kerinchi\n59200 Kuala Lumpur\n\n\n\nMedical Specialists\n\n\n\nNational Registry of Aesthetic\nMedical Practice\n\n\n\nNon-dermatologists\n\n\n\nApply to CDLM\n\n\n\nCase by case basis\n\n\n\nLCP issued by CDLM\n\n\n\nDermatologists\n\n\n\nApply to CDLM\n\n\n\nLCP issued by CDLM\n\n\n\nFigure 1 Process of registration for medical specialists.\n\n\n\n\n\n\n\n\n51MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nB O O K R E V I E W\n\n\n\nTextbook of Laser and Light Derm a t o l o g y\nin the Asian Skin\n\n\n\nEdited by Yong-Kwang Tay and Yuin Chew Chan\nPublished by World Scientific Publishing Co Pte 2011.  140 pp.\n\n\n\nI S B N - 1 3 : 9 7 8 - 9 8 1 4 3 3 8 8 6 8\n\n\n\nIt was a pleasure to review this well illustrated and informative textbook of laser and light dermatology.\nThis is the latest textbook of laser and light dermatology for Asian skin just released in 2011. It is written\nand edited by Tay Yong Kwang and Chan Yuin Chew along with a further 10 other contributors. The book\nhas 12 chapters and its contributors are all experienced dermatologists including Prof Goh Chee Leok,\nJoyce Lim, Chua SH and Melvin Ee from Singapore who gave practical pearls of wisdom and tips\ntreating darker skin phenotypes.\n\n\n\nThe book is divided into 12 chapters covering a comprehensive range of laser and light based devices.\nIt's only 140 pages, full of color images and is very readable. One of the outstanding features of the text\nis that it has numerous actual case presentations and the author would include the laser settings to be used\nin the treatment. Each chapter begins with an introduction giving the reader a general overview of the\ntopic followed by mechanism of action, patient selection and treatment procedure including the laser\nparameters, precautions and post operative care. In some chapters the chapter would end with clinical\ncase histories. The book include chapters on laser tissue interactions, CO2 laser, vascular, pigment, hair\nremoval, ablative resurfacing, non ablative resurfacing, fractional laser, IPL and photodynamic therapy.\n\n\n\nOf special interests are chapters on treatment of pigmented lesions, fractionated lasers, intense pulsed\nlight devices and photodynamic therapy in the Asian skin. Conditions unique to the Asian skin such as\nNevus of Ota, Hori\u2019s nevus, melasma, and post inflammatory hyperpigmentation were well covered in\nthe text.\n\n\n\nCurrently there are very few reference textbook of laser and light devices on Asian skin. The Textbook\nof Laser and Light Dermatology in the Asian Skin will serve as a valuable reference textbook and an\nessential companion for all dermatologists and medical practitioners managing patients of Asian descent\nwith laser and light based devices. The clinical information and the high-quality photographs will make\nthis color textbook an enduring addition to any personal or institutional medical library.\n\n\n\nHenry Foong Boon Bee FRCP (Edin)\nIpoh, Malaysia\n\n\n\n\n\n\n\n\n52 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDr. Sorya A. Aziz hailed from Johor Bahru where\nshe was the eldest in her fa m i ly. She completed her\nearly school years in Johor and completed her MCE at Sekolah\nSeri Puteri, Kuala Lumpur. She found her calling in Medicine and went on to do her\nMD at the Universiti Kebangsaan Malaysia (UKM) and subsequently her Masters in Internal Medicine\nat the  Universiti Sains Malaysia (USM). She served as a physician at Hospital Melaka for a few years\nbefore she pursued her dream to train in Dermatology. She joined the Department of Dermatology,\nHospital Kuala Lumpur in 1998 and completed her fellowship training in 2001. \n\n\n\nShe developed an interest in Infectious Dermatology and went on to subspecialise in this field at the\nUniversity of Amsterdam in 2003. She was involved in research projects involving Multiplex PCR in\nnon-tuberculous mycobacterium. She returned to Malaysia in 2004 and headed the Infectious Disease\nSpecialised Service in the Department of Dermatology, Hospital Kuala Lumpur.\n\n\n\nUnfortunately, her health declined gradually and she was diagnosed with end stage renal failure in 2006\nand commenced on renal replacement therapy. Despite all this, Sorya remained in high spirits and\ncontinued to work full-time as a Dermatologist which was commendable. She was transferred as the\nHead, Department of Dermatology, Hospital Sultan Ismail, Johor Bahru in 2008 where she served until\nher untimely demise in 2011.\n\n\n\nSorya will be remembered by all who knew her as exemplary and dedicated Dermatologist with immense\npatience and courage. More importantly, she was a true friend and great listener who was with us through\nthick and thin. In her unassuming ways, she was an astute diagnostician in our department.  She was a\nmentor not only to her juniors but also to her colleagues.\n\n\n\nSorya will also be remembered as a fun-loving person who was in high spirits until the end. She remained\noptimistic despite all the hurdles that came her way. We are sure that Sorya would like us to celebrate her\nlife as she lived it.\n\n\n\nTo a great Dermatologist, a superb teacher,\na true friend and a wonderful person.\n\n\n\nWe miss you\u2026.\nAl- fatihah \nSemoga Allah mencucuri rahmat ke atas rohnya \n\u201cMay her soul rest in eternal peace\u201d \n\n\n\nAsmah Johar, Suganthi Thevarajah, Dawn Ambrose, Noor Zalmy Azizan\n\n\n\nT R U E G R I T\nDR. SORYA A. AZIZ (1958-2011)\n\n\n\n\n\n\n\n\n53MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nANSWER TO CLINICOPATHOLOGIC CHALLENGE\n\n\n\n49 year-old lady referred by nephrologist for increasing number of skin nodules on both legs for past 2\nyears. Systemic lupus erythematosus with lupus nephritis was diagnosed 10 years ago when she\npresented with Raynauld\u2019s phenomenon, hair loss and nephrotic syndrome. Patient was treated initially\nwith monthly pulses of IV cyclophosphamide and oral prednisolone ranging between 30-10mg. Her renal\nfunction is preserved with instituted treatment. On presentation, she was still on prednisolone 7.5mg,\nmycophenolate mofetil 500mg bd and telmisartan for hypertension which she developed 5 years ago. On\nfurther questioning, patient did notice progressive hardening of both legs for 2 years but attributed it to\npast cellulitis in 2008. Hence, she only consulted her nephrologist when prickly lesions on thighs caused\ndiscomfort. She has no associated ulceration or discharge. She still has Raynauld\u2019s phenomenon but did\nnot have difficulty in swallowing, thickening of facial skin or skin on her upper limbs. Fig 3 Biopsy of\na lesion on her right calf showed atrophy of skin with loss of rete pegs, thickened collagen in haphazard\narrangement and subcutaneous calcinosis\n\n\n\nFigure 3  shows calcinosis in the subcutaneous tissue.\n\n\n\n\n\n\n\n\n54 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nFigure 4  A & B show diffuse fluffy calcinosis affecting soft tissues of both lower limbs.\n\n\n\n\n\n\n\n\n55MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThe detached subcutaneous tissue (Fig. 4) also\nshowed obvious calcification. Hence, patient\u2019s\nchief complaint was due to calcinosis cutis.\nCalcification of the skin and subcutaneous tissue\nis known to occur in a variety of disorders and\nm ay be classified as dystrophic, metastatic,\nidiopathic or iatrogenic calcification, and\ncalciphylaxis1. Dystrophic calcification appears\nas a result of local tissue damage in patients with\nn o rmal serum calcium and phosphate leve l s .\nMetastatic calcification is characterized by an\nabnormal calcium and/or phosphate metabolism,\nleading to the precipitation of calcium in\ncutaneous and subcutaneous tissues. Idiopathic\nc a l c i fication occurs without any underly i n g\ntissue damage or metabolic disorder. Iatrogenic\ncalcinosis cutis is a side effect of therapy\nreported after IV calcium gluconate infusion.\nC a l c i p hylaxis is defined as small-ve s s e l\ncalcification mainly affecting blood vessels of the\nd e rmis or subcutaneous fat. There may be\ndisturbed calcium and phosphate metabolism and\nhy p e rp a r a t hyroidism. This potentially fa t a l\nsyndrome predominantly occurs in patients with\nend-stage renal disease.\n\n\n\nBlood investigations including full blood count,\nrenal function tests, muscle enzymes, seru m\ncalcium and phosphate were unremarkabl e .\nHence, patient has dystrophic calcinosis cutis.\nWidespread fluffy opacities affecting both legs\nand thighs were seen on radiography (Fig.5).\nDystrophic calcinosis cutis is the most common\ntype of cutaneous calcification. T h e\nectopic calcified mass typically consists\nof hy d r oxyapatite and amorp h o u s\ncalciumphosphate1. The pathophysiology of the\ndisorder is still unclear although it has been\nsuggested that phosphate-bound denatured\nproteins of necrotic cells serve as a nidus for\nectopic calcification, and that alterations in\ncollagen, elastin and subcutaneous fat promote\nthe calcification process. Histopatholog i c a l ly,\ncalcium deposits stain dark blue with\nhematoxyline and eosin stain and black with von\nKossa stain. Fine granules of calcium are usually\nseen in the dermis while large, irregular calcium\nmasses occur in the subcutaneous tissue. A\nforeign body reaction with inflammation and\nfibrosis may be seen around larger calcified\ndeposits.\n\n\n\nDystrophic calcification is associated with a\nvariety of disorders, including connective tissue\ndiseases, inherited disorders, cutaneous\nneoplasms and infections. Among the connective\ntissue dieases, calcinosis is most commonly seen\nin juvenile dermatomyosistis. Calcinosis cutis in\nsystemic lupus erythematosus (SLE) is rare and\nu s u a l ly asymptomatic. Calcinosis cutis is a\ncommon finding in systemic sclerosis (SS),\ne s p e c i a l ly in the limited cutaneous form of\nsystemic sclerosis (CREST syndrome)2 , 3.\nSubcutaneous or intracutaneous calcifi c a t i o n\noccurs in 25% to 40% of patients with limited\nsystemic sclerosis (LcSS), typically 10 years or\nmore after disease onset. Clinically, nodules and\nplaques of calcium deposits occur at sites of\nr e c u rrent microtrauma such as the forearm s ,\nelbows, or fingers. Ulceration of the overlying\nskin and discharge of chalky material may occur.\nD i ffuse and tumoral calcinosis is rare bu t\nreported in localised systemic sclerosis.\n\n\n\nSo does patient has SS, SLE or ovelap syndrome\nwith calcinosis cutis? Closer examination of\npatient\u2019s biopsy showed atrophy of epidermal\nlayer with loss of rete pegs and atrophic eccrine\nglands (Fig.2), haphazardly arranged thickened\ncollagen and scanty inflammatory infi l t r a t e s ,\ns u p p o rting a diagnosis of systemic sclerosis.\nSLE has much more inflammatory infiltrates\nwith immunog l o bulin deposition at the\ndermoepidermal junction and within small blood\nvessels whereas direct immunoflourescence\nstudies are usually nega t ive in SS. Indirect\nimmunofloresecence test showed positive ANA\nwith titre of 1:640 and a homog e n o u s ly\ndistributed speckled pattern in the nucleus which\nis characteristic of anti-centromere antibody4,5.\nEnzyme-linked immunoassay was negative for\ndouble-stranded DNA, anti-Smith, anti-RNP, anti\nSSA, anti-SSB, antiJo1 and anti-topoisomerase\n(anti-Scl 70). Anti-topoisomerase and anti-\ncentromere antibodies are the classic ANA found\nin systemic sclerosis4 , 5. T h ey are intrinsically\nspecific for SSC and rarely found in healthy\nindividual or patients with other connective tissue\ndisease. Anti-topoisomerase antibody is\nassociated with diffuse SS and predicts early\nincidence of interstitial lung disease, renal and\nheart involvement4,5. Anti-centromere antibody in\nSS patient is associated with limited cutaneous\ndisease\n\n\n\n\n\n\n\n\n56 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\ndisease, peripheral vascular damage, calcinosis\nand later onset of pulmonary hypertension. When\nanticentromere antibody is found in patients with\nR ay n a u l d \u2019s phenomenon, it predicts future\nd evelopment of localised cutaneous systemic\nsclerosis. Final diagnosis is limited cutaneous\nsystemic sclerosis with dystrophic calcification.\n\n\n\nThere is no recommended standard treatment for\ncalcinosis cutis6,7. Success had been reported with\nuse of warfarin, diltiazem, aluminium hydroxide,\nm i n o cycline, cefuroxime, laser therapy and\nexcision6,7.\n\n\n\nReferences\n\n\n\n1. Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis\ncutis: part I. Diagnostic pathway. J Am Acad Dermatol\n2011; 65(1):1-12.\n\n\n\n2. Katsumoto TR, W h i t field ML, Conolly MK. T h e\npathogenesis of systemic sclerosis. Annu. Rev. Pathol.\nMech. Dis 2011;6:509-37.\n\n\n\n3. Derk CT, Jimenez SA. Systemic sclerosis: current view\nof its pathogenesis. Autoimmunity Rev 2003;\n2:181-191.\n\n\n\n4. Czompoly T, Simon D, Czirjak L, Nemeth P. Anti-\ntopoisomerase 1 autoantibodies in systemic sclerosis.\nAutoimmunity Rev 2009;8:692-696.\n\n\n\nR\n\n\n\n5. Hamaguchi Y. Antibody profile in systemic sclerosis:\nPredictive value for clinical evaluation and prognosis. J\nDermatol 2010;37:42-53.\n\n\n\n6. Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis\ncutis: part II. Treatment options. J Am Acad Dermatol\n2011;65(1):15-22.\n\n\n\n7. L P Robertson, R W Marshall, P Hickling Treatment of\ncutaneous calcinosis in limited systemic sclerosis with\nminocyclineAnn Rheum Dis 2003;62:267-269.\n\n\n\n\n\n\n\n\n57MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nN O T E S\n\n\n\n\n\n\n\n\n58 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nN O T E S\n\n\n\n\n\n\n\n\n59MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nN O T E S\n\n\n\n\n\n\n\n\n60 MJD 2012 July Vol 28\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nN O T E S\n\n\n\n\n\n\n\n\nContents\nGENERAL DERMATOLOGY\n\n\n\n Original Article\n\n\n\n1 Antibiotic sensitivity of propionibacterium \n acnes isolated from patients with acne \n vulgaris in Hospital Kuala Lumpur, \n Malaysia\n Tang JJ, Heng A, Chan LC et al\n\n\n\n9 Comparison of the efficacy and safety of \n Sungai Buloh Augmented Multiple Drug \n Therapy (SBA-MDT) and the World \n Health Organisation Multiple Drug \n Therapy (WHO-MDT) in the Treatment\n of Leprosy in Malaysia\n Felix BB Yap, Chang CC, Asmah J et al\n\n\n\n Case Report\n\n\n\n18 Disseminated fusariosis in a patient with \n acute lymphoblastic leukaemia: A case \n report and literature review\n Tang Jyh Jong\n\n\n\n22 Asymptomatic infant with high titre of \n immunoglobulin M Mycobacterium Leprae \n antibody whose mother has Morbus \n borderline lepromatous leprosy\n Wahyu Lestari, Sri Lestari, Qaira Anum et al\n\n\n\nPAEDIATRIC DERMATOLOGY\n\n\n\n Case Report\n\n\n\n27 Cutis marmorata telangiectatica congenita\n Sabeera BKI. Mardziah A\n\n\n\n30 Neonatal lupus erythematosus presenting\n as multiple photosensitive annular plaques \n with skin atrophy\n Sabeera BKI. Mardziah A\n\n\n\nDERMATOLOGY THERAPEUTICS\n\n\n\n Original Article\n\n\n\n34 Effect of oral or pulse cyclosphosphamide\n in recalcitrant pemphigus: an audit of \n eighteen patients from Hospital\n Kuala Lumpur\n Tang MM, Priya G, Suganthi T\n\n\n\nCLINICOPATHOLOGIC CHALLENGE\n\n\n\n41 A lady with prickly nodules on both lower \n limbs\n Choon SE, FRCP\n\n\n\nCONTINUOUS MEDICAL EDUCATION\n\n\n\n43 Contact & Occupational Dermatitis Update\n\n\n\n43 Phototherapy Course\n\n\n\n43 Paediatric Dermatology\n\n\n\n44 National Skin Centre Dermatology\n Update 2012\n\n\n\n44 Malaysian Dermatology Congress & AGM\n\n\n\n45 ADVANCE MASTERS IN\n DERMATOLOGY - THESIS\n\n\n\n47 Aesthetic Medical Practice \n Guidelines for Medical Specialists\n\n\n\n51 BOOK REVIEW\n\n\n\n52 TRUE GRIT - Sorya\n\n\n\n53 ANSWER TO CLINICOPATHOLOGIC \n CHALLENGE\n\n\n\n\n\n\n\n\n\n"
"\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 i\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence. Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: tanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in \nthe article. The article should be no more than 2-3 pages in \nlength.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Discussion, \nConclusion and References. A Structured Abstract of not \nmore than 250 words must be included. It should consist of \nfour paragraphs, labelled Background, Methods, Results and \nConclusion. It should describe the problem studies, how the \nstudy was performed, the main results, and what the author(s) \nconcluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to six \nauthors: if more than six authors, include the first six authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; \n(5) volume number; (6) first and final page numbers of the \narticle.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) \nreferred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine 2002. \np.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a delay \nto publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48ii\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\nREVIEW\n\n\n\nManagement of Ingrown Nails\nHaneke E\n\n\n\n2\n\n\n\n17\n\n\n\n25\n\n\n\n38\n\n\n\n48\n\n\n\n58\n\n\n\n66\n\n\n\n76\n\n\n\n80\n\n\n\n84\n\n\n\n87\n\n\n\nCASE REPORT \n\n\n\nCase Report of A Rare Case of Adult-Onset Multi-\nsite Lichen Striatus in An Adult\nSelvarajah SB, Wan Ahmad Kammal WSL, Jamil A\n\n\n\nDisseminated Cutaneous Sporotrichosis with Fungal \nSinusitis As An Initial Presentation of Underlying \nMyeloproliferative Neoplasm\nChang WH, Lee JWT, Gan SC, Ng TG \n\n\n\nA Unique Drug Rash: Bleomycin-induced Flagellate \nErythema in A Patient with Hodgkin Lymphoma\nTan SL, Mohd Joni NF, Mohd Affandi A\n\n\n\nNo Epidermis: Is it the drug, COVID-19 or \nSomething Else?\nTai V, Tee CT, Tang MM\n\n\n\nACKNOWLEDGEMENT\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Prospective Cohort Study of Laboratory \nAbnormalities During Isotretinoin Treatment For \nAcne Vulgaris\nRathakrishnan K, Tan LK, Syed Nong Chek SR, Zuraida \nCH, Low DE\n\n\n\nImpact of Psoriasis on Quality of Life of Family \nMembers and Its Association with Anxiety and \nDepression\nWong SB, Raja T, Teoh TY\n\n\n\nEvaluation of Knowledge, Disease Severity and \nQuality of Life of Patients with Psoriasis\nGan SP, Ahmad Latif A, Cheah HM, Ramalingam R\n\n\n\nThe Socio-demographic and Quality of Life of \nPeople Living with HIV (PLHIV) Presenting \nwith Cutaneous Manifestation: A Cross-Sectional \nStudy in the Department of Dermatology, Sarawak \nGeneral Hospital\nEe SL, Muniandy P\n\n\n\nDermatoses in Human Immunodeficiency Virus \nInfected Patients with A Focus on Infections: A \n12-month Cross-sectional Study in Hospital Sungai \nBuloh\nYahya ZA, Jamil A, Mohammed Noor NM\n\n\n\nClinical Characteristics of Anogenital Warts Among \nPatients Attending Genitourinary Medicine Clinic \nHospital Kuala Lumpur Between 2015 and 2020\nTan KS, Krishnasamy V, Thevarajah S, Tang MM\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 iii\n\n\n\nEditor-in-Chief\n\n\n\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm     \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm Wilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm Wilayah Persekutuan Kuala Lumpur   \n    \nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDermatological Society of Malaysia | Persatuan Dermatologi Malaysia\n\n\n\nExecutive Committee\nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPresident\nDr Sabeera Begum, MMed - Vice President\nDr Tan Wooi Chiang, Adv M Derm - Secretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDr Chan Lee Chin, MMed - Past President\nDr Tang Jyh Jong, Adv M Derm - Committee \nMember\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2022 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - Committee \nMember\nDr Nazirin Ariffin, MRCP - Committee Member\n\n\n\nDermatological Society of Malaysia \nMedical Academics of Malaysia, Unit 1.6, \nLevel 1, Enterprise 3B, Technology Park Ma-\nlaysia, Jalan Innovasi 1, Lebuhraya Puchong- \nSg Besi, Bukit Jalil, 57000 Kuala Lumpur, \nMalaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 482\n\n\n\nREVIEW\n\n\n\nManagement of Ingrown Nails\n\n\n\nEckart Haneke, MD, PhD\n\n\n\nDept Dermatol Inselspital, Univ Berne, Bern, Switzerland\nDermatol Practice Dermaticum, Freiburg, Germany\nCentro Dermatol Epidermis, Inst CUF, Matosinhos, Porto, Portugal\nDept Dermatol, Univ Hosp Ghent, Gent, Belgium\n\n\n\nAbstract\nIngrown nails mainly affect the great toes, much less frequently lesser toes and rarely fingers. There are many \nspeculations as to their etiology and pathogenesis; however, at the end, there is almost always a imbalance \nbetween too wide the nail plate and too narrow the (distal) nail bed. Ingrown nails occur at all age periods, \nfrom newborns to the over-100s though with different frequency, clinical characteristics, and management \noptions. In recent years, conservative treatment options \u2013 taping, packing, gutter, braces, and many more - were \ndeveloped avoiding the often disfiguring results of inadequate surgery. However, they require consistent and \nlong-term therapy. Surgery is either aimed at narrowing the wide nail plate or reducing the hypertrophic lateral \nnail folds. The number of operation methods is vast; already 150 ago, more 75 different surgical techniques had \nbeen known, and there is virtually a new one published every week. Despite ingrown nails being a matter of \nconcern for medical doctors since antique, new aspects continue to be detected, such as retronychia. Further, it \nwas found that orthopedic foot abnormalities are very frequently seen in association with ingrown nails. Their \ntreatment is often necessary to prevent recurrences.\n\n\n\nKey words: Ingrown nails; etiology; pathogenesis; conservative treatment; surgery; recurrence risk\n\n\n\nCorresponding Author\nProfessor Eckart Haneka\nSchlippehof 5, 79110 Freiburg, Germany\nEmail: haneke@gmx.net\n\n\n\nIntroduction\nIngrown nails belong to the frequent and painful \nconditions affecting predominantly youngsters \nin their most active physical phase. They may \nconsiderably decrease the quality of life and, \nin extreme cases, even cause suicide ideation. \nThey are typically chronic and the patients\u2019 and \nother lay persons\u2019 efforts to get relief usually \naggravates the signs and symptoms. There \nis still an ongoing dispute on the etiology, \nparticularly whether the wide nail plate or the \nhypertrophic nail folds are primarily to blame; \nthis is also reflected by the terminology of \nunguis incarnatus vs. onychocryptosis.\n\n\n\nTypes of ingrown nails\nNails may grow into their surrounding soft \ntissue at any age; newborns may be delivered \nwith ingrown nails and even 100-year-old \npersons may experience a painful ingrown nail.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 3\n\n\n\nNeonatal ingrown nail\nDuring intrauterine development, the big \ntoenails usually have reached the tip of the toe, \nwhich is then overlapped by the nail at birth. \nHowever, occasionally, the great toenail has not \novergrown the distal bulge and abuts it growing \ninto the distal bulge causing erythematous \ninflammation and pain. This may be a short \nself-healing phase or require gentle treatment, \nusually by the mother. A bit of petrolatum or \na similar fatty ointment is applied on the nail \nand then gently massaged in distal direction \nto push the distal bulge away while the baby \nis in a warm bath and held by the mother. The \nproblem is usually solved within a few days. \nAnother variant of neonatal ingrown nail is the \nbilateral distal ingrown nail (Fig. 1); here again, \nthe nail has not yet overgrown the toe tip but is \npinched distally from both sides. The treatment \nis analogous by gentle massage in a warm bath.\n\n\n\nFigure 1. Neonatal ingrown big toenails\n\n\n\nInfantile ingrown nail\nThere are two different types of ingrown nails \nin infants: the hypertrophic medial lip and \ncongenital malalignment.\n\n\n\nThe medial nail fold, rarely the lateral one, is \nhypertrophic and overlaps a part of the nail \nplate, sometimes more than the half. This \ncreates a deep crypt with accumulation of \ncellular debris and foreign material that degrade \nand cause an inflammation, a so-called cryptitis. \nAlthough this is rarely painful the mother may \nbe scared and look for medial help. Usually, the \noverlapping nail fold can be massaged away as \ndescribed above; however, if this is not effective \nit may be taken away with an electrical loop, \n\n\n\nwhich is an operation taking a few seconds.\n\n\n\nCongenital malalignment is seen at birth or in \nthe first months of life; however, it may also \ndevelop later if there is a genetic predisposition. \nOften a preceding trauma is then the \nprecipitating event. Originally, the disease was \ncalled congenital dystrophy of the big toenail \nuntil Baran recognized that the underlying \nabnormality was a lateral deviation of the \nlong axis of the nail relative to the axis of the \ndistal phalanx.3  In the last 25 years, more and \ndifferent types of congenital toenail dystrophy \nhave been observed, such as upward growing, \ncongenital pincer nails or medial deviation.4 \n\n\n\nVery often, congenital lateral malalignment is \nassociated with a hallux valgus or particularly \nhallux valgus interphalangeus. The nail is thick, \ndirty yellowish, triangular, medially overcurved, \nwith many transverse furrows and a slightly \nlaterally curved longitudinal axis. \n\n\n\nClose inspection reveals a high degree \nof onycholysis, which is indeed the \nmost important prognostic factor.5 \n\n\n\nThe detachment of the nail plate from the nail \nbed leads to loss of counterpressure of the toe \npulp during crawling and gait, which therefore \nbecomes distorted dorsally thus forming a distal \nbulge with shortening and disappearance of the \nnail bed (Fig. 2). This is clearly seen after cutting \naway the onycholytic nail, which also reveals an \nimpression of the nail margins into the soft tissue.6 \n\n\n\nAs the bone is not yet fully developed it tends to \nbecome curved upwards aggravating the distal \nbulge. The condition is apparently genetic as \nit is seen in monozygous twins, siblings and \nsometimes unilaterally; this also happens in \ntwins. \n\n\n\nThis is clearly seen after cutting away the \nonycholytic nail, which also reveals an \nimpression of the nail margins into the soft \ntissue.  As the bone is not yet fully developed \nit tends to become curved upwards aggravating \nthe distal bulge. The condition is apparently \ngenetic as it is seen in monozygous twins, \nsiblings and sometimes unilaterally; this also \nhappens in twins.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 484\n\n\n\nFigure 2. Congenital malalignment of the big \ntoenails in a 3\u00bd-year-old boy\n\n\n\n \nAdolescent ingrown nail\nThis is the most frequent type of ingrown nail. \nIt often starts at school age and may last into \nyoung adulthood. One or both nail folds of one \nor both big toes become red and inflamed, are \nswollen and painful upon touch and pressure. \nThis is generally called grade one (Fig. 3).\n\n\n\nFigure 3. 11-year-old boy with imminent \ningrowing nail, grade 1. Note the marked hallux \nvalgus interphalangeus and hyperextension of the \ninterphalangeal joint\n\n\n\n\n\n\n\nWith time, swelling, inflammation and redness \nincrease, oozing and sanguino-purulent \ndischarge develop; this is grade two. Finally, \ngranulation tissue develops, which is sometimes \nmistaken for pyogenic granuloma (Fig. 4). \n\n\n\nFigure 4. Ingrown toenail grade 2 in a 6-year-old \ngirl \n\n\n\nIn long-standing ingrown nails, swelling \nand granulation tissue may reach enormous \ndimensions rendering daily activities difficult to \nimpossible; this is grade three (Fig. 5).9\n\n\n\nFigure 5. 21-year-old man with chronic ingrown \ntoenail, grade 3\n\n\n\nMany youngsters with ingrown big toenails are \ntall, sub-diabetic, have sweaty feet and the nail \nis markedly curved.10 The nail is often cut too \nshort, particularly at its corners, but the corners \nmay also have broken spontaneously.11 This \nallows the distal nail bed to be pinched together \nmaking it narrower so that the regrowing nail \nhas not enough space and grows into the distal \nlateral sulcus. Quite often, the lateral nail \nplate margin has a saw-like appearance as the \npatient tries to cut the offending margin, which \naggravates the condition.\n\n\n\nThe exact pathomechanism is not known. \nWe believe that the tendency to hallux valgus \ninterphalangeus leads to an asymmetric distal \nphalanx bone with a higher medial condylus \nthat potentially pushes the matrix in medial-\ndistal direction directly leading to the lateral \ndeviation. However, this hypothesis is not yet \nproven. A hypertrophy of the dorsal-lateral \nligament of the distal interphalangeal joint was \nforwarded as another explanation;7   however, \nsurgical elongation of this ligament did not cure \nthe condition.8\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 5\n\n\n\nAdult-type ingrown nail\nIn adults, the ingrown nails are usually thick, \nstrongly curved or asymmetrically kinked, the \naffected nail fold is thick and fibrotic (Fig. 6). \nInflammatory changes may be less marked or \nlike those in adolescents. Pain is usually less \nintense. Often, a precipitating single trauma is \nremembered or repeated trauma is found out.\n\n\n\nFigure 6. Adult type ingrown big toenail with \nsharply bent nail, a pointed spicule is seen at the \nmedial margin of the nail\n\n\n\nOvercurvature\nNail overcurvature is a frequent condition. It \nmay be entirely painless or cause excruciating \npain, which is \u2013 curiously \u2013 independent from \nthe severity of the curvature; in contrast, nails \nthat show a curvature of 360\u00b0 or even more \nare commonly symptomless. The condition is \nknown under several terms, such as pincer nail \nor unguis constringens as the nail bed is pinched \ntogether, trumpet nail as it may look like the \nfunnel of a trumpet, omega nail as the frontal \nview of the nail and pinched nail bed resemble \nthe Greek capital letter omega.12 The genetic \nform is apparently an autosomal dominant trait, \nit is symmetric and virtually always associated \nwith lateral deviation of the nail and distal \nphalanx of the big toe. Lesser toenails may \nalso be involved and show a medial deviation. \nSystematic X-ray examinations always showed \na lateral deviation and asymmetry of the distal \nphalanx with marked bony appositions on the \ncondyli of the base of the distal phalanx which \nwere always bigger on the medial side and \noften had a hook-like appearance with the tip \nshowing distally.13 This leads to an increase \n\n\n\nof the width of the base of the distal phalanx \nwith a consecutive widening of the curvature \nof the matrix. The proximal uncurving causes \nthe distally increasing overcurving of the nail.14 \nThis phenomenon is bilateral-symmetric in the \ngenetic form of pincer nails (Fig. 7).15  \n\n\n\nFigure 7. Pincer nails in a 40-year-old woman; note \nthe lateral nail deviation of the big toenail and the \nmedially pointing nail axis of the 2nd toe\n\n\n\nDistal ingrowing\nWhen the big toenail is too short over a longer \nperiod or has been avulsed the tip of the \ntoe\u2019s soft tissue is slowly dislodged dorsally \nas the nail plate is lacking and cannot exert \ncounterpressure during gait. With each step, \nthe entire body weight is on the toe tip, but the \nweight is increased by a factor of 2.5 due to \nthe kinetic energy of the forward thrust during \nwalking; this factor is even higher during \nrunning and other similar sports activities. \n\n\n\nThe distal bulge thus developing is a physical \nobstacle for the growing nail. In addition, after \navulsion, the distal edge of the regrowing nail \nis usually slightly bent downward digging into \nthe flesh.16-17 This may lead to the appearance \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 486\n\n\n\nof granulation tissue or, more frequently, cause \nan arrest of forward growth of the nail with \nconsecutive thickening of the plate and yellow \ndiscoloration (Fig. 8). \n\n\n\nFigure 8. Distal nail ingrowing in a 20-year-old \nsoccer player who had lost his big toenail seven \ntimes\n\n\n\nRetronychia\nRetrograde ingrowing of the nail is called \nretronychia. Although only described in 1999 \nfor the first time it is not a rare condition, \nparticularly considering the frequent non-\ninflammatory chronic forms that we have \ntermed compression nail in accordance with D. \nLubach. The etiology of retronychia is not yet \nfully understood although the pathomechanism \nis known: a heavy acute or chronic repeated \ntrauma leads to subtotal onycholysis. As the nail \nis not firmly attached to the nailbed, which is in \nfact the stable support for the nail on the dorsal \naspect of the distal phalanx, any compression \nmovement of the nail is directly transferred to \nthe matrix, which is a very fragile tissue. This \nleads to shearing off the nail plate from the \nmatrix with microscopically visible horizontal \nsplits in the nail. The nail is no longer transported \nforward although the matrix produces new nail \nsubstance. Thus, a new layer is formed under \nthe old one raising the proximal margin of the \nold one. \n\n\n\nWith each new compression trauma that pushes \nthe nail backward another horizontal rupture \nis caused leading to a further new nail. The \nproximal edge of the old nail is hardening \nand cuts into the overlying proximal nail \n\n\n\nfold\u2019s undersurface that reacts with swelling, \ninflammation and granulation tissue finally \nemerging from under the free margin of the nail \nfold (Fig. 9).18 This is a painful condition and \nunfortunately rarely diagnosed correctly but \nerroneously treated with antibiotics as a primary \ninfectious paronychia. Ultrasound examination \nof the proximal nail fold may help to make \nthe correct diagnosis.19 The chronic form of \nretronychia usually remains without heavy \ninflammation and has still a certain potential \nof the nail to grow forward (Fig. 10); however, \nthere are usually many layers of nail similar to \nonychogryposis that are formed under the old \nnail, which is eventually seen as an obliquely \ndownward showing nail digging into the distal \nbulge that had developed because of the long-\nstanding onycholysis. Another chronic form \nwas called the horseshoe crab nail20 or shrimp \nnail21 because of the clinical aspect (Fig. 11).\n\n\n\nRetronychia is one of the very rare conditions \nwhere nail avulsion is indicated22 although in \nlight cases topical steroids and in moderate cases \nsteroid injections into the nail fold are often \nhelpful.23 For chronic retronychia, conservative \ndermatologic-podologic treatment is highly \nefficient.24\n\n\n\nFigure 9. Acute retronychia in a 20-year-old girl. \n(A) Clinical aspect with swelling and redness of the \nproximal nail folds. (B) The avulsed nail seen from \nits proximal shows the V-shaped apical portion with \nthe hard and very sharp superficial margin\n\n\n\nA\n\n\n\nB\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 7\n\n\n\nFigure 10. 43-year-old woman with chronic \nretronychia\n\n\n\nFigure 11. Compression nail also called horseshoe \ncrab or shrimp nail as a chronic repeated form of \nretronychia\n\n\n\nFrequency\nIngrown nails are frequent conditions, \nparticularly between the ages of  6-25 years. \nExact numbers of the incidence are, however, \nlacking. Sports activities, tight shoes, foot \nmaceration, inadequate foot hygiene are all \ncontributing factors. Ingrown toenails are less \nfrequent in populations walking barefoot.25 \nAbout 20% of those presenting to general \npractitioners with foot problems suffer from \ningrown toenails and a survey from the \nNetherlands gave a prevalence of 54/10,000 in \nDutch general practice.26-27\n\n\n\nLocalization\nThe great toe is by far the most common \nlocalization. The lesser toes, particularly 2 and \n3, may rarely be involved. Ingrowing fingernails \nare mainly seen in patients under treatment with \nepidermal growth factor receptor inhibitors \nduring targeted cancer therapy, retinoids, \nHAART for acquired immunodeficiency \nsyndrome and some other rare conditions that \nsoften the epidermis in the lateral nail sulcus \n(Fig. 12).\n\n\n\nFigure 12. Ingrown fingernail in a 65-year-old man \nwith colon cancer under targeted cancer treatment \nwith cetuximab\n\n\n\nEtiology\nThe cause of neonatal ingrown nails is the \nincomplete length of the toenail in relation to \nthe nail bed (Fig. 1).\n\n\n\nIn congenital malalignment, the medial \ncondylus of the distal phalanx bone is higher \npushing the medial matrix horn forward and \nthus leading to an obliquely oriented matrix. \nThe medial and sometimes also the lateral \nmargin of the triangular nail are bent downward \nand press on the soft tissue. In addition, there \nis usually a disappeared nailbed with a receded \nhyponychium and a large distal bulge (Fig. 2).28\n\n\n\nThe most frequent type seen in school children, \nadolescents and young adults has a disbalance \nof a distally too narrow nail bed and a wide \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 488\n\n\n\nnail plate. Additionally, the nail is usually \nmarkedly curved, and the lateral margins press \ninto the lateral nail sulcus. Particularly when \nthe nail edges are cut too short or broken the \ncontinuously growing nail will then dig into the \nskin and pierce it. This is painful and the patient \ntries to cut away the offending nail corner \naggravating the condition. \n\n\n\nPathogenesis \nThe nail is a continuously growing keratin \nplaque. It is embedded on both sides in the nail \nsulci. When the distal nail corners overlap the \ntoe, they can slide out without complication. \nHowever, when they are cut round the nail \nbed is compressed laterally, and the regrowing \nnail has not enough space and pierces into the \nsoft tissue. Inflammation, serous and putrid \nexudation, granulation tissue and finally fibrosis \nfollow (Fig. 13).\n\n\n\nFigure 13. Long-standing ingrown big toenail with \ngranulation tissue and massive fibrotic swelling of \nthe distal portion of the lateral nail fold\n\n\n\nClinical Features\nThey are already briefly outlined with the \ndescription of the various forms and shall only \nbe given in more detail for the most common, \nthe adolescent type.\n\n\n\nIn grade 1, the distal portion of the nail fold is \nswollen, red and tender. In grade 2, seropurulent \nsecretion is seen in addition and there is \nspontaneous pain. In grade 3, the toe is swollen, \n\n\n\nred on one or both sides, the nail corner is hidden \nby the nail fold tissue, and granulation tissue \nhas developed (Figs. 3-5). In long-standing \nsevere cases, the inflammation has turned \ninto fibrosis and all the signs mentioned are \nvery pronounced.9 Extreme cases demonstrate \novergrowth of granulation and fibrotic tissue \n(Fig. 13). The patients usually have stopped \ntheir physical activities because of pain.\n\n\n\nHistopathology\nHistopathologic examinations are rarely \nperformed.29 They show a very dense \ninflammatory infiltrate by lymphocytes with an \nenormously high percentage of plasma cells. \nThe epidermis of the lateral nail fold is often \nhyperplastic. Specimens of wedge excisions \nwith nail show the direct contact of the nail plate \nwith the dermis and a considerable neutrophilic \ncomponent attacking the nail keratin. The nail \nkeratin is slowly digested by the neutrophils \nrendering it soft and fragile (Fig. 14).30\n\n\n\nFigure 14. Histopathology slide of a wedge excision \nspecimen of an ingrown big toenail\n\n\n\nTreatment\nThe management has to be divided into general, \nconservative and surgical measures.\n\n\n\nGeneral measures\nFoot hygiene with daily washing and drying, \nwearing of adequate shoes and socks, as well \nas changing socks daily are self-evident. The \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 9\n\n\n\nmost important is cutting the nail square and \nleaving the corners of the nail overlapping \nthe toe tip. Routine antibiotics although often \ngiven are of no use as it is the nail that causes \nthe inflammation and not a primary infection. It \nalso appears that \u201cprophylactic antibiotics\u201d do \nnot prevent post-operative infections.31-32 \n\n\n\nConservative treatment\nThere are many ways to treat an ingrown \nnail without surgery. However, this usually \nrequires patience and compliance, which many \npersons do not have. On the other side, skilled \ncaretakers can achieve phantastic results with \ntaping, packing, insertion of a gutter, dental \nfloss, orthonyx braces, or artificial nails.33 \n\n\n\nTaping is the simplest way, particularly in the \nearly stage. A tape is firmly applied on the dry \nskin of the distal portion of the lateral nail fold \nin order to pull it away from the offending nail \nmargin (Fig. 15). Although this may hurt during \ntape application the pain disappears almost \nimmediately once the tape is in place. If possible, \nthe tape should be moved under the corner of \nthe nail making the procedure more effective \nand additionally bringing a buffer between the \nnail and the soft tissue. The tape is applied daily \nwith increasing pull. Several layers of tape may \nbe applied to anchor the first one.34\n\n\n\nFigure 15. Early but painful ingrowing. (A) Before; \n(B) after applying a tape to pull the soft tissue away \nfrom the offending nail corner\n\n\n\nA\n B\n\n\n\nPacking is the technique of inserting a whisp of \ncotton under the corner or lateral margin of the \nnail to keep it away from the soft tissue (Fig. 16). \nAgain, it may hurt when the cotton is inserted \nbut the pain is immediately gone afterwards. \nThis must be repeated until the corner of the nail \nhas overgrown the toe tip. Packing and taping \nmay be combined.\n\n\n\nFigure 16. Packing as a treatment for chronic \ningrown nail with fibrosis of the lateral nail folds in \nan 18-year-old man\n\n\n\nA \u201dcotton cast\u201d may be inserted on the lateral \naspect of the toenail and pressed from the nail to \nthe lateral nail fold thus distancing the fold from \nthe lateral nail margin.35-36 Gutter treatment \ncomprises the insertion of a gutter over as \nmuch of the nail margin length as possible. \nUsually, a local anesthesia is necessary for this \nprocedure.37  The gutter may be tailored from the \ntube of a drip infusion, which is cut lengthwise \nand moved over the lateral nail margin. It is then \nfixed by tape, a stitch or acrylic resin.34\n\n\n\nArtificial nails may be used alone: a thick and \nlong lateral nail margin is modelled so that this \noverlaps the toe and cannot cut into the sulcus \nskin anymore.38 As most ingrown nails have a \nconsiderable transverse curvature flattening \nthe curved nail is another approach. There are \ninnumerable different types of nail braces, from \nplastic bands that are glued on the nail to steel \nbraces that can be readapted. The simplest \nbrace consists of a narrow band of an elastic \npolymer that is glued onto the lateral margin \nand then pressed on the medial to lateral third \nof the opposite side of the nail. Other plastic \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4810\n\n\n\nbands cover the entire width of the nail. As their \nforce is relatively small, they must be worn for \nmany months to slowly uncurve the nail. More \nforce can be exerted with steel braces. They \nare hooked under the lateral nail margin and \nscrewed together over the middle of the nail.39-40  \nIn the course of months the nail will be flatter; \nhowever, as the cause of the overcurvature is \nnot tackled the curvature returns within a few \nweeks to its original shape.\n\n\n\nShape-memory alloy clips are a new approach \nto uncurve nails.41 The nail must be cut straight \nand the clip is pushed over its free margin. In \norder not to lose the clip it may be fixed with \nacrylic glue. It slowly unbends the nail. This \nmethod has the advantage that the application \nis not painful.42\n\n\n\nIdeally, conservative therapeutic measures are \ncombined thus enhancing the success rate.34-43\n\n\n\nAll these conservative methods require a skilled \nperson to demonstrate the technique and therapy \nadherence from the side of the patient. Whereas \nsome groups have excellent results11-34 many \nothers soon gave up and resorted to surgery. \nApparently, it is also a question of mentality \nwhether patients are willing to adhere to the \nnoninvasive treatment.44\n\n\n\nSurgical treatment\nSurgery has been the mainstay of ingrown nail \ntherapy since many centuries and innumerable \narticles deal with a vast variety of different \nsurgical techniques. According to the opinion \non etiology and pathogenesis either the nail \nis made narrower when a wide nail is thought \nto be responsible for the condition, or the \nhypertrophic nail fold is reduced or excised if \nthis is thought to be cause. Most of the countless \nvariations of wedge excisions, which excise both \na part of the nail bed and the lateral nail fold are \nwrong in their design and should absolutely be \nabandoned.\n\n\n\nThe terminal Syme operation was advocated \nfor chronic ingrown nails. It comprises the \namputation of the distal half of the big toe with \nremoval of the matrix and nailbed (Fig. 17).45 \nThis is a totally inadequate and mutilating \n\n\n\nmethod of treating a benign condition for which \nextremely efficacious, minimally invasive \nmethods exist.1\n\n\n\nFigure 17. Late result after the terminal Syme \noperation\n\n\n\nAnother kind of overtreatment is the Zadik \nprocedure in which the nail matrix is completely \nexcised and the proximal nail fold sutured over \nthe defect as an advancement flap.46 Both the \nterminal Syme and the Zadik procedures may \nleave nail spicules, which is proof of poor \nsurgery (Fig. 18).\n\n\n\nFigure 18. Several spicules after Zadik operation \nalio loco in a 14-year-old girl\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 11\n\n\n\nNail narrowing methods\nAs there is a discrepancy between too wide a \nnail plate and too narrow a nail bed, reducing \nthe nail\u2019s width is a logical consequence. \nWhichever method for the selective lateral/\nmedial matrix horn removal is used is not \ncritical. It is important to excise, ablate, or \ncauterize the matrix horn in a manner that no \nmatrix remnants remain, which would give \nrise to a nail spicule or a recurrence.1,47  Nail \nnarrowing should not be combined with nail \nfold excision, thus wedge excisions should not \nbe performed.\n\n\n\nSelective nail matrix narrowing\nIn order to render a wide nail narrower, the lateral \nor medial matrix horn should be removed. We do \nnot advocate to routinely operate on both sides \nas this leaves a very narrow and unsightly nail. \nIf one side is narrowed the entire nail has more \nspace and after a short period of conservatively \ncushioning the lateral nail margin, this will \nneither be offending nor grow in anymore. \n\n\n\nSurgical matrix horn resection is done \nunder sterile conditions and truncal or distal \nanesthesia.  If there is considerable infection \nan antibiotic prophylaxis may be indicated. \nThe foot is thoroughly disinfected and prepped \nfor the surgery. A tourniquet is applied. Excess \ngranulation tissue is removed with a curette \nor scissors. The ingrowing lateral nail strip is \ndetached from the nail bed back to the blind end \nof the matrix, cut longitudinally and avulsed. An \noblique or L-shaped incision is made from the \njunction of the proximal and lateral nail folds \nin proximal-lateral direction to allow the space \nof the matrix horn to be opened. An incision \nis carried out down to the bone at about 5 mm \nmedially from the lateral matrix border and the \nentire lateral matrix horn is dissected. This is \noften challenging as it reaches far laterally and \nproximally. \n\n\n\nCare has to be taken to remove the entire matrix \nhorn from the bone. Finally, the incision of \nthe nail fold is closed with either two stitches \nor suture strips. A bulky padded dressing is \napplied, and the foot kept up to minimize \n\n\n\nbleeding and swelling. Postoperative pain is \nminimal to moderate, but analgesics may be \ngiven according to the patient\u2019s needs. Healing \nis fast and the patient can usually return to \nschool or work after 3 days to a week.49\n\n\n\nThe lateral matrix horn may also be destroyed \nby electrodesiccation. Some radiofrequency \ndevice manufacturers offer special insulated \nspade-shaped electrodes for destruction of the \nmatrix.50 Conventional electrosurgery is not \nrecommended as it generates too much heat that \nmay damage the underlying periosteum and \nlead to long-term pain.\n\n\n\nLaser is another option to ablate the matrix. Most \ncommonly, CO2 lasers were used, however, \nthe 1064 nm neodymium-YAG was also used \nto heat-damage it.51,52 Chemical matrix horn \ncautery is now generally used. Which product \n- phenol, trichloroacetic acid, bichloroacetic \nacid, sodium hydroxide - is used is not critical \nprovided it is able to necrotize the full thickness \nof the matrix epithelium. Liquefied phenol is \nthe most widely used nowadays.53 Phenol has \nfour advantages: It is a strong protein coagulant \nthus able to necrotize the matrix epithelium; \nit is a strong disinfectant; it has a neurolytic \naction; and it is inactivated by blood. This \nmeans that we do not need to give antibiotics \neven in severely inflamed toes, postoperative \npain is minimal, and as soon as the tourniquet \nis opened phenol is \u201cneutralized\u201d rendering \n\u201calcohol neutralization\u201d unnecessary.\n\n\n\nPhenol matrix horn cauterization, also called \nphenolization, is a simple, time-honoring \nmethod with the lowest recurrence rate of all \nsurgical methods. After complete anesthesia \nand application of a tourniquet, the lateral nail \nstrip is avulsed. Excess granulation tissue may \nbe curetted. A small cotton ball dipped into \nliquefied phenol is vigorously rubbed into the \nbloodless matrix horn under the proximal nail \nfold for 3 to 4 minutes; we use a fresh cotton \nwith phenol 4 times for a minute each. Excess \nphenol is wiped away. The tourniquet is opened \nafter the 4-min phenol application. If available \nsmall tapered antibiotic tablets containing \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4812\n\n\n\nframycetin (Leukase\u00ae-Kegel) may be inserted \ninto the wound cavity; they keep the wound open \nand allow the postoperative drainage to escape \n(Fig. 19). A circular dressing with a petrolatum-\nbased ointment is applied for 24 hours, which is \nchanged after a day. \n\n\n\nThe patient is asked to elevate the foot for 48 \nhours as this minimizes postoperative swelling, \nbleeding, and pain. The postoperative care \nconsists of once \u2013 or if in hot climate \u2013 twice \ndaily rinsing the wound under a jet of tap water. \nThis considerably shortens the healing time, \nprevents postoperative infection, and oozing. \nThe patients can resume their daily activities \nwithin a few days as there is no risk of wound \ndehiscence. Rubbing the phenolized matrix with \n20% ferric chloride at the end of the procedure \nshortens the period of drainage.54\n\n\n\nFigure 19. (A) Right big toenail with broken lateral \ndistal nail corner causing considerable pain though \ninflammation is barely visible. (B) Immediately \nafter phenolization. (C) End of the phenolization \nprocedure with Leukase\u00ae tablets put into the lateral \nmatrix horn and the small wound. (D) 24 hours \npostoperatively. (E) 3 weeks post-op. (F) 8 weeks \npost-op\n\n\n\nA\n \n\n\n\nB\n\n\n\nC\n \n\n\n\nD\n\n\n\nE\n \n\n\n\nF\n\n\n\nAnother option is to use 85 -100% trichloroacetic \nacid for 1 - 3 minutes.55 It is said to cause even \nless postoperative pain and oozing; however, \n\n\n\na comparative study did not show a more \nrapid healing than phenol.56 Recently, also \nbichloroacetic acid was used instead of TCA.57 \nHowever, bichloroacetic acid continues to \npenetrate if its action is not stopped by either \nrinsing or neutralizing it.\n\n\n\nSodium hydroxide is another chemical to \ncauterize the matrix horn; in contrast to the \naforementioned substances, it is an alkaline \nchemical. It is used for either 2 min or 1 min \nafter curettage of the matrix. Both regimens \nwere well tolerated and yielded the same good \nresults.58 A recent literature meta-analysis, \nhowever, found that there was no significant \ndifference in the recurrence rate between NaOH \nand placebo.59\n\n\n\nReduction of periungual soft tissue\nSome nail surgeons consider a narrow nail \nplate a cosmetic disadvantage. They propose to \nreduce or completely excise the lateral nail fold. \nDepending on the amount of surplus soft tissue \nthis may be done as a limited excision or as a \nradical removal.60 \n\n\n\nIf the nail fold hypertrophy is mild to moderate \na fusiform excision from the lateral aspect of \nthe distal phalanx may be performed. Upon \nsuturing the fold is reduced and pulled away \nfrom the offending lateral nail margin.61 Another \npossibility is to do a large and deep excision \nto remove a big volume of the soft tissue; the \nwound may then be sutured.62\n\n\n\nQuite often, the lateral distal portion of the nail \ndigs into the soft tissue, which forms a bridge \nfrom the lateral fold to the hyponychium. This \nis usually the result of a nail corner cut too short. \nA small banana-like excision may pull this false \nextension of the lateral nail fold down. The \nsmall defect may be stitched with 2-0 sutures \nthat are knotted up to ten times. This maxi-knot \nis placed under the nail corner elevating it and \nallowing the nail to grow over this obstacle.63\n\n\n\nThe Vandenbos technique removes both nail \nfolds starting about 5 mm in the lateral aspect \nof the proximal nail fold and excising the lateral \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 13\n\n\n\nfold as a large soft tissue wedge down to the \nmiddle of the lateral distal phalanx and distally \nto the hyponychium including one third of it. \nThis is done on both sides thus about one third \nof the toe\u2019s circumference is removed and only \nthe central third of the hyponychium is left. The \nlarge wound heals by secondary intention, which \nmay take 4 \u2013 6 weeks. The aesthetic result is \nusually good. The recurrence rate is lower than \nthat of Winograd\u2019s wedge resection.64 \n\n\n\nSimilar though even more radical is the \nsuper U technique. The lateral nail folds and \nthe hyponychium are generously cut away \nfreeing three sides of the nail. The wound is \nleft for second intention healing, which takes \nseveral weeks. There is a risk of a parrot beak \nnail deformity because of shrinking of the \nhyponychial scar.65\n\n\n\nIt is beyond the scope of this short review to \nmention all reported variations of the methods \ndescribed in the literature. The understanding \nof the pathomechanism is the basis for all \ntreatments. Radical surgeries like the terminal \nSyme operation, Zadik procedure or most wedge \nexcisions are obsolete and demonstrate that the \nsurgeon does not understand the condition.\n\n\n\nComplications\nComplications of ingrown nails are infection, \npain, disability to walk and serious impairment \nof all physical activities.\n\n\n\nPostoperative complications may be wound \ninfection, particularly after scalpel surgery. \nThis is the reason why many general surgeons \nroutinely administer antibiotics. It is usually not \nnecessary for phenol matrix horn cautery. This \nmethod is also blessed by minimal postoperative \npain.\n\n\n\nPotential long-term and permanent \ncomplications of ingrown nail surgery are nail \ndystrophy, deviation of the nail toward the \noperated side, and toe mutilation (Figs. 20 & \n21).\n\n\n\nFigure 20. Result of bilateral wedge excisions with \nnail avulsions for ingrown nails in a 39-year-old \nwoman\n\n\n\n\n\n\n\nFigure 21. Nail dystrophy after bilateral wedge \nexcisions\n\n\n\nRecurrence\nRecurrences after treatment of ingrown nails are \ncommon. Unfortunately, ingrown nail surgery \nis delegated in many surgery departments to \nyoung and unexperienced staff.66 They do their \nsurgical operations often without surveillance \nof experienced specialists and thus believe it is \ncorrect what they do. This poor surgery is then \ntaken as routine with both poor to catastrophic \nresults and very high recurrence rates. Even \ntextbooks of \u201cminor surgery\u201d display wrong \nincision lines for wedge excisions that virtually \ninvite recurrences as the authors of such books \napparently do not know the anatomy of the \nmatrix of the big toe.\n\n\n\nWith properly executed phenolization the \nrecurrence rate is between 1 \u2013 3% whereas \npublications on wedge excisions mention \nrecurrences in 25 \u2013 50% or even more.67\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4814\n\n\n\nIngrown nail patients should not be left alone \nafter surgery. A follow-up after 3 \u2013 6 months and \nanother one after a year is important to recognize \nany imminent recurrence or complications and \ndemonstration of what to do in such a case are \ncrucial.\n\n\n\nConclusion\nIngrown toenails are frequent conditions, \nparticularly in youngsters. They may \nconsiderably impair the quality of life due to \npain and restrictions of physical activities. \nTheir treatment should be initiated as soon as \npossible as early stages are usually amenable \nto conservative therapy. Prevention is often \neasy with correct nail trimming, avoidance of \ninadequate footwear and prevention of soggy \nfeet. Conservative modalities are varied with \ntaping, packing, gutter placement, orthonyxia \nbraces, shape-memory alloy clips, and many \nmore methods. They require some dexterity and \nabove all compliance.\n\n\n\nIf conservative methods are not successful \nsurgery is indicated. Of the many approaches, \nselective matrix horn removal, either surgically \nor by chemocautery, is the treatment of choice. \nSoft tissue resection takes weeks to heal but \nusually gives good results.\n\n\n\nConflict of Interest Declaration \nThe author have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n1. Haneke E. Controversies in the treatment of ingrown nails. \n\n\n\nDermatol Res Pract 2012;2012:783924.\n2. Thakur V, Vinay K, Haneke E. Onychocryptosis - \n\n\n\ndecrypting the controversies. Int J Dermatol 2020;59:656-\n69.\n\n\n\n3. Baran R, Bureau H, Sayag J. Congenital malalignment of \nthe big toe nail. Clin Exp Dermatol 1979;4:359-60.\n\n\n\n4. Haneke E. Toenails: Where orthopedics and onychology \nmeet. In Baran R, ed. Advances in Nail Disease and \nManagement. Updates in Clinical Dermatology. Springer \n\n\n\nSwitzerland 2021:71-85.\n5. Baran R, Haneke E. Etiology and treatment of nail \n\n\n\nmalalignment. Dermatol Surg 1998;4:719-21.\n6. Haneke E. Therapie von Nagelfehlbildungen. In: \n\n\n\nLandthaler M, Hohenleutner U: Fortschritte der operativen \nDermatologie 12:180-187, Blackwell Wiss-Verl, Berlin \u2013 \nWien 1997.\n\n\n\n7. Gu\u00e9ro S, Guichard S, Fraitag SR. Ligamentary structure of \nthe base of the nail. 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Liu CW, Huang YC. Combination of two types of nail \nbrace for the treatment of complicated ingrown toenails. \nIndian J Dermatol Venereol Leprol 2017;83:722-5.\n\n\n\n41. Ishibashi M, Tabata N, Suetake T, Omori T, Sutou Y, \nKainuma R, Yamauchi K, Ishida K. A simple method to \ntreat an ingrowing toenail with a shape-memory alloy \ndevice. J Dermatolog Treat 2008;19:291-2.\n\n\n\n42. Arai H, Arai T, Haneke E. Simple and effective non-\ninvasive treatment methods for ingrown and pincer nail \nincluding acrylic affixed gutter splint, anchor taping, \nsculptured nails, shape memory alloy nail clip and plastic \nnail braces as well as 40% urea paste. J Kochi Med Ass \n2011;16:37-56.\n\n\n\n43. Villa Verde RB, Ramirez-Oliveros JF, Takamitsu HM, \nLeverone AP, Nakamura RC. Treatment of nail fold \n\n\n\nhypertrophy by combining conservative techniques. Skin \nAppendage Disord 2021;7:373-6.\n\n\n\n44. Tsunoda M, Tsunoda K. Patient-controlled taping for the \ntreatment of ingrown nails. Am Fam Med 214;12:553-5.\n\n\n\n45. Gibson TW, Westberry DE, Carpenter AM, Colucciello N, \nCarson L. Terminal Syme amputation of the great toe in the \npediatric population. J Pediatr Orthop 2021;41:e823-7.\n\n\n\n46. Vanhooteghem O, Henrijean A, Andr\u00e9 J, Richert B, De \nLa Brassinne M. Un ongle d\u2019inclusion: une complication \nde la cure chirurgicale d\u2019ongle incarn\u00e9 selon la technique \nde Zadik [Ingrown nails: a complication of surgery for \nan in-growing toe-nail using the Zadik procedure]. Ann \nDermatol Venereol 2006;133:1009-10.\n\n\n\n47. Baran R, Haneke E. Matricectomy and nail ablation. Hand \nClin 2002;18:693-6, viii; discussion 697.\n\n\n\n48. Haneke E. Surgical treatment of ingrowing toenails. Cutis \n1986;37:251-6.\n\n\n\n49. Haneke E: Segmentale Matrixverschm\u00e4lerung zur \nBehandlung des eingewachsenen Zehennagels [Segmental \nmatrix excision in the treatment of ingrowing toenails]. \nDtsch med Wschr 1984;109:1451-3.\n\n\n\n50. Chan J, Pehr K. Electrodessication matricectomy with \nmodified hyfrecator tip: case series and literature review. \nJ Cutan Med Surg 2021;25:418-23.\n\n\n\n51. Andr\u00e9 P. Ingrowing nails and carbon dioxide laser surgery. \nJ Eur Acad Dermatol Venereol 2003;17:288-90.\n\n\n\n52. S\u00e1nchez LC, Zalaca\u00edn-Vicu\u00f1a AJ. Onychoplasty with \n1064-nm laser: Matrixectomy for treatment of ingrown \ntoenails. J Am Podiatr Med Assoc 2019;109:401-6.\n\n\n\n53. Ramesh S, Shenoi SD, Nayak SUK. Comparative \nefficacy of 10% sodium hydroxide, 88% phenol, and \n90% trichloroacetic acid as chemical cauterants for \npartial matricectomy in the management of great toe nail \nonychocryptosis. J Cutan Aesthet Surg 2020;13:314-8.\n\n\n\n54. Aksakal AB, Atahan C, Ozta\u015f P, Oruk S. Minimizing \npostoperative drainage with 20% ferric chloride after \nchemical matricectomy with phenol. Dermatol Surg \n2001;27:158-60.\n\n\n\n55. Barreiros H, Matos D, Goul\u00e3o J, Serrano P, Jo\u00e3o A, Brand\u00e3o \nFM. Using 80% trichloroacetic acid in the treatment of \ningrown toenails. An Bras Dermatol 2013;88:889-93.\n\n\n\n56. Andr\u00e9 MS, Caucanas M, Andr\u00e9 J, Richert B. Treatment of \ningrowing toenails with phenol 88% or trichloroacetic acid \n100%: A comparative, prospective, randomized, double-\nblind study. Dermatol Surg 2018;44:645-50.\n\n\n\n57. Terzi E, Guvenc U, Tursen B, Tursen U, Kaya TI. The \neffectiveness of matrix cauterization with bichloracetic \nacid in the treatment of ingrown toenails. Dermatol Surg \n2017;43:728-33.\n\n\n\n58. Ozdemir E, Bostanci S, Ekmekci P, Gurgey E. Chemical \nmatricectomy with 10% sodium hydroxide for the treatment \nof ingrowing toenails. Dermatol Surg 2004;30:26-31.\n\n\n\n59. Chang HC, Lin MH. Comparison of chemical matricectomy \nwith trichloroacetic acid, phenol, or sodium hydroxide for \ningrown toenails: a systematic review and network meta-\nanalysis. Acta Derm Venereol 2020;100:adv00065. doi: \n10.2340/00015555-3379.\n\n\n\n60. Di Chiacchio N, Di Chiacchio NG. Best way to treat an \ningrown toenail. Dermatol Clin 2015;33:277-82.\n\n\n\n61. DeBrule MB. Operative treatment of ingrown toenail by \nnail fold resection without matricectomy. J Am Podiatr \nMed Assoc 2015;105:295-301.\n\n\n\n62. No\u00ebl B. Surgical treatment of ingrown toenail without \nmatricectomy. Dermatol Surg 2008;34:79-83.\n\n\n\n63. Ince B, Dadaci M, Altuntas Z. Knot technique: a new \ntreatment of ingrown nails. Dermatol Surg 2015;41:250-4.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4816\n\n\n\n64. Nasr Y, Nasr A, Bettolli M. The effectiveness of nail excision \nversus Vandenbos procedure for the surgical management \nof ingrown toenails in children: A retrospective chart \nreview. J Pediatr Surg 2021;56:1857-60.\n\n\n\n65. Di Chiacchio N, BV Kadunc, AR Trindade de Almeida, \nCL Madeira. Treatment of transverse overcurvature of the \nnail with a plastic device: measurement of response.  J Am \nAcad Dermatol 2006;55:1081-4.  \n\n\n\n66. Lau YS, Yeung JM. Surgical treatment of in-growing \ntoenails performed by senior house officers: are they good \nenough? Scott Med J 2005;50:22-3.\n\n\n\n67. Mitchell S, Jackson CR, Wilson-Storey D. Surgical \ntreatment of ingrown toenails in children: what is best \npractice? Ann R Coll Surg Engl 2011;93:99-102.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 17\n\n\n\nORIGINAL ARTICLE\n\n\n\nA Prospective Cohort Study of Laboratory Abnormalities During \nIsotretinoin Treatment For Acne Vulgaris\n\n\n\nKanimoli Rathakrishnan1, MRCP, Lay Kim Tan2, PhD, Sharifah Rosniza Binti Syed Nong Chek1, AdvMDerm, \nChe Hassan Zuraida2, BSc, Dyoi E Low3, AdvMDerm \n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Wilayah Persekutuan, Malaysia\n2Sector for Biostatistics & Data Repository, Office of NIH Manager, National Institute of Health, Ministry of \nHealth Malaysia, Selangor, Malaysia\n3Dermatology Unit, Hospital Serdang, Selangor, Malaysia\n\n\n\nAbstract\nBackground \nAcne vulgaris is a chronic inflammatory condition of the pilosebaceous unit. Isotretinoin is used to \ntreat moderate to severe acne that is resistant to antibiotics and topical agents. However, it may cause \nalterations in lipids and liver enzymes.\n\n\n\nMethods   \nA total of 129 patients with acne vulgaris (moderate to severe facial acne) treated with isotretinoin \nwere recruited between May 2020 and July 2021 from the dermatology clinics at Hospital Serdang \nand Hospital Kuala Lumpur. Of these, 120 patients with complete data of lipid panel (total cholesterol, \nlow density lipoprotein cholesterol [LDL], triglycerides [TG], and high density lipoprotein cholesterol \n[HDL]) and hepatic panel (alanine transaminase [ALT] and aspartate transaminase [AST]) levels at \nbaseline, and in three subsequent follow-up visits (i.e., one, three, and six months) were included in \nthe analyses. Abnormalities were graded according to standard laboratory values and their severity \naccording to the National Cancer Institute Common Terminology Criteria for Adverse Events \n(CTCAE)grading system. \n\n\n\nResults \nOf the 120 study participants, 83% were female and 37% were male between the ages of 15 and 36 \nyears. We observed a significant increase in median values at baseline and at the six-month follow-up \nfor total cholesterol (p<0.0001), triglycerides (p<0.0001), LDL (p<0.0001), ALT (p<0.0001), and \nAST (p<0.0001). We observed a significant correlation between body mass index and the HDL (r2=-\n0.26, p=0.01) and ALT (r2=0.383, p=7.9x10-06) levels. Based on the CTCAE grading system, almost \nall study participants with abnormal results had grade 1 abnormalities. Only one patient had a grade 2 \nabnormality in ALT, which required treatment discontinuation.\n\n\n\nConclusion  \nLow dose isotretinoin therapy for acne vulgaris may cause mild and non-progressive elevation of \nLDL, total cholesterol, and liver transaminases which do not require treatment withdrawal in most \ncases.  \n\n\n\nKey words: Acne vulgaris; Isotretinoin; Lipid profile; liver transaminases\n\n\n\nCorresponding Author\nDr Kanimoli Rathakrisnan\nDepartment of Dermatology,\nHospital Kuala Lumpur,\n\n\n\nJalan Pahang, \n50586 Wilayah Persekutuan Kuala Lumpur\nEmail: r_kanimoli@hotmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4818\n\n\n\nIntroduction\nAcne vulgaris is the formation of comedones, \npapules, pustules, nodules, and/or cysts as \na result of obstruction and inflammation of \npilosebaceous units (hair follicles and their \naccompanying sebaceous glands).1 Acne \nvulgaris can be classified as non-inflammatory \n(characterized by comedones) and inflammatory \n(characterized by papules, pustules, nodules, \nand cysts).2 \n\n\n\nAn estimated 9.4% of the global population \nis affected by acne, making it the eighth-most \nprevalent disease worldwide.3-5 Approximately \n80% of people are affected by acne between \nthe onset of puberty and 30 years of age.4 In \nthe local scenario, a study conducted among \nmedical students aged 19-25 years at Hospital \nUniversity Kebangsaan Malaysia between 2011 \nand 2012 showed that the prevalence of acne \nwas 68.1%, with a comparable ratio of males to \nfemales (1:1.1).6\n\n\n\nIsotretinoin or 13-cis-retinoic acid (i.e., a synthetic \nanalogue of vitamin A) is recommended for the \ntreatment of severe inflammatory acne of the \nnodulocystic or conglobate types and for cases \nof acne vulgaris with evidence of resistance to \nprevious treatments with antibiotics or topical \nmedication. Isotretinoin acts on the sebaceous \nglands by binding to specific retinoid receptors, \nmodifying gene transcription.7 It reduces the \nactivity and size of the gland, decreasing the \nquantity of sebum it produces and reducing the \nnumber of Cutibacterium acnes.7 It produces \na significant reduction in comedogenesis by \ndecreasing hyperkeratinization.8\n\n\n\nIsotretinoin also may cause clinical side effects \nand laboratory changes, the most important \nbeing teratogenicity.9 Mucocutaneous side \neffects include cracked lips, dryness of the skin \nand nasal mucosa, skin redness, eye dryness, \nand eye irritation.3,10\n\n\n\nIsotretinoin treatment may increase liver \ntransaminases (alanine aminotransferase, \nALT and aspartate aminotransferase, AST), \nserum triglycerides (TGs), and low-density \n\n\n\nlipoproteins (LDL) cholesterol and reduce \nthe level of high-density lipoprotein (HDL) \ncholesterol.10,13 Abnormalities in serum lipid \nlevels were common during isotretinoin therapy, \nwhile abnormalities in transaminase levels were \nless common and generally mild.13 High levels of \nTGs and low levels of HDL cholesterol are risk \nfactors for coronary heart disease and ischaemic \nstroke.13 Isotretinoin causing drug-induced \npancreatitis through hypertriglyceridemia has \nbeen reported but is rare.14\n\n\n\nThere are very limited data on changes in \nthe liver enzymes and lipid levels among \nisotretinoin users in Malaysia. Laboratory \nmonitoring of serum lipids and liver function \ntests are also at the discretion of the physician, \nand there is wide variation in the type and \nfrequency of monitoring that is performed. The \naim of this study was to evaluate alterations \nin lipid parameters (i.e., total cholesterol, TG, \nLDL, HDL) and liver transaminases (i.e., AST \nand ALT) in acne vulgaris patients treated with \nlow dose isotretinoin.\n\n\n\nMaterials and Methods  \nThis was a prospective cohort study conducted \nbetween May 2020 and July 2021 in the \ndermatology clinics of Hospital Kuala Lumpur \nand Hospital Serdang. \n\n\n\nUsing the two population means formulae, \npaired t-test (published mean of ALT at three \nmonths=18.2 (\u00b14.59), published mean of ALT at \nsix months=23.3 (\u00b120.23), \u03b1-value=0.05, power \nof statistical test=80%, confidence level=95%, \nfour follow-up visits, and consideration of 20% \ndropout rate), the calculated sample size was \n117 study participants. A total of 129 eligible \nstudy participants diagnosed with acne vulgaris \n(moderate to severe) who did not respond to \ncombined therapy (i.e., topical, and systemic \ntreatment) were screened and recruited. Of \nthese, 120 participants completed the study. \n\n\n\nParticipants were briefed about the study \nand their written consent was obtained by the \nclinicians. Acne vulgaris patients with the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 19\n\n\n\nfollowing conditions were excluded from the \nstudy: i) pregnant or planning for pregnancy, \nii) history of hypersensitivity reactions to \nisotretinoin, iii) pre-existing liver disease, \niv) hematological disorders, or v) receiving \nisotretinoin therapy for conditions other than \nacne.\n\n\n\nThe severity of acne in the study participants \nwas assessed and determined using the \nComprehensive Acne Severity Scale criteria.2 \nA standardized data collection form was used \nto collect sociodemographic data as well as \nthe laboratory biochemical tests of lipid profile \n(i.e., total cholesterol, TG, LDL, and HDL) \nand liver transaminases (i.e., ALT and AST) at \nrecruitment (baseline). Patients were followed \nup at three different visits, i.e., at one month, \nthree months, and six months. At each follow-\nup visit, the patients were assessed by their \ntreating clinicians, and the isotretinoin dose was \nadjusted, whenever necessary, according to the \nstandard clinical practice at both study sites. \n\n\n\nBlood was also drawn from patients to quantify \nlipid profile and liver transaminases. Outcomes \nwere recorded based on standard laboratory \nvalues and their severity according to the \nNational Cancer Institute Common Terminology \nCriteria for Adverse Events (CTCAE) v3.0 \ngrading system.16 \n\n\n\nThis study was conducted in accordance with \nthe ethical principles of the Declaration of \nHelsinki and the Malaysian Good Clinical \nPractice Guidelines. Ethical approval was \nobtained from the Medical Research and Ethics \nCommittee of the Malaysian Ministry of Health \n[KKM/NIHSEC/P20-925(12)]. \n\n\n\nDescriptive statistics were performed to \ndescribe the characteristics of the study \npopulation and data set. Numerical values \nwere presented as mean and standard deviation \n(SD) or median and interquartile range (IQR), \nwhile categorical variables were presented as \nabsolute number and percentage. The Friedman \ntest, a nonparametric alternative to the one-way \nANOVA with repeated measures, was used \n\n\n\nto test for median differences in lipid profiles \nand liver transaminases between different \nclinical visits. The Spearman correlation test \nwas performed to investigate the correlation \nbetween lipid profile and liver transaminases \nand ody mass index (BMI). Results with p<0.05 \nwere considered statistically significant. All \ndata analyses were performed using IBM SPSS \nStatistics for Windows version 21.0.\n\n\n\nResults\nNine study participants defaulted follow-up, \nhence excluded from the data analyses. Of the \n120 remaining participants, 83 (69.2%) were \nfemale and 37 (30.8%) were male, with ages \nranging between 15 and 36 years. Of the 120 \nparticipants, 36 (30%) were overweight and \nobese, while only three individuals (2.5%) had \ncomorbidities. Eighty-six patients (71.7%) were \ndiagnosed with moderate acne and 34 (28.3%) \nwith severe acne, with the mean duration of \nacne being 6\u00b14.20 years.\n \nAll the study subjects were treated with low \ndoses of isotretinoin ranging from 0.2 to 0.4 \nmg/kg, with daily doses of between 10 to 30 mg \ndaily, which is the standard clinical practice at \nthe study sites (see Table 1). Our data showed \nthat 89.2%, 65%, and 80.8% of participants \nwere treated with the lowest isotretinoin dose of \n10 mg daily at baseline, which was continued at \nfirst and third months of follow-up, respectively \ntill 6th month of treatment (Table 1). \n\n\n\nA total of 107 patients received 10 mg daily \nduring the first month. At the second follow-\nup, the dose was increased to 20 mg daily in \n28 (26%) of the patients for the subsequent 2 \nmonths.  At the third follow-up, the treatment \ndose was reduced back to 10 mg daily in 14 \n(50%) of the 28 patients for the final 3 months. \nThese adjustments were based on the clinical \nresponses and the biochemical test results (i.e., \nlipid profile and liver transaminase). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4820\n\n\n\nTable 1. Patient characteristics and isotretinoin \ndoses on repeated follow-up\n\n\n\nVariables (n=120) Mean\u00b1SD n (%)\n\n\n\nAge\n15-25\n26-29\n30-36\n\n\n\n23\u00b15.0\n96 (80)\n13 (11)\n11 (9)\n\n\n\nSex\nMale \nFemale\n\n\n\n37 (30.8)\n83 (69.2)\n\n\n\nEthnicity\nMalay\nChinese\nIndian\nOthers\n\n\n\n110 (91.7)\n6 (5.0)\n2 (1.7)\n2 (1.7)\n\n\n\nBody Mass Index (kg/m2)\nHealthy (18.5-24.9)\nOverweight (25.0-29.9)\nObese (\u226530.0)\n\n\n\n22.9\u00b13.96\n84 (70.0)\n29 (24.2)\n7 (5.8)\n\n\n\nComorbidities\nAbsent\nPresent\n\n\n\n117 (97.5)\n3 (2.5)\n\n\n\nSeverity of acne\nModerate\nSevere\n\n\n\n86 (71.7)\n34 (28.3)\n\n\n\n1st treatment with isotretinoin\n2nd treatment with isotretinoin\n\n\n\n                        118 (98.3)\n                            2 (1.7)\n\n\n\nDuration of acne (years)                           6 \u00b1 4.20\n\n\n\nIsotretinoin dose (mg) at 1st \nmonth\n(1st visit)\n\n\n\n10                         107 (89.2)\n\n\n\n20                          12 (10.0)\n\n\n\n30                             1 (0.8)\n\n\n\nIsotretinoin dose (mg) at 2nd \n\n\n\nand 3rd month\n(2nd visit)\n\n\n\n10                         78 (65.0)\n\n\n\n20                        41 (34.2)\n\n\n\n30                           1 (0.8)\n\n\n\nIsotretinoin dose (mg) at 4th-\n6th month\n(3rd visit)\n\n\n\n10                        97 (80.8)\n\n\n\n20                        22 (18.3)\n\n\n\n30                         1 (0.8)\n\n\n\nLipid profile and liver transaminase\nOur data demonstrated significantly higher \nlevels of the total cholesterol, TG, and LDL, \nbut not the HDL, at the six-month follow-up \nwhen compared with the baseline. Likewise, \na significant increasing trend was observed in \nthe liver transaminases, i.e., ALT and AST as \nshown in Table 2.\n\n\n\nWe further compared the incidence of abnormal \nlaboratory parameters (i.e., lipid profiles and liver \ntransaminase) at baseline and in each follow-up \n\n\n\nvisit. Since the majority of our patients (n=107) \nwere prescribed the lowest dosage (10mg) \nof isotretinoin at baseline, our analysis of the \nincidence of abnormal laboratory parameters \nincluded only these study participants. In \naddition, we investigated whether dose \nadjustment at different clinical visits affects the \nincidence of abnormal laboratory parameters. \nInterestingly, we observed a significant increase \nin the incidence of abnormal LDL from 65.4% \nto 81.3% (p<0.05) (see Table 3). \n\n\n\nTable 2. Effects of oral isotretinoin on repeated \nmeasures of lipid profiles and liver transaminases \n\n\n\nLaboratory \nvariable\n\n\n\nBaseline \nMedian \n(IQR)\n\n\n\n1st \nmonth \nMedian \n(IQR)\n\n\n\n3rd \nmonth  \nMedian \n(IQR)\n\n\n\n6th \nmonth \nMedian \n(IQR)\n\n\n\np-value\n\n\n\nTotal \ncholesterol 4.8 (1) 4.9 (1) 5.1 (1) 4.9 (1) <0.001\n\n\n\nTriglycerides 0.8 (0.5) 0.8 (0.5) 0.9 (0.5) 0.9 (0.5) <0.001\n\n\n\nLDL 2.98 (0.9) 3.1 (0.8) 3.1 (0.7) 3.1 (0.7) <0.001\n\n\n\nHDL 1.4 (0.4) 1.4 (0.3) 1.4 (0.4) 1.4 (0.4) 0.656\n\n\n\nALT 12 (10) 12 (9) 14 (11) 15 (12) <0.001\n\n\n\nAST 18 (5) 19 (6) 20 (7) 20 (6) <0.001\n\n\n\nAlthough increasing trends of abnormal \nincidence were observed for total cholesterol, \nTGs, HDL, ALT and AST, these were however \nnonsignificant. We further observed that, of the \n28 participants prescribed with an increment of \nisotretinoin dosage at the 1st-month follow-up \nvisit (from 10 mg daily to 20 mg daily), half \nof these participants (n=14, 50%) were adjusted \nto the initial starting dosage of 10 mg at the 3rd \nmonth by the treating clinicians based on the \nclinical observations and laboratory findings \n(see Table 3). \n\n\n\nWe then investigated the relationship between \nbody mass index (BMI) and the baseline \nlaboratory parameters, i.e., lipid profile and \nliver transaminases, which were quantified. Our \ndata showed a significant negative correlation \nbetween BMI and HDL level (r2=-0.26, \np=0.01), indicating the higher the BMI of the \nparticipants in this study cohort, the lower the \nHDL level. On the other hand, we observed a \npositive correlation between BMI and ALT \n(r2=0.383, p=7.9X10-06). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 21\n\n\n\nTable 3. Incidence of acne vulgaris patients with abnormal levels of lipids and liver transaminase \nparameters\n\n\n\nBiochemistry \n\n\n\nTest\n\n\n\nBaseline 1st month 3rd month 6th month\n\n\n\nNormal \n\n\n\n(n, %)\n\n\n\nAbnormal \n\n\n\n(n, %)\n\n\n\nNormal \n\n\n\n(n, %)\n\n\n\nAbnormal \n\n\n\n(n, %)\n\n\n\nDose \n\n\n\nadjustment\n\n\n\nNormal\n\n\n\n (n, %)\n\n\n\nAbnormal \n\n\n\n(n, %)\n\n\n\nDose \n\n\n\nadjustment\n\n\n\nNormal \n\n\n\n(n, %)\n\n\n\nAbnormal \n\n\n\n(n, %)\n\n\n\nTotal \n\n\n\nCholesterol\n\n\n\n79 (73.8) 28 (26.2) 72 (67.3) 35 (32.7) Overall 65 \n\n\n\n(60.7)\n\n\n\n42 (39.3) Overall 65 \n\n\n\n(60.7)\n\n\n\n42 (39.3)\n\n\n\n10 mg daily 48 \n\n\n\n(73.8)\n\n\n\n30 (71.4) 10 mg daily 54(83.1) 34 (81)\n\n\n\n20 mg daily 17 \n\n\n\n(26.2)\n\n\n\n11 (26.2) 20 mg daily 11(16.9) 8(19)\n\n\n\n30 mg daily 0 (0) 1 (2.4) 30 mg daily 0 0\n\n\n\nTG 107 \n\n\n\n(100%)\n\n\n\nNA 105 \n\n\n\n(98.1)\n\n\n\n2 (1.9) Overall 105 \n\n\n\n(98.1)\n\n\n\n2 (1.9) Overall 105 \n\n\n\n(98.1)\n\n\n\n2 (1.9)\n\n\n\n10 mg daily 77 \n\n\n\n(73.3)\n\n\n\n1 (50) 10 mg daily 87(82.9) 1(50)\n\n\n\n20 mg daily 27 \n\n\n\n(25.7)\n\n\n\n1 (50) 20 mg daily 18(17.1) 1(50)\n\n\n\n30 mg daily 1 (1) 0 30 mg daily 0 0\n\n\n\nLDL 37 \n\n\n\n(34.6%)\n\n\n\n70 (65.4) * 25 (23.4) 82 (76.6) * Overall 20 \n\n\n\n(18.7)\n\n\n\n87 (81.3) * Overall 20 \n\n\n\n(18.7)\n\n\n\n87 (81.3) *\n\n\n\n10 mg daily 16 (80) 62 (71.3) 10 mg daily 17(85) 71(82)\n\n\n\n20 mg daily 4 (20) 24 (27.6) 20 mg daily 3(15) 16(18.4)\n\n\n\n30 mg daily 0 1 (1.1) 30 mg daily 0 0\n\n\n\nHDL 28 \n\n\n\n(26.2%)\n\n\n\n79 (73.8) 24 (22.4) 83 (77.6) Overall 26 \n\n\n\n(24.3)\n\n\n\n81 (85.7) Overall 26 \n\n\n\n(24.3)\n\n\n\n81 (75.7)\n\n\n\n10 mg daily 20 \n\n\n\n(76.9)\n\n\n\n58 (71.6) 10 mg daily 22 \n\n\n\n(84.6)\n\n\n\n66 (81.5)\n\n\n\n20 mg daily 6 (23.1) 22 (27.2) 20 mg daily 4 (15.4) 15 (1.2)\n\n\n\n30 mg daily 0 (0) 1 (1.2) 30 mg daily 0 (0) 0 (0)\n\n\n\nALT 105 \n\n\n\n(98.1)\n\n\n\n2 (1.9) 112 \n\n\n\n(95.3)\n\n\n\n5 (4.7) Overall 100 \n\n\n\n(93.5)\n\n\n\n7 (6.5) Overall 100 \n\n\n\n(93.5)\n\n\n\n7 (6.5)\n\n\n\n10 mg daily 73 (73) 5 (71.4) 10 mg daily 82 (82) 6 (85.7)\n\n\n\n20 mg daily 26 (26) 2 (28.6) 20 mg daily 18 (18) 1 (14.3)\n\n\n\n30 mg daily 1 (1) 0 (0) 30 mg daily 0 (0) 0 (0)\n\n\n\nAST 106 \n\n\n\n(99.1)\n\n\n\n1 (0.9) 116 \n\n\n\n(99.1)\n\n\n\n1 (0.9) Overall 106 \n\n\n\n(99.1)\n\n\n\n1 (0.9) Overall 106 \n\n\n\n(99.1)\n\n\n\n1 (0.9)\n\n\n\n10 mg daily 77 \n\n\n\n(72.6)\n\n\n\n1 (100) 10 mg daily 87 \n\n\n\n(82.1)\n\n\n\n1 (100)\n\n\n\n20 mg daily 28 \n\n\n\n(26.4)\n\n\n\n0 (0) 20 mg daily 19 \n\n\n\n(17.9)\n\n\n\n0 (0)\n\n\n\n30 mg daily 1 (1) 0 (0) 30 mg daily 0 (0) 0 (0)\n*Statistically significant increase in the incidence of abnormal level of LDL at 6th month compared with baseline\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4822\n\n\n\nDiscussion\nOur study explored the changes in liver enzymes \n(AST and ALT) and lipid profile (total cholesterol, \nTG, LDL, and HDL) during typical treatment \nwith oral isotretinoin over a six-month period. \nThis study showed a statistically significant \nincrease in total cholesterol, LDL, TG, and liver \ntransaminases (ALT and AST). Liver enzymes \nwere less affected by isotretinoin therapy than \nlipid profiles. No significant changes were \nobserved in HDL. Several studies evaluating \nthe effects of isotretinoin on liver enzymes and \nlipids suggest that oral isotretinoin may cause \nchanges to varying degrees, alterations in liver \ntransaminases (AST and ALT), and lipid profiles \n(particularly TG, LDL, and total cholesterol).1,4 \nMany studies suggest that isotretinoin use is \nassociated with increases in TG and LDL and \ndecreases in HDL levels.8,10,14\n\n\n\nZane et al. studied 13,772 patients with acne \nwho received oral isotretinoin therapy between \n1995 and 2002. They reported a cumulative \nincidence of new abnormalities in patients with \n\n\n\nnormal baseline values with a frequency of \n44% for TG, 31% for total cholesterol levels, \nand 11% for transaminase levels. Moreover, \nthese abnormalities were generally transient \nand reversible.11 Most studies show a moderate \nincrease in serum lipids (but a decrease in HDL) \nin a minority of patients, usually occurring \nat baseline and plateauing or declining in \nsubsequent weeks.15\n\n\n\nOur study supports these findings. However, \nthis study is limited to observation of treatment \nover a 6-month period, so the subsequent \nconsequences of abnormalities in test results \nat the end of treatment could not be evaluated. \nInterestingly, most abnormalities were observed \nin the first 3 months of treatment, with no \nfurther changes toward the end of treatment. \nOf the study participants with abnormal \nresults, almost all had grade 1 abnormalities in \nboth lipids and liver transaminases (based on \nCTCAE grading). Only one patient developed \na grade 2 abnormality at ALT, which required \ntreatment discontinuation. The abnormalities \n\n\n\n11 \n \n\n\n\nFigure 1. Correlation between baseline lipid profile and liver transaminase with BMI 3 \n\n\n\n 4 \n\n\n\n 5 \n\n\n\n 6 \n\n\n\n 7 \n\n\n\nTotal cholesterol Triglycerides LDL \n\n\n\n\n\n\n\nr2=0.07, p=0.22 \n \n\n\n\nr2=0.101, p=0.136 \n \n\n\n\nr2=0.086, p=0.175 \n\n\n\nHDL ALT AST \n\n\n\n \nr2=-0.26, p=0.01 \n\n\n\n \nr2=0.383, p=7.9X10-06 \n\n\n\n \nr2=0.125, p=0.09 \n\n\n\nFigure 1. Correlation between baseline lipid profile and liver transaminase with BMI\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 23\n\n\n\nin this cohort were generally mild and did not \nrequire treatment interruption.\n\n\n\nAlthough many studies have reported significant \nchanges in total cholesterol and TG and liver \ntransaminases, other studies have reported that \nthese adverse effects are minimal and do not \naffect the course of treatment.17 Alcalay et al \nstudied 907 patients who had completed five \nto nine months of treatment. They reported that \nonly 1.5% of patients had serum TG levels above \n400 mg/dL. Serum levels of liver enzymes were \nnot sufficiently elevated to a degree necessitating \ndiscontinuation of treatment.18 In addition, \nBrito et al conducted a prospective clinical and \nlaboratory evaluation of 150 patients treated with \noral isotretinoin before initiation of therapy, one \nmonth after initiation, and every three months \nthereafter until completion of treatment. They \nfound no statistically significant changes in \nliver transaminases, TG, or cholesterol levels.1 \nIn another study of 30 participants, Baxter et \nal also reported no significant changes in TG \nor cholesterol levels measured at baseline or \nduring.19\n\n\n\nAll our patients received an isotretinoin dose \nof 0.2-0.4 mg/kg, with 89.2% (n=107) of the \npatients receiving an isotretinoin dose of 10 mg \nat baseline. In approximately 42% of the study \nparticipants, the dose was increased during \nthe first 3 months of treatment. A statistically \nsignificant increase in abnormal LDL levels \n(p<0.05) from baseline to follow-up at month 6 \nwas observed in most participants who received \na 10 mg dose at baseline. Increasing trends \nin the occurrence of abnormalities were also \nobserved for total cholesterol, TGs, HDL, ALT, \nand AST, but these were not significant. The \nlow isotretinoin dose used for clinical treatment \nin this cohort may be a contributing factor to the \nmild biochemical changes and better tolerability \nin patients. A study by Bettoli et al. showed \nthat a low initial dose of 0.1-0.2 mg/kg/day, or \nabout 10 mg daily, and a gradual increase to \nthe highest dose tolerated by the patient, is a \nsuccessful way to achieve good clinical results \nwhile minimizing side effects compared with a \nstandard dose of 0.5 mg/kg/day.20\n\n\n\nApproximately 27.5%, 79%, and 74% of \nstudy participants had abnormal baseline total \ncholesterol, LDL, and HDL, respectively. Our \ndata showed that 30% of the study participants \nfell into the overweight and obese category \n(BMI). This study was conducted during the \nCovid pandemic, in which most people had \na sedentary lifestyle compared with the pre-\npandemic period. This may have contributed \nto the unhealthy BMI and lipid abnormalities \nat baseline. However, changes in BMI and its \ncorrelation with blood levels were not studied \nduring the six-month follow-up period. These \nparticipants also had a negative correlation \nbetween BMI and HDL (the higher the BMI, \nthe lower the HDL). Significantly low HDL \nlevels accompanied by high LDL levels and an \nunhealthy BMI at baseline suggest a potential \nrisk for metabolic syndrome and cardiovascular \ndisease. A positive correlation between BMI \nand ALT in this study may indicate the risk of \nfatty liver in participants. Close monitoring of \nlipid profile and liver enzyme parameters is \nparticularly important in patients at high risk of \ndeveloping metabolic syndrome.\n\n\n\nAlthough our study demonstrated statistically \nsignificant increases in total cholesterol, \nLDL, TG, ALT, and AST, they are clinically \ninsignificant as low-dose isotretinoin was well \ntolerated by the study participants. Nevertheless, \nlipid profiling and liver function tests should \nbe routinely performed in all patients starting \ntreatment with isotretinoin. This should be \nfollowed by repeat blood testing after two \nmonths. If repeat test results are normal after \ntwo months, further laboratory monitoring may \nnot be necessary. If abnormalities are present, \nor a higher dose adjustment is required, more \nfrequent monitoring is recommended.\n\n\n\nLimitations\nLow-dose isotretinoin was used in this study \nwith most patients receiving 0.2-0.3 mg/kg.  \nThis may explain the mild changes observed in \nliver transaminases and lipid panels. This study \nwas conducted in the Klang Valley area only, \nhence the results may not represent the whole \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4824\n\n\n\npopulation of Malaysia.\n\n\n\nConclusion\nLow-dose isotretinoin therapy for acne may \ncause mild and non-progressive elevation of \nLDL, total cholesterol, and liver transaminases \nwhich do not require the withdrawal of treatment \nin most cases. \n\n\n\nConflict of Interest Declaration \nThe author have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for the permission \nto publish this paper.\n\n\n\nReferences\n1. Brito Mde F, Sant\u2019Anna IP, Galindo JC, Rosendo LH, \n\n\n\nSantos JB. Evaluation of clinical adverse effects and \nlaboratory alterations in patients with acne vulgaris treated \nwith oral isotretinoin. Dermatologia 2010;85:331-7.\n\n\n\n2. Malaysia Health and Technology Assessment Section \nof the Ministry of Health (MaHTAS) Clinical Practice \nGuidelines of Acne: Available at http://www.dermatology.\norg.my/pdf/CPG%20-%20Management%20of%20\nAcne%202.pdf. Accessed on 18/6/22.\n\n\n\n3. K\u0131z\u0131lyel O, Metin MS, Elmas \u00d6F, \u00c7ay\u0131r Y, Aktas A. \nEffects of oral isotretinoin on lipids and liver enzymes in \nacne patients. Cutis 2014;94:234-8.\n\n\n\n4. Hanisah A, Omar K, Shah SA. Prevalence of acne and its \nimpact on the quality of life in school-aged adolescents in \nMalaysia.J Prim Health Care 2009;1:20.\n\n\n\n5. Tan JK, Bhate K. A global perspective on the epidemiology \nof acne. Br J Dermatol 2015;172:3-12.\n\n\n\n6. Muthupalaniappen L, Tan HC, Puah JW, Apipi M, \nSohaimi AE, Mahat NF et al. Acne prevalence, severity, \nand risk factors among medical students in Malaysia. Clin \nTer 2014;165:187-92.\n\n\n\n7. Vieira AS, Beijamini V, Melchiors AC. The effect of \nisotretinoin on triglycerides and liver aminotransferases. \nAn Bras Dermatol 2012;87:382-7.\n\n\n\n8. Dalziel K, Barton S, Marks R. The effects of isotretinoin \non follicular and sebaceous gland differentiation. Br J \nDermatol 1987;117:317-23.\n\n\n\n9. Draghici CC, Miulescu RG, Petca RC, Petca A, \nDumitra\u0219cu MC, \u0218andru F. Teratogenic effect of \nisotretinoin in both fertile females and males (Review). \nExp Ther Med 2021;21:534.\n\n\n\n10. Al Haddab M, Alhuqayl A, Alsharif H. Results of \nlaboratory monitoring in patients taking isotretinoin for \nacne. Cutis 2021;108:43-5.\n\n\n\n11. Zane LT, Leyden WA, Marqueling AL, Manos MM. A \npopulation-based analysis of laboratory abnormalities \n\n\n\nduring isotretinoin therapy for acne vulgaris. Arch \nDermatol 2006;142:1016-22.\n\n\n\n12. Bershad S, Rubinstein A, Paterniti JR, Le NA, Poliak S, \nHeller B et al. Changes in Plasma Lipids and Lipoproteins \nduring Isotretinoin Therapy for Acne. N Engl J Med \n1985;313:981-5. \n\n\n\n13. Lee JS, Chang PY, Zhang Y, Kizer JR, Best LG, Howard \nBV. Triglyceride and HDL-C dyslipidemia and risks of \ncoronary heart disease and ischemic stroke by glycemic \ndysregulation status: The strong heart study. Diabetes \nCare 2017;40:529-37. \n\n\n\n14. Atiq MU, Raza A, Ashfaq A. Idiosyncratic reaction \ncausing a rare side effect: Isotretinoin-induced pancreatitis. \nCureus 2019;11:e6102. doi:10.7759/cureus.6102.\n\n\n\n15. Lee YH, Scharnitz TP, Muscat J, Chen A, Gupta-Elera \nG, Kirby JS. Laboratory monitoring during isotretinoin \ntherapy for acne. JAMA Dermatol 2016;152:35-44.\n\n\n\n16. National Cancer Institute. Common Terminology Criteria \nfor Adverse Events v3.0 (CTCAE). Bethesda, Md: \nNational Cancer Institute; 2003.\n\n\n\n17. Marsden JR, Trinick TR, Laker MF, Shuster S. Effects \nof isotretinoin on serum lipids and lipoproteins, liver and \nthyroid function. Clin Chim Acta 1984;143:243-51.\n\n\n\n18. Alcalay J, Landau M, Zucker A. Analysis of laboratory \ndata in acne patients treated with isotretinoin: is there \nreally a need to perform routine laboratory tests?. J \nDermatol Treat 2001;12:9-12.\n\n\n\n19. Baxter KF, Ling TC, Barth JH, Cunliffe WJ. Retrospective \nsurvey of serum lipids in patients receiving more \nthan three courses of isotretinoin. J Dermatolog Treat \n2003;14:216-8.\n\n\n\n20. Bettoli V, Guerra-Tapia A, Herane MI, Piquero-Mart\u00edn \nJ. Challenges and solutions in oral isotretinoin in acne: \nReflections on 35 years of experience. Clin Cosmet \nInvestig Dermatol  2019;12:943-51.\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 25\n\n\n\nORIGINAL ARTICLE\n\n\n\nImpact  of  Psoriasis  on  Quality  of  Life  of  Family  Members  and  Its \nAssociation with Anxiety and Depression \n\n\n\nSiu Bee Wong, MRCP, Teeba Raja, AdvMDerm, Tze Yuen Teoh, AdvMDerm\nDepartment of Dermatology, Selayang Hospital, Ministry of Health, Malaysia \n\n\n\nAbstract\nBackground\nPsoriasis is a chronic immune-mediated, multisystem inflammatory skin disease that can profoundly impact the \nquality of life (QoL) of both patients and their families. This study aimed to analyse the impact of psoriasis on \nthe QoL of  patients\u2019 family members and its association with anxiety and depression. \n\n\n\nMethods\nThis was a cross-sectional study which had a total of 240 subjects (80 patients, 80 family members, and 80 \nhealthy controls). The Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate the QoL of \npatients, and the Family Dermatology Life Quality Index (FDLQI) questionnaire was used to assess the QoL \nof family members. In addition, the Hospital Anxiety and Depression Scale (HADS) was used to evaluate the \nstate of anxiety or depression of all subjects, including the healthy controls.\n\n\n\nResults\nUp to 82.5% of family members of psoriasis patients had impaired QoL (FDLQI \u22652). The mean DLQI was \n8.89\u00b17.58, whereas the mean FDLQI scores was 7.58\u00b16.09, showing the considerable impact of psoriasis on \nboth patients and family members\u2019 quality of life. There was a positive correlation between family members\u2019 \nQoL with patients\u2019 anxiety (rs=0.348; p=0.002) and depression (rs=0.276; p=0.013) level. However, no \nassociation was found between family members\u2019 QoL with patients\u2019 psoriasis severity (rs=0.173; p=0.126) \nand  the DLQI scores (rs=0.137; p=0.224). Based on the HADS, the mean anxiety scores was 5.29\u00b14.07 and \nthe mean depression scores was 4.54\u00b14.20 for family members. An anxiety disorder was suggested in  32.5%, \nwhile depression was suggested in 23.8% of family members. \n\n\n\nConclusion\nPsoriasis has a significant impact on both patients and their family members, who experienced \nimpairment of their QoL and higher levels of anxiety and depression. \n\n\n\nKey words: DLQI; FDLQI; HADS; psoriasis; quality of life\n\n\n\nCorresponding Author\nDr Wong Siu Bee\nDepartment of Dermatology, \nSelayang Hospital,\nB21, Lebuhraya Selayang-Kepong, \n68100, Batu Caves, Selangor, Malaysia  \nEmail: helensbwong@gmail.com\n\n\n\nIntroduction\nPsoriasis is a chronic, immune-mediated, \nmultisystem inflammatory disease with \nvariable prevalence among populations, \naffecting between 0.5 to 11.4 percent among \nadults.1-3 It is characterised by well-demarcated \nerythematous and scaly papules and plaques \nthat are usually accompanied by burning \nsensation, pain and itching. Patients with \ndisfiguring psoriasis plaques over visible or \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4826\n\n\n\nsensitive areas of the body, may encounter a \nhigh level of  stigmatisation, social isolation \nand psychological distress.4-6 This substantially \ncompromise their social functioning, personal \nrelationship, work, daily activities, and health-\nrelated quality of life (QoL), especially in those \nwith moderate-to-severe disease.7 \n\n\n\nFurthermore, the negative impact of psoriasis \nhas been shown to extend beyond the patients \ninto their families. Family members often \nexperience physical and mental exhaustion, \nsocial disruption, marital problems and \nfinancial implications in their lives due to the \nchronic nature of psoriasis.8 Numerous studies \nhave examined the influence of psoriasis on \nthe quality of life and psychosocial health of \npatients.9-12 However, the studies that have \nanalysed the secondary impact on individuals \nliving with psoriatic patients are limited.13-18 \n\n\n\nThere was a higher level of anxiety and \ndepression among individuals living with \npsoriatic patients. Research studies had shown \nthat the severity of psoriasis disease was not \nthe main factor that contributed to the mental \nimpairment among family members.19 Instead, \nthe extent of their psychological distress was \nmainly related to the level of psychological \ndistress of the patients.13-14 Family quality of \nlife and psychosocial health is considered an \nessential factor in patient management and \nshould be analysed additionally to the quality \nof life of the patients.13 Nevertheless, clinicians \nusually overlook this for various reasons, \nincluding time limitation and difficulty in \nassessing it. Data on the impact of psoriasis on \nthe quality of life of their family members in \nMalaysia was also not well-established, and it \nhas not received much attention yet.  \n\n\n\nTherefore, this study aimed to analyse the \nimpact of psoriasis on the quality of life of \nfamily members of psoriatic patients, to assess \nthe potentially related factors and to explore the \nimpact of psoriasis on family members\u2019 mental \nhealth. \n\n\n\nMaterials and Methods\nStudy Design and Subject Selection \nThis was a cross-sectional, questionnaire-\nbased study conducted at the dermatology \nclinic in Selayang Hospital, Malaysia, from \nJune 2020 to January 2021. We analysed three \ngroups: patients with psoriasis, patients\u2019 family \nmembers, and healthy controls. \n\n\n\nPatients \nMale and female patients were eligible for this \nstudy if they met the following criteria: aged \n18 years old and above, could give informed \nconsent and had a clinical diagnosis of plaque \npsoriasis for at least 6 months. Patients were \nexcluded if they had another dermatological \ndisease, severe medical or psychiatric disorders \nthat might influence their judgment or QoL. \n\n\n\nFamily members  \nFamily members enrolled in this study were \nusually first degree relatives aged 18 years old or \nolder, who were the main caregivers and stayed \nwith patients for the past year. Most patients \nhad a single caregiver. However, in the event of \nmultiple caregivers, one of them was randomly \nselected for the study. Family members with \ndermatological diseases, severe medical or \npsychiatric disorders that might influence their \njudgment or QoL were excluded.\n\n\n\nHealthy controls \nControls were healthy subjects with no personal \nor family history of psoriasis (in a first-degree \nrelative) or other dermatological diseases. \nAlso, they were age-and-sex matched to \nfamily members. They were mainly healthcare \nstaffs or their family members. They were \nexcluded if they had other medical illnesses and \npsychological problems, that might influence \ntheir overall psychological health. \n\n\n\nStudy Procedures \nPatients who were clinically diagnosed with \nplaque psoriasis were approached along with \na family member. The detailed information \nregarding the study was given by the clinical \ninvestigators. Eligible patients\u2019 medical records \nwere reviewed by investigators to verify the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 27\n\n\n\ndiagnosis of psoriasis and duration of disease. \nAfter consent, each subject\u2019s demographics, \nincluding age, sex, occupation, marital status, and \nlevel of education were gathered and recorded.  \nThis step was followed by an assessment of \ndisease severity by using the psoriasis area and \nseverity index (PASI). The impact of psoriasis \non the QoL of the patients was determined by \nusing the 10-item Dermatology Life Quality \nIndex (DLQI). The impact of psoriasis on the \nQoL of family members was measured with \nthe Family Dermatology Life Quality Index \n(FDLQI).  The Hospital Anxiety Depression \nScale (HADS) was used to evaluate the state of \nanxiety or depression of all subjects, including \nthe healthy controls.\n\n\n\nDisease Severity Assessment\nPsoriasis area and severity index(PASI)  \nThe PASI was used to measure of the physical \nseverity of psoriasis. Skin lesions are graded \nbased on the extent and character of psoriasis \n(i.e. erythema, induration, and scaling) and \nprovides a severity score ranging from 0 to 72.20-\n\n\n\n21 A score of  less than 10 suggest mild psoriasis, \nwhile 10-20 and >20 indicating moderate \npsoriasis and severe psoriasis, respectively. \n\n\n\nQuality of Life Instruments \nDermatology Life Quality Index (DLQI)\nThe DLQI is a 10-item questionnaire validated \nto evaluate the health-related quality of \nlife  of adult patients suffering from skin \ndiseases.22-24 Published in 1994, the DLQI was \nthe first dermatology-specific quality of life \nquestionnaire. This questionnaire asks about \nthe impact of skin disease on symptoms, self-\nperception, shopping, clothing choice, social \nactivity, physical activity, working/studying, \npersonal relationships, sexual functioning, and \ntreatment. With this questionnaire, patients \ndefine how much their skin disease has affected \ntheir life,  with the scoring for each item ranging \nfrom \u201cnot at all\u201d to \u201cvery much\u201d. Each response is \nscored on a scale from 0 to 3. Then, the numbers \nare summed to obtain the total score out of 30 \npoints. A greater DLQI score indicates a greater \nquality of life impairment. Therefore, the DLQI \npunctuation is interpreted as 0\u20131=no effect at \n\n\n\nall; 2\u20135=small effect; 6\u201310=moderate effect; \n11\u201320=very large effect; and 21\u201330=extremely \nlarge effect.\n\n\n\nFamily Dermatology Life Quality Index \n(FDLQI)\nThe FDLQI is a dermatology-specific \nquestionnaire designed for the family members \nof patients with any skin disease.25 It measures \nthe adverse impact on the health-related QoL \nof family members. The FDLQI consists of 10 \nitems with possible answers on a 4-point scale: \nnot at all/not applicable, a little, quite a lot, and \nvery much. The items concern the impact of \na patient\u2019s skin disease on different aspects of \nthe family caregivers\u2019 QoL (i.e. emotional and \nphysical wellbeing, relationships, social life, \nleisure activities, burden of care, impact on job/\nstudy, housework, and expenditure). The scores \nof individual items (0\u20133) are added to give \na total score that ranges from 0 to 30. Higher \ntotal FDLQI scores indicate greater impairment \nof the family member\u2019s quality of life and vice \nversa. FDLQI could be interpreted similarly to \nDLQI: 0\u20131=no effect at all; 2\u20135=small effect; \n6\u201310=moderate effect; 11\u201320 =very large effect; \nand 21\u201330=extremely large effect.\n\n\n\nHospital Anxiety Depression Scale (HADS)\nThe HADS is a validated instrument for \nscreening of depression and anxiety.26-27  This \nquestionnaire consists of seven questions in \neach sub-scale of anxiety and depression. The \nitems are scored on a four-point scale from zero \n(not present) to three (severe). The item scores \nare then summed,  giving sub-scale scores on \nthe HADS-A and the HADS-D from 0 to 21. A \nlower score indicates less severity and vice versa. \nScores consistent with anxiety or depression are \neach defined by subscale scores of 8 or greater, \nand categorised as normal (score of 0-7), mild \n(score of 8-10), moderate (score of 11-14), and \nsevere (score of 15-21). Several researchers \nhave explored HADS data to establish the cut-\noff points for caseness of anxiety or depression. \nFor example, Bjelland et al. (2002)28, through a \nliterature review of a large number of studies, \nidentified a cut-off point of 8/21 for anxiety or \ndepression. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4828\n\n\n\nFor anxiety (HADS-A), this gave a specificity \nof 0.78 and a sensitivity of 0.9. For depression \n(HADS-D), this gave a specificity of 0.79 and a \nsensitivity of 0.83. Importantly, HADS has been \nvalidated for use in a range of different languages \nand conditions.28-29 This study utilised both \nEnglish and translated Malay versions of the \noriginal tool. The translated Malay version of \nHADS showed good sensitivity and specificity \n(sensitivity 90.0% and specificity 86.2% for \nanxiety; sensitivity 93.2% and specificity \n90.8% for depression) and, therefore, is a valid \ninstrument for use in the Malaysian population.29\n\n\n\nStudy Analysis \nStatistical analyses were performed using \nStatistical Package for Social Sciences version \n26 (SPSS, IBM Corporation, Chicago, IL, USA). \nDescriptive statistics for continuous variables \nwere expressed as mean\u00b1standard deviation \nwhile categorical variables as frequencies and \npercentages. Comparisons involving categorical \ndata were performed using the chi-square test. \nThe significance of differences was assessed \nusing independent-samples t-test for continuous \ndata in the univariate analysis when normality \nand equal variance assumptions were satisfied.  \nOne-way analysis of variance (ANOVA) with \na post hoc analysis was used to determine \nsignificance between three or more groups. \nAssociations between continuous variables \nwere analysed using the Spearman coefficient of \nrank correlation (rs). Particularly, the correlation \ncoefficient between 0.1 and 0.25 was considered \nlow, while the value between 0.26 and 0.5 was \nconsidered moderate, and those over 0.5 were \nconsidered high. A multivariate analysis was \ncarried out using multiple linear regression to \ndetermine the independent associated factors of \nFDLQI. Statistical significance was set at p<.05.\n\n\n\nEthical Approval\nThis study was registered with the National \nMedical Research Registry (NMRR-19-4047-\n51235). Ethical approval for the study was \nobtained from the Medical Research and Ethics \nCommittee, Ministry of Health, Malaysia. \n\n\n\nResults \nDemographic Characteristics \nA total of 240 subjects were enrolled in this \nstudy (i.e. 80 patients with psoriasis, 80 \nfamily members and 80 healthy controls). The \ndemographic characteristics of study subjects \nare shown in Table 1. The mean age of patients \nwas 44.09\u00b114.2 years, and 48 patients (60%) \nwere men. Forty-nine patients (61.3%) had mild \ndisease, 23 patients (28.7%) with moderate \ndisease and 8 patients (10%) had severe disease \nbased on PASI scores. Their mean PASI score \nwas 8.18\u00b18.79. \n\n\n\nClinical characteristics of patients with \npsoriasis are presented in Table 2.  More than \nhalf of patients had scalp (82.5%) and nails \n(78.8%) involvement. Thirty-eight (47.5%) \npatients had joints involvement, and only 6 \n(7.5%) patients had genital involvement. The \nmean age of family members was 42.66\u00b112.5, \nranging from 20 to 73 years. Twenty-eight \n(35%) family members were men, and 52 (65%) \nwere women. Most of the family members were \nmarried (81.2%), employed (66.3%)  and with \nsecondary educational level (61.3%). There \nwere 80 healthy controls, where there were \nwith 27 males and 52 females with a mean \nage of 43.00\u00b112.69. There were no significant \ndifferences among the groups with regard to age \n(p=0.774) and ethnicity (p=0.109).\n\n\n\nDLQI\nThe mean DLQI score was 8.89\u00b17.58, with a \nrange of 0 to 29 in patients. As shown in Figure \n1,  a total of 29 (36.3%) patients had a DLQI \nscore of more than 10, indicating psoriasis had \na very large to extremely large effect on their \nQoL. There were 14 (17.5%) psoriatic patients \nwho reported psoriasis had a moderate effect on \ntheir QoL, while 25 (31.3%) patients reported \npsoriasis had a small effect on their quality \nof life. There was no statistically significant \nrelationship between DLQI and  patients\u2019 age, \nsex, ethnicity, marital status, education level, \noccupation, and disease severity (Table 3). \nAlthough the DLQI score was higher in patients \nwith severe disease and those with joints \ninvolvement, the difference was not statistically \nsignificant (p>0.05).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 29\n\n\n\nTable 1. Demographic characteristics of 240 study \nsubjects\n\n\n\nDemographic Patients,\nn=80\n\n\n\nFamily \nmembers, \n\n\n\nn=80\n\n\n\nHealthy \ncontrols, \n\n\n\nn=80\n\n\n\np-value\n\n\n\nMean\u00b1SD \nor n (%)\n\n\n\nMean\u00b1SD \nor n (%)\n\n\n\nMean\u00b1SD \nor n (%)\n\n\n\nAge (years)\nAge range\n\n\n\n44.09\u00b114.2\n(18-78)\n\n\n\n42.66\u00b112.5\n(20-73)\n\n\n\n43.00\u00b112.7\n(22-72)\n\n\n\n0.774a\n\n\n\nSex \n\n\n\nMale 48 (60) 28 (35) 27 (33.8) 0.001b\n\n\n\nFemale 32 (40) 52 (65) 53 (66.3)\n\n\n\nEthnicity\n\n\n\nMalay 45 (56.2) 45 (56.3) 44 (55.0) 0.109b\n\n\n\nChinese 23 (28.7) 23 (28.7) 28 (35.0)\n\n\n\nIndian 9 (11.3) 9 (11.3) 7 (8.8)\n\n\n\nOther ethnics \nminorities\n\n\n\n3 (3.75) 3 (3.75) 1 (1.3)\n\n\n\nMarital status \n\n\n\nSingle 23 (28.7) 15 (18.8) 36 (45.0) 0.004b\n\n\n\nMarried 57 (71.3) 65 (81.2) 43 (53.8)\n\n\n\nDivorced 0 (0) 0 (0) 1 (1.3)\n\n\n\nEducation\n\n\n\nPrimary 4 (5) 5 (6.3) 2 (2.5) <0.001b\n\n\n\nSecondary 52 (65) 49 (61.3) 8 (10.0)\n\n\n\nTertiary 24 (30) 25 (31.3) 70 (87.5)\n\n\n\nIlliterate 0 (0) 1 (1.3) 0 (0)\n\n\n\nOccupation \n\n\n\nEmployed 58 (72.5) 53 (66.3) 79 (98.8) <0.001b\n\n\n\nUnemployed 22 (27.5) 27 (33.8) 1 (1.2)\naANOVA; bChi-Square test; SD: Standard deviation \n\n\n\nTable 2. Clinical characteristics of psoriatic \npatients (n=80)\n\n\n\nVariables Patients,  n (%)\n\n\n\nPASI \n\n\n\n    Mild ( <10) 49 (61.3)\n\n\n\n    Moderate (10-20) 23 (28.7)\n\n\n\n    Severe (>20) 8 (10.0)\n\n\n\nScalp involvement\n\n\n\n    Yes 66 (82.5)\n\n\n\n    No 14 (17.5)\n\n\n\nNails involvement \n\n\n\n    Yes 63 (78.8)\n\n\n\n    No 17 (21.2)\n\n\n\nJoints involvement \n\n\n\n    Yes 38 (47.5)\n\n\n\n    No 42 (52.5)\n\n\n\nGenital involvement \n\n\n\n    Yes 6 (7.5)\n\n\n\n    No 74 (92.5)\n\n\n\nMedical comorbidities\n\n\n\n   Yes 29 (36.2)\n\n\n\n   No  51(63.8)\n\n\n\nTable 3. DLQI and FDLQI scores related to \ndemographics and clinical parameters \n\n\n\nDLQI p-value FDLQI p-value\n\n\n\nMean\u00b1SD Mean\u00b1SD\n\n\n\nMeans 8.89\u00b17.58 7.58\u00b16.09\n\n\n\nAge(years)\n\n\n\nrs 0.104 0.359 0.035 0.760\n\n\n\nSex \n\n\n\nMale 9.71\u00b17.37 0.238a 6.82\u00b15.66 0.420a\n\n\n\nFemale 7.65\u00b17.85 7.98\u00b16.33\n\n\n\nEthnicity\n\n\n\nMalay 9.31\u00b17.96 0.256b 7.40\u00b16.24 0.978b\n\n\n\nChinese 8.22\u00b17.20 7.96\u00b16.79\n\n\n\nIndian 10.44\u00b17.58 7.22\u00b14.55\n\n\n\nOthers 3.00\u00b12.00 8.33\u00b14.04\n\n\n\nMarital status \n\n\n\nSingle 10.83\u00b19.02 0.064a 4.07\u00b12.94 <0.001a\n\n\n\nMarried 8.11\u00b16.85 8.38\u00b16.36\n\n\n\nEducation\n\n\n\nPrimary 6.75\u00b14.65 0.399b 3.20\u00b12.59 0.051b\n\n\n\nSecondary 8.85\u00b17.37 9.00\u00b16.69\n\n\n\nTertiary 9.33\u00b18.54 5.72\u00b14.44\n\n\n\nIlliterate - 6.00\u00b10.00\n\n\n\nOccupation \n\n\n\nEmployed 8.60\u00b17.14 0.590a 6.92\u00b15.71 0.183a\n\n\n\nNon-\nemployed \n\n\n\n9.64\u00b18.79 8.85\u00b16.72\n\n\n\nDisease \nseverity\n\n\n\nMild 8.51\u00b17.52 0.369b 6.86\u00b16.46 0.301b\n\n\n\nModerate 8.43\u00b16.94 8.14\u00b14.71\n\n\n\nSevere 12.50\u00b19.62 10.11\u00b16.85\n\n\n\nScalp involvement \n\n\n\nYes 8.89\u00b17.61 1.000a 7.85\u00b16.04 0.268a\n\n\n\nNo 8.89\u00b17.79 5.44\u00b16.44\n\n\n\nNail involvement \n\n\n\nYes 8.40\u00b17.40 0.268a 8.17\u00b16.03 0.090a\n\n\n\nNo 10.71\u00b18.23 5.35\u00b15.98\n\n\n\nJoint involvement \n\n\n\nYes 7.92\u00b16.41 0.281a 7.38\u00b15.48 0.771a\n\n\n\nNo 9.76\u00b18.48 7.78\u00b16.72\n\n\n\nGenital involvement \n\n\n\nYes 10.50\u00b16.47 0.591a 9.17\u00b16.11 0.509a\n\n\n\nNo 8.76\u00b17.69 7.45\u00b16.11\naIndependent T-test; bANOVA; rs: Spearman coefficient of rank \ncorrelation; SD: standard deviation\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4830\n\n\n\nFigure 1. Quality of life impairment among patients and family members based on DLQI and FDLQI scores   \n\n\n\nFDLQI \nUp to 82.5% of family members of psoriasis \npatients had impaired QoL(FDLQI \u22652). A total of \n42 (52.5%) family members reported an FDLQI \nscore of>6, indicating moderate to severe QoL \nimpairment as a result of psoriasis (Figure 1). \nThe mean FDLQI score of the family members \nwas 7.58\u00b16.09, and it ranged from minimal \nscore 0 to a maximum score of 27. We compared \nFDLQI scores with demographics and clinical \nparameters (Table 3). Married family members \nwere more affected than those who were single \n(8.38\u00b16.36 vs. 4.07\u00b12.94; p< 0.001). There was \n\n\n\nno statistically significant correlation between \nFDLQI scores with family members\u2019 age,  sex, \nethnicity, education level, and occupation. The \npresence of nails, scalp or genital psoriasis in \npatients did not significantly affect the mean \nFDLQI scores of family members (p>0.05). As \nshown in Figure 2, family members\u2019 QoL was \nmost highly affected in the aspect of emotion, \nthe burden of care, housework and extra \nhousehold expenditure. Social life and leisure \nactivities were the aspect of life that was least \naffected by psoriasis.\n\n\n\nFigure 2. Degree of impairment by psoriasis to quality of life based on Family Dermatology Life Quality Index \n(FDLQI) category in 80 family members\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 31\n\n\n\nThe FDLQI scores of family members did not \nshow statistical correlation with DLQI scores \n(rs=0.137; p=0.224) and psoriasis disease \nseverity (rs=0.173; p=0.126), as shown in Table \n4. However, there was a positive correlation \nbetween FDLQI scores with patients\u2019 anxiety \n(rs=0.348; p=0.002) and depression (rs=0.276; \np=0.013) level. Family members\u2019 QoL was \nstrongly correlated with their anxiety and \ndepression level (rs=0.505; p<0.001 and  \nrs=0.420; p<0.001, respectively) as shown \nin Table 4 and Figure 3.  The mean FDLQI \nscores  was higher among family members \nwith moderate to severe anxiety and depressive \nsymptoms. \n\n\n\nTable 4. Correlation between clinical features and  \nFamily Dermatology Life Quality Index (FDLQI) \nscores in family members \n\n\n\n FDLQI scores \n\n\n\nDLQI rs=0.137 p=0.224\n\n\n\nDisease severity(PASI) rs=0.173 p=0.126\n\n\n\nPatients\u2019 anxiety rs=0.348 p=0.002\n\n\n\nPatients\u2019 depression                  rs=0.276 p=0.013\n\n\n\nFamily members\u2019 anxiety rs=0.505 p<0.001\n\n\n\nFamily members\u2019 depression rs=0.420 p<0.001\n\n\n\nFigure 3. Mean FDLQI scores with different anxiety and depression levels in family members (n=80)\n\n\n\nMultivariate linear regression revealed an \nassociation between family members\u2019 anxiety \nand FDLQI scores, regardless of their age, sex, \neducational level, occupation, and depression \nlevel and the PASI and DLQI scores of the \npatients (standardised \u00df=0.453; p=0.001).\n\n\n\nTable 5. Multiple linear regression analysis of \nindependent predictors associated with Family \nDermatology Life Quality Index*\nPredictors Unstandardised \n\n\n\nB\nStandardised \nCoefficients \nBeta\n\n\n\nt p-value\n\n\n\nPatient\u2019s variables\n\n\n\nDLQI 0.051 0.063 0.641 0.523\n\n\n\nPASI 1.041 0.118 1.214 0.229\n\n\n\nFamily member\u2019s variables \n\n\n\nAge -0.029 -0.061 -0.593 0.555\n\n\n\nSex 0.283 0.022 0.213 0.832\n\n\n\nEducational \nlevel\n\n\n\n0.408 0.040 0.372 0.711\n\n\n\nOccupation 1.101 0.087 0.775 0.441\n\n\n\nAnxiety level 0.674 0.453 3.334 0.001\n\n\n\nDepression \nlevel\n\n\n\n0.207 0.143 1.013 0.315\n\n\n\nConstant -0.102 0.919\n*Dependent variable: Family Dermatology Life Quality Index, \nAdjusted R square=0.279 (p=0.001)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4832\n\n\n\nTable 6. Comparison of anxiety and depression among psoriasis patients, their family members and healthy \ncontrols (n =240)\nVariables Subjects Significant case n (%)a Mean\u00b1SD p-value Mean difference (95% CI)\n\n\n\nHADS-A Patients 32 (40.1) 6.25\u00b14.18 0.041 1.46 (0.02, 2.90)*\n\n\n\nFamily members 27 (33.8) 5.29\u00b14.07 0.50 (-0.94,1.94)*\n\n\n\nControls 26 (32.5) 4.79\u00b12.95  \n\n\n\nHADS-D Patients 29 (36.3) 5.45\u00b13.94 0.025 1.50 (0.09, 2.91) \u2020\n\n\n\nFamily members 19 (23.8) 4.54\u00b14.20 0.59 (-0.83,2.00)\u2020\n\n\n\nControls 12 (15.0) 3.93\u00b12.87\n\n\n\naSignificant case means a score of 8\u201321 for each subscale of HADS \np-value generated using the ANOVA test\n*Post-hoc analysis: Bonferroni test was applied. A significant difference (p< 0.05) was found between patients vs controls (p= 0.045), no significant difference \nwas found between patients vs family members (p= 0.324) and family members vs controls (p= 1.000)\n\u2020Post-hoc analysis: Bonferroni test was applied. A significant difference was found between patients vs controls (p= 0.034); no significant difference was found \nbetween patients vs family members (p=0.363) and family members vs controls (p= 0.953)\nSD: Standard deviation\n\n\n\nFigure 4. Bifurcation of subjects as normal, borderline abnormal or abnormal cases of anxiety in patients, \nfamily members and  healthy controls (n=240)\n\n\n\nAnxiety \nThe mean HADS anxiety scores (HADS-A) was \n6.25\u00b14.18 for patients, 5.29\u00b14.07 for family \nmembers, and 4.79\u00b12.95 for healthy controls, \nwith significant differences (p=0.041) being \ndetected among the groups (Table 5). Patients \nand family members had similar anxiety levels \n(p=0.324) and patients\u2019 anxiety level was \nsignificantly higher  than  the healthy controls \n(6.25 vs 4.79; p=0.045). However, no significant \ndifference was found between the anxiety level \nof family members and healthy controls based \n\n\n\non post-hoc analysis (p=1.000). \n\n\n\nThirty-two (40.1%) of the psoriatic patients had \na HADS-A score \u2265 8, whereas 27 (33.8%) of the \nfamily members had a HADS-A score \u22658, which \nis suggestive of anxiety disorder, as shown \nin Figure 4. Even though 26 (32.5%) healthy \ncontrols reported anxiety symptoms, but most \nof them only had mild symptoms (n=24).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 33\n\n\n\nFigure 5. Bifurcation of subjects as normal, borderline abnormal or abnormal cases, for depression in patients, \nfamily members and  healthy controls (n=240)\n\n\n\nTable 7. Correlation study (rs coefficient and \np-value) between family members\u2019 anxiety scores \nand other study variables: Psoriasis Area Severity \nIndex (PASI) and patients\u2019 anxiety and depression, \nand family members\u2019 depression scores\n\n\n\nFamily members\u2019 anxiety \nscores \n\n\n\nDisease severity(PASI) rs=0.128 p=0.256\n\n\n\nPatients\u2019 anxiety rs=0.414 p<0.001\n\n\n\nPatients\u2019 depression rs=0.359 p<0.001\n\n\n\nFamily members\u2019 \ndepression  rs=0.674 p<0.001\n\n\n\nThe anxiety level of family members was \ncorrelated to the patient\u2019s anxiety and depression \nlevel (rs=0.414; p<0.001 and rs=0.359; p<0.001, \nrespectively), as shown in Table 7. The anxiety \nlevel of family members was also strongly \ncorrelated with their own depression level \n(rs=0.674; p<0.001). However, no significant \ncorrelation was found between family members\u2019 \nanxiety level and the patient\u2019s psoriasis severity \n(rs=0.128; p=0.256).\n\n\n\nDepression \nThe mean depression scores (HADS-D) was \n5.45\u00b13.94 for patients, 4.54\u00b14.20 for family \nmembers, and 3.93\u00b12.87 for healthy controls, \n\n\n\nwith significant differences (p<0.001; Table 6) \ndetected among the groups. Depression levels \nwere similar between patients and family \nmembers (p=0.363). Patients\u2019 depression level \nwas significantly higher than the control group \n(5.45 vs 3.93; p=0.034), but there was no \nsignificant difference between the depression \nlevel of family members and the control group \nbased on post-hoc analysis (p=0.953). \n\n\n\nTwenty-nine (36.3%) psoriatic patients had \na depression score\u22658, and 19 (23.8%) family \nmembers had a depression score\u22658, which \nis suggestive of depression disorder. Twelve \n(15.0%) healthy controls reported depression \nscores \u22658, as shown in Figure 5.\n\n\n\nThe depression level of the family members had \na positive correlation with the patients\u2019 anxiety \nand  depression level (rs=0.430; p<0.001 and \nrs= 0.416, p<0.001, respectively; Table 8). \nAs expected, the depression level of family \nmembers was strongly correlated with their own \nanxiety level ((rs=0.674 ; p<0.001). However, \nno association found between family members\u2019 \ndepression level and psoriasis disease severity \n(rs=-0.004; p=970). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4834\n\n\n\nTable 8. Correlation of the family members\u2019 \ndepression score with patient\u2019s psoriasis area  severity \nindex (PASI) score and patient\u2019s psychological state\n\n\n\nFamily members\u2019 depression scores\n\n\n\nDisease \nseverity(PASI) rs=-0.004 p=0.970\n\n\n\nPatients\u2019 anxiety rs=0.430 p <0.001\n\n\n\nPatients\u2019 depression rs=0.416 p <0.001\n\n\n\nThe study subjects with a HADS-A or HADS-D \nscore\u22658 were informed, and with their \npermission, they were referred to a psychiatrist \nfor further assessment. \n\n\n\nDiscussion\nPsoriasis is associated with significant \npsychosocial morbidity and profoundly impacts \npatients\u2019 quality of life. The burden of disease \nis not limited to the patients but may extend to \nthe rest of the family. Therefore, family impact \ndata are potentially essential measurements of \nthe overall burden of skin disease. The impact \nof psoriasis on patients\u2019 quality of life in \nMalaysia has been reported previously,30-32 but \nonly limited data is available on the secondary \nimpact of psoriasis on close family members.  \n\n\n\nThe most important finding of this study is the \nconsiderable burden of psoriasis on the QoL \nof patients and their families. In this study, \nthe mean DLQI of patients was 8.89\u00b17.58,  \nwith one-third (36.3%) of the patients having \na DLQI score of more than 10, showing the \nconsiderable impact of the disease on patients\u2019 \nlife. This finding was similar to the 10-year \nreview of the Malaysian Psoriasis Registry,31 in \nwhich the mean DLQI was reported as 8.5\u00b16.6, \nwith 33.1% of the patients scoring more than 10. \nAnother local study on 223 patients,32 evaluating \nthe health-related QoL of psoriatic patients \nusing DLQI, also showed a similar finding with \n30% of the psoriatic patients experienced severe \nimpairment of QoL with a median DLQI of 7. \n\n\n\nThe present study results revealed that psoriasis \nhad significantly impaired the quality of life of  \nclose family members. A total of 42 (52.5% ) \n\n\n\nfamily members reported a moderate-to-severe \nimpairment in their QoL. The mean FDLQI \nscore of family members was 7.58\u00b16.09, with \n27.5% (n=22) of family members sustained \nsevere QoL impairment with a score of more \nthan 10. The most highly affected areas were \nthe emotional distress, the burden of care, \nhousework and extra household expenditure. \nEmotional impairment had been reported as the \nmost affected item in previous studies that based \non the FDLQI questionnaire.15,33 As expected, \nfamilies of patients with moderate to severe \npsoriasis based on PASI reported significantly \nhigher scores on the FDLQI compared to those \nwith mild psoriasis. A greater impact was also \nfound in married family members, implying \na potential negative effect of psoriasis on the \ncouple relationships. Patient sexual dysfunction \ngreatly impairs partners\u2019 quality of life.34 \nAccording to previous studies, after getting \npsoriasis, a reduction in the frequency of sexual \nintercourse occurred in more than 90% of the \nrelationship and 40% of psoriasis partners suffer \nfrom sexual dysfunction.35-36\n\n\n\nIn our study, no significant correlation could be \nfound between PASI and FDLQI scores of family \nmembers.  There was also no association found \nbetween PASI and the psychological state of both \npatients and family members. This observation \nsuggests that psychosocial distress and quality \nof life are not always proportional to the disease \nseverity. Instead, the degree of deterioration in \nthe quality of life of family members was more \nstrongly influenced by patients\u2019 psychological \ndistress. These findings were consistent with \nprevious studies that examine the impact of \npsoriasis on patients and families\u2019 lives.36-38 This \nmay be due to the pitfalls of the disease severity \nassessment tool i.e. PASI, which does not attach \nadditional importance to small, yet visible or \nsensitive body parts such as the face, hands and \ngenitals. Furthermore, psoriasis affects patients\u2019 \nperception of themselves and patients may still \nhave a significant psychosocial disability even \nwith limited skin disease.40  Psoriatic patients \nusually have an unfavourable self-perceptions \nwith lowered self-esteem and negative body \nimage. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 35\n\n\n\nThe presence of anxiety and depression has \nbeen established in patients with psoriasis. In \naddition, it has been reported that the point \nprevalence of mental disorders was higher in \npatients with psoriasis than in patients with other \ndermatological conditions.41-43 We discovered a \nsignificantly higher prevalence of moderate to \nsevere anxiety (18.8% vs. 2.5%) and depression \n(10.0% vs. 2.5%) among psoriatic patients \nthan controls. These findings were comparable \nwith a similar study using HADS for psoriatic \npatients in Singapore. In their research, 17% of \ntheir cohort of psoriatic patients had anxiety, \nand 15% had a depressive disorder with a score \nof more than 11.44 In comparison with another \nsimilar study by Bakar RS et al. in Malaysia45, \nour study had a higher prevalence of anxiety \n(40.1% vs 16.9%)) and  depression (36.3% \nvs 8.5%) among psoriatic patients based on \nthe cut-off point of 8 on HADS. These could \nbe possibly due to differences in the socio-\neconomic background of the study population, \nas our study was done in an urban population \nand the ongoing COVID-19  pandemic could \nalso be a contributing factor as well.  \n\n\n\nIn this study, the prevalence of family \nmembers with anxiety symptoms was 32.5% \nwith a HADS-A mean score of 5.29\u00b14.07, \nwhereas for depression, there were 23.75% \nof family members who had experienced \ndepressive symptoms with a HADS-D mean \nscore of 4.54\u00b14.20. It was comparable to \nthe control group, in which the prevalence of \nanxiety and depression was 25% and 21.25%, \nrespectively. However, most of the controls \nonly experienced mild anxiety and depressive \nsymptoms compared to the family members \nwho had higher percentages of moderate to \nsevere anxiety and depressive symptoms. \nThe prevalence of anxiety and depression \nof healthy controls was significantly higher \ncompared to the overall national prevalence of \ndepression and anxiety, which ranges between \n8 and 12%.46-49 This is probably due to the \nongoing COVID-19 pandemic. The emergence \nof the COVID-19 pandemic has negatively \naffected mental health either due to its direct \npsychological effects or long-term economic \n\n\n\nand social consequences.50-52 A substantial \nincrease in the prevalence and burden of major \ndepressive disorder and anxiety disorders as \na result of the COVID-19 pandemic has been \nreported.53 \n\n\n\nIt is crucial to identify psychiatric comorbidity \namong psoriasis patients and their family \nmembers as it would negatively affect the \nresponse to psoriasis treatment.53  Future studies \nare needed to determine the mechanism by \nwhich psoriasis is associated with depression, \nanxiety, and approaches to prevent such \nadverse outcomes in patients with psoriasis and \nfamilies. Our study results support the adoption \nof an integrated approach that recognises that \npsoriasis does not affect the patients alone. We \nshould treat the patient holistically, considering \nnot only the QoL and psychological health of \npatients, but it is also essential to ensure the \noverall well-being of their family members. \nMoreover, healthcare policy should consider not \nonly patients\u2019 needs but also their cohabitants.\n\n\n\nLimitations\nThis study was limited by its cross-sectional \ndesign, which allowed for correlation but \nno causation. Furthermore, the number of \nparticipants in our study was relatively small, \nand it was a single centre study that may not \nreflect the actual characteristic of the local \npopulation. Further studies with larger numbers \nof patients and cohabitants are needed before \nany comparisons can be made among groups \nof different psoriasis severity. In addition, \nmany patients included in this study had \nmild to moderate psoriasis, which could have \ndepreciated the results. Moreover, controls in \nthe present study were mainly healthcare staffs, \nwhose psychological stress might be higher \nthan that of the general population during the \nCOVID-19 pandemic.54 Assessing  the quality \nof life in healthcare settings is challenging, \nsince psychometric instruments can often not \naccurately translate the magnitude of the impact \nimposed by any disease on an individual\u2019s life. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4836\n\n\n\nConclusion\nIn summary, this study showed that psoriasis has \na profound impact on the QoL and psychological \nhealth of the patients and their family members. \nTherefore, healthcare professionals should \nadopt a comprehensive approach while \ntreating psoriasis patients, taking into account \nthe physical aspect and the quality of life and \npsychosocial health of both patients and their \nfamily members. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director-\nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nReferences\n1. Michalek IM, Loring B, John SM. A systematic review of \n\n\n\nworldwide epidemiology of psoriasis. J Eur Acad Dermatol \nVenereol 2017;31:205-12.\n\n\n\n2. Parisi R, Iskandar IYK, Kontopantelis E, Augustin M, \nGriffiths CEM, Ashcroft DM. Global Psoriasis Atlas. \nNational, regional, and worldwide epidemiology of \npsoriasis: systematic analysis and modelling study. Br J \nDermatol 2020;369:m1590.\n\n\n\n3. Springate DA, Parisi R, Kontopantelis E, Reeves D, Griffiths \nCE, Ashcroft DM. Incidence, prevalence and mortality of \npatients with psoriasis: a U.K. population-based cohort \nstudy. Br J Dermatol 2017;176:650-8.\n\n\n\n4. \u0141akuta P, Marcinkiewicz K, Bergler-Czop B, Brzezi\u0144ska-\nWcis\u0142o L, S\u0142omian A. Associations between site of skin \nlesions and depression, social anxiety, body-related \nemotions and feelings of stigmatisation in psoriasis patients. \nPostepy Dermatol Alergo 2018;35:60-6.\n\n\n\n5. 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Lancet 2021;398:1700-12.\n\n\n\n53. Fortune DG, Richards HL, Kirby B,  McElhone K, Markham \nT, Rogers S et al. Psychological distress impairs clearance of \npsoriasis in patients treated with photochemotherapy. Arch \nDermatol 2003;139:752-6.\n\n\n\n54. Salari N, Khazaie H, Hosseinian-Far A, Khaledi-Paveh \nB, Kazeminia M, Mohammadi M et al. The prevalence of \nstress, anxiety and depression within front-line healthcare \nworkers caring for COVID-19 patients: a systematic review \nand meta-regression. Hum Resour Health 2020;18:100.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4838\n\n\n\nORIGINAL ARTICLE\n\n\n\nEvaluation of Knowledge, Disease Severity and Quality of Life of Patients \nwith Psoriasis\n\n\n\nSiew Pei Gan1, BPharm, Athirah Binti Ahmad Latif1, BPharm, Huey Miin Cheah1, BPharm, Rajalingam \nRamalingam2, AdvMDerm\n\n\n\n1Department of Pharmacy, Hospital Sultan Haji Ahmad Shah, Pahang, Malaysia \n2Department of Dermatology, Hospital Tengku Ampuan Afzan, Pahang, Malaysia \n\n\n\nAbstract\nBackground\nPsoriasis vulgaris is a chronic immune-mediated inflammatory multi-system disease characterised by \nkeratinocyte hyperproliferation. Data regarding patients\u2019 disease severity, knowledge and quality of \nlife (QOL) is important to optimize treatment strategies for psoriasis. This study aims to evaluate and \ninvestigate the relationship between disease severity, knowledge and QOL of patients with psoriasis. \n\n\n\nMethods\nA cross-sectional multicentre study utilizing a socio-demographic data collection form, Psoriasis \nKnowledge Assessment Questionnaire (PKAQ), Dermatology Life Quality Index (DLQI) and Psoriasis \nArea and Severity Index (PASI was conducted. Correlations between PKAQ, DLQI and PASI were \nanalysed using Spearman\u2019s test. \n\n\n\nResults\nA total of 114 subjects participated in this study. Majority of them had mild psoriasis (n=73, 64%) \nbased on PASI. The mean score of PKAQ was fourteen out of a total possible score of twenty-five, \nwhereas the DLQI had a non-parametric distribution with a median (interquartile range) of 7 (10). \nMost subjects (32.5%) stated that psoriasis had a \u2018moderate effect\u2019 on their QOL, while only 3.5% said \nthat it had an \u2018extremely large effect\u2019 on their QOL. There was a statistically significant correlation \nbetween PASI and DLQI (rs = 0.264, p = 0.004), with higher PASI scores corresponding to higher \nDLQI scores. No statistically significant correlation was found between DLQI and PKAQ (rs= -0.048, \np= 0.612), and between PASI and PKAQ (rs= 0.058, p= 0.542). \n\n\n\nConclusion\nImpairment of QOL was positively associated with severity of psoriasis. However, there was no \nsignificant relationship between knowledge and quality of life, as well as between knowledge and \npsoriasis severity. \n\n\n\nKey words: Psoriasis, DLQI, PASI, quality of life, patient knowledge, Malaysia\n\n\n\nCorresponding Author\nCheah Huey Miin\nPharmacy Department, \nHospital Sultan Haji Ahmad Shah, \nJalan Maran, \n28000 Temerloh, Pahang, Malaysia\n\n\n\nEmail: hueymiin@moh.gov.my\n\n\n\nIntroduction\nPsoriasis vulgaris is a chronic immune-\nmediated inflammatory multi-system disease \ncharacterised by keratinocyte hyperproliferation \nand uncontrolled epidermal differentiation. \nPsoriasis is characterised by bilateral, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 39\n\n\n\nsymmetrical beefy-red plaques with thick, \nadherent silvery scales, often affecting nails and \njoints.1 The global prevalence of psoriasis is \nabout 2 to 3%,2 and men have a slightly higher \nincidence compared to women, with a ratio of \n1.3 to 1.3\n\n\n\nThe symptoms of psoriasis are highly variable \nwithin the population, with skin pain and \nredness being the primary reported symptoms.4 \nOther symptoms include desquamation (68%), \npruritus (41%), dry skin (40%) and erythema \n(30%). Although psoriasis is neither contagious \nnor curable, the symptoms can be well-\ncontrolled with a range of treatment modalities \nsuch as topical and systemic medication, as well \nas phototherapy.5\n\n\n\nIn addition to the unpleasant pain and itchy \nsensation, psoriasis can also negatively affect \none\u2019s physical, physiological, psychological \nand social wellbeing. With regards to the \nphysical and physiological wellbeing, psoriasis \nis associated with an increased prevalence \nof other chronic conditions such as obesity, \nhypertension, dyslipidemia and diabetes \nmellitus.3,6 In addition to that, the psychological \nand social wellbeing of patients with psoriasis \nare often compromised, with cases of depression \nand anxiety frequently reported among them.7 \nTo mitigate these issues, more information is \nrequired regarding disease severity, disease \nknowledge and quality of life (QOL). With \nbetter information, suitable interventions can \nbe planned to minimise the negative impacts of \npsoriasis on patients. \n\n\n\nPrevious studies identified a few predictors of \npoor QOL including young age, single status, \nactive employment, sport activity, extensive \npsoriatic lesions, psoriatic arthropathy and nail \ndystrophy.8,9 Despite many of the determinants \nbeing unavoidable, educational intervention was \nfound to be effective in improving QOL. Azmi \net al.10 demonstrated a significant improvement \nin QOL based on the Dermatology Life Quality \nIndex (DLQI) scores [8.64(5.66) vs 5.60(5.35), \n95% CI 2.23-3.86] after 2 months of a flipchart \neducation counselling intervention, suggesting \n\n\n\nthat knowledge of psoriasis may be associated \nwith QOL and/or disease severity.\n\n\n\nWhile QOL among psoriasis patients and \nthe factors associated with it has been widely \ninvestigated, few studies described the \nknowledge level of patients regarding the \ndisease, as well as evaluated the association \nbetween knowledge level with patient\u2019s QOL \nand disease severity, especially among the \nMalaysian population. Hence, the objective of \nthis research is to evaluate and investigate the \nrelationship between disease severity, disease \nknowledge and QOL of patients with psoriasis, \nand assess their knowledge regarding psoriasis \nand QOL.\n\n\n\nMaterials and Methods\nStudy Population\nThis was a cross-sectional multicenter study \nconducted in the dermatology clinics of \nHospital Sultan Haji Ahmad Shah (HoSHAS) \nand Hospital Tengku Ampuan Afzan (HTAA), \ntwo tertiary-care hospitals located in Pahang, \nMalaysia between January 2019 and January \n2020. Patients were eligible to participate in the \nstudy if they were diagnosed with psoriasis at \nleast six months prior to recruitment. Patients \nwho were less than eighteen years old, pregnant, \nand cognitively impaired were excluded from \nthis study. \n\n\n\nSample Size Calculation\nThe study was designed to include at least 50 \npatients to have a 95% confidence interval and \npower of 80%. This calculation was based on \nan estimated psoriasis population of 3%2 and a \ndrop-out rate of 10%. \n\n\n\nStudy Design\nData collection was carried out during patients\u2019 \nroutine clinic appointments. Written informed \nconsent was obtained from the subjects before \nrecruitment, after which they were given a set of \nquestionnaires to be answered. These included \na socio-demographic data collection form, \nPsoriasis Knowledge Assessment Questionnaire \n(PKAQ) and Dermatology Life Quality Index \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4840\n\n\n\n(DLQI) questionnaire. The attending doctor \nthen evaluated and completed the Psoriasis \nArea and Severity Index (PASI) score for each \nsubject. All forms and questionnaires were \nthen verified by one of the investigators to \nensure data completeness and all data were then \nentered into a database for analysis. A second \ninvestigator cross-checked all entries to ensure \naccuracy during data transfer.\n\n\n\nMeasurement of Outcomes\nPsoriasis Area and Severity Index (PASI)\nPASI is a commonly used validated tool to \nassess the severity of psoriasis.11In PASI, the \nbody surface area is divided into four sections: \nhead and neck, trunk, upper extremities and \nlower extremities. The assessment of severity \nof the symptoms, namely erythema (redness), \ninduration (thickness) and desquamation \n(scaling), is performed separately for each \nregion, resulting in a total score ranging from \nzero to seventy-two. The severity of psoriasis \nis then categorised based on the total score, \ngiving a three-tier severity of mild (<7), \nmoderate (7-12) and severe (>12).12A different \ndisease severity classification compared to the \nMalaysian Clinical Practice Guidelines for the \nmanagement of psoriasis vulgaris was used.13\n\n\n\nPsoriasis Knowledge Assessment \nQuestionnaire (PKAQ)\nPKAQ is a validated questionnaire to assess \nthe knowledge of study subjects in psoriasis.14 \nThe questionnaire consisted of twenty-five \nstatements related to psoriasis, including the \nbasic facts (nine items), the triggering factors \n(five items), the disease process (seven items) \nand the treatment aspects (four items). Subjects \nwere requested to mark each statement as \u2018true\u2019, \n\u2018false\u2019 or \u2018do not know\u2019. A correct response \nwas scored as one, while incorrect and \u2018do not \nknow\u2019 responses were scored as zero. The final \npossible score ranged from zero to twenty-\nfive. The questionnaire which is available in \nthe English language, was translated to the \nMalay version for ease of comprehension. Face \nand content validation were performed by a \ndermatology pharmacist and a dermatologist \nwith native language background. Cronbach\u2019s \n\n\n\nalpha tested on ten random samples had a score \nof 0.595. \n\n\n\nDermatology Life Quality Index (DLQI)\nThe DLQI questionnaire15is a self-explanatory, \nvalidated questionnaire used to measure \npatients\u2019 QOL affected by skin disease over the \npast seven days. The questionnaire consisted \nof ten questions which were categorised into \nsix domains of QOL: symptoms and feelings \n(question 1 and 2), daily activities (question \n3 and 4), leisure (question 5 and 6), work and \nschool (question 7), personal relationships \n(question 8 and 9), and treatment (question 10). \nEach question had four possible responses: \u2018not \nat all\u2019, \u2018a little\u2019, \u2018a lot\u2019 or \u2018very much\u2019, with \ntheir corresponding scores of zero, one, two and \nthree, respectively. Patients were only allowed \nto choose one response for each question. The \nDLQI was then calculated by summing the \nscores of all questions, resulting in a final index \nscore ranging from zero to thirty. The higher the \nindex score, the greater the impairment of QOL. \nThe scores were categorised into several bands \nof ascending impact levels: no effect (DLQI \n0-1), small effect (DLQI 2-5), moderate effect \n(DLQI 6-10), very large effect (DLQI 11-20) \nand extremely large effect (DLQI 21-30).16The \nquestionnaire is available in multiple languages. \nThe Malay and English bilingual version were \nused in this study. Cronbach\u2019s alpha tested on \nten samples had a score of 0.784. \n\n\n\nStatistical Analysis\nDescriptive statistics were presented using mean, \nmedian, standard deviation (SD), interquartile \nrange (IQR) and percentage, as appropriate. \nCorrelations between PKAQ, DLQI and PASI \nscores were analysed using Spearman\u2019s test. \nA value of p<0.05 was considered significant. \nAll analysis was conducted using IBM SPSS \nStatistics for Macintosh, Version 26.0. Armonk, \nNY: IBM Corp\n\n\n\nEthics Approval\nEthical approval was obtained from the Medical \nResearch and Ethics Committee (MREC), \nMinistry of Health Malaysia prior to data \ncollection (KKM/NIHSEC/P19-1040(6)).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 41\n\n\n\nResults\nDemographic\nA total of 114 subjects participated in this study. \nThe mean age of the study population was 48.8 \n\u00b1 15.15 (Table 1). The study population was \nequally distributed among women (50.9%) \nand men (49.1%). Most of the subjects were \nMalay (76.3%), followed by Chinese (13.2%), \nIndian (9.6%) and Indonesian (0.9%). Only \nfive (4.4%) subjects did not have any formal \nschooling, while thirty-seven (32.5%) subjects \nattained the highest qualification in education at \nuniversity level. At the time of the study, a high \nproportion of the subjects were married (78.1%) \nand were presently employed (55.3%). The \nmedian duration of suffering from psoriasis was \n8 years (range 1-59). The most common type \nof psoriasis encountered was plaque psoriasis \n(88.6%), followed by pustular psoriasis (4.4%), \nguttate psoriasis (3.5%), and erythrodermic \npsoriasis (2.6%). Approximately 1% of subjects \nhad concomitant psoriatic arthropathy.\n\n\n\nPsoriasis Area Severity Index (PASI)\nThe median PASI score was 4.4 (IQR = 7.7). \nMajority of the subjects (64%) had mild \npsoriasis, defined by a PASI score of less than \n7, while 20.2% of subjects had severe psoriasis \n(PASI >12), and 15.8% moderate psoriasis \n(PASI 7-12) (Table 1).\n\n\n\nPsoriasis Knowledge Assessment \nQuestionnaire (PKAQ)\nThe mean score for PKAQ was 14.2\u00b14.4. The \nlowest score reported was one, whereas the \nhighest was 23. Half of the subjects (50.9%) had \nthe misconception that psoriasis is contagious. \nIn addition to that, 78.1 % of subjects also \nbelieved that psoriasis is curable. A majority \nof the subjects were aware that psoriasis can \naffect both men and women (93%), can affect \nthe entire skin (88.6%) and joints (55.3%), and \ncan happen at any age (91.2%). More than half \nof the subjects were able to correctly identify \nstress (72.8%), certain medications (63.2%) \nand infection (64%) as triggering factors for \npsoriasis (Table 2). \n\n\n\nHowever, 55.3% of them did not know that \ninjury to the skin may also trigger the disease. \nMore than half of the subjects were able to \ncorrectly identify that psoriasis can affect the \nnails (63.2%), palms and soles (55.3%), but \nnot the brain (51.8%). Furthermore, most of \nthe subjects (70.2%) were aware that psoriasis \nwas not transmitted through sex and sharing \nof food. Nevertheless, 57.9% subjects had the \nmisconception that diet restrictions may cure \npsoriasis. More than two-thirds (70.2%) of \nthe subjects were aware of the possibility of \nside effects from certain medications used in \nthe treatment of psoriasis. A large proportion \nof subjects were also aware that moisturizers \n(87.7%) and oral medications (63.9%) helped \ntreat psoriasis. Conversely, only 39.5% subjects \nrecognised phototherapy as an effective \ntreatment modality (Table 2). \n\n\n\nDermatology Life Quality Index (DLQI)\nThe median DLQI score was 7 (IQR = 10), with \nthe minimum score being zero and the maximum \nwas 26. Figure 1 depicts the DLQI score and their \nrespective frequencies within each category, \nwhile Figure 2 details the degree of impairment \nwithin each domain. Most subjects experienced \na moderate impairment to their QOL (Figure \n1). In comparison to other domains, the highest \nnumber of subjects (43.9%) reported psoriasis \nas having \u2018a lot of\u2019 to \u2018very much\u2019 effect on their \nsymptoms, feelings, work or school. The least \naffected domain was \u2018personal relationships\u2019, \nwhere 54.4% of subjects were not affected by \ntheir disease, while only 1.8% of subjects were \nextremely affected. \n\n\n\nCorrelation between PASI, PKAQ and DLQI\nThere was a significant association between \nPASI and DLQI (rs = 0.264, p = 0.004) (Figure \n3). A higher PASI score correlated with a higher \nDLQI score. However, there was no statistical \nsignificance between the PASI and PKAQ scores \n(rs = 0.058, p = 0.542), as well as between DLQI \nand PKAQ scores (rs = -0.048, p = 0.612). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4842\n\n\n\nTable 1. Baseline demographics and clinical characteristics of subjects (n=114) \nAge        \n\n\n\nMean (\u00b1SD)   48.8 (\u00b115.15)   \n\n\n\nRange    18-83         \n\n\n\nGender        \n\n\n\nMale    56 (49.1%)     \n\n\n\nFemale    58 (50.9%) \n\n\n\nRace        \n\n\n\nMalay    87 (76.3%)    \n\n\n\nChinese    15 (13.2%)   \n\n\n\nIndian    11 (9.6%)  \n\n\n\nIndonesian   1 (0.9%) \n\n\n\nMarital Status       \n\n\n\nMarried    89 (78.1%)   \n\n\n\nSingle    16 (14%) \n\n\n\nDivorced or Widowed   9 (7.9%) \n\n\n\nEducation Level \n\n\n\nNo formal education  5 (4.4%) \n\n\n\nPrimary education   14 (12.3%) \n\n\n\nSecondary education  58 (50.9%) \n\n\n\nTertiary education   37 (32.5%) \n\n\n\nOccupational Status \n\n\n\nEmployed   63 (55.3%) \n\n\n\nUnemployed   51 (44.7%) \n\n\n\nType of Psoriasis \n\n\n\nPlaque    101 (88.6%) \n\n\n\nPustular     5 (4.4%) \n\n\n\nGuttate    4 (3.5%) \n\n\n\nErythrodermic   3 (2.6%) \n\n\n\nPsoriatic Arthropathy  1 (0.9%)  \n\n\n\nPASI Category \n\n\n\nMedian (range)   4.4 (0-36) \n\n\n\nMild    73 (64%) \n\n\n\nModerate    18 (15.8%) \n\n\n\nSevere    23 (20.2%) \n\n\n\nDuration of Disease (years) \n\n\n\nMedian (range)   8 (1-59) \n\n\n\nDLQI   \n\n\n\nMedian (range)   7 (0-26) \n\n\n\nPKAQ \n\n\n\nMedian (range)   15 (1-23) \n\n\n\nSD: standard deviation; PASI: Psoriasis Area and Severity Index; DLQI: Dermatology Life Quality Index; \nPKAQ: Psoriasis Knowledge Assessment Questionnaire \n\n\n\nSD: standard deviation; PASI: Psoriasis Area and Severity Index; DLQI: Dermatology Life Quality Index; PKAQ: Psoriasis Knowledge \nAssessment Questionnaire\n\n\n\nTable 1. Baseline demographics and clinical characteristics of subjects (n=114)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 43\n\n\n\nTable 2. Distribution of responses to each of the items of PKAQ (n=114). The shaded boxes represent the \ncorrect response\n\n\n\nNo Statements True % False % Don\u2019t \nKnow %\n\n\n\n1 Psoriasis is contagious. 58 50.9 41 36 15 13.2\n\n\n\n2 Psoriasis may begin at any age. 104 91.2 3 2.6 7 6.1\n\n\n\n3 Psoriasis can affect the entire skin. 101 88.6 7 6.1 6 5.3\n\n\n\n4 Psoriasis affects both men and women. 106 93 3 2.6 5 4.4\n\n\n\n5 Psoriasis is a curable disease. 89 78.1 15 13.2 10 8.8\n\n\n\n6 The exact cause of psoriasis is known. 33 28.9 21 18.4 60 52.6\n\n\n\n7 Psoriasis can be associated with joint pain. 63 55.3 23 20.2 28 24.6\n\n\n\n8 Specific food intake or restrictions may cure psoriasis. 66 57.9 24 21.1 24 21.1\n\n\n\n9 In psoriasis, skin cells are multiplying too slowly. 40 35.1 38 33.3 36 31.6\n\n\n\n10 Injury to the skin may cause psoriasis to appear at that site in \npersons already having psoriasis. 51 44.7 33 28.9 30 26.3\n\n\n\n11 Psoriasis never occurs in the nails. 21 18.4 72 63.2 21 18.4\n\n\n\n12 Certain drugs may increase the severity of psoriasis in \npersons already having psoriasis. 72 63.2 19 16.7 23 20.2\n\n\n\n13 Certain infections may increase the severity of psoriasis in \npersons already having psoriasis. 73 64 8 7 33 28.9\n\n\n\n14 Stress plays no role in psoriasis. 17 14.9 83 72.8 14 12.3\n\n\n\n15 Psoriasis increases in winter. 16 14 41 36 57 50\n\n\n\n16\nHaving close blood relatives affected with psoriasis \ndetermines to great extent whether a person will have \npsoriasis or not.\n\n\n\n55 48.2 30 26.3 29 25.4\n\n\n\n17 Psoriasis never occurs in the palms and soles. 29 25.4 63 55.3 22 19.3\n\n\n\n18 Psoriasis damage brain. 6 5.3 59 51.8 49 43\n\n\n\n19 Psoriasis is transmitted through sharing food. 12 10.5 80 70.2 22 19.3\n\n\n\n20 Psoriasis is transmitted among sexual partners. 8 7 80 70.2 26 22.8\n\n\n\n21 Photo / light therapy is useful in treating psoriasis. 45 39.5 17 14.9 52 45.6\n\n\n\n22 Oral medications are useful in psoriasis. 74 64.9 16 14 24 21.1\n\n\n\n23 Certain drugs which are used to treat psoriasis may have side \neffects. 80 70.2 10 8.8 24 21.1\n\n\n\n24 Psoriasis is seen all over the world. 100 87.7 3 2.6 11 9.6\n\n\n\n25 Treatment of psoriasis can include moisturizers. 100 87.7 2 1.8 12 10.5\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4844\n\n\n\nFigure 1. DLQI scores of subjects (n=114) \n\n\n\n*DLQI 0-1= No effect. 2-5= Small effect. 6-10= Moderate effect. \n11-20= Very large effect. 21-30= Extremely large effect\n\n\n\nFigure 2. Quality of life impairment in psoriasis patients based on categories of Dermatology Life Quality \nIndex\n\n\n\nDiscussion\nThis study demonstrated that the severity of \npsoriasis significantly affected QOL, with \npoorer QOL seen among patients with more \nsevere disease. This was in consensus with \nseveral local8,9 and international studies.17-18A \nTaiwanese study of 305 patients found that for \nevery 1-point increment in the PASI score, there \nwas an estimated increase in DLQI by 0.24 \npoints (p-value 0.0086). Similar findings were \nnoted when Psoriasis Disability Index (PDI) \n\n\n\nwas used as a parameter of QOL, with higher \nPDI scores having a greater impact on QOL, \nespecially among those with higher PASI scores \n(p<0.001 and p=0.005).19-20 Hence, to minimize \nthe impact of psoriasis on patients\u2019 QOL, PASI \nscores need to be reduced by optimally treating \npsoriasis.\n\n\n\nThis study also revealed that patients did not \nhave adequate knowledge about psoriasis. \nIn the future, a leaflet about psoriasis should \nbe provided to the newly diagnosed patients. \nPatients should also be allowed time to ask \nquestions at every clinic visit. A study by \nJankowiak et al.21 found that patients with a \nhigher education level had greater knowledge \nconcerning psoriasis. This may explain the \nmoderately low mean score of PKAQ (14.2) \nin this study, where a majority of the subjects \n(67.6%) had secondary education and below. \nA lack of knowledge regarding psoriasis \namong patients had also been highlighted in \nseveral studies. In a previous study using the \nsame PKAQ by Nagarajan et al14, 52% of 200 \nsubjects had inadequate knowledge. The same \nstudy discovered that a large number of subjects \n(49%) did not know that psoriasis was incurable, \nsimilar to our study where 78.1% thought \npsoriasis was curable. An alarming 50.9% of \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 45\n\n\n\nFigure 3. Correlation between (a) DLQI and PKAQ; \n(b) PASI and PKAQ; (c) PASI and DLQI\n\n\n\nSpearman\u2019s correlation = -0.048 (p= 0.612)\n(a)\n\n\n\nSpearman\u2019s correlation = 0.058 (p= 0.542)\n(b)\n      \n\n\n\nSpearman\u2019s correlation = 0.264 (p= 0.004)\n(c)\n\n\n\nsubjects had the misconception that psoriasis \nwas contagious. These findings highlight the \nneed for proper patient education by healthcare \nproviders to clarify patients\u2019 doubts and reduce \nmisconceptions about the disease. Most subjects \n(72.8%) were able to identify stress as a trigger, \nsimilar to a study by Wahl et al22 who used a \n49-item Psoriasis Knowledge Questionnaire \n(PKQ). They also found that more than half of \nthe study subjects did not know that sunburn and \ninfections could trigger psoriasis. Meanwhile in \nour study, 55.3% of subjects could not identify \ninjury as a triggering factor. Equally alarming \nwas that 57.9% of our study subjects wrongly \nbelieved that diet restrictions could cure \npsoriasis, which poses a risk of malnutrition \namong them. This prevalence is much higher \ncompared to another study which documented \na misconception of only 28.5%.14 With regards \nto treatment, a majority (60.5%) of subjects \nwere unable to identify phototherapy as one of \nthe treatment modalities of psoriasis. Nagarajan \net al14 also found that 85% of their subjects did \nnot know about phototherapy being used to treat \npsoriasis. One possible reason for our finding \ncould be that the majority of our subjects had \nmild disease (64%), which did not necessitate \nphototherapy as a treatment option.\n\n\n\nMost of our subjects\u2019 QOL was moderately \naffected by psoriasis, as evidenced by their \nDLQI scores. This is similar to another local \nstudy by Nyunt et al,8 involving 223 patients, \nwith a median DLQI score of 7 (IQR = 7). \nIn comparison, another study from Taiwan \ninvolving 480 patients had a mean DLQI score \nof 9.16 \u00b1 6.3.23 A closer examination into \nindividual components revealed that the most \naffected domains were \u2018symptoms and feelings\u2019, \nand \u201cwork or school\u2019, while the least affected \ndomain was \u2018personal relationships\u2019. This was \nalso consistent with findings from Nyunt et al,8 \nTang et al9 and Lin et al23 On the other hand, \na study of 72 Mexicans showed that the most \nimpacted domain was \u2018symptoms and feelings\u2019 \n(157 points), but the least impacted domain was \n\u2018school or work\u2019 (25 points).18 Patients\u2019 negative \nfeelings may be due to the affected skin areas \nthat were difficult to conceal, thus stigmatization \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4846\n\n\n\ncan ensue.24  Therefore, patients\u2019 self-esteem \nand perception towards self-body image should \nalso be taken into consideration when managing \na patient with psoriasis. Troubling symptoms \nsuch as itchiness and pain need to be identified \nand treated appropriately. The least affected \n\u201cpersonal relationships\u201d domain could be due to \ngood psychosocial support and acceptance from \nthe patients\u2019 families, partners and community.\nOur results found no statistically significant \nrelationship between disease severity and \nknowledge score of psoriasis patients. This is \nin agreement with a study by Fortune et al.25 \n\n\n\nwho also did not find any significant association \nbetween severity of psoriasis and beliefs held \nby patients about their condition, measured \nusing the Illness Perception Questionnaire \n(IPQ). However, two studies by Wahl et al22, 26 \nat different periods confirmed that patients with \ngreater disease severity had stronger beliefs \nabout the chronicity, negative consequences \nand emotional impact of psoriasis, in addition to \nbetter baseline knowledge. In comparison to the \nmilder cases, patients with severe disease may \nbe more interested to learn about the disease to \nhave better control over the symptoms. However \nin our study, patients\u2019 knowledge score could \nbe diminished due to factors such as their level \nof education and treatment modality. This is \nespecially so when only 32.5 % of our patients \nattended universities and 64% of the cases \nwere mild. Thus, they were unable to identify \nphototherapy as one of the treatment options.\n\n\n\nWe also found no significant relationship \nbetween knowledge scores and QOL. A study \nfound that patients with more knowledge about \npsoriasis had a better QOL, since they were \nless worried about the disease and perceived \nless severe consequences.21 Despite the lack of \nobjective evidence in the literature to support the \nassociation between knowledge and QOL, there \nare several studies which have demonstrated \nan improvement in QOL following an active \neducational intervention.10,27-28 Balato et al27used \nmobile phone text messages to send educational \ninformation and reminders to patients for a \nperiod of 12 weeks, which resulted in   an \nincrease in patients\u2019 QOL after the intervention \n\n\n\ncompared to the control group (p<0.05).  \nBostoen et al28created a 12-week educational \nprogramme of 2-hour sessions twice a week \nand showed a significant reduction in the mean \nDLQI score from 8.4 to 4.4 after the programme. \nIn another study, the researchers used the PDI \nscore to measure QOL before and after a 12-\nweek video-teaching programme, and found \na decrease in disability scores from 15.6\u00b16.9 \nto 9.9 \u00b15.1 after 3 months of intervention.29 \n\n\n\nThese observations highlight that the clinicians\u2019 \nefforts to educate patients translate into positive \nQOL. However, there might be the potential of \nobserver bias (Hawthorne Effect) in intervention \nstudies. Since educational intervention was not \ncarried out in our study, the effect of knowledge \nincrement on reducing the impact on QOL could \nnot be observed.\n\n\n\nThis study had a few limitations. The major \nlimitation was that most of the subjects had \nmild psoriasis. As a consequence, the result \nmay not adequately represent patients with \nmoderate and severe psoriasis. In addition, \nthere was misclassification bias among patients \nwith special sites such as the genitalia, face and \npalms. They may be wrongly classified as having \nmild psoriasis since disease severity was based \non PASI, and special sites are not considered in \nPASI calculation. Future research should study \nthe effect of educational intervention towards \nimproving QOL among patients suffering from \npsoriasis. \n\n\n\nConclusion\nIn summary, severe psoriasis was associated with \nhigher impairment in QOL. However, there was \nno correlation between knowledge and severity \nof psoriasis, as well as between knowledge and \nQOL. Future research should quantify the effect \nof patient education intervention, to investigate \nif knowledge increment will improve their \ndisease severity and QOL.\n\n\n\nConflict of Interest Declaration\nThe author have no conflict of interest to declare.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 47\n\n\n\nAcknowledgement\nThe authors would like to acknowledge the \nDirector General of Health Malaysia for his \npermission to publish this article. Our deepest \ngratitude is also extended to Dr Firhan Bin \nHassan, Dr Justin Tan Yu Kuan and Ms Sanggeri \nfor their assistance in data collection. Thanks \nto Dr Kumitaa from Proofreaders United who \nchecked the grammatical accuracy of this final \ncontent.\n\n\n\nReferences \n1. Mahajan R, Handa S. Pathophysiology of psoriasis. Indian \n\n\n\nJ Dermatol Venereol Leprol 2013;79:S1-9. \n2. National Psoriasis Foundation. Psoriasis statistics. Oregon \n\n\n\n(US): National Psoriasis Foundation; 2020. [updated 2020 \nAug 10; cited 2021 Nov 22]. Available from: https://www.\npsoriasis.org/psoriasis-statistics.\n\n\n\n3. Robinson S, Tang MM, Ramalingam R, Voo SY, Kwan Z, \nThevarajah S. The Tenth Report of the Malaysian Psoriasis \nRegistry 2007-2018, Kuala Lumpur, Malaysia 2020.\n\n\n\n4. Martin ML, Gordon K, Pinto L, Bushnell DM, Chau D, \nViswanathan HN. The experience of pain and redness \nin patients with moderate to severe plaque psoriasis. J \nDermatolog Treat 2015;26:401-5.\n\n\n\n5. Prins M, Krabbe PF, Swinkels QO, de Boo T, van de \nKerkhof PC, van der Valk PG. The effect of treatment on \nquality of life in psoriasis patients. Acta Derm Venereol \n2005;85:304-10. \n\n\n\n6. Azizam NA, Ismail A, Sulong S, Md Nor N. Cost-\neffectiveness analysis of psoriasis treatment modalities in \nMalaysia. Int J Health Policy Manag 2019;8:394-402.\n\n\n\n7. Mart\u00ednez-Ortega JM, Nogueras P, Mu\u00f1oz-Negro JE, \nGuti\u00e9rrez-Rojas L, Gonz\u00e1lez-Domenech P, Gurpegui \nM. Quality of life, anxiety and depressive symptoms in \npatients with psoriasis: a case-control study. J Psychosom \nRes 2019;124:109780.\n\n\n\n8. Nyunt WW, Low WY, Ismail R, Sockalingam S, Min \nAK. Determinants of health-related quality of life in \npsoriasis patients in Malaysia. Asia Pac J Public Health \n2015;27:662-73.\n\n\n\n9. Tang MM, Chang CC, Chan LC, Heng A. Quality of life \nand cost of illness in patients with psoriasis in Malaysia: a \nmulticenter study. Int J Dermatol 2013;52:314-22.\n\n\n\n10. Azmi NL, Ahmad SS, Sia RGL, Ku Jaya TNE, Mohamad \nSalim SR, Amran AN. Impact of educational aid in \npharmacist counselling on quality of life in psoriasis \npatients. Int Res J Pharm 2019;18:48-51.\n\n\n\n11. Oakley A. PASI score. DermNet NZ. Available at: https://\ndermnetnz.org/topics/pasi-score (last accessed 17th May \n2021).\n\n\n\n12. Schmitt J, Wozel G. The psoriasis area and severity index is \nthe adequate criterion to define severity in chronic plaque-\ntype psoriasis. Dermatology 2005;210:194-9.\n\n\n\n13. Ministry of Health Malaysia. Clinical practice guidelines: \nmanagement of psoriasis vulgaris. Malaysian Health \nTechnology Assessment Section. 2013.\n\n\n\n14. Nagarajan P, Karunagari K, Thappa D. A questionnaire-\nbased survey of patients\u2019 knowledge regarding psoriasis. \nInt J Ment Health Nurs 2016;2:18.\n\n\n\n15. Finlay A & Khan G. Dermatology Life Quality Index \n(DLQI)-a simple practical measure for routine clinical use. \nClin Exp Dermatol 1994;19:210-6.\n\n\n\n16. Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay \nAY. Translating the science of quality of life into practice: \nWhat do dermatology life quality index scores mean? J \nInvest Dermatol 2005;125:659-64.\n\n\n\n17. Tsai TF, Ho JC, Chen YJ, Hsiao PF, Lee WR, Chi CC et al. \nHealth-related quality of life among patients with moderate \nto severe plaque psoriasis in Taiwan. Dermatologica Sinica \n2018;36:190-5.\n\n\n\n18. Garc\u00eda-S\u00e1nchez L, Montiel-Jarqu\u00edn \u00c1J, V\u00e1zquez-Cruz E, \nMay-Salazar A, Guti\u00e9rrez-Gabriel I, Lor\u00eda-Castellanoso J. \nQuality of life in patients with psoriasis. J Cutan Med Surg \n2017;15:29-36.\n\n\n\n19. Pakran J, Riyaz N, Nandakumar G. Determinants of \nquality of life in psoriasis patients: A cluster analysis of 50 \npatients. Indian J Dermatol 2011;56:689-93.\n\n\n\n20. Aghaei S, Moradi A, Ardekani GS. Impact of psoriasis on \nquality of life in Iran. Indian J Dermatol Venereol Leprol \n2009;75:220.\n\n\n\n21. Jankowiak B, Krajewska-Kulak E, Van Damme-\nOstapowicz K, Wronska I, Lukaszuk C, Niczyporuk W \net al. The need for health education among patients with \npsoriasis. Dermatol Nurs 2004;16:439.\n\n\n\n22. Wahl AK, Moum T, Robinson HS, Langeland E, Larsen \nMH, Krogstad AL. Psoriasis patients\u2019 knowledge \nabout the disease and treatments. Dermatol Res Pract \n2013;2013:921737. \n\n\n\n23. Lin TY, See LC, Shen YM, Liang CY, Chang HN, Lin \nYK. Quality of life in patients with psoriasis in northern \nTaiwan. Chang Gung Med J 2011;34:186-96.\n\n\n\n24. Kwan Z, Bong YB, Tan LL, Lim SX, Yong ASW, Ch\u2019ng \nCC et al. Determinants of quality of life and psychological \nstatus in adults with psoriasis. Arch Dermatol Res \n2018;310:443-51.\n\n\n\n25. Fortune DG, Richards HL, Main CJ, Griffiths CE. What \npatients with psoriasis believe about their condition. J Am \nAcad Dermatol 1998;39:196-201.\n\n\n\n26. Wahl AK, Robinson HS, Langeland E, Larsen MH, \nKrogstad AL, Moum T. Clinical characteristics associated \nwith illness perception in psoriasis. Acta Dermato-\nVenereologica 2014;94:271-5.\n\n\n\n27. Balato N, Megna M, Di Costanzo L, Balato A, Ayala F. \nEducational and motivational support service: A pilot \nstudy for mobile-phone-based interventions in patients \nwith psoriasis. Br J Dermatol 2013;168:201-5.\n\n\n\n28. Bostoen J, Bracke S, De Keyser S, Lambert J. An \neducational programme for patients with psoriasis and \natopic dermatitis: A prospective randomized controlled \ntrial. Br J Dermatol 2012;167:1025-31. \n\n\n\n29. Nagarajan P, Thappa DM. Effect of an educational and \npsychological intervention on knowledge and quality of \nlife among patients with psoriasis. Indian Dermatol Online \nJ 2018;9:27-32.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4848\n\n\n\nORIGINAL ARTICLE\n\n\n\nThe Socio-demographic and Quality of Life of People Living with HIV \n(PLHIV) Presenting with Cutaneous Manifestation: A Cross-Sectional \nStudy in the Department of Dermatology, Sarawak General Hospital\n\n\n\nSiew Li Ee, MRCP, Pubalan Muniandy, FRCP\n\n\n\nDepartment of Dermatology, Sarawak General Hospital, Kuching, Sarawak, Malaysia\n\n\n\nAbstract\nBackground\nPeople living with Human Immunodeficiency Virus (PLHIV) are living longer with the advent of \nhighly active antiviral therapy (HAART). Aside from extending the life span, quality of life is vital in \nPLHIV management. However, there is a paucity of data on the cutaneous manifestations in PLHIV \non HAART. The objective of this study is to ascertain the prevalence of cutaneous manifestations, \neffect on daily lives, and relation to CD4 levels.\n\n\n\nMethods\nThis is a prospective cross-sectional study comparing 2 groups of PLHIV patients on HAART and not \non HAART therapy done from March 2020 to November 2020.\n \nResults\nA total of 259 patients were recruited in this study with a mean age of 40 years. There were 216 \n(83.4%) male and 43 (16.6 %) female. Men having sex with men accounts for 49%. The most common \ncutaneous disorder was post-inflammatory pigmentation (20.4%). Infective dermatoses were 43 \n(6.7%), and cutaneous malignancy 3 (0.6%). Mean DLQI in PLHIV on HAART were 2, as compared \nto PLHIV not on HAART which scored 3. Bidayuh ethnicity accounts for 30% of adverse drug \nreactions with Bactrim being the most common drug.\n\n\n\nConclusion\nThere is a high prevalence of dermatoses in PLHIV. HAART increases the CD4 count of patients \nthereby reducing the risk of opportunistic infection and related disorders. However, it did not reduce \nthe cutaneous manifestations in PLHIV, as HAART itself may increase the risk of adverse cutaneous \ndrug reactions. DLQI is not the best tool to assess quality of life. \n\n\n\nKey words: Human Immunodeficiency Virus, quality of life, cutaneous manifestation\n\n\n\nCorresponding Author\nDr Ee Siew Li \nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur, Malaysia.\nEmail: lilyee83@gmail.com\n\n\n\nIntroduction \nHuman Immunodeficiency Virus (HIV) is \na multifaceted burden of modern society. \nThe march on awareness and control of HIV \ninfections resulted in a successful reduction \nin the number of new infections and deaths. \nHowever, there is a continuous increase in the \nnumber of people living with HIV (PLHIV) \nglobally. In 2019,  Malaysia recorded a total of \n87 000 HIV cases, of which 5 600 are newly \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 49\n\n\n\ndiagnosed with 2 600 deaths from HIV.1 \n\n\n\nHIV was first described in 1981 in light of 5 \ncases of Pneumocystis carinii pneumonia (PCP) \namong previously healthy young men. There \nis no cure but a lifelong manageable therapy. \nHighly Active Antiviral Therapy (HAART) \ninhibits HIV proliferation hence suppresses the \nviral load and leads to improvement of CD4 \nfunction. Due to the nature of persistent viral \nreservoir, complete eradication is not possible \nwith current therapy.2 HAART extends the \nlife span of people living with HIV (PLHIV) \nand sustains the nation\u2019s powerhouse as this \ninfection predominates in young to middle-\naged adults.3 The focus on the quality of life in \nPLHIV is emerging in the literature across the \nworld as researches for cure are underway.\n\n\n\nThe prevalence of cutaneous manifestations in \nacute HIV-infected patients is greater than 90%.4 \nThey range from subtle to severe impairment \nin the quality of life. On the contrary, data \non mucocutaneous disorder in chronic HIV \ninfection is lacking. These data are crucial to \naid in understanding and improving the quality \nof life in PLHIV.\n\n\n\nThis study aims to determine the prevalence \nof dermatoses with its impact on the quality of \nlife and to determine the correlation between \nvarious factors (demographic, HAART, severity \nof immunosuppression) in PLHIV.\n\n\n\nMaterials and Methods\nThis is a prospective, cross-sectional study \nconducted on adult HIV-infected patients from \nMarch to November 2020 (8 months). Patients \nwere recruited from the HAART Clinic of \nSarawak General Hospital, a tertiary referral \ncenter in East Malaysia. \n\n\n\nApproval from the Medical Research and \nEthics Committee was obtained before the \ncommencement of this study (NMRR approval \ncode: NMRR-19-3446-52216). Consented \nsubjects were examined, notes reviewed and \nthen subjected to Dermatology Life Quality \nIndex (DLQI) questionnaire. \n\n\n\nDLQI is a user-friendly validated tool used to \nassess impact of skin diseases on the quality \nof life. In this study, validated DLQI both in \nBahasa Melayu and English language were \nused. It consists of 10 questions concerning \npatients\u2019 perception on different aspect of daily \nliving in the past weeks. The DLQI is calculated \nby adding the score of each question, resulting \nin a maximum of 30 and a minimum of 0. \nThe higher the score, the more quality of life \nis impaired. Impact on the quality of life is as \nfollow;\n\n\n\n\u2022\t 0 \u2013 1 no effect at all on patient\u2019s life\n\u2022\t 2 \u2013 5 small effects on patient\u2019s life\n\u2022\t 6 \u2013 10 moderate effects on patient\u2019s life\n\u2022\t 11 \u2013 20 very large effect on patient\u2019s life\n\u2022\t 21 \u2013 30 extremely large effect on pa-\n\n\n\ntient\u2019s life. \n\n\n\nCases that required further management will \nbe referred to the Dermatology Department of \nSarawak General Hospital. Stable HAART is \ndefined as the duration of HAART treatment for \nmore than 1 year.5 \n\n\n\nData on demographic, dermatological diagnosis, \nand characteristics were recorded and analyzed \nusing SPSS Version 21. Descriptive statistics \nwere presented as counts and percentages for \ncategorical variables. Fisher\u2019s exact test was \nused for analysis of dermatoses comparing \nHAART treated and HAART not treated group \nas the data collected were of small sample size \nand non-parametric distribution. Statistical \nsignificance was set at p<0.05. As for the \ncorrelation analysis, Spearmann\u2019s rho method \nanalysis was used data.\n\n\n\nResults\nA total of 261 patients were seen in HAART \nClinic. Out of these, 1 patient declined to \nparticipate while another patient had false-\npositive result of HIV. This resulted in a final \nsample size of 259. Among the study population, \n13.1% required dermatology referral, 35.9% \nwere given a prescription, and 1.1% had skin \nbiopsy done. Demographic characteristics are \nshown in Table 1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4850\n\n\n\nTable 1. Characteristics of the study population \nCharacteristics n %\n\n\n\nAge 40.7\u00b112.68 (18-87)\n\n\n\n    18-29 61 23.6\n\n\n\n     30-39 76 29.3\n\n\n\n     40-49 61 23.6\n\n\n\n     >50 61 23.6\n\n\n\nGender\n\n\n\n     Male 216 83.4\n\n\n\n     Female 43 16.6\n\n\n\nEthnicity\n\n\n\n     Malay 82 31.7\n\n\n\n     Bidayuh 62 23.9\n\n\n\n     Chinese 58 22.4\n\n\n\n     Iban 47 18.1\n\n\n\n     Others 3 1.2\n\n\n\n     Indian 2 0.8\n\n\n\n     Kayan 2 0.8\n\n\n\n     Melanau 1 0.4\n\n\n\n     Kelabit 1 0.4\n\n\n\n     Kenyah 1 0.4\n\n\n\nEducation\n\n\n\n     None 1 0.4\n\n\n\n     Primary 40 15.4\n\n\n\n     Secondary 132 51\n\n\n\n     Tertiary 86 33.2\n\n\n\nMarital status\n\n\n\n     Single 172 66.4\n\n\n\n     Married 77 29.7\n\n\n\n     Divorced 9 3.5\n\n\n\n     Widowed 1 0.4\n\n\n\nOccupation\n\n\n\n     White collar 39 15.1\n\n\n\n     Blue collar 131 50.6\n\n\n\n     Housewife 11 4.2\n\n\n\n     Unemployed 78 30.1\n\n\n\nMode of Transmission\n\n\n\n     Homosexual 105 40.5\n\n\n\n     Heterosexual 96 37.1\n\n\n\n     Bisexual 23 8.9\n\n\n\n     Unknown 20 7.7\n\n\n\n     IVDU usage 12 4.6\n\n\n\n     Vertical 3 1.2\n\n\n\nCD4\n\n\n\n     >500 68 26.3\n\n\n\n     200-499 115 44.4\n\n\n\n     <200 74 28.6\n\n\n\n     Not available 2 0.8\n\n\n\nViral load\n\n\n\n     <200 copies/ml 197 76.1\n\n\n\n     >200 copies/ml 35 13.5\n\n\n\n     Not available 27 10.4\n\n\n\nOn HAART treatment\n\n\n\n     No 38 14.7\n\n\n\n     Yes 221 85.3\n\n\n\nDuration on HAART\n\n\n\n     <1 years 57 25.8\n\n\n\n     >1 years 164 74.2\n\n\n\n \nTable 2. Comorbidities in PLHIV \nComorbidities n %\n\n\n\nBefore HIV diagnosis 68 26.3\n\n\n\nAfter HIV diagnosis 45 17.4\n\n\n\n\n\n\n\nNon-infective  83.2\n Dyslipidaemia 26 15\n\n\n\n Hypertension 25 14.5\n\n\n\n Atopic Diseases 24 13.9\n\n\n\n Diabetes mellitus 18 10.4\n Chronic Kidney Disease 6 3.5\n Psychiatry disorders 5 2.9\n Gastritis 5 2.9\n Adrenal insufficiency 4 2.3\n G6PD 3 1.7\n Malignancy 3 1.7\n Ischemic heart disease 3 1.7\n Seizure 3 1.7\n Stroke 2 1.2\n Gout 2 1.2\n Pregnant 1 0.6\n Liver cirrhosis 1 0.6\n Anaemia 1 0.6\n Others 16 9.2\n\n\n\nInfective  16.8\n Syphilis 31 17.9\n Tuberculosis 20 11.6\n Hepatitis C 5 2.9\n Hepatitis C and Syphilis 4 2.3\n Hepatitis B and Tuberculosis 4 2.3\n Hepatitis B 3 1.7\n Hepatitis C and Tuberculosis 3 1.7\n Tuberculosis and Syphilis 3 1.7\n Hepatitis B and Hepatitis C 2 1.2\n Hepatitis B and Syphilis 1 0.6\n\n\n\nThe mean age in this study population was \n40.1 years (ranging from 18 to 87 years). The \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 51\n\n\n\nmean age of HIV diagnosis was 35.7 years. \nThere were 216 (83.4%) males and 43 (16.6 %) \nfemales, with a ratio of male to female being \n5 to 1. Eighty-two subjects are Malay (31.7%), \nfollowed by Bidayuh (23.9%), Chinese (22.4%), \nIban (18.1%) and foreigners (1.2 %).\n\n\n\nThe literacy rate was high (99.6%), of which \n51% PLHIV had secondary school education, \nand 33.2% had tertiary education, meanwhile \nonly one subject did not have any formal \neducation. Hence the corresponding DLQI was \nobtained via assistance. There is a great role for \ndesigning interactive questionnaires for low-\nliterate persons. Majority of the participants \nwere single (66.4 %), whereas only 29.7% of \nthe subjects were married. Blue-collar workers \nrecorded the highest distribution which accounts \nfor 50.6%, whereas unemployment was 30 %. \nSexual transmission was the most common mode \nof infection. Homosexuality accounted for 40.5 \npercent, followed by heterosexuality (37.1%), \nIVDU (4.6%), and vertical transmission (1.2%).\n\n\n\nThe mean CD4 count was 362 cells/m\u00b3 with 74 \nparticipants (28.6%) who had CD4 level below \n200 cells/mm\u00b3. There were 85.3% of participants \nwho were on HAART treatment with the mean \nduration of 2.9 years (ranges up to 18 years \nfrom the initiation of treatment). In addition, \nprior HIV diagnosis, 26.3% had pre-existing \ncomorbidity, where else 17.4 % developed \nnew comorbidity after HIV diagnosis. Non-\ninfective comorbidities in this study population \nwere dyslipidemia 15%, hypertension 14.5%, \ndiabetes mellitus 10.4%, atopic diseases 13.9%, \npsychiatry disorders 2.9% and others (Table \n2). Infective comorbidities account for 16.8% \nof the participants which include syphilis \n17.9%, tuberculosis 11.6 %, hepatitis C 2.9%, \n\n\n\nand hepatitis B 1.7%, while the remainder is \nattributed to mixed infection. \n\n\n\nThe overall prevalence of cutaneous \nmanifestations in PLHIV was 90.7%, whereas \nfor PLHIV on HAART was 78.9%. In this \nstudy, 64.9% of PLHIV had more than 1 type of \ncutaneous diagnosis. Two types of dermatoses \nwere the highest, accounting for 92 participants \n(41.6%). The highest number of dermatoses \nwere 6 (0.9 %) (Table 3). In this study, stable \nPLHIV on HAART with CD4 more than 200 \ncells/mm\u00b3 accounts for 64.7%, where as, CD4 \nless than 200 cells/mm\u00b3 were 9.5%. A total of \n481 dermatoses were found in 259 patients. \nTable 4. As high as 48.6% participants in this \nstudy complained of pruritus, whereas aesthetic \nconcerns were 29.5 %, scaly skin 18.6%, and \npain 3.2%. \n\n\n\nThe types of dermatoses were divided into \ninfective 8.1%, non-infective 87.9%, malignant \n0.6%, and drug-induced adverse events 1%. \nIn comparison between HAART-treated and \nuntreated ones, drug-induced maculopapular \neruption was statistically significant (p = 0.01). \nTable 4.\n\n\n\nThe negative correlation coefficient between \nthe severity of immunosuppression with DLQI \nwas not statistically significant (Spearman\u2019s rho \ncorrelation coefficient, p = -0.23). There was an \nextremely large effect on the quality of life in \nPLHIV with severe immunosuppression (Table \n5). Untreated HIV participants had a mean \nDLQI of 3, meanwhile treated HIV participants \nhad a mean DLQI of 2. However, there was \nno statistically significant difference in DLQI \nbetween the treated and untreated group.\n\n\n\nTable 3. Number of dermatoses in the study population in correlation with CD4 and duration of HAART \nDuration HAART CD4, cells/mm\u00b3 Number of dermatoses, n\n\n\n\n0 1 2 3 4 5 6\n< 1 years >500 2 1 2 1 0 0 0\n\n\n\n201-499 3 7 7 6 1 0 0\n<200 1 4 15 5 1 1 0\n\n\n\n> 1 years >500 7 14 23 11 4 1 0\n201-499 9 25 36 9 2 1 1\n<200 0 5 9 3 3 0 1\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4852\n\n\n\nTable 4. Distribution of dermatosis in PLHIV on HAART and without HAART\n\n\n\nDermatosis Not on HAART, n (%) On HAART, n (%) p-value\n\n\n\nN=68 N=413  \nInfective dermatosis  \nFungal\n    Tinea coporis 1(1.5) 9(2.1) 0.98\n    Tinea pedis 0 9(2.1) 0.36\n    Tinea Cruris 2(2.9) 3(0.7) 0.16\n    Tinea capitis 1(1.5) 1(0.2) 0.27\n    Onychomychosis 0 2(1.5) 0.10\n\n\n\n   \nBacterial\n    Impetigo 1(1.5) 1(0.2) 0.27\n    Ecthyma 0 1(0.2) 0.98\n    Syphilis 0 1(0.2) 0.98\n     \nViral\n    Genital warts 3(4.4) 6(1.5) 0.13\n    Non genital warts 2(2.9) 2(4.9) 0.10\n    Herpes zoster 1(1.5) 2(4.9) 0.31\n    Molluscum contagiosum 0 2(4.9) 0.97\n     \nParasites    \n  0 0 NA\n     \nNon infective Dermatosis\nInflammatory disorder  \n    Post inflammatory pigmentation 15(22.1) 83(20.1) 0.86\n    Xerosis 9(13.2) 70(16.9) 0.45\n    Folliculitis 5(7.4) 25(6.1) 0.78\n    Eczema 2(2.9) 22(5.3) 0.55\n    Contact dermatitis 0 19(4.6) 0.09\n    Seborrheic Dermatitis 4(5.9) 12(2.9) 0.23\n    Acne vulgaris 2(2.9) 7(1.7) 0.62\n    Psoriasis 2(2.9) 5(1.2) 0.27\n    Nail pitting 1(1.5) 4(1) 0.55\n    Chronic spontaneous urticaria 0 4(1) 0.92\n    Livedo reticularis 1(1.5) 2(0.5) 0.14\n    Stasis eczema 0 2(0.5) 0.93\n    Cheilitis 0 1(0.2) 0.97\n    Prurigo nodularis 0 1(0.2) 0.97\n    Ulcer 0 1(0.2) 0.97\n    Post Infective desquamation 1(1.5) 0 0.15\n    Thrombophlebitis 1(1.5) 0 0.15\n    Pruritic papular eruption 0 0 NA\n    Oral lesions 0 0 NA\n     \nNon-inflammatory disorder  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 53\n\n\n\n    Scars 2(2.9) 24(5.8) 0.39\n    Tattoo 3(4.4) 16(3.9) 0.75\n\n\n\n    Melanonychia 3(4.4) 15(3.6) 0.73\n\n\n\n    Chronic paronychia 1(1.5) 14(3.4) 0.71\n\n\n\n    Scabs 0 9(2.2) 0.36\n    Subungual hematoma 1(1.5) 1(0.2) 0.27\n    Sebaceous cyst 0 1(0.2) 0.98\n    Scrotal angioma 0 1(0.2) 0.98\n    Acanthosis nigrican 0 1(0.2) 0.98\n    Striae 0 1(0.2) 0.98\n    Lipoid atrophy 0 1(0.2) 0.98\n    Lipoma 0 1(0.2) 0.98\n    Tophi 0 1(0.2) 0.98\n    Delusional parasitosis 0 1(0.2) 0.98\n    Ganglion cyst 0 1(0.2) 0.98\n    \nDegenerative disorder  \n    Deformed nail 0 8(1.9) 0.61\n    Seborrheic keratosis 0 4(1) 0.90\n    Cherry angioma 0 3(0.7) 0.95\n    Alopecia 0 3(0.7) 0.95\n    Skin tag 0 3(0.7) 0.95\n    Callus 0 2(0.5) 0.97\n    Guttate hypomelanosis 0 1(0.2) 0.99\n     \nMalignant\n    Kaposi Sarcoma 1(1.5) 2(0.5) 0.38\n    Squamous cell carcinoma 0 0 NA\n    Basal cell Carcinoma 0 0 NA\n    Melanoma 0 0 NA\n     \nDrugs adverse event\n    Maculopapular lesion 3(4.4) 1(0.2) 0.011\n    Acne 0 1(0.2) 0.98\n     \n\n\n\nNA: not available as the statistic analysis is unable to perform for the comparison to obtain p-value\np-value is obtain from Fisher exact test \n*One patient may have multiple mucocutaneous manifestations; the percentage reported is based on total patients in each group\n\n\n\nTable 5. Correlations of severity of immunosuppression with DLQI in PLHIV \nCD4, \n\n\n\ncells/mm\u00b3\nDLQI, n (%)\n\n\n\nNo effect Small \neffect\n\n\n\nModerate \neffect\n\n\n\nVery Large \neffect\n\n\n\nExtremely \nLarge effect\n\n\n\n>500 57(22.2) 9(3.5) 2(0.8) 0 0\n\n\n\n200-499 79(30.8) 25(9.8) 9(23.5) 1(0.4) 1(0.4)\n<200 41(16) 20(7.8) 10(3.9) 1(0.4) 2(0.8)\n\n\n\nSpearmann\u2019s rho corelation shows negative corelation with insignificant p =0.224\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4854\n\n\n\nFigure 1. Atopy and allergies distribution in PLHIV in this study\n\n\n\n20\n9 1\n\n\n\n198\n\n\n\n29\n\n\n\n2\n15 9 6\n\n\n\n143\n\n\n\n21\n\n\n\n65\n\n\n\n0\n\n\n\n50\n\n\n\n100\n\n\n\n150\n\n\n\n200\n\n\n\n250\n\n\n\nnone food med none food med\n\n\n\nAllergy in HIV\n\n\n\nBefore HIV After HIV\n\n\n\nNon atopy\nAtopy\n\n\n\nNone: no allergy; Food: allergy to food; Med: allergy to medication\n\n\n\nA quarter of the allergies (25.1%) in PLHIV \nwere attributed to medication. In non-atopy \narm, 143 participants (55%) remain allergy-free \nafter initiation of HAART (Figure 1). Allergy \nincidents before and after HIV diagnosis \nwere 41(16%) and 101(39.3%) respectively. \nHowever, these differences were not statistically \nsignificant. (Table 6).\n\n\n\nTable 6. Overview of DLQI scores in this study \nDLQI Severity DLQI score n %\n\n\n\nNo effect 0 125 48.3\n\n\n\n 1 53 20.5\n\n\n\nSmall effect 2 29 11.2\n 3 11 4.2\n 4 8 3.1\n\n\n\n 5 7 2.7\n\n\n\nModerate effect 6 5 1.9\n 7 7 2.7\n 8 3 1.2\n 9 3 1.2\n\n\n\n 10 3 1.2\n\n\n\nVery large effect 11 1 0.4\n\n\n\n 15 1 0.4\n\n\n\nVery large effect 22 1 0.4\n 24 1 0.4\n\n\n\n 25 1 0.4\n\n\n\nA total of 91 participants had adverse drug \nevent. Despite the Malay race having the highest \nprevalence of PLHIV in this study, Bidayuh \nethnicity had the most frequent adverse drug \nreactions (30.8%). Bactrim accounts for the \n\n\n\nhighest incidence 64.8%, followed by HAART \n12.1%, dapsone 8.8%, antibiotics 7.7 %, and \nothers 6.7%. (Table 7).\n\n\n\nTable 7. Distribution of adverse drug event based on \nethnicity in PLHIV in Sarawak\n\n\n\nEthnic\\\nDrugs\n\n\n\nBactrim Dapsone HAART Antibiotics Others\n\n\n\nBidayuh 19 4 2 2 1\n\n\n\nChinese 11 1 2 1 1\n\n\n\nIban 13 1 4 3 2\n\n\n\nMalay 13 2 3 1 2\n\n\n\nIndian 1 0 0 0 0\n\n\n\nOther 1 0 0 0 0\n\n\n\nKelabit 1 0 0 0 0\n\n\n\nMelanau 0 0 0 0 0\n\n\n\nKayan 0 0 0 0 0\n\n\n\nKenyah 0 0 0 0 0\n\n\n\nDiscussion\nHIV infection is complex and multifactorial. \nThe male gender, compounded by homosexual \npractice, raises the risks of HIV infection. This \nis consistent with our local6 and international \nstudies.7-8 Anal intercourse is associated with a \nhigher rate of infection due to biological factors \nas compared to vaginal intercourse. However, \nin other parts of the world, females are the \npredominant gender.9-10 This is supported by \nliteratures on the differences in HIV acquisition \nby gender11 and pathophysiology of sex and \nhormone levels with inflammation induced by \nthe microbiome.12-13\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 55\n\n\n\nAdults, young to middle-aged are the most \noften infected group. This study majority of \nPLHIV is in between 18 to 39 years old. This \nis supplemented by our national HIV data in \n2018 which shows that 67 % prevalence of HIV \ninfection occurs in those who are 20 to 39 years \nold. Data from CDC US in 2019 states that, the \nrate of HIV infection was highest for persons \naged 25\u201334. Curiosity and the drive to be \nunique are probably the key factors to the rate \nof infection in this region. Additionally, social \nmedia, population density, adaptive change \nin urbanisation and information accessibility \ncould be the other contributing factors.\n\n\n\nComorbidities observed in stable HIV were \nmainly non-infective, where as in acute HIV \ninfection, infective disorders predominate.14 \nSignificant metabolic disorders in this \npopulation are attributed to HAART itself and \nthe other conventional risk factors such as diet, \nlifestyles, and genetic predispositions. Once \nPLHIV is stable, clinicians are left with another \nhurdle to manage the arising comorbidity and \nfocus on the quality of life.\n\n\n\nThis study recorded 74.2% of stable PLHIV on \nHAART. In this group, the number of diseases \nis expected to reduce because of improved \nimmune systems. On the contrary, the number \nof dermatoses observed have increased. Non-\nHIV related cutaneous malignancy was not \nobserved in this study despite the older HIV-\ninfected population. Kaposi sarcoma with \nan incident of 1.2% was the only cutaneous \nmalignancy observed. It is associated with men \nwho have sex with men (MSM) practice. Usage \nof saliva as a lubricant was postulated to be the \nmain principle of transmission as the viral load \nof Kaposi sarcoma in the semen is substantially \nlow.15  Also called human herpesvirus-8, has \nsince been shown to be the etiologic agent for \nseveral other tumors and diseases, including \nprimary effusion lymphoma (PEL Half of the \nKaposi sarcoma in this study failed to achieve \ncomplete resolution despite being stable \nHAART, which is consistent with the previous \nresearch.16 These findings can be explained \nby immune deviation instead of normalising \n\n\n\nimmune function due to HAART via persistent \nHIV replication in memory T lymphocytes \ndespite optimal HIV virus control.17 There \nwere no statistically significant differences \nbetween cutaneous manifestations in a treated \nand untreated patient in this study (p = 0.357). \nAs PLHIV are surviving longer, degenerative \ncutaneous disorders are more apparent in our \nstudy. However, more comparison data is \nrequired to conclude this finding. \n\n\n\nThe occurrence of genital warts was higher in \nPLHIV not on HAART, as compared to those \non HAART. High-risk Human Papillomavirus \n(HPV) types commonly affect the anogenital \nand the oral cavity.18 Prolonged life span in \nstable HAART group predisposes to oncogenic \ntransformation.19 HAART had not been  shown  \nto  reduce  incidents  of  HPV-related cervical \ndiseases in women living with HIV.20 The \nimpact of HAART on cervical cancer, however, \nremains uncertain. The objective of this review \nis to summarize the last ten years of registry-\nbased and clinical research into the impact of \nHAART on human papillomavirus Census from \nHuman Papillomavirus and Related Diseases \nReport Malaysia recorded significant HPV-\nrelated cervical cancer in the high-risk type of \nHPV in the non-HIV population. Data on HPV \nrelated cancer in the treated HIV population in \nthis region is lacking. HPV vaccination have \nsince been included in the national vaccination \nscheme for 13-year-old girls in schools since \n2012. Data on the effective regime of HPV \nvaccination in PLHIV is lacking,21 hence more \ntrials are needed before implementation in the \nnational health scheme. \n\n\n\nImpact on living due to cutaneous manifestation \nwas highest in the stable HIV with higher \nCD4 levels. This is due to a higher number \nof dermatosis and demand on quality of life \nas a struggle to blend into stigmatised society \ntowards HIV. However, a lower mean DLQI \nscore compare to a recent study, could be \nexplained by different expectations of the \nquality of life in different urban populations; \nJohor (East Malaysia)22 and Kuching, Sarawak \n(West Malaysia). Furthermore, population \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4856\n\n\n\nwith lower socioeconomic status are more \nignorant of the non-life-threatening nature of \nthe cutaneous manifestation, resulting in an \nunderrepresentation of the actual situation. \nDespite 85.3% of PLHIV are on HAART in \nKuching which is higher than the national \nstatistics record of 48%, the unemployment \nrate is significant at 30% in contrast to local \nunemployment rates of 15% (2018, Sarawak \nstatistics). This result is also observed in France \nwhere the unemployment rate in PLHIV is \n15.9% as compare to 6.1% in the population \nin 2011.23 unemploymet has increased among \npeople living with HIV. Employment is one of \nthe important defining factors on the quality \nof life. The high unemployment rate in the \nbackground of high literacy rate is the result \nof social stigma, discriminatory policies \nprohibitive laws and ultimately, the lack of \nsocietal support. Another factor with great \nimpact on the quality of living is the side effect \nof HAART which is statistically significant in \nthis study. Due to the nature of this study, no \nsevere cutaneous adverse reactions syndrome \n(SCARS) was reported as most SCARS would \nnecessitate inpatient treatment. \n\n\n\nThe limitation of this study is the small sample \nsize and the absence of data from suburban \nareas. Covid-19 pandemic has a significant \nimplication on both the quality and quantity of \nthe data collected in this study.\n\n\n\nConclusion\nThere is a shift in the mode of transmission \nfrom intravenous to sexual route and from \ninfective to non-infective disorders in PLHIV. \nUltimately, our findings revealed that, despite \nthe introduction of HAART, the number of \ncutaneous manifestations in HIV patients have \nnot significantly reduced. Quality of living in \nPLHIV is best defined by unemployment rate \nand ADR rather than DLQI scoring due to the \nsocioeconomic factors. As we embark on our \nquest to cure HIV and raise the standard of living \nof those living with HIV, we will constantly \nface new challenges. A comprehensive registry \nand awareness are needed to provide a clearer \n\n\n\npicture to redefine management guidelines.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare. There is no affiliation or significant \nfinancial involvement in any organisation or \nentity with direct financial interest in the subject \nmatter or materials discussed in the manuscript.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth, Malaysia for permission to publish this \npaper.\n\n\n\nReferences \n1. Ministry of Health Malaysia. Country Progress Report \n\n\n\non HIB/AIDS 2019 Malaysia. Available at https://www.\nmoh.gov.my/moh/resources/Penerbitan/Laporan/Umum/\nReport_GAM_2019_(Final).pdf. Accessed on 7/6/2021\n\n\n\n2. Ginat DT, Schaefer PW. Highly active antiretroviral \ntherapy (HAART). In: Neuroimaging Pharmacopoeia. \nSpringer International Publishing;2015:203-12. \n\n\n\n3. Koenig LJ, Hoyer D, Purcell DW, Zaza S, Mermin J. \nYoung people and HIV: A call to action. Am J Public \nHealth 2016;106:402-5. \n\n\n\n4. Uthayakumar S, Nandwani R, Drinkwater T, Nayagam \nAT, Darley CR. The prevalence of skin disease in \nHIV infection and its relationship to the degree of \nimmunosuppression. Br J Dermatol 1997;137:595-8. \n\n\n\n5. Waldrop G, Doherty M, Vitoria M, Ford N. Stable patients \nand patients with advanced disease: consensus definitions \nto support sustained scale up of antiretroviral therapy. \nTrop Med Int Health 2016;21:1124-30. \n\n\n\n6. Jing W. A retrospective survey of mucocutaneous \nmanifestations of HIV infection in Malaysia: Analysis of \n182 cases. J Dermatol 2000;27:225-32. \n\n\n\n7. Huang XJ, Li HY, Chen DX, Wang XC, Li ZC, Wu YS et \nal. Clinical analysis of skin lesions in 796 Chinese HIV-\npositive patients. Acta Derm Venereol 2011;91:552-6. \n\n\n\n8. Spira R, Mignard M, Doutre MS, Morlat P, Dabis F. \nPrevalence of cutaneous disorders in a population of HIV-\ninfected patients. Southwestern France, 1996. Groupe \nd\u2019Epid\u00e9miologie Clinique du SIDA en Aquitaine. Arch \nDermatol 1998;134:120. \n\n\n\n9. Dellar RC, Dlamini S, Karim QA. Adolescent girls \nand young women: Key populations for HIV epidemic \ncontrol. J Int AIDS Soc 2015;18:19408.\n\n\n\n10. Glynn JR, Cara\u00ebl M, Auvert B, Kahindo M, Chege J, \nMusonda R et al. Why do young women have a much \nhigher prevalence of HIV than young men? A study in \nKisumu, Kenya and Ndola, Zambia. AIDS 2001;15:S51-\n60.\n\n\n\n11. Scully EP. Sex Differences in HIV Infection. Curr HIV/\nAIDS Rep 2018;15:136-46. \n\n\n\n12. Naranbhai V, Abdool Karim SS, Altfeld M, Samsunder \nN, Durgiah R, Sibeko S et al. Innate immune activation \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 57\n\n\n\nenhances HIV acquisition in women, diminishing the \neffectiveness of tenofovir microbicide gel. J Infect Dis \n2012;206:993-1001.\n\n\n\n13. Arnold KB, Burgener A, Birse K, Romas L, Dunphy \nLJ, Shahabi K et al. Increased levels of inflammatory \ncytokines in the female reproductive tract are associated \nwith altered expression of proteases, mucosal barrier \nproteins, and an influx of HIV-susceptible target cells. \nMucosal Immunol 2016;9:194-205. \n\n\n\n14. Chan GP, Nithianandan M, Thevarajah S, Tang MM. \nCutaneous Manifestations in Patients Infected with \nHuman Immunodeficiency Virus: An Audit in the \nDepartment of Dermatology Hospital Kuala Lumpur. \nMalaysian J Dermatol 2020;45:11-21.\n\n\n\n15. Gon\u00e7alves PH, Uldrick TS, Yarchoan R. HIV-associated \nKaposi sarcoma and related diseases. AIDS 2017;31:1903-\n16. \n\n\n\n16. Nguyen HQ, Magaret AS, Kitahata MM, Van Rompaey \nSE, Wald A, Casper C. Persistent Kaposi sarcoma in the \nera of highly active antiretroviral therapy: characterizing \nthe predictors of clinical response. AIDS 2008;22:937-45. \n\n\n\n17. Patterson BK, McCallister S, Schutz M, Siegel JN, \nShults K, Flener Z et al. Persistence of intracellular \nHIV-1 mRNA correlates with HIV-1-specific immune \nresponses in infected subjects on stable HAART. AIDS \n2001;15:1635-41.\n\n\n\n18. Sirera G, Videla S, Pi\u00f1ol M, Ca\u00f1adas MP, Llatjos \nM, Ballesteros AL et al. High prevalence of human \npapillomavirus infection in the anus, penis and mouth in \nHIV-positive men. AIDS 2006;20:1201-4. \n\n\n\n19. Chelidze K, Thomas C, Chang AY, Freeman EE. HIV-\nRelated Skin Disease in the Era of Antiretroviral Therapy: \nRecognition and Management. Am J Clin Dermatol \n2019;20:423-42.\n\n\n\n20. Adler DH. The impact of HAART on HPV-related cervical \ndisease. Curr HIV Res 2010;8:493-7.\n\n\n\n21. Lacey CJ. HPV vaccination in HIV infection. \nPapillomavirus Res 2019;8:100174. \n\n\n\n22. Lim YT, Tey KE, Choon SE. Prevalence and Types of \nMucocutaneous Disorders, Their Correlation to CD4 \nCount and Their Impact on Quality of Life in Adults with \nHIV Infection. Malaysia J Dermatol 2021;46:11-20. \n\n\n\n23. Annequin M, Lert F, Spire B, Dray-Spira R, ANRS-\nVespa2 Study Group.  Increase in unemployment over the \n2000\u2019s: Comparison between people living with HIV and \nthe French general population. PLoS One 2016;11:32-49.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4858\n\n\n\nORIGINAL ARTICLE\n\n\n\nDermatoses in Human Immunodeficiency Virus Infected Patients with A \nFocus on Infections: A 12-month Cross-sectional Study in Hospital Sungai \nBuloh\n\n\n\nZareen Aidah Yahya1, MRCP, Adawiyah Jamil2, AdvMDerm, Norli Marwyne Mohammed Noor1, AdvMDerm\n\n\n\n1 Dermatology Unit, Department of Medicine, Hospital Sungai Buloh, Ministry of Health, Malaysia\n2 Dermatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Ministry of \nHealth, Malaysia\n\n\n\nAbstract\nBackground\nCutaneous disorders are common clinical manifestations of the Human Immunodeficiency Virus \n(HIV). In the era of antiretroviral therapy (ART), the spectrum of cutaneous disorders in HIV-infected \npatients has changed. We assessed the types of dermatoses, including cutaneous infections in HIV-\npositive patients and the association between the peripheral CD4 cell count and the severity of skin \ninfection.\n\n\n\nMethods\nAll HIV-positive patients referred to the Dermatology Department of Hospital Sungai Buloh from \nJanuary 2021 \u2013 December 2021 were enrolled in a prospective cross-sectional study. Patients were \nsubjected to a complete medical and physical examination and appropriate investigation to confirm \nthe diagnosis. \n\n\n\nResults\nA total of 112 (92.6%) male and 9 (7.4%) female patients with a mean age of 38.76 \u00b1 SD years \nparticipated. The majority of patients were Malay (56.2%), with MSM (54.5%) being the commonest \nmode of transmission. 65.2% of patients had CD4\u2265350 cells/ mm3 and 86.7% of patients were on ART. \nInfections (56.1%) were the most common group of mucocutaneous manifestations, with 45.6% of \nthese due to viral infections. There was no statistically significant correlation between the CD4 count \nand the severity of skin involvement in bacterial (p=0.302), viral (p=0.145) and fungal (p=0.533) \ninfections.\n\n\n\nConclusion\nViral infection were the commonest cutaneous manifestations in HIV- positive patients. The frequency \nand severity of the cutaneous infections were much more common in patients with more advanced \nimmunosuppression.\n\n\n\nKeywords: HIV, mucocutaneous manifestations, CD4 count\n\n\n\nCorresponding Author \nDr Zareen Aidah Yahya \nDermatology Unit, \nDepartment of Medicine, \nHospital Sungai Buloh, \nJalan Hospital, \n47000 Sungai Buloh, Selangor, Malaysia\nEmail: zareenyahya@yahoo.com\n\n\n\nIntroduction\nCutaneous disorders are common clinical \nmanifestations of the Human Immunodeficiency \nVirus (HIV). These skin manifestations are not \nonly associated with terminal immunodeficiency \nbut also occur throughout the course of HIV \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 59\n\n\n\ninfection.1 More than 90% of patients will \ndevelop skin lesions at some time during their \nillness.2-3  \n\n\n\nSkin diseases have been proven to be a sensitive \nand useful measure by which HIV progression \ncan be monitored. With diminished and \ndysregulated cell-mediated immunity, HIV-\ninfected individuals are susceptible to myriad \nskin conditions4, which can be broadly classified \ninto infectious and noninfectious dermatoses. \nAlthough these skin manifestations are also \nencountered in immunocompetent individuals, \ntheir occurrence in HIV-infected patients tend to \npresent earlier, are often atypical, more severe, \nexplosive, extensive or resistant to therapy.5  \n\n\n\nThe clinical spectrum and prevalence of skin \ndisorders in HIV- infected patients are well \ndocumented in western populations. However, \nthere are fewer data available from Asia. Bender \net al. found significant racial differences in the \nprevalence and risk of dermatological conditions \nin patients with HIV.6 Studies in Singapore \nand Thailand reported notable differences in \nthe prevalence and types of skin conditions in \ntheir local population of HIV- infected patients \ncompared to the Western cohorts.7\n\n\n\nThis study aimed to determine the type of \ndermatoses affecting HIV-infected patients, \ndescribe the types of cutaneous infections and \ndetermine the relationship between HIV-related \nimmunodeficiency with type and severity of \ncutaneous infection in a Malaysian HIV-infected \npopulation.\n\n\n\nMaterials and Methods\nA prospective cross-sectional study was \nperformed. The study population was all HIV-\npositive patients referred to the Dermatology \nDepartment in Hospital Sungai Buloh for \nassessment who fulfilled the inclusion and \nexclusion criteria during the study period from \nJanuary 2021 \u2013 December 2021. Hospital \nSungai Buloh is the main referral center for \nInfectious diseases and HIV in Malaysia and \nserves a large number of Klang Valleys HIV-\n\n\n\npositive population. Accessibility to a large \ncohort of HIV-positive individuals provides an \nopportunity to fully explore the prevalence of \nskin infections of HIV-infected patients in our \nlocal population. The inclusion criterion was \nMalaysian, HIV- positive patients aged 18 and \nabove. HIV-infected patients with adverse drug \nreactions were excluded from the study.\n\n\n\nAll patients were subjected to a detailed face-\nto-face interview and physical examination.  \nInformation was collected on demography \ndetails, mode of transmission of HIV infection, \nAnti-retroviral therapy (ART) treatment, \nmost recent CD4 count and viral load. When \nrequired to confirm a diagnosis, appropriate \ninvestigations were performed as per standard \nclinical management. This included, when \nnecessary, skin biopsies, tissue cultures, tzank \nsmears, skin scrapings and PCR analysis.  \nThe mucocutaneous manifestations were \nclassified as skin infections (bacterial, fungal, \nviral and parasitic infections) or inflammatory \ndermatoses (eczematous, psoriasis, seborrheic \ndermatitis and Pruritic Papular Eruption in \nHIV). Cutaneous infections were subsequently \nsubclassified into superficial or subcutaneous \nskin infections.\n\n\n\nThe sample size of this study was calculated \nbased on a cross-sectional study by Uthayakumar \net.al8 Sample size estimation was calculated \nusing the population proportion formula. The \nprevalence of cutaneous manifestations in HIV-\ninfected patients was 0.914. The population size \nof 1000 was based on Hospital Sungai Buloh\u2019s \ninternal database. The Type I error probability \nin rejecting the null hypothesis was 0.05. With \nthe additional 5% dropout rate, the sample size \nrequired was 114 patients.\n\n\n\nAnalysis of the data was done using the IBM- \nStatistical Package for the Social Sciences \n(IBM-SPSS\u00ae) version 25.0 for Windows. \nDescriptive statistics described the sample \ncharacteristics. Continuous variables were \nexpressed as mean and standard deviation. \nFor non-normally distributed data, median and \ninterquartile ranges were used. For categorical \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4860\n\n\n\nvariables, frequency and percentage were used \nto present the data. Fischer exact test tested the \nhypothesis of whether there was an association \nbetween type of infection and CD4 count \ncategories. The level of significance was set \nat 0.05 with two-tailed probabilities. A p value \nless than 0.05 concludes significant associations \nbetween two categorical variables.\n\n\n\nThis study was conducted in compliance with \nethical principles outlined in the Declaration of \nHelsinki and Malaysian Good Clinical Practice \nGuidelines. Data collection was commenced \nafter obtaining Medical Research and Ethics \nCommittee approval. (Approval reference: \nKKM/NIHSEC/P20-2250(11)).\n\n\n\nResults\nA total of 121 HIV-positive patients were \nenrolled. Of these, 112 (92.6%) were male and 9 \n(7.4%) were female. The majority of the patients \nwere Malay (56.2%), followed by Chinese \n(33.9%) and Indians (9.9%). Their average age \nwas 38.7 years. The commonest mode of HIV \ntransmission was men who have sex with men \n(MSM) (54.5%).  Heterosexual and intravenous \ndrug use (IVDU) accounted for 29.8% and \n10.7% of transmission respectively. A total of \n79 patients (65.2%) had CD4 \u2265 350 cells/mm3 \nand 34.7% had CD4 < 200-349 cells/mm3. The \nmajority of the patients were on antiretroviral \ntherapy (ART) (86.7%). Characteristics of the \nstudy population are summarized in Table 1. \n\n\n\nWhen screening for cutaneous infections, 43.8% \nof the patients had non-infective skin dermatoses \ncommonly associated with HIV, including \nseborrheic dermatitis (11.5%), psoriasis (3.3%), \neosinophilic folliculitis (6.6%), pruritic papular \neruption in HIV (14.8%) and papular eczema \n(7.4%). This is summarized in Table 2.\n\n\n\nThe most common cutaneous manifestations \nseen were infectious in origin. Of the 121 patients \nenrolled in the study, 68 (56.1%) patients had \ninfectious lesions.  Table 3 summarizes the type \nof cutaneous infections in the study population. \nSixteen out of the 68 patients (23.5%) in this \n\n\n\nsubgroup had cutaneous bacterial infections. \nThis included botryomycosis (1.4%), folliculitis \n(11.8%), cutaneous tuberculosis (4.4%) and \ncutaneous manifestations of syphilis (5.9%).\n\n\n\nThe diagnosis of botryomycosis was suspected \nclinically. The patient presented with a fleshy, \nsubcutaneous nodule which developed into a \nnon-healing ulcer over the dorsum of the hand. \nTissue culture grew Staphylococcus aureus. The \npatient was treated with amoxycillin/clavulanic \nacid and responded well with resolution of the \nlesion after 2 weeks of treatment.\n\n\n\nViral Infections accounted for the majority \nof infective cutaneous lesions (45.6%). Ten \npatients (14.7%) had cutaneous lesions due to \nhuman papillomavirus (condyloma acuminata), \n7.4% of patients had lesions due to poxvirus \n(molluscum contagiosum), herpes simplex virus \n(oral and anogenital ulcers) and human herpes \nvirus (Kaposi sarcoma). 8.8% of patients had \nlesions due to Varicella zoster virus infection \n(Varicella Zoster). \n\n\n\nCutaneous fungal infections accounted for \n26.5% of infectious lesions. Talaromycosis \n(14.7%), histoplasmosis (1.4%), sporotrichosis \n(2.9%) and dermatophyte infection (7.4%) were \nthe second most common infectious causes seen \nin the study population after viral infections. \nThree (4.4%) cases of parasitic infections \n(scabies) were encountered.\n\n\n\nSub analysis was done to determine the \nassociation between cutaneous infections \nwith the CD4 count. The cutaneous infections \nencountered were grouped based on their \ninvasiveness or severity. Superficial cutaneous \ninfections were defined as infections of the \nepidermis, hair and nails. These included \nmolluscum contagiosum, folliculitis, varicella \nzoster infection, scabies, tinea corporis, tinea \ncruris, genital warts and herpes simplex \ninfection.\n\n\n\nInfections that penetrated the epidermis and the \ndermis to infect the deeper tissues were classed \nas subcutaneous or systemic infections. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 61\n\n\n\nTable 1: Characteristics of the study population\n\n\n\nCharacteristics       Mean\u00b1SD or n (%)\n\n\n\nAge, in years    38.76\u00b110.96\n  Minimum                 18\n  Maximum                 74 \n\n\n\nGender\n   Male        112 (92.6)\n   Female               9 (7.4)\n\n\n\nEthnicity\n   Malay          68 (56.2)\n   Chinese          41 (33.9)\n   Indian          12 (9.9)\n\n\n\nDuration of HIV diagnosis (months)  58.41\u00b142.59\n  Minimum                 12\n  Maximum           240  \n\n\n\nMode of transmission  \n  MSM         66 (54.5)\n  Heterosexual        36 (29.8)\n  IVDU         13 (10.7)\n  Undisclosed          6 (5.0)\n\n\n\nCD4 count\n  CD4 \u2265 350 cells/mm3       79 (65.2)\n  CD4 < 200 -349 cells/mm3       42 (34.7)\n\n\n\nViral load      \n  Suppressed (< 200 copies/ ml)      67 (55.3)\n  Not suppressed (> 200 copies/ ml)      54 (46.6)\n  Not Available            5 (4.1)\n\n\n\nART \n  No           16 (13.2)\n  Yes       105 (86.7)\n\n\n\nSystemic co-morbidities\n  Diabetes         7 (5.7)\n  Hypertension         7 (5.7)\n  Hepatitis/ Liver Cirrhosis      11 (9.1)\n  Syphilis        12 (9.9)\n  Tuberculosis       10 (8.2)\n\n\n\nTable 2:  Types of non-infective dermatoses affecting \nHIV-infected patients in Sungai Buloh Hospital\n\n\n\nType of Dermatoses   n (%)\nSeborrheic Dermatitis   14 (11.5)\nPsoriasis     4 (3.3)\nEosinophilic Folliculitis   8 (6.6)\nEczematous Dermatoses\n      Pruritic Papular Eruption in HIV  18 (14.8)\n      Papular Eczema     9 (7.4)\n\n\n\nThese included kaposi sarcoma, cutaneous \ntuberculosis, sporotrichosis, secondary syphilis, \nhistoplasmosis, botryomycosis and penicilliosis. \nTable 4 summarizes these findings.\n\n\n\nAmongst patients with subcutaneous or systemic \nbacterial infections, 77.8 % had a CD4 < 200-\n349 cells/mm3 and 22.2% had a CD4 \u2265 350 cells/\nmm3. Majority of cutaneous viral infections were \nin patients with CD4 < 200-349 cells/mm3, for \nboth superficial and subcutaneous infections. \nIn patients with subcutaneous/ systemic fungal \ninfections,11 patients had a CD4 < 200-349, \ncompared to 2 patients with CD4 > 350 cells/\nmm3. Subcutaneous or systemic viral infections \nwere found in all patients with CD4 <200-349 \ncells/mm3. There was no significant association \nbetween CD4 count with severity of infection\n\n\n\nOverall, when comparing all types of superficial \ninfections (bacterial, viral and fungal), 22 \npatients had a CD4 < 200-349 cells/mm3 and \n17 patients had a CD4 \u2265 350 cells/mm3. The \ndifference was more obvious when comparing \nsubcutaneous/ systemic infections with 24 \npatients having CD4 < 200-349 cells/mm3 and \nonly 6 patients with CD 4 \u2265 350 cells/mm3\n\n\n\nTable 3: Types of cutaneous infection in the study \npopulation\n\n\n\nType of Infection    n (%)\n\n\n\nBacteria      16 (23.5)\n  Botryomycosis    1 (1.4)\n  Folliculitis    8 (11.8)\n  Cutaneous Tuberculosis   3 (4.4)\n  Syphilis     4 (5.9)\n\n\n\nViral      31 (45.6)\n  Herpes simplex Virus   5 (7.4)\n  Varicella Zoster Virus   6 (8.8)\n  Human Papillomavirus (condyloma acuminata) 10 (14.7)\n  Poxvirus (molluscum contagiosum)  5 (7.4)\n  Human Herpes Virus (Kaposi Sarcoma) 5 (7.4)\n\n\n\nFungal      18(26.5)  \n \n  Talaromycosis    10 (14.7)\n   Histoplasmosis    1 (1.4)\n   Sporotrichosis    2 (2.9)\n   Dermatophytes     5 (7.4)\n\n\n\nParasitic     3 (4.4%)\n  Scabies     3 (4.4)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4862\n\n\n\nTable 4: Relationship between HIV-related \nimmunodeficiency based on CD4 count with the \ntype of cutaneous infection\nType of \ninfection, n \n(%)\n\n\n\nCD4 count p-value\n< 200 -349 \ncells/mm3\n\n\n\nn (%)\n\n\n\n\u2265350 cells/ \nmm3\n\n\n\nn (%)\nBacteria (n=16)\n\n\n\n0.302  Superficial 3 (42.9) 4 (57.1)\n  ubcutaneous 7 (77.8) 2 (22.2)\nVirus (n=31)\n\n\n\n0.145  Superficial 16 (64.0) 9 (36.0)\n  ubcutaneous 6 (100) 0 (0)\nFungus (n=18) 0.533\n  Superficial 3 (60.0) 2 (40.0)\n  ubcutaneous 11 (84.6) 2 (15.4)\n\n\n\nDiscussion\nIt is estimated that 87,041 people live with HIV \n(PLHIV) in Malaysia at the end 2018.9 Skin \ndisorders are extremely common in PLHIV and \nin many patients, they may be the earliest sign \nof HIV disease.10\n\n\n\nThe epidemiologic profile of dermatologic \nillnesses in relation to HIV varies between \ncountries.10 Tan et al and Jing et al found \nthat this is mainly affected by economic and \npolitical factors pertaining to the availability of \nHAART, as well as the risk-taking behavior of \npatients.10-11 This study prompted us to revisit \nthese conditions and examine the changing \nincidence and prevalence of these conditions in \nthe local population of Malaysia.\n\n\n\nDemographic and Clinical Characteristics\nIn this study, the majority of the patients were \nMalay males with a mean age of 38. This is \nconsistent with our national data 9 stating that \n> 70% of HIV- infected patients were males \nbetween the age of 20 and 39 years. Similar data \nwere reported in 2 other studies in the region, \nreported by Huang et al in China and Goh et.al \nin Singapore.1,7 The trend of HIV epidemic in \nMalaysia has now shifted to sexual transmission \nsince 2011. Men who have sex with men \n(MSM) were expected to become the main \ndriver for the epidemic 9 and this is reflected \nin the results of this study with the commonest \nmode of transmission being MSM (54.5%).  \n\n\n\nThe main aim of the Global AIDS Monitoring \nindicators was to have at least 90% of people \nwho know their HIV-positive status accessing \nART by 2020.12 In this study, 86.7% of the study \npopulation were on ART, with 55.3% having \nsuppressed viral loads.\n\n\n\nTypes of dermatoses affecting HIV-infected \npatients\nSkin disease may be uniquely associated \nwith HIV infection or AIDS, but is more \noften due to common disorders that are more \nsevere and recalcitrant to treatment in HIV \npatients.13 Seborrheic dermatitis, psoriasis and \nvaricella zoster virus infection are examples \nof common clinical skin conditions that are \nboth more frequent and more severe with \nadvanced immunosuppression. Kaposi sarcoma \nand pruritic papular eruption (PPE) in HIV \nare examples of skin disorders that serve \nas a marker of disease progression.14 These \ncutaneous conditions can also present as \nnew dermatological manifestations related to \nImmune reconstitution inflammatory syndrome \n(IRIS) or as worsened forms of previous \ndisease.15\n\n\n\nIn this study, 43% and 56.1% of patients had \nnon-infective and infective lesions respectively. \nOf the non-infective lesions, purpuric papular \neruption (PPE) in HIV was the most common \ndiagnosis (14.8%). These results were \ncomparable with Goh et al and Chan et al \nwho reported PPE as the most common non-\ninfectious manifestations in their study cohort \nat 14.9% and 31% respectively.7,16 It is well \nrecognized that PPE is a cutaneous marker of \nadvanced HIV infection7 and this was confirmed \nin this study with all patients diagnosed with \nPPE having a CD4 < 200-349 cells/mm3.\n\n\n\nSeborrheic dermatitis (SD) is an early skin \nmanifestation that is mostly seen in patients who \nhave CD4 > 200.17 In this study, SD was found \nto be the second most common noninfectious \nmanifestation (11.5%), which was also reported \nby Edith et al.17 Four (3.3%) of patients in this \nstudy were diagnosed with psoriasis. These \nresults are comparable to an audit done by \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 63\n\n\n\nDavarpanah et al and Supanaranond et al which \nreported 2.9% and 4.7% of their study population \nwho were diagnosed with psoriasis.18-19\n\n\n\nEosinophilic folliculitis (EF) is a common skin \ndisorder in individuals with HIV who have \nCD4 count < 250cells/mm3 and is uncommon \nin persons without HIV.13 Eight (6.6%) patients \nin this study were diagnosed with EF. Similar \nresults were reported by Goh et al reporting 4% \nof their cohort being diagnosed with EF.7\n\n\n\nCutaneous infections in HIV-infected patients\nIn HIV-infected individuals, typical skin lesions, \nwith more inflamed, widespread, disfiguring \nand destructive presentations may be the result \nof diminished CD4-positive T cell- mediated \nimmune response.4 In the era of ART, the \nspectrum of cutaneous infections has changed.  \nHowever, common cutaneous infections from \nmethicillin-resistant Staphylococcus aureus \n(MRSA) and human papillomavirus (HPV) \nare growing causes of morbidity and mortality \ndespite overall seemingly improved immune \nfunction with antiretroviral therapy.15\n\n\n\nWe found that the most common dermatoses in \nour cohort of patients were infectious in origin \n(56.1%). Similar results were reported with \nslightly higher prevalence by, S. Uthayakumar \net al.  in the UK, Chan et al in Malaysia and \nBasida et al in India.8,16,20\n\n\n\nCutaneous viral infections have been reported \nas the most common dermatological disorder \namong HIV patients in various studies in the \npast decade. Similar results were observed in \nthis study and in China, Taiwan and India.1,2,3 \nIn this study, condyloma acuminata contributed \nthe majority of the total viral- related dermatoses \n(14%). Uthayakumar et al similarly observed \ncondyloma acuminata (14%) to contribute to \nthe majority of cutaneous viral infections.8 \nHuman papillomavirus (HPV) infection is \nmore common in the HIV/AIDS population, \nas   HPV has been found to facilitate HIV gene \nexpression.13 Diagnosis and treatment of these \nlesions are important because of the risk of \nHPV-associated anal and cervical carcinomas.\n\n\n\nIt is well recognized that Kaposi sarcoma (KS) \ndevelops almost exclusively in HIV positive \nhomosexual men and that homosexual contact \nis a risk factor for human herpes virus-8 (HHV-\n8) acquisition.7 In this study, Kaposi Sarcoma \nwas diagnosed as frequently as the common \ncutaneous lesions due to herpes simplex \nvirus and pox virus (7.4%), suggesting that \nKS still represents one of the more common \nHIV associated cutaneous conditions in this \npopulation. Interestingly, other studies in this \nregion, i.e., Singapore and Thailand reported \nno cases of KS in their cohorts.7,21 The apparent \nabsence of KS in their study to be due to the \nsignificantly lower proportion of homosexual \nindividuals in their study population. This \nis another contrast to the demography this \nstudy, where the majority (54.5%) of the study \npopulation were homosexual individuals.\n\n\n\nFungal infections were the second most \ncommon cutaneous infection observed in this \nstudy (26.5%). Talaromycosis accounted for \nthe majority (14%) of fungal dermatoses, a \nresult which was similarly reported by Chan et \nal and Wiwanitkit.16,21 The high prevalence of \nTalaromycosis in this region relative to western \nstudies is likely due to Penicillium marneffei \nbeing endemic to tropical Asia and is now \nconsidered an AIDS-defining illness in endemic \nareas.4\n\n\n\nDermatophyte infections only accounted for \n7.4% of total cutaneous fungal infections in \nour study cohort, which differs from findings \nin previous studies. Vasudevan et al reported \ndermatophytosis as the most common cutaneous \nfungal infection.22 The reason for this difference \nseen in this study may be referral bias. Patients \nwith milder skin disorders, that are treatable \nby HIV physicians may have not been referred \nto us and therefore, may not represent the true \nprevalence in the HIV population.\n\n\n\nStaphylococcus aureus is the most common \ncutaneous and systemic bacterial pathogen in \nHIV- infected individuals. Approximately 54% \nof AIDS patients experience symptoms due to S. \naureus.13 The high frequency of S. aureus skin \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4864\n\n\n\ninfections in HIV-infected patients is attributed \nto high rates of recurrent or chronic nasal \ncarriage in this population, including carriage \nof methicillin-resistant organisms.4 This is \nreflected in the results of this study with 9 out of \n16 patients with cutaneous bacterial infections \ndiagnosed with S. aureus skin manifestations; \ni.e., folliculitis and botryomycosis.\n\n\n\nRelationship between immunodeficiency and \nseverity of infection\nHIV attacks the helper/Inducer T cells (CD4+ \ncells), resulting in syncytial formation and lysis \nwith slow but progressive destruction of this cell \npopulation. In general, the CD4+ cells (%CD4+ \nor absolute count) progressively decreases as \nHIV disease advances.20\n\n\n\nTraditionally lower CD4 counts are reported \nto be associated with infective dermatoses.23 \nCutaneous infections encountered among those \nwith CD4 <200-349 cells/mm3 in our cohort \nwere 2 times more than those with CD4 >500 \ncells/mm3. These results are comparable to \nChan et al who reported 2.7X more cutaneous \ninfections in patients with a CD4< 500 cells/\nmm.3,16\n\n\n\nOverall, when comparing the severity and \ninvasiveness of these cutaneous infections, \nwe observed that those with advanced HIV \n(CD4 <200-349 cells/mm3) had relatively \nhigher percentages rates for both, superficial \nand subcutaneous manifestation for all types \nof cutaneous infections. S Uthayakumar et \nal similarly reported an increasing severity \nindex in the skin lesions associated with a CD4 \ncount of less than 200cells/mm3.8 Fleischer et \nal and Kaplan et al. demonstrated a significant \nassociation between the number and severity of \ncutaneous abnormalities and low CD4 count.24,25\n\n\n\nThe difference was not statistically significant in \nthis study. Supanaranond et al and Coopman et \nal reported no statistically significant association \nbetween the incidence of skin infections and the \nlevel of CD4 counts.19,26 The reason for these \nresults may be the small sample size in this sub- \ngroup analysis.\n\n\n\nSimilar studies previously done in Malaysia \nwere retrospective in nature. However, the data \nfrom this prospective study is limited by the \nrelatively modest sample size. Further larger-\nscale prospective studies are needed to better \ndescribe the mucocutaneous manifestations of \nHIV-infected individuals, its changing spectrum \nin the era of ART and its evolution through the \ndifferent stages of HIV.\n\n\n\nConclusion\nThe spectrum of cutaneous disorders in our \nstudy differs slightly from data around South \nEast Asia, namely Singapore and Thailand with \nthe preponderance of infective lesions observed \nin our study. MRSA infections, malignant \ntransformations of HPV disease and Kaposi \nsarcoma due to HHV-8 infection are likely to \ncontinue to increase as HIV populations have \nlonger life expectancies in the era of ART. \nAwareness of the varied types and patterns of \nthese manifestations would help in the early \ndiagnosis and management of HIV infection and \nultimately decrease the morbidity and improve \nthe quality of life of HIV-infected patients.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n1. Huang XJ, Li HY, Chen DX, Wang XC, Li ZC, Wu YS et \n\n\n\nal. Clinical Analysis of Skin Lesions in 796 Chinese HIV-\npositive Patients. Acta Derm Venereol 2011;91:552-6.\n\n\n\n2. Kumarswamy N, Solomon S, Madhivanan P, Ravikumar B, \nThyagarajan SP, Yesudian P. Dermatologic manifestations \namong immunodeficiency virus patients in South India. \nInt J Dermatol 2000;39:192-5.\n\n\n\n3. Tzung TY, Yang CY, Chao SC, Lee JY. Cutaneous \nmanifestations of human immunodeficiency virus \ninfection in Taiwan. Kaohsiung J Med Sci 2004;20:216-\n24.\n\n\n\n4. Hogan MT. Cutaneous Infections Associated with HIV/\nAIDS. Dermatol Clin 2006;24:473-95.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 65\n\n\n\n5. Chawhan SM, Bhat DM, Solanke SM. Dermatological \nmanifestations in human immunodeficiency virus infected \npatients: Morphological spectrum with CD4 correlation. \nIndian J Sex Transm Dis AIDS 2013;34:89-94.\n\n\n\n6. Bender AM, Tang O, Khanna R, St\u00e4nder S, Kang S, \nKwatra SG. Racial differences in dermatologic conditions \nassociated with HIV: A cross-sectional study of 4679 \npatients in an urban tertiary care centre. J Am Acad \nDermatol 2020;82:1117-23.\n\n\n\n7. Goh BK, Chan RK, Sen P, Theng CT, Tan HH, Wu YJ et al. \nSpectrum of skin disorders in human immunodeficiency \nvirus-infected patients in Singapore and the relationship \nto CD4 lymphocyte counts. Int J Dermatol 2007;46:695-\n9.\n\n\n\n8. Uthayakumar S, Nandwani R, Drinkwater T, Nayagam \nAT, Darley CR. The prevalence of skin disease in \nHIV infection and its relationship to the degree of \nimmunosuppression. Br J Dermatol 1997;137:595-8.\n\n\n\n9. Ministry of Health Malaysia. Country Progress Report \non HIB/AIDS 2019 Malaysia. Available at https://www.\nmoh.gov.my/moh/resources/Penerbitan/Laporan/Umum/\nReport_GAM_2019_(Final).pdf. Accessed on 7/6/2021\n\n\n\n10. Tan J, Pina A, Borges-Costa J. Skin diseases in the Era \nof Highly Active Antiretroviral therapy: A retrospective \nstudy of 534 patients. J Int Assoc Provid AIDS Care. \n2018;17:2325957417752255.\n\n\n\n11. Wang J, Ismail R. Mucocutaneous manifestations of HIV \ninfection: a retrospective analysis of 145 cases in a Chinese \npopulation in Malaysia. Int J Dermatol 1999;38:457-63.\n\n\n\n12. Joint United Nations Programme on HIV/AIDS. Global \nAIDS Monitoring 2020. Geneva: UNAIDS 2019.\n\n\n\n13. Lewis DJ, Feldman SR. Cutaneous manifestations \nof human immunodeficiency virus/ acquired \nimmunodeficiency syndrome: A comprehensive review. J \nDermatol Surg 2020;24:66-73.\n\n\n\n14. 1993 revised classification system for HIV infection \nand expanded surveillance case definition for AIDS \namong adolescents and adults. MMWR Recomm Rep \n1992;41(RR-17)):1-19. \n\n\n\n15. Rodgers S, Leslie KS. Skin infections in HIV-infected \nindividuals in the era of HAART. Curr Opin Infect Dis \n2011;24:124-9.\n\n\n\n16. Chan GP, Nithianandan M, Thevarajah S., Tang MM. \nCutaneous Manifestations in patients infected with Human \nImmunodeficiency Virus: An audit in the Department \nof Dermatology Hospital Kuala Lumpur. Malaysian J \nDermatol 2020;45:11-21.\n\n\n\n17. Nnoruka EN, Chukwuka JC, Anisuiba B. Correlation of \nmucocutaneous manifestations of HIV/AIDS infection \nwith CD4 counts and disease progression. Int J Dermatol \n2007;46:14-8. \n\n\n\n18. Davarpanah MA, Motazedian N, Jowkar F. Dermatological \nManifestations of HIV/ AIDS Individuals in Shiraz, South \nof Iran. J Glob Infect Dis 2018;10:80-3. \n\n\n\n19. Supanaranond W, Desakorn V, Sitakalin C, Naing N, \nChirachankrul P. Cutaneous manifestations in HIV \npositive patients. Southeast Asian J Trop Med Public \nHealth 2001;32:171-6.\n\n\n\n20. Basida SD, Basida B, Zalavadiya N, Trivedi AP. \nDermatological Opportunistic Infections in HIV \nSeropositive Patients: An Observational Study. Cureus \n2021;13:e16852.\n\n\n\n21. Wiwanitkit V. Prevalence of dermatological disorders in \nThai HIV-infected patients correlated with different CD4 \nlymphocyte count statuses: a note on 120 cases. Int J \nDermatol 2004;43:265-8.\n\n\n\n22. Vasudevan B, Sagar A, Bahal A, Mohanty A. Cutaneous \nmanifestations of HIV \u2013 a detailed study of morphological \nvariants, markers of advanced disease and the changing \nspectrum. Med J Armed Forces India 2012;68:20-7.\n\n\n\n23. Oninla OA. Mucocutaneous Manifestations of HIV and \nthe Correlation with WHO clinical staging in a Tertiary \nHospital in Nigeria. AIDS Res Treat 2014;2014:360970.\n\n\n\n24. Fleischer AB, Gallagher PN, Van der Horst \nC. Mucocutaneous abnormalities predicted by \nlymphocyte counts in patients infected with the human \nimmunodeficiency virus. South Med J 1992;85:687-90. \n\n\n\n25. Kaplan MH, Sadick N, McNutt NS, Meltzer M, \nSarngadharan MG, Pahwa S. Dermatologic findings \nand manifestations of AIDS. J Am Acad Dermatol \n1987;16:485-506.\n\n\n\n26. Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous \ndisease and drug reactions in HIV infection N Engl J Med \n1993;328:1670-4.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4866\n\n\n\nORIGINAL ARTICLE\n\n\n\nClinical Characteristics of Anogenital Warts Among Patients Attending \nGenitourinary Medicine Clinic Hospital Kuala Lumpur Between 2015 and \n2020\n\n\n\nKhai Shin Tan, MBBS, Vijayaletchumi Krishnasamy, Dip. STD/AIDS, Suganthi Thevarajah, MMed, Min Moon \nTang, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur Kuala Lumpur, Malaysia\n\n\n\n \nAbstract\nBackground\nAnogenital human papillomavirus (HPV) is the most frequent reported sexually transmitted infection in \nthe world. We aim to describe the local demographic data and the clinical characteristics of anogenital \nwarts (AGWs).\n\n\n\nMethods\nThis is a retrospective study on all patients with AGWs who attended the GUM clinic between 2015 \nand 2020. Data was obtained from case notes and further analysed.\n\n\n\nResults\nA total of 935 patients with AGWs attended the GUM clinic between 2015 and 2020.  The mean \nage was 30.4 years (range 12-84). The male to female ratio was 2.35:1. Majority were Malaysian \n(97%). Majority of the Malaysian were Malays (61.5%) followed by Chinese (27.7%) and Indian \n(8.9%). About 5.6% had a history of substance abuse. While the majority (57.9%) were heterosexual, \n34.8% were homosexual and 6.4% were bisexual. About 59.8% had more than one sexual partner. \nA quarter (25.6%) was infected with the human immunodeficiency virus. The most frequent site of \nAGWs in males was the perianal area (52.6%), followed by the penis (45.7%), and with a fifth of \nthem having lesions at multiple sites. For female patients, the most frequent site of AGWs was the \nposterior fourchette (45.2%) followed by the labia minora (33%) with 46.6% had involvement at \nmultiple sites. Approximately 17.6% had other concomitant sexually transmitted infections. Local \ntreatment application used included cryotherapy (86.4%), podophyllin (35.3%), tri-chloroacetic acid \n(26.8%) and imiquimod (2.6%). About 41.5% required combination of these modalities. Nearly 6.2% \nexperienced recurrence. About 2% required surgical intervention.\n\n\n\nConclusions\nAGWs was more commonly observed in male. The most frequent site of involvement was perianal for \nmale (52.6%) and posterior fourchette in female (45.2%). \n\n\n\nKey words: Sexually transmitted infections, anogenital warts, Human Papilloma Virus, Human Immunodeficiency Virus\n\n\n\nCorresponding Author\nDr Tan Khai Shin \nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur, Malaysia\nEmail: khaishin39@gmail.com\n\n\n\nIntroduction\nAnogenital human papillomavirus (HPV) is the \nmost frequently reported sexually transmitted \nviral infection in the world.1 HPV 6 and 11 \naccount for the majority of anogenital wart \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 67\n\n\n\n(AGWs) cases and are highly infectious; \napproximately 65% of individuals with an \ninfected partner develop AGWs within 3 weeks \nand 8 months.2 Recent prospective studies \nreported that the median time between infection \nwith HPV types 6 or 11 and the development \nof AGWSs was 11 to 12 months among males \nand 5 to 6 months among young females.2 The \ntransmission are predominantly through oral, \nanal and genital sexual contact, and, in rare \ninstances, through vertical transmission and \nautoinoculation.2 AGWs were strongly believed \nto be associated with high sexual partner \nnumbers and unprotected sexual intercourse. \nThis diagnosis was more common in men \nwho have sex with men (MSM) and in women \nreporting sex with women.1,2  \n\n\n\nFour distinct sub-types of AGWs have \nbeen described which include condylomata \nacuminata (pointed warts), flat/macular lesions, \npapular, and keratotic lesions.3 The first two \nsub-types are mainly found on moist, non-\nkeratinized epithelia, while the latter two are \nusually present on keratinized epidermis.3 They \nmanifest as visible lesions, namely as single \nor multiple papules on the vulva, perineum, \nperianal area, vagina, cervix, penis, anus, \nscrotum and urethra.3 Clinical symptoms may \ninclude pruritus, burning, vaginal discharge and \nbleeding.  In rare cases, AGWs can be associated \nwith malignant lesions, namely Buschke \nLowenstein tumours.3 Although AGWs do not \nusually result in major immediate morbidity or \nmortality, the psychological morbidity and very \nsubstantial healthcare costs   is significant.4\n\n\n\nThis study aims to describe the local demographic \ndata and the clinical characteristics of AGWs at \nGenitourinary Medicine Clinic, Department of \nDermatology, Hospital Kuala Lumpur (HKL).\n\n\n\nMaterials and Methods\nThis is a retrospective study on all patients with \nAGWs attended GUM clinic, HKL between \n1st July 2015 and 30th June 2020. Information \nincluding demographics, clinical features, \n\n\n\nhuman immunosuppressive virus (HIV) \nstatus, co-morbidities, co-infections, treatment \ndurations, treatment modalities and recurrent \nrate was recorded into data collection form. \nData collected was further analysed using SPSS \nversion 21.\n\n\n\nResults\nA total of 935 patients with AGWs attended the \nGUM clinic, HKL between 2015 and 2020. A \nquarter (25.6%) of them was infected with the \nhuman immunodeficiency virus (HIV). The \ndemographic data is shown in Table 1. The \nmean age of all the patients at presentation was \n30.4 years (range 12-84), with a significant \nyounger mean age among those infected with \nHIV. Majority of the patients (55.8%) were in \nthe age group between 20-29 years. The male \nto female ratio was 2.35:1. More than 98% of \nthose infected with HIV were male. Majority \nwere Malaysians (97%) whereby 61.5% were \nMalays, followed by Chinese, (27.7%) and \nIndian (8.9%). \n\n\n\nWhile majority (57.9%) were heterosexual, \n34.8% were homosexual and 6.4% were \nbisexual. Interestingly, 80.3% of those infected \nwith HIV were homosexual (vs non-HIV \n19.1%, p<0.0001). A significant higher number \nof patients infected with HIV engaged casual \nsex partner (71.1% vs 28.3%, p<0.0001). About \n59.8% had more than one sexual partner 6 months \nprior to presentation and it was significantly \nhigher among HIV infected patients (83.3% \nvs 51.7%, p<0.0001). Fifty-two patient (5.6%) \nwere documented to have substance abuse. \nAbout 17.6% had other concomitant sexually \ntransmitted infections. Except chlamydial \ninfection, the rate of syphilis, gonorrhea and \nherpes genitalis were significantly higher among \nthose infected with HIV. Seventy females (25% \nof all female patients), all non-HIV infected, \nwere pregnant at presentation. Furthermore, \nthree patients (0.3%) had active malignancy \nand were undergoing anti-cancer treatment at \npresentation. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4868\n\n\n\nTable 1: Demographic characteristics of 935 patients attending GUM clinic Hospital Kuala Lumpur with \nanogenital warts \nCharacteristics Total\n\n\n\nn = 935 (%)\n\n\n\nHIV status\nPositive\n\n\n\nn= 239 (%)\nNegative\n\n\n\nn=696 (%)\np\n\n\n\nGender Male 656 (70.2) 235 (98.3) 421 (60.5) <0.0001\nFemale 279 (29.8) 4 (1.7) 275 (39.5)\n\n\n\nMean age in years (range) 30.4 (12-84) 28.3 (15-68) 31.2 (12-84) <0.001\nAge group in years, n (%) <20 32 (3.4) 9 (3.8) 23 (3.3) <0.001\u00a7\n\n\n\n20-29\u00a7 522 (55.8) 158 (66.1) 364 (52.3)\n30-39 258 (27.6) 52 (21.8) 206 (29.6)\n40-49 61 (6.5) 10 (4.2) 51 (7.3)\n50-59 37 (3.95) 8 (3.3) 29 (4.2)\n60-69 17 (1.8) 2 (0.8) 15 (2.2)\n>70 8 (0.85) 0 (0) 8 (1.1)\n\n\n\nEthnicity, n (%) Malay 558 (59.7) 141 (59.0) 417 (59.9)\n0.02Chinese\u03c6 251 (26.8) 78 (32.6) 173 (24.9)\n\n\n\nIndian 81 (8.7) 10 (4.2) 71 (10.2)\nOthers \n(Bumiputera \nSabah, Sikh)\n\n\n\n17 (1.8) 7 (2.9) 10 (1.4)\n\n\n\nForeigner 28 (3.0) 3 (1.3) 25 (3.6)\nSexual orientation, n (%) Heterosexual 541 (57.9) 15 (6.3) 526 (75.6)\n\n\n\n<0.0001\u00b6\nHomosexual\u00b6 325 (34.8) 192 (80.3) 133 (19.1)\nBisexual 60 (6.4) 28 (11.7) 32 (4.6)\nMissing data 9 (1) 4 (1.7) 5 (0.7)\n\n\n\nType of sexual partners, n (%) Casual\u03c6 367 (39.3) 170 (71.1) 197 (28.3) <0.0001\u03c6\n\n\n\nRegular 239 (25.6) 52 (21.8) 187 (26.9)\nSpouse 233 (24.9) 3 (1.3) 230 (33.0)\nSex worker 24 (2.56) 1 (0.4) 23 (3.3)\nMore than 1 type 48 (5.13) 4 (1.6) 44 (6.3)\nNo partner 24 (2.56) 9 (3.8) 15 (2.2)\n\n\n\nNumber of patients with 2 or more partners in the \npast 6 months, n (%)\n\n\n\n559 (59.8) 199 (83.3) 360 (51.7) <0.0001\n\n\n\nNumber with documented substance abuse, n (%) 52 (5.6) 13 (5.4) 39 (5.6) 0.94\nConcomitant sexually \ntransmitted infections (STI), n \n(%)\n\n\n\nSyphilis 83 (8.9) 59 (24.7) 24 (3.4) <0.0001\nGonorrhoea 44 (4.7) 18 (7.5) 26 (3.7) 0.02\nHerpes genitalis 25 (2.7) 12 (5.0) 13 (1.9) 0.02\nChlamydial \ninfection\n\n\n\n24 (2.6) 3 (1.3) 19 (2.7) 0.29\n\n\n\nMultiple other \nSTI* \n\n\n\n18 (1.9) 16 (6.7) 2 (0.3) <0.0001\n\n\n\nComorbidities, n (%) Pregnancy 65 (7.0) 0 (0) 65 (9.3) -\nDiabetes mellitus 50 (5.3) 4 (1.7) 46 (6.6) <0.001\nPregnant with \ndiabetes mellitus\n\n\n\n5 (0.5) 0 (0) 5 (0.7) -\n\n\n\nMalignancy 3 (0.3) 0 (0) 3 (0.4) -\nOthers 33 (3.5) 4 (1.7) 29 (4.2) -\n\n\n\nHIV \u2013 human immunodeficiency virus; * including hepatitis B and hepatitis C viruses\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 69\n\n\n\nTable 2: Clinical Characteristics and treatments of anogenital warts (AGWs) in 935 patients attending GUM \nclinic, Hospital Kuala Lumpur\nCharacteristics Total\n\n\n\nn = 935 (%)\n\n\n\nHIV status\nPositive\n\n\n\nn= 239 (%)\nNegative\n\n\n\nn=696 (%)\np\n\n\n\nDistribution of AGWs in men, Total 656 235 421\nPerianal 345 (52.6) 206 (87.7) 139 (33.0) <0.0001\n\n\n\nPenis 300 (45.7) 38 (16.2) 262 (62.2) <0.0001\nScrotum 67 (10.2) 10 (4.3) 57 (13.5) <0.0001\n\n\n\nIntra-anal 14 (2.1) 47 (20.0) 20 (4.8) <0.0001\nIntra-urethral 11 (1.7) 2 (0.9) 16 (3.8) 0.02\n\n\n\nMon pubis 1 (0.2) 0 (0) 1 (0.2) -\nMultiple sites 135 (20.6) 66 (28.1) 69 (9.9) 0.0002\n\n\n\nDistribution of AGWs in \nwomen, \n\n\n\nTotal 279 4 275\nPosterior \n\n\n\nfourchette \n125 (44.8) 0 (0) 125 (45.4) -\n\n\n\nLabia minora 92 (33,0) 3 (75) 89 (32.4) 0.11\nLabia majora 80 (28.7) 3 (75) 73 (26.5) 0.07\n\n\n\nClitoris 88 (31.5) 0 (0) 88 (32.0) -\nPerineum 7 (2.5) 0 (0) 7 (2.5) -\n\n\n\nMons pubis 1 (0.4) 0 (0) 1 (0.4) -\nUrethra 1 (0.4) 0 (0) 1 (0.4) -\nVagina 29 (10.4) 0 (0) 29 (10.5) -\nCervix 1 (0.4) 0 (0) 1 (0.4) -\n\n\n\nAnus 6 (2.2) 0 (0) 6 (57.1) -\nMultiple sites 130 (46.6) 3 (75) 127 (46.2) 0.30\n\n\n\nTreatment provided Cryotherapy 808 (86.4) 214 (89.5) 594 (85.8) 0.09\nPodophyllin 330 (35.3) 107 (44.8) 223 (32.0) 0.0004\n\n\n\nTri-chloroacetic \nacid\n\n\n\n251 (26.8) 90 (37.7) 161 (23.1) <0.0001\n\n\n\nImiquimod 24 (2.6) 5 (2.1) 19 (2.7) 0.62\nCombined \nmodalities\n\n\n\n388 (41.5) 131 (54.8) 257 (36.9) <0.0001\n\n\n\nNumber who improved with treatment provided, \nn (%)\n\n\n\n717 (76.7) 176 (73.6) 541 (77.7) 0.20\n\n\n\nNumber who required surgical intervention, n \n(%)\n\n\n\n17 (1.8) 6 (2.5) 11 (1.6) 0.37\n\n\n\nMean number of treatments (range) 3.84 (0-62) 5.21 (1-62) 3.38 (0-28) <0.001\nMean duration of treatment received in months \n(range)\n\n\n\n2.16 (0-26) 3.09 (0-26) 1.84 (0-19) <0.001\n\n\n\nRecurrence within 6 months, n (%) 58 (6.2) 14 (5.8) 44 (6.3) 0.82\nLost to follow up 417 (44.6) 121 (50.6) 296 (42.5) 0.03\n\n\n\nHIV \u2013 human immunodeficiency virus\n\n\n\nThe characteristics of AGWs and type of \ntreatments provided are shown in Table 2. \nThe most common site of AGWs in males was \nperianal (52.6%) followed by warts at penis \n(45.7%) and 20.6% had lesions at multiple sites. \nInterestingly, HIV infected male patients had \na significant higher rate of AGWs at perianal \nand intra-anal region, with nearly 30% of them \n\n\n\nhad involvement at multiple sites. For female \npatients, the most frequent site of AGWs was \nposterior fourchette (44.8%) followed by labia \nminora (33%) and about 46.6% had involvement \nof multiple sites. Biopsy was performed in 5 \npatients (0.5%) and they showed condylomata \nacuminata, with no dysplasia or carcinoma. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4870\n\n\n\nLocal ablative treatment provided included \ncryotherapy (86.4%), podophyllin (35.3%), \ntri-chloroacetic acid (26.8%) and imiquimod \n(2.6%). About 41.5% required combination of \nthese modalities and the rate was significantly \nhigher rate among those infected with HIV \n(54.8% vs 36.9%, p<0.0001). Majority of our \npatients (76.7%) improved with these treatment \nmodalities. The mean number of treatments was \n3.84 with a range of 0-62. Patients who had \nvery large lesions (2%) that were not suitable \nfor local ablative treatment were referred for \nsurgical intervention. The mean duration of \ntreatment was 2.16 months with a range of \n0-26 months. The duration and number of \ntreatments for AGWs with concurrent HIV \ninfected patients were significantly higher (both \np<0.001). The overall rate of lost to follow up \nwas high at 44.6%, higher among those infected \nwith HIV. There were 126 patients (13.5%) lost \nto follow up after the first visit itself. Nearly \n6.2% experienced recurrence with the rates \nwere similar between those infected with HIV \nand without HIV. \n\n\n\nDiscussion\nPrevious audits done in Hospital Kuala Lumpur \nshowed that AGWs are one of the most \ncommon sexually transmitted infections (STIs) \nencountered in GUM clinic as shown in Table \n3.5,6,7 A 10-year retrospective study on changing \npattern of sexually transmitted infections in \nHospital Kuala Lumpur showed that there was \nan overall decrease in bacterial STIs but an \nincrease in viral STIs (genital warts, genital \nherpes and HIV).5 In the United Kingdom, \nthe number of genital warts in 2004 showed a \n32% increase compared to 1995.3 AGWs are a \ncommon manifestation of an HPV infection, \nparticularly among young men and women. The \nprevalence of AGWs was estimated to range \nbetween 0.13% and 0.20% typically in most \nstudies.2 \n\n\n\nMost of our local studies showed a male \npredominance in STI acquisition and sexual \nexperience.5,6,8 Multiple partner behaviour \nwas found to be significantly associated with \n\n\n\nmale gender.8 Our data is similar to other \ncountries (Table 4) whereby there was a male \npredominance for anogenital warts.2,9,10,11 One \nof the reasons stated in some studies is that \nmales who initially present with symptoms \nusually seek consultations with urologists or \ndermatologists whereas females routinely visit \ngynaecologists.  The specialty of the physicians \nmost frequently performing the initial diagnosis \nof AGWs varies depending on the healthcare \nsystem of individual countries, which could \ncontribute to the differences in reported AGWs \namong genders.2\n\n\n\nThe most common age group presenting with \nwarts was from 20 to 29 years and this was also \nobserved in other reports worldwide (Table 4).2,9-\n\n\n\n12,13-22 This age group is more sexually active and \nhas a higher risk of behavioural vulnerability \nto acquiring STIs given the number of sexual \npartners. There are also more frequent partner \nchanges compared to the older group. Another \nstudy found that anogenital wart incidence \npeaked among younger males due to high-risk \nsexual behaviour; this peak corresponded to new \npartner acquisition as well.2 In the United States \nthe median age of those with genital warts was \n31.3 years among men who reported having sex \nonly with women and 33.2 years among men \nwho have sex with men (MSM)10 and the mean \nage group in our cohort is 30.4. \n\n\n\nAGWs was also reported to be higher among men \nwho have sex with men (MSM) and in women \nreporting sex with women.12,23 In Thailand the \nrate of human immunodeficiency virus (HIV) \ninfection among those with anogenital warts \nwas 15%.13 Our data, however, showed a \nmuch higher rate of HIV in those with AGWs \nat 25.6%. The Genitourinary clinic, Hospital \nKuala Lumpur is the one of the main referral \ncentres for treatment of anogenital warts in HIV \ninfected patients from health clinics around the \nvicinity of Kuala Lumpur and Selangor. This is \nbecause we provide ablative treatments. \n\n\n\nAGWs are strongly associated with multiple \npartners and unprotected sex. Additional risk \nfactors include the use of oral contraceptives, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 71\n\n\n\nTable 3: Comparison of clinic-epidemiological trend on anogenital warts (AGWs) in Genitourinary Medicine \nClinic, Hospital Kuala Lumpur from 1995-2017\nStudy Study year n % of AGWs among of all \n\n\n\nsexually transmitted diseases\nAge group with highest frequency \n\n\n\nof AGWs or \nMean age in years\n\n\n\nLim et al.5,2007 1995-1999 171 5.43 30-49\n2001-2005 301 10.35 20-39\n\n\n\nHariyadurai et al.6, 2019 2015-2016 389 30.2 32.09 \u00b1 12.080\nKrishnasamy et al.7, 2019 2013-2017 273 43.2 31.2\n\n\n\nTable 4: Comparison of clinic-epidemiological studies on anogenital warts in other countries\nAuthor, year, country n Male to female \n\n\n\nratio of anogenital \nwart\n\n\n\nMean Age \nin years \nor most \n\n\n\nfrequently \naffected age \n\n\n\ngroup\n\n\n\nHIV \n(%)\n\n\n\nMost frequent \naffected site\n\n\n\nTreatment modalities \nused\n\n\n\nMale Female\n\n\n\nTan et al, 2022, Malaysia \n(present study)\n\n\n\n935 2.35:1 30.4 25.6 Male \u2013 perianal;\nFemale - Posterior \n\n\n\nfourchette\n\n\n\nCryotherapy, \npodophyllin, tri-\nchloroacetic acid, \n\n\n\nimiquimod\n\n\n\n656 279\n\n\n\nNy\u00e1ri et al.14, 2004, \nHungary\n\n\n\n397 0 397 35.5 N/A N/A N/A\n\n\n\nDinh et al.15, 2007, USA 11 454 1:1.12 35- 44 N/A N/A N/A\n\n\n\nKjaer SK et al.16, 2007, \nNordic countries\n\n\n\n7351 0 7351 31.8 N/A N/A Suggest prophylactic \nHPV vaccine\n\n\n\nNyitray et al.17, 2008, \nUSA\n\n\n\n222 222 0 18 \u201329 0 N/A N/A\n\n\n\nSuligoi et al.18, 2008, \nItaly\n\n\n\n63 0 63 25\u201334 0 N/A Advice vaccination\n\n\n\nCastellsague et al.19, \n2009, Spain\n\n\n\n56 446 1.29:1 31 N/A N/A Imiquimod or \npodophyllotoxin\n\n\n\nMarra et al.20, 2009, \nCanada\n\n\n\n39 493 N/A N/A 20-29 N/A N/A N/A\n\n\n\nLin et al.21, 2010, Hong \nKong\n\n\n\n721 4.55:1 18-30 N/A N/A N/A\n\n\n\nLee et al.22, 2010, South \nKorea\n\n\n\n167 767 1:2.33 30\u201334 N/A N/A N/A\n\n\n\nJiamton et al13, 2014, \nThailand\n\n\n\n181 181 0 31.1 15 Penile shaft Suggest quadrivalent \nHPV vaccine\n\n\n\nSonnenberg P et al12, \n2018, UK\n\n\n\n9 902 1:1.45 20-25 N/A N/A Advice vaccination\n\n\n\nN/A \u2013 Not available; HIV -  human immunodeficiency virus; HPV \u2013 human papilloma virus; N/A \u2013 data not available\n\n\n\nhistory of ever having used cocaine or street \ndrugs, history of sexually transmitted infections, \nsmoking, or immunosuppression.15,24 This was \nsimilarly reflected in our observation as more \nthan half of our cohort had more than one sexual \npartner while 17.6% had other concomitant \nsexually transmitted infections. \n\n\n\nLimited data is available on the prevalence of \nAGWs in pregnant women. Our cohort showed \n\n\n\nthat a quarter of the female patients with AGWs \nwere pregnant. AGWs in pregnancy has an \nimplication on the mode of treatment and \ndelivery. Caesarean delivery is indicated for \nwomen with genital warts if the pelvic outlet is \nobstructed or if vaginal delivery would result \nin excessive bleeding.1 Rarely, HPV types 6 \nand 11 can cause respiratory papillomatosis \nin infants and children.24,25 Whether caesarean \nsection prevents respiratory papillomatosis in \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4872\n\n\n\ninfants and children is however, unclear.25 \n\n\n\nTreatment options for AGWs include patient-\napplied (podofilox, imiquimod), physician \napplied (podophyllin, trichloroacetic acid, \ninterferon) and ablative treatments (cryotherapy, \nsurgical removal, laser treatment).24 We provide \nall modalities of treatment for AGWs at our \ncentre except podofilox, interferon and laser \ntreatment. If we exclude those who were \nreferred for surgical excision of the lesions, an \naverage duration of 2.16 months is required to \nremove the visible lesions in nearly 80% of our \npatients the treatment modalities provided.  A \nstudy done in Canada also reported an average \nepisode of care for genital warts of about 2 to 3 \nmonths.20 \n\n\n\nHPV type 16, 18 31 33 and 35 are occasionally \nfound in anogenital warts (usually as \ncoinfection with HPV 6 or 11).  It is associated \nwith foci of high grade squamous intraepithelial \nlesions particularly in persons who have HIV \ninfections.1 Squamous cell carcinomas arising \nin or resembling genital warts might occur more \nfrequently among immunosuppressed persons. \nWhile AGWs are diagnosed based on clinical \nappearance, a biopsy to assess lesions suspicious \nof malignant transformation may be indicated. \nScreening for anal intraepithelial neoplasia \nby cytology can be considered in view of the \nincreased incidence of anal cancer in HIV infected \nMSM.27 A study demonstrated that biopsies of \ngenital lesions consistent with condylomata \nacuminata from immunosuppressed patients \ncontained significantly more HPV types than \nlesions from the control group.28 HPV types \nassociated with an increased risk of dysplasia \n(high-risk types) were in 100% specimens from \nimmunosuppressed patients in which 24 patients \nwere immunosuppressed, with a third were \norgan transplant recipients and the remaining \nwere infected with HIV.28 \n\n\n\nGenital warts in HIV infected patients are more \ndifficult to treat with frequent recurrences.29 Our \nHIV infected patients required higher number \nand longer treatment duration in order to achieve \nabout 70% clinical improvement. Interestingly \n\n\n\nthe recurrence rate among our HIV cohort did \nnot differ from those without HIV infection. The \nhigh recurrence rate described in the literature \nmay be due to defects in cell-mediated immunity \nand untreated asymptomatic subclinical \ninfections that may act as an unnoticed source \nof infection.13 \n\n\n\nAGWs can be prevented by the administration \nof the human papilloma virus vaccine. Three \nprophylactic vaccines, Cervarix\u00ae, Gardasil\u00ae \n(quadrivalent HPV) and Gardasil\u00ae9 (nano \nvalent HPV), have been approved by the Food \nand Drug Administration (FDA) in the United \nStates to protect against HPV infections.30 \nGardasil\u00ae vaccine protects against HPV 6 \nand 11, which are associated with 90% of \ngenital warts and 95% of recurrent respiratory \npapillomatosis.31 In clinical trials conducted \nwith 92 to 319 HIV patients, seroconversion to \nHPV was observed in 75-100% of vaccinated \nHIV patients.32-34 Gardasil\u00ae9 is also expected \nto protect against ~80-85% cases of HPV-\nassociated vaginal cancers, 90-95% of HPV-\nassociated anal cancers, 85-90% of HPV-\nassociated vulvar cancers.35 \n\n\n\nGardasil\u00ae has been the vaccine of choice \nworldwide. It has been chosen by health \nauthorities in the United States, Australia, New \nZealand, Canada, Switzerland, Italy, Spain, and \nSweden for regional or national vaccination \nprogrammes against cervical cancer.36 The \nUnited Kingdom substituted the bivalent \nvaccine with the quadrivalent one in 2012, \nsince the government clarified that the aim is to \nprotect girls against the types of HPV that cause \ncervical cancer and those that cause genital \nwarts.37 In Spain, there was a decline in genital \nwarts when female subjects were vaccinated \nwith quadrivalent HPV vaccine.38 In Australia \n& New-Zealand, cases of genital warts reduced \nafter the introduction of HPV vaccine.26,39\n\n\n\nIn Malaysia, the routine vaccination was started \nin 2010 for all teenage girls. The only vaccine \nproposed by the ministry to be used in hospitals \nand clinics of ministry of health is bivalent type \n(Cervarix\u00ae) from GlaxoSmithKline (GSK) \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 73\n\n\n\nBiological manufacturer to prevent a cervical \ncancer caused by HPV type 16 and type 18.40 \nHowever, evidence has shown that bivalent \nvaccine does not confer cross-protection against \ngenital warts caused by HPV 6 and 11, therefore \nteenage girls who have been vaccinated with \nCervarix\u00ae can still contract genital warts.12 \n\n\n\nBased on this knowledge, it would be best that \nquadrivalent vaccine (Gardasil) or Gardasil 9 be \nadministered instead. Gardasil\u00ae should also be \noffered to MSM (up to and including 45 years \nof age) as studies have shown that MSM have \na higher incidence of HPV infection and related \ndiseases.37, 41 This knowledge, along with the \nexpectation that MSM will benefit less from \nherd protection from the vaccination of women, \nquadrivalent vaccination should be offered to \nMSM attending sexual health and HIV clinics, \nas a cost-effective intervention.12,42\n\n\n\nThe biggest challenge we face in our setting is to \nensure patients stay in contact with our tertiary \nmedical services and adhere to the treatment \nplan. If the AGWs are inadequately managed, \nthese patients will be a risk to others. There are \nseveral factors contributing to the high rate of \nlost to follow up in our cohort. Patients tend to \nmiss their appointments once they experience \nresolution of symptoms. Other reasons included \nthe inability to adhere to frequent follow-up as \npatients are normally seen every two weeks in the \nGUM clinic until complete resolution of visible \nwarts. Effective lost to follow up strategies need \nto be endorsed and enforced to overcome this \nissue as described by Rayment et al.43 Primary \ncare physicians and other health care provider \nsuch as home visit health care team may need \nto be involved in this initiative. Further studies \nare needed to determine the causes of the high \nlost to follow up rate. Strategies that can be \nimplemented to reduce this high rate include \nstructured patient education on first consultation \nand a more flexible appointment system etc. \n\n\n\nConclusion\nAGWs was more commonly observed in \nmale. The most frequent site of involvement \nwas perianal for male (52.6%) and posterior \n\n\n\nfourchette in female (45.2%).  The most \nfrequent treatment modality used was \ncryotherapy (86.4%) and about 41.5% required \ncombination of treatments. About 6.2% \nexperienced recurrence. The human papilloma \nvirus vaccination in our national immunization \nshould be promoted to male students to reduce \nthe prevalence of genital warts.\n\n\n\nConflict of Interest Declaration \nAll authors have no financial/conflict of interest \nto disclose.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director of \nHealth Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n1. Workowski KA, Bolan GA; Centers for Disease Control \n\n\n\nand Prevention. Sexually transmitted diseases treatment \nguidelines, 2015. MMWR Recomm Rep 2015;64:1-137.\n\n\n\n2. Patel H, Wagner M, Singhal P, Kothari S. Systematic \nreview of the incidence and prevalence of genital warts. \nBMC Infect Dis 2013;13:39.\n\n\n\n3. Lacey CJ, Lowndes CM, Shah KV. Chapter 4: Burden and \nmanagement of non-cancerous HPV-related conditions: \nHPV-6/11 disease. Vaccine 2006;24:35-41.\n\n\n\n4. Graziottin A, Serafini A. HPV infection in women: \npsychosexual impact of genital warts and intraepithelial \nlesions. J Sex Med 2009;6:633-45.\n\n\n\n5. Lim P, Gangaram HB, Hussein SH. A 10-year \nRetrospective Study on Changing Pattern of Sexually \nTransmitted Infections in Hospital Kuala Lumpur, \nMalaysia. Malaysian J Dermatol 2007;19:41-6.\n\n\n\n6. Hariyadurai HR, Syed Nong Chek SR, Johar A. Prevalence \nof Sexually Transmitted Infections in Genito-Urinary \nMedicine Clinic, Hospital Kuala Lumpur between 2015-\n2016. Malaysian J Dermatol 2019;42:8-13.\n\n\n\n7. Krishnasamy V, Tang MM, Thevarajah S. Pattern of \nSexually Transmitted Infections among Females attending \nGenitourinary Medicine Clinic, Hospital Kuala Lumpur \nbetween 2013 and 2017. Malaysian J Dermatol 2019;42:2-\n7.\n\n\n\n8. Anwar M, Sulaiman SAS, Ahmadi K. Khan TM. Awareness \nof school students on sexually transmitted infections \n(STIs) and their sexual behavior: a cross-sectional study \nconducted in Pulau Pinang, Malaysia. BMC Public \nHealth 2010;10:47 \n\n\n\n9. Castellsagu\u00e9 X, Cohet C, Puig-Tintor\u00e9 LM, Acebes LO, \nSalinas J, San Martin M et al. Epidemiology and cost of \ntreatment of genital warts in Spain. Eur J Public Health \n2009;19:106-10.\n\n\n\n10. Llata E, Stenger M, Bernstein K, Guerry S, Kerani R, \nPugsley R et al. Prevalence of genital warts among \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4874\n\n\n\nsexually transmitted disease clinic patients-sexually \ntransmitted disease surveillance network, United States, \nJanuary 2010 to December 2011. Sex Transm Dis \n2014;41:89-93.\n\n\n\n11. Lin C, Lau JT, Ho KM, Lau MC, Tsui HY, Lo KK. \nIncidence of genital warts among the Hong Kong general \nadult population. BMC Infect Dis 2010;10:272. \n\n\n\n12. Sonnenberg P, Tanton C, Mesher D, King E, Beddows \nS, Field N et al. Epidemiology of genital warts in the \nBritish population: implications for HPV vaccination \nprogrammes. Sex Transm Infect 2019;95:386-90.\n\n\n\n13. Jiamton S, Leeyaphan C, Maneeprasopchoke P, \nOmcharoen V. Prevalence And Clinical Manifestations \nOf Male Patients With Anogenital Warts Attending A \nSexually Transmitted Disease Clinic Prior HPV Vaccine \nRecommendation. Southeast Asian J Trop Med Public \nHealth 2014;45:1337-43.\n\n\n\n14. Ny\u00e1ri TA, Kalm\u00e1r L, De\u00e1k J, Sz\u00f5ll\u00f5si J, Farkas I, Kov\u00e1cs \nL. Prevalence and risk factors of human papilloma \nvirus infection in asymptomatic women in southeastern \nHungary. Eur J Obstet Gynecol Reprod Biol 2004;115:99-\n100.\n\n\n\n15. Dinh TH, Sternberg M, Dunne EF, Markowitz LE. \nGenital warts among 18- to 59-year-olds in the United \nStates, national health and nutrition examination survey, \n1999--2004. Sex Transm Dis 2008;35:357-60. \n\n\n\n16. Kjaer SK, Tran TN, Sparen P, Tryggvadottir L, Munk C, \nDasbach E et al. The burden of genital warts: a study of \nnearly 70,000 women from the general female population \nin the 4 Nordic countries. J Infect Dis 2007;196:1447-54. \n\n\n\n17. Nyitray A, Nielson CM, Harris RB, Flores R, Abrahamsen \nM, Dunne EF et al. Prevalence of and risk factors for anal \nhuman papillomavirus infection in heterosexual men. J \nInfect Dis 2008;197:1676-84. \n\n\n\n18. Suligoi B, Vittori G, Salfa MC, Timelli L, Corsini D, \nFattorini G et al. Genital Warts 2 (GW2) Working Group. \nPrevalence and incidence of external genital warts in a \nsample of Italian general female population. BMC Infect \nDis 2017;17:126. \n\n\n\n19. Castellsagu\u00e9 X, Cohet C, Puig-Tintor\u00e9 LM, Acebes LO, \nSalinas J, San Martin M et al. Epidemiology and cost of \ntreatment of genital warts in Spain. Eur J Public Health \n2009;19:106-10.\n\n\n\n20. Marra F, Ogilvie G, Colley L, Kliewer E, Marra CA. \nEpidemiology and costs associated with genital warts in \nCanada. Sex Transm Infect 2009;85:111-5.\n\n\n\n21. Lin C, Lau JT, Ho KM, Lau MC, Tsui HY, Lo KK. \nIncidence of genital warts among the Hong Kong general \nadult population. BMC Infect Dis 2010;10:272.\n\n\n\n22. Lee CB, Choe HS, Hwang SJ, Lee SJ, Cho YH. \nEpidemiological characteristics of genital herpes and \ncondyloma acuminata in patients presenting to urologic \nand gynecologic clinics in Korea. J Infect Chemother \n2011;17:351-7.\n\n\n\n23. Jim\u00e9nez-Vieyra CR. Prevalence of condyloma \nacuminata in women who went to opportune detection of \ncervicouterine cancer. Ginecol Obstet Mex 2010;78:99-\n102.\n\n\n\n24. Yanofsky VR, Patel RV, Goldenberg G. Genital warts: \na comprehensive review. J Clin Aesthet Dermatol \n2012;5:25-36. \n\n\n\n25. Silverberg MJ, Thorsen P, Lindeberg H, Grant LA, Shah \nKV. Condyloma in pregnancy is strongly predictive \nof juvenile-onset recurrent respiratory papillomatosis. \nObstet Gynecol 2003;101:645-52. \n\n\n\n26. Read TR, Hocking JS, Chen MY, Donovan B, Bradshaw \n\n\n\nCS, Fairley CK. The near disappearance of genital warts \nin young women 4 years after commencing a national \nhuman papillomavirus (HPV) vaccination programme. \nSex Transm Infect 2011;87:544-7.\n\n\n\n27. Chiao EY, Giordano TP, Palefsky JM, Tyring S, El Serag \nH. Screening HIV-infected individuals for anal cancer \nprecursor lesions: a systematic review. Clin Infect Dis \n2006;43:223-33.\n\n\n\n28. Brown DR, Schroeder JM, Bryan JT, Stoler MH, Fife \nKH. Detection of multiple human papillomavirus types \nin Condylomata acuminata lesions from otherwise \nhealthy and immunosuppressed patients. J Clin Microbiol \n1999;37:3316-22.\n\n\n\n29. De Panfilis G, Melzani G, Mori G, Ghidini A, \nGraifemberghi S. Relapses after treatment of external \ngenital warts are more frequent in HIV-positive \npatients than in HIV-negative controls. Sex Transm Dis \n2002;29:121-5.\n\n\n\n30. CDC US. Human Papillomavirus (HPV) Vaccination: \nWhat Everyone Should Know? Available at https://www.\ncdc.gov/vaccines/vpd/hpv/public/index.html accessed on \n28th May 2022. \n\n\n\n31. Lacey CJ, Lowndes CM, Shah KV. Chapter 4: Burden and \nmanagement of non-cancerous HPV-related conditions: \nHPV-6/11 disease. Vaccine. 2006;24:S3/35-41. \n\n\n\n32. Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer \nWA 3rd, Read JS et al. Safety and immunogenicity of a \nquadrivalent human papillomavirus (types 6, 11, 16, and \n18) vaccine in HIV-infected children 7 to 12 years old. J \nAcquir Immune Defic Syndr 2010;55:197-204. \n\n\n\n33. Kojic EM, Kang M, Cespedes MS, Umbleja T, Godfrey \nC, Allen RT et al. Immunogenicity and safety of the \nquadrivalent human papillomavirus vaccine in HIV-1-\ninfected women. Clin Infect Dis 2014;59:127-35.\n\n\n\n34. Toft L, Storgaard M, M\u00fcller M, Sehr P, Bonde J, \nTolstrup M et al. Comparison of the immunogenicity \nand reactogenicity of Cervarix and Gardasil human \npapillomavirus vaccines in HIV-infected adults: a \nrandomized, double-blind clinical trial. J Infect Dis \n2014;209(8):1165-73.\n\n\n\n35. Signorelli C, Odone A, Ciorba V, Cella P, Audisio RA, \nLombardi A et al. Human papillomavirus 9-valent vaccine \nfor cancer prevention: a systematic review of the available \nevidence. Epidemiol Infect 2017;145(10):1962-82.\n\n\n\n36. Luk\u00e1cs A, M\u00e1t\u00e9 Z, Farkas N, Mik\u00f3 A, Tenk J, Hegyi P \net al. The quadrivalent HPV vaccine is protective against \ngenital warts: a meta-analysis. BMC Public Health \n2020;20:691.\n\n\n\n37. Kmietowicz Z. UK will use Gardasil in its HPV \nvaccination programme from next September. BMJ \n2011;343:d7694. \n\n\n\n38. Navarro-Illana E, L\u00f3pez-Lacort M, Navarro-Illana \nP, Vilata JJ, Diez-Domingo J. Effectiveness of HPV \nvaccines against genital warts in women from Valencia, \nSpain. Vaccine 2017;35:3342-6. \n\n\n\n39. Oliphant J, Stewart J, Saxton P, Lo M, Perkins N, Ward \nD. Trends in genital warts diagnoses in New Zealand five \nyears following the quadrivalent human papillomavirus \nvaccine introduction. N Z Med J 2017;130:9-16.\n\n\n\n40. Muhamad NA, Buang SN, Jaafar S, Jais R, Tan PS, \nMustapha N et al. Achieving high uptake of human \npapillomavirus vaccination in Malaysia through school-\nbased vaccination programme. BMC Public Health \n2018;18:1402.\n\n\n\n41. Steben M, Garland SM. Genital warts. Best Pract Res \nClin Obstet Gynaecol 2014;28:1063-73.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 75\n\n\n\n42. Lin A, Ong KJ, Hobbelen P, King E, Mesher D, Edmunds \nWJ et al. Impact and Cost-effectiveness of Selective \nHuman Papillomavirus Vaccination of Men Who Have \nSex With Men. Clin Infect Dis 2017;64:580-8.\n\n\n\n43. Rayment M, Bull L, Evans C, Rooney G, Delpech V, \nJones R. A Successful Strategy to Reduce Loss to Follow-\nUp in HIV Outpatient Care: Experiences of a Large Urban \nClinic in the United Kingdom. J Acquir Immune Defic \nSyndr 2016;72:e19-20.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4876\n\n\n\nCASE REPORT\n\n\n\nCase Report of A Rare Case of Adult-Onset Multi-site Lichen Striatus in \nan Adult\n\n\n\nSai Banu Selvarajah1, MD, Wan Syazween Lyana Wan Ahmad Kammal2, AdvMDerm, Adawiyah Jamil1, \nAdvMDerm\n\n\n\n1Dermatology Unit, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia\n2Dermatology Unit, Internal Medical Department, Faculty of Medicine and Health, University Putra Malaysia, \nSelangor, Malaysia\n\n\n\nSummary\nLichen striatus (LS) is a rare self-limiting inflammatory dermatosis characterized by Blaschkoid \ndistribution. We report a 34-year-old woman with a 1-year history of asymptomatic unilateral rashes \non her left trunk and limbs. Physical examination revealed light to dark brown papules, macules, \npatches and plaques with some erythematous areas in a Blaschkoid pattern with proven skin biopsy \nas well. Patient received potent topical corticosteroid therapy which resulted in the resolution of the \nlesion. This case report highlights two rare aspect of lichen striatus; involvement of multiple sites \nand late adult-onset.  It is also a reminder that lichen striatus should be included in the differentials of \nacquired linear dermatoses.\n\n\n\nKey words: Lichen striatus, adult onset, linear dermatoses\n\n\n\nCorresponding Author\nDr Sai Banu Selvarajah\nDermatology Unit, Faculty of Medicine, \nNational University of Malaysia, \nJalan Yaacob Latif, Bandar Tun Razak \n56000 Cheras, Kuala Lumpur, Malaysia\nEmail: sbsvix@gmail.com\n\n\n\nIntroduction \nLichen striatus is a self-limiting, localised \nblaschkolinear inflammatory condition. There \nare three clinical patterns; typical LS, LS albus \nand nail LS.1 Typical LS is as in present case \ndiscussion whereas LS albus, is characterized \nby hypopigmented lesions at the onset of the \neruption and nail LS with longitudinal ridging, \nsplitting.\n\n\n\nThe pathophysiology of LS remains to be \nelucidated,  interaction of environmental stimuli \nin a genetically predisposed individual has \nbeen postulated.2 The Blaschkoid distribution \nsuggests a form of cutaneous mosaicism. \nSomatic mutation during early embryogenesis \nresults in abnormal epithelial cell clones, \nleading to LS formation upon exposure to \nenvironmental stimuli.2 Environmental factors \nthat may trigger LS include viral infection, \nvaccination, drugs and cutaneous injury.3-4 \nFamilial occurrences support the theory that \ngenetic factor contributes to LS development.3,5\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 77\n\n\n\nMultiple adult-onset LS is uncommon. LS \ntypically presents as a single lesion in children \nbetween the age of 3 to 15 years old.1 In \nadults, the mean age of onset is 30.3 years. \nFemales are approximately four times more \ncommonly affected than males.6 We present \na case of multi-site lichen striatus in an adult \nfemale, successfully treated with potent topical \ncorticosteroid. \n\n\n\nFigure 1. Linear hyperpigmented and erythematous \npapules, macules and plaques with minimal fine \nscales on the left side of her trunk (a) and posterior \nleft leg (b)\n\n\n\n\n\n\n\nFigure 2. a) Band like infiltration of \nlymphohistiocytes at superficial dermis with basal \nlayer vacuolar degeneration; b) Lymphohistiocyte \ninfiltrates at superficial perifollicular and peri-\neccrine areas\n\n\n\nCase Report\nA 34-year-old woman with bronchial asthma \npresented with relapsing and remitting \nasymptomatic rashes affecting her left side \nfor one year.  Physical examination revealed \nhyperpigmented papules, macules and plaques \ninterspersed with a few erythematous papules \nand plaques with minimal fine scales arranged \nin a linear pattern on the left side of her trunk \nand posterior left leg (Figure 1). There were no \nnail, hair or mucosal abnormalities. There was \nno any aggravating relieving factors for the \nrashes.  \n\n\n\nThe differential diagnoses include lichen \nstriatus, linear lichen planus, inflammatory \nlinear verrucous epidermal nevus, incontinentia \npigmenti and linear porokeratosis. A skin \nbiopsy was performed and histopathology \nfeatures include dense bandlike infiltration of \nlymphohistiocytes at superficial dermis with \nvacuolar alteration of the basal layer (Figure 2a). \nSimilar infiltrates were observed at superficial \nperivascular, perifollicular and around the \neccrine glands (Figure 2b). A diagnosis of lichen \nstriatus was made. The patient was treated with \na potent topical corticosteroid (TCS) which \nresulted in complete resolution of the rash.  \n\n\n\nDiscussion\nLS most commonly present as asymptomatic \nerythematous or skin-coloured, flat-topped \npapules that coalesce to form a continuous or \ninterrupted linear plaque. About 11% of cases \ncomplained of pruritis, almost all of these \npatients had atopy.3 And that\u2019s when patient \nusually comes for consultation. Typical LS \noccurs on the lower limbs. Other less common \nsites include the trunk, upper limbs and face.3-4\n\n\n\nLS is diagnosed clinically. However, a skin \nbiopsy is helpful to differentiate it from other \nBlashkoid dermatoses. The histopathological \nfinding of LS is often confused with linear \nlichen planus.8 A characteristic feature of LS is \nlymphohistiocytic infiltrate seen around eccrine \nglands and hair follicles.6-7 Other non-specific \nfindings include exocytosis, hyperkeratosis, \n\n\n\na b\n\n\n\na\n\n\n\nb\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4878\n\n\n\nspongiosis, necrotic keratinocytes, parakeratosis \nand perineural infiltrate.7\n\n\n\nThe options for treatment usually includes \ntopical corticosteroids or intralesional \ncortiocosteroid, salicylic acid or coal tar. \nHowever, many studies on Vitamin D analgoues \nand cryotherapy are also emerging now. Lichen \nstriatus has been successfully treated with \nother topical (pimecrolimus) or oral (acitretin, \ncyclosporin, or corticosteroids) agents\n\n\n\nAs for topical steroid, there are conflicting \nreports about whether topical steroids shorten \nthe duration of the lesions. In a retrospective \nstudy of 115 children with LS, Patrizi et al3 \ndid not conclude in any shortening of the \nduration of either the inflammatory stage of \nLS or the duration of the post-inflammatory \nhypopigmentation in patients treated with \ntopical steroids as compared to those who were \nnot treated.\n\n\n\nOn the other hand, combination topical \ncorticosteroid with vitamin D analogue or \nretinoid has been used with success.8 Complete \nresolution of lesions with 2 sessions of \ncryotherapy 2 weeks apart was reported in a \npatient.9\n\n\n\nAs the cause of LS is uncertain, and recent \nstudies has hypothesised that LS is a T-cell \nmediated inflammatory skin disease associated \nwith autoimmune response to mutated \nkeratinocyte cloning.10-11 Accordingly there is a \nrole of topical tacrolimus13 and pimecrolimus14 \nas the new choice treatment for LS. Korean \nliterature has reported the effects of this \ntreatment whereby 1% pimecrolimus cream is \nfound to be beneficial and efficacious treatment \noption for lichen striatus in children because it \ncarries no risk for skin atrophy compared with \ntopical corticosteroid application.12\n\n\n\nThis case report highlights the need to consider \nLS in the differential diagnosis of Blashkoid \nand linear rash despite its rarity in adult \npopulation and its distribution. Although in \nsome circumstances, very few potent TCS \n\n\n\nalone or in combination with topical retinoids, \nTCI monotherapy and cryotherapy are one \nof the many treatments options that may be \nconsidered.\n\n\n\nConclusion\nThis case report has demonstrated the efficacy \nand tolerability of corticosteroid treatment of \nLS in the adult population for the first time. \nOur patient\u2019s clinical presentation was not \nuniformly pathognomonic for either blaschkitis \nor lichen striatus. The involvement of the \nchest and her adult age matched the classic \nclinical presentation of blaschkitis; however, \nthe involvement of the right upper extremity \nwas more characteristic of lichen striatus. The \npathology features of her skin biopsies - an \ninflammatory band-like infiltrate of lymphocytes \nand histiocytes along with the presence of \nnecrotic keratinocytes which was consistent \nwith lichen striatus. Lichen striatus typically \nresolves spontaneously within six to 12 months \nand does not recur as it did for our patient. Topical \ncorticosteroids may be used for the treatment \nof lichen striatus especially if it\u2019s associated \npruritus. However, they usually do not reduce \nthe duration of the disease or the occurrence \nof post-inflammatory dyspigmentation. Lichen \nstriatus has been successfully treated with \nother topical (pimecrolimus) or oral (acitretin, \ncyclosporin, or corticosteroids) agents. Ideally, \na placebo-controlled, randomized study would \nbe helpful to confirm the superior efficacy of \nthe combination treatment as delineated in this \nstudy.\n\n\n\nConflict of Interest Declaration \nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for the permission \nto publish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 79\n\n\n\nReferences \n1. Hajihoseini M, Eidy M, Molania T, Golpour M, Salehi \n\n\n\nM. Lichen Striatus: Review article. Int J Med Invest \n2018;7:39-44.\n\n\n\n2. Gupta A, Gautam RK, Bhardwaj M. Bilateral lichen \nstriatus: A case report with review of literature. Indian \nDermatol Online J 2017; 8:264-6.\n\n\n\n3. Patrizi A, Neri I, Fiorentini C, Bonci A, Ricci G. Lichen \nstriatus: Clinical and laboratory features of 115 children. \nPediatr Dermatol 2004;21:197-204.\n\n\n\n4. Peramiquel L, Baselga E, Dalmau J, Ro\u00e9 E, del Mar \nCampos M, Alomar A. Lichen striatus: clinical and \nepidemiological review of 23 cases. Eur J Pediatr \n2006;165:267-9.\n\n\n\n5. Racette AJ, Adams AD, Kessler SE. Simultaneous lichen \nstriatus in siblings along the same Blaschko line. Pediatr \nDermatol 2009;26:50-4.\n\n\n\n6. Baek YS, Seo JY, Seo SH, Ahn HH, Song HJ, Kye YC \net al. Adult-onset lichen striatus versus adult blaschkitis: \na clinicopathological review of 40 cases of acquired \nblaschkolinear inflammatory dermatosis. Eur J Dermatol \n2019;29:281-6.\n\n\n\n7. Zhang Y, McNutt NS. Lichen striatus. Histological, \nimmunohistochemical, and ultrastructural study of 37 \ncases. J Cutan Pathol 2001;28:65-71.\n\n\n\n8. Yousseff SM, Teng JM. Effective topical combination \ntherapy for treatment of lichen striatus in children: a case \nseries and review. J Drugs Dermatol 2012;11:872-5.\n\n\n\n9. Stojanovi\u0107 S, Jovanovi\u0107 M, Vu\u010dkovi\u0107 N. Cryotherapy \nfor lichen striatus in an adult \u2013 A case report. Serbian J \nDermatology Venereol 2015;7:163-71.\n\n\n\n10. Gianotti R, Restano L, Grimalt R, Berti E, Alsessi E, Caputo \nR. Lichen striatus- a cameleon: an histopathological and \nimmunohistological study of forty-one cases. J Cutan \nPathol 1995;22:18-22.\n\n\n\n11. Zhang Y, McNutt NS. Lichen striatus. Histological, \nimmunohistochemical and ultrastructural study of 37 \ncases. J Cutan Pathol 2001;28:65-71.\n\n\n\n12. Park SY, Lee SH, Yoon TJ. Lichen Striatus in a girl: \nsuccessful treatment with pimecrolimus. Ann Dermatol \n2007;19:157-9.\n\n\n\n13. Fujimoto N, Tajima S, Ishibashi A. Facial lichen striatus: \nsuccessful treatment with tacrolimus ointment. Br J \nDermatol 2003;148:587-90.\n\n\n\n14. Kus S, Ince U. Lichen striatus in an adult patient treated \nwith pimecrolimus. J Eur Acad Dermatol Venereol \n2006;20:360-1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4880\n\n\n\nCASE REPORT\n\n\n\nDisseminated Cutaneous Sporotrichosis with Fungal Sinusitis As An \nInitial Presentation of Underlying Myeloproliferative Neoplasm\n\n\n\nWei Hsi Chang1, MRCP, Juliana Wai Theng Lee1, MBBS, Soo Ching Gan2, MPath, Ting Guan Ng1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia\n2Department of Pathology, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia\n\n\n\nSummary\nSporotrichosis is a rare and chronic granulomatous subcutaneous mycotic infection caused by \na dimorphic fungus, Sporothrix schenckii. We describe a patient with disseminated cutaneous \nsporotrichosis who was later diagnosed with myeloproliferative neoplasm and discuss the challenges \nand importance in diagnosing this rare condition.\n\n\n\nKey words: Disseminated sporotrichosis, fungal sinusitis, myeloproliferative neoplasm\n\n\n\nCorresponding Author\nDr Chang Wei Hsi\nDepartment of Dermatology, \nHospital Tengku Ampuan Rahimah,\nJalan Langat, \n41200 Klang, Selangor, Malaysia \nEmail: elizzchang@gmail.com\n\n\n\nIntroduction\nSporotrichosis is a chronic granulomatous \nsubcutaneous mycotic infection caused by \nSporothrix schenckii, a dimorphic fungus found \nin soil, sphagnum moss and contaminated \norganic matter.1,2 It presents as nodules, plaques, \nand subcutaneous swellings which often make \nclinical diagnosis a challenge, particularly \nin nonendemic areas.1 Here, we report a \ncase of recalcitrant disseminated cutaneous \nsporotrichosis with fungal rhinosinusitis in an \napparent immunocompetent individual, who \nwas later diagnosed with myeloproliferative \nneoplasm.\n\n\n\nCase Report\nA 49-year-old man presented with painful \nulcerated nodules on his face, trunk and \nextremities for the past 1 month associated \nwith low-grade fever, malaise, appetite loss and \nweight loss. His past medical history includes \nhypertension, coronary artery disease and \ngout. He works in a plant nursery and has a \nwild cat at home. On examination, there were \nmultiple ulcerated nodules and hyperkeratotic \nplaques on the face, trunk, and extremities \n(Figure 1a&b). Lung examination was normal. \nAbdominal examination revealed a non-tender \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 81\n\n\n\nsplenomegaly. No enlarged lymph nodes \nwere detected. Blood investigations revealed \nleukocytosis of 11.88 x 109/L, normocytic \nnormochromic anaemia with a Hb of 11.5 g/dL, \nand mild thrombocytosis of 542 x 109/L. Liver \nfunction, renal function, blood glucose, serum \ncortisol, human immunodeficiency virus (HIV) \ntest, viral hepatitis test, and chest radiograph \nresults were normal. Histopathological \nexamination (HPE) of the skin biopsy showed \na chronic granulomatous inflammation in the \ndermis (Figure 2a). Myobacterium leprae \nand Mycobacterium tuberculosis were not \ndetected. Fungal culture from the skin lesions \ngrew S. schenckii, confirming the diagnosis \nof disseminated cutaneous sporotrichosis. His \nclinical response to 6 months of oral itraconazole \nand 3 months of combined oral itraconazole \nand terbinafine was poor. A repeated skin \nbiopsy showed similar HPE and fungal culture \nfindings. Abdominal ultrasonography revealed \nhepatomegaly and massive splenomegaly. \n\n\n\nBone marrow aspirate and trephine biopsy \ndemonstrated features of myeloproliferative \n\n\n\nneoplasm (MPN). He was positive for JAK \nV617F, which is pathognomonic for MPN. \nHe experienced intermittent epistaxis for the \npast few months. Functional Endoscopic Sinus \nSurgery revealed ulcerated and perforated \nnasal septum with crusted necrotic tissues over \nthe middle and inferior turbinate. HPE of the \nnasal septum was consistent with a chronic \ngranulomatous inflammation with fungal \nyeasts morphologically consistent with S. \nschenckii (Figure 2a&b). Fungal culture from \nnasal septum isolated S. schenckii. Computed \ntomography scan showed mucosal thickening \nof maxillary sinuses and hyperdense soft tissue \nover the right frontal sinus. He was admitted for \ntreatment with intravenous (IV) amphotericin B, \nand for further workup of the newly diagnosed \nMPN.  Regular nasal irrigation was performed \nby the otorhinolaryngologist. After two weeks \nof IV amphotericin B, he was discharged \nfrom the hospital against medical advice and \nopted for conservative management for his \nmyeloproliferative disease. Unfortunately, \nhe succumbed to severe sepsis secondary to \ninfected cutaneous ulcers three months later.  \n\n\n\nFigure 1. (a) Disseminated sporotrichosis on left upper limb and (b) anterior trunk, demonstrating numerous \nerythematous nodules with occasional ulceration\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4882\n\n\n\nFigure 2. (a) Left arm skin biopsy, haematoxylin and eosin stain (20X) showing chronic granulomatous \ninflammation in the dermis; (b) Nasal septum biopsy, Gomori methenamine stain (40X) demonstrating ovoid \nand elongated fungal spores\n\n\n\nDiscussion\nSporotrichosis is a cutaneous fungal \ninfection reported worldwide.2,3 Its clinical \nmanifestations depend on the route of infection, \nburden of inoculum and immune status \nof the host.4,5 Dissemination may occur in \nimmunocompromised individuals.4 Infection \nwith HIV, iatrogenic immune suppression, \nand haematological malignancies are some \nof the reported predisposing conditions.4 \n\n\n\nMyeloproliferative conditions like myelofibrosis \nare also associated with extracutaneous \nsporotrichosis.1 The newly diagnosed MPN in \nthis case may have contributed to the progression \nof disseminated disease. \n\n\n\nCutaneous infection is commonly associated \nwith trauma during outdoor activities.3 S. \nschenckii may enter the body directly through \na thorn prick, abrasion or blunt injury, or \nindirectly through animal bites or scratches.6 \n\n\n\nOur case does significant outdoor work and is \nthought to have contracted the infection through \nskin inoculation, from traumatic implantation \nof thorns and splinters, or inhalation. The \nactivation and proliferation of macrophages \nand T lymphocytes are involved in controlling \nfungal infection.7 The immune response \nagainst S. schenckii infections is most likely \na combination of humoral, cellular and innate \nimmune responses.2\n\n\n\nTreatment with amphotericin B was \ninitiated according to the current guideline \nrecommendations in Malaysia.8 Several studies \n\n\n\nhave reported the in vitro efficacy of other agents \nsuch as amphotericin B and posaconazole against \ndisseminated sporotrichosis.4,9 In a similar case \nreport, Bunce et al. (2012) reported a significant \nimprovement using a combined antifungal \ntreatment of amphotericin B and posaconazole \nin a patient with disseminated sporotrichosis \nwho had underlying hairy cell leukemia that \nwas refractory to initial therapy with liposomal \namphotericin B and oral itraconazole.4 The \npatient, who worked as an outdoor contractor, \nachieved resolution of symptoms after 8 months \nof treatment with amphotericin B, and remains \nstable on posaconazole after 5 months.4 Thus, \nthis supported the use of amphotericin B in our \npatient. \n\n\n\nConclusion\nIn summary, we have reported a case of \ndisseminated S. schenckii infection in a patient \nwith newly diagnosed MPN initially refractory \nto oral itraconazole and terbinafine, and \neventually required IV amphotericin B. A high \nindex of clinical suspicion is important for early \ndiagnosis to prevent further complications of \nthis disease.\n\n\n\nConflict of Interest Declaration\nThe authors declare that there is no conflict of \ninterest in this work.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 83\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health, Malaysia for his permission \nto publish this case report. \n\n\n\nReferences\n1. Mahajan VK. Sporotrichosis: An overview and therapeutic \n\n\n\noptions. Dermatol Res Pract 2014;272376.\n2. Barros MB, de Almeida Paes R, Schubach AO. Sporothrix \n\n\n\nschenckii and sporotrichosis. Clin Microbiol Rev \n2011;24:633-54.\n\n\n\n3. Morris-Jones R. Sporotrichosis. Clin Exp Dermatol \n2002;27:427-31. \n\n\n\n4. Bunce PE, Yang L, Chun SH, Zhang SX, Trinkaus MA, \nMatukas LM. Disseminated sporotrichosis in a patient \nwith hairy cell leukemia treated with amphotericin B and \nposaconazole. Med Mycol 2012;50:197-201. \n\n\n\n5. Ramos-e-Silva M, Vasconcelos C, Carneiro S, Cestari T. \nSporotrichosis. Clin Dermatol 2007;25:181-7. \n\n\n\n6. Bhutia PY, Gurung S, Yegneswaran PP, Pradhan J, Pradhan \nU, Peggy T et al. A case series and review of sporotrichosis \nin Sikkim. J Infect Dev Ctries 2011;5:603-8.\n\n\n\n7. Maia DC, Sass\u00e1 MF, Placeres MC, Carlos IZ. Influence \nof Th1/Th2 cytokines and nitric oxide in murine systemic \ninfection induced by Sporothrix schenckii. Mycopathologia \n2006;161:11-9. \n\n\n\n8. Ministry of Health Malaysia. Third Edition National \nAntimicrobial Guideline 2019. Available at https://\nwww.pharmacy.gov.my/v2/en/documents/national-\nantimicrobial-guideline-nag-2019-3rd-edition.html. \nAccessed on 22nd December \n\n\n\n9. Mario DB, Guarro J, Santurio JM, Alves SH, Capilla J. \nIn vitro and in vivo efficacy of amphotericin B combined \nwith posaconazole against experimental disseminated \nsporotrichosis. Antimicrob Agents Chemother \n2015;59:5018-21. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4884\n\n\n\nCASE REPORT\n\n\n\nA Unique Drug Rash: Bleomycin-induced Flagellate Erythema in a Patient \nwith Hodgkin Lymphoma\n\n\n\nSee Ling Tan, MRCP,  Nurul Farhana Bt Mohd Joni, MD, Azura Bt Mohd Affandi, AdvMDerm \n\n\n\nDepartment of Dermatology, Hospital Ampang, Selangor, Malaysia\n\n\n\nSummary\nFlagellate erythema is characterized by \u201cwhiplike\u2019\u2019 linear streaks, usually following bleomycin \nchemotherapy or is associated with consumption of shiitake mushrooms, dermatomyositis, adult onset \nstill disease as well as human immunodeficiency disease. Here, we describe a case of bleomycin-\ninduced flagellate erythema in a patient with Hodgkin lymphoma.\n\n\n\nKey words: Bleomycin-induced flagellate rash, flagellate erythema, Hodgkin lymphoma\n\n\n\nCorresponding Author \nDr Tan See Ling\nHospital Ampang, \nJalan Mewah Utara, Pandan Indah, \n68000 Selangor, Malaysia\nEmail: ttseeling@gmail.com\n\n\n\nIntroduction \nFlagellate erythema is a unique patterned \neruption, which is described as \u201cwhiplike\u2019\u2019 \nlinear streaks, usually following bleomycin \nchemotherapy or is associated with consumption \nof shiitake mushrooms, dermatomyositis, \nadult onset still disease as well as human \nimmunodeficiency disease.1.2 In severe cases, \nit may cause intolerable pruritus. The onset \nof the eruption is between 1 day  to 9 weeks \nafter the administration of bleomycin in a dose \ndependent manner.3 During the recovery phase, \nthe lesions may have a brown appearance, \ncommonly known as flagellate pigmentation. \n\n\n\nCase Report \nWe herein report a case of a 44-year-old man \nwith refractory Hodgkin lymphoma stage \nIV, having completed 4 cycles of ABVD \nchemotherapy (adriamycin, bleomycin, \nvinblastine, dacarbazine) and post autologous \nstem cell transplant. He presented with multiple \nhyperpigmented, haphazard, linear streaks over \nhis back (Fig 1a and 1b). \n\n\n\nThe lesions appeared 2 weeks after the first \ncycle of chemotherapy. He denied any pruritus \nor pain. His presentation was compatible with \nthe diagnosis of bleomycin-induced flagellate \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 85\n\n\n\nerythema. No treatment was given as the patient \nwas asymptomatic.\n\n\n\nFigure 1. (a&b) Multiple hyperpigmented, \nhaphazard, linear streaks over his back\n\n\n\na\n \n\n\n\nb\n\n\n\nDiscussion\nBleomycin is an antitumor drug, commonly \nused in the treatment of Hodgkin lymphoma \nand squamous cell carcinoma.4 Adverse effects \nof bleomycin predominantly occur in the lungs \nand skin due to bleomycin hydrolase, which \nis a cytosolic cysteine proteinase enzyme for \ninactivation of bleomycin.5 Bleomycin-induced \n\n\n\nflagellate erythema was first reported by Moulin \net al in 1970 with the reported incidence rate of \n8-22%.6 However, it is infrequently reported in \nclinical practice. \n\n\n\nThe appearance of bleomycin-induced flagellate \nerythema can occur irrespective of any routes of \nadministration: intravenously, intramuscularly, \nsubcutaneously or even intrapleurally.7 The \nexact pathogenesis of bleomycin-induced \nflagellate erythema remains uncertain. A number \nof theories have been postulated with regards \nto the etiology of bleomycin-induced flagellate \nerythema. Heat-recall and reduced epidermal \nturnover allowing prolonged melanocytes and \nkeratinocytes contact may contribute to the \nappearance of the rash.7 One of the theories is \nthat scratching causes vasodilatation with local \nbleomycin accumulation in the skin leading to \nsubsequent fixed drug eruption.8\n\n\n\nThe rashes are self-limiting and normally \nimprove 3-4 months following discontinuation \nof bleomycin.9 However, permanent post-\ninflammatory hyperpigmentation is a common \ncomplication.10 Antihistamines and topical \ncorticosteroid can be used for symptomatic \nrelief.11\n\n\n\nConclusion \nBleomycin-induced flagellate erythema is a \nrare and unique adverse effect. This report \nemphasizes the significance of awareness \nand early recognition of this classical rash by \nthe clinician in order to make an appropriate \njudgment on modifying or discontinuing the \nchemotherapy regime. \n\n\n\nConflict of Interest Declaration \nThe author have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for the permission \nto publish this paper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4886\n\n\n\nReferences\n1. Ziemer M, Goetze S, Juhasz K, Elsner P. Flagellate \n\n\n\ndermatitis as a bleomycin-specific adverse effect of \ncytostatic therapy. Am J Clin Dermatol 2011;12,68-76.\n\n\n\n2. Biswas A, Julka PK. Bleomycin induced flagellate \nerythema in a patient with thalamic mixed germ cell \ntumour: Report of a rare adverse effect. J Egypt Natl Canc \nInst 2016;28:129-32.\n\n\n\n3. Rubeiz NG, Salem Z, Dibbs R, Kibbi AG. Bleomycin-\ninduced urticarial flagellate drug hypersensitivity reaction. \nInt J Dermatol 1999;38:140-1.\n\n\n\n4. Dantzig PI. Immunosuppressive and cytotoxic drugs in \ndermatology. Arch Dermatol 1974;110:393-406.\n\n\n\n5. Mowad CM, Nguyen TV, Elenitsas R, Leyden JJ. \nBleomycin\u2010induced flagellate dermatitis: a clinical and \nhistopathological review. Br J Dermatol 1994;131:700-2.\n\n\n\n6. Moulin G, Fi\u00e8re B, Beyvin A. Cutaneous pigmentation \ncaused by bleomycin. Bull Soc Fr Dermatol Syphiligr \n1970;77:293-96.\n\n\n\n7. Lee HY, Lim KH, Ryu Y, Song SY. Bleomycin-induced \nflagellate erythema: A case report and review of the \nliterature. Oncol Lett 2014;8:933-5.\n\n\n\n8. Yamamoto T. Bleomycin and the skin. Br J Dermatol \n2006;155:869-75.\n\n\n\n9. Todkill D, Taibjee S, Borg A, Gee BC. Flagellate erythema \ndue to bleomycin. Br J Haematol 2008;142:857. \n\n\n\n10. Chen YB, Rahemtullah A, Breeden E, Hochberg EP. \nBleomycin-induced flagellate erythema. J Clin Oncol \n2007;25:898-900.\n\n\n\n11. Boussios S, Moschetta M, McLachlan J, Banerjee S. \nBleomycin-Induced Flagellate Erythema in a Patient \nDiagnosed with Ovarian Yolk Sac Tumor. Case Rep in \nOncol Med 2015;2015:574708.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 87\n\n\n\nCASE REPORT\n\n\n\nNo Epidermis: Is it the drug, COVID-19 or Something Else?\n\n\n\nVivian Tai, MD, Chiaw Ting Tee, MRCP, Min Moon Tang, AdvMDerm\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Ministry of Health, Kuala Lumpur, Malaysia \n\n\n\nSummary\nStaphylococcal toxic shock syndrome (TSS) is a clinical disease with acute onset of fever, rash, \nhypotension and multi-organ system involvement. Staphylococcal scalded skin syndrome (SSSS), \nmostly described in neonate and children, is a superficial blistering disease caused by the exfoliative \ntoxin of specific strains of Staphylococcus aureus. TSS and SSSS rarely occur concurrently in adults. \nWe here describe a 35-year-old woman who was initially referred to dermatology team as toxic \nepidermal necrolysis. She presented with a rapid epidermal detachment without mucosal involvement, \nfever and shock, associated with acute kidney injury and transaminitis, severe metabolic acidosis, \ncomplicated by COVID-19 infection, and finally succumbed within 36 hours of hospitalization. Early \nrecognition and prompt treatment are the key factors in the management as TSS itself can lead to \nmortality. Staphylococcal TSS and SSSS are important differential diagnosis to consider in acute \nepidermal detachment, as not all cases are drug-induced. \n\n\n\nKey words: Epidermal detachment, toxic shock syndrome, Staphylococcus aureus, Staphylococcal scalded skin syndrome\n\n\n\nCorresponding Author\nDr Tai Vivian\nDepartment of Dermatology,\nHospital Kuala Lumpur,\nJalan Pahang,\n50586 Kuala Lumpur\nEmail: viviantai.91@gmail.com \n\n\n\nIntroduction\nStaphylococcal toxic shock syndrome (TSS) is a \nlife-threatening clinical condition characterized \nby the rapid onset of fever, hypotension, skin \nrashes (diffuse macular erythroderma, followed \nby desquamation 1-2 weeks later), with \nmultisystem involvement.1 At least three or \nmore of the following systems are affected in \nTSS which include gastrointestinal symptoms \n(vomiting and watery diarrhoea), muscle \n(severe myalgia with raised muscle enzyme), \ncentral nervous system involvement (headache \nand confusion which may lead to delayed \npresentation, seizure, loss of consciousness, \nagitation), mucous membrane hyperemia \n(vaginal, oropharyngeal, or conjunctival), kidney \nand liver impairment, and thrombocytopenia.1 \n\n\n\nIt was first described in paediatric patients in \n1978 by Todd.2 Subsequently there was a peak \nof cases when highly absorbable tampons were \nintroduced in the 1980s.3 However, the overall \nincidence of TSS remains low. The incidence \nof TSS is around 0.8 to 3.4 per 100,000 in the \nUnited States.4 TSS has also been described in \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4888\n\n\n\nnon-menstruating individuals, including in the \npaediatric population and male patients.5 Non-\nmenstrual cases are associated with higher \nmortality, earlier onset of fever and rash, with \nmore pronounced renal and central nervous \nsystem complications, but less musculoskeletal \ninvolvement.6 \n\n\n\nStaphylococcal scalded skin syndrome (SSSS), \nalso known as Ritter disease, is a cutaneous \nemergency mostly described in neonate and \nchildren.7 It is caused by exfoliative toxin \nproduced by specific strains of Staphylococcus \naureus, resulting in rapid blister formation \non a widespread tender erythroderma with \ntissue paper-like wrinkling of the skin at the \nperiorificial or flexural area.7 It typically spares \nthe mucous membrane.7 The initial source of \nStaphylococcal aureus infection is usually \nlocalized at upper respiratory tract, inner ear, \nconjunctiva, umbilical stump and others.7\n\n\n\nHere we describe a young female who \nsuccumbed to Staphylococcal toxic shock \nsyndrome with possible coexistent SSSS, who \nwas initially referred to dermatology team as \ntoxic epidermal necrolysis.\n\n\n\nCase Report\nA 35-year-old Myanmarese waitress, with no \nknown medical illness or allergy, presented \nto the emergency department with a GCS of \nE3V5M6. Based on the history given by her \nhousemate, she had severe painful skin peeling \nover bilateral lower limbs and suprapubic area \nfor a week. She had history of swimming in \nseawater 2 days before she developed itchiness \nover the bilateral lower limbs. She denied any \ntrauma, burn or bite. There was no known drug, \nsupplement, or traditional medication exposure \nprior to the incident. She did not seek treatment \nfor her symptoms. Instead, she used topical \nmedications bought over the counter to the \naffected pruritic area. The painful rash followed \nby skin peeling developed rapidly and was \nassociated with difficulty in ambulation. \n\n\n\nThere was no documented fever at home. She \nhad no history of abdominal pain, vomiting or \n\n\n\ndiarrhoea, limb weakness, numbness or muscle \nache. There was no facial, eye, oral or genital \ninvolvement as well. She completed 2 doses of \nCoronaVac (Sinovac, China) vaccination and \nwas unaware of any COVID contact. She did \nnot smoke, consume alcohol or use recreational \ndrugs. She had been living in Malaysia for \nmore than 10 years. She was single with no \nsignificant sexual history. However, there was \nno information regarding her menstrual history \nand tampon practice. She had no pets. \n\n\n\nOn arrival, she was hypotensive with blood \npressure of 53/28mmHg, tachycardic with \na heart rate of 121/minute, and febrile with a \ntemperature of 39.5\u00b0C. Oxygen saturation \nwas 98% under room air. Her estimated body \nmass index was 25 kg/m2. There was epidermal \ndetachment over anterior and posterior aspects \nof bilateral lower thighs, extending to the knees \nand legs sparing the soles as shown in Figure \n1(a) involving nearly 35% of body surface \narea. There was a small erosion over right labia \nmajora. Confluent erythema associated with \noedema was noted over lower abdomen and \nsuprapubic region. No other skin lesions were \nseen. There was no enanthem and no mucosal \nerosions. \n\n\n\nShe had treatment-resistant hypoglycaemia, \nwith glucometer readings ranging from 2.3 to \n3.2mmol/l, and was oliguric. The patient was \ngiven aggressive fluid resuscitation followed \nby maximum inotropic support, boluses and \nmaintenance dextrose solution. A dose of \nintravenous Cefuroxime 1.5g was given at 1 \nhour after presentation and sodium bicarbonate \ninfusion was initiated. She was then intubated \nfor respiratory support in view of severe \nmetabolic acidosis (pH=7.23, bicarbonate \n9.2mEq/L, lactate 4.9mmol/L).\n\n\n\nBlood investigations showed microcytic \nhypochromic anaemia (haemoglobin 10.2 \ng/dL), leucocytosis (total white cell count \n14.6 x109/L) with neutrophil predominant, \nthrombocytopenia (platelet 106 x109/L). She \nhad acute kidney injury (urea 31.6 mmol/L, \ncreatinine 416\u00b5mol/L), hyponatraemia \n(127mmol/L), elevated creatinine kinase (360 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 89\n\n\n\nU/L), hypoalbuminaemia (15g/L), mildly raised \ntotal bilirubin (27\u00b5mol/L), transaminitis (ALT \n175 U/L), and coagulopathy (PT 17.6sec, INR \n1.6). C-reactive protein was markedly elevated \nat 263.5 mg/L. Her troponin T was raised as well \n176 ng/L (normal <15). Her electrocardiograph \nshowed sinus tachycardia, with no features of \nischaemia. There were ground glass opacities \nseen over bilateral lungs on her chest X-ray as \nshown in Figure 1b. Her tracheal aspirate for \n2019-NCoV PCR was detected, with CT value \nof 24.5.\n\n\n\nOur provisional diagnosis was Staphylococcal \nToxic Shock Syndrome (TSS) with COVID-19 \nco infection. Differential diagnosis such as \nStaphylococcal Scalded Skin Syndrome \n(SSSS), generalized bullous fixed drug \neruption (GBFDE), toxic epidermal necrolysis, \nand COVID-19 multisystem inflammatory \nsyndrome were also considered.\n\n\n\nIntravenous piperacillin-tazobactam was later \ninitiated with five doses given over the course of \nless than 2 days. Despite aggressive intravenous \nantibiotic administration, fluids resuscitation \nand inotropic support, the patient continued \nto deteriorate. She progressed to disseminated \nintravenous coagulopathy and succumbed 36 \nhours after admission. Her blood culture was \nlater reported to grow Methicillin-Sensitive \nStaphylococcus aureus (MSSA).\n\n\n\nFigure 1. (a) confluent epidermal detachment over anterior and posterior aspect of bilateral lower limbs and \nlower abdomen leaving raw erosion involving 35% body surface area; (b) chest X-ray (supine, rotated film) \nshows ground glass opacities in bilateral lungs fields\n\n\n\nDiscussion\nAccording to the United States Centre for Disease \nControl and Prevention (CDC), the clinical \ncriteria for a confirmed case of Staphylococcal \nTSS includes fever with temperature \u226538.9\u2070C, \nhypotension with systolic blood pressure \n\u226490mmHg, diffuse macular erythroderma \nfollowed by desquamation one or two weeks \nlater, involvement of \u22653 organ systems, positive \ncultures for Staphylococcus aureus and negative \nfor alternative pathogens with serologic tests \nnegative for other conditions.8 Our patient\u2019s \npresentation fulfilled  the clinical criteria for \nStaphylococcal TSS.\n\n\n\nSSSS is characterized by oedematous erythema \nof the eyelids and nostril, generalized cutaneous \npain, erythema, superficial blistering, and \ndesquamation, associated with fever, with no \nmucous membrane involvement.7,9 Although \nSSSS is more common in the paediatric \npopulation, adult SSSS has been reported at \nan annual incidence of 0.98 cases/million.10  \nThe three criteria that are required to make a \ndiagnosis of SSSS include (1) a clinical pattern \nof erythroderma, desquamation or bullae \nformation; (2) histopathological evidence of \nintraepidermal cleavage through the stratum \ngranulosum and (3) isolation of an exotoxin \nA (ETA) and/or exotoxin B (ETB) producing \nStaphylococcus aureus from the skin lesions.11 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4890\n\n\n\nThere are only 5% of Staphylococcus aureus \nisolates produce exfoliative toxin ETA and ETB. \nThese exfoliative toxins are serine proteases \nthat target and cleave desmoglein 1 (Dsg1), \nwhich is a desmosomal cadherin maintaining \nkeratinocytes adhesion. Staphylococcal \nexfoliative toxin results in hydrolysis of the \namino-terminal extracellular domain of Dsg1. \nHence, skin biopsy on a SSSS lesion typically \nshows splitting within the stratum granulosum \nwithout inflammatory cells or bacterial cocci.\n\n\n\nAdult SSSS was associated with a higher \nmortality and complications.12 Interestingly, \nabout 60% of adults SSSS grow Staphylococcus \naureus in the blood culture.9 Co-existence of \nTSS and SSSS has been described rarely in \nadults and was associated with underlying renal \nimpairment and immunosuppression.13,14 Similar \nto children, adults with SSSS demonstrate a \nfever and lesions over the face.7,12 Our patient, \nalthough presented with scalded like erosions \nover the lower abdomen and both thighs, she \nhad no lesions over the face which is the primary \naffected site in SSSS. \n\n\n\nEpidermal detachment could be a manifestation \nof generalized bullous fixed drug eruption \n(GBFDE) or drug-induced epidermal necrolysis \nwhich includes Steven Johnson Syndrome \n(SJS), Toxic Epidermal Necrolysis (TEN) \nor SJS/TEN overlap syndrome. In GBFDE, \na history of similar eruptions at the same site \nwith each exposure to a similar drug, with \nwidespread blisters and erosions involving \nmore than 10% BSA in at least three out of \nsix sites (head and neck, anterior trunk, back, \nupper limbs, lower limbs and genitalia) should \nbe elicited.15 However; GBFDE has limited \nmucous membrane involvement.  Drug induced \nepidermal necrolysis should be considered if it \nis accompanied with severe erosions at two or \nmore mucous membranes.16 There was, however, \nno prior history of drug exposure in this patient. \nIn addition, she had minimal mucosal erosions \n(at the right labia majora only).\n\n\n\nCOVID-19 multisystem inflammatory \nsyndrome might be considered as well, as \n\n\n\nthis patient was diagnosed with COVID-19 \ninfection via tracheal aspirate PCR, with \nmulti-organ involvement. However, the most \ncommonly reported cutaneous manifestations \nof COVID-19 were morbiliform rash, pernio-\nlike acral lesions, urticaria, macular erythema, \nvesicular and/or papulosquamous eruption, and \nretiform purpura.17 Epidermal detachment as \nthe only manifestation of COVID-19 infection \nhas not been described in the literature. \n\n\n\nInterestingly, Yilin et al. reported a case of \nnon-fatal TSS post-COVID-19. In that case, \nthe patient presented with high grade fever, \nhypotension, erythematous and dusky-coloured \nplaques with bullae and superficial flaking, as \nwell as yellow crusting, scaling, and widespread \nerosions which involved 40% of total body \nsurface area. Although cultures were negative, \nskin biopsy was reported to favour TSS.18 There \nwas an interval between the COVID-19 infection \nand the rash onset in the case reported. However, \nour patient presented with skin lesions and was \ndiagnosed to have COVID-19 concurrently. \nThere were no respiratory symptoms reported \nprior to her presentation. \n\n\n\nTSS can be caused by Staphylococcus aureus \nor Streptococcus pyogenes. Both are normal \nflora of skin and mucous membrane in humans. \nStaphylococcus aureus contributes to almost \nall menstrual TSS and half of non-menstrual \nTSS. Streptococcus pyogenes causes only non-\nmenstrual TSS.19 In addition to menstruating \nfemales, Staphylococcal TSS can occur in \npostpartum and postsurgical states especially \nwhen packings are used, in cases where barrier \ncontraceptives are used, in staphylococcal \npneumonia, sinusitis, and superinfected skin \nlesions.20 Streptococcal TSS is preceded by \ntrauma to the skin.\n\n\n\nStaphylococcal TSS can be caused by both \nmethicillin-susceptible or methicillin-resistant \nStaphylococcus aureus (MRSA), and is \nassociated with mortality.21,22 Staphylococcus \naureus produces TSS toxin-1 (TSST-1), a type \nof exotoxin, which acts as a superantigen that \ncan activate T cells, causing massive cytokine \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 91\n\n\n\nproduction.23 Insufficient antibody response to \nTSST-1 is found to be the cause of toxic shock \nsyndrome.24 Apart from exotoxin, enterotoxins \nproduced by Staphylococcus aureus may play \nan important role in the disease manifestations. \nInflammatory mediators including interleukin \n(IL)-1, IL-2, tumour necrosis factor (TNF)-\nalpha, TNF-beta, and interferon (IFN)-gamma \nare produced in large amounts.25 Due to the \npresence of IL-1, high fever is noted. IL-1 is \nalso involved in proteolysis of skeletal muscle; \nresulting in myalgia and high creatinine kinase.25 \nThis explains the raised creatinine kinase and \nTroponin T level in our patient. TNF inhibits \npolymorphonuclear leukocyte functions, hence \npurulence is not observed.25 \n\n\n\nTo assist with the diagnosis, cultures from the \nblood, wound sites and mucosal sites including \nvaginal canal and nares, should be obtained. Any \nforeign material such as tampons, contraceptive \nsponges or intrauterine devices in vaginal canal \nshould be promptly removed.26 TSST-1 assays \nare useful in diagnosis, however the test is not \navailable in our setting. It would have been \nimportant to perform a vaginal examination in \nthis case to remove any foreign material and \nto take a vaginal swab for culture. Apart from \nthat, to assess the possibility of concurrent \nSSSS, isolation of ETA and/or ETB producing \nStaphylococcus aureus from denuded skin \nas well as a skin biopsy would be helpful. \nRegrettably, our patient was intubated very \nsoon on arrival before verbal consent could be \nobtained to examine the genitalia as well as \nskin biopsy. In addition, there was no next of \nkin who could give the consent on behalf of her.  \n\n\n\nThe management of Staphylococcal TSS and \nSSSS involves aggressive treatment of shock, \nantibiotic therapy, intravenous fluids regimens, \nand surgical debridement of the primary source \nif indicated. Anti-Staphylococcal antibiotics are \nthe mainstay of treatment and it is recommended \nto be administered within 1 hour upon \nrecognition of septic shock.27,28 Beta-lactam \nantibiotics, such as penicillin or cephalosporins \nshould be combined with clindamycin for \nTSS due to MSSA, while vancomycin can be \n\n\n\ncombined with clindamycin for TSS secondary \nto MRSA.28 Vancomycin, clindamycin and \npiperacillin-tazobactam/cefepime/carbapenem \ncan be started empirically if staphylococcal TSS \nis highly suspected. The rationale of adding \nclindamycin (bacteriostatic) to beta-lactams \n(bactericidal) is due to the lower effectiveness of \nbeta-lactams on bacteria in stationary phase of \ngrowth, especially in large inoculations, where \nthere are loss of several penicillin-binding \nproteins.29 In addition, Clindamycin has the \nadditional benefit of inhibiting bacterial toxins \nfrom Staphylococcus aureus. The duration of \nantibiotic treatment ranges from 10 to 14 days \nin cases without bacteraemia or other focus of \ninfection. \n\n\n\nThe  effectiveness  of  intravenous  \nimmunoglobulin (IVIG) in the treatment of \nTSS is debatable.27 There are studies which \nare  unable to draw a conclusion regarding \nthe efficacy of IVIG in TSS.27 However, \nthere are observational studies that reported \nlower mortality rates with the use of IVIG in \naddition to antibiotic, compared with the use \nof antibiotics alone.30 Since IVIG neutralizes \nthe superantigens and halts the cytokine \nproduction, it can be accepted as an adjuvant \ntreatment option in the management of TSS, \nafter considering the side effects, which include \ntransfusion reactions, thromboembolic events, \nkidney failure and aseptic meningitis.31\n\n\n\nThe use of systemic corticosteroids has been \nreported in TSS. A comparative retrospective \nanalysis done by James et al in 1984 concluded \nthat corticosteroids result in significantly \nreduced illness severity when given in the first \n2 to 3 days of TSS.2,32 Latest evidence suggested \nthat hydrocortisone 200mg per day should be \ngiven intravenously to adults with septic shock, \nespecially those who  require norepinephrine \nor epinephrine dose of \u22650.25mcg/kg/min.27 \nOur patient succumbed despite intensive \nmanagement, likely due to advanced sepsis and \nconcurrent COVID-19 infection. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4892\n\n\n\nConclusion\nWe describe a COVID-19 infected female \nwho succumbed to Staphylococcal TSS with \npossible concomitant SSSS that was initially \nreferred to dermatology team as toxic epidermal \nnecrolysis. Staphylococcal TSS and SSSS \nshould be considered in patients who present \nwith acute painful erythema followed by \nepidermal detachment, associated with high \ngrade fever, and hypotension with multisystem \ninvolvement. Early recognition and prompt \ntreatment are the keys points in the management \nespecially in TSS, as it can lead to rapid \nfulminant deterioration resulting in mortality.\n\n\n\nConflict of Interest Declaration\nThe author have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for the permission \nto publish this paper.\n\n\n\nReferences\n1. Wharton M, Chorba TL, Vogt RL, Morse DL, Buehler JW. \n\n\n\nCase definitions for public health surveillance. MMWR \nRecomm Rep 1990;39:1-43.\n\n\n\n2. Todd JK. Toxic shock syndrome. Clin Microbiol Rev \n1988;1:432-46.\n\n\n\n3. Dugourd PM, Dupont A, Hubiche T, Chiaverini C, Alkhalifa \nA, Roudiere L et al. Staphylococcal toxic shock syndrome \nshould be considered in the event of diffuse erythema with \nfever and shock. Ann Dermatol Venereol 2019;146:287-91. \n\n\n\n4. Lappin E, Ferguson AJ. Gram-positive toxic shock \nsyndromes. Lancet Infect Dis 2009;9:281-90.\n\n\n\n5. Hajjeh RA, Reingold A, Weil A, Shutt K, Schuchat A, \nPerkins BA. TSS in the United States: Surveillance update, \n1979-1996. Emerg Infect Dis 1999;5:807-10.\n\n\n\n6. Kain KC, Schulzer M, Chow AW. Clinical spectrum of \nnonmenstrual toxic shock syndrome (TSS): Comparison \nwith menstrual TSS by multivariate discriminant analyses. \nClin Infect Dis 1993;16:100-6. \n\n\n\n7. Ladhani S, Joannou CL, Lochrie DP, Evans RW, Poston \nSM. Clinical, microbial, and biochemical aspects of the \nexfoliative toxins causing staphylococcal scalded-skin \nsyndrome. Clin Microbiol Rev 1999;12:224-42.\n\n\n\n8. CDC National Notifiable Diseases Surveillance System. \nToxic Shock Syndrome (Other Than Streptococcal) TSS. \nAvailable at https://ndc.services.cdc.gov/case-definitions/\ntoxic-shock-syndrome-2011/ Accessed on 19th May 2022\n\n\n\n9. Patel S, Cadwell JB, Lambert WC. Comparison of adult \nvs. paediatric inpatients with staphylococcal scalded skin \nsyndrome: a retrospective database analysis. Br J Dermatol \n\n\n\n2021;184:767-9.\n10. Staiman A, Hsu DY, Silverberg JI. Epidemiology of staph-\n\n\n\nylococcal scalded skin syndrome in US adults. J Am Acad \nDermatol 2018;79:774-6. \n\n\n\n11. Falk DK, King LE. Criteria for the diagnosis of staphylo-\ncoccal scalded skin syndrome in adults. Cutis 1983;31:431-\n4.\n\n\n\n12. Handler MZ, Schwartz RA. Staphylococcal scalded skin \nsyndrome: diagnosis and management in children and \nadults. J Eur Acad Dermatol Venereol 2014;28:1418-23. \n\n\n\n13. Brewer JD, Hundley MD, Meves A, Hargreaves J, McEvoy \nMT, Pittelkow MR. Staphylococcal scalded skin syndrome \nand toxic shock syndrome after tooth extraction. J Am Acad \nDermatol 2008;59:342-6.\n\n\n\n14. Rahmanian SD, Molenda M, Fox C, Zirwas M, Sood N. \nA 42-year-old man with fever, shock, and rash. Chest \n2010;138:1256-9. \n\n\n\n15. Anderson HJ, Lee JB. A review of fixed drug eruption with \na special focus on generalized bullous fixed drug eruption. \nMedicina (Kaunas) 2021;57:925.\n\n\n\n16. Lipowicz S, Sekula P, Ingen-Housz-Oro S, Liss Y, Sassolas \nB, Dunant A et al. Prognosis of generalized bullous \nfixed drug eruption: Comparison with Stevens-Johnson \nsyndrome and toxic epidermal necrolysis. Br J Dermatol \n2013;168:726-32.\n\n\n\n17. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, \nKovarik C, Desai SR et al. The spectrum of COVID-19-\nassociated dermatologic manifestations: An international \nregistry of 716 patients from 31 countries. J Am Acad \nDermatol 2020;83:1118-29.\n\n\n\n18. Feng Y, Armenti ST, Albin OR, Mian SI. Novel case of \nan adult with toxic shock syndrome following COVID-19 \ninfection. Am J Ophthalmol Case Rep 2020;20:100843. \n\n\n\n19. Reiss MA. Toxic shock syndrome. Prim Care Update Ob \nGyns 2000;7:85-90.\n\n\n\n20. Chan BC, Maurice P. Images in clinical medicine. \nStaphylococcal toxic shock syndrome. N Engl J Med \n2013;369:852.\n\n\n\n21. Contou D, Colin G, Travert B, Jochmans S, Conrad M, \nLascarrou JB et al. Menstrual toxic shock syndrome: A \nFrench nationwide multicentre retrospective study. Clin \nInfect Dis 2022:74:246-53.\n\n\n\n22. Durand G, Bes M, Meugnier H, Enright MC, Forey F, \nLiassine N et al. Detection of new methicillin-resistant \nStaphylococcus aureus clones containing the toxic shock \nsyndrome toxin 1 gene responsible for hospital- and \ncommunity-acquired infections in France. J Clin Micriobiol \n2006:44:847-53.\n\n\n\n23. Schlievert PM. Role of superantigens in human disease. J \nInfect Dis 1993;167:997-1002.\n\n\n\n24. Bonventre PF, Linnemann C, Weckbach LS, Staneck JL, \nBuncher CR, Vigdorth E et al. Antibody responses to toxic-\nshock-syndrome (TSS) toxin by patients with TSS and by \nhealthy staphylococcal carriers. J Infect Dis 1984;150:662-\n6.\n\n\n\n25. Parsonnet J. Mediators in the pathogenesis of toxic shock \nsyndrome: overview. Rev Infect Dis 1989;11:S263-9.\n\n\n\n26. Silversides JA, Lappin E, Ferguson AJ. Staphylococcal \ntoxic shock syndrome: Mechanisms and management. Curr \nInfect Diss Rep 2010;12:392-400.\n\n\n\n27. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith \nCM, French C et al. Surviving sepsis campaign: international \nguidelines for management of sepsis and septic shock 2021. \nIntensive Care Med 2021;47:1181-247.\n\n\n\n28. Annane D, Clair B, Salomon J. Managing toxic shock \nsyndrome with antibiotics. Expert Opin Pharmacother \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 48 93\n\n\n\n2004;5:1701-10.\n29. Stevens DL, Gibbons AE, Bergstrom R, Winn V. The Eagel \n\n\n\neffect revisited: efficacy of clindamycin, erythromycin \nand penicillin in the treatment of Streptococcal myositis. J \nInfect Dis 1988;158:23-8.\n\n\n\n30. Wilkins AL, Steer AC, Smeesters PR, Curtis N. Toxic shock \nsyndrome \u2013 the seven Rs of management and treatment. J \nInfect 2017;74:S147-52.\n\n\n\n31. Amreen S, Brar SK, Perveen S, Chaudhry MR, AlBabtain S, \nKhan S. Clinical Efficacy of Intravenous Immunoglobulins \nin Management of Toxic Shock Syndrome: An Updated \nLiterature Review. Cureus 13:e12836. \n\n\n\n32. Todd JK, Ressman M, Caston SA, Todd BH, Wiesenthal \nAM. Corticosteroid therapy for patients with toxic shock \nsyndrome. JAMA 1984;252:3399-402.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Jun Vol 4894\n\n\n\nACKNOWLEDGEMENT\nJun Issue 2022\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Dr Ch\u2019ng Chin Chwen\n4. Dr Chan Lee Chin\n5. Dr Chang Choong Chor\n6. Dr Chong Yew Thong\n7. Dr Dawn Ambrose\n8. Assoc Professor Dr Felix Yap Boon Bin\n9. Dr Henry Foong Boon Bee\n10. Dr Khor Yek Huan\n11. Dr Kwan Zhenli\n12. Dr Irene Lee Chew Kek\n13. Dr Lo Kang Shang Chit\n14. Dr Ng Ting Guan\n15. Dato\u2019 Dr Noor Zalmy Azizan\n16. Dr Priya Gill\n17. Dr Rajalingam Ramalingam\n18. Dr Tang Jyh Jong\n\n\n\n\n\n"
"\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. 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It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and \nfax numbers and an email address of the corresponding \nauthor who will be responsible for reading the proofs must \nalso be given on the title page. The author(s) must also \ndeclare any affiliation or significant financial involvement \nin any organizations or entity with a direct financial \ninterest in the subject matter or materials discussed in the \nmanuscript on this page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and \nopinions expressed do not necessarily reflect those of \nthe publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher \nand Editors of the products advertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40\n\n\n\nContents\n\n\n\nREVIEW ARTICLE\n\n\n\n2 Review of Current Leprosy Programme and \nAchievement in Malaysia\n\n\n\n A Johar\n\n\n\nORIGINAL ARTICLE\n\n\n\n5 Retrospective Analysis of Patch Test Results Between \n2011 and 2013 in Hospital Selayang, Malaysia\n\n\n\n Ng FY, WSA Wan Ahmad Kamal, L Sinnaiyah, \n H Ab Halim, R Ridzwan \n\n\n\n10\t Comparison\tof\tthe\tEfficacy\tof\tIntralesional\t\nTriamcinolone Acetonide and Silicone Gel Sheeting \nfor the Treatment of Keloids\n\n\n\n Tee SH, Ng TG, NZ Azizan\n\n\n\n22 Food and Aeroallergens Sensitization Pattern \namongst Atopic Dermatitis Children in Hospital \nKuala Lumpur\n\n\n\n Wee AL, Leong KF, S Begum\n\n\n\n27 Patch Testing in Children and Adolescents: 7 Years\u2019 \nExperience in Hospital Kuala Lumpur\n\n\n\n S Rosniza, Tang MM, Leong KF, S Begum, A Johar\n\n\n\n36 Cutaneous Adverse Drug Reactions in Sabah\n Gan TS, Lim YM, Tan YP, S Raman, Kwan MSK, \n A Johar\n\n\n\n41 Leprosy in pregnancy: A Case Series in 4 \nDermatology Clinics in Malaysia\n\n\n\n Loh KC, Tang MM, Tan WC, Chan LC, Voo MSY, S \nThevarajah\n\n\n\nCASE REPORT \n\n\n\n49 Rhabdomyosarcoma Arising in A Giant Congenital \nMelanocytic Nevus\n\n\n\n S Begum, Heah SS, Leong KF, Lee BR\n\n\n\n53 Diagnostic Biopsy Site in Cutaneous Angiosarcoma: \nReflections\tfrom\t3\tCases\n\n\n\n FZ Nordin, A Jamil, Low DW, NM Mohammed Noor, N \nMd Nor, Lee BR\n\n\n\n59 Verrucous Hemangioma of the Thumb in Children: \nA Rare Presentation\n\n\n\n MI Hamzan, N Basiron, F Kassim\n\n\n\n62 A Case of Basal Cell Carcinoma on the Left Cheek \nin a 62-year-old Woman, Operated by Wide \nExcision With V-Y Subcutaneous Tissue Pedicle \nIsland\tAdvancement\tFlap\tUnder\tBilevel\tSurgical\t\nTumescent Anesthesia\n\n\n\n S Lestari, T Ariani, YF Salim\n\n\n\n65\t Efficacy\tof\tUsing\tTopical\tImmunotherapy\twith\t\nSquaric Acid Dibutylester in the Treatment of \nAlopecia Areata \u2013 A Case Series of 11 patients\n\n\n\n Ang TS, Tang JJ\n\n\n\n69\t Phacomatosis\tPigmentovascularis\tType\tII:\tCase\t\t\nReport\n\n\n\n Wong KW, Tey KE\n\n\n\n73 Dapsone Hypersensitivity Syndrome and Dapsone-\ninduced\tLiver\tInjury\tin\tFour\tMalaysian\tIndigenous\t\nIndividuals\twith\tLeprosy\n\n\n\n R Ramalingam, Too CL, Tang MM\n\n\n\nCORRESPONDENCE \n\n\n\n80 Dermatologists and The History of Hair Restoration \nSurgery\n\n\n\n R Nathan\n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 1\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm \nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office \nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nExecutive Committee\nDr Agnes Heng Yoke Hui, MRCP - President\nRohna Ridzwan, MRCP - Vice President\nNoor Zalmy Azizan, Adv M Derm - Secretary\nChan Lee Chin, MMed - Treasurer\nHenry Foong Boon Bee, FRCP - Past President \nSabeera Begum, MMed - Committee Member\nTan Wooi Chiang, Adv M Derm - \nCommittee Member\n\n\n\nAzura Mohd Affandi, Adv M Derm - \nCommittee Member\nDr Ruban Nathan, FRCP - Committee Member\n\n\n\nDermatological Society of Malaysia \n(Rumah Dermatology)\nG1, Medical Academics of Malaysia, 210, \nJalan Tun Razak, 50400 Kuala Lumpur, \nMalaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang.\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2018 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, \nAdv M Derm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 402\n\n\n\nREVIEW\n\n\n\nReview of Current Leprosy Programme and Achievement in Malaysia\nAsmah Johar, MMed\n\n\n\nDepartment of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary:\nLeprosy is still a relevant public health concern in Malaysia. Efforts made to eliminate leprosy go \nbeyond the elimination phase. Aspects that need to be taken into consideration include disability \nprevention, rehabilitation and ensuring maintenance of skills for diagnosing and treating the small \nnumber of new cases that will continue to occur. This review article discussed about the experiences \nof the past, achievement at present and the future challenges during the implementation of National \nLeprosy Control Program in Malaysia. \n\n\n\nKey words: Leprosy, Hansen\u2019s disease, National Leprosy Control Program, Malaysia\n\n\n\nIntroduction\nLeprosy control programme in Malaysia was started \nin 1969 when the National Leprosy Control Centre \n(NLCC) was built in Sungai Buloh, Selangor. With \nthe implementation of multidrug therapy (MDT) \nin 1985, the prevalence of leprosy was reduced \nfrom 5.7 per 10,000 population in 1983 to 1.7 per \n10,000 in 1992.1 Malaysia has managed to eliminate \nleprosy in 1994 when the prevalence was less than \n1 case per 10,000 population. In 1994, the incidence \nwas 1.7 per 100,000 population.2 This achievement \nwas maintained throughout the years and in 2016, \nthe prevalence was 0.1 case per 10,000 population \nand incidence was 0.6 per 100,000 population.3\n\n\n\nIn East Malaysia such as Sabah, where the earth \nterrain can pose logistic problems contributed \nto as high as 30% of the yearly total case load in \nMalaysia. The overall leprosy control in Malaysia \nwas good with a prevalence of 0.7 case per 10,000 \npopulation from 1999. However, the prevalence of \nleprosy in districts like Kudat, Lahad Datu, Kota \nKinabalu and Semporna were more than one case \nper 10,000 population.4 In 2016, Tawau, Lahad \n\n\n\nDatu and Kota Kinabalu were still having a lot of \nnew cases of leprosy.3\n\n\n\nIn some publications, leprosy is now quoted as one \nof the neglected tropical disease in Southeast Asian \nNations (ASEAN).5,6 However in Malaysia, it is not \na neglected disease as many programmes are still \nactive either in the Ministry of Health lead by TB/\nKusta sector, individual state public health, health \ncenters and public hospitals with resident or visiting \ndermatologists.  Active case detection is still on-\ngoing through screening of contacts, rapid survey \nprogrammes in pockets of endemic areas especially \namong the indigenous community and screening of \nforeign workers.7\n\n\n\nIncreasing number of foreign workers in Malaysia \nis one of the significant contributing factors to the \npersistent cases of leprosy. In year 2015, as high as \n40.5% of the notified leprosy cases were foreigners.2 \nThis factor contributes to the transmission of \ndisease among local population although there are \nalso active transmission among the Malaysians. \nAnother important indicator for active transmission \nin the community is the new cases that were \ndetected among children. There were 22 and 11 \nchildren diagnosed with leprosy in 2014 and 2015 \nrespectively in Malaysia. Of the 11 children with \nleprosy in 2015, 8 had grade 2 deformity.2 With \ngrade 2 deformity, the patient may have either poor \neye sight (<6/60 or unable to count fingers at 6 \nmeter), lagophthalmos, iridocyclitis, opaque cornea \nor obvious limbs deformity.7 \n \n\n\n\nCorresponding Author\nDatin Dr Asmah binti Johar\nDepartment of Dermatology, Level 6, \nSpecialist Complex and Ambulatory Care Centre, \nHospital Kuala Lumpur, Jalan Pahang, \n50586 Kuala Lumpur, Malaysia\nEmail: asdr2001@hotmail.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 3\n\n\n\nNational Leprosy Control Program in \nMalaysia\nThe national strategic plan for leprosy programme in \nMalaysia for 2016-2020 has been published in 2017 \nand uploaded for reference.2 The main objectives \ninclude achieving elimination status in certain \ndistrict areas, to achieve less than 2 per 100,000 \npopulation of grade 2 deformity and no children \nwith grade 2 deformity. Hopefully by 2020, we can \nachieve all the objectives outlined in the national \nstrategic plan which is in line with the World Health \nOrganisation (WHO) global leprosy strategy 2016 \nto 2020. \n\n\n\nDiagnosis of Leprosy\nMouse footpad (MFP) culture is considered relevant \nin Malaysia as many dermatology clinics in various \nstates are still sending MFP culture to determine \nthe resistance pattern of Mycobacterium leprae. \nThe MFP cultures of 651 patients with borderline \nlepromatous and lepromatous leprosy which were \nsent to the Leprosy Unit, National Public Health \nLaboratory, Sungai Buloh between 1997 to 2013 \nwere retrospectively studied.8 Earlier, Jamil A et \nal reported a 22.1% intermediate and high level \ndapsone resistance between 1997 and 2008.9 Low \nlevel resistance was observed in 31% of cases. \nDalawi I et al in our latest study reported dapsone \nresistance rate of 55% (32.3% with low degree of \nresistance), clofazimine resistance rate of 23.5% \nand rifampicin resistance rate of 2.9%.8 Rifampicin, \nclofazimine and dapsone are being used in the \nMDT regime for the treatment of leprosy for \nmany years and therefore continuous monitoring \nof drug resistance is important to ensure that these \nantibiotics can still be used in MDT regime.\n\n\n\nThe molecular methods for detection of mutations \nin Mycobacterium leprae associated with dapsone, \nrifampicin and fluoroquinolone resistance are not \nyet widely provided in Malaysia. However, it is \navailable in the National Public Health Laboratory \nin Sungai Buloh to support the diagnosis of leprosy \nvia the detection of Mycobacterium leprae using \nPCR-based gene amplification assays on skin \nbiopsy specimens.10 Missense mutations in the \nDNA region of folP1, rpoB and gyrA were found \nto correspond to resistance to dapsone, rifampicin \nand quinolones respectively using the gold standard \nmouse footpad cultivation.11,12 However, there \nis none to test on resistance to clofazimine and \nminocycline. Minocycline is being used for second \nline treatment. Due to this matter, MFP is still \n\n\n\nrevelant and the knowledge and skill still need to \nbe maintained.\n \nMDT Treatment\nMultidrug therapy regime in Malaysia was \nstarted since 1985 with the use of Sungai Buloh \nAugmented MDT (SBA-MDT) which was modified \nby the Malaysian National Leprosy Control Centre. \nIt consisted of an initial intensive phase of 3 \nweeks or until the morphological index was 0 in \nmultibacillary leprosy. It was then followed with \na longer duration of treatment subsequently. For \npaucibacillary (PB), the treatment was 1 year and \nfor multibacillary (MB), the treatment was 3 years \nor until the bacteriological index was 0. Based on \nthe results of the paper published by Yap et al in \n2012 which compared the treatment outcome and \nside effects of SBA-MDT and WHO-MDT, the \nMDT regime was modified to shorter period.13 Now \nthe treatment for PB consist of 600mg rifampicin \nmonthly and 100mg dapsone daily for a six months \nduration. For MB, the regime consists of 600mg \nrifampicin and 300mg clofazamine monthly with \n100mg dapsone and 50mg clofazamine daily for \ntwelve months for BI < 4 and 18 months for BI >4.7\n\n\n\nYap FBB et al reviewed patients\u2019 records treated \nfrom 1985 to 2009 and found a relapse rate of 1.7% \nwith SBA-MDT and 1.4% with WHO-MDT (p = \n0.79). For multibacillary leprosy, the relapse rate \nwas 0.9% with SBA-MDT and 0 with WHO-MDT (p \n= 0.32). For paucibacillary leprosy, it was 3.1% and \n5.0% respectively (p = 0.52). The relapse interval \nranges from 3 months to 59 months13. Longer period \nof surveillance is important for future reference \nin determining the success of treatment regime \nespecially when the duration of MDT is getting \nshorter and the BI of patients are still positive after \ncompleted MDT. It is also important as there may \nbe a rise of resistant rate in the future when the first \nline antibiotics have not changed since MDT was \nfirst introduced.\n\n\n\nBesides the Ministry of Health and some public \nuniversities who play a big role in controlling this \ndisease, none profit organisation such as Malaysian \nLeprosy Relief Association (MaLRA) which was \nformed in 1959 is still assisting the older generation \nof leprae patients with various deformity in their old \nage. They provide financial aids for various amenities \nsuch as wheelchair, walking sticks, artificial limbs \nand many more including rehabilitation services \nwhich covers the medical, social and vocational \nassistance.8\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 404\n\n\n\nConclusion\nMalaysia National Leprosy Control Program is \nrunning in line with WHO recommendation and \ntarget. MDT services have been integrated within \nthe general health services. However, an effective \nreferral system needs to be maintained at an \nappropriate level to deal with problems which \nmay need specialized care. Continuous education \nand training are crucial to ensure the continuity of \nquality care.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe author has no conflict of interest to declare.  \n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health Malaysia, TB/Kusta Sector of Disease \nControl Division, Ministry of Health Malaysia, for \ntheir permission and all other members that have \ncontributed in the care of Leprosy in Malaysia.\n\n\n\nReferences\n\n\n\n1. Jayalakshmi P. Leprosy in Malaysia. Malays J Pathol \n1994;16:7-9. \n\n\n\n2. Bahagian Kawalan Penyakit, Kementerian Kesihatan \nMalaysia. Pelan Strategik Program Kawalan Kusta \nKebangsaan 2016-2020. Kementerian Kesihatan Malaysia \n2017.\n\n\n\n3. Disease Control Division, TB/Kusta Sector, Ministry of \nHealth Malaysia 2017 (Unpublished data).\n\n\n\n4. Dony JF, Ahmad J, Khen Tiong Y. Epidemiology of \ntuberculosis and leprosy, Sabah, Malaysia. Tuberculosis \n(Edinb) 2004;84:8-18.\n\n\n\n5. Hotez PJ, Bottazz ME, Strych U, Chang LY, Lim \nYA, Goodenow et al. Neglected Tropical Diseases \namong the Association of Southeast Asian Nations \n(ASEAN): Overview and Update. PLoS Negl Trop Dis \n2015;9(4):e0003575.\n\n\n\n6. Hotez P, Aksoy S. PLoS Neglected Tropical Diseases: \nTen years of progress in neglected tropical disease control \nand elimination \u2026 More or less. PLoS Negl Trop Dis \n2017;11(4):e0005355.\n\n\n\n7. Manual Pengurusan Kusta, Disease Control Division, \nTB/Kusta Sector, Ministry of Health Malaysia 2014; 2nd \nEdition. \n\n\n\n8. Dalawi I, Tang MM, Osman AS, Ismail M, Abu Bakar RS, \nDony JF et al. Drug Resistance Pattern of Mycobacterium \nleprae from mouse footpad cultivation between 1997 to \n2013 In Malaysia. Lepr Rev 2017;88:463-77.\n\n\n\n9. Jamil A, Noor NM, Osman AS, Baseri MM, \nMuthupalaniappen L. Primary dapsone resistant \nMycobacterium leprae in a non-endemic country. Indian J \nDermatol Venereol Leprol 2013;79:527-9.\n\n\n\n10. Martinez AN, Talhari C, Moraes MO, Talhari S. PCR-Based \nTechniques for Leprosy Diagnosis: from the laboratory to \nthe clinic. PLoS Negl Trop Dis 2014;8(4):e2655.\n\n\n\n11. Guerrero MI, Colorado CL, Torres JF, Le\u00f3n CI. Is drug-\nresistant Mycobacterium leprae a real cause for concern? \nFirst approach to molecular monitoring of multibacillary \nColombian patients with and without previous leprosy \ntreatment. Biom\u00e9dica 2014;34:137-47.\n\n\n\n12. Kai M, Nguyen Phuc NH, Nguyen HA, Pham TH, Nguyen \nKH, Miyamoto Y et al. Analysis of Drug-Resistant Strains \nof Mycobacterium leprae in an Endemic Area of Vietnam. \nClin Infect Dis 2011;52:e127-e132. \n\n\n\n13. Yap FBB, Chor CC, Johar A, Baba R. Comparison of \nthe efficacy and safety of Sungai Buloh Augmented \nMultiple Drug Therapy (SBA-MDT) and the World Health \nOrganisation Multiple Drug Therapy (WHO-MDT) in the \nTreatment of Leprosy in Malaysia. Malaysian J Dermatol \n2012;28:9-17.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 5\n\n\n\nORIGINAL ARTICLE\n\n\n\nRetrospective Analysis of Patch Test Results Between 2011 and 2013 \nin Hospital Selayang, Malaysia\nFei Yin Ng1, AdvMDerm, Wan Ahmad Kamal Wan Syameen Afira2, AdvMDerm, Logesh A/P Sinnaiyah2, MD, Hazfaneza \nBt Ab Halim2, MPH, Rohna Ridzwan2, MRCP\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia\n2Department of Dermatology, Hospital Selayang, Batu Caves, Selangor, Malaysia\n\n\n\nAbstract\nIntroduction:\nPatch test is the gold standard diagnostic test for contact allergy. Periodic analysis of the trend of \ncontact allergy provides a valuable guide to clinicians. We aim to study the pattern of contact allergy \nin adults at Hospital Selayang.\n\n\n\nMethods:\nThis is a retrospective review of patch test data in adults suspected with allergic contact dermatitis \nbetween January 2011 and December 2013 at Hospital Selayang.\n\n\n\nResults: \nThere were 705 subjects with 247 males (35%) and 458 females (65%). At least 1 positive reaction \nwas detected in 546 (77.4%) subjects patch tested with European Baseline Series (EBS) and additional \nseries. The top 5 common allergens in the EBS were nickel sulfate (28.7%), cobalt chloride (13.6%), \nparaben mix (11.6%), balsam of peru (10.6%), and potassium dichromate (10.5%). Among those \npatch tested with rubber additives series, the top 3 allergens were N,N-Diphenylguanidine (DPG), \nN-Cyclohexyl-N-phenyl-4-phenylenediamine (CPPD), and N-Cyclohexylthiophthalimide.  Of the \ntop 5 common allergens in the group tested with fragrance series, all except Ylang ylang oil were \ncomponents of fragrance mix I. Among the subjects tested with fragrance series, the top 5 common \nallergens were individual components of fragrance mix I and Ylang ylang oil.\n\n\n\nConclusion:\nA multicentre study would reflect better the pattern of allergen exposure of the nation. Further \nevaluation of the prevalence of contact allergy to DPG, CPPD, N-Cyclohexylthiophthalimide and \nYlang ylang oil would guide the need to incorporate these allergens in routine testing along with EBS.\n\n\n\nKey words: Allergic contact dermatitis, Patch test, European baseline series, Additional series\n\n\n\nIntroduction\nAllergic contact dermatitis (ACD) is a delayed, cell-\nmediated hypersensitivity reaction to a substance in \na previously sensitized person. Patch test is the gold \nstandard investigative method to aid in establishing \nthe diagnosis. Patch test is routinely preformed using \na standard series supplemented with the additional \nseries when required. Various regional standard \nseries have been constructed in different regions \nof the world. Periodic review of allergen trends is \n\n\n\nCorresponding Author\nDr Ng Fei Yin\nDepartment of Dermatology, \nHospital Tengku Ampuan Rahimah, Jalan Langat, \n41200 Klang, Selangor, Malaysia\nEmail: willow_fy02@yahoo.com \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 406\n\n\n\nThe sensitization rate of patch testing with both the \nEuropean Baseline Series and additional series was \n77.4%. Among the subjects tested with European \nBaseline Series alone, 466 (66.1%) had positive \nreaction to at least 1 allergen. There were 61 subjects \n(8.7%) who reacted positively to the additional \nseries exclusively.  The frequently utilized additional \nseries were rubber additives series (462), shoe series \n(191), plastic and glue series (169), fragrance series \n(144), cosmetic series (136) and textile and dye \nseries (111).\n\n\n\nTable 2. Top 10 common allergens in the modified European \nBaseline Series \n\n\n\nWe analyzed further the top 5 common allergens of \nboth rubber additives and fragrance series. Among \nthose with positive reaction to the rubber additives, \n60% were female subjects. Similarly, two-thirds \nof the subjects who reacted to the fragrance series \nwere females. The main sites affected in rubber \nsensitization were hands (27.0%), feet (20.0%) and \nhands and feet combination (18.4%).   Fragrance \nsensitization had a similar distribution: hands \n(22.2%), hands and feet combination (20.4%), feet \n(13.0%).\n\n\n\nTable 3. Top 5 common allergen of Rubber Additives Series \n\n\n\nTable 4. Top 5 common allergen of Fragrance Series \n\n\n\nnecessary to understand the local epidemiology and \ndetect changes in the community allergen exposure \nfrom the past.\n\n\n\nThis study aimed to review the allergen trends in the \nEuropean baseline series and the additional series \nin Hospital Selayang between the year of 2011 and \n2013.\n\n\n\nMaterials and Methods\nThis is a retrospective review of the patch test \nresults performed on patients attending the \nDermatology Clinic from January 2011 till \nDecember 2013. The information were retrieved \nfrom the medical records. All subjects were patch \ntested with European baseline series. Additional \nseries were applied to subjects based on clinical \njudgement from the history taking. The allergens \nwere products of Chemotechnique Diagnostics. \nThe allergens were applied on the subjects using \nFinn chambers. Reading of patch test reactions was \nperformed on day 3 and day 5. Patch test results \nwere interpreted according to the recommendation \nof the International Contact Dermatitis Research \nGroup (ICDRG). The data were analyzed using \nSPSS version 21.\n\n\n\nResults\nA total of 705 patients suspected with allergic contact \ndermatitis were patch tested. The subjects\u2019 age \nranged from 3 to 87 years. The patient demography \nis shown in table 1. Hand eczema was the most \ncommon presentation of suspected contact allergy.\n\n\n\nTable 1. Patients Demographic and Characteristics\n\n\n\nCharacteristics Frequency, n (%) \nAge, mean 35.9\n\n\n\nGender\n      Male 247 (35.0)\n      Female 458 (65.0)\n\n\n\nEthnicity\n      Malay 363 (51.5)\n      Chinese 241 (34.2)\n      Indian 95 (13.5)\n      Others 6 (0.8)\n\n\n\nSite of dermatitis\n      Hands 154 (21.8)\n      Feet 117 (16.5)\n      Hand and feet 93 (13.2)\n      Face 65 (9.2)\n      Trunk 38 (5.4)\n      Various combinations 238 (33.8)\n\n\n\nAllergen Frequency of tested Positive, n (%) \nNickel sulfate 202 (28.7)\nCobalt chloride 96 (13.6)\nParaben mix 82 (11.6)\nBalsam of peru 75 (10.6)\nPotassium dichromate 74 (10.5)\nFormaldehyde 49 (7.0)\nCl+Me-isothiazolinone 46 (6.5)\nNeomycin sulfate 45 (6.4)\nColophony 45 (6.4)\nPara phenylenediamine 37 (5.2)\n\n\n\nAllergen Frequency of tested Positive, n (%) \nN=144\n\n\n\nCinnamic alcohol 28 (19.4)\nYlang ylang oil 21 (14.6)\nCinnamic aldehyde 17 (11.8)\nEugenol 16 (11.1)\nIsoeugenol 14 (9.7)\n\n\n\nAllergen Frequency of tested Positive, n (%) \nN=462\n\n\n\nN,N-Diphenylguanidine, DPG 51 (11.0)\nN-Cyclohexyl-N-phenyl-4-\nphenylenediamine, CPPD\n\n\n\n17 (3.7)\n\n\n\nN-Cyclohexylthiophthalimide 17 (3.7)\nTetramethylthiuram \nmonosulfide, TMTM\n\n\n\n16 (3.5)\n\n\n\nN-Isopropyl-N-phenyl-4-\nphenylenediamine, IPPD\n\n\n\n14 (3.0)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 7\n\n\n\nDiscussion\nApart from confirming the suspected allergens \nelicited from detail history and physical \nexamination, patch test also had an important role \nin unveiling the hidden causal allergens.1,2 Fleming \net al. had demonstrated that clinical history alone \ncould only provide accurate allergen identification \nin half the cases.3 Positive reaction to an allergen is \nan evidence of previous sensitization and may not \nnecessarily indicate the source of current dermatitis. \nUnderstanding the possible pitfalls of patch test \nalong with cautious interpretation is of practical \nimportance.4,5\n\n\n\nThe available patch test standard series consist of a \nmixture of common allergens based on the statistics. \nResearch groups periodically review and update the \nstandard series, which expand with time. Variations \nin the standard series among nations are related to \nthe regional differences in exposure. \n\n\n\nIn contrary to the historical belief that standard \nseries can detect 70-80% of the allergic contact \ndermatitis cases,6 a large European multicentre \ntrial involving 4824 patients revealed a wide range \nof sensitivity between 37 and 73% using standard \npatch test series.7\n\n\n\n \nThere is always a tendency to underdiagnose \ncontact allergy when testing with standard series \nalone. The essential role of supplementary allergens \nor series have been evaluated. Previous data had \ndemonstrated that 7-40% of contact allergies would \nhave been missed without the supplementary \nallergens. 8,9 \n\n\n\nAlongside with our study, How et al10 performed \na 5-year retrospective review of contact allergy in \nanother tertiary centre within the nation. The rate of \npositive reaction to at least 1 allergen were similar \n(76.6% vs 77.4%). Using additional series improved \nthe detection of contact allergy in both centres. We \nhad a higher proportion of cases with at least 1 \npositive reaction to the additional series allergens \nbut negative reaction to EBS (11.6% vs 4.5%). \nNickel sulfate was the top most common allergen \nin both centres. Among the top 10 allergens, both \ncentres shared 8 common allergens. Paraben mix \nand formaldehyde which were present in our list \nof top 10 common allergens were taken over by \nfragrance mix I and II in our counterpart.10 Being \na multiracial nation, this differences in patterns of \ncontact allergy can be explained by the diversity of \nthe cultural practices and the distribution of ethnic \n\n\n\ngroups in various regions.\n\n\n\nWe compared our results with other the studies from \nSingapore, China and the United States of America \n(Table 5). The standard series were not identical. \nNickel sulfate which is widely used in cosmetic \njewelry, clothing, electronics, coins and household \nobjects remains as the highest ranking allergen \nacross the countries. Contact allergy to metals, \npreservatives and fragrance was most prevalent in \nour centre. In contrast to the other 3 centres, the \nfragrance mixes did not yield high sensitization \nrates. In both the other Asian centres, rubber allergy \nseemed more common.11-13\n\n\n\nThe European baseline series has a wide coverage \nof rubber and fragrance allergens. Thiuram mix, \nN-Isopropyl-N-phenyl-4-phenylenediamine \n(IPPD), mercapto mix and 2-mercaptobenzothiazole \nare the rubber additives allergens in European \nbaseline series. Balsam of peru, lyral, fragrance mix \nI and II which consist of 14 haptens are the main \nfragrance components in European baseline series. \n\n\n\nIn this study, we analysed the top 5 common rubber \nand fragrance allergens in the additional series. \nIn the rubber additives series, the top 3 allergens \nN,N-Diphenylguanidine (DPG), N-Cyclohexyl-\nN-phenyl-4-phenylenediamine (CPPD), and \nN-Cyclohexylthiophthalimide were not present \nwithin the rubber mixes in European baseline \nseries. The other 2 allergens, tetramethylthiuram \nmonosulfide (TMTM), a component of thiuram mix, \nand N-Isopropyl-N-phenyl-4-phenylenediamine \n(IPPD) had since long been incorporated in the \nEuropean baseline series.\n\n\n\nRubber additives play an essential role in the \nmanufacturing process of many household \nproducts, stationary, sports equipments, personal \nand healthcare products. They are widely used in \nthe automotive industry as well. Rubber additives \nserve their functions as accelerators, antioxidants, \nantidegradants, bonding agents, retarders, stabilisers \nor plasticizers. DPG is a rubber accelerator, CPPD \nan antidegradant, and N-Cyclohexylthiophthalimide \na retarder.14\n\n\n\nThe European Surveillance System on Contact \nAllergies (ESSCA) network gathered data from \nfrom 12 European countries between 2009 and 2012 \nreviewing the pattern of rubber allergy. Prevalence \nof thiuram mix showed a trend of decline (1.87%). \nOn the other hand, carba mix allergy was on a \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 408\n\n\n\nrise (2.29%). Diphenylguanidine is a component \nof carba mix. The shift was due to the gradual \nreplacement of thiuram mix in manufactured \ngloves by dithiocarbamates. The main use of \nN-Cyclohexylthiophthalimide is in producing thick \nrubber goods like tyres. ESSCA detected a prevalence \nof contact allergy to N-Cyclohexylthiophthalimide \nof 0.49%.15 Our study data was in agreement with \nthe trend of rubber allergy observed by the ESSCA \nnetwork. \n\n\n\nN-Cyclohexyl-N-phenyl-4-phenylenediamine \nis a member of the black rubber mix which is \npresent in the standard series in few countries. \nBendelwald et al, in their 8-year retrospective \nreview of patch testing 773 patients with rubber \nallergens described the following sensitization \nrates to the allergens: thiuram mix (7.6%), DPG \n(7.5%), N-Cyclohexylthiophthalimide (5.2%),  \nN-Cyclohexyl-N-phenyl-4-phenylenediamine \n(1.3%).16 \n\n\n\nWith the exception of Ylang ylang oil, the other \n4 most common fragrance allergens - cinnamic \nalcohol, cinnamic aldehyde, eugenol and isoeugenol \nare components of fragrance mix I. Ylang ylang \noil which is extracted from the flowers of the  \nCananga odorata tree, is popular with its presence \nin  aromatherapy, cosmetics and body products. \nIt also has been used in food preparation, and in \nethnomedicine where it serves as an anxiolytic, \nmosquito repellent and treatment for malaria.17 \n\n\n\nWetter et al. and Uter et al. studied the patch test \n\n\n\nMalaysia\nCurrent Study\n\n\n\nN=705\n\n\n\nMalaysia\nHow et al10\n\n\n\nN=689\n\n\n\nSingapore\nOchi et al12\n\n\n\nN=2598\n\n\n\nChina\nCheng et al11\n\n\n\nN=1354\n\n\n\nAmerica\nWarshaw et al13\n\n\n\nN=4238\nStudy \nperiod 2011-2013 2011-2015 2009-2013 2001-2006 2011-2012\n\n\n\nTop 10 \ncommon \nallergens\n\n\n\nNickel sulfate (28.7%) Nickel sulfate (35.5%) Nickel Sulfate (23.9%) Potassium dichromate \n(50.1%)\n\n\n\nNickel Sulfate (18.5%)\n\n\n\nCobalt chloride (13.6%) Potassium dichromate (16.5%) Fragrance Mix l (6.7%) Nickel Sulfate (42.9%) Fragrance Mix l (12.1%)\nParaben mix (11.6%) Methylchloroisothiazolinone\n\n\n\n+Methylisothiazolinone (12.9%)\nPPD (6.2%) Carba mix (24.9%) Neomycin sulfate (9.1%)\n\n\n\nBalsam of peru (10.6%) Fragrance Mix l (12.6%) Colophony (4.6%) Fragrance Mix l (22.2%) Balsam of Peru (7.9%)\nPotassium dichromate \n(10.5%)\n\n\n\nCobalt chloride (10.2%) Potassium dichromate \n(4.6%)\n\n\n\nThimerosal (21.0%) Bacitracin (7.8%)\n\n\n\nFormaldehyde (7.0%) Fragrance mix II (8.7%) Balsam of Peru (4.2%) Paraben mix (20.0%) Cobalt chloride (7.3%)\nCl+Me-isothiazolinone \n(6.5%)\n\n\n\nBalsam of peru (7.3%) Fragrance mix II (3.9%) Formaldehyde (15.8%) Formaldehyde (6.6%)\n\n\n\nNeomycin sulfate (6.4%) PPD (6.7%) Neomycin sulfate (2.5%) PPD (13.5%) Quatermium-15 (6.4%)\nColophony (6.4%) Neomycin sulfate (6.1%) Lyral (1.9%) Benzocaine (12.7%) PPD (6.3%)\nPPD (5.2%) Colophony (5.7%) Thiuram mix (1.9%) Ethylenediamine\n\n\n\ndihydrochloride (12.2%)\nFragrance Mix lI (5.2%)\n\n\n\nresults in patients with suspected cosmetic or \nfragrance contact dermatitis. The sensitization rates \nto Ylang ylang oil ranged from 0.9% to 3.1%.18,19\n\n\n\nThe subjects tested with the supplementary series \nwere a selected group with high suspicion of allergy \nto the respective allergens. Therefore, the results \nwould have shown a higher detection rate.\n\n\n\nHowever, it should concern us that using \nsupplementary series is not a routine practice in all \npatch test centres. With reference to our data, 11% \nof the rubber allergy and 14.6% of the fragrance \nallergy cases would have been missed without \ntesting diphenylguanidine and Ylang ylang oil.  \nBearing in mind that this study only involved a \nsingle centre in the country, it may not reflect the \nexact epidemiology of the nation.\n\n\n\nVoon et al20 in their single-centre study on \npreservative allergy involving 243 patients over a \n12-month period in 2011, illustrated paraben mix as \nthe allergen with the highest sensitization rate. The \nretrospective analysis studied patients tested with \nboth the European Baseline Series and additional \nseries. Our study data which extended from 2011 \nto 2013, still showed paraben mix as the highest \nranking preservative allergen in the European \nBaseline Series. Paraben mix allergy is still prevalent \nin Thailand and China. In the European countries, \nthe legislation controlling the concentration of \nparaben mix in cosmetics have led to a reduction in \nthe prevalence of contact allergy.20\n\n\n\nTable 5. Comparison of the top 10 common allergens among different centres\n\n\n\nPPD = p-phenylenediamine\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 9\n\n\n\nConclusion\nOur study has illustrated the pattern of allergen \nsensitization in subjects with suspected allergic \ncontact dermatitis in Selayang Hospital. We \nhave highlighted the potential significance of \ndiphenylguanidine, N-Cyclohexylthiophthalimide \nN-phenyl-4-phenylenediamine and Ylang ylang oil \nin establishing the diagnosis of rubber and fragrance \nallergy. To demonstrate a more representative \nthe pattern of  contact allergy of the nation, a \nmulticentre study involving the rest of the patch \ntest centres in Malaysia is required. This 4 allergens \ncould be considered to be incorporated to modify \nour baseline series in the future.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Ale IS, Maibacht HI. The diagnostic value to patch \ntesting. In: Wilhelm KP, Zhai H, Maibach HI, editors. \nDermatotoxicology 8th Edition. London: Informa \nHealthcare, 2012.p360-77.\n\n\n\n2. Ale IS, Maibacht HA. Diagnostic approach in allergic \nand irritant contact dermatitis. Expert Rev Clin Immunol \n2010;6:291-310.\n\n\n\n3. Fleming CJ, Burden AD, Forsyth A. Accuracy of questions \nrelated to allergic contact dermatitis. Am J Contact Dermat \n2000;11:218-21.\n\n\n\n4. Ale SI, Maibach HI. Clinical relevance in allergic contact \ndermatitis. Dermatosen 1995;43:119-21. \n\n\n\n5. Dujardin B, Van den Ende J, Van Gompel A, Unger JP, Van \nder Stuyft P. Likelihood rations: A real improvement for \nclinical decision making? Eur J Epidemiol 1994;10:29.\n\n\n\n6. James WD, Rosenthal LE, Brancaccio RR, Marks JG. \nAmerican Academy of Dermatology Patch Testing Survey \n(use and effectiveness of this procedure). J Am Acad \nDermatol 1992;26:991-4.\n\n\n\n7. Menn\u00e9 T, Dooms-Goossens A, Wahlberg JE, White IR, \nShaw S. How large a proportion of contact sensitivities \nare diagnosed with the European standard series? Contact \nDermatitis 1992;26:201-2.\n\n\n\n8. Cohen DE, Brancaccio R, Andersen D, Belsito DV. Utility \nof a standard allergen series alone in the evaluation of \nACD: a retrospective study of 732 patients. J Am Acad \nDermatol 1997;36:914-8.\n\n\n\n9. Veien NK, Hattel T, Justesen O. Patch testing with \nsubstances not included in the standard series. Contact \nDermatitis 1983;9:304-8. \n\n\n\n10. How KN, Tang MM, Kaur R, Johar A. Contact sensitisation \nin adults: a 5-year retrospective review in Hospital Kuala \nLumpur. Med J Malaysia 2017;72:113-8.\n\n\n\n11. Cheng S, Cao M, Zhang Y, Peng S, Dong J, Zhang D et \nal. Time trends of contact allergy to a modified European \nbaseline series in Beijing between 2001 and 2006. Contact \nDermatitis 2011;65:22-7.\n\n\n\n12. Ochi H, Cheng SWN, Leow YH, Goon ATJ. Contact allergy \ntrends in Singapore - a retrospective study of patch test data \nfrom 2009 to 2013. Contact Dermatitis 2017;76:49-50. \n\n\n\n13. Warshaw EM, Maibach HI, Taylor JS, Sasseville D, \nDeKoven JG, Zirwas MJ et al. North American contact \ndermatitis group patch test results: 2011-2012. Dermatitis \n2015;26:49-59.\n\n\n\n14. Warburton KL, Uter W, Geier J, Spiewak R, Mahler V, \nCr\u00e9py MN et al. Patch testing with rubber series in Europe: \na critical review and recommendation. Contact Dermatitis \n2017;76:195-203.\n\n\n\n15. Warburton KL, Bauer A, Chowdhury MM, Cooper S, \nKr\u0119cisz B, Chomiczewska-Sk\u00f3ra D et al. ESSCA results \nwith the baseline series, 2009-2012: Rubber allergens. \nContact Dermatitis 2015;73:305-12. \n\n\n\n16. Bendewald MJ, Farmer SA, Davis MDP. An 8-year \nretrospective review of patch testing with rubber allergens: \nThe mayo clinic experience. Dermatitis 2010;21:33-40. \n\n\n\n17. Tan LTH, Lee LH, Yin WF, Chan CK, H Abdul Kadir, \nChan KG et al. Traditional Uses, Phytochemistry, and \nBioactivities of Cananga odorata (Ylang-Ylang). Evid \nBased Complement Alternat Med 2015;2015:1-30. \n\n\n\n18. Wetter DA, Yiannias JA, Prakash AV, Davis MDP, Farmer \nSA, El-Azhary RA. Results of patch testing to personal care \nproduct allergens in a standard series and a supplemental \ncosmetic series: An analysis of 945 patients from the Mayo \nClinic Contact Dermatitis Group, 2000-2007. J Am Acad \nDermatol 2010;63:789-98. \n\n\n\n19. Uter W, Schmidt E, Geier J, Lessmann H, Schnuch A, \nFrosch P. Contact allergy to essential oils: Current patch \ntest results (2000-2008) from the Information Network of \nDepartments of Dermatology (IVDK). Contact Dermatitis \n2010;63:277-83. \n\n\n\n20. Yee VS, Rohna R. Patch testing with preservatives \nsensitizers. A year retrospective study from Selayang \nHospital. Malaysian J Dermatol 2013;30:1-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4010\n\n\n\nORIGINAL ARTICLE\n\n\n\nComparison of the Efficacy of Intralesional Triamcinolone Acetonide \nand Silicone Gel Sheeting for the Treatment of Keloids\nShwu Hoon Tee1, AdvMDerm, Ting Guan Ng2, AdvMDerm, Noor Zalmy Azizan3, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Serdang, Kajang, Selangor, Malaysia\n2Department of Dermatology, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia\n3Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntoduction:\nThere are multiple treatment modalities for keloids but no single modality has been proven to be the \ngold standard. This study aims to compare the efficacy of intralesional triamcinolone acetonide (TAC)  \nwith silicone gel sheeting (SGS) in treating keloids and their effect on patients\u2019 quality of life(QoL).\n\n\n\nMethods: \nThis was a two-arm randomized-controlled trial involving 56 subjects in which intralesional TAC 20 \nmg/mL after dilution with 2% lignocaine was administered on keloids monthly for patients in group \n1 while patients in group 2 applied SGS on keloids daily. Patients were treated for 12 weeks and \nfollowed-up for 16 weeks. Patient and Observer Scar Assessment Scale (POSAS) and Dermatology \nLife Quality Index (DLQI)  were assessed to monitor treatment efficacy and patients\u2019 QoL respectively. \n\n\n\nResults: \nThere was 44.2% of improvement in the mean of total score of POSAS in group 1 as compared to \n11.6% in group 2 (p<0.001). Both groups showed significant improvement in vascularity, pigmentation, \nthickness and pliability but the improvement was more significant in group 1. Subjects in group 1 \ndemonstrated a 67.3% of DLQI score improvement as compared to 13.1% in group 2 (p<0.001). Side \neffects reported were pain during procedure in group 1 and pruritus in group 2.  \n\n\n\nConclusion: \nIntralesional TAC was superior than SGS in treating keloids as well as improving patients\u2019 QoL and \nhence recommended as the first-line treatment. SGS can be considered as an alternative treatment for \npatients who are intolerable to pain  or as an adjunctive treatment.\n\n\n\nKey words: Intralesional triamcinolone, Silicone gel, Keloid\n\n\n\nCorresponding Author\nDr Tee Shwu Hoon\nDepartment of Dermatology, Hospital Serdang, \nJalan Puchong, 43000 Kajang, Selangor, Malaysia\nEmail: shwuhoontee@gmail.com\n\n\n\nIntroduction\nKeloids give rise to pain and pruritus in 80% \nof patients,1 cause functional impairment and \npsychological burden, both of which affect patients\u2019 \nquality of life (QoL). Literature has shown that \nkeloids give acceptability problems in up to 91% \nof patients and influence social functioning in 82% \nof patients especially those on visible body sites.1 \nA study in 130 patients with scars reported a lower \nquality of life in patients with keloids.2 Another \nstudy comparing QoL in patients with keloids and \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 11\n\n\n\nhypertrophic scars with patients with psoriasis \nreported that the QoL of patients with keloids and \nhypertrophic scars are impaired as much as that of \nthose with psoriasis. Total DLQI scores of patients \nwith keloids and hypertrophic scars and psoriasis \nwere comparable and significantly higher than that \nof healthy control.3  \n\n\n\nThere are substantial differences between Asian \nand Caucasian skin which contribute to a higher \nrisk of scar formation in Asian population. A \nretrospective review of 180 patients who underwent \ncleft lip repair reported a threefold increased rate of \nhypertrophic scarring in Asian patients as compared \nto Caucasians.4 Asians have a thicker dermis than \nequivalently pigmented Caucasians.5 There is a \ntendency toward a more vigorous fibroblastic \nresponse during wound healing in Asian patients \nwhich results in hypertrophic scarring and prolonged \nerythema during scar maturation.5,6 Besides, Asian \nskin has increased melanin,6,7 and a greater number \nof sebaceous glands, leading to increased sebum \nproduction. Hence, there is a greater propensity \ntoward hyperpigmentation and scar formation after \nskin injury. Furthermore, Asian skin is characterized \nby a higher rate of fibroblast proliferation resulting \nin a more vigorous collagen formation and \nfibroplasia during wound healing.5 Therefore, the \nscars in Asian patients may require a longer time for \nmaturation and healing which further complicates \ntheir management.5  \n\n\n\nAlthough multiple treatment modalities exist \nfor keloids, due to lack of level-one evidence, no \nsingle treatment has been defined as gold standard. \nThese include non-invasive treatments such as \nsilicone sheets or gels, tape, compression therapy \nand physiotherapy, as well as invasive treatments \nsuch as intralesional corticosteroid injections, \n5-fluorouracil injections, cryotherapy, radiotherapy \nand laser therapy. They can be used as monotherapy \nor in combination. An article published in the \nJournal of American Academy of Dermatology in \nJanuary 2012 commented that both intralesional \ncorticosteroids and silicone gel sheeting as level-\nthree evidence treatment modalities for scars.8 \nFor Asian population, steroid monotherapy is \neffective for symptom management for keloids and \nrecommended as first-line treatment.9 Combination \nof excision plus steroid injections or other adjuvant \ntherapies such as silicone dressing, cryotherapy, \nlaser, intralesional 5-fluorouracil, pressure therapy \nis effective and safe.9\n\n\n\nIt is crucial to explore the efficacy of various \ntreatment modalities for keloids in view of the great \nimplication of keloids on patients physically as \nwell as psychologically. Trials evaluating silicone \ngel sheeting as a treatment for keloid scarring are \ncommented as poor quality and highly susceptible \nto bias by the Cochrane Database systematic \nreview.10 Despite discouraging Cochrane review, it \nis still widely used due to its good safety profile. It \nis non-invasive, easy to be used but compliance can \nbe a major issue. Side effects include skin itchiness, \nirritation or rashes. The efficacy of silicone gel \nsheeting in treating keloids in local population has \nnot been studied before. \n\n\n\nTherefore, we aim to compare the efficacy of \nintralesional triamcinolone acetonide with silicone \ngel sheeting in the treatment of keloids by employing \na validated scar assessment scale (POSAS) which \ntake into account both the patient and provider \nperspective. In addition to evaluating the physical \ncharacteristics of a scar (eg, vascularization, \npigmentation, thickness, relief, and pliability) the \nPOSAS also asks patients to rate any pain and \npruritus associated with their scar on a 1-10 ordinal \nscale. We also aim to assess patients\u2019 quality of life \nby using a validated assessment tool (DLQI).\n \nTo minimize the risk of bias in our trial, our study \nfocused only on keloid patients as the results may \nvary depending on the types of scars. Clinical \ndifferentiation between hypertrophic and keloid \nscars is crucial before the initiation of treatment due \nto increased recurrence rates of keloid.  \n\n\n\nWe hope that the results of this study will clarify \nthe efficacy of intralesional steroid and silicone gel \nsheeting in keloid management and facilitate further \nresearch. \n\n\n\nMaterials and Methods  \nThis was a two-armed 16-week randomized \ncontrolled trial conducted in Dermatology clinic \nHospital Tengku Ampuan Rahimah (HTAR), \nSelangor, Malaysia from 1st August 2014 to 31st \nDecember 2014. The target population was patients \nwith clinical diagnosis of keloid attending the \nclinic during the study period. Inclusion criteria \nwere patients above 12 years of age with keloids \nmeasuring between 1cm x1cm to 6cm x 6cm. \nFor patients with more than one keloid, only one \nkeloid was c  hosen for the purpose of this study. \nExclusion criteria were patients with hypertrophic \nscars or keloids aged less than 1 year, patients \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4012\n\n\n\nwho had received another topical or systemic scar \ntreatment in the last one month prior to recruitment, \npatients who were pregnant or breastfeeding and \npatients with known hypersensitivity to any of the \nconstituents of triamcinolone acetonide, lignocaine \nor silicone gel sheeting. \n\n\n\nThis study was funded by the Department of \nDermatology, HTAR. Recruited patients were \nrandomized into group 1(intralesional triamcinolone \nacetonide) or group 2 (silicone gel sheeting), \ninterviewed followed by physical examination. \nRandomization was done through sealed envelope \nsystem. Once a patient has consented to enter the \nstudy, an envelope was opened and the patient was \nthen offered the allocated treatment regimen. The \nPOSAS blinded to the treatment was assessed.\n\n\n\nPatients in group 1 received intralesional \ntriamcinolone acetonide 20 mg/ml 4 weekly for 12 \nweeks. Triamcinolone acetonide at concentration \nof 20 mg/ml was prepared by mixing 1ml of \ntriamcinolone at concentration of 40 mg/ml with \n1ml of 2% lignocaine. Keloid was injected by using \n1ml syringe and 26-gauge needle. Needle was \ninserted parallel to the skin surface into the mid-\ndermis of keloid, then triamcinolone injected slowly \nwhile withdrawing the needle until the injection site \nwas elevated slightly and blanched  (usually 0.1 to \n0.2mls was injected per cm2). Maximum dosage per \npatient per treatment session was 40mg. \n\n\n\nCicacare silicone gel sheet which was a commercially \navailable product was used for patients in group \n2. The Cicacare silicone gel sheet was measured \naccording to the size of keloid then cut and trimmed \nslightly larger than the size of the keloid. Patients \nwere educated and demonstrated on proper technique \nof silicone gel sheeting application on keloid. They \nwere required to self-apply the silicone gel sheet on \nthe keloid for 4 hours per day on the first 2 days, 8 \nhours per day the next 2 days, and increased usage \ntime by 2 hours per day until the optimal 12 hours \nper day was achieved. The silicone gel sheet was \nchanged after 14 days and continued for 12 weeks.\n\n\n\nThe duration of treatment for all patients was 12 \nweeks. Follow-up assessments were performed \nat week 4, 8 and 12 and 16 by using POSAS and \nDLQI score. POSAS score was recorded at week \n0, 4, 8 and 12 and 16. Assessment was done by one \nobserver (investigator). The use of POSAS in keloid \nassessment was tested on ten patients for two months \nat monthly interval prior to the study to ensure the \n\n\n\nconsistency in the assessment of different variables \nin the scale and to avoid intra-observer variability.\n\n\n\nThe POSAS consists of a Patient Scale and an \nObserver Scale. The Patient Scale gives the POSAS \nan important extra dimension because the patient\u2019s \nopinion is mandatory for a complete scar evaluation. \nThe first publication on the POSAS (Version 1.0) was \nin 2004 by Draaijers et al. With one extra item for \nthe Observer Scale and minor textual modifications \nPOSASv2.0 was tested on linear scars and published \nin 2005 by Van de Kar et al.\n\n\n\nBesides, DLQI score was recorded at week 0, 12 \nand 16. For patients in group 1, pain score during \nintralesional TAC injection was assessed by using \nthe 0 to 10 Numeric Pain Rating Scale. Digital \nphotographs were taken with the same camera \nsettings and under the same lighting conditions \nbefore treatment, and at week 0, 12 and 16. \n\n\n\nTo evaluate for safety and tolerability, the patients \nwere interviewed at every visit after initiation \nof treatment and any side effects reported will be \ndocumented and managed accordingly. Compliance \nof patients in group 2 was monitored by additional \nclinic visit weekly in the first month of enrolment. \n\n\n\nStatistical analysis was performed with IBM SPSS \nStatistics for Windows software (Version 20.0. \nArmonk, NY: IBM Corp). Descriptive statistics \nwere presented as frequencies and percentage for \ncategorical data, the numerical data which was \nnormally distributed was presented as mean and \nstandard deviation. If not normally distributed, \nthe data was presented as median and interquartile \nrange. Comparing outcome for numerical data \nbetween two groups was analyzed by using the \nindependent t-test and Mann-Whitney test if the \nassumptions of independent t-test were not met. \nThe changes in mean scores over three or more \ntime points within or between groups were analyzed \nusing repeated measures ANOVA. Two-tailed tests \nwere used for all analyses, and the probability value \nof less than 0.05 (p-value < 0.05) was considered as \nstatistically significance.\n\n\n\nResults\nFifty six subjects participated in this study which \ncomprised of 28 subjects in group 1 and 28 subjects \nin group 2. However, only 51 participants (26 in \ngroup 1; 25 in group 2) completed the entire study as \n2 subjects from group 1 and 3 subjects from group 2 \ndefaulted follow-up during the study period due to \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 13\n\n\n\nlogistic reason (2 at week-4; 1 at week-8; 1 at week-\n20). Demographic and baseline characteristics of \nthe subjects are shown in Table 1. \n\n\n\nThe male to female ratio for subjects in our study \nwas 1.15 to 1. The mean age was 27.9 ranging from \n12 to 79 years old. Malays made up the largest \nethnic group; followed by Chinese and Indian. \nMajority of subjects has Fitzpatrick skin type III \n(44.6%) and IV (48.2%). Almost half of the subjects \nhad Fitzpatrick type IV which corresponds to the \nskin type in Asians. Median area of keloid was \n\n\n\nCharacteristics Overall\n(n=56)\n\n\n\nTriamcinolone Acetonide \n(n=28)\n\n\n\nSilicone Gel Sheeting\n(n=28)\n\n\n\np-value\n\n\n\nMean age (SD) 27.9 (13.56) 28.6 (10.33) 27.2 (16.34) 0.690c\n\n\n\nGender, n (%)\nMale\nFemale\n\n\n\n28  (50.0)\n28  (50.0)\n\n\n\n14 (50.0)\n14 (50.0)\n\n\n\n16 (57.1)\n12 (42.9)\n\n\n\n0.592a\n\n\n\nEthinicity, n (%)\nMalay \nChinese\nIndian\n\n\n\n40  (71.4)\n9  (16.1)\n7  (12.5)\n\n\n\n18 (64.3)\n  5 (17.9)\n  5 (17.9)\n\n\n\n22 (78.6)\n  4 (14.3)\n  2 (  7.1)\n\n\n\n0.411b\n\n\n\nFitzpatrick Skin Type, n (%)\nII\nIII\nIV\nV\nVI\n\n\n\n2  (  3.6)\n25  (44.6)\n27  (48.2)\n1  (  1.8)\n1  (  1.8)\n\n\n\n  1 (  3.6)\n12 (42.9)\n14 (50.0)\n  0 (  0.0)\n  1 (  3.6)\n\n\n\n  1 (  3.6)\n13 (46.4)\n13 (46.4)\n  1 (  3.6)  \n  0 (  0.0)\n\n\n\n1.000b\n\n\n\nMedian area of keloid\ncm2 (Range) 4.25 (1 \u2013 75) 4.5 (1 - 75) 4.3 (1 - 32) 0.577d\n\n\n\nAge of keloids, n (%)\n\u2264 2 years\n> 2 years\n\n\n\n12  (21.4)\n44  (78.6)\n\n\n\n5 (17.9)\n23 (82.1)\n\n\n\n7 (25.0)\n21 (75.0 )\n\n\n\n0.515a\n\n\n\nNumber of keloids, n (%)\n1\n2\n>2\n\n\n\n32  (57.1)\n9  (16.1)\n15  (26.8)\n\n\n\n19 (67.9)\n4 (14.3)\n5 (17.9)\n\n\n\n13 (46.4)\n5 (17.9)\n10 (35.7)\n\n\n\n0.247b\n\n\n\nLocation of keloids, n (%)\nHead / Neck\nUpper extremities\nThorax\nAbdomen\nBack\nLower extremities\n\n\n\n8  (14.3)\n22  (39.3)\n14  (25.0)\n3  (  5.4)\n5  (  8.9)\n4  (  7.1)\n\n\n\n  4 (14.3)\n11 (39.3)\n  5 (17.9)\n  2 (  7.1)\n  4 (14.3)\n  2 (  7.1)\n\n\n\n  4 (14.3)\n11 (39.3)\n  9 (32.1)\n  1 (  3.6)\n  1 (  3.6)\n  2 (  7.1)\n\n\n\n0.694b\n\n\n\nEtiology of keloid, n (%)\nSurgery\nInjury\nVaccination\nAcne\nUnknown\n\n\n\n6  (10.7)\n21  (37.5)\n6  (10.7)\n10  (17.9)\n13 (23.3)\n\n\n\n3 (10.7)\n11 (39.3)\n4 (14.3)\n5 (17.9)\n5 (14.3)\n\n\n\n3 (10.7)\n10 (35.7)\n2 (  7.1)\n5 (17.9)\n8 (21.4)\n\n\n\n0.951b\n\n\n\n4.25 cm2. Almost 80% of subjects had keloid for \nmore than 2 years. Majority of subjects had a single \nkeloid. Almost two-third of the keloids were located \nat upper extremities and thorax, followed by head \nand neck, back, lower extremities and abdomen. \nMost of the keloids were due to previous injury. \n23.3% of subjects were unsure of the cause for their \nkeloids. Table 2 presents the baseline POSAS and \nDLQI score of subjects. There was no statistically \nsignificant difference between the two groups in \nterms of baseline demographic characteristics, \nPOSAS and DLQI score. \n\n\n\nTable 1. Demographic and baseline characteristics between patients with keloids randomized to either intralesional Triamcinolone \n\n\n\naChi-Squared Test, bFisher Exact Test, cIndependent t-test, dMann Whitney Test, SD standard deviation\n\n\n\nacetonide orsilicone gel sheeting treatment \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4014\n\n\n\nTable 2. Baseline POSAS and DLQI score between patients with keloids randomized to either intralesional Triamcinolone Acetonide \nor Silicone Gel Sheeting treatment \n\n\n\nScore Triamcinolone Acetonide \nMean (SD)\n\n\n\nSilicone Gel Sheeting\nMean (SD)\n\n\n\np-valuea\n\n\n\nTotal POSAS \n(Subject\tScale\t\t+\tObserver\tScale)\n\n\n\n72.4 (13.90) 63.6 (19.63) 0.059\n\n\n\nTotal Observer Scale 34.7 (8.11) 29.9 (11.05) 0.070\nTotal\tSubject\tScale 37.7 (10.33) 33.7 (12.01) 0.187\nDLQI 10.1 (5.72) 7.9 (5.61) 0.156\n\n\n\naIndependent t-test\n\n\n\nTo measure the improvement with treatment at the \nend of the study, the significance of the difference \nbetween the POSAS and DLQI score at week-16 \nand baseline were analyzed. The analysis compared \nthe scores between baseline and week-16. Table 3 \nsummarizes the changes in the score from baseline \nto week-16 for each of the parameters measured in \nthe POSAS as well as the DLQI score. At week 16, \nsubjects treated with intralesional triamcinolone \nacetonide reported a significant improvement in all \nthe parameters in POSAS Patient Scale (p<0.001) \nwhich signified an improvement in the symptom \nof pain and pruritus as well as quality of keloids \n(color, stiffness, thickness and irregularities). \nObserver reported a significant improvement in \nall the parameters in POSAS Observer Scale, \ni.e. vascularity, pigmentation, thickness, relief, \npliability and surface area of keloids in group 1.\n\n\n\nSubjects treated with silicone gel sheeting reported a \nsignificant improvement in all the parameters in the \nPOSAS Patient Scale except scale 2 (Has the scar \nbeen itching the past few weeks?) (p=0.537). This \nmeans they have a significant reduction in pain and \nimprovement in terms of color, stiffness, thickness, \nand irregularities of keloids. Observer found a \nsignificant improvement in terms of vascularity, \npigmentation, thickness and pliability of keloids \nbut not in terms of relief (p=0.055) and surface area \n(p=0.137) in this group. The improvement in total \nscore of the POSAS in both groups was significant. \n\n\n\nBesides, subjects in group 1 demonstrated a \nsignificant improvement in QoL after the treatment. \nHowever, subjects in group 2 did not manifest a \nsignificant improvement in QoL (p=0.081).\n\n\n\nScore Triamcinolone acetonide (n=26)\np-valuea\n\n\n\nSilicone Gel Sheeting (n=25)\np-valuea\n\n\n\nPOSAS\nPatient Scale 1:\nHas the scar been painful the past few weeks? 0.001 0.023\n\n\n\nPatient Scale 2: \nHas the scar been itching the past few weeks? < 0.001 0.537\n\n\n\nPatient Scale 3:\nIs the scar color different from the color of your normal skin at present? < 0.001 0.007\n\n\n\nPatient Scale 4:\nIs the stiffness of the scar different from your normal skin at present? < 0.001 0.031\n\n\n\nPatient Scale 5:\nIs the thickness of the scar different from your normal skin at present? < 0.001 < 0.001\n\n\n\nPatient Scale 6:\nIs the scar more irregular than your normal skin at present? < 0.001 0.003\n\n\n\nPatient Scale Overall < 0.001 < 0.001\nTotal Patient Scale < 0.001 0.003\nObserver Scale 1: Vascularity < 0.001 0.011\nObserver Scale 2: Pigmentation < 0.001 0.021\nObserver Scale 3: Thickness < 0.001 0.005\nObserver Scale 4: Relief < 0.001 0.055\nObserver Scale 5: Pliability < 0.001 0.005\nObserver Scale 6: Surface area < 0.001 0.137\nObserver Scale Overall < 0.001 0.020\nTotal Observer Scale < 0.001 0.004\nTotal POSAS score (Patient score + Observer score) < 0.001 0.001\nDLQI < 0.001 0.081\n\n\n\nTable 3. POSAS and DLQI score changes from baseline to week-16 between patients with keloids randomized to either intralesional \nTriamcinolone Acetonide or Silicone Gel Sheeting treatment \n\n\n\naRepeated measure ANOVA (Time Effect) for each Group \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 15\n\n\n\nFigure 1 demonstrated the means of the total score \nof POSAS during each follow-up visit. At the end \nof the study, there was 44.2% of improvement in \nthe mean of total score of the POSAS in group 1 \nas compared to 11.6% in group 2. The mean total \nPOSAS score in group 1 decreased tremendously \nfrom 72 at baseline to 49.5 after treatment at week \n12 and 40.2 at week-16. The reduction in the score \nin group 2 was less than group 1.\n\n\n\nIn this result, the POSAS patterns were significantly \ndifferent between 2 groups (p<0.001). The patterns \nwere statistically significant at week-4 to week-\n8 (p=0.008), week-8 to week-12 (p=0.001) and \nweek-12 to week-16 (p<0.001) (Post-hoc analysis \ndone by using Bonferroni procedure and p-values \nwere adjusted for multiple comparison). The data \nindicated that the appearance of keloids became \ncloser to the normal adjacent skin in subjects \nwho were treated with intralesional triamcinolone \nacetonide as compared to silicone gel sheeting. \n\n\n\nFigure 2 presents the comparison of means of \nDLQI score between the 2 groups. Subjects in \ngroup 1 demonstrated a 67.3% of improvement in \nDLQI score as compared to 13.1%  in group 2. The \npatterns were statistically significant at baseline to \nweek-12 period (p=0.004) and week-12 to week-\n16 (p=0.044). (Post-hoc analysis done by using \nBonferroni procedure and p-values were adjusted \nfor multiple comparisons).\n\n\n\nWith regards to side effects of treatment, subjects \nin group 1 experienced pain during intralesional \ntriamcinolone acetonide administration with an \naverage mean pain score of 5 while subjects received \nsilicone gel sheeting did not experience any pain. \nSubjects treated with silicone gel sheeting reported \npruritus on skin with treatment (mean pruritus score \nincreased from 4.4 at baseline to 4.8 at week-16) \nwhile this was not observed in subjects treated with \nintralesional triamcinolone. \n\n\n\nFigure 1. Comparison of means of total POSAS score between 2 groups\n\n\n\nFigure 2. Comparison of means of DLQI score between 2 groups\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4016\n\n\n\nDiscussion \nThere was a slight male preponderance in our study. \nPrevious study in Taiwan showed that women were \nmore prone to develop keloids with a female to male \nratio of 1.33 to 1 with the incidence rate of 0.15% \nfor the general Taiwan population which mainly \nconsists of ethnic Chinese.11 The mean age of our \nsubjects was 27.9 years old which is compatible with \nother studies done.12-14 Lu WS 2015 et al found that \nkeloids occurred typically between the ages of 10 \nand 30 years, and the mean age of initial onset was \n21.14 \u00b1 13.45 years in females and 22.55 \u00b1 11.36 \nyears in males. The difference in the mean age of \nonset was not significant between males and females \n(p>0.05). Adegbidi H showed that the mean age was \n29 for patients with acne keloides nuchae.13\n\n\n\nMalay made up the largest of the ethnic group \nfollowed by Chinese and India. This is surprising as \nit did not reflect the ethnic distribution of the clinic \nattendees to HTAR which comprised of 60% Indian, \n20% of Malays and 20% of Chinese. The influence \nof ethnicity on keloid formation is significant. \nKeloids are an important clinical problem in certain \nethnic populations, as there is a higher prevalence of \nkeloids in individuals with colored skin.15-17 Keloids \nare reported to be particularly high in individuals \nof African, Asian and Hispanic descent. A strong \ngenetic predisposition for keloids have been \nsuggested due to familial preponderance, increased \nprevalence in certain ethnicities and the reported \npresence of keloids in identical twins.18 ommon \ngenetic factor predisposing to the development \nof keloid was shared by the Chinese Han and \nJapanese populations with the loci 1q41 and 15q21.3 \nbeing detected in both populations.19 \n\n\n\nMajority of our subjects had keloids for more \nthan 2 years while. Subjects with keloids aged \nless than 1 year were excluded in our study. This \nis crucial to ensure that only patients with keloids \nand not hypertrophic scars were recruited. While \nhypertrophic scars usually develop within 3 months \nof injury, keloid scars often form within or beyond \nthe first year of injury and tends to persist over time, \ncontinuing to grow over the years.20 40% of our \npatients had more than one keloid. A retrospective \nstudy involving 868 patients demonstrated that \nyounger age of onset and the presence of family \nhistory were significantly associated with the \noccurrence of keloids at multiple sites.21\n\n\n\nKeloids occur predominantly on the upper chest, \nshoulders, upper back, and head and neck, especially \n\n\n\non the ear. The locations of keloids in our subjects \nin order of frequency included upper extremities, \nthorax, head and neck, back, abdomen and lower \nextremities. The common etiology for keloid in \nour subjects in order of frequency included trauma, \nacne, surgery and vaccination. Keloid can form \nspontaneously22 as in 13% of our subjects who were \nunsure of the etiology of their keloid formation.\n\n\n\nTo the best of our knowledge and from the MEDLINE \nsearch, there were 3 previous studies which \ncompared intalesional triamcinolone acetonide with \nsilicone gel sheeting in treating scars (Table 4). The \nresults on comparison of efficacy of intralesional \ntriamcinolone acetonide and silicone gel sheeting \nin our study may not be directly comparable to \nother studies as different methodology was used. \nBesides, there were also variations in term of type \nof scars, duration of study which may affect the \nstudy outcome.\n        \nWe found that intralesional triamcinolone acetonide \nwas superior to silicone gel sheeting in treating \nkeloids. Our results were in keeping with E Tan \net al which was also done in Asian population \nin Singapore. E Tan et al reported intralesional \ntriamcinolone was superior to silicone gel sheeting \nin keloid size reduction of at least 50% at week \n12 (94% versus 12%); causing improvement in \npatients\u2019 pain (59% versus 6%) and erythema of \nkeloids (18% versus 0%). The authors therefore did \nnot support the use of silicone gel sheeting as an \neffective treatment for keloids and concluded that \nintralesional triamcinolone acetonide should remain \nthe mainstay of treatment. \n\n\n\nE Tan et al is thus far the most similar study to our \npresent study as the study was conducted on subjects \nwith keloid scars while JE et al and Kelemen et al \nwere done on subjects with hypertrophic scars. 2 \nstudies on hypertrophic scars as shown in Table 4 \nhave demonstrated a promising outcome.24,25 Sproat \nJE et al compared these two treatment modalities \non 14 subjects with post-sternotomy scars by \nassigning one half of scars to each treatment \nmodality. The study demonstrated that silicone gel \nsheets provided earlier symptomatic relief and a \nmore aesthetic scar and are the preferred treatment \nof patients.24 Keleman et al randomized 24 subjects \nwith hypertrophic scars into either intralesional \ntriamcinolone or silicone gel sheeting group. The \nresults showed that both methods were equally \nefficient although intralesional steroid resulted a \nmore rapid effect and lasted longer than silicone \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 17\n\n\n\nPr\nes\n\n\n\nen\nt s\n\n\n\ntu\ndy\n\n\n\n, 2\n01\n\n\n\n5,\n M\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\nTa\nn \n\n\n\net\n a\n\n\n\nl, \n19\n\n\n\n99\n, S\n\n\n\nin\nga\n\n\n\npo\nre\n\n\n\nSp\nro\n\n\n\nat\n e\n\n\n\nt a\nl, \n\n\n\n19\n99\n\n\n\n, C\nan\n\n\n\nad\na\n\n\n\nK\nel\n\n\n\nem\nan\n\n\n\n e\nt a\n\n\n\nl, \n20\n\n\n\n07\n, H\n\n\n\nun\nga\n\n\n\nry\nTy\n\n\n\npe\ns o\n\n\n\nf s\nca\n\n\n\nr\nK\n\n\n\nel\noi\n\n\n\nd\nK\n\n\n\nel\noi\n\n\n\nd\nH\n\n\n\nS\nH\n\n\n\nS\nSt\n\n\n\nud\ny \n\n\n\ndu\nra\n\n\n\ntio\nn\n\n\n\n16\n w\n\n\n\nee\nks\n\n\n\n12\n w\n\n\n\nee\nks\n\n\n\n12\n w\n\n\n\nee\nks\n\n\n\nU\nnc\n\n\n\nle\nar\n\n\n\nPa\nrt\n\n\n\nic\nip\n\n\n\nan\nts\n\n\n\n, n\n56\n\n\n\n (a\nge\n\n\n\n: 1\n2-\n\n\n\n79\n)\n\n\n\n20\n (a\n\n\n\nge\n: 1\n\n\n\n9-\n40\n\n\n\n)\n14\n\n\n\n (a\nge\n\n\n\n: 3\n3-\n\n\n\n81\n)\n\n\n\n24\n (a\n\n\n\nge\n: 1\n\n\n\n7-\n67\n\n\n\n)\nSt\nud\ny\t\nde\nsi\ngn\n\ta\nnd\n\tIn\n\n\n\nte\nrv\nen\ntio\nns\n\n\n\nR\nC\n\n\n\nT\nG\n\n\n\np \n1:\n\n\n\n T\nA\n\n\n\nC\n 2\n\n\n\n0m\ng/\n\n\n\nm\nl \n\n\n\nG\np \n\n\n\n2:\n S\n\n\n\nG\nS \n\n\n\n12\n H\n\n\n\n/d\nay\n\n\n\nR\nC\n\n\n\nT \nw\n\n\n\nith\n c\n\n\n\non\ntr\n\n\n\nol\n1 \n\n\n\n- c\non\n\n\n\ntro\nl\n\n\n\n1 \n- S\n\n\n\nG\nS \n\n\n\n12\n H\n\n\n\n/d\nay\n\n\n\n \n1 \n\n\n\n- T\nA\n\n\n\nC\n 4\n\n\n\n0m\ng/\n\n\n\nm\nl  \n\n\n\nM\nat\n\n\n\nch\ned\n\n\n\n d\nes\n\n\n\nig\nn\n\n\n\nH\nal\n\n\n\nf -\n T\n\n\n\nA\nC\n\n\n\n 2\n0m\n\n\n\ng/\nm\n\n\n\nL \nH\n\n\n\nal\nf :\n\n\n\n S\nG\n\n\n\nS \n12\n\n\n\nH\n/d\n\n\n\nay\n \n\n\n\nR\nC\n\n\n\nT\nG\n\n\n\np \n1:\n\n\n\n T\nA\n\n\n\nC\n 4\n\n\n\n0m\ng/\n\n\n\nm\nL\n\n\n\nG\np \n\n\n\n2:\n S\n\n\n\nG\nS \n\n\n\n12\n H\n\n\n\n/d\nay\n\n\n\nO\nut\n\n\n\nco\nm\n\n\n\ne \nas\n\n\n\nse\nss\n\n\n\nm\nen\n\n\n\nt t\noo\n\n\n\nls\n1.\n\n\n\n P\nO\n\n\n\nSA\nS\n\n\n\n2.\n D\n\n\n\nLQ\nI\n\n\n\n1.\n S\n\n\n\nca\nr l\n\n\n\nen\ngt\n\n\n\nh,\n w\n\n\n\nid\nth\n\n\n\n, h\nei\n\n\n\ngh\nt, \n\n\n\nch\nan\n\n\n\nge\n in\n\n\n\n \nco\n\n\n\nlo\nur\n\n\n\n &\n te\n\n\n\nxt\nur\n\n\n\ne\n\n\n\n2.\n P\n\n\n\nai\nn \n\n\n\n&\n p\n\n\n\nru\nrit\n\n\n\nus\n re\n\n\n\nlie\nf \n\n\n\n1.\n S\n\n\n\nca\nr l\n\n\n\nen\ngt\n\n\n\nh,\n w\n\n\n\nid\nth\n\n\n\n, h\nei\n\n\n\ngh\nt, \n\n\n\nch\nan\n\n\n\nge\n in\n\n\n\n \nco\n\n\n\nlo\nur\n\n\n\n,  \nte\n\n\n\nxt\nur\n\n\n\ne\n\n\n\n2.\n P\n\n\n\nai\nn \n\n\n\n&\n p\n\n\n\nru\nrit\n\n\n\nus\n re\n\n\n\nlie\nf\n\n\n\n1.\n V\n\n\n\nan\nco\n\n\n\nuv\ner\n\n\n\n sc\nar\n\n\n\n sc\nal\n\n\n\ne\n\n\n\n2.\n S\n\n\n\nub\nje\n\n\n\nct\niv\n\n\n\ne \npa\n\n\n\ntie\nnt\n\n\n\n e\nxp\n\n\n\ner\nie\n\n\n\nnc\ne \n\n\n\n(5\n-p\n\n\n\noi\nnt\n\n\n\n \nLi\n\n\n\nke\nrt \n\n\n\nsc\nal\n\n\n\ne)\nR\n\n\n\nes\nul\n\n\n\nts\n1.\n\n\n\n T\not\n\n\n\nal\n P\n\n\n\nO\nSA\n\n\n\nS \nsc\n\n\n\nor\ne \n\n\n\nim\npr\n\n\n\nov\nem\n\n\n\nen\nt:\n\n\n\n \n44\n\n\n\n.2\n%\n\n\n\n (T\nA\n\n\n\nC\n) v\n\n\n\ns\n 1\n\n\n\n1.\n6%\n\n\n\n (S\nG\n\n\n\nS)\n\n\n\n2.\n\tD\nL\nQ\nI\ts\nco\nre\n\tim\n\n\n\npr\nov\nem\n\n\n\nen\nt:\n\n\n\n \n67\n\n\n\n.3\n%\n\n\n\n (T\nA\n\n\n\nC\n) v\n\n\n\ns \n13\n\n\n\n.1\n%\n\n\n\n (S\nG\n\n\n\nS)\n\n\n\n1.\n  S\n\n\n\niz\ne \n\n\n\nre\ndu\n\n\n\nct\nio\n\n\n\nn \n> \n\n\n\n50\n%\n\n\n\n: \n94\n\n\n\n%\n  (\n\n\n\nTA\nC\n\n\n\n) v\ns\n\n\n\n12\n%\n\n\n\n  (\nSG\n\n\n\nS)\n\n\n\n1.\n T\n\n\n\nim\ne \n\n\n\nto\n im\n\n\n\npr\nov\n\n\n\nem\nen\n\n\n\nt:\n3.\n\n\n\n9 \n+ \n\n\n\n0.\n62\n\n\n\n d\nay\n\n\n\ns  \n(S\n\n\n\nG\nS)\n\n\n\n v\ns\n\n\n\n6.\n8+\n\n\n\n1.\n86\n\n\n\n d\nay\n\n\n\ns  \n(T\n\n\n\nA\nC\n\n\n\n)\n\n\n\n2.\n P\n\n\n\nat\nie\n\n\n\nnt\n\u2019s\n\n\n\n p\nre\n\n\n\nfe\nre\n\n\n\nnc\ne:\n\n\n\n11\n (S\n\n\n\nG\nS)\n\n\n\n v\ns 2\n\n\n\n (T\nA\n\n\n\nC\n)\n\n\n\nB\not\n\n\n\nh \nm\n\n\n\net\nho\n\n\n\nds\n w\n\n\n\ner\ne \n\n\n\neffi\nci\n\n\n\nen\nt b\n\n\n\nut\n T\n\n\n\nA\nC\n\n\n\n w\nas\n\n\n\n \nm\n\n\n\nor\ne \n\n\n\neff\nec\n\n\n\ntiv\ne,\n\n\n\n w\nor\n\n\n\nke\nd \n\n\n\nfa\nst\n\n\n\ner\n a\n\n\n\nnd\n re\n\n\n\ndu\nce\n\n\n\nd\nsu\n\n\n\nbj\nec\n\n\n\ntiv\ne \n\n\n\nsy\nm\n\n\n\npt\nom\n\n\n\ns a\n lo\n\n\n\nt q\nui\n\n\n\nck\ner\n\n\n\n th\nan\n\n\n\n \nSG\n\n\n\nS\n\n\n\nC\non\n\n\n\ncl\nus\n\n\n\nio\nn\n\n\n\nIn\ntra\n\n\n\nle\nsi\n\n\n\non\nal\n\n\n\n T\nA\n\n\n\nC\n is\n\n\n\n su\npe\n\n\n\nrio\nr t\n\n\n\nha\nn \n\n\n\nSG\nS \n\n\n\nin\n \n\n\n\ntre\nat\n\n\n\nin\ng \n\n\n\nke\nlo\n\n\n\nid\ns.\n\n\n\nIn\ntra\n\n\n\nle\nsi\n\n\n\non\nal\n\n\n\n T\nA\n\n\n\nC\n si\n\n\n\ngn\nifi\n\n\n\nca\nnt\n\n\n\nly\n m\n\n\n\nor\ne \n\n\n\neff\nec\n\n\n\ntiv\ne \n\n\n\nth\nan\n\n\n\n S\nG\n\n\n\nS \nan\n\n\n\nd \nsh\n\n\n\nou\nld\n\n\n\n re\nm\n\n\n\nai\nn \n\n\n\non\ne \n\n\n\nof\n th\n\n\n\ne \npr\n\n\n\nim\nar\n\n\n\ny \nm\n\n\n\net\nho\n\n\n\nds\n fo\n\n\n\nr t\nhe\n\n\n\n tr\nea\n\n\n\ntm\nen\n\n\n\nt \nof\n\n\n\n k\nel\n\n\n\noi\nds\n\n\n\n.\n\n\n\nSG\nS \n\n\n\npr\nov\n\n\n\nid\ned\n\n\n\n e\nar\n\n\n\nlie\nr s\n\n\n\nym\npt\n\n\n\nom\nat\n\n\n\nic\n re\n\n\n\nlie\nf \n\n\n\nan\nd \n\n\n\na \nm\n\n\n\nor\ne \n\n\n\nae\nst\n\n\n\nhe\ntic\n\n\n\n sc\nar\n\n\n\n a\nnd\n\n\n\n w\ner\n\n\n\ne \nth\n\n\n\ne \npr\n\n\n\nef\ner\n\n\n\nre\nd \n\n\n\ntre\nat\n\n\n\nm\nen\n\n\n\nt o\nf p\n\n\n\nat\nie\n\n\n\nnt\ns\n\n\n\nSG\nS \n\n\n\nre\nco\n\n\n\nm\nm\n\n\n\nen\nde\n\n\n\nd \nas\n\n\n\n th\ne \n\n\n\nfir\nst\n\n\n\n-li\nne\n\n\n\n \ntre\n\n\n\nat\nm\n\n\n\nen\nt f\n\n\n\nor\n p\n\n\n\nrim\nar\n\n\n\ny \nlin\n\n\n\nea\nr H\n\n\n\nS \nw\n\n\n\nhi\nle\n\n\n\n \nTA\n\n\n\nC\n a\n\n\n\ns s\nec\n\n\n\non\nd-\n\n\n\nlin\ne.\n\n\n\nTa\nbl\n\n\n\ne \n4.\n\n\n\n S\ntu\n\n\n\ndi\nes\n\n\n\n d\non\n\n\n\ne \nin\n\n\n\n c\nom\n\n\n\npa\nrin\n\n\n\ng \nin\n\n\n\nta\nle\n\n\n\nsi\non\n\n\n\nal\n T\n\n\n\nria\nm\n\n\n\nci\nno\n\n\n\nlo\nne\n\n\n\n A\nce\n\n\n\nto\nni\n\n\n\nde\n w\n\n\n\nith\n S\n\n\n\nili\nco\n\n\n\nne\n G\n\n\n\nel\n S\n\n\n\nhe\net\n\n\n\nin\ng \n\n\n\nin\n tr\n\n\n\nea\ntin\n\n\n\ng \ndi\n\n\n\nffe\nre\n\n\n\nnt\n ty\n\n\n\npe\ns o\n\n\n\nf s\nca\n\n\n\nrs\n  \n\n\n\nR\nC\n\n\n\nT \nra\n\n\n\nnd\nom\n\n\n\niz\ned\n\n\n\n c\non\n\n\n\ntro\nlle\n\n\n\nd \ntri\n\n\n\nal\n, H\n\n\n\nS \nH\n\n\n\nyp\ner\n\n\n\ntro\nph\n\n\n\nic\n sc\n\n\n\nar\ns, \n\n\n\nTA\nC\n\n\n\n tr\nia\n\n\n\nm\nci\n\n\n\nno\nlo\n\n\n\nne\n a\n\n\n\nce\nto\n\n\n\nni\nde\n\n\n\n, S\nG\n\n\n\nS \nsi\n\n\n\nlic\non\n\n\n\ne \nge\n\n\n\nl s\nhe\n\n\n\net\nin\n\n\n\ng,\n v\n\n\n\ns v\ner\n\n\n\nsu\ns\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4018\n\n\n\ngel sheeting.25 From the results of these studies, it \nis evident that silicone gel sheeting appears to be \neffective in treating primary hypertrophic scars but \nnot recurrent linear hypertrophic scars or keloids. \nThe ultimate benefit of silicone gel sheeting on \nkeloids remains to be evaluated.\n\n\n\nOur subjects treated with intralesional triamcinolone \nacetonide showed a significant improvement in \nall the parameters in POSAS Patient Scale as \nwell as POSAS Observer Scale. Our results were \ncomparable with multiple previous studies which \nshowed positive results. In a long-term study done \non 94 Asian patients with 109 keloids who were \ntreated with intralesional TAC 1 to 10 mg/mL every \nfour weeks, 83% of patients receiving more than 10 \ninjections reported reduction of itching and pain. \nExcellent or good improvement of prominence \nand redness was observed in 39% of patients who \nreceived 20 to 30 injections over three to five \nyears.29 Intralesional triamcinolone monotherapy \nhas been useful in reducing the volume of keloids \nin most of the patients.30-33  Previous studies has \nshowed a significant reduction in scar volumes \nafter monthly intralesional steroid injections.29,34 \nThe disadvantages of intralesional steroid injection \ninclude pain during the injections, skin atrophy or \ndyspigmentation, and recurrence rates of 9% to \n50%.35 Multiple previous studies have demonstrated \nthe effectiveness of intralesional steroids (as \nmonotherapy or combination) in treating keloids \nand hypertrophic scars.29, 36-41\n\n\n\n \nOur subjects treated with silicone gel sheeting \nreported a significant improvement in the color, \nstiffness, thickness and irregularities of keloids. \nFrom the perspective of observer, we noted a \nsignificant improvement in terms of scar vascularity, \npigmentation, thickness and pliability. This is \nsupported by previous study which showed that \nsilicone gel sheeting has proven to initially improve \ntexture, then pigmentation, then height of keloids.28 \nNevertheless, there were no significant improvement \nin relief (irregularities) and surface area.\n\n\n\nOur subjects in group 2 reported a significant \nimprovement in the symptom of pain but not in \npruritus. On the contrary, they reported a worsening \nof pruritus after treatment. This is in consistent \nwith a previous study which reported that persistent \npruritus (reported by 80% of patients) was the main \nproblem associated with the use of silicone gel sheet \nfor hypertrophic scars in the hot climate of Saudi \nArabia.42 Possible explanation for this finding is that \n\n\n\nprolonged application of silicone gel sheet for long \nhours might result in skin irritation which gives rise \nto pruritus. This is especially so if the hygiene of the \ntopical silicone gel sheet was not well-maintained \nwith regular washing and cleaning. Sweating \ninduced by hot climate is another contributing \nfactor. \n\n\n\nPrevious studies that demonstrated a promising \nresult of silicone gel sheeting were mainly done on \nhypertrophic scars rather than keloids.43-47\n\n\n\nThe improvement in quality of life measured via \nDLQI was significant in subjects treated with \nintralesional triamcinolone but not with silicone gel \nsheeting. When compared between the two treatment \nmodalities, intralesional triamcinolonewas superior \nthan silicone gel sheeting in improving patients\u2019 \nDLQI score from baseline at week 0 to week 12 and \nfrom week 12 to week 16. Previous study had shown \nthat the DLQI was useful in assessing the quality of \nlife in patients suffering from all types of scars and \nin monitoring the progress of scar treatments.48\n\n\n\nFrom the results of our study, we would like to \nrecommend intralesional triamcinolone acetonide \nas the first-line treatment in keloids in view of its \nsuperiority to silicone gel sheeting. According \nto the Update on Scar Management: Guidelines \nfor Treating Asian Patients, steroid monotherapy \nwas recommended as the primary method for the \ntreatment of keloids.9 However, the guideline also \nrecommended that silicone gel therapy can be used \nas first-line treatment for the management of both \nhypertrophic and keloid scars in selected patients. \nSilicone gel sheeting may still be a useful alternative \nin a selected group (especially children) who may \nnot tolerate the pain and inconvenience of other \ntreatment procedures. Besides, silicone gel sheeting \ncould be recommended as an adjunctive treatment \ntogether with intralesional triamcinolone acetonide \nin view of its positive results as shown in our study.  \n\n\n\nOur study has several strengths. Treatment of \nhypertrophic and keloid scars is dependent on \nscar grading, location and age of scar. Therefore, \nit is crucial to classify and define the type of \nscar. Besides, clinical differentiation between \nhypertrophic and keloid scars is central before the \ninitiation of treatment due to increased recurrence \nrates of keloid. Realizing this fact, our study \nrecruited subjects with keloids only and subjects \nwith hypertrophic scars were excluded. In our study, \nkeloids were differentiated from hypertrophic scars \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 19\n\n\n\nclinically and based on duration of the lesions. \n\n\n\nTo produce reliable results, a scar needs to be \nassessed using validated scar assessment tools, \nand consideration must be given both to objective \naspects of the scar such as pigmentation and height \nand to subjective aspects that reflect the individual\u2019s \nresponse to the scar such as pain and itching. \nHowever, an ideal SAT is not available currently, \nand there still is no general agreement on the most \nappropriate tool for scar evaluation. We used a \nvalidated scar assessment tool POSAS. Draaijers \net al compared the reliability and validity of the \nPOSAS to the most frequently used scale, the Visual \nAnalogue Scale (VSS), and found less variability \nand greater reliability for single observers.49\n\n\n\nThere were few limitations in our study. The duration \nof our study period (only 16 weeks) and patients\u2019 \ncompliance may be the confounding factors that \ncould influence our results. Previous study showed \nthere was significant improvement in scars treated \nwith silicone cushions over a period of few weeks to \n12 months.26 Therefore, it will be ideal if our study \ncan be conducted for a longer duration to assess the \nclinical response of keloids to silicone gel sheeting. \n\n\n\nSilicone gel sheeting should be applied for at \nleast 12 hours a day for up to 3 months in order to \nexert its effects in treating hypertrophic scars and \nkeloids.27,28 Although every effort had been carried \nout painstakingly to ensure patients\u2019 compliance, \nsubjects\u2019 compliance to treatment remained a \nlimitation in our study.\n\n\n\nBesides, there was a risk of bias of assessment as \nthere was only a single investigator in the study. A \nsecond investigator for measurements is useful to \navoid bias. Treatment na\u00efve patients would be more \nideal to be recruited in the study. Dental syringe and \nneedle is more preferred than conventional needle \nas causing less pain. \n\n\n\nFurther studies should be done for a longer duration \non wider range of keloid scars such as typical post \nsternotomy scar versus burn scars or keloids in \nvarious areas. Ideally, patients recruited in future \nstudies should be treatment na\u00efve. The use of new \ntechnologies such as digital imaging in future \nstudies would be of great help in scar assessment.\n\n\n\nConclusion\nIntralesional triamcinolone acetonide was more \neffective than silicone gel sheeting in improving \nthe vascularity, pigmentation, thickness, relief, \npliability and surface area of keloids as well as \npatients\u2019 quality of life. From the perspective of \npatients, intralesional triamcinolone was superior \nto silicone gel sheeting in reducing the symptom of \npruritus as well as improving the stiffness, thickness \nand irregularities of keloids. The effectiveness of \nintralesional triamcinolone acetonide was well \ndemonstrated by this study and should remain one \nof the primary methods for the treatment of keloids. \n\n\n\nAlthough inferior to intralesional triamcinolone, \nsilicone gel sheeting has shown a significant \nimprovement in terms of vascularity, pigmentation, \nthickness and pliability of keloids and the symptom \nof pain.  Therefore, silicone gel sheeting may \nbe considered as an alternative treatment in \nselected group who are unable to tolerate the pain \nduring intralesional steroid injection or even as \nan adjunctive treatment in between intralesional \ntriamcinolone injections. 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Mustoe TA, Cooter RD, Gold MH,  Hobbs FD, Ramelet \nAA, Shakespeare PG  et al. International clinical \nrecommendations on scar management. Plast Reconstr \nSurg 2002;110:560-71.\n\n\n\n32. Wu WS, Wang FS, Yang KD, Huang CC, Kuo YR. \nDexamethasone induction of keloid regression through \neffective suppression of VEGF expression and keloid \nfibroblast proliferation. J Invest Dermatol 2006;126:1264-\n71.\n\n\n\n33. Boyadjiev C, Popchristova E, Mazgalova J. \nHistomorphologic changes in keloids treated with \nKenacort. J Trauma 1995;38:299-302. \n\n\n\n34. Atiyeh BS. Nonsurgical management of hypertrophic \nscars: evidence-based therapies, standard practices, and \nemerging methods. Aesthetic Plast Surg 2007;31:468-92.\n\n\n\n35. Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the \nnature of hypertrophic scars and keloids: a review. Plast \nReconstr Surg 1999;104:1435-58.  \n\n\n\n36. Emad M, Omidvari S, Dastgheib L, Mortazavi A, Ghaem \nH. Surgical excision and immediate postoperative \nradiotherapy versus cryotherapy and intralesional steroids \nin the management of keloids: a prospective clinical trial. \nMed Princ Pract 2010;19:402-5.\n\n\n\n37. Al Aradi IK, Alawadhi SA, Alkhawaja FA, Alaradi I. Earlobe \nkeloids: a pilot study of the efficacy of keloidectomy with \ncore fillet flap and adjuvant intralesional corticosteroids. \nDermatol Surg 2013;39:1514-9. \n\n\n\n38. Son IP, Park KY, Kim B, Kim MN. Pilot study of the \nefficacy of 578 nm copper bromide laser combined with \nintralesional corticosteroid injection for treatment of keloids \nand hypertrophic scars. Ann Dermatol 2014;26:156-61. \n\n\n\n39. Sadeghinia A, Sadeghinia S. Comparison of the efficacy \nof intralesional triamcinolone acetonide and 5-fluorouracil \ntattooing for the treatment of keloids. Dermatol Surg \n2012;38:104-9.\n\n\n\n40. Davison SP, Dayan JH, Clemens MW, Sonni S, Wang \nA, Crane A. Efficacy of intralesional 5-fluorouracil and \ntriamcinolone in the treatment of keloids. Aesthet Surg J \n2009;29:40-6. \n\n\n\n41. Gupta S, Sharma VK. Standard guidelines of care: Keloids \nand hypertrophic scars. Indian J Dermatol Venereol Leprol \n2011;77:94-100.\n\n\n\n42. Nikkonen MM, Pitkanen JM, Al-Qattan MM. Problems \nassociated with the use of silicone gel sheeting for \nhypertrophic scars in the hot climate of Saudi Arabia. \nBurns 2001;27:498- 501.\n\n\n\n43. Carney SA, Cason CG, Gowar JP, Stevenson JH, McNee J, \nGroves AR et al. Cica-Care gel sheeting in the management \nof hypertrophic scarring. Burns 1994;20:163-7.\n\n\n\n44. Lee SM, Ngim CK, Chan YY, Ho MJ. A comparison of Sil-K \nand Epiderm in scar management. Burns 1996;22:483-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 21\n\n\n\n45. Li-Tsang CW, Lau JC, Choi J, Chan CC, Jianan L. A \nprospective randomized clinical trial to investigate the \neffect of silicone gel sheeting (Cica-Care) on posttraumatic \nhypertrophic scar among the Chinese population. Burns \n2006;32:678-83.\n\n\n\n46. Momeni M, Hafezi F, Rahbar H, Karimi H. Effects of \nsilicone gel on burn scars. Burns 2009;35:70-4.\n\n\n\n47. de Oliveira GV, Nunes TA, Magna LA,  Cintra ML, Kitten \nGT, Zarpellon S et al. Silicone versus nonsilicone gel \ndressings: a controlled trial. Dermatol Surg 2001;27:721-6.\n\n\n\n48. Reinholz M, Poetschke J, Schwaiger H, Epple A, Ruzicka \nT, Gauglitz GG. The dermatology life quality index as a \nmeans to assess life quality in patients with different scar \ntypes. J Eur Acad Dermatol Venereol 2015;29:2112-9. \n\n\n\n49. Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer \nWE, Middelkoop E, Kreis RW et al. The patient and \nobserver scar assessment scale: a reliable and feasible tool \nfor scar evaluation. Plast Reconstr Surg 2004;113:1960-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4022\n\n\n\nORIGINAL ARTICLE\n\n\n\nFood and Aeroallergens Sensitisation Pattern amongst Atopic \nDermatitis Children in Hospital Kuala Lumpur\nAi Leen Wee1, MRCPCH, Kin Fon Leong2, MRCPCH, Sabeera Begum2, MMed\n\n\n\n1Paediatric Department, Hospital Melaka, Melaka, Malaysia\n2Paediatric Dermatology Unit, Paediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.\n\n\n\nAbstract\nIntroduction:\t\nVarious foods and aeroallergens are commonly attributed as the cause and exacerbating factors of \natopic dermatitis (AD) in children. This study aim to describe the common food and aeroallergens \nImmunoglobulin E (IgE) sensitisation pattern and the association between atopic dermatitis (AD) \nchildren of varying eczema severities and age groups.  \n\n\n\nMethods: \nPatients who fulfil the criteria of AD were recruited and their eczema severities were assessed using \nEczema Area and Severity Index (EASI) score. Skin prick test (SPT) was performed and serum total \nIgE and specific IgE taken for 6 common foods (cow\u2019s milk, soya, egg white, peanut, wheat and \nchicken) and 4 aeroallergens [cat dander (Felix domesticus) and house dust mites (Dermatophagoides \npteronyssinus, Dermatophagoides farinae and Blomia tropicalis)]. IgE sensitisation was diagnosed \npositive when the SPT yield a wheal of \u22653mm compared with the negative control and/or serum \nspecific IgE level of >0.35ku/L. Data was analysed using SPSS\u00aev20.\n\n\n\nResults: \nOverall IgE sensitisation to at least one food and/or aeroallergen was 95%. The most prevalent \nfood allergen in Group A [\u22641 year old] (n=10) was egg white in which both tests showed statistical \nsignificant results when compared with Group B [>1 year old] (n=50). Other common food allergens \nincluded cow\u2019s milk and peanut. D. pteronyssinus was the commonest aeroallergen. Aeroallergens \nwere significantly more prevalent in Group B when comparing both groups. \n\n\n\nConclusion: \nFood and aeroallergen sensitisations were very common among AD children. Food allergens were \nmore common in infants and aeroallergens in older children. Bigger sample size may provide more \nrepresentative results.\n\n\n\nKey words: Atopic dermatitis, Skin prick test (SPT), Specific IgE test\n\n\n\nIntroduction\nVarious foods and aeroallergens are commonly \nattributed as the cause and exacerbating factors of \natopic dermatitis (AD) in children.1,2 Food avoidance \nis commonly seen in AD infants, occasionally to \nthe extent of resulting in malnutrition.3 To our \nknowledge, there is no similar study in Malaysia till \ndate. Immunoglobulin E (IgE) food/ aeroallergen \nsensitisation is diagnosed by skin prick test (SPT) \n\n\n\nCorresponding Author\nDr Wee Ai Leen\nHospital Melaka, Jalan Mufti Haji Khalil, \n75400 Melaka, Malaysia\nEmail: weeaileen78@yahoo.com \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 23\n\n\n\nand/or serum specific IgE test. The main objective \nof this study is to describe the common food and \naeroallergens IgE sensitisation pattern. We also aim \nto investigate the association of IgE sensitisation \namong the varying severities and age groups of AD \nchildren at our centre. \n\n\n\nMaterials and Methods\nAll paediatric patients, aged 12 years and below, \nwho fulfilled the UK Working Party diagnostic \ncriteria of atopic dermatitis4, seen at paediatric \ndermatology clinic Hospital Kuala Lumpur \nwere recruited over a study period of 8 months \n(November 2014 to June 2015). Children diagnosed \nwith immunodeficiency disorders were excluded \nfrom this study. Written consent was obtained from \nparents. Atopic dermatitis severity was assessed \nusing Eczema Area and Severity Index (EASI) \nscore5. Skin prick test (SPT) was performed \nin paediatric clinic or paediatric dermatology \nlaboratory. Blood was taken for total IgE and serum \nspecific IgE; analysed in the hospital laboratory \nusing Phadia\u00ae Immunocap machine. The tested food \nallergens were cow\u2019s milk, soya, egg white, peanut, \nwheat and chicken. The aeroallergens studied were \ncat dander (Felix domesticus, F. domesticus) and \nhouse dust mites (Dermatophagoides pteronyssinus, \nD. pteronyssinus; Dermatophagoides farinae. D. \nfarinae; and Blomia tropicalis, B. tropicalis).\n\n\n\nTable 1. Demographic data of the two groups of patients\n\n\n\nOverall 95% of them had at least one IgE positive \nresult by skin prick test or serum specific Ig E, food \nor aeroallergen. Only 3 participants were negative \nfor all. The overall commonest IgE sensitisation \nfor food allergen based on serum IgE results were \ncow\u2019s milk (n=34; 57%) followed by egg white (n= \n\n\n\nIgE mediated allergen sensitisation was diagnosed \npositive when the skin prick test resulted in an \nindurated wheal of 3 mm or more compared with \nnegative control and serum specific IgE level of \ngreater than 0.35 ku/L. Subjects were divided into 2 \ngroups based on age (Group A: \u2264 1 year old; Group \nB: > 1year old). According to eczema severities, \npatients were divided into 2 groups (mild: EASI \nscore < 6 and moderate to severe: EASI score \u2265 \n6). Sensitisation patterns were studied between \nthese groups. SPSS\u00aev20 was utilised to analyse the \ndata using non-parametric tests namely chi-square \ntest (CST) or fisher exact test (FST), based on the \nsuitability of the data.\n\n\n\nResults\nA total of 60 patients were recruited. They were \ndivided into Group A (\u22641-year-old) and Group \nB (>1 year old), consisted of 10 patients and 50 \npatients respectively. All patients in Group A were \n6 months old and above. Out of the 50 patients \nin Group B, 19 patients were >1-3 years old, 15 \npatients were >3-6 years old, 8 patients were >6-9 \nyears old and 8 patients were >9-12 years old. \nGroup A had 30% girls and 70% boy whereas Group \nB had 49% girls and 51% boys. There were 70% \nMalays, 30% Chinese and no Indians in Group A; \n86% Malays, 8% Chinese and 6% Indians in Group \nB. Demographically, no difference was observed \nbetween the two groups (Table 1). \n\n\n\nAge groups Group A\n(Age\t\u2264\t1\tyear\told)\t(%)\n\n\n\nn=10\n\n\n\nGroup B\n(Age > 1 year old) (%)\n\n\n\nn=50\n\n\n\np value\n\n\n\n10 (16.7) 50 (83.3) 0.439\n\n\n\nRace Group A\n(Age\t\u2264\t1\tyear\told)\t(%)\n\n\n\nn=10\n\n\n\nGroup B\n(Age > 1 year old) (%)\n\n\n\nn=50\n\n\n\np value\n\n\n\nMalay 7 (70) 43(86)\n0.116Chinese 3 (30) 4 (8)\n\n\n\nIndian 0 (0) 3 (6)\n\n\n\nGender Group A\n(Age\t\u2264\t1\tyear\told)\t(%)\n\n\n\nn=10\n\n\n\nGroup B\n(Age > 1 year old) (%)\n\n\n\nn=50\n\n\n\np value\n\n\n\nFemale 3 (30) 19 (49)\n0.727Male 7 (70) 31 (51)\n\n\n\n29; 48%) and peanut (n=23; 38%). Based on SPT \nresults, the commonest food allergen were egg white \n(n=25; 42%) and peanut (n=25; 42%) followed by \ncow\u2019s milk (n=6; 10%). The overall commonest \nIgE sensitisation for aeroallergen based on serum \nspecific IgE results were D. pteronyssinus (n=50; \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4024\n\n\n\n83%), D. farinae (n=49; 82%) and F. domesticus \n(n=38; 63%). Similar results were obtained for \nSPT, which were D. pteronyssinus (n=34; 57%), D. \nfarinae (n=28; 47%) and B. tropicalis (n=22; 37%).\n\n\n\nWhen comparing Group A and Group B, egg \nwhite was the only food allergen that showed \nsignificant statistical results with serum specific IgE \n(p=0.039) (Table 2) and SPT (p=0.011) (Table 3). \nThe serum specific IgE for cow\u2019s milk and peanut \nwere the second and third commonest sensitisation \nrespectively among the infants in Group A. In the \nolder children in Group B, serum specific IgE for \n\n\n\nAllergen Number with positive \nserum\tspecific\tIgE\t(%)\n\n\n\np value\n\n\n\nGroup A:\n\u2264\t1\tyear\told\nn=10 (%)\n\n\n\nGroup B:\n> 1 year old\nn=50 (%)\n\n\n\nCow\u2019s milk 7 (70) 27 (54) 0.491 (FET)\nSoya 4 (40) 18 (36) 1.000 (FET)\nEgg white 8 (80) 21 (42) 0.039 (FET)\nPeanut 6 (60) 17 (34) 0.161 (FET)\nChicken 1 (10) 17 (34) 0.256 (FET)\nWheat 3 (30) 17 (34) 1.000 (FET)\nF. domesticus 2 (20) 13 (26) 1.000 (FET)\nD. pteronyssinus 5 (50) 45 (90) 0.008 (FET)\nD. farinae 4 (40) 45 (90) 0.001 (FET)\nB. tropicalis 1 (10) 37 (74) 0.000 (FET)\n\n\n\nTable 2: Comparison between age groups and serum specific IgE using fisher exact test (FET) (p value \u2264 0.05)\n\n\n\ncow\u2019s milk and soya were more commonly seen. \nHowever when these food allergens were compared \nbetween the 2 age groups, the results were not \nstatistically significant. \n\n\n\nHouse dust mite sensitisation was more common \namong older AD children in Group B as compared to \ninfant in Group A (Table 2 and Table 3). The results \nfor serum specific IgE were statistically significant \n(p<0.05) for all 3 types of dust mites including D. \npteronyssinus, D. farinae and B. tropicalis. For SPT, \nonly D. farinae and B. tropicalis were statistically \nsignificant.\n\n\n\nOn another aspect, the more severe AD appeared to \nbe associated with higher total IgE. However, this \nresult was not statistically significant. In terms of \ncomparison between disease severities and serum \nspecific IgE, IgE sensitisation for soya, wheat and \n\n\n\nTable 3: Comparison between age groups and skin prick test using fisher exact test (FET) (p value \u2264 0.05)\n\n\n\nAllergen Number with positive \nskin prick test (%)\n\n\n\np value\n\n\n\nGroup A:\n\u2264\t1\tyear\told\nn=10 (%)\n\n\n\nGroup B:\n> 1 year old\nn=50 (%)\n\n\n\nCow\u2019s milk 3 (30) 3 (6) 0.052 (FET)\nSoya 0 (0) 0 (0) -\nEgg white 6 (60) 9 (18) 0.011 (FET)\nPeanut 1 (10) 3 (6) 0.528 (FET)\nChicken 1 (10) 2 (4) 0.427 (FET)\nWheat 0 (0) 3 (6) 1.000 (FET)\nF. domesticus 0 (0) 9 (18) 0.333 (FET)\nD. pteronyssinus 3 (30) 31 (62) 0.085 (FET)\nD. farinae 0 (0) 28 (56) 0.010 (FET)\nB. tropicalis 0 (0)  22 (44) 0.010 (FET)\n\n\n\ncat dander were significantly higher among patients \nwith moderate to severe AD as compared to the \ngroup with mild AD (Table 4). However for the SPT \ngroup, there were no association between the IgE \nsensitisation and eczema severities groups.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 25\n\n\n\nNo. Allergen EASI\tscore p value\nMild\n\n\n\n(EASI\tscore\t<\t6)\nn=19 (%)\n\n\n\nModerate-severe\n(EASI\tscore\t\u2265\t6)\n\n\n\nn=41 (%)\n1. Cow\u2019s milk 9 (47) 25 (60.9) 0.322 (CST)\n2. Soya 2 (10.5) 20 (48.8) 0.004 (CST)\n3. Egg white 7 (36.8) 22 (53.7) 0.225 (CST)\n4. Peanut 4 (21.1) 19 (46.3) 0.061 (CST)\n5. Chicken 3 (15.8) 15 (36.6) 0.102 (CST)\n6. Wheat 2 (10.5) 18 (43.9) 0.011 (CST)\n7. F. domesticus 1 (5.3) 14 (34.1) 0.023 (FET)\n8. D. pteronyssinus 16 (84.2) 34 (82.9) 1.000 (FET)\n9. D. farinae 15 (78.9) 33 (80.5) 1.000 (FET)\n10. B. tropicalis 11 (57.9) 27 (65.9) 0.552 (FET)\n\n\n\nDiscussion\n\n\n\nTable 4: Comparison of eczema severity (EASI score) with serum specific IgE using chi-square test (CST) or fisher exact test (FET) \n\n\n\nAtopic dermatitis (AD) is a common inflammatory \nskin disease characterised by chronically relapsing \nand pruritic eczematous flares. In 1915, Schloss first \nreported AD patients who improved by avoiding \noffending food allergens6. Since then, many studies \nfocused on the relationship between AD and food \nhypersensitivity. Of late, many well designed studies \nhave demonstrated strong association between AD \nchildren with Ig E food allergy.6 \n\n\n\nIn our study, egg white sensitisation was \nsignificantly higher among the infants (Group A) \nfor both SPT and serum specific IgE. Cow\u2019s milk \nand peanut showed similar pattern but the results \nwere not statistically significant when comparing \nthe 2 age groups. This is in keeping with some \nprevious reported studies.1,2 Many studies, including \nthis study, showed that egg allergy was the most \ncommon allergy in AD children.1,2,7,9 Kim HO et \nal and Ho MHK et al reported egg white to be the \ncommonest food allergen of 17.9%9 and 51.9%1 in \ntheir respective studies. \n\n\n\nAeroallergen sensitisation has been shown to be \nmore prevalent among the older AD children and \nthis study supported this association as reported \nin previous studies.7,8 Naspitz CK et al reported \nsimilar findings of high overall prevalence of D. \npteronyssinus (66.7%), D. farinae (64.5%) and B. \ntropicalis (55.2%) and significantly higher in older \nchildren.10 \n\n\n\nTotal IgE has been repeatedly reported to be \nhigher in more severe AD patients.6 Thus it is not \nsurprising that our study showed similar association. \nHowever, the result in this study was of no statistical \nsignificance. Interestingly, the serum specific IgE \n\n\n\nfor wheat, soya and cat dander showed positive \nassociation with eczema severities (Table 4). This \nassociation was not seen in SPT. These results were \nunexpected and we were unable to explain this \npositive inter-relationship but we reckoned that this \nmay be just a random coincidence.  \n\n\n\nWe have high food sensitization among our AD \nchildren. However, sensitisation does not equate to \nallergy and the diagnosis of food allergy is never \na straightforward process.  Double-blind, placebo-\ncontrolled oral food challenge test is the gold \nstandard for the diagnosis of food hypersensitivity.9 \nPrudent and sensible use of allergen testing in \nconcurrence with clinical history association may \nassist in the diagnosis. \n\n\n\nThe limitation of this study was the small sample \nsize and the number of subjects in Group A was \nmuch smaller than Group B. Hence, there may be \nbias when comparing the IgE sensitisation of these 2 \nage groups. Further study involving a larger cohort \nencompassing both the urban and rural eczema \nchildren may be able to generate better notable \nresults and outcome.\n\n\n\nConclusion \nIgE food and aeroallergen sensitisation was very \ncommon in this small number of AD children. \nSensitization to food was more common among \nthe younger children (Group A) while sensitisation \nto aeroallergen seen more commonly in the older \nchildren (Group B). Nevertheless, this study focuses \non sensitization pattern and the positive results \nmay not equate to allergy. Thus careful clinical \nassessment and association is essential to tie-in the \npositive results to the individual patients. A bigger \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4026\n\n\n\nsample to represent the paediatric population, \ncoupled with more detailed history of participants \nmay yield more accurate pattern and results. \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Ho MHK, Aung KPP, Wong WHS, Chan YET, Lee TL, \nChong CY et al. IgE Food Sensitizations Amongst Children \nwith Atopic Eczema. HK J Paediatr 2011;16:155-163.\n\n\n\n2. Hon KL, Leung TF, Ching G, Chow CM, Luk V, Ko WS \net al. Patterns of food and aeroallergen sensitization in \nchildhood eczema. Acta Paediatr 2008;97:1734-7.\n\n\n\n3. Hon KL, Nip SY, Cheung KL. A tragic case of \natopic dermatitis: Malnutrition and infections despite \nmultivitamins and supplements. Iran J Allergy Asthma \nImmunol 2012;11:267-70.\n\n\n\n4.  Williams HC, Burney PG, Pembroke AC, Hay RJ. The \nU.K. Working Party\u2019s Diagnostic Criteria for Atopic \nDermatitis III: Independent hospital validation. Br J \nDermatol 1994;131:406-16.\n\n\n\n5.  Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, \nGraeber M. The Eczema area and severity index (EASI): \nAssessment of reliability in atopic dermatitis. EASI \nEvaluator Group. Exp Dermatol 2001;10:11-8.\n\n\n\n6. Hill DJ, Hosking CS, de Benedictis FM, Oranje AP, \nDiepgen TL, Bauchau V et al. Confirmation of the \nassociation between high levels of immunoglobulin E food \nsensitization and eczema in infancy: an international study. \nClin Exp Allergy 2008;38:161-8.\n\n\n\n7. Yadav A, Naidu R. Clinical manifestation and sensitization \nof allergic children from Malaysia. Asia Pac Allergy \n2015;5:78-83.\n\n\n\n8. Yamazaki S, Shima M, Nakadate T, Ohara T, Omori T, \nOno M et al. Patterns of Sensitization to Inhalant Allergens \nin Japanese Lower-Grade Schoolchildren and Related \nFactors. Int Arch Allergy Immunol 2015;167:253-63.\n\n\n\n9. Kim HO, Cho SI, Kim JH, Chung BY, Cho HJ, Park CW et \nal. Food hypersensitivity in patients with childhood atopic \ndermatitis in Korea. Ann Dermatol 2013;25:196-202.\n\n\n\n10. Naspitz CK, Sole D, Jacob CA, Sarinho E, Soares FJP, \nDantes V et al. Sensitization to inhalant and food allergens \nin Brazilian atopic children by in vitro total and specific \nIgE assay. Allergy Project \u2013 PROAL. J Pediatr (Rio J) \n2004;80:203-10. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 27\n\n\n\nORIGINAL ARTICLE\n\n\n\nPatch Testing in Children and Adolescents: 7 Years\u2019 Experience in \nHospital Kuala Lumpur\nSharifah Rosniza1, AdvMDerm, Min Moon Tang1, AdvMDerm, Kin Fon Leong2, MRCPCH, Sabeera Begum2, MMed, \nAsmah Johar1, MMed\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Paediatric Dermatology Unit, Paediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nAbstract\nIntroduction:\t\nAllergic contact dermatitis (ACD) was thought to be infrequent in children. However, there is \nincreasing number of case reports and cross-sectional studies that indicate ACD is not as rare as \npreviously thought.  This study aims to explore the pattern of allergic contact dermatitis in children \nand adolescent patients.  \n\n\n\nMethods: \nThis is a retrospective study of children and adolescent patients between 5 and 19-years-old who \nunderwent patch test in the Department of Dermatology, Hospital Kuala Lumpur, Malaysia from \nJanuary 2010 to December 2016.  Patch tests were performed with European Baseline Series and \nother additional commercial series.  Readings were recorded according to the International Contact \nDermatitis Research Group recommendation. \n\n\n\nResults: \nThere were 116 children and adolescent patients who underwent patch test.  The median age of patients \nwas 14 years (range: 5-19) with a male to female ratio of 1: 2.7. Seventy patients had dermatitis \ninvolving the upper limbs (60.3%), followed by 61(52.6%) patients with dermatitis involving the \nlower limbs, 36(31.0%) patients with face and ears involvement and 31(26.7%) patients with truncal \ninvolvement. Of the 116 patients, 74(63.8%) had at least one positive patch test reaction.  The 5 \nmost common allergens were nickel sulfate (39.2%), fragrance mix (17.6%), potassium dichromate \n(14.9%), cobalt chloride (12.2%), methylcholoroisothiozolinone and methylisothiozolinone (Kathon \nCG) (8.1%) and thimerosal (8.1%).  \n\n\n\nConclusion: \nAround 64% of our children and adolescents had a positive patch test reaction.  Patch testing should \nbe recommended for children and adolescents suspected to have allergic contact dermatitis.\n\n\n\nKey words: Patch test, Paediatric, Adolescent, Allergic contact dermatitis, Nickel sulfate \n\n\n\nCorresponding Author\nDr. Sharifah Rosniza Binti Syed Nong Chek\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586 Kuala Lumpur, Malaysia.\nEmail: srsyed@doctors.net.uk \n\n\n\nIntroduction\nAllergic contact dermatitis (ACD) was thought to \nbe infrequent in children. However, recent reports \nhave proven otherwise. There is now an increasing \nawareness about this condition amongst both \nthe paediatricians and dermatologists, which has \nresulted in the increased use of patch tests and \nconsequently the number diagnosed. Recent review \narticles which included studies involving 65 to 2460 \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4028\n\n\n\nsubjects revealed that positive patch test reactions \nhave been detected in 26.6% to 95.6% of children \nand sensitization was found even at infantile \nstage.1,2  Most of the studies involved children with \natopic dermatitis.1 This wide range of sensitization \nwas due to several factors including the populations \nstudied, their age, sex, inclusion criteria, choice of \npatch test series, and patch test methodology.1,2  \n \nAllergic contact dermatitis is a type IV delayed \nhypersensitivity reaction and thus it involves an \nimmunological mechanism that requires an initial \nsensitization phase followed by elicitation phase \nthat causes the skin lesions.  The legs and feet, hands \nand face are the sites most frequently affected in \npaediatric ACD, which is mainly caused by metals, \nfootwear, topical medications and cosmetics.3 There \nare numerous allergens that may contribute to ACD, \nhowever the most common allergens in children \nwere nickel, thimerosal, cobalt, fragrance, lanolin \nand neomycin.2 In adolescents, they were nickel, \nthimerosal, cobalt, fragrance, potassium dichromate, \nand Myroxylon pereirae.2 \n\n\n\nExposure to allergens that have the potential to \ncause ACD varies according to the geographical \ndistribution.  This is partly due to the local regulations \nwhich may restrict the usage of certain chemicals. \nIn addition, in the cases of ACD caused by allergens \nfound in natural products, it may also represent the \ntypes of natural remedies available in that region. \nApart from that, patients\u2019 cultural beliefs do play \nimportant roles.  Most of the data involving ACD \nin children are derived from studies conducted in \nEurope and North America.  In the South East Asian \ncontinent, a study conducted in Singapore between \n1986 and 2003 showed that 45.4% of subjects \nless than 20 years old was sensitized with nickel \nbeing the most common sensitizing allergens.4 \nACD was first reported in Malaysian children in \n1994.5 In this 2-year audit on all 346 subjects with \npositive reaction in patch test, nickel was the most \nsensitizing allergen. Interestingly, 6 children (below \n14 years old) were found to be sensitized to rubber \nchemicals.5 Furthermore ACD to cosmetics was \nalso reported in children of Malaysian population.6 \n\n\n\nA more recent 15-month audit done in Hospital \nSelayang Malaysia in 2013 revealed that 60.7% of \n84 school children studied developed at least one \npositive reaction in the patch test. The sensitizing \nallergens include nickel, preservatives, rubber \nchemicals, fragrances and topical medicaments.7 \n\n\n\nRecognizing the need of a more tailored approach \n\n\n\nto ACD in our local population, this study aims to \nexplore the pattern of allergic contact dermatitis in \nchildren and adolescents in Hospital Kuala Lumpur, \nMalaysia.\n\n\n\nMaterials and Methods\nThis is a retrospective review of all children and \nadolescent patients between the age of 5 to 19-year-\nolds who underwent patch test in Hospital Kuala \nLumpur between January 2010 to December \n2016. Based on the definition by World Health \nOrganization, patients were categorized as children \nif they are less than 10 years old and adolescents \nif they are between 10 to 19 years old. Patch test \nwas performed using IQ chambers and allergens \npurchased from Chemotechnique Diagnostics.  \nPatients were patch tested with European Baseline \nSeries, other appropriate series and patients\u2019 own \nproducts as directed and recorded in the patients\u2019 \nclinical notes.  For example, patients with feet \ndermatitis were tested with European Baseline \nSeries and shoe series, and patients with cheilitis \nwere tested with European Baseline Series, dental \nseries, cosmetic series and their own lip products.  \nPatients\u2019 own products were diluted according to \nthe nature of the products and were based on the \nrecommendations from the book by Frosch et al.8 \nCosmetics such as eye make-up, lipstick, facial \npowder, facial foundation, moisturizers, perfumes \nand deodorants were tested as is. Cleaning products \nsuch as soap bar, shampoo, shower gel and toothpaste \nwere diluted with water to 1% (w). Readings were \nrecorded according to the recommendations by the \nInternational Contact Dermatitis Research Group.9,10\n\n\n\nResults\nThere were 116 children and adolescent patients who \nunderwent patch test (Table 1). Nineteen (16.4%) \npatients were categorized as children (<10 years) \nand 97 (83.6%) patients were adolescents (10-19 \nyears). Most of the patients (88%) were of school-\ngoing ages (7 to 17) and there was no occupation \nrecorded in any of our patients. Seventy-four \npatients (63.8%) had at least one positive patch test \nreaction.  There were 11 (57.9%) positive patch test \nin children and 63 (66.0%) in adolescent patients \nand this difference was not statistically significant \n(p=0.56).\n\n\n\nThere were 85 females and 31 male patients (Table \n2). Positive patch test reactions were recorded in 51 \nfemales (60.0%) as compared to 23 male patients \n(74.2%) and the difference was not statistically \nsignificant (p=0.16). When comparison was made \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 29\n\n\n\nbetween female children and female adolescents, \n5 (41.7%) female children had positive patch \ntest reactions as compared to 46 (63.0%) female \nadolescents and this difference was however not \nstatistically significant (p=0.16).  When comparison \n\n\n\nwas made between male children and male \nadolescents, 6 (85.7%) male children had positive \npatch test reactions as compared to 17 (70.8%) male \nadolescents and this difference was not statistically \nsignificant (p=0.43)\n\n\n\nTable 1.  Characteristics of 116 children and adolescents who underwent patch test\n\n\n\nCharacteristics n=116\n\n\n\nMedian age in years (range) 14 (5-19)\nMale : female ratio 1 : 2.7\nEthnicity, n (%) Malay 75 (64.7)\n\n\n\nChinese 25 (21.6)\nIndian 15 (12.9)\nOthers 1   (0.9)\n\n\n\nSite of lesions, n (%) Upper limbs 70 (60.3)\nLower limbs 61 (52.6)\nFace and ears 36 (31.0)\nTrunk 31 (26.7)\nGeneralized 3   (2.6)\n\n\n\nClinical diagnosis, n (%) Contact dermatitis 87 (75.0)\nEczema 6  (5.2)\nAtopic eczema 5  (4.3)\nHand and foot eczema 5  (4.3)\nFoot eczema 4  (3.4)\nHand eczema 3  (2.6)\nDiscoid eczema 3  (2.6)\nPompholyx 1  (0.9)\nFacial eczema 1  (0.9)\nLip eczema 1  (0.9)\n\n\n\nPatch test series used, n (%) European Standard 115 (99.1)\nShoe 31 (26.7)\nRubber 29 (25.0)\nCosmetic 20 (17.2)\nPlastic and glue 10 (8.6)\nTextile and dye 9 (7.8)\nMetal 7 (6.0)\nMedicaments 3 (2.6)\nDental 3 (2.6)\nPhotoallergen 1 (0.9)\n\n\n\nAll of the patients were patch tested with European \nBaseline Series, except for 1 patient who was patch \ntested only to shoe and plastic and glue series. \nOther extended series which were used in this \nstudy include shoe series, rubber series, cosmetic \nseries, plastic and glue series, textile and dye series, \nmetal series, medicaments series, dental series and \nphotoallergen series.  Seventeen patients (14.7%) \nwere also tested with their own products which \ninclude various brands of make-up and personal \ncare products. From the total number of patients \ntested, 17 (14.7%) developed positive patch test \nreactions only to the extended series and not to the \nEuropean Standard series.\n\n\n\nThe most common sensitizing allergens in this \n\n\n\nstudy were nickel sulfate, fragrance mix, potassium \ndichromate, cobalt chloride, MCI/MI (Kathon CG) \nand thimerosal (Table 3). In children, the most \ncommon allergen was nickel sulfate, followed \nby paraphenylenediamine, disperse orange 3 and \nsesquiterpine lactone (SQL).  In adolescents, the \nmost common allergen was also nickel sulfate, \nfollowed by fragrance mix, potassium dichromate, \ncobalt chloride and thimerosal.  Nickel sensitization \nwas found in 22 (25.9%) female patients and 7 \n(22.6%) male patients. There was no statistically \nsignificant difference between nickel sensitization \nin female or male patients in our study (p=0.13). \nIn patients with positive patch test to nickel sulfate, \n5 (17.2%) patients were also positive to cobalt \nchloride and 6 (20.7%) of these patients were also \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4030\n\n\n\npositive to potassium dichromate.\n\n\n\nThe most common site of involvement was the upper \nlimbs. Seventy patients had dermatitis involving \nthe upper limbs (60.3%), followed by 61 (52.6%) \npatients with dermatitis involving the lower limbs, \n36 (31.0%) patients with face and ears involvement \n\n\n\nChildren Adolescent\nTotal patch tested (n) Number sensitized n (%) Total patch tested (n) Number sensitized n (%)\n\n\n\nOverall 19 11 (57.9) 97 63 (64.9)\nGender Female 12 5 (41.6) 73 46 (63.0)\n\n\n\nMale 7 6 (85.7) 24 17 (70.8)\nTen most sensitizing\n\n\n\nallergens, n (%)\n\n\n\nNickel sulfate, 6 (54.5) Nickel sulfate, 23 (63.9)\n4-phenylenediamine base, 2 (18.2) Fragrance mix, 12 (19.1)\nDisperse orange 3, 2 (18.2) Potassium dichromate, 11 (17.5)\nSesquiterpine lactone, 2 (18.2) Cobalt chloride, 8 (12.7)\nCobalt chloride, colophony, mercapto mix, \npalladium, fragrance mix, N-isopropyl N-phenyl \nparaphenylenediamine, neomycin, epoxy resin, MCI/\nMI, formaldehyde, benzoyl peroxide, acid yellow 36, \n4-aminobenzene, 1 each (9.1)\n\n\n\nThimerosal, 6 (9.5)\n\n\n\nMCI/MI, 5 (7.9)\n\n\n\nColophony, neomycin, formaldehyde, 4 each (6.3)\nChloromycetin, 3 (4.8)\n\n\n\nand 31 (26.7%) patients with truncal involvement. \nIn patients with upper limb involvement, 54 (78.3%) \npatients had hand eczema.  Positive patch test was \nrecorded in 53.7% of patients with hand eczema. In \nall of the sites of lesions, nickel sulfate was found to \nbe to most common sensitizing allergen.\n\n\n\nTable 2. Patch test results according to age and gender (n=116)\n\n\n\nMCI/MI-methylcholoroisothiozolinone/methylisothiozolinone\n\n\n\nMCI/MI: methylcholoroisothiozolinone / methylisothiozolinone; MDBGN: methyldibromoglutaronitrile; SQL: sesquiterpine lactone\n\n\n\nDiscussion\nAround 64% of our patients had positive patch test \nreactions and this confirms the notion that allergic \ncontact dermatitis is not rare amongst our children \nand adolescent. As shown in Table 4, the reported \ncontact sensitization rates in these groups of patients \nranges between 27.0 - 95.6% in different countries.1 \n\n\n\nThe sensitization rates were remarkably higher in \nstudies with smaller number of subjects.\n\n\n\nThe most common allergen is nickel sulfate, and \nthis finding is similar to other studies11-36 (Table 4).  \nFemale patients could be exposed to nickel from \njewelleries and ear piercing.37 Girls and female \n\n\n\nTable 3. The contact sensitization pattern in the current cohort (n=116)\n\n\n\nPositive patch test n (%)\nNickel sulfate 29 (39.2)\nFragrance mix 13 (17.6)\nPotassium dichromate 11 (14.9)\nCobalt chloride 9 (12.2)\nMCI/MI (Kathon CG) and thimerosal 6 each (8.1)\nColophony, neomycin, formaldehyde 5 each (6.8)\n4-phenylenediamine base and SQL mix 4 each (5.4)\nDisperse orange 3, acid yellow 36, 4-aminobenzene, epoxy resin, mercaptobenzothiazole 3 each (4.1)\nMercapto mix, dibutylthiourea, paraben mix, palladium chloride, cocomidopropylbetaine, tixocortol-21-pivalate, \nN-isopropyl N-phenyl paraphenylenediamine, thiuram mix\n\n\n\n2 each (2.7)\n\n\n\nBalsam of Peru, primin, disperse yellow 9, benzoyl peroxide, MDBGN, mercury ammonium chloride, disperse red 1, \nwool alcohol, 4-ter-butylphenol formaldehyde resin, benzocaine, amalgam, mercury, copper oxide, copper sulphate, \nlead chloride, chlorocresol, dimethylaminopropylamine, gold sodium thiosulphate, hexamethylene tetramene, \ndisperse blue mix 106/124, dithiodimorpholine, amalgam alloying metal\n\n\n\n1 each (1.4)\n\n\n\nadolescents are also exposed to makeup, although \ndirect associations between nickel containing eye \nmakeup and cosmetic dermatitis have not been found. \nMake-up applicators (ferrules) such as eyelash \ncurlers, hairdressing scissors, hair curlers, and eye \nshadow and makeup applicators can also become \nthe sources for nickel in this population.38 Other \ncommon items that contain nickel include zippers, \nbelts, tools and dental appliances.  Toys were often \noverlooked as a source for nickel exposure and a \nstudy have found that nickel was released in 34.4% \ntoys bought from Denmark and the United States.39 \nAnother common nickel-containing appliances that \nare increasingly used in children and adolescents are \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 31\n\n\n\nRegion Country Author & year n Age \n(year)\n\n\n\nSensitization rate \n(%)\n\n\n\nRelevance rate \n(%)\n\n\n\nTop 3 sensitizing allergens\n\n\n\nUnited State & \nCanada\n\n\n\nUSA Zug et al, 200811 391 0-18 65.7 51.2 Nickel, cobalt, thimerosal\nCanada Hogeling et al, 200812 100 4-18 70.0 55.8 Nickel, cobalt, fragrance mix\nUSA Jacob et al, 200813 65 1-18 83.0 77.0 Nickel, thimerosal, Myroxylon \n\n\n\npereirae\nUSA Hammonds et al, \n\n\n\n200914\n136 3-18 61.0 53.0 Nickel, cobalt, gold\n\n\n\nUSA Jacob et al, 201015 69 6m-18 95.6 76.7 Nickel, cocamidopropylbetaine, \nMyroxylon pereirae\n\n\n\nSouth America Brazil Duarte et al, 200316 102 10-19 56.0 100 Nickel, tosylamide-formaldehyde \nresin\n\n\n\nEuropean France Roul et al, 199917 337 1-15 67.1 NA Nickel, fragrance, wool alcohol\n\n\n\nAustria W\u04e6hrl et al. 200318 79 1-10 62.0 NA Nickel, ethyl mercury, thimerosal\n\n\n\nGermany Heine et al, 200419 285 6-12 52.6 NA Thimerosal, benzylperoxide, \nphenylmercuricacetate\n\n\n\n2175 13-18 49.7 NA Nickel, thimerosal, \nbenzylperoxide\n\n\n\nUK Lewis et al 200420 191 <16 41.0 51.7 Nickel, fragrance mix, thiuram\n\n\n\nUK Clayton et al, 200521 500 0-16 27.0 61.0 Nickel, fragrance mix, cobalt\n\n\n\nSpain Vozmediano et al \n200522\n\n\n\n96 <15 54.2 57.7 Fragrance mix, thimerosal, nickel\n\n\n\nItaly Seidenari et al, 200523 1094 <12 52.1 70.0 Neomycin, nickel, \nlanolinalcohols/ thimerosal\n\n\n\nUK Beattie et al 200624 114 3-15 53.5 100 Nickel, cobalt, rubberchemical\n\n\n\nTurkey Onder et al, 200825 360 2-16 32.8 93.2 Nickel, cobalt, PPD\n\n\n\nNetherlands De Waard-van der \nSpek, 200926\n\n\n\n79 1-18 50.6 84.7 Nickel, ownshoes, potassium \ndichromate\n\n\n\nPoland Czarnobilska et al, \n200927\n\n\n\n96 7 43.8 NA Nickel, thimerosal, cobalt\n\n\n\n133 16 52.6\nGreece Milingou et al, 201028 232 <16 47.8 NA Nickel, cobalt, potassium \n\n\n\ndichromate\n255 60.0 Nickel, thimerosal, cobalt\n\n\n\nSpain Toledo et al, 201129 111 0-15 46.8 77.6 Nickel, MCI/MI, fragrance mix I\n\n\n\nPoland Czarnobilska et al, \n201130\n\n\n\n103 7-8 67.0 NA Nickel, propolis, thimerosal\n\n\n\n93 16-17 58.1 NA Thimerosal, nickel, Cobalt\n\n\n\nItaly Fortina et al, 201131 321 3months \n\u2013 3 years\n\n\n\n62.3 49.3 Nickel, potassium dichromate, \ncocamidopropylbetaine\n\n\n\nEdinburgh \nUK\n\n\n\nDarling et al, 201232 41 <18 41 NA Mercaptobenzothiazole, mercapto \nmix, potassium dichromate\n\n\n\nPoland Silny et al, 201333 104 1-20 45.2 NA Nickel, cobalt, potassium \ndichromate\n\n\n\nDundee UK Vongyer et al, 201534 137 3-15 36.5 NA Nickel, potassium dichromate, \nwoolalcohol\n\n\n\n11 European \ncountries\n\n\n\nBelloni-Fortina et al, \n201535\n\n\n\n6708 1-16 36.9 NA Nickel, cobalt, potassium \ndichromate\n\n\n\nAsia Pacific Singapore Goon et al, 20064 2340 <21 45.4 NA Nickel, thimerosal, colophonium\n\n\n\nIndia Sarma et al, 201036 70 1-15 80.0 60.7 Nickel, cobalt, potassium \ndichromate\n\n\n\nMalaysia Current study, 2017 116 5-19 63.8 NA Nickel, fragrance mix, potassium \ndichromate\n\n\n\nTable 4. Patch test results in children and adolescents reported by various countries\n\n\n\nUK: United Kingdom; US: United State of America\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4032\n\n\n\nthe tablets laptops and smartphones that have metal \ncasings.40 Nickel allergy can manifest in different \nways and apart from causing eczema at the contact \narea, nickel allergy can be associated with systemic \ncontact dermatitis.  The baboon syndrome is a typical \npresentation of systemic contact dermatitis which \nshows a classical distribution of maculopapular \nerythematous lesions, pruritic and confluent, located \nin the gluteal and flexural regions.37 In Europe, there \nare mandatory restrictions for nickel content in \nconsumer products.  This may explain the striking \nfindings in some European countries where nickel \nsulfate was no longer the most common sensitizing \nallergen.  In Denmark, it has been demonstrated \nthat regulation of the nickel content has reduced \nthe risk of developing allergic contact dermatitis \nand the associated costs arising from excess nickel \nexposure.41 It would be interesting to observe if \nstringent regulation regarding the permissible nickel \ncontent in consumer products in Malaysia would \nproduce similar result.\n\n\n\nOther metals such as cobalt chloride and potassium \ndichromate were also common allergens in this \nstudy.  Patients who are sensitized to nickel are \nmore prone to be sensitized to other metals such \nas cobalt and chromium and this may explain the \nhigh sensitization to cobalt chloride and potassium \ndichromate in our patients.37 Cobalt is used in the \nproduction of metal alloys and pigments such as \ncobalt blue and cobalt green.  Most of the sources \nof cobalt are found in costume jewelleries but \ndetergents and cosmetics may also contain this \nallergen.42 Chromium is used in the tanning process \nof leather and in children, the most common source \nof chromium is leather and it is associated with shoe \ncontact dermatitis.42\n\n\n\nFragrances and preservatives were also found to be \ncommon allergens in this study and these could be \ndue to exposure to toiletries and cosmetic products \naimed at children and adolescent population. There \nis an increasing interest in the choice of \u201cnatural\u201d \nskin care products which are perceived to be less \nallergenic for their children but these products may \nalso contain fragrances and preservatives which \nmay elicit ACD.43\n\n\n\nFragrances are a large and heterogenous group of \nchemical and continuous exposure to these allergens \non a daily basis is not uncommon.  While obvious \nsources are perfumes, toiletries and cosmetics, \nthey are also widely used in household cleaning \nproducts, topical medications and even in foods and \n\n\n\nspices.44 Children\u2019s cosmetics contain fewer and \nless concentrated allergenic fragrance ingredients \nthan those of adults.45 Fragrances that are derived \nfrom botanical products and in particular, usage of \nessential oils have been associated with ACD.46,47  \nFragrances are also used in foods consumed by \nchildren and adolescent population and these \ninclude chewing gum, soft drinks and ice creams.  \nThese fragrances could be synthetic or natural in \norigin. The natural sources include clove, vanilla \nand cinnamon. Ingestion of these allergens in \nsusceptible subjects may give rise to systemic \ncontact dermatitis.44\n\n\n\nTwo preservatives namely methylcholoro-\nisothiozolinone / methylisothiozolinone (MCI/MI) \nand thimerosal were in the list of 5 most common \nallergens in this study.  MCI/MI is a combination \npreservative found in personal care such as \ncosmetics, wet wipes and household products \nincluding cleaning products and paints. In an attempt \nto reduce the incidence of ACD to this preservative, \nMI alone has been increasingly used in these \nproducts.48 Methylisothiozolinone was initially \nthought to be safer as MCI was a significantly more \npotent allergen than MI.49 However, it is now known \nthat allergic contact dermatitis can also occur to MI; \nwith the first few cases of allergic contact dermatitis \nto MI in cosmetics reported in 2010.50\n\n\n\nThimerosal on the other hand is used as a \npreservative in vaccines and can also be found in \nophthalmic solutions and cosmetics. However, \nmany tertiary centres including the North American \nContact Dermatitis Group (NACDG) have removed \nthis allergen from their screening panel due to the \nhigh positive patch test reactions without clinical \nrelevance.51 Currently, the inactivated influenza \nvaccine recommended for children below the age of \nseven is the only vaccine that contains thimerosal.52 \nHowever, it is still important to enquire about \nthe usage of cosmetics and ophthalmic solutions \nas patients may still be exposed to thimerosal in \nthese products and patch testing with patients\u2019 own \nproducts should be considered to determine the \nrelevance of the positive finding. \n\n\n\nOur results are also similar to a study conducted in \nan adult population in our centre, whereby nickel \nsulfate, potassium dichromate, MCI/MI, fragrance \nmix and cobalt chloride were also reported to be the \ntop five sensitizing allergens.53 The similar finding \nmeans that positivity to allergens during childhood \nand adolescence may persist into adulthood and this \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 33\n\n\n\ninformation may be used as a guide when choosing \ntheir future occupations.  Interestingly, their study \nfound that nickel sensitization is significantly more \ncommon in female; which was not shown in our \ncohort of patients.  This may reflect the increased \nexposure to nickel in females as they grow older, \npossibly from costume jewelleries.\n\n\n\nThere were concerns from dermatologist and \nparents alike on whether patch test is practical for \npatients especially in the younger children.  Limited \narea on patient\u2019s back is definitely going to affect \nthe number of allergens that can be tested.  There \nwere also concerns whether the concentration used \nfor adults might give rise to more irritant contact \ndermatitis in this population.  To address this issue, \nEACCI (European Academy of Allergy and Clinical \nImmunology) has published a position paper on patch \ntesting in children with allergic contact dermatitis \nin 2015.54 This paper noted that most of authors \nused the same concentration of allergens as in adult \npopulation, although the risk of irritant reactions \nmay be higher in infants when tested with metal \nsalts.  This paper also advocated 9 allergens to be \ntested in standard series for children (nickel sulfate, \nthiuram mix, colophonium, mercaptobenzothiazole, \nfragrance mix I, fragrance mix II, mercapto mix, \nMCI/MI and SQL mix); together with additional \nallergens based on clinical history and allergen \nexposure. Testing with additional expanded series is \nimportant. This is shown in our study where 14.7% \nof positive patch test reactions would have been \nmissed if the patients were only tested to European \nStandard series.\n\n\n\nThere were several limitations to this study. This \nwas a single centre study and our findings may not \nbe similar to the rest of Malaysian children and \nadolescent population. The records on the relevance \nof the positive patch test reactions were lacking and \ntherefore the positive allergens found in the patch \ntest may not necessarily be the cause of patients\u2019 \nclinical condition. \n\n\n\nConclusion\nIn conclusion, contact sensitization is not rare in our \nchildren and adolescence as 64% of our patients in \nthis study developed at least one positive reaction \nto patch test. Our top 3 sensitizing allergens were \nnickel, fragrance mix and potassium dichromate.  \nPatch test should be considered in children and \nadolescents presenting with history and clinical \nfindings suggestive of contact dermatitis.  Findings \nfrom this study could contribute to the development \nof paediatric baseline series suited for Malaysian \npopulation.  \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Simonsen, AB, Deleuran M, Johansen JD, Sommerlund M.  \nContact allergy and allergic contact dermatitis in children \u2013 \na review of current data. Contact Dermatitis 2011;65:254-\n65.\n\n\n\n2. Rodrigues DF, Goulart EMA. Patch-test results in children \nand adolescents: systematic review of a 15-year period. An \nBras Dermatol 2016;91:64-72.\n\n\n\n3. Pigatto P, Martelli A, Marsili C, Fiocchi A. Contact \ndermatitis in children. Ital J Pediatr 2010;36:2.\n\n\n\n4. Goon AT, Goh CL. Patch testing of Singapore children \nand adolescents: our experience over 18 years. 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Prevalence of contact allergy in \nchildren suffering from atopic dermatitis, seborrhoeic \ndermatitis and in healthy controls.  Ann Agric Environ Med \n2013;20:55-60.\n\n\n\n34. Vongyer GA and Green C. Allergic contact dermatitis in \nchildren; has there been a change in allergens?. Clin Exp \nDermatol 2015;40:31-4.\n\n\n\n35. Belloni Fortina A, Cooper SM, Spiewak R, Fontana E, \nSchnuch A, Uter W. Patch test results in children and \nadolescents across Europe. Analysis of the ESSCA Network \n2002\u20132010. Pediatr Allergy Immunol 2015;26:446-55.\n\n\n\n36. Sarma N, Ghosh S.  Clinico-allergological pattern of \nallergic contact dermatitis among 70 Indian children.  \nIndian J Dermatol Venereol Leprol 2010;76:38-44.\n\n\n\n37. Brand\u00e3o MH, Gontijo B.  Contact sensitivity to metals \n(chromium, cobalt and nickel) in childhood. An Bras \nDermatol 2012;87:269-76.\n\n\n\n38. Jacob SE, Silverberg JI, Rizk C, Silverberg N. Nickel \nFerrule Applicators: A Source of Nickel Exposure in \nChildren. Pediatr Dermatol 2015;32:e62\u20133.\n\n\n\n39. Jensen P, Hamann D, Hamann CR, Jellesen MS, Jacob SE, \nThyssen JP.  Nickel and cobalt release from children\u2019s toys \npurchased in Denmark and the United States.  Dermatitis \n2014;25:356-65.\n\n\n\n40. Jacob SE, Admani S.  iPad\u2014Increasing Nickel Exposure \nin Children. Pediatrics 2014;134:e580-2. \n\n\n\n41. Garg S, Thyssen JP, Uter W, Schnuch A, Johansen JD, \nMenn\u00e9 T et al. Nickel allergy following European Union \nregulation in Denmark, Germany, Italy and the UK. Br J \nDermatol 2013;169:854\u20138.\n\n\n\n42. Rietschel RL, Fowler JF Jr. Metals. In: Rietschel R, Fowler \nJF Jr, editors. Fisher\u2019s contact dermatitis. 6th ed. Hamilton, \nOntario: BC Decker Inc; 2008. p.641-99.\n\n\n\n43. Admani S, Hill H, Jacob SE.  Cinnamon Sugar Scrub \nDermatitis: \u201cNatural\u201d Is Not Always Best. Pediatr \nDermatol 2017;34:e42\u20133.\n\n\n\n44. Arribas MP, Soro P, Silvestre JF. Allergic \nContact Dermatitis to Fragrances. Part 1 \nActas Dermosifiliogr 2012;103:874-9.\n\n\n\n45. Rastogi SC, Johansen JD, Menn\u00e9 T, Frosch P, Bruze M, \nAndersen KE et al.  Contents of fragrance allergens in \nchildren\u2019s cosmetics and cosmetic-toys. Contact Dermatitis \n1999;41:84-8. \n\n\n\n46. Ridzwan R, Zainudin BH. Contact Allergic Dermatitis to \nCosmetics and Topical Anti-ageing Products. Malaysian J \nDermatol 2017;39:10-21.\n\n\n\n47. Uter W, Schmidt E, Geier J, Lessmann H, Schnuch A and \nFrosch P.  Contact allergy to essential oils: current patch \ntest results (2000\u20132008) from the Information Network of \nDepartments of Dermatology (IVDK). Contact Dermatitis \n2010;63:277\u201383.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 35\n\n\n\n48. de Unamuno B, Zaragoza Ninet V, Sierra C, de la \nCuadra J.  Descriptive Study of Sensitization to \nMethylchloroisothiazolinone and Methylisothiazolinone in \na Skin Allergy Unit.  Actas Dermosifiliogr 2014;105:854-\n9.\n\n\n\n49. Bruze M, Engfeldt M, Gon\u00e7alo M, Goossens A. \nRecommendation to include methylisothiazolinone in \nthe European baseline patch test series \u2013 on behalf of the \nEuropean Society of Contact Dermatitis and the European \nEnvironmental and Contact Dermatitis Research Group. \nContact Dermatitis 2013;69:263-70\n\n\n\n50. Garc\u00eda-Gav\u00edn J, Vansina S, Kerre S, Naert A, Goossens A.  \nMethylisothiazolinone, an emerging allergen in cosmetics? \nContact Dermatitis 2010;63:96-101. \n\n\n\n51. Belsito DV.  Thimerosal: contact (non) allergen of the year.  \nAm J Contact Dermat 2002;13:1\u20132.\n\n\n\n52. Hurley AM, Tadrous M, Miller ES. Thimerosal-Containing \nVaccines and Autism: A Review of Recent Epidemiologic \nStudies. J Pediatr Pharmacol Ther 2010;15:173-81.\n\n\n\n53. How KN, Tang MM, Kaur R, Johar A.  Contact sensitization \nin adults: a retrospective review in hospital Kuala Lumpur.  \nMed J Malaysia 2017;72:113-8.\n\n\n\n54. de Waard-van der Spek FB, Darsow U, Mortz CG, Orton \nD, Worm M, Muraro A et al. EAACI Position Paper for \npractical patch testing in Allergic Contact Dermatitis in \nchildren. Pediatr Allergy Immunol 2015;26:598\u2013606.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4036\n\n\n\nORIGINAL ARTICLE\n\n\n\nCutaneous Adverse Drug Reactions in Sabah: A 3-year study between \n2014 - 2016\nTeck Sheng Gan1, MRCP, Yin Man Lim1, MRCP, Yui Ping Tan2, MPHARM, Sivaraj A/L Raman3, MPHARM, \nMelinda Kwan See Kee4, MPHARM, Asmah Johar5, MMed\n\n\n\n1Department of Medicine, Hospital Tawau, Tawau, Sabah, Malaysia  \n2Department of Pharmacy, Hospital Tawau, Tawau, Sabah, Malaysia \n3Department of Pharmacy, Hospital Keningau, Keningau, Sabah, Malaysia  \n4Department of Pharmacy, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia \n5Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n\n\n\nAbstract\nIntroduction:\t\nCutaneous adverse drug reactions are one of the most common adverse drug reactions. Publications \non clinical correlation between cutaneous presentations and causative agents are limited among the \nlocal population. This study aims to determine the clinical presentations of cutaneous adverse drug \nreactions and the causative drugs in the local population.  \n\n\n\nMethods: \nA retrospective, cross sectional study was conducted from the pharmacy cutaneous adverse drug \nreaction database from January 2014 to December 2016 in Tawau, Keningau & Queen Elizabeth (Kota \nKinabalu) Hospitals.\n\n\n\nResults: \nA total of 859 cases of cutaneous adverse drug reactions were identified. Out of these, 53.3% (n=458) \nwere females and 46.7% (n=401) were males. The mean age was 36 years old. Majority of patients were \n20-29 years old (16.6%) followed by 50-59 years old (15.1%). Most of the cases were reported among \nthe Chinese community (16.4%), followed by the Malay (15.9%), Dusun (14.7%) and Bajau (14.0%) \npopulations. The most common cutaneous manifestations were urticaria and or angioedema (49%, n= \n421) and maculopapular rash (39.6%, n=340). Severe cutaneous adverse reactions (SCAR) constituted \n2.8% in total. The major causative agent was antibiotic which accounted for 55.1% (n=473), followed \nby nonsteroidal anti-inflammatory drugs (NSAIDs), 28.1% (n=241) and analgesics, 10.8% (n=93). \n\n\n\nConclusion: \nThe types of cutaneous manifestations and causative drugs in Sabah are similar to those reported in \nother states of the country and abroad. This study provides evidence of local cutaneous adverse drug \nreaction characteristics in different ethnic group. \n\n\n\nKey words: Cutaneous adverse drug reactions (CADRs), Maculopapular rash, Urticaria\n\n\n\nCorresponding Author\nDr Gan Teck Sheng\nDepartment of Medicine, Hospital Tawau,                  \nPeti Surat 67, 91007 Tawau, Sabah.\nEmail: gan_ts@hotmail.com\n\n\n\nIntroduction\nCutaneous adverse drug reactions (CADRs) are \ncommonly reported in different forms in our clinical \npractice, with a prevalence of 0.2% to 3.3%.1,2 The \nclinical presentations of CADRs vary from mild \nurticaria and maculopapular eruption to potentially \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 37\n\n\n\nlife-threatening severe cutaneous adverse reactions \n(SCAR), which include drug reaction with \neosinophilia and systemic symptoms (DRESS) \nsyndrome, acute generalised exanthematous \npustulosis (AGEP), Stevens-Johnson syndrome \n(SJS) and toxic epidermal necrolysis (TEN). A \nrecent study from US using the inpatients sample \ndata base showed high health care cost and mean \nadjusted mortality rate of 4.8%, 14.8%, 19.4% for \nSJS, TEN and SJS/TEN respectively.3\n\n\n\nSabah is the 3rd most populous state in Malaysia, and \nthe ethnic distributions are vastly different from the \nrest of Malaysia. As clinical manifestations and the \ncausative drugs vary among different populations, \nand the data available in our local setting is limited, \nthis study aims to providing a better understanding \nof the cutaneous adverse drug reactions in Sabah.\n\n\n\nMaterials and Methods\nThis is a retrospective cross sectional study done in \nTawau, Keningau and Queen Elizabeth Hospitals \nfrom January 2014 to December 2016. Tawau and \nKeningau Hospitals are district hospitals in the \nrespective towns, whereas Queen Elizabeth Hospital \nis a tertiary hospital in Kota Kinabalu. Pharmacists \nwere the main reporters. Data was collected and \nretrieved from database of adverse drug reaction \nregistry from January 2014 to December 2016. Data \nwere analysed using Microsoft Office Excel. \n\n\n\nResults\nA total of 925 cases of adverse drug reactions were \nreported during the study period from 1st January \n2014 to 31st December 2016, of which 859 cases \n(92.9%) were cutaneous and 66 cases (7.1%) were \nnon-cutaneous. Among the cutaneous adverse \ndrug reactions reported, Queen Elizabeth Hospital \ncontributed to 389 cases (45.3%), followed by 296 \ncases (34.5%) from Tawau Hospital and 174 cases \n(20.3%) from Keningau Hospital.\n\n\n\nThe mean age was 36.0 \u00b1 21.2 years, ranging from \n15 to 57 years old. The highest number of cases \nwas seen in the age group of 20-29 years (16.6%) \nfollowed by the age group of 50-59 years (15.1%) \nas shown in Figure 1. Among the total of 859 \ncutaneous cases, 458 were females and 401 were \nmales. The female-to-male ratio was 1.1:1.\n\n\n\nCutaneous adverse drug reactions were most \ncommonly observed among the Chinese community \n\n\n\n(16.4%), followed by the Malay (15.9%), Dusun \n(14.7%) and Bajau (14.0%) populations as shown \nin Table 1. This is unsurprising given that Chinese \nmade up 29.8% of the population combined in \nKota Kinabalu, Tawau and Keningau. Other ethnic \ngroups are Dusun (29.9%), Bajau (22.5%), Malay \n(10.7%) and Murut (7.1%).4\n\n\n\nUrticaria and or angioedema (n=421, 49%) and \nmaculopapular rash (n=340, 39.6%) made up \nthe majority of manifestations of cutaneous drug \nreactions. Severe cutaneous adverse reactions \n(SCAR) constituted 2.2% in all. Amongst the \nlife-threatening skin conditions, Stevens-Johnson \nsyndrome (n=10, 1.2%) was the commonest, \nfollowed by DRESS (n=6, 0.7%), AGEP (n=5, \n0.6%), SJS-TEN overlap (n=2, 0.2%) and TEN \n(n=1, 0.1%) as shown in Table 2. Antibiotics \n(55.1%) were implicated in more than half of the \ncutaneous drug reactions. This was followed by \nNSAIDs (28.1%), analgesics (10.8%) and anti-\nhistamines (3.7%) as shown in Table 3. In this study, \npenicillin group accounted for 68.7% of antibiotics \ncausing CADRs. The most common NSAIDs and \nanalgesics associated with CADRs were diclofenac \nand paracetamol respectively. Other common drugs \npresenting with CADRs were ranitidine, phenytoin \nand allopurinol.\n\n\n\nAllopurinol was implicated in 5 of the 24 cases \n(20.8%) of SCAR reported, making it the leading \ncause of SCAR in this population. Drugs reported \nto cause SCAR are listed in Table 4.\n\n\n\nFigure 1. The distribution of CADRs according to age group\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4038\n\n\n\nTable 1. Prevalence of CADRs according to ethnicity \n\n\n\nEthnicity Number, n Percentage, %\nMalay 137 15.9\nChinese 141 16.4\nIndian 9 1.0\nBajau 120 14.0\nDusun 126 14.7\nKadazan 65 7.6\nBugis 65 7.6\nMurut 50 5.8\nTidung 14 1.6\nJawa 12 1.4\nOthers 120 14.0\nTotal 859 100\n\n\n\nTable 2. Prevalence of different CADRs\n\n\n\nTable 4. Drugs causing severe cutaneous adverse reactions \n(SCAR)\n\n\n\nTypes of reaction Number, n Percentage, %\nUrticaria/\t\nAngioedema 421 49.0 \n\n\n\nMaculopapular rash 340 39.6\nDrug-induced \npruritus 47 5.5\n\n\n\nSJS 10 1.2 \nDRESS 6 0.7 \nAGEP 5 0.6\nVesiculobullous \nreaction 4 0.5\n\n\n\nExfoliative \ndermatitis 4 0.5\n\n\n\nErythema \nmultiforme 3 0.3\n\n\n\nSJS-TEN Overlap 2 0.2\nTEN 1 0.1\nOthers 16 1.9\nTotal 859 100.0\n\n\n\nTable 3. Types of drugs causing cutaneous adverse drug \n\n\n\nSJS = Stevens-Johnson syndrome; DRESS = Drug reaction \nwith eosinophilia and systemic symptoms; AGEP = Acute \ngeneralised exanthematous pustulosis; TEN = Toxic epidermal \nnecrolysis; SJS-TEN overlap = Stevens-Johnson syndrome \u2013 \ntoxic epidermal necrolysis overlap\n\n\n\ne) Anti-Hypertensives\n1. Calcium channel \n\n\n\nblocker\n2. Angiotensin-converting \n\n\n\nenzyme inhibitor\n3. Beta blocker\n4. Thiazide diuretic\n\n\n\n18\n8 \n5\n\n\n\n3\n2\n\n\n\n2.1\n0.9\n0.6\n\n\n\n0.3\n0.2\n\n\n\nf) Anti-Convulsants\n1. Phenytoin\n2. Carbamazepine\n3. Benzodiazepine\n4. Gabapentin\n\n\n\n21\n15\n2\n2\n2\n\n\n\n2.4\n1.7\n0.2\n0.2\n0.2\n\n\n\ng) Anti-Gout\n1. Allopurinol\n2. Colchicine\n\n\n\n10\n9\n1\n\n\n\n1.2\n1.1\n0.1\n\n\n\nh) Others\n1. Vitamin & mineral \n\n\n\nsupplement\n2. Topical\n3. Anaesthetic drug\n4. CT Contrast\n5. Steroid\n6. Statin\n7. Proton pump inhibitor\n8. Anti-hyperthyroid\n9. Anti-platelet\n10. Mucolytic\n11. Vaccine\n12. Disease modifying \n\n\n\nantirheumatic drug\n13. Miscellaneous\n\n\n\n89\n8\n\n\n\n7\n6\n6\n5\n4\n4\n3\n3\n3\n2\n2\n\n\n\n36\n\n\n\n10.4\n0.9\n\n\n\n0.8\n0.7\n0.7\n0.6\n0.5\n0.5\n0.3\n0.3\n0.3\n0.2\n0.2\n\n\n\n4.2\n\n\n\nType Drug implicated Number, n\nAGEP Penicillin 3\n\n\n\nCarbamazepine 1\nClopidogrel 1\n\n\n\nDRESS Allopurinol 3\nTrimethoprim/sulfamethoxazole 1\nAnti-tuberculous 1\nPhenytoin 1\n\n\n\nSJS Amoxycillin 2\nPenicillin 1\nCeftriaxone 1\nCefuroxime 1\nPyrazinamide 1\nMefenamic acid 1\nPhenytoin 1\nAllopurinol 1\nErgotamine 1\n\n\n\nTEN Allopurinol 1\nSJS-TEN Phenytoin 1\n\n\n\nErythromycin 1\n\n\n\nAGEP = Acute generalised exanthematous pustulosis ; DRESS \n= Drug reaction with eosinophilia and systemic symptoms ; \nSJS = Stevens-Johnson syndrome; TEN = Toxic epidermal \nnecrolysis; SJS-TEN overlap = Stevens-Johnson syndrome \u2013 \ntoxic epidermal necrolysis overlap\n\n\n\nreactions \n\n\n\nDrug groups Number, n Percentage, %\na) Antibiotics\n\n\n\n1. Penicillin\n2. Cephalosporin\n3. Sulfonamide\n4. Macrolide\n5. Tetracycline\n\n\n\n473\n325\n71\n39\n37\n13\n\n\n\n55.1\n37.8\n8.3\n4.5\n4.3\n1.5\n\n\n\nb) NSAIDs\n1. Diclofenac\n2. Ibuprofen\n3. Mefenamic acid\n\n\n\n241\n89\n85\n48\n\n\n\n28.1\n10.4\n9.9\n5.6\n\n\n\nc) Analgesics\n1. Paracetamol\n2. Opioid\n\n\n\n93\n60\n33\n\n\n\n10.8\n7.0\n3.8\n\n\n\nd) Anti-Histamines\n1. Ranitidine\n2. Chlorphenamine\n\n\n\n32\n15\n10\n\n\n\n3.7\n1.7\n1.2\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 39\n\n\n\nDiscussions\nThe majority of cases reported in this study were \namong the 20-29 years age group. This finding is \ndifferent from a previous study in Malaysia by Talib \net al, who reported an older mean age of 47.0.1 It is \nsimilar to a study in a tertiary centre in India.5 This \ncould be due to under-reporting of adverse drug \nreactions among the elderly population in our setting \nas cases were mainly reported by pharmacists. \nMild skin manifestations may be neglected and \nhence unreported. Under-reporting is a common \nproblem in our country due to uncertainty of type \nof reactions and lack of awareness of adverse drug \nreactions (ADR) reporting system. As high as 81% \nof physicians who suspected ADR did not report it.6 \nFurthermore, our data are collected from hospitals \nwhich may not fully represent the population, as \na significant proportion of adverse reactions from \npublic health clinics may not be reported.\n\n\n\nThe male to female ratio was equal in this study, \nwhich was similar to other studies.1,5 The mean age \ngroup of 36 years is similar to a local study.7 The \nmost common cutaneous manifestation was urticaria \nand or angioedema followed by maculopapular \nrash. This was in discordant with other studies done \nin Johor and Kuala Lumpur tertiary hospitals, with \nthe most common cutaneous manifestations being \nmaculopapular rash.1,7,8 However, a study in Turkey \nshowed a similar result with a predominance of \nurticaria and or angioedema.9 Urticaria is a common \ndisorder worldwide with the lifetime incidence \nof 8.8%.10 Not only due to drugs, urticaria could \nbe caused by underlying infections. About half \nof the patients with acute urticaria were having \ninfections, especially those with upper respiratory \ntract infections, either bacteria or viral and \ngastrointestinal tract infection, such as Helicobacter \npylori infection.11,12 \n\n\n\nCADRs normally occur within hours to days of \ndrug consumption. A detailed drug history, time of \ndrug ingestion and the onset of adverse reactions \nshould be explored in order  to diagnose CADRs. \nIt would be helpful for pharmacists to improve on \nthe knowledge of common morphology of skin \nreactions in order to identify CADRs accurately. The \ndevelopment of CADRs are determined by several \nfactors, include drug dose and frequency, patient\u2019s \nage and gender, underlying disease and allergy, as \nwell as socially related habits such as smoking and \nalcohol.13\n\n\n\nNumerous local and oversea data were compared \n\n\n\nas shown in Table 5. Antibiotics were the most \ncommon culprit drug associated with CADRs across \nthe world, either mild or life threatening, followed \nby NSAIDs, analgesics and anticonvulsants.\n\n\n\nIn this study, antibiotics were the major causative \ndrugs of CADRs (55.1%) which is consistent with \nMalaysian and overseas studies.1,7,8,15 Penicillin, \ncephalosporin, sufonamide and macrolide were \nthe common antibiotics reported. Comparable \nto another study in Malaysia, allopurinol was \nthe main contributor to SCAR.8 There is a strong \nassociation between allopurinol-induced SCARs \nand HLA-B*58:01 allele.16 The prevalence of this \nallele carriers in the ethnically diversed population \nin Malaysia is estimated to be 12.4%. As there \nis no provision to screen for this allele prior to \nthe initiation of allopurinol, due caution must be \npractised in all patients receiving this drug.17\n\n\n\n \nLimitations of study\nAlthough the research has its aims, there were some \nunavoidable limitations. Firstly, the information \nwas retrieved from adverse drug reaction registry \nwhich will be submitted to Malaysian Adverse \nDrug Reactions Advisory Committee (MADRAC). \nTherefore, to generate better and more accurate \nresults, the study should have involved more \npatient interaction during data collection. Secondly, \npharmacists were the main reporters of adverse drug \nreactions based on patient\u2019s description and self \ndiagnosis. Moreover, with the lack of dermatology \nexpertise in district hospitals, the description of skin \nreactions vary and hence less accurate. Thirdly, there \nis lack of information on types of patients, either \ninpatients or clinic attendees.  Finally, we did not \nfollow up on patients with severe cutaneous adverse \nreactions (SCARs) and therefore the outcome and \nmortality rate data is not available. \n\n\n\nConclusion\nIn conclusion, this study described the adverse drug \nreactions (ADRs) at three main hospitals in Sabah, \nwith majority reported as cutaneous manifestations. \nThe most commonly implicated drugs were \nantibiotics and NSAIDs which were similar to \nother local and oversea studies. All ethnic groups \nin Sabah were predisposed. However, this may not \nfully represent the local population due to under-\nreporting. Reporting rate need to be improved by \nincreasing the awareness on the importance of being \ninformed on drugs which commonly cause ADRs \namong the local community. \n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4040\n\n\n\nConflict\tof\tInterest\tDeclaration\t\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the staff of Tawau, \nKeningau and Queen Elizabeth Hospital for their \nassistance in conducting this study. The authors \nwould like to thank the Director General of Health, \nMalaysia for permission to publish this paper.\n\n\n\nReferences\n\n\n\n1. Talib NH, Leelavathi M & Hamzah Z. Common adverse \ncutaneous drug reaction patterns and the causative drugs in \nMalaysia. S Afr Fam Pract 2015;57:227-30.\n\n\n\n2. Turk BG, Gunaydin A, Ertam I, Ozturk G. Adverse \ncutaneous drug reactions among hospitalized patients: \nFive-year surveillance. Cutan Ocul Toxicol 2013;32:41-5.\n\n\n\n3. Hsu DY, Brieva J, Silverberg NB, Silverberg JI. Morbidity \nand Mortality of Stevens-Johnson Syndrome and Toxic \nEpidermal Necrolysis in United States Adults. J Invest \nDermatol 2016;136:1387-97.\n\n\n\n4. Population by States and Ethnic Group. Department of \nInformation, Ministry of Communications and Multimedia, \nMalaysia. 2015. Retrieved 10 March 2018.\n\n\n\n5. Ruchika N, Anita G, and Arif H. Cutaneous adverse drug \nreactions in a tertiary care teaching hospital: A North \nIndian perspective. Int J Appl Basic Med Res 2011;1:50-3.\n\n\n\n6. Aziz Z, Tan CS, Badarudin NS. Reporting of adverse \ndrug reactions: predictors of under-reporting in Malaysia. \nPharmacoepidemiol Drug Saf 2007;16:223-8.\n\n\n\n7. Choon SE, Lai NM. An epidemiological and clinical \nanalysis of cutaneous adverse drug reactions seen in a \ntertiary hospital in Johor, Malaysia. Indian J Dermatol \nVenereol Leprol 2012;78:734\u20139.\n\n\n\n8. Ding WY, Lee CK, Choon SE. Cutaneous adverse drug \nreactions seen in a tertiary hospital in Johor, Malaysia. Int \nJ Dermatol 2010;49:834-41.\n\n\n\n9. Akpinar F, Dervis E. Drug eruptions: an 8-year study \nincluding 106 in patients at a dermatology clinic in Turkey. \nIndian J Dermatol 2012;57:194\u20138.\n\n\n\nTable 5. Comparison table of CADRs among different populations 1,5,7,14\n\n\n\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\tCountry/\t\t \n                                       State\nTypes of drugs\n\n\n\nMalaysia India China\nSabah Kuala Lumpur Johor\n\n\n\nAntibiotics 55.1% 36.6% 40.3% 48.3% 29.2%\nNSAIDs 28.1% - 9.9% 21.9% -\nAnalgesics 10.8% 13.4% - - 17.1%\nAnti-Histamines 3.7% - - - -\nAnti-Convulsants 2.4% - 22.4% 13.2% 26%\nAnti-Hypertensives 2.1% 10.4% - - -\nTraditional & complementary \nmedicine\n\n\n\n- 17.9% - - 2.2%\n\n\n\nAnti-Gout 1.2% - 13.8% - 11%\nAnti-Rheumatics - - 2.7% - -\nAntacids - - - - 5.8%\nCombination - - - 4.39% -\nAnaesthetics - - - - 3%\nOthers - 7.4% - 8.79% -\n\n\n\n10. Zuberbier T, Balke M, Worm M, Edenharter G, Maurer M. \nEpidemiology of urticaria: a representative cross-sectional \npopulation survey. Clin Exp Dermatol 2010;35:869-73.\n\n\n\n11. Liu TH, Lin YR, Yang KC, Chou CC, Chang YJ, Wu \nHP. First attack of acute urticaria in pediatric emergency \ndepartment. Pediatr Neonatol 2008;49:58\u201364.\n\n\n\n12. Imran M, Qazi M. Chronic idiopathic urticaria, \ngastrointestinal symptoms and Helicobacter pylori \ninfection. JPAD 2008;18:207-11. \n\n\n\n13. Abubakar AR, Simbak N, Haque M. Adverse Drug \nReactions: Predisposing Factors, Modern Classifications \nand Causality Assessment. Research J Pharm Tech  \n2014;7:1091-8.\n\n\n\n14. Deng Q, Fang X, Zeng Q, Lu J, Jing C, Huang J.  Severe \ncutaneous adverse drug reactions of Chinese inpatients: a \nmeta-analysis. An Bras Dermatol 2017;92:345-9.\n\n\n\n15. Tejas KP, Sejal HT, Sharma DC. Cutaneous adverse drug \nreactions in Indian population: A systematic review. IDOJ \n2014;5:76-86.\n\n\n\n16. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang \nHP et al. HLA-B 5801 allele as a genetic marker for severe \ncutaneous adverse reactions caused by allopurinol. Proc \nNatl Acad Sci USA 2005;102:4134-9. \n\n\n\n17. Chong HY, Lim YH, Prawjaeng J, Tassaneevakul W, \nMohamed Z, Chaiyakunapruk N. Cost-effectiveness \nanalysis of HLA-B*58:01 genetic testing before \ninitiation of allopurinol therapy to prevent allopurinol-\ninduced Stevens\u2013Johnson syndrome/toxic epidermal \nnecrolysis in a Malaysian population. Pharmacogenet \nGenomics 2018;28:56-67.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 41\n\n\n\nORIGINAL ARTICLE\n\n\n\nLeprosy in Pregnancy: A Case Series in 4 Dermatology Clinics in \nMalaysia \nKen Chen Loh1, MRCP, Min Moon Tang1, AdvMDerm, Wooi Chiang Tan2,3, AdvMDerm, Lee Chin Chan2, MMed, Sook \nYee Michelle Voo4, AdvMDerm, Suganthi Thevarajah1, MMed\n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia \n2Department of Dermatology, Hospital Pulau Pinang, Georgetown, Penang, Malaysia\n3Department of Dermatology, Hospital Sultanah Bahiyah, Alor Setar, Kedah, Malaysia\n4Department of Dermatology, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia\n\n\n\nAbstract  \nIntroduction\nManagement of leprosy in pregnancy is challenging. Here we aim to describe the clinical characteristics \nand the management of leprosy in pregnancy.  \n\n\n\nMethods\nThis is a retrospective study on pregnant women with leprosy managed in the Department of \nDermatology in Hospital Kuala Lumpur, Hospital Pulau Pinang, Hospital Sultanah Bahiyah and \nHospital Queen Elizabeth between 1994 and 2015.\n\n\n\nResults\nThere were ten patients with 12 pregnancies with a median age of 27.5 years (range: 16-33).  Five \nwere foreigners. There were four cases of lepromatous leprosy, two cases of borderline lepromatous, \ntwo cases borderline tuberculoid leprosy and one case each for tuberculoid and mid borderline leprosy.  \nSeven pregnancies (58%) were documented to have reactions.  Four reversal reactions (33%), three \nerythema nodusom leprosum (25%) and two Lucio\u2019s phenomenon (17%) were documented. Both \npatients with Lucio\u2019s phenomenon had undiagnosed leprosy and presented with preterm labour, \nanemia, oligohydramnios and intrauterine growth restriction. Mortality was recorded in one patient \ndue to dapsone induced hypersensitivity syndrome complicated with septicaemia. All patients were \nprescribed multidrug therapy but in three pregnancies, the patients chose to defer the treatment. There \nwas a spontaneous miscarriage at second trimester and a case of early neonatal death.  The neonatal \ncomplications recorded for the 10 live deliveries were low birth weight, jaundice and clofazimine-\ninduced hyperpigmentation.\n\n\n\nConclusion\nThe majority of our patients with leprosy had complications throughout the pregnancies. Early \ndetection and prompt treatment can prevent unfavorable fetal outcome & threatened maternal health. \n\n\n\nKey words: Leprosy, Pregnancy, Eyrthema nodusom leprosum, Lucio\u2019s phenomenon, Reversal reactions\n\n\n\nCorresponding Author\nDr Loh Ken Chen\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586\nEmail: kenchenloh@yahoo.com\n\n\n\nIntroduction\nLeprosy or Hansen\u2019s disease is a chronic infectious \ndisease caused by Mycobacterium leprae which \nprimarily affects the skin and nerves. Women \nare described as cases of \u201ctriple jeopardy\u201d in \nleprosy as they are discriminated because of their \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4042\n\n\n\ngender, the disabilities that can result from leprosy \nand the societal stigmatization.1 In 2016 WHO \nweekly epidemiology report (WER) stated that \nthe proportions of females affected by leprosy \nwere ranging between 22.5% and 54.4% of all \nnew cases globally.2 In Malaysia, 35.7% of the \nnew cases detected in 2016 were female patients.2 \nThe percentage of females affected by leprosy was \nregularly monitored and analyzed by WHO in order \nto understand the access to leprosy services for \nwomen and the possible effects of discrimination \nagainst women with leprosy.2 There is lack of \nscientific evidence that men are more prone to \nleprosy compared to women. Risk of leprosy \ntransmission is higher within households through \ncontact.3,4 Hence, females affected by leprosy are \nan important potential source of infection to other \nfamily members including children if not detected \nand treated early. An audit among 271 children with \nleprosy (aged less than 15 years) in Ethiopia showed \nthat 53% of the children had a relative with leprosy. \nThe likelihood for the mother of these children \nhaving active leprosy was greater especially if the \nchildren developed leprosy at a much younger age.5\n\n\n\nPregnancy in women with leprosy may lead to \nserious repercussions. Leprosy affects every phase \nof pregnancy including the puerperium and lactating \nperiod.5 It may manifest for the first time during \npregnancy. In addition, relapses of leprosy during \npregnancy have been reported predominantly in the \nthird trimester. Pregnant women with leprosy are \nvulnerable to serious complications from the disease. \nPregnancy induces a state of immunological changes \nwhich may lead to worsening of leprosy in the mother \nand precipitation of leprae reactions.6-8 Without \nprompt treatment, the damage to the skin, nerves, \nlimbs, and eyes can have serious consequences.  \n\n\n\nIn addition, the placenta and its functions are \naffected in pregnant women with leprosy9 resulting \nin premature babies with low birth weight. \nMycobacterium leprae has been isolated from the \nbreast milk of mothers with untreated lepromatous \nleprosy.10 About 5% of children whose mothers \nhad active lepromatous leprosy developed leprosy \nbefore the age of two.11 In another review, 16% of \nadolescents whose mothers had leprosy developed \nindeterminate leprosy at puberty. Therefore, it is \nimportant to manage leprosy aggressively in women \nmore so when they are pregnant. Here we describe \na case series of patients with leprosy in pregnancy \nin Malaysia.\n\n\n\nMaterials & Methods\nThis is a retrospective study of all cases of leprosy \nwith pregnancy treated at the Dermatology Clinics \nof Hospital Kuala Lumpur, Hospital Pulau Pinang, \nHospital Sultanah Bahiyah and Hospital Queen \nElizabeth between 1994 and 2015.\n\n\n\nResults\nThere was a total of ten patients with 12 pregnancies \nencountered.  There were two patients with two \npregnancies while on treatment.  The median age of \nthe patient at the time of pregnancy was 27.5 years \nold (range 16-34). There were five Malaysians, \nfour Indonesians and one Burmese. Among all the \nMalaysians, there were four Malays and one from \nan indigenous tribe. The majority of the cases (70%) \nwere from Hospital Kuala Lumpur.\n\n\n\nIn term of Ridley-jopling classification, there were \nfour cases of Lepromatous leprosy (LL), two cases \nof Borderline lepromatous (BL) and Bsorderline \nTuberculoid (BT), one case of Mid borderline (BB) \nand Tuberculoid leprosy (TT) respectively. The \nmean bacteriologic index was 2.4 ranging from \n0-4.7. \n\n\n\nFour patients were diagnosed as having leprosy \nat second trimester of gestation and three at third \ntrimester of gestation. Another four pregnancies \noccurred after the leprosy was diagnosed. Of note, \nfour patients had the symptoms of leprosy at least \none year before the pregnancy and yet were not \ncaptured or diagnosed.  \n\n\n\nAll patients were prescribed multidrug therapy but \nin three pregnancies, patients deferred the treatment.  \nSix patients received the Sungai Buloh Augmented \nregime and three patients took the WHO regime.  One \npatient chose to defer her treatment in her second \npregnancy as she had spontaneous miscarriage at \nsecond trimester while taking multidrug therapy \n(Table 1, Patient 4).  \n\n\n\nSeven pregnancies (58%) were documented to have \nleprae reactions; four reversal reactions (33%), \nthree erythema nodusom leprosum (25%) and two \nLucio\u2019s phenomenon (17%). Interestingly, two cases \nof Lucio\u2019s phenomenon had concurrent erythema \nnodusum leprosum which is rarely reported in the \nliterature. We detected 3 (30%) of the patients had \nWHO Grade 2 deformity which is defined as visible \ndeformity or damage present due to leprosy.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 43\n\n\n\nThe two lepromatous leprosy patients who \npresented with Lucio\u2019s phenomenon shared many \nsimilarities in their clinical characteristics. Both \npatients had have signs and symptoms of leprosy \nthat went undiagnosed about three years before \ntheir pregnancy.  They were only diagnosed at \n3rd trimester of pregnancy when they presented \nwith severe Lucio\u2019s phenomenon, concurrent \nerythema nodusum leprosum and WHO grade 2 \ndeformity. They were both started on systemic \nsteroid and multidrug therapy. Their pregnancies \nwere also complicated with preterm labour, anemia, \noligohydramnios and intrauterine growth restriction. \nThey underwent emergency caesarean sections due \nthe severe oligohydramnios (Table1, Patient 9 and \n10). They were both started on systemic steroid \nand multidrug therapy after diagnosis. On contact \nscreening, patient 9 had a 9-year-old child who was \nsubsequently diagnosed with tuberculoid leprosy.  \nTheir newborns have not been diagnosed with \nleprosy to date.\n\n\n\nThere was a mortality in our cohort. This was a \n21-year-old Indonesian, gravida 2 (table 1, patient \n6) who was diagnosed with borderline lepromatous \nleprosy in her second trimester of pregnancy. WHO \nmultidrug regime was initiated without delay. \nHowever, she presented with exfoliative dermatitis, \nfever, profound jaundice at 27 weeks of gestation \n(6 weeks after initiation of MDT).  Laboratory \ninvestigations revealed severe hemolytic anemia \n(Hemoglobin: 6.6g/dL; reticulocytes count:12.8 \n%), raised white cell count (13x109/L); normal \nplatelet count (317x109/L); normal eosinophil \ncount (0 x109/L); raised creatinine (124mol/L); \nelevated alanine transferase (116u/L) and alkaline \nphosphatase (306u/L); markedly raised direct \nbilirubin (326mol/L); raised indirect bilirubin \n(101mol/L); and a  prolonged coagulation profile \n(INR=4.28). Peripheral blood film revealed \nincreased polychromasia with spherocytosis \nsuggestive of hemolysis. Hepatitis B, Hepatitis C \nand Human Immunodeficiency Virus (HIV) serology \nwere negative. Her subsequent blood culture grew \nAcinetobacter sp. Ultrasound of the hepatobiliary \nsystem revealed no obstructive features in the \nbiliary tract. She was suspected to have dapsone \ninduced hypersensitivity syndrome complicated \nby septicaemia. She was started on intravenous \nhydrocortisone and antibiotics which included \nceftriaxone, later meropenem and piperacillin-\nsulbactam. She had premature delivery on the third \nday of admission. The birth weight of the newborn \nwas 850g. Unfortunately, the baby passed away \n\n\n\nafter one day due to severe prematurity. The mother \neventually succumbed at day nine of admission \ndespite of aggressive treatment and vigorous \nresuscitation.\n\n\n\nIn total there was one miscarriage and three preterm \ndeliveries in the 12 pregnancies. Neonatal jaundice \nwas noted in one newborn. Another newborn had \nclofazimine-induced hyperpigmentation which \nresolved on follow up. No congenital malformations \nwere detected among the newborns. However, \ninformation for most of the infants was lacking \nand incomplete. Some of the adverse events of \nleprosy treatments during pregnancy reported were \nfever, nausea, vomiting, lethargy, new peripheral \nneuropathy and worsening of reversal reactions.\n\n\n\nDiscussion\nThe relationship between leprosy and pregnancy is \ntortuous. There are only a handful of case series12-16 \ndescribing the effect of pregnancy on leprosy \nas shown in Table 2. Most of them had adverse \nconsequences not only during the pregnancies, but \nduring post-partum and lactation as well. Multidrug \ntherapy consisting of rifampicin, clofazimine and \ndapsone, is considered safe in pregnancy. However, \nit does come with side effects that need stringent \nmonitoring. Furthermore, the neonates and infants \nof mother with leprosy are susceptible to morbidity \ntoo. Children born to mothers with leprosy are at \nhigher risk of acquiring leprosy when they grow \nolder. \n\n\n\nPregnancy is known to cause a relative decrease \nin cellular immunity especially in third trimester, \nwhich enables the organism M. leprae to \nproliferate.6   Thus, symptoms of leprosy are more \nsevere during pregnancy. Case studies have shown \nneuritis especially silent neuritis affects almost \nhalf of the pregnant women with leprosy.6-8 Studies \nhave shown lepra reactions can be triggered by \npregnancy due to variations in cell mediated and \nhumoral immunity. Both types of reactions can \ncontinue long into lactation.6-8 In our cohort, 58% \nof patients developed reactions.  Type 1 reaction \n(reversal reaction) typically occurred post partum6, \nbut all our four patients who had reversal reactions \ndeveloped the symptoms in their early pregnancy.  \nClassically erythema nodosum leprosum peaks \nduring late pregnancy6, but one of our patients (Table \n1, Patient 8) had ENL from the pre-pregnancy stage \nthat continued into her early pregnancy before she \ndefaulted.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4044\n\n\n\nTa\nbl\n\n\n\ne \n1.\n\n\n\n C\nha\n\n\n\nra\nct\n\n\n\ner\nis\n\n\n\ntic\ns o\n\n\n\nf t\nen\n\n\n\n p\nre\n\n\n\ngn\nan\n\n\n\nt p\nat\n\n\n\nie\nnt\n\n\n\ns w\nith\n\n\n\n le\npr\n\n\n\nos\ny\n\n\n\nN\no\n\n\n\nA\nge\n\n\n\n(y\nea\n\n\n\nrs\n)\n\n\n\nN\nat\n\n\n\nio\nna\n\n\n\nlit\ny\n\n\n\n\tC\nla\nss\nifi\nca\ntio\nn\t\nof\n\t\n\n\n\nL\nep\n\n\n\nro\nsy\n\n\n\nB\nas\n\n\n\nel\nin\n\n\n\ne \nSl\n\n\n\nit \nsk\n\n\n\nin\n sm\n\n\n\nea\nr\n\n\n\nG\nra\n\n\n\nvi\nda\n\n\n\nD\nia\n\n\n\ngn\nos\n\n\n\nis\n o\n\n\n\nf L\nep\n\n\n\nro\nsy\n\n\n\n in\n \n\n\n\nre\nla\n\n\n\ntio\nn \n\n\n\nw\nith\n\n\n\n te\nrm\n\n\n\ns o\nf \n\n\n\nth\ne \n\n\n\npr\neg\n\n\n\nna\nnc\n\n\n\ny\n\n\n\nD\nur\n\n\n\nat\nio\n\n\n\nn \nof\n\n\n\n le\npr\n\n\n\nos\ny \n\n\n\nSy\nm\n\n\n\npt\nom\n\n\n\ns \nbe\n\n\n\nfo\nre\n\n\n\n \npr\n\n\n\neg\nna\n\n\n\nnc\ny\n\n\n\nL\nep\n\n\n\nro\nsy\n\n\n\n tr\nea\n\n\n\ntm\nen\n\n\n\nts\n \n\n\n\ndu\nri\n\n\n\nng\n p\n\n\n\nre\ngn\n\n\n\nan\ncy\n\n\n\nR\nea\n\n\n\nct\nio\n\n\n\nns\n \n\n\n\ndu\nri\n\n\n\nng\n \n\n\n\npr\neg\n\n\n\nna\nnc\n\n\n\ny\n\n\n\nM\nat\n\n\n\ner\nna\n\n\n\nl \nO\n\n\n\nut\nco\n\n\n\nm\ne \n\n\n\nFe\nta\n\n\n\nl \nO\n\n\n\nut\nco\n\n\n\nm\ne\n\n\n\nN\neo\n\n\n\nna\nta\n\n\n\nl \nC\n\n\n\nom\npl\n\n\n\nic\nat\n\n\n\nio\nns\n\n\n\nB\nI\n\n\n\nM\nI\n\n\n\n1.\n33\n\n\n\nIn\ndo\n\n\n\nne\nsi\n\n\n\nan\nTT\n\n\n\n0\n0\n\n\n\nG\n4 \n\n\n\nP2\n+1\n\n\n\n2nd\n  t\n\n\n\nrim\nes\n\n\n\nte\nr\n\n\n\n1 \nye\n\n\n\nar\nW\n\n\n\nH\nO\n\n\n\n P\nB\n\n\n\n re\ngi\n\n\n\nm\ne \n\n\n\n6 \nm\n\n\n\non\nth\n\n\n\ns\nN\n\n\n\no \nA\n\n\n\nliv\ne\n\n\n\nTe\nrm\n\n\n\n B\nab\n\n\n\ny \nN\n\n\n\n/A\n\n\n\n2.\n \n\n\n\n32\nM\n\n\n\nal\nay\n\n\n\nsi\nan\n\n\n\nB\nT\n\n\n\n0\n0\n\n\n\nG\n8 \n\n\n\nP7\n2nd\n\n\n\n  t\nrim\n\n\n\nes\nte\n\n\n\nr  \n2 \n\n\n\nye\nar\n\n\n\ns\nSg\n\n\n\n B\nul\n\n\n\nuh\n \n\n\n\nA\nug\n\n\n\nm\nen\n\n\n\nte\nd \n\n\n\nre\ngi\n\n\n\nm\ne\n\n\n\nR\nev\n\n\n\ner\nsa\n\n\n\nl\nA\n\n\n\nliv\ne\n\n\n\nTe\nrm\n\n\n\n  B\nab\n\n\n\ny \nN\n\n\n\n/A\n\n\n\n34\nG\n\n\n\n9 \nP8\n\n\n\nPr\neg\n\n\n\nna\nnt\n\n\n\n d\nur\n\n\n\nin\ng\n\n\n\ntre\nat\n\n\n\nm\nen\n\n\n\nt \n-\n\n\n\nSg\n B\n\n\n\nul\nuh\n\n\n\n \nA\n\n\n\nug\nm\n\n\n\nen\nte\n\n\n\nd \nre\n\n\n\ngi\nm\n\n\n\ne\nR\n\n\n\nev\ner\n\n\n\nsa\nl\n\n\n\nA\nliv\n\n\n\ne\nTe\n\n\n\nrm\n  B\n\n\n\nab\ny\n\n\n\nN\n/A\n\n\n\n3.\n27\n\n\n\nM\nal\n\n\n\nay\nsi\n\n\n\nan\nB\n\n\n\nT\n0.\n\n\n\n9\n0\n\n\n\nG\n1 \n\n\n\nP0\n2nd\n\n\n\n tr\nim\n\n\n\nes\nte\n\n\n\nr\nN\n\n\n\nA\nW\n\n\n\nH\nO\n\n\n\n M\nB\n\n\n\n re\ngi\n\n\n\nm\ne \n\n\n\n12\n m\n\n\n\non\nth\n\n\n\ns\nR\n\n\n\nev\ner\n\n\n\nsa\nl\n\n\n\nA\nliv\n\n\n\ne\nTe\n\n\n\nrm\n B\n\n\n\nab\ny \n\n\n\nC\nlo\n\n\n\nfa\nza\n\n\n\nm\nin\n\n\n\ne \n\u2013i\n\n\n\nnd\nuc\n\n\n\ned\n \n\n\n\nhy\npe\n\n\n\nrp\nig\n\n\n\nm\nen\n\n\n\nta\ntio\n\n\n\nn\n, N\n\n\n\neo\nna\n\n\n\nta\nl J\n\n\n\nau\nnd\n\n\n\nic\ne \n\n\n\n4\n26\n\n\n\nIn\ndo\n\n\n\nne\nsi\n\n\n\nan\nB\n\n\n\nB\n2.\n\n\n\n3\n0.\n\n\n\n9\nG\n\n\n\n1 \nP0\n\n\n\n2nd\n tr\n\n\n\nim\nes\n\n\n\nte\nr\n\n\n\nN\nA\n\n\n\nSg\n B\n\n\n\nul\nuh\n\n\n\n \nA\n\n\n\nug\nm\n\n\n\nen\nte\n\n\n\nd \nre\n\n\n\ngi\nm\n\n\n\ne\nR\n\n\n\nev\ner\n\n\n\nsa\nl \n\n\n\nA\nliv\n\n\n\ne\nA\n\n\n\nbo\nrti\n\n\n\non\n-\n\n\n\n27\nG\n\n\n\n2 \nP0\n\n\n\n+1\nPr\n\n\n\neg\nna\n\n\n\nnt\n d\n\n\n\nur\nin\n\n\n\ng \ntre\n\n\n\nat\nm\n\n\n\nen\nt\n\n\n\n-\nD\n\n\n\nef\ner\n\n\n\nre\nd \n\n\n\ntre\nat\n\n\n\nm\nen\n\n\n\nt\nN\n\n\n\no\nA\n\n\n\nliv\ne\n\n\n\nTe\nrm\n\n\n\n, L\nB\n\n\n\nW\n \n\n\n\nba\nby\n\n\n\n (1\n.8\n\n\n\nkg\n)\n\n\n\nN\no\n\n\n\n5.\n16\n\n\n\nM\nal\n\n\n\nay\nsi\n\n\n\nan\nB\n\n\n\nL\n3.\n\n\n\n2\n5.\n\n\n\n0\nG\n\n\n\n2 \nP1\n\n\n\nPr\neg\n\n\n\nna\nnt\n\n\n\n d\nur\n\n\n\nin\ng \n\n\n\ntre\nat\n\n\n\nm\nen\n\n\n\nt\n-\n\n\n\nD\nef\n\n\n\ner\nre\n\n\n\nd \ntre\n\n\n\nat\nm\n\n\n\nen\nt \n\n\n\nN\no \n\n\n\nA\nliv\n\n\n\ne\nTe\n\n\n\nrm\n B\n\n\n\nab\ny \n\n\n\nN\n/A\n\n\n\n6\n21\n\n\n\nIn\ndo\n\n\n\nne\nsi\n\n\n\nan\n   \n\n\n\nB\nL \n\n\n\n3.\n5\n\n\n\n2.\n5\n\n\n\nG\n2 \n\n\n\nP1\n1s\n\n\n\nt  t\nrim\n\n\n\nes\nte\n\n\n\nr\n 6\n\n\n\n m\non\n\n\n\nth\ns\n\n\n\nW\nH\n\n\n\nO\n M\n\n\n\nB\n re\n\n\n\ngi\nm\n\n\n\ne \n12\n\n\n\n m\non\n\n\n\nth\ns \n\n\n\n N\no \n\n\n\nD\nec\n\n\n\nea\nse\n\n\n\nd \nPr\n\n\n\net\ner\n\n\n\nm\n , \n\n\n\nLB\nW\n\n\n\n b\nab\n\n\n\ny \n( \n\n\n\n0.\n85\n\n\n\n k\ng \n\n\n\n ) \n\n\n\n D\nec\n\n\n\nea\nse\n\n\n\nd \naf\n\n\n\nte\nr 1\n\n\n\n d\nay\n\n\n\n7.\n28\n\n\n\nB\nur\n\n\n\nm\nes\n\n\n\ne\nLL\n\n\n\n2.\n6\n\n\n\n0\nG\n\n\n\n2 \nP0\n\n\n\n+1\nPr\n\n\n\neg\nna\n\n\n\nnt\n d\n\n\n\nur\nin\n\n\n\ng \ntre\n\n\n\nat\nm\n\n\n\nen\nt\n\n\n\n-\nD\n\n\n\nef\ner\n\n\n\nre\nd \n\n\n\ntre\nat\n\n\n\nm\nen\n\n\n\nt\nN\n\n\n\no \nA\n\n\n\nliv\ne\n\n\n\nTe\nrm\n\n\n\n B\nab\n\n\n\ny \nN\n\n\n\n/A\n\n\n\n8.\n31\n\n\n\nIn\ndo\n\n\n\nne\nsi\n\n\n\nan\nLL\n\n\n\n4.\n7\n\n\n\n4.\n6\n\n\n\nG\n4 \n\n\n\nP3\n3rd\n\n\n\n  t\nrim\n\n\n\nes\nte\n\n\n\nr\nN\n\n\n\nA\nSg\n\n\n\n B\nul\n\n\n\nuh\n \n\n\n\nA\nug\n\n\n\nm\nen\n\n\n\nte\nd \n\n\n\nre\ngi\n\n\n\nm\ne\n\n\n\nEN\nL\n\n\n\nA\nliv\n\n\n\ne\nTe\n\n\n\nrm\n B\n\n\n\nab\ny \n\n\n\nN\n/A\n\n\n\n\n\n\n\n9.\n31\n\n\n\nM\nal\n\n\n\nay\nsi\n\n\n\nan\nLL\n\n\n\n2.\n3\n\n\n\n4.\n8\n\n\n\nG\n5 \n\n\n\nP3\n+1\n\n\n\n3rd\n tr\n\n\n\nim\nes\n\n\n\nte\nr  \n\n\n\n3 \nye\n\n\n\nar\ns\n\n\n\nSg\n B\n\n\n\nul\nuh\n\n\n\n \nA\n\n\n\nug\nm\n\n\n\nen\nte\n\n\n\nd \nre\n\n\n\ngi\nm\n\n\n\ne\nLu\n\n\n\nci\no\u2019\n\n\n\ns \nph\n\n\n\nen\nom\n\n\n\nen\non\n\n\n\n \nan\n\n\n\nd \nEN\n\n\n\nL\n\n\n\nA\nliv\n\n\n\ne\nPr\n\n\n\net\ner\n\n\n\nm\n,  \n\n\n\nLB\nW\n\n\n\n b\nab\n\n\n\ny \n \n\n\n\n(1\n.9\n\n\n\nkg\n )\n\n\n\n N\no\n\n\n\n10\n.\n\n\n\n23\nM\n\n\n\nal\nay\n\n\n\nsi\nan\n\n\n\nLL\n4.\n\n\n\n5\n0.\n\n\n\n7\nG\n\n\n\n2 \nP1\n\n\n\n \n3rd\n\n\n\n tr\nim\n\n\n\nes\nte\n\n\n\nr  \n3 \n\n\n\nye\nar\n\n\n\ns\nSg\n\n\n\n B\nul\n\n\n\nuh\n \n\n\n\nA\nug\n\n\n\nm\nen\n\n\n\nte\nd \n\n\n\nre\ngi\n\n\n\nm\ne\n\n\n\nLu\nci\n\n\n\no\u2019\ns \n\n\n\nph\nen\n\n\n\nom\nen\n\n\n\non\nan\n\n\n\nd \nEN\n\n\n\nL\n\n\n\nA\nliv\n\n\n\ne\nPr\n\n\n\net\ner\n\n\n\nm\n , \n\n\n\nLB\nW\n\n\n\n b\nab\n\n\n\ny \n(2\n\n\n\n.2\nkg\n\n\n\n ) \n\n\n\n N\no\n\n\n\nTT\n \u2013\n\n\n\n tu\nbe\n\n\n\nrc\nul\n\n\n\noi\nd \n\n\n\nle\npr\n\n\n\nos\ny;\n\n\n\n B\nT \n\n\n\n\u2013 \nbo\n\n\n\nrd\ner\n\n\n\nlin\ne t\n\n\n\nub\ner\n\n\n\ncu\nlo\n\n\n\nid\n le\n\n\n\npr\nos\n\n\n\ny;\n B\n\n\n\nB\n \u2013\n\n\n\n m\nid\n\n\n\n b\nor\n\n\n\nde\nrli\n\n\n\nne\n le\n\n\n\npr\nos\n\n\n\ny;\n B\n\n\n\nL \n\u2013 \n\n\n\nbo\nrd\n\n\n\ner\nlin\n\n\n\ne l\nep\n\n\n\nro\nm\n\n\n\nat\nou\n\n\n\ns l\nep\n\n\n\nro\nsy\n\n\n\n; L\nL \n\n\n\n\u2013 \nle\n\n\n\npr\nom\n\n\n\nat\nou\n\n\n\ns l\nep\n\n\n\nro\nsy\n\n\n\n;  \nLB\n\n\n\nW\n- L\n\n\n\now\n b\n\n\n\nirt\nh \n\n\n\nw\nei\n\n\n\ngh\nt; \n\n\n\nEN\nL \n\n\n\n\u2013 \nEr\n\n\n\nyt\nhe\n\n\n\nm\na  \n\n\n\nN\nod\n\n\n\nus\num\n\n\n\n L\nep\n\n\n\nro\nsu\n\n\n\nm\n; N\n\n\n\n/A\n \u2013\n\n\n\n D\nat\n\n\n\na \nno\n\n\n\nt a\nva\n\n\n\nila\nbl\n\n\n\ne;\n W\n\n\n\nH\nO\n\n\n\n P\nB\n\n\n\n re\ngi\n\n\n\nm\ne \n\n\n\n\u2013 \nW\n\n\n\nor\nld\n\n\n\n H\nea\n\n\n\nlth\n O\n\n\n\nrg\nan\n\n\n\nis\nat\n\n\n\nio\nn \n\n\n\n P\nau\n\n\n\nci\nba\n\n\n\nci\nlla\n\n\n\nry\n  r\n\n\n\neg\nim\n\n\n\ne;\n W\n\n\n\nH\nO\n\n\n\n M\nB\n\n\n\n re\ngi\n\n\n\nm\ne \n\n\n\n-  \nW\n\n\n\nor\nld\n\n\n\n H\nea\n\n\n\nlth\n O\n\n\n\nrg\nan\n\n\n\nis\nat\n\n\n\nio\nn \n\n\n\nM\nul\n\n\n\ntib\nac\n\n\n\nill\nar\n\n\n\ny \nre\n\n\n\ngi\nm\n\n\n\ne \n  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 45\n\n\n\nTa\nbl\n\n\n\ne \n2.\n\n\n\n L\nite\n\n\n\nra\ntu\n\n\n\nre\n re\n\n\n\nvi\new\n\n\n\n o\nn \n\n\n\nca\nse\n\n\n\n se\nrie\n\n\n\ns o\nf l\n\n\n\nep\nro\n\n\n\nsy\n in\n\n\n\n p\nre\n\n\n\ngn\nan\n\n\n\nt w\nom\n\n\n\nen\n fr\n\n\n\nom\n d\n\n\n\niff\ner\n\n\n\nen\nt c\n\n\n\nou\nnt\n\n\n\nrie\ns  \n\n\n\nA\nut\n\n\n\nho\nr, \n\n\n\nye\nar\n\n\n\nC\nou\n\n\n\nnt\nry\n\n\n\nN\no \n\n\n\nof\n p\n\n\n\nre\ngn\n\n\n\nan\nt \n\n\n\nw\nom\n\n\n\nen\n st\n\n\n\nud\nie\n\n\n\nd\nN\n\n\n\no \nof\n\n\n\n p\nre\n\n\n\ngn\nan\n\n\n\nci\nes\n\n\n\n%\n o\n\n\n\nf w\nom\n\n\n\nen\n w\n\n\n\nith\n \n\n\n\nle\npr\n\n\n\nom\nat\n\n\n\nou\ns l\n\n\n\nep\nro\n\n\n\nsy\nIm\n\n\n\npo\nrt\nan\nt\tfi\nnd\nin\ngs\n\n\n\nK\nin\n\n\n\ng \net\n\n\n\n a\nl12\n\n\n\n, 1\n95\n\n\n\n8\nU\n\n\n\nni\nte\n\n\n\nd \nSt\n\n\n\nat\ne\n\n\n\n26\n52\n\n\n\n10\n0\n\n\n\n\u2022\t\n78\n\n\n\n%\n o\n\n\n\nf p\nre\n\n\n\ngn\nan\n\n\n\nci\nes\n\n\n\n w\nith\n\n\n\n u\nnt\n\n\n\nre\nat\n\n\n\ned\n le\n\n\n\npr\nos\n\n\n\ny \nha\n\n\n\nd \ndi\n\n\n\nse\nas\n\n\n\ne \nag\n\n\n\ngr\nav\n\n\n\nat\nio\n\n\n\nn \nve\n\n\n\nrs\nus\n\n\n\n o\nnl\n\n\n\ny \n21\n\n\n\n.7\n%\n\n\n\n o\nf \n\n\n\npr\neg\n\n\n\nna\nnc\n\n\n\nie\ns h\n\n\n\nad\n d\n\n\n\nis\nea\n\n\n\nse\n p\n\n\n\nro\ngr\n\n\n\nes\nsi\n\n\n\non\n w\n\n\n\nhe\nn \n\n\n\nth\ney\n\n\n\n w\ner\n\n\n\ne \ntre\n\n\n\nat\ned\n\n\n\n w\nith\n\n\n\n su\nlfo\n\n\n\nne\n d\n\n\n\nru\ngs\n\n\n\n.\nH\n\n\n\nar\nda\n\n\n\ns e\nt a\n\n\n\nl13\n, 1\n\n\n\n97\n2\n\n\n\nIn\ndi\n\n\n\na\n59\n\n\n\nEa\nch\n\n\n\n ra\nng\n\n\n\ned\n fr\n\n\n\nom\n \n\n\n\n3-\n17\n\n\n\nN\nA\n\n\n\n\u2022\t\n61\n\n\n\n%\n (3\n\n\n\n6 \nof\n\n\n\n 5\n9 \n\n\n\nw\nom\n\n\n\nen\n) d\n\n\n\nev\nel\n\n\n\nop\ned\n\n\n\n fi\nrs\n\n\n\nt s\nym\n\n\n\npt\nom\n\n\n\ns o\nf l\n\n\n\nep\nro\n\n\n\nsy\n d\n\n\n\nur\nin\n\n\n\ng \npu\n\n\n\ner\npe\n\n\n\nriu\nm\n\n\n\n, 1\n5.\n\n\n\n2%\n d\n\n\n\nur\nin\n\n\n\ng \nla\n\n\n\nct\nat\n\n\n\nio\nna\n\n\n\nl a\nm\n\n\n\nen\nor\n\n\n\nrh\noe\n\n\n\na,\n 1\n\n\n\n0.\n1%\n\n\n\n d\nur\n\n\n\nin\ng \n\n\n\npr\neg\n\n\n\nna\nnc\n\n\n\ny.\n\n\n\nD\nun\n\n\n\nca\nn \n\n\n\net\n a\n\n\n\nl14\n,1\n\n\n\n5 , \n19\n\n\n\n81\n &\n\n\n\n 1\n98\n\n\n\n2\nEt\n\n\n\nhi\nop\n\n\n\nia\n11\n\n\n\n4\n11\n\n\n\n9\n28\n\n\n\n.1\n\u2022\t\n\n\n\nIn\ncr\n\n\n\nea\nse\n\n\n\nd \nle\n\n\n\npr\nos\n\n\n\ny \nac\n\n\n\ntiv\nity\n\n\n\n in\n 4\n\n\n\n9.\n4%\n\n\n\n o\nf w\n\n\n\nom\nen\n\n\n\n d\nur\n\n\n\nin\ng \n\n\n\npr\neg\n\n\n\nna\nnc\n\n\n\ny\n\u2022\t\n\n\n\nA\nbo\n\n\n\nut\n 4\n\n\n\n8%\n o\n\n\n\nf w\nom\n\n\n\nen\n w\n\n\n\nith\n \u201c\n\n\n\ncu\nre\n\n\n\nd\u201d\n tu\n\n\n\nbe\nrc\n\n\n\nul\noi\n\n\n\nd \nle\n\n\n\npr\nos\n\n\n\ny \nre\n\n\n\nla\nps\n\n\n\ned\n w\n\n\n\nith\n n\n\n\n\new\n le\n\n\n\nsi\non\n\n\n\ns o\nr n\n\n\n\ner\nve\n\n\n\n \nda\n\n\n\nm\nag\n\n\n\ne.\n \n\n\n\n\u2022\t\n50\n\n\n\n%\n o\n\n\n\nf R\nR\n\n\n\n o\ncc\n\n\n\nur\nre\n\n\n\nd \ndu\n\n\n\nrin\ng \n\n\n\nfir\nst\n\n\n\n 6\n m\n\n\n\non\nth\n\n\n\ns o\nf l\n\n\n\nac\nta\n\n\n\ntio\nn\n\n\n\n\u2022\t\n68\n\n\n\n%\n o\n\n\n\nf E\nN\n\n\n\nL \noc\n\n\n\ncu\nrr\n\n\n\ned\n d\n\n\n\nur\nin\n\n\n\ng \nth\n\n\n\nird\n tr\n\n\n\nim\nes\n\n\n\nte\nr o\n\n\n\nf p\nre\n\n\n\ngn\nan\n\n\n\ncy\n o\n\n\n\nr t\nhe\n\n\n\n fi\nrs\n\n\n\nt 6\n m\n\n\n\non\nth\n\n\n\ns o\nf l\n\n\n\nac\nta\n\n\n\ntio\nn\n\n\n\nN\nog\n\n\n\nue\nira\n\n\n\n e\nt a\n\n\n\nl16\n, 2\n\n\n\n01\n5\n\n\n\nB\nra\n\n\n\nzi\nl\n\n\n\n49\n49\n\n\n\nN\nA\n\n\n\n\u2022\t\nSy\n\n\n\nm\npt\n\n\n\nom\ns o\n\n\n\nf l\nep\n\n\n\nro\nsy\n\n\n\n o\ncc\n\n\n\nur\nre\n\n\n\nd \nin\n\n\n\n th\ne \n\n\n\nla\nst\n\n\n\n tr\nim\n\n\n\nes\nte\n\n\n\nr o\nf p\n\n\n\nre\ngn\n\n\n\nan\ncy\n\n\n\n in\n 3\n\n\n\n6.\n3%\n\n\n\n\u2022\t\n22\n\n\n\n.3\n%\n\n\n\n o\nf c\n\n\n\nas\nes\n\n\n\n w\nith\n\n\n\n lo\nw\n\n\n\n b\nirt\n\n\n\nh \nw\n\n\n\nei\ngh\n\n\n\nt n\new\n\n\n\nbo\nrn\n\n\n\n (<\n2k\n\n\n\ng)\n\u2022\t\n\n\n\n18\n.6\n\n\n\n%\n w\n\n\n\nith\n le\n\n\n\npr\nae\n\n\n\n re\nac\n\n\n\ntio\nns\n\n\n\n\u2022\t\n5.\n\n\n\n5%\n h\n\n\n\nad\n re\n\n\n\nla\nps\n\n\n\ne \nof\n\n\n\n le\npr\n\n\n\nos\ny\n\n\n\nLo\nh \n\n\n\net\n a\n\n\n\nl, \n20\n\n\n\n18\nM\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n10\n12\n\n\n\n40\n\u2022\t\n\n\n\n58\n.3\n\n\n\n%\n o\n\n\n\nf t\nhe\n\n\n\n w\nom\n\n\n\nen\n h\n\n\n\nad\n le\n\n\n\npr\nos\n\n\n\ny \ndi\n\n\n\nag\nno\n\n\n\nse\nd \n\n\n\ndu\nrin\n\n\n\ng \npr\n\n\n\neg\nna\n\n\n\nnc\nie\n\n\n\ns\n\u2022\t\n\n\n\n20\n%\n\n\n\n o\nf t\n\n\n\nhe\n p\n\n\n\nat\nie\n\n\n\nnt\ns d\n\n\n\nev\nel\n\n\n\nop\ned\n\n\n\n E\nN\n\n\n\nL \nan\n\n\n\nd \nLP\n\n\n\n\u2022\t\nO\n\n\n\nne\n m\n\n\n\nat\ner\n\n\n\nna\nl m\n\n\n\nor\nta\n\n\n\nlit\ny \n\n\n\ndu\ne \n\n\n\nto\n d\n\n\n\nap\nso\n\n\n\nne\n in\n\n\n\ndu\nce\n\n\n\nd \ndr\n\n\n\nug\n h\n\n\n\nyp\ner\n\n\n\nse\nns\n\n\n\niti\nvi\n\n\n\nty\n sy\n\n\n\nnd\nro\n\n\n\nm\ne \n\n\n\nco\nm\n\n\n\npl\nic\n\n\n\nat\ned\n\n\n\n \nw\n\n\n\nith\n se\n\n\n\nps\nis\n\n\n\nR\nR\n\n\n\n- r\nev\n\n\n\ner\nsa\n\n\n\nl r\nea\n\n\n\nct\nio\n\n\n\nn,\n E\n\n\n\nN\nL-\n\n\n\n e\nry\n\n\n\nth\nem\n\n\n\na \nno\n\n\n\ndo\nsu\n\n\n\nm\n le\n\n\n\npr\nos\n\n\n\num\n, L\n\n\n\nP-\n L\n\n\n\nuc\nio\n\n\n\n\u2019s\n p\n\n\n\nhe\nno\n\n\n\nm\nen\n\n\n\non\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4046\n\n\n\nLucio\u2019s phenomenon (LP) is an occlusive condition \nof small vessels in dermis caused by invasion of \nendothelial cells by Mycobacterium leprae.17 It \nis characterized by irregularly shaped purpuric \nor necrotic macules or plaques with sharply \nmarginated serrated borders.18 The mortality \nrate of LP is high.19 Pregnancy is a well-known \npredisposing factor of LP due to a thrombophilic \nand immunosuppressive state.19,20 Both  our patients \nwith LP were successfully treated with Sungai \nBuluh Augmented Multidrug therapy and systemic \ncorticosteroids. Benard G et al21 had reported a rare \ncase of a pregnant lady with concurrent ENL and \nLucio\u2019s phenomenon in 2009, which also occurred \nin two of our patients (Table 1, Patient 9 and 10). \nLucio\u2019s phenomenon and ENL arise from different \npathogenetic mechanisms.21 ENL is the result of an \nimmune complex mediated reaction whereas LP \nis due to invasion of endothelial cells by bacilli.  \nHowever, necrotic ENL can sometimes mimic LP \nin clinical presentation. There are several distinctive \nhistopathological and clinical features in both \nentities.17,21,22 This distinction is important because \na decrease in bacillary load through multidrug \ntherapy is the main target in LP, whereas in ENL, \nconcomitant reduction of the reaction by means of \nhigh-dose steroids is recommended.\n\n\n\nOf note, four patients had the symptoms of leprosy \nat least one year before pregnancy including the two \npatients with LP.  Delay in diagnosis for leprosy is \na common problem worldwide.23 Common reasons \nidentified included patients\u2019 ignorance to the \nsymptoms and misdiagnosis by doctors due to low \nawareness of the disease.24-27 Although Malaysia \nhas achieved the WHO target of elimination of \nleprosy as a public health problem to less than a \ncase per 10,000 population in 1994, new cases of \nleprosy continued to be detected every year. Hence, \nthe continuous training of primary care doctors to \nimprove their diagnostic skills is needed.  Vigilant \ncontact tracing, early detection and treatment may \nprevent all the sequelae.\n\n\n\nBabies of mothers with leprosy especially in the \nlepromatous leprosy pole are associated with lower \nbirth weight, smaller placentae, developmental \ndelay, more infections and higher infant mortality.11,28 \nThree low birth weight babies (27%) were born in \nour cohort. Congenital leprosy was well described \nby Duncan et al in 1983.11 The postulated routes \nof transmission include skin-to-skin contact, \nthrough breast milk, inhalation of droplets or \ntransplacentally.11 None of the babies born in our \n\n\n\ncohort had congenital leprosy at their mothers\u2019 last \nvisit. Another study reported 16% of adolescent \nwith leprous mothers developed leprosy at puberty.28 \nThus continuous follow up and screening of the \nchildren whose mothers have leprosy is vital.\n\n\n\nThe benefits of treating leprosy during pregnancy \nfar outweigh the risks of the medications. Since \n1998, WHO has recommended that the standard \nregime which consists of rifampicin, dapsone and \nclofazamine is safe and not teratogenic.29 Therefore, \nthis standard regime should be continued unchanged \nduring pregnancy. Dapsone may however cause \nhemolytic anemia in the mother or baby. In \naddition, it may cause dapsone hypersensitivity \nsyndrome which is a severe adverse drug reaction. \nThis syndrome may lead to mortality as shown in \npatient 6 in our cohort. As a result, very stringent \nmonitoring of the blood count and the liver function \ntest with the interval of weekly at the beginning \nis mandatory. Immediate cessation of dapsone is \nimperative should hemolytic anemia and dapsone \nhypersensitivity syndrome develop. Clofazamine \ncauses reversible skin discoloration in the fetus.16,30 \nDrugs such as quinolones and minocycline should be \navoided in pregnancy.  For babies born to untreated \nmulti-bacillary mothers, a different handling \nprotocol is recommended.  Newborns should be \nisolated until morphological index of the mother \nreaches zero. Furthermore, the direct latching mode \nof breastfeeding is not encouraged.29,30\n\n\n\nBefore the era of MDT, it was found that the mortality \nrate for lepromatous patients was four times more as \ncompared with the general population.31 Leprosy is \noften not considered a direct cause of death. However, \nleprosy patients are exposed to increase mortality \nrisks due to its indirect effects.  A study in Brazil \nreported the burden of leprosy deaths was higher \nfor lepromatous leprosy, among males, elderly, the \nblack race and in leprosy-endemic regions.32 Rocha \net al in 2016 reported significant mortality rates in \nLucio\u2019s phenomenon and mostly associated with \npregnancy and secondary infection.19 The mortality \ncase in our cohort had borderline lepromatous \nleprosy. She had unfortunately developed severe \ndapsone hypersensitivity reaction complicated \nwith hemolytic anemia and septicaemia. The \nidiosyncratic drug hypersensitivity reaction resulted \nin an adverse outcome to the fetus and the mother.\n\n\n\nThere is always considerable anxiety among the \npregnant women and clinicians with regards to \nthe effect of MDT to the fetus, as demonstrated in \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 47\n\n\n\n8. Fatola CO, Venyo AK, Venyo LK, Maloney DJL. Leprosy \nin pregnancy \u2013 a review of the literature. HMJ 2015;8:83-\n96.  \n\n\n\n9. Duncan ME, Fox H, Harkness RA, Rees RJ. The placenta \nin leprosy. Placenta 1983;5:189-98.\n\n\n\n10. Girdhar A, Girdhar BK, Ramu G, Desikan KV. Discharge \nof M leprae in milk of leprosy patients. Lepr India \n1981;53:590-4.\n\n\n\n11. Duncan ME, Melsom R, Pearson JM, Menzel S, Barnetson \nRS. A clinical and immunological study of four babies \nof mothers with lepromatous leprosy, two of whom \ndeveloped leprosy in infancy. Int J Lepr Other Mycobact \nDis 1983;51:7-17.\n\n\n\n12. King JA, Marks RA. Pregnancy and leprosy; a review of \n52 pregnancies in 26 patients with leprosy. Am J Obstet \nGynecol 1958;76:436-42.\n\n\n\n13. Hardas U, Survey R, Chakrawarti D. Leprosy in \ngynecology and obstetrics. Int J Lepr Other Mycobact Dis \n1972;40:399-401.\n\n\n\n14. Duncan ME, Melsom R. Pearson JM, Ridley DS. The \nassociation of pregnancy and leprosy. I. New cases, relapse \nof cured patients and deterioration in patients on treatment \nduring pregnancy and lactation--results of a prospective \nstudy of 154 pregnancies in 147 Ethiopian women. Lepr \nRev 1981;52:245-62.\n\n\n\n15. Duncan ME, Pearson JM, Ridley DS, Melsom R, Bjune \nG. Pregnancy and leprosy: the consequences of alterations \nof cell-mediated and humoral immunity during pregnancy \nand lactation. Int J Lepr Other Mycobact Dis 1982;50:525-\n35.\n\n\n\n16. Nogueira PS, Moura ER, Dias AA, Am\u00e9rico CF, Aguiar \nLR, Valente MM. Characteristics of pregnant and lactating \nwomen with leprosy. Rev Soc Bras Med Trop 2015;48:96-\n8.\n\n\n\n17. Vargas-Ocampo F. Diffuse leprosy of Lucio and Latapi: a \nhistologic study. Lepr Rev 2007;78:248-60.\n\n\n\n18. Rea TH, Levan NE. Lucio\u2019s phenomenon and diffuse \nnonnodular lepromatous leprosy. Arch Dermatol \n1978;114:1023-8.\n\n\n\n19. Rocha RH, Emerich PS, Diniz LM, Oliveira MB, Cabral \nAN, Amaral AC. Lucio\u2019s phenomenon: exuberant case \nreport and review of Brazilian cases. An Bras Dermatol \n2016;91:60-3.\n\n\n\n20. Aranegui B, Abalde T, Pe\u00f3n G, Alvarez-\u00c1lvarez C, de \nla Torre C. Lucio\u2019s phenomenon after childbirth. Int J \nDermatol 2014;53:127-9.\n\n\n\n21. Benard G, Sakai-Valente NY, Bianconcini Trindade MA. \nConcomitant lucio phenomenon and erythema nodosum in \na leprosy patient: clues for their distinct pathogeneses. Am \nJ Dermatopathol 2009;31:288-92.\n\n\n\n22. Helmer KA, Fleischfresser I, Kucharski-Esmanhoto \nLD, Neto JF, Santamaria JR. The Lucio\u2019s phenomenon \n(necrotizing erythema) in pregnancy. An Bras Dermatol \n2004;79:205\u201310.\n\n\n\n23. Henry M, GalAn N, Teasdale K, Prado R, Amar H, Rays \nMS et al. Factors Contributing to the Delay in Diagnosis \nand Continued Transmission of Leprosy in Brazil--An \nExplorative, Quantitative, Questionnaire Based Study. \nPLoS Negl Trop Dis 2016;10:e0004542.  \n\n\n\n24. Lockwood DN, Reid AJ. The diagnosis of leprosy is \ndelayed in the United Kingdom. QJM 2001;94:207-12.\n\n\n\n25. Chen XS, Li WZ, Jiang C, Ye GY. Leprosy in China: \ndelay in the detection of cases. Ann Trop Med Parasitol \n2000;94:181-6.\n\n\n\none of our patients (Table 1, Patient 4) who had \nan abortion while taking MDT, and she adamantly \nrefused treatment during her next pregnancy. In \naddition, a lack of understanding about the disease \nand its complications will certainly affect the \ncompliance.  Therefore, proper counselling is crucial \nto convince mothers with leprosy to complete their \ntreatment. Home visits must be made immediately \nwhen patient defaults follow up. Another method is \ndirect observed therapy similar to the treatment for \ntuberculosis. A responsible person like community \nvolunteer or a family member should be involved to \nsupervise the treatment of the patient at home.  This \nis called Accompanied MDT.34    \n\n\n\n\n\n\n\nConclusion\nOur review showed that majority of mothers with \nleprosy had severe reactions, neonatal complications. \nRegrettably one third of them had already developed \npermanent WHO Grade 2 deformity at presentation. \nNearly 40% had symptoms of leprosy undiagnosed \nat least 1 year before pregnancy. Therefore, early \ndetection and early treatment is the key to prevent \nunfavorable fetal outcome and threatened maternal \nhealth.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nWe would like to thank to our Director General of \nHealth Malaysia for his permission to publish the \nstudy.\n\n\n\nReferences\n\n\n\n1. Griffey H. Triple jeopardy: tackling the discrimination \nfacing girls and women with leprosy. Geneva: ILEP; 2015.\n\n\n\n2. WHO. Global leprosy update 2015: time for action, \naccountability and inclusion. WER 2016;91:405-20.\n\n\n\n3. Moet FJ, Meima A, Oskam L, Richardus JH. Risk factors \nfor the development of clinical leprosy among contacts, \nand their relevance for targeted interventions. Lepr Rev \n2004;75:310-26.\n\n\n\n4. Bratschi MW. Steinmann P, Wickenden A, Gillis TP. \nCurrent knowledge on Mycobacterium leprae transmission: \na systematic literature review. Lepr Rev 2015;66:142-55.\n\n\n\n5. Duncan ME. Leprosy. Disease of Children in the Subtropics \nand Tropics. (Edited by Stanfield P et al), page 553. Edward \nArnold. London, 1991.\n\n\n\n6. Duncan ME. An historical and clinical review of the \ninteraction of leprosy and pregnancy: a cycle to be broken. \nSoc Sci Med 1993;37:457-72.\n\n\n\n7. Lockwood DN, Sinha HH. Pregnancy and leprosy: a \ncomprehensive literature review. Int J Lepr Other Mycobact \nDis 1999;67:6-12.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4048\n\n\n\n26. Zhang F, Chen S, Sun Y, Chu T. Healthcare seeking behavior \nand delay in diagnosis of leprosy in a low endemic area of \nChina. Lepr Rev 2009;80:416-23.\n\n\n\n27. Deps PD, Guedes BV, Bucker Filho J, Andreatta MK, \nMarcari RS, Rodrigues LC. Delay in the diagnosis of \nleprosy in the Metropolitan Region of Vit\u03ccria, Brazil. Lepr \nRev 2006;77:41-7.\n\n\n\n28. Duncan ME, Miko T, Howe R, Hansen S, Menzel S, \nMelsom R et al. Growth and development of children of \nmothers with leprosy and healthy controls. Ethiop Med J \n2007;45:9-23. \n\n\n\n29. WHO. Model Prescribing. Information. Drugs Used in \nLeprosy. Geneva. 1998.\n\n\n\n30. Ozturk Z, Tatliparmak A. Leprosy treatment during \npregnancy and breastfeeding: A case report and brief \nreview of literature. Dermatol Ther 2017;30:1-2.\n\n\n\n31. Guinto RS, Doull JA, De Guia L. Mortality of persons \nwith leprosy prior to sulfone therapy, Cordova and Talisay, \nCebu, Philippines. Int J Lepr 1954;22:273-84\n\n\n\n32. Martins-Melo FR, Assun\u00e7\u00e3o-Ramos AV, Ramos AN Jr, \nAlencar CH, Montenegro RM Jr , Wand Del-Rey de \nOliveira ML, Heukelbach J. Leprosy-related mortality in \nBrazil: a neglected condition of a neglected disease. Trans \nR Soc Trop Med Hyg 2015;109:643-52.\n\n\n\n33. Chen XS, Li WZ, Jiang C, Ye GY. Leprosy in China: \ndelay in the detection of cases. Ann Trop Med Parasitol \n2000;94:181-8.\n\n\n\n34. World  Health Organization Regional Office South East \nAsia. Enhanced global strategy for further reducing the \ndisease burden due to leprosy (2011\u20132015) Operational \nguidelines (updated) SEA-GLP-2009.4. New Delhi, India; \n2009. Available from: http://www.searo.who.int/entity/\nglobal_leprosy_programme/documents/enhanced_global_\nstrategy_2011_2015_operational_guidelines.pdf.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 49\n\n\n\nIntroduction\nCongenital melanocytic naevus (CMN) is a benign \nproliferation of melanocytic naevus cells that is \npresent at birth or develops shortly after birth.  \nGiant congenital melanocytic naevus (GCMN) is \ndefined as predicted diameter greater than 20cm \nby adulthood, commonly occurs in newborns in \napproximately 1in 20 000 live births.\n\n\n\nA variety of malignancies have been reported to arise \nwithin congenital melanocytic nevi, most commonly \nmalignant melanoma, but rarely rhabdomyosarcoma, \nliposarcoma, and malignant peripheral nerve sheath \ntumor as well. Neurocutaneous melanocytosis is a \nrare condition characterized by the proliferation of \nmelanocytes in the central nervous system (brain \nand spinal cord) in presence of a CMN and its \nestimation of 5-10% of people with GCMN.\n\n\n\nThere have been seven documented cases of \nrhabdomyosarcoma developing within congenital \nmelanocytic nevi, one of which was associated with \nneurocutaneous melanosis.1-3 We report a newborn \nwith rhabdomyosarcoma arising within a giant \ncongenital melanocytic nevus and associated with \nneurocutaneous melanosis. \n\n\n\nCASE REPORT\n\n\n\nRhabdomyosarcoma Arising in A Giant Congenital Melanocytic \nNevus \nSabeera Begum1, MMed, Sheau Szu Heah1, MRCPCH, Kin Fon Leong1, MRCPCH, Bang Rom Lee2, MPath \n\n\n\n1Paediatric Dermatology Unit, Paediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Department of Pathology, Hospital Serdang, Kajang, Selangor\n\n\n\nSummary\nA variety of malignancies have been documented to arise within congenital melanocytic nevi (CMNs). \nAlthough the most frequent malignancy arising within a CMN is melanoma, the association between \nrhabdomyosarcoma and CMN has rarely been documented. We report a 4-month-old girl presented \nwith ulcerated nodule overlying a giant CMN at the posterior back that exhibited rapid growth. \nBiopsy of the nodule revealed embryonal rhabdomyosarcoma in association with CMN. She received \nchemotherapy with vincristine and actinomycin D. This the first case of rhabdomyosarcoma associated \nwith giant CMN reported in our local setting. Clinicians must consider rhabdomyosarcoma as one of \nthe differential diagnosis in patients presenting with ulcerated nodules on giant CMN. \n\n\n\nKey words: Rhabdomyosarcoma, Giant congenital melanocytic nevus, Malignant transformation\n\n\n\nCorresponding Author\nDr Sabeera Begum\nPaediatric Dermatology Unit, Paediatric Institute, \nHospital Kuala Lumpur, Jalan Pahang, \n50586 Kuala Lumpur, Malaysia\nEmail: dr_sabeera@yahoo.com\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4050\n\n\n\nCase Report  \nA full term female infant was born with giant \nCMN, covering the whole of lower back extending \nanteriorly to the abdomen, buttock and both lower \nthighs, described as bathing trunk naevus. There \nwere numerous hyperpigmented satellite nevi of \nvariable size over the face, upper chest, upper back \nand bilateral extremities. Also noted an ulcerated \nnodule measuring 5cm X 6cm over the left lower \nback at birth, which rapidly increased in size into a \nfungating mass as shown in figure 1a. \n\n\n\nShe was thriving well and other systemic \nexaminations were normal with normal \nneurodevelopment milestone. The ulcerated mass \nwas excised and histopathological examination \nshowed a lesion with two distinct components. \nBeneath an ulcerated epidermis, there was an \nexpansile hypercellular proliferation of pleomorphic \ncells within a fibromyxoid stroma in the dermis \n\n\n\nand sub- cutaneous tissue (Figure 1b). Most of the \nneoplastic cells were spindled with hyperchromatic \nnuclei. In some areas of the tumor, they were oval \nto round with abundant eosinophilic cytoplasm \nand eccentric nuclei (Figure 1c). Some had cross-\nstriations characteristic of rhabdomyoblasts. \nNumerous abnormal mitotic figures were identified. \nThese cells were strongly immunoreactive for \ndesmin and myogenin (Figure 1d). They were \nnegative for S-100 protein and HMB-45.\n \nMRI of brain showed increase melanin patches over \nthe left cerebellum consistent with neurocutaneous \nmelanosis. Computed tomography scans of the \nchest, abdomen, and pelvis showed no evidence \nof metastatic disease. Bone marrow aspiration was \nnegative for tumour cell. She received chemotherapy \nconsisting vincristine and Actinomycin D in 3 \nblocks.  She tolerated chemotherapy and remained \nwell at 6 months follow-up.\n\n\n\nFigure 1. (a) Note the large, ulcerated and fleshy fungating tumour over left lumbar region of the back measured 6cm x 5cm with minimal \ncontact bleeding. Also note the giant congenital melanocytic naevus with satellite lesions over the upper back; (b) Histopathological \nexamination (H&E) x 100 shows superficial dermis is composed of irregular nests of larger melanocytic cells closer to the dermoepidermoal \njunction containing coarse melanin pigments; (c) H&E x 600 magnification shows a large part of the lesion is infiltrated and replaced by \nmalignant spindle shaped cells seen arranged either loosely or compact cellular pattern with mitotic figures; (d) Immunohistochemical \nstudies x 600 magnification shows tumour cells are strongly immunoreactive to Desmin and Myogenin but negative to S100, HMB45, \nCaldesmon and Cytokeratin\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 51\n\n\n\nDiscussion \nCongenital melanocytic nevi are cutaneous mal-\ndevelopmental lesions of the ectoderm, specifically \nthe neural crest. There is evidence the CMNs arise as \na result of an oncogenic mutation, most commonly \ninvolving NRAS, occurring in a melanoblast or \nneural crest precursor cell before its migration \nalong the dorsolateral pathway to the skin.1-2 These \nlesions are commonly characterized according to \nthe greatest predicted diameter they may attain in \nadulthood as small (<1.5 cm), medium (1.5\u201320 cm), \nlarge (>20 cm), and giant (occupying a significant \nproportion of the cutaneous surface).1-2 \n\n\n\nCongenital giant melanocytic nevi may occur in \nassociation with leptomeningeal melanocytosis, a \nrelated neural crest maldevelopmental abnormality.3 \n\n\n\nThis lethal condition is characterized by a benign \nor malignant melanocytic proliferation in the \ncentral nervous system in association with a giant \ncongenital melanocytic nevus. \n\n\n\nMalignant melanoma is the most frequent neoplasm \ncomplicating giant congenital melanocytic nevi, \nwith a reported incidence of 2% to 13%.4-6 Other \nmalignancies have been reported include malignant \nmelanoma with rhabdomyoblastic differentiation, \nsarcoma with liposarcomatous and rhabdomyoblastic \ndifferentiation, rhabdomyosarcoma, and malignant \nperipheral nerve sheath tumor.8-9 There have \nbeen only seven previously documented cases of \nrhabdomyosarcoma originating from congenital \nmelanocytic nevi3,5,7-11 as summarized in table 1.\n\n\n\nTable 1. Summary of the clinical, histology and outcome of seven cases previously reported with rhabdomyosarcoma originating from \ncongenital melanocytic nevi\n\n\n\nAuthors Age at presentation Site Rhabdomyo-sarcoma sub-type Treatment & Outcome \nChristman et al 4 months old Bathing suit \n\n\n\ndistribution\nEmbryonal Chemotherapy & alive at 6 years follow-up \n\n\n\nHoung et al 4 years old Left gluteal & sacral Embryonal Refused chemotherapy, died 13 months after \ndiagnosis\n\n\n\nZuriga et al Newborn Post neck & upper \nback\n\n\n\nEmbryonal Had leptomeningeal melanosis Chemotherapy, \ndied at Day 30 of life\n\n\n\nSchmidt et al 7 months old Trunk & thigh Embryonal Chemotherapy, alive at 1-year follow-up\nHendrikson et al 7 months old Left cheek & scalp Mixed with liposarcoma Chemotherapy, alive at 3-years follow-up\nChikhalkar et al 21 years old Gluteal and sacral Alveolar Chemotherapy died 1 month after diagnosis\nIlyas et al 4 months old Bathing suit \n\n\n\ndistribution\nEmbryonal Chemotherapy, alive at 1-year follow-up\n\n\n\nHistologically, giant CMN demonstrate mixtures \nof tissues derived from the neural crest that show \nmelanocytic and occasionally neural supportive \ndifferentiation5. It is likely that the common \npluripotent stem or neural crest cells from which \nthese elements are derived cause these combined \nfeatures. \n\n\n\nReports of proliferating mesenchymal elements \nwithin CMN are rare, which might suggest that the \nculprit oncogenic mutations occur in more primitive \nprecursor or stem cells before their differentiation \ninto a melanoblast. \n\n\n\nConclusion\nRhabdomyosarcoma is a rare tumour associated \nwith congenital melanocytic naevus, nevertheless, \nclinicians should consider rhabdomyosarcoma in \nthe differential diagnosis of lesions arising within \nthe nevus.\n\n\n\nConflict\tof\tInterest\tDeclaration \nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement \nThe authors would like to thank to our Director \nGeneral of Health Malaysia for his permission to \npublish the study.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4052\n\n\n\nReference \n\n\n\n1. Barnhill RL, Cerroni L, Cook M, Elder DE, Kerl H, LeBoit \nPE et al. State of the art, nomenclature, and points of \nconsensus and controversy concerning benign melanocytic \nlesions: outcome of an international workshop. Adv Anat \nPathol 2010;17:73\u201390.\n\n\n\n2. Kinsler VA, Thomas AC, Ishida M, Bulstrode NW, \nLoughlin S, Hing S et al. Multiple congenital melanocytic \nnevi and neurocutaneous melanosis are caused by \npostzygotic mutations in codon 61 of NRAS. J Invest \nDermatol 2013;133:2229\u201336. \n\n\n\n3. Hoang MP, Sinkre P, Albores-Saavedra J. \nRhabdomyosarcoma arising in a congenital melanocytic \nnevus. Am J Dermatopathol 2002;24:26\u20139. \n\n\n\n4. Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart \nRS. Large congenital melanocytic nevi and the risk for \ndevelopment of malignant melanoma and neurocutaneous \nmelanocytosis. Pediatrics 2000;106:736\u201341. \n\n\n\n5. Hendrickson MR, Ross JC. Neoplasms arising in congenital \ngiant nevi: morphologic study of seven cases and a review \nof the literature. Am J Surg Pathol 1981;5:109\u201335. \n\n\n\n6. Reed WB, Becker SW Sr, Becker SW Jr, Nickel WR. \nGiant pigmented nevi, melanoma, and leptomeningeal \nmelanocytosis: a clinical and histopathological study. Arch \nDermatol 1965;91:100\u201319. \n\n\n\n7. Zuniga S, Las Heras J, Benveniste S. Rhabdomyosarcoma \narising in a congenital giant nevus associated with \nneurocutaneous melanosis in a neonate. J Pediatr Surg \n1987;22:1036\u20138. \n\n\n\n8. Schmitt FC, Bittencourt A, Mendonca N, Dorea M. \nRhabdomyosarcoma in a congenital pigmented nevus. \nPediatr Pathol 1992;12:93\u20138. \n\n\n\n9. Ilyas EN, Goldsmith K, Lintner R, Manders SM. \nRhabdomyosarcoma arising in a giant congenital \nmelanocytic nevus. Cutis 2004;73:39\u201343. \n\n\n\n10. Chikhalkar S, Gutte R, Holmukhe S, Khopkar U, Desai S, \nGupta S. Alveolar rhabdomyosarcoma arising in a giant \ncongenital melanocytic nevus in an adult case report with \nreview of literature. Int J Dermatol 2013;52:1372\u20135. \n\n\n\n11. Christman MP, Kerner JK, Cheng C, Piris A, Nepo AG, \nSepehr A et al.  Rhabdomyosarcoma arising in a congenital \nmelanocytic nevus. Pediatr Dermatology 2014;31:584\u20137.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 53\n\n\n\nCASE REPORT\n\n\n\nDiagnostic Biopsy Site in Cutaneous Angiosarcoma: Reflections \nfrom 3 Cases \nFatimah Zanirah Nordin1, MBBS, Adawiyah Jamil1, AdvMDerm, Low Dy Win1, MRCP, Norli Marwyne Mohammed \nNoor2, AdvMDerm, Norazirah Md Nor1, AdvMDerm, Lee Bang Rom3, MPath\n\n\n\n1Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia\n2Department of Dermatology, Hospital Sungai Buloh, Sg Buloh, Selangor, Malaysia\n3Pantai Premier Pathology, Gleneagles Kuala Lumpur, Malaysia\n\n\n\nSummary\nAngiosarcoma is a rare, malignant vascular endothelium neoplasm with poor prognosis. Cutaneous \nangiosarcoma makes up a majority of its presentation. Diagnosis is often delayed due to the nature of \nits clinical presentation. We report 3 cases of cutaneous angiosarcoma to focus on the importance of \nbiopsy site selection in securing the histopathological diagnosis. \n\n\n\nKey words: Angiosarcoma, Soft tissue sarcoma, Radiotherapy, Skin biopsy\n\n\n\nCorresponding Author\nAssociate Prof Adawiyah Jamil\nDepartment of Medicine, \nUniversity Kebangsaan Malaysia Medical Centre, \nBandar Tun Razak, Cheras, \n56000 Kuala Lumpur, Malaysia \nEmail: adda_jamil@yahoo.com\n\n\n\nIntroduction\nAngiosarcoma is a rare and aggressive malignancy \nof the blood or lymphatic endothelium. It accounts \nfor about 3.9%-5% of all soft tissue sarcomas,1,2 \n15% of the soft tissue sarcomas located in the head \nand neck3 and 1.6% of all cutaneous soft tissue \nsarcomas.4 Angiosarcoma occurs at anywhere but it \nhas a predilection for the head and neck.3,4,5 The skin \nis a common site of angiosarcoma presentation.2,6 \nThere are 3 types of cutaneous angiosarcomas: \nprimary sporadic, post-radiation, and chronic \nlymphedema-associated angiosarcoma. \n\n\n\nCutaneous angiosarcoma classically present as \npurpuric, ecchymotic or erythematous swelling, \npatches or plaques that may look benign initially. \nEarly diagnosis of cutaneous angiosarcoma based \non clinical features alone is challenging as it can \nmimic other conditions like ecchymoses, rosacea, \nvasculitis and cellulitis. Tissue biopsy is important \nin establishing the diagnosis and the biopsy site \naffects the histopathological yield. Inconclusive \nhistopathology will further delay the diagnosis and \ntreatment of patients. In this report, we demonstrate \nthe importance of the correct biopsy site and \nrecommend the best site for biopsy. Three cases of \ncutaneous angiosarcoma diagnosed in our center \nfrom 2007 to 2017 are presented.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4054\n\n\n\nCase 1 \nA 78-year-old Chinese man with transglottic \nlaryngeal squamous cells carcinoma presented with \na 3 weeks history of blood stained secretions from \nhis tracheostomy stoma. Total laryngectomy was \nperformed for the T3N0M0 laryngeal carcinoma \nabout 2 years ago, the surgery was followed by \nradiotherapy. He has been well since completion \nof his cancer treatment. He noticed a rash on his \nchest 2 months prior to his bleeding tracheostomy \nstoma. The rash was asymptomatic but spread \nrapidly. He was a chronic smoker and had type 2 \ndiabetes mellitus, hypertension, and dyslipidemia. \n\n\n\nOn examination, blood stained secretions and small \nblood clots were observed at the stoma. There were \npurpuric plaques, papules and nodules surrounding \nthe stoma, extending to his upper anterior chest. \nThe lesions were non-tender, the larger nodules \nand plaques were fluctuant while the papules were \nfirm. Telangiectatic patches were seen especially \nat the edges of the abnormal skin area on the \nchest (Figure 1A & 1B). Computed tomography \n(CT) scan of neck, thorax, and abdomen showed \na left posterior cervical mass with matted cervical \nlymphadenopathy measuring 6.0x 4.8x 7.0 cm.\n\n\n\nFigure 1A & 1B. Multiple purpuric plaques, nodules and papules with telangiectatic patches on the anterior chest. A: site of the first \nbiopsy. B: site of the repeat biopsy\n\n\n\nPunch biopsy was performed on a well formed \npurpuric patch, unfortunately it did not reveal \nany specific abnormality. A second biopsy was \nthen performed at a purpuric, fluctuant nodule. It \nshowed intradermal proliferation of atypical plump \nepithelioid endothelial cells with hyperchromatic \nnuclei and moderate amount of granular eosinophilic \ncytoplasm. The atypical cells formed indiscernible \nvascular spaces containing few red blood cells. \nMitoses were easily seen. Chronic inflammatory \ncells with scattered melanophages were seen \ninterspersed throughout the specimen. The deeper \ndermis displayed areas of hemorrhage and solar \nelastosis (Figure 2). The atypical cells were diffusely \npositive to CD31, focally positive to CD34 and \nnegative to CKAE1/AE3 and S100.  The findings \nwere consistent with angiosarcoma. Treatment \nwith radiotherapy stopped the bleeding from the \ntracheostomy stoma. The patient did not return for \nfollow up after completion of radiotherapy.\n\n\n\nFigure 2. Irregular dilated vascular channels lined by plump \nendothelial cells with hyperchromatic and pleomorphic nuclei \n(H&E x 40)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 55\n\n\n\nCase 2\nAn 82-year-old Malay man presented with swelling \nand redness of his left face of 3 months duration. \nIt was thought to occur following an insect bite on \nhis left pinna, the swelling later spread to forehead, \norbital and cheek. He was treated with cloxacillin for \nchronic left perichondritis and preseptal cellulitis, \nhowever the lesion persisted. His co-morbidities \nincluded hypertension, gouty arthritis, lumbar \nspondylolisthesis and chronic kidney disease. \nOn examination, there was a large, non-tender, \nindurated, erythematous plaque involving the left \nretro-auricular region extending to the pinna, left \ntemple, cheek and periorbital area with marked \neyelid oedema (Figure 3).\n\n\n\nCT scan showed thickened and enhanced \nsubcutaneous tissue at left forehead, preseptal \nregion, left anterior cheek and pinna including the \npre and post auricular regions. The left globe was \nnormal. The masseter muscles, infra-temporal and \nmasticator spaces were normal without fat stranding \nor enhancement within. There were no significantly \nenlarged lymph nodes. Punch biopsy was performed \non a thick, indurated area at the pre-auricular area \n(Figure 3). Histopathological examination showed \nirregular anastomosing vascular channels, which \ndissect trough the fibro-collagenous stroma. \nPapillary tufting was seen within the vascular \nspaces which were lined by atypical endothelial \ncells displaying irregular and hyperchromatic \n\n\n\nFigure 3. Swollen, erythematous, indurated left face and pinna \nwith periorbital oedema. Biopsy site is marked with a black \n\n\n\nnuclei. The surrounding stroma is sclerotic and \nheavily infiltrated by lymphocytes and histiocytes \n(Figure 4A & 4B). Immunohistochemistry showed \nthe atypical endothelial cells were reactive towards \nCD31. A diagnosis of cutaneous angiosarcoma was \nmade. Surgery was not feasible as the tumour was \nextensive. Radiotherapy was recommended but the \npatient refused. He succumbed to the condition six \nmonths later.\n\n\n\nFigure 4A (H&E x40) &4B (H&E x60). Anastomosing, dilated vascular channels. Papillary tufting was seen within the vascular spaces \nwhich were lined by atypical endothelial cells displaying irregular and hyperchromatic nuclei\n\n\n\ncircle\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4056\n\n\n\nCase 3\nA 55-year-old Chinese man presented a plaque on \nthe forehead of 3 months duration. The initial lesion \nwas described as a reddish papule. He was a chronic \nsmoker with type II diabetes mellitus, hypertension \nand dyslipidemia. On examination, there was a \nlarge purpuric plaque over the forehead with an \nulcerated, necrotic area. The plaque was fluctuant \naround the ulcer and indurated laterally. A purplish \nhue was observed around the plaque extending to \nthe periorbital and upper cheek areas. There was \nbilateral periorbital oedema (Figure 5).\n\n\n\nSkin biopsy was performed at an indurated area \nnear the edge of the plaque. It showed non-specific \nacute on chronic inflammation. A second biopsy \nwas performed at a fluctuant area at the edge of \nthe ulcer, extending into the ulcer (Figure 5). The \nhistopathology was consistent with angiosarcoma, \npositive to CD31 immunohistochemically. There \nwere infiltration of the papillary dermis, dermis \nand subcutis by malignant endothelial cells. The \nmalignant cells lined the vascular spaces and displays \noval, plump nuclei and inconspicuous nucleoli. \nMitosis and areas of necrosis are seen (Figure 6). \nCT scan showed soft tissue swelling of forehead and \n\n\n\nFigure 6A (H&E x 40) & 6B (H&E x 60). Infiltration of the skin by malignant endothelial cells. The cells displays oval, plump nuclei \nand inconspicuous nucleoli\n\n\n\nDiscussion\nCutaneous angiosarcoma is more common in \nelderly males.2,4,7 All of our patients were male, \nhowever, one of our patient with primary sporadic \ntype was of slightly younger age. Of the 3 types \nof cutaneous angiosarcoma, the primary sporadic \ntype typically affects sun-damaged skin of the head \n\n\n\nscalp with no distant metastasis. Complete surgical \nexcision was not possible, therefore the patient was \ntreated with tomotherapy. However, he succumbed \nafter about 10 months.\n\n\n\nFigure 5. A large purpuric plaque over the forehead with an \nulcerated, necrotic area. The plaque was fluctuant around the \nulcer and indurated at the peripheries. Area marked B was the \nsite of the first biopsy, area marked A was the site of the second \nbiopsy\n\n\n\nand neck region in elderly males. Post-radiation \nangiosarcoma may occur as early as 1 year after \nthe exposure. The latency period for breast cancer \npatients is shorter compared to patients that \nreceived radiation therapy for other types of cancer.8 \nThe risk is highest between 5 to 10 years for post \nbreast cancer radiation therapy.9,10 The latency \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 57\n\n\n\nperiod for post-radiation sarcoma in patients with \nnasopharyngeal carcinoma is around 9-10 years.11,12 \nOur patient developed angiosarcoma much earlier. \nA latency period of less than 3 years is rare.11,12  \n  \nThe clinical features of cutaneous angiosarcoma \nmay delay the diagnosis as it frequently mimics \nother diseases. Due to its rarity, it may not be \nclinically recognized or suspected, especially for \nthe primary sporadic type. Histopathology is the key \nfor diagnosis. Obtaining a good biopsy specimen for \nhistopathological examination will prevent further \ndelay in the diagnosis and treatment. The diagnoses \nin two of our patients were delayed as their first \nbiopsies from well- formed purpuric patches at the \nperiphery of the lesion showed non-specific findings. \nFrom our experience with these 3 cases, we would \nlike to recommend the biopsy to be performed at \nthe center of the lesion where it is thickest, most \nindurated or most fluctuant. This would be the area \nwhere the lesion initially appeared.   \n \nAngiosarcoma usually spread aggressively through \nthe lymphatic or hematogenous route. The lung is \nthe most common site of distant metastasis followed \nby bone, liver and lymph nodes.5,13 About 20% to \n30% of patients had metastases at presentation.5,6,13 \nCombination of surgery and radiotherapy is the \nmainstay treatment for cutaneous angiosarcoma. \nIt results in better overall survival compared to \nsurgery or radiation alone.6,14,15,16 Regional lymph \nnodes were not affected and distant metastases were \nnot found in our patients at presentation. Case 3 \nsuccumbed within 6 months of diagnosis despite \nradiotherapy. The prognosis for angiosarcoma is \npoor. The 5-year disease specific survival rate is \nbetween 40% to 60%.6,13,17,18,19,20 The benefit of \nchemotherapy is still unclear.16,19 Promising results \nhave been demonstrated with taxanes.21 None of our \npatients received chemotherapy.\n\n\n\nConclusion\nCutaneous angiosarcoma should be considered \nin purpuric lesions affecting the head and neck \nof elderly males and in those with prior radiation \ntherapy. The thickest, most indurated or most \nfluctuant area where the lesion first appeared yields \nthe best diagnostic biopsy outcome.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Honor\u00e9a C, M\u00e9eus P, Stoeckle E, Bonvalot S. Soft tissue \nsarcoma in France in 2015: epidemiology, classification and \norganization of clinical care. J Visc Surg 2015;152:223-30.\n\n\n\n2. Toro JR, Travis LB, Wu HJ, Zhu K, Fletcher CD, Devesa \nSS. Incidence patterns of soft tissue sarcomas, regardless \nof primary site, in the Surveillance, Epidemiology and End \nResults program, 1978\u20132001: an analysis of 26,758 cases. \nInt J Cancer 2006;119:2922\u201330.\n\n\n\n3. Galy-Bernadoy C, Garrel R. Head and neck soft-tissue \nsarcoma in adults. Eur Ann Otorhinolaryngol Head Neck \nDis 2016;133:37\u201342.\n\n\n\n4. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous \nsoft tissue sarcoma incidence patterns in the U.S. An \nanalysis of 12,114 cases. Cancer 2008;113:616\u201327.\n\n\n\n5. Naka N, Ohsawa M, Tomita Y, Kanno H, Uchida A, Aozasa \nK. Angiosarcoma in Japan. A review of 99 cases. Cancer \n1995;75:989\u201396.\n\n\n\n6. Buehler D, Rice SR, Moody JS, Rush P, Hafez GR, Attia \nS et al. Angiosarcoma outcomes and prognostic factors: \na 25-year single institution experience. Am J Clin Oncol \n2014;37:473\u20139.\n\n\n\n7. Ambujam S, Audhya M, Reddy A, Roy S. Cutaneous \nangiosarcoma of the head, neck, and face of elderly in type \n5 skin. J Cutan Aesthet Surg 2013;6:45-7. \n\n\n\n8. Brenn T, Fletcher CD. Radiation-associated cutaneous \natypical vascular lesions and angiosarcoma: \nclinicopathologic analysis of 42 cases. Am J Surg Pathol \n2005;29:983-96.\n\n\n\n9. Mery CM, George S, Bertagnolli MM, Raut CP. Secondary \nsarcomas after radiotherapy for breast cancer; sustained \nrisk and poor survival. Cancer 2009;115:4055-63.  \n\n\n\n10. Yap J, Chuba PJ, Thomas R, Aref A, Lucas D, Severson RK \net al. Sarcoma as a second malignancy after treatment for \nbreast cancer. Int J Radiat Oncol Biol Phys 2002;52:1231-\n7.\n\n\n\n11. Yang Q, Mo Y, Zhao Q, Ban X, He M, Cai P et al. Radiation-\ninduced sarcomas of the head and neck in post-radiation \nnasopharyngeal carcinoma. Radiol Med 2017;122:53-60.\n\n\n\n12. Cai PQ, Wu YP, Li L, Zhang R, Xie CM, Wu PH et al. \nCT and MRI of radiation induced sarcomas of the head \nand neck following radiotherapy for nasopharyngeal \ncarcinoma. Clin Radiol 2013;68:683-9.\n\n\n\n13. Fayette J, Martin E, Piperno-Neumann S, Le Cesne A, \nRobert C, Bonvalot S et al. Angiosarcomas, a heterogeneous \ngroup of sarcomas with specific behavior depending on \nprimary site: a retrospective study of 161 cases. Ann Oncol \n2007;18:2030-6.\n\n\n\n14. Vorburger SA, Xing Y, Hunt KK, Lakin GE, Benjamin \nRS, Feig BW et al. Angiosarcoma of the breast. Cancer \n2005;104:2682-8. \n\n\n\n15. Pawlik TM, Paulino AF, McGinn CJ, Baker LH, Cohen \nDS, Morris JS et al. Cutaneous angiosarcoma of the scalp: \na multidisciplinary approach. Cancer 2003;98:1716\u201326.\n\n\n\n16. Mark RJ, Poen JC, Tran LM, Fu YS, Juillard GF. \nAngiosarcoma. A report of 67 patients and a review of the \nliterature. Cancer 1996;77:2400-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4058\n\n\n\n17. Dettenborn T, Wermker K, Schulze HJ, Klein M, Schwipper \nV, Hallermann C. Prognostic features in angiosarcoma of \nthe head and neck; a retrospective monocenter study. J \nCraniomaxillofac Surg 2014;42:1623-8. \n\n\n\n18. Deyrup AT, McKenney JK, Tighiouart M, Folpe AL, \nWeiss SW. Sporadic cutaneous angiosarcoma: a proposal \nfor risk stratification based on 69 cases. Am J Surg Pathol \n2008;32:72-7. \n\n\n\n19. Guadagnolo BA, Zagars GK, Araujo D, Ravi V, \nShellenberger TD, Sturgis EM. Outcomes after definitive \ntreatment of cutaneous angiosarcoma of the face and scalp. \nHead Neck 2011;33:661-7. \n\n\n\n20. Albores-Saavedra J, Schwartz AM, Henson D, Kostun L, \nHart A, Angeles-Albores D et al. Cutaneous angiosarcoma. \nAnalysis of 434 cases from the Surveillance, Epidemiology, \nand End Results Program, 1973-2007. Ann Diagn Pathol \n2011;15:93-7.\n\n\n\n21. Penel N, Lansiaux A, Adenis A. Angiosarcomas and \ntaxanes. Curr Treat Options Oncol 2007;8:428-34.\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 59\n\n\n\nCASE REPORT\n\n\n\nVerrucous Hemangioma of the Thumb in Children: A Rare Presentation \nMuhammad Izzuddin Hamzan1,2, MD, Normala Basiron1, MS, Fauziah Kassim3, MPath\n\n\n\n1Department of Plastic and Reconstructive Surgery, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Reconstructive Science Unit, Hospital Universiti Sains Malaysia and School of Medical Sciences Universiti Sains \nMalaysia, Kubang Kerian, Kelantan, Malaysia\n3Department of Pathology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nVerrucous Hemangioma (VH) is a rare capillary vascular anomaly, frequently clinically mistaken to \nAngiokeratoma. It\u2019s frequently reported to manifest in lower extremity and is commonly unilateral. \nOther locations of its presentation are scarcely reported. We demonstrated a Verrucous Hemangioma \nof unusual location at the thumb of child and its surgical management which remain as a primary \nmodality of the treatment. \n\n\n\nKey words: Verrucous Hemangioma, Vascular Malformation, Vascular Tumor\n\n\n\nCorresponding Author\nDr Muhammad Izzuddin Hamzan\nDepartment of Plastic & Reconstructive Surgery, \nHospital Kuala Lumpur, Jalan Pahang, \n50586 Kuala Lumpur, Malaysia.\nEmail: drmizzud@gmail.com\n\n\n\nIntroduction\nVerrucous hemangioma (VH) is an uncommon \ncapillary anomaly, frequently mistaken for its mimic; \nAngiokeratoma. About 95% of the cases arise from \nlower extremity and are commonly unilateral. It \nmight involve unusual anatomic locations such as \nthe abdomen, arm, and glans penis.1 Worldwide only \na few had it reported at upper extremity with a mere \ncases occurred on digits. Verrucous haemangioma \nif left incompletely excised has a great chance of \nrecurrence. In this report, we demonstrated VH of \nunusual location on the right thumb in a child and \nits surgical management with a cutaneous skin graft \nthat was successfully used as skin coverage without \nrelapse.\n\n\n\nCase Report\nA two years and six months old boy presented to the \nout-patient clinic with a swelling on his right thumb \nnoted since birth. The lesion gradually increased \nin size, was painless and occasionally bled upon \ncontact. Physical examination revealed a well-\ndefined 2 cm x 2 cm hard dome shaped mass with \nmultiple dark bluish blebs on the skin overlying the \nulnar aspect of right interphalangeal thumb (Figure \n1a). The mass was firm, immobile, non-tender, non-\npulsatile, no ulceration nor bleeding noted. Based \non clinical findings a provisional diagnosis of a low \nflow vascular malformation was made. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4060\n\n\n\nFigure 1. (a) Vascular anomaly of the right thumb; (b) The epidermis showed hyperkeratosis and acanthosis with intact granular layer \nas well as elongation of the rete ridges (H&E: 40x); (c) There was proliferation of capillaries within epidermis and dermis (H&E: 100x);  \n\n\n\nThe child underwent an excision with a cutaneous \ngraft as coverage for the defect. The graft take was \n100%. Histopathological examination revealed \nproliferation of anastomosing capillaries with focal \ncavernous dilatation. The epidermis layer showed \nhyperkeratosis and acanthosis (Figure 1b). There \nwas intact basal granular layer with elongation of \nthe rete ridges. Vascular proliferation was also seen \n\n\n\n(d) These capillaries were lined by flattened endothelial cells without nuclear atypia and no mitosis was seen (H&E: 400x)\n\n\n\nat mid-dermis (Figure 1c) and these capillaries were \nlined by flattened endothelial cells without nuclear \natypia and no mitosis noted (Figure 1d). Hence \nthe final diagnosis of Verrucous Haemangioma \nwas made. Six months post-operative follow up \nshowed the skin graft healed well with no functional \nlimitation. There was also no residual or new \nvascular anomaly to note. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 61\n\n\n\nDiscussion\nThe clinic-pathologic characteristics of VH were \nfirst reported by Imperial and Helwig in 1967 in \na study of 21 cases and distinguished it from its \nimitator, Angiokeratoma. Verrucous Hemangioma \nsignifies a rare congenital vascular anomaly that \npresents at birth or in early childhood. It is usually \nunilateral and localized to the lower limbs. Verrucous \nHemangioma in upper limb is very unusual and \nalthough few had described it on digits in adult but \nno literature had ever reported it at thumb in children \nas in our case. It does not involute spontaneously \nand can persist after inadequate excision. With \ntime it darkens, thickens to become hyperkeratotic, \nand occasionally bleed with ulceration, without \nregression.2\n\n\n\nContrarily to other forms of vascular anomalies, \nin VH categorisation as a vascular neoplasm or \nvascular malformation cannot be established. \nIts classification is still uncertain because it \ndemonstrates clinical features alike to those seen \nin vascular malformations, but expresses an \nimmune-profile similar to vascular neoplasms \n(WT1 and Glut-1 positivity).3 Regardless of its \nmisrepresentative name, VH is considered by most \na malformation rather than a true hemangioma.4 \nand it was lately been categorized as provisionally \nunclassified vascular anomalies in the 2014 \nInternational Society for the Study of Vascular \nAnomalies (ISSVA) classification. However, North \net al. textbook on vascular anomalies pathology as \nwell as per McCuaig CC proposal (2017), proposes \nthat Verrucous Venulocapillary Malformation is a \nmore appropriate designation for this lesion.2 \n\n\n\nBy histopathology examination, it should be \ndistinguished from other vascular anomalies by \nthe presence of epidermal verrucous hyperplasia \nalong with dilated capillaries and venules extending \ndeep into the dermis with a low mitotic rate.1 It \nalso marks proliferative response of the epidermis \nhighlighting hyperkeratosis, irregular epidermal \nacanthosis and papillomatosis. There is presently no \nspecific immune-histochemical marker for VH and \ntherefore the diagnosis should be considered after \nvigilant clinic-pathological correlation.4\n\n\n\nEarly diagnosis and intervention is vital in \nselected patients for timely surgical excision and \nbetter cosmetic outcome as they do not involute \nspontaneously. As in our case, early diagnosis and \nsurgical excision is essential to prevent further \ngrowth and recurrence. However the excision of the \n\n\n\nlesion to a free margin had left the defect too large \nto be closed primarily hence a full thickness skin \ngraft was utilized to cover the defect. The lesion \nwas surgically excised and showed no relapse at 6 \nmonths, indicating that surgery remain as a primary \nmodality of treatment for a localized VH.\n\n\n\nConclusion\nVerrucous Hemangioma or Verrucous \nVenulocapillary Malformation is a rare condition, \nmust be distinguished early for surgical intervention \nand for better cosmetic outcome. We present this \ncase for its sheer rarity of its presentation, its \nnotoriety for recurrence and the use of cutaneous \ngraft as a successful coverage after an excision.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nWe would like to thank to our Director General of \nHealth Malaysia for his permission to publish the \nstudy.\n\n\n\nReferences\n\n\n\n1. Nargis T, Pinto M, Bhat S, Shenoy M. Linear verrucous \nhemangioma of the upper limb: a rare case. Dermatol \nOnline J 2017;23:5.\n\n\n\n2. McCuaig CC. Update on classification and diagnosis of \nvascular malformations. Curr Opin Pediatr 2017;29:448-\n54. \n\n\n\n3. Mestre T, Amaro C, Freitas I. Verrucous haemangioma: \na diagnosis to consider. BMJ Case Rep 2014;2014:pii: \nbcr2014204612.\n\n\n\n4. Clairwood MQ, Bruckner AL, Dadras SS. Verrucous \nhemangioma: a report of two cases and review of the \nliterature. J Cutan Pathol 2011;38:740-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4062\n\n\n\nCASE REPORT\n\n\n\nA Case of Basal Cell Carcinoma on the Left Cheek in a 62-Year-Old \nWoman, Operated by Wide Excision with V-Y Subcutaneous Tissue \nPedicle Island Advancement Flap Under Bilevel Surgical Tumescent \nAnesthesia \nSri Lestari1,2, Tutty Ariani1,2, Yessy Farina Salim1.2\n\n\n\n1Dermato-Venereology Department, Dr. M. Djamil Hospital\n2Faculty of Medicine, Andalas University, Padang, West Sumatra, Indonesia\n\n\n\nSummary\nBasal cell carcinoma (BCC) is a nonmelanocytic skin cancer that arises from basal cells, slow-growing \ntumors that almost never metastasize. Untreated BCCs have the potential to continue to grow and \ndestroy surrounding skin and nearby structures leading to physical deformity. The key to treatment \nis to ensure that there is no more cancer left in the skin. Reconstruction with V-Y skin flaps can be \nperformed in several areas of the face. We reported a 62-year-old female patient with pigmented \nnodular BCC tumor on left cheek who was successfully treated with wide excision with V-Y skin flap \nunder bilevel surgical tumescent anesthesia. \n\n\n\nKey words: Basal cell carcinoma, Wide excision, V-Y flap\n\n\n\nCorresponding Author\nDr Sri Lestari\nFaculty of Medicine, Andalas University, Padang, \nWest Sumatra, Indonesia\nEmail: srilestari_07@yahoo.com\n\n\n\nIntroduction\nThe incidence of skin tumors is increasing in parallel \nwith num bers of elderly patients. Furthermore, \nbecause skin tumors are asymptomatic, outpatient \ndepartment visits are commonly delayed. Basal cell \ncarcinoma (BCC) is defined by the World Health \nOrganization Committee on the histological typing \nof skin tumours as \u201ca locally invasive, slowly \nspreading tumour which rarely metastasise, arising \nin the epidermis or hair follicles and in which, in \nparticular, the peripheral cells usually simulate the \nbasal cells of the epidermis\u201d. Basal cell carcinoma \n(BCC) is the most common skin cancer with \nsignificant local tissue invasion and morbidity.1,2\n\n\n\nCurrent treatment modalities for skin cancers and \npremalignant lesions include surgical excision, \nelectrocautery, curettage, cryotherapy, and ir-\nradiation, but surgical excision has been reported to \nbe the best treatment modality for cancer treatment \nand preventing recur rence. On the other hand, \nsurgeons select the methods of recon struction for \nthe soft tissue defects after surgical excision based \non considerations of the tumor type and location, \npatient age, and cosmetic and functional factors. \nThere are four methods of reconstruction: primary \nclosure, skin grafting, and local and free flaps.1,3\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 63\n\n\n\nNo single flap is optimal for every defect. Each \ndefect must be individually analyzed for depth, \ndistortion of surrounding subunits, and normal \ntissue available for reconstruction.3-5 Flaps include \nadvancement, pivotal, transpositional, rhombic, and \nbilobed flaps. Advancement flaps are subclassified as \nsimple, single pedicle, bipedicle, and V-Y flaps. The \nsubcutaneous pedicled V-Y flap is an advancement \nflap first described by Barron and Emmett. This flap \nusually has random vascularization. Technically, it \nconsists of a triangular island designed adjacent to \nthe defect, with its base along one of the borders of \nthe defect. The width of the flap should be similar \nto the width of the defect and its length should be \ntwice the height of the defect.6,7 Dissection of the \ndeep part of the flap is avoided as this will be its \nvascular pedicle. If necessary, the incisions that \nmake up the triangle can be curved in those areas \nin which the tension lines suggest such a design, \nas this will better camouflage the scar. The design \nof a V-Y flap is very simple. The concept is to use \nskin from an area of relative excess to fill an area \nof deficiency. A \u2018\u2018V\u2019\u2019-shaped flap is incised adjacent \n\n\n\nFigure 1. (a) Pigmented tumor 2x2x0.3cm in size with irregular border; (b) V-Y advancement flap design; (c) From the preauricular \nregion, we injected local anesthesia of pehacain\u00ae (lidocaine 20mg, adrenalin 12.5 mcg) to insicion this area for inserting infiltrator \ncannula 3mm, then the tumescent solution 100cc (ringer lactat 100cc, lidocaine 2% 10cc, epinephrine HCl 0.2 cc) injected subcutaneously \nusing infiltrator cannula under the lesion and its surroundings then wait for 20 minutes for local anesthesia to work maximally; (d) Tumor \nresection; (e) Tumor has been removed; (f) Pedicle island is freed from the surrounding tissue, but subcutaneous tissue under \u2018island\u2019 \nremains intact for the blood supply to the tissue remains, then undermined by blunt scissors on the area around the incision lines; (g) \nThe tumor has been removed and the donor site is then closed in a straight line, which gives rise to the \u2018\u2018Y\u2019\u2019- shaped closure; (h) Result \nat 10 months follow-up\n                 \n\n\n\nto and advanced into the defect. The donor site is \nthen closed in a straight line, which gives rise to the \n\u2018\u2018Y\u2019\u2019- shaped closure.8,9\n\n\n\nCase Report\nWe present a case 62-year-old female, farmer by \noccupation came with complaints pigmented skin \ntumor on left cheek since ten months,.There was \ngradual increasing in size of the pigmented tumor. \nThere was no history of bleeding or discharge. \nPatient refuses to use sunscreen and denies use \nof long-sleeved shirts, hat or other forms of \nprotection against UV rays. She did not know about \noccurrence of skin cancer in her family. Vitals and \ngeneral examination were normal on presentation. \nBased on dermatological examination there was \npigmented tumor 2x2x0,3 cm in size with irregular \nborder (Figure 1a). Histopathological examination \nrevealed the diagnosis of nodular BCC. Patient was \noperated by V-Y subcutaneous tissue pedicle island \nadvancement flap under bilevel surgical tumescent \nanesthesia (Figure 1b - g).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4064\n\n\n\nDiscussion\nBasal cell carcinoma, also known as basal cell \ncancer, is the most common type of skin cancer. \nSimilar to other non-melanoma skin cancers, its \nincidence is rising. Recently, the incidence of BCC \nhas been increasing among Asians. It often appears \nas a painless raised area of skin, that may be shiny \nwith small blood vessels running over it or it may \npresent as a raised area with ulceration. Basal \ncell carcinoma grows slowly and can damage the \ntissue around it but is unlikely to spread to distant \nareas or result in death. The nodular, superficial \nspreading and infiltrating variants are the three most \ncommonly encountered types of BCC in descending \norder of prevalence.1,2\n\n\n\nA number of different techniques have been \ndescribed for reconstruction of the face defects \nafter excision of malignant tumors. To date, there \nare no clear criteria for the selection of one or the \nother technique.8,10 We used V-Y advancement flaps \nto reconstruct soft tissue defects after the surgical \nexcision of skin tumors of the face. The advantages \nof the V-Y advancement flap are the preservation of \nsensation and length, and good soft tissue coverage. \nV-Y advancement flap was designed as these flaps \nhave an excellent blood supply from subcutaneous \ntissue. Thus, by using V-Y advancement flaps we \nhave achieved excellent cosmetic outcomes in the \nfacial region.11,12\n\n\n\nAppropriate margins for malignant tumors depend \non the cancer type, tumor size, tumor irregularity, \nand time elapsed from onset. In cases of basal cell \ncarcinoma, an appropriate excision margin would \nbe 2 to 5 mm from the tumor.12 In our case, we used \nmean safety margins of 3 mm, and all margins were \nproved to be free by histopathological examination. \n\n\n\nFollow up 10 months after surgery (Figure 1h), \nthere was no tumor recurrence. Eyelid closure was \nadequate and there were no any sensory neuropathy, \nnumbness, paresthesia. Patient is satisfied with the \nresult of surgery. Although there are various methods \nfor reconstructing skin defects created by skin tumor \nresection, we believe that the V-Y advancement flap \nproduces good treatment outcomes in cases with \nsmall-to-medium defects. \n\n\n\nConclusion\nAesthetic reconstruction of facial defects should \nadhere to the priority goals of first preserving function \nand second achieving cosmesis. According to the \nsize of the defect, location on the cheek, relationship \n\n\n\nto adjacent structures, available donor tissue, and \nexisting skin tension lines, a host of techniques is \navailable for closure. Useful in coverage of large \ncheek wounds, the V-Y advancement flap is equally \neffective for small defects or those approximating \nthe lid or lateral cheek.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n\n\n\n1. Samarasingle V, Madan V, Lear JT. Focus on basal cell \ncarcinoma. J Skin Cancer 2011;2011:1-5.\n\n\n\n2. Grichnick JM, Rhodes AR, Sober AJ. Benign neoplasia \nand hyperplasia of melanocytes. In: Goldsmith LA, Katz \nSI, Gilchrest BA, Paller AS, Leffel DJ, Wolff K, editors. \nFitzpatrick\u2019s dermatology in general medicine. 8th edition. \nNew York: McGrawHill 2012. p.1377-410. \n\n\n\n3. Baker SR. Advancement flaps. In: Baker SR, editor. Baker \nlocal flaps in facial reconstruction. 2nd edition. Philadelphia: \nMosby Elsevier 2007. P,157-87.\n\n\n\n4. Khrisnan R, Garman M, Gussman JN, Orengo I. \nAdvancement flaps: A basic theme with many variations. \nDermatol Surg 2005;31:986-94.\n\n\n\n5. Patel KG, Sykes JM. Concepts and local flap design and \nclassification. Operative Techniques in Otolaryngology \n2011;22:13-23. \n\n\n\n6. Kwon KH, Lee DG, Koo SH, Jo MS, Shin H, Seul JH. \nUsefulness of V-Y advancement flap for defects after skin \ntumor excision. Archives of Plastic Surgery 2012;39:619-\n25.\n\n\n\n7. Seo BF, Ko HS, Kwon H, Jung SN. V-Y advancement \nflap: Aesthetic reconstruction for auriculotemporal keloid \nexcision. Arch Aesthetic Plast Surg 2017;23:164-7.\n\n\n\n8. Suarez JE, Sadigh PL, Jeng SF. Aesthetic subunit \nreconstruction facilitated with V-Y island advancement \nflaps on the face: A case report. Plast Reconstr Surg Glob \nOpen 2014;2:1-3.\n\n\n\n9. Griffin GR, Weber S, Baker SR. Outcomes following V-Y \nadvancement flap reconstruction of large upper lip defects. \nArch Facial Plast Surg 2012;14:193-7.\n\n\n\n10. Rao JK, Shende KS. Overview of local flaps of the face \nfor reconstruction of cutaneous malignancies: Single \ninstitutional experience of seventy cases. Journal of \nCutaneous and Aesthetic Surgery 2016;9:220-5.\n\n\n\n11. Mercut R, Georgescu C, Popescu SD, Ciurea M, Scrieciu \nM, Georgescu CC. Face basosquamous carcinoma, a case \nreport. Curr Health Sci J 2014;40:277-80.\n\n\n\n12. Deshmukh P, Sharma YK, Dogra BB, Chaudhari \nND. Superficial large basal cell carcinoma over face, \nReconstructed by V-Y plasty. J Cutan Aesthet Surg \n2014;7:65-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 65\n\n\n\nCASE REPORT\n\n\n\nEfficacy of Topical Immunotherapy with Squaric Acid Dibutylester in \nthe Treatment of Alopecia Areata \u2013 A case series of 11 patients  \nTick Sheng Ang, MD, Jyh Jong Tang, Adv M Derm\n \nDepartment of Dermatology, Raja Permaisuri Bainun Hospital, Ipoh, Perak, Malaysia\n\n\n\nSummary\nAlopecia Areata (AA) is a common autoimmune mediated, non-scarring alopecia directed against \nthe anagenic hair follicle. Various treatment modalities have been used for the treatment of severe/\nrecalcitrant AA. Topical immunotherapy is the best documented treatment so far for severe and \nrefractory AA. Dinitrochlorobenzene (DNCB), squaric acid dibutylester (SADBE) and diphencyprone \n(DPCP) are the contact sensitizers used for this treatment. We report the SADBE treatment experience \namong AA patients at Department of Dermatology, Hospital Raja Permaisuri Bainun, Ipoh, Malaysia. \n\n\n\nKey words: Squaric acid, SADBE, Alopecia\n\n\n\nCorresponding Author\nDr Tang Jyh Jong\nDepartment of Dermatology, \nRaja Permaisuri Bainun Hospital, \nJalan Raja Ashman Shah, \n31350 Ipoh, Perak, Malaysia\nEmail: tangjyhjong@yahoo.com\n\n\n\nIntroduction\t\nAlopecia areata (AA) is an autoimmune mediated \nnon-scarring hair loss directed at anagenic hair \nfollicle, most commonly on the scalp.1-3 The \nseverity ranges from alopecia areata to severe form \nof alopecia totalis (AT) and alopecia universalis \n(AU). Squaric acid dibutylester (SADBE) is a form \nof contact sensitizer used as immunotherapy in AA \nwith promising outcome and good tolerability with \nless side effects. This study aimed to determine \nSABDE treatment outcome and side effects among \nAA patients at Dermatology Department, Hospital \nRaja Permaisuri Bainun, Ipoh, Malaysia.\n\n\n\nMaterials and Methods\nThis was a retrospective cross-sectional single \ncenter study conducted from December 2015 to \nJuly 2017 among patients diagnosed with AA. All \npatients who failed conventional treatment and had \ncompleted SADBE treatment for at least 3 months \nwere recruited in this study. The data collected \ninclude patient\u2019s demography, disease subtype, \nduration of presentation before SADBE treatment, \nclinical response to SADBE and side effects. The \nvarious concentrations of SADBE in acetone \nwere prepared by the hospital pharmacy. SADBE \ntreatment regime was designed as such that AA \npatients were first sensitized with 2% SADBE. This \nwas then followed by weekly application of SADBE \nwith initial concentration of 0.001% which then \nincreased gradually to 0.01%, 0.1%, 0.2%, 0.5%, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4066\n\n\n\n1% till a maximum of 2%. The SADBE was painted \nin a linear fashion without overlap to the affected \nareas and left on for 8 hours. Optimal SADBE \nconcentration was determined by the manifestation \nof mild dermatitis (mild erythema and pruritus). \nSevere reactions such as persistent irritation \n(defined as itchiness, erythema and scaliness lasting \nmore than 3 days), vesicle or blister formation were \ndocumented as side effects and was treated with \ntopical steroids. SADBE was then withheld for 2 \nweeks and restarted at a lower concentration. Once \nthe patient reached optimal SADBE concentration, \nthis treatment was continued once a week till \nsignificant hair growth with good response noted. \n\n\n\nClinical response to SADBE was determined by \nMcDonald Hull and Norris\u2019s grading system4 as \nfollow: \nGrade 1  - Regrowth of vellus hair\nGrade 2 - Regrowth of sparse pigmented terminal \n\n\n\nhair\nGrade 3 - Regrowth of terminal hair with patches \n\n\n\nof alopecia \nGrade 4  - Regrowth of terminal hair on scalp \n\n\n\nAchievement of grade 3 and 4 were considered as \ngood response, otherwise the grade 1 and 2 were \nconsidered as no response. Results were presented \nmedian (IQR) and frequency (%).\n\n\n\nResults\nA total of 11 patients were recruited in this review. \nPatients\u2019 median age were 13 (IQR: 9, 33), majority \nof them were female (73%) and Malay ethnicity \n(55%). Five (45.5%) of them were identify to \nhave AA affecting less than 50% of the scalp and \n6 (54.5%) were having severe types (1 patient had \nAT and 5 patients had AU). The median duration of \npresentation to initial SADBE was 24 months (IQR: \n12, 60). \n\n\n\nOverall, 8 patients (72%) had achieved good \nresponse. Patients with less than 50% scalp \ninvolvement had a better response rate than those \nwith severe form of AA (80% vs 66%). The median \nduration taken to achieve good response was 5.5 \nmonths (IQR: 4, 7) among the 8 patients responded \nto SADBE treatment, 4 of them required 10 sessions \nof SADBE to elicit the regrowth of vellus hair at \nthe concentration of 0.1 to 0.5% and the remaining \n4 required more than 10 sessions before vellus hair \nformation. Of 3 patients who were not responded to \nthe treatment, 2 patients were unable to be sensitized \nat the concentration of 2% and 1 responded with the \nformation vellus hair but failed to develop terminal \nhair. Three out of 11 patients had suffered from \nminor side effects including persistent irritation, \nvesicle and blister formation.\n\n\n\nTable 1. Clinical characteristic and Treatment outcome of patients on SADBE       \n\n\n\nSex Age Subtype Previous\nTreatment\n\n\n\nDisease\nDuration\n\n\n\nOutcome\nof\n\n\n\nSADBE\n\n\n\nDuration to\nachieve\n\n\n\ngood response\n\n\n\nSide\teffect\n\n\n\n1 F 6 AA TCS 1 y GR 7 m  -\n2 F 33 AU TCS, PUVA, CS 2 y GR 7m -\n3 F 10 AU TCS, PUVA 4 y GR 16m -\n4 M 13 AA TCS 7 y GR 4 m -\n5 M 31 AU TCS, IDK, CS 1 y GR 6 m -\n6 F 61 AA TCS, CS 1 y GR 4 m -\n7 F 4 AA TCS 5 m GR 3.5 m Irritation\n8 F 32 AT TCS, PUVA, IDK 2 y GR 5 m Blister\n9 F 9 AU TCS, CS 5 m NR - -\n\n\n\n10 M 12 AA TCS, IDK 1 y NR - Vesicle\n11 F 42 AU TCS, PUVA 7 y NR - -\n\n\n\nF: Female, M: Male,TCS: Topical corticosteroid, PUVA: Topical psoralen and ultraviolet A therapy, IDK: Intralesional corticosteroid, \nCS: Oral corticosteroid, y: year, m: month, GR: Good response, NR: Non response\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 67\n\n\n\nFigure 1. 61 year old lady with progressively worsening of AA (left) who failed to repond to topical and oral corticosteroids. Regrowth \nof terminal hair after 4 months of SADBE (right) \n  \n\n\n\nFigure 2. AA in a 4 years old girl who failed to respond to topical corticosteroids (left) but responded well after 4 months of SADBE \n(right)\n   \n\n\n\nDiscussion\n\n\n\nAlopecia areata\nAA is a common autoimmune disease, mediated by \nautoreactive CD8+ T cells, characterized by non \nscarring hair loss involving commonly on the scalp \nand the life time risk is 2%.1-3 AA predominantly \naffects female as in our study (72% female) which \nwas consistent with a study by Dall\u2019oglio et al (53% \nfemale).1 Current recommendations for treatment \nranges from the use of corticosteroids (either topical, \noral or intralesional) to phototherapy depending on \nage, subtype and severity.  \n\n\n\nSADBE\nSADBE is a form of contact allergens of topical \nimmunotherapy in treatment of AA whereby the \nrecruited suppressor CD8+ T cells generate an \ninhibitory effect on the immune process against \nhair follicles, thus allowing hair growth. SADBE \nis an  ideal non-mutagenic sensitizer as it is not \nwidely found in nature, does not cause significant \nadverse events and does not cross reaction with \nother chemicals.2-3\n\n\n\nClinical Response\nThe clinical response to SADBE was according to \na grading system proposed by Mcdonald Hull and \nNorris4\n\n\n\nGrade 1  - Regrowth of vellus hair\nGrade 2 - Regrowth of sparse pigmented terminal \n\n\n\nhair\nGrade 3 - Regrowth of terminal hair with patches \n\n\n\nof alopecia \nGrade 4  - Regrowth of terminal hair on scalp \n\n\n\nComparison with Other Studies\n\n\n\nSuccess cases of SADBE\nOur study showed 72% of patients with AA \nresponded to SADBE and the response is better \nwith less severe form of AA (80%) as compared \nto severe form AA (AT/AU) (66%). This result is \nsupported by Case et al which also showed AA \nresponded better than AT and AU at 73% and 30% \nrespectively. Another study by Micali et al showed \nthat 80% with less severe type of AA had good \nresponse to SADBE compared to 49% of more \nsevere form of AA. Dall\u2019oglio also showed that \n80% of the treatment group had experienced hair \ngrowth compared to 50% of the control group. Ajith \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4068\n\n\n\net al too showed higher success rate in patients < \n50% scalp involvement (68%) compared to diffuse \ntype (29%).2\n\n\n\nFailure cases of SADBE\nThere are cases that fail to respond to SADBE. \nCaserio et al only had 28.5% patients with significant \nhair growth after using SADBE.2 The non responder \nrate in our series was 28% which is consistent with \n20% of non responders in study by Case et al.2\n\n\n\nPrognostic Factors\nThere are multiple factors that determine the disease \nresponse to SADBE. Indicators of poorer response \ninclude severity of alopecia, longer duration of \ndisease and presence of nail factor.5 Our study \nshowed that 2 patients suffered from AU did not \nrespond to SADBE. On the other hand, early \ndevelopment of contact dermatits within 10 weeks \nafter sensitization is a good prognostic factor.4 In our \nstudy, 4 patients had early contact dermatitis with \nvellus hair formation after 10 sessios of SADBE and \nthey eventually showed good response to treatment.\n\n\n\nSide\teffects\nIn general, SADBE is considered as a safe treatment \nbut side effects may occur during the treatment \nwhich include auto-eczematization, blistering, \nswelling of regional lymph nodes, urticaria and \ncontact leukoderma.2,4 In our study , only 3 patients \nsuffered minor side effects such as persistent \nirritation, vesicle and blister formation. \n\n\n\nConclusion\nMajority of AA patients with different level of \nseverity responded and tolerated  SADBE treatment. \nMinor side effects were experienced by small \nnumber of patients. Hence, SADBE immunotherapy \nshould be considered for patients with AA that \nfailed to respond to topical or intralesional steroid \ninjection. \n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for his permission \nto publish this paper.\n\n\n\nReferences\n\n\n\n1. Dall\u2019oglio F, Nasca MR, Musumeci ML, La Torre G, \nRicciardi G, Potenza C et al. Topical immunomodulator \ntherapy with squaric acid dibutylester (SADBE) is effective \ntreatment for severe alopecia areata (AA): Results of an \nopen-label, paired-comparison, clinical trial. J Dermatolog \nTreat 2005;16:10-4. \n\n\n\n2. Hill ND, Bunata K, Hebert AA.Treatment of alopecia areata \nwith squaric dibutylester. Clin Dermatol 2015;33:300-4.\n\n\n\n3. Tiwary AK, Mishra DK, SS Chaudhary. Comparative study \nof efficacy and safety of topical squaric Acid dibutylester \nand diphenylcyclopropenone for the treatment of alopecia \nareata. N Am J Med Sci 2016;8:237-42.\n\n\n\n4. Singh G, Lavanya M. Topical immunotherapy in alopecia \nareata. Int J Trichology 2010;2:36-9.\n\n\n\n5. Van der Steen PH, van Baar HM, Perret CM, Happle R. \nTreatment of alopecia areata with diphenylcyclopropenone. \nJ Am Acad Dermatol 1991;24:253-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 69\n\n\n\nCASE REPORT\n\n\n\nPhacomatosis Pigmentovascularis Type II: Case Report \nKit Wan Wong, MRCP, Kwee Eng Tey, MRCP\n\n\n\nDepartment of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia\n\n\n\nSummary\nPhacomatosis pigmentovascularis is a rare syndrome first described by Ota et al, in 1947. It is \ncharacterized by a combination of capillary malformation and other pigmented naevi. It had originally \nbeen classified into four major types. A fifth type, in which the vascular lesion is cutis marmorata \ntelangiectatica congenita (CMTC), was subsequently added. Each type was further categorized \naccording to the absence or presence of associated extra-cutaneous signs as types (a) and (b), \nrespectively. We reported this case due to its rare clinical presentation, with probable overlap Klippel-\nTrenaunay syndrome.\n\n\n\nKey words: Phacomatosis pigmentovascularis, Klippel-Trenaunay syndrome\n\n\n\nCorresponding Author\nDr Wong Kit Wong\nDepartment of Dermatology, \nHospital Sultanah Aminah Johor Bahru, \nJalan Persiaran Abu Bakar Sultan \n80100 Johor Bahru, Malaysia\nEmail: w_kitwan@yahoo.com\n\n\n\nIntroduction\nPhacomatosis pigmentovascularis (PPV) is a rare \nsyndrome first described by Ota et al, in 1947. It \nis characterized by a combination of capillary \nmalformation and other pigmented naevi.1 It arises \nsporadically, with no sex predilection. \n\n\n\nCase Report\nWe report a 3-week old Malay male infant who is \na product of a non-consanguineous marriage. He \nwas born full term via spontaneous vagina delivery, \nweighing 3.8kg. The child\u2019s mother had varicella \nzoster at 11 weeks of pregnancy but she did not \ntake any medications. The child\u2019s mother also had \nanaemia during pregnancy and was transfused with \ntwo pints of blood at 34 weeks of pregnancy. This \nis her firstborn and there is no family history of any \nvascular or pigmentary disorder. \n\n\n\nThe child presented with extensive erythematous \nto violaceous patches on his face, trunk and limbs \nwith aberrant blue patches noted since birth. On \nexamination, he was found to have port-wine stain \n(naevus flammeus) involving the left side of his \nface, bilateral upper limbs, trunk and back (Figure \n1a&c). He also has extensive aberrant Mongolian \nspots over a large part of the trunk, back, gluteal \nand all four limbs (Figure 1d). There were bilateral \noculocutaneous melanoses (Naevi of Ota) (Figure \n1b). A mild degree of soft tissue hypertrophy of the \nleft upper limb was also noted (Figure 1e). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4070\n\n\n\nFigure 1. (a) Naevus flammeus involving left side of the face; (b) Oculocutaneous melanoses (Naevus of Ota); (c) Naevus flammeus \nand Mongolian spots on trunk, bilateral upper and lower limbs; (d) Extensive aberrant Mongolian spots and naevus flammeus over large \npart of the back and gluteal region; (e) A mild degree of soft tissue hypertrophy of the left limb\n\n\n\nUltrasound cranium, left arm and hepatobiliary \nsystem was done for this patient. The ultrasound \ncranium was normal with no focal brain \nparenchymal lesion, no cerebral atrophy, no \nintracranial haemorrhage and no hydrocephalus. \nLiver, spleen and bilateral kidneys are all normal. \nThere is an increase in left arm muscle bulk with \nantero-posterior diameter on the left measuring \n1.1cm compared to the right which measures 0.6cm. \nNo definite collection was seen and colour Doppler \nstudy was normal.  \n\n\n\nDiscussion\nPhacomatosis pigmentovascularis, which was \nfirst described by Ota in 1947, is a rare congenital \nmalformation syndrome characterised by vascular \nand melanocytic components. It arises sporadically \nand there is no sex predilection.  PPV had \noriginally been classified into four major types.2 \n\n\n\nA fifth type, in which the vascular lesion is cutis \nmarmorata telangiectatica congenita (CMTC), \nwas subsequently added.3 Each type was further \ncategorized according to the absence or presence \nof associated extracutaneous signs as types (a) \nand (b), respectively. In 2005, Happle proposed a \nnew, simplified classification encompassing four \ngroups, using descriptive terms: phacomatosis \ncesioflamea; phacomatosis spilorosea; \n\n\n\nType (according \nto Happle)\n\n\n\nType \n(according to \nHasegawa)\n\n\n\nVascular \nlesion\n\n\n\nPigmentary \nlesion\n\n\n\nexcluded nevus I Nevus \nflammeus\n\n\n\nVerrucous and \npigmented\n\n\n\nCesioflammea II\nNevus \nflammeus \u00b1 \nanemic nevus\n\n\n\nMongolian spot\n\n\n\nSpilorosea III\nNevus \nflammeus \u00b1 \nanemic nevus\n\n\n\nNevus spilus\n\n\n\nNon-classifiable IV\nNevus \nflammeus \u00b1 \nanemic nevus\n\n\n\nMongolian spot, \nNevus spilus\n\n\n\nCesiomarmorata V\n\n\n\nCutis \nmarmorata \ntelangiectatica \ncongenita\n\n\n\nMongolian spot\n\n\n\nAdapted from: Hasegawa Y et al2, Torrelo A et al3 and Happle \nR et al4\n\n\n\n \nAll subtypes, in accordance with Hasegawa, are subdivided into \ntypes (a) or (b) - with and without systemic involvement (which \ncould involve ocular, vascular, neurological and skeletal) \nrespectively.\n\n\n\nphacomatosis cesiomarmorata and phacomatosis \npigmentovascularis of non-classifiable type.4 In \ncontrast to the traditional classification, this involves \nno subdivision between presentation with or without \nsystemic symptoms. Furthermore, type I is excluded \nbecause there are no reported cases to date.\n\n\n\nTable 1. Classification of Phacomatosis Pigmentovascularis\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 71\n\n\n\nThe pathogenesis of PPV is not fully known, \nhowever it has been linked to abnormal development \nand migration of vasomotor nerves and melanocytes \nderived from the neural crest.5 Abnormalities in the \nneural regulation of blood vessels may be important \nin the development of the vascular component, \nwhereas anomalies in the migration of neural crest \nderived melanocytes may result in Naevus of Ota, \nnaevus spilus or Mongolian spots.6\n\n\n\nA genetic phenomenon called twin spotting \nwhich was described by Happle and Steijen has \nbeen hypothesized to explain this. Twin spots are \npaired patches of mutant tissues on nearby genes \nwhich lead to mosaic spots that differ genetically \nfrom each other, likely occurring due to loss of \nheterozygosity.3,7\n\n\n\nDermal melanocytoses occur when fetal melanocytes \nundergo a migration failure from the neural crest to \nthe dermal basal layer.  Mongolian spot is the most \ncommon, followed by blue naevus and Naevus \nof Ota. It is considered aberrant when it occurs \non atypical sites (dorsum, shoulders, extremities \nand face) and with the tendency to persist, unlike \nconventional Mongolian spots. In this case, the \nMongolian spots which are generally extensive with \ninvolvement of more than 50% of the body surface \ntogether with the Naevus of Ota are considered \naberrant Mongolian spots.8\n\n\n\nThe vascular component is usually extensive in \nPPV. There is histopathological difference when \ncompared with other capillary malformations such \nas presence of vasomotor neural cells and prominent \nendothelial cells. \n\n\n\nThis case presents manifestations that classify it as \nPPV Type II, which is characterized by extensive \nbilateral lesions of capillary malformation and \naberrant Mongolian spots. It is recommended \nthat all patients with PPV to be investigated for \nsystemic complications depending on the sites \ninvolved. Approximately 50% of patients with \nPPV have extra-cutaneous involvement.9 Central \nnervous system, eye and skeletal abnormalities \nare the most common systemic complications in \nPPV.10 Neurologic conditions include psychomotor \nretardation, seizures and cerebral atrophy; with \nsymptoms typically presenting within the first few \nmonths of life.11 The most common ophthalmologic \nassociations include conjunctival melanocytosis, \nepiscleral vascular malformation and glaucoma.12\n\n\n\nIn this child who has Nevus of Ota, he will \nrequire a careful examination and follow-up by \nan ophthalmologist to assess for complications of \nglaucoma and melanoma. Other eye conditions \nreported in PPV include iris hamartomas, iris \nmammilations and iris nodules.  Some patients with \nPPV also have Sturge Weber or Klippel- Trenaunay \nsyndrome.  Since this patient has enlargement of the \nleft upper limb, he probably has Klippel-Trenaunay \nsyndrome. The classical triad of Klippel-Trenaunay \nsyndrome comprises of vascular malformations \nof the capillary, venous and lymphatic vessels, \nvaricosities of unusual distribution, and unilateral \nsoft and skeletal tissue hypertrophy.13 At present, \nmany of these symptoms may be treated, but there \nis no cure for Klippel\u2013Trenaunay syndrome. Close \nfollow-up is important for this patient with PPV and \nprobably Klippel-Trenaunay syndrome, as systemic \nmanifestations can become evident with time, \nwhich can alter the patient\u2019s disease classification \nand prognosis. \n\n\n\nPPV without systemic involvement has a naturally \nbenign course and does not require any treatment. \nHowever, a patient\u2019s quality of life and self \u2013esteem \nmay be improved by treating naevus flammeus \nwith pulsed dye laser and by treating pigmentary \nnaevus with Q-switched laser.14 It is suggested that \ncombined laser treatment to be done in childhood \npreferably before school age to reduce the number \nof treatment, increase the cost-effectiveness of \nthe treatment and improve the patient\u2019s quality \nof life.15 Medical treatment of PPV with systemic \ncomplications requires individualized plans \nand multidisciplinary management from other \nspecialties such as ophthalmologist, neurologist and \nvascular specialist. \n\n\n\nConclusion\nTherefore, it is important to recognize this rare \nsyndrome and to follow-up patients with PPV closely \nas systemic manifestations can become evident \nwith time. This helps in identifying any associated \ncondition early in the course of the disease, which \nmay determine the patients\u2019 outcome.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health Malaysia for his permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4072\n\n\n\nReferences\n\n\n\n1. Sen S, Bala S, Halder C, Ahar R, Gangopadhyay A. Case \nreport: Phakomatosis pigmentovascularis presenting with \nSturge- Weber syndrome and Klippel Trenaunay syndrome, \nIndian J  Dermatol 2015;60:77-9. \n\n\n\n2. Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis \ntype IVa. Arch Dermatol 1985;121:651-5.\n\n\n\n3. Torrelo A, Zambrano A, Happle R. Cutis marmorata \ntelangiectatica congenita and extensive Mongolian spots: \ntype 5 phacomatosis pigmentovascularis. Br J Dermatol \n2003;148:342-5.\n\n\n\n4. Happle R, Steijlen PM. Phacomatosis pigmentovascularis \ninterpreted as a phenomenon of twin spots. Hautarzt \n1989;40:721-4. \n\n\n\n5. Huang C, Lee P. Phakomatosis pigmentovascularis IIb \nwith renal anomaly. Clin Exp Dermatol 2000;25:51-4.\n\n\n\n6. Chow KY. Case 1: A child with Phakomatosis \nPigmentovascularis, Hong Kong Dermatology & \nVenereology Bulletin 1998;6:11-3.\n\n\n\n7. Vidaurri-de la Cruz H, Tamayo- Sanchez L, Duran-\nMcKinster C, Orozco-Govarrubias Mde L, Ruiz-\nMaldonado R. Phakomatosis pigmentovascularis IIA \nand IIB: clinical findings in 24 patients. J Dermatol \n2003;30:381-8.\n\n\n\n8. Segatto MM, Schmitt EU, Hagemann LN, Silva RC, \nCattani CA. Phacomatosis pigmentovascularis type IIa-\ncase report. An Bras Dermatol 2013;88:85-8. \n\n\n\n9. Fernandez-Guarino M, Boixeda P, de Las Heras E, \nAboin S, Garcia-Millan C, Osasolo PJ. Phakomatosis \npigmentovascularis: clinical findings in 15 patients and \nreview of the literature. J Am Acad Dermatol 2008;58:88-\n93.\n\n\n\n10. Michele M, Elisa F, Manuela BSG, Omar L.  Phakomatosis \nPigmentovascularis. J Am Acad Dermatol 2009; 60:AB143.\n\n\n\n11. Requena L, Sangueza OP. Cutaneous vascular anomalies. \nPart 1. Hamartomas, malformations, and dilation of \npreexisting vessels. J Am Acad Dermatol 1997;37:523-49.\n\n\n\n12. Teekhasaenee C, Ritch R. Glaucoma in phakomatosis \npigmentovascularis. Opthalmology 1997;104:150-7. \n\n\n\n13. Karim T, Singh U, Nanda NS. A rare presentation of \nKlippel-Trenaunay syndrome. Indian Dermatol Online J \n2014;5:154-6.\n\n\n\n14. Jehangir M, Quyoom S, Bhat J, Sajad P, Sofi I, Amin A \net al Phakomatosis pigmentovascularis with lower limb \nabnormalities in a young Kashmiri male child \u2013 Report \nof first child from Kashmir Valley (India) and review of \nliterature. Our Dermatol Online 2016;7:87-90.\n\n\n\n15. Kono T, Ercocen AR, Chan HH, Kikuchi Y, Hori K, Uezono \nS et al. Treatment of Phacomatosis Pigmentovascularis: \nA Combined Multiple Laser Approach. Dermatol Surg \n2003;29:642\u20136.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 73\n\n\n\nCASE REPORT\n\n\n\nDapsone Hypersensitivity Syndrome and Dapsone-induced Liver \nInjury in Four Malaysian Indigenous Individuals with Leprosy \nRajalingam Ramalingam1 AdvMDerm, Chun Lai Too2, PhD, Min Moon Tang3 AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia \n2Allergy and Immunology Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia\n3Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\n\n\n\nDapsone is part of the multi-drug therapy used in the treatment of leprosy. It can cause life-threatening \nhypersensitivity syndromes resulting in significant morbidity and mortality, especially among \nsusceptible individuals such as those who are carriers of HLA-B*13:01 allele. Avoidance of dapsone \nin these susceptible individuals reduces the risk of dapsone-related adverse events. Herein, we report \nfour indigenous patients with leprosy who developed dapsone hypersensitivity syndrome.\n\n\n\nKey words: Leprosy, Dapsone, Severe cutaneous adverse reaction, HLA-B*13:01, Malaysia\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam \nDepartment of Dermatology, \nHospital Tengku Ampuan Afzan, Jalan Tanah Putih, \n25100 Kuantan, Pahang, Malaysia \nEmail: raj.blueheart@gmail.com \n\n\n\nIntroduction\nDapsone (4, 4-diaminodiphenysulfone) has been \nused to treat leprosy since the 1940\u2019s. It is an \nessential part of the multi-drug therapy (MDT) \nfor both multi- and pauci-bacillary leprosy. \nDapsone has also been documented to cause drug \nhypersensitivity syndromes (DHS), namely, drug \nreaction with eosinophilia and systemic symptoms \n(DRESS) as well as drug-induced liver injury \n(DILI).1-3 DHS is a life-threatening drug reaction, \nwhich has been reported in approximately 2% of the \npatients with leprosy who were on dapsone therapy \nand with 12.5% mortality.4-6 Thus, DHS is one of the \nmajor causes of death in leprosy patients.7\n\n\n\nAlthough leprosy has been officially eliminated in \nMalaysia since 1994 (prevalence of leprosy of less \nthan 1 per 10,000 according to WHO definition), \nnew cases continue to be diagnosed.8 Between 2006 \nand 2015, the incidence and prevalence of leprosy \nin Malaysia range between 0.7-1.1 per 100,000 \nand 0.1-0.3 per 10,000 population respectively.8 \nThe largest state in Peninsular Malaysia, Pahang, \nrecords the fourth highest number of leprosy cases \nin the country, following Sabah, Selangor and \nSarawak.8 The large majority of these individuals \nare indigenous peoples. \n\n\n\nHerein, we report four indigenous individuals with \nleprosy who developed adverse effects secondary to \ndapsone treatment (Table 1). \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4074\n\n\n\nCase Report\n\n\n\nCase 1\nMr VO, a 30-year-old unemployed gentleman with \nno past medical history, presented to us on 26 April \n2016 complaining of multiple erythematous plaques \nand nodules over his trunk and limbs for a duration \nof one year. He had no systemic symptoms and was \notherwise well. He has a younger sister (CASE 2) \nbeing treated for midborderline leprosy at our center. \n\n\n\nPhysical examination revealed a well-built individual \nwith multiple erythematous nodules over both arms, \nand multiple hypopigmented anaesthetic patches \nover the upper chest. There were no thickened \nperipheral nerves, joint swelling, organomegaly or \ndeformities noted. \n\n\n\nSlit skin smear (SSS) showed a bacteriological \nindex (BI) of 3.5 and a morphological index (MI) of \n1.9. Skin biopsy showed clumps of acid-fast bacilli \nwithin foamy macrophages. All blood parameters \nwere within normal limits. \n\n\n\nMr VO was diagnosed with lepromatous leprosy \nand promptly started on World Health Organization \n(WHO) multibacillary (MB) MDT regimen \nbeginning 24 May 2016, which consists of monthly \nrifampicin, daily clofazimine and daily dapsone. \nBlood investigation repeated in June 2016 remained \nnormal.\n\n\n\nHe presented to us unexpectedly on 29 July 2016 \nwith generalized exfoliative dermatitis including \nfacial oedema associated with fever. He denied \ntaking any traditional and complimentary medicines \nor consuming alcohol. His blood count revealed \na total eosinophil count of 3,110/mcL (18.3%), \nwith elevated platelet counts (427,000/mcL). His \nhaemoglobin was 10.8 g/dL. His liver function tests \nand renal profile were normal. \n\n\n\nHe was diagnosed with drug reaction with \neosinophilia and systemic symptoms (DRESS) \nsecondary to dapsone and was duly admitted to \nthe ward for systemic corticosteroids and topical \nemollients. His MDT was withheld. \n\n\n\nOver the course of his one-week admission, his \ncondition improved dramatically, with normalization \nof his eosinophil count and reduction in erythema \nand scaliness. Upon review in the outpatient clinic, \nhis exfoliative dermatitis had completely resolved \nand his blood parameters remained normal. Dapsone \n\n\n\nwas replaced with ofloxacin, while rifampicin and \nclofazimine were continued. Oral prednisolone was \ntapered until stopped in November 2016. \n\n\n\nMr VO continues to improve on subsequent clinic \nvisits. HLA-B genotyping revealed the presence of \nHLA-B*13:01 and HLA-B*18:01 alleles.\n\n\n\nCase 2\nMiss NAO, the 19-year-old sister of Mr VO \n(CASE 1), with no past medical history, was seen \nin our clinic on the same day as her brother. She \nhad no complaints but was noted to have several \nerythematous plaques over her trunk and limbs for \nan uncertain duration of time. She was otherwise \nwell. \n\n\n\nPhysical examination revealed multiple \nhypopigmented anaesthetic patches over her trunk \nand upper limbs. There were no thickened peripheral \nnerves, joint swelling, organomegaly or deformities \nnoted. \n\n\n\nThe bacteriological index (BI) and morphological \nindex (MI) of slit skin smear (SSS) was zero. \nSkin biopsy showed numerous perineural and \nperivascular epithelioid granulomas. No acid-fast \nbacilli were seen. All blood parameters were within \nnormal limits. \n\n\n\nMiss NAO was diagnosed with midborderline \nleprosy, in view of more than five lesions were \npresent, and promptly started on World Health \nOrganization (WHO) multibacillary (MB) MDT \nregimen beginning 29 July 2016. Blood investigation \nrepeated in July remained normal.\n\n\n\nShe presented to us on 25 August 2016 with a \ngeneralized maculopapular eruption.  She had no \nfever and was hemodynamically stable. She denied \ntaking any traditional and complimentary medicines \nor consuming alcohol. Her blood count revealed a \ntotal eosinophil count of 940/mcL (16.1%). Her \nhemoglobin was 9.6 g/dL. The liver function tests \nshowed markedly elevated hepatic enzymes, with \nalanine aminotransferase (ALT) at 468 U/L and \naspartate aminotransferase (AST) at 373 U/L. Renal \nprofile was normal. \n\n\n\nShe was diagnosed with drug reaction with \neosinophilia with systemic symptoms (DRESS) \nsecondary to dapsone and was duly admitted to \nthe ward for systemic corticosteroids and topical \nemollients. Her MDT was withheld. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 75\n\n\n\nHer condition improved over the next one week, \nwith normalization of eosinophil count and liver \ntransaminases as well as resolution of her rash. Upon \nreview in the outpatient clinic, her blood parameters \nwere normal. Dapsone was replaced with ofloxacin, \nwhile rifampicin and clofazimine were continued. \nOral prednisolone was tapered slowly until stopped \nin November 2016. \n\n\n\nMiss NAO continues to improve on subsequent \nclinic visits. Like her brother, the HLA-B genotyping \nrevealed the presence of HLA-B*13:01 and HLA-\nB*18:01alleles.\n\n\n\nCase 3\nMr GS, a 71-year-old elderly gentleman with no past \nmedical history, presented to us on 23 August 2016 \ncomplaining of multiple hypopigmented patches \nover his trunk and upper limbs for a duration of one \nmonth. \n\n\n\nPhysical examination revealed four discrete, large \nhypo pigmented, non-scaly patches over his trunk, \nboth upper limbs and buttocks. These patches were  \nhypo-aesthetic. No thickened peripheral nerves, \ndeformities or neuropathic ulcers were appreciated.\n\n\n\nSlit skin smear examination showed both BI and MI \nof zero. Skin biopsy showed multiple non-caseating \nepithelioid granulomas. Acid fast bacilli were seen. \nAll blood parameters were within normal limits.\n\n\n\nMr GS was diagnosed with midborderline leprosy \nand started on WHO multibacillary MDT regimen \nbeginning 6 October 2016. He was seen in our \noutpatient clinic on 1 November 2016 with no \nnew complaints and with normal repeated blood \nparameters. \n\n\n\nHe was presented unexpectedly to our clinic on \n5 December 2016 with exfoliative dermatitis \nassociated with fever, jaundice, pallor, dehydration, \nbilateral pitting pedal oedema and tender \nhepatomegaly. There were no crops of new nodules \nor papules noted to suggest leprae reactions. He was \nhemodynamically stable. He denied consuming any \nalcohol or traditional herbal remedies. His eosinophil \ncount was 1,200/mcL (9.9%), haemoglobin 10.2 g/\ndL and platelets 176,000/mcL. His liver function test \nwas abnormal with slightly elevated serum bilirubin \n(28.4 \u00b5mol/L) while the transaminases were also \nelevated (ALT 66 U/L; AST 75 U/L). Non-oliguric \nrenal impairment was noted. \n\n\n\nMr GS was diagnosed with drug-related eosinophilia \nwith systemic symptoms (DRESS) secondary to \ndapsone and was admitted to the ward for systemic \ncorticosteroids and topical emollients. His MDT \nwas withheld. \n\n\n\nHis condition continued to deteriorate over the next \none week. The liver transaminases were markedly \nelevated, with ALT and AST levels persistently \nabove 750 U/L, serum bilirubin above 300 \n\u00b5mol/L, thrombocytopenia, coagulopathy, anaemia \nand oliguric renal failure. Despite intravenous \nN-acetylcysteine rescue, we did not manage to \nresolve his acute liver injury.\n\n\n\nMr GS eventually passed away from fulminant \nhepatic failure on 13 December 2016. HLA-B \ngenotyping was not carried out.\n\n\n\nCase 4\nMr MRJ, a 19-year-old gentleman with no past \nmedical history, was referred to us from a district \nhospital on 31 January 2017 for facial erythema \nand swelling associated with low-grade fever for \na duration of three months. His maternal aunt and \nlate maternal grandmother had been diagnosed with \nleprosy. \n\n\n\nPhysical examination revealed madarosis, thickened \nand nodular bilateral earlobes and multiple large \nand confluent erythematous plaques over his face. \nMost of the fingers of both hands were sausage-\nshaped and tender, while both his wrist and ankle \njoints were also swollen and tender. He had no \nother lesions elsewhere on his body. There was \nalso no pallor, jaundice, organomegaly, thickened \nperipheral nerves, deformities or neuropathic ulcers \nappreciated.\n\n\n\nSlit skin smear examination showed a BI of 3.5 \nand an MI of 1.0. Apart from mild normochromic \nnormocytic anaemia, all other blood parameters \nwere within normal limits.\n\n\n\nMr MRJ was diagnosed with lepromatous leprosy \nwith erythema nodosum leprosum (ENL) and was \nduly started on WHO multibacillary MDT regimen \nalong with systemic corticosteroids and hematinics \non the same day. He was seen in our outpatient clinic \non 14 February 2017 with complete resolution of \nhis joint swelling and reducing facial erythema. \nRepeated blood parameters were all normal.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4076\n\n\n\nTa\nbl\n\n\n\ne \n1.\n\n\n\n F\nou\n\n\n\nr M\nal\n\n\n\nay\nsi\n\n\n\nan\n in\n\n\n\ndi\nge\n\n\n\nno\nus\n\n\n\n in\ndi\n\n\n\nvi\ndu\n\n\n\nal\ns w\n\n\n\nith\n le\n\n\n\npr\nom\n\n\n\nat\nou\n\n\n\ns l\nep\n\n\n\nro\nsy\n\n\n\n tr\nea\n\n\n\nte\nd \n\n\n\nw\nith\n\n\n\n d\nap\n\n\n\nso\nne\n\n\n\n a\ns p\n\n\n\nar\nt o\n\n\n\nf m\nul\n\n\n\ntid\nru\n\n\n\ng \nth\n\n\n\ner\nap\n\n\n\ny\n\n\n\nM\n- M\n\n\n\nal\ne;\n\n\n\n F\n- f\n\n\n\nem\nal\n\n\n\ne;\n D\n\n\n\nR\nES\n\n\n\nS \n- D\n\n\n\nru\ng \n\n\n\nre\nac\n\n\n\ntio\nn \n\n\n\nw\nith\n\n\n\n e\nos\n\n\n\nin\nop\n\n\n\nhi\nlia\n\n\n\n a\nnd\n\n\n\n sy\nst\n\n\n\nem\nic\n\n\n\n sy\nm\n\n\n\npr\nom\n\n\n\ns;\n D\n\n\n\nIL\nI -\n\n\n\n D\nru\n\n\n\ng \nin\n\n\n\ndu\nce\n\n\n\nd \nliv\n\n\n\ner\n in\n\n\n\nju\nry\n\n\n\nC\nas\n\n\n\ne\nA\nge\n/G\nen\nde\nr\n\n\n\nTy\npe\n\n\n\n o\nf L\n\n\n\nep\nro\n\n\n\nsy\nTe\n\n\n\nm\npo\n\n\n\nra\nl p\n\n\n\ner\nio\n\n\n\nd \nbe\n\n\n\ntw\nee\n\n\n\nn \nin\n\n\n\niti\nat\n\n\n\nio\nn \n\n\n\nof\n D\n\n\n\nap\nso\n\n\n\nne\n a\n\n\n\nnd\n \n\n\n\ndr\nug\n\n\n\n r\nea\n\n\n\nct\nio\n\n\n\nn \n(m\n\n\n\non\nth\n\n\n\ns)\n\n\n\nA\ndv\n\n\n\ner\nse\n\n\n\n \nre\n\n\n\nac\ntio\n\n\n\nn\nH\n\n\n\nig\nhe\n\n\n\nst\n e\n\n\n\nos\nin\n\n\n\nop\nhi\n\n\n\nl \nco\n\n\n\nun\nt d\n\n\n\nur\nin\n\n\n\ng \nda\n\n\n\nps\non\n\n\n\ne \nhy\n\n\n\npe\nrs\n\n\n\nen\nsi\n\n\n\ntiv\nity\n\n\n\n sy\nnd\n\n\n\nro\nm\n\n\n\ne,\nx1\n\n\n\n09 /L\n\t(%\n\n\n\n)\n\n\n\nH\nig\n\n\n\nhe\nst\n\n\n\n a\nla\n\n\n\nni\nne\n\n\n\n a\nm\n\n\n\nin\no \n\n\n\ntr\nan\nsf\ner\nas\ne\t\n(\u03bc\nL\n)\n\n\n\nO\nut\n\n\n\nco\nm\n\n\n\ne\nH\n\n\n\nL\nA\n\n\n\n-B\n \n\n\n\nge\nno\n\n\n\nty\npi\n\n\n\nng\n\n\n\n1 2 3 4\n\n\n\n30\n/M\n\n\n\n19\n/F\n\n\n\n71\n/M\n\n\n\n19\n/M\n\n\n\nLe\npr\n\n\n\nom\nat\n\n\n\nou\ns\n\n\n\nM\nid\n\n\n\nbo\nrd\n\n\n\ner\nlin\n\n\n\ne\n\n\n\nM\nid\n\n\n\nbo\nrd\n\n\n\ner\nlin\n\n\n\ne\n\n\n\nLe\npr\n\n\n\nom\nat\n\n\n\nou\ns\n\n\n\n2 1 2 1.\n5\n\n\n\nD\nR\n\n\n\nES\nS\n\n\n\nD\nR\n\n\n\nES\nS\n\n\n\nD\nR\n\n\n\nES\nS\n\n\n\nD\nIL\n\n\n\nI\n\n\n\n3.\n11\n\n\n\n (1\n8.\n\n\n\n3%\n)\n\n\n\n0.\n94\n\n\n\n (1\n6.\n\n\n\n1%\n)\n\n\n\n1.\n2 \n\n\n\n(9\n.9\n\n\n\n%\n)\n\n\n\n0\n\n\n\n42 46\n8\n\n\n\n76\n2\n\n\n\n41\n3\n\n\n\nC\nom\n\n\n\npl\net\n\n\n\ne \nre\n\n\n\nso\nlu\n\n\n\ntio\nn \n\n\n\nof\n ra\n\n\n\nsh\n a\n\n\n\nnd\n \n\n\n\nno\nrm\n\n\n\nal\niz\n\n\n\nat\nio\n\n\n\nn \nof\n\n\n\n e\nos\n\n\n\nin\nop\n\n\n\nhi\nl c\n\n\n\nou\nnt\n\n\n\nC\nom\n\n\n\npl\net\n\n\n\ne \nre\n\n\n\nso\nlu\n\n\n\ntio\nn \n\n\n\nof\n ra\n\n\n\nsh\n a\n\n\n\nnd\n \n\n\n\nno\nrm\n\n\n\nal\niz\n\n\n\nat\nio\n\n\n\nn \nof\n\n\n\n e\nos\n\n\n\nin\nop\n\n\n\nhi\nl c\n\n\n\nou\nnt\n\n\n\nD\nea\n\n\n\nth\n\n\n\nD\nea\n\n\n\nth\n\n\n\nH\nLA\n\n\n\n-B\n*1\n\n\n\n3:\n01\n\n\n\nH\nLA\n\n\n\n-B\n*1\n\n\n\n8:\n01\n\n\n\nH\nLA\n\n\n\n-B\n*1\n\n\n\n3:\n01\n\n\n\nH\nLA\n\n\n\n-B\n*1\n\n\n\n8:\n01\n\n\n\nN\not\n\n\n\n d\non\n\n\n\ne\n\n\n\nN\not\n\n\n\n d\non\n\n\n\ne\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 77\n\n\n\nHe presented to the Emergency Department on \n18 March 2017 with right hypochondriac pain \nassociated with fever, jaundice, hypotension and \ntachycardia. There were no crops of new nodules \nor papules to suggest leprae reactions. Bedside \nultrasonographic examination did not reveal any \nfeatures of biliary obstruction. He was diagnosed \nwith dapsone hypersensitivity syndrome and \npromptly admitted to the ward. Inotropic support \nand empirical broad-spectrum antimicrobials \nwere initiated. Blood investigations revealed \na total eosinophil count of zero on admission, \nhaemoglobin 10.3 g/dL and platelets 441,000/mcL. \nHis liver function test were abnormal with markedly \nelevated total serum bilirubin of 296.2 \u00b5mol/L (i.e. \ndirect bilirubin: 228.3 \u00b5mol/L; indirect bilirubin: \n67.9 \u00b5mol/L). ALT was 92 U/L, AST 189 U/L and \nalkaline phosphatase (ALP) 1,365 U/L. There was \nalso deranged coagulation profile, and blood gases \nshowed mild, compensated metabolic acidosis. \nRenal function however, remained normal. \n\n\n\nMDT was withheld and he was commenced \non intravenous hydrocortisone in place of oral \nprednisolone which he has been on. Imaging studies \ncarried out over the following few days, including \nendoscopic retrograde cholangiopancreatography \nand computed tomography of the abdomen, revealed \nno abnormalities. Blood and urine cultures were \nnegative. \n\n\n\nNevertheless, Mr MRJ developed several life-\nthreatening complications during his 18th-day \nhospitalization, including fulminant hepatic \nfailure (i.e. ALT and AST peaking above 400 U/L; \nALP persistently above 2,000 U/L), recalcitrant \nhypokalemia secondary to salt-wasting nephropathy, \nrefractory hypoglycaemia and a nosocomial \nchest infection. Intravenous N-acetylcysteine \nand methylprednisolone were given for drug-\ninduced liver injury (DILI) secondary to dapsone, \nbut to no avail. He was then being considered for \nliver transplant and was planned for transplant \nevaluation.  Despite aggressive interventions, \nMr MRJ eventually succumbed to complications \narising from fulminant hepatic failure on 6 April \n2017 before HLA typing was arranged.  \n\n\n\nDiscussion\nDapsone has been used to treat leprosy since the \n1940\u2019s. Till date, dapsone has played a vital role in \neliminating leprosy in many countries, including \nMalaysia. Nevertheless, dapsone is not without its \nadverse effects.  \n\n\n\nSeveral adverse effects have reported following \nexposure to dapsone. These adverse effects are (i) \ndose-dependent (pharmacological), which include \nhemolytic anemia and methemoglobinemia, or (ii) \ndose-independent (idiosyncratic) such as dapsone \nhypersensitivity syndrome (DHS) and DRESS, \na potentially lethal syndrome with multiorgan \ninvolvement including pyrexia, hepatitis, \nlymphadenopathy and atypical lymphocytosis.9-\n\n\n\n11DHS has been reported to occur in 0.5 to 3.6% \nof patients treated with dapsone12 and is usually \nmanifested 4 to 6 weeks after the initiation of \ntherapy. The estimated prevalence of the dapsone \nhypersensitivity syndrome is 1.4%, and the \nassociated mortality is 9.9%.5 To date, there are no \ntests to predict the risk of acquiring DHS. \n\n\n\nNevertheless, some population studies suggest both \ngenetic and environmental factors are probably \ninvolved in determining the quantity of toxic \noxidative metabolites of dapsone, such as the \nactivity and quantity of polymorphic isoenzymes of \ncytochrome P450 and concomitant drug or chemical \nexposure, like alcohol or tobacco smoke.10\n\n\n\nOf late, we have come to learn that genetic \npredisposition contributes towards drug-\ninduced hypersensitivity reactions. For example \nHLA-B*15:02 allele predicts the risk of \ncarbamazepine13-15 as well as phenytoin16-19 induced \nStevens\u2013Johnson syndrome (SJS)/toxic epidermal \nnecrolysis (TEN) in Southeast Asian populations, \nwhile the HLA-A*31:01 allele was associated with \ncarbamazepine-induced hypersensitivity reactions \nin European populations.20 Furthermore it was \nreported recently that the HLA-B*15:13 allele was \nassociated with phenytoin-induced SJS/TEN among \nMalays in Malaysia.16\n\n\n\nLikewise, HLA-B*13:01 allele has been reported to \nbe a predictor for dapsone-induced hypersensitivity \nsyndrome (DHS) among patients with leprosy with \na sensitivity of 85.5% and a specificity of 85.7%21, \nwhile its absence is associated with a reduction \nin risk by a factor of 7.22 In the study carried out \nby Zhang et al., the authors concluded that the \nrisk of DHS among individuals with single copy \n(heterozygous) of the HLA-B*13:01 allele is \n33.6 times higher compared to those without the \nsusceptible allele.22 The risk among individuals \nwith double copies of HLA-B*13:01 allele \n(homozygous) increased 100.7 times.22 A Thailand \nstudy recently described 12 of 15 (80%) non leprosy \npatients who developed dapsone-induced severe \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4078\n\n\n\ncutaneous adverse reactions (SCARs) i.e. DRESS \nand Stevens Johnson syndrome/toxic epidermal \nnecrolysis, were carriers of HLA-B*13:01 allele. \nWhen compared with the dapsone-tolerant controls, \nthe odd ratio of dapsone-induced SCARs in Thais \npopulation who carried the HLA-B*13:01 allele \nwas 54.0 (95% CI of 7.96\u2013366.16, p = 0.0001). \nThe OR was 26.11 when compared with the Thais \ngeneral population (p=0.0001).23 In Taiwan, it was \nalso found that HLA-B*13:01 allele was present \nin 85.7% of patients with dapsone induced DRESS \n(OR=49.64;95%CI=5.89-418.13) whereas only \n10.8% of general populations control carried the \nallele.24\n\n\n\nThe HLA-B*13:01 allelic distribution varies \nacross different ethnic populations worldwide. For \nexample, the frequency of  HLA-B*13:01  ranging \nfrom 2% to 20% in the Han Chinese populations, \n1.5% in the Japanese population, 1 \u2013 12% in \nIndians, 2 \u2013 4% in Southeast Asians, 13.3% in Thais \nand 28% in Papuans and Australian aborigines.22-25 \nHowever, this allele is largely absent in Europeans \nand Africans22,23,25. Notably, the HLA-B*13:01 \nallele has also been found among the three main \nindigenous groups in Peninsular Malaysia, namely \nthe Temuan, Jehai and Kensiu, with the Kensiu \npeoples having the highest allele frequency.26 \n\n\n\nIn this case series report, both the siblings VO and \nNAO carry single copy of HLA-B*13:01 allele. \nWe performed the HLA-B genotyping for their \nfather and younger brother. The findings revealed \ncarriage of double copies (homozygous) and \nsingle copy (heterozygous) of HLA-B*13:01 allele \nfor the father and younger brother, respectively. \nInterestingly, while their father did not have \nleprosy, their younger brother was diagnosed with \nlepromatous leprosy and completed treatment with \nMDT uneventfully. It is noteworthy that in addition \nto the HLA-B*13:01 allele, all three siblings with \ndiagnosed leprosy (i.e. VO, NAO and their younger \nbrother) were also carriers of HLA-B*18:01 \nallele. Based on the HLA-B genotyping findings \nof these three siblings and their father, we cannot \nexclude the possible explanation of synergy act \nbetween HLA-B*13:01 and HLA-B*18:01 in risk \nof leprosy that may complicate the development of \nDHS in these individuals.  It is regrettable that the \nhaplotype of Mr GS and Mr MRJ were not able to \nbe determined, given their clinical presentation and \ntragic outcome.\n\n\n\nIt is probably clinically vital to screen for \n\n\n\nHLA-B*13:01 in dapsone-related treatment \nregimens, especially for high-risk individuals in \ncertain populations identified to be susceptible \nin having adverse reactions with dapsone. It \nis advocated based on the recently published \nsystematic review and meta-analysis.27 Identification \nof carriers of the HLA-B*13:01 allele may justify \nthe need to modify treatment, such as switching to \na safer second-line options, and thus significantly \nreducing the risk for DHS. However, the cost-\nbenefit implications need to be addressed too, as \nthe frequency of HLA-B*13:01 allele varies greatly \nacross populations. Taken together, the next course \nof action would be prospective study to determine \nthe odds ratio of dapsone induced SCARs among \nsubjects who carry HLA-B*13:01 allele comparing \nto dapsone tolerant subjects and Malaysian general \npopulation.\n\n\n\nConclusion\nIn conclusion, we described four Malaysian \nindigenous individuals with leprosy who developed \ndapsone-induced hypersensitivity syndrome and \nhad resulted mortality in two of them. HLA-B*13:01 \nallele was found to be carried by two of the related \nleprosy patients. Medical practitioners must be \naware of this potentially fatal syndrome, particular \nin geographical areas with high prevalence rates of \nleprosy, and where the presence of DHS predisposing \ngenetic factor such as HLA-B*13:01 is common.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health Malaysia for his permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Kosseifi SG, Guha B, Nassour DN, Chi DS, Krishnaswamy \nG. The Dapsone Hypersensitivity Syndrome revisited: \na potentially fatal multisystem disorder with prominent \nhepatopulmonary manifestations. J Occup Med Toxicol \n2006;1:9.\n\n\n\n2. Sener O, Doganci L, Safali M, Besirbelliogiu B, Bulucu \nF, Pahsa A. Severe dapsone hypersensitivity syndrome. J \nInvestig Allergol Clin Immunol 2006;16:268-70.\n\n\n\n3. Sheen YS, Chu CY, Wang SH, Tsai TF. Dapsone \nhypersensitivity syndrome in non-leprosy patients: a \nretrospective study of its incidence in a tertiary referral \ncenter in Taiwan. J Dermatolog Treat 2009;20:340-3.\n\n\n\n4. Pandey B, Shrestha K, Lewis J, Hawksworth RA, Walker \nSL. Mortality due to dapsone hypersensitivity syndrome \ncomplicating multi-drug therapy for leprosy in Nepal. Trop \nDoct 2007;37:162-3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 79\n\n\n\n5. Lorenz M, Wozel G, Schmitt J. Hypersensitivity reactions \nto dapsone: a systematic review. Acta Derm Venereol \n2012;92:194-9.\n\n\n\n6. Tian W, Shen J, Zhou M, Yan L, Zhang G. Dapsone \nhypersensitivity syndrome smong leprosy patients in \nChina. Lepr Rev 2012;83:370-7.\n\n\n\n7. Shen J, Liu M, Zhou M, Li W. Cases of death among active \nleprosy patients in China. Int J Dermatol 2011;50:57-60.\n\n\n\n8. Bahagian Kawalan Penyakit, Kementerian Kesihatan \nMalaysia. Pelan Strategik Program Kawalan Kusta \nKebangsaan 2016-2020. Kementerian Kesihatan Malaysia \n2017.\n\n\n\n9. Agrawal S, Agarwalla A. Dapsone hypersensitivity \nsyndrome: a clinico-epidemiological review. J Dermatol \n2005;32:883-9.\n\n\n\n10. Prussick R, Shear NH. Dapsone hypersensitivity syndrome. \nJ Am Acad Dermatol 1996;35:346-9.\n\n\n\n11. Chalasani P, Baffoe-Bonnie H, Jurado RL. Dapsone therapy \ncausing sulfone syndrome and lethal hepatic failure in an \nHIV-infected patient. South Med J 1994;87:1145-6.\n\n\n\n12. Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: \noverview and update. J Am Acad Dermatol 2001;45:420-\n34.\n\n\n\n13. Chang CC, Too CL, Murad S, Hussein SH. Association of \nHLA-B*15:02 allele with carbamazepine-induced toxic \nepidermal necrolysis and Stevens-Johnson syndrome in \nthe multi-ethnic Malaysian population. Int J Dermatol \n2011;50:221-4.\n\n\n\n14. Kulkantrakorn K, Tassaneeyakul W, Tiamkao S, \nJantararoungtong T, Prabmechai N, Vannaprasaht S et al. \nHLA-B*15:02 strongly predicts carbamazepine-induced \nStevens-Johnson syndrome and toxic epidermal necrolysis \nin Thai patients with neuropathic pain. Pain Pract \n2012;12:202-8.\n\n\n\n15. Wang Q, Zhou JQ, Zhou LM, Chen ZY, Fang ZY, Chen \nSD et al. Association between HLA-B*15:02 allele \nand carbamazepine-induced severe cutaneous adverse \nreactions in Han people of southern China mainland. \nSeizure 2011;20:446-8.\n\n\n\n16. Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung \nWH et al. Association of HLA-B*15:13 and HLA-B*15:02 \nwith phenytoin-induced severe cutaneous adverse reactions \nin a Malay population. Pharmacogenomics J 2017;17:170-\n3.\n\n\n\n17. Cheung YK, Cheng SH, Chan EJ, Lo SV, Ng MH, Kwan \nP. HLA-B alleles associated with severe cutaneous \nreactions to antiepileptic drugs in Han Chinese. Epilepsia \n2013;54:1307-14.\n\n\n\n18. Locharernkul C, Loplumlert J, Limotai C, Korkij W, \nDesudchit T, Tongkobpetch S et al. Carbamazepine \nand phenytoin induced Stevens-Johnson syndrome is \nassociated with HLA-B*15:02 allele in Thai population. \nEpilepsia 2008;49:2087-91.\n\n\n\n19. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui \nRC et al. Common risk allele in aromatic antiepileptic-\ndrug induced Stevens-Johnson syndrome and toxic \nepidermal necrolysis in Han Chinese. Pharmacogenomics \n2010;11:349-56.\n\n\n\n20. McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, \nKasperavi\u010di\u016bt\u0117 D, Carrington M et al. HLA-A*3101 and \ncarbamazepine-induced hypersensitivity reactions in \nEuropeans. N Engl J Med 2011;364:1134-43.\n\n\n\n21. Wang N, Parimi L, Liu H, Zhang FA Review on Dapsone \nHypersensitivity Syndrome among Chinese Patients with \nan Emphasis on Preventing Adverse Drug Reactions with \nGenetic Testing. Am J Trop Med Hyg 2017;96:1014-8.\n\n\n\n22. Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ et \nal. HLA-B*13:01 and the Dapsone Hypersensitivity \nSyndrome. N Engl J Med 2013;369:1620-8.\n\n\n\n23. Tempark T, Satapornpong P, Rerknimitr P, Nakkam N, \nSaksit N, Wattanakrai P et al. Dapsone-induced severe \ncutaneous adverse drug reactions are strongly linked with \nHLA-B*13:01 allele in the Thai population. Pharmacogenet \nGenomics 2017;27:429-37.\n\n\n\n24. Chen WT, Wang CW, Lu CW, Chen CB, Lee HE, Hung \nSI et al. The function of HLA-B*13:01 involved in the \npathomechanism of dapsone-induced severe cutaneous \nadverse reactions. J Invest Dermatol 2018; doi: 10.1016/j.\njid.2018.02.004.\n\n\n\n25. Gonzalez-Galarza FF, Christmas S, Middleton D, Jones \nAR. Allele frequency net: a database and online repository \nfor immune gene frequencies in worldwide populations. \nNucleic Acids Res 2011;39:913-9.\n\n\n\n26. Jinam TA, Saitou N, Edo J, Mahmood A, Phipps ME. \nMolecular analysis of HLA Class I and Class II genes in \nfour indigenous Malaysian populations. Tissue Antigens \n2009;75:151-8.\n\n\n\n27. Tangamornsuksan W, Lohitnavy M. Association between \nHLA-B*1301 and Dapsone-Induced Cutaneous Adverse \nDrug Reactions: A Systematic Review and Meta-analysis. \nJAMA Dermatol 2018;154:441-6. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4080\n\n\n\nCORRESPONDENCE\n\n\n\nDermatologists & The History of Hair Restoration Surgery \nRuban Nathan, FRCP, FAAD \n\n\n\nDr Ruban\u2019s Skin & Hair Clinic, Bangsar, Kuala Lumpur, Malaysia \n\n\n\nCorresponding Author\nDr Ruban Nathan\nDr Ruban\u2019s Skin & Hair Clinic, \nUnit 2-3A & 2-5, Level 2, \nMenara UOA Bangsar, Jalan Bangsar Utama 1, \n59000 Kuala Lumpur, Malaysia\nEmail: ruban@drruban.com\n\n\n\nDear Editor,\nI was introduced to Hair Transplant Surgery very \nearly on. It was back in 1994 that I became a patient \nof Dr Dow Stough and then his pupil. Indeed, he \nhad a profound effect on my career.\n\n\n\nIn terms of every conceivable hat that we are allowed \nto wear he was a complete dermatologist. A pioneer \nin Superpulsed carbon dioxide laser resurfacing, \n(who famously uttered to me once \u201cRuban\u2026. you \nshould trust a Laser Sales person as far as you \ncan throw him\u201d) a dedicated Mohs surgeon and \nPhototherapist, whilst performing Hair Transplant \nSurgery twice a week. He ran a Clinical Fellowship \nin Hair Transplant surgery and Dermatology Surgery \nfor the American Academy of Dermatology.\n\n\n\nThe role of Dermatology in the evolution of Hair \nRestoration Surgery is undeniable. From the \nearliest prewar days of Okuda to O Tar Norwoods \nclassification of Androgenetic Alopecia in Men1 to \nDow Stough founding of the International Society \nof Hair Restoration Surgeons (ISHRS) and all that \ncame in between and after we hope to present a \nbrief summary of the evolution of this procedure \nwhich continues to improve the quality of life of the \nfollicularly compromised.\n\n\n\nHair transplants true forefathers were the Japanese \nDermatologist Sheiji\t Okuda2 and the Urologist \nHajime\tTamura. Both performed successful grafts \nin the 1930s, initially on the scant eyebrows of \nHansens patients.\n\n\n\nThe Father of modern Hair Transplants is arguably \nthe New York Dermatologist Orentreich who took \nup the reigns in 1952 focusing on Androgenetic \nAlopecia whilst using 4mm punch grafts to \ntransolocate hair from the genetically protected \nSafe lower occipital region, to the vertex and crown \narea, which  resulted in the unfortunate \u2018dolls hair \n\u2018 plugs that gave the procedure a sullied reputation \nfor decades.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 81\n\n\n\nIt wasn\u2019t until 1984 when the pathologist John \nHeadington defined the anatomical follicular unit \nas harboring one to four hairs3 that dermatologists \nbegan to harvest and replant with the goal of \nmaintaining these units. \n \nThus, it was that in 1988 the first single hair \nunit transplantations were performed by Bobby \nLimmer, from an elliptical donor strip followed \nby stereo microscopic dissection of the individual \ngrafts after which micro tunnels are created in the \nrecipient area for the insertion of the prepared grafts \nwhich forms the basis of the Modern hair Transplant \ntechnique by FUT (Follicular Unit Transplantation) \nas defined by Bernstein and Rassman.4\n\n\n\nThus, single hair Follicular units (FU) would be \nplaced in the hair line, whilst the double and triple \nFUs would be placed further away creating greater \ndensity where necessary. Mario Marzola refined \nthe donor strip harvesting technique by introducing \nTrichophytic closure which allows for much finer \nscars.\n\n\n\nVarious Hair line designs have been proposed and \npublished in the ISHRS journals which have resulted \nin a move away from the straight lines of the past. \nThe use of tumescent anaesthesia as conceived by \nDermatologist Jeffery Klein, the forefather of in- \noffice Liposuction5-6 has allowed this procedure to \nbe performed safely with negligible bleeding. \n\n\n\nEmergence\tof\tthe\tFUE\ttechnique\t\nIn 1988 \u2013 Masumi\t Inaba \u2013 extracted individual \nfollicles with a single 1mm bore needle, which \npaved the way for Rassman& Bernstein \u2018s seminal \npaper on Follicular Unit extraction / FUE, published \nin 2002.7\n\n\n\nNumerous device companies (Harris, WAW pedal) \nhave since emerged to assist in the deft technique of \nFollicular extraction with the use of drill machines \nmanually used to extract individual follicles. The \ndevelopment of a Robot (Artus technologies) \nhopes to make this part of the procedure easier. The \nSurgeon and team in this case remains involved \nin the planning and creation of recipient sites, but \nmay relax and have a coffee during the extraction \nphase. Unfortunately, the expense of the Robot and \nthe added discomfort to the patient as mobility is \nstrictly restrained are limiting factors. \n\n\n\nControversies:\nFUE versus FUT \n\n\n\nFUT \u2013 Traditional strip harvesting \u2013 where a strip \nof skin is taken usually from the occiput in the zone \nbetween the ears, after which technicians sliver and \ndissect into individual graft. Full scalp shaving is \nNOT required.\n\n\n\nFUE \u2013 Extraction of the individual follicles spread \nover the entire Occipital region using a drill device. \nFull scalp shaving is usually required . Useful when \nBeard or Body to scalp transplants are required or \nwhen a Buzz cut is sported by the patient.\n\n\n\nDue to harvesting from upper zones in the occiput \nwhich may be in danger of loss in the future, the \npermanent status of the follicles in the recipient area \nmay not be such a surety.\n\n\n\nThe extracted follicles often lack the fat protection \nthat dissected grafts enjoy thus making them more \nfragile. \n\n\n\nThe scaring that ensues from harvesting from a wide \nswathe of skin, results in distortion of the remaining \ngrafts making follicular extraction more challenging \nif a subsequent procedure is required in the future. \nThus, one would be inclined NOT to chose FUE in \na younger patient. In brief a complete Transplant \nSurgeon should be adept at both techniques.\n\n\n\nThe internet has complicated matters by putting \nFUE on a pedestal, dominating infommercials on \nthis procedure giving the public a skewed version \nof the truth. Still by obviating the need for full scalp \nshaving allowing the patient to return to work as \nsoon as possible FUT is able to retain its appeal to \nmany.\n\n\n\nHair Transplant surgery is an extremely rewarding \ntechnique when performed with the attention it \ndeserves, heeding the voices of Dermatologists past \nand present.\n\n\n\nConflict\tof\tInterest\tDeclaration\nThe author has no financial / conflict of interest to \ndisclose.\n\n\n\nAcknowledgement\nThe author would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 4082\n\n\n\nReferences\n\n\n\n1. Norwood OT. Male pattern baldness: classification and \nincidence. South Med J 1975;68:1359-65.\n\n\n\n2. Okuda S. Clinical and experimental studies on hair \ntransplanting of living hair (in Japanese). Jpn J Dematol \nUrol 1939;46:537-87.\n\n\n\n3. Headington JT. Transverse microscopic anatomy of the \nhuman scalp. A basis for a morphometric approach to \ndisorders of the hair follicle. Arch Dermatol 1984;120:449-\n56.\n\n\n\n4. Bernstein RM, Rassman WR, Seager D, Shapiro R, Cooley \nJE, Norwood OT et al. Standardizing the classification \nand description of follicular unit transplantation and \nmini-micrografting techniques. The American Society for \nDermatologic Surgery, Inc. Dermatol Surg 1998;24:957-\n63.\n\n\n\n5. Klein JA. The tumescent technique for liposuction surgery. \nJ Am Acad Cosmetic Surg 1987;4:263\u20137.\n\n\n\n6. Klein JA, Jeske DR. Estimated Maximal Safe Dosages of \nTumescent Lidocaine. Anesth Analg 2016;122:1350-9.\n\n\n\n7. Rassman WR, Bernstein RM, McClellan R, Jones R, \nWorton E, Uyttendaele H. Follicular unit extraction: \nminimally invasive surgery for hair transplantation. \nDermatol Surg 2002;28:720-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2018 June Vol 40 83\n\n\n\nACKNOWLEDGEMENT\nJune\tIssue\t2018\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Datin Dr Asmah Johar\n4. Dr Azura Mohd Affandi\n5. Dr Ch\u2019ng Chin Chwen\n6. Dr Chan Lee Chin\n7. Dr Chang Choong Chor\n8. Dr Chong Yew Thong\n9. Dr Dawn Ambrose\n10. Assoc Professor Dr Felix Yap Boon Bin\n11. Dr Henry Foong Boon Bee\n12. Dr Michelle Voo Sook Yee\n13. Dr Ng Ting Guan\n14. Dato\u2019 Dr Noor Zalmy Azizan\n15. Assoc Professor Dr Norashikin bt Shamsudin\n16. Dr Pubalan Muniandy\n17. Dr Rohna Ridzwan\n18. Dr Sabeera Begum\n19. Dr Tang Jyh Jong\n20. Dr Tang Min Moon\n21. Dr Tey Kwee Eng\n\n\n\n\n\n"
"\n\nVolume 23   |  Dec 2009   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.my\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA    DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\nMJD 2009 December Vol 23\n\n\n\nCosmesis for port wine\n\n\n\nTest your diagnostic \nskill\n\n\n\nCutaneous adverse \ndrug reactions\n\n\n\nMimicry of the\ngreat mimicker\n\n\n\nContact allergen in \nMalaysians with hand \n& feet dermatitis\n\n\n\n1\n\n\n\n19\n\n\n\n21\n\n\n\n28\n\n\n\n41\n\n\n\nHighlights\n\n\n\nPersistent groin pruritus12\n\n\n\nNursing care plan  for nurses55\n\n\n\nADR with intramuscular\nVitamin K\n\n\n\n23\n\n\n\nSelf assessment\n- Diagnostic skill\n\n\n\n14\n\n\n\nMistaken for hand dermatitis15\n\n\n\n\n\n\n\n\nMJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nEditor-in-Chief (Administrative)\n\n\n\nRohna Ridzwan, MRCP \n\n\n\nEditorial Office\nDepartment of Dermatology\n\n\n\nSelayang Hospital\n\n\n\nLebuhraya Selayang Kepong\n\n\n\n68100 Batu Caves\n\n\n\nSelangor Darul Ehsan, Malaysia\n\n\n\nEmail : rohnaridzwan@yahoo.com\n\n\n\nAdvertisement Committee\n\n\n\nIndependent team members\n\n\n\nEditorial Board\n\n\n\nGangaram Hemandas, FRCP (Chief Editor)\nKuala Lumpur\n\n\n\nHenry Foong Boon Bee, FRCP\nIpoh, Perak\n\n\n\nChan Lee Chin, MMed\nPenang\n\n\n\nAgnes Heng Yoke Hui, MRCP\nIpoh, Perak\n\n\n\nAllan Yee Kim Chye, FRCP\n(Deceased)\n\n\n\nEditor Emeritus\n\n\n\nSuraiya Hani Hussein FRCP\nKuala Lumpur\n\n\n\nExecutive Staff\n\n\n\nMardziah Alias, MMed (Paeds) - President\nKoh Chuan Keng, MRCP - Vice President\nHenry Foong Boon Bee, FRCP - Secretary\nNajeeb Ahmad Mohd Safdar, MRCP - Treasurer\nGangaram Hemandas, FRCP\nAgnes Heng Yoke Hui, MRCP\nOng Cheng Leng, MRCP\nChan Lee Chin, MMed\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2(Remis)\nPantai Panorama Condominium\nJalan 112, Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\nPrinted by Cetak Sri Jaya, 11, Jalan Ambong Kanan 3, Kepong Baru, 52100 Kuala Lumpur, Malaysia.\n\n\n\n\u00ae 2009 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nThe inclusion of an advertisement in MJD is not to be construed or publicized as an endorsement or\napproval by the Society of any product, service or company; nor may the advertiser represent that its\nadvertising claims have been approved or endorsed by the Society.\n\n\n\n\n\n\n\n\ni MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nNotice to Authors\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts\non all aspects of cutaneous medicine and surgery in the form of\noriginal articles, research papers, case reports and\ncorrespondence. Contributions are accepted for publication on\ncondition that they are submitted exclusively to the Malaysian\nJournal of Dermatology. The Publisher and Editors cannot be\nheld responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and\nopinions expressed do not necessarily reflect those of the\npublisher and Editors, neither does the publication of\nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:\nrohnaridzwan@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology can\nbe sent to me at\n\n\n\nDr. Rohna Ridzwan\nDepartment of Dermatology\nSelayang Hospital, Lebuhraya Selayang Kepong\n68100 Batu Caves, Selangor Darul Ehsan, Malaysia\nEmail : rohnaridzwan@yahoo.com\n\n\n\nContributions should be written for one of the following\ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than three\nillustrations. This category offers a means for rapid\ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation.\nThis category provides rapid publications and is meant to be a\nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five\nreferences. The author may express his or her opinion without\ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and\npathological photographs in color. The diagnosis and legends\nfor the photographs should be listed after the references in the\narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not\nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. Article\ntypes may include Review, Report or Case Report Format. \n\n\n\nOriginal Article\nAn original article including, whenever possible, an\nIntroduction, Materials and Methods, Results, Comment, and\nReferences. A Structured Abstract of not more than 240 words\nmust be included. It should consist of four paragraphs, labeled\nBackground, Methods, Results, and Conclusions. It should\ndescribe the problem studies, how the study was performed, the\nmain results, and what the author(s) concluded from the results. \n\n\n\nReview\nBy invitation only. A major didactic article that clarifies and\nsummarizes the existing knowledge in a particular field. It\nshould not be an exhaustive review of the literature, and\nreferences should not exceed 100 in number. Tables, diagrams,\nand selected figures are often helpful. The length is left to the\njudgment of the author, although it generally should not exceed\n\n\n\n5000 words. Topics may include updates in clinically relevant\nbasic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of the\npaper, the author(s)' name(s), degrees, and affiliation(s), the\ncategory of the article, the number of figures and tables, and\nthree key words for indexing purposes. The name and full postal\naddress (including a street address), phone and fax numbers and\nan email address of the corresponding author who will be\nresponsible for reading the proofs must also be given on the title\npage. The author(s) must also declare any affiliation or\nsignificant financial involvement in any organizations or entity\nwith a direct financial interest in the subject matter or materials\ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. 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M J Dermatol 2006;19:52-\n55\n\n\n\nReferences to books should include: (1) author(s) or editor(s);\n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4)\nplace of publication; (5) publisher; (6) year; (7) page(s) referred\nto. \n\n\n\nFor example:\nFoong HBB.  Transcontinental Dermatology: Virtual Grand\nRounds. In: Wootton R and Oakley A, editors. Teledermatology.\nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of\nall references; incomplete references may result in a delay to\npublication. \n\n\n\nTables should be typed, double-spaced with a heading, each on\na separate sheet, and should only include essential information.\nDrawings, graphs, and formulas should be submitted on\nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of\nphotomicrographs, the stain type and original magnification\nshould be stated. Each figure should bear a reference number\ncorresponding to a similar number in the text. \nTo minimise the publication time of your manuscript it is\nimportant that all electronic artwork is supplied to the Editorial\nOffice in the correct format and resolution. \n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible for errors\nor any consequences arising from the use of information\ncontained in this journal; the views and opinions expressed do\nnot necessarily reflect those of the publisher and Editors, neither\ndoes the publication of advertisements constitute any\nendorsement by the publisher and Editors of the products\nadvertised.\n\n\n\n\n\n\n\n\niiMJD 2009 December Vol 23\n\n\n\nJURNAL DERMATOLOGI MALAYSIA\n\n\n\nVOLUME 23  |  NOVEMBER 2009  |  ISSN: 1511-5356\n\n\n\nContents\nDERMATOSURGERY\n\n\n\nOriginal Article\n1 Treatment response of port-wine to \n\n\n\n585nm pulse dye laser: A five-year \nretrospective review\nNorashikin S, AdvMDerm (UKM),\nGangaram HB, FRCP, Suraiya HH, FRCP\n\n\n\nGENERAL DERMATOLOGY\n\n\n\nOriginal Article\n7 Hidradenitis suppurativa: a review of 15 \n\n\n\npatients \nLeelavathi M, GDFPD, Barath Y, MD,\nGangaram HB, FRCP, Suraiya HH, FRCP, \nNorazirah MN, MRCP, Mazlin MB, MRCP \n\n\n\n11 A 5-year retrospective study on \nonychomycosis and its causative \norganisms in University Malaya Medical \nCentre (UMMC)\nLau SL, Wong SM, MRCP\n\n\n\nShort Communication\n16 Persistent groin itch\n\n\n\nTang MM, AdMDerm, Chang CC, AdMDerm,\nAsmah J, MMed\n\n\n\n18 Herpes zoster presenting as cellulitis of \nthe nose\nKader M, MRCP\n\n\n\nSelf Assessment\n19 Diagnostic skill testing for primary care \n\n\n\nproviders\nRR\n\n\n\nADVERSE DRUG REACTIONS\n\n\n\nUpdate from Malaysian National \nPharmaceutical Control Bureau\n\n\n\n21 Cutaneous adverse drug reactions:\na medical concern?\nTan LS, Fuziah AR, Ng SP\n\n\n\nCase Reports\n24 Aplasia cutis congenita secondary to \n\n\n\nmaternal exposure to carbimazole during \npregnancy \nTey KE, MRCP, Chong YT, Choon SE, MRCP\n\n\n\n27 Cetirizine induced bullous fixed drug \neruptions\nTan WC, MRCP, Chan LC, MMed\n\n\n\nUpdate\n30 Intravenous Vitamin K administration\n\n\n\nNorkasihan I, Fadilah O, Norliza MA, Zainon A\n\n\n\nShort Communication\n31 Cutaneous hypersensitivity to \n\n\n\nintramuscular vitamin K \nRaoul RS, MBBS, Rohna R, MRCP\n\n\n\nAUTOIMMUNE DISORDERS \n\n\n\nCase Reports\n33 Pemphigus foliaceous and Thymoma:\n\n\n\nA report of 2 cases\nTang MM, AdMDerm, Lee YY, AdMDerm,\nSuganthi T, MMed\n\n\n\n38 Mimicry of the great mimicker \nLee YY, AdMDerm, Priya G, MRCP,\nSuganthi T, MMed\n\n\n\nCONTACT DEMATITIS & OCCUPATIONAL\nDERMATOSES \n\n\n\nOriginal Article\n41 Clinical pattern and causative allergens \n\n\n\nof hand and / or feet eczema identified \nfrom patch test - a retrospective 5 year \nstudy\nPriya G, MRCP, Asmah J, MMED,\nGangaram HB, FRCP, Suraiya HH, FRCP\n\n\n\nGRANULOMATOUS DISEASES\n\n\n\nCase Report\n51 Cutaneous Sarcoidosis mimicing \n\n\n\nTuberculoid Leprosy\nChong YT, MRCP, Tey KE, MRCP,\nChoon SE, FRCP\n\n\n\nANNOUNCEMENT\n\n\n\nContinuous Professional Development\n(iii) 19th Regional Conference of Dermatology\n56 22nd World Congress of Dermatology\n\n\n\nAdministrative Update\n51 Monitoring doctors\u2019 performance in skin \n\n\n\nbiopsy using CUSUM technique\nChang CC, Azizan NZ, Roshidah B\n\n\n\nNURSING\n\n\n\nQuiz\n57 Dermatology Care Plan Quiz for nurses\n\n\n\nRR\n\n\n\nANSWERS TO QUIZES\n\n\n\n58 Answers to Clinical Diagnostic Skill Test\n\n\n\n60 Answers to Dermatology Care Plan Quiz\n\n\n\nMalaysian Journal of  Dermatology\n\n\n\n\n\n\n\n\niii MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nANNOUNCEMENT\nContinuous Professional Development\n\n\n\n19th Regional Conference of Dermatology\n\n\n\n(Asian - Australasian)\n\n\n\nOrganizers : Dermatological Society of Malaysia\n\n\n\nTheme : Dermatology without Borders\n\n\n\nVenue : Sutera Habour Resort Hotel, Kota Kinabalu, Sabah\n\n\n\nDate : 28-31 October 2010\n\n\n\nProgram : Incorporation of the 2nd Meeting of the AAVD\n\n\n\n\n\n\n\n\n1MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDERMATOSURGERY - Original Article\n\n\n\nTreatment response of port-wine stain to 585-nm pulsed\n\n\n\ndye laser: a five-year retrospective review                           \n\n\n\nNorashikin S1, Adv MDerm (UKM), Gangaram HB2, FRCP, Suraiya H Hussein2 FRCP\n\n\n\nAbstract\n\n\n\nBackground The treatment of port-wine stains (PWS) with the pulsed dye laser (PDL) is well\nestablished in patients with lighter skin phototypes with few complications. Evidence is emerging\nthat PDL also produces favourable outcome in patients with darker skin types. This review aimed to\nevaluate the efficacy of flashlamp-pumped PDL for PWS in our centre and to assess the\ncomplications of treatment.\n\n\n\nPatients and Methods A retrospective review of 36 patients with PWS treated with PDL (585-nm,\n450 microseconds pulse width, Candela Sptl-1b) at the Department of Dermatology, Hospital Kuala\nLumpur over a five-year period from 2003 to 2007 was undertaken.  All patients (28 females, 8\nmales; 25 Chinese, 10 Malays and 1 Indian) were of Fitzpatrick skin types IV (30/36) and V (6/36)\nwith ages ranged from 1 to 59 years (mean 18.9 years). The site of lesion was mainly facial (34/36)\nwith colour varying from red (24/36) to pink (4/36), dark purple (1/36) and mixed (7/36). Response\nwas graded as 0-25% = nil to minimal lightening; 26-50% = moderate lightening; 51-75% = marked\nlightening; 76-100% = excellent based on the last treatment visit.\n\n\n\nResults The number of sessions ranged from 2 to 16 over 4 to 52 months (mean 5.9 months). The\naverage treatment interval was 4.6 months (range, 1 to 13 months). In a total of 213 sessions,\nminimal lightening was observed in 19(53%) patients after a mean of 4.2 sessions, moderate\nlightening in 8(22%) patients after a mean of 8.1 sessions, marked lightening in 3(8%) patients after\na mean of 6 sessions and excellent in 6(17%) patients after a mean of 6.8 sessions. No patient\nshowed complete clearance. 1 patient developed both textural change and scarring.\n\n\n\nConclusion The flashlamp-pumped PDL is a useful and safe treatment modality for PWS in Asian\npatients of darker skin phototypes.\n\n\n\nKeywords port-wine, 585 nm Pulse dye laser\n\n\n\nCorrespondence\nNorashikin Shamsudin, Adv MDerm\n1Department of Medicine\nFaculty of Medicine and Health Sciences\nUniversity Putra Malaysia, 43400 Serdang\nSelangor, MALAYSIA\nE-mail : aliffarhan@yahoo.com\n\n\n\n2Department of Dermatology, Kuala Lumpur Hospital\n\n\n\nIntroduction\nPort-wine stains (PWS) are congenital capillary\nmalformations that afflict 0.3% to 0.5% of\nnewborns with an equal sex distribution1.\nHistologically, it consists of dilated post-capillary\nvenules with increased numbers of normal looking\ncapillaries.\n\n\n\nIt is often unilateral with half of the cases occurring\non the face. The lesions are flat, pinkish-red to deep\npurple in colour and tend to darken and thicken\nwith time, often becoming raised and nodular as\nvessel diameter increases with age1. The major\nconsequences of PWS are physical and\npsychosocial impairment because of gradual\nhypertrophy and disfigurement, although it can be\nassociated with ocular (glaucoma) and neurological\ncomplications (Sturge-Weber syndrome). \n\n\n\nThe pulsed dye laser (PDL) is undoubtedly the\ntreatment of choice for port-wine stains. It is based\non the principle of selective photothermolysis with\noxyhaemoglobin as the chromophore. PDL has\nshown excellent cosmetic results in fair-skinned\nindividuals with low incidence of side-effects2.\nFavourable\n\n\n\n\n\n\n\n\n2 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nFavourable results on darker skin types of Asian\npatients have been also been achieved3,4,5. At present\nhowever, there is no published data on the efficacy\nand complications of treating PWS with PDL in\nlocal patients who are mainly of darker skin types.\n\n\n\nThe aims of this review were to evaluate the\ntherapeutic response of PWS to the 585-nm flash-\nlamp pumped PDL in patients treated at the\nDepartment of Dermatology, Hospital Kuala\nLumpur and to assess the complications of\ntreatment.\n\n\n\nPatients and methods\nA retrospective review of 36 patients with PWS\ntreated with the 585-nm flash-lamp pumped PDL\n(450 microseconds pulse width, Candela Sptl-1b) at\nthe Department of Dermatology, HKL from 2003 to\n2007 was undertaken. The demographic details,\nclinical features and laser parameters were\nreviewed. The therapeutic responses recorded at\neach session and at 3 to 6 months after\nthe final treatment session (if available) were\nanalyzed. Complications such as hyper and\nhypopigmentation, textural changes and scarring\nrecorded at every visit were also reviewed.\n\n\n\nOut of 36 patients, 2 had previously received\nPDL laser treatments elsewhere with minimal\nimprovement and no side-effects. The first patient\nhad 8 sessions in 1997 and from 2003 to 2006 and\nthe second patient had unknown number of sessions\nfrom 1995 to 1996. Response was graded as 0-25%\n= nil to minimal lightening; 26-50% = moderate\nlightening; 51-75% = marked lightening; 76-100%\n= excellent lightening based on patients\u2019 assessment\nin the last treatment visit.\n\n\n\nResults\nThe demographic profile and skin photo types are\nshown in Table 1. All patients were of Fitzpatrick\nskin type IV (30/36) and V (6/36). Majority of\npatients were female and there were\ndisproportionately more Chinese patients (n=25,\n69.4%) as compared to the clinic attendance during\nthe 5 year study period (Malays 53.8%, Chinese\n22.6%, Indians 21%, others 2.6%). Table 2\nsummarizes the clinical features of these patients.\nThe PWS lesions were mainly on the face and neck\n(30/36), red (24/36) and macular (25/36). 3 patients\nhad associated glaucoma and Sturge-Weber\nsyndrome.\n\n\n\nThe number of treatment sessions ranged from 2 to\n16 over 4 to 52 months (mean, 5.9 treatments) with\nan average treatment interval of 4.6 months (range,\n1 to 13 months). Laser parameters used were spot\nsize, 7mm; fluence, 5 -7.5 J/cm2; fixed wavelength\n(585-nm); pulse width (450 microseconds) with10-\n20% overlapping of spots. Adults tolerated the\ntreatment well with ice pack cooling while 5 out of\n16 children were treated under general anaesthesia.\n\n\n\nTable 1 Demographic profile and skin photo types\n\n\n\nSex \n\n\n\nAge \n\n\n\nRace\n\n\n\nSkin photo type\n\n\n\nF:M = 28:8 (3.5:1)\n\n\n\n1-59 years (mean 18.9)\n\n\n\nMalay\n\n\n\nChinese \n\n\n\nIndian\n\n\n\nIV\n\n\n\nV\n\n\n\n10 (27.8%) \n\n\n\n25 (69.4%)\n\n\n\n1 (2.8%)\n\n\n\n30 (83.3%)\n\n\n\n6 (16.7%)\n\n\n\nTable 2 Clinical features of port-wine stain\n\n\n\nSite \n\n\n\nColour \n\n\n\nMorphology \n\n\n\nGlaucoma and \nSturge-Weber \nsyndrome\n\n\n\nface and neck\n\n\n\ntrunk \n\n\n\nextremities\n\n\n\npink\n\n\n\nred\n\n\n\ndark purple\n\n\n\nMixed (red to light purple)\n\n\n\nentirely macular \n\n\n\nmostly macular with some \npapules\n\n\n\nentirely papular \n\n\n\nentirely plaques \n\n\n\nmostly plaques with some \nnodules\n\n\n\n3 (8.3%)\n\n\n\n30 \n\n\n\n5 \n\n\n\n2 \n\n\n\n4 (11.1%) \n\n\n\n24 (66.7%) \n\n\n\n1 (2.8%) \n\n\n\n7 (19.4%) \n\n\n\n25 (69.4%) \n\n\n\n5 (13.9%)\n\n\n\n1 (2.8%) \n\n\n\n3 (8.3%) \n\n\n\n2 (5.6%)\n\n\n\n\n\n\n\n\n3MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nIn a total of 213 sessions, minimal lightening was\nobserved in 17(47%) patients after a mean of 4\nsessions, moderate lightening in 10(28%) patients\nafter a mean of 8 sessions, marked lightening in\n3(8%) patients after a mean of 6 sessions and\nexcellent in 6(17%) patients after a mean of 7\nsessions (Table 3). None of these patients showed\ncomplete clearance. Figure 1and 2 show 2 patients\nwho achieved excellent response to PDL.\n\n\n\nThe treatment response was compared with respect\nto age at intervention, site and morphology of PWS\nand number of treatment sessions (Table 4.1- 4.4).\nThe only factor that seemed to affect the treatment\noutcome was the age at intervention (p=0.17,\nFischer\u2019s exact test). Younger patients (<16 years)\nwith PWS appeared to respond better to PDL\n\n\n\ncompared to older patients. Similarly, majority of\nadult patients with PWS showed minimal lightening\n(60% adults versus 31% paediatrics) and more\npaediatric patients showed moderate lightening\n(44% versus 15%) compared to their adult\ncounterparts. Otherwise, the sample size was too\nsmall to make any meaningful comparisons\nbetween other attributes such as anatomical\nlocation, morphology, number of treatment sessions\nand the treatment outcome.\n\n\n\nComplications are rare as none of our patients\ndeveloped hyper- or hypopigmentation and only\none developed both scarring and textural change.\nMinor blistering and crusting were accepted as\nusual consequences of PDL treatment and not\nconsidered as an adverse event.\n\n\n\nFigure 1 Pink-coloured PWS over the left face. More than 75% lightening after 5 sessions\n\n\n\nFigure 2 Red-coloured PWS over the left cheek. More than 75% lightening after 3 sessions\n\n\n\n\n\n\n\n\n4 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 3 Treatment response to pulsed dye laser\n\n\n\nLightening\nresponse\n\n\n\nNil to minimal\n(0-25%)\n\n\n\nModerate\n(26-50%)\n\n\n\nMarked\n(51-75%)\n\n\n\nExcellent\n(76-100%)\n\n\n\n17 (47.2%) \n\n\n\n10 (27.8%)\n\n\n\n3 (8.3%) \n\n\n\n6 (16.7%) \n\n\n\n2-12 (4.2)\n\n\n\n3-14 (8.1)\n\n\n\n3-11 (6)\n\n\n\n4-10 (6.8)\n\n\n\nNo. of patients\n(%)\n\n\n\nNo. of sessions\n(mean)\n\n\n\nTable 4.1 Comparison of response with age at intervention\n\n\n\nResponse\n\n\n\n0-25%\n\n\n\n26-50%\n\n\n\n51-75%\n\n\n\n76-100%\n\n\n\n5 (31.3%)\n\n\n\n7 (43.8%)\n\n\n\n2 (12.5%)\n\n\n\n2 (12.5%)\n\n\n\n<16\n(n= 16)\n\n\n\n12 (60%)\n\n\n\n3 (15%)\n\n\n\n1 (5%)\n\n\n\n4 (20%)\n\n\n\n\ufffd16\n(n=20) \n\n\n\nAge at intervention (years)\n\n\n\nTable 4.3 Comparison of response with morphology of port-wine stain\n\n\n\nResponse\n\n\n\n0-25%\n\n\n\n26-50%\n\n\n\n51-75%\n\n\n\n76-100%\n\n\n\nmacular\n\n\n\nn=25  \n\n\n\n9  (36%)\n\n\n\n7  (28%)\n\n\n\n3  (12%)\n\n\n\n6  (24%)\n\n\n\nmacular with\npapules\n\n\n\nn=5\n\n\n\n3 (60%)\n\n\n\n2 (40%)\n\n\n\n0\n\n\n\n0\n\n\n\nentirely popular\n\n\n\nn=1\n\n\n\n1 (100%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\nentirely plaques\n\n\n\nn=3\n\n\n\n3 (100%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\nplaques with\nnodules\n\n\n\nn=3\n\n\n\n1 (50%)\n\n\n\n1 (50%)\n\n\n\n0\n\n\n\n0\n\n\n\nMorphology\n\n\n\nTable 4.2 Comparison of response with site of port-wine stain\n\n\n\nResponse\n\n\n\n0-25%\n\n\n\n26-50%\n\n\n\n51-75%\n\n\n\n76-100%\n\n\n\n15 (44.1%)\n\n\n\n10 (29.4%)\n\n\n\n2 (28.8%)\n\n\n\n6 (17.6%)\n\n\n\nSite of PWS\nFace and           neck              trunk\nextremities\n(n=34) (n=3)\n\n\n\n3 (100%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n(n=2)\n\n\n\n2 (100%)\n\n\n\n0\n\n\n\n0\n\n\n\n0\n\n\n\n\n\n\n\n\n5MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nDiscussion\nIn our study 53% of the cases showed greater than\n25% lightening after a mean of 7 sessions. In\ncomparison with previous studies on Asian patients\nof dark skin types, PDL appears slightly less\neffective in this study (Table 5). Majority of our\npatients achieved minimal response (47.2%) as\nopposed to the other two studies, in which majority\nof their patients achieved at least a moderate\nresponse. However, the proportion of patients who\nachieved excellent response was comparable\nbetween the three studies. The laser parameters\nused in all three studies were comparable with\nrespect to the wavelength and pulse width used. In\none of the study, the investigators used spot size of\n5 to 10 mm to target vessels at varying depth3.\n\n\n\nThe use of PDL treating PWS in patients of\nFitzpatrick skin types I to III is well established,\n\n\n\nwith one series of fifty-two patients showing >75%\nimprovement in 44% of patients2,6. In general, up to\n60% of patients can achieve a good reduction in\nsize and a lightening of the colour, whereas\ncomplete clearance can only be achieved in about\n10% of patients7. None of our patients achieved\ncomplete removal of their lesions.\n\n\n\nThe lower efficacy of PDL in dark-skinned\nindividuals is due to the fact that at 585-nm, some\nabsorption by epidermal melanin does occur.\nMelanin acts as a competing chromophore resulting\nin less energy reaching the target vessels and\ncausing vascular damage. Higher fluences are\ntherefore required to produce greater absorption by\nthe target vessels. The thermal damage with higher\nfluence can be prevented by using a cooling device.\nHowever, with our pulse dye laser (SPTL-1b), there\nis no cooling device incorporated, hence we were\nunable to use too high a fluence to cause the\nnecessary vascular damage. The lower efficacy in\nthis study could also be explained by the long\naverage treatment interval (4.6 months) which was\nlargely due to administrative reasons and patients\nfailing to turn up for their treatment visit and had to\nbe rescheduled. The recommended treatment\ninterval is 6-8 weeks. Most patients also need up to\n10 or more treatments for optimal results. We used\na fixed wavelength, pulse duration and spot size for\nall types of PWS irrespective of their colour and\nthickness. Longer wavelength PDLs with longer\npulse widths (595-nm, 1.5-40 ms) are more\neffective in targeting deeper and larger-calibre\nvessels which would have been more effective in\nadults and those with hypertrophic nodular lesions. \n\n\n\nTable 4.4 Comparison of response with number of treatment \nsessions\n\n\n\nResponse\n\n\n\n0-25%\n\n\n\n26-50%\n\n\n\n51-75%\n\n\n\n76-100%\n\n\n\n1-5\n(n= 21)\n\n\n\n14 (66.7%)\n\n\n\n4 (19%)\n\n\n\n2 (9.5%)\n\n\n\n1 (4.8%)\n\n\n\n6-10\n(n=10) \n\n\n\n2 (20%)\n\n\n\n3 (30%)\n\n\n\n0\n\n\n\n5 (50%)\n\n\n\n>10\n(n=5) \n\n\n\n1 (20%)\n\n\n\n3 (60%)\n\n\n\n1 (20%)\n\n\n\n0\n\n\n\nNo. of sessions\n\n\n\nTable 5 Comparison with other studies of Asian patients\n\n\n\nEthnic group/skin\nphototype/study type\n\n\n\nIndian /IV and V4\n\n\n\nn=27 \nProspective\n\n\n\nAsian or Libyan/V3\n\n\n\nn=13 \nRetrospective\n\n\n\nHKL /IV and V*\nn=36 \nRetrospective\n\n\n\nFluence (J/cm2)/spot\nsize (mm)\n\n\n\n5-7.5/7\n\n\n\n6-7.25/5 \n5.5 -7/7\n4.5-4.75/10\n\n\n\n5-7.5 /7\n\n\n\n<25%\n\n\n\n22.2\n\n\n\n15.4\n\n\n\n47.2\n\n\n\n26-75%\n\n\n\n59.2\n\n\n\n61.5\n\n\n\n36.1\n\n\n\n>75%\n\n\n\n18.5\n\n\n\n15.4\n\n\n\n16.7\n\n\n\nComplication rates \n\n\n\n29.6% -pigmentary changes only\n\n\n\n53.7% - pigmentary changes\n15% - atrophic scarring\n\n\n\n2.8%- textural change\n2.8%- scarring\n\n\n\nLightening response (% of patients)\n\n\n\n\n\n\n\n\n6 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe results of PDL treatment in general depend on\nthe patient\u2019s age, the localization of the lesion and\nthe colour of the PWS7,12. This study shows that the\npatient\u2019s age has a significant effect on the\ntreatment response which is in keeping with\nprevious findings8,9. The pulse duration of 450\nmicroseconds is at the lower end of the thermal\nrelaxation time range for skin vasculature and may\nexplain why PDL is more effective in children than\nin adults, in whom the caliber of ectatic vessels\nincreases with age1.\n\n\n\nPWS located in the face respond better to laser\ntherapy than those in the trunk and extremities.\nKatugampola and Lanigan obtained good results in\n52% of facial lesions in contrast to 18% of non-\nfacial lesions. We could not demonstrate this in our\nreview due to our small sample size. A study by\nNguyen et al concluded that the location of PWS\nwas the most important factor in lesion clearing,\nfollowed by size, then age9. According to the\nliterature, about 30% of PWS do not respond to\nPDL treatment7. There are various explainations for\nthis. Firstly, a 0.45 ms exposure is too long for small\nvessels but too short for more ectatic vessels;\nsecondly, vessels in adult patients and dark PWS\nmay be located deep in the dermis. For these\nlesions, other lasers such as long-pulsed tunable dye\nlaser (LPTDL), pulsed Nd:YAG and IPL systems\nmay be used.\n\n\n\nHyperpigmentation can be observed in up to 30%\nand hypopigmentation in up to 2% of patients7.\nBecause of higher melanin content, there is a higher\nrisk of hyper- or hypopigmentation in dark-skinned\npatients as shown by previous studies, but this is not\nseen in our study.\n\n\n\nThis study has all the limitations of a retrospective\nanalysis. We relied heavily on patients\u2019 assessment\nof the treatment response and did not use serial\nphotographs taken in identical settings or a blinded\nobserver for assessment.\n\n\n\nThe results of this study indicate that although the\nPDL treatment of PWS in dark-skinned patients is\nless effective in comparison with lighter skin, PDL\ntreatment is worthwhile as some patients can\nachieve a good response and should not be deprived\nfrom the potential cosmetic benefit that can be\ngained.\n\n\n\nConclusion\nThe flash lamp-pumped PDL is an effective and\nsafe treatment modality for PWS. Although the\nresults of this review are less encouraging than\nprevious studies on dark-skinned patients, it is\npossible to get a good response and complications\nare rare. PDL is likely to remain as the standard of\ncare in the treatment of PWS and newer PDL\nsystems are probably better suited for resistant,\nnodular or hypertrophic cases. However, further\nrandomized controlled studies using different laser\nparameters are required to determine the optimal\nlaser settings for Asian patients with PWS.\n\n\n\nReferences\n\n\n\n1. MF Stier, SA Glick, RJ Hirsch. Laser treatment of\npediatric vascular lesions: port wine stains and\nhemangiomas J Am Acad Dermatol 2008; 58(2): 261-\n285\n\n\n\n2. Katugampola GA, Lanigan SW. Five years\u2019 experience\nof treating portwine stains with the flashlamp-pulsed\ndye laser. Br J Dermatol 1997; 137:750-754\n\n\n\n3. Sommer S, Sheehan-Dare RA. Pulsed dye laser\ntreatment of port-wine stains in pigmented skin. J Am\nAcad Dermatol 2000;42:667-671\n\n\n\n4. VK Sharma, S Khandpur. Efficacy of pulsed dye laser\nin facial port-wine stains in Indian patients. Dermatol\nSurg 2007;33:560-566\n\n\n\n5. Ho WS, Chan HH, Ying SY et al. Laser treatment of\ncongenital facial port wine stains: long term efficacy\nand complications in Chinese patients. Lasers Surg\nMed 2002; 30: 44-47\n\n\n\n6. Garden Jm, Polla LL, Tan OT. The treatment of port-\nwine stains by the pulsed dye laser. Arch Dermatol\n1988; 124: 89-96\n\n\n\n7. Landthaler M, Hohenleutner U. Laser therapy of\nvascular lesions. Photodermatology, Photoimmunology\n& Photomedicine 2006; 22: 324-332\n\n\n\n8. Reyes BA, Geronemus R. Treatment of port-wine stains\nduring childhood with the flashlamp-pumped pulse dye\nlaser. J Am Acad Dermatol 1990;23:1142-1148\n\n\n\n9. Nguyen CM, Yohn JJ, Huff C et al. Facial port-wine\nstains in childhood: prediction of the rate of\nimprovement as a function of the age of the patient, size\nand location of the port-wine stain and the number of\ntreatments with the pulsed dye (585 nm) laser. Br J\nDermatol 1998; 138: 821-825\n\n\n\n\n\n\n\n\n7MJD 2009 December Vol 23\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nHidradenitis Suppurativa: A review of 15 patients\n\n\n\nLeelavathi M1, MMed, Barath Y2, MD, Gangaram HB2, FRCP, Suraiya HH2, FRCP, Norazirah MN3, MRCP,\nMazlin MB3, MRCP\n\n\n\nAbstract\n\n\n\nIntroduction Hidradenitis suppurativa is a chronically recurring inflammatory, scarring disease of\nthe apocrine bearing skin. Its diagnosis is mainly clinical, characterized by recurrent multiple\nabscesses, sinuses and scarring of apocrine gland in the intertriginous areas. The aim of this study is\nto determine the demography and clinical features of patients with Hidradenitis suppurativa.\n\n\n\nMethods A retrospective study was conducted to look at the demography and clinical features of\npatients with hidradenitis suppurativa over five years at the Dermatology clinic of Hospital Kuala\nLumpur.\n\n\n\nResults A total of 15 cases were identified. The most frequently affected age group was 21 to 30\nyears (62.5%) with a mean of 27.8 years. Hidradenitis was more common in males (73.4%) as\ncompared to females (26.6%). There was no ethnic preponderance for developing this condition. The\nmost commonly involved site was the axilla (73.3%) and the groin (73.3%) followed by the buttock\n(60.0%). The groin was the most commonly involved area among females (100%) while the axilla\nwas more commonly involved among males (63.6%). The most common associated feature with this\ncondition was  acne. None of the patients had all the four features of follicular occlusion tetrad. One\npatient developed well differentiated squamous cell carcinoma (SCC) after seven years of diagnosis. \n\n\n\nConclusions Since the diagnosis of hidradenitis suppurativa is mainly clinical, commonly involved\nareas should be examined. Clinicians should be aware of the possible progression to squamous\ncarcinoma hence all atypical lesions are best subjected for biopsy and histopathological examination.\n\n\n\nKeywords Hidradenitis suppurativa, apocrine glands\n\n\n\nCorrespondence\nDr Leelavathi M, MMed\nConsultant Family Medicine Specialist & Lecturer\n1Department of Family Medicine, Faculty of Medicine\nPusat Perubatan Universiti Kebangsaan Malaysia\nJalan Yaacob Latif, Bandar Tun Razak\n56000 Cheras, Kuala Lumpur\nEmail : drleelaraj@yahoo.com\n\n\n\n2Department of Dermatology, Hospital Kuala Lumpur\n3Dermatology Unit, Faculty of Medicine\nPusat Perubatan University Kebangsaan Malaysia\n\n\n\nIntroduction\nHidradenitis suppurativa is a chronic recurring,\ninflammatory, scarring disease of the apocrine\nbearing skin. Its diagnosis is mainly clinical,\ncharacterized by recurrent multiple abscesses,\nsinuses and scarring of apocrine gland in the\nintertriginous areas such as the axilla, inguinal,\n\n\n\ninframammary, groin, gluteal cleft and buttock1,2,3.\nThe non-intertriginous areas are not exempted but\nare less commonly involved4. The chronic nature of\nthe disease leads to decreased quality of life with\nthe formation of sinuses, foul smelling discharge\nand disfiguring scars4,5.\n\n\n\nAlthough commonly considered as a rare\ndermatological disorder, some studies report a point\nprevalence of 1-4.1% in the general population1. It\nis found more frequently among females compared\nto males in a ratio ranging from 2-5:1. The exact\naetiology is not well understood but some studies\nhave shown a dominance inheritance pattern in\n27%, although a specific gene location has yet to be\nidentified6. The suggested pathogenesis of this\ndisorder is an initial event of follicular\nhyperkeratosis leading to secondary apocrine\ninvolvement, bacterial infection and rupture7,8. The\nrole of androgens in this sequence of pathogenesis\nis undetermined1.\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n\n\n\n\n\n8 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nAcne conglobata, dissecting foliculitis of scalp and\npilonidal sinus have been described to occur\nconcurrently with hidradenitis suppurativa. The co-\nexistence of these conditions is collectively known\nas follicular occlusion tetrad. The morphological\nfeatures of these conditions are found to be similar\nwhile epidemiological features and response to\ntherapy are different. This suggests that the\nassociation of these conditions could be due to a co-\noccurrence rather than a genetic or an underlying\ncommon pathology9.\n\n\n\nHistologically, early lesions demonstrate spongiosis\nof infra-fundibular region, dilatation of follicular\ninfundibular region and comedone formation.\nInflammation of the apocrine gland is considered a\nsecondary event1. Obesity and tobacco use were\nfound to have inconsistent association with the\ndisease and it is not known whether these are the\nrisk factors for hidradenitis suppurativa or a mere\nconsequence of the chronic nature of this disorder.\nHowever a definite causal relationship has not been\ndemonstrated for smoking and obesity10,11.\n\n\n\nMany modalities of therapy have been have been\nused for the treatment of hidradenitis suppurativa\nwith varying results. The reason for this is perhaps\ndue to the limited knowledge of the exact\npathogenesis of this disease. Medical therapy such\nas topical and systemic antibiotics, retinoid,\nhormonal modulators and surgical therapies have\nbeen tried with varying results. Recently, treatments\nwith immunosuppressive agents have been shown\nto produce remission, although the results were\ninconsistent. This modality of treatment however\nrequires long term follow up as the risk of\nmalignancy associated with these drugs is not\nknown1.\n\n\n\nMaterials and methods\nThis is a retrospective study to describe the\ndemographic details and clinical features of patients\nwith hidradenitis suppurativa over 5 years, from 1st\nJanuary 2002 to 31st December 2006 at the\nDermatology clinic, Hospital Kuala Lumpur.\n\n\n\nAll patients who had the history and clinical\nfeatures of hidradenitis suppurativa of recurrent\ninfected papules, nodules, sinuses or scars were\nincluded in the study. List of patients clinically\ndiagnosed as hidradentis suppurativa was obtained\nfrom a computerized data base. Case notes of these\npatients were reviewed and their details collected\nusing data collection forms and analyzed.\n\n\n\nResults\nA total of 15 patients were identified and their case\nnotes analyzed. Patient\u2019s age ranged from 20 to 70\nyears with a mean of 27.8 years. The most\nfrequently affected age group was 21 to 30 years\n(62.5%). The condition was found to be more\ncommon among males (73.4%) as compared to\nfemales (26.6%). The disease was found among\n40% of the Malay ethnic group, 33% Indians and\n27% Chinese. Family history of hidradenitis was\nelicited in 20% of the study population. The most\ncommon associated clinical feature with\nhidradenitis suppurativa was acne conglobata\nfollowed by smoking and obesity. None of the\npatients presented with all four features of the\nfollicular occlusion tetrad. The other associated\nfeatures are presented in Table 1. \n\n\n\nAreas most commonly involved are axilla (73.3%),\ngroin (73.3%) and buttock (60.0%). In females the\nmost commonly affected site is the groin (100%)\nfollowed by axilla (75%). Among males, axilla was\nmost frequently (63.3%) involved followed by\nbuttock (54.5%). Site preponderance among the\ntwo genders is given in Table 2.\n\n\n\nFour patients (26.7%) underwent a skin biopsy.\nThree out of the four showed histopathological\nfeatures supporting hidradenitis suppurativa while\none showed conversion to malignancy (squamous\ncell carcinoma) after a period of seven years.\nResults are displayed in Table 3.\n\n\n\nDiscussion and conclusions\nIn this study, hidradenitis suppurativa was found to\nbe almost three times more common among males\nas compared to females (2.8:1). The number of\nmale and female patients who attended the\ndermatology clinic during the year of study is\nalmost equal (1:1.2). This finding is in contrast to\nstudies among western population where\nhidradenitis is 2 to 5 times more common\namong females1,2. One possible explanation is\nunderreporting. Female patients in Malaysia may be\nmore reluctant to approach practitioners for\ntreatment as lesions are commonly located in areas\nthat may be embarrassing for them to expose for\nexamination. Most (62.5%) of patients in this study\nwere young adults in the age group of 21 to 30\nyears. This finding is similar to earlier studies6.\n\n\n\nThe ethnic distribution of the population that\nattended the clinic in the study period is 3:1:1 for\nthe Malay, Chinese and Indian while the ratio of\ndisease\n\n\n\n\n\n\n\n\n9MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 1 Associated features of Hidradenitis suppurativa\n\n\n\nPercentage\n\n\n\n33.3\n\n\n\n13.3\n\n\n\n13.3\n\n\n\n6.7\n\n\n\n33.4\n\n\n\n100.0\n\n\n\nAssociated Features\n\n\n\nAcne conglobata\n\n\n\nSmoking\n\n\n\nObesity\n\n\n\nAlcohol consumption\n\n\n\nNo documentation\n\n\n\nTotal\n\n\n\nTable 3 Histopathology summary\n\n\n\nHistopathology  report\n\n\n\nChronic inflammation with scarring. Consistent with hidradenitis suppurativa \n\n\n\nFollicular plugging, focal acanthosis with numerous vascular endothelial, superficial\n\n\n\nand deep inflammatory infiltrate.\n\n\n\nDermis has dense infiltration of acute and chronic inflammatory cells forming micro\n\n\n\nabscesses. Features consistent with hidradenitis suppurativa \n\n\n\nSeveral biopsies:\n\n\n\n1998 Left  buttock: sinus\n\n\n\n1999 Right buttock: epidermal cyst\n\n\n\n2005 Chin and back: epidermal cyst\n\n\n\n2007 Right buttock: well differentiated  SCC\n\n\n\nPatients\n\n\n\nA\n\n\n\nB\n\n\n\nC\n\n\n\nD \n\n\n\nTable 2 Site preponderance of Hidradenitis Suppurativa\n\n\n\nSite\n\n\n\nAxilla\n\n\n\nGroin\n\n\n\nButtock\n\n\n\nChest\n\n\n\nInframammary\n\n\n\nAbdomen\n\n\n\nMale %\n\n\n\n63.6\n\n\n\n36.4\n\n\n\n54.5\n\n\n\n9\n\n\n\n0\n\n\n\n18.1\n\n\n\nFemale %\n\n\n\n75\n\n\n\n100\n\n\n\n25\n\n\n\n25\n\n\n\n25\n\n\n\n0\n\n\n\ndisease of occurrence is 1.5:1:1.2 respectively. This\nstudy does not demonstrate any ethnic\npreponderance of hidradenitis suppurativa. Some\nearlier studies have noted a greater preponderance\nin black population1 while others found no racial\npreponderance11. Positive family history was found\nin 20% of the patients which is almost similar to\nwestern data6,12.\n\n\n\nIn this study, axilla is a common site for this\ncondition among males and females while groin\nlesions were commoner among females. This is\nsimilar to western data1, but some studies show that\nanogenital lesions are more common in men than\nwomen6 while others show that axillary lesion has\nno gender preponderance1. Hence there may be a\ndiscrepancy in the distribution of the lesions in\nrelation to gender without any significance.\n\n\n\nAbout 20% of patient had at least one other\ncomponent of follicular occlusion tetrad. The\ncommon ones being acne conglobata (13.3%) and\ndissecting foliculitis (6.6%) but none of these\npatients had all four components supporting the\npossibility that the association of these conditions\nmay be due to an incidental co-occurrence9. One\nmale patient, developed squamous cell carcinoma at\nthe age of 73 years. This was confirmed by a biopsy\nat the site of initial lesion after seven years of\ndiagnosis. Many studies in the past have found\nassociation between hidradenitis suppurativa and\nnon melanoma cancer. Lapins et al, found a\nsignificant (50%) association between hidradenitis\nsuppurativa and malignant neoplasms. The\ncommonest type is squamous cell carcinoma at the\nsite of lesion followed by buccal and primary liver\ncancer. The average age at which patients developed\ncancer\n\n\n\n\n\n\n\n\n10 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ncancer in that study was 51 to 55 years which is\nabout 1 to 32 years after diagnosis. It is postulated\nthat the chronic event of inflammation and infection\nwith coagulase-negative staphylococci may cause\nproliferative epidermal changes leading to cancer.\nMore females compared to males were found to be\nassociated with non melanoma cancer. This could\nbe due to the earlier onset of this disease among\nfemales compared to males causing prolonged\nexposure to chronic inflammatory process and\nhence malignant transformation13.\n\n\n\nThe occurrence of hidradenitis suppurativa may not\nbe as infrequent as previously assumed but may be\nunder diagnosed. Since the diagnosis is mainly\nclinical, clinicians should have a high index of\nsuspicion of this skin disease. Commonly involved\nareas should be examined and appropriate referral\nto the nearest skin facility should be made. This is\nbecause the management of this condition is\ndifficult in view of inconsistent treatment response\nand frequent recurrences. Clinicians should be\naware of the possibility of the lesions progressing to\nsquamous cell carcinoma, hence atypical lesions\nare best biopsied for histolopathological\nexamination. Although an exact causal relationship\nbetween smoking and hidradenitis suppurativa has\nnot been identified, it would be interesting to\nconduct a prospective study looking at the progress\nof the disease in relationship with cessation of\nsmoking.\n\n\n\nOne of the limitations of this study is the small\nsample size. Severity of symptoms and treatment\noutcomes could not be measured due to the\nretrospective nature of this study.\n\n\n\nReferences\n\n\n\n1. Lee RA, Yoon A, Kist J, Hidradenitis Suppurativa: An\nUpdate. Advances in Dermatology 2007; 23:289-306\n\n\n\n2. Buimer MG, Wobbes T, Klinkenbijl JH. Hidradenitis\nsuppurativa. Br J Surg 2009; 96(4):350-60\n\n\n\n3. Alikhan A, Lynch PJ, Eisen DB Hidradenitis\nsuppurativa: a comprehensive review. J Am Acad\nDermatol 2009; 60(4):539-61\n\n\n\n4. Greer KE, Letter: Facial involvement with hidradenitis\nsuppurativa. Arch Dermatol 1974; 109:408\n\n\n\n5. Morgan WP Huges LE, The distribution, size and\ndensity of the apocrine glands in hidradenitis\nsuppurativa. Br J of Surg1979; 66:853-856\n\n\n\n6. Marni CW. Hiradenitis suppurativa: A Review.\nDermatologic Therapy 2004;17:50-54\n\n\n\n7. Yu CCW, Cook MG. Hidradenitis suppurativa: disease\nof follicular epithelium, rather than apocrine glands. Br\nJ Dermatol 1990; 12:763-769\n\n\n\n8. Attanoos RL, Appleton MAC, Douglas Jones AG. The\npathogenesis of hidradenitis suppurativa : a closer look\nat apocrine and apoecctine glands. Br J Dermatol 1990;\n133: 254-258\n\n\n\n9. Gregor B. E. Jemec, Jean Revuz, James J. Leyden\neditors. Hidradenitis Suppurativa. Springer, New York;\n2006. Chapter 6; p 38-39\n\n\n\n10. Koing A, Lehmann C, Rompel R, Happler R. Cigarette\nsmoking as a triggering factor of hidradenitits\nsuppurativa. Dermatology 1999; 198:261-264\n\n\n\n11. Revuz, JE, Canoui-Poitrine, F, Wolkenstein, P, et al.\nPrevalence and factors associated with hidradenitis\nsuppurativa: results from two case-control studies. J\nAm Acad Dermatol 2008; 59:596\n\n\n\n12. Jansen T, Altmeyer P, Pllewig G. Acne inversa JEADV\n2001;15:532-540\n\n\n\n13. Lapins J, Ye W, Emtestam L. Incidence of cancer among\npatients with hidradenitis suppurativa. Arch Dermatol\n2001;137:730-734\n\n\n\n\n\n\n\n\n11MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nA 5-year retrospective study on onychomycosis and its\n\n\n\ncausative organisms in University Malaya Medical Centre\n\n\n\n(UMMC)\n\n\n\nLau SL1, MBBS, Wong SM2, MRCP\n\n\n\nAbstract\n\n\n\nIntroduction Onychomyosis is a common infection of the nails, caused by dermatophytes, non-\ndermatophyte moulds or yeasts. There are four main types of onychomycosis which include lateral\nand distal onychomycosis, proximal onychomycosis, superficial white and total dystrophic\nonychomycosis. We performed a retrospective analysis looking into the recent trends of\nonychomycosis in a University Hospital in Malaysia.\n\n\n\nMaterials and methods Data was collected from all patients who had their nail clippings cultured\nfor fungal infection from January 2004 to December 2008, and were analysed.\n\n\n\nResults There were 272 nail specimens in total. The majority of specimens were from adults\n(65.8%), followed by the elderly (23.9%) and children and adolescents made up 10.3%. The mean\nage of the study population was 49.9 \u00b1 19SD years. Of the 189 specimens with positive fungal\nculture, 110 (40.4%) were non-dermatophyte moulds, followed by yeasts predominantly Candida\nspecies (17.6%), 3 (1.1%) were dermatophytes, and 28 (10.3%) were a mixed infection of\ndermatophytes, non-dermatophyte moulds and yeasts. \n\n\n\nConclusion From this study, it was found that onychomycosis in our hospital from 2004 to 2008\nwere mainly caused by non-dermatophyte moulds. Treatment may be challenging as non-\ndermatophyte onychomycosis are more resistant to treatment.\n\n\n\nKeywords Onychomycosis, causative organism\n\n\n\nCorrespondence\nSM Wong, MRCP\n2Dermatology Unit, Department of Medicine, \nUniversity Malaya Medical Center, Kuala Lumpur\nE-mail : smwong@um.edu.my\n\n\n\n1Medical student, MBBS, \nUniversity Malaya, Kuala Lumpur\n\n\n\nIntroduction\nOnychomycosis is defined as an infection of the\nnails caused by fungi, including dermatophytes,\nnon-dermatophyte moulds and yeasts. When\ninfection is caused by dermatophytes, the term tinea\nunguium is often used. Onychomycosis may affect\ntoenails or fingernails, but toenail infections are\nparticularly common. Onychomycosis is common\nand comprises 20% of all nail disease. Studies have\nshown that 30% of patients with dermatophyte\n\n\n\ninfection on other parts of the body have tinea\nunguium1. The disease is more common in males\nand the prevalence increases with age2. Children\nhave infection rates thirty times lower than adults\ndue to smaller nail surfaces and faster nail growth.\nThe majority of onychomycosis in children is\nrelated to the presence of fungal infection in other\nfamily members3.\n\n\n\nThe general risk factors for any type of\nonychomycosis are increasing age, male gender,\ndiabetes mellitus, nail trauma (onychogryphosis),\nhyperhidrosis, peripheral vascular diseases, poor\nhygiene, tinea pedis, especially the \"moccasin type\"\nand immunodeficiencies4. In cases of candidal\nonychomycosis in particular, chronic exposure of\nthe nails to water can be a significant risk factor.\n\n\n\nBased on the form of infection and the associated\nclinical appearance, onychomycosis can be divided\ninto 4 clinical types: distal and lateral subungual\nonychomycosis\n\n\n\n\n\n\n\n\n12 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nonychomycosis (DLSO) which is the most common\ntype, proximal subungual onychomycosis (PSO),\nwhite superficial onychomycosis (WSO), and total\ndystrophic onychomycosis.\n\n\n\nWe conducted a retrospective analysis looking into\nrecent trends of onychomycosis in a University\nHospital in Malaysia. \n\n\n\nMaterials and methods\nThis was a retrospective study carried out at the\nUniversity Malaya Medical Centre (UMMC) from\nJanuary 2004 to December 2008. During the study\nperiod, data was collected from patients who had\ntheir nail clippings cultured for fungal infection. All\npatients who presented to the skin clinic, medical\nward and also other in-patient wards in UMMC\nwere included. Patients were categorized into\nchildren and adolescents (1-20 years old), adults\n(21-64 years old) and the elderly (65 years old).\n\n\n\nResults of mycological investigations were\nreviewed at the Medical Microbiology Department.\nNail specimens were obtained by clipping and\nspecimens were sent to the mycology laboratory for\nmicroscopic examination in potassium hydroxide\n40% (KOH) and also fungal culture in Sabouraud\ndextrose agar (SDA). All media were supplemented\nwith gentamicin and chloramphenicol. The fungal\nculture in SDA plates were incubated at 30\u00b0C and\ncultures were examined twice a week for up to 4\nweeks. The presence of fungal elements on direct\nmicroscopy including mycelium, arthrospores and\nyeasts was considered to be positive. No growth at\nthe 4th week was considered as culture negative.  \n\n\n\nThe causative organisms either dermatophytes,\nnon-dermatophyte moulds or yeasts were identified\nfrom the mycology reports. The trend of these\nfungal infections were studied and compared with\nother similar studies done.\n\n\n\nResults\nAmong the 272 nail specimens collected from\nJanuary 2004 to December 2008, 162 patients were\nfemale (59.6%) and 110 patients (40.4%) were\nmale. Most of the specimens were from Chinese\npatients, (102, 37.5%), followed by Malays (83,\n30.5%), Indians (69, 25.4%) and 18 from other\nraces (6.6%). The majority of specimens were from\nadults (179, 65.8%), followed by the elderly (65,\n23.9%) and children and adolescents made up\n10.3%. The mean age of the study population was\n\n\n\n49.9 \u00b1 19SD years. The specimens were mainly\nobtained from the skin clinic (84.2%). The general\ndemography of patients in this study is summarized\nin Table 1.\n\n\n\nOut of the 272 specimens which were examined by\ndirect microscopy, only 240 had recorded results.\n170 (62.5%) were negative for fungal elements and\n70 (25.7%) were positive for fungal elements.\nAmong the 170 specimens which were negative on\ndirect microscopy, 110 specimens were found to be\npositive on fungal culture. As for the specimens\nwhich were positive on direct microscopy, 54\nspecimens were culture positive and 16 were\nnegative on fungal culture (Table 2).\n\n\n\nOf the 189 specimens with positive fungal culture,\n110 (4 Aspergillus species was the most common of\nthe non-dermatophyte moulds, followed by\nFusarium species. The Fusarium species that were\nisolated include F. solani and F. oxysporum. 0.4%)\nwere non-dermatophyte moulds, followed by yeasts\npredominantly Candida species (48, 17.6%), 3\n(1.1%) were dermatophytes, and 28 (10.3%) were a\nmixed infection of dermatophytes, non-\ndermatophyte moulds and yeasts. Scytalidium\ndimidiatum made up of 13.7% all moulds isolated.\nOther moulds isolated were Curvularia lunata\n(3.6%), Mycelia sterilia (3.6%), Penicillium species\n(2.7%), Non-sporulating chrysosporium (2.7%),\nPaecilomyces species (1.8%), Malbranchea species\n(0.9%), Stemphylium species (0.9%), Madurella\ngrisea (0.9%) and Collectotrichum coccodes\n(0.9%).\n\n\n\nCandida parapsilosis was the most common yeast\nisolated. It made up 60.4% of all yeasts isolated.\nThis was followed by C. albicans (20.8%) and C.\ntropicalis (12.5%). C. guilliermondii, C. glabrata\nand trichosporon sp. made up 2.1% respectively.\n\n\n\nFor dermatophytes, Trichophyton species was the\nmost common isolated dermatophyte (67.7%),\nfollowed by Microsporum nanum (33.3%).\n\n\n\nMixed infections of dermatophytes, yeasts and\nmoulds were found in 10.3% of the patients. The\nmost common mixed infections were C.\nparapsilosis +Aspergillus sp. (17.9%) followed by\nC. albicans + Penicillium sp. (7.1%) and C. albicans\n+ Scytalidium dimidiatum (7.1%). One of the\nmixed infections was contaminated with bacteria,\nCladosporium sp. + Anaerobic actinomycetes.\n(Table 3).\n\n\n\n\n\n\n\n\n13MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 1 Demography of patients\n\n\n\nNo. of patients, (%)   n=272Patient characteristics\n\n\n\nGender\n\n\n\nEthnic\n\n\n\nAge group\n\n\n\nLocation\n\n\n\nMale \n\n\n\nFemale\n\n\n\nMalay\n\n\n\nChinese\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nAdult (21-64 year old)\n\n\n\nElderly (65 year old )\n\n\n\nChildren and adolescent (1-20 years old)\n\n\n\nMean age\n\n\n\nSkin clinic\n\n\n\nMedical ward\n\n\n\nOther in-patient ward\n\n\n\nNot specified \n\n\n\n110 (40.4%)\n\n\n\n162 (59.6%)\n\n\n\n83 (30.5%)\n\n\n\n102 (37.5%)\n\n\n\n69 (25.4%)\n\n\n\n18 (6.6%)\n\n\n\n179 (65.8%)\n\n\n\n65 (23.9%)\n\n\n\n28 (10.3%)\n\n\n\n229 (84.2%)\n\n\n\n14 (5.1%)\n\n\n\n28 (10.3%)\n\n\n\n1 (0.4%)\n\n\n\nTable 2 Comparison on direct microscopy and fungal culture\n\n\n\nPositive, n (%)\n\n\n\n54 (77.1%)\n\n\n\n110 (64.7%)\n\n\n\nNegative, n (%)\n\n\n\n16 (22.9%)\n\n\n\n60 (35.3%)\n\n\n\nFungal Culture\n\n\n\nDirect microscopy\n\n\n\nPositive (n=70)\n\n\n\nNegative (n=170)\n\n\n\nDiscussion\nOnychomycosis affects approximately 5% of the\npopulation worldwide. In developing countries,\nhigher priorities in socioeconomic concerns and\nhealth issues for other diseases have resulted in a\nlower awareness of onychomycosis by physicians\nand the general public alike. Despite improved\npersonal hygiene and living environment,\nonychomycosis continues to spread and persist.\nOnychomycosis is too often regarded as merely a\ncosmetic problem of relatively minor importance\nthat is hardly worth the effort to seek treatment in\nmany cases.\n\n\n\nThe epidemiology and aetiology of onychomycosis\nmay vary in different countries due to geographical\ndifferences. The climate, exposure of population\nand the health economics is a major contributing\nfactor. In the European study and survey, higher\nprevalence rate of onychomycosis were shown in\nmales5. In our study however, a female\npreponderance was shown with a female to male\nratio of 3:2. Similar trends were reported in studies\nfrom East Asia (China, South Korea and Taiwan).\nThis is not surprising as females may be more\nconcerned about nail appearances and therefore\nmore inclined to seek treatment.\n\n\n\n49.9 \u00b1 19 SD years\n\n\n\n\n\n\n\n\n14 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nTable 3 The prevalence of fungus isolated from nail clippings\n\n\n\nCausative organisms\n\n\n\nNo Growth\n\n\n\nMoulds\nAspergillus species\n\n\n\nAspergillus sp.\nA. niger\n\n\n\nFusarium species\nFusarium sp.\nF. solani\nF. oxysporum\n\n\n\nScytalidium dimidiatum\nCurvularia lunata\n\n\n\nMycelia sterilia\nPenicillium species\nNon-sporulating chrysosporium\nPaecilomyces species\nMalbranchea species\nStemphylium species\nMadurella grisea\nCollectotrichum coccodes\n\n\n\nYeasts\nCandida species\n\n\n\nC. parapsilosis\nC. albicans\nC. tropicalis\nC. guilliermondii\nC. glabrata\n\n\n\nTrichosporon species\n\n\n\nDermatophytes\nTrichophyton species\nMicrosporum nanum\n\n\n\nMixed infections\nC. parapsilosis +Aspergillus sp. \nC. albicans + Penicillium sp.\nC. albicans + Scytalidium dimidiatum\nC. parapsilosis + A. niger \nC. parapsilosis + Curvularia lunata\nC. parapsilosis + Cladosporium sp.\nC. parapsilosis + Fusarium sp.\nC. parapsilosis + C. albicans\nC. tropicalis + Aspergillus sp. \nC. glabrata + Aspergillus sp. \nAspergillus sp. + Penicillium sp.\nAspergillus sp. + Fusarium sp.\nAspergillus sp. +  Mucor sp.\nAspergillus sp. + Bipolaris sp.\nAspergillus sp. +  Scytalidium dimidiatum\nFusarium sp. +  Scytalidium dimidiatum\nScytalidium dimidiatum + mycelia sterilia\nCladosporium sp. +  Trichosporon sp.\nCladosporium sp. + Non-sporulating chrysosporium\nPenicillium sp. + Non-sporulating chrysosporium\nPaecilomyces voriotti + Malbranchea sp.\nCladosporium sp. + Anaerobic actinomycetes\n\n\n\n83 (30.5)\n\n\n\n110 (40.4)\n\n\n\n37 (13.6)\n13 (4.8)\n\n\n\n19 (7.0)\n3 (1.1)\n3 (1.1)\n\n\n\n15 (5.5)\n4 (1.5)\n4 (1.5)\n3 (1.1)\n3 (1.1)\n2 (0.7)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n\n\n\n48 (17.6)\n\n\n\n29 (10.7)\n10 (3.7)\n6 (2.2)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n\n\n\n3 (1.1)\n2 (0.7)\n1 (0.4)\n\n\n\n28 (10.3)\n5 (1.8)\n2 (0.7)\n2 (0.7)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n1 (0.4)\n\n\n\nNo. of patients, No. (%), n=272\n\n\n\n\n\n\n\n\n15MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nSeveral studies have reported that prevalence of\nonychomycosis increases with age, with the highest\nprevalence among elderly more than 60 years old.\nThe reasons for which may include poor peripheral\ncirculation, diabetes, repeated nail trauma, longer\nexposure to pathogenic fungi, sub optimal immune\nfunction, inactivity or the inability to cut the toe\nnails or maintain good foot care. However from our\nstudy, we have observed the highest incidence in the\nadult age group (21-64 years old). Our postulation\nis that since 84.2% of the samples were collected\nfrom the skin clinic, which is an outpatient clinic,\nthe population reflected is most probably of the\nworking age group.\n\n\n\nPrevious studies done in Malaysia, Singapore and\nHong Kong showed that dermatophytes were\npersistently reported as the most common causative\norganism in onychomycosis, followed by yeasts\nand non-dermatophyte moulds2,6,7,8. Our study\ninterestingly showed non-dermatophyte moulds as\nthe most common causative organism. This is\nfollowed by yeasts, mixed infections and\ndermatophytes. There is an obvious change in the\ntrend of causative organisms compared with a\nprevious study done in the same hospital from\n1996-19986. However, our study is similar to a\nstudy done in Thailand, where more than half of\ntheir patients who were clinically diagnosed with\nonychomycosis had non-dermatophyte infections9.\n\n\n\nIn contrast with the previous study done in our\nhospital which showed that dermatophytes were the\nmost common isolated organism (36.1%), followed\nby moulds (35.5%). Our study on the other hand,\nshowed non-dermatophyte moulds to be the most\ncommon pathogen and dermatophytes to be the\nleast common. In addition, among the non-\ndermatophyte moulds isolated in the previous local\nstudy, the most isolated was A. niger, A. fumigates\nand Hendersonula toruloidea (now known as\nScytalidium dimidiatum). Whereas in our study\nAspergillus sp., A. niger, Fusarium sp. and\nScytalidium dimidiatum were the moulds most\nisolated. As for yeasts, C. albicans was previously\nmost isolated followed by C. parapsilosis. Our study\nshowed a change in trend in which C. parapsilosis\nwas the most isolated yeast followed by C. albicans\nand C. tropicalis. The mixed infection in our study\nwas higher (10.3%) compared to 1.1% of the\nprevious study. It is obvious that the trend of\n\n\n\nonychomycosis has changed from the 1990s to the\n21st century in that non-dermatophyte moulds are\nemerging as the more dominant causative pathogen.\nThis may be important knowledge in terms of\ntreatment as non-dermatophyte onychomycosis is\ngenerally more difficult to treat and resistant to the\nusual oral anti-fungals.\n\n\n\nConclusions\nFrom this study, it was found that onychomycosis in\nour hospital from January 2004 to December 2008\nwere mainly caused by non-dermatophyte moulds.\nThis is something to be looked into by physicians\nand dermatologists as non-dermatophyte moulds\nare difficult to eradicate. Furthermore, treatment of\nnon-dermatophyte onychomycosis is not well\nstandardized, and can be difficult. Therefore, it is\nimportant that mycological studies to identify the\ncausative organisms are carried out before systemic\nantifungal therapy is started on patients who are\nclinically diagnosed with onychomycosis.\n\n\n\nReferences\n\n\n\n1. Freedberg IM, Erzen AZ, Wolff K, Austen KF,\nGoldsmith LA, Katz SI, Fitzpatrick TB. Fitzpatrick\u2019s\ndermatology in general medicine, 5th edition\n\n\n\n2. Cheng S, Chong L. A prospective epidemiological\nstudy on tinea pedis and onychomycosis in Hong Kong.\nChinese Medical Journal, 2002;115: 860-865\n\n\n\n3. Gupta AK, Sibbald RG, Lynde CW, Hull PR, Prussick\nR, Shear NH, De Doncker P, Daniel CR, 3rd, Elewski\nBE. Onychomycosis in children: prevalence and\ntreatment strategies. J Am Acad Dermatol\n1997;36:395-402.86\n\n\n\n4. Cohen JL, Scher RK, Pappert AS. 1992. The nail and\nfungus infections, p. 106-122. In B. Elewski (ed.),\nCutaneous fungal infections. Igaku-Shoin, Inc, New\nYork\n\n\n\n5. Haneke E, Roseeuw D. The scope of onychomycosis:\nepidemiology and clinical features. Int J Dermatol\n1999; 38(suppl.2): 7-12\n\n\n\n6. Ng KP, Saw TL, Madasamy M, Soo Hoo TS.\nOnychomycosis in Malaysia. Mycopathologia 1999;\n147:29-32\n\n\n\n7. Tan HH. Superficial Fungal Infections Seen at the\nNational Skin Centre, Singapore. Jpn J Med Mycol\n2005;46:77-80\n\n\n\n8. Lim JTE, Chua HC, Goh CL. Dermatophyte and non-\ndermatophyte onychomycosis in Singapore. Austral J\nDermatol 1992; 33:159-163\n\n\n\n9. Kotrajaras R, Chongsathien S, Rojanavanich V,\nBuddhavadhikrai P, Viriyayudhakom S. Hendersonula\ntoruloidea infection in Thailand. Int J Dermatol 1988;\n27:391-395\n\n\n\n\n\n\n\n\n16 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Short Communication\n\n\n\nPersistent groin itch\n\n\n\nTang MM, AdMDerm, Chang CC, AdMDerm, Asmah J, MMed\n\n\n\nCorrespondence\nTang Min Moon, AdMDerm\nDermatologist, Department of Dermatology\nHospital Kuala Lumpur, Kuala Lumpur\nE-mail : minmoon2005@yahoo.com\n\n\n\nDear Editor,\nWe would like to share with you our experience in\nthe management of a 14-year-old schoolgirl with a\npersistent itch over the groin. She was referred to us\nfor a 6-month history of intense pruritic rash over\nthe groin and abdomen. The rash was persistent\ndespite repeated application of topical antifungal\ntherapy for the last 6 months.\n\n\n\nClinically, there were confluent hyperpigmented\nlichenified plaques with excoriations over the groin\ninvolving the inguinal folds, thighs, pubic region\nand a discrete plaque over the left lower abdomen\n(Figure 1).\n\n\n\nThere were no similar lesions on other parts of the\nbody. Scraping for microscopic examination of the\nlesions with 20% potassium hydroxide revealed a\nbody louse (Figure 2).\n\n\n\nA diagnosis of pediculosis corporis with secondary\neczematization was made. She was treated with 1%\ngamma-benzene hexachloride (Lindane) and\nmedium potency topical corticosteroid for the\nchronic eczematous lesions.  Loratidine 10mg/day\nduring the day and oral chlorpheniramine maleate\n4mg before sleep were also prescribed to reduce the\npruritus. She was given specific instructions to soak\nthe bed sheet, pillow case and the garments in\nboiled water for at least 15minutes and then dry\nunder the sun. Two weeks after the treatment, the\nitch was less and the chronic eczema improved\nremarkably as shown in Figure 3.\n\n\n\nDiscussion\nPediculosis corporis is caused by human body louse\nPediculus humanus var corporis. Lice are wingless,\nblood-sucking ectoparasites with high human host\nspecificity1. An adult body louse measures between\n2-4mm in length and have a lifespan of about 18\ndays. A female louse lays 270-300 ova in its lifetime\nand these ova are deposited in the clothes of\ninfested individuals. The ova hatch into nymph after\n8-10 days. Each nymph matures into adult in 2\nweeks time. The optimum temperature for its\ndevelopment is 30-32\u02daC.\n\n\n\nFigure 1 Pediculosis corporis before treatment\n\n\n\nFigure 2 Pediculosis humanus var corporis (body louse) \ndemonstrated under microscopic examination of \nskin scraping(x40)\n\n\n\nFigure 3 Two weeks after treatment with 1% gamma-\nbenzene hexachloride and topical corticosteroid\n\n\n\n\n\n\n\n\n17MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nThe body louse clings to textile fiber and lives in\nthe seams of clothing. It feeds on human blood but\ndoes not live on the skin. In massive infestations\nthey may be seen moving about the body. Body lice\nare very active at 30\u02daC, crawling with a remarkable\nspeed of a meter in 3 minutes. The thermal death\npoint is about 44\u02daC. In our case, it was interesting to\nfind the louse in the skin scraping. It is likely that\nthe louse caught on the scraping was feeding on the\nschoolgirl\u2019s blood.\n\n\n\nPediculosis corporis is found worldwide but\ngenerally is limited to persons who live under\nconditions of crowding and poor hygiene2.\nInfestation occurs only when clothes are not\nchanged or washed regularly. The indigent,\nhomeless, nursing homes and refugee-camp\npopulations are commonly affected3,4. Our patient,\nwho is staying in a flat with both her father and\nbrother, did not share a common bedroom with\nthem. Her parents were separated. According to her\nmother who is living separately, the house was\nuntidy and did not receive adequate sunlight. The\nclothes were hand-washed and hanged to dry.\nTherefore, suboptimal personal hygiene was the\nmost likely explanation for the body louse\ninfestation in our patient.\n\n\n\nIn body-louse infestation, the axillae, groin and\ntruncal areas are usually more severely affected.\nSevere pruritus is accompanied by papules related\nto bite reactions as well as excoriations that may\nbecome secondarily infected. Secondary\neczematization commonly results from continuous\nscratching. In chronically affected patients, post-\ninflammatory hyperpigmentation is observed. \n\n\n\nCertain pathogenic bacteria, such as Rickettsia\nprowazekii, Borrelia recurrentis and Bartonella\nquintana which are carried by body lice are the\ngreatest fear in patients who have pediculosis. They\ncan cause life threatening infections such as\nepidemic typhus, relapsing fever, trench fever\nand bacillary angiomatosis1-4. Transmission of\nmicroorganisms from body lice to humans is not\n\n\n\ndirectly due to the lice bite, but by contaminated\nfaecal pellets being scratched into the bite site, or\nby inhalation of dry, powdery lice faeces from\ninfested bedding or clothing. Hence, it is important\nto treat this condition to prevent the transmission of\nbacterial infection.\n\n\n\nIn order to eradicate body lice, bed linens and\nclothing belonged to the patients must be\ndecontaminated. Most clinicians recommend\npatients to decontaminate the clothes and bed linens\nby heating them to above 60\u02daC for 15-30 minutes.\nHowever in the past, some physicians advise the\nclothes and bed linens of infested patients to be\ndiscarded in tightly sealed plastic bags and burned3.\nTopical pediculocides are often prescribed, which\ninclude 5% permethrin cream, 1% gamma benzene\nhexachloride (Lindane) and 5-10% sulfur in a\npetrolatum base. The treatment regimes are no\ndifferent from those used in scabies5. An outbreak\nnecessitates delousing of individuals with 1%\npermethrin dusting powder, decontaminating the\nbed linens and garments using heat methods as well\nas ensuring basic sanitation and personal hygiene. \n\n\n\nIn conclusion, we reported a schoolgirl who had\npediculosis corporis mimicking dermatophyte\ninfection of the groin. Body lice should be\nconsidered as a differential diagnosis of pruritic\ndermatoses in patients with poor personal hygiene.\n\n\n\nReferences\n\n\n\n1. Matheson R. The Order Anoplura: The Biting and\nSucking Lice. Medical Entomology Second Edition.\nVail-Ballou Press, Inc., Binghamton, N. Y. 1950:VII:\n194-217\n\n\n\n2. Centres for Disease Control and Prevention. Body Lice.\nDivisions of Parasitic Diseases (DPD) 2008;\nhttp://www.cdc.gov/lice/body/index.html\n\n\n\n3. Chosidow O. Scabies and pediculosis. Lancet 2000;\n355:819-26\n\n\n\n4. Feldmeier H, Heukelbach J. Epidermal parasitic skin\ndiseases: a neglected category of poverty-associated\nplagues. Bull World Health Organ 2009;87:152-159\n\n\n\n5. Roos TC, Alam M, Roos S et al. Pharmacotherapy of\nEctoparacitic Infections. Drugs 2001;61(9):1067-1088\n\n\n\n\n\n\n\n\n18 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGENERAL DERMATOLOGY - Short Communication\n\n\n\nHerpes Zoster presenting as cellulitis\n\n\n\nKader B Mohamed\n\n\n\nCorrespondence\nKader B. Mohamed\nConsultant Dermatologist Dept. of Dermatology\nSultanah Fatimah Specialist Hospital\n84000 Muar, Malaysia\n\n\n\nDear Editor,\nWe have encountered a 56-year old man who was\nreferred to us as cellulitis of the nose when he\npresented with erythematous, crusted pustule,\npainful and warm lesions over the left side of the\nnose for the past 5 days. The lesions were strictly\nunilateral and well-delineated although there was\ntender swelling over the right side of the nose\n(Figure 1). There was a history of pain preceeding\nvesicular eruption. The ipsilateral lower eye lid,\nupper lip and the nasal septum were involved. These\nareas are supplied by the infra orbital nerve which\nis the continuation of the maxillary division of the\ntrigeminal nerve. The palate was not involved. He\nresponded well to aciclovir and cephalosporin but\nsuffered from post-herpetic neuralgia.\n\n\n\nPain preceding unilateral vesicular eruptions, in a\ndermatomal distribution prompts the diagnosis of\nherpes zoster of the infraorbital branch of the\nmaxillary division of the trigeminal nerve.\n\n\n\nFigure 1 Crusted vesicular and pustular \nlesions on a swollen nose\n\n\n\n\n\n\n\n\n19MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nA\nADR\ntumour\nappendageal disorders\nbacterial infection\nautoimmune disorders\npseudolymphoma\nlupus erythematosus\nlymphoma\nleprosy\nrosacea\n\n\n\nB\nADR\ntumour\nappendageal disorders\nbacterial infection\nautoimmune disorders\npseudolymphoma\nlupus erythematosus\nlymphoma\nleprosy\nrosacea\n\n\n\nC\npsoriasis\nkeratoderma\nacanthosis\nerythroderma\nscabies\nlichen planus\ncontact dermatitis\nfungal infection\nsecondary syphilis\nrosacea\n\n\n\nSlide A\n\n\n\nTick at the provided space [\ufffd] against answers that correlate to the slide. \nCheck your answer on page 58. Refer to the given criteria in page 59 to discover your clinical diagnostic skill\nstatus.\n\n\n\nSlide B\n\n\n\nSlide C\n\n\n\nGENERAL DERMATOLOGY - Self Assessment\n\n\n\nClinical diagnostic skill test\n\n\n\n\n\n\n\n\n20 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nD\npomphylx\nkeratoderma\nacanthosis\nerythroderma\nscabies\nlichen planus\ncontact dermatitis\nvasculitis\nbullous disease\nscalding\n\n\n\nE\nADR\nnon-infective inflammation\nfungal infection\ntumour\ndermatitis\npost-inflammatory hyperpigmentation\ncongenital naevus\nacanthosis\narsenic poisoning\nmycosis fungoides\n\n\n\nF\ndermatitis\nnon-infective inflammation\nfungal infection\nviral infection\nappendageal disorders\npityriasis versicolor\npsoriasis\nherpes viral infection\ndiscoid dermatitis\npityriasis rosacea\n\n\n\nSlide D\n\n\n\nSlide E\n\n\n\nSlide F\n\n\n\n\n\n\n\n\n21MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMany people perceive that dermatological\ncondition is not as serious or life-threatening as the\nother more publicized medical conditions like\ncancer, heart disease or even diabetes. They think\nthat it will do no harm other than invoking\nembarrassment or the occasional itchiness and pain.\nHowever, we should not forget that dermatological\nconditions involve the largest organ in a human\u2019s\nbody - the skin. \n\n\n\nBesides cutaneous infections, autoimmune skin\ndiseases and chronic non-infective dermatological\nconditions, a major cause of concern in the\ndermatological field is drug-induced skin reaction.\nCutaneous adverse drug reaction (ADR) is a\ncondition whereby a patient suddenly develops an\nunwanted symmetrical cutaneous eruption after\ntaking medications.\n\n\n\nWorld Health Organization define Cutaneous ADR\nas a noxious, unintended morphological skin\nchanges with or without systemic involvement,\ndeveloped after the local or systemic administration\nof drugs in dosages commonly used for prevention,\ndiagnosis or treatment of disease or modification of\nphysiological functions1. \n\n\n\nThe severity of adverse drug reactions is often\nunderestimated. It is responsible for significant\nmorbidity, mortality and socioeconomic costs.\nCurrently, most of the available epidemiological\nstudies refer to ADRs in general and are conducted\nbased on hospitalised patients. For example, in one\nof these studies which were carried out by Bates et\n\n\n\nKeywords Cutaneous adverse drug reaction, Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis,\nPrevalence\n\n\n\nADVERSE DRUG REACTIONS - Update from Malaysian National Pharmaceutical \nControl Bureau\n\n\n\nCutaneous adverse drug reaction: a medical concern?\n\n\n\nTan LS, Fuziah AR, Ng SP\n\n\n\nal.2 using data from the Boston Collaborative Drug\nSurveillance Programme, it was found that ADRs\nwere reported in 6.1% of hospitalized patients.\n\n\n\nPirmohamed et al.3 conducted a prospective study\nin two UK National Health Service hospitals in\nMerseyside, comprising of 18,820 patients admitted\nover a 6-month period. It was found that 1,225\n(6.5%) admissions were related to an ADR. In\nSingapore, a 2-year prospective study which was\ncarried out by Thong et al.4, detected 366 cases of\nreported drug allergy from a total of 90,910\ninpatients. As for the epidemiological data on\ncutaneous adverse drug reaction, it is still very\nscarce and limited. However, there was one\nparticular study which concluded that cutaneous\nadverse drug reaction occurred in 2 - 3% of all\nhospitalized patients. Apart from this, there is also a\nlack of comprehensive data or studies amongst out-\npatients on both ADRs in general and cutaneous\nadverse drug reaction in particular. This inadequacy\nof data could be due to several reasons like\ndiagnostic dilemmas and lack of awareness to\nreport such cases. \n\n\n\nTo date, in Malaysia, no such specific studies on the\nprevalence of ADRs were conducted or carried out\nin both inpatients and outpatients settings. The only\nrelevant data which was obtained from the National\nPharmaceutical Control Bureau (NPCB) showed\nthat out of the 4,826 adverse drug reactions reports\nreceived in 2008, about one third (31.8%) of these\nwere classified under spontaneous skin reactions\nwhich is used interchangeably with cutaneous\nadverse drug reaction in this article. This is\nconsistent with the findings in a study carried out\nby Gomes et al5.\n\n\n\nSeveral studies were conducted worldwide and\nconcluded that medications which are commonly\nknown for causing cutaneous reactions include\nantimicrobial agents, nonsteroidal anti-\ninflammatory\n\n\n\nCorrespondence\nSu-Ann\nPusat Pasca Pendaftaran Produk\nBiro Pengawalan Farmaseutikal Kebangsaan\nJalan Universiti, Peti Surat 319\n46730 Petaling Jaya, Selangor\nE-mail : suephay@bpfk.gov.my\n\n\n\n\n\n\n\n\n22 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\ninflammatory drugs (NSAIDs), cytokines,\nchemotherapeutic agents, anticonvulsants, and\npsychotropic agents. A retrospective case-control\nstudy from Singapore conducted by Kidon et al.6\nshowed that almost 70% of the reported ADR cases\nin pediatrics involved the use of antibiotics\n(especially \ufffd-lactam antibiotics (45%) and NSAIDs\n(18.5%) were the second most implicated group.\nBorch et al.7 also reported that \ufffd-lactam antibiotics\nis the most implicated drug group in cutaneous\nADR contributing to 22.8% of the cases studied. \n\n\n\nAs for Malaysia in Year 2008, 45% of ADR notified\nwere antibiotics induced skin reaction followed by\nNSAIDs (13%) and antiepileptic. Figure 1 shows\nthe top ten drugs most commonly reported for\ncutaneous adverse drug reaction in the year 2008.\nFifty percent of these top ten medications reported\nfalls into the antibiotic group and the penicillin-\nbased \ufffd-lactam antibiotics are the most commonly\nimplicated drug.\n\n\n\nThe analysis of the data by Chatterjee et al.8 showed\n\n\n\nthat urticaria and fixed drug rashes were the most\ncommon morphological reaction-types. A summary\nof various studies showed that the most common\nmorphological reactions encountered in cutaneous\nadverse drug reactions are exanthematous eruption\n(maculopapular eruption), urticaria, fixed drug\neruption and erythema multiforme. There is a\nvariation in terms of incidence rate for each of these\nmorphological reactions due to different patterns of\ndrug usage and different ethnic group\ncharacteristics. In our country, the most common\nmanifestations of drug-induced skin reactions are\nitching, pruritic maculopapular rashes and\nerythematous rashes. These manifestations were\nreported in about 95% of the 1535 skin spontaneous\nreports received in 2008. This is similar as\ncompared to the prospective study carried out by\nThong et al.4 in Singapore whereby cutaneous\nmanifestations were the most common clinical\npresentation contributing to 95.7% of the total\ncases. This type of drug eruptions is usually mild,\nself-limited, and resolve after the offending\nmedication has been discontinued.\n\n\n\nFigure 1 Malaysian top ten most commonly reported drug induced cutaneous adverse drug reactions (Year 2008)\n\n\n\nALLOPURINOL\n\n\n\nCO-TRIMOXAZOLE\n\n\n\nDICLOFENAC SODIUM\n\n\n\nCLOXACILLIN\n\n\n\nAMOXYCILLIN\n\n\n\nACETYLSALICYLIC ACID\n\n\n\nAMOXYCILLIN / CLAVULANIC ACID\n\n\n\nERYHTROMYCIN\n\n\n\nMEFENAMIC ACID\n\n\n\nPHENYTOIN\n\n\n\nNo. of Reports\n\n\n\nM\ne\nd\n\n\n\nic\na\nti\n\n\n\no\nn\n\n\n\ns\n\n\n\n0 10 20 30 40 50 60 70 80\n\n\n\n\n\n\n\n\n23MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nHowever, more severe and potentially life-\nthreatening adverse drug reactions may also occur.\nA variety of studies were carried out to identify the\nmortality rate of ADRs in general. In the USA, a\nstudy done by Lazarou et al.9 showed that 0.32% of\nhospitalized patients died from ADRs. On the other\nhand Pirmohamed et al.3 found that the overall\nfatality related to ADRs was 0.15%. In the study of\nFattinger et al., the estimated incidence of possible\nADR-related deaths was similar at 0.14%10. Even\nthough these studies did not investigate the\nmortality rate of cutaneous adverse drug reaction in\nparticular; it has always been known that the two\nmost common potentially life-threatening\ncutaneous ADRs are Stevens - Johnson syndrome\n(SJS) and Toxic Epidermal Necrolysis (TEN).\nThese two conditions not only may cause prolonged\nhospitalisation, they significantly contribute to\nhigher mortality rates in cutaneous adverse drug\nreaction. It was reported that SJS has a mortality\nrate of less than 5%, whereas the rate for TEN\napproaches 20-30%11 as most patients die from\nsepsis. A total of 38 cases of SJS and 12 cases of\nTEN associated with adverse drug reactions were\nreported in Malaysia last year. These figures\ncontributed to 3.2% of the total skin spontaneous\nreaction reports received. Fortunately, among these\nreported cases, none were known to be fatal.\nHowever, the socioeconomic cost due to these cases\nis still yet to be determined.\n\n\n\nIn conclusion, cutaneous adverse drug reaction may\nnot have as high a fatality rate as some other\nmedical conditions, but it is proven to be a\ndistressing issue in the medical field because\ninstead of providing medication relief to patients, it\ncauses iatrogenic disease. However with the number\nof new drugs which are being developed and\nentering the market on a daily basis, this is\ninevitable. Therefore, it is the responsibility of all\nhealth professionals to weigh the benefits and risks\nof each and every therapeutic decision carefully.\nCurrently, with the increasing trend of self-\nmedication by patients and poly-pharmacy\nprescribing, healthcare professionals have to be\nalert in detecting these potential adverse events and\nif possible, prevent them from happening. It is\nimportant to educate the general public that no\nmedicines are without risk or totally safe to use.\n\n\n\nThroughout these years, the WHO has been\npromoting pharmacovigilance in most countries. By\nworking with the WHO Collaborating Centre for\nInternational Drug Monitoring (Uppsala\nMonitoring Centre), it aims to enhance and improve\npatient care and patient safety in relation to the use\nof medicines, thus encouraging safer and more\neffective use of medicines. Therefore it is important\nto emphasize the responsibility of all health\nprofessionals to be more vigilant and to report the\nrelevant cases to the regulatory authority at national\nlevel for regular monitoring. This medical issue\nshould not be taken lightly or ignored.\n\n\n\nReferences\n\n\n\n1. Gardner P, Cluff LE. The Epidemiology of Adverse\nDrug Reactions. A Review and Perspective. Johns\nHopkins Med J 1970; 126:77-87\n\n\n\n2. Bates DW, Cullen DJ, Laird N, et al. Incidence of\nAdverse Drug Events and Potential Adverse Drug\nEvents. JAMA 1995; 274:29-34\n\n\n\n3. Pirmohamed M, James S, Meakin S, et al. Adverse\nDrug Reactions As Cause of Admissions to Hospital:\nPropestive Analysis of 18820 Patients. BMJ 2004;\n329:15-19\n\n\n\n4. Thong BY, Leong KP, Tang CY, et al. Drug Allergy in\na General Hospital: Results of a Novel Prospective\nInpatient Reporting System. Ann Allergy Asthma\nImmunol 2003; 90:342-347\n\n\n\n5. Gomes ER, Demoly P. Epidemiology of\nHypersensitivity Drug Reactions. Curr Opin Allergy\nClin Immunol 2005; 5:309-316\n\n\n\n6. Kidon MI, See Y. Adverse Drug Reactions in Singapore\nChildren. Singapore Med J 2004; 45:574-577\n\n\n\n7. Borch JE, Andersen KE, Bindsley-Jensen C. Cutaneous\nAdverse Drug Reactions Seen at a University Hospital\nDepartment of Dermatology. Acta Derm Venereol\n2006; 86:523-527\n\n\n\n8. Chatterjee S, Ghosh AP, Barbhuiya J, et al. Adverse\nCutaneous Drug Reactions: A One Year Survey at a\nDermatology Outpatient Clinic of a Tertiary Care\nHospital. Indian J Pharmacol 2006; 38:429-31\n\n\n\n9. Lazarou J, Pomeranz BH, Corey PN. Incidence of\nAdverse Drug Reactions in Hospitalised Patients: A\nMeta-Analysis of Prospective Studies. JAMA 1998;\n279:1200-1205\n\n\n\n10. Fattinger K, Roos M, Vergeres P, et al. Epidemiology of\nDrug Exposure and Adverse Drug Reactions in Two\nSwiss Departments of Internal Medicine. Br J Clin\nPharmacol 2000; 49:158-167\n\n\n\n11. Navak S, Acharjya B. Adverse Cutaneous Drug\nReaction. Indian Journal of Dermatology 2008;\n53(1):2-8\n\n\n\n\n\n\n\n\n24 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nKeywords Aplasia cutis congenita, carbimazole,\npregnancy\n\n\n\nIntroduction\nAplasia cutis congenita (ACC) is a rare anomaly\npresenting with absence of skin. It was first\nreported by Cordon in 1767. About 70% of cases\nmanifests as a solitary defect on the scalp, but\nsometimes it may occur as multiple lesions. The\nlesions are typically well demarcated, non-inflamed,\nand they range in size from 0.5cm to 10cm. ACC\nmay be circular, oval, linear, or stellate in\nconfiguration.  At birth, lesions may appear as scars\nor ulcers1. They may appear as parchment-like scars\nwith alopecia.\n\n\n\nMost lesions occur on the scalp vertex just lateral to\nthe midline, but defects may also occur on the face,\nthe trunk, or the limbs, sometimes symmetrically.\nThe depth may involve only the epidermis and the\nupper dermis, resulting in minimal alopecic\nscarring, or the defect may extend to the deep\ndermis, the subcutaneous tissue, or rarely the\nperiosteum, the skull, and the dura.\n\n\n\nACC is most often a benign isolated defect, but it\ncan be associated with other physical anomalies or\nmalformation syndromes. Frieden classified them\ninto 9 groups based on the number and presence or\nabsence of other anomalies1. Nearly 86 percent\nbelong to the first group with a solitary lesion. We\nreport a case of Aplasia Cutis Congenita secondary\nto maternal exposure to carbimazole during\npregnancy.\n\n\n\nADVERSE DRUG REACTIONS - Case Report\n\n\n\nAplasia cutis congenita secondary to maternal exposure\n\n\n\nto carbimazole during pregnancy. A case report\n\n\n\nTey KE, MRCP, Chong YT, Choon SE, MRCP\n\n\n\nCase report\nA 2 month old baby girl of non-consanguineous\nparents was referred to us in 2009 for a hairless\npatch on the scalp noted at birth. She was delivered\nfull term vaginally. Her mother has thyrotoxicosis\nsince 2006 and was on carbimazole during her first\nmonth of pregnancy. There was no similar skin\nlesion in the family.  Examination revealed a 1.5 cm\nsemicircular atrophic parchment-like scar within\nwhich there was a total absence of hair (Figure 1).\n\n\n\nThere were no other organ abnormalities on clinical\nexamination. Radiological examination and\nultrasonography of the abdomen revealed no\nabnormalities. Routine baseline investigations were\nwithin normal limits. The parents declined a skin\nbiopsy.\n\n\n\nDiscussion\nACC is an uncommon disorder presenting at birth.\nThe most common presentation is the solitary\nlesion on the scalp, as present in our patient.\n\n\n\nFrieden classified ACC into 9 groups based on the\nnumber and presence or absence of other\nanomalies1.\n\n\n\nCorrespondence\nTey KE, MRCP\nDepartment of Dermatology\nHospital Sultanah Aminah, Johor Bahru, 80100 Johor\nE-mail : ketey08@yahoo.com\n\n\n\nFigure 1 A semicircular atrophic parchment-like scar with \nabsence of hair on the scalp measuring 1.5 cm in \ndiameter\n\n\n\n\n\n\n\n\n25MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nGroup 1: This is scalp ACC without multiple\nanomalies. Nearly 86% of all solitary lesions occur\non the scalp. It can be autosomal dominant or\nsporadic. \n\n\n\nGroup 2: This is scalp involvement with limb\nanomalies. Adams-Oliver syndrome is a distinct\nsubtype in which distal limb reduction\nabnormalities are found in association with solitary\nmidline scalp defects. More than 15 such cases have\nbeen reported, usually with an autosomal dominant\ninheritance pattern and variable genetic\nexpression2,3. The scalp lesions tend to be large. The\nmost common limb malformation is hypoplastic or\nabsent distal phalanges. Other anomalies may\ninclude cutis marmorata telangiectasia congenita,\nhemangiomas, cranial arteriovenous malformation,\nskin tags, supernumerary nipples, and woolly hair.\n\n\n\nGroup 3: This is scalp ACC with epidermal and\nsebaceous (organoid) nevi, which also involve the\nscalp, usually adjacent to the cutis aplasia. Some\npatients have also had ophthalmic and neurologic\nfindings typical of epidermal nevus syndrome,\nincluding seizures, mental retardation, corneal\nopacities, and eyelid colobomas. Inheritance is\nsporadic. \n\n\n\nGroup 4: This is ACC often with a hair collar\noverlying deeper embryologic malformations.\nExamples include meningomyelocele,\nporencephaly, leptomeningeal angiomatosis, cranial\nstenosis, spinal dysraphism, gastroschisis, and\nomphalocele. The inheritance pattern in this group\nvaries with the associated underlying condition. \n\n\n\nGroup 5: This is ACC associated with fetus\npapyraceous or placental infarct. Extensive truncal\nand limb ACC in a linear or stellate configuration is\nassociated with the presence of fetus papyraceous.\nFetus papyraceous is found at the time of delivery\nand results from the death of a twin fetus early in\nthe second trimester. The surviving fetus is affected\nwith ACC and is usually otherwise normal. \n\n\n\nGroup 6: This is ACC associated with simplex,\njunctional, or dystrophic types of epidermolysis\nbullosa (EB). Many reports describe ACC, usually\noccurring on the lower extremities, in patients\neventually diagnosed with EB. Initially described as\nBart syndrome, this type of presentation represents\na variant of dystrophic EB. A subgroup includes the\n\n\n\nassociation of pyloric or duodenal atresia, ureteral\nstenosis, renal abnormalities, craniofacial\nabnormalities, nail dystrophy, and ACC. \n\n\n\nGroup 7: This is ACC localized to the extremities\nwithout EB. At least 2 families have been reported\nin which multiple members had extensive ACC on\nthe pretibial lower extremities and the dorsal\naspects of the hands and the feet. \n\n\n\nGroup 8: This is ACC due to teratogens. A few\ncases of ACC have been linked to intrauterine\ninfection with herpes simplex virus or varicella-\nzoster virus or to exposure to methimazole in the\ntreatment of maternal thyrotoxicosis during\npregnancy4,5,6,7. Imperforate anus has been\nassociated with methimazole or carbimazole\nexposure during gestation. \n\n\n\nGroup 9: This is ACC associated with malformation\nsyndromes. ACC has been reported as a\ncharacteristic in many syndromes and more will be\nreported. Various syndromes and dysplasias include\ntrisomy 13 (Patau syndrome) with large\nmembranous scalp defects, 4p- (Wolf-Hirschhorn)\nsyndrome with midline scalp defects, Setleis\nsyndrome with bitemporal ACC and abnormal\neyelashes, Johanson-Blizzard syndrome with\nstellate scalp defects, focal dermal hypoplasia\n(Goltz syndrome), amniotic band disruption\ncomplex, oculocerebrocutaneous (Delleman)\nsyndrome, scalp-ear-nipple syndrome (Finlay-Mark\nsyndrome), and 46XY gonadal dysgenesis.\nReticulolinear ACC on the face and the neck is a\ndistinctive cutaneous manifestation in several\nsyndromes linked to Xp22.\n\n\n\nThe clinical description of our patient points to type\n8 of Frieden's classification  as the mother had\nexposure to carbimazole during early pregnancy.\nMore than 18 cases of ACC with possible\nassociation with maternal exposure to methimazole\nor carbimazole were reported in the literature4,5,6,7.\n\n\n\nIn very few reports are histological details\navailable; histological features vary depending on\nthe depth of aplasia and duration. Ulcers are seen at\nbirth. After healing, the epidermis appears flattened\nwith proliferation of fibroblasts within a connective\ntissue stroma. Total absence of the epidermal\nappendages remains a characteristic feature1. If the\ndefect is small it can be partially excised and then\nclosed surgically.\n\n\n\n\n\n\n\n\n26 MJD 2009 December Vol 23\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nReferences\n\n\n\n1. Frieden IJ. Aplasia Cutis Congenita: a clinical review\nand proposal for classification cited  in Rook / Ebling /\nWilkinson, textbook of dermatology 6th edition. Ed: R.\nH. Champion et al 1998, Blackwell science Ltd.\n\n\n\n2. Balasubramanian M, Collins AL. Aplasia cutis\ncongenita, terminal limb defects and periventricular\nleukomalacia in one sibling with minor findings in the\nother-probable autosomal recessive Adams-Oliver\nSyndrome. Eur J Med Genet. May 3 2009; [Medline]\n\n\n\n3. Bilginer B, Onal MB, Bahadir S, Akalan N. Aplasia\ncutis congenita of the scalp, skull and dura associated\nwith Adams-Oliver syndrome. Turk Neurosurg.  Apr\n2008; 18(2):191 [Medline]\n\n\n\n4. Izhar R, Ghani T. Aplasia cutis congenita and\nantithyroid drugs. J Pak Med Assoc. Nov 2002; 52(11):\n526-8. [Medline]\n\n\n\n5. Karg E, Bereg E, Gaspar L, et al. Aplasia cutis\ncongenita after methimazole exposure in utero. Pediatr\nDermatol. Jul-Aug 2004;21(4):491-4. [Medline]\n\n\n\n6. Mandel SJ, Brent GA, Larsen PR. Review of\nantithyroid drug use during pregnancy and report of a\ncase of aplasia cutis. Thyroid. Spring 1994;4(1):129-\n33. [Medline]\n\n\n\n7. Nakamura S, Nishikawa T, Isaji M, et al. Aplasia cutis\ncongenita and skull defects after exposure to\nmethimazole in utero. Intern Med. Nov 2005;\n44(11):1202-3\n\n\n\n\n\n"
"\n\nVolume 36   |  Jul 2016   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.myIndexed in: Western Pacific Research Index Medicus\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA     DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\nM\nA\n\n\n\nLA\nY\n\n\n\nS\nIA\n\n\n\nN\n J\n\n\n\nO\nU\n\n\n\nR\nN\n\n\n\nA\nL O\n\n\n\nF D\nE\n\n\n\nR\nM\n\n\n\nA\nT\n\n\n\nO\nLO\n\n\n\nG\nY\n\n\n\n     Volum\ne 36   |  Jul 2016  |  ISSN\n\n\n\n: 1511-5356\n\n\n\n\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2016 Jul Vol 36\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence.  Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email:\nwoodzlamp@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology \ncan be sent to me at:\nwoodzlamp@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories: \n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject. \n\n\n\nClinical Trial\nAn article of 700-1200 words concerning a drug evaluation. \nThis category provides rapid publications and is meant to be a \nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately five \nreferences. The author may express his or her opinion without \ncomplete documentation. \n\n\n\nClinicopathological Challenge\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in the \narticle. The article should be no more than 2-3 pages in length. \n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, two figures, and 10 references. \n\n\n\nDermatological Surgery \nAn article relating to the surgical aspects of treatment. 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All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1 MJD 2016 Jul Vol 36\n\n\n\nTROPICAL DERMATOLOGY - Letter to Editor\n\n\n\nA RARE CASE OF CUTANEOUS ACTINOMYCOSIS\nOF THE UPPER LIMB\nXT Wu1, JY Pan2 \n\n\n\nCorresponding Author and Reprint Request \nDr Xiaotian Wu\n1E Kent Ridge Road, Singapore 119228 \nNUHS Tower Block, Level 11\nEmail: wuxiaotian@u.nus.edu\n\n\n\n1 Yong Loo Lin School of Medicine, National University \n of Singapore\n2 National Skin Centre, Singapore\n\n\n\n3 clinical types: cervicofacial - the most common \nform described in literature, abdominal-pelvic, \nand pulmonary-thoracic. Actinomycosis of the \nextremities is extremely rare, with less than 50 cases \ndescribed in the literature worldwide2, and is usually \npostulated to be due to hematogenous spread of the \nmicro-organism, although inoculation of the wound \nwith saliva has also been less commonly reported2-3.\n\n\n\nThe clinical presentation of primary cutaneous \nactinomycosis of the extremity is heterogeneous and \ncan be similar to other dermatological conditions, \nwhich makes the condition a diagnostic challenge. \nNodular lesions, subcutaneous abscesses and even \na mass lesion mimicking a neoplasm have been \nreported in the literature3. Actinomycosis presenting \nas a cystic lesion, as in our patient, is uncommon, \nwith only 2 other reported cases in English \nliterature4-5. There might be a history of intermittent \nand recurring symptoms which improves with \nantibiotic treatment. Local spread to surrounding \nstructures such as subcutaneous tissue, muscle and \nbone has been described2.\n\n\n\nSir,\n\n\n\nA 66-year-old Chinese healthy female presented to \nthe National Skin Centre in Singapore with a tender \nand erythematous lump on the medial aspect of her \nright arm of 2 days duration. The lump has been \npresent for many years with no change in nature \npreviously. She was unable to recall any trauma. \nOn examination, a 1.5 x 2cm tender, cystic lesion \nwith a central punctum and surrounding erythema \nwas noted (Fig. 1). She was otherwise well. A \ndiagnosis of an inflamed epidermal cyst was made \nclinically and the patient underwent incision and \ndrainage of cyst contents, where a ruptured capsule \nwas seen and copious amount of pus was extruded. \nThe pus was sent for pyogenic culture. The patient \nwas also started on oral amoxicillin-clavunalate. \nActinomyces species was cultured from the pus \nspecimen. The patient underwent surgical excision \nof the lesion and was treated with 6 weeks of \nphenoxymethylpenicllin for actinomycosis. \n\n\n\nActinomycosis is a rare infection caused by bacteria \nbelonging to the Actinomyces genus, which are \ncommensals of the oropharynx, aerodigestive and \nfemale genital tract. The usual pathogen involved \nis Actinomyces israelii, an anaerobic, non-spore-\nforming Gram-positive bacillus.\n\n\n\nDue to its low virulence, actinomyces cannot \npenetrate intact mucosa, and traumatic injury is \nusually required to cause a break in the mucosa and \nto create the anaerobic conditions for the organism to \nproliferate1. Actinomycosis is usually classified into \n\n\n\nFigure 1. A 66-year-old Chinese female presented with a \ntender and erythematous cystic lesion of 2 days duration. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2MJD 2016 Jul Vol 36\n\n\n\nImaging modalities such as CT and MRI, while \nhelpful in determining the extent of involvement, \nare usually non-contributory to establishing the \ndiagnosis6. The diagnosis of actinomycosis is usually \nmade only after histopathological examination or \nmicrobiological culture. Due to the fastidious nature \nof the organism, it is often difficult to culture2 and \ndiagnosis is often made on histological examination \nof the characteristic \u201csulphur granules\u201d extruded in \npus. In this reported case, we managed to culture \nActinomyces spp. from the pus specimen after 1 \nweek of incubation. Contamination of the pus from \nnormal flora was unlikely because of sterile surgical \ntechnique. A subsequent Actinomyces-specific \nculture was attempted, but yielded negative results. \nThis is likely because the patient had already been \nstarted on antibiotic treatment for actinomycosis.\n\n\n\nThe treatment of actinomycosis usually consists \nof surgical excision and a prolonged course of \nsuitable antimicrobial therapy to ensure eradication. \nActinomyces spp. are generally susceptible to \npenicillin1, and it remains the drug of choice. \nTetracyclines can be given to patients allergic to \npenicillin. Our patient responded well to surgical \nexcision and a 6-week course of antibiotics.\n\n\n\nIn summary, this is a case of cutaneous actinomycosis \nof the upper extremity presenting as an inflamed \nepidermal cyst. Actinomycosis is difficult to \ndiagnose clinically and requires a high degree of \nsuspicion. Accurate diagnosis and prompt treatment \nis important to prevent the recurrence of symptoms.\n\n\n\nReferences\n \n1. Bowden GHW. Actinomyces, Propionibacterium \n\n\n\npropionicus, and Streptomyces. Baron S (ed). Medical \nMicrobiology, 4th ed. Galveston (TX): University of Texas \nMedical Branch at Galveston; 1996. Chapter 34.\n\n\n\n2. Reiner SL, Harrelson JM, Miller SE, Hill GB, Gallis HA. \nPrimary Actinomycosis of an Extremity: a Case Report \nand Review. Rev Infect Dis. 1987; 9(3): 581-9.\n\n\n\n3. Yang CH. Primary Cutaneous Actinomycosis of an \nExtremity: a Case Report. J Intern Med Taiwan 2010; 21: \n290-3.\n\n\n\n4. Min KW, Park SY, Paik SS. Penile Actinomycosis clinically \ndiagnosed as an epidermal Cyst: a Case Report. Ann R \nColl Surg Engl. 2012; 94(1): e22-23. http://dx.doi.org/1.\n1308/003588412X13171221499388 (accessed 2 March \n2016).\n\n\n\n5. Jain A, Narula V, Alam K, Shukla I. Cervicofacial \nActinomycosis mimicking sebaceous Cyst.. BMJ Case \nRep. 2013. doi:10.1136/bcr-2012-008429 (accessed 2 \nMarch 2016).\n\n\n\n6. Hossain MI, Khan AKMS. Primary cutaneous \nActinomycosis of lower Extremity: a rare Case Report. \nAnwer Khan Modern Medical College Journal 2015; 6(1): \n55-57.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3 MJD 2016 Jul Vol 36\n\n\n\nINFECTIOUS DISEASE DERMATOLOGY - Letter to Editor\n\n\n\nBELL\u2019S PALSY SECONDARY TO PROBABLE HERPES ZOSTER \nINFECTION IN A PSORIASIS PATIENT ON INFLIXIMAB AND \nHIGH-DOSE METHOTREXATE\nSu P1, Pan JY2\n\n\n\nCorresponding Author and Reprint Request \nDr Xiaotian Wu\n1E Kent Ridge Road, Singapore 119228 \nNUHS Tower Block, Level 11\nEmail: wuxiaotian@u.nus.edu\n\n\n\n1 Yong Loo Lin School of Medicine, National University \n of Singapore\n2 National Skin Centre, Singapore\n\n\n\npalsy and with ectropion of the lower eyelid. There \nwas no vesiculation but he had a prodrome of \npersistent pain and tingling of the left side of the \nface and ear. He was treated for possible Ramsay-\nHunt syndrome with acyclovir, and switched to \nsecukinumab with improvement of his psoriasis and \narthritis.\n\n\n\nThe risk of herpes zoster has been reported to be \nas high as 61% in patients with rheumatoid arthritis \nreceiving anti-tumour necrosis factor (anti-TNF) \nblockers4. Disseminated zoster infection has also \nbeen reported in patients with inflammatory arthritis \non methotrexate5,6. These patients were successfully \ntreated with parenteral acyclovir.\n\n\n\nAlthough Bell\u2019s palsy has been reported in children \nfollowing immunization with inactivated trivalent \ninfluenza vaccine (TIV) and hepatitis B virus (HBV) \nvaccine, it has not been reported in association \nwith methotrexate or biologics7. To our knowledge, \nthe current case is the first report of Ramsay-\nHunt syndrome with Bell\u2019s palsy associated with \nbiologics. In such patients, other than treatment with \nacyclovir, lowering the dose of immunosuppressive \nagents should be considered.\n\n\n\nSecukinumab is relatively new US FDA approved \nhuman interleukin-17A (IL-17A) antagonist, for the \ntreatment of plaque psoriasis. Trials evaluating the \nefficacy and safety of secukinumab have shown it to \nhave good tolerability although the risk of infections, \nparticularly respiratory infections, appear to be a \ncommon side effect8.\n\n\n\nSecukinumab, however, may be less \nimmunosuppressive than the other biologics and \nthus could have a lower risk of infections. Long-\nterm safety data for secukinumab are still lacking. \nWith the increasing use of biologic therapy in \nthe treatment of psoriasis, physicians should be \ncognisant of the potential risks of adverse effects.\n\n\n\nSir,\n\n\n\nIn recent years, the use of biologics has revolutionised \nthe treatment of psoriasis. However, the efficacy \nof these treatments must be balanced against \npotential adverse events. A recent multicentre, \nlongitudinal study found a higher risk of serious \ninfections, particularly pneumonia and cellulitis, \nwith adalimumab and infliximab compared with \nnon-methotrexate and non-biologic therapies1. \nHerpes zoster infections may also be increased in \npatients receiving methotrexate and biologics2. In \naddition, combination treatment with methotrexate \nand biologics may increase the risk of Herpes zoster \ninfection further3.\n\n\n\nIn the present study, we describe a patient who \ndeveloped Ramsay-Hunt syndrome complicated by \nBell\u2019s palsy whilst on infliximab.\n\n\n\nA 49 year old Malay man had psoriasis with \npsoriatic arthritis.  His previous treatments included \nphototherapy, methotrexate, ciclosporin, acitretin \nand biologic therapy.\n\n\n\nHis first biologic was ustekinumab but he had \na paradoxical flare of her disease with pustular \npsoriasis. He was switched to adalimumab but \ndeveloped secondary failure. Infliximab was \ncommenced and methotrexate up to 20mg/week was \nadded for better control of his arthritis. However, \nafter 3 months of therapy, his response remained \nsuboptimal and he developed a profound left Bell\u2019s \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4MJD 2016 Jul Vol 36\n\n\n\nReferences\n \n1. Kalb RE, Fiorentino DF, Lebwohl MG at al. Risk of \n\n\n\nSerious Infection With Biologic and Systemic Treatment \nof Psoriasis: Results From the PsoriasisLongitudinal \nAssessment and Registry (PSOLAR). JAMA Dermatol. \n2015; 151(9): 961-9.\n\n\n\n2. Dreiher J, Kresch FS, Comaneshter D et al. Risk of Herpes \nzoster in patients with psoriasis treated with biologic drugs. \nJ Eur Acad Dermatol Venereol. 2012; 26(9): 1127-32. \n\n\n\n3. Shalom G, Zisman D, Bitterman H et al. Systemic Therapy \nfor Psoriasis and the Risk of Herpes Zoster: A 500,000 \nPerson-year Study. JAMA Dermatol. 2015; 151(5): 533-8.\n\n\n\n4. Che H, Likas C, Morel J et al. Risk of herpes/herpes zoster \nduring anti-tumor necrosis factor therapy in patients with \nrheumatoid arthritis. Systematic review and meta-analysis. \nJoint Bone Spine. 2014; 81(3): 215-21. \n\n\n\n5. Patel N, Singh D, Patel K et al. Atypical Presentation \nof Disseminated Zoster in a Patient with Rheumatoid \nArthritis. Case Rep Med. 2015; 2015: 124840.\n\n\n\n6. Agarwal V, Singh R, Chauhan S. Remission of rheumatoid \narthritis after acute disseminated varicella-zoster infection. \nClin Rheumatol. 2007; 26(5): 779-80.\n\n\n\n7. Rowhani-Rahbar A, Klein NP, Lewis N at al. Immunization \nand Bell\u2019s palsy in children: a case-centered analysis. Am J \nEpidemiol. 2012; 175(9): 878-85\n\n\n\n8. Ryoo JY, Yang HJ, Ji E et al. Meta-analysis of the Efficacy \nand Safety of Secukinumab for the Treatment of Plaque \nPsoriasis. Ann Pharmacother. 2016; 50(5): 341-51.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5 MJD 2016 Jul Vol 36\n\n\n\nINFECTIOUS DISEASE DERMATOLOGY - Original Article\n\n\n\nSTAPHYLOCOCCUS AUREUS ANTIBIOTIC RESISTANCE\nIN ATOPIC ECZEMA\nLee CK1,2, Yusof MY3, Lee YY2,4, Tan ESS1, PhD, Wong SM2, Ch\u2019ng CC2, Koh CK2\n\n\n\nAbstract\n\n\n\nBackground: Atopic Dermatitis (AD) is a chronic relapsing, pruritic inflammation of the skin which \nis often colonized by Staphylococcus aureus. Antibiotic resistance of S. aureus is a constant challenge \nfor clinicians who manages atopic dermatitis. \n\n\n\nAim: To determine S. aureus antibiotic resistance pattern among patients with non-infected atopic \ndermatitis and its association with disease severity.\n\n\n\nMethods: One hundred and seventy eight participants (89 AD patients and 89 controls) were recruited \nfrom Universiti Malaya Medical Centre (UMMC). Participants were subjected to a questionnaire on \ndemographics, personal and family medical conditions as well as antibiotic administration. AD severity \nwere determined using Scoring Atopic Dermatitis (SCORAD). Skin swab was taken from eczematous \nlesion in patients and from left forearm in controls. Antibiotic susceptibility towards methicillin, \nvancomycin, rifampicin, fusidic acid, erythromycin, gentamicin, clindamycin, sulphamethoxazole, \ncefuroxime and penicillin were determined using disk diffusion method. Results for antibiotic \nresistance were categorized as none, sensitive and resistant.\n\n\n\nResults: Colonization of S. aureus in AD were significantly higher than control (p<0.001). Highest \nantibiotic resistance was reported for Penicillin (32/39, 82.1%), followed by Fusidic Acid (7/39, \n17.9%) as well as Clindamycin and Erythromycin (3/39, 7.7% respectively). Two AD patient (5.1%) \nwere resistant to Gentamicin. In addition, 1 AD patient (2.6%) was resistant towards Methicillin, \nSulfamethoxazole and Cefuroxime respectively. No antibiotic resistance was reported for Vancomycin \nand Rifampicin among the AD patients.\n\n\n\nConclusion: High resistance were found for Penicillin and Fusidic acid. Their usage and prescription \nshould be reduced to preserve its sensitivity. \n\n\n\nKeywords: antibiotic resistance, atopic dermatitis, Staphylococcus aureus, SCORAD\n\n\n\nCorresponding Author and Reprint Request \nDr Irene Lee Chew Kek, MRCP\nSchool of Anti-aging,\nAesthetic and Regenerative Medicine,\nFaculty of Medicine and Health Sciences,\nUCSI University\nEmail: chewkek@hotmail.com\n\n\n\n1 School of Anti-aging, Aesthetic and Regenerative \n Medicine, Faculty of Medicine, UCSI University, \n Kuala Lumpur, Malaysia\n2 Department of Medicine, Universiti Malaya,\n Kuala Lumpur, Malaysia\n3 Department of Microbiologi, Universiti Malaya,\n Kuala Lumpur, Malaysia \n4 Sunway Medical Centre, Selangor, Malaysia\n\n\n\nIntroduction\nAtopic dermatitis (AD) is a chronic relapsing, \npruritic inflammation of the skin, affecting 10-\n20% of children and 1-3% of adults worldwide1. \nStaphylococcus aureus can colonised both the \nlesional and non-lesional skin2. In fact, S. aureus is \nthe main colonizer in more than 90% of AD without \ncausing apparent skin infections2-4.\n\n\n\nDue to the compromised physical skin barrier, \npatients with AD are more susceptible to recurrent \npyogenic infections due to S. aureus such as \nimpetigo, folliculitis and furunculosis3. Infections \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6MJD 2016 Jul Vol 36\n\n\n\ndue to S. aureus tend to be more common during \nsevere exacerbation of the disease6. These recurrent \ninfections results in the recurrent usage of topical \nand systemic antibiotics, especially among patients \nwith severe AD6.\n\n\n\nAntibiotics resistance is on the rise. The recurrent \nusage of antibiotics may encourage the development \nof antibiotics resistance among this group of patient. \nHence, it is important to recognise the resistance \npattern of S. aureus and its association with AD \nseverity to guide clinicians on the antibiotic of \nchoice for the treatment of AD associated pyogenic \ninfections.\n\n\n\nMaterial and methods\nEighty-nine AD patients as well as 89 ethnicity-, \nage- and gender-matched control were recruited in \nUniversity Malaya Medical Centre (UMMC).\n\n\n\nQuestionnaires were administered to gather \ninformation on demographics and clinical \ncharacteristics. \n\n\n\nAD severity was determined by a dermatologist \nusing Scoring Atopic Dermatitis (SCORAD). \nSCORAD results were catergorised as mild (<25), \nmoderate (25-50) and severe (>50). Skin swab  of \nwas taken from 1cm2 exzematous lesion in patients \nand from 1cm2 left forearm in controls for cultures \nas well as antibiotic sensitivity towards methicillin, \nvancomycin, rampicin, fusidic acid, erythromycin, \ngentamicin, clindamycin, sulphamethoxazole, \ncefuroxime and penicillin. Antibiotic resistances \n\n\n\nwere determined using agar disk diffussion method \nin accordance to the Clinical and Laboratory \nStandards Institute (CLSI). Antibiotic resistance \nwere classified based on zone diameter interpretive \nstandards. \n\n\n\nData obtained were analyzed using Predictive \nAnalytics Software (PASW) Version 18.0. \nAssociation between categorical variables were \nanalyzed using the chi-square test. Statistical \nsignifance was determined as p<0.05.\n\n\n\nResults\nPatient and control group were statistically \nhomogeneous (Table 1). Positive cultures for S. \naureus in AD group were significantly higher than \ncontrol (39 patients, 43.8% vs 2 controls, 2.2%, \np<0.001). Meanwhile, 22 out of 48 (45.8%) patients \nbelow 16 years grew S. aureus compared to 17 out \nof 41 (41.5%) patients above 16 years (p=0.679).\n\n\n\nHighest antibiotic resistance was reported for \nPenicillin (32/39, 82.1%), followed by Fusidic \nAcid (7/39, 17.9%) as well as Clindamycin and \nErythromycin (3/39, 7.7% respectively). Two AD \npatient (5.1%) were resistant to Gentamicin. In \naddition, 1 resistant AD patient (2.6%) was reported \nfor Methicillin, Sulfamethoxazole and Cefuroxime \nrespectively. Only 1 AD patient showed no resistance \nto the tested antibiotics. No antibiotic resistance was \nreported for Vancomycin and Rifampicin among \nAD patients. Out of the two cultures in the control \narm, only one culture was resistant to penicillin. No \nother antibiotic resistance was reported. (Table 2).\n\n\n\nDemographics\n\n\n\nGender, no (%)\nMale\nFemale\n\n\n\nEthnicity, no (%)\nMalay\nChinese\nIndian\n\n\n\nAge (median, IQR)\n\n\n\nAge Group, no (%)\n<16 years\n\u2265 16 years \n\n\n\nParticipants\n\n\n\nPatient\n(n=89)\n\n\n\n 34 (38.2)\n 55(6.8)\n\n\n\n 50 (56.2)\n 26 (29.2)\n 13 (14.6)\n\n\n\n 15 (13.5)\n\n\n\n 48 (53.9)\n 41 (46.1)\n\n\n\nControl\n(n=89)\n\n\n\n 35 (39.3)\n 54 (60.7)\n\n\n\n 49 (55.1)\n 27 (30.3)\n 13 (14.6)\n\n\n\n 15 (14.5)\n\n\n\n 47 (52.8)\n 42 (47.2)\n\n\n\np-value\n\n\n\np=0.878\n\n\n\np=0.986\n\n\n\np=0.974\n\n\n\np=0.881\n\n\n\nTable 1. Demographics of Patients and Controls.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7 MJD 2016 Jul Vol 36\n\n\n\nAmong patients with positive cultures, disease \nseverity were mild in 6 patients (15.4%), moderate \nin 17 patients (43.6%) and severe in 12 patients \n(30.8%). Penicillin resistance was reported in 14 \npatients with moderate AD (82.4%) and 11 patients \nwith severe AD (91.7%). Only one patient with mild \nAD did not show any antibiotic resistance (Table 3).  \n\n\n\nMost patients showed resistance to a single antibiotic \n(28/39, 71.8%). Multiple antibiotic resistance \n(Table 4) were found for 2 antibiotics (6/39, 15.4%), \n3 antibiotics (1/39, 2.6%) and 7 antibiotics (1/39, \n2.6%). Three patients with moderate AD (18%) \nand 4 patients with severe AD (36%) had multiple \nantibiotic resistance. One case of 2 antibiotic \nresistance had missing data on disease severity.\n\n\n\nAntibiotic\nResistance\n\n\n\nPenicillin\n\n\n\nFusidic Acid\n\n\n\nClindamycin\n\n\n\nErythromycin\n\n\n\nGentamicin\n\n\n\nMethicillin\n\n\n\nSulfamethoxazole\n\n\n\nCefuroxime\n\n\n\nVancomycin\n\n\n\nRifampicin\n\n\n\nNone\n\n\n\nParticipants\n\n\n\nPatient, no (%)\n(n=39)\n\n\n\n 32 (82.1)\n\n\n\n 7 (17.9)\n\n\n\n 3 (7.7)\n\n\n\n 3 (7.7)\n\n\n\n 2 (5.1)\n\n\n\n 1 (2.6)\n\n\n\n 1 (2.6)\n\n\n\n 1 (2.6)\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\nControl, no. (%)\n(n=2)\n\n\n\n 1 (50)\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n 1 (50)\n\n\n\nTable 2. S. aureus antibiotic resistance pattern in AD patients and controls.\n\n\n\nAntibiotic\nResistance\n\n\n\nPenicillin\n\n\n\nFusidic Acid\n\n\n\nClindamycin\n\n\n\nErythromycin\n\n\n\nGentamicin\n\n\n\nMethicillin\n\n\n\nSulfamethoxazole\n\n\n\nCefuroxime\n\n\n\nVancomycin\n\n\n\nRifampicin\n\n\n\nNone\n\n\n\nDisease Severity (SCORAD)\n\n\n\nMild, no (%)\n(n=6)\n\n\n\n 4 (66.7)\n\n\n\n 1 (16.7)\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n 1 (6.7)\n\n\n\nModerate, no. (%)\n(n=17)\n\n\n\n 14 (82.4)\n\n\n\n 2 (11.8)\n\n\n\n 2 (11.8)\n\n\n\n 2 (11.8)\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\nSevere, no (%)\n(n=12)\n\n\n\n 11 (91.7)\n\n\n\n 3 (25.0)\n\n\n\n 1 (8.3)\n\n\n\n 1 (8.3)\n\n\n\n 2 (16.7)\n\n\n\n 1 (8.3)\n\n\n\n 1 (8.3)\n\n\n\n 1 (8.3)\n\n\n\n -\n\n\n\n -\n\n\n\n -\n\n\n\nTable 3. S. aureus antibiotic resistance and disease severity.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8MJD 2016 Jul Vol 36\n\n\n\nConcurrent antibiotic resistance\n\n\n\n2 antibiotics\nFusidic Acid & Penicillin*\nErythromycin & Clindamycin\nGentamicin & Penicillin\n\n\n\n3 antibiotics\nErythromycin, Clindamycin & \nPenicillin\n\n\n\n7 antibiotics\nMethicillin, Erythromycin, \nSulfamethoxazole, Gentamicin, \nClindamycin, Penicillin & \nCefuroxime\n\n\n\nMild, no (%)\n(n=6)\n\n\n\n-\n-\n-\n\n\n\n-\n\n\n\n-\n\n\n\nModerate, no. (%)\n(n=17)\n\n\n\n1 (5.9)\n1 (5.9)\n\n\n\n-\n\n\n\n1 (5.9)\n\n\n\n-\n\n\n\nSevere, no (%)\n(n=12)\n\n\n\n2 (16.7)\n-\n\n\n\n1 (8.3)\n\n\n\n-\n\n\n\n1 (8.3)\n\n\n\nTable 4. Multiple S. aureus resistance and disease severity.\n\n\n\nDisease Severity (SCORAD)\n\n\n\n* One case had missing data for disease severity\n\n\n\nAntibiotic\nResistance\n\n\n\nPenicillin\n\n\n\nFusidic Acid\n\n\n\nClindamycin\n\n\n\nErythromycin\n\n\n\nGentamicin\n\n\n\nMethicillin\n\n\n\nSulfamethoxazole\n\n\n\nCefuroxime\n\n\n\nVancomycin\n\n\n\nRifampicin\n\n\n\nPercentage of Resistance\n\n\n\nThis Study (%)\n\n\n\n 82.1\n\n\n\n 17.9\n\n\n\n 7.7\n\n\n\n 7.7\n\n\n\n 5.1\n\n\n\n 2.6\n\n\n\n 2.6\n\n\n\n 2.6\n\n\n\n -\n\n\n\n -\n\n\n\nNSAR (%)\n\n\n\n 82.4\n\n\n\n 13.0\n\n\n\n 11.2\n\n\n\n 18.3\n\n\n\n 14.0\n\n\n\n 17.3\n\n\n\n 12.2\n\n\n\n 13.4\n\n\n\n -\n\n\n\n 2.2\n\n\n\nTable 5. S. aureus antibiotic resistance pattern in AD patients versus\nMalaysian National Surveillance of Antibiotic Resistance (NSAR).\n\n\n\nDiscussion\nFrequent prescription as well as prolonged usage of \ntopical and oral antibiotics promotes its resistance. \nOwing to increased prevalence of antibiotic \nresistances, some authors discouraged to use \nantibiotics for purpose of decolonization without \nclinical signs of infections7.\n\n\n\nS. aureus antibiotic resistance in this study is \ncompared to Malaysian National Surveillance of \nAntibiotic Resistance (NSAR) report (Table 5). \n\n\n\nAntibiotic resistances reported in NSAR are based \non S. aureus all isolates that were analyzed during \nroutine laboratory test results done in hospitals.\n\n\n\nPenicillin resistance rates in this study (82.1%) \nare surprisingly comparable to hospital antibiotic \nresistance rates (82.4%). Several studies also \nreported similar penicillin resistance rates among \nAD patients; Poland (82%), and Singapore (91.7% \nin adults and 93.3% in children). According to \nKedzierska et al., resistance towards penicillin did \nnot increased in recolonized lesion8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n9 MJD 2016 Jul Vol 36\n\n\n\nAlarmingly, fusidic acid resistance (17.9%) in \nthis study is higher by 4.9% compared to NSAR. \nProlonged use of fusidic acid had been associated \nwith increased antibiotic resistances. Kedzierska \net al. found increased resistance from 0 to 18% in \ncases of subsequent recolonization within 75 days \nof treatment8. In another separate incidence, 78% \nof atopic eczema patient who had applied topical \nfusidic acid over the past 6 months were found to be \nresistant to fusidic acid9. In addition, its resistance \ntripled during prolonged application from infancy \nto adolescents10. \n\n\n\nFusidic acid is a commonly used anti-staphylococcal \ndrug. Recently, emergence of resistance to fusidic \nacid is escalating particularly in impetigo where it is \nrecommended as the first line medication11. Fusidic \nacid resistance is also found among methicillin \nresistant S. aureus (MRSA)12. In line with this, \nANVISA (Brazilian National Health Surveillance \nAgency) now requires prescription for fusidic acid \neffective 2011. Mason et al. reported significant \ncorrelation between prescription of fusidic acid and \nits resistance (p=0.001) with average resistance of \n2.8%13.\n\n\n\nResults had shown low rate of resistance for \nerythromycin, clindamycin and gentamicin among \nAD patients. Their resistances were lower than \nNSAR data; erythromycin (18%), clindamycin \n(11%) and gentamicin (14%). Erythromycin is often \nprescribed in cases of penicillin allergy. \n\n\n\nIn this study, low resistances were found for \nmethicillin, sulfamethoxazole and cefuroxime with \nnearly full susceptibility. Their resistances were lower \nthan NSAR data of antibiotic resistances; methicillin \n\n\n\n(17%), sulfamethoxazole (12%) and cefuroxime \n(13%). Hoeger reported full susceptibility among \n115 pediatric in Germany with moderate to severe \nAD towards cefuroxime and methicillin as well14.  \nMethicillin\u2019s low resistances rate in AD were also \ncomparable to other study in Germany, United \nStates, New Zealand and Singapore15-18.\n\n\n\nFull susceptibilities were found for vancomycin and \nrifampicin in this study. Similarly, NSAR reported \nno vancomycin resistant S. aureus; however 2% of \nresistance was reported for Rifampicin. \n\n\n\nConcurrent antibiotic resistances are largely \nunexplored. Giliani et al. reported concurrent \nantibiotic resistance between penicillin with \nintermediate fusidic acid resistance (24%) as well \nas penicillin with complete fusidic acid (10%) \n(19). Similar trend were observed for 8% of our \nAD patient; 1 with moderate and 2 with severe \ndisease severity. Incidences of concurrent antibiotic \nresistances increase with disease severity. \n\n\n\nClinicians are recommended to conduct \nsusceptibility tests of clinical S. aureus towards \nantibiotic resistance before each therapy. In \naddition, it is also worthwhile to monitor rates of \nresistance in cases of prolong application. Lastly, \nstrong consideration is posed to reduce prescription \nof penicillin and fusidic acid to preserve their \nsensitivity. \n\n\n\nAcknowledgement\nThis study was supported by research grant from \nPersatuan Dermatologi Malaysia. Authors would \nlike to extend their appreciation for their financial \nsupport.\n\n\n\nReferences\n \n1. Roll A, Cozzio A, Fischer B, Schmid-Grendelmeier P. \n\n\n\nMicrobial colonization and atopic dermatitis. Curr Opin \nAllergy Clin Immunol. 2004;4(5):373-8.\n\n\n\n2. Matsui K, Nishikawa A, Suto H, Tsuboi R, Ogawa H. \nComparative study of Staphylococcus aureus isolated from \nlesional and non-lesional skin of atopic dermatitis patients. \nMicrobiol Immunol. 2000;44(11):945-7.\n\n\n\n3. Hoare C, Li Wan Po A, Williams H. Systematic review \nof treatments for atopic eczema. Health Technol Assess. \n2000;4(37):1-191.\n\n\n\n4. Guzik TJ, Bzowska M, Kasprowicz A, Czerniawska-Mysik \nG, Wojcik K, Szmyd D, et al. Persistent skin colonization \nwith Staphylococcus aureus in atopic dermatitis: \nrelationship to clinical and immunological parameters. \nClin Exp Allergy. 2005;35(4):448-55.\n\n\n\n5. Hanifin JM, Rogge JL. Staphylococcal infections \nin patients with atopic dermatitis. Arch Dermatol. \n1977;113(10):1383-6.\n\n\n\n6. DiNubile MJ, Lipsky BA. Complicated infections of skin \nand skin structures: when the infection is more than skin \ndeep. J Antimicrob Chemoth. 2004;53(Supp. S2):ii37 - \nii50.\n\n\n\n7. Buys LM, D. P, B.C.P.S. Treatment Options for Atopic \nDermatitis. Am Fam Physician. 2007;75(4):523 - 8.\n\n\n\n8. Kedzierska A, Kapinska-Mrowiecka M, Czubak-\nMacugowska M, Wojcik K, Kedzierska J. Susceptibility \ntesting and resistance phenotype detection in \nStaphylococcus aureus strains isolated from patients \nwith atopic dermatitis, with apparent and recurrent skin \ncolonization. Brit J Dermatol. 2008;159(6):1290-9.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10MJD 2016 Jul Vol 36\n\n\n\n9. Shah M, Mohanraj M. High levels of fusidic acid-resistant \nStaphylococcus aureus in dermatology patients. Brit J \nDermatol. 2003;148(5):1018-20.\n\n\n\n10. Arkwright PD, Daniel TO, Sanyal D, David TJ, Patel \nL. Age-related prevalence and antibiotic resistance of \npathogenic staphylococci and streptococci in children with \ninfected atopic dermatitis at a single-specialty center. Arch \nDermatol. 2002;138(7):939-41.\n\n\n\n11. Koning S, van Suijlekom-Smit LW, Nouwen JL, Verduin \nCM, Bernsen RM, Oranje AP, et al. Fusidic acid \ncream in the treatment of impetigo in general practice: \ndouble blind randomised placebo controlled trial. BMJ. \n2002;324(7331):203-6.\n\n\n\n12. Howden BP, Grayson ML. Dumb and dumber - the \npotential waste of a useful antistaphylococcal agent: \nemerging fusidic acid resistance in Staphylococcus aureus. \nClin Infec Dis. 2006;42(3):394-400.\n\n\n\n13. Mason BW, Howard AJ, Magee JT. Fusidic acid resistance \nin community isolates of methicillin-susceptible \nStaphylococcus aureus and fusidic acid prescribing. J \nAntimicrob Chemother. 2003;51(4):1033-6.\n\n\n\n14. Hoeger PH. Antimicrobial susceptibility of skin-colonizing \nS. aureus strains in children with atopic dermatitis. Pediatr \nAllergy Immunology. 2004;15(5):474-7.\n\n\n\n15. Goh C-L, Wong JS, Giam YC. Skin colonization of \nStaphylococcus aureus in atopic dermatitis patients seen \nat the National Skin Centre, Singapore. Int J Dermatol. \n1997;36(9):653-7.\n\n\n\n16. Niebuhr M, Mai U, Kapp A, Werfel T. Antibiotic treatment \nof cutaneous infections with Staphylococcus aureus in \npatients with atopic dermatitis: current antimicrobial \nresistances and susceptibilities. Exp Dermatol. \n2008;17(11):953-7.\n\n\n\n17. Matiz C, Tom WL, Eichenfield LF, Pong A, Friedlander \nSF. Children with atopic dermatitis appear less likely to \nbe infected with community acquired methicillin-resistant \nStaphylococcus aureus: the San Diego experience. Pediatr \nDermatol. 2011;28(1):6-11.\n\n\n\n18. Hill SE, Yung A, Rademaker M. Prevalence of \nStaphylococcus aureus and antibiotic resistance in children \nwith atopic dermatitis: A New Zealand experience. \nAustralas J Dermatol. 2011;52(1):27-31.\n\n\n\n19. Gilani SJK, Gonzalez M, Hussain I, Finlay AY, Patel GK. \nStaphylococcus aureus re-colonization in atopic dermatitis: \nbeyond the skin. Clin Exp Dermatol. 2005;30(1):10-3.\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. Staphylococcus aureus antibiotics resistance is high in patients with atopic eczema, with penicillin \n resistance highest followed by fucidic acid. This is not surprising as penicillin based antibiotics \n are frequently prescribed and in most times inappropriately for multiple reasons. Resistance to \n fucidic acid is also not surprising as this is the most prescribed topical antibiotics for patients \n with eczema. Combination of fucidic acid and steroid cream are also frequently used in patients \n with eczema, usually prolonged over many months. Thus, it is important for health care settings to \n limit use of such topical antibiotics alone or in combination to 2 weeks treatment to prevent \n resistance.\n\n\n\n2. Resistance to clindamycin and erythromycin was also a problem in this study. These antibiotics are \n highly utilized both in oral and topical forms in the treatment of acne and in most times \n inappropriately prolonged. Again, time limit to the use of such medication is vital.\n\n\n\n3. This is the experience of Universiti Malaya Medical Centre and it is imperative that all hospitals \n and medical centres have their own antibiotic resistance pattern and a committee looking into its use \n including the topical antibiotics to reduce antibiotic resistance. It is also encouraged in the GP \n setting where antibiotics are freely prescribed.\n\n\n\nYap FBB MD MRCP AdvMDerm\nEditor-in-Chief, MJD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11 MJD 2016 Jul Vol 36\n\n\n\nINFECTIOUS DISEASE DERMATOLOGY - Original Article\n\n\n\nCLINICAL PRESENTATION AND OUTCOME OF HERPES \nZOSTER INFECTION IN A TERTIARY DERMATOLOGY \nOUTPATIENT REFERRAL CLINIC IN MALAYSIA\nYeoh CA, MRCP1, Chan LC, M Med2; Tan WC, MRCP1, Wee HC, MD3\n\n\n\nAbstract\n\n\n\nIntroduction: Herpes zoster (HZ) is a common acute, cutaneous viral infection caused by reactivation \nof latent varicella zoster virus with devastating effects on quality of life. This study aims to describe \nthe demographic and clinical characteristic and complications of HZ. \n\n\n\nMethodology: This was a retrospective study of 179 HZ patients from the Dermatology department of \nPenang Hospital between January 2010 and June 2013.\n\n\n\nResults: The 179 patients had a median age of 53 years. Chinese ethnicity was more affected. \nMajority of the patients came late to seek treatment with the median of disease duration of 4 days. The \ncommonest presenting complaint was pain (98.9%), followed by itching (25.7%) and fever (9.5%). \nSingle dermatome involvement was seen in 90.5% of the patients, of which the thoracic dermatome \n(54.9%) being the commonest. The incidence of complications such as secondary bacterial infection, \npost-herpertic neuralgia, eye complication(s) and scar were 36.3%, 4.5%, 5.6% and 2.8% respectively. \nThe complications were not statistically different between the younger and the older patient. However, \nit was more common among male patients.\n\n\n\nConclusion: Patients with HZ in Penang presented late and tend to have complications. Hence, public \neducation and vaccination should be recommended.\n\n\n\nKeywords: Herpes zoster, postherpetic neuralgia, Malaysia\n\n\n\nCorresponding Author and Reprint Request \nDr Yeoh Chin Aun,\nDepartment of Dermatology,\nHospital Sultanah Bahiyah, Alor Setar, Kedah\nEmail: ychinaun@gmail.com\n\n\n\n1 Dermatology Department, Sultanah Bahiyah Hospital\n2 Dermatology Department, Penang Hospital\n3 Clinical Research Centre, Penang Hospital\n\n\n\nAmerica, Europe and Asia-Pacific ranged between \n3 and 5/1000 person-years1. The age-specific \nincidence rate of HZ rises significantly after 50 \nyears of age1.\n\n\n\nCharacteristically, HZ presents with a self-limiting \nlocalized dermatomal painful blistering rash. The \nmost common complication of HZ is post-herpetic \nneuralgia, which can cause devastating effects on \npatients\u2019 quality of life and significant global health \nburden1. Other complications are neurological \nsequelae, secondary bacterial infection, HZ \nophthalmicus with eye involvement, disseminated \ndisease, and scar formation.\n\n\n\nIntroduction\nHerpes zoster (shingles) is a common acute, \ncutaneous viral infection caused by reactivation \nof latent varicella zoster virus (VZV) that has \nremained dormant within the dorsal root ganglia. \nThe incidence rate of Herpes zoster (HZ) in North \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12MJD 2016 Jul Vol 36\n\n\n\nthe Dermatology department of Penang Hospital \nwere included. Random sampling methods were \nused. All patients aged more than 18 years old \ndiagnosed as HZ from January 2010 to June \n2013 were included into this study. The diagnosis \nof HZ was established by historical and clinical \npresentations of the patient. Demographic data that \nwere available for this study included age, gender, \nrace, referral centres and onset of the disease. \nOther disease-related data such as medical history, \npresentation, Herpes Zoster related complication, \nimmune status, treatment responses and disease \noutcome were also retrieved for statistical analysis.\n\n\n\nWe characterized the patients as having              \ncomplications if they developed either one of \nthe following signs: post HZ scars, post-herpetic \nneuralgia, visceral involvement, Ramsay hunt, \neyes complications and secondary infections. \nPost herpetic neuralgia is was defined as pain \nthat persists more than 30 days after cutaneous \nhealing2. Conjunctivitis, keratitis, uveitis or \nocular cranial-nerve palsies was considered as \neye complications. The patients were categorized \nas immunocompromised if they were having \nmalignancy, diabetes mellitus, chronic kidney \ndisease, end stage kidney failure, HIV or taking \nimmunosuppressants.\n\n\n\nTo our knowledge, there is no published study \non HZ especially on clinical presentation in \nMalaysia. Additionally in the latest progress in \nHZ, vaccination for HZ is getting more important \nin the prevention of this disease. Vaccination can \nhelp to reduce the severity of complications due \nto HZ. Thus, it is important to look into our local \npopulation on clinical presentation of HZ to ensure \nthat our patients present or develop complication(s) \nsame like other country or study population. This \ncan help us to plan for a good cost effective strategy \nto combat HZ in our country.\n\n\n\nThe primary objective of our study was to describe \nthe demographic and clinical characteristic of HZ \npatients in our dermatology clinic. We also describe \nthe involvement of dermatome among two age \ngroups and sex, and to explore factors associated \nwith HZ complications. This descriptive clinical \ninformation can provide the local health care \nprovider with a better understanding of the disease \nand to further define the disease characteristics \nunique to our local multi-ethnic population.\n\n\n\nMaterials and methods\nThis was a single-centre, hospital-based, \nretrospective-descriptive study. A total of 179 \nclinically diagnosed Herpes zoster infections from \n\n\n\nVariables\n\n\n\nAge ( years)\n\n\n\nAge Group ( years)\n\n\n\nYoung [ < 60]\n\n\n\nOld [ \u2265 60]\n\n\n\nGender\n\n\n\nMale\n\n\n\nFemale \n\n\n\nEthnicity\n\n\n\nMalay \n\n\n\nChinese\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nReferral sources\n\n\n\nPrimary care\n\n\n\nOther than Primary Care \n\n\n\nSelf referral\n\n\n\nMedian (IQR)\n\n\n\n     53 (34)a\n\n\n\nFrequency, n (%)\n\n\n\n 106 (59.2)\n\n\n\n 73 (40.8)\n\n\n\n 103 (57.5)\n\n\n\n 76 (42.5)\n\n\n\n 75 (41.9)\n\n\n\n 85 (47.5)\n\n\n\n 11(6.1)\n\n\n\n 8 (4.5)\n\n\n\n 133 (74.3)\n\n\n\n 43 (24.0)\n\n\n\n 3 (1.7)\n\n\n\nTable 1. Demographic of the HZ (n=179)\n\n\n\na Skewed Data        IQR = Interquartile Range\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13 MJD 2016 Jul Vol 36\n\n\n\nwere male (n=103; 57.4%) and 47.5% (n=85) were \nof Chinese ethnic origin. About 27.9% (n=50) of \nthe patients were immunocompromised as they \nwere having malignancy, diabetes mellitus, chronic \nkidney disease, end stage kidney failure, HIV or \ntaking immunosuppressant. None of these diseases \nhad a significant association with the age group of \nthe patients (< 60 or \u2265 60 years old) despite younger \npatients co-existed with immunocompromised state.\n\n\n\nMore than half of the patients (n=98; 54.8%) came \nlate to seek treatment with the median of disease \nduration of 4 days. All the referral for HZ cases \nwere seen within the same day.\n\n\n\nClinical Presentation and treatment\nThe commonest presenting complaint of our cohort \nwas pain (n=164; 98.9%), followed by itching \n(n=42; 25.7%), fever (n=16; 9.5%), skin swelling \n(n=2; 1.7%) and acute abdomen (n=1; 0.6%).\n\n\n\nStatistical Analysis\nStatistical analysis was performed using Statistical \nPackage for the Social Sciences software (Version \n15.0). Continuous variables were expressed \nas median \u00b1 with interquartile range (IQR); \ncategorical variables were expressed as a frequency \nand percentage (%). Simple logistic regression \nwas used to investigate the factors influencing HZ \ncomplications. The odds ratios (ORs) and their 95% \nconfidence intervals (CIs) for HZ complications \nwere shown in the final results, with p < 0.05 \nconsidered to be statistically significant.\n\n\n\nResults\nA total of 179 patients\u2019 data with diagnosis of HZ \nwere retrieved from the clinic cards.\n\n\n\nDemographics of the patients\nThe median age of this cohort was 53 \u00b1 34 years \nold with 59.2% (n=106) of the patients less than 60 \nyears old (young patients). Majority of the patients \n\n\n\nDermatome\n\n\n\nThoracic\n\n\n\nCervical\n\n\n\nV1 (Trigeminal)\n\n\n\nLumbar\n\n\n\nV2, V3 (Trigeminal)\n\n\n\nSacral\n\n\n\nTotal\n[n, %]\n\n\n\n 89 (54.9)\n\n\n\n 22 (13.6)\n\n\n\n 21 (13.0)\n\n\n\n 19 (11.7)\n\n\n\n 8 (4.9)\n\n\n\n 3 (1.9)\n\n\n\nYoung \n(< 60 years)\n\n\n\n n (%)\n\n\n\n 54 (55.7)\n\n\n\n 10 (10.3)\n\n\n\n 12 (12.4)\n\n\n\n 12 (12.4)\n\n\n\n 7 (7.2)\n\n\n\n 2 (2.0)\n\n\n\nOlder \n( \u2265 60 years)\n\n\n\nn (%)\n\n\n\n 35 (53.8)\n\n\n\n 12 (18.5)\n\n\n\n 9 (13.8)\n\n\n\n 7 (10.8)\n\n\n\n 1 (1.5)\n\n\n\n 1(1.5)\n\n\n\nP valuea\n\n\n\np= 0.464\n\n\n\nTable 2. Comparison of the distribution of dermatome involved between two age groups (n= 162).\n\n\n\na Fisher Exact test\n\n\n\nDermatome\n\n\n\nThoracic\n\n\n\nCervical\n\n\n\nV1 (Trigeminal)\n\n\n\nLumbar\n\n\n\nV2,V3 (Trigeminal)\n\n\n\nSacral\n\n\n\nTotal\n[n, %]\n\n\n\n 89 (54.9)\n\n\n\n 22 (15.5)\n\n\n\n 21 (12.9)\n\n\n\n 16 (9.9)\n\n\n\n 8 (4.9)\n\n\n\n 3 (1.9)\n\n\n\nMale\n[ n,%]\n\n\n\n 51 (56.0%)\n\n\n\n 11 (12.1%)\n\n\n\n 15 (16.5%)\n\n\n\n 6 (6.6%)\n\n\n\n 6 (6.6%)\n\n\n\n 2 (2.2%)\n\n\n\nFemale\n( \u2265 60 years old)\n\n\n\n[n,%]\n\n\n\n 38 (53.5%)\n\n\n\n 11 (15.5%)\n\n\n\n 6 (8.5%)\n\n\n\n 13 (18.3%)\n\n\n\n 2 (2.8%)\n\n\n\n 1 (1.4%)\n\n\n\nTable 3. Comparison of the distribution of unilateral dermatome involved between genders (n=162).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14MJD 2016 Jul Vol 36\n\n\n\nsuch as secondary bacterial infection, eye \ncomplication(s), post-herpetic neuralgia and scar \nwere 36.3% (n=36.3), 5.6% (n=10), 4.5% (n=8) and \n2.8% (n=5) respectively. For post-herpetic neuralgia, \nthere was no statistical significance between the two \nage groups (p=0.274).\n\n\n\nAmong our patients with V1 branch of trigeminal \nnerve involvement (n=21), 14.3% (n=3) of \nthem developed visual disturbance due to \nophthalmoplegia. All these cases were co-managed \nwith our ophthalmology colleagues. All of them had \nconjunctivitis.  Two of them also had unilateral third \ncranial nerve palsy and one of them had unilateral \nsixth cranial nerve palsy.\n\n\n\nTable 4 shows the simple logistic regression analysis \nto investigate the likely factors that were associated \nwith herpes zoster complication. To identify the \nrelevance of the variables affecting complication of \nHerpes Zoster univariate and multivariate regression \nmodels were used. Variables used for modeling were \npatient age, sex, ethnicity, immunocompromised \nstatus and disease onset. After adjusting for other \nfactors, HZ complication were shown to be 50% \nless likely in females than males (Adjusted OR \n0.50, 95% CI 0.26, 0.93; P=0.029).\n\n\n\nUpon examination, 97.8% (n=162) of them had \nvesicular lesions, which mainly involved the \nthoracic dermatomal distribution (n= 89; 54.9 %). \nOther skin lesions noted were crusted plaque (n= 19; \n10.6%), pustule (n=16; 8.9%), erosion (n=7; 3.9%) \nand haemorrhagic bullae (n=1; 0.6%). None of the \nclinical presentation and demographics variables \nhad a statistically significant association with \nduration of disease on presentation to the clinic.\n\n\n\nAnalysis of the dermatomal involvement, were done \nfor 162 patients only (17 missing data). Majority \n(n=162; 90.5%) of the study population had single \ndermatome involvement. Thoracic dermatome \n(54.9%) was the commonest site. Table 2 showed \nthe comparison of the distribution of dermatome \ninvolved between two age groups. Table 3 showed \ncomparison of the distribution of unilateral \ndermatome involved between genders. Fisher Exact \ntest did not show any significant difference for the \ndistribution of dermatome involved between two \nage groups (p=0.464) and gender (p=0.132).\n\n\n\nNone of our patients had ever received HZ \nvaccination. All of them were treated with the oral \nantiviral, acyclovir. The incidence of complications \n\n\n\nVariable\n\n\n\nMale\n\n\n\nFemale\n\n\n\n<60\n\n\n\n\u226560\n\n\n\nChinese\n\n\n\nNon-Chinese\n\n\n\nEarly\n\n\n\nLate\n\n\n\nn\n\n\n\n103\n\n\n\n76\n\n\n\n106\n\n\n\n73\n\n\n\n85\n\n\n\n94\n\n\n\n75\n\n\n\n91\n\n\n\nComplication\nn (%)\n\n\n\n51 (49.5)\n\n\n\n25 (32.9)\n\n\n\n49 (46.2)\n\n\n\n27 (37.0)\n\n\n\n35 (41.2)\n\n\n\n41 (43.6)\n\n\n\n30 (40)\n\n\n\n38 (41.8)\n\n\n\nNo complication\nn (%)\n\n\n\n52 (50.5)\n\n\n\n51 (67.1)\n\n\n\n57 (53.8)\n\n\n\n46 (63.0)\n\n\n\n50 (58.8)\n\n\n\n53 (56.4)\n\n\n\n45 (60)\n\n\n\n53 (58.2)\n\n\n\nX2Statistica\n\n\n\n(df)\n\n\n\n5.00\n(1)\n\n\n\n1.52\n(1)\n\n\n\n0.11\n(1)\n\n\n\n0.05\n(1)\n\n\n\nP Values\n\n\n\n0.025\n\n\n\n0.218\n\n\n\n0.741\n\n\n\n0.819\n\n\n\nOR\n(95% CI)\n\n\n\n1\n\n\n\n0.50      (0.3-0.9)\n\n\n\n1\n\n\n\n0.68      (0.4-1.3)\n\n\n\n1\n\n\n\n0.90 (0.5-1.6)\n\n\n\n1\n\n\n\n1.00 (0.5-2.0)\n\n\n\nTable 4. Factors associated with Herpes Zoster complication (using simple logistic regression).\n\n\n\n* 13 missing data               a Likelihood Ratio (LR) test           OR = unadjusted odds ratio\n\n\n\nGENDER\n\n\n\nAGE GROUP\n\n\n\nETHNICITY\n\n\n\nPRESENTATION ONSET (n=166)*\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15 MJD 2016 Jul Vol 36\n\n\n\nthe Singapore study where only 3% of their study \npopulation had ophthalmic dermatome involvement \ndespite both of the studies were done in the tertiary \ndermatology referral center.\n\n\n\nThis dermatome involvement can cause serious \nirreversible complication to the eye. Among our HZ \nophthalmicus group, all of them had conjunctivitis \nand 14.3% had cranial nerve involvement. This \nwas higher than a reported incidence of extraocular \nmuscle palsies in HZ ophthalmicus in North Africa, \nwhich was 5.8% 9. This problem can give rise to eye \nmotility disorders with diplopia. This finding added \nour worry to our local population on complication \nof HZ other than the post-herpetic neuralgia \ncomplication.\n\n\n\nMore than 50% of our patients presented or \nwere diagnosed late. This had caused a delay in \ntreatment.  Early diagnosis followed by appropriate \ntreatment is essential to improve the disease \noutcome. Acute pain management and prevention of \nsecondary infection can be offered early to reduce \nthe severity of the disease. Antiviral treatment, \npreferably started within 72 hour of rash onset, \ncan help to resolve the acute disease and inhibit \nlate inflammatory recurrences10. A study done in \nSingapore, has concluded that there is a need to \neducate patients at risk to identify the prodrome and \nskin eruptions of herpes zoster so that early antiviral \ntherapy can be considered8. Unfortunately, even \nwith early treatment, the incidence of post-herpetic \nneuralgia is not significantly reduced with antiviral \ntreatment11,12. Thus, an alternative solution should \nbe offered to our patients in reducing the severity of \nHZ and post-herpetic neuralgia. Proactive strategy \nwith vaccination to the elderly population may be \nis a good solution to prevent the disease from our \npopulation group who tend to seek treatment late.\n\n\n\nHerpes zoster vaccine was licensed in 2006 and \nrecommended by the Advisory Committee on \nImmunization Practices in 2008 for prevention of \nherpes zoster and its complications among adults \naged \u226560 years13. It is a live attenuated vaccine. \nThus, it should not be given to a patient who is \nreceiving immunosuppressive therapy, including \nhigh-dose corticosteroids, has primary or acquired \nimmunodeficiency state, including leukemia, \nlymphoma, or other malignant neoplasm affecting \nthe bone marrow or lymphatic system, or with \nacquired immunodeficiency syndrome or other \nclinical manifestation of infection with human \nimmunodeficiency viruses13.\n\n\n\nDiscussion\nHerpes Zoster is a common disease which is \ncaused by reactivation of latent varicella zoster \nvirus. Most of the reactivation can be either \nprevented or quickly aborted with the presence \nof adequate T cell-mediated immune response. \nHowever, in immunocompromised or age-related \nimmunosenescence patients, immune response \nmight be inadequate to contain the reactivation of \nVZV. This explains the more severe form of the \ndisease in these groups of patients. The incidence \nrate of HZ was about 6-8/1000 person-years at 60 \nyears of age and 8\u201312/1000 person years at 80 years \nof age1.  The age-specific incidence rates of HZ \nwere similar across countries, with a steep rise after \n50 years of age1.\n\n\n\nIn our study, 40.8% of the study population was from \nage group more than 60 years old, and the median \nage was 53 years old. Patients younger than 60 years \nold had more complications of HZ when compared \nwith older group. This is possible due to the fact that \nthe study was done in a hospital-based dermatology \nclinic with more in-patient referrals. The younger \npopulation had more immunocompromised state \nas defined by presence of malignancy, diabetes \nmellitus, chronic kidney disease, end stage kidney \nfailure, HIV or taking immunosuppressant.\n\n\n\nThe prevalence of HZ in our study for both genders \nwas almost the same. This finding is similar to \nother researchers\u2019 result which found no difference \nby sex in HZ3,4. Majority of our study population \nwas Chinese despite our clinic attendees mainly is \nMalay ethnicity. The racial distribution in the study \ndermatology clinic were 63.5%, 24.9%, 10.1% and \n1.5% respectively for Malay, Chinese, Indian and \nothers. A study done in United Kingdom indicated \nthat zoster risk in patients was 54% lower among \nblacks5. However, the reasons for these racial \ndifferences are unknown.\n\n\n\nIn HZ, the stages of eruption elements are macula, \npapules, blisters, crusting then followed by scar \nor post inflammatory hypo/hyperpigmentation \nformation. Majority of HZ patients presented with a \nself-limiting localized dermatomal painful blistering \nrash. In general, thoracic, cervical, and ophthalmic \ninvolvement are most common6,7. We noted a similar \npresentation among our patients. Goh and Khoo \nfrom Singapore also reported the same findings8. In \nour study, both genders and age groups presented \nwith similar dermatomal distribution. V1 division of \nTrigeminal nerve was the third most common (13%) \ndermatome in our study. This is much higher than \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16MJD 2016 Jul Vol 36\n\n\n\nglobal health burden, especially post herpetic \nneuralgia1. Although all of our patients received \nsystemic antiviral treatment, up to 42.5% of our \npatients developed complications of HZ. 36.3% of \nour study cohort had secondary bacterial infection. \nThese might be due to late presentation of the \npatients.\n\n\n\nTo our knowledge, this is the first published \nobservational study that gave the overview picture \nof the HZ in Malaysia. The main limitation of our \nstudy was that this is a retrospective single center \nstudy. Some useful data like education level, family \nincome, transportation accessibility and economic \nimpact of HZ to the patients were not available. There \nwas also presence of incomplete documentation that \nlimit our further analysis.\n\n\n\nConclusion\nDespite majority of the HZ patients in our study \npresented with typical presentation of HZ majority \nof them were still late for treatment (> 3 days). \nComplication of HZ is common in our study \npopulation. Hence, we suggest proactive strategies \nwith education of the disease and HZ vaccination \nshould be recommended to our community.\n\n\n\nWith vaccination, the risk of having HZ, the \nburden of disease, and the incidence of post-\nherpetic neuralgia reduced by 51%, 61%, and 66% \nrespectively, over 3 years period13,14. However, none \nof our patients has ever received HZ vaccination. \nThere was no statistical significance in terms of \ncomplication of HZ between the two age groups, \nethnicity, immune status or late/early presentation \nin this study. The  non-significance among the two \nage groups might be due to higher proportion of \nimmunocompromised patient among the younger \nage group, which was 46.2% (49/106). Whereas, \nthere was only 37.0% (27/73) of older age group \nwho was immunocompromised. Post multivariate \nanalysis, male gender was found to be the only risk \nfactor to get the HZ complications. \n\n\n\nThis finding is contradicts other studies which found \nwomen with zoster might also be at increased age-\nspecific risk for developing post herpetic neuralgia \ncompared with men17,18. However the studies did \nnot look into other complication of HZ except post \nherpetic neuralgia.\n\n\n\nAll the complication of HZ can cause devastating \neffects on patients\u2019 quality of life and significant \n\n\n\nReferences\n \n1. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review \n\n\n\nof incidence and complications of herpes zoster: towards a \nglobal perspective. BMJ open 2014; 4(6): e004833.\n\n\n\n2. Gnann JW, Whitley RJ. Clinical practice for Herpes zoster. \nThe New England journal of medicine 2002; 347:340-6\n\n\n\n3. Di Luzio PU, Arpinelli F, Visona G. Herpes zoster and its \ncomplications in Italy: an observational survey; J Infect \n1999; 38(2): 116-120.\n\n\n\n4. Donahue JG, Choo PW, Manson JE et al. The incidence of \nherpes zoster; Arch Intern Med 1995; 155(15): 1605-1609.\n\n\n\n5. Thomas SL, Hall AJ. What does epidemiology tell us about \nrisk factors for herpes zoster?; Lancet Infect Dis 2004; \n4(1): 26-33.\n\n\n\n6. Schmader KE, Oxman MN. Varicella and Herpes Zoster. \nIn: Fitzpatrick\u2019s Dermatology in General Medicine (8th \neds) 2012; The McGraw-Hill Companies, Inc. \n\n\n\n7. Kost RG, Straus SE. Postherpetic neuralgia---pathogenesis, \ntreatment, and prevention. N Eng J Med 1996; 335:32--42.\n\n\n\n8. Goh CL, Khoo L. A retrospective study of the clinical \npresentation and outcome of herpes zoster in a tertiary \ndermatology outpatient referral clinic. International \njournal of dermatology 1997; 36(9):667-672. \n\n\n\n9. Kahloun R, Attia S, Jelliti B et al. Ocular involvement and \nvisual outcome of herpes zoster ophthalmicus: review of 45 \npatients from Tunisia, North Africa; Journal of ophthalmic \ninflammation and infection 2014; 4:25. \n\n\n\n10. Dworkin RH, Johnson RW, Breuer J et al: Recommendations \nfor the management of herpes zoster. Clinical infectious \ndiseases 2007; 44 (Suppl 1): S1-26. \n\n\n\n11. Schmader K. Herpes zoster in older adults. Clinical \ninfectious diseases 2001; 32:1481-6.\n\n\n\n12. Volpi A, Gross G, Hercogova J, et al. Current management \nof herpes zoster: the European view. American journal of \nclinical dermatology 2005; 6: 317-25.\n\n\n\n13. Schmader K. Herpes zoster in older adults. Clinical \ninfectious diseases 2001; 32:1481-6.\n\n\n\n14. Volpi A, Gross G, Hercogova J et al. Current management \nof herpes zoster: the European view. American journal of \nclinical dermatology 2005; 6: 317-25.\n\n\n\n15. Harpaz R, Ortega-Sanchez IR, Seward JF et al. Prevention \nof herpes zoster: recommendations of the Advisory \nCommittee on Immunization Practices (ACIP). MMWR. \nRecommendations and reports: Morbidity and mortality \nweekly report. Recommendations and reports / Centers for \nDisease Control. 2008; 57:1-30.\n\n\n\n16. Oxman MN, Levin MJ, Johnson GR et al. A vaccine to \nprevent herpes zoster and postherpetic neuralgia in older \nadults. The New England journal of medicine 2005; 352: \n2271-84.\n\n\n\n17. Schmader K. Postherpetic neuralgia in immunocompetent \nelderly people. Vaccine 1998; 16:1768-70.\n\n\n\n18. Yawn BP, Saddier S, Wollan P et al. A population-based \nstudy of the incidence and complications of herpes zoster \nbefore zoster vaccine introduction. Mayo Clin Proc 2007; \n82:1341--9.\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17 MJD 2016 Jul Vol 36\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. The study showed that the median age of patients was 53 years with 59.2% less than 60 years old. \n There is a recent observation that the incidence of herpes zoster is increasing in immunocompetent \n young adults and also in children. Thus, it is imperative that clinicians do not miss the diagnosis in \n the younger individuals to prevent morbidities.\n\n\n\n2. In this study, majority of patients presented late with a median of 4 days from initial symptoms/\n signs. This is not uncommon as the symptom of pain usually precedes the sign by a few days, \n delaying the diagnosis. \n\n\n\n3. This study found a higher incidence of herpes zoster in the Chinese population. However, this might \n be due to the demographics of the population in Penang. \n\n\n\n4. Complications and morbidities of herpes zoster is high and thus it is vital that clinicians make an \n early and accurate diagnosis. This will allow early treatment to prevent such complications. \n Education of health care workers and patients are also vital as has been alluded by the authors. \n Another point is that patients with herpes zoster affecting the ophthalmic branch of the trigeminal \n nerve should be screened by opthlamologist, more so in those with the nasociliary branch \n involvement. All health care workers and junior doctors need to be aware of this as to prevent \n devastating eye complications of herpes zoster.\n\n\n\n5. This study highlighted males to have higher complications rate than females. This might be related \n to the delayed diagnosis and treatment among males. Nevertheless, aggressive treatment is \n necessary for herpes zoster irrespective of gender. Clinicians should be more wary of complications \n of the disease among male patients.\n\n\n\n6. Vaccination of herpes zoster to prevent the disease and its complications is effective and \n recommended in those more than 60 years. Education of health care workers and general public \n about availability of such vaccination is important as mentioned by the authors and will lead to \n reduction of herpes zoster and its complications in the elderly.\n\n\n\nYap FBB MD MRCP AdvMDerm\nEditor-in-Chief, MJD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Original Article\n\n\n\nKNOWLEDGE, ATTITUDE AND PRACTICES OF ADULTS\nIN RELATION TO SUN EXPOSURE AND PHOTODAMAGE\nSam SYY1, Lim JSJ1, Liau MMQ1, Toh MHS2, Aw DCW1\n\n\n\nAbstract\n\n\n\nBackground: Protection from sun exposure is key in the prevention of photodamage and skin cancer, \nand is particularly important in countries that experience high ultraviolet exposure. We compare the \nknowledge, attitude and behaviour towards sun exposure in Singapore between adults with and without \nphotodamage. We also describe the clinical features of patients with photodamage in Singapore. \n\n\n\nMethods: 532 subjects were recruited from the dermatology specialist outpatient of a tertiary hospital \nin Singapore. Each subject was assessed clinically by a dermatologist for evidence of photodamage, \nand answered a questionnaire assessing his knowledge, attitude and behaviour towards sun exposure \nand protection.\n\n\n\nResults: Subjects with photodamage were older, and had lower education and employment rates \ncompared to subjects without photodamage. There was no significant difference in knowledge on the \nharmful effects of sun exposure and on sun protection or in sun avoidance behaviour (other than use \nof protective sunglasses) between the two groups, though more patients with photodamage felt that \nthey take adequate sun protection measures. Of note, only a low percentage of subjects in both groups \n(24.5% of subjects with photodamage and 23.1% of subjects without photodamage) practise regular \nuse of sunscreen.\n\n\n\nConclusion: There was no significant difference between the knowledge, attitudes and behaviours \nof subjects with and without photodamage, though demographic differences between the two groups \nexist. Regular sunscreen usage is low in Singapore, a country with high exposure to ultraviolet light, \nand measures to educate and modify the behaviour of the public need to be developed.\n\n\n\nKeywords: UVA protection, UVB protection, photodamage, sunscreen, sunprotection\n\n\n\nCorresponding Author and Reprint Request \nDr Sam Shiyao Yang, MBBS, MRCP(UK)\nNational University Health System, Singapore\nDepartment of Dermatology, 1E Kent Ridge Road\nTower Block, Level 10, Singapore 119228\nEmail: samsyyang@gmail.com\n\n\n\n1 Division of Dermatology,\n National University Health System, Singapore\n2 Saw Swee Hock School of Public Health,\n National Health Group, Singapore\n\n\n\n(1968 \u2013 1972) to 8.9/100,000 person-years (1993-\n1997), affecting mainly older adults2. Singapore \nis located near the equator, and experiences one \nof the highest ultraviolet (UV) exposures in the \nworld throughout the year, with UV index scores \nranging from 10 to 13 based on the World Health \nOrganisation UV Index values3.\n\n\n\nUV radiation is recognized as a group 1 carcinogen \nto humans by the International Agency for Research \non Cancer4-8. It is responsible for photodamage4-6, \nphotoaging, photocarcinogenesis, and eventually \nskin cancer7,8. Skin cancer and photodamage are \nhighly preventable by adequate sun protection \n\n\n\nIntroduction\nSkin cancer is the 6th most common cancer in both \nmen and women in Singapore1. Its incidence has \nincreased from a rate of 6.0/100,000 person-years \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19 MJD 2016 Jul Vol 36\n\n\n\nMethodology\nWe performed a cross-sectional study over a 6-month \nperiod on patients aged 21 years and above, at the \ndermatology specialist outpatient clinic at a tertiary \ncentre in National University Hospital, Singapore. \nPatients with photodermatitis and photoaggravated \ndermatoses were excluded.\n\n\n\nmeasures9,10, such as avoiding sun exposure between \n10am and 2pm, seeking shade, using sunscreen, and \nwearing protective clothing10-12.\n\n\n\nWe intend to study the knowledge, attitudes, and \nbehaviour of adults in Singapore relating to sun \nexposure, and whether this has any impact on \nphotodamage. \n\n\n\nKnowledge\nAssessment\n\n\n\nAttitude \nAssessment\n\n\n\nDetermination \nof \u201cNatural \nSun Avoidance \nBehaviour\u201d\n\n\n\nUV rays can cause skin cancer later in life.\n\n\n\nUV rays promote early aging.\n\n\n\nUV rays can cause irregular pigmentation\neg. freckles of the skin.\n\n\n\nThe higher the Sun Protection Factor (SPF) of a \nsunscreen product, the better the protection against \nsunburns.\n\n\n\nMost UV rays pass through the clouds on a cloudy \nday.\n\n\n\nApplying sunscreen promotes vitamin D deficiency.\n\n\n\nWhen in the day is the sun most harmful?\n\n\n\nWhich of the following skin type needs the greatest \nprotection\nfrom the sun?\n\n\n\nWhich skin tone do you find more attractive?\n\n\n\nDo you think that you are currently protecting \nyourself adequately from the sun?\n\n\n\nSun screen is too expensive.\n\n\n\nSun screen too inconvenient to apply.\n\n\n\nSun screen feels uncomfortable on skin.\n\n\n\nI believe sun screen cannot protect me from the sun.\n\n\n\nI forget to apply sun screen. \n\n\n\nI don\u2019t see the need to apply sun screen.\n\n\n\nHow often do you\u2026\n\n\n\nWear a hat/cap outside at mid-day?\n\n\n\nWear shoulder-covering clothes?\n\n\n\nWear protective sunglasses?\n\n\n\nPrefer to be in the shade when outside?\n\n\n\nSeek sheltered areas at midday>\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nMorning (0730 \u2013 1000)\nMid-day (1000 \u2013 1500)\nLate afternoon (1500 \u2013 1700) \nEvening (1700 \u2013 1900) \nThroughout the day\n\n\n\nVery fair\nFair\nDark\nAll of the above\n\n\n\nTanned Skin\nFair Skin\nIt does not matter\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nYes / No\n\n\n\nFrequency\n\n\n\nAlways Often Sometimes Seldom Never\n\n\n\nAlways Often Sometimes Seldom Never\n\n\n\nAlways Often Sometimes Seldom Never\n\n\n\nAlways Often Sometimes Seldom Never\n\n\n\nAlways Often Sometimes Seldom Never\n\n\n\nTable 1. Patient Questionnaire Form (Correct answers indicated in bold).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20MJD 2016 Jul Vol 36\n\n\n\nThe first two questions surveyed attitudes towards \nskin colour attractiveness and adequacy of personal \nsun protection. The next five questions studied \nperceptions on the use of sunscreen. Those who \nanswered \u2018no\u2019 in at least 5 of the 6 statements on \nsunscreen were taken to have a positive attitude \ntowards the use of sunscreen. (See Table 2).\n\n\n\nBehavioural Assessment\nQuestions were asked on the frequency and extent \nof application, and the amount of sunscreen applied. \nNatural sun avoidance behavioral activities were \nalso assessed (Table 3). Responses indicating \n\u2018sometimes, often, or always\u2019 were classified as \nhaving practiced the stated sun avoidance behaviour. \nA response of \u201cnever\u201d or \u201cseldom\u201d would be deemed \nas a negative response. A patient would be classified \nas having \u2018natural sun avoidance behaviour\u2019 if they \npracticed 3 out of the 5 behavioural activities.\n\n\n\nQuestionnaire\nThe questionnaire assessed participants\u2019 knowledge, \nattitude and behaviour with respect to sun exposure \nand protection, and was designed based on the \nAmerican Skin Association recommendations13, \nWHO Fact Sheet (2010)14 and Reinau15. Certain \nquestions with established reliability and validity \npertaining to sunscreen use, frequency of acquiring \ntans or sunburns, shade-seeking behaviour, and the \nwearing of protective clothes were included16.\n\n\n\nEight questions were asked about UV exposure and \nits cutaneous effects, and protection from using \nsunscreen. Each correct answer scored 1 point. \nKnowledge scores were classified into \u2018high\u2019 (7-8 \npoints), \u2018medium\u2019 (5-6 points), or \u2018low\u2019 (0-4 points).\n\n\n\nCategory\n\n\n\nGender\n\n\n\nEthnicity\n\n\n\nAge (years)\n\n\n\nEducation \nlevel\n\n\n\nEmployment\n\n\n\nExposure to \nsunlight at \nwork\n\n\n\nYes\nN=220 (41.4%)\n\n\n\nn (%)\n\n\n\n 115 (52.3)\n\n\n\n 105 (47.7)\n\n\n\n 168 (76.4)\n\n\n\n 11 (5.0)\n\n\n\n 21 (9.5)\n\n\n\n 20 (9.1)\n\n\n\n 55.3 \u00b113.3\n\n\n\n 12 (5.5)\n\n\n\n 15 (6.8)\n\n\n\n 38 (17.3)\n\n\n\n 63 (28.6)\n\n\n\n 65 (29.5)\n\n\n\n 27 (12.3)\n\n\n\n 31 (14.1)\n\n\n\n 74 (33.6)\n\n\n\n 54 (24.5)\n\n\n\n 61 (27.7)\n\n\n\n 133 (60.5)\n\n\n\n 87 (39.5)\n\n\n\n 43 (19.5)\n\n\n\n 177 (80.5)\n\n\n\n 0.6 \u00b11.5\n\n\n\nNo\nN=312 (58.6%)\n\n\n\nn (%)\n\n\n\n 161 (51.6)\n\n\n\n 151 (48.4)\n\n\n\n 234 (75.0)\n\n\n\n 23 (7.4)\n\n\n\n 27 (8.7)\n\n\n\n 28 (9.0)\n\n\n\n 33.2 \u00b112.0\n\n\n\n 155 (49.7)\n\n\n\n 80 (25.6)\n\n\n\n 44 (14.1)\n\n\n\n 20 (6.4)\n\n\n\n 7 (2.2)\n\n\n\n 6 (1.9)\n\n\n\n 8 (2.6)\n\n\n\n 43 (13.8)\n\n\n\n 98 (31.4)\n\n\n\n 163 (52.2)\n\n\n\n 240 (76.9)\n\n\n\n 72 (23.1)\n\n\n\n 63 (20.2)\n\n\n\n 249 (79.8)\n\n\n\n 0.6 \u00b11.8\n\n\n\nP value\n\n\n\n 0.930\n\n\n\n 0.733\n\n\n\n <0.001\n\n\n\n <0.001\n\n\n\n <0.001\n\n\n\n 0.854\n\n\n\n 0.788\n\n\n\nPhotodamage\n\n\n\nTable 2. Comparison of demographic data between patients with photodamage and patients \nwithout photodamage.\n\n\n\nMale\n\n\n\nFemale\n\n\n\nChinese\n\n\n\nMalay\n\n\n\nIndian\n\n\n\nOthers\n\n\n\nMean \n\n\n\n21-29\n\n\n\n30-39\n\n\n\n40-49\n\n\n\n50-59\n\n\n\n60-69\n\n\n\n70+\n\n\n\nNo formal education/ \nprimary\n\n\n\nSecondary\n\n\n\nJunior college/ \nPolytechnic/Diploma\n\n\n\nUniversity/\npost-graduate\n\n\n\nEmployed\n\n\n\nUnemployed\n\n\n\nYes\n\n\n\nNo\n\n\n\nMean duration of sun \nexposure (hrs)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21 MJD 2016 Jul Vol 36\n\n\n\nLevel of Knowledge \n(classified according to the \nscores obtained from the \nKnowledge Assessment \nQuestionnaire - see Table 1)\n\n\n\nHigh (7-8 points)\n\n\n\nMedium (5-6 points)\n\n\n\nLow (0-4 points)\n\n\n\nWas previously given advice \non sun protection by health \ncare provider\n\n\n\nYes\nN=220 (41.4%)\n\n\n\nn (%)\n\n\n\n 81 (36.8) \n\n\n\n 126 (57.3)\n\n\n\n 13 (5.9)\n\n\n\n 64 (29.1)\n\n\n\n 156 (70.9)\n\n\n\nNo\nN=312 (58.6%)\n\n\n\nn (%)\n\n\n\n 120 (38.5)\n\n\n\n 175 (56.1)\n\n\n\n 17 (5.4)\n\n\n\n 53 (17.0)\n\n\n\n 259 (83.0)\n\n\n\nP value\n\n\n\n0.917\n\n\n\n0.001\n\n\n\nPhotodamage\n\n\n\nTable 3. Knowledge of the harmful effects of excessive sun exposure and on sun protection - \ncomparison between patients with photodamage and patients without photodamage.\n\n\n\nYes\n\n\n\nNo\n\n\n\nCategory\n\n\n\nSkin colour preference\n\n\n\nTanned skin\n\n\n\nFair skin\n\n\n\nNo preference for either tanned or fair skin\n\n\n\nSelf-assessment of own current protection measures\n\n\n\nPerception that current protection measures are adequate\n\n\n\nAttitude toward sunscreen \n\n\n\nSun screen too expensive (answered \u2018Yes\u2019)\n\n\n\nSun screen too inconvenient to apply (answered \u2018Yes\u2019)\n\n\n\nSun screen feels uncomfortable on skin (answered \u2018Yes\u2019)\n\n\n\nI believe sun screen cannot protect me from the sun (anwered \u2018Yes\u2019)\n\n\n\nI forget to apply sun screen  (answered \u2018Yes\u2019)\n\n\n\nI don\u2019t see the need to apply sun screen (answered \u2018Yes\u2019) \n\n\n\nOverall positive attitude towards use of sun screen\n(answered \u2018No\u2019 to at least 5 of the above 6 questions on sun screen)\n\n\n\nYes\nN=220 (41.4%)\n\n\n\nn (%)\n\n\n\n 32 (14.5)\n\n\n\n 89 (40.5)\n\n\n\n 99 (45.0)\n\n\n\n 116 (52.7)\n\n\n\n 93 (42.3%)\n\n\n\n 107 (48.6%)\n\n\n\n 107 (48.6%)\n\n\n\n 51 (23.2%)\n\n\n\n 130 (59.1%)\n\n\n\n 108 (49.1%)\n\n\n\n 103 (46.8%)\n\n\n\nNo\nN=312 (58.6%)\n\n\n\nn (%)\n\n\n\n 57 (18.3)\n\n\n\n 109 (34.9)\n\n\n\n 146 (46.8)\n\n\n\n 130 (41.7)\n\n\n\n 109 (34.9%)\n\n\n\n 165 (52.9%)\n\n\n\n 187 (59.9%)\n\n\n\n 54 (17.3%)\n\n\n\n 190 (60.9%)\n\n\n\n 130 (41.7%)\n\n\n\n 147 (47.1%)\n\n\n\nP value\n\n\n\n0.330\n\n\n\n0.012\n\n\n\n0.086\n\n\n\n0.334\n\n\n\n0.010\n\n\n\n0.094\n\n\n\n0.675\n\n\n\n0.090\n\n\n\n0.946\n\n\n\nPhotodamage\n\n\n\nTable 4. Comparison of the attitude towards skin preference and sunscreen use between patients with \nphotodamage and patients without photodamage.\n\n\n\nStatistical analysis\nData analysis was performed using the IBM \nStatistical Package for the Social Science (SPSS) \nversion 22.0. The unpaired t-test was used to \ncompare means, chi-square or Fisher\u2019s exact test for \ncomparing proportional data. A probability (p) of \n<0.05 was considered statistically significant.\n\n\n\nClinical assessment\nAll patients were assessed by their attending \ndermatologist for evaluation on their Fitzpatrick \nSkin Type, severity of photodamage using the \nGlogau Photoaging classification, and also the areas \nof involvement such as the face, neck or limbs.\n\n\n\nIn addition, we screened for presence of risk factors \nfor malignant melanoma17,18. This included a history \nof sunburns, and sun-tanning habits.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22MJD 2016 Jul Vol 36\n\n\n\nEducation and Employment\nMore patients with photodamage lacked tertiary \neducation (72.3% vs 47.8% of patients without \nphotodamage; p < 0.001). More patients with \nphotodamage also lacked employment (76.9% vs \n60.5% of patients without photodamage,; p < 0.001). \n\n\n\nThere was no significant difference in gender, \nethnicity and exposure to sunlight at work between \npatients with and without photodamage.\n\n\n\nKnowledge on sun exposure and protection \n(Table 5)\nBoth groups of patients scored almost equally \nin the knowledge domain. However, those with \nphotodamage were significantly more likely to have \nreceived advice on sun damage than those without. \n(29.1% vs 17.0%, p=0.001); the temporal sequence \nbetween development of photodamage and reception \nof advice could not be established.\n\n\n\nResults\nOf a total of 609 administered questionnaires, 532 \nwere completed with a response rate of 87.3%. Of \nthe 532 participants, 220 (41.4%) were assessed to \nhave photodamaged skin, and 312 (58.6%) did not \nhave photodamaged skin. We then go on to compare \nthe demographic differences between these two \ngroups of patients, and also assess for differences \nin their knowledge, attitude and practices pertaining \nto sun-exposure and sun-avoidance behaviours. \nFinally, we also characterize this group of 220 \npatients with sun-damaged skin as seen in Tables 8 \nand 9 respectively.\n\n\n\nDemographic differences between patients \nwith photodamage and patients without \nphotodamage (Table 4)\nAge & Ethnicity\nThe mean age of our participants was 42.3 \u00b116.6 \nyears. There were approximately equal numbers \nof males and females (ratio 1.08:1). 75.6% of \nparticipants were Chinese, 9% were Indians, 6.4% \nwere Malays, and 9% were of \u2018other\u2019 ethnicities. \nPatients with photodamage were more likely to be \nolder than patients without photodamage (mean age \n55.3 \u00b1 13.3 vs 33.2 \u00b1 12.0, p < 0.001).\n\n\n\nCategory\n\n\n\nUsers of sun screen (once or several times/day)\n\n\n\nNon-users (never/ only when necessary)\n\n\n\nArea(s) of use for sunscreen in sun screen users (percentages expressed are that of sunscreen users in each category only) \n\n\n\nFace+\n\n\n\nNeck+\n\n\n\nArms+\n\n\n\nLegs+\n\n\n\nAmount of sunscreen applied each time (percentages expressed are that of sunscreen users in each category only) \n\n\n\nRice-grain \n\n\n\nPea-size\n\n\n\nHalf tea-spoon  \n\n\n\nSun avoidance behavior\n\n\n\nWear hat/cap\u2020 \n\n\n\nWear shoulder-covering clothes\u2020 \n\n\n\nProtective sunglasses\u2020\n\n\n\nPrefer to be shade when outside\u2020\n\n\n\nSeek sheltered areas at midday\u2020\n\n\n\nNatural sun avoidance behaviour*\n\n\n\nYes\nN=220\nn (%)\n\n\n\n 54 (24.5)\n\n\n\n 166 (75.5)\n\n\n\n 53 (98.1)\n\n\n\n 22 (40.7)\n\n\n\n 18 (33.3)\n\n\n\n 6 (11.1)\n\n\n\n 21 (16.9)\n\n\n\n 58 (46.8)\n\n\n\n 45 (36.3)\n\n\n\n 56 (25.5)\n\n\n\n 120 (54.5)\n\n\n\n 106 (48.2)\n\n\n\n 204 (92.7)\n\n\n\n 204 (92.7)\n\n\n\n 154 (70.0)\n\n\n\nNo\nN=312 \nn (%)\n\n\n\n 72 (23.1)\n\n\n\n 240 (76.9)\n\n\n\n 70 (97.2)\n\n\n\n 32 (44.4)\n\n\n\n 17 (23.6)\n\n\n\n 5 (6.9)\n\n\n\n 15 (8.8)\n\n\n\n 98 (57.6)\n\n\n\n 57 (33.5)\n\n\n\n 63 (20.2)\n\n\n\n 176 (56.4)\n\n\n\n 113 (36.2)\n\n\n\n 273 (87.5)\n\n\n\n 293 (93.9)\n\n\n\n 217 (69.6)\n\n\n\nP value\n\n\n\n 0.695\n\n\n\n 0.736\n\n\n\n 0.678\n\n\n\n 0.228\n\n\n\n 0.412\n\n\n\n 0.061\n\n\n\n 0.151\n\n\n\n 0.670\n\n\n\n 0.006\n\n\n\n 0.051\n\n\n\n 0.588\n\n\n\n 0.912\n\n\n\nPhotodamage\n\n\n\nTable 5. Comparison of behaviour relating to Sunscreen use and Natural Sun Avoidance between patients with \nphotodamage and patients without photodamage.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23 MJD 2016 Jul Vol 36\n\n\n\nCategory\n\n\n\nSkin type (Fitzpatrick)\n\n\n\n1\n\n\n\n2\n\n\n\n3\n\n\n\n4\n\n\n\n5\n\n\n\n6\n\n\n\nPhotoaging grade (Glogau)\n\n\n\nMild\n\n\n\nModerate\n\n\n\nAdvanced\n\n\n\nSevere\n\n\n\nSkin condition\n\n\n\nDyspigmentation\n\n\n\nFreckles\n\n\n\nIrregular pigmentation\n\n\n\nSolar lentigines\n\n\n\nCollagen degeneration\n\n\n\nSolar elastosis\n\n\n\nStatic wrinkles\n\n\n\nPre-malignant and malignancies\n\n\n\nActinic keratoses\n\n\n\nBasal cell carcinoma\n\n\n\nSquamous cell carcinoma in-situ\n\n\n\nAreas of sun damage\n\n\n\nFace\n\n\n\nNeck and \u2018V\u2019\n\n\n\nLimbs \n\n\n\nPatients with clinical features of \nphotodamage (%)\n\n\n\nN = 220\n\n\n\n 1 (0.4)\n\n\n\n 18 (8.2)\n\n\n\n 54 (24.7)\n\n\n\n 116 (52.7)\n\n\n\n 24 (10.9)\n\n\n\n 7 (3.2)\n\n\n\n 62 (28.2)\n\n\n\n 98 (44.5)\n\n\n\n 59 (26.8)\n\n\n\n 1 (0.5)\n\n\n\n 64 (29.1)\n\n\n\n 155 (70.5)\n\n\n\n 102 (46.4)\n\n\n\n 76 (34.5)\n\n\n\n 114 (51.8)\n\n\n\n 7 (3.2)\n\n\n\n 3 (0.6)\n\n\n\n 1 (0.2)\n\n\n\n 201 (91.4)\n\n\n\n 83 (37.7)\n\n\n\n 96 (43.6)\n\n\n\nTable 6. Clinical features of patients with photodamage.\n\n\n\nBehaviour Relating to Sunscreen Use and \nNatural Sun-avoidance (Table 7)\nThere was no significant difference in frequency \nof application of sunscreen in patients with and \nwithout photodamage, the areas of application, and \nthe amount of sunscreen applied. \n\n\n\nOnly 70.0% of those with photodamage had natural \nsun avoidance behaviour, the commonest of which \nwere preference for shade when outside (92.7%) \nand seeking sheltered areas at midday (92.7%). \nPatients with photodamage were more likely to \nwear protective sunglasses when outside (48.2% vs \n36.2%, p = 0.006).\n\n\n\nAttitudes toward skin colour and sun screen \n(Table 6)\nIn general, there was no significant difference in \nattitude towards using sunscreen between patients \nwith and without photodamage.  More patients \nwith photodamage tended to think that they had \ntaken adequate protection measures (52.7% with \nphotodamage vs 41.7% without photodamage, \np = 0.012).The commonest reason for not using \nsunscreen was forgetfulness (59.1%), followed \nfailing to see a need for it (49.1%). Interestingly, \nmore patients without photodamage felt that \nsunscreen was uncomfortable on the skin (59.9% vs \n48.6% of patients with photodamage, p=0.010).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24MJD 2016 Jul Vol 36\n\n\n\nAge is indeed a significant factor in photoaging and \nis also an established factor in wrinkling5. In a study \nlooking at skin cancer trends in Singapore, Sng et al2 \nalso found that preponderance of skin cancer (BCC, \nSCC, and malignant melanoma) cases in Singapore \noccurred among older persons. \n\n\n\nGiven the significant association between \nphotodamaged patients and unemployment, one \nexplanation could be a reduction of overall sun-\nexposure due to being indoors during work-hours in \nemployed people. It is heartening to note that having \na lower education level did not translate to lower \nknowledge scores. \n\n\n\nBoth photodamaged and those without photodamage \nhave mostly high and medium knowledge scores. \nMore photodamaged patients received information \nabout sun-protection by healthcare providers \ncompared to those without. Advice given by \nphysicians has been shown to be associated with \nhigher sun-safety compliance20 compared to media \ncampaigns21, and in the study by Nyiri, schools and \nparents were shown to comply if a doctor advised \nsun protection measures19. The lack of difference \nin knowledge scores may suggest that a greater \nemphasis needs to be placed on the translation of \nknowledge to actual practice.\n\n\n\nClinical Features and Types of Photodamage \n(Table 8) \nOf the 220 (41.4%) patients with photodamage, \nmost were of skin type 4 (52.7%) and had a moderate \ndegree of (44.5%) photoaging by Glogau grading. \nThe most common signs observed were irregular \npigmentation (70.5%) and static wrinkles (51.8%), \nwith the face being the predominant site (91.4%).\n\n\n\nRisk factors for skin cancer/malignant \nmelanoma (Table 9)\nA surprising finding was that most patients with \nphotodamage were less frequently sunburnt than \nthose without photodamage. More patients with \nphotodamage actually do not sun-tan, 93.4% vs \n87.1%, (p = 0.041).\n\n\n\nDiscussion\nFew studies have been done to assess the knowledge, \nattitude, and sun-protection behaviour in Singapore \nand of the photodamaged-skin cancer population. A \nprevious study by Nyiri19  assessed sun-protection \nattitude, measures and incidence of sunburn of \nSingapore\u2019s school children and found that over \n50% of school children had sunburns during their \nfirst 10 years, supporting the importance of sun-\nsafety campaigns in schools. \n\n\n\nRisk Factors\n\n\n\nHistory of sunburn over the past year\n\n\n\nNever\n\n\n\n1-2x\n\n\n\n3-5x\n\n\n\n5-10x\n\n\n\n>10x\n\n\n\nFrequency of sun-tanning \n\n\n\nDaily\n\n\n\nOnce a week\n\n\n\nOnce every 2 week\n\n\n\nOnce every 4 weeks\n\n\n\nLess than once a month\n\n\n\nNever\n\n\n\nTime of day when sun-tanning under natural sunlight\n\n\n\nMorning\n\n\n\nMid-day\n\n\n\nLate afternoon\n\n\n\nYes\nN=219 (41.2%)\n\n\n\nn (%)\n\n\n\n 105 (63.3)\n\n\n\n 36 (21.7)\n\n\n\n 14 (8.4)\n\n\n\n 6 (3.6)\n\n\n\n 5 (3.0)\n\n\n\n 3 (1.8)\n\n\n\n 3 (1.8)\n\n\n\n 0 (0.0)\n\n\n\n 1 (0.6)\n\n\n\n 4 (2.4)\n\n\n\n 155 (93.4)\n\n\n\n 8 (3.6)\n\n\n\n 2 (0.9)\n\n\n\n 4 (1.8)\n\n\n\nNo\nN=211 (58.8%)\n\n\n\nn (%)\n\n\n\n 101 (42.1)\n\n\n\n 103 (42.9)\n\n\n\n 20 (8.3)\n\n\n\n 11 (4.6)\n\n\n\n 5 (2.1)\n\n\n\n 2 (0.8)\n\n\n\n 4 (1.7)\n\n\n\n 2 (0.8)\n\n\n\n 4 (1.7)\n\n\n\n 19 (7.9)\n\n\n\n 209 (87.1)\n\n\n\n 18 (5.8)\n\n\n\n 14 (4.5)\n\n\n\n 7 (2.2)\n\n\n\nP value\n\n\n\n<0.001\n\n\n\n0.120\n\n\n\n0.041\n\n\n\n0.062\n\n\n\nPhotodamage\n\n\n\nTable 7. Comparison of risk factors for skin cancer between patients with photodamage and patients without \nphotodamage.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25 MJD 2016 Jul Vol 36\n\n\n\nWith respect to the frequency of sunburns and \nsunbed use as a risk factor for melanoma17,28, those \nwith photodamage were significantly less frequently \nsun burnt and tended to refrain from sun tanning \npractices compared to those without photodamage. \nA likely reason for this unusual finding is that a \nprevious experience of having been sunburnt before \nmay have caused a behavioural change to avoid \nexcessive sun exposure. Additionally, sun-tanning \npractices are not common in Singapore because of \nyear-round high temperature and strong sunlight. \n\n\n\nStudy Limitations\nOur study population, taken from a tertiary \ndermatology clinic, may have a different profile \nfrom that of the general population and its \nfindings may not be fully generalisable to the \ngeneral Singaporean population. Limitations of \na self-report questionnaire include recall bias and \nunderreporting of actual harmful practices (e.g. \nfrequency of sunburn and suntanning) because \nof the need to provide socially desirable answers. \nCausal relationships cannot be established.\n\n\n\nConclusion\nIn conclusion, our study showed our patients had \nsimilar knowledge and attitude towards sunscreen \nuse regardless of presence of photodamage. However, \nphotodamaged patients were more informed by \nhealthcare providers on sun-safety, placed less value \non tanned skin, and had less frequency of sunburns \nand sun-tanning. Subsequent sun-safety studies \non the general public, and on skin-cancer patients \ncould be undertaken in the future. We would advise \nundertaking public education campaigns on sun \nprotection, especially regarding sunscreen use, and \ntargeting the ones at risk of photodamage such as \nthe elderly and the lower educated. Emphasis may \nneed to be placed on behavioural modification \ninstead of merely imparting knowledge. Prospective \nstudies can be considered to evaluate if changes to \nknowledge, attitude and behaviours of patients from \na young age can have an impact on the development \nof photodamage.\n\n\n\nThe general study population either preferred fair \nskin or had no preference for skin colour. Similarly, \na sun-safety study done on a Chinese population \nshowed more than half found a suntan unattractive22. \nThis is significantly different from Caucasian \npopulations, where a tan is deemed more visually \nappealing23.   \n\n\n\nOf note, in our study population, less than half of \nthe entire study population had a positive attitude \ntowards sunscreen. Only about a quarter of each \ngroup applied sunscreen daily despite having high-\nmedium knowledge scores. The most common barrier \nto sunscreen use was discomfort on the skin, which \nwe believe to be compatible with a hot and humid \nclimate in Singapore. In contrast, forgetfulness \nand inconvenience were most commonly cited in \na Canadian outpatient population20.  Additionally, \nour photodamaged responders also applied a lesser \namount of sunscreen than non-photodamaged. \nThis difference approached statistical significance \nwith a p value of 0.061. It is conceivable that \nthe photodamaged skin be a reflection of lower \nprotection. The recommended amount of sunscreen \nfor an entire face is half a tea-spoon24, and may \nshow deficiency in knowledge of sunscreen users. In \ngeneral, the perception and use of sunscreen in our \npopulation is low \u2013 and more is required to promote \nits use nation-wide. \n\n\n\nIn contrast, a Chinese study by Cheng et al22 and \na Western study by Halpern et al25, showed that \nsunscreen use was the most popular preventive \nbehaviour with 58.8% and 85% of responders \nusing sunscreen respectively. In a study on skin \ncancer patients, there was a marked increase in the \napplication of sunscreen after diagnosis26. Sunscreen \nis the gold standard against photodamage27 and skin \ncancer, and its use should be emphasized more to \nthe public.\n\n\n\nWhen characterizing the features of photoaging \namongst our photodamaged patients, we noted that \nmost were of skin type 4 (52.7%) and had moderate \n(44.5%) photoaging by Glogau grading. Consistent \nwith excessive and unprotected sun exposure, our \ncommonest observation was irregular pigmentation \n(70.5%) and static wrinkles (51.8%) on the face.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26MJD 2016 Jul Vol 36\n\n\n\nReferences\n \n1. Teo MC, Soo KC. Cancer trends and incidences in \n\n\n\nSingapore. Jpn J ClinOncol2013;43:219-224.\n2. Sng J, Koh D, Siong WC, Choo TB. Skin cancer trends \n\n\n\namong Asians living in Singapore from 1968 to 2006. J \nAm AcadDermatol2009;61:426-432. \n\n\n\n3. World Health Organization 2014. Ultraviolet radiation and \nthe INTERSUN Programme. [WWW document]. URL \nhttp://www.who.int/uv/intersunprogramme/activities/uv_\nindex/en/index3.html\n\n\n\n4. Eun HC. Cutaneous photodamage in Asians. J Dermatol \n2001;28:614-616.\n\n\n\n5. Chung JH, Lee SH, Youn CSet al. Cutaneous photodamage \nin Koreans: influence of sex, sun exposure, smoking, and \nskin color. Arch Dermatol 2001; 137:1043-1051. \n\n\n\n6. Chung JH. Photoaging in Asians. Photodermatol \nPhotoimmunolPhotomed 2003; 19:109-121. \n\n\n\n7. Gonzaga ER. Role of UV light in photodamage, skin \naging, and skin cancer: importance of photoprotection. Am \nJ ClinDermatol 2009; 10Suppl 1:S19-24. \n\n\n\n8. Grether-Beck S, Wlaschek M, Krutmann J, Scharffetter-\nKochanek K. Photodamage and photoaging--prevention \nand treatment. J DtschDermatolGes 2005; 3Suppl 2:S19-\n25.\n\n\n\n9. Armstrong BK, Kricker A. The epidemiology of UV \ninduced skin cancer. J PhotochemPhotobiol B 2001; 63:8-\n18.\n\n\n\n10. Phillips TJ, Bhawan J, Yaar M et al. Effect of daily versus \nintermittent sunscreen application on solar simulated \nUV radiation-induced skin response in humans. J Am \nAcadDermatol2000; 43:610-618.\n\n\n\n11. O\u2019Riordan DL, Nehl E, Gies Pet al. Validity of covering-\nup sun-protection habits: Association of observations and \nself-report. J Am AcadDermatol2009; 60:739-744. \n\n\n\n12. Berret J, Liardet S, Scaletta C et al. Use of sunscreens \nin families living in Switzerland. Dermatology 2002; \n204:202-208.\n\n\n\n13. American Skin Association 2012. Sun Safety. [WWW \ndocument]. URL www.americanskin.org/resource/safety.\nphp#\n\n\n\n14. World Health Organization 2014. Ultraviolet radiation and \nthe INTERSUN Programme \u2013 Sun protection. [WWW \ndocument]. URL www.who.int/uv/sun_protection/en/\n\n\n\n15. Reinau D, Meier C, Gerber N et al. Sun protective behavior \nof primary and secondary school students in North-\nWestern Switzerland. Swiss Med Wkly2012; 142:w13520. \ndoi: 10.4414/smw.2012.13520\n\n\n\n16. Falk M, Anderson CD. Measuring sun exposure habits and \nsun protection behavior using a comprehensive scoring \ninstrument--an illustration of a possible model based on \nLikert scale scorings and on estimation of readiness to \nincrease sun protection. Cancer Epidemiol2012; 36:e265-\n269. doi: 10.1016/j.canep.2012.03.004. \n\n\n\n17. Diffey BL, Norridge Z. Reported sun exposure, attitudes to \nsun protection and perceptions of skin cancer risk: a survey \nof visitors to Cancer Research UK\u2019s SunSmart campaign \nwebsite. Br J Dermatol2009; 160:1292-1298. \n\n\n\n18. Thomson CS, Woolnough S, Wickenden M, Hiom S, \nTwelves CJ. Sunbed use in children 11-17 in England: face \nto face quota sampling surveys in the National Prevalence \nStudy and Six Cities Study. BMJ2010; 340:c877. doi: \n10.1136/bmj.c877. \n\n\n\n19. Nyiri P. Sun protection in Singapore\u2019s schools. Singapore \nMed J2005; 46:471-475. \n\n\n\n20. Boggild AK, From L. Barriers to sun safety in a Canadian \noutpatient population. J Cutan Med Surg 2003; 7:292-299. \n\n\n\n21. Smith BJ, Ferguson C, McKenzie J et al. Impacts from \nrepeated mass media campaigns to promote sun protection \nin Australia. Health PromotInt2002; 17:51-60. \n\n\n\n22. Cheng S, Lian S, Hao Y et al. Sun-exposure knowledge \nand protection behavior in a North Chinese population: a \nquestionnaire-based study. Photodermatol Photoimmunol \nPhotomed2010; 26:177-181.\n\n\n\n23. Jones B, Oh C, Corkery E et al. Attitudes and perceptions \nregarding skin cancer and sun protection behavior in an \nIrish population. J Eur Acad Dermatol Venereol 2007; \n21:1097-1101. \n\n\n\n24. Schneider J. The teaspoon rule of applying sunscreen. Arch \nDermatol2002; 138:838-839. \n\n\n\n25. Halpern AC, Kopp LJ. Awareness, knowledge and attitudes \nto non-melanoma skin cancer and actinic keratosis among \nthe general public. Int J Dermatol2005; 44:107-111.\n\n\n\n26. Soto E, Lee H, Saladi RN et al. Behavioral factors of \npatients before and after diagnosis with melanoma: a cohort \nstudy \u2013 are sun-protection measures being implemented? \nMelanoma Res 2010; 20:147-152. \n\n\n\n27. DeBuys HV, Levy SB, Murray JC et al. Modern approaches \nto photoprotection. DermatolClin2000; 18:577-590. \n\n\n\n28. Whiteman D, Green A. Melanoma and sunburn. Cancer \nCauses Control1994; 5:564-572.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27 MJD 2016 Jul Vol 36\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. This study highlight the fact that knowledge among individuals, even with photodamage, will not \n necessarily translate into better sun protection practice. This phenomenon is not only seen in \n Singapore but also in Malaysia where most are educated via various sources about the harm of \n sun exposure and the importance of sun avoidance but still have poor sun avoidance habits. Usage \n of sunscreen is generally poor among Southeast Asians. \n\n\n\n2. The two main reasons for not using regular sunscreen in this study were forgetfulness and not \n seeing the need for regular use. This also occurs in those with photodamaged skin. Thus, more \n campaigns need to be done to encourage regular use of sunblock. Medical practitioners not only \n in the field of dermatology and aesthetics but all across the board should encourage their patients \n to use sunscreen to prevent the complications of sun exposure especially skin cancers. Advise and \n reinforcements by medical practitioners proved to have the highest rate of compliance.\n\n\n\nYap FBB MD MRCP AdvMDerm\nEditor-in-Chief, MJD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28MJD 2016 Jul Vol 36\n\n\n\nCOSMETIC DERMATOLOGY - Original Article\n\n\n\nSIGNIFICANT LIGHTENING EFFECT OF A WHITENING \nFORMULA (AEBRITENING COMPLEX-01) COMPARED\nTO 4% HYDROXYQUINONE\nShazlina ZA1, Saadiah S1, Sharifah I2, Maryam AJ2, Elaine TS L3\n\n\n\nAbstract\n\n\n\nIntroduction: Fair skin complexion is much preferred by the Asian population. Four percent \nhydroquinone has been known to be effective as a whitening agent albeit unwanted effects such as \nworsening pigmentation, onchronosis and irritation have been well documented. This study aims to \ncompare the lightening effects and the safety profile of a novel topical formulation derived from \nVitamin C in combination with plant\u2019s extract ,known as AEBritening Complex- 01 with a standard \nformulation containing four percent Hydroquinone. \n\n\n\nMaterial & Method: A case control study was conducted to evaluate the efficacy of AEBritening \nComplex-01 versus 4% Hydroquinone cream in lightening normal skin colour. AEBritening \nComplex-01* contains refined stabilized vitamin C Complex and plant\u2019s extract as active ingredient . \nAll 20 subjects were applied with  AEBritening Complex-01 on their  right arm , 4% hydroquinone on \ntheir left arm  twice a day for 28 days. Their left forearm were left untreated. Visual and colorimeter \nassessment of the right arm, left arm and left forearm were done on day 0, Day7, Day 14, Day 21 and \nDay 28.\n\n\n\nResults: Skin areas treated with AEBritening Complex-01 showed significant  degree of lightening \neffect (+1.69) after 21 days of treatment compared to areas treated with 4% hydroquinone (+0.47) and \nuntreated area (+0.13). This was tested using using Skin Colorimeter Konica Minolta CR 10.  There \nwas further improvement at day 28 of the treated area with AEBritening Complex-01 (+1.96), 4% \nhydroquinone (+0.66) and untreated area (-0.09). The AEBritening Complex-01  formulation showed \nsignificant skin lightening effect compared to standard 4 % Hydroxyquinone with p< 0.05.\n\n\n\nConclusion: The AEBrightening Complex-01 formulation is significantly effective to lighten normal \nskin colour compared to 4% Hydroquinone.\n\n\n\nKeywords: lightening cream, brightening cream, whitening cream, sunprotection, photoprotection.\n\n\n\nCorresponding Author and Reprint Request \nDr Saadiah Sulaiman  \nKlinik Pakar Kulit dan Alahan Annur,\nHospital Pakar Annur, Seksyen 9, Bangi,\n43650 Selangor\nEmail: saadiahazim@yahoo.co.uk\n\n\n\n1 Klinik Pakar Kulit dan Alahan Annur,\n Hospital Pakar Annur, Bangi ,Selangor, Malaysia\n2 Healthmedic Research, Bandar Permaisuri, Cheras   \n Kuala Lumpur Malaysia\n3 Ample Effect Sdn Bhd,Taman Industri Mega, \n Semenyih, Selangor Malaysia\n\n\n\nIntroduction\nAs opposed to the tanned skin sought by Caucasians, \nfair complexion is preferred by Asians who are \nexposed to countless hours of highly intense sun \nexposure that contribute to skin darkening. In order \nto achieve a fair skin complexion, many methods \nhave been practiced. The most convenient of which \nis the use of whitening cream which has gained \nconsiderable interest among women. Four percent \nhydroquinone has been known to be effective as \nwhitening agent, however its unwanted effects \nsuch as worsening pigmentation, onchronosis and \nirritation is well documented. For this reason, we \nconduct this study to compare the lightening effect \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29 MJD 2016 Jul Vol 36\n\n\n\nThe colorimetric measurements for skin lightening \neffects were taken on both treated and untreated area \nat the beginning of the study (T0) and after day 7 \n(T7), Day 14(T14), Day 21 (T21) and Day 28 (T28) \nof treatment procedure. The data collected were \nanalysed using Excel. A paired samples Student \nt-test was performed where the differences between \nthe two groups of data were considered significant if \nthe probability p value \u2264 0.05.\n\n\n\nResult\nA total of 20 female subjects completed the study, \nage range was between 23-52 years old, mean age \nobtained 36 \u00b1 9.46.The study was done between  27th \nMay 2015 and 30th June 2015. The study involved \n14 Malays, 4 Indians and 2 Chinese subjects.\n\n\n\nUsing the Student T test, the area treated with \ntest material A (AEBritening Complex-01) has \nsignificant lightening effect compared to 4% \nHydroquinone  at day 21 and 28. P = 0.0001 and \n0.0005 respectively, as shown in Table 2a.\n\n\n\nUsing the Student T test, the area treated with \ntest material A has significant lightening effect \ncompared to untreated area at day 21 and 28. P = \n0.001 and 0.0007 respectively, as shown in table 2b.\n\n\n\nand the safety profile of a novel topical formulation \nderived from Vitamin C in combination with plant \nextracts, namely AEBritening Complex-01 with a \nstandard formulation containing 4% hydroquinone.\n\n\n\nMaterials And Methods\nA case control study was conducted at Makmal \nBioserasi dan Klinikal Cheras. Criteria for \ninclusion into the study are healthy, non pregnant, \nnon lactating adult female, age range between 18 \nto 65 years free of skin diseases and those with no \nhistory of intolerance to drugs,cosmetic products \nand allergy to nickle or any other allergens.\n\n\n\nThe study was to evaluate the efficacy of AEBritening \nComplex-01 with that of 4% Hydroquinone cream \nin skin lightening. Each subject was treated with \nAEBritening Complex-01 on their right arm, while \ntheir left arm was treated with 4% hydroquinone. \nTheir left forearm were left untreated. The \napplication of test material was made twice a \nday, morning and night on the test sites (see table \n1) for 28 days under close supervision and close \nmonitoring throughout the study.\n\n\n\nAll test materials was applied on the treatment \narea of the skin evenly twice a day (morning and \nnight). This procedure of application was repeated \neveryday for 28 days.\n\n\n\nTreatment area\n\n\n\nDorsal aspect of right arm\n(AEBritening Complex-01)\n\n\n\nDorsal aspect of left arm \n(4% Hydroxyquinone)\n\n\n\nUntreated area (control)\n\n\n\nUntreated  area (control)\n\n\n\nDorsal aspect of left forearm (Control)\n\n\n\nTable 1. Area of topical application.\n\n\n\nMean different A\n\n\n\nMean different B\n\n\n\nStudent T test\np value\n\n\n\nDay 7 (T7-T0)\n\n\n\n0.87 \u00b1 1.63\n\n\n\n0.46\u00b1 1.66\n\n\n\n0.27\n\n\n\nDay 14 (T14-T0)\n\n\n\n1.07 \u00b1 1.31\n\n\n\n0.56 \u00b1 1.66\n\n\n\n0.07\n\n\n\nDay 21 (T21-T0)\n\n\n\n1.69 \u00b1 1.45\n\n\n\n0.47 \u00b1 1.1\n\n\n\n0.0001\n\n\n\nDay 28 (T28-T0)\n\n\n\n1.96 \u00b1 1.81\n\n\n\n0.66 \u00b1 1.28\n\n\n\n0.0005\n\n\n\nTable 2a. The improvement of lightening of area treated with test material A \n(AEBritening Complex-01) and  test material B (4% Hydroxyquinone) compared to \nbaseline at day 7, day 14, day 21 and day 28. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30MJD 2016 Jul Vol 36\n\n\n\nto upper class income due to the associated financial \ncost. The use of sunscreen is also only highlighted \nfor the last 10 years and many are still are not aware \nof its pigmentation protection benefit. However, \nwhitening cream has gained significant interest \namong women of the East due to the perception of \nassociation of fairer skin and beauty. This has led \nto competitive production of whitening cream due \nto increasing demand. Bernstein\u2019s research in China \nbeauty market in 2010, showed whitening skincare \nproducts accounted approximately 70% of the total \nmarket value2.\n\n\n\nDiscussion\nIntense UV light exposure can stimulate melanocytes \nto produce more melanosome, causing patchy \nhyperpigmentation on sun exposed area such as the \nface, neck and arms1.The hyperpigmentation cause \nmuch dismay with social and psychological effect. \nThis condition is a social inconvenience especially \nto the professionals and the skin health conscious \nindividuals. In Malaysia, majority are not aware of \nthe need to protect the skin against the sun from early \nage. The use of sunscreen only lingered in the middle \n\n\n\nMean different A\n\n\n\nMean different C\n\n\n\nStudent T test\np value\n\n\n\nDay 7(T7-T0)\n\n\n\n0.87 \u00b1 1.63\n\n\n\n0.22 \u00b10.95\n\n\n\n0.094\n\n\n\nDay 14 (T14-T0)\n\n\n\n1.07 \u00b1 1.31\n\n\n\n0.44 \u00b1 0.94\n\n\n\n0.123\n\n\n\nDay 21 (T21-T0)\n\n\n\n1.69 \u00b1 1.45\n\n\n\n0.13 \u00b1 0.95\n\n\n\n0.001\n\n\n\nDay 28 (T28-T0)\n\n\n\n1.96 \u00b1 1.81\n\n\n\n-0.09 \u00b1 1.09\n\n\n\n0.0007\n\n\n\nTable 2b. Student T test for the degree in changes following treatment (compared to \nthe initial value) between treated area with test material A (AEBritening Complex-01) \nand untreated area at day 7, day 14, day 21 and day 28.\n\n\n\n0.87\n\n\n\n1.07\n\n\n\n1.69\n\n\n\n1.96\n\n\n\nD\neg\n\n\n\nre\ne \n\n\n\nof\n L\n\n\n\nig\nht\n\n\n\nen\nin\n\n\n\ng \n\u201cL\n\n\n\n\u201d\n\n\n\nTime (Days)\n\n\n\nDAY 0 DAY 7 DAY 14 DAY 21 DAY 28\n\n\n\n0.44\n\n\n\n0.22\n0.13\n\n\n\n0.09\n0\n\n\n\n0.46\n0.56\n\n\n\n0.47\n\n\n\n0.66\n\n\n\nAEBritening Complex-01 (A)\n\n\n\n4% Hydroquinone (B)\n\n\n\nUntreated Area (C)\n\n\n\nFigure 1. is a line chart that demonstrate the degree lightening effect \nof the AEBritening Complex-01 (A) and 4% Hyroxyquinone (B) and \nthe untreated area (C) compared to baseline at different time interval.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31 MJD 2016 Jul Vol 36\n\n\n\nThe treated area with the AEBritening Complex-01 \nshowed significant lightening effect compared \nto non treated area after 21 days of treatment. \nThe measurement of degree of lightening was \ndone objectively using skin colorimeter by the \nsame trained observer. This is done to alleviate \ninterobserver bias and subjective colour assessment.\nAs the test was done on normal skin, the lightening \neffect compared to the baseline colour can be \ndue to the photoprotective properties that prevent \ninteraction of UV rays and the skin and also the \navailability of antioxidant under the skin that \ncan indirectly inhibit activation of melanosome \nproduction.\n\n\n\nHydroquinone which has the ability to inhibit the \nenzyme tyrosine kinase thereby inhibit melanin \nsynthesis was not use in this study. Hydroquinone \nelicits reversible depigmentation of the skin by \ninhibiting enzymatic oxidation of tyrosine to 3, 4 - \ndihydroxyphenylalanine (DOPA) and also suppresses \nother melanocyte metabolic processes11,12.\n\n\n\nThis study showed the ability of AEBritening \nComplex-01 to significantly lightening  the treated \nskin compared to 4% hydroquinone. The  area treated \nwith AEBritening Complex-01  have +1.96 L \u2018Degree \nof Lightening compared to 4% hydroxyquinone and \nuntreated skin. No skin irritation was observed in \nthe AEBritening Complex-01  cream compared to \nirritation caused by 4 % hydroquinone.\n\n\n\nIt is expected that this formulation may contribute \nto safe and effective treatment for melasma in the \nfuture. The ingredient for lightening effect may have \ntreatment effect towards melasma as both condition \nneed photoprotective properties and inhibition of \nmelanosome production. Based on study by Grimes \net al, hyperpigmentation in melasma showed an \nincreased in deposition of melanin in the epidermis \nand dermis whereas in hyperpigmented tone, there \nis a quantitative increase in melanocytes which are \nlarger and intensely stained with very prominent \ndendrites. Electron microscopy also revealed more \nmelanosomes in keratinocytes, melanocytes, and \ndendrites in the hyperpigmented skin13. Now that \nAEBritening Complex-01 formulation is proven to \nbe able to lighten the normal colour skin far better \nthan 4% Hydroxyquinone, it is anticipated it could \nalso lighten the pigmentation of melasma.\n\n\n\nThe ideal lightening cream functions to prevent \ninteraction of the ultraviolet rays with the skin, \nthus facilitating scavenging of free radicals. This \ninhibits the activity of melanosome production. The \ncombination effect prevents hyperpigmentation and \nmaintains pigmentat free skin4,5.\n\n\n\nAEBritening Complex-01 formulation is developed \nfree of hydroxyquinone. It is formulated with a \nrefined, stabilised vitamin C and plant extract, \nChamomile Recutitita extract. The ingredients \nprovide antioxidant properties and photoprotection \nfor the skin contributing to the significant lightening \neffect.\n\n\n\nVitamin C is a water soluble vitamin and is known \nas potent naturally occurring  antioxidant which is \nacquired from natural sources such as citrus fruits, \ngreen leafy vegetables, papaya and strawberries4.        \nL Ascorbic acid (LAA) is the biologically active form \nof Vitamin C used in medicinal or cosmetic products. \nVitamin C forms a part of complex enzymatic and \nnon-enzymatic antioxidants that coexist to protect \nskin from reactive species (ROS) generated by \nthe ultraviolet rays. It also protects the skin from \noxidative stress by donating electrons to neutralize \nfree radicals. Vitamin C also interacts with copper \nions at the tyrosinase \u2013 active site and inhibits the \naction of tyrosinase, thereby decreasing the melanin \nformation. Additionally, it acts on perifollicular \npigment. Hence, this helps in lightening the skin \ntone5,6. Apart from acting as antioxidant, Vitamin \nC also function as anti-inflammatory agent. It \ninhibits NFkB which is responsible for activation of \ninflammatory cytokines such as TNF-alfa, IL1, IL6 \nand IL8, therefore promoting wound healing and \npost inflammatory hyperpigmentation which occurs \nafter chronic or intense exposure to ultraviolet \nlight7.\n\n\n\nOther main ingredient in this novel complex is \nChamomile vecutita extract which is also known \nto have wound healing property and regulate \nimmunodulatory effect in the skin8. \n\n\n\nTitanium dioxide is also use as ingredient for \nphotoprotective properties in this novel complex. \nIt helps hasten the lightening effect by reflecting \nand blocking the UV rays, thereby reduce activity \nof melanosome9. Low dose of UVA radiation can \ninduce lipid peroxidation of both keratinocytes and \nfibroblasts via pathway involving singlet oxygen and \niron promoting hyperpigmentation and blocking this \nray is essential in the process of skin lightening10.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32MJD 2016 Jul Vol 36\n\n\n\nConclusion\nThe AEBritening Complex-01 formulation is \neffective in lightening the skin. The effect could \nbe more significant if the study is conducted \nlonger duration. We recommend for the study to be \nconducted on subjects with melasma.\n\n\n\nOur suggestion for future would be to test the \nAEBritening Complex-01 formulation in a \ndouble blind randomized trial on melasma using \nMASI (Melasma Assesment Score Index and \nPatient /Physician Asessment of Improvement) in \ncombination with skin colorimetric measurement \nfor objective assessment.\n\n\n\nReferences\n \n1. Brenner M and Hearing VJ. The protective role of melanin \n\n\n\nagainst UV damage in human skin. Photochem Photobiol \n2008; 84(3): 539-549.\n\n\n\n2. Elysia Pan. Beautiful White: An illumination of Asian \nskin \u2013 whitening culture. Degree Thesis. Duke University \nDurham, North Carolina USA.\n\n\n\n3. Afaq F. Natural Agents : Cellular and molecular \nmechanisms of photoprotection. Arch Biochem Biophys \n2011; 508 (2);144-151.\n\n\n\n4. Pumori ST. Vitamin C in dermatology. Indian Dermatol \nOnline J. 2013; 4 (2): 143-146.\n\n\n\n5. Ebanks JP, Wickett RR and Boissy RE. Mechanisms \nregulating skin pigmentation: The rise and fall of \ncomplexion coloration. Int J Mol Sci. 2009; 10: 4066-\n4087.\n\n\n\n6. Matsuda S et al. Inhibitory effects of Novel Ascorbic \nderivative VCP \u2013 IS-2Na on melanogenesis. Chem Pharm \nBull.2008; 56:292-7.\n\n\n\n7. Traikovich SS. Use of topical ascorbic acid and its\u2019 effect \non photodamaged skin topography. Arch.Othorhinol Head \nand Neck Surg.1999; 125: 1091-8.\n\n\n\n8. Safety assessment of Chamomilla Recutita-Derived \ningredients as used in cosmetics. Cosmetic Ingredient \nReview Expert Panel report 2013.\n\n\n\n9. Jansen R, Wang SQ, Burnett M, et al. Photoprotection: part \n1. Photoprotection by naturally occurring, physical and \nsystemic agents. J Am Acad Dermatol 2013; 69(6): 853. \ne1-12.\n\n\n\n10. Gaiba S et al. Biological Effects Induced by Ultraviolet \nRadiation in Fibroblast. Flow Cytometry-Recent \nPerspectives. M.Sc.Ingrid Schmid (Ed) 2012: 439-455.\n\n\n\n11. Smit N , Vicanova J and Pavel S. The hunt for natural skin \nwhitening agents.Int.J.Mol.Sci. 2009; 10: 5326-5349.\n\n\n\n12. Solano, F, Bringati, S, Picardo, M, Ghanem, G., \nHypopigmenting agents: an updated review on biological, \nchemical and clinical aspects. Pigment Cell Res. 2007; 19: \n550\u2013571. \n\n\n\n13. Grimes PE, Yamada N, Bhawan J. Light microscopic, \nimmunohistochemical and ultrastructural alterations in \npatients with melasma. Am J Dermatopathol. 2005.27 (2): \n96-101.\n\n\n\nLEARNING POINTS FROM THIS STUDY\n\n\n\n1. This new lightening agent seems to reduce the tone of the skin compared to placebo and 4% \n hydroquinone. However, the number of patients in this study is small and the effect is somewhat \n comparable to 4% hydroquinone. More studies with higher number of patients are needed to \n confirm this effect.\n\n\n\n2. The authors suggest that the cream might be beneficial for melasma. However, large scale case \n control or split face study is needed. A more comprehensive methodology needs to be undertaken \n including photographs, quality of life tool, calorimeter and preferably skin biopsy to determine the \n effectiveness of this cream.\n\n\n\nYap FBB MD MRCP AdvMDerm\nEditor-in-Chief, MJD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33 MJD 2016 Jul Vol 36\n\n\n\nONCOLOGIC DERMATOLOGY - Case Report\n\n\n\nA CASE OF PRIMARY COLONIC MELANOMA \nTee SH, Mohd Affandi A, Lee BR\n\n\n\nCorresponding Author and Reprint Request \nDr Tee Shwu Hoon\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586 Kuala Lumpur, Malaysia\nEmail: shwuhoontee@hotmail.com\n\n\n\n1 Department of Dermatology, Kuala Lumpur Hospital\n2 Department of Pathology, Faculty of Medicine,   \n Universiti Putra Malaysia\n\n\n\nCase Report\nWe report a 53 year old lady who was referred by \nthe surgical team to rule out primary cutaneous \nmelanoma. She presented with altered bowel habit \nand constitutional symptoms. Colonoscopy revealed \na fungating mass arising from the ascending colon. \nTissue biopsy from the ascending colon showed \nulcerated colonic mucosa with solid sheets of \ntumour cells and adjacent necrosis. The malignant \ncells exhibited hyperchromatic and pleomorphic \nnuclei with prominent macronucleoli and scanty \ncytoplasm. The immunohistochemistry was positive \nfor S100 and HMB-45 confirming the diagnosis of \nmalignant melanoma (Figure 1 a-b).\n\n\n\nOn examination, we observed multiple depigmented \npatches, resembling vitiligo on the face and chest \n(Figure 2), multiple, irregular, hyperpigmented \nmacules and patches over both axillae (Figure 3) \nand a hyperpigmented patch, surrounded by a rim \nof hypopigmentation on the left calf (Figure 4).\n\n\n\nShe denied prior history of skin cancer, excised \nmelanotic nevi, ocular lesions, or family history \nof melanoma. Skin biopsies taken from both areas, \nright axilla and left calf excluded primary cutaneous \nmelanoma. Ophthalmology assessment was normal.\n\n\n\nIntroduction\nGastrointestinal involvement by malignant \nmelanoma is predominantly a metastatic \nphenomenon from a primary cutaneous or ocular \nmelanoma. Only 20% of all malignant melanoma \nof GIT presented with GI tract involvement as the \nfirst site of the disease1. Primary colonic melanoma \ndiffers from the cutaneous form of melanoma in its \nbiology, clinical manifestations and management. \nDiagnosis of primary colonic melanoma is usually \nlate due to a lack of early or specific signs and the \nlocation of lesions in areas that are difficult to access \nduring physical examination. We herein describe a \ncase of primary colonic melanoma associated with \nvitiligo-like depigmentation.\n\n\n\nFigure 1. Histopathologic and immunohistochemistry findings of ascending colon.\n\n\n\nA: Ascending colon mass biopsy showed ulcerated \ncolonic mucosa with solid sheets of tumour cells \nwhich exhibited hyperchromatic and pleomorphic \nnuclei with prominent macronucleoli and scanty \ncytoplasm. (H & E, x 400) \n\n\n\nB: Immunohistochemistry of the tissue showing \nS-100 positivity. (x400)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34MJD 2016 Jul Vol 36\n\n\n\nthat were either excised or spontaneously regressed. \nSkin examination however revealed atypical lesions \non her axillas and left calf, but biopsies from these \ntwo sites excluded primary cutaneous melanoma. \nIt is also important to rule out ocular melanoma \nas the primary source, which was excluded in our \npatient. This patient presented with vitiligo on her \nface concomitant with the onset of altered bowel \nhabit. The prevalence of vitiligo among melanoma \npatients is estimated to be between 3% and 6%3. \nThe association between vitiligo and melanoma \nis probably the result of a dual immune response \nagainst antigens present in both melanocytes \nand melanoma cells3,4, where the primary \nimmunogenic effect would be tumor rejection, but \nwith a simultaneous secondary autoimmune effect \ncharacterized by hypopigmented macules5. Longer \nsurvival has been observed in patients  who develop \nleukoderma associated with melanoma3.\n\n\n\nCT scan of thorax, abdomen and pelvis demonstrated \nan ascending colonic mass with regional lymph \nnodes enlargement with no metastases elsewhere. \nShe was diagnosed of stage II primary malignant \nmelanoma of the ascending colon and subsequently \nunderwent right hemicolectomy. During her follow-\nup, she recovered well post-operatively. Her skin \nlesions remained stable with no progression of \ndepigmented lesions. \n\n\n\nDiscussion\nPrimary colonic melanoma is rare with 12 cases \nbeing reported to date2. The rarity of colonic \nmelanoma rightfully raises suspicion for a regressed \nprimary cutaneous melanoma. An extensive \ndermatologic workup is warranted to identify any \npotential metastatic sources for the disease. Our \npatient had no history of previous cutaneous lesions \n\n\n\nFigure 2. Depigmented patches on the chest of a \n53 year-old woman.\n\n\n\nFigure 3. Irregular, hyperpigmented macules and \npatches on the right axilla.\n\n\n\nFigure 4. A hyperpigmented patch, surrounded by \na rim of hypopigmentation on the left calf (with the \nbiopsy site marked with ink).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35 MJD 2016 Jul Vol 36\n\n\n\nFor all GIT melanoma, it is fundamental to \ninvestigate for a primary source of malignant \nmelanoma, possibly from tumor regression or occult \nmalignant melanoma.  Oculocutaneous melanomas \nbeing the most common primary melanoma must \nbe excluded. Every effort must be made to obtain \na thorough history (prior excised lesions, prior skin \nand ocular lesions, personal and family history of \nmelanoma) and perform a comprehensive physical \nexamination. \n\n\n\nThere is no universal staging system for mucosal \nmelanoma. Ballantyne et al proposed a simplified \nstaging system that can be applied to all types of \nmucosal melanoma: stage 1: Localized disease; \nstage II: Regional lymph node involvement and \nstage III: Distant metastasis6. Our patient had stage \nII primary colonic melanoma as evidenced by lymph \nnodes metastases. The mainstay of treatment for \nlocoregional mucosal melanoma is surgical excision \nwith or without radiation therapy to achieve local \ncontrol. Mucosal melanomas are more aggressive \ncompared to cutaneous melanomas7. However, \nthe prognosis of primary colonic melanoma of \ncolon appears to be better than metastatic colonic \nmelanoma with a reported mortality rate of 22.2%2  \nand 47.1%8 respectively.\n\n\n\nReferences\n \n1. K Patel, S.T. Ward, T. Packer et al. Malignant melanoma of \n\n\n\nthe gastrointestinal tract:A case series. Int J Surg 2014; 12: \n523-7.\n\n\n\n2. Khalid U, Saleem T, Imam AM, Khan MR. Pathogenesis, \ndiagnosis and management of primary melanoma of the \ncolon. World J Surg Oncol. 2011;9:14\n\n\n\n3. G\u00fcl \u00dc, Kilic\u00b8 A, Tulunay \u00d6, Kaygusuz G. Vitiligo associated \nwith malignant melanoma and lupus erythematosus. J \nDermatol.2007;34:142---5.\n\n\n\n4. Arpaia N, Cassano N, Vena GA. Regressing cutaneous \nmalignant melanoma and vitiligo-like depigmentation. Int \nJ Dermatol. 2006;45:952---6.\n\n\n\n5. Ram\u00edrez-Montagut T, Turk MJ, Wolchok JD et al. Immunity \nto melanoma: unraveling the relation of tumor immunity \nand autoimmunity. Oncogene. 2003;22:3180---7.\n\n\n\n6. Ballantyne AJ. Malignant melanoma of the skin of the \nhead and neck. An analysis of 405 cases. Am J Surg. \n1970;120:425\n\n\n\n7. R. Ballester Sanchez, B. de Unamuno Bustos, M. Navarro \nMira et al. Mucosal melanoma:An update. Actas Dermo-\nSifiliograficas. 2015; 106:96-103\n\n\n\n8. Barth A, Wanek LA, Morton DL. Prognostic factors in \n1,521 melanoma patients with distant metastases. J Am \nColl Surg. 1995;181:193\u2013201.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Case Report\n\n\n\nGENOTYPING FOR SNP RS17822931 IN ABCC11 GENE\nCAN HELP IN THE DIAGNOSIS OF BODY MALODOUR \nHo WT1, Wang HY2, Pan JY3\n\n\n\nCorresponding Author and Reprint Request \nDr Wen-Tsao Ho\nDepartment of Dermatology\nHo Wen Tsao Skin Clinic, Taipei City, Taiwan\nEmail: varec.clinic@gmail.com\n\n\n\n1 Department of Dermatology,\n Ho Wen Tsao Skin Clinic, Taipei City, Taiwan\n2 Department of Plastic and Reconstructive Surgery, \n Taipei Ars Plastic Clinic, Taipei City, Taiwan; \n3 Department of Dermatology, National Skin Centre,\n 1 Mandalay Road, 308205 Singapore\n\n\n\nCase Report\nA 37-year old healthy, white-collar, Taiwanese \nmale without any underlying diseases has a chief \ncomplaint of excessive perspiration and body odor \nsince he was in his twenties, and has been bothered \nby it for a period of time. This is especially so during \nthe summer or after strenuous exercise, causing \nembarrassing wet marks on his shirts and severe \nmalodour. These problems have seriously affected \nhis personal relationships with others especially the \nopposite sex. He had consulted many doctors with \nmany different diagnoses. Use of antiperspirant \ngave him some relief. His body mass index was 24.5 \nand Wood\u2019s lamp examination was negative. Wet \nearwax was not found in a physical examination \nand he described an ambiguous type of earwax \nwhen taking his medical history. In the family, only \nhis father had body odor but not severe. Recently \nthere were many articles reporting about wet ear \nwax and the strong genotype relationship and \nfamilial association3,4,5. We decided to do a genetic \nstudy which was positive for SNP rs1782291 with \nG genotype. Polymerase chain reaction (PCR) \namplification with around 300bp product including \nrs17822931 was performed. Restriction fragment \nlength polymorphism analysis (RFLP) was done \nwith non-template control. The existence of allele \nA generates a 200bp and 100bp product following \nBseMII digestion. The AG and AA genotypes \nof rs17822931 gave three bands and two bands \nrespectively in 2% agarose gel electrophoresis \n(Fig.1). Sequencing chromatogram of the sample \nindicated AG heterozygous (Fig.2). Both methods \nhad identical results as AG heterozygous. With \nthis evidence, we managed to make a strong case \nfor body malodor, and submitted him for axillary \nsurgery which resulted in a very good outcome.\n\n\n\nIntroduction\nBromhidrosis is an unpleasant axillary odour \ndue to the interaction of apocrine glands with \nmicroorganisms, especially in postpubertal \nindividuals. On physical examination, it is often \nfound to be associated with wet earwax. Earwax \nis a dimorphic inhabitant trait of wet and dry \ntypes1. An experienced doctor can usually give the \ncorrect diagnosis and treatment to patients with \nbromhidrosis, based on a physical examination \nfor malodor, wet ear wax, or family history2. The \ntreatments included nonsurgical intervention such \nas botox or 1440nm laser and surgical intervention \nsuch as liposuction-assistant curettage or minimal \ninvasive surgery. Complete surgical removal of \napocrine glands is thought to be eradicated for \nbody malodour. In many cases, we still encounter \nsituations where diagnosis is difficult or results \nare ambiguous, thereby making it a problem for \nphysicians to decide on the appropriate treatment. \nAccording to the literature, the single nucleotide \npolymorphism (SNP) rs17822931 in the ATP-\nbinding cassette transporter sub-family C member \n11 (ABCC11) genes determines the earwax type; the \nAA genotype corresponds to dry earwax and GA or \nGG to the wet type. Here, we have report a case who \nhad excessive sweating but dry earwax whom we \nperformed a genetic analysis of the ABCC11 gene.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n37 MJD 2016 Jul Vol 36\n\n\n\nThe mechanism was believed that the ABCC11 gene \nencodes an apical efflux pump and apolipoprotein D \n(ApoD), an odor precursor carrier, which is crucial \nfor the formation of the characteristic axillary \nodor. The mRNA expression levels of ApoD are \nsignificantly higher in the apocrine glands of GG/\nGA genotypes, which enhance the transition of odor \nprecursors via the ApoD pathway6.\n\n\n\nThe majority of body malodor can easily be diagnosed \nclinically and proper treatment be administered. \nHowever, some cases can be a challenge. Such is \nour patient whom the wet earwax is not obvious, \nthus delaying the diagnosis. We cannot explain why \nthe inconsistency between earwax character and \nbromhidrosis. Hence, further studies investigating \nthe genotype and phenotype correlation are \nessential.  Although the mutation found in this \nreport is not novel, we would like to emphasize \nthat genetic studies can help in the diagnosis of of \nsuspicious patients with bromhidrosis.\n\n\n\nDiscussion \nAccording to literature, Yoshiura et al. published \nthat a SNP, 538G > A (rs17822931), in the ABCC11 \ngene, can determine a dry or wet type of earwax3. \nThe AA genotype corresponds to dry earwax, and \nthe GA and GG to the wet type. Also, because of \nstrong clinical correlations between earwax and \naxillary osmodrosis, Motoi Nakano further reported \nan important finding of a total of 78 (98.7%) of 79 \naxillary bromhidrosis patients who had either the GG \nor GA genotype, while these genotypes were found \nonly in 35.4% (57/161) of the subjects from the \ngeneral population. The strong association between \nthe wet earwax-related genotypes (GG and GA) and \nbromhidrosis suggest the SNP genotype can be a \ngood marker for the diagnosis of bromhidrosis5.\n\n\n\nFigure 1. RFLP analysis for patient\u2019s sample \n(labeled 1) and non-template control (labeled \n2) showed AG and AA genotype with three \nbands and two bands respectively in 2% \nagarose gel electrophoresis\n\n\n\nFigure 2. Sequencing chromatogram of the sample \nindicated AG heterozygous.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38MJD 2016 Jul Vol 36\n\n\n\nReferences\n \n1. Matsunaga E.  The dimorphism in human normal cerumen.  \n\n\n\nAnn Hum Genet. 1962;25:273-86.   \n2. Miura K, Yoshiura K, Miura S, et al. A strong association \n\n\n\nbetween human earwaxtype and apocrine colostrum \nsecretion from the mammary gland. Hum. Genet. \n2007;121: 631\u20133.\n\n\n\n3. Yoshiura K, Kinoshita A, Ishida T, et al. A SNP in the \nABCC11 gene is the determinant of human earwax type. \nNat. Genet. 2006; 38: 324\u201330.\n\n\n\n4. Shang D, Zhang X, Sun M, et al.. Strong association of the \nSNP rs17822931 with wet earwax and bromhidrosis in a \nChinese family. J Genet. 2013;92: 289-91.\n\n\n\n5. Motoi N, Nobutomo M, Akiyoshi H, et al. A strong \nassociation of axillary osmidrosis with the wet earwax type \ndetermined by genotyping of the ABCC11 gene. BMC \nGenetics 2009; 10: 42.\n\n\n\n6. Zhu Z, Zhang H, Luo G, et al. Association between the \nABCC11 gene polymorphism and the expression of \napolipoprotein D by the apocrine glands in axillary \nosmidrosis. Mol Med Rep. 2015;11:4463-7.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n39 MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Case Report\n\n\n\nA CHALLENGING CASE OF MEDIUM VESSEL VASCULITIS \nLong V1, Yang S2, Aw DCW1,2, Teo LLS4, Aisha L1,3, Teng GG1,3\n\n\n\nCorresponding Author and Reprint Request \nDr Aisha Lateef\nDivision of Rheumatology, University Medicine Cluster, \nNational University Health System,\nNUHS Tower Block, 1E Kent Ridge Road,\nSingapore 119228, Singapore. \nEmail: Aisha_lateef@nuhs.edu.sg\n\n\n\n1 Department of Medicine, Yong Loo Lin School \n of Medicine, National University of Singapore and \n National University Health System, Singapore\n2 Division of Dermatology, University Medicine Cluster, \n National University Health system, Singapore \n3 Division of Rheumatology, University Medicine \n Cluster, National University Health System, Singapore\n4 Department of Diagnostic Imaging,\n National University Health system, Singapore \n\n\n\nHis chest pain resolved, but his upper abdominal \ndiscomfort persisted. \n\n\n\nA Computer Tomography (CT) scan with \ncontrast revealed bilateral scattered areas of renal \nparenchymal perfusion defects.  This was deemed \nto be related to infection and he was treated \npresumptively for pyelonephritis with intravenous \nceftriaxone followed by oral ciprofloxacin. Yet, his \nurinalysis was bland and no cultures were obtaine.\n\n\n\nHe was discharged with oral antibiotics and \nantiplatelet agents but returned to the hospital 5 \ndays later with worsening digital pain. He denied \nany constitutional symptoms, joint pain or swelling, \nrashes, oral or genital ulcers, loss of appetite or \nweight, sicca symptoms or hair loss. Examination \nnow revealed dusky discoloration and tenderness \nat tips of several fingers and toes. Neurological \nexamination showed motor strength of 3/5 of the left \nwrist flexion and extension. Sensation was intact.\n\n\n\nIn view of recent coronary angiography, \natheroembolic phenomenon with resultant acral \nischemia was considered the most likely diagnosis. \nTransoesophageal echocardiogram (TEE) did \nnot show any intracardiac thrombosis or valvular \nvegetations. CT aortogram showed normal and \npatent thoracic and abdominal aorta, upper and lower \nlimb arteries were without focal stenosis. Routine \nblood investigations such as full blood count, renal \npanel and creatinine were unremarkable. He had \nraised liver transaminases and alkaline phosphatase \nlevels.\n\n\n\nMagnetic Resonance Imaging (MRI) of the brain \ndemonstrated multiple small foci of acute infarction \nprimarily in the cerebellum, occipital lobes, and \nalso in both left and right medial cerebral arterial \nterritories. In view of widespread infarctions \ninvolving central nervous system, progressive \ndigital pain, relative sparing of renal vasculature \nand absence of significant atheromatous load on \nangiography, the diagnosis of athero-embolic \nphenomena was questioned and an underlying \nvasculitis was considered. Of note, he had elevated \n\n\n\nIntroduction\nSystemic vasculitis, a great mimicker, can present \nwith a wide range of clinical manifestations which \nare often nonspecific and diagnostically challenging. \nWe report a difficult case of medium vessel \nvasculitis, which presented with ischemic features \nof the cutaneous, cardiac, renal and neurological \nsystems over a three month period, requiring multiple \nhospital admissions and extensive investigations \nbefore the definitive diagnosis was made.\n\n\n\nCase Report\nA 47 year-old Indian man with hypertension, \nhyperlipidemia and 30 pack-years of cigarette \nsmoking presented with worsening central non-\nradiating chest pain for one week associated with \nmild dyspnea.\n\n\n\nHe also reported pain at his fingertips but denied \nany discoloration. He also had a non-specific upper \nabdominal pain that was non-radiating and was \nunrelated to meals lasting for 3 weeks prior to \nadmission. \n\n\n\nPhysical examination was unremarkable. Initial \ninvestigations were suggestive of a non-ST elevation \nmyocardial infarction (NSTEMI) with raised \ncreatine kinase and tropinin I levels.  He was treated \nappropriately with aspirin, clopidogrel and low \nmolecular weight heparin. Subsequently, a coronary \nangiogram revealed minor coronary artery disease. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40MJD 2016 Jul Vol 36\n\n\n\nHe was treated with nifedipine, intravenous \nhydrocortisone followed by tapering oral \nprednisolone course. He improved symptomatically. \nHowever, the patient was admitted to our institution \nthree weeks later, with increasing pain of his digits. \nOn examination, ulcerations over his fingertips had \ndeveloped; with increasing duskiness and frank \ngangrene over the fingers and toes (Figure 1a and \n1b).\n\n\n\nC-reactive protein of 46.3 mg/L and erythrocyte \nsedimentation rate of 108 mm/hour. Complement \nlevels, cryoglobulin, homocysteine, Protein C and S, \nanti-thrombin III, anti-cardiolipin immunoglobulin \n(Ig) M and IgG as well as anti-b2 glycoprotein \nIgM and IgG were within normal ranges. There \nwas no hypereosinophilia. Lupus anticoagulant \nand Factor V Leiden mutation were negative. \nAntinuclear antibody and both anti-proteinase 3 and \nanti-myeloperoxidase anti-neutrophil cytoplasmic \nantibody were negative. There was no evidence of \ngammaglobulinopathies. Hepatitis B, C and Human \nImmnodeficiency Virus serology were also negative.  \nNerve conduction velocities were normal.\n\n\n\nFigure 1. Frank gangrene of the fingers (1a) and toes (1b).\n\n\n\nFigure 1a Figure 1b\n\n\n\nFigure 2. Cardiac MRI revealing infarction, highly \nsuggestive of vasculitis.\n\n\n\nFigure 3. Improvement of the fingers after treatment.\n\n\n\n2a 2b\n\n\n\n2c 2d\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n41 MJD 2016 Jul Vol 36\n\n\n\nartery. In addition to mechanical occlusion of small \narteries, CES mimics a systemic vasculitis because \ncholesterol crystals also incite a foreign-body \ninflammatory response, intravascular thrombus \nformation followed by endothelial proliferation and \neventually fibrosis. Although cholesterol emboli \ncan lodge in the microvasculature of any organ, feet \ninvolvement is much more common than the upper \nlimb due to the presence of atheromatous plaques \nresiding in the abdominal aorta4,5. This patient also \nhad CT evidence of multiple renal infarcts and MRI \nevidence of multiple intracranial infarcts after the \ncoronary angiogram. Whilst renal involvement may \nbe in keeping with cholesterol embolism, retrograde \nshowers of cholesterol emboli to the brain are less \nlikely to occur in the absence of carotid plaques6. \nFurthermore, his entire CT aortogram was fairly \nclean of atherosclerotic plague. Hence, the diagnosis \nof CES was in doubt.\n\n\n\nDue to the variability of its clinical manifestations, \nand the lack of a discriminatory laboratory feature, \nthe diagnosis of CES normally relies on histologic \nconfirmation on biopsy specimens of the involved \norgan where crescenteric intraluminal arteriolar \nclefts or birefringent cholesterol crystals are seen \nwithin the vessels of the skin7. Results from a skin \nbiopsy specimen had high specificity and favorable \nsensitivity (positive in up to 92% of cases)4. If \nhistology does not show the typical birefringent \ncholesterol crystals, serial sectioning of the biopsy \nspecimen is suggested.\n\n\n\nA negative skin biopsy result in our patient was \nhelpful to rule out CES. Anticoagulants and steroids \nhave no influence on the course of the disease \nprocess. No definitive treatment has been identified \nand the outcome is poor5 with renal failure, extensive \ngangrene and mortality8 as common sequelae.\n\n\n\nBuerger\u2019s disease (thromboangiitis obliterans)\nas differential diagnosis \nBuerger\u2019s disease (thromboangiitis obliterans) was \nsuspected given the heavy smoking history in a \nmiddle aged male9. It is a segmental inflammatory \nocclusive vasculopathy of small to medium sized \narteries and veins in both hands and feet. However, \nit is unusual for it to affect multiple organs and ESR \nand CRP levels are normal or slightly elevated. \nAngiography remains the diagnostic gold standard. \nOur patient\u2019s CT angiography of the limbs was \nnormal, lacking the distal arterial occlusion and \ncorkscrew collaterals that may otherwise suggest \nBuerger\u2019s disease. This entity is a diagnosis of \n\n\n\nSkin biopsy from the unaffected left middle \nfinger showed minimal perivascular lymphocytic \ninfiltrates with patent blood vessels and a negative \ndirect immunofluorescence. A cardiac MRI revealed \ninfarction features highly suggestive of vasculitis \n(Figure 2). Although histology was non-conclusive, \nthe clinical and radiological findings were \nconsistent with medium-vessel systemic vasculitis \ninvolving the cerebral, cardiac, renal and digital \narteries. High dose prednisolone at 1mg/kg/day \nwas re-instituted and slowly tapered. He was also \ngiven intravenous cyclophosphamide 700mg/m2 \nwith marked improvement of the digital ulcerations \nand complete pain resolution after the second dose \n(Figure 3).  Motor functions of the left upper limb \nalso improved.\n\n\n\nDiscussion\nVasculitis is defined by the presence of leukocytes in \nthe vessel wall with reactive inflammatory damage \nto mural structures, leading to end organ ischemia \nand infarction. Vasculitides may present in different \nways and this is dependent on the size of the affected \nblood vessel and the organ involved. Hence, it \nmay range from purely cutaneous manifestations \nsuch as palpable purpura, to multi-organ systemic \ninvolvement such as mononeuritis multiplex, \nglomerulonephritis, and pulmonary hemorrhage\n\n\n\nDefining a primary systemic vasculitis in our \npatient was a convoluted analytical process. His \ninitial presentation of the pain in his fingertips \nsuggestive of digital ischemia was overlooked \ndue a more overwhelming presentation of acute \ncoronary syndrome, particularly in an Indian man \nwith multiple cardiovascular risk factors. Later, \nthe cardiac catheterization became a red herring to \nsubsequent evaluation of the involvement of other \nmajor organs, namely the kidney and brain. The \nsuccessive manner of multiple organ manifestations \nin no specific chronological order has been well \ndescribed at the onset of vasculitis1-3. Further, \nthere was lack of histological evidence, other \ncardinal signs of autoimmune disorders and specific \nimmunological tests to point towards a specific \nvasculitic entity. \n\n\n\nCholesterol embolism syndrome\nas differential diagnosis \nCholesterol embolism syndrome (CES) was \nrepeatedly considered as his acral ischemia and \ndigital ulcerations seemed to have developed or \nevolved after the intravascular instrumentation. He \nhad cardiac catherisation done via the right radial \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42MJD 2016 Jul Vol 36\n\n\n\nwith cyclophosphamide11. Despite such dilemma, \ntreatment had to be instituted aggressively based on \nthe presumptive clinical diagnosis of medium vessel \nvasculitis, of the idiopathic type, with the goal of \npreventing morbidity and mortality of multiple \norgan infarction and failure. \n\n\n\nIn conclusion, medium vessel vasculitis can truly \nbe a diagnostic challenge owing to its protean \nmanifestations and the lack of a true set of diagnostic \ncriteria. In face of evolution of patient\u2019s clinical \npresentations over time, clinicians need to rethink \na diagnosis, maintain their clinical judgment and \nbe pragmatic in instituting appropriate and timely \ntreatment, despite limitations of angiography, \nimmunological markers and non-specific \nhistopathology.\n\n\n\nexclusion and the presence of visceral arterial \nlesions, especially in the setting of markedly \nelevated acute-phase reactants, mandated exclusion \nof another vasculitis.\n\n\n\nThis case illustrates a challenge of ascribing a \ndiagnostic label to a patient where the manifestations \ndid not fit any defined entity according to the most \nrecent 2012 International Chapel Hill Consensus \nConference on the Nomenclature of Vasculitides10 \n\n\n\n(CHCC2012). Inferring from the CHCC2012 \nnomenclature (which is neither a classification \nnor diagnostic criteria), this patient most closely \nresembles a polyarteritis nodosa phenotype but \nincompletely so. A case series of isolated acral \nischemia have been described as forme-fruste of \nan unclassified vasculitis; all cases were treated \n\n\n\nReferences\n \n1. Suresh E. Diagnostic approach to patients with suspected \n\n\n\nvasculitis. Postgrad Med J. Aug 2006; 82(970): 483\u2013488. \n2. Roane D, Griger D. An approach to diagnosis and initial \n\n\n\nmanagement of systemic vasculitis. Am Fam Physician \n1999;60:1421\u201330. \n\n\n\n3. Luqmani R, Pathare S, Kwok-Fai T. How to diagnose and \ntreat secondary forms of vasculitis? Best Pract Res Clin \nRheumatol 2005;19:321\u201336.  \n\n\n\n4. Vincent F, Michael J, Wishwa N. The cutaneous \nmanifestations of cholesterol crystal embolization. Arch \nDermatol. 1986; 122 (10): 1194-8\n\n\n\n5. Schipper H, Gordon M, Berris B. Atheromatous embolic \ndisease. Can Med Assoc J 1975;113:640-644\n\n\n\n6. Winter W. Atheromatous emboli: A cause of cerebral \ninfarction. Arch Pathol Lab Med 1957;64:137-142.\n\n\n\n7. Anna J,  Francesc M, Cristina M. Cholesterol embolism: \nstill an unrecognized entity with a high mortality rate.  J \nAm Acad Dermatol 2006; 55: 786-93\n\n\n\n8. Henk D, Beert B, Dick H. Cholesterol embolism as a \ncomplication of left heart catheterisation. A report of seven \ncases. Br Heart J 1984; 52: 339-42\n\n\n\n9. Ma\u0142ecki R, Kluz J, Przezdziecka-Do\u0142yk J et al. The \npathogenesis and diagnosis of thromboangiitis obliterans: \nis it still a mystery? Adv Clin Exp Med. 2015 Nov-\nDec;24(6):1085-97.\n\n\n\n10. Jennette J, Falk R, Bacon P et al. 2012 Revised International \nChapel Hill Consensus Conference Nomenclature of \nVasculitides. 2013 Arthritis & Rheumatism, 65: 1\u201311.\n\n\n\n11. Pipitone N, Holl-Ulrich K, Gross WL. Unclassified \nvasculitis with acral ischemic lesions: \u201cforme fruste\u201d or \nidiopathic vasculitis? Clin Exp Rheumatol. 2008 May-\nJun;26(3 Suppl 49):S41-6.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n43 MJD 2016 Jul Vol 36\n\n\n\nONCOLOGIC DERMATOLOGY - Case Report\n\n\n\nRENAL CELL CARCINOMA WITH CUTANEOUS METASTASES \nRESEMBLING PYOGENIC GRANULOMA \nAnisha B, Norashikin S\n\n\n\nCorresponding Author and Reprint Request \nDr Anisha Bhullar \nDepartment of Medicine,\nFaculty of Medicine and Health Sciences\nUniversiti Putra Malaysia, 43300 Serdang, Malaysia\nEmail: anishabhullar@gmail.com\n\n\n\nHe was subsequently referred 16 months later to the \ndermatology unit by the nephrologists for a growth \non the nose of one month duration. The lesion \ninitially developed as a papule rapidly progressing \ninto a nodule in the span of one month. There was \nno history of trauma or insect bite to the area prior \nto the development of the skin lesion. This nodule \nwas not tender to touch but had the tendency to \neasily bleed. Clinical examination revealed a firm \nerythematous nodule measuring 1cm by 1cm on the \ntip of the nose (Figure 1 and 2). It was irregular in \nshape and had erosive as well as crusted surface, \npartly haemorrhagic. The examination of the scalp, \nhead and neck region was unremarkable. There was \nno regional lymph nodes palpable or evidence of \nsystemic involvement. The differential diagnoses \ninclude pyogenic granuloma, vascular tumours, \nappendageal tumours and cutaneous metastasis. An \nexcisional biopsy of the nodule was performed.\n\n\n\nHistology of the skin biopsy showed a well \ncircumscribed lesion within the dermis composing \nof tumour cells infiltrates in a tubular and \npseudopapillary pattern forming multiple lobules. \nThe lobules are separated by thin fibrous septae and \nthin vascular channels. The enlarged tumour cells \ncontain prominent eosinophilic nucleoli with mitosis \n(Figure 3, 4). The immunochemistry staining were \ndiffusely positive for EMA (Epithelial membrane \nantigen) and CD10 (Figure 5 and 6). This result was \nconsistent with renal cell carcinoma.\n\n\n\nIn this case, the nodular lesion on the nose was the \nfirst manifestation of metastatic disease.\n\n\n\nPost excision, this patient was referred to oncology \nfor further management and was followed-up by a \nmultidisciplinary medical team. The tumour on the \nnose had rapidly regrown to its previous size shortly \nafter the excision. He managed to complete 3 sessions \nof palliative radiotherapy to the nose. Thereafter, he \ndeveloped a right intertrochanteric fracture of femur \nand was found to have lung metastases on his chest \nX-ray. Shortly after, he succumbed to his illness.\n\n\n\nIntroduction\nRenal cell carcinoma (RCC) is a malignant \ntumour that accounts for approximately 2-3% of \nadult malignancies with the incidence increasing \nannually1. The incidence of cutaneous metastasis of \nRCC is reported to be 3.4% and most reported cases \nhaving occurred in males2,3. The pattern of metastasis \nfrom RCC is poorly defined and as such there have \nbeen several case reports of RCC presenting with \natypical presentations and rare metastatic sites. \nThis is due the complex lymphatohaematogenous \nsupply of the kidneys. The most common metastatic \nextension foci of RCC are in the lymph nodes, \nlungs, liver, and bone2.\n\n\n\nCutaneous lesions that appear in post cancer patients \nmay be an indication of malignancy recurrence. It \nmay be misleading in its appearance and morphology. \nWe report a case of cutaneous metastases arising \nfrom RCC presenting as a pyogenic granuloma like \nlesion on the tip of the nose.\n\n\n\nCase Report\nA 64 year old Malay gentleman with a background \nof diabetes and hypertension was diagnosed with \nrenal cell carcinoma in 2012 following an episode \nof hematuria and flank pain. A right sided renal \nmass measuring 6.4 x 5.6cm was detected after a CT \nscan for which a curative intent right nephrectomy \nwas performed. Further adjuvant chemotherapy and \nradiotherapy was not deemed required. The patient \ncontinued to be monitored in renal outpatient clinic \nwith regular computer tomography (CT) abdomen \nand blood tests.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44MJD 2016 Jul Vol 36\n\n\n\nFigure 1. An erythematous nodule with a \nweepy surface measuring 1cm by 1cm on \nthe tip of the nose.\n\n\n\nFigure 2. Haemorrhagic crusts seen on the surface of the nodule.\n\n\n\nFigure 3. Islands of well circumscribed tumour \ncells forming an extensive network of lobules \n(H&E, magnification X 10).\n\n\n\nFigure 5. Positive immunohistochemistry with \nEpithelial membrane antigen (EMA, magnification \nX 100).\n\n\n\nFigure 4. Enlarged tumour cells contain prominent \neosinophilic nucleoli with mitosis is seen (H&E, \nmagnification X 600).\n\n\n\nFigure 6. Positive immunohistochemistry staining \nwith CD10 (CD10, magnification X 100).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n45 MJD 2016 Jul Vol 36\n\n\n\nIn our patient the purplish and non-pulsatile nodule \nwas suggestive of a pyogenic granuloma. In the \nliterature there have been a few cases of both \nvisceral and cutaneous malignancies masquerading \nas pyogenic granulomas9-11. These nodules are \nrapidly growing with a propensity to bleed. Other \nclinical description of metastatic RCC lesions are \nvaried from abscesses, pulsating to non- pulsating \nnodules, cutaneous horn, pyogenic granulomas and \nzosteriform pattern12-15. Common sites are the scalp, \nforehead, upper lip and chin, submandibular neck \nand gland and parotid gland.\n\n\n\nThis case highlights the importance of \ncomprehensive clinical history as it heightens the \nclinical suspicion of examination findings. When \na patient presents with a background history of \ninternal malignancy, the degree of suspicion for \nthese cutaneous lesions are high and excisions \nwith further histopathology correlation is needed. \nIn this case, the patient presented with an atypical \nmanifestation of metastatic renal cell carcinoma \nwith the only presentation being a solitary skin \nnodule. Cutaneous metastasis often reflects poor \nprognosis due to late presentations with high \nmetastatic burden, and this helps to guide clinical \ndecision making with respect to therapeutic and \nmanagement options. Often, in late disease, the \ntreatment is usually palliative or symptom directed. \nHence we would suggest comprehensive and yearly \ninterval skin checks in patients with renal cell \ncarcinomas. This could add value to the current \nclinical paradigms in managing patients with solid \norgan malignancies that are deemed to be cured or \nin remission.\n\n\n\nDiscussion\nThe skin is a rare site of metastases in visceral \nmalignancies. A large case series done in Taiwan \ninvolving 12,146 cases of internal malignancy \ndemonstrated a low percentage of cutaneous \ninvolvement 1.02%3. In this series, breast carcinoma \nwas found to have the highest rate of cutaneous \nmetastasis followed by lung carcinoma3.\n\n\n\nKoga et al, found cutaneous metastasis of RCC to \nbe a late manifestation of the disease, carrying a \npoor prognosis with most cases having synchronous \nvisceral metastasis and an expected survival of \n23.4 months. These lesions can occur years after \nsurgical resection of an organ-confined tumour. One \ncase (1/6) in that series had evidence of cutaneous \nmetastases at the time of diagnosis of RCC5. The \nlesions have a tendency to mimic common skin \nlesions in appearance and patients are not subjected \nto routine screening skin examinations hence their \ndetection rates are low and often late. There have \nbeen reported, albeit rare, of skin metastasis prior to \nthe detection of the primary renal cell malignancy6.\nWhen suspecting the possibility of cutaneous \nmetastasis in these cases, and extensive workup to \ndetect the primary malignancy is warranted.\n\n\n\nRCC is the commonest histological subtype of \nrenal malignancies and is known to be aggressive \nin nature. In RCC, haematogenous and lymphatic \nsystems are considered the common mode of \nspread of the tumour cells. The anatomical site of \nmetastases is unpredictable as it has been shown \nto spread to rare sites such as the orbit, paranasal \nand nasal cavities, thyroid and parotid glands, heart \nand muscle and joints4,7. The lungs followed by the \nbones have been reported as the commonest site of \nmetastatic spread8.\n\n\n\nReferences\n \n1. Ljungberg B, Bensalah K, Bex A, et al Canfield Guidelines \n\n\n\non renal cell carcinoma. European Association of Urology, \n2013.\n\n\n\n2. Mueller TJ, Wu H, Greenberg RE, et al. Cutaneous \nmetastases from genitourinary malignancies. Urology \n2004 Jun 30;63(6):1021-6.\n\n\n\n3. Hu SC, Chen GS, Wu CS, et al. Rates of cutaneous \nmetastases from different internal malignancies: \nexperience from a Taiwanese medical center.  J Am Acad \nDermatol 2009 60(3):379-87.    \n\n\n\n4. Lookingbill DP, Spangler N, Helm KF, et al. Cutaneous \nmetastases in patients with metastatic carcinoma: a \nretrospective study of 4020 patients. J Am Acad Dermatol \n1993 ; 29(2):228-36.\n\n\n\n5. Koga S, Tsuda S, Nishikido M, et al. Renal cell carcinoma \nmetastatic to the skin. Anticancer Res 2000; 20: 1939-\n1940.\n\n\n\n6. Amador A, Monforte NG, Bejarano N, et al. Cutaneous \nmetastasis from hepatocellular carcinoma as the first \nclinical sign. J Hepato-biliary-pancreatic Surg. 2007; \n14(3):328-30.\n\n\n\n7. Sountoulides P, Metaxa L, Cindolo L. et al. Atypical \npresentations and rare metastatic sites of renal cell \ncarcinoma: a review of case reports. J Med Case Rep. \n2011; 5(7):429.8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46MJD 2016 Jul Vol 36\n\n\n\n8. Porter NA,Anderson H,Al-Dujaily,et al. Renal cell \ncarcinoma presenting as a solitary    cutaneous facial \nmetastases: case report and review of the literature.Int \nSemiin Surg Oncol.2006;3(1):27-30\n\n\n\n9. Tashiro J, Perlyn CA, Melnick SJ, et al. Non-pigmented \nmelanoma with nodal metastases masquerading as \npyogenic granuloma in a 1-year old. J  Pediatr Surg 2014; \n49(4):653-5.\n\n\n\n10. Mitamura Y, Nakahara T, Furue M. Clear cell \nhidradenocarcinoma mimicking pyogenic granuloma after \nrepeated surgical excision. Dermatol Surg 201 ; 40(2):211-\n2.\n\n\n\n11. Lee MC, Huang YL, Yang CH et al. Cutaneous seeding \nof hepatocellular carcinoma due to percutaneous ethanol \ninjection and masquerading as a pyogenic granuloma. \nDermatol Surg 2004; 30(3):438-40.\n\n\n\n12. Snow S, Madjar D, Reizner G, et al. Renal cell carcinoma \nmetastatic to the scalp: case report and review of the \nliterature. Dermatol Surg 2001; 27(2):192-4.\n\n\n\n13. Peterson JL, McMarlin L. Metastatic Renal\u2010Cell Carcinoma \nPresenting as a Cutaneous Horn.  J Dermatol Surg Oncol \n1983; 9(10):815-8.\n\n\n\n14. Guadalupe EC, Maria EV, Rosa ML, et al. Scalp metastases \nof a renal cell carcinoma. Dermatol for the Clinician \n2006;5(3):148-50.\n\n\n\n15. Dincer D, Tunca M, Akar A, et al. Zosteriform cutaneous \nmetastasis of renal cell carcinoma. Indian J Dermatol, \nVenereology, and Leprology. 2011; 77(3):340.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n47 MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Case Report\n\n\n\nLUPUS ERYTHEMATOSUS PANNICULITIS: A CASE SERIES \nLiew HM1, Long V2, Koh MJA1\n\n\n\nCorresponding Author and Reprint Request \nDr H.M. Liew\nDermatology Service,\nKK Women\u2019s and Children\u2019s Hospital,\nSingapore, 100 Bukit Timah Road, 229899 \nEmail: Liew.Hui.Min@singhealth.com.sg\n\n\n\nHistological examination revealed septo-lobular \npanniculitis associated with a mid-to-deep dermal \nperivascular and peri-adnexal chronic lympho-\nhistiocytic infiltrate (Fig. 2a). Focal rimming of the \nadipocytes by lymphocytes was seen with mild \nhyaline necrosis.\n\n\n\nAlcian blue stain showed focal deposition of mucin \nin the dermis and subcutis (Fig. 2b). Most of the \nlymphocytes stained positively for CD3 and CD4, \nwith smaller numbers of CD8+ lymphocytes and \nCD20+ B cells.\n\n\n\nIntroduction\nLupus erythematosus panniculitis (LEP) is a rare \nvariant of cutaneous lupus erythematosus. Its \npresentation is variable and slowly progressive, \nleading to many patients not seeking early medical \nintervention. LEP is very rare in children, with \napproximately 20 reported cases1. We report 3 \npediatric cases of LEP.\n\n\n\nCase Series\nCase 1\nPatient 1 is a 6 year-old Chinese girl, referred for \nrecurring left cheek swelling, first noticed at 3 years \nof age.  Physical examination revealed lower facial \nasymmetry caused by a pronounced fullness of her \nleft lower cheek with faint overlying erythema and \ntelangiectasias, extending into the submental area \n(Fig. 1).\n\n\n\nFigure 1. Patient 1 demonstrates linear \ntelangiectatic atrophic skin on the left \nlower cheek with facial asymmetry.\n\n\n\nFigure 2a. A lobular panniculitis consisting mostly \nof small lymphocytes and histiocytes, with mild fat \nnecrosis and fat rimming. The inflammatory cells \ndo not exhibit atypia. (H&E, magnification X200).\n\n\n\nFigure 2b. Alcian blue stain shows mucin \ndeposition in the deep dermis (Magnification X40).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48MJD 2016 Jul Vol 36\n\n\n\nCase 3\nPatient 3 is a 4 year-old Chinese boy, referred for an \nenlarging, annular rash on the right lower quadrant \nof the abdomen for 6 months. Examination revealed \nan annular, erythematous indurated plaque, at the \nright lower quadrant of the abdomen, extending \nonto the right thigh (Fig. 5). \n\n\n\nHistological examination revealed a lobular \npanniculitis associated with mild fat necrosis. There \nwas an associated superficial and deep perivascular \nand perieccrine lymphohistiocytic dermal infiltrate \n(Fig. 6a). Alcian blue stain was positive for mucin in \nthe dermis and subcutis (Fig. 6b). The histological \nfindings were suggestive of LEP. \n\n\n\nAfter clinical-histopathological correlation, a \ndiagnosis of LEP was made.  The patient was first \ntreated with potent topical corticosteroids and \ntopical tacrolimus. Hydroxychloroquine 50mg once \ndaily (2.5mg/kg/day) was started subsequently, with \nsignificant improvement seen after 5 months of \ntreatment.  There was no recurrence or evidence of \nsystemic lupus after 22 months of follow-up.\n\n\n\nCase 2\nPatient 2 is an 8 year-old Chinese boy, referred for \nan enlarging, painless erythematous plaque on the \nforehead for 6 months. On examination, there was \nan annular, erythematous, indurated plaque over his \nright forehead, affecting the right eyebrow (Fig. 3). \n \nHistology showed lympho-histiocytic lobular \npanniculitis with scattered plasma cells. There \nwas focal fat rimming by the lymphocytes but fat \nnecrosis was not prominent. There was an associated \nchronic mononuclear peri-vascular, peri-adnexal \nand peri-neural infiltrate in the dermis (Fig. 4a). The \nalcian blue stain highlighted focal mucin deposition \n(Fig. 4b). The histological findings were suggestive \nof LEP.\n\n\n\nThe patient was started on hydroxychloroquine \n50mg once daily (2mg/kg/day). After 4 months, \ninduration and erythema had completely resolved \nwith mild residual atrophy. Hydroxychloroquine \nwas stopped after 5 months, with no evidence of \nrecurrence or systemic involvement at 15 months \nfollow-up.\n\n\n\nFigure 3. Patient 2 exhibits annular erythematous \nindurated plaque on the right forehead.\n\n\n\nFigure 4a. A lympho-histiocytic lobular panniculitis \nwith scattered plasma cells. There was focal fat \nrimming by the lymphocytes but fat necrosis was \nnot prominent.   There was an associated chronic \nmononuclear peri-vascular, peri-adnexal and peri-\nneural infiltrate in the dermis. (H&E, magnification \nX200).  \n\n\n\nFigure 4b. Alcian blue stain highlighted focal \nmucin deposition. (Magnification X200).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n49 MJD 2016 Jul Vol 36\n\n\n\ndifferentiating them confidently. Although not \nentirely diagnostic, the use of immunophenotyping \nand TCR gene rearrangement studies can assist \nin distinguishing both entities. Clonality of T-cell \nreceptor genes can usually be demonstrated on \nmolecular analysis in SPTCL.\n\n\n\nThe histopathologic features of morphea can also \noverlap with LEP, especially in early cases.  Common \nhistologic features include lymphoplasmacytic \ninflammation around superficial and deep vessels, \nadnexae and nerves; thickened septa, lymphocytic \nvasculitis, mucinous change, and the presence of \noccasional eosinophils4. Morphea however lacks \nsome typical changes of lupus, for example interface \nactivity and epidermal atrophy4.\n\n\n\nHydroxychloroquine 50mg daily (2.5mg/kg/day) \nwas commenced. The plaque completely resolved \nwithin 6 months. Treatment was stopped after 8 \nmonths, with no recurrence or progression after a \nfurther 10 months follow-up.\n\n\n\nThe full blood count and erythrocyte sedimentation \nrate were within normal ranges. Anti-nuclear \nantibodies (ANA), anti-double-stranded DNA \nantibodies and extractable nuclear antibodies were \nnegative in all patients.\n\n\n\nDiscussion \nLEP commonly presents as an erythematous, \ndepressed patch or subcutaneous nodules, on the \nface and upper arms2.  Disease duration is variable, \nbut can be progressive for months to years2.  Mean \nage of onset is 8 years of age1. \n\n\n\nClinical-histopathological correlation is important \nin the diagnosis of LEP. In view of its variable \nclinical manifestations, LEP can be confused \nclinically and histopathologically with other \ndiagnoses, in particular, subcutaneous panniculitis-\nlike T-cell lymphoma (SPTCL) and morphea.\n\n\n\nLEP and SPTCL may exhibit overlapping \nseveral similar histological features, including \nlobular lymphocytic infiltrate, eosinophilic fat \nnecrosis, lymphocytic angioinvasion, histiocytic \nphagocytosis of debris, and eccrinotropic lymphoid \ninfiltrates3. Histologic features that favor a diagnosis \nof LEP include numerous plasma cells, areas \nof hyalinization, reactive germinal centers, and \nepidermal and dermal changes2. Despite these \nhistological criteria, there may still be difficulty \n\n\n\nFigure 5. Patient 3 exhibits annular \nerythematous indurated plaque on the \nright lower abdomen.\n\n\n\nFigure 6a. A lobular panniculitis associated with mild \nfat necrosis. There was an associated superficial and \ndeep perivascular and perieccrine lymphohistiocytic \ndermal infiltrate. (H&E magnification X200).\n\n\n\nFigure 6b. Alcian blue stain was positive for mucin in \nthe dermis and subcutis. (Magnification X 200).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50MJD 2016 Jul Vol 36\n\n\n\nTwo of our cases showed features of lipodystrophy, \ndespite treatment with anti-malarials. It is known \nthat as the inflammation subsides, significant \nlipodystrophy can occur, possibly due to hyaline fat \nnecrosis.\n\n\n\nAlthough LEP can present with a recurrent clinical \ncourses2,  pediatric cases seem to be more responsive \nto treatment with hydroxycholoroquine, with rare \nrecurrences1. However, as long term follow-up data \nis lacking, regular work-up to exclude SLE needs to \nbe considered, and in atypical cases, repeat biopsies \nto exclude SPTCL.\n\n\n\nIn conclusion, clinical-histopathological correlation \nis important in the making diagnosis, in particular \nto distinguish it from morphea and SPTCL. We \npresented 3 pediatric cases of LEP, responding to \nhydroxychloroquine, which should be considered as \nfirst line treatment.\n\n\n\nThe occurrence of systemic lupus erythematosus \n(SLE) in the background of LEP is rare.  Whilst \nit has been shown that adults with LEP may have \nANA titres greater than 1:120, only 4 out of 40 \npatients with LEP fulfills the criteria for SLE5. In \na case review of 16 pediatric patients, only 4 had \nANA titres greater than 1:120 but none of them \ndemonstrated any evidence of SLE1. None of our \npatients demonstrated clinical evidence of SLE \nthroughout follow-up. However, there has been 4 \nreported pediatric cases of LEP occurring in the \nbackground SLE6,7. A recent report described a case \nof pediatric linear LEP progressing to SLE within 6 \nmonths of diagnosis8.\n\n\n\nLEP can be successfully treated with antimalarials, \ne.g. hydroxychoroquine.  All our patients responded \nto oral hydroxychloroquine. Ophthalmological \nassessment is recommended as retinopathy is \na serious potential side-effect. Other systemic  \ntreatment options that can be considered in \nrefractory cases include systemic corticosteroids, \nthalidomide, mycophenolate mofetil, cyclosporine \nand cyclophosphamide7.\n\n\n\nReferences\n \n1. J Weigngartner, D Zedek, D Morrell, et al. Lupus \n\n\n\nErythematosus Panniculitis in Children: Report of Three \nCases and Review of Previously Reported Cases. Pediatr \nDermatol 2012; 29:169-76. \n\n\n\n2. HS Park, JW Choi, BK Kim, et al. Lupus Erythematosus     \nPanniculitis: Clinicopathological, Immunophenotypic, and \nMolecular Studies. Am J Dermatopathol 2010; 32: 24-30.  \n\n\n\n3. L Pincus, P LeBoit , TH McCalmont, et al. Subcutaneous \npanniculitis-like T-cell lymphoma with overlapping \nclinicopathologic features of lupus erythematosus: \ncoexistence of 2 entities? Am J Dermatopathol 2009; 31: \n520-6. \n\n\n\n4. D Arps, R Patel. Lupus Profundus (Panniculitis): A \nPotential Mimic of Subcutaneous Panniculitis-like T-Cell \nLymphoma.  Arch Pathol Lab Med 2013; 137: 1211\u201315. \n\n\n\n5. Martens PB, Moder KG, Ahmed I. Lupus panniculitis: \nclinical perspectives from a case series. J Rheumatol 1999; \n26: 68\u201372. \n\n\n\n6. Bacanli A, Uzun S, Alpsoy, et al. A case of lupus \nerythematosus profundus with unusual manifestations. \nLupus 2005; 14: 403-5. \n\n\n\n7. Guissa VR, Trudes G, Jesus AA et al. Lupus erythematosus \npanniculitis in children and adolescents. Acta Reumatol \nPort 2012; 37:82-5.  \n\n\n\n8. Fernandes S, Santos S, Freitas I, et al. Linear lupus \nerythematosus profundus as an initial manifestation of \nsystemic lupus erythematosus in a child. Pediatr Dermatol \n2014; 31: 378-80.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n51 MJD 2016 Jul Vol 36\n\n\n\nONCOLOGIC DERMATOLOGY - Case Report\n\n\n\nATYPICAL GRANULAR CELL TUMOR\nLong V\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nTan Tock Seng Hospital, 11 Jalan Tan Tock Seng, \n308433 Singapore\nEmail: valencialong@gmail.com\n\n\n\nA excisional biopsy of the nodule on the left \nabdomen showed a diffuse dermal interstitial \nproliferation of epithelioid cells with abundant \nfinely granular, eosinophilic cytoplasm (Figure 3). \nThese cells were positive for S100 (Figure 4a) and \nCD68 (Figure 4b) but negative for high and low \nmolecular weight keratins (Figure 4c) and Mart-1/\nMelan-A (Figure 4d). There was focal spindling \nof the granular cells (Figure 5). The granular cells \nshow nuclei that are variably pleomorphic, some \nwere intermittently vesicular with large nucleoli \n(Figure 6). These findings were consistent with \natypical granular cell tumor.\n\n\n\nThe two nodules in the right axilla were diagnosed \nas hidradenitis suppurativa. One was excised for \npathological diagnosis and showed an inflammatory \nreaction consistent with hidradentis suppurativa.\n\n\n\nIntroduction\nGranular cell tumors (GCTs) are neoplasms that \narise from Schwann cells, and may affect patients \nof all ages. Although most GCTs are benign, their \nclinical evolution is often unclear and there may \nbe difficulty distinguishing between atypical and \nmalignant GCTs. We report a case of GCT arising \nin a middle-aged woman showing atypical features, \nin which follow-up and treatment depended on \nrisk assessment as well as physician-patient shared \ndecision-making to guide subsequent management \nof her GCT.\n\n\n\nCase history\nA 55 year-old woman presented with three \npainful, erythematous nodules. A solitary nodule \non her left abdomen measured 8mm in diameter                        \n(Figure 1) and had persisted for two months while \ntwo firm nodules in her left axilla measuring 7mm \nin diameter (Figure 2) had been present for one \nweek. She has no significant comorbidities and does \nnot take any medications.\n\n\n\nFigure 1. Solitary, erythematous nodule in the left \nabdomen measuring 8mm in diameter.\n\n\n\nFigure 2. Firm nodules in the axilla measuring \n7mm in diameter.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52MJD 2016 Jul Vol 36\n\n\n\nFigure 3. Low magnification x2 showing a diffuse \ndermal interstitial proliferation of epithelioid and \nspindle cells.\n\n\n\nFigure 4a. The  epithelioid and spindle cells were \npositive for S100.\n\n\n\nFigure 4c. The ephithelioid and spindle cells were \nnegative for high molecular weight cytokeratin \n(HMCK).\n\n\n\nFigure 4b. The ephithelioid and spindle cells were \npositive for CD68.\n\n\n\nFigure 4d. The ephithelioid and spindle cells were \nnegative for Mart-1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n53 MJD 2016 Jul Vol 36\n\n\n\nFigure 5. Focal spindling of tumor cells (H&E, \nmagnification X400).\n\n\n\nFigure 6. Granular cells showing nuclei that are \nvariably pleomorphic with vesicular and large \nnucleoli and occasional mitotic figures (H&E, \nmagnification X400).\n\n\n\npredict behavior2. Although histological criteria may \nindicate an increased risk of malignant evolution, \nsome GCTs with apparent benign appearance may \nmetastasize2.\n\n\n\nIt is understood that a small percentage (2%) of \nthese lesions may demonstrate malignant behaviour. \nIn 1998, Fanburg-Smith et al. established that six \nhistological criteria3 could predict malignant \nbehaviour: sarcomatoid spindling of the tumor cells, \npresence of vesicular nuclei with large nucleoli, \nincreased mitotic rate (2 mitoses per 10 high-\npower fields at 200x magnification), high nuclear \nto cytoplasmic (N:C) ratio, pleomorphism, and \nnecrosis.\n\n\n\nIf a GCT demonstrates three or more of these \ncriteria, it is classified as \u201cmalignant\u201d and those \nthat show one or two are classified as \u201catypical,\u201d \nand if it exhibits none of the criteria or only focal \npleomorphism, it is classified as \u201cbenign.\u201d Most \nmalignant GC tumors have at least 5 or 6 of the \ncriteria with necrosis or increased mitotic activity3. \nKi-67 and p53 were significantly higher in atypical \nand malignant tumors than in benign ones3.\n\n\n\nBased on these histological criteria, the likelihood \nof malignancy for this patient is low. A review by \nMachado et al demonstrates that GCT with atypical/\nuncertain features almost never metastasize, and \nmany of these tumors could behave in a benign \nfashion or recur locally similar to the behaviour of \nincompletely excised benign tumors2.\n\n\n\nDiscussion\nGranular cell tumor (GCT) was first described in \n1926 by Abrikossoff1 on the tongue. It is thought \nthat GCTs arise from Schwann cells1 as these tumor \ncells are positive for S100 protein. There are also \nsimilarities between the ultrastructural features of \nthese tumor cells and those of Schwann cells1.\n\n\n\nGCTs may occur in patients of all ages, and most \ncommonly occur in the fourth and sixth decades of \nlife. Women tend to be affected more commonly \nthan men. GCTs are rare in childhood. They can \narise anywhere on the body, and commonly presents \nas a solitary painless nodule affecting the skin, \ntongue, oral cavity and less frequently, the breast, \ngastrointestinal tracts.\n\n\n\nDifferential diagnoses for skin colored painful \nnodules include rhabdomyosarcoma, paraganglioma, \noncocytic tumor, neuroma and leiomyoma. While \nrhabdomyomas may bear histological resemblance \nto GCTs, the former usually are desmin and \nmyoglobin positive.\n\n\n\nThe diagnosis of atypical granular cell tumor is \nproblematic. To date, the clinical evolution of \nGCTs is poorly understood. Although most GCTs \nare benign, some display malignant features. The \ndistinction between benign, atypical, and malignant \nGCT is controversial due to morphological and \nimmunohistochemical overlap and the lack of \nconsistent histological and phenotypic criteria that \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54MJD 2016 Jul Vol 36\n\n\n\nno associations established between the occurrence \nof both granular cell tumor and hidradenitis \nsuppurativa in the medical literature, and their co-\nexistence in this patient is presumed to be sporadic. \nThe clinician treating a patient with atypical GCT \nfaces a few challenges - in particular the extent to \nwhich the patient should be investigated. A sensible \napproach would be to discuss the present state of \nknowledge with the patient and come to a shared \ndecision about how to proceed. The diagnosis \nand management of GCTs provide a stimulating \nlearning opportunity for the clinician and represent \na meaningful opportunity for continuing medical \neducation.\n\n\n\nWith regard to treatment, wide local excision is \nan appropriate treatment for benign and atypical \ntumors to ensure negative margins4. The role \nof adjuvant chemotherapy and radiotherapy is \nuncertain, but should be considered in patients with \nrecurrent malignant GCTs or metastatic disease. All \npatients should be followed up for recurrence and \ndistant metastasis regardless of the initial nature of \nthe disease4 as the appearance of metastasis remains \nto be the most unequivocal measure of malignancy.\n\n\n\nThis patient was also diagnosed with hidradenitis \nsuppurativa affecting her left axilla. It appears that \nher axillary lesions are not related to her diagnosis of \nan atypical GCT on her abdomen. There have been \n\n\n\nReferences\n \n1. Spencer D. Granular cell tumour of tongue: A case report. \n\n\n\nSaudi Dent J. 2009;21(2):75\u20138. \n2. Machado I, Cruz J, Lavernia J et al. Solitary, multiple, \n\n\n\nbenign, atypical, or malignant: the \u201cGranular Cell Tumor\u201d \npuzzle. Virchows Arch. 2016;468(5):527-38. \n\n\n\n3. Fanburg-Smith JC, Meis-Kindblom JM, Fante R, \nKindblom LG. Malignant granular cell tumor of soft tissue: \ndiagnostic criteria and clinicopathologic correlation. Am J \nSurg Pathol. 1998;22:779\u201394. \n\n\n\n4. Singh VA, Gunasagaran J, Pailoor J. Granular cell \ntumour: malignant or benign? Singapore Medical Journal. \n2015;56(9):513-517.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n55 MJD 2016 Jul Vol 36\n\n\n\nONCOLOGIC DERMATOLOGY - Case Report\n\n\n\nA PAINFUL ERYTHEMATOUS PLAQUE ON THE NECK\nShamharini N1, Anisha B1, Zuliatul FB2, Azura MA1\n\n\n\nCorresponding Author and Reprint Request \nDr Shamharini Nagaratnam\nNo 1, Jalan 33/41 Kemuning Utama, Kemuning Permai \n40400 Shah Alam,Selangor, Malaysia.\nEmail: shamharininagaratnam@yahoo.com\n\n\n\n1 Department of Dermatology, Hospital Kuala Lumpur\n2 Department of Pathology, Hospital Kuala Lumpur\n\n\n\nOn physical examination, there was a large, \nindurated, erythematous plaque (measuring \n10\u00d74cm) with surrounding smaller papules on the \nbase of the right neck extending to the anterior chest \nwall (Figure 1, 2). Multiple enlarged cervical lymph \nnodes were palpable on both sides of the neck.\n\n\n\nIn our patient, cutaneous metastasis was our primary \nsuspicion. Possible differentials included cutaneous \nlymphoma, mycobacterial infection, radiation \ndermatitis and contact dermatitis. We proceeded \nwith a skin biopsy to confirm our diagnosis. The \nhistopathology report revealed dilated lymphatic \nspaces showing tumor emboli. The tumor cells had \npleomorphic nuclei, prominent nucleoli and ample \ncytoplasm with mitotic figures readily seen (Figure \n3, 4).\n\n\n\nThese cells were immunoreactive to CDX2, CK7 \nand CK20 (Figure 5, 6, 7).The biopsy concluded \nmetastatic adenocarcinoma consistent with \ncolorectal origin.\n\n\n\nIntroduction\nSkin is a relatively uncommon site of spread for \nmetastatic carcinomas. Nevertheless, a prompt \ndiagnosis is important as it represents advanced \ndisease. The detection of cutaneous metastasis \nradically alters therapeutic plans as it signals poor \nprognosis. Presentation is often rather vague, as \nit mimics many other benign skin conditions. \nTherefore, a high clinical suspicion is warranted to \nclinch the diagnosis early.\n\n\n\nWe present a case of a 72-year-old lady with a \nhistory of recurrent colorectal carcinoma, who \npresents with a painful erythematous rash on her \nneck.\n\n\n\nCase history\nA 72-year-old Chinese female presents with \na painful plaque on the right side of her neck, \nassociated with neck swelling for the last 3 months. \nThe lesion initially started as erythematous non-\npruritic papules in a linear distribution, which \nsubsequently coalesced to form a tender plaque. \nThere was no fever, loss of weight or appetite.\n\n\n\nShe was diagnosed with colonic adenocarcinoma \n(T3N0MO) in 2012, whereby she was treated \nsurgically with a hemicolectomy and received \nadjuvant chemotherapy. She received another \ncourse of chemotherapy in 2014 for suspected local \nrecurrence.\n\n\n\nFigure 1. Violaceous plaque distributed along \nthe base of the neck.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56MJD 2016 Jul Vol 36\n\n\n\nFigure 2. On closer inspection, multiple excoriations \nwith serous discharge is visible on the plaque.\n\n\n\nFigure 4. On higher magnification, tumor emboli \nis seen within the lymphovascular space (H&E, \nmagnification X400).\n\n\n\nFigure 6. Tumor cells are immunoreactive to CK7.\n\n\n\nFigure 3. The image above shows two fragments \nof skin tissue containing scattered tumor infiltrates \nwithin the dermis with areas of subcutaneous fat \nwith haemorrhage (H&E, magnification X100).\n\n\n\nFigure 5. Immunohistochemistry shows positive \nstaining for CDX2.\n\n\n\nFigure 7. Immunohistochemistry shows positive \nstaining for CK20.\n\n\n\nSubcutaneous fat \nwith haemorrhage\n\n\n\nScattered tumor infiltrates\n\n\n\nTumor cells\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n57 MJD 2016 Jul Vol 36\n\n\n\nis considered to be in remission. Histopathology \nexamination is essential to clinch the diagnosis. \nDemonstration of tumour cells resembling the \nprimary tumour, with positive immunohistochemical \nmarkers will favour the diagnosis of cutaneous \nmetastasis.\n\n\n\nIn this lady, the skin lesion was the first sign of \ndistant spread which prompted her to seek treatment. \nIt is therefore essential for the treating physician to \nhave a high index of suspicion of recurrence in this \ncohort of patients who present with new onset skin \nlesions. Cutaneous infiltration is a sign of advanced \nmetastatic disease and treatment options may be \nlimited. There is a role for wide local excision with \nclear margins in those with isolated skin lesions. \nHowever, majority of these patients have widespread \ndisease and will often require multidisciplinary \ncare and further management with an oncologist. \nThe treatment is usually centered on palliative care \naiming to prolong survival. Similarly, in the case \nof our patient, she was referred to the oncology \nteam for further assessment and staging. Contrast \nenhanced computed tomography (CECT) showed \nlocal recurrence of colorectal carcinoma with \nwidespread metastasis to the lungs, liver, spleen and \nlymph nodes. She is currently undergoing palliative \nchemotherapy.\n\n\n\nDiscussion\nColorectal carcinoma is a common malignancy seen \nin both men and women. The incidence of cutaneous \nmetastasis has been reported to be within 2.3-6% of \nall colorectal carcinomas1,2. It usually occurs within \nthe first 2 years of resection of the primary tumour3.  \nMetastatic dissemination to the skin occurs via the \nlymphatics, hematogenous spread, direct extension \nand surgical implantation. The most common site of \nmetastasis is the abdominal wall including surgical \nincision scars. Other cutaneous sites commonly \ninvolved include the pelvis, back, chest, upper \nextremities, head and neck. Identification of skin \nmetastasis is a poor prognostic sign and reflects \nwidespread disease with simultaneous metastasis to \nother sites such as lung, liver and peritoneum4.\n\n\n\nMetastatic carcinoma can present in various \nmorphological appearances. The most common \npresentation is as single or multiple painless skin \ncolored to violaceous nodules. Occasionally it can \nmimic benign dermatoses such as epidermal cysts, \nneurofibromas, lipomas and cicatricial morphea-\nlike plaques2. Rarely, it can resemble inflammatory \nlesions known as carcinoma erysipelatoides with \nwell-defined indurated erythema. Cutaneous \nmetastasis may be present de novo, when the patient \n\n\n\nReferences\n \n1. Pereira WA, Humaire CR, Silva CS, Fernandes LH. Sister \n\n\n\nMary Joseph\u2019s nodule: a sign of internal malignancy. An \nBras Dermatol. 2011; 86: S118\u2013S120. \n\n\n\n2. Lookingbill DP, Spangler N, Helm KF. Cutaneous \nmetastases in patients with metastatic carcinoma: a \nretrospective study of 4020 patients. J Am Acad Dermatol. \n1993; 29: 228\u2013236. \n\n\n\n3. Verardino GC, Silva RS, Obadia DL, et al. Rare cutaneous \nmetastasis from a probable basaloid carcinoma of the \ncolon mimicking pyogenic granuloma. An Bras Dermatol. \n2011; 86: 537\u2013540.\n\n\n\n4. Lookingbill DP, Spangler N, Sexton FM. Skin involvement \nas the presenting sign of internal carcinoma. A retrospective \nstudy of 7316 cancer patients. J Am Acad Dermatol. 1990; \n22: 19\u201326.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Commentary\n\n\n\nDERMATOLOGY IN VIETNAM WAR\nLong V\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nNational University Hospital, 5 Lower Kent Ridge Rd, \nSingapore 119074\nEmail: valencialong@gmail.com\n\n\n\nPorphyria Cutanea Tarda(PCT)\nPCT is more rarely associated with TCDD \nexposure. PCT is characterised by blistering in sun \nexposed areas, hypertrichosis, milia formation and \ndevelopment of sclerodermoid plaques in affected \nareas. Despite studies of Vietnam veterans not \nfinding a clear increased risk of PCT development \nafter exposure4, PCT is regarded as an eligible \ncondition for veterans to seek evaluation under the \nU.S Department of Veterans Affairs. \n\n\n\nMelanoma and non-melanoma cancer\nAlthough melanoma and non-melanoma skin cancer \nhave been associated with TCDD exposure, most of \nthe human dioxin exposure studies till date have not \nshown an increased incidence of skin cancers.\n\n\n\nNon-Hodgkin Lymphoma\nNon-Hodgkin lymphomas, in particular cutaneous \nT/B-cell lymphomas are associated with Agent \nOrange exposure. Studies5 have shown that patients \nwith mycosis fungoides and previous Agent Orange \nexposure have a higher prevalence of the palmaris \net plantaris presentation subtype suggesting that \nhigher disease concentration on affected areas could \narise from direct herbicide exposure. \n\n\n\nSoft-tissue sarcoma\nMost studies6 have failed to demonstrate an \nincreased risk of soft-tissue sarcoma in Vietnam \nveterans. However, 1 study has cited veterans \ndeveloping leiomyosarcomas, dermatofibrosarcoma \nprotuberans and other soft-tissue sarcomas.\n\n\n\nOther skin conditions \nAt least 1 epidemiologic study7 has cited veterans \nbeing at increased risk for eczema, benign fatty \ntumors, milia, epidermoid cysts, dyschromias, \nincreased skin sensitivity and non specific rashes.\n\n\n\nIntroduction\nThe Vietnam War, though over for nearly four \ndecades, had left veterans suffering from a multitude \nof ailments and dermatological conditions from \nperhaps the most memorable organochlorine \nexposure - Agent Orange. This note serves to \nremind us about the dermatoses arising from the \nVietnam War and is a tribute to those who have \nfought valiantly in it.\n\n\n\nDuring the war, herbicides such as Agent Orange \nwere used to defoliate enemy crops in the Operation \nRanch Hand (ORH) campaign. Throughout the \ndecade long campaign, almost 20 million gal of \nAgent Orange (estimated 366kg of TCDD) was \napplied to over 3.6 million acres of South Vietnam1. \nThe exposure to Agent Orange containing 2, 3, 7, \n8 - tetrachlorodibenzo-p-dioxin (TCDD) has led to \nvarious skin disorders. \n\n\n\nChloracne\nChloracne is the most recognized dermatosis arising \nfrom the Vietnam war. It presents with multiple non-\ninflammatory comedone-like lesions interspersed \nwith straw-colored cysts commonly affecting the \nmalar crescent around the eyes and periauricular \nareas. There is sometimes genital and truncal \ninvolvement. Hypertrichosis, grey discoloration \nand folliculitis are associated2,3. Perhaps the most \nnotable figure to have been affected by chloracne \nwas former President Viktor Yushchenko in the \n2004 poisoning case. Chloracne is known to regress \nbetween 6 months to 3 years3.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n59 MJD 2016 Jul Vol 36\n\n\n\nReferences\n \n1. Dunagin WG. Cutaneous signs of systemic toxicity due to \n\n\n\ndioxins and related chemicals. J Am Acad Dermatol. 1984; \n10(4):688-700\n\n\n\n2. Burton JE, Michalek JE, Rahe AJ. Serum dioxin, \nchloracne, and acne in veterans of Operation Ranch Hand. \nArch Environ Health. 1998;53(3):199-204.\n\n\n\n3. Tindall JP. Chloracne and chloracnegens. J Am Acad \nDermatol. 1985;13:539-558.\n\n\n\n4. Kim JS, Lim HS, Cho SI et al. Impact of Agent Orange \nexposure among Korean Vietnam veterans. Ind Health. \n2003;41:149-157.\n\n\n\n5. Jang MS, Jang JG, Han SH, et al. Clinicopathological \nfeatures of mycosis fungoides in patients exposed to Agent \nOrange during the Vietnam War. J Dermatol. 2013;40:606-\n612.\n\n\n\n6. The Selected Cancers Cooperative Study Group. The \nassociation of selected cancers with service in the US \nmilitary in Vietnam. II. Soft-tissue and other sarcomas. \nArch Intern Med. 1990;150(12):2485-2492\n\n\n\n7. Patterson A, Kaffenberger B, Keller R, et al. Skin diseases \nassociated with Agent Orange and other organochlorine \nexposures. J Am Acad Dermatol. 2016; 74(1):143-70.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n60MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Commentary\n\n\n\nDERMATOLOGY AND LOVE\nLong V\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nNational University Hospital, 5 Lower Kent Ridge Rd, \nSingapore 119074\nEmail: valencialong@gmail.com\n\n\n\nearly in 19083, kissing nevi have been described to \nbe located on the upper and lower eyelids, recalling \nperhaps, a most delicate and tender kiss between \ntwo lovers holding each other\u2019s hearts.\n\n\n\nKissing ulcers have been commonly used to \nportray ulcers occurring on opposing surfaces of \nthe vulva due to Herpes simpex infection, or other \nnon herpetic infections such as salmonellosis4 and \ninfectious mononucleosis5.\n\n\n\nThe honey-crusted appearance of impetigo inspires \na sweet feeling of love.\n\n\n\nTenderness is a term sprinkled liberally through the \nannals of dermatology, and a paradigm example is \nthe exact localisation of tenderness with the help of \na pin head in a glomus tumor - also referred to as \nLove\u2019s sign6.\n\n\n\nHeart shaped lesions have been observed as unusual \npresentations of many common conditions7 -  \nincluding cafe au lait macules, solar lentigines, nevus \nspilus, congenital melanocytic nevi, hemangiomas, \nand even ulcers. Love perhaps, is found in the least \nexpected of places, in the common every-day life.\n\n\n\nGifts and flowers often escort love, with all its \nstrangeness. The singular plant that has captured the \nimagination of lovers and dermatologists alike is the \nrose.\n\n\n\nThe rosette is a popular sign used to describe \nhistological appearances of interstitial granulomatous \ndermatitis and peripheral neuroblastomas, clinically \nin linear IgA disease and dermatoscopically in \nsquamous cell carcinoma8.\n\n\n\nPigmented fungiform papillae of the tongue appear \ndermatoscopically as rose petals9.\n\n\n\nVaricella zoster infection manifests as \u201cdew-drops \non a rose petal\u201d.\n\n\n\nThe term Pityriasis rosea reminds us of the greatest \nsymbol of love \u2013 the rose.\n\n\n\nIntroduction\nAmong the many passionate addresses1 Vladimir \nNabokov, one of Russia\u2019s greatest literary giants to \nhis great love and wife was, \u201cI love you, my sun, \nmy life, I love your eyes - closed - all the little tails \nof your thoughts, your stretchy vowels, your whole \nsoul from head to heels.\u201d\n\n\n\nDermatology, like love, is infused with metaphor \nand blessed by the intricacies of language. Terms \nof endearment, both historical and modern, \nhave been woven intimately with dermatological \ndescriptions. In fact, to many dermatologists, how \ncan dermatology not itself be a form of love?\n\n\n\nCherubism reminds us of the rosy-cheeked child-\nangel when we gaze into the eyes of our beloved \nones. Then, as we plant a gentle angel kiss squarely \nin the middle of their forehead, we might recollect \nthe nevus simplex upon a newborn\u2019s face.\n\n\n\nThe term \u201cVenereal\u201d was derived from Latin \nvenerus, from Venus, Roman goddess of love, \nbeauty, sex.\n\n\n\nHer son, Cupid, went on to inspire \u201cCupid\u2019s disease\u201d \nas a description of syphilis.\n\n\n\nRosacea brings to mind the blush of a lover\u2019s \ncountenance, as do the red, almost himself or herself \nfiery, papules of Sweet\u2019s syndrome.\n\n\n\nKissing lesions in flexural areas affected by Paederus \ndermatitis2 are also recognised.\n\n\n\nKissing nevi are rare congenital melanocytic nevi \nthat are located on adjacent places at which division \nhad previously occurred during embryogenesis. \nSince the first report of such nevi by Von Micheal \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n61 MJD 2016 Jul Vol 36\n\n\n\nMore Than Skin Deep\nDermatology has passed through time, collecting \nmorphological descriptions inspired by the \ngrandness of nature and the exuberance of love. For \ndermatology, as lovers would quite agree, is more \nthan skin-deep, and certainly more than what meets \nthe eye.\n\n\n\nRoseola infantum is caused by the human herpes \nvirus.\n\n\n\nTyphoid fever produces rose spots. Is love itself not \na feverish dream? \n\n\n\nReferences\n \n1. Nabokov V. (2014). Letters to V\u00e9ra. London: Penguin \n\n\n\nBooks Ltd\n2. Haddad Junior V. \u201cSign of the kiss\u201d in dermatitis caused by \n\n\n\nvesicant beetles (\u201cpot\u00f3s\u201d or Paederus sp.) Anais Brasileiros \nde Dermatologia. 2014; 89(6): 996-997. \n\n\n\n3. Hamming N. Anatomy and embryology of the eyelids: \na review with special reference to the development of \ndivided nevi. Pediatr Dermatol. 1983; 1: 51\u201358\n\n\n\n4. Pelletier  F, Aubin  F, Puzenat  E. Lipschutz genital \nulceration: a rare manifestation of paratyphoid fever. Eur J \nDermatol 2003; 13 (3): 297- 298\n\n\n\n5. Portnoy  J, Ahronheim  GA, Ghibu  F, et al. Recovery \nof Epstein-Barr virus from genital ulcers. N Engl J Med \n1984; 311 (15): 966- 968\n\n\n\n6. Love JG. Glomus tumors: diagnosis and treatment. Proc \nStaff Meet Mayo Clin. 1944; 19: 113\u20136.\n\n\n\n7. Bree AF, Cole P, Siegfried EC. A Love of Dermatology. \nJAMA Dermatol. 2014; 150(2): 121-122. \n\n\n\n8. Rubegni  P, Tataranno  DR, Nami  N, Fimiani  M.  Rosettes: \noptical effects and not dermoscopic patterns related to skin \nneoplasms. Australas J Dermatol. 2013; 54(4): 271-272.\n\n\n\n9. V. Pinos-Le\u00f3n. Dermoscopic Features of Pigmented \nFungiform Papillae of the Tongue. Actas Dermo-\nSifiliogr\u00e1ficas 2015; 106(7): 593.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n62MJD 2016 Jul Vol 36\n\n\n\nGENERAL DERMATOLOGY - Commentary\n\n\n\nTURMERIC- AN INDIAN GOLDEN CURRY SPICE,\nA GOLDEN CURE?\nLong V\n\n\n\nCorresponding Author and Reprint Request \nDr Valencia Long\nNational University Hospital, 5 Lower Kent Ridge Rd, \nSingapore 119074\nEmail: valencialong@gmail.com\n\n\n\nTurmeric may also inhibit the expression of TNF-a \ninduced interleukins thought to be contributory \nin inflammatory psoriasis3. Recently, a Chinese \nstudy4 supports turmeric efficacy in  mouse models \nshowing significant inhibition of interleukin (IL) - \n17, IL-22, IFN-g, IL-2, IL-8 and TNF-a in T cells. \n\n\n\nTurmeric and wound healing \nTurmeric may be efficacious in various forms \nof wound healing including thermal burns, \nopen wounds, and wounds sustained by \nimmunocompromised patients. Studies performed \non diabetic rats demonstrated that oral administration \nof curcumin reduced the oxidative stress and levels \nof serum lipid peroxidation, decreased glycation \nand collagen cross-linking in the rat\u2019s tail tendon \nand skin5. Curcumin\u2019s role in downregulating both \ninflammatory and fibrogenic cytokines in mice \nexposed to ionizing radiation also makes it effective \nin ameliorating radiation-induced delays in wound \nrepair6.\n\n\n\nTurmeric against skin cancers\nSeminal work by Azuine and Bhide7 demonstrated \nthat dietary turmeric (2%) could prevent DMBA-\ninduced skin tumorigenesis. Since then, other \nstudies8 have shown that turmeric could modulate \nseveral cytochromes (cytochrome P-450, hepatic \ncytochrome b5) conferring protective effects. \nTo date, many in-vitro studies have shown that \ncurcuminoids protect normal keratinocytes from \nfree oxygen radical stress9, and induces apoptosis \nin human basal carcinoma cells, and mouse \nmelanoma cells. A phase I clinical study10 on \nhumans with Bowen\u2019s disease has demonstrated that \nadministration of large doses of curcumin (up to 8g/\nday for 3 months) led to histologic improvement \nof precancerous lesions in around 33% of patients \nwithout toxicity.\n\n\n\nTurmeric, or Curcuma longa L. is an important \nspice used in Indian folk medicine. Apart from its \nuse in treating hepatobiliary disorders, turmeric is \nregarded as an anti-septic, analgesic and wound-\nhealing agent. Preclinical studies have demonstrated \nthat turmeric and curcumin, its principle compound, \nare effective in treating psoriasis, aids wound healing \nand preventing UV-induced skin damage. This note \nrecaps the history of turmeric and explores some of \nits uses that are applicable and validated by modern \nmedicine.\n\n\n\nTurmeric is a tropical plant native to India. Its name \noriginated from the medieval Latin term terramerita \n- meaning \u201cmeritorious earth\u201d1. In India, turmeric \nis closely linked with the socio-cultural life of \nthe populace, and is used extensively in various \nreligious and auspicious ceremonies.\n\n\n\nAncient Indian medicinal texts cite turmeric\u2019s role \nin treating various skin conditions. In Ayurveda, \nturmeric is known as Varna datri and was found \nto be useful for inflammations, abscesses, eczema, \nleukoderma, urticaria, psoriasis, acne, and bruises.\n\n\n\nTurmeric and psoriasis \nTurmeric is an experimental drug for treating \npsoriasis. Human studies have shown that topical \napplication of a gel preparation of 1% curcumin \ninduced quicker resolution than calcipotriol \nointment (Dovonex).\n\n\n\nIt is thought that curcumin may inhibit the \nproliferation of keratinocytes via decreasing \nthe levels of keratinocyte transferring receptor \n(TRR) expression, the severity of parakeratosis \nand the density of epidermal CD8+ T cells2. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n63 MJD 2016 Jul Vol 36\n\n\n\nalternative for patients who are not amenable to \nsurgery or have multiple precancerous lesions such \nas transplant patients. Despite growing evidence \nof its efficacy, it is important to note that turmeric \ncannot be applied directly on skin lesions because \nof potential allergic contact dermatitis11,12,13.\n\n\n\nTurmeric\u2019s efficacy against progression and \nprevention of basal cell carcinoma, squamous cell \ncarcinoma and melanoma - globally important skin \ncancers- makes it a valuable compound for further \nresearch. It potentially represents a low risk oral \n\n\n\nReferences\n \n1. Ishita C, Kaushik B, Uday B, et al. Turmeric and curcumin: \n\n\n\nbiological actions and medicinal applications. Curr Sci. \n2004;87:44\u201353. \n\n\n\n2. Heng M, Song M, Harker J et al. Drug-induced suppression \nof phosphorylase kinase activity correlates with resolution \nof psoriasis as assessed by clinical, histological and \nimmunohistochemical parameters. Br J Dermatol. \n2000;143:937\u201349.\n\n\n\n3. Cho JW, Lee KS, Kim CW. Curcumin attenuates the \nexpression of IL-1beta, IL-6, and TNF-alpha as well as \ncyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB \nand MAPKs as potential upstream targets. Int J Mol Med. \n2007;19:469\u201374.\n\n\n\n4. Kang D, Bowen L, Lei L et al. Cucurmin shows excellent \ntherapeutic effect on psoriasis in mouse model. Biochimie \n2016. Article in press.\n\n\n\n5. Sajithlal GB, Chithra P, Chandrakasan G. Effect of curcumin \non the advanced glycation and cross-linking of collagen in \ndiabetic rats. Biochem Pharmacol. 1998;56:1607\u201314.\n\n\n\n6. Okunieff P, Xu J, Hu D, et al. Curcumin protects against \nradiation-induced acute and chronic cutaneous toxicity in \nmice and decreases mRNA expression of in fl ammatory \nand fi brogenic cytokines. Int J Radiat Oncol Biol Phys. \n2006;65:890\u20138.\n\n\n\n7. Azuine MA, Bhide SV. Chemopreventive effect of turmeric \nagainst stomach and skin tumors induced by chemical \ncarcinogens in Swiss mice. Nutr Cancer. 1992;17:77\u201383.  \n\n\n\n8. Villase\u00f1or IM, Simon MK, Villanueva AM. Comparative \npotencies of nutraceuticals in chemically induced skin \ntumor prevention. Nutr Cancer. 2002;44:66\u201370.\n\n\n\n9. Bont\u00e9 F, Noel-Hudson MS, Wepierre J, et al. Protective \neffect of curcuminoids on epidermal skin cells under free \noxygen radical stress. Planta Med. 1997;63:265\u20136.\n\n\n\n10. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial \nof curcumin, a chemopreventive agent, in patients with \nhigh-risk or pre-malignant lesions. Anticancer Res. \n2001;21(4B):2895\u2013900.\n\n\n\n11. Fischer L, Agner T. Cucurmin allergy in relation to yellow \nchlorhexidine solution used for skin disinfection prior to \nsurgery. Contact Dermatitis 2004; 51: 39-40 \n\n\n\n12. Chaudari S et al. Cucurmin: A contact allergen. J Clin \nAesth Dermatol 2015; 8: 43-8\n\n\n\n13. Goh C et al. Allergic contact dermatitis to Curcuma longa \n(turmeric). Contact Dermatitis 1987; 17: 186\n\n\n\n \n\n\n\n\n\n\n\n\nNOTES\n\n\n\n\n\n\n\n\nNOTES\n\n\n\n\n\n\n\n\n\n\n\n\n\n"
"\n\nVolume 49  |  Dec 2022  |  ISSN: 1511-5356\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 i\n\n\n\nNotice to Authors\nThe Malaysian Journal of Dermatology welcome manuscripts \non all aspects of cutaneous medicine and surgery in the \nform of original articles, research papers, case reports and \ncorrespondence. Contributions are accepted for publication on \ncondition that they are submitted exclusively to the Malaysian \nJournal of Dermatology. The Publisher and Editors cannot \nbe held responsible for errors or any consequences arising \nfrom the use of information contained in this journal; the \nviews and opinions expressed do not necessarily reflect those \nof the publisher and Editors, neither does the publication of \nadvertisements constitute any endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: tanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and legends \nfor the photographs should be listed after the references in \nthe article. The article should be no more than 2-3 pages in \nlength.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should not \nexceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. Article \ntypes may include Review, Report or Case Report Format.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Discussion, \nConclusion and References. A Structured Abstract of not \nmore than 250 words must be included. It should consist of \nfour paragraphs, labelled Background, Methods, Results and \nConclusion. It should describe the problem studies, how the \nstudy was performed, the main results, and what the author(s) \nconcluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to six \nauthors: if more than six authors, include the first six authors \nfollowed by et al.; (2) title of paper; (3) title of the journal as \nabbreviated in the Index Medicus; (4) year of publication; \n(5) volume number; (6) first and final page numbers of the \narticle.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or editor(s); \n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4) \nplace of publication; (5) publisher; (6) year; (7) page(s) \nreferred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine 2002. \np.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a delay \nto publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference number \ncorresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49ii\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n2\n\n\n\n12\n\n\n\n20\n\n\n\n25\n\n\n\n28\n\n\n\n33\n\n\n\n37\n\n\n\nCASE REPORT \n\n\n\nA Case of Churg-Strauss Syndrome Mimicking \nCutaneous and Tuberculous Lymphadenitis\nChang WH, Gunasekaran R, Chandran M, Ng FY, \nAbdul Rahman IR, Ng TG\n\n\n\nSpontaneous Re-pigmentation of Vitiligo Following \nExcision of Halo Congenital Melanocytic nevi: An \nInteresting Case Report\nGosavi AP, Chavan RB, Bhatt N, Kundale DR\n\n\n\nA Report of Staphylococcus Scalded Skin Syndrome \nin Adult\nTeo JK, Zakaria SB, Wan Abdullah WNH\n\n\n\nSuccessful Treatment of Recalcitrant Ungual \nWart with Tuberculin Purified Protein Derivative \nImmunotherapy \nBalakrishnan K, Wan Ahmad Kammal WSL, Mohd Nor \nN\n\n\n\nCoevality of Secondary Syphilis with Condyloma \nAcuminata in a HIV reactive MSM: Rare Triple \nSexually Transmitted Infections\nPatrick S, Kar S, Nandwani S\n\n\n\nACKNOWLEDGEMENT\n\n\n\nORIGINAL ARTICLE\n\n\n\nBringing the Treatment of Atopic Eczema into a \nNew Era with Janus Kinase Inhibitors \u2013 A Position \nStatement by the Persatuan Dermatologi Malaysia\nAzizan NZ, Jamil A, Chang CC, Ambrose D, Foong \nBBH, How KN, Ramalingam R, Kader Ibrahim SB, \nSyed Nong Chek SR, Tan WC, Wong HL \n\n\n\nSerum Vitamin B12 Level and Dietary intake in \nAdult Atopic Dermatitis: A Case Control Study\nChe Abdul Rahim AR, Rusdu MB, Jamil A, Ramalingam \nR\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 iii\n\n\n\nEditor-in-Chief\n\n\n\nAssoc Prof Dr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, Adv M Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nEditorial Board\nAssoc Prof Dr Henry Foong Boon Bee FRCP, \nFAMM Ipoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nDr Norashikin Shamsudin FRCP, Adv M Derm     \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed, Adv M \nDerm Wilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, Adv \nM Derm Wilayah Persekutuan Kuala Lumpur   \n    \nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nAssoc Prof Dr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDermatological Society of Malaysia | Persatuan Dermatologi Malaysia\n\n\n\nExecutive Committee\nDr Sabeera Begum, MMed - President\nDr Tan Wooi Chiang, Adv M Derm - Vice \nPresident\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nSecretary\nDr Sharifah Rosniza Syed Nong Chek, Adv M \nDerm - Treasurer\nDato Dr Noor Zalmy Azizan, Adv M Derm - \nPast President\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2022 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - Committee \nMember\nDr Nazirin Ariffin, MRCP - Committee Member\nDr Kelvin How Kang Nien, Adv M Derm - \nCommittee Member\nDr Teeba Raja, Adv M Derm - Committee \nMember\n\n\n\nDermatological Society of Malaysia \nMedical Academics of Malaysia, Unit 1.6, Level 1, Enterprise 3B, Technology Park Malaysia, Jalan \nInnovasi 1, Lebuhraya Puchong- Sg Besi, Bukit Jalil, 57000 Kuala Lumpur, Malaysia\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 492\n\n\n\nORIGINAL ARTICLE\n\n\n\nBringing the Treatment of Atopic Eczema Into a New Era with Janus Kinase \nInhibitors: A Position Statement By the Persatuan Dermatologi Malaysia\n\n\n\nNoor Zalmy Azizan1, AdvMDerm, Adawiyah Jamil2, AdvMDerm, Chang Choong Chor3, AdvMDerm, Dawn \nAmbrose4, MRCP, Henry Foong Boon Bee5, FRCP, How Kang Nien6, AdvMDerm, Rajalingam Ramalingam7, \nAdvMDerm, Sabeera Begum Bt Kader Ibrahim8, MPaeds, Sharifah Rosniza Binti Syed Nong Chek1, AdvMDerm, \nTan Wooi Chiang9, AdvMDerm, Wong Hoi Ling10, MRCPCH\n\n\n\n1Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Hospital Canselor Tuanku Muhriz, UKM, Kuala Lumpur, Malaysia\n3Gleneagles Kuala Lumpur, Malaysia \n4Hospital Pantai Kuala Lumpur, Malaysia\n5Foong Skin Specialist Clinic, Ipoh, Malaysia\n6Hospital Pengajar Universiti Putra Malaysia, Serdang, Malaysia\n7Hospital Tengku Ampuan Afzan, Kuantan, Malaysia\n8Hospital Tunku Azizah, Kuala Lumpur, Malaysia\n9Hospital Pulau Pinang, Pulau Pinang, Malaysia\n10Hospital Wanita dan Kanak-kanak, Kota Kinabalu, Sabah, Malaysia\n\n\n\nAbstract\nAtopic eczema (AE) is a complex, chronic and recurrent inflammatory pruritic skin condition that \nimpacts the quality of life and exerts an economic toll on patients and their families. One of the factors \ncontributing to AE is the immune dysregulation of the Janus kinase-signal transducers and activators \nof transcription (JAK-STAT) inflammatory pathway. This has prompted the conduct of various large \nclinical trial programs to evaluate the efficacy and safety of Janus kinase inhibitors (JAK-i) for AE. \nThe overall and significant benefit of these drugs from clinical studies resulted in regulatory approvals \nfor JAK-i to treat moderate-to-severe atopic eczema. The objective of this position paper was to \nevaluate the safety, efficacy and role of upadacitinib, baricitinib and abrocitinib in managing AE and \nupdate the current recommended treatment algorithm within the 2018 Malaysian Clinical Practice \nGuidelines for the Management of Atopic Eczema. The Persatuan Dermatologi Malaysia recommends \nthat these JAK-i can be considered as an option for systemic therapy in severe AE.  \n\n\n\nKey Words: Atopic dermatitis, JAK-i, Recommendations\n\n\n\nCorresponding Author\nDato\u2019 Dr. Noor Zalmy Azizan\nDepartment of Dermatology, \nHospital Kuala Lumpur, \nTingkat 6, Kompleks Pakar & Rawatan Harian, \nPersiaran Hospital, \n50586 Kuala Lumpur.\nEmail: noorzalmy@yahoo.com\n\n\n\nIntroduction\nAtopic eczema (AE), also known as atopic \ndermatitis, is a complex, chronic and recurrent \ninflammatory pruritic skin condition that \ndevelops in early childhood and can persist into \nadulthood.\n\n\n\nThe global prevalence of AE ranges between \n15-30% in children1,2 and 2-10% in adults.1 In \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 3\n\n\n\nMalaysia, the prevalence of AE has not been \nwell studied. Malaysia participated in the \nInternational Study of Asthma and Allergies \nin Childhood (ISAAC). The prevalence of \nchildhood AE in 1996 in the 6-7 year and \n13\u201314 year age groups increased from 9.5% \nand 8.9% in 1996 to 12.6% and 9.9% in 2006, \nrespectively.3 A more recent cross-sectional \nsurvey by Goh YY, et al. involving 384 children \naged 1-6 years old attending kindergarten in \nKuala Lumpur revealed eczema in 13.4%.4 In \na retrospective, cross-sectional study conducted \nin the Department of Dermatology, Hospital \nKuala Lumpur, from the 1st January 2008 to 31st \nDecember 2014, eczema was the most common \ndisease (39.07%) treated in the skin clinic, of \nwhich 6.9% were AE.5\n\n\n\nAE, particularly in those with moderate-to-\nsevere disease, significantly impacts the patient\u2019s \nand their family\u2019s quality of life (QoL).2,6-8 The \nsymptoms of AE are significantly associated \nwith the severity of disease. AE symptoms \nlead to sleep disturbance, anxiety, depression \nand embarrassment in children and adults.6,8 \nThe effects of AE on children extend beyond \nthe short-term and have been associated with \nan increased risk of developing psychosocial, \ncognitive and functional impairment and \nbehavioural problems.2 A more recent study \ndemonstrated an increased risk in children with \nallergic disorders developing attention deficit \nhyperactivity disorders or autism spectrum \ndisorder.9\n\n\n\nAE incurs a hefty financial burden on the \nfamilies of children with AE and adult patients. \nThe direct cost of AE is estimated to range \nfrom USD199-USD74310 and \u20ac2242 to \u20ac6924.7 \nIndirect cost including loss of work and \nproductivity ranges from \u20ac7277 to \u20ac14,236 in \nadult AE patients.7 \n\n\n\nThe Malaysian Clinical Practice Guideline \n(CPG) for the management of AE was published \nin 2018. The objectives are to guide the correct \nand early diagnosis, and outline effective and \nsafe treatments for AE.11 It contains evidence-\n\n\n\nbased recommendations for the diagnosis, \nseverity assessment, investigations, and \navailable therapy for AE. The Janus kinase \ninhibitors (JAK-i), which are small molecule \nagents for targeted therapy, have been available \nfor use in various diseases such as rheumatoid \narthritis and psoriatic arthritis. These drugs \nhave recently been approved by the Ministry of \nHealth, Malaysia for treating moderate-to-severe \nAE. Baricitinib was approved for moderate-to-\nsevere AE in adults in September 2021,12 and \nupadacitinib in adults and adolescents aged 12 \nyears and above in May 2022.13\n\n\n\nThe recent (September 2022) EuroGuiDerm \nGuideline on Atopic Eczema recommends \nJAK-i for AE patients who are candidates for \nsystemic treatment.14 In Asia, the 2021 Japanese \nguidelines for atopic dermatitis (ADGL) and \n2022 Taiwan guidelines for the diagnosis and \nmanagement of paediatric atopic dermatitis \nrecommend JAK-i as a treatment option for \nsevere AE.15,16 Hence, the primary objective of \nthis paper is to revisit and update the current \nAE treatment recommendations with regard to \nthe position of JAK-i for treating AE within \nthe Malaysian context. We examine the role \nof the Janus kinase (JAK) enzyme in AE \npathophysiology and the mechanism of action, \nsafety and efficacy of JAK-i for this purpose.\n\n\n\nThe role of JAK enzymes in AE\nThe various pathophysiological factors \ncontributing to AE development are complex \nand include skin barrier dysfunction, immune \ndysfunction and altered cutaneous microbiome.17\n\n\n\nThe JAK enzymes constituting JAK1, JAK2, \nJAK3 and tyrosine kinase 2 (TYK2) are a \nclass of cytoplasmic tyrosine kinases. The skin \nbarrier dysfunction activates T-helper cells (TH) \nresulting in different cytokine expressions. \nAfter binding to their receptor, these cytokines \nactivate the JAK-STAT signalling pathway \nto mediate their cytokine response. This \ncontributes to the inflammatory cascade leading \nto AE. (Figure 1).18,19\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 494\n\n\n\nFigure 1. JAKs attach to the intracellular sections of the cytokine receptor chains to produce functional signalling \ncomplexes and regulate the inflammatory process through activating the intracytoplasmic transcription factors \n(STATS). These STATs move into the nucleus and regulate downstream inflammatory mediators\n\n\n\nCRLF2, cytokine receptor-like factor 2; IL, interleukin; JAK, Janus kinase; OSM; oncostatin M; STAT, signal transducer and activator of transcription; \nTSLP, thymic stromal lymphopoietin; TYK2, tyrosine kinase 2. Adapted from Chovatiya R, et al. J Allergy Clin Immunol 2021.19\n\n\n\nThe mechanism of action of JAK-i in AE\nJAK-i are small molecule compounds that \ntarget AE-associated cytokine-mediated \ninflammatory pathways. By inhibiting the \nJAK enzymes selectively and reversibly, they \nallow for a targeted approach to treating AE. \nThe three JAK-i currently available for AE \nare indicated for treating moderate-to-severe \ndisease. Abrocitinib and upadacitinib inhibit \nJAK1, whilst Baricitinib inhibits both JAK1 \nand JAK2 enzymes (Figure 1). The inhibition \nof JAK-dependent cytokines (e.g., interleukin \n[IL]-6 and IL-31) reduces the inflammation and \nitch in AE, while the inhibition of the JAK2 \nappears to reduce the pathological changes.18,20\n\n\n\nEfficacy and safety of JAK-i in treating AE\n\n\n\nEfficacy outcomes compared to placebo\nAmong the three JAK-i available for treating \nAE, the BREEZE-AD clinical programme for \nbaricitinib has the most extensive number of \n\n\n\nclinical trials (BREEZE-AD 1-7). However, \nall the studies were placebo-controlled. The \nlandmark trials for baricitinib are BREEZE-\nAD 1 and 2,21 while BREEZE-722 investigated \nits efficacy in combination with topical \ncorticosteroid (TCS). \n\n\n\nThe study population involved in the BREEZE-\nAD were patients aged \u226518 years, who had \na diagnosis of AE for \u226512 months before \nscreening and a documented history of an \ninadequate response to topical therapies and \nfailure to systemic immunosuppressants.23 \nEczema Area and Severity Index (EASI) \nscore of \u226516, a validated Investigator\u2019s Global \nAssessment (vIGA) score of \u22653 and \u226510% body \nsurface area (BSA) involvement were other \ninclusion criteria. Some important exclusion \ncriteria were a history of eczema herpeticum \na year before screening or \u22652 prior episodes \nof eczema herpeticum and current or recent \nserious infections, including herpes zoster and \ntuberculosis (TB).23\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 5\n\n\n\nUpadacitinib (MEASURE UP) and abrocitinib \n(JADE) efficacy trials were similar. They \ninvolved patients who were \u226512 years old with \na body weight of \u226540 kg and were placebo-\ncontrolled. These trials\u2019 inclusion and exclusion \ncriteria were similar to the BREEZE-AD.24,25 \nLike in BREEZE-AD 7, the abrocitinib \ntrial involving adolescents (JADE TEEN)26 \ninvestigated its efficacy on a background of \nTCS use.\n\n\n\nThe trials all had a fair representation of the \nAsian population with 20-30% of the total \nsubjects in each treatment and placebo arm. \nSignificantly more patients in the treatment \narms for all agents achieved vIGA (0,1) and \nEASI 75 compared to placebo (Tables 1-3). The \nefficacies were dose-dependent, with higher \ndoses and concomitant use of TCS eliciting \nbetter outcomes.\n\n\n\nTable 1. Baricitinib vs placebo efficacy outcomes \nStudy\n(Total subjects)\n\n\n\nParameters Proportion of patients achieving \noutcomes at 16 weeks (%)\nBaricitinib \n4 mg\n\n\n\nBaricitinib \n2 mg\n\n\n\nPlacebo\n\n\n\nBREEZE-AD121\n\n\n\n(N=624)\nvIGA (0,1) 16.8*** 11.4* 4.8\nEASI 75 24.8*** 18.7** 8.8\nItch NRS 21.5*** 12.0 7.2\n\n\n\nBREEZE-AD221\n\n\n\n(N=615)\nvIGA (0,1) 13.8*** 10.6* 4.5\nEASI 75 21.1*** 17.9*** 6.1\nItch NRS 18.7*** 15.1** 4.7\n\n\n\nBREEZE-AD722 \n(N=329)\n\n\n\nvIGA (0,1) 31 24 15\nEASI 75 48*** 43 23\nItch NRS 44*** 38 20\n\n\n\nSignificance compared with placebo: *P\u22640.05; **P\u22640.01; ***P\u22640.001. \nThe primary outcome was the proportion of patients achieving vIGA \n(0,1) with 4 mg and 2 mg baricitinib at 16 weeks, and those achieving \nEASI 75 and Itch NRS were secondary outcomes. Itch NRS referred to \npatient-rated improvement in itch with a change of \u22654 points. \nBREEZE-AD 7 allowed concomitant TCS during the study, and \nBREEZE-AD 1,2 allowed TCS as rescue treatment only. \nEASI 75, 75% improvement from baseline Eczema Area and Severity \nIndex; NRS, Numeric Rating Scale; TCS, topical corticosteroids; vIGA \n(0,1), validated Investigator\u2019s Global Assessment achieving clear or \nalmost clear skin.\n\n\n\nA network meta-analysis comparing the \nefficacies of targeted systemic therapies used \nin treating AE without the addition of topical \ncorticosteroids and/or topical calcineurin \nwas recently published.27 It included phase \n3 and 4 placebo- or active intervention-\ncontrolled studies involving JAK, interleukin-4 \nand interleukin-13 inhibitors in adults and \nadolescents with moderate to severe AE. Based \n\n\n\non 11 clinical trials (N=6254), upadacitinib \n30 mg daily demonstrated better and earlier \nefficacy, followed by abrocitinib 200 mg daily, \nupadacitinib 15 mg daily, abrocitinib 100 mg \ndaily and baricitinib 4 mg daily. However, \ncaution must be applied as network meta-\nanalyses are susceptible to the methodological \nquality of the included studies, reporting biases \nand choices of study eligibility criteria and do \nnot replace comparisons of multiple head-to-\nhead RCTs.27\n\n\n\nTable 2. Upadacitinib vs placebo efficacy outcomes\n\n\n\nStudy \n(Total \nsubjects)\n\n\n\nParameters Proportion of patients achieving \noutcomes at 16 weeks (%)\nUpadacitinib \n30 mg\n\n\n\nUpadacitinib \n15 mg\n\n\n\nPlacebo\n\n\n\nMEASURE \nUP-128\n\n\n\n(N=847)\n\n\n\nvIGA (0,1) 62*** 48*** 8\nEASI 75 80*** 70*** 16\n\n\n\nMEASURE \nUP-228\n\n\n\n(N=836)\n\n\n\nvIGA (0,1) 52*** 39*** 5\nEASI 75 73*** 60*** 13\n\n\n\nSignificance compared with placebo: ***P\u22640.001. The proportion \nof patients achieving vIGA (0,1) and EASI 75 were the co-primary \noutcomes for both studies. Concomitant TCS and other medicated \ntopical therapy were prohibited, but rescue therapy was permitted from \nweek 4.\nEASI 75, 75% improvement from baseline Eczema Area and Severity \nIndex; TCS, topical corticosteroids; vIGA (0,1), validated Investigator\u2019s \nGlobal Assessment achieving clear or almost clear skin.\n\n\n\nTable 3. Abrocitinib vs placebo efficacy outcomes\nStudy\n(Total subjects)\n\n\n\nParameters Proportion of patients achieving \noutcomes at 16 weeks (%)\nAbrocitinib \n200 mg\n\n\n\nAbrocitinib\n100 mg\n\n\n\nPlacebo\n\n\n\nJADE MONO-\n129\n\n\n\n(N=387)\n\n\n\nIGA (0,1) 44*** 24* 8\nEASI 75 63*** 40*** 12\n\n\n\nJADE MONO-\n230\n\n\n\n(N=391)\n\n\n\nIGA (0,1) 38.1*** 28.4*** 9.1\nEASI 75 61*** 44.5*** 10.4\n\n\n\nJADE TEEN26\n\n\n\n(N=285)\nIGA (0,1) 46.2** 41.6** 24.5\nEASI 75 72** 68.5** 41.5\n\n\n\nSignificance compared with placebo: *P=0.0037; **P\u22640.05; \n***P\u22640.001. The proportion of patients achieving vIGA (0,1) and EASI \n75 were the co-primary outcomes for all studies. \nIn the JADE-MONO 1,2, concomitant use of TCS and other medication \ntopical medications were not allowed, and rescue medications were \nprohibited. In the JADE-TEEN study, standardised regimens of non-\nmedicated and medicated topical therapy were required, and oral \nhistamines were also permitted. \nEASI 75, 75% improvement from baseline Eczema Area and Severity \nIndex; TCS, topical corticosteroids; vIGA (0,1), validated Investigator\u2019s \nGlobal Assessment achieving clear or almost clear skin.\n\n\n\nHead-to-head studies with dupilumab\nDupilumab is a human monoclonal \nimmunoglobulin (Ig) G4 antibody that binds to \nIL-4R\u03b1 and inhibits IL-4 and IL-13 signalling. It \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 496\n\n\n\nhas been approved for the treatment of moderate \nto severe AE in adults and children aged 6 and \nabove.31\n\n\n\nHead-to-head comparison between JAK-i \nand dupilumab has been conducted with \nupadacitinib and abrocitinib.32,33 Upadacitinib \n30 mg daily and abrocitinib 200 mg daily had \nsignificantly better primary outcomes (EASI 75 \nfor both and IGA for abrocitinib only) compared \nwith dupilumab 300 mg every other week at \nweek 12 and 16, respectively. The efficacy of \nabrocitinib 100 mg daily was comparable to \ndupilumab. Upadacitinib 30 mg and abrocitinib \n200 mg demonstrated superiority for improving \nitch scores as early as the first (mean 31.4% vs \n8.8%; p<0.001) and second week (difference \nfrom dupilumab 22.1%; p<0.001), respectively. \nA longer-term trial, JADE DARE, to determine \nthe efficacy of abrocitinib 200 mg compared to \ndupilumab is ongoing (treatment duration \u2013 26 \nweeks).34\n\n\n\nLong-term efficacy\nSo far, baricitinib has the longest follow-up \ndata for efficacy at 68 weeks from BREEZE-\nAD 3. The subjects were derived from the \nBREEZE-AD 1, 2 trials. The efficacy outcomes \n[vIGA (0,1), EASI 75 and Itch NRS] remained \nrelatively stable in both responders and partial \nresponders, indicating that baricitinib could be \nan option for long-term therapy for adult patients \nwith moderate-to-severe AE.35 Upadacitinib \nhas demonstrated sustained efficacy up to 52 \nweeks from treatment initiation among the \npatients from the MEASURE UP 1, 2 studies.36 \nThe JADE REGIMEN trial evaluated the \nsustainability of abrocitinib-induced responses \nover 40 weeks. The primary outcome to \ndetermine the probability of a flare during the \nmaintenance period was 18.9%, 42.6% and \n80.9% with abrocitinib 200 mg, abrocitinib 100 \nmg and placebo, respectively.37\n\n\n\nSafety outcomes\nThe three JAK-i available for treating AE have \ngood safety and tolerability profiles. The most \nfrequent treatment-emergent adverse events \n(TEAE) were mild to moderate in severity and \nincluded upper respiratory tract infections, \n\n\n\nnasopharyngitis, gastrointestinal symptoms \n(e.g., nausea, vomiting and diarrhoea) and \nheadache.21,28-30 The younger population in the \nupadacitinib and abrocitinib trials could explain \nthe development of acne in up to 17% of patients. \n\n\n\n28 The most frequent biochemical TEAE in all \ntreatment arms was elevated plasma creatine \nphosphokinase (CPK). \n\n\n\nThe occurrences of TEAE of eczema herpeticum \nand herpes zoster were very low for all three \nJAK-i (none to two cases per study).21,28-30 \nHowever, the proportion of patients developing \nTEAE of herpes simplex with baricitinib was \nslightly higher than in the placebo arms (range: \n3.3%-7.2%) and was not dose-dependent.21 \nThere was no reactivation of TB reported in \nany of the trials. The rate of discontinuation of \nthe drug due to adverse events was low in all \nstudies.\n\n\n\nSerious adverse events were uncommon and \nsimilar across the treatment and placebo arms \nin all studies. The serious adverse events were \ndose-independent and ranged from none to \napproximately 4%, except for baricitinib 1 mg \nin the BREEZE-AD2 (7.3%). \n\n\n\nBaricitinib\u2019s long-term safety profile was \nderived based on a pooled safety analysis \nacross its clinical programme and included \nthe long-term extension studies (N=2531 with \n2247 patient-years). The most common serious \nadverse events were eczema herpeticum (n=11; \nincidence rate 0.5), cellulitis and pneumonia.38 \nNasopharyngitis, headache, elevated CPK \nlevels and diarrhoea were the most frequently \nreported TEAE.\n\n\n\nLong-term (52 weeks) safety studies \nof upadacitinib revealed that treatment \ndiscontinuation due to TEAE was low overall. \nBoth upadacitinib doses (15 mg and 30 mg) \nwere well tolerated and did not demonstrate any \nnew safety signals.36\n\n\n\nBaseline investigations and monitoring\nThe recent EuroGuiDerm Guideline on Atopic \nDermatitis (June 2022) recommends that \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 7\n\n\n\nthe same baseline screening and treatment \nmonitoring investigations should be conducted \nfor all JAK-i (Table 4). \n\n\n\nTable 4. Baseline screening and monitoring for all \nJAK-i14\n\n\n\nBaseline screening Monitoring at 4 weeks after \ninitiation and then 3-monthly \n\n\n\nwhile on treatment\n\n\n\n\u2022\t Full blood count\n\u2022\t Renal and liver function \n\n\n\ntests\n\u2022\t Fasting lipid profile\n\u2022\t Serum creatine \n\n\n\nphosphokinase\n\u2022\t Viral hepatitis and TB \n\n\n\nscreening, including a \nchest radiograph\n\n\n\n\u2022\t Full blood count\n\u2022\t Renal and liver function \n\n\n\ntests\n\u2022\t Fasting lipid profile\n\u2022\t Serum creatine \n\n\n\nphosphokinase\n\n\n\nPrecautions and contraindications\nThe JAK-i are contraindicated in patients with \nhypersensitivity to the active substance or any \nof its excipients and those with active TB or \nserious infections, severe hepatic impairment \nand pregnancy.39-41 In case of latent TB or \nthose with a high risk of TB infection, anti-TB \ntherapy should be considered before starting \nthese agents.\n\n\n\nThere is a dose-dependent increase in lipid \nparameters with JAK-i that can be monitored \nand controlled with statin therapy. If liver \nenzymes levels increase (alanine transaminase \n\u22655-times and aspartate transaminase \u226510-times \nthe upper limit of normal) and drug-induced \nliver injury is suspected, the agents should be \ntemporarily discontinued until liver injury is \nexcluded. 41\n\n\n\nAll three JAK-i have been associated with \nincreased serum levels of creatine phosphokinase \n(CPK) in patients with inflammatory disorders \nbut not in patients with myeloproliferative \ndisease or healthy subjects treated for a limited \nduration. 42 Most patients do not report myalgia \nor other symptoms associated with CPK \nelevation. However, the exact mechanism of \nJAK-i-associated myalgias has not yet been \nfully elucidated. 43\n\n\n\nJAK-i should be used with caution in patients \nwith risk factors for venous thromboembolism \n\n\n\n(e.g., older age, obesity and prior history \nof venous thromboembolic events) and \ndiscontinued if the patients exhibit any features \nof the condition. A recent meta-analysis of two \nlarge cohort studies and 15 RCTs (N=466 993) \nfound no significant association of increased \nrisk of venous thromboembolic events in AE \npatients treated with JAK-i. 44 Patients with \ndiverticular disease should be prescribed \nbaricitinib with caution.\n\n\n\nTemporary discontinuation of these agents \nshould be made if the absolute neutrophil count \nis <1 x 109 cells/L, absolute lymphocyte counts \nis <0.5 x 109 cells/L or haemoglobin is <8 g/dL. \nTreatment can be resumed once the levels reach \nabove these values.\n\n\n\nWomen of childbearing age should use effective \ncontraception during and for at least one week \nafter stopping treatment.\n\n\n\nThe drug-drug interaction profiles relating to \nmetabolization via the CYP450 enzymes also \ndiffer between JAK-i (Table 5). 45-47\n\n\n\nTable 5. Summary table for baricitinib, upadacitinib \nand abrocitinib\n\n\n\nJAK-i Target JAK Dosing Common adverse \nevents\n\n\n\nBaricitinib21,41 JAK 1 and \nJAK 2 \n(selective)\n\n\n\n4 mg/day\n2 mg/day if \n\u226575 years old \nor eGFR 30-60 \nml/m3\n\n\n\nNasopharyngitis, \nheadache, \nincreased blood \nCPK levels, URTI\n\n\n\nUpadacitinib\u202028,40 JAK 1 more \nthan JAK \n2, JAK 3 or \nTYK2\n\n\n\n15 mg/day\nCan be \nincreased to \n30 mg/day if \nnecessary\nIf \u226565 years \nold, 15 \nmg/day is \nrecommended\n\n\n\nAcne, URTI, \nnasopharyngitis, \nheadache, \nincreased CPK \nlevels\n\n\n\nAbrocitinib\u202130,39 JAK 1 \n(selective)\n\n\n\n100 mg/day\nCan be \nincreased to \n200 mg/day if \nnecessary\n50 mg/day is \nrecommended \nif eGFR 30-60 \nml/m3\n\n\n\nNausea, \nnasopharyngitis, \nheadache, URTI, \nacne, vomiting, \nupper abdominal \npain, increased \nCPK levels, \nfolliculitis, \nthrombocytopenia\n\n\n\nCPK, creatine phosphokinase; eGFR, estimated glomerular filtration \nrate; JAK, Janus kinase; JAK-i, Janus kinase inhibitors; TYK2, tyrosine \nkinase 2; URTI, upper respiratory tract infection.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 498\n\n\n\nTable 5. Summary of drug-drug interactions of the different JAK-i relating to CYP450 enzymes\n\n\n\nInteraction with CYP450 \nenzyme\n\n\n\nBaricitnib46 Upadacitinib45 Abrocitinib47\n\n\n\nMetabolization via CYP450 \nenzymes\n\n\n\n<10% by \nCYP3A4\n\n\n\nMainly by CYP3A4 ~53% by CYP2C19\n~30% by CYP2C9\n~11% by CYP3A4\n~6% by CYP2B6\n\n\n\nRelevance for CYP450 drug \ninteractions\n\n\n\nNone Yes: CYP3A4 inducers or inhibitors can affect \nupadacitinib exposure\n\n\n\nYes: CYP2C19 and CYP2C9 inhibitors or \ninducers can affect abrocitinib exposure\n\n\n\nDosing considerations for \nCYP450 drug interactions\n\n\n\nUpadacitinib 15 mg OD should be used \nwith caution in patients receiving chronic \ntreatment with strong CYP3A4 inhibitors \n(e.g. clarithromycin, erythromycin, diltiazem, \nverapamil, itraconazole, ketoconazole and \nritonavir)\n\n\n\nUpadacitinib 30 mg OD dose is not \nrecommended for patients with AE receiving \nchronic treatment with strong CYP3A4 inhibitors\n\n\n\nFood or drink containing grapefruit should be \navoided during treatment with upadacitinib\n\n\n\nPatients should be monitored for changes in \ndisease activity if upadacitinib is co-administered \nwith strong CYP3A4 inducers\n\n\n\nIn patients receiving dual strong inhibitors of \nCYP2C19 and moderate inhibitors of CYP2C9, \nor strong inhibitors of CYP2C19 alone (e.g. \nfluvoxamine, fluconazole, fluoxetine and \nticlopidine), the recommended dose should be \nreduced by half to 100 mg or 50 mg once daily\n\n\n\nTreatment is not recommended concomitantly \nwith moderate or strong inducers of CYP2C19/\nCYP2C9 enzymes (e.g. rifampicin, apalutamide, \nefavirenz, enzalutamide, phenytoin)\n\n\n\nOD, once daily.\n\n\n\nImportant notice: As of September 1st 2021, and based on a review of a large, randomised safety clinical trial, the United States Food and Drug \nAdministration (US FDA) requires a black box warning for all JAK-i for serious infections, malignancy and thrombosis. The US FDA concluded an \nincreased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots and death with tofacitinib. This warning is to be extended \nto all JAK-i due to similar mechanisms of action. 47\n\n\n\nUpdated AE treatment algorithm\n\n\n\nFigure 2. The updated treatment algorithm for AE includes biologics and JAK-i. Biologics and JAK-i have been \nadded as treatment options for severe to very severe AE. IGA, Investigators\u2019 Global Assessment; JAK-i, Janus \nkinase inhibitors; TCS, topical corticosteroids; TCI, topical calcineurin inhibitors. Adapted from the Ministry \nof Health Malaysia, Persatuan Dermatology Malaysia. Clinical Practice Guidelines for the management of \natopic eczema. 2018.11\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 9\n\n\n\nConclusion\nAfter evaluating the data on the efficacy \nand safety of baricitinib, upadacitinib and \nabrocitinib, we recommend that JAK-i can be \nconsidered as an option for systemic therapy \nin severe AE. These newer agents are currently \nundergoing long-term extension studies, and \nthus, the recommendation may vary from time \nto time when more evidence arises. \n\n\n\nConflict of Interest Declaration\nDato\u2019 Dr Noor Zalmy Azizan has received \nhonorarium for chairing meetings from Zuellig \nPharma Therapeutics, Novartis and Eucerin. \nShe is also the President of the Persatuan \nDermatologi Malaysia (2020-2022), which is \nan unpaid position. Received drug samples \nfrom Zuellig Pharma Therapeutics and Abbvie.\n\n\n\nAssociate Professor Dr Adawiyah Jamil \nhas received sponsorship for the Annual \nDermatology Congress Malaysia 2022 from \nZuellig Pharma Therapeutics and participated \nin an advisory board meeting by Boehringer \nIngelheim.\n\n\n\nDr Chang Choong Chor has received drug \nsamples from Zuellig Pharma Therapeutics.\n\n\n\nDr Dawn Ambrose, Dr Foong Boon Bee, Henry, \nDr Rajalingam Ramalingam, Dr Sharifah \nRosniza Binti Syed Nong Chek, Dr Sabeera \nBegum bt Kader Ibrahim and Dr Wong Hoi \nLing have no conflict of interests to declare.\n\n\n\nDr How Kang Nien has received consulting \nfees from Boehringer Ingelheim and honoraria \nfrom Janssen, Beiersdorf and Zuellig Pharma \nTherapeutics. He has also received support for \nmeeting attendance from Novartis, and is an \nExecutive Committee Member in the Persatuan \nDermatologi Malaysia.\n\n\n\nDr Tan Wooi Chiang has participated in advisory \nboard meetings for Zuellig Pharma Therapeutics \nand Pfizer. He is also the vice president of the \nPersatuan Dermatologi Malaysia (2022-2024).\n\n\n\nFunding\nPersatuan Dermatologi Malaysia received a \ngrant from Zuellig Pharma (M) Sdn Bhd for the \neditorial support of this manuscript.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n1. Birdi G, Cooke R, Knibb RC. Impact of atopic dermatitis \n\n\n\non quality of life in adults: a systematic review and meta-\nanalysis. Int J Dermatol 2020;59:e75-91.\n\n\n\n2. Na CH, Chung J, Simpson EL. Quality of life and disease \nimpact of atopic dermatitis and psoriasis on children and \ntheir families. Children (Basel) 2019;6:133.\n\n\n\n3. Asher MI, Montefort S, Bj\u00f6rkst\u00e9n B, Lai CKW, \nStrachan DP, Weiland SK et al. Worldwide time trends \nin the prevalence of symptoms of asthma, allergic \nrhinoconjunctivitis, and eczema in childhood: ISAAC \nphases one and three repeat multicountry cross-sectional \nsurveys. Lancet 2006;368:733-43.\n\n\n\n4. Goh YY, Keshavarzi F, Chew YL. Prevalence of atopic \ndermatitis and pattern of drug therapy in Malaysian \nchildren. Dermatitis 2018;29:151-61.\n\n\n\n5. Heah SK, Mohd Noor N, Johar A. Prevalence of skin \ndiseases in Dermatology Outpatient Clinic, Hospital \nKuala Lumpur. Malaysian J Dermatol 2017;38:19-24. \n\n\n\n6. Ghani AAA, Norhayati NM, Muhamad R, Ismail Z. \nQuality of life and its associated factors among children \nwith atopic eczema in Kelantan, Malaysia. Int J Collab \nRes Intern Med Public Health 2012;4:1816-27. \n\n\n\n7. Girolomoni G, Luger T, Nosbaum A, Gruben D, Romero \nW, Llamado LJ et al. 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Executive summary: Japanese \nguidelines for atopic dermatitis (ADGL) 2021. Allergol \nInt 2022;71:448-58.\n\n\n\n16. Yao TC, Wang IJ, Sun HL, Ou LS, Yu HH, Wang L et \nal. Taiwan guidelines for the diagnosis and management \nof pediatric atopic dermatitis: Consensus statement of \nthe Taiwan Academy of Pediatric Allergy, Asthma and \nImmunology. J Microbiol Immunol Infect 2022;55:561-\n72.\n\n\n\n17. David Boothe W, Tarbox JA, Tarbox MB. Atopic \ndermatitis: Pathophysiology. Adv Exp Med Biol \n2017;1027:21-37.\n\n\n\n18. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, \nO\u2019Shea JJ. JAK inhibition as a therapeutic strategy for \nimmune and inflammatory diseases. Nat Rev Drug Discov \n2017;16:843-62.\n\n\n\n19. Chovatiya R, Paller AS. JAK inhibitors in the treatment of \natopic dermatitis. J Allergy Clin Immunol 2021;148:927-\n40.\n\n\n\n20. He H, Guttman-Yassky E. JAK Inhibitors for atopic \ndermatitis: An update. Am J Clin Dermatol 2019;20:181-\n92.\n\n\n\n21. Simpson EL, Lacour JP, Spelman L, Galimberti R, \nEichenfield LF, Bissonnette R et al. Baricitinib in patients \nwith moderate-to-severe atopic dermatitis and inadequate \nresponse to topical corticosteroids: Results from two \nrandomized monotherapy phase III trials. Br J Dermatol \n2020;183:242-55.\n\n\n\n22. Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield \nLF, Bieber T et al. Efficacy and safety of baricitinib \ncombined with topical corticosteroids for treatment of \nmoderate to severe atopic dermatitis: A randomized \nclinical trial. JAMA Dermatol 2020;156:1333-43.\n\n\n\n23. ClinicalTrials.gov. A multicenter, randomized, doubles-\nblind, placebo-controlled, phase 3 study to evaluate \nthe efficacy and safety of baricitinib in combination \nwith topical corticosteroids in adult patients with \nmoderate to severe atopic dermatitis (Protocol I1V-MC-\nJAIY(a)).2018. Available at: https://clinicaltrials.gov/\nProvidedDocs/01/NCT03733301/Prot_000.pdf. Accessed \nDecember 2022.\n\n\n\n24. ClinicalTrials.gov. Study evaluating efficacy and safety \nof PF-04965842 in subjects aged 12 years and older \nwith moderate to severe atopic dermatitis (JADE Mono-\n2). Available at: https://clinicaltrials.gov/ct2/show/\nNCT03575871. Accessed December 2022.\n\n\n\n25. ClinicalTrials.gov. Evaluation of upadacitinib in \nadolescent and adult patients with moderate to severe \natopic dermatitis (eczema) (Measure Up 1). Available \nat: https://clinicaltrials.gov/ct2/show/NCT03569293. \nAccessed December 2022.\n\n\n\n26. Eichenfield LF, Flohr C, Sidbury R, Siegfried E, Szalai \nZ, Galus R et al. Efficacy and safety of abrocitinib \nin combination with topical therapy in adolescents \nwith moderate-to-severe atopic dermatitis: The JADE \n\n\n\nTEEN randomized clinical trial. JAMA Dermatol \n2021;157:1165-73.\n\n\n\n27. Silverberg JI, Hong HC, Thyssen JP, Calimlim BM, \nJoshi A, Teixeira HD et al. Comparative efficacy of \ntargeted systemic therapies for moderate to severe atopic \ndermatitis without topical corticosteroids: Systematic \nreview and network meta-analysis. Dermatol Ther \n(Heidelb) 2022;12:1181-96.\n\n\n\n28. Guttman-Yassky E, Teixeira HD, Simpson EL, Papp KA, \nPangan AL, Blauvelt A et al. Once-daily upadacitinib \nversus placebo in adolescents and adults with moderate-to-\nsevere atopic dermatitis (Measure Up 1 and Measure Up \n2): Results from two replicate double-blind, randomised \ncontrolled phase 3 trials. Lancet 2021;397(10290):2151-\n68.\n\n\n\n29. Simpson EL, Sinclair R, Forman S, Wollenberg A, \nAschoff R, Cork M et al. Efficacy and safety of abrocitinib \nin adults and adolescents with moderate-to-severe atopic \ndermatitis (JADE MONO-1): A multicentre, double-\nblind, randomised, placebo-controlled, phase 3 trial. \nLancet 2020;396:255-66.\n\n\n\n30. Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, \nChan G, Feeney C et al. Efficacy and safety of abrocitinib \nin patients with moderate-to-severe atopic dermatitis: A \nrandomized clinical trial. JAMA Dermatol 2020;156:863-\n73.\n\n\n\n31. Dupixent (Dupilumab) 300 mg solution for injection \nin pre-filled pen. Summary of Product Characteristics. \nAvailable at: https://www.medicines.org.uk/emc/\nproduct/11321/smpc#gref. Accessed December 2022.\n\n\n\n32. Bieber T, Simpson EL, Silverberg JI, Tha\u00e7i D, Paul C, \nPink AE et al. Abrocitinib versus placebo or dupilumab \nfor atopic dermatitis. N Eng J Med 2021;384:1101-12.\n\n\n\n33. Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De \nBruin-Weller M, Barbarot S et al. Efficacy and safety \nof upadacitinib vs dupilumab in adults with moderate-\nto-severe atopic dermatitis: A randomized clinical trial. \nJAMA Dermatol 2021;157:1047-55.\n\n\n\n34. ClinicalTrials.gov. Study of abrocitinib compared with \ndupilumab in adults with moderate to severe atopic \ndermatitis on background topical therapy. Available at: \nhttps://www.clinicaltrials.gov/ct2/show/NCT04345367. \nAccessed December 2022.\n\n\n\n35. Silverberg JI, Simpson EL, Wollenberg A, Bissonnette \nR, Kabashima K, DeLozier AM et al. Long-term efficacy \nof baricitinib in adults with moderate to severe atopic \ndermatitis who were treatment responders or partial \nresponders: An extension study of 2 randomized clinical \ntrials. JAMA Dermatol 2021;157:691-9.\n\n\n\n36. Simpson EL, Papp KA, Blauvelt A, Chu CY, Hong \nHCH, Katoh N et al. Efficacy and safety of upadacitinib \nin patients with moderate to severe atopic dermatitis: \nAnalysis of follow-up data from the Measure Up 1 and \nMeasure Up 2 randomized clinical trials. JAMA Dermatol \n2022;158:404-13.\n\n\n\n37. Blauvelt A, Silverberg JI, Lynde CW, Bieber T, Eisman \nS, Zdybski J et al. Abrocitinib induction, randomized \nwithdrawal, and retreatment in patients with moderate-to-\nsevere atopic dermatitis: Results from the JAK1 Atopic \nDermatitis Efficacy and Safety (JADE) REGIMEN phase \n3 trial. J Am Acad Dermatol 2022;86:104-12.\n\n\n\n38. Bieber T, Thyssen JP, Reich K, Simpson EL, Katoh N, \nTorrelo A et al. Pooled safety analysis of baricitinib in adult \npatients with atopic dermatitis from 8 randomized clinical \ntrials. J Eur Acad Dermatol Venereol 2021;35:476-85.\n\n\n\n39. Cibinqo (Abrocitinib) 100 mg film-coated tablets. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 11\n\n\n\nSummary of Product Characteristics. Avalable at: https://\nwww.medicines.org.uk/emc/product/12873/smpc#gref. \nAccessed December 2022.\n\n\n\n40. Rinvoq (Upadacitinib) 15 mg prolonged-release tablets. \nSummary of Product Characteristics. Available at: https://\nwww.medicines.org.uk/emc/product/10972/smpc#gref. \nAccessed December 2022.\n\n\n\n41. Olmiant (Baricitinib) 2 mg film-coated tablets. Summary \nof Product Characteristics. Available at: https://www.\nmedicines.org.uk/emc/product/2434/smpc#gref. \nAccessed December 2022.\n\n\n\n42. Queeney K, Housley W, Sokolov J, Long A. \nFRI0131 Elucidating the mechanism underlying creatine \nphosphokinase upregulation with upadacitinib. Annals of \nthe Rheumatic Diseases 2019;78:734-5.\n\n\n\n43. Clarke B, Yates M, Adas M, Bechman K, Galloway J. \nThe safety of JAK-1 inhibitors. Rheumatology (Oxford) \n2021;60:ii24-30.\n\n\n\n44. Chen TL, Lee LL, Huang HK, Chen LY, Loh CH, Chi CC. \nAssociation of risk of incident venous thromboembolism \nwith atopic dermatitis and treatment with Janus kinase \ninhibitors: A systematic review and meta-analysis. JAMA \nDermatol 2022;158:1254-61.\n\n\n\n45. Rinvoq 15 mg prolonged-release tablets (Great Britain). \nSummary of Product Characteristics. Available at: https://\nwww.medicines.org.uk/emc/product/10972/smpc#gref. \nAccessed December 2022. \n\n\n\n46. Olumiant 2 mg Film-Coated Tablet. Summary of Product \nCharacteristics. Available at: https://www.medicines.org.\nuk/emc/product/2434/smpc#gref. Accessed December \n2022. \n\n\n\n47. Cibinqo 100 mg Film-coated Tablets. Summary of Product \nCharacteristics. Available at: https://www.medicines.org.\nuk/emc/product/12873/smpc#gref. Accessed December \n2022. \n\n\n\n48. United States Food and Drug Administration. FDA \nrequires warnings about increased risk of serious \nheart-related events, cancer, blood clots, and death for \nJAK inhibitors that treat certain chronic inflammatory \nconditions. Available at: https://www.fda.gov/drugs/\nfda-drug-safety-podcasts/fda-requires-warnings-about-\nincreased-risk-serious-heart-related-events-cancer-blood-\nclots-and-death. Accessed December 2022.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4912\n\n\n\nORIGINAL ARTICLE\n\n\n\nSerum Vitamin B12 Level and Dietary intake in Adult Atopic Dermatitis: A \nCase Control Study\n\n\n\nAbdul Rahman Che Abdul Rahim\u00b9, MRCP, Mohammad Basri Rusdu\u00b2, BSc, Adawiyah Jamil\u00b3, AdvMDerm, \nRajalingam Ramalingam\u00b9, AdvMDerm\n\n\n\n\u00b9Department of Dermatology Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\u00b2Department of Dietetics and Food Service Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\u00b3Dermatology Unit, Department of Medicine, Hospital Tuanku Muhriz Universiti Kebangsaan Malaysia, Bangi, \nSelangor, Malaysia\n\n\n\nAbstract\nBackground\nVitamin B12 is a contributing factor in pruritus and peripheral nerve regeneration. Its role in atopic \ndermatitis (AD) is still unclear. This study aimed to compare vitamin B12 level between AD patients and \nhealthy controls, determine its correlation with pruritus and AD severity, and evaluate dietary pattern with \nenergy, macro and micronutrient intakes.\n\n\n\nMethods\nThis was a case control study involving adult AD patients and age-, gender-, ethnicity- and body mass \nindex-matched healthy controls.  All adult patients who fulfilled UK Working Party AD diagnostic criteria \nwere included. Exclusion criteria include patients on systemic agents, diseases known to affect B12 level \nand vegan diet.  AD severity was determined using SCORing Atopic Dermatitis (SCORAD) index. Serum \nvitamin B12 level were measured. A three-day 24-hour dietary recall was collected and analyzed.\n\n\n\nResults\nA total of 42 AD patients and 42 controls were recruited. Mean SCORAD index was 39.2\u00b116.6, and \nAD duration was 12.7 \u00b1 8.1 years. Vitamin B12 was lower among AD (215.6 \u00b1 110.2 pmol/L) versus \ncontrol (295.1\u00b1 119.9 pmol/L), p<0.01 despite similar dietary B12 intake in both groups. There were no \nsignificant correlations between AD duration and severity with vitamin B12 level.  Energy intake (kcal/\nday) was significantly lower in AD (p=0.04). There were no significant differences in proportion of main \nfood groups consumed and other macronutrient and micronutrient intakes.\n\n\n\nConclusion \nSerum vitamin B12 level was significantly lower in AD patients despite similar dietary pattern and nutrient \nintake with healthy controls. There were no correlations with AD severity or disease duration. Dietary \npattern of AD patients should be routinely assessed to ensure adequate nutrition.\n\n\n\nKey Words: Cobalamin, B12, Atopic dermatitis, Nutrition\n\n\n\nCorresponding Author\nDr Abdul Rahman Che Abdul Rahim\nDepartment of Dermatology, \nHospital Tengku Ampuan Afzan, \nJalan Tanah Putih, \n25100 Kuantan, Pahang, Malaysia\nEmail: namhara85@gmail.com\n\n\n\nIntroduction\nAtopic dermatitis (AD) is a common chronic \ninflammatory, pruritic skin disorder affecting up \nto 10% of the adult population.1 Micronutrients \nmay have an impact on atopic dermatitis as \nproper nutrition, especially vitamins, minerals, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 13\n\n\n\nand trace elements play an active role in immune \nhealth. The relationship between nutrition and \natopic pathogenesis has been debated for many \nyears.2 Current knowledge is still not sufficient \nto discern the exact role of specific vitamins and \ntrace minerals on AD.\n\n\n\nVitamin B12 (cobalamin) is a chemical \ncompound with vitamin properties, that is \nmainly present in sufficient amount in animal-\nderived foods.3 Self-imposed dietary restriction \n( i.e.  red meat, egg, seafood) without consulting \na doctor or dietitian is a common practice among \nAD patients.4,5 The lack of supervision of these \ndietary modifications has been associated with \nrisk of nutrient deficiency in both children \nand adults.6-8 A local study in toddlers with \nAD6 yielded a non-significant lower level of \nserum vitamin B12 among food restricted \ngroup. However, clinical manifestation of \nB12 deficiency from diminished intake or \nabsorption may not manifest for several years \nafter the depletion of body stores.9 Furthermore, \nprevalence of vitamin B12 deficiency is \ndifficult to assess since under-diagnosis is \nlikely and subclinical disease is considered not \nuncommon.10\n\n\n\nVitamin B12 precursor has been shown to have \na potent action as a nitric oxide scavenger in \ninflammatory conditions. The ability of vitamin \nB12 to regulate inflammatory cytokines suggests \nthat it may have antioxidative properties.11 \nTopical vitamin B12 has some efficacy in the \ntreatment of atopic dermatitis.12\n\n\n\nHence, the aim of this case control study is to \ncompare serum vitamin B12 level between AD \npatients and healthy volunteers.   Correlations \nbetween serum B12 level with AD severity, \ndisease duration and pruritus were determined. \nDietary pattern, energy and other macro- and \nmicronutrient intakes were also assessed.\n\n\n\nMaterials and Methods \nA case control study was performed. Patients \nwith AD attending Dermatology clinic Hospital \nTengku Ampuan Afzan were screened and \n\n\n\nrecruited from August 2020 until May 2021. \nHealthy age, gender, ethnicity and body mass \nindex-matched volunteers constituted the \ncontrol group. We included patients aged 18 \nyears old and older who  met the criteria for \natopic dermatitis based on the UK Working \nParty Atopic Dermatitis diagnostic criteria.13 \nExclusion criteria were  (i) patients  on systemic \nagents which include azathioprine, methotrexate \nand cyclosporin (ii) patients with other pruritic \nconditions including urticaria,  (iii) generalized \nhyperpigmentation, (iv) atrophic glossitis, (v) \npatients conditions known to affect vitamin \nB12 level which include pernicious anemia , \nhypochlorhydria due to atrophic gastritis, partial \nor total gastrectomy, bariatric surgery,  ileal \nresection of >20 cm, malabsorptive disorders, \nshort bowel syndrome, inflammation of the \nileum \u2013 eg: Crohn\u2019s disease, celiac disease, \nchronic pancreatitis, small intestine bacterial \novergrowth, Whipple\u2019s disease, ongoing/\nprevious history of gastric cancer/gastrectomy, \n(vi) patients on medications affecting vitamin \nB12 level which include B12 supplement, \nproton pump inhibitor, H2 receptor antagonist \nand metformin, (vii) patients on vegan diet, and \n(viii) pregnancy.\n\n\n\nDemographic data of the participants and their \nbody mass index (BMI; weight [kg]/height m2) \nand waist circumference (cm) were recorded, \nas was the SCORing Atopic Dermatitis \n(SCORAD),14 and Dermatology Life Quality \nIndex (DLQI) score15 for the cases. Severity \nin the SCORAD index is classified as mild \n(<25), moderate (25-50), and severe (>50). The \nmaximum score is 103. All participants were \nasked to recall their 3-day dietary intake which \nconsists of two weekdays and one weekend. \nDescription include the type of food or beverage \nconsumed and portion size and cooking \nmethods. Portion size was determined using a \ncommon food guide (cups, bowls, tablespoon, \nteaspoons, glasses). \n\n\n\nParticipants are first asked about all the food they \nconsumed within the last 24-hours, followed \nby a thorough probing whereby they detailed \ninformation for each food/beverage, for the \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4914\n\n\n\ntype, amount, any addition to the food/toppings, \npreparation methods including the type of oil/fat \nused is obtained. If the food was packaged, the \nbrand name, as well as the amount consumed, \nwas obtained. Finally, the record of foods and \nthe amount consumed was reviewed, to provide \nthe investigator  a chance to clarify any unclear \ninformation.16 To understand food preferences, \nmain food groups consumed, meat (chicken, \nbeef, and pork), seafood (fish, crustaceans, and \nmollusk), vegetables, egg, milk and peanut, \ncakes and sweets were examined.\n\n\n\nDietary intake was analyzed using Nutritionist \nPro\u2122 Software (Axxya Systems, the United \nStates Department of Agriculture (USDA) \nStandard Reference Database, First DataBank, \nInc., San Bruno, California) for macronutrients \nand micronutrients. The Nutritionist ProTM \nsoftware contains Malaysian Food composition \ndatabases as well as other international databases \nsuch as USDA Food Database, Canadian \nFood Database, and Mexican Food Database. \nSchofield\u2019s equation was used to determine the \nbasal metabolic rate (BMR). The Energy Intake \n(EI): BMR ratio was used to identified under \nreporters. Classification of the EI: BMR ratio \ninto under reporters (EI: BMR<1.2), plausible \n(EI: BMR 1.2-2.4), and over reporters (EI: \nBMR>2.4) were used.17\n\n\n\nVenous blood was obtained for serum B12 levels. \nAssays for serum B12 level was performed \nusing Access\u00ae Immunoassay System Model \nDxI 800 UniCel\u00ae, which use chemiluminescent \nparamagnetic microparticle immunoassay \n(assay range 133 \u2013 675 pmol/L) from (Beckman \nCoulter, USA). Basic hematological profile was \nmeasured as well. These tests were conducted in \nthe Pathology Department of Hospital Tengku \nAmpuan Afzan, Pahang.\n\n\n\nThis study was approved by Medical Research \nand Ethical Committee (MREC), Malaysia with \nresearch code NMRR-20-1768-55814. The \nsample size of this study was calculated using \nthe statistical online software OpenEpi Version \n318  based on the case-control study by Polat, M., \net al.19 Fourty two subjects in each group were \n\n\n\nneeded to be able to reject the null hypothesis \nwith a probability power of 0.9. \n\n\n\nStatistical analysis was performed using \nStatistical Package for the Social Sciences \n(SPSS Version 24.0, IBM Corp). Most \ncontinuous variables were normally distributed \nand were summarized as mean and standard \ndeviation (SD). Qualitative data were expressed \nas percentages. The chi\u2010square test and t test \nwere used in analyzing differences between \ngroups. The significance level was set at p \n< 0.05. Correlations between variables were \ntested with the Pearson correlation analysis. \nSignificance was determined according to the \ntwo tailed alternative hypothesis, and results \nwere deemed significant for p values < 0.05. \n\n\n\nResults\nA total 33 men and 31 women were enrolled \nin the study.  The case and control groups were \nmatched for age, sex, race and body mass index. \nThe mean age of participants was 28.1 \u00b1 7.2 \nyears. Majority of the participants are female \n(60.7%) and Malays (86.9%). The mean BMI \nwas similar with 25.3 \u00b1 5.9 and 23.8 \u00b15.1 in \nthe case and control groups, respectively, (p \n= 0.2114). There was significant difference in \nthe proportion with comorbidities between AD \npatients (45.2%) and controls (16.7%), p <0.01.\n\n\n\nTable 3 shows there is lower energy intake \namong AD patients AD 1589.85 kcal\u00b1406.69 \nversus control 1755.61 kcal\u00b1331.12, p=0.04). \nHowever despite trend of lower intake of \nprotein, carbohydrate, and fat, these differences \nwere not significant (p=0.27, p=0.06, p=0.22 \nrespectively). No significant differences noted \non intake of all other micronutrients.\n\n\n\nSerum vitamin B12 levels were within the \nnormal range of  133\u2013675 pmol/L. In the case \ngroup, the mean serum vitamin B12 level was \nlower 215.6\u00b1110.2 pmol/L and in the control \ngroup it was 295.1\u00b1119.9 pg/ml, which was \nstatistically significant (p=0.002179). The \nmean dietary B12 intake were not statistically \ndifference in both group(AD 3.09 \u00b1 2.07 mcg/\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 15\n\n\n\nday  versus control 3.55\u00b11.78 mcg/day, p=0.29).\n\n\n\nThe mean eosinophil  and platelet to lymphocyte \nratio were significantly higher (AD 7.6 \u00b17.3 and \n14.4%\u00b17.5%, respectively) compared to control \ngroup (p=0.0002953; p=0.02058 respectively). \nThere is significant correlation of eosinophil \nwith the SCORAD which showed that higher \neosinophil percentage correlated with higher \nSCORAD index score (p=0.009, Pearson \ncorrelation r=0.397).\n\n\n\nMean duration of disease among AD patients \nwere 12.7\u00b18.1 years. The mean SCORAD index \nscores in the case group was 39.2\u00b116.6. Pearson \ncorrelation analysis showed higher SCORAD \ncorrelated with higher DLQI (r=0.457, \np=0.002). However there were no significant \ncorrelations between serum vitamin B12 level \nand disease severity (SCORAD) (r=0.068, \np=0.669), VAS pruritus (r=-0.021, p=0.896), \nand duration of disease(r=-0.111, p=0.486).\n\n\n\nTable 1. Demographic data\n\n\n\nDemographic \ndata\n\n\n\nTotal (n=84)\n\n\n\np \u2013 valueCase (n=42)\nMean\u00b1SD\nor n (%)\n\n\n\nControl (n=42)\nMean\u00b1SD\nor n (%)\n\n\n\nAge, in yearsa 28.0 \u00b1 7.2 28.2 \u00b1 7.1 0.94\n\n\n\nGenderb\n\n\n\nMale 16 (38.1%) 17 (40.5%)\n0.82\n\n\n\nFemale 26 (61.9%) 25 (59.5%)\n\n\n\nRaceb\n\n\n\nChinese 4 (9.5%) 5 (11.9%)\n0.92\n\n\n\nIndian 1 (2.4%) 1 (2.4%)\n\n\n\nMalay 37 (88.1%) 36 (85.7%)\n\n\n\nComorbidities 19 (45.2%) 7 (16.7%)\n\n\n\n<0.01\n\n\n\nBronchial \nasthma\n\n\n\n1 0(23.8%) 0\n\n\n\nAllergic \nRhinitis\n\n\n\n4 (9.5% ) 0\n\n\n\nEndometriosis 1 (2.3% ) 0\n\n\n\nHypertension 1 (2.3% ) 0\n\n\n\nAcne 7 (16.7% ) 7 (16.7% )\n\n\n\nSmoking 5 (11.9%) 5 (11.9%) 1.00\n\n\n\nAlcohol 1 (2.4) 1 (2.4) 1.00\naIndependent t test; bChi Square test\n\n\n\nSignificant differences were noted among \n\n\n\nthe proportion of AD subjects, there were no \nsignificant differences between proportion of \nfood pattern intake among participants (Table \n4). There was less proportion (5/42 subjects) \namong AD subjects who consumed nuts \n(which include peanut/ groundnut, almond , \nand cashew) however this was not statistically \nsignificant (11.9% in AD subjects versus 28.6% \nin control, p=0.06).\n\n\n\nTable 2. Clinical characteristic and laboratory \nparameters\n  Case (n=42)\n\n\n\nMean \u00b1 SD \nor n (%)\n\n\n\nControl (n=42)\nMean \u00b1 SD or \nn (%)\n\n\n\np value\n\n\n\nClinical \ncharacteristicsta\n\n\n\nBMI\u00b9, in kg/m2 25.3 \u00b1 5.9 23.8 \u00b1 5.1 0.21\n\n\n\nWaist circumference, \nin cm\n\n\n\n81.1 \u00b1 10.7 79.7 \u00b1 9.7 0.56\n\n\n\nSCORAD\u00b2 39.2 \u00b1 16.6 NA NA\n\n\n\nSeverity\n\n\n\nMild(<25) 11(26.2%) NA NA\n\n\n\nModerate (25-50) 20(47.6%) NA NA\n\n\n\nSevere(>50) 11(26.2%) NA NA\n\n\n\nVAS pruritus 6.1 \u00b1 1.7 NA NA\n\n\n\nDuration of atopic \ndermatitis, in years\n\n\n\n12.7 \u00b1 8.1 NA NA\n\n\n\nDLQI score\u00b3 12.9 \u00b1 6.2 NA NA\n\n\n\nLaboratory \nParametera\n\n\n\nSerum vitamin \nB12(pmol/L)\n\n\n\n215.6 \u00b1 110.2 295.1 \u00b1 119.9 <0.01\n\n\n\nHemoglobin (g/dl) 13.9 \u00b1 1.5 13.7 \u00b1 1.6 0.55\n\n\n\nPCV\u2074 (%) 41.6 \u00b1 3.9 40.4 \u00b1 4.1 0.16\n\n\n\nMCV\u2075 (fL) 80.1 \u00b1 9.0 81.6 \u00b1 7.1 0.37\n\n\n\nMCH\u2076 (pg) 26.8 \u00b1 3.4 27.8 \u00b1 2.7 0.13\n\n\n\nWBC\u2077 (10\u02c69/L) 9.6 \u00b1 5.7 8.4 \u00b1 4.3 0.31\n\n\n\nNeutrophil (%) 57.4 \u00b1 13.3 57.9 \u00b1 9.5 0.84\n\n\n\nLymphocyte (%) 26.6 \u00b1 10.2 30.6 \u00b1 8.4 0.06\n\n\n\nEosinophil (%) 7.6 \u00b1 7.3 3.1 \u00b1 2.6 <0.01\n\n\n\nPlatelet (10\u02c69/L) 330.3 \u00b1 76.7 316.3 \u00b1 70.7 0.39\n\n\n\nAbsolute neutrophil \ncount(ANC)\n\n\n\n5.2 \u00b1 2.7 4.9 \u00b1 2.8 0.61\n\n\n\nNeutrophil to \nLymphocyte Ratio \n(NLR)\n\n\n\n2.7 \u00b1 1.9 2.1 \u00b1 1.0 0.10\n\n\n\nPlatelet to Lymphocyte \nRatio\n(PLR)\n\n\n\n14.4 \u00b1 7.5 11.2 \u00b1 4.1 0.02\n\n\n\naIndependent t test; bChi Square test; \u00b9Body Mass Index; \u00b2SCORing \nAtopic Dermatitis; \u00b3Dermatology Life Quality Index; \u2074Packed Cell \nVolume; \u2075Mean Corpuscular Volume; \u2076Mean Corpuscular Hemoglobin; \n\u2077White Blood Cell; NA: Not applicable; VAS: Visual Analogue Score\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4916\n\n\n\nTable 3. Energy and nutrient intake\n\n\n\nNutrient intake \nper day\n\n\n\nTotal (n=84)a\n\n\n\np \u2013 valueCase (n=42)\nMean \u00b1 SD\n\n\n\nControl (n=42)\nMean \u00b1 SD\n\n\n\nBMR1(kcal) 1513.50 \u00b1 234.12 1496.48 \u00b1 280.91 0.76\nEI2 (kcal) 1589.85 \u00b1 406.69 1755.61 \u00b1 331.12 0.04\nEI: BMR Ratio 1.07 \u00b1 0.28 1.19 \u00b1 0.23 0.02\nProtein (g) 67.94 \u00b1 20.82 72.81 \u00b1 19.45 0.27\nCarbohydrate (g) 208.24 \u00b1 64.78 234.16 \u00b1 61.15 0.06\nFat (g) 53.38 \u00b1 19.61 58.17 \u00b1 15.85 0.22\nSFA3 (g) 11.53 \u00b1 6.82 10.44 \u00b1 5.61 0.42\nMSFAT4 (g) 11.70 \u00b1 7.66 11.97 \u00b1 7.62 0.87\nPUFAT5 (g) 9.09 \u00b1 5.29 10.95 \u00b1 7.25 0.18\nVitamin A (IU) 4582.65 \n\n\n\n\u00b12571.05\n4700.60 \u00b1 3340.15 0.86\n\n\n\nBeta Carotene \n(\u00b5g)\n\n\n\n954.87 \u00b1 1238.95 1038.39 \u00b11642.26 0.79\n\n\n\nVitamin C (mg) 34.24 \u00b1 34.48 34.16 \u00b1 33.71 0.99\nVitamin D (IU) 45.85 \u00b1 56.77 48.21 \u00b1 75.46 0.88\nVitamin E (IU) 6.61 \u00b1 3.94 7.82 \u00b1 5.60 0.26\nThiamine (mg) 0.74 \u00b10.40 0.71 \u00b1 0.30 0.72\nRiboflavin (mg) 1.14 \u00b1 0.56 1.07 \u00b1 0.46 0.53\nNiacin (mg) 14.43 \u00b1 6.38 15.08 \u00b1 7.33 0.66\nPyridoxine (mg) 0.93 \u00b1 0.54 0.92 \u00b1 0.54 0.93\nPantothenic acid \n(mg)\n\n\n\n1.04 \u00b1 0.78 1.11 \u00b1 1.23 0.75\n\n\n\nFolate (\u00b5g) 103.71 \u00b1 65.00 100.35 \u00b1 73.99 0.83\nVitamin B12 (\u00b5g) 3.09 \u00b1 2.07 3.55 \u00b1 1.78 0.29\nCalcium (mg) 353.84 \u00b1 198.35 372.54 \u00b1 182.04 0.65\nPhosphorus (mg) 926.17 \u00b1 338.32 913.28 \u00b1 254.88 0.84\nIron (mg) 19.46 \u00b1 9.74 19.77 \u00b1 10.71 0.89\nZinc (mg) 4.41 \u00b1 1.80 4.42 \u00b1 2.31 0.98\nCopper (mg) 0.69 \u00b1 0.40 0.64 \u00b1 0.33 0.54\nMagnesium (mg) 122.76 \u00b1 57.69 118.79 \u00b1 57.57 0.75\nTotal dietary \nfiber (g)\n\n\n\n5.07 \u00b1 3.75 3.89 \u00b1 3.32 0.13\n\n\n\naIndependent t test; 1Basal Metabolic Rate; 2Energy intake; 3Saturated \nfatty acids; 4Monounsaturated fat;\n 5Polyunsaturated fat\n\n\n\nTable 4. Dietary pattern\n\n\n\nDietary Pattern\nTotal (n=84) b\n\n\n\np \u2013 valueCase (n=42) \nn (%)\n\n\n\nControl (n=42) \nn (%)\n\n\n\nPoultry 35 (83.3%) 39(92.9%) 0.18\n\n\n\nBeef 10 (23.8%) 14 (33.3%) 0.33\n\n\n\nFish 26 (61.9%) 27 (64.3%) 0.82\n\n\n\nWheat 24 (57.1%) 28 (66.7%) 0.37\n\n\n\nDairy 5 (11.9%) 9 (21.4%) 0.24\n\n\n\nEgg 24 (57.1%) 30 (71.4%) 0.17\n\n\n\nNuts 5 (11.9%) 12 (28.6%) 0.06\n\n\n\nShellfish 9 (21.4%) 12 (28.6%) 0.45\n\n\n\nVegetables 31 (73.8%) 28 (66.7%) 0.47\n\n\n\nFruits 9 (21.4%) 10 (23.8%) 0.79\n\n\n\nCakes & sweets 15 (35.7%) 15 (35.7%) 1.00\nbChi Square test\n\n\n\nThere were 32 (38.1%) under reporters \n(EI:BMR ratio <1.2) and 52 (61.9%) plausible \nreporters (EI:BMR ratio 1.2-2.4). There was no \nover reporters (EI: BMR ratio >2.4) among the \nparticipants (Table 5).\n\n\n\nTable 5. Energy Intake - BMR ratio (EBR)\n\n\n\nEI1:BMR2 ratio (EBR)\nParticipants\n\n\n\nTotal (%)\nCase Control\n\n\n\nEBR <1.2 (under reporters) 14 18 32 (38.1)\n\n\n\nEBR 1.2-2.4 (Plausible) 28 24 52 (61.9)\n\n\n\nEBR >2.4 (over reporters) 0 0 0\nEnergy intake; Basal Metabolic Rate\n\n\n\nDiscussion\nVitamin B12 supports myelinization and axonal \ntransport, thus helping regeneration of peripheral \nnerve cells.20 Its deficiency plays a role in the \netiology of neuropathic itching by causing \nsmall-fiber neuropathy.21 Anti-inflammatory \nand anti-oxidative properties of vitamin B12 are \nexerted by downregulation of pro-inflammatory \ncytokines and reduction of nitric oxide. Low \nvitamin B12 has been associated with chronic \npruritic dermatoses including generalized \npruritus19 and chronic spontaneous urticaria.22 \nRobust itch sensations, increased neuronal \nactivity, and hyperinnervation are observed in \nAD skin.23 Chesini and Caminati24 described \na patient with severe, refractory AD and low \nserum vitamin B12. Subsequent correction of \nhis vitamin B12 level with oral supplementation \nresulted in significant AD improvement. \nTherefore, assessment of vitamin B12 level \nin patients with difficult-to-control atopic \ndermatitis was suggested.24 Emerging data \nindicate that a topical vitamin B12 preparation \nmay prevent atopic dermatitis flares due to its \nhigh affinity binding to nitric oxide produced by \nkeratinocyte.25,26\n\n\n\nOur findings showed significantly lower serum \nvitamin B12 level in AD patients compared \nto healthy controls despite similar dietary \npatterns and intake of macronutrients and other \nmicronutrients. Mean serum vitamin B12 levels \nwere within normal limits in both groups. We \npostulate that long standing utilization of tissue \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 17\n\n\n\nvitamin B12 in maintaining and regenerating \nperipheral nerve cells in AD may have resulted \nin reduction in the level of serum vitamin B12. \nThe historical lower normal value for serum \nvitamin B12 was 148 pmol/L27 compared \nto our reference value of 133 pmol/L with \noverall coefficient of variation of performance \nof 5\u201315% between different assays and inter-\nmethod biases of plus 10% or minus 20% from \nthe all-laboratory trimmed mean.28 However, it \nis still unknown whether serum B12 correlated \nwith its tissue level. Additionally, level that \nrepresent subclinical deficiency, i.e., a low \nserum vitamin B12 in the absence of clinical \nsymptoms is unclear.29,30 Raising the lower \nrange to 258 ng/L has been considered, but the \nbenefit of detecting subclinical deficiencies \nmay be limited as there are few associated \nmetabolic abnormalities31 and a small number of \nsubclinical deficiencies that progress to clinical \ndeficiencies. Low-normal levels with potential \neffect on patients\u2019 health are often ignored by \nphysicians and even genuinely low levels may \nbe ignored if neuropathy or anaemia are not \nevident. Further testing using a functional test \nsuch as methylmalonic acid (MMA) assay is \nrecommended for levels <221 pmol/L.32\n\n\n\nSubclinical reduction in vitamin B12 due \nto subclinical malabsorption and increased \nutilization of proliferating tissue have been \npostulated to contribute to inflammation in AD \n(33). Vitamin B12 modulates inflammation \ncascade by suppressing production of T \nlymphocytes-derived cytokines, in particular \ninterleukin-6 (IL-6), interferon-gamma (IFN-\ngamma), and interleukin-1 beta (IL-1 beta).34 \nInverse correlations between chronicity of AD \nand severity of pruritus with serum vitamin B12 \nlevel was demonstrated in our cohort, which \nsupports this postulation. However, our study \nwas not sufficiently powered to determine this \nrelationship.  \n\n\n\nDietary pattern and nutrient intake were \nestimated using 3 days diet recall in our \nstudy. Vitamin B12 was slight lower than \nthe recommended nutrient intake (RNI) for \nMalaysia at 4 microgram per day.35 This was not \n\n\n\na contributing factor to the lower level of serum \nB12 in our AD cohort as the intake for both \ncases and control was similar. The validity of \n24-hour dietary recall is dependent on the degree \nof accuracy in which respondents recall their \nfood consumption. Under reporting of energy \nintake is defined as  EI:BMR ratio below 1.2.36 \nThe prevalence of underreporting in our study \nwas lower than Arumugam et al (77.4%)37 and \nZainuddin et al (61%).17 Factors associated with \nunderreporting include obesity, age, gender, \nsocial status and controlled eating habits.38,39 \nReporting bias may lead to a misinterpretation \nof the individual\u2019s nutritional state and may \nresult in misleading associations between diet \nand disease.\n\n\n\nApart from that, serum eosinophils levels were \nalso noted to be significantly higher in our \ncohort and the degree of severity also correlated \nwith eosinophil level. This was consistent \nwith previous studies.40-42  We also notice a \nhigher platelet to lymphocyte ratio which was \nin line with previous studies.43-45 These simple \nindicators may serve as a potential adjunct \nmarkers of ongoing systemic inflammation in \natopic dermatitis patients in the future.43\n\n\n\nIn our cohort, AD severity correlated well \nwith the DLQI indicating its effect on patients\u2019 \nquality of life. This has to be emphasized in \nregards to aiming for optimal disease control to \nimprove patients\u2019 daily activity and emotional \nburden. Patients with subclinical vitamin \nB12 deficiency are prone to symptoms of  \ndepression46-48 and anxiety,49 thus exacerbation \nor worsening of depressive symptoms may \noccur with a concomitant chronic disease like \nAD that significantly affects quality of life.\n\n\n\nLimitation\nOur study is limited by the possibility of \nrecall bias with the 3-days dietary recall. \nComprehensive evaluation of other biomarkers \nlike homocysteine and methylmalonic acid \nwere not possible due to unavailability of the \nassays at our centre. Other micronutrients level \nincluding vitamin D, zinc, folate and trace \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4918\n\n\n\nmineral were beyond the scope of this study. \nConcurrent parasitic infestation was not tested \nin this study. \n\n\n\nConclusion\nSerum vitamin B12 level was significantly lower \nin AD patients. There were no differences in \ndietary pattern, macronutrient and micronutrient \nintakes between patients with AD and healthy \ncontrols. Serum vitamin B12 level did not \ncorrelate with AD severity or disease duration. \nAlthough the role of vitamin B12 in AD is still \nunclear, dietary patterns of AD patients should \nbe assessed to ensure adequate nutrient intake.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to \ndeclare.\n\n\n\nAcknowledgement\nWe would like to thank the Director of General \nof Health Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n1. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. \n\n\n\nLancet 2020;396:345-60.\n2. Bronsnick T, Murzaku EC, Rao BK. Diet in dermatology: \n\n\n\nPart I. Atopic dermatitis, acne, and nonmelanoma skin \ncancer. J Am Acad Dermatol 2014;71:1039. e1-12.\n\n\n\n3. Gille D, Schmid A. Vitamin B12 in meat and dairy \nproducts. Nutr Rev 2015;73:106-15.\n\n\n\n4. Hon KL, Leung TF, Kam WY, Lam MC, Fok TF, Ng PC. \nDietary restriction and supplementation in children with \natopic eczema. Clin Exp Dermatol 2006;31:187-91.\n\n\n\n5. Finch J, Munhutu MN, Whitaker-Worth DL. Atopic \ndermatitis and nutrition. Clin Dermatol 2010;28:605-14. \n\n\n\n6. Low DW, Jamil A, Md Nor N, Kader Ibrahim SB, Poh BK. \nFood restriction, nutrition status, and growth in toddlers \nwith atopic dermatitis. Pediatr Dermatol 2020;37:69-77.\n\n\n\n7. Fayet F, Flood V, Petocz P, Samman S. Avoidance of meat \nand poultry decreases intakes of omega-3 fatty acids, \nvitamin B12, selenium and zinc in young women. J Hum \nNutr Diet 2014;27 Suppl 2:135-42.\n\n\n\n8. Bath-Hextall F, Delamere FM, Williams HC. Dietary \nexclusions for established atopic eczema. Cochrane \nDatabase Syst Rev 2008;2008:CD\n\n\n\n9. Green R, Allen LH, Bj\u00f8rke-Monsen AL, Brito A, Gu\u00e9ant \nJL, Miller JW et al. Vitamin B12 deficiency. Nat Rev Dis \nPrimers 2017;3:317040.\n\n\n\n10. Carmel R. Subclinical cobalamin deficiency. Curr Opin \n\n\n\nGastroenterol 2012;28:151-8. \n11. Birch CS, Brasch NE, McCaddon A, Williams JH. A \n\n\n\nnovel role for vitamin B(12): Cobalamins are intracellular \nantioxidants in vitro. Free Radic Biol Med 2009;47:184-8. \n\n\n\n12. St\u00fccker M, Pieck C, Stoerb C, Niedner R, Hartung J, \nAltmeyer P. Topical vitamin B12\u2014a new therapeutic \napproach in atopic dermatitis\u2014evaluation of efficacy \nand tolerability in a randomized placebo\u2010controlled \nmulticentre clinical trial. Br J Dermatol 2004;150:977-83.\n\n\n\n13. Williams HC, Burney PG, Hay RJ, Archer CB, Shipley \nMJ, Hunter JJ et al. The U.K. Working Party\u2019s Diagnostic \nCriteria for Atopic Dermatitis. I. Derivation of a minimum \nset of discriminators for atopic dermatitis. Br J Dermatol \n1994;131:383-96. \n\n\n\n14. Severity scoring of atopic dermatitis: the SCORAD index. \nConsensus Report of the European Task Force on Atopic \nDermatitis. Dermatology 1993;186:23-3.\n\n\n\n15. Finlay AY, Khan G. Dermatology Life Quality Index \n(DLQI)\u2014a simple practical measure for routine clinical \nuse. Clin Exp Dermatol 1994;19:210-6.\n\n\n\n16. Moshfegh AJ, Rhodes DG, Baer DJ, Murayi T, Clemens \nJC, Rumpler WV et al. The US Department of Agriculture \nAutomated Multiple-Pass Method reduces bias in the \ncollection of energy intakes. Am J Clin Nutr 2008;88:324-\n32.\n\n\n\n17. Zainuddin AA, Norazmir MN, Md Yusof S, Ibrahim \nAIN,  Aris T, Foo LH. Under-reporting of energy and \nnutrient intake is a persistent issue in the Malaysian Adult \nNutrition Surveys. Mal J Nutr 2019;25:261-71.\n\n\n\n18. Dean AG, Soe MM. OpenEpi: Open Source Epidemiologic \nStatistics for Public Health, Version. www.OpenEpi.com, \nupdated 2013/04/06.\n\n\n\n19. Polat M, Oztas P, Ilhan MN, Yalcin B, Alli N. Generalized \npruritus: a prospective study concerning etiology. Am J \nClin Dermatol 2008;9:39-44. \n\n\n\n20. Baltrusch S. The Role of Neurotropic B Vitamins in Nerve \nRegeneration. Biomed Res Int 2021;2021:9968228. \n\n\n\n21. Misery L, Brenaut E, Le Garrec R, Abasq C, Genestet S, \nMarcorelles P et al. Neuropathic pruritus. Nat Rev Neurol \n2014;10:408-16. \n\n\n\n22. Mete N, Gulbahar O, Aydin A, Sin AZ, Kokuludag A, \nSebik F. Low B12 levels in chronic idiopathic urticaria. J \nInvestig Allergol Clin Immunol 2004;14:292-9. \n\n\n\n23. Ikoma A, Rukwied R, St\u00e4nder S, Steinhoff M, Miyachi \nY, Schmelz MJ. Neuronal sensitization for histamine-\ninduced itch in lesional skin of patients with atopic \ndermatitis. Arch Dermatol 2003;139:1455-8.\n\n\n\n24. Chesini Ms D, Caminati Md M. Vitamin B12 and \nAtopic Dermatitis: Any Therapeutic Relevance For Oral \nSupplementation? J Diet Suppl 2022;19:238-42. \n\n\n\n25. Januchowski R. Evaluation of topical vitamin B(12) for \nthe treatment of childhood eczema. J Altern Complement \nMed 2009;15:387-9.\n\n\n\n26. Nistico SP, Del Duca E, Tamburi F, Pignataro E, De \nCarvalho N, Farnetani F et al. Superiority of a vitamin \nB12-barrier cream compared with standard glycerol-\npetrolatum-based emollient cream in the treatment of \natopic dermatitis: A randomized, left-to-right comparative \ntrial. Dermatol Ther 2017;30. doi:10.1111/dth.12523.\n\n\n\n27. Snow CF. Laboratory diagnosis of vitamin B12 and folate \ndeficiency: A guide for the primary care physician. Arch \nIntern Med 1999;159:1289-98.\n\n\n\n28. Devalia V, Hamilton MS, Molloy AM; British Committee \nfor Standards in Haematology. Guidelines for the \ndiagnosis and treatment of cobalamin and folate disorders. \nBr J Haematol. 2014;166:496-513.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 19\n\n\n\n29. Carmel R, Sarrai M. Diagnosis and management of \nclinical and subclinical cobalamin deficiency: advances \nand controversies. Curr Hematol Rep 2006;5:23-33. \n\n\n\n30. Volkov I, Press Y, Rudoy I. Vitamin B12 could be a \n\u201cmaster key\u201d in the regulation of multiple pathological \nprocesses. J Nippon Med Sch 2006;73:65-9.\n\n\n\n31. Carmel R, Green R, Rosenblatt DS, Watkins D. Update \non cobalamin, folate, and homocysteine. Hematology Am \nSoc Hematol Educ Program 2003:62-81.\n\n\n\n32. Moridani M, Ben-Poorat S. Laboratory investigation of \nvitamin B12 deficiency. Lab Med 2006;37:166-74. \n\n\n\n33. Marks J, Shuster S. Vitamin B12 excretion in patients \nwith various skin diseases. Br Med J 1970;3:618-21. \n\n\n\n34. Yamashiki M, Nishimura A, Kosaka Y. Effects of \nmethylcobalamin (vitamin B12) on in vitro cytokine \nproduction of peripheral blood mononuclear cells. J Clin \nLab Immunol 1992;37:173-82.\n\n\n\n35. National Coordinating Commitee on Food and Nutrition, \nMinistry of Health Malaysia. A report of the technical \nworking group on nutritional guidelines. Recommended \nnutrient intake for Malaysia 2017. Ministry of Health \nMalaysia, Putrajaya.\n\n\n\n36. Goldberg GR, Black AE, Jebb SA, Cole TJ, Murgatroyd \nPR, Coward WA et al. Critical evaluation of energy intake \ndata using fundamental principles of energy physiology: \n1. Derivation of cut-off limits to identify under-recording. \nEur J Clin Nutr 1991;45:569-81. \n\n\n\n37. Arumugam M, Jamil A, Krishnasamy S, Nor NM. Energy \nand Dietary Intakes in Adult Atopic Dermatitis. Mal J \nMed Health Sci 2021;17:77-86. \n\n\n\n38. Azizi F, Esmaillzadeh A, Mirmiran P. Correlates of under- \nand over-reporting of energy intake in Tehranians: body \nmass index and lifestyle-related factors. Asia Pac J Clin \nNutr 2005;14:54-9. \n\n\n\n39. Kye S, Kwon SO, Lee SY, Lee J, Kim BH, Suh HJ et al. \nUnder-reporting of Energy Intake from 24-hour Dietary \nRecalls in the Korean National Health and Nutrition \nExamination Survey. Osong Public Health Res Perspect \n2014;5:85-91. \n\n\n\n40. Jenerowicz D, Czarnecka-Operacz M, Silny W. \nPeripheral blood eosinophilia in atopic dermatitis. Acta \nDermatovenerol Alp Pannonica Adriat 2007;16:47-52.\n\n\n\n41. Uehara M, Izukura R, Sawai T. Blood eosinophilia in \natopic dermatitis. Clin Exp Dermatol 1990;15:264-6.\n\n\n\n42. Inokuchi-Sakata S, Ishiuji Y, Katsuta M, Kharma B, \nYasuda KI, Tominaga M et al. Role of eosinophil \nrelative count and neutrophil-to-lymphocyte ratio in the \nassessment of severity of atopic dermatitis. Acta Derm \nVenereol 2021;101:adv00491.\n\n\n\n43. Jiang Y, Ma W. Assessment of neutrophil-to-lymphocyte \nratio and platelet-to-lymphocyte ratio in atopic dermatitis \npatients. Med Sci Monit 2017;23:1340-6. \n\n\n\n44. Batmaz SB. Simple Markers for Systemic Inflammation \nin Pediatric Atopic Dermatitis Patients. Indian J Dermatol \n2018;63:305-10. \n\n\n\n45. Muhanad Z, Al Aubydi MA. Demographic investigations \nof some atopic dermatitis patients in Baghdad/Iraq.  J \nUniv Shanghai Sci Technol 2020;22:1270-80.\n\n\n\n46. Sepp\u00e4l\u00e4 J, Koponen H, Kautiainen H, Eriksson JG, \nKampman O, Leivisk\u00e4 J et al. Association between \nvitamin B12 levels and melancholic depressive symptoms: \na Finnish population-based study. BMC Psychiatry \n2013;13:145.\n\n\n\n47. Bell IR, Edman JS, Morrow FD, Marby DW, Mirages S, \nPerrone G, et al. B complex vitamin patterns in geriatric \nand young adult inpatients with major depression. J Am \n\n\n\nGeriatr Soc 1991;39:252-7.\n48. Mischoulon D, Burger JK, Spillmann MK, Worthington \n\n\n\nJJ, Fava M, Alpert JE. Anemia and macrocytosis in the \nprediction of serum folate and vitamin B12 status, and \ntreatment outcome in major depression. J Psychosom Res \n2000;49:183-7. \n\n\n\n49. Smith AD, Refsum H. Do we need to reconsider the \ndesirable blood level of vitamin B12? J Intern Med \n2012;271:179-82.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4920\n\n\n\nCASE REPORT\n\n\n\nA Case of Eosinophilic Granulomatosis with Polyangiitis Mimicking \nCutaneous Tuberculosis and Tuberculous Lymphadenitis\n\n\n\nChang Wei Hsi1, MRCP, Rajeswari A/P Gunasekaran1, MD, Manisha Chandran1, MRCP, Ng Fei Yin1, \nAdvMDerm, Ireen Razini Ab Rahman2, MPath, Ng Ting Guan1, AdvMDerm\n\n\n\n1Department of Dermatology, Hospital Tengku Ampuan Rahimah, Selangor, Malaysia\n2Department of Pathology, Hospital Tengku Ampuan Rahimah, Selangor, Malaysia\n\n\n\nSummary\nEosinophilic granulomatosis with polyangiitis (EGPA), or Churg-Strauss Syndrome (CSS) is a rare \ngranulomatous necrotizing vasculitic disease characterized by the presence of asthma, sinusitis, and \nhypereosinophilia. We describe a patient who was initially diagnosed with tuberculous lymphadenitis \nand later diagnosed with EGPA. \n\n\n\nKey Words: Churg-Strauss syndrome, Eosinophilic Granulomatosis with Polyangiitis, Tuberculous lymphadenitis, \nRituximab\n\n\n\nCorresponding Author\nDr Chang Wei Hsi\nDepartment of Dermatology,\nHospital Tengku Ampuan Rahimah,\nJalan Langat, \n41200 Klang, Selangor, Malaysia. \nEmail: elizzchang@gmail.com\n\n\n\nIntroduction\nEosinophilic granulomatosis with polyangiitis \n(EGPA), or Churg-Strauss syndrome (CSS) is \na rare granulomatous necrotizing vasculitic \ndisease characterized by the presence of asthma, \nsinusitis, and hypereosinophilia.1-3 EGPA causes \nvasculitis of small-to-medium blood vessels \nthat affects many organ systems such as the \ncardiovascular, pulmonary, renal, nervous and \nvascular systems.4 Vasculitis of extrapulmonary \norgans is a major cause of morbidity and mortality \nin this disease.3 Corticosteroids are considered \nthe first-line of treatment for EGPA patients to \nachieve remission.4 Rituximab is an anti-CD20 \nmonoclonal antibody that is approved for use \nin the treatment of lymphoid malignancies, \nrheumatoid arthritis, and granulomatosis with \npolyangiitis (GPA) and microscopic polyangiitis \n(MPA).5 We report a challenging case of \nactive severe EGPA mimicking cutaneous \ntuberculosis and tuberculous lymphadenitis \nwho initially responded to intravenous (IV) \npulse corticosteroid and Rituximab, relapsed \nand retreated, but succumbed to Coronavirus \ndisease 2019 (COVID-19) infection. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 21\n\n\n\nCase Report\nA 38-year-old female with underlying bronchial \nasthma and rhinosinusitis presented to the \ndermatology clinic with multiple erythematous \npapules, plaques and ulcerated nodules on her \nleft eye lid (Figure 1A), dorsum of the right \nindex finger (Figure 1C), forearms, and chest \n(Figure 1E) with intermittent fever for 6 months. \nSystemic review was otherwise unremarkable.  \nShe had been empirically treated for smear-\nnegative tuberculous lymphadenitis by the \ntreating physician for a year but showed no \nimprovement. \n\n\n\nFigure 1. Churg-Strauss syndrome. (A) Erythematous \nmultilobulated plaque with ulcerated haemorrhagic \ncrust on left eye lid; (B) Eye lid post-treatment, resolved \nlesion; (C) Erythematous juicy ulcerated nodule with \ncontact bleeding on right dorsal index finger; (D) Index \nfinger post-treatment, resolved lesion; (E) Multiple \npink elongated papules over anterior chest; (F) Chest \npost-treatment, resolved lesions with keloid scars.\n\n\n\nLaboratory tests revealed leukocytosis (16820/\nmm3) with eosinophilia (1050/mm3). Perinuclear \nanti-neutrophil cytoplasmic antibodies \n(P-ANCA), chest radiograph, echocardiograph \nand Tuberculosis Quantiferon results were \nnormal. Computed tomography (CT) scan of \nthorax, abdomen and pelvis revealed multiple \nnon-necrotic cervical, mediastinal, inguinal \nlymphadenopathy with lung, liver and bone \n\n\n\nnodules. Positron emission tomography (PET) \nscan showed avid lytic lesions with rims of \nsclerosis along vertebra, bilateral ileum and \nright tibia representing chronic granulomatous \nbone changes. Magnetic resonance imaging and \nangiography (MRI/MRA) brain showed multiple \nsupratentorial non enhancing hyperintense foci. \n\n\n\nBiopsies taken from the lymph node and \nskin plaque showed a mixture of neutrophils, \neosinophils and histiocytes in aggregates, \nforming granulomas. Blood vessels showed \nevidence of vasculitis with eosinophils (Figure \n2). Immunohistochemical staining for S100 and \nCD1a were positive, whereas langerin (CD207) \nstaining was negative. Culture and polymerase \nchain reaction (PCR) for Mycobacterium \ntuberculosis from skin biopsy were negative. \nA diagnosis of EGPA was made based on the \nclinical manifestations, histopathological \nfindings of eosinophilic granulomas as well as \nsmall vessel vasculitis. \n\n\n\nFigure 2. Dermal small vessel vasculitis in CSS. \nHistopathologic findings of infiltrated plaque on chest \nshowing dermal eosinophilic vasculitis and focal \ngranuloma. Hematoxylin-eosin stain, magnification \nX200.\n\n\n\nInduction of remission was achieved with \ncombined pulse IV methylprednisolone 500 \nmg daily for 3 days and IV Rituximab 375 mg/\nm2 weekly for 4 doses. Cyclophosphamide was \nnot used due to type 1 hypersensitivity reaction \nof urticaria eruption. There was significant \nimprovement in clinical signs, eosinophilia and \nradiological features in our patient following \ntreatment. Remission was achieved for 6 \nmonths, with tapering oral corticosteroid and \nazathioprine (2 mg/kg/day) as maintenance \ntherapy. Her disease relapsed with hip joint \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4922\n\n\n\nsynovitis confirmed by MRI, multiple areas of \nhypermetabolic disease involving mediastinal \nnodes, subcutaneous, bones and joints on PET/\nCT scan, and raised inflammatory markers. \nAzathioprine was switched to mycophenolate \nmofetil (2000 g/day), with a subsequent second \ncycle of IV Methylprednisolone and Rituximab \n15 months after the first cycle. Her symptoms \nimproved significantly whilst maintaining on \nmycophenolate mofetil, with plans for follow-\nup scans. Unfortunately, she succumbed \nto COVID-19 with category 5 severity, \ncomplicated with organizing pneumonia and \npulmonary embolism 10 weeks after the second \ncycle of IV Rituximab. \n\n\n\nDiscussion\nEGPA is a rare granulomatous necrotizing \nvasculitis with a very low incidence of 0.5 \nto 6.8 new cases per million patients every \nyear.1,4 It affects both men and women equally \nand the average age at diagnosis is 48 years.4 \nThe exact cause of EGPA is unknown.1 \n\n\n\nClinical diagnosis of EGPA is based on the \nAmerican College of Rheumatology (ACR) \nCriteria which requires any 4 or more of the \nfollowing clinical criteria to be present: asthma, \neosinophilia > 10%, pulmonary infiltrates, \nparanasal sinus abnormality, neuropathy, or \nextravascular eosinophils.4 Our patient fulfilled \nthe ACR Criteria for EGPA, presenting with \nperipheral eosinophilia, asthma,  paranasal \nsinus abnormalities and biopsy containing a \nblood vessel with extravascular eosinophils.6\n\n\n\nThe sequence of pathophysiological events \nin EGPA includes 3 stages.4 Firstly, the pre-\nvasculitic phase can be characterized by asthma \nand other allergies, along with blood and tissue \neosinophila.4,7 Next, infiltration of eosinophils \ninto tissues occurs in organs such as the lungs, \ngastrointestinal tract, or heart.4,7 The last stage is \nwhen vasculitis occurs, which can be necrotizing \nor non-necrotizing, and EGPA is diagnosed.4 \n\n\n\nHowever, this sequence of events may vary in \ndifferent patients, and multiple manifestations \nmay appear at the same time.7 The most \nfrequently observed clinical manifestations of \n\n\n\nEGPA are asthma, allergic rhinitis, peripheral \nnervous system involvement, gastrointestinal \nsymptoms, cardiac involvement, and renal \ndisease.7-9 Anti-neutrophil cytoplasmic \nantibodies (ANCA) have been reported in \n6\u201377% of EGPA patients.6  In our patient, ANCA \nwas not detected. \n\n\n\nUp to 81% of EGPA patients experience \ncutaneous manifestations, and approximately \n14% of cases present such manifestations as \na sign of the disease.7 Palpable purpura of the \nextremities is the most common cutaneous \nmanifestation, affecting up to 50% of EGPA \npatients, followed by urticarial lesions and less \ncommonly, livedo reticularis, papules, cutaneous \ninfarctions, Raynaud\u2019s phenomenon, vesicles, \nand pustules.7,9 The major histopathological \nfeatures of EGPA include vasculitis, eosinophilic \ninfiltration, and extravascular granuloma.7\n\n\n\nOur patient was initially treated for smear-\nnegative tuberculous lymphadenitis based \non clinical findings of persistent fever, \nconstitutional symptoms and lymphadenopathy. \nHowever, there was no clinical improvement \nupon completion of anti-tuberculosis treatment \nfor a year. Upon suspicion of EGPA, the \ndermatologist and rheumatologist were \nconsulted, and we proceeded with a skin and \nlymph node biopsy, culture and PCR, which \nsuggested the diagnosis of EGPA and excluded \ntuberculosis. \n\n\n\nPrior to the use of alkylating agents, survival \nwith this disease was quite poor, current \ntreatment regimens have reversed this poor \nprognosis, but treatments are still associated \nwith toxicity.  Most EGPA patients respond \nwell to immunosuppressive therapy and can \nachieve long-term remission.4,9 Generally, \ncorticosteroids act as the first-line therapy \nfor EGPA patients to achieve remission and \nimprove survival.4 Corticosteroids can either \nbe used alone or in combination with one \nor more immunosuppressive drugs such as \ncyclophosphamide or methotrexate, especially \nin cases where recurrences are more frequent \nor associated with a severe form of necrotizing \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 23\n\n\n\nvasculitis in other organs.4,7 Therapy typically \nconsists of two stages of treatment: remission \ninduction and maintenance of remission.10 \n\n\n\nAccording to the 2021 American College of \nRheumatology/Vasculitis Foundation Guideline \nfor the management of ANCA-associated \nvasculitis, the recommended treatment for \nremission induction in patients with active, \nsevere EGPA is pulse glucocorticoids or high-\ndose oral glucocorticoids with either rituximab \nor cyclophosphamide.11 For maintenance, \nmethotrexate, azathioprine, or mycophenolate \nmofetil or leflunomide is recommended after \nremission induction.11\n\n\n\nOur patient had active severe EGPA, she \nachieved initial clinical remission of 6 months \nafter the first cycle of pulse glucocorticoid \nsteroid and Rituximab, and was maintained \nwith azathioprine. Subsequently, her disease \nrelapsed and required another cycle of pulse \nglucocorticoid steroid and Rituximab and \nswitching of azathioprine to mycophenolate \nmofetil, in which she showed improved \nclinical symptoms. Unfortunately, our patient \nsuccumbed to severe COVID-19 infection 10 \nweeks after the second cycle of Rituximab. \nGrowing evidence has suggested that treatment \nwith anti-CD20 therapy such as Rituximab, \nincreases the risk of developing severe \noutcomes from COVID-19 (risk ratio: 1.7\u2013\n5.5).12 Several studies have demonstrated that \nhumoral immune responses after COVID-19 \nvaccination are poor in patients receiving anti-\nCD20 therapy, even after two doses of the \nvaccine.12. Physicians should be aware of such \nrisks and discuss possible alternative treatments \nwith patients who are receiving or would initiate \ntreatment with Rituximab over the remainder of \nthe COVID-19 pandemic.\n\n\n\nConclusion\nIn summary, we report a case of a patient \nwho was initially treated for tuberculous \nlymphadenitis and eventually diagnosed with \nEGPA. In order to establish a diagnosis of EGPA, \nclinicians must have a high index of suspicion \n\n\n\nin patients with background of bronchial \nasthma, rhinosinusitis, persistent eosinophilia \nand organs involvement that is histologically \nconsistent with an eosinophilic granulomatous \nreaction. It is essential to diagnose this rare \ndisease early so that effective treatment can be \ninitiated in time to improve the prognosis of \nEGPA patients. Therapies like Rituximab and \nother immunosuppressants can be effective in \ncontrolling the disease activity. However, the \ncourse of the disease and response to therapy \nis unpredictable. Increased risk of severe \nCOVID-19 infection while on Rituximab may \nbe detrimental, and thus, poses great therapeutic \ndilemma and challenges to physicians, especially \nin this era of the COVID-19 pandemic.\n\n\n\nConflict of Interest Declaration\nThe authors declare that there is no conflict of \ninterest in this work.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish \nthis article.\n\n\n\nReferences\n1. Ghosh S, Bhattacharya M, Dhar S. Churg-Strauss \n\n\n\nSyndrome. Indian J Dermatol 2011;56:718-21.\n2. Choi JH, Ahn IS, Lee HB, Park CW, Lee Heon C, Ahn \n\n\n\nHK. A case of Churg-Strauss Syndrome. Ann Dermatol \n2009;21:213-6.\n\n\n\n3. King TE. 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Arthritis Rheum \n1990;33:1094-100.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4924\n\n\n\n7. Bosco L, Peroni A, Schena D, Colato C, Girolomoni G. \nCutaneous manifestations of Churg-Strauss syndrome: \nreport of two cases and review of the literature. Clin \nRheumatol 2011;30:573-80.\n\n\n\n8. Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, \nCasessus P. Churg-Strauss syndrome: clinical study and \nlong-term follow-up of 96 patients. Medicine (Baltimore). \n1999;78:26-37.\n\n\n\n9. Della Rossa A, Baldini C, Tavoni A, Tognetti A, Neglia D, \nSambuceti G et al. Churg-Strauss syndrome: clinical and \nserological features of 19 patients from a single Italian \ncentre. Rheumatology (Oxford). 2002;41:1286-94.\n\n\n\n10. Geetha D, Kallenberg C, Stone JH, Salama AD, Appel \nGB, Duna G et al. Current therapy of granulomatosis \nwith polyangiitis and microscopic polyangiitis: the role of \nrituximab. J Nephrol 2015;28:17-27.\n\n\n\n11. Chung SA, Langford CA, Maz M, Abril A, Gorelik M, \nGuyatt G et al. 2021 American College of Rheumatology/\nVasculitis Foundation Guideline for the management of \nantineutrophil cytoplasmic antibody-associated vasculitis. \nArthritis Rheumatol 2021;73:1366-83.\n\n\n\n12. Boekel L, Wolbink GJ. Rituximab during the COVID-19 \npandemic: time to discuss treatment options with patients. \nLancet Rheumatol 2022;4:e154-5.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 25\n\n\n\nCASE REPORT\n\n\n\nSpontaneous Re-pigmentation of Vitiligo Following Excision of Halo \nCongenital Melanocytic nevi: An Interesting Case Report\n\n\n\nAnil Prakash Gosavi, MD, Ravindranath Brahmadeo Chavan, MD, Neelam Bhatt, MD, Darshana Rajendra \nKundale, MD\n\n\n\nDepartment of Dermatology, Venereology and Leprosy, Byramjee Jeejeebhoy Government Medical College, \nPune, India\n\n\n\nSummary\nHalo nevi (HN) are benign skin lesion that represent melanocytic nevi in which an inflammatory \ninfiltrate develops, resulting in zone of depigmentation around nevus. Although Sutton originally \ndescribed the lesion in 1916 as leukoderma acquista centrifugum, the lesions were noted earlier as \nevidenced in the painting by Matthias Grunwald cica 1512-1516. The prevalence of HNs in the general \npopulation is 1%, and HNs usually appear in childhood or early adulthood. Up to 26% of patients \nwith HN have vitiligo, but in very few instances is there an association of HN around congenital \nmelanocytic nevi (CMN) and vitiligo. The exact mechanisms responsible for the development of \nvitiligo and HN and its resolution are unknown. One of the most accepted hypotheses considers that \nboth phenomena are a result of a self-limited immunologic response to pigmented cells, either in the \n\u201cnormal\u201d skin or within the melanocytic lesion. Hereby we present a rare case report of a girl with \nhalo CMN and infraorbital vitiligo. The halo CMN was excised which was followed by spontaneous \nimprovement of vitiligo.\n\n\n\nKey Words: Leukoderma acquista centrifugum, Vitiligo, Excision\n\n\n\n\n\n\n\nCorresponding Author\nDr Ravindranath B Chavan\nDepartment of Dermatology, Venereology and \nLeprosy, \nBJGMC, Pune, \n411001 India.\nEmail: drravindranathchavan@gmail.com\n\n\n\nIntroduction\nHalo nevus, also called Sutton\u2019s nevus, is a \nmelanocytic nevus surrounded by a halo of \ndepigmentation, which is usually symmetrically \nround or oval. Halo nevi affect up to 5% children \nin the age group of six to fifteen years old.1,2 \n\n\n\nin an equal sex distribution. The most common \nlocation is the back. HN has been shown to be \nassociated with many autoimmune diseases, of \nwhich vitiligo is the most closely related with \nreported incidence of between 1-48%.3,4 There \nare limited reports in the literature, especially \nwith regard to CMN excision.\n\n\n\nCase Report\nA 11-year-old girl presented to the Dermatology \nOutpatient department for a congenital \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4926\n\n\n\nmelanocytic nevus (CMN). The lesion had \nbeen present since birth and a hypopigmented \nhalo developed around the congenital nevus 3 \nyears ago. She also developed hypopigmented \npatches developed over left periorbital region, \napproximately 13 months prior. Her past history \nand family history were unremarkable. On \nphysical examination, the congenital nevus, \nmeasuring 0.5 cm diameter was located on the \nleft side of nape of neck. The nevus was dark \nbrown in colour with a depigmented halo. \nExamination of other body parts revealed \na linear depigmented patch over the left \ninfraorbital area. The clinical diagnosis of \nhalo congenital melanocytic nevus associated \nwith vitiligo was established. (Figure 1) The \npatient\u2019s parents were concerned about the \nappearance of the halo and vitiligo and requested \nto remove the CMN. Excision of the nevus \nwith punch biopsy was performed. Pathologic \nexamination revealed compound melanocytic \nnevus with congenital features and minimal \nlymphocytes and no macrophage infiltration, \ncompletely excised. Patient was followed up \nafter a week to reveal a healing wound over \nthe excision site and followed up monthly. At \n5 month follow-up, the patient\u2019s halo nevus \nsite was in a resolution phase and the vitiligo \nin the left infraorbital region was noted to be \nspontaneously repigmented (Figure 2 & 3).\n\n\n\nFigure 1. Pre-excision: Halo CMN of 0.5cm in \ndiameter with left infraorbital vitiligo\n\n\n\nFigure 2. Gradual reduction in the size of nevi post \nexcision in monthly visits\n\n\n\nFigure 3. Spontaneous resolution of vitiligo in the \nleft infraorbital area in monthly visits\n\n\n\nDiscussion\nHalo nevi with vitiligo is well described,5 but \nhalo formation around congenital nevi is much \nless common.6 It has been thought that similar \nautoimmune mechanisms, in which cytotoxic \nT-lymphocytes and antibodies to melanocytes \n(specifically IgM) cause depigmentation \nof the affected skin, cause vitiligo and halo \nnevi.6,7 CMN with halo or vitiligo needs to be \nmonitored clinically. The natural history of the \nlesion varies, because the CMN may remain \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 27\n\n\n\nstable or undergo complete regression.8 The risk \nof malignant transformation of CMN is reported \nto be between 1% and 5%, depending on size.10 \nSurgical excision of CMN is indicated if the \nlesion is significantly irregular or its appearance \nis unstable. The resolution of vitiligo after \nexcision is not an expected outcome, with only \none prior report of excision of halo CMN with \nsubsequent re-pigmentation of vitiligo.\n\n\n\nIn this case, excision was indicated based \non the request of the patient\u2019s parents. To the \nbest of our knowledge, there are only three \nprior reports of excision of halo CMN with \nsubsequent re-pigmentation of vitiligo8,9 in \nthe literature. The mechanism is not quite \nclear. The theory of autoimmune mechanism \nof vitiligo and halo formation assumed that \nthe removal of the nevus (potent \u201cantigen\u201d) \nresulted in downregulation of melanocytic \nantibodies, leading to gradual re-pigmentation \nof the patient\u2019s vitiligo without further therapy. \nAccording to prior reports, re-pigmentation of \nthe halo area often takes place over months \nor years, however, it does not always occur. \nWorkman et al reported an incredibly similar \ncase to ours, but they observed reoccurrence \nof depigmentation around the buttock scar 18 \nmonths after surgery. The reported reoccurrence \nwas thought to be due to undetected residual \nmelanocytes or antigen-presenting cells outside \nthe margin of resection.10 \n\n\n\nConclusion\nIn our case the rapid recovery could be due to \nthe small size of nevus and vitiliginous area. \nThe outcome was promising. It suggests that \nwhen antigens are removed and antibodies are \ncleaned out of the circulation, vitiligo may be \nresolved. Removing the inciting agent may be a \npromising way to control vitiligo.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n1. Aouthmany M, Weinstein M, Zirwas MJ, Brodell RT. The \n\n\n\nnatural history of halo nevi: A   retrospective case series. J \nAm Acad Dermatol 2012;67:582-6.\n\n\n\n2. Nedelcu RI, Zurac SA, Br\u00eenzea A, Cioplea MD, Turcu G, \nPopescu R et al. Morphological features of melanocytic \ntumors with depigmented halo: Review of the literature and  \npersonal results. Rom J Morphol Embryol 2015;56:659-\n63.\n\n\n\n3. Frank SB, Cohen HJ. The halo nevus. Arch Dermatol \n1964;89:367-73.\n\n\n\n4. Wayte DM, Helwig EB. Halo nevi. Cancer 1968;22:69-90.\n5. Gauthier Y, Surleve-Bazeille JE, Gauthier O, Texier L. \n\n\n\nUltrastructure of halo nevi. J Cutan Pathol 1975;2:71-81.\n6. Hofmann UB, Brocker EB, Hamm H. Simultaneous onset \n\n\n\nof segmental vitiligo and a halo surrounding a congenital \nmelanocytic naevus. Acta Derm Venereol 2009;89:402-6. \n\n\n\n7. Stierman SC, Tierney EP, Shwayder TA. Halo congenital \nnevocellular nevi associated with extralesional vitiligo: a \ncase series with review of the literature. Pediatr Dermatol \n2009;26:414-24.\n\n\n\n8. Tokura Y, Yamanaka K, Wakita H, Kurokawa S, Horiguchi \nD, Usui A et al. Halo congenital nevus undergoing \nspontaneous regression: involvement of T cell immunity in \ninvolution and presence of circulating antinevus cell IgM \nantibodies. Arch Dermatol 1994;130:1036-41.\n\n\n\n9. Price HN, Schaffer JV. Congenital melanocytic nevi - \nwhen to worry and how to treat: facts and controversies. \nClin Dermatol 2010;28:293-302.\n\n\n\n10. Workman M, Sawan K, El Amm C. Resolution and \nrecurrence of vitiligo following excision of congenital \nmelanocytic nevus. Pediatric Dermatol 2013;30:e166-8.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4928\n\n\n\nCASE REPORT\n\n\n\nA Report of Staphylococcus Scalded Skin Syndrome in Adult\n\n\n\nTeo Jen Keat1, MD, Siti Badariah Zakaria2, MMed, Wan Noor Hasbee Wan Abdullah3, AdvMDerm\n\n\n\n1Department of Internal Medicine, Hospital Universiti Sains Malaysia, Kota Bharu, Kelantan\n2Department of Dermatology, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan\n\n\n\nSummary\nStaphylococcal scalded skin syndrome (SSSS) is typically a clinical diagnosis,1 affecting primarily \nneonates and children. It is characterised by a diffuse skin disorder with tenderness, erythema, large \nwrinkled superficial blistering, and desquamation caused by the hematogenous dissemination of \nexotoxin-producing strains of staphylococcus aureus to the skin.4,10 Hospital admission is required for \nintravenous anti-staphylococcal antibiotic therapy and supportive care.\n\n\n\nThe rarity of SSSS in adults is best explained by the presence of exotoxins neutralizing antibodies and \nrenal elimination of the toxins.2 Two major risk factors are kidney failure and immunosuppression. \nTherefore, SSSS in adults warrants thorough evaluation.3 Mortality is also greater than 60% in adults, \nattributed to predisposing comorbid conditions.1,4\n\n\n\nOne of the mimickers of SSSS is toxic epidermal necrolysis (TEN). Here, we report a successful \ntreatment of SSSS in an adult with recreational drug abuse and incidental liver cirrhosis possibly \nsecondary to hepatitis C viral infection, after careful exclusion of TEN.\n\n\n\nKey Words: Staphylococcal scalded skin syndrome, Staphylococcus aureus, Toxic epidermal necrolysis, Immunodeficiency, \nPenicillin\n\n\n\nCorresponding Author\nDr Wan Noor Hasbee Wan Abdullah\nDepartment of Dermatology, \nHospital Raja Perempuan Zainab II, \n15586 Kota Bharu, Kelantan.\nEmail: vianona@yahoo.com\n\n\n\nIntroduction\nSSSS commonly spread from a nidus \nof Staphylococcus aureus infection, \nwith exfoliative toxins A and B cleaving \ndesmoglein-1, leading to epidermal granular \nlayer separation. These toxins are secreted by \nsome 5% of Staphylococcus aureus infection \nand species.3,4,8,9 Currently, the overall \nprevalence of SSSS in adults is approximately \n1 case per 1 million adults and increasing \nincidence has been reported worldwide.5 The \ntrue incidence is also possibly underestimated \nin Asia, where Staphylococcus aureus is an \nimportant nosocomial pathogen for developing \ncountries14.\n\n\n\nAdult SSSS is frequently identified in \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 29\n\n\n\nindividuals who have renal insufficiency \nand primary inherited defects in the immune \nsystem or secondary immunodeficiencies; \nheroin  addiction,  HIV,  malnutrition  with \nchronic  alcohol  abuse,  glucocorticoids, \nimmunomodulator drugs, malignancy, and \n\u2018immuno-paralysis\u2019 during severe sepsis.7,12-13\n\n\n\nAdult SSSS is commonly misdiagnosed as \ntoxic epidermal necrolysis (TEN).11 Clinical \npresentation is as in children with striking skin \ntenderness, pathognomic Nikolsky sign, and \ntypical mucous membranes sparing mark their \ndistinction, usually. Majority of adult cases \nare complicated with bacteremia, a result of \nincreased severity and the underlying comorbid \nconditions.3  The poor prognostic factors are \nsepsis, electrolyte imbalance, and dehydration.1,4\n\n\n\nCase Report\nA 50-year-old gentleman an electrical \nlabourer, presented with abrupt onset of fever \naccompanied by the eruption of tiny vesicles \nover the face that rapidly devolved into \nbullae with frank pus and peri-oral \u2018honey-\ncrusted\u2019 erosions over the span of 2 days that \nsubsequently became generalised. The flaccid \nbullae had accentuated epidermal detachment, \nexposing extremely tender, erythematous raw \nareas over flexural and decubitus areas. No \nenanthema was observed.\n\n\n\nHe reported dysuria and lower back pain 5 days \nprior and had taken diclofenac sodium (OlfenTM)\nbought over the counter. There were no history \nof respiratory symptoms, no burn or trauma, \nand no topical application to the skin.\n\n\n\nHis past medical history was significant for \nchronic mechanical lower back pain, receiving \nregular short courses of piroxicam (Feixicam), \ndexamethasone (Dexasone), diclofenac (Voren) \nalmost weekly for the past 3 years. His social \nhistory recorded active recreational drug use \n(heroin, morphine), last taken 2 days prior. \nThere was no family history of any blistering \nskin diseases.\n\n\n\nVital signs on admission recorded blood \npressure 100/66 mmHg, heart rate 100 bpm \nand temperature 36\u00b0C. Physical examination \nrevealed skin lesions covering approximately \n30% of the body surface area and Nikolsky sign \nwas positive.\n\n\n\nUrinalysis revealed trace leukocyte, negative \nnitrite, protein 1+ and erythrocyte 3+. \nLaboratory evaluations showed leukocytosis \nwith left-shifted neutrophils, serum blood urea \nnitrogen 21.6 mmol/L, serum creatinine 190 \nmicromol/L, serum aspartate aminotransferase \n323, serum alanine aminotransferase 88, serum \ncreatinine kinase 417 U/L, C-reactive protein \n318 mg/L. Electrolytes were within normal \nlimits. Chest X-ray had heterogeneous opacities \nover the left lung fields.\n\n\n\nAt that juncture, the dilemma was on whether \nthis patient had SSSS or drug-induced TEN. \nHowever, given the overall clinical picture of \nurinary tract infection (UTI), pneumonia and \nsepsis with the lack of mucosal involvement, \ndrug-induced TEN was less favoured. He was \ndiagnosed with SSSS, admitted to the high \ndependency unit, and intravenous cloxacillin \nwas administered with supportive care.\n\n\n\nMicrobiologic culture from forehead bullae \n(pus aspirate) and peripheral blood sent grew \nmethicillin-susceptible Staphylococcus aureus \n(MSSA), resistant to penicillin G. No vegetation \nwas found on echocardiogram. Sputum culture \nwas not available. We had ordered infectious \ndisease screening which was reactive for \nHepatitis C Antigen. Ultrasound abdomen \nrevealed multiple hyperechoic liver lesions in \nthe background of liver cirrhosis and features of \nearly bilateral renal parenchymal disease.\n\n\n\nThese were consistent with the diagnosis of \ndisseminated Staphylococcus aureus bacteremia \nwith SSSS. We did not perform staphylococcus \naureus phage-typing, as this is not routinely \navailable in our hospital laboratory and a skin \nbiopsy was also unnecessary.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4930\n\n\n\nFigure 1 a & b. Superficial pus-filled blisters over face with shallow erosions over the axilla and inner \nforearm. Inset showed perioral honey crusted lesion. Mucosal surfaces spared. No purpuric macules or \ntargetoid lesions. c. Wrinkled superficial blistering extended to nape.  \n\n\n\ndisease screening which was reactive for Hepatitis C Antigen. Ultrasound abdomen revealed \nmultiple hyperechoic liver lesions in the background of liver cirrhosis and features of early \nbilateral renal parenchymal disease. \n \nThese were consistent with the diagnosis of disseminated staphylococcus aureus bacteremia \nwith SSSS. We did not perform staphylococcus aureus phage-typing, as this is not routinely \navailable in our hospital laboratory and a skin biopsy was also unnecessary. \n \n \nFigure 1 a & b. Superficial pus-filled blisters over face with shallow erosions over the axilla and inner \nforearm. Inset showed perioral honey crusted lesion. Mucosal surfaces spared. No purpuric macules or \ntargetoid lesion. c. Wrinkled superficial blistering extended to nape.   \n \n\n\n\nHe received intravenous cloxacillin 2 gram 6 hourly and his renal function improved with \nhydration. He was also given morphine infusion for pain control, emollients and non-adhesive \ndressings for thermoregulation and to enhance wound healing. \n \nThe lesions were superficial and healed without scaring barring areas with previous \nsuperimposed bacterial infection after a period of 12 days. No pathogens were isolated on \nrepeated cultures.   \n \nFigure 2. Right back lesions healing, re-epithelialization with no significant scarring \n\n\n\na b c \n\n\n\nHe received intravenous cloxacillin 2 gram 6 \nhourly and his renal function improved with \nhydration. He was also given morphine infusion \nfor pain control, emollients and non-adhesive \ndressings for thermoregulation and to enhance \nwound healing.\n\n\n\nThe lesions were superficial and healed \nwithout scaring barring areas with previous \nsuperimposed bacterial infection after a period \nof 12 days. No pathogens were isolated on \nrepeated cultures.  \n\n\n\nFigure 2. Right back lesions healing, re-\nepithelialization with no significant scarring\n\n\n\nFigure 3. Sheet-like desquamation of the anterior \nchest wall skin and re-epithelization at axilla\n\n\n\nDiscussion\nAlthough SSSS is also reported in healthy \nadults, there clearly appear to be undisputed \nfactors that influence the susceptibility of \nadult individuals to SSSS. Our patient had \nrecreational drug use, chronic glucocorticoid \nuse, incidental liver cirrhosis and lesions \nsuggestive of hepatocellular carcinoma with \npossible underlying hepatitis C, which suggest \nan immunocompromised state. Steroid therapy \nalso significantly increases bacterial burden by \nfacilitating its growth.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 31\n\n\n\nHe presented with typical features of SSSS in \nwhich diffuse tender, erythematous shallow \nerosions form ruptured flaccid bullae with \nflexural accentuation and most importantly, \nwithout enanthema, thus ruling out the \npossibility of TEN. Either pneumonia or UTI \ncould be the primary source of infection. Toxins \nproduced could be overwhelming and exceeded \nwhat his kidneys could cope with, given the \nbaseline renal parenchymal disease and the \nseverity of illness.\n\n\n\nManagement of SSSS differs from TEN as \nsystemic glucocorticoid used for TEN is \ncontraindicated irrespective oral or topical \nadministration.16 Prompt adequate parenteral \nsemisynthetic penicillins are the choice of \nantimicrobial as Staphylococcus aureus \nstrains isolated in SSSS are found to be \npenicillin-resistant and penicillinase-resistant.15 \nConsideration for methicillin-resistant \nStaphylococcus aureus (MRSA) coverage \nshould also be made in endemic areas in which \nPanton Valentine Leukocidin (PVL) toxin \nassociated Staphylococcus aureus is also a \nparticular concern due to its association with \nmore severe infection.\n\n\n\nBecause the extent of body surface area involved \nwas great, corresponding to severe burns (more \nthan 20%), the supportive management towards \nthe loss of the skin barrier function should be \nintensified. Patients should remain adequately \nhydrated and managed like major burn patients; \nemollients should be applied to eroded skin areas, \nand antiseptics deployed to impede secondary \ncolonization. We used an antiseptic with broad-\nspectrum efficacy and most of all, well-tolerated \nwithout risk of systemic absorption. Warming \nblankets were also used to compensate for the \nchange in core body temperature as we had to \nadhere to strict cool temperature standards in \nthe high dependency unit. Alternating pressure \nair mattresses are preferred to the seemingly \nless efficient two-hourly repositioning. This \nalso minimises the risk of mechanical trauma \nand sleep deprivation.19\n\n\n\nIt is also imperative that pain control in this \nextremely painful condition is not overlooked as \n\n\n\nthis could potentially cause significant distress \nto the patients. The World Health Organization \npain ladder is used as a guide for the prescription \nof analgesia and the preferred choice is opiates. \nThe role of non-steroidal anti-inflammatories \n(NSAIDs) in the development of SSSS remains \nelusive. However, it should be omitted due to its \npotential detrimental effect on kidney function, \nwhich further complicates the disorder.\n\n\n\nSkin lesions heal without significant scarring after \nprompt and adequate management confirming \nthe diagnosis of SSSS. As desmoglein-1 is \nmainly expressed in the superficial upper layers \nof the epidermis, skin lesions usually heal within \n14 days without scarring. Mucosal membranes \nwhich lack desmoglein-1 are thus spared.15\n\n\n\nConclusion\nClinicians should be aware of the clinical \nspectrum of adult SSSS which is a potentially \nendemic, life-threatening disorder. Early \nrecognition requires a great deal of clinical \nfinesse for prompt management of this high \nmortality disease entity. It appears that prudent \neffort is still required for the prevention and \nmanagement of SSSS since its first description \nin 1972 and screening for immediate family \nmembers of the diagnosed patients as potential \ncarriers of the ET- A and B producing strains \nof Staphylococcus aureus should be done to \nprevent outbreaks.\n\n\n\nConflict of Interest Declaration\nThe authors declare that there is no conflict of \ninterest in this work.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth Malaysia for his permission to publish this \narticle.\n\n\n\nReferences \n1. Leung AKC, Barankin B, Leong KF. Staphylococcal-\n\n\n\nscalded skin syndrome: Evaluation, diagnosis, and \nmanagement. World J Pediatr 2018;14:116-20.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4932\n\n\n\n2. Mishra AK, Yadav P, Mishra A. A Systemic Review on \nStaphylococcal Scalded Skin Syndrome (SSSS): A Rare \nand Critical Disease of Neonates. Open Microbiol J \n2016;10:150-9. \n\n\n\n3. Handler MZ, Schwartz RA. Staphylococcal scalded skin \nsyndrome: diagnosis and management in children and \nadults. J Eur Acad Dermatol Venereol 2014; 28:1418-23.\n\n\n\n4. Ross A, Shoff HW. Staphylococcal Scalded Skin \nSyndrome. 2022. In: StatPearls [Internet]. Treasure Island \n(FL): StatPearls Publishing; 2022 Jan\u2013.\n\n\n\n5. Staiman A, Hsu DY, Silverberg JI. Epidemiology of \nstaphylococcal scalded skin syndrome in US adults. J Am \nAcad Dermatol 2018;79:774-6.\n\n\n\n6. Paller A, Mancini A. Hurwitz Clinical Pediatric \nDermatology: A Textbook of Skin Disorders of Childhood \nand Adolescence. 5th ed. Edinburgh. Elsevier 2016. p. \n403-419.\n\n\n\n7. Chinen J, Shearer WT. Secondary immunodeficiencies, \nincluding HIV infection. J Allergy Clin Immunol \n2010;125(2 Suppl 2):S195-203. \n\n\n\n8. Jordan KS. Staphylococcal Scalded Skin Syndrome: A \nPediatric Dermatological Emergency. Adv Emerg Nurs J \n2019;41:129-34.\n\n\n\n9. Ladhani S. Recent development in Staphylococcal scalded \nskin syndrome. Clin microbiol infection 2001;7:301-7.\n\n\n\n10. Kanathur S, Sarvajnyamurthy S, Somaiah SA \nCharacteristic facies: An index of the disease. Indian J \nDermatol Venereol Leprol 2013;79:439-43.\n\n\n\n11. Napoli B, D\u2019Arpa N, D\u2019Amelio L, Chimenti S, Pileri D, \nAccardo-Palumbo , et al. Staphylococcal scalded skin \nsyndrome: criteria for differential diagnosis from Lyell\u2019s \nsyndrome. Two cases in adult patients. Ann Burns Fire \nDisasters 2006;19:188-91.\n\n\n\n12. Neefe LI, Tuazon CU, Cardella TA, Sheagren JN. Case \nreport. Staphylococcal scalded skin syndrome in adults: \ncase report and review of the literature. Am J Med Sci \n1979; 277:99-110.\n\n\n\n13. Acland KM, Darvay A, Griffin C, Aali SA, Russell-Jones \nR. Staphylococcal scalded skin syndrome in an adult \nassociated with methicillin-resistant Staphylococcus \naureus. Br J Dermatol 1999;140:518-20.\n\n\n\n14. Tong SY, Davis JS, Eichenberger E, Holland TL, \nFowler VG Jr. Staphylococcus aureus infections: \nepidemiology, pathophysiology, clinical manifestations, \nand management. Clin Microbiol Rev 2015;28:603-61. \n\n\n\n15. Verma G, GR Tegta, Renu Rattan, Reena Sharma, Prajul \nMehta, Nancy Lalnunpuii. Staphylococcal scalded skin \nsyndrome in an immunocompetent healthy adult patient: \nA rare presentation. Open J Clin Med Case Rep 2019;5:1-\n5.\n\n\n\n16. Patel GK. Treatment of staphylococcal scalded skin \nsyndrome. Expert Rev Anti Infect Ther 2004;2:575-87. \n\n\n\n17. Cutting K, Westgate S. The use of wound cleansing \nsolutions in chronic wounds. Wounds UK 2012;8:130-3.\n\n\n\n18. Melish M E, Glasgow LA. The staphylococcal scalded \nskin syndrome: development of an experimental model. \nN Engl J Med 1970; 282:1114-9.\n\n\n\n19. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, \nGoldstein EJ, Gorbach SL et al. Infectious Diseases \nSociety of America. Practice guidelines for the diagnosis \nand management of skin and soft tissue infections: 2014 \nupdate by the Infectious Diseases Society of America. \nClin Infect Dis 2014;59:147-59. \n\n\n\n20. Sharp CA, Schulz Moore JS, McLaws ML. Two-Hourly \nRepositioning for Prevention of Pressure Ulcers in the \nElderly: Patient Safety or Elder Abuse? J Bioeth Inq \n\n\n\n2019;16:17-34. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 33\n\n\n\nCASE REPORT \n\n\n\nSuccessful Treatment of Recalcitrant Ungual Wart with Tuberculin Purified \nProtein Derivative Immunotherapy \n\n\n\nKanimoliyaal Balakrishnan1, MBBS, Wan Syazween Lyana Wan Ahmad Kammal2, AdvMDerm, Norazirah Md \nNor1, AdvMDerm\n1Dermatology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, \nMalaysia\n2Dermatology Unit, Department of Medicine, Faculty of Health and Medical Sciences, Universiti Putra \nMalaysia, Serdang, Selangor, Malaysia. \n\n\n\nSummary\nDespite a variety of therapeutic options that is available, treatment of warts remains challenging and \nrate of recurrence is high. Intralesional immunotherapy is an emerging therapy for warts. Tuberculin \npurified protein derivative (PPD) is one of the immunotherapeutic antigens used for the treatment \nof warts. Here we report a case of recalcitrant periungual wart successfully treated with tuberculin \nimmunotherapy.\n\n\n\nKey Words: Immunotherapy; Tuberculin; Purified protein derivative; Periungual wart\n\n\n\nCorresponding Author\nDr Kanimoliyaal Balakrishnan\nDermatology Unit, \nDepartment of Medicine, \nUniversiti Kebangsaan Malaysia Medical \nCentre, 56000 Cheras, Kuala Lumpur, Malaysia\nEmail: bkani_89@yahoo.com\n\n\n\nIntroduction\nWart is a benign skin tumour caused by Human \nPapillomavirus.1 It typically presents as well-\ncircumscribed single or multiple papules with a \nhyperkeratotic surface.1 Ungual wart is common \nand can be painful as it burrows deep and erode \nthe underlying tuft of the distal phalanx. It can \nalso cause fissures, which predisposes the nail \nto paronychia.1\n\n\n\nUngual warts can be difficult to treat. Previous \nliterature has reported various therapies, \nincluding topical keratolytic, cryotherapy, \nelectrocautery, or laser therapy.1-2 However, the \nexpected cure rate ranges from 60 \u2013 70% only.1 \n\n\n\nFurthermore, none of the treatments is free \nfrom side effects such as blisters, pigmentary \nchanges, ulcers and onychodystrophy.1-2 \n\n\n\nRecurrences are common as warts may be \npartially visible around the nail. The remaining \nwart may extend underneath the nail plate, \nwhich makes it challenging to deliver effective \ntreatment.1 Prevalence of recurrence rate of \nungual warts range from 6% to 100% in adults.3 \nTotal or partial nail avulsion may be employed \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4934\n\n\n\nto counter this problem. However, it is not the \nfirst-line treatment as there is a risk of destroying \nthe nail bed, nail matrix or underlying bone.1\n\n\n\nImmunotherapy is an emerging modality for \nthe treatmentof ungual warts. It stimulates \ncell-mediated immunity, which results in \nwart clearance.1-4 Here, we report a case of \nrecalcitrant periungual wart, successfully \ntreated with intralesional immunotherapy of \ntuberculin purified protein derivative (PPD). \n\n\n\nCase Report\nAn 18-year-old immunocompetent male patient \npresented with a painful periungual growth of \nthe left thumb for 2-years duration. He failed \nprevious therapies, which were a partial nail \navulsion and 10 sessions of cryotherapies. The \ncryotherapy involved liquid nitrogen spray, \ndelivered at 10 -15 seconds with 2 freeze-thaw \ncycles.  On examination, there was a 15 x 10 mm \nhyperkeratotic, dark brown plaque on the left \nthumbnail bed. Removal of the surface with a \nsurgical blade revealed thrombosed capillaries. \nThe surrounding nail was dystrophic.  A \ndiagnosis of ungual wart was made. \n\n\n\nHe received an intralesional injection of \ntuberculin PPD at a dose of 2.5 Tuberculin \n\n\n\nUnit (0.14ml). The injection was done using a \n1 ml-syringe and 26-gauge needle.5 Two weeks \nlater, the wart\u2019s size reduced to almost 50% \n(8.57x5.22mm). Another tuberculin PPD of the \nsame dose was administered. At 4-week follow \nup, the wart resolved entirely (Figure 1). He \nreported pain during injection, which resolved \nspontaneously three to four hours later. There \nwas no erythema, blister or oedema observed \nat the injection site. There was also no fever, \nmalaise, myalgia or arthralgia.\n\n\n\nDiscussion\nImmunotherapy exerts its effects in treatment \nof wart by mounting a delayed-type of \nhypersensitivity reaction4.6 which involved \nstimulation of  Th1 cytokines.These cytokines \nthen activates cytotoxic and natural killer cells \nto eradicate the HPV from the epidermis.6\n\n\n\nTuberculin is a purified protein derivative \nextracted from Mycobacterium tuberculosis \ncultures.7 It is used widely for tuberculosis \nscreening, especially in countries where the \ndisease is endemic, such as in Malaysia. \nTuberculin is used across all age groups, \nincluding infants, children and pregnant \nwomen.7 As tuberculosis is endemic in our \n\n\n\nFigure 1: (a) Pre-treatment; (b) Week 2 post-injection; (c) Week 4 post-injection\n\n\n\nImmunotherapy is an emerging modality for the treatmentof ungual warts. It stimulates cell-\nmediated immunity, which results in wart clearance.1-4 Here, we report a case of recalcitrant \nperiungual wart, successfully treated with intralesional immunotherapy of tuberculin purified \nprotein derivative (PPD).  \nCase Report \nAn 18-year-old immunocompetent male patient presented with a painful periungual growth of \nthe left thumb for 2-years duration. He failed previous therapies, which were a partial nail \navulsion and 10 sessions of cryotherapies. The cryotherapy involved liquid nitrogen spray, \ndelivered at 10 -15 seconds with 2 freeze-thaw cycles.  On examination, there was a 15 x 10 \nmm hyperkeratotic, dark brown plaque on the left thumbnail bed. Removal of the surface with \na surgical blade revealed thrombosed capillaries. The surrounding nail was dystrophic.  A \ndiagnosis of ungual wart was made.  \n\n\n\n \nHe received an intralesional injection of tuberculin PPD at a dose of 2.5 Tuberculin Unit \n(0.14ml). The injection was done using a 1 ml-syringe and 26-gauge needle.5 Two weeks later, \nthe wart\u2019s size reduced to almost 50% (8.57x5.22mm). Another tuberculin PPD of the same \ndose was administered. At 4-week follow up, the wart resolved entirely (Figure 1). He reported \npain during injection, which resolved spontaneously three to four hours later. There was no \nerythema, blister or oedema observed at the injection site. There was also no fever, malaise, \nmyalgia or arthralgia. \n \nFigure 1: (a) Pre-treatment; (b) Week 2 post injection; (c) Week 4 post injection  \n\n\n\n   \n \n \nDiscussion \nImmunotherapy exerts its effects in treatment of wart by mounting a delayed-type of \nhypersensitivity reaction4.6 which involved stimulation of  Th1 cytokines.These cytokines then \nactivates cytotoxic and natural killer cells to eradicate the HPV from the epidermis.6 \n\n\n\n \nTuberculin is a purified protein derivative extracted from Mycobacterium tuberculosis \ncultures.7 It is used widely for tuberculosis screening, especially in countries where the disease \nis endemic, such as in Malaysia. Tuberculin is used across all age groups, including infants, \nchildren and pregnant women.7 As tuberculosis is endemic in our country, this therapy may be \n\n\n\na b c \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 35\n\n\n\ncountry, this therapy may be useful in our \npopulation as majority of patients are sensitized \nto it. We chose tuberculin because it is readily \navailable in our centre. \n\n\n\nPrevious literature works have reported \ntuberculin\u2019s efficacy rate in treating warts, \nranging from 29.4% to 93%.8-13 A network \nmeta-analysis reported that tuberculin and \nMMR were the most effective treatments for \nachieving complete primary and distant wart \nrecovery compared to other immunotherapeutic \nagents,  cryotherapy and imiquimod.14 Abou-\nTaleb et al15 compared intralesional (IL) vitamin \nD3 vs IL PPD in treatment of multiple warts, \nand significantly, higher clearance rates for all \nwarts were observed with IL PPD compared to \nIL vitamin D. In the study by Wan Syazween \net al5, comparing efficacy and safety between \nTuberculin PPD and cryotherapy, complete wart \nclearance rates were higher with immunotherapy \nthan cryotherapy; also immunotherapy has a \npositive effect on distant, untreated warts. \n\n\n\nThe most common adverse events reported \nwere local injection site reaction such as pain, \nerythema and oedema.14 These side effects \nwere often transient and resolved after a few \ndays. Very rarely, immunotherapy may result \nin painful digit syndrome. La Pelusa et al and \nPerman et al reported distal pain, swelling, and \npurple hue of  finger pos-immunotherapy. Both \npatients, however, recovered with complete \nresolution of the wart after the event with \ntreatment with oral prednisolone.17-18 \n\n\n\nConclusion\nThis case report highlights the efficacy of \ntuberculin immunotherapy on recalcitrant \nungual wart. This treatment should be \nrecommended for treatment of recalcitrant wart \nparticularly in difficult to treat area such as \nsubungal and periungal region. More studies are \nneeded locally to treat recalcitrant warts using \nintralesional immunotherapy for patients who \nfail liquid nitrogen cryotherapy.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest.\n\n\n\nAcknowledgement\nWe would like to thank the Director General of \nHealth, Malaysia, for his permission to publish \nthis article.\n                     \n\n\n\nReferences \n1. Moghaddas N. Periungual verrucae diagnosis and \n\n\n\ntreatment. Clin Podiatr Med Surg 2004;21:651-61.\n2. Herschthal J, McLeod MP, Zaiac M. Management of \n\n\n\nungual warts. Dermatol Ther 2012;25:545-50.\n3. Ciccarese G, Drago F, Granger C, Parodi A. Efficacy \n\n\n\nAssessment of a Topically Applied Nitric-Zinc Complex \nSolution for the Treatment of External Ano-genital Warts \nin 100 Patients. Dermatol Ther (Heidelb) 2019;9:327-35.\n\n\n\n4. Lipke MM. An armamentarium of wart treatments. Clin \nMed Res 2006;4:273-93.\n\n\n\n5. Wan Ahmad Kammal WSL, Jamil A, Md Nor N. \nEfficacy and safety of intralesional tuberculin purified \nprotein derivative versus cryotherapy in the treatment of \nwarts: An assessor-blinded, randomized controlled trial. \nDermatol Ther 2021;34:e15080.\n\n\n\n6. Chandrashekar L. Intralesional immunotherapy for the \nmanagement of warts. Indian J Dermatol Venereol Leprol \n2011;77:261-3. \n\n\n\n7. Pahal P, Sharma S. PPD Skin Test.  Treasure Island (FL): \nStatPearls Publishing;2022:2-10.\n\n\n\n8. Amirnia M, Khodaeiani E, Fouladi DF, Masoudnia S. \nIntralesional immunotherapy with tuberculin purified \nprotein derivative (PPD) in recalcitrant wart: A \nrandomized, placebo-controlled, double-blind clinical trial \nincluding an extra group of candidates for cryotherapy. J \nDermatolog Treat 2016;27:173-8. \n\n\n\n9. Kus S, Ergun T, Gun D, Akin O. Intralesional tuberculin \nfor treatment of refractory warts. J Eur Acad Dermatol \nVenereol 2005;19:515-6.\n\n\n\n10. Kaimal S, Gopinath H, Premalatha V. Intralesional \nimmunotherapy with purified protein derivative (PPD) for \ncryotherapy-resistant warts. Int J Dermatol 2020;59:726-\n9.\n\n\n\n11. Nimbalkar A, Pande S, Sharma R, Borkar M. Tuberculin \npurified protein derivative immunotherapy in the treatment \nof viral warts. Indian J Drugs Dermatol 2016;2:19-23.\n\n\n\n12. Abd-Elazeim FM, Mohammed GF, Fathy A, Mohamed \nRW. Evaluation of IL-12 serum level in patients \nwith recalcitrant multiple common warts, treated by \nintralesional tuberculin antigen. J Dermatolog Treat \n2014;25:264-7.\n\n\n\n13. Siriwan W,  Susheera C, Pornpat K. Intralesional \nimmunotherapy using tuberculin PPD in the treatment \nof palmoplantar and periungual warts. Asian Biomed \n2009;3:739-43.\n\n\n\n14. Salman S, Ahmed MS, Ibrahim AM, Mattar OM, El-\nShirbiny H, Sarsik S et al. Intralesional immunotherapy \nfor the treatment of warts: A network meta-analysis. J Am \nAcad Dermatol 2019;80:922-30.\n\n\n\n15. Abou-Taleb DAE, Abou-Taleb HA, El-Badawy O, \nAhmed AO, Thabiet Hassan AE, Awad SM. Intralesional \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4936\n\n\n\nvitamin D3 versus intralesional purified protein derivative \nin treatment of multiple warts: A comparative clinical and \nimmunological study. Dermatol Ther 2019;32:e13034. \n\n\n\n16. Garc\u00eda-Oreja S, \u00c1lvaro-Afonso FJ, Tard\u00e1guila-Garc\u00eda A, \nL\u00f3pez-Moral M, Garc\u00eda-Madrid M, L\u00e1zaro-Mart\u00ednez JL. \nEfficacy of cryotherapy for plantar warts: A systematic \nreview and meta-analysis. Dermatol Ther 2022;35:e15480. \n\n\n\n17. Perman M, Sterling JB, Gaspari A. The painful purple \ndigit: an alarming complication of Candida albicans \nantigen treatment of recalcitrant warts. Dermatitis \n2005;16:38-40.\n\n\n\n18. La\u2019Pelusa A, Rorex J, Weir NM, Travers JB. An aberrant \nreaction to Candida albicans antigen used for recalcitrant \nwarts successfully treated with oral prednisone. JAAD \nCase Rep 2018;4:242-4. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 37\n\n\n\nCASE REPORT\n\n\n\nCoevality of Secondary Syphilis with Condyloma Acuminata in a HIV \nreactive MSM: Rare Triple Sexually Transmitted Infections\n\n\n\nSafa Patrick, MD, Sumit Kar, MD, Subhor Nandwani, MBBS\n\n\n\nDepartment of Dermatology, Venereology & Leprosy, Mahatma Gandhi Institute of Medical Sciences, \nSewagram, Maharashtra, India \n\n\n\nSummary\nSecondary syphilis is a rare infectious sexually transmitted disease caused by Treponema pallidum in \npresent era. It affects skin as well as other organs of the body. We hereby present a case of an adult \nmale who presented with a one-month history of multiple brownish red maculopapular lesions all over \nthe skin of the body involving the palms, soles, oral cavity and genitalia. His serology was positive \nfor HIV, VDRL and TPHA with a low CD4 count. The patient was treated with three weekly doses of \nparenteral  Benzathine penicillin G, antiretroviral therapy and podophyllin for condyloma acuminata \nto which he responded well.\n\n\n\nKey Words:  Syphilis, Immunocompromised host, Condyloma acuminata, Chancre, Penicillin\n\n\n\nCorresponding author \nDr Sumit Kar\nDepartment of Dermatology, Venereology & \nLeprosy, \nMahatma Gandhi Institute of Medical Sciences,\nSewagram, Maharashtra, \n442102 India. \nEmail: karmgims@gmail.com\n\n\n\nIntroduction\nSyphilis is a chronic infectious granulomatous \ndisorder caused by Treponema pallidum, a \nspirochete. Transmission occurs chiefly via \nsexual contact and to some extent by blood \ntransfusion of infected blood, via transplacental \nroute or by accidental exposure to the infectious \nmaterial. Micro or macroscopic trauma in the \nsquamous or columnar epithelium may allow \nentry of the organism.1 Syphilitic chancre on \nglans penis or rectal mucosa provides a portal \nof entry for the HIV virus. Once the organism \nenters the human body it invades all the organs \nof the body most notably skin.2 The incidence of \nsecondary syphilis has decreased nowadays, but \nwith the emergence of HIV, syphilis may show \nan unpredictable course and can present with an \nunusual clinical picture.3 \n\n\n\nHIV-infected males having history of sex with \nmen should undergo screening for syphilis. \nThis might reduce the incidence of the \ndisease in those who test positive and also its \nconsequences.4 Genital human papillomavirus \n(HPV) infection is the most common sexually \ntransmitted disease and is second only to human \nimmunodeficiency virus (HIV) infection in \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4938\n\n\n\ncausing morbidity and mortality. Perianal HPV \ninfection produces a wide range of disease \npresentations, from asymptomatic infection to \nbenign genital warts to invasive cancer.5 Patient \nherein had secondary syphilis with condyloma \nacuminata with HIV co-infection rarely reported \nuntil now.\n\n\n\nCase Report\nA 28-year-old unmarried male working as \nteaching faculty in college presented with \nmultiple brownish red raised lesions all over \nthe skin of the body including palms, soles, \ngenitalia and oral cavity along with a growth in \nthe perianal region since 1 month and a small \nulcer over the glans penis since 1 month. He \nalso complained of intermittent fever, redness \nof eyes, weight loss and loose motions for 1 \nmonth. On detailed and persistent enquiry, \nthe patient gave history of unprotected sexual \ncontact with his roommates while pursuing his \neducation. He reported that most of the time he \nwas acting as a passive receptive partner for \npeno-anal intercourse. There was no history of \nintravenous drug abuse or blood transfusion or \nheterosexual contact in past. The patient was \nof average built and had generalized painless \nfirm lymphadenopathy involving suboccipital, \npostauricular, submandibular, upper jugular, \nsupraclavicular and superficial inguinal group \nof lymph nodes. Systemic examination was \nwithin normal range.\n\n\n\nCutaneous examination revealed multiple \nbrownish red papulonodular rashes all over the \nbody involving palms and soles and external \ngenitalia ranging in size from 0.5 to 2 cm (Figure \n1-4). Superficial painless erosions were present \nover the hard palate. The Buschke-Ollendorff \nsign was positive. Genital examination showed \na whitish pink growth covering the anal opening \nconsistent with condyloma acuminata. A single \nsuperficial healing painless ulcer was present \nover the glans of the penis with an indurated \nbase. \n\n\n\nHis serology was positive for HIV-1 and syphilis \nwith VDRL (1:128) and TPHA reactivity.  CSF \n\n\n\nanalysis showed no biochemical or cellular \nabnormality. Total CD4 count by flow cytometry \nwas in the low range 312 cells/mm3 (normal \nvalues: 500 cells/mm3 to 1,200 cells/mm3).\n\n\n\nFigure 1. Multiple erythematous maculopapular \nsecondary syphilides present over back\n\n\n\nFigure 2. Multiple papular syphilides over both \npalms\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 39\n\n\n\nFigure 3. Superficial painless ulcer over glans penis \nwith an indurated base\n\n\n\nFigure 4. Warty growth over anal opening consistent \nwith condyloma acuminata\n\n\n\nThe patient was treated with three doses of \nparenteral benzathine penicillin 2.4 million \nunits a week apart. The VDRL titre was reduced \nto 1:32 after treatment in 1 month. In view \nof co-existing HIV infection and low CD4 \ncount, the patient was started on highly active \nantiretroviral therapy (ZLN regime), however \na week later the patient developed nevirapine-\ninduced maculopapular drug rash. In view \n\n\n\nof his NVP induced skin rash, his HAART \nwas changed to efavirenz-based regimen. \nCondyloma acuminata was treated with weekly \napplication of podophyllin resin, which required \n5 sittings, 1 week apart for complete clearance \nof lesions. Partner was called for evaluation \nbut the partner did not come for evaluation and \nmanagement.\n\n\n\nDiscussion\nThe patient reported in our case has coeval three \nsexually transmitted diseases simultaneously in \nthe form of HIV infection, syphilis and genital \ncondyloma acuminata. Syphilis with HIV \ninfection is extremely rare in today\u2019s era due to \nrampant and injudicious use of antibiotics.6 But \nit has been observed in various epidemiologic \nstudies that the incidence of syphilis has \nincreased in homosexual men especially among \nthose who are infected with HIV. Increase in \nhigh risk behaviour and decrease in mortality \ndue to HAART can be the cause of this increase. \n\n\n\nSyphilis and HIV co-infection may lead to \naggravation and early development of tertiary \nsyphilis. It is believed that the sexually \ntransmitted disease including syphilis which \nproduces an ulcerative or warty lesion over \nthe genital organs creates a portal of entry \nfor the HIV virus due to ample availability of \ninflammatory cells. As a result of co-existing \nHIV infection, syphilis may rapidly progress \nto the tertiary stage in a short time period \nand despite an adequate treatment, relapses \nor treatment failure may occur. Patients with \nHIV and syphilis may show a poor response \nto anti-syphilitic treatment. Serofastness is \nnot observed in patients of syphilis with HIV \ncoinfection.8 \n\n\n\nHPV infection among MSM is highest in those \ncoinfected with HIV.9 Anal HPV infection, \nespecially high-risk type, is independently \nassociated with HIV acquisition. The \nmechanisms are not clear yet, but there is a \nbiological plausibility that HPV infection leads \nto an active cell-mediated immune response \nthrough recruitment of macrophages and T \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 4940\n\n\n\nlymphocytes, which are HIV-susceptible cells \nand may facilitate HIV acquisition.10 Anogenital \ndisease in the HIV-positive population tends \nto be more aggressive, multifocal, rapidly \nprogressive, and recalcitrant to standard \ntherapies, compared with disease occurring in \nHIV-negative patients. HIV-positive patients, \ntherefore, require aggressive screening, \ntreatment, and follow-up. \n\n\n\nOur case had coexistence of syphilis and \nHPV with HIV infection, which has not been \nreported until now.  Also in spite of being \nimmunocompromised our patient responded \nwell to first line treatment for syphilis and \ncondyloma acuminata as opposed to the dictum \nof lesions recalcitrant to standard therapies. In \naddition, our patient was a teacher in a rural \nwhere in school-based sexual health education \nand comprehensive approach to promoting \nsexual health among young people was also \nundertaken. \n\n\n\nConclusion\nIn spite of being literate and having awareness \nabout harmful effects of unprotected sexual \ncontact, still he continued with high-risk \nbehavioral activity. Hence, we must rethink our \nsexual health awareness program.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences\n1. Mehta B. A clinico-epidemiological study of \n\n\n\nulcerative sexually transmitted diseases with human \nimmunodeficiency virus status. Indian J Sex Transm Dis \nAIDS 2014;35:59-61.\n\n\n\n2. Cruz AR, Ramirez LG, Zuluaga AV, Pillay A, Abreu \nC, Valencia CA et al. Immune evasion and recognition \nof the syphilis spirochete in blood and skin of secondary \nsyphilis patients: two immunologically distinct \ncompartments. PLoS Negl Trop Dis 2012;6:e1717.\n\n\n\n3. Rallis E, Paparizos V. Malignant syphilis as the first \n\n\n\nmanifestation of HIV infection. Infect Dis Rep 2012;4:e15.\n4. Tuite AR, Burchell AN, Fisman DN. Cost-effectiveness \n\n\n\nof enhanced syphilis screening among HIV-positive men \nwho have sex with men: a microsimulation model. PLoS \nOne 2014;9:e101240.\n\n\n\n5. Chang GJ, Welton ML. Human papillomavirus, \ncondylomata acuminata, and anal neoplasia. Clin Colon \nRectal Surg 2004;17:221-30.\n\n\n\n6. Zhong F, Liang B, Xu H, Cheng W,  Fan L, Han Z et al. \nIncreasing HIV and decreasing syphilis prevalence in a \ncontext of persistently high unprotected anal intercourse, \nsix consecutive annual surveys among men who have sex \nwith men in Guangzhou, China, 2008 to 2013. PLoS One \n2014;9:e103136.\n\n\n\n7. Abdul Wahab A, Rahman MM, Mohammad M, Hussin S. \nCase series of syphilis and HIV co-infections. Pak J Med \nSci 2013;29:856-8.\n\n\n\n8. Yang CJ, Lee NY, Chen TC, Lin YH, Liang SH, Lu PL \net al. One dose versus three weekly doses of benzathine \npenicillin G for patients co-infected with HIV and \nearly syphilis: a multicenter, prospective observational \nstudy. PLoS One 2014;9:e109667.\n\n\n\n9. Quinn R, Salvatierra J, Solari V, Calderon M, Ton TG, \nZunt JR. Human papillomavirus infection in men who \nhave sex with men in Lima, Peru. AIDS Res Hum \nRetroviruses 2012;28:1734-8.\n\n\n\n10. Gao L, Zhou F, Li X, Yang Y, Ruan Y, Jin Q. Anal HPV \ninfection in HIV-positive men who have sex with men \nfrom China. PLoS One 2010;5:e15256.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nMJD 2022 Dec Vol 49 41\n\n\n\nACKNOWLEDGEMENT\nDec Issue 2022\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n\n\n\n2. Dr Agnes Heng Yoke Hui\n\n\n\n3. Dr Ch\u2019ng Chin Chwen\n\n\n\n4. Dr Chan Lee Chin\n\n\n\n5. Dr Chang Choong Chor\n\n\n\n6. Dr Chong Yew Thong\n\n\n\n7. Dr Henry Foong Boon Bee\n\n\n\n8. Dr Kwan Zhenli\n\n\n\n9. Dr Lo Kang Shang Chit\n\n\n\n10. Dr Ng Ting Guan\n\n\n\n11. Dato\u2019 Dr Noor Zalmy Azizan\n\n\n\n12. Dr Rajalingam Ramalingam\n\n\n\n13. Dr Tang Jyh Jong\n\n\n\n14. Dr Tang Min Moon\n\n\n\n\n\n\n\n\n\n\n \ncover\n\n\nBooklet A4_Malaysian Journal of  Dermatology-Dec 2022-Inner_C\n\n\n\n"
"\n\nMalaysian Journal of Dermatology\n\n\n\n22MJD 2013 Dec Vol 31\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nNEVUS OF OTA: PRESENTATION OF A CASE WITH ORAL\nPIGMENTATION AND CODICIL TO TANINO\u2019S CLASSIFICATION \n\n\n\nSrikanth H Srivathsa, MDS\n\n\n\nKeywords: Bluish hyperpigmentation, Palatal pigmentation, trigeminal nerve, congenital melanocytosis, \nmelanocytic hamartoma\n\n\n\nAbstract\nNevus of Ota is a rare pigmented disorder affecting \nthe skin along the distribution of trigeminal nerve.  \nOral involvement of this pigmented lesion is very \nrare. Classification of Nevus of Ota given by Tanino \nrepresents the skin manifestations well but does not \ninclude the extra cutaneous manifestations. Hence \nan addition to this classification is being proposed \nthrough this case report which describes the 17th \ncase of palatal involvement in a male patient in a \nfemale dominant Nevus of Ota. \n\n\n\nIntroduction\nCongenital or acquired melanocytoses are benign \npigmented lesions of the skin or mucosa1. Nevus \nof Ota also known as nevus fuscocaeruleus \nophthalmomaxillaris is a congenital dermal \nmelanocytosis first described by Ota in 1939 as a \nmelanocytic hamartoma. It clinically presents as \nbluish hyperpigmentation along the branches of the \ntrigeminal nerve2.\n\n\n\nCase Report\nA 22-year old male patient visited for a routine dental \ncheck up. His medical, surgical, drug and personal \nhistories were non contributory. Examination of the \nfacial skin revealed a brownish grey pigmentation \nof the left eyebrow region of 1-1.2 cm size and \nassociated slate-grey pigmentation of the left \nconjunctiva (Figure 1). Examination of the ipsilateral \nand contralateral side of face revealed no additional \npigmentation. On oral examination, the hard palate \non the left side showed irregular greyish macule on \n\n\n\nCorrespondence\nDr Srikanth H Srivathsa, MDS\nReader\nDepartment of Oral Medicine and Radiology, \nAnnoor Dental College and Hospital, Perumattom, \nMuvattupuzha - 686673 Ernakulum Dist, Kerala\nEmail: Srikanth_vathsa2000@yahoo.com\n\n\n\nthe left side with a few surrounding scattered similar \ncoloured macules (Figure 2). The rest of the oral \nmucosa appeared normal. Upon eliciting the history \nof the pigmentation,  patient was unaware of the \noral lesions but the eye pigmentation was present \nsince birth. Evaluation by an ophthalmologist and \notolaryngologist did not reveal any pigmentation in \nthe nasal or aural mucosa and no eye complications \nwere present. Based on the history and clinical \nappearance a diagnosis of Nevus of Ota was \narrived at. An attempt to classify was futile as an \neffective classification is unavailable and hence a \ncodicil is being proposed to the existing Tanino\u2019s \nclassification.\n\n\n\nDiscussion\nAlthough Hulke in 1861 first described oculodermal \nmelanosis, in 1939 Ota M coined the explanatory \nname for this condition as nevus fuscocaeruleus \nophthalmomaxillaris. Subsequently the condition is \nknown as nevus of Ota3.\n\n\n\nThe exact etiology of this disorder is yet to be \ndetermined. But it is suggested that amelonocytic \nnevoid cells present at birth become pigmented in the \nteenage life or later due to many triggering factors \nsuch as ultraviolet light exposure, female hormones, \ninfection or trauma4,5. Another suggestion is that \nit may be due  to non migration of melanocytes \nfrom the neural crest to the epidermis during the \nembryonic stage. Other theories postulated is an \nactive production by intradermal melanocytes6,7. \nAlthough most patients have a negative family \nhistory, rarely familial cases have been described, \nrepresenting heredity as a possible aetiology8.\n\n\n\nThe original classification by Tanino in 1939 has \nremained the most useful clinical classification, \nalthough mucosal pigmentations or extra \ncutaneous manifestations are not included. Tanino\u2019s \nclassification is summarized in table 13.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23 MJD 2013 Dec Vol 31\n\n\n\nType\n\n\n\nType-I\n\n\n\nType-II\n\n\n\nType-III\n\n\n\nType IV\n\n\n\nSubtypes\n\n\n\nIA\n\n\n\nIB\n\n\n\nIC\n\n\n\nID\n\n\n\nAreas involved\n\n\n\nMild orbital type - distribution over the upper and lower eyelids, periocular and temple region.\n\n\n\nMild zygomatic type - infrapalpebral fold, nasolabial fold and zygomatic regions are affected\n\n\n\nMild forehead type - only forehead is affected.\n\n\n\nAla nasi alone is affected.\n\n\n\nModerate type-The lesions affect upper and lower eyelids, periocular, zygomatic, cheek and \ntemple regions\n\n\n\nThe condition is distributed over the scalp, forehead, eyebrows and nose.\n\n\n\nBilateral type\n\n\n\nTable 1 \n\n\n\nFigure 1  Pigmentation on the left conjunctiva and left eye brow region.\n\n\n\nFigure 2  : Palatal pigmentation.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24MJD 2013 Dec Vol 31\n\n\n\nA modification has been suggested to include the \npresence of Nevus of Ito in association with Ota as \nType V and Type VI3. It is suggested that the letter \n\u201cE\u201d may be suffixed when nevus is associated with \nextra cutaneous manifestations3. However, another \nmodification has been suggested for oral lesions \nas IE5. As the former uses letter E to represent \nextra cutaneous manifestations the latter uses \nthe letter E to represent oral lesions resulting in \nmuch confusion and ineffective representation of \nmucosal pigmentation. Therefore a comprehensive \nclassification is proposed, which is as below :\n\n\n\nType I to IV: As suggested by Tanino  \nType V:   Nevus of Ota with Nevus of Ito\nType VI:  Nevus of Ota with extra-cutaneous \n  manifestations\n  VI A: Ocular\n  VI B: Oral - Palate, Buccal \n   mucosa or other areas\n  VI C:  Nasal \n  VI D:  Tympanic \n  VI E:  Leptomeninges\n\n\n\nThe reported incidence is about 0.2% to 1% in \nthe Japanese population9. The exact prevalence in \nIndians is not known but the male to female sex \nratio is 1:4.82,10. Nevus of Ota is most common in \nAsians and blacks and rare cases affecting whites \nhave also been reported. Onset is usually at birth \nbut may appear at adolescence in some and during \npregnancy in a few women3,7.  \n\n\n\nClinically, it appears as blue-grey macular \npigmentation on the skin with the borders being \nirregular. Classically, it is noted on the skin supplied \nby the branches of the trigeminal nerve. In 95 % \nof cases, it is unilateral and bilateral in the rest11. A \nsimilar pigmentation may be found on the tympanic \nmembrane, oral cavity, eye and leptomeninges5.  \nOral lesions appear as blue-grey macules or plaques \nwith irregular borders5. Associated abnormalities \ninclude congenital glaucoma, Duane\u2019s syndrome \nand melanoma5,7. Only 16 cases with palatal \npigmentation has been reported, and this is the  \n17th. \n\n\n\nIt is important to differentiate N. of Ota from other \nconditions. Acquired, bilateral nevus of Ota-like \nmacules (ABNOM) or Hori\u2019s nevus is located \nbilaterally on the face, appears later in life, is blue-\nbrown or slate-grey in color and commonly seen \nin middle-aged women of Asian descent. It is not \naccompanied by macules on the ocular and mucosal \nmembranes12,13.\n\n\n\nMongolian spots (MS) are birthmarks that are \npresent at birth and their most common location is \nsacrococcygeal or lumbar area. Aberrant MS over \nocciput, temple, mandibular area, shoulders and \nlimbs have been reported14. Nevus of Ito occurs \nin the territory supplied by the acromioclavicular \nnerve1, and hence found on the shoulder, neck, \nupper arm and supra clavicular area5.\n\n\n\nHistopathology of the affected skin shows the \npresence of dendritic cells containing melanin in \nthe dermis11.\n\n\n\nDifferent modalities have been proposed for                  \nthe management of Nevus of Ota. This includes \nselective photothermolysis with Q switched ruby \nlaser or Nd:YAG laser which is considered to be \na safe and effective treatment4,15, dermabrasion, \ncryotherapy and historically surgical excision2.\n\n\n\nMalignant transformation of the melanocytoses, \nthough very rare, has been reported including nevus \nof Ota1.\n\n\n\nIn conclusion, Nevus of Ota is a hamartomatous \nproliferation of melanocytes. This entity is still \na rarity in India especially the extra-cutaneous, \noral mucosal manifestation. The importance of \nrecognizing this entity needs to be emphasized,  as \na magnitude of pigmented lesions is noted on the \noral mucosa. Also, long term follow-up is essential \nas very rarely dermal melanocytosis can undergo \nmalignant transformation.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25 MJD 2013 Dec Vol 31\n\n\n\nReferences\n\n\n\n1. Mart\u00ednez-Pe\u00f1uela A, Iglesias ME, Mercado MR, Mart\u00ednez-\nPe\u00f1uela JM. Malignant Transformation of a Nevus of \nIto: Description of a rare Case. Actas Dermosifiliogr \n2011;102:817-820.\n\n\n\n2. Mehta V, Balachandran C. Bilateral nevus of Ota. J \nof Pakistan Assoc of Dermatologists 2007; 17: 59-61.\nMukhopadhyay AK.  Unilateral Nevus of Ota with Bilateral \nNevus of Ito and Palatal Lesion: A Case Report with a \nProposed Clinical Modification of Tanino\u2019s Classification. \nIndian J Dermatol 2013; 58: 286\u2013289.\n\n\n\n3. Tan HH, Kono T. Nevus of Ota: clinical aspects and \nmanagement. SKINMed 2003;2:89-98.\n\n\n\n4. Mahima VG, Patil K, Srikanth HS, Malleshi SN. Report of \nrare palatal expression of Nevus of Ota with amendment to \nTanino\u2019s classification. Indian J of Dent Res 2011;22:850-\n52. \n\n\n\n5. Sharma G, Nagpal A. Nevus of Ota with Rare Palatal \nInvolvement: A Case Report with Emphasis on Differential \nDiagnosis. Case Reports in Dentistry Volume 2011, Article \nID 670679, 4 pages.  doi:10.1155/2011/670679.\n\n\n\n6. Cronemberger S, Calixto N, Freitas HL. Nevus of Ota: \nclinical-ophthalmological findings. Rev Bras Oftalmol. \n2011; 70: 278-83.\n\n\n\n7. Kumari R, Thappa DM. Familial Nevus of Ota. Indian J \nDermatol. 2006:51;(3) 198-99.\n\n\n\n8. Turnbull JR, Assaf Ch, Zouboulis C, Tebbe B Bilateral \nnaevus of Ota: a rare manifestation in a Caucasian.. J Eur \nAcad Dermatol Venereol. 2004 May;18(3):353-55.\n\n\n\n9. Mukhopadhyay AK. Nevus of Ota associated with nevus of \nIto. Indian J Dermatol Venereol Leprol 2004;70:112-3.\n\n\n\n10. Rahim H, Yousefi M, Mirnezami M, Asadi-Kani Z. Bilateral \ncongenital nevus of Ota in association with Mongolian \nspot. Iran J Dermatol 2011; 14: 68-70.\n\n\n\n11. Park JH, Lee MH. Acquired, bilateral nevus of Ota-like \nmacules (ABNOM) associated with Ota\u2019s nevus: case \nreport. J Korean Med Sci. 2004 Aug;19(4):616-18.\n\n\n\n12. Manuskiatti W, Sivayathorn A, Leelaudomlipi P, Fitzpatrick \nRE. Treatment of acquired bilateral nevus of Ota-like \nmacules (Hori\u2019s nevus) using a combination of scanned \ncarbon dioxide laser followed by Q-switched ruby laser. J \nAm Acad Dermatol 2003;48:584-91.\n\n\n\n13. Gupta D,  Thappa DM. Mongolian spots. Indian J of \nDermatol Venerol Leprol 2013;79:469-78.\n\n\n\n14. Kunachak S , Leelaudomlipi P. Q-Switched Nd:YAG \nLaser Treatment for Acquired Bilateral Nevus of Ota-Like \nMaculae: A Long-Term Follow-Up. Lasers in Surgery and \nMedicine 2000; 26:376\u2013379.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26MJD 2013 Dec Vol 31\n\n\n\nGENERAL DERMATOLOGY - Short Case\n\n\n\nCLASSIC DERMATOMYOSITIS FOLLOWING BREAST CANCER: \nA CASE REPORT \n\n\n\nChee Yong Chuang1, Choon Siew Eng, FRCP2\n\n\n\nKeywords: paraneoplastic sign, ductal carcinoma, proximal myopathy\n\n\n\nIntroduction\nDermatomyositis and polymyositis are idiopathic \ninflammatory myopathies characterized by \nsymmetrical proximal muscle weakness and \ndistinctive skin manifestations1-4. It is a rare disease \nwith an estimated combined annual incidence of 2 \nper 100,000 population5. Population-based studies \nfrom Sweden, Australia, and Scotland showed that \ndermatomyositis, and to a lesser extent polymyositis, \ncarried an increased risk of malignancies6-8. Cancers \nsuch as adenocarcinomas of the lung, pancreas, \ncervix and stomach as well as haematological \ncancers including Hodgkin\u2019s and non-Hodgkin\u2019s \nlymphoma accounted for approximately 70% of the \ncancers associated with inflammatory myopathies9. \nTypes of malignancy associated with inflammatory \nmyopathies may depict local prevalence of certain \nforms of malignancy. For instance, nasopharyngeal \ncarcinoma is commonly reported in Southeast Asian \npatients with dermatomyositis9,10. Breast cancer \nis the most common accompanying malignancy \namong women with dermatomyositis/polymyositis \nin Korea and Taiwan. The onset of dermatomyositis/\npolymositis may precede, coincide with or follow \nthe diagnosis of breast cancer11,12. We report a case \nof classic dermatomyositis that developed 3 months \nafter the discovery of breast cancer.\n\n\n\nCase report\nA 25 year old nulliparous Vietnamese lady, married \nto a Malaysian, was referred to us for the evaluation \nof a rash that developed 3 months after the discovery \n\n\n\nCorrespondence\nChoon Siew Eng, FRCP\n2Department Of Dermatology\nHospital Sultanah Aminah, Johor Bahru  \n80100 Johor, Malaysia\nEmail: choonse@yahoo.co.uk\n\n\n\n1Medical student, School of Medicine &\nHealth Sciences, Monash University, Sunway Campus\n\n\n\nof a breast lump by self examination. She had no \nfamily history of malignancy and was otherwise \nwell before the breast lump was removed by a wide \nlocal excision in a private hospital. A week post-\nprocedure, she noticed asymptomatic rashes that \nstarted over the forehead and gradually spreading \nin a descending fashion to involve the eyes, face, \nchest, neck, extensors of the upper limb, dorsum of \nthe hands and the inner thighs. \n\n\n\nIt was associated with symmetrical muscle \nweakness affecting the proximal muscles of both \nupper and lower limbs. The weakness was profound \nas she found herself unable to carry out activities \nof daily living. She had difficulty sitting up from \na lying position, climbing stairs or rising from \na seated or squatting position. She also found it \ndifficult to perform activities that require holding \nthe arms up like washing her hair or reaching into \noverhead cupboards. She also experienced neck \nweakness, where she had difficulty raising her head \nfrom a pillow or holding it up while standing. She \nalso complained of difficulty swallowing, nasal \nregurgitation and hoarseness of voice. Her weakness \ndeteriorated rapidly till she was bed bound.\n\n\n\nPhysical examination revealed profound proximal \nmuscle weakness and classic skin lesions. She \nhad bilateral violaceous erythematous rash \nwith periorbital and eye lid edema consistent                        \nwith heliotrope rash (Figure 1). Photo-distributed \nerythema with V-neck sign and shawl sign were noted \nover the anterior chest and upper back respectively. \nGottron\u2019s sign characterized by elevated violaceous \npapules and plaques over bony prominences were \nalso present in addition to nail fold changes namely \nperiungual erythema, telangiectasia and ragged \ncuticles (Figure 2).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27 MJD 2013 Dec Vol 31\n\n\n\nFigure 1  Violaceous erythematous macules and patches in sun-\nexposed areas exhibiting classic Heliotrope and V-neck signs.\n\n\n\nFigure 2  Gottron\u2019s papules, periungual erythema and ragged cuticles.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28MJD 2013 Dec Vol 31\n\n\n\nMyositis was confirmed by elevated muscle enzymes \n(creatine kinase; 10720 U/L, lactate dehydrogenase; \n840U/L, alanine aminotransferase;149 U/L, aspartate \naminotransferase;  491 U/L), electromyography and \nmuscle biopsy. Both erythrocyte sedimentation rate \n(42mm/hour) and C-reactive protein (12.1 mg/L) \nwere elevated. Anti-nuclear antibody was positive \nwith a titre of 1280 demonstrating a speckled \npattern. Anti-double-stranded DNA, anti-Jo1 and \nanti-topoisomerase antibodies were all negative. \nHistology of her breast lump revealed poorly \ndifferentiated infiltrating ductal carcinoma [(Bloom \nand Richardson\u2019s Grade III, Clinical Staging: \nT2N1M0, Stage II A].\n\n\n\nIn spite of the institution of high dose prednisolone, \nshe developed increasing dyspnoea with acute \nhypoxemic respiratory failure complicated by \nnosocomial pneumonia. She was ventilated and \ntreated with multiple intravenous antibiotics, \nintravenous methyprednisolone and subsequently \nintravenous immunoglobulin. Aggressive care \nallowed weaning her off the ventilator support \nbut patient declined an urgent mastectomy and \naxillary clearance which was scheduled with the \nhope of alleviating her myositis. She opted for \ntreatment back in Vietnam and requested to be \ndischarged at her own risk from hospital while still \non prednisolone 40 mg daily. She succumbed to the \ndisease in Vietnam one month after discharge before \nany surgical intervention.\n\n\n\nDiscussion\nIdiopathic inflammatory myopathies are a mixed \ngroup of disorders characterized by symmetrical \nproximal muscle weakness and evidence of \ninflammation involving striated skeletal muscles. \nPatients with dermatomyositis fulfil criteria for \npolymyositis in addition to having characteristic \ncutaneous manifestations3-4.\n\n\n\nDermatomyositis is usually an idiopathic \nautoimmune connective tissue disease but about 15-\n30 % of adult-onset dermatomyositis have underlying \nmalignancies1-2,9-12. In our patient, dermatomyositis \nwas diagnosed based on the \u201crevised criteria for \nthe diagnosis of inflammatory myositis\u201d proposed \nby Bohan and Peters3-4. She had paraneoplastic \ndermatomyositis following breast cancer that had \nmetastasized to axillary nodes. The relationship \nbetween dermatomyositis and malignancy has been \nestablished in various studies. Malignancy may be \ndiagnosed before, simultaneously or following the \ndevelopment of dermatomyositis. The majority \nof the diagnosis of cancer was made within two \nyears pre- or post-diagnosis of the inflammatory \nmyopathy6-7.\n\n\n\nIn Finland, Denmark and Sweden, the common \ncancer associated with dermatomyositis are ovarian, \nbreast, lung, pancreatic, stomach and colorectal \ncancer6-8. Whereas in Southeast Asian countries like \nSingapore, Korea and Taiwan10,11,12, breast, stomach \nand nasopharyngeal cancer (NPC) predominated. \nBreast cancer is the top cancer in women both in \nthe developed and the developing world, comprising \n16% of all female cancers13. Thus, it is not surprising, \nthat it is also a common cancer seen in patients \nwith dermatomyositis. Breast cancer accounted for \n21.3% of malignancies in 89 Taiwanese women \nwith paraneoplastic dermatomyositis / polymyositis.  \nThe mean age of patients with either adult onset \ndermatomyositis or breast cancer is usually more \nthan 50 years old5,9. Here, we report a rare case of \na young patient with rapidly progressive and fatal \ndermatomyositis following a newly diagnosed \nbreast cancer.\n\n\n\nReferences\n\n\n\n1. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. \nLancet 2003; 362:971.\n\n\n\n2. Plotz PH, Dalakas M, Leff RL, et al. Current concepts in \nthe idiopathic inflammatory myopathies: polymyositis, \ndermatomyositis, and related disorders. Ann Intern Med \n1989; 111:143.\n\n\n\n3. Bohan A, Peter JB. Polymyositis and dermatomyositis (first \nof two parts). N Engl J Med 1975; 292:344.\n\n\n\n4. Bohan A, Peter JB. Polymyositis and dermatomyositis \n(second of two parts). N Engl J Med 1975; 292:403.\n\n\n\n5. Jacobson DL, Gange SJ, Rose NR, Graham NM. \nEpidemiology and estimated population burden of selected \nautoimmune diseases in the United States. Clin Immunol \nImmunopathol 1997; 84:223.\n\n\n\n6. Sigurgeirsson B, Lindel\u00f6f B, Edhag O, Allander E. Risk of \ncancer in patients with dermatomyositis or polymyositis. A \npopulation-based study. N Engl J Med 1992; 326:363.\n\n\n\n7. Buchbinder R, Forbes A, Hall S, et al. Incidence of \nmalignant disease in biopsy-proven inflammatory \nmyopathy. A population-based cohort study. Ann Intern \nMed 2001; 134:1087.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29 MJD 2013 Dec Vol 31\n\n\n\n8. Stockton D, Doherty VR, Brewster DH. Risk of cancer in \npatients with dermatomyositis or polymyositis, and follow-\nup implications: a Scottish population-based cohort study. \nBr J Cancer 2001; 85:41.\n\n\n\n9. Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer \nL, Airio A, Evans SR, Felson DT: Frequency of specific \ncancer types in dermatomyositis and polymyositis: a \npopulation-based study. Lancet 2001, 357:96-100\n\n\n\n10. Ang P, Sugeng MW, Chua SH. Classical and amyopathic \ndermatomyositis seen at the National Skin Centre of \nSingapore: a 3-year retrospective review of their clinical \ncharacteristics and association with malignancy. Ann Acad \nMed Singapore 2000; 29:219\n\n\n\n11. Lee SW, Jung SY, Park MC, Park YB, Lee SK: Malignancies \nin Korean patients with inflammatory myopathy. Yonsei \nMed J 2006, 47:519-523\n\n\n\n12. Y. L. Huang, Y. J. Chen, M. W. Lin et al., \u201cMalignancies \nassociated with dermatomyositis and polymyositis in \nTaiwan: a nationwide population-based study,\u201d British \nJournal of Dermatology, vol. 161, no. 4, pp. 854\u2013860, \n2009\n\n\n\n13. WHO Global Burden of Disease, 2004. Accessed on 27 \nSeptember 2013 www.who.int/entity/healthinfo/global_\nburden_disease/2004_report_update/en/\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30MJD 2013 Dec Vol 31\n\n\n\nDERMATOLOGY INFECTION - Review Article\n\n\n\nCLINICAL CHARACTERISTICS OF PATIENTS WITH LEPROSY\nIN HOSPITAL KUALA LUMPUR\n\n\n\nTarita Taib1, AdvnMDerm, Roshidah Baba2, FRCP\n\n\n\nAbstract\n\n\n\nBackground: Nearly half of the new leprosy cases reported in Malaysia were foreigners from \nneighbouring Asian countries.\n\n\n\nObjectives: To determine the clinical characteristics of leprosy and its difference, among the Malaysian \nand the foreign patients \n\n\n\nMethods: This is a 4-year retrospective analysis of 75 leprosy patients who attended Hospital Kuala \nLumpur Hansen\u2019s Clinic. Variables included the disease clinical characteristics, clinical severity and \nthe complications.\n\n\n\nResults: Foreigners accounted for 51% of total patients with mean age of 35.8 years. Malaysians \npresented at mean age of 40.8 years. The gender ratio (male: female) was 2.7:1 in the former and 2.3:1 \nin the latter.  The Malaysians tend to present later (average after three years) to the clinic. The clinical \npresentations in both groups of patients didn\u2019t significantly differ.\n\n\n\nConclusion: In Malaysia. Leprosy shouldn\u2019t be labelled as the disease of the immigrants. Social \nawareness on the disease should be equally highlighted to both locals and foreigners, especially among \nfemales.\n\n\n\nKeywords: granulomatous disease, Hansen\u2019s disease, Malaysia\n\n\n\nIntroduction\nLeprosy is a chronic granulomatous infection caused \nby Mycobacterium leprae (M leprae), principally \naffecting the skin and peripheral nervous system. M \nleprae is an obligate acid-fast bacillus, and humans \nare its principal reservoir.\n\n\n\nCorrespondence\nDr. Tarita Taib, AdvMDerm\n1University Technology Mara (UiTM) Medical Faculty,\nSelayang Campus, Jalan Prima Selayang 7,\n68100 Batu Caves, Selangor.\nEmail: taritataib@salam.uitm.edu.my\n\n\n\n2Department of Dermatology, Kuala Lumpur Hospital, \nKuala Lumpur, Malaysia.\n\n\n\nIn Malaysia, leprosy remains to be a disease burden \ndespite a tremendous reduction in its prevalence \nfor the past 20 years. Leprosy prevalence rate in \nMalaysia from year 2005 to 2007 was 0.3 per 10 \n000 populations in three consecutive years1. The \nincident rate in 2007 was 0.7 per 100 000, a decline \nfrom 1.1 per 100,000 in 2005.\n\n\n\nThe proportion of foreigners diagnosed with leprosy \nfrom the total new cases in Malaysia increased from \n24.5% in year 2000 to 44.0% in 20071. In year 2007, \nforeigners\u2019 contribution to all new leprosy cases in \nMalaysia had showed an increasing trend of 13% \nfrom the previous year.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31 MJD 2013 Dec Vol 31\n\n\n\nIn  developed country like the United States, 200-300 \ncases are reported each year, mainly from the states \nwith large immigrant populations (eg, California, \nNew York, Florida)2,3. The disease spreads by \naerosolized droplets from lepromatous patients and, \nless commonly, through direct skin contact. \n\n\n\nLeprosy can have a protracted and insidious onset. \nAfter exposure, person who is susceptible to leprosy \nmay develop a single skin lesion after an incubation \nperiod averaging 5 to 7 years (range from 3 months \nto 40 years). Therefore clinical signs may not \nmanifest until after the immigration process is \ncomplete. Given that the majority of new migrants \nwith leprosy manifested the disease within 1 year \nof immigration, it is postulated that stress or socio-\neconomic factors associated with migration may \nhave pushed the disease from being quiescent to \nsymptomatic.  Host immunity, particularly the cell-\nmediated immune response, plays an important role \nin its tissue damage. The severity of deformities \ncaused by nerve tissue damage was influenced \nby the type and extent of bacillary spread and \nmultiplication, also the occurrence of immunologic \ncomplications i.e. lepra reactions.\n\n\n\nMalaysia as one of the fastest growing developing \ncountries in Asia is facing the same issue as in \ndeveloped country, with the high influx of foreign \nworkers attributing to the higher number of medical \ncases. Given that leprosy is still prevalent in certain \ncountries in Asia like Cambodia and Nepal4, where \nit is not easily treated due to poor socio-economic \nconditions, the unprecedented mobility of these \nforeigners crossing the Malaysian borders has \nincreased the number of leprosy patients. Thus, it is \nimportant for Malaysian health care providers to be \nfamiliar with the clinical characteristics of leprosy \nlocally.\n\n\n\nObjective\nWe sought to determine the clinical characteristics of \npatients with leprosy, and the differences in clinical \ncharacteristics between local Malaysian patients and \nforeign patients.\n\n\n\nMethods\nStudy Design and patients\nA retrospective analysis was performed. Study \npopulation included patients diagnosed with \nleprosy in Hospital Kuala Lumpur, a tertiary \nreferral hospital, between the year 2006 and 2009. \nThis review focused on demography, classification, \ndeformities, lepra reactions and drug resistance.\n\n\n\nA total of 75 patients (52 male and 23 female), aged \nbetween 10 and 75 years, were analyzed according \nto group; Malaysians and foreigner.  Foreign patients \nwere further subdivided into permanent resident or \nnot. Patients who had incomplete medical record \nand who defaulted follow-up were excluded from \nthe study.\n\n\n\nAll patients diagnosed with leprosy had slit skin \nsmears taken from the suspected sites of skin lesions \nand stained with Fite method. Skin biopsy was \nperformed to those who had negative finding from \nslit skin smears, those who had bacillary Index of \nmore than 3, and to those who presented only with \nnerve lesion.\n\n\n\nData Collection\nAll data were derived retrospectively from the \nmedical records and were recorded in data sheets \nin the computer.  The variables used for comparison \nin clinical presentations included the type or \nseverity of leprosy in accordance to Ridley-Jopling \nClassification, drug resistance to one or more \ndrugs using mouse foot pad culture and disease \ncomplications including lepra reactions and \nneurological complications.\n\n\n\nStatistical analysis\nStatistical analysis was performed using Fisher\u2019s \nexact test for the comparison of proportions. A \nvalue of P less than 0.05 was considered statistically \nsignificant. All analyses were performed using \nSPSS (Statistical Package for Social Science) \nprogramme version 14. Comparisons of frequencies \nbetween local and foreign patients were conducted \nwith independent sample T test or Mann U Whitney \nTest.\n\n\n\nResults\nA total of 75 patients (aged from 10 to 75 years) were \nreviewed. Thirty eight of the 75 patients (50.7%) \nwere foreigners. The average age in both groups \nfell on the second bimodal age distribution, with \npeaks at the age of 35-44 years. The nationalities of \nforeign patients were shown in Figure 1.\n\n\n\nThe ethnic distribution of local patients was \ndemonstrated in Figure 2. Malay and Chinese ethnic \naccounted for 38% each of all Malaysian patients \nForeigners, mostly Indonesians, accounted for 51% \nof total patients. Twelve of them, all Indonesians, \nwere permanent residents.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32MJD 2013 Dec Vol 31\n\n\n\nMultibacillary leprosy predominated in each group, \n86% among Malaysians and 95% in foreigners, as \nshown in Table 1. The Malaysian patients had higher \nprevalence (35.1%) of lepromatous leprosy (LL) \nwhereas foreign patients presented with more cases \n(34.2%) of borderline lepromatous (BL) as shown \nin Table 2.\n\n\n\nThe overall mean duration of symptoms                   \nbefore diagnosis was 2 years (8 months-5 years).  \nMalaysians tend to present later, with a mean of 3 \nyears after onset of symptoms, as compared to the \nforeigners (Figure 3).\n\n\n\nPatient\u2019s groups\n\n\n\nMalaysian \n\n\n\nForeigner\n\n\n\nTotal /No (%)\n\n\n\nPaucibacillary\n\n\n\n 4 (11.0%)\n\n\n\n 1 (2.5%)\n\n\n\n 5 (7.0%)\n\n\n\nMultibacillary\n\n\n\n 32 (86.0%)\n\n\n\n 36 (95.0%)\n\n\n\n 68 (91.0%)\n\n\n\nNeural\n\n\n\n 1 (3.0%)\n\n\n\n 1 (2.5%)\n\n\n\n 2 (2.0%)\n\n\n\nTotal  \n\n\n\n37\n\n\n\n38   \n\n\n\n75\n\n\n\nTable 1  Patients distributed into WHO leprosy classification.\n\n\n\nFigure 1  Distribution of foreign patients by nationality Figure 2  Distribution of Malaysian patients by race\n\n\n\nNeural\n\n\n\nIndeterminate\n\n\n\nTuberculoid\n\n\n\nBorderline Tuberculoid\n\n\n\nBorderline\n\n\n\nBorderline Lepromatous\n\n\n\nLepromatous\n\n\n\nMalaysian\n\n\n\n 2.7%\n\n\n\n 5.4%\n\n\n\n 8.1%\n\n\n\n 24.3%\n\n\n\n 2.7%\n\n\n\n 21.6%\n\n\n\n 35.1%\n\n\n\nForeigner\n\n\n\n 2.6%\n\n\n\n 0.0%\n\n\n\n 2.6%\n\n\n\n 21.1%\n\n\n\n 10.5%\n\n\n\n 34.2%\n\n\n\n 28.9%\n\n\n\nTable 2  Patients distributed into Ridley-Jopling classification of \nleprosy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33 MJD 2013 Dec Vol 31\n\n\n\nFifty percent of Malaysian patients were \ndiagnosed with grade 1 deformity and 8% were \ndiagnosed with grade 3 deformity (Figure 4). \nAmong the foreigners, twenty-one percent \npresented with grade 1 deformity and 8% with \ngrade 3 deformity. Half of the foreign patients \n(50%) had already had grade 1 deformity at \npresentation (Figure 4).\n\n\n\nAmong all patients who developed lepra \nreactions, 22 patients were diagnosed with type \n1 (reversal) reaction, 27 patients with type 2 \nreaction (erythema nodosum leprosum) and 2 \npatients with Lucio\u2019s reaction. Full dapsone \nresistance was confirmed by mouth foot-pad \nculture in one Malaysian patient.\n\n\n\nType 2 lepra reaction (ENL) occurred in 39.5 % \nof Malaysians and in 32.4 % of foreign patients.\nThe occurrence of lepra reactions, deformities \nand drug resistance did not differ significantly \nbetween the two groups of patients. (Table 3)\n\n\n\nFigure 3  Duration (year) from onset of symptom to time of diagnosis, of study patients.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34MJD 2013 Dec Vol 31\n\n\n\nClinical features\n\n\n\nHypoaesthetic/anaesthetic skin\n\n\n\nNerve thickening\n\n\n\nPeripheral Neuropathy\n\n\n\nPositive slit-skin smears\n\n\n\nBacillary index (BI)\n\n\n\nMorphology index (MI)\n\n\n\nPartial Dapsone \n\n\n\nResistance\n\n\n\nFull Dapsone \n\n\n\nResistance\n\n\n\nSensitive to all MDT\n\n\n\nDrug sensitivity not done\n\n\n\nMouse foot pad culture result not \navailable\n\n\n\nFrequency (%)\nN = 75\n\n\n\n80\n\n\n\n79\n\n\n\n73\n\n\n\n87\n\n\n\n3.5 + 1.7\n\n\n\n3.1 + 2.2\n\n\n\nMalaysians\nN = 37\n\n\n\n45\n\n\n\n36\n\n\n\n33\n\n\n\n40\n\n\n\n3.4+ 1.7\n\n\n\n3.7+ 2.7\n\n\n\n2 (5.4%)\n\n\n\n1 (2.7%)\n\n\n\n4\n\n\n\n11\n\n\n\n19\n\n\n\nForeigners\nN = 38\n\n\n\n35\n\n\n\n43\n\n\n\n40\n\n\n\n47\n\n\n\n3.6 + 1.7\n\n\n\n2.5 + 1.5\n\n\n\n8 (10.7%)\n\n\n\n0\n\n\n\n6\n\n\n\n5\n\n\n\n19\n\n\n\nTable 3 Clinical presentations in both groups of patient.\n\n\n\nMean + SD\n\n\n\nFrequency\n\n\n\nMDT- Multidrug Therapy\n\n\n\nFigure 4  Frequency of neurological deformity in both groups of patients.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35 MJD 2013 Dec Vol 31\n\n\n\nDiscussion\nIn this case series, there was a male predominance \nwith a male-to-female ratio of 2.3 to 1. This is \nconsistent with other studies done in other states of \nMalaysia and also most part of the world excluding \nAfrica, Thailand and Japan1,5. In the past decade, \nMalaysian women received equal education as \nthe man but most Asian women had higher social \nembarrassment that leads to higher social stigma on \nleprosy. The possibility of the disease being under \ndiagnosed in females of this country has never \nbeen investigated although; it is believed that the \ndifference between the genders in post pubertal age is \nreal6. However, the male: female ratio in this review \nwas accentuated (baseline: a male to female ratio of \n1\u00b75-2\u00b70 to 1), probably due to delayed presentation \nby the female patients. There was no evidence of \nracial predilection in this disease.\n\n\n\nThe main complication of leprosy is disability \ncaused by nerve damage, a consequence from \nSchwann cell invasion by Mycobacterium leprae and \nthe patient\u2019s immune response. Previous studies6,7,8 \nshowed that prevalence of neurological impairment \nincreases with late presentation. Other risk factors \nfor chronic or recurrent neuropathy include leprosy \nclassification (both WHO and Ridley-Jopling) and \nLepra reactions. The disease severity, and occurrence \nof deformity, reaction and drug resistance among \nthe Malaysian and foreigners was comparable. \nSurprisingly most Malaysian presented later than 1 \nyear from onset of symptom, hence may contribute \nto higher percentage of Malaysian patient found to \nhave grade 3 deformities at presentation. \n\n\n\nA study done in Malaysia between 1985-19909 \nshowed a high percentage of dapsone resistance \n(22.4%). This study reported 10 partial and 1 full \ndapsone resistance out of 21 patients with MFP \nculture results (Table 3), hence no conclusive \nstatistically significant data on dapsone drug \nresistance can be made on this study population.\n\n\n\nWithin a short period of less  than 4 years (Jan \n2006 until October 2010), our study cohort of \nleprosy diagnosed in Hospital Kuala Lumpur \n(HKL) consists of  more (50.7%) foreigners than \nthat was seen in studies conducted in a longer \nstudy period (10 to 14 years) in Penang (22.2%) \nand Johor Bahru (33%). Kuala Lumpur being the \ncentre of Malaysian economic activities has more \nforeign workers, hence more imported cases being \ndiagnosed. Most of the foreigners were from the \nneighbouring Asian countries. This is not surprising \n\n\n\nas the World Health Organization in 2001 reported \nthat Indonesian and Myanmar were still leprosy \nendemic countries. All foreign patients presented \nwithin 4 years after the onset of symptoms. As most \nof them had passed the routine medical screening \nbefore working in Malaysia, more study should be \ndone to obtain information on triggering factors of \nsymptomatic disease onset. Leprosy transmission \nmay have occurred in their country of origin as \nMycobacterium leprae has a long incubation period. \nIt is also alarming to know that subclinical infection \nwas found in up to 5% of healthy Indonesian in their \ncountry10.\n\n\n\nIt is also important to highlight whether leprosy cases \namong the locals in Kuala Lumpur had remained \nunder diagnosed. Most Malaysian patients presented \nwithin 3 years of symptom onset. However, 13% \nof them presented later than 4 years, attributing to \nsignificant morbidity at the time of diagnosis. There \nare many reasons of the delayed diagnosis which \nincludes, patients soughing healthcare advice only \nafter symptoms caused inconvenience, patients \npreferred traditional treatment at early stage of \ndisease, early disease undiagnosed by primary \nhealthcare practitioners and lastly, patients delayed \ntreatment due to social, geographical or financial \nreasons. There is an urgent need for Malaysians to \nbe continuously educated about leprosy, as early \ntreatment would significantly improve morbidity \nand reduced the country economic burden.\n\n\n\nConclusion\nClinical characteristics of leprosy in terms of \ndisease severity, prevalence of lepra reactions, \nneurological deformity and frequency of drug \nresistance were comparable between local and \nforeign patients.  Hence in Malaysia, leprosy should \nno longer be labelled as a disease of the immigrant \nor imported disease. Public education on leprosy is \nvery important, particularly among the orang asli, \nbumiputera Sabah and Sarawak.\n \nCompared to foreign patients, local patients \ntend to present later after the onset of symptoms, \nattributing to higher non-reversible neurological \ndisability or deformity. \u2018Social stigma\u2019 on leprosy \namong Malaysian population should be replaced by \nawareness that the disease is curable and that the \nresultant neuropathy is treatable if treated early.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director of \nHealth of Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36MJD 2013 Dec Vol 31\n\n\n\nReferences\n\n\n\n1. Epidemiological Report on Leprosy. Ministry of Health, \nMalaysia. 2007.\n\n\n\n2. Boggild et al.  Leprosy: a primer for Canadian physicians. \nCMAJ, 2004; 170(1): 71-78.\n\n\n\n3. Truman RW, Singh P, Sharma R, et al. Probable zoonotic \nleprosy in the southern United States. N Engl J Med. \n2011;364(17):1626-33\n\n\n\n4. WHO Epidemiological Review of Leprosy in the Western \nSpecific Region. 2007.\n\n\n\n5. Britton WJ, Lockwood DN.  Leprosy. Lancet. 2004. 363; \n1209-1219\n\n\n\n6. ES Peters and AL Eshiet. Male-female (sex) differences in \npatients in South Eastern Nigeria: females present late for \ndiagnosis and treatment and have higher rates of deformity. \nLepr Rev 2002 :73 ; 262\u2013267.\n\n\n\n7. DN Lockwood, AJ Reid, The diagnosis of previous leprosy \nterm is delayed in the United Kingdom, QJM 2001: 94; \n207\u2013212.\n\n\n\n8. Joyce MP, Scollard DM. Leprosy (Hansen\u2019s Disease). \nConn\u2019s Current Therapy. 2004;100-105\n\n\n\n9. Fadzilah K. Mouse footpad studies in National Leprosy \nControl Centre. Proceedings of the National Leprosy \nSeminar, Malaysia. 1992 July; 26-29.\n\n\n\n10. M Hatta, SM van Beers, B Madjid et al. Distribution and \npersistence of Mycobacterium leprae nasal carriage among \na population in which leprosy is endemic in Indonesia. \nTrans R Soc Trop Med Hyg 1995: 89: 381\u2013385.\n\n\n\n11. Joshua D. Leprosy: A Case Series and Review. South Med \nJ. 2004;97(12): 1252-56\n\n\n\n12. Mohammad et al. Burden of skin diseases. Expert Review \nof Pharmaco-economics and Outcomes Research July \n2009\n\n\n\n13. Diana N J Lockwood. Leprosy elimination - a virtual \nphenomenon or a reality? BMJ 2002;324:1516-1518\n\n\n\n14. Norihisa I. Recent advances in the treatment of leprosy. \nDermatology Online Journal 9 (2): 5\n\n\n\n15. Ramaratnam S. Leprosy. www.emedicine.com. 2007\n16. Felisa S L. Leprosy. www.emedicine.com. 2007\n17. Lockwood D N J. Treatment of leprosy. BMJ  2004 ; \n\n\n\n328(7454):1447-1448\n18. James L.K. Leprosy. Microsoft\u00ae Encarta\u00ae Online \n\n\n\nEncyclopedia 2007. http://encarta.msn.com \u00a9 1997-2007\n19. WHO Report of the global forum on elimination of leprosy \n\n\n\nas a public health problem, Geneva. 2006.\n20. Jayalakshmi P. Leprosy in Malaysia. Malaysian J of Pathol. \n\n\n\n1994; 16 (1): 7-9\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n37 MJD 2013 Dec Vol 31\n\n\n\nDERMATOLOGY INFECTION - Short Case\n\n\n\nPERIANAL TUBERCULOSIS:\nA CASE REPORT AND LITERATURE REVIEW \n\n\n\nSelvarani S1, Tang JJ1, Norain K2\n\n\n\nKeywords: anal tuberculosis, periorificial tuberculosis, ano-perianal tuberculosis, extrapulmonry tuberculosis\n\n\n\nIntroduction\nPeriorificial tuberculosis is a rare manifestation of \ncutaneous tuberculosis which is characterized by \npainful ulcerative lesions affecting oral, genital, anal \nmucosa and adjacent skin of the orifices. It occurs \nfollowing auto-inoculation of mycobacteria from \npulmonary, gastrointestinal or genitourinary foci \nthat affect traumatized mucocutaneous areas around \nthe orifices1. Rarely, haematogenous, lymphatic or \ndirect spread from neighbouring organs can lead to \nthis condition. The tongue is the most frequently \naffected site, but the perianal area can also be \naffected2. Herein, we report a rare case of perianal \ntuberculosis presented with non-healing perianal \nulcer for 2 years and to emphasize the importance \nof considering tubercular etiology in the work up of \npersistent perianal ulcer.\n\n\n\nCase report\nA 54 year-old Chinese man presented with persistent \nperianal ulcer of 2 years. He was seen by many \ndoctors and was treated with multiple topical and \noral antibiotics without much improvement. The \nperianal ulcer was getting bigger and associated \nwith pain and serous discharge. He had persistent \nlow grade fever, night sweat with significant loss of \nappetite and loss of weight. There was also history \nof intermittent constipation for 2 years which \nwas associated with few episodes of per rectum \nbleeding. He underwent colonoscopy in 2010 but \nwas essentially normal. There was no history of \nchronic cough or haemoptysis. \n\n\n\nCorrespondence\nTang Jyh Jong, AdvMDerm\n1Department of Dermatology,\nHospital Raja Permaisuri Bainun Ipoh, Perak, Malaysia.\nEmail: tangjyhjong@yahoo.com\n\n\n\n2Department of Pathology,\nHospital Raja Permaisuri Bainun Ipoh, Perak, Malaysia.\n\n\n\nHe has no family history of tuberculosis and he \ndenied contact with any patients with tuberculosis. \nHe was married with 3 children and worked as a lorry \ndriver.  He denied history of anal intercourse, sexual \npromiscuity or homosexuality. He was an ex smoker \nand did not consume alcohol.  On examination, he \nwas afebrile and pink. Perianal examination revealed \nan ulcer extending from base of scrotum to an area \nof 3 cm around the perianal region (Figure 1). The \nulcer was tender with hyperpigmented margin and \ncovered with mucopurulent discharge. There was \nno inguinal lymphadenopathy. Examination of other \nsystems including respiratory system was essentially \nnormal.\n\n\n\nOur initial differential diagnosis included perianal \nCrohn\u2019s disease, perianal Tuberculosis, Chancroid,  \nHailey-Hailey disease, Langerhans cell histiocytosis \nand neoplastic conditions such as extramamary \nPaget\u2019s disease and Marjolin ulcer. Laboratory \nfindings of complete blood count, renal profile, \nliver function tests and urinalysis were normal, \nexcept for ESR which was raised at 52mm/hr.  The \nVDRL, TPHA, Hepatitis B, C and HIV serology \nwere negative. Chest X-ray revealed scattered \nmicrogranular opacity in both upper zone of lung. \nSputum for Acid Fast Bacilli was however negative. \nA skin biopsy taken from the margin of an ulcer \nshowed granulomatous lesion with presence of \nLangerhans-type multinucleated giant cells and \nZiehl Neelson stain showed abundant acid fast bacilli \nwithin the tissue (Figure 3 and 4). Skin biopsy was \npositive for Mycobacterium tuberculosis culture.  \nThe patient was also referred to surgical team for \ncolonoscopy but it was not performed due to the risk \nof bowel perforation.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38MJD 2013 Dec Vol 31\n\n\n\nFigure 1  Perianal ulceration covered by mucopurulent \ndischarge.\n\n\n\nFigure 3  Skin Biopsy showed granulomatous lesion with \nLanghan\u2019s type multinucleated giant cell.\n\n\n\nFigure 2  Complete resolution of perianal ulceration \nfollowing two months intensive phase of anti-tuberculous \ntherapy.\n\n\n\nFigure 4  Ziehl Neelson stain showed abundant of acid \nfast bacilli within the tissue.\n\n\n\nThese findings established a diagnosis of perianal \ntuberculosis. He was started on antituberculosis \ndrug with Isoniazid 300mg od, Rifampicin 600mg \nod, Pyrazinamide 150mg od and Ethambutol \n1200mg od. The patient showed a tremendous \nimprovement with antituberculous therapy. The \nperianal ulcer completely healed following two \n\n\n\nmonths of intensive anti-tuberculous treatment                                                      \n(Figure 2). There was also significan improvement \nof lung radiological findings. He is currently on \nmaintenance phase of antituberculous therapy with \nIsoniazid and Rifampicin. There was no relapse \nof lesion and he is planned for a total of 1 year \nantituberculous therapy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n39 MJD 2013 Dec Vol 31\n\n\n\nDiscussion\nTuberculosis is a major health problem worldwide. \nAlthough there was a significant decrease in \nmorbidity and mortality of tuberculosis due to \ndevelopment of antituberculosis therapy, the number \nof cases of tuberculosis has increased in recent years \nin Malaysia due to rising number of AIDS cases and \nthe increased of immigrants from countries that \nhave a higher prevalence of tuberculosis. \n\n\n\nExtra-pulmonary tuberculosis is responsible for \n15% of all cases of tuberculosis. Extra-pulmonary \nspread were to the pleura (26%), lymph nodes \n(17%), genitourinary tract (15%), bones and joints \n(14%), meninges (6%), peritoneum (4%), miliary TB \n(8%) and  gastrointestinal tract (1%)3. Periorificial \ntuberculosis is a rare form of extra-pulmonary \ntuberculosis and is clinically characterized by \nulcerative lesions affecting oral, genital, or anal \nmucosa and surrounding cutaneous areas, as a \nresult of infectious spread from a primary focus \nin the respiratory, urinary, or gastrointestinal tracts \nrespectively4. Perianal tuberculosis is an uncommon \nmanifestation of periorificial tuberculosis which \ncomprises less than 10% of all perianal diseases and \n0.7% of all tuberculosis cases5. This condition is \nmore frequently seen in men than women (4:1 ratio) \nand more commonly occurs in the 4th decade of life6. \nThe most widely accepted mechanism for perianal \ntuberculosis is that skin lesions are a consequence of \nautoinoculation from swallowed sputum containing \nbacilli that cause secondary digestive lesion4. Other \nmechanism through lymphatic, haematogenous or \ndirect spread from neighboring organs are rare1. \nPerianal tuberculosis has also been reported without \nany presence of gastrointestinal or pulmonary \ntuberculosis7. \n\n\n\nPerianal tuberculosis may manifest as an ulcerative, \nverrucous, lupoid, military and fissure form1,2. The \nmost common type is the ulcerative lesion which \ntends to be painful with well-defined, undermined \nboundaries and covered by mucopurulent discharge \nor pseudomembranous material1,2. The verrucous \ntype tends to extend into the anal passage from \nthe perianal region with a development pattern \nsimilar to that of a wart3. However, it may appear \nas a haemorrhoidal nodule, perianal abscess or \nanal fistula5. In our case, the patient presented \n\n\n\nwith persistent perianal ulceration as his initial \nmanifestation of tuberculosis. Even though his chest \nx ray showed significant radiological changes, he did \nnot show any symptoms of pulmonary tuberculosis. \nIn addition to that, his sputum for Acid fast Bacilli was \nalso negative  and this may be due to poor specimen \ncollection as the patient was totally asymptomatic \nfor pulmonary tuberculosis. We believe he may have \nacquired pulmonary tuberculosis initially and then \ndue to the long duration of untreated pulmonary \ntuberculosis, tuberculosis bacilli could have \ndisseminated to the perianal region via ingestion of \ncontaminated sputum or autoinoculation.\n\n\n\nDiagnosis of perianal tuberculosis is difficult                   \nand needs a high index of suspicion, especially \nin patients with perianal involvement as the first \npresentation of tuberculosis. The diagnosis of \nperianal tuberculosis is made based on at least \none of the following criteria: (i) positive acid-\nfast bacilli (AFB) stain from the tissue biopsies; \n(ii) histopathological demonstration of typically \ncaseating granulomatous necrosis; (iii) positive \npolymerase chain reaction (PCR) for M. tuberculosis \non tissue specimen and ( iv) tissue biopsy culture \npositive for  M. tuberculosis8. The diagnosis is \nfurther supported by the clinical response to anti-\ntuberculosis therapy.\n\n\n\nDifferential diagnosis of perianal tuberculosis           \nthat should be considered are Crohn\u2019s disease, \nulcerative colitis, pyoderma gangrenosum, syphilis, \nlymphogranuloma venereum, granuloma inguinale, \nchancroid, leishmaniasis, deep mycoses, amoebiasis \nherpes, HSV, CMV, HIV, varicella zoster virus, \nCryptococcus neoformans, Mycobacterium avium/ \nintracellulare, sarcoidosis and neoplasias5. \n\n\n\nPerianal tuberculosis required antituberculosis \ntherapy for at least 6 to 12 months8. Those \npatients with complicated fistulae will need longer \nantituberculosis therapy for 9 to 18 months8. \nPrognosis is usually good if this condition is \nrecognized early. Complete remission of the perianal \nlesion is achieved with intensive antituberculosis \ndrugs. Our patient showed complete recovery of \nperianal ulceration after 2 months of intensive \nantituberculosis therapy and he was planned to \ncomplete 1 year antituberculous therapy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40MJD 2013 Dec Vol 31\n\n\n\nConclusion\nPerianal tuberculosis is an extremely rare aetiological \ncause in patients with perianal discharge and \nulceration. Perianal tuberculosis should be kept in \nmind for all patients with any intractable perianal \nlesion as diagnosis based on the clinical picture is \noften difficult. Diagnosis is even more difficult to \n\n\n\nmake when there is no previous or active pulmonary \ninfection. Histopathological and microbiological \ninvestigations are mandatory in order to confirm \nthis condition since treatment with antituberculosis \nregime provides complete recovery. Diagnosis \nof perianal tuberculosis requires high index of \nsuspicion and early recognition will improve the \noutcome of the disease.\n\n\n\nReferences\n\n\n\n1. Ljubka Miteva, Emil Bardarov. Perianal Tuberculosis: A \nRare Case of Skin Ulceration? A case report. Acta Derm \nVenereol. 2002;82(6):481-2.\n\n\n\n2. Se Rim Choi, Jin Ki Kim, Dong Hyun Kim, Moon Soo \nYoon, et al. A Case of Tuberculosis Cutis Orificialis \nwith Perianal Involvement. Case report. Ann Dermatol. \n2009;21(4):443-446.\n\n\n\n3. E. Akgun, F. Tekin, S. Ersin, H. Osmanoglu et al.  Isolated \nperianal tuberculosis. Netherlands. J  Med.2005; 63(3): \n115-117.\n\n\n\n4. G. Monsel a, V. Martinez a, H. Izzedine b, B. Moryc, F. \nBricaire a, E. Caumesa et al. Anal tuberculosis complicated \nby secondary amyloidosis. A case report. M\u00e9decine et \nmaladies infectieuses 2011;41:264\u2013266.\n\n\n\n5. P. Tabarsi, D. Mansouri, O Edrissian, A. Alaei, M. Amiri, \nS. M. Mirsaeidi et al. Perianal tuberculosis in an HIV-\npositive patient. Eastern Mediterranean Health Journal. \n2006;12(6):923-926.\n\n\n\n6. Soniya Mathew. Anal tuberculosis: Report of a case and \nreview of literature. International Journal of Surgery \n2008;6:36-39. \n\n\n\n7. Guzin Ozarmagan, Sinem Keles, K Didem Yazganoglu, \nNecmettin Sokucu et al.  Delayed diagnosis in a case of \nperianal tuberculosis. Differential diagnosis in perianal \nulceration. Indian J Dermatol. 2010;55(3):309\u2013310.\n\n\n\n8. Tai WC, Hu TH, Lee CH  et al.  Ano-perianal tuberculosis: \n15 years of clinical experiences in Southern Taiwan. \nColorectal Disease 2009;12:114-120.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n41 MJD 2013 Dec Vol 31\n\n\n\nObituary\n\n\n\nProfessor Unandar Budimulja\nMD, SpKK, Ph.D, FAADV\n\n\n\n12 August 1930 - 2nd April 2013\n\n\n\nProfessor Unandar Budimulja\npassed away peacefully on Tuesday,\nApril 2, 2013 at 10.35 pm. \n\n\n\nHe had dedicated himself selflessly to the  \ndevelopment of dermatology in Indonesia and the \nregion. His efforts as a founder council member of the \nLeague of Asean Dermatological Societies resulted \nin the signing of the Bali Declaration of LADS in \n1984. As the Founder President, his support and \nguidance was instrumental in the formation of the \nAsian Academy of Dermatology and Venereology \nin 2009. \n\n\n\nHis involvement and love for teaching spanned \nmany decades since 1962 and he was the Professor \nof Dermato-Venereology, University of Indonesia \nsince 1991. He was a great leader in clinical \ndermatology and was a constant figure in all the \nRegional Conferences of Dermatology (Asian-\nAustralasian) since its inception in 1974. His \npassion for medical mycology as the Founder \nand Chairman of Indonesian Medical & Animal \nMycology Organization was truly legendary. He \ncontinued to serve as the Advisor of the Indonesian \nMedical Human & Animal Mycology Organization \nsince 1996 and Chairman of the Study Group of \nDermatomycosis Indonesia Perdoski. \n\n\n\nProfessor Unandar was steadfast in the advocacy \nof high standards in postgraduate dermatologic \ntraining in his capacity as the Promoter, Examiner \nand Assessor of the Faculty of Medicine, University \nof Indonesia and several other universities in \nIndonesia since 1986. \n\n\n\nHe served on the Editorial Board of Media Dermato-\nVenereology Indonesia and the International Editorial \nAdvisory Board of the Asian Dermatological News \nand the Indian Journal of Dermatology. He was \nthe Peer Reviewer of the Indonesian Journal of \nPharmacology and Therapeutics. \n\n\n\nIn recognition of his achievements he had received \nnumerous awards including the Satya Lencana \nKarya Satya Nasional Medal from the President \nof the Republic of Indonesia in 1990, Lencana \nAdi Satya Utama Medal from Indonesian Doctors \nAssociation in 1997 and the Lencana Satya Bakti \nWira Krida Medal from Perdoski in 1999.\n \nIn his passing, our dermatology fraternities in Asia \nhave lost an illustrious figure and a friend. He leaves \nbehind a beloved wife and three children and three \ngrandchildren.\n\n\n\nSteven Chow\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42MJD 2013 Dec Vol 31\n\n\n\nObituary\n\n\n\nDr. Sivasundram s/o Kathirgamu Alagar\n1939 - 17th March 2013\n\n\n\nDr Sivasundram s/o Kathirgamu Alagar was born in Kuala \nPilah, Negeri Sembilan in 1939 and studied medicine at \nthe University of Ceylon where he qualified in 1965.\n\n\n\nDr. Siva returned to Malaysia in January 1966 after his \nhousemenship and served as a medical officer in General \nHospitals in the states of Selangor and Kelantan. In 1975 \nhe went on to train in dermatology at St John\u2019s Hospital for \ndiseases of the skin in London. On his return he worked \nin Kota Bharu, Kelantan and later in the dermatology \ndepartment in Hospital Besar Kuala Lumpur where he \nwas gazetted as a Consultant Dermatologist in 1985.\n\n\n\nDr. Siva was then posted to Hospital Tengku Ampuan \nRahimah in Klang, Selangor in 1985. He was the Head \nand Senior Consultant Dermatologist in Klang Hospital \nfrom 1985 till March 2004. In Klang, he worked zealously \nand aided by Dr Saras a senior doctor in the department, \nwent on to establish dermatological services for the state \nof Selangor. As the only State Dermatologist in Selangor \n(before the opening of Selayang Hospital), despite his \nbusy schedule in his Department, without fail he used \nto visit other district hospitals on a monthly basis in \nSelangor, such as in Banting, Kajang, Tanjung Karang \nand Kuala Kubu Baru. \n\n\n\nDr. Siva dedicated his whole working life to the service of \nhis patients, especially those less fortunate. Throughout \nhis years of service, he treated his patients to the best of \nhis ability and knowledge. He has been noted to be kind, \ncaring, friendly and sympathetic  to his patients.\n\n\n\nTo the junior doctors who worked and were trained by \nhim, he was regarded as a good mentor, gentle, kind, \nhelpful, easily approachable, knowledgeable, and willing \nto teach and share his knowledge and ideas and was like \na father-figure.\n\n\n\nHe got along well with his Department staff and worked \ntogether as a team. He contributed immensely to the \norganization and development of his Department and \npaid special attention to the career prospects of his staff. \nHe was found to be very friendly with a good sense of \nhumour well loved by all. He had a good rapport with \nother departments in the hospital and worked along well \nwith their consultants.\n \nHe had a special interest in dermatological therapeutics \nand regularly attended the PDM meetings to keep abreast \nof the recent advances in dermatology.\n\n\n\nHe retired in 2004 and subsequently served as a visiting \nConsultant Dermatologist in Klang Hospital on a part \ntime basis till 2006. After retiring from Government \nService in 2006, he entered private practice and served as \na visiting Consultant Dermatologist in K.P.J (Shah Alam) \n& Pantai Hospital Klang.\n\n\n\nDr Sivasundram suffered a stroke in 2012 and became \nbed bound and passed away peacefully after a period of \n10 months.\n\n\n\n He leaves behind his loving and devoted wife Pathmavathy \nd/o Selvadurai, a retired secondary school teacher, all his \nsiblings and a host of relatives and close friends. \n \nDato\u2019 Dr SK Ratti, Dr. Gangaram Hemandas and\nDr. Saraswathy\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n43 MJD 2013 Dec Vol 31\n\n\n\nWelcome to the\n23rd WORLD CONGRESS\n\n\n\nOF DERMATOLOGY\n\n\n\nIMPORTANT DATES\n\n\n\nOnline Abstract Submission Opens\nJanuary 15, 2014\n\n\n\nEarly Bird Registration Fee Deadline\nJanuary 31, 2014\n\n\n\nWebsite: http://derm2015.org\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44MJD 2013 Dec Vol 31\n\n\n\nRCD\n2014\n\n\n\nIMPORTANT DATES\n\n\n\nEarly\nRegistration \n\n\n\n31st October 2013\n\n\n\nAbstract\nSubmission \n\n\n\n31st October 2013\n\n\n\nCongress Administration \nG-1, Medical Academies of Malaysia, 210, Jalan Tun Razak, 50400 Kuala Lumpur, Malaysia \n\n\n\nTel: +603 4023 4700, +603 4025 4700, +603 4025 3700     Fax: +603 4023 8100 \nEmail: secretariat@asianderm.org\n\n\n\n\n\n\n\n\nDERMATOLOGY THERAPEUTIC\n\n\n\n Original Article\n1 Adherence to topical medication\n is poor among patients with atopic  \n eczema\n Mazlin MB, Aniza I, Jong Yi F et al\n\n\n\nGENERAL DERMATOLOGY \n\n\n\n Original Article\n8 Lichen planus and hepatitis C \n infection: Exploring the association \n among Malaysian patients\n Norazirah MN, Mazlin MB,\n Adawiyah et al\n\n\n\n13 Pattern of allergic contact \n dermatitis in school children in \n Selayang Hospital, Malaysia\n Sharifah Rosniza SNC, Rohna R,\n Kasmawati T et al\n\n\n\n Case Report\n19 Trigeminal trophic syndrome.\n A case report and literature review \n Esther A, Tang JJ, Norain K\n\n\n\n22 Nevus of Ota: presentation of a case \n with oral pigmentation and codicil \n to Tanino\u2019s classification \n Srikanth H Srivathsa\n\n\n\n26 Classic Dermatomyositis following \n breast cancer: A case report \n Chee YC, Choon SE\n\n\n\nDERMATOLOGY INFECTION\n\n\n\n Review Article\n30 Clinical characteristics of patients \n with leprosy in Hospital\n Kuala Lumpur\n Tarita T, Roshidah B\n  \n Case Report\n37 Perianal tuberculosis:\n A case report and literature review\n Selvarani S, Tang JJ, Norain K\n\n\n\n OBITUARY\n\n\n\n41 Professor Unandar Budimulja\n\n\n\n42 Dr. Siva s/o Kathirgamu Alagar\n\n\n\n CONTINUOUS MEDICAL EDUCATION\n\n\n\n43 Regional Conference of Dermatology 2014\n & 6th Asian Academy of Dermatology and\n Venereology Meeting\n\n\n\n44 23rd World Congress of Dermatology 2015\n\n\n\nContents\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\n\n"
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"\n\nVolume 25   |  Dec 2010   |  ISSN: 1511-5356\n\n\n\nwww.dermatology.org.my\n\n\n\nDermatology\nM a l a y s i a n  J o u r n a l  o f\n\n\n\nJ U R N A L  D E R M A T O L O G I  M A L A Y S I A\n\n\n\nPERSATUAN DERMATOLOGI  MALAYSIA    DERMATOLOGICAL SOCIETY OF MALAYSIA\n\n\n\n\n\n\n\n\nMJD 2010 December Vol 25\n\n\n\nMethotrexate in Psoriasis\n- local patients\u2019 response \n\n\n\nManaging persistent\nENL with high dose\nchlofazimine\n\n\n\nFusarium infection in\nAcute Lymphoblastic\nLeukaemia\n\n\n\nCosmesis for infantile\nhaemangiomas\n\n\n\nTest your diagnostic skill\n\n\n\n1\n\n\n\n7\n\n\n\n1 0\n\n\n\n1 5\n\n\n\n3 6\n\n\n\nH i g h l i g h t s\n\n\n\n42  Erythroderma in newborn\n\n\n\n31  Facial ulcer\n\n\n\n26  Leg deformity in a child\n\n\n\n36  Umbilicated papule 36  Angioedema with dera m t i t i s\n\n\n\n\n\n\n\n\nMJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nEditor-in-Chief (Administrative)\nRohna Ridzwan, MRCP\nEmail : rohnaridzwan@yahoo.com\n\n\n\nEditorial Office\nMalaysian Dermatological Society \nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJln 112 Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nAdvertisement Committee\nIndependent team members\n\n\n\nEditorial Board\nGangaram Hemandas, FRCP\n(Chief Editor) Kuala Lumpur\n\n\n\nHenry Foong Boon Bee, FRCP\nIpoh, Perak\n\n\n\nChan Lee Chin, MMed\nPenang\n\n\n\nAgnes Heng Yoke Hui, MRCP\nIpoh, Perak\n\n\n\nEditor Emeritus\nSuraiya Hani Hussein FRCP\nKuala Lumpur\n\n\n\nFounding Editor\nSteven Chow Kim Wing FRCPI\n\n\n\nExecutive Staff\n\n\n\nMardziah Alias, MMed (Paeds) - President\nKoh Chuan Keng, MRCP - Vice President\nHenry Foong Boon Bee, FRCP - Secretary\nNajeeb Ahmad Mohd Safdar, MRCP - Treasurer\nAgnes Heng Yoke Hui, MRCP\nOng Cheng Leng, MRCP\nChan Lee Chin, MMed\nNoor Zalmy Azizan, MRCP\nRohna Ridzwan, MRCP\n\n\n\nDermatological Society of Malaysia\nRumah Dermatolgy\n2-16, 16th Floor, Blk 2 (Remis)\nPantai Panorama Condominium\nJalan 112, Off Kerinchi\n59200 Kuala Lumpur, Malaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Cetak Sri Jaya, Jalan Ambong Kanan 3, Kepong Baru, 52100 Kuala Lumpur, Malaysia.\n\n\n\n\u00ae2010 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nThe inclusion of an advertisement in MJD is not to be construed or publicized as an endorsement or\napproval by the Society of any product, service, or company; nor may the advertiser represent that its\nadvertising claims have been approved or endorsed by the Society.\n\n\n\n\n\n\n\n\ni MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nNotice to Au t h o rs\n\n\n\nThe Malaysian Journal of Dermatology welcomes manuscripts\non all aspects of cutaneous medicine and surg e ry in the form of\noriginal articles, research papers, case reports and\nc o rrespondence.  Contributions are accepted for publication on\ncondition that they are submitted ex c l u s ive ly to the Malay s i a n\nJ o u rnal of Derm a t o l og y. The Publisher and Editors cannot be\nheld responsible for errors or any consequences arising from the\nuse of information contained in this journal; the views and\nopinions expressed do not necessarily reflect those of the\np u blisher and Editors, neither does the publication of\na d ve rtisements constitute any endorsement by the publ i s h e r.\n\n\n\nManuscripts should be submitted via email:\nro h n a r i d z wa n @ ya h o o . c o m\n\n\n\nQuestions regarding the Malaysian Journal of Derm a t o l og y\ncan be sent to me at:\nro h n a r i d z wa n @ ya h o o . c o m\n\n\n\nC o n t r i butions should be written for one of the follow i n g\nc a t egories: \n\n\n\nCase Report *\nA report of 400-600 words, illustrated by no more than three\nillustrations. This categ o ry offers a means for rapid\ncommunication about a single subject. \n\n\n\nClinical Tr i a l\nAn article of 700-1200 words concerning a drug eva l u a t i o n .\nThis categ o ry provides rapid publications and is meant to be a\nsuccinct presentation with a minimum of graphs and tables. \n\n\n\nC o m m e n t a r y *\nAn editorial 700-1200 words in length with approx i m a t e ly five\nreferences. The author may express his or her opinion without\ncomplete documentation. \n\n\n\nC l i n i c o p a t h o l ogical Challenge\nA photographic essay that includes both clinical and\np a t h o l ogical photographs in color. The diagnosis and leg e n d s\nfor the photographs should be listed after the references in the\na rticle. The article should be no more than 2-3 pages in length. \n\n\n\nC o r re s p o n d e n c e *\nLetters to the editor and short notes. Contributions should not\nexceed 600 words, two figures, and 10 references. \n\n\n\nD e r m a t o l ogical Surgery \nAn article relating to the surgical aspects of treatment. A rt i c l e\ntypes may include Rev i ew, Report or Case Report Fo rmat. \n\n\n\nOriginal A rt i c l e\nAn original article including, wh e n ever possible, an\nIntroduction, Materials and Methods , Results, Comment, and\nReferences. A Structured Abstract of not more than 240 wo r d s\nmust be included. It should consist of four paragraphs, labelled\nB a c k gr o u n d, Methods, Results, and Conclusions. It should\ndescribe the problem studies, how the study was perform e d, the\nmain results, and what the author(s) concluded from the results. \n\n\n\nR ev i ew\nBy invitation only. A major didactic article that clarifies and\nsummarizes the existing knowledge in a particular field. It\nshould not be an ex h a u s t ive rev i ew of the literature, and\nreferences should not exceed 100 in number. Ta bles, diagr a m s ,\nand selected figures are often helpful. The length is left to the\njudgment of the author, although it generally should not ex c e e d\n5000 words. Topics may include updates in clinically releva n t\nbasic science and cutaneous biolog y. \n\n\n\n*No abstract required \n\n\n\nManuscripts should include a title page bearing the title of the\np a p e r, the author(s)' name(s), degrees, and affiliation(s), the\nc a t eg o ry of the article, the number of figures and tables, and\nthree key words for indexing purposes. The name and full postal\naddress (including a street address), phone and fax numbers and\nan email address of the corresponding author who will be\nr e s p o n s i ble for reading the proofs must also be given on the title\npage. The author(s) must also declare any affiliation or\ns i g n i ficant financial invo l vement in any organizations or entity\nwith a direct financial interest in the subject matter or materials\ndiscussed in the manuscript on this page. \n\n\n\nAll measurements should be according to the metric system. If\nconfusion could result, please include other measurement\nsystems in parentheses. \n\n\n\nRefer to patients by number or letters; names or initials should\nnot be used.\n\n\n\nReferences must be listed in the order in which they appear in\nthe manuscript. References from journals should include: (1)\nname(s) followed by the initials of the author(s), up to four\nauthors: if more than four authors, include the first three authors\nf o l l owed by et al.; (2) title of paper; (3) title of the journal as\na b b r eviated in the Index Medicus; (4) year of publication; (5)\nvolume number; (6) first and final page numbers of the article. \n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH.  Sporotrichosis: A\nHospital Kuala Lumpur experience. M J Dermatol 2006;19:52-\n5 5 .\n\n\n\nReferences to books should include: (1) author(s) or editor(s);\n(2) chapter (if any) book titles; (3) edition, volume, etc.; (4)\nplace of publication; (5) publisher; (6) year; (7) page(s) referr e d\nto. \n\n\n\nFor example:\nFoong HBB.  Transcontinental Derm a t o l ogy: Vi rtual Grand\nRounds. In: Wootton R and Oakley A, editors. Te l e d e rm a t o l og y.\nLondon. Royal Society of Medicine 2002. p.127-134.\n\n\n\nThe author is responsible for the accuracy and completeness of\nall references; incomplete references may result in a delay to\np u blication. \n\n\n\nTa bles should be typed, double-spaced with a heading, each on\na separate sheet, and should only include essential inform a t i o n .\nD r awings, graphs, and formulas should be submitted on\nseparate pages. \n\n\n\nSend illustrations as tiff or jpeg files. In the case of\np h o t o m i c r ographs, the stain type and original magnifi c a t i o n\nshould be stated. Each figure should bear a reference number\nc o rresponding to a similar number in the tex t .\n\n\n\nTo minimise the publication time of your manuscript it is\ni m p o rtant that all electronic art work is supplied to the Editorial\nO ffice in the correct format and resolution. \n\n\n\nD i s c l a i m e r\nThe Publisher and Editors cannot be held responsible for err o r s\nor any consequences arising from the use of inform a t i o n\ncontained in this journal; the views and opinions expressed do\nnot necessarily reflect those of the publisher and Editors, neither\ndoes the publication of adve rtisements constitute any\nendorsement by the publisher and Editors of the products\na d ve rt i s e d .\n\n\n\n\n\n\n\n\niiMJD 2010 December Vol 25\n\n\n\nJ U R NAL DERMATOLOGI MALAY S I A\n\n\n\nVOLUME 25  |  DECEMBER 2010  |  ISSN: 1511-5356\n\n\n\nC o n t e n t s\n\n\n\nDERMATOLOGY THERAPEUTICS\n\n\n\nOriginal Article\n1 Local Experience on the use of \n\n\n\nmethotrexate in the treatment of psoriasis \nin Hospital Sultanah Aminah,\nJohor Bahru\nChong YT, MRCP, Tey KE, MRCP, Choon SE, FRCP\n\n\n\nCase Reports\n7 Treatment of erythema nodosum \n\n\n\nleprosum with high-dosed clofazimine in \npatients with lepromatous leprosy   \nOng ML, MRCP, Rohna R, MRCP\n\n\n\n10 Fusarium cutaneous infection in a \nneutropenic girl with acute lymphoblastic \nleukaemia\nPan JY, Ker KJ, Audrey T\n\n\n\nDERMATOSURGERY\n\n\n\nOriginal Article\n15 Treatment of infantile haemangiomas\n\n\n\nwith 585 nm pulse dye laser\nSabeera B, MMED (Paeds),\n\n\n\nMardziah A, MMED(Paeds), Gangaram HB, FRCP\n\n\n\nGENERAL DERMATOLOGY\n\n\n\nCase Reports\n21 Churg Strauss Syndrome in a 40 year old \n\n\n\nwoman\nTan SS, Chan LC, Tan WC\n\n\n\n25 Childhood disabling pansclerotic \nmorphoea complicated by leg ulcers,\ncontractures and gangrene\nPan JY, FAMS, Ker KJ, MBBS, Tang MBY, FAMS\n\n\n\n31 Wegener\u2019s granulomatosis: a case report\nand literature review\nTang JJ, Tang MM, Lee BR\n\n\n\nSelf Assessment\n36 3rd Diagnostic clinical skill test for \n\n\n\nprimary care providers\nRR\n\n\n\nPAEDIATRIC DERMATOLOGY\n\n\n\nOriginal Article\n38 A study of the cause and prognosis of \n\n\n\nchronic urticaria in Malaysian children\nSabeera B, MMED(Paeds), Asmah J MMED,\n\n\n\nMardziah A MMED (Paeds)\n\n\n\nShort Communication\n42 Netherton Syndrome presenting with \n\n\n\nerythroderma in newborn\nRaoul RS, MBBS, Muzhirah AH, MRCPCH,\n\n\n\nSuhaila O, MRCPCH, Rohna R, MRCP\n\n\n\nNetherton Syndrome presenting with \nerythroderma in newborn\nRaoul RS, MBBS, Muzhirah AH, MRCPCH,\n\n\n\nSuhaila O, MRCPCH, Rohna R, MRCP\n\n\n\nM a l aysian Journal of  Dermatology\n\n\n\n\n\n\n\n\niii MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nA N N O U N C E M E N T\nContinuous Professional Development\n\n\n\n22nd World Congress of Derm a t o l o g y\n\n\n\nOrganizers : International Leagues of Dermatological Societies \n(ILDS) with the support of the Korean Dermatological \nAssociation (KDA)\n\n\n\nTheme : Connecting the World Through Innovative Dermatology \n\n\n\nVenue : Seoul, Korea \n\n\n\nDate : 24 - 29 May 2011\n\n\n\nProgram : website: www.wcd2011.org\n\n\n\nAbstract submission deadlines for Free papers: 31 October 2010\n\n\n\n\n\n\n\n\n1MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nD E R M ATOLOGY THERAPEUTICS - Original Art i c l e\n\n\n\nLocal experience on the use of Methotrexate in the\nt reatment of Psoriasis in Hospital Sultanah Aminah,\nJohor Bahru                                                               \nChong YT1, MRCP, Tey KE2, MRCP, Choon SE2, FRCP\n\n\n\nAbstract\n\n\n\nIntroduction The efficacy of methotrexate in the treatment of psoriasis is well established. However,\nhigh-quality data concerning its efficacy and side effects are sparse. The initial administration dose\ndiffers among various centres. In Hospital Sultanah Aminah, Johor Bahru, methotrexate is initiated\nat a starting dose of 0.3mg/kg body weight weekly and is continued until significant clinical\nresponse before being tapered to the lowest maintenance dose.\n\n\n\nThe aim of this study is to determine the profile of our local psoriasis patients treated with\nmethotrexate, their response to treatment, their tolerability and the side-effects experienced.\n\n\n\nMethods This is a retrospective study of all patients who were on methotrexate from January 2005\nto December 2008 at the Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru.\n\n\n\nResults Out of a total of 128 patients, 111 were started on an initial dose of methotrexate of between\n15mg/week to 25mg/week. The mean age was 43 years old. 56.8% (63) were males and 43.2% (48)\nfemales. The mean body weight was 66 kg, ranging from 39 kg to 103 kg. Methotrexate was\nindicated for moderate to severe psoriasis in 77.5% (86), psoriatic arthropathy in 7.2% (8) and 15.3%\n(17) for both indications. Methotrexate was started as a first line in 57.7% (64) of patients, whereas,\n19.8% (22) had received phototherapy, 14.4% (16) acitretin and 7.2% (8)  cyclosporine in the past\nprior to being given methotrexate. Good response was noted in 79.3%, (88) of patients, 17.7% (19)\nmoderate and 2.7% (3) had a poor response. Side-effects were noted in 19.8% (22) of patients within\nthe first 6 months, 12.6% (14) due to raised liver enzymes, 3.6% (4) to bone marrow suppression,\n2.7% (3) to gastro-intestinal symptoms and 0.9% (1) to central nervous system symptoms.\nMethotrexate was stopped due to adverse events in 15.3% (17) of patients.\n\n\n\nConclusion Methotrexate is effective in the treatment of psoriasis but is limited by side effects,\nespecially raised liver enzymes. However, most of the side effects are mild and reversible on\nstopping the drug.\n\n\n\nKeywords Methotrexate, psoriasis, side effects\n\n\n\nCorrespondence\nChong Yew Thong\nDepartment of Dermatology\nHospital Kuala Lumpur\n50586 Kuala Lumpur Malaysia\nE-mail : cytusm@yahoo.com\n\n\n\n1D e p a rtment of Derm a t o l og y, Hospital Kuala Lumpur\n2D e p a rtment of Derm a t o l og y, Hospital Sultanah A m i n a h ,\nJohor Bahru\n\n\n\nIntroduction\nMethotrexate has been used for the treatment of\npsoriasis for the past 50 years. Its use predates the\nage of randomized clinical trials. Recommended\nstarting dose used to be between 0.2-0.4 mg/kg\nbody we i g h t2 2. Howeve r, high-quality data\nconcerning its efficacy and side effects are sparse20.\nMost guidelines have recommended start i n g\nmethotrexate at doses of 5.0 to 7.5 mg/week, after a\ntest dose of 2.5-5.0 mg8,11. Nevertheless, differences\nwere reported among derm a t o l ogists in their\nprescribing and monitoring practices20, in particular\n\n\n\n\n\n\n\n\n2 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nthe dosing regimen, as well as a broad range of\nmaximum weekly doses from 5 to 70mg weekly. In\nHospital Sultanah Aminah, Johor Bharu ,\nm e t h o t r exate is initiated at a starting dose of\n0.3mg/kg body weight weekly. It is continued until\nsignificant clinical response before being tapered to\nthe lowest maintenance dose.\n\n\n\nThe aim of this study was to determine the\nd e m ographic profile of psoriasis patients, their\nresponse to methotrexate treatment, tolerability and\nthe side-effects experienced.\n\n\n\nMaterials and methods\nThis is a retrospective study of records from\npatients who were on methotrexate from January\n2005 to December 2008 at the Department of\nD e rm a t o l og y, Hospital Sultanah Aminah, Johor\nB a h ru. The diagnosis of psoriasis was made\nc l i n i c a l ly by the attending doctors. Inclusion\ncriteria included patients who were started on\nmethotrexate for a minimum duration of at least 4\nweeks. Pretreatment assessment of all patients\nincluded a full blood count, renal profile, liver\nenzymes, and serology screening for virus hepatitis\nB and C. Blood counts and liver enzymes were\nmonitored reg u l a r ly during follow up, initially\nevery week and then every two to six weeks.\nM e t h o t r exate was initiated in a single we e k ly\nintramuscular or oral dose of 0.3 mg per kg body\nweight, or a maximum dose of 25 mg. It was\ncontinued until there was clinical improvement of\nthe skin lesions and then tapered to the lowest\npossible maintenance dose. All the patients had\nfailed to respond to topical treatment before\ninitiation of methotrexate and during the treatment,\nthe topical medications were continued. In addition,\nfolic acid 5 mg once daily was prescribed to reduce\nthe possible side effects of methotrexate. Patients\nwho were started on an initial lower dose of\nmethotrexate or follow up duration of less than four\nweeks were excluded from the analysis.\n\n\n\nShort-term response to treatment (within 6 months)\nwas assessed using the following criteria : \n\n\n\nGood: Defined as significant clinical response with\ncontinuation of treatment to the lowest maintenance\ndose within the first six months.\n\n\n\nModerate: Defined as initial clinical response with\ntapering to maintenance dose, but had a flare-up\nrequiring increased dose within the first six months,\n\n\n\nor inability to taper to a lower dose from the initial\ndose.\n\n\n\nPo o r : D e fined as discontinuation of treatment\nwithin 6 months due to poor clinical response.\n\n\n\nSide effects of methotrexate, in particular any\nabnormality of the blood counts and liver enzymes\nwere noted. The severity of the adverse events were\ngraded as mild, if the side effect was tolerable\nwithout stopping the drug; moderate, if the drug\nwas stopped and the side effect recovered fully; and\nsevere, if the drug was stopped as well as needing\nhospitalization or permanent disability.\n\n\n\nThe data were analyzed using SPSS\u00ae Version 12.0.\n\n\n\nResults\nA total of 128 case records of patients on\nm e t h o t r exate was retrieve d, out of which, 111\npatients were started on an initial dose of\nm e t h o t r exate of between 15mg/week to\n25mg/week. Seventeen patients were excluded from\nthe analysis as 2 were started on an initial lower\ndose of methotrexate (7.5 mg/week) and 15  had\ndefaulted after being on methotrexate for less than\nfour weeks. \n\n\n\n63 (56.8%) were males and 48 (43.2%) females.\nThe mean age was 43 years old with a range of 16\nto 76 years old. The mean body weight was 66 kg,\nwith a range of 39  to 103 kg. The duration of\ndisease varied from less than a year to 44 years. Ten\npatients (9%) had a family history of psoriasis.\nMajority (92%) had plaque psoriasis while 32%\nhad arthritis. Concomitant diseases were present in\n40 (36%) patients. See Table 1.\n\n\n\nThe most common indications for methotrexate\nwere for moderate to severe psoriasis (more than\n10% body surface involvement) in 86 patients\n(77.5%), followed by psoriatic arthropathy in 8\npatients (7.2%) and for both in 17 patients (15.3%).\nMethotrexate was started as first line in 64 patients\n(57.7%), whereas, 22 (19.8%) had receive d\np h o t o t h e r a py, 16 (14.4%) acitretin, 15 (13.5%)\nmethotrexate, 8 (7.2%) cyclosporine and 4 (3.6%)\nsulphasalazine in the past before being give n\nmethotrexate. The initial starting dose ranged from\n15 mg/week to 25 mg/week and the  majority of\npatients (62.1%) were able to taper to a\nmaintenance dose of 10 mg/week or less. See\nTable 2.\n\n\n\n\n\n\n\n\n3MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nTable 1 Patient demographics and baseline clinical \ncharacteristics\n\n\n\nFigure 1 Clinical response\n\n\n\nCharacteristics\n\n\n\nAge\n01 - 20\n21 \u2013 39\n40 \u2013 59\n60 - 79\n\n\n\nSex\nMale\nFemale\n\n\n\nEthicity\nMalay\nChinese \nIndian\n\n\n\nAge of onset\n\n\n\nDuration of disease\n\n\n\nFamily History\nYes\nNo\n\n\n\nType of psoriasis\nPlaque \nPustular\nErythroderma\n\n\n\nArthritis\nYes\nNo\n\n\n\nConcomitant disease\nDiabetes mellitus\nHypertension\nIschaemic heart disease\nDyslipidaemia\n\n\n\nN=111\n\n\n\nMean = 43.8 + 13.2\nrange (16 -73)\n\n\n\n2 (2%)\n37 (33%)\n61 (55%)\n11 (10%)\n\n\n\n63 (57%)\n48 (43%)\n\n\n\n49 (44%)\n42 (38%)\n20 (18%)\n\n\n\nMean = 34 + 13, range (7 - 71)\n\n\n\nMean = 9.8 + 8.5, range (1 - 44)\n\n\n\n10 (9%)\n101 (91%)\n\n\n\n102 (91.9%)\n4 (3.6%)\n5 (4.5%)\n\n\n\n35 (32%)\n76 (68%)\n\n\n\n12 (10.8%)\n27 (24.3%)\n\n\n\n5 (4.5%)\n5 (4.5%)\n\n\n\nTable 2 Patients\u2019 treatment profile\n\n\n\nCharacteristics\n\n\n\nPrior treatment\nNone\nPhototherapy\nRetinoids\nMethotrexate\nSulphasalazine\nCyclosporin\n\n\n\nIndication for methotrexate\nModerate to severe psoriasis\nPsoriatic arthropathy\nBoth\n\n\n\nBody weight\n\n\n\nInitial dose\n25 mg/week\n20 mg/week\n15 mg/week\n\n\n\nMaintenance dose\n20 mg/week\n15 mg/week\n12.5 mg/week\n10 mg/week\n7.5 mg/week\n5 mg/week\n\n\n\nN=111\n\n\n\n64 (57.7%)\n22 (19.8%)\n16 (14.4%)\n15 (13.5%)\n\n\n\n4 (3.6%)\n8 (7.2%)\n\n\n\n86 (77.5%)\n8 (7.2%)\n\n\n\n17 (15.3%)\n\n\n\nMean 66 kg, range (39-103 kg)\n\n\n\n7 (6.3%)\n62 (55.9%)\n42 (37.8%)\n\n\n\n5 (4.5%)\n17 (15.3%)\n20 (18.0%)\n23 (20.7%)\n30 (27.0%)\n16 (14.4%)\n\n\n\nModerate\n20\n(18%)\n\n\n\nGood\n88\n(79%)\n\n\n\nPoor\n3\n(3%)\n\n\n\n\n\n\n\n\n4 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nA total of 88 (79.3%) patients were estimated to\nh ave a good response, while 19 (17.7%) had\nmoderate and 3 (2.7%) a poor response. See\nFigure 1. Adverse events, were seen in 22 (19.8%)\npatients within the first 6 months, of which, 14\n(12.6%) were due to raised liver enzymes, 4 (3.6%)\nto bone marrow suppression, 3 (2.7%) to gastro-\nintestinal symptoms and 1 (0.9%) to central\nnervous system symptoms. No serious event was\nr e p o rted. In 17 (15.3%) patients, methotrex a t e\ntreatment was terminated due to adverse events, 15\nbefore 6 months and 2 after. As of 31st May 2009,\n45 (40.5%) patients were still on methotrexate\ntreatment while 66 (50.5%) had stopped treatment\ndue to various reasons. See table 3.\n\n\n\nDiscussion and conclusion\nFor more than 50 years, ever since the discovery of\nthe beneficial effects of  folic acid antagonist\naminopterin by Gubner in 1951 and the\nintroduction of methotrexate treatment by\nEdmundson and Guy in 1958, the use of\nm e t h o t r exate in psoriasis has undergone few\nchanges with regards to its regimens and dosing23.\n\n\n\nThe initial schedule reported by Rees and co-\nworkers1 used methotrexate in small daily dose for\n\n\n\nabout seven days before restarting another course.\nVan Scott and co-workers2 recommended the use of\na large parenteral dose of methotrexate at an\naverage of 25 to 50 mg intramuscularly once\nwe e k ly, while Roenigk et al3 a d m i n i s t e r e d\nmethotrexate orally in slightly lower doses of 12.5\nto 20 mg weekly. In 1971, Weinstein and Frost\nintroduced a new schedule of administering\nmethotrexate orally in small doses of 2.5 to 7.5 mg\nat 12-hour intervals for a total of three doses at\nweekly intervals. It has the advantages of lower total\ndose per week and better tolerable toxicity4.\n\n\n\nThe first guidelines on methotrexate therapy for\npsoriasis were introduced in 19725 and have since\nbeen revised several times6,7,8. Despite this, variation\nin the schedules have been reported. Previously,  the\nstarting dose of methotrexate was in the higher\nrange (15mg to 25mg per week)9. Kumar et al10\n\n\n\nreported a protocol of initiating methotrexate at a\nfull therapeutic dose, and tapering when the disease\nwas controlled. Methotrexate was given in a single\nweekly oral dose ranging from 0.3 to 0.5 mg/kg,\nsubject to a maximum of 30 mg and then reduced\nby 2.5-5mg every fortnight once clearance of 90%\nor more had been achieved. \n\n\n\nThe American Academy of Dermatology8 and the\nBritish Association of Derm a t o l og y1 1 h ave\nrecommended a starting dose of 2.5 to 5.0 mg per\nweek with gradual increment up to clinical response\nor maximum dose of 30 mg per week.\n\n\n\nS i m i l a r ly, guidelines published by the\nD e rm a t o l ogical Society of Malay s i a1 2 a l s o\nrecommend the starting dose of 2.5 to 5.0 mg per\nweek with gradual increment of dose to maximum\n25 mg per week.\n\n\n\nIn Hospital Sultanah Aminah, Johor Bahru, it has\nbeen a standard practice that methotrex a t e\ntreatment is initiated at a starting dose of 0.3\nmg/body weight (maximum 25 mg) and gradually\ntapered to a maintenance dose according to clinical\nresponse.\n\n\n\nDespite the efficacy of methotrexate, good quality\ndesign studies are sparse. In a systemic review of\nfive systemic treatments for severe psoariasis, none\nof the studies  on methotrexate could be included\nm a i n ly because of the \u2018obsolete dosages and\noutdated dosing schemes used\u2019 which wa s\nconsidered too high13. In addition, many of the\npublished\n\n\n\nTable 3 Adverse events\n\n\n\nCharacteristics\n\n\n\nAdverse event within 6 months\nNone\nBone marrow suppression\nRaised liver enzymes\nGastro-intestinal symptoms\nHeadache\n\n\n\nSeverity\nMild\nModerate\nSevere\n\n\n\nReason for stopping\nAdverse event\nNo response\nRemission\nExceeded recommended cumulative dose\nDefault\nPatient\u2019s wish\nPlanned pregnancy\nStill on\n\n\n\nN=111\n\n\n\n89 (80.2%)\n4 (3.6%)\n\n\n\n14 (12.6%)\n3 (2.7%)\n1 (0.9%)\n\n\n\n7 (6.3%)\n15 (13.5%)\n0 (0%)\n\n\n\n17 (15.3%)\n10 (9%)\n12 (10.8%)\n2 (1.8%)\n\n\n\n20 (18%)\n4 (3.6%)\n1 (0.9%)\n\n\n\n45 (40.5%)\n\n\n\n\n\n\n\n\n5MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\npublished data were case series with inadequate\ndocumentation. In their sub-analysis of four studies\nthat partially satisfied the inclusion criteria, there\nwere a total of 99 patients treated, out of which, the\npercentages of patients with clearance and good,\nmoderate and poor responses were, respectively,\n51%, 65%, 23% and 12%.\n\n\n\nA number of randomized controlled studies\ni nvolving methotrexate published in the recent\nyears used different starting, maintenance and\nmaximum dosages in their protocols1 4 , 1 5 , 1 6. T h i s\nreflects non-standardized practices among the\nd e rm a t o l ogists worldwide despite the va r i o u s\nguidelines. Thus, the efficacy in achieving PASI 75\n(75% improvement in Psoriasis Area Scoring\nIndex) at 16 weeks ranged from 35% when the\nstarting dose was low (7.5mg/week)15, to 60% when\nthe starting dose was higher (15mg/week)14.\n\n\n\nIt is of particular note that Saurat et al15 reported the\nfirst doubl e - bl i n d, placebo-controlled study of\nmethotrexate versus adalimumab (a biologic). They\nused a starting dose of 7.5 mg/week for the first 2\nweeks, 10 mg/week for the next 2, 15 mg/week for\nthe next 4, and thereafter slow ly increased\ndepending on the response and toxicity. After 16\nweeks, the mean methotrexate dose was 19 mg.\nH oweve r, their primary end point of PASI 75\na c h i evement at 16 weeks was only 35.5% for\nmethotrexate, as compared to placebo (18.9%) and\nadalimumab (79.6%).\n\n\n\nOn the other hand, Heydendael et al14 compared\nmethotrexate to cyclosporine without a placebo\narm. There were 44 patients in methotrexate arm.\nMethotrexate was initiated at a dose of 15 mg/kg\nand after 4 weeks, only 4 patients had the dose\nfurther increased up to 22.5 mg/week. At 16 weeks,\n26 patients (60%) achieved PASI 75.  \n\n\n\nKumar et al10 in their short term methotrexate\ntherapy in psoriasis using higher starting dose and a\ntapering down regime reported an impressive 88%\nof patients achieving 75% improvement in 8.5+5.1\nweeks. Similar findings were documented in two\nother studies from India17,18, although the number of\npatients was small.\n\n\n\nWe were not able to document the efficacy of\nmethotrexate objectively in our patients as this was\na retrospective study and measuring of PASI score\nwas not done routinely. We estimated that if the\n\n\n\ninitial dose of methotrexate was tapered to a lower\nmaintenance dose, then the patients probably had\ngood response. This was noted in the majority of the\npatients (79%). Moderate response was taken as the\ninability of methotrexate dose to be lowered or if\nthe initial dose was lowe r e d, but patients had\ndeveloped flare within the first six months requiring\nthe need of increasing the maintenance dose. Only\nfew patients (3%) needed to stop methotrexate\ntreatment within six months due to failed response.\n\n\n\nIn terms of adverse events, our study revealed\nraised liver enzymes as the most common followed\nby abnormal blood counts, gastrointestinal and\nn e u r o l ogical symptoms. This is in contrast to\np r evious studies1 4 , 1 6 where ga s t r o i n t e s t i n a l\nsymptoms were the most common side effects. This\ncould probably be due to the fact that the\ngastrointestinal symptoms were mild and were not\nproperly documented. Fourteen patients (12.6%)\nhad raised liver enzyme with a mean ALT (alanine\namino transferase) level of 79 IU/L and the highest\nALT was 155 IU/L. Four patients did not stopped\ntreatment as their ALT level were less than 60 IU/L.\nFour patients had abnormal blood counts, 2 were\ndue to anaemia (haemoglobin of 8.2-9.3 gm/dl) and\n2  to leucopenia (white cell counts of 3.5-3.9 x 109).\nAll the blood abnormalities resolved on stopping\nmethotrexate. A 38-year-old man, with psoriasis of\n13 years duration, had taken methotrexate for 56\nweeks, with an accumulated dose of 445 mg. The\nresponse was good. However, the treatment was\nstopped due to nose bleed and was later diagnosed\nto have nasopharyngeal carcinoma.\n\n\n\nThirty patients (24%) dropped out of the treatment\nprogramme within the first 6 months with 15\npatients because of adverse events. In the 15\npatients who were excluded from analysis as they\nhad taken methotrexate for less than 4 weeks, none\nhad any abnormality of the blood counts or liver\nenzymes after the initiation of methotrex a t e .\nHeydendael et al14 reported a drop out rate of 29%,\nall due to raised liver enzymes. It should be noted\nthat folic acid supplementation was not give n .\nHowever, in the Indian series, most of the patients\ntolerated the regime well with only a small drop out\nrate. In contrast, two other studies which started\nwith a low dose15,16, had a low drop out rate. See\nTable 4.\n\n\n\nThe limitations of the current report are the\nretrospective nature of the study as well as the\ninadequacy\n\n\n\n\n\n\n\n\n6 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\ninadequacy of an objective clinical assessment (e.g.\nPASI 75) and documented side effects. Future\nstudies should adopt a well-designed protocol to\nlook into the different regimes of start i n g\nm e t h o t r exate in respect to its effi c a cy and\nt o l e r a b i l i t y, using standardized assessment\noutcomes, for example Psoriasis Area and Severity\nIndex (PASI) and quality of life scores19.\n\n\n\nConclusion\nM e t h o t r exate is eff e c t ive in the treatment of\npsoriasis but has side effects, especially raised liver\nenzymes. However, most of the side effects are mild\nand reversible on stopping the drug. Proper patient\nselection and appropriate monitoring is crucial in\norder to minimize the toxic effects of methotrexate\n\n\n\nReferences\n\n\n\n1. Rees RB, Bennet JH, Maibach HI, et al: Methotrexate\nfor psoriasis. Arch Dermatol 1967; 95:2-11.\n\n\n\n2. Van Scott EJ, Auerbach R, Weinstein GD: Parenteral\nm e t h o t r exate in psoriasis. Arch Dermatol 1964;\n89:550-556.\n\n\n\n3. Roenigk HH, Fow l e r- B e rgfeld W, Curtis GH.\nMethotrexate for psoriasis in weekly oral dose. Arch\nDermatol 1969; 99:86-93.\n\n\n\n4. Weinstein GD, Frost P. Methotrexate for psoriasis. Arch\nDermatol 1971;103:33-38.\n\n\n\n5. Roenigk HH Jr, Maibach HI, Weinstein GD.\nGuildelines on methotrexate therapy for psoriasis. Arch\nDermatol 1972; 105:363-365.\n\n\n\n6. Roenigk HH Jr, Auerbach R, Maibach HI, Weinstein\nG D. Methotrexate guidelines-revised. J Am A c a d\nDermatol 1982; 6:145-155.\n\n\n\n7. Roenigk HH Jr, Auerbach R, Maibach HI, Weinstein\nGD. Methotrexate in psoriasis: revised guidelines. J Am\nAcad Dermatol 1988; 19:145-156.\n\n\n\n8. Roenigk HH Jr, Auerbach R, Maibach H, Weinstein G,\nL e b wohl M. Methotrexate in psoriasis: Consensus\nconference. J Am Acad Dermatol 1998; 38:478-485.\n\n\n\n9. Haustein UF, Rytter M. Methotrexate in psoriasis: 26\nyears\u2019 experience with low-dose long-term treatment. J\nEur Acad Dermatol Venereol 2000; 349:658-65.\n\n\n\n10. Kumar B, Saraswat A, Kaur I. Short-term methotrexate\ntherapy in psoriasis: a study of 197 patients. Int J\nDermatol 2002; 41:444-448.\n\n\n\n11. Chakravarty K, McDonald H, Pullar T, Taggart A,\nChalmers R, Oliver S, Mooney J, Somerville M,\nBosworth A. BSR & BHPR guideline for disease-\nmodying anti-rheumatic drug therapy (DMARD) in\nconsultation with the British Association of\nDermatologists. Rheum 2006; 1-18. (? Volume)\n\n\n\n12. D e rm a t o l ogical Society of Malaysia. Consensus\nStatement on the Management of Psoriasis 1996.\n\n\n\n13. Spuls PI, Witkamp L, Bossuyt PM et al. A systematic\nreview of five systemic treatments for severe psoriasis.\nBr J Dermatol 1997; 137:943-949.\n\n\n\n14. H eydendael VMR, Spuls PI, Opmeer BC et al.\nM e t h o t r exate versus cyclosporine in moderate-to-\nsevere chronic plaque psoriasis. N Engl J Med 2003;\n349:658-65.\n\n\n\n15. Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG,\nOrtonne JP, Unnebrink K, Kaul M, Camez A. Efficacy\nand safety results from the randomized controlled\ncomparative study of adalimumab vs. methotrexate vs.\nplacebo in patients with psoriasis (CHAMPION). Br J\nDermatol 2007; 158:558-566.\n\n\n\n16. Flystrom I, Stenberg B, Svensson A, Bergbrant IM.\nMethotrexate vs. ciclosporin in psoriasis: effectiveness,\nquality of life and safety. A randomized controlled trial.\nBr J Dermatol 2008; 158:116-121.\n\n\n\n17. Sandhu K, Kaur I, Kumar b, Saraswat A. Efficacy of\ncyclosporine versus methotrexate in severe psoriasis: a\nstudy from North India. J Dermatol 2003; 30:458-63.\n\n\n\n18. Kaur I, Dogra S, De D, Kanwar A J. Systemic\nmethotrexate treatment in childhood psoriasis: further\nexperience in 24 children from India. Pediatr Dermatol\n2008, 25:184-188.\n\n\n\n19. Harries MJ, Butterworth A, Griffiths CEM, Chalmers\nRJG. Methotrexate for psoriasis. (Protocol) Cochrane\nDatabase of Systematic Reviews 2005, Issue 2. Art.\nNo.: CD005204. DOI:10.1002/14651858.CD005204.\n\n\n\n20. Kalb RE, Strober B, Weinstein G, Lebwohl M.\nMethotrexate and psoriasis: 2009 National Psoriasis\nFoundation Consensus Conference. J Am A c a d\nDermatol 2009; 60:824-837.\n\n\n\n21. Collin B, Srinathan SK, Finch TM. Methotrex a t e :\nprescribing and monitoring practices among the\nconsultant membership of the British Association of\nDermatologists. Br J Dermatol 2008; 158:793-800.\n\n\n\n22. Burns T, Breathnach S, Cox N, Griffiths C. Rook\u2019s\nTextbook of Dermatology. 4th ed. 1986, pg 1500.\n\n\n\n23. Kuijpers AL, van de Kerkhof PC. Risk-Benefi t\nAssessment of Methotrexate in the Treatment of Severe\nPsoriasis. Am J Clin Dermatol 2000; 1:27-39.\n\n\n\n\n\n\n\n\n7MJD 2010 December Vol 25\n\n\n\nD E R M ATOLOGY THERAPEUTICS - Case Report\n\n\n\nTreatment of Erythema Nodosum Leprosum (ENL) with\nhigh-dose Clofazimine in patients with Lepro m a t o u s\nL e p ro s y\nOng ML, MRCP, Rohna R, MRCP\n\n\n\nCorrespondence\nOng May Lea, MRCP\nDepartment of Dermatology \nSelayang Hospital, Selangor \nE-mail : jacqui.ong@gmail.com\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nKeywords erythema nodosum leprosum;\nmultibacillary leprosy; clofazimine;\nsteroid-dependent\n\n\n\nI n t ro d u c t i o n\nENL is a type ll leprosy reaction and occurs in\npeople with borderline lepromatous and\nlepromatous leprosy, usually as a complication\nfollowing treatment. The treatment of choice for\nENL is prednisolone in view of its\u2019 r e a d y\navailability and aff o r d a b i l i t y1. Howeve r,\nglucocorticoid therapy, even in low doses, can\nproduce substantial toxicity. The risk is clearly\ngreater as the dose increases. However, in cases\nwhere there are steroid-induced complications,\nhigh-dosed clofazimine may be used to reduce or\nw i t h d r aw corticosteroids in steroid-dependant\ncases2,3. We described 2 steroid-dependent ENL\npatients with steroid-induced complications who\nare successfully managed with the addition of high-\ndosed clofazimine and the resultant weaning down\nof systemic glucocorticoids.\n\n\n\nCase re p o rt\nCase 1\nA 54 years old Chinese lady presented with\nmultiple tender red nodules involving the\nextremities, gluteus and lower back of 4 months\nduration.\n\n\n\nBiopsy taken on the left arm revealed macrophage\ngranuloma with occasional acid fast bacilli. Grenz\nzone was absent. Slit skin smear done showed a\nbacteriological index (BI) of 3.3 and morphological\nindex (MI) of 2.1. Hence, she was diagnosed to\nhave lepromatous leprosy with ENL. \n\n\n\nShe was commenced on intensive multidru g\ntherapy (MDT) regime comprising of rifampicin\n600mg daily, dapsone 100mg daily and clofazimine\n100mg daily. After a month of intensive therapy, her\nmorphological index was noted to be 0. Thus she\nwas commenced on maintenance therapy using\nSungei Buloh regime (modified World Health\nO rganization regime) consisting of rifa m p i c i n\n500mg and chlofazimine 300mg monthly, dapsone\n100mg daily and chlofazimine 50mg daily.\n\n\n\nHer ENL was treated with oral prednisolone 25mg\nper day. Her fever resolved and the ENL was less\ntender and reduced in number and pain. However,\nthe nodules were persistent so the prednisolone\ndose was increased gradually over 2 weeks until 60\nmg per day and was continued on this dose for 1\nmonth to no avail. During this time, she developed\nsteroid-induced diabetes (fasting blood glucose was\n11.1mmol/l) requiring diamicron 40mg twice a day\nfor control.\n\n\n\nWhen the clofazimine dose was increased to 100mg\ntwice daily, ENL was controlled within 8 weeks and\nher prednisolone was able to be tapered down to\n22.5 mg per day over 12 weeks. After 12 weeks, the\nclofazimine dose was reduced to 150mg per day\nand her prednisolone was able to be weaned down\nto 17.5mg per day over 4 weeks with no recurrence\nof ENL reaction. Her repeated fasting bl o o d\nglucose was within the normal range without oral\nhypoglycaemic agent. She is currently on a monthly\nfollow-up with a plan to withdraw her prednisolone\ncompletely in 3 months time.\n\n\n\nCase 2\nA 67 years old Chinese gentleman was diagnosed\nwith multibacillary leprosy when he presented with\nhypoaesthetic erythematous plaques with thickened\nulnar nerves. Slit skin smear revealed a\nb a c t e r i o l ogical index (BI) of 4.2 and a\nmorphological index (MI) of 4.8. He was started on\nintensive MDT comprising of rifampicin 600mg\ndaily, dapsone 100mg daily and clofazimine 100mg\nd a i ly. Maintenance therapy on modified W H O\nregime was commenced 1 month later when his\nmorphological index became 0.\n\n\n\n\n\n\n\n\n8 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nHe developed ENL, 6 months into his treatment and\nwhich resolve within a week with prednisolone at\n30mg daily. It was not possible to tail down the\nprednisolone below 15mg daily because of the\nfrequent reactivation of the erythema nodosum\nleprosum. Therefore, he was restarted back on\nprednisolone 30mg daily and remained on 3 cycles\nof increasing and tapering dose of prednisolone\nover 1 ye a r. He developed steroid-induced\npsychosis, diabetes and hy p e rtension, purp u r a ,\nweight-gain. \n\n\n\n18 months following intensive MDT therapy, his\nclofazimine was increased to 150mg daily.  ENL\nwent into remission within 8 weeks and his\nprednisolone was finally able to be tapered down to\n5mg alternate with 2.5mg daily within 12 weeks.\n\n\n\nDiscussion \nENL is an inflammatory cutaneous and systemic\ncomplication of multibacillary leprosy, usually as a\ncomplication of the treatment but sometimes, even\nbefore treatment4. It has been reported to occur in\n24 percent5 and 31 percent6 of multibacillary\nlepromatous patients on MDT regime in India and\nBrazil respectively.\n\n\n\nENL is characterized by crops of painful and tender,\nerythematous or deep purple subcutaneous nodules,\nwhich are variably distributed on the body but\nwhich mostly occur on the legs, arms and face.\nDuring the episode, the patients may suff e r\nadditional symptoms, including feve r, art h r i t i s ,\ndactylitis, myositis, lymphadenitis, iridocy c l i t i s ,\norchitis and neuritis. The skin signs are obligatory\ncriteria whereas the general signs are optional7,8.\n\n\n\nThere are several treatments for ENL, but the\nm a i n s t ays of initial treatment are systemic\ncorticosteroids and thalidomide. But for the reason\nof well-known teratogenic side effects, WHO does\nnot support use of thalidomide for the management\nof ENL in leprosy3. On the other hand, systemic\ng l u c o c o rticoids also have adverse effects that\nranges from just purpura and Cushingoid\nappearance to osteoporosis and cataract and life-\nthreatening complications like serious infections. \n\n\n\nAccording to the World Health Orga n i z a t i o n\n(WHO) and International Federation of A n t i -\nLeprosy Association (ILEP) guidelines for\nmanagement of erythema nodosum leprosum,\nclofazimine may be extremely useful for reducing\n\n\n\nor withdrawing corticosteroids in steroid-dependant\ncases. Clofazimine is a riminophenazine dye used\nin combination with rifampicin and dapsone as\nMDT for the treatment of leprosy as well as its\nreaction, ENL. It has been used in combination\nwith other anti-mycobacterial drugs to treat\nMycobacterium avium infections9 , 1 0 in acquired\nimmune deficiency syndrome patients and multi-\ndrug resistant tuberculosis. The availability of loose\nclofazimine is limited to the treatment of severe\nENL reactions only. The \u201coff-label\u201d use of\nc l o fazimine is active ly discouraged by W H O\nbecause it is a first line drug for the treatment of\nleprosy, and its indiscriminate use must be guarded\nagainst to prevent resistance. A systematic review\nof 13 randomized controlled trials found\nclofazimine to be superior to prednisolone and\nthalidomide for the treatment of ENL11. However,\nclofazimine should never started as the sole agent\nfor the treatment of severe ENL since it takes 4 to 6\nweeks to develop its full effect2.\n\n\n\nThe dose of clofazimine needed to control ENL is\nhigher than the dose used in MDT. The guideline\nrecommended supplementing the prednisone\ntherapy with higher doses of clofazimine initially.\nThe patients may be started on clofazimine 100mg\nthrice a day to for up to 12 weeks. This is then\nreduced to 100mg clofazimine twice a day for 12\nweeks and then 100mg once a day for 12 to 24\nweeks. The dose and duration of clofazimine may\nbe adjusted by the physician according to individual\npatient's needs. The ENL reaction is usually\ncontrolled within 2 to 4 months of treatment with\nclofazimine, and then the prednisone can gradually\nbe reduced and eventually withdrawn2,3. The dose of\nclofazimine was increased from 100mg per day to\n200mg per day and from 100mg per day to 150mg\nper day in patient 1 and patient 2 respectively. These\nrelatively small increases were sufficient to control\nthe ENL lesions and to reduce their steroids\nrequirement in both our patients within 8 weeks.\n\n\n\nD i s a d vantages of continuous high doses of\nc l o fazimine are gastrointestinal symptoms like\ncrampy abdominal pain and diarrhoea, particularly\nwith doses above 100mg daily. The other\nsignification side effect is skin pigmentation which\nusually develops within a few weeks after starting\nclofazimine treatment and may take two or more\nyears after stopping treatment to disappear2,12. Both\nour patients developed obvious skin pigmentation\n\n\n\n\n\n\n\n\n9MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\npigmentation which is accepted because they\nappreciate the efficacy of clofazimine in controlling\nENL.\n\n\n\nIn conclusion, clofazimine appears to be an\ne ff e c t ive and safe treatment for managing\nlepromatous patients with ENL when corticosteroid\nis needed to be reduced to the lowest possible dose.\n\n\n\nReferences\n\n\n\n1. Vazquez-Botet M, S\u00e1nchez JL: Erythema nodosum\nleprosum. Int J Dermatol 26:436-437, 1987\n\n\n\n2. The International Federation of A n t i - L e p r o s y\nAssociations (ILEP). The management of erythema\nnodosum leprosum. ILEP Technical Bulletin 1996,\nissue 9\n\n\n\n3. World Health Organization. WHO Guidelines for the\nmanagement of severe erythema nodosum leprosum\n(ENL) reactions. Ava i l a ble from\nhttp://www.who.int/lep/research/WHOenlguide.pdf)\n\n\n\n4. Rea TH and Levan NE. Erythema nodosum leprosum\nin a general hospital. Arch Dermatol 1975; 111:1575-\n80.\n\n\n\n5. Pocaterra L, Jain S, Reddy R, Muzaffarullah S et al.\nClinical course of erythema nodosum leprosum: an 11-\nyear cohort study in Hyderabad India. Am J Trop Med\nHyg 2006; 74:846-79\n\n\n\n6. Nery JA, Vieira LM, deMatos HJ, Gallo ME, Sarno EN.\nReactional states in multibacillary Hansen disease\npatients during multidrug therapy. Revista do Instituto\nde Medicina Tropical de S\u00e3o Paulo 1998;40(6):363-\n70.)\n\n\n\n7. Smith WC, Nicholls PG. Special workshop on repeated\nand late reactions. International Journal of Leprosy and\nOther Mycobacterial Diseases 2002;70(4):339-41\n\n\n\n8. Smith WC, Nicholls PG. Special workshop on repeated\nand late reactions. International Journal of Leprosy and\nOther Mycobacterial Diseases 2002;70(4):339-41\n\n\n\n9. Field SK and Cowie RL. Treatment of Mycobacterium\navium-intracellulare complex Lung Disease With a\nMacrolide, Ethambutol, and Clofazimine. Chest\nOctober 2003 124:1482-1486\n\n\n\n10. Shafran SD, Singer J, Zarowny DP, Phillips P, Salit l,\nWalmsley SL, Fong IW, Gill MJ, Rachlis AR Fanning\nMM, Tsoukas CM. N Engl J Med. 1996 A u g\n8;335(6):377-83\n\n\n\n11. Van Veen NHJ, Lockwood DNJ, van Brakel WH,\nRamirez Jr J, Richardus JH. Interventions for erythema\nnodosum leprosum. Cochrane Database of Systematic\nReviews 2009, Issue 3.\n\n\n\n12. Lockwood DN. The management of erythema nodosum\nleprosum: current and future options. Leprosy Review\n1996;67(4):253-9\n\n\n\n\n\n\n\n\n10 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nD E R M ATOLOGY THERAPEUTICS - Case Report\n\n\n\nFusarium Cutaneous Infection in a neutropenic girl\nwith Acute Lymphoblastic Leukaemia\nPan JY1, Ker KJ1, Audrey T1, Colin T1, Tan AM2, Tan HH1\n\n\n\nCorrespondence\nPan Jiun Yit, FAMS (Dermatology)\nNational Skin Centre, Singapore\nE-mail : jypan@nsc.gov.sg\n\n\n\n1National Skin Centre, Singapore\n2Kandang Kerbau Women\u2019s and Children\u2019s Hospital\n\n\n\nKeywords Fusarium, Acute Lymphoblastic\nLeukaemia\n\n\n\nAn immunocompromised girl with acute\nlymphoblastic leukaemia and previous autologous\nbone marrow transplant presented with fever and a\npainful rash on her extremities and trunk. There\nwere multiple tender erythematous papules and\nnodules with central necrosis. Neutropenia was also\npresent.  A skin biopsy revealed hyphae and spores\nin the lower dermis and tissue culture gr ew\nFusarium species. The patient responded well to\nsystemic amphotericin B therapy with resolution of\nskin lesions and recovering neutropenia.\n\n\n\nI n t ro d u c t i o n\nFusarium species are common plant pathog e n s\npresent in the environment but can cause invasive\ninfections in immunocompromised patients,\nespecially those with haematologic malignancies\nand bone marrow transplant recipients1. Tissue and\nblood cultures are especially important as they offer\na high diagnostic yield in invasive fusariosis2-3.\nAmphotericin B has been used as the mainstay of\nt r e a t m e n t4 although resistant rates are high,\ne s p e c i a l ly in Fusarium solani s p e c i e s5. T h e\ntreatment outcome is also closely related to rate of\nrecovery of neutropenia6.\n\n\n\nCase re p o rt\nA 10-year-old Chinese girl was diagnosed with\nacute lymphoblastic leukaemia in November 2003.\nInitial full blood count showed bicy t o p e n i a\n\n\n\n(neutropenia and anemia) with no blasts. Her first\nbone marrow aspirate showed 65% lymphoblasts\nwith a flow cytometry consistent with precursor B-\ncell acute lymphoblastic leukaemia. Involvement of\nthe central nervous system was confi rmed on\nlumbar puncture. She completed a course of\nchemotherapy and cranial irradiation, but had a\nrelapse two years later and underwe n t\nchemotherapy. Nine months later in October 2007,\nshe underwent an autologous bone marr ow\ntransplant complicated by two episodes of\nneutropenic fever and graft-versus-host disease of\nthe skin. Two months later, she suffered a relapse\ni nvolving the central nervous system and\ni n t r aventricular chemotherapy was initiated. A\nsubsequent bone marr ow aspirate and lumbar\npuncture showed no evidence of B lymphoblasts.\n\n\n\nThe patient had cytomegalovirus infection in March\n2008 which was treated with intravenous foscarnet\nand changed to oral valganciclovir due to acute\nrenal impairment. She was also treated with\nintravenous ganciclovir for 2 weeks in May 2008\ndue to cy t o m ega l ov i rus reactivation. In A u g u s t\n2008, the patient had disseminated varicella-zoster\ntreated with intravenous acyclovir and cloxacillin\n(for possible bacterial superinfection). In November\n2008, she developed neutropenic fever with septic\nshock from Salmonella typhi and ESBL-positive\nEscherichia coli bacteraemia treated with\nintravenous meropenem and amikacin. This was\nfollowed by a second relapse of acute lymphoblastic\nleukaemia, and intraventricular chemotherapy was\ninitiated. \n\n\n\nShe also had acute appendicitis and cholecystitis in\nFebruary 2009 that was treated conservatively with\ni n t r avenous ceftriaxone, gentamicin and\nmetronidazole.\n\n\n\n\n\n\n\n\n11MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nIn March 2009, the patient presented with a day\u2019s\nduration of fever and painful rash involving her\nlimbs. The rash started as erythematous patches on\nthe abdomen, upper and lower limbs; they\nsubsequently developed into dusky red papules and\nnodules with central areas of necrosis. She was\nunable to move her legs due to the painful rash.\nThere was no history of trauma or insect bites to the\naffected areas. Systemic review was unremarkable.\nShe was clinically in remission at this time and was\nnot on chemotherapy.\n\n\n\nOn examination, the child was febrile but other vital\nsigns were normal. Examination of her\nc a r d i ova s c u l a r, respiratory and ga s t r o i n t e s t i n a l\nsystems did not reveal any abnormalities. She had\noral candidiasis of the tongue and buccal mucosa.\nMultiple erythematous plaques and nodules\nnodules with central necrosis were seen on her\nchest, arms and legs which were tender and warm to\n\n\n\npalpation. (Figure 1 and 2) There was no discharge\nfrom the lesions or ulceration. All her nails were\nnormal. Her hips, knees and ankles were held in\nflexion due to pain.\n\n\n\nThe differential diagnoses include inflammatory\ncauses like erythema nodosum, atypical erythema\nm u l t i f o rme, early pyo d e rma ga n grenosum and\nsarcoidosis; infective causes like deep funga l\ninfections (aspergillosis and fusariosis), erythema\ninduratum and ecthyma gangrenosum; neoplastic\ncauses like leukaemia cutis; and medium-vessel\nvasculitis like polyarteritis nodosa.\n\n\n\nHer full blood count showed bicytopenia; total\nwhite count was 0.56 x 109/L with neutropenia\n(Absolute neutrophil count: occasional neutrophils\nseen only) with thrombocytopenia (platelet count\n28 x 109/L). Multiple blood and urine bacterial and\nfungal cultures were negative.\n\n\n\nFigure 1 Erythematous dusky tender nodule on calf with \ncentral necrosis \n\n\n\nFigure 3 H&E stain (10 x 4 magnification): Superficial and deep perivascular infiltrate of\nlymphocytes and neutrophils with fat necrosis and an abscess seen in the lower dermis\n\n\n\nFigure 2 Dusky indurated tender lesions on the the calf with \ncentral necrosis upper thighs\n\n\n\n\n\n\n\n\n12 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nA skin biopsy performed was consistent with deep\nfungal infection. (Figure 3) Periodic acid-Schiff and\nGrocott's Methenamine Silver stains demonstrated\nhyphae and spores in the lower dermis. (Figure 4\nand 5) Fungal tissue culture grew Fusarium species,\nsubtyping was not performed. Tissue pyog e n i c\nculture was negative. A bone marrow culture was\nnot performed as the skin histology results and the\nfungal tissue culture were sufficient to determine\nthe diagnosis.\n\n\n\nNew papules appeared with persistent fever despite\ntreatment with intravenous ceftazidime and\ngentamicin that was subsequently changed to\ni n t r avenous piperacillin/tazobactam. Her feve r\n\n\n\nlysed with the introduction of intrave n o u s\namphotericin (1mg/kg/day). The patient wa s\nd i s c h a rged with infusion pump-delive r e d\nintravenous amphotericin and completed a twenty-\none day course, with gradual resolution of the\nlesions after therapy. Her absolute neutrophil count\non discharge had recovered to 2.84 x 109/L.\n\n\n\nDiscussion\nFusarium spp. are saprophytes pervasively found in\nsoil, water or air7. Only a few out of the 50 different\nFusarium species are pathogenic in humans and\namong these, half of the reported invasive fusariosis\ninfections in humans are due to Fusarium solani. In\nFusarium infection, primary sites of entry are the\nskin\n\n\n\nFigure 4 PAS stain (10 x 40 magnification): Hyphae and spores in the lower dermis / subcutis\n\n\n\nFigure 5 GMS stain (10 x 40 magnification): Hyphae and spores in the lower dermis / subcutis\n\n\n\n\n\n\n\n\n13MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nskin and respiratory tract6, less commonly\nparanasal sinuses and gastrointestinal tract7.\nDisseminated fusariosis has also been associated\nwith central venous catheters, continuous\nambulatory peritoneal dialysis catheters8, patients\nwith extensive burns and neutropenic patients with\nlocalized skin and nail infections. In our patient, she\nwas neutropenic and had fusariosis of the skin\nwithout evidence of fungaemia, respiratory or\ngastrointestinal invo l vement. The skin was the\npresumed portal of entry.\n\n\n\nThe initial presentation of invasive fusariosis in\nneutropenic patients is persistent fever despite\nbroad-spectrum antibiotics7. This was the case in\nour patient. Despite prophylactic or empiric\ntreatment with amphotericin B or triazoles,\nbreakthrough fusariosis infections are common due\nto high resistance rates to antifungals7. Our patient\nhad solely cutaneous involvement without nail or\nrespiratory involvement. This is unusual. She also\nhad no penetrating injury or trauma to the lower\nlimb.\n\n\n\nUse of glucocorticoids impair anticonidial\nmacrophage function and predispose patients to\nfusariosis9. The mortality rate from fusariosis of\nh a e m a t o l ogic cancer patients receiv i n g\nglucocorticoids has been reported to be more than\ntwice of those not on glucocorticoids10. Our patient\nhad not received glucocorticoids in the recent\nmonths preceding the onset of skin lesions.\n\n\n\nThe histopathology of Fusarium lesions is similar to\nthat of A s p e rgillus species and may cause\nmisidentification11. However, differences in hyphae\ndiameter and degree of branching have been\nreported12.\n\n\n\nThe gold standard to differentiate betwe e n\nFusarium and A s p e rgillus species requires\nappropriate tissue culture. The Fusarium colony is\nseen microscopically as a white patch that\np r ogresses to a pink, purple or ye l l ow centre\nsurrounded by a lighter periphery11. Microconidia,\nmacroconidia and chlamydospores are diff e r e n t\ntypes of Fusarium conidia present in cultures, with\ncanoe-shaped macroconidia being the hallmark of\nthe Fusarium genus11.\n\n\n\nD i fferences have been reported in clinical\ncharacteristics between fusariosis and inva s ive\naspergillosis (IA). First, 50-70% of patients with\n\n\n\ndisseminated fusariosis have positive bl o o d\ncultures7 while disseminated IA is seldom isolated\nin cultures3. Positive Fusarium blood cultures can be\nobtained early in disseminated infections whereas\nthose in disseminated IA manifest late in the course\nof the infection3. Secondly, 50-70% of invasive\nfusariosis cases exhibit skin lesions compared with\nless than 10% in disseminated aspergillosis3. Most\npatients have concomitant myalgia7. These signs\nand symptoms were present in our patient. She had\nextremely tender erythematous papules and nodules\nwith central necrosis on her extremities which\nresulted in great pain, resulting in her holding her\nlimbs in flexion.\n\n\n\nTraditionally, Amphotericin B has been used as the\nmainstay of treatment against Fusarium infections,\nalbeit with mediocre in vitro susceptibility13 and\nhigh resistance rates especially with F u s a r i u m\nsolani species14. In current clinical practice, high\ndoses of amphotericin B are prescribed as there are\nr e p o rts of lower mortality rates (>50%)1 5.\nLiposomal formulations have been useful in\ni m p r oving bioava i l a b i l i t y. In our patient,\n1 mg/kg/day of Amphotericin B was administered\nfor 21 days. \n\n\n\nNew broad-spectrum triazoles like voriconazole\nand posaconazole show promise in the treatment of\nfusariosis16-19. Voriconazole was recently approved\nby U.S. FDA for treatment of refractory fusariosis.\nIt is most effective against non-solani Fusarium\nspecies. Pfaller et al19 reported voriconazole to be\neffective in a neutropenic leukaemic patient with\ndisseminated fusariosis where amphotericin B\ntreatment had failed. Upon completion of\nvoriconazole, there were no recurrences of\nfusariosis even after re-commencement of\nchemotherapy19.\n\n\n\nPrompt recovery of neutrophil counts is associated\nwith good prognosis in patients with fusariosis. In\nprofound, prolonged neutropenia, there is a 100%\nmortality rate for fusariosis compared to 30% when\nneutrophil counts are normal20. Therapies have been\ninitiated utilizing recombinant granulocyte colony-\nstimulating gr owth factor (G-CSF) and\ngranulocyte-macrophage colony-stimulating factor\n(GM-CSF) or granulocyte transfusion21. Our patient\ndid not receive any gr a n u l o cyte-stimulating or\ntransfusion therapies but her skin lesions responded\nto intravenous amphotericin B and neutrophil\ncounts had recovered on discharge.\n\n\n\n\n\n\n\n\n14 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nFinally, in patients with hematologic malignancies,\nthe suspected source of Fusarium infection should\nbe remove d, be it nail avulsion in Fusarium\nonychomycosis, surgical debridement of infected\ntissue or removal of infected catheters7.\n\n\n\nReferences\n\n\n\n1. Child FJ, Fuller LC, Higgins EM et al. Cutaneous\npresentation of Fusarium solani infection in a bone\nmarrow transplant recipient. J R Soc Med 1996; 89:\n647-8\n\n\n\n2. Kontoyiannis DP, Sumoza D, Tarrand J, Bodey GP,\nStorey R, Raad II. Significance of aspergillemia in\npatients with cancer: a 10-year study. Clin Infect Dis\n2000;31:188-189\n\n\n\n3. Nucci M, Anaissie E. Cutaneous infection by Fusarium\nspecies in healthy and immunocompromised hosts:\nimplications for diagnosis and management. Clin Infect\nDis 2002;35:909-920\n\n\n\n4. Walsh TJ, Hiemenz JW, Seibel NL, et al. Amphotericin\nB lipid complex for invasive fungal infections: analysis\nof safety and efficacy in 556 cases. Clin Infect Dis\n1998;26:1383-1396\n\n\n\n5. Johnson EM, Szekely A, Warnock DW. In-vitro activity\nof voriconazole, itraconazole and amphotericin B\nagainst filamentous fungi. J Antimicrob Chemother\n1998;42:741-745\n\n\n\n6. Nelson PE, Dignani MC, Anaissie EJ. Ta x o n o my,\nbiology, and clinical aspects of Fusarium species. Clin\nMicrobiol Rev 1994;7:479-504\n\n\n\n7. Boutati EI, Anaissie EJ. Fusarium, a signifi c a n t\ne m e rging pathogen in patients with hematolog i c\nmalignancy: ten years' experience at a cancer center\nand implications for management. Blood 1997;90:999-\n1008\n\n\n\n8. Musa MO, Al Eisa A, Halim M, et al. The spectrum of\nFusarium infection in immunocompromised patients\nwith haematological malignancies and in non-\nimmunocompromised patients: a single institution\nexperience over 10 years. Br J Haematol 2000;108:544-\n548 \n\n\n\n9. Rinehart JJ, Balcerzak SP, Sagone AL, LoBuglio AF.\nEffects of corticosteroids on human monocyte function.\nJ Clin Invest 1974;54:1337-1343 \n\n\n\n10. Nucci M, Anaissie E, Queiroz-Telles F, et al. Outcome\npredictors of 84 patients with hematolog i c\nmalignancies and Fusarium infection. Cancer\n2003;98:315-319 \n\n\n\n11. To rres HA, Ko n t oyiannis DP. Hyalohy p h o my c o s e s\n(other than A s p e rgillosis and Penicilliosis). In:\nDismukes WE, Pappas PG, Sobel JD, eds. Oxford\nTextbook of Clinical Mycology. 1st ed. New York:\nOxford University Press; 2003: 252-270\n\n\n\n12. Van Burik JA, Myerson D, Schreckhise RW, Bowden\nRA. Panfungal PCR assay for detection of fungal\ninfection in human blood specimens. J Clin Microbiol\n1998;36:1169-1175\n\n\n\n13. Anaissie EJ, Bodey GP, Rinaldi MG. Emerging fungal\npathogens. Eur J Clin Microbiol Infect Dis 1989;8:323-\n330 \n\n\n\n14. Kontoyiannis DP, Lewis RE. Antifungal drug resistance\nof pathogenic fungi. Lancet 2002;359:1135-1144\n\n\n\n15. Walsh TJ, Hiemenz JW, Seibel NL, et al. Amphotericin\nB lipid complex for invasive fungal infections: analysis\nof safety and efficacy in 556 cases. Clin Infect Dis\n1998;26:1383-1396\n\n\n\n16. Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole\ntreatment for less-common, emerging, or refractory\nfungal infections. Clin Infect Dis 2003;36:1122-1131\n\n\n\n17. Consigny S, Dhedin N, Datry A, Choquet S, Leblond V,\nChosidow O. Successful voriconazole treatment of\ndisseminated Fusarium infection in an\nimmunocompromised patient. Clin Infect Dis\n2003;37:311-313\n\n\n\n18. Marta Stanzani, Fabio Tumietto, Nicola Vianelli et al.\nUpdate on the treatment of disseminated fusariosis:\nFocus on voriconazole. Therapeutics and Clinical Risk\nManagement 2007:3(6) 1165-1173\n\n\n\n19. Pfaller MA, Messer SA, Hollis RJ, Jones RN, and the\nS e n t ry Pa rticipants Group A n t i f u n gal activities of\nposaconazole, ravuconazole, and vo r i c o n a z o l e\ncompared to those of itraconazole and amphotericin B\ntested against 239 clinical isolates of Aspergillus spp.\nand other filamentous fungi: report from the SENTRY\nantimicrobial surveillance program, 2000. Antimicrob\nAgents Chemother 2002;46:1032-1037\n\n\n\n20. Kontoyiannis DP, Bodey GP, Hanna H, et al. Outcome\ndeterminants of fusariosis in a tertiary care cancer\ncenter: the impact of neutrophil recove ry. Leuk\nLymphoma 2004;45: 141-143 \n\n\n\n21. Farmaki E, Roilides E. Immunotherapy in patients with\nsystemic mycoses: a promising adjunct. BioDru g s\n2001;15: 207-214\n\n\n\n\n\n\n\n\n15MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nD E R M AT O S U R G E RY - Original Art i c l e\n\n\n\nTreatment of Infantile Haemangiomas with\n585nm pulsed dye laser                                                         \nSabeera BKI1,  Mardziah A, MMED(Paeds)1, Gangaram HB, FRCP2\n\n\n\nAbstract\n\n\n\nHaemangiomas usually develop within the first few weeks of life, most regressing spontaneously\nbefore the age of 7 to 10 years. Some may ulcerate or compromise a vital function, in which case\nsystemic corticosteroids, surgery or radiotherapy may be helpful. All of these treatment modalities\nare associated with significant morbidity. Treatment with 585nm flashlamp pulsed dye laser is safe\nand effective in the management of ulcerated and superficial proliferating haemangiomas. We report\na retrospective review of 33 children under the age 12 months, who were treated at our centre with\n585nm pulsed dye laser over a period of 4 years. Forty eight percent of these children presented with\nr a p i d ly proliferating haemangiomas causing functional impairment, 40% with ulcerated\nhaemangiomas and others for re-growth after stopping oral treatment.  Patients were treated with the\n585nm pulsed dye laser (fluence: 5.5-7J/cm2; spot size: 7mm and duration: 0.45s). Patients received\ntreatment until the lesion was almost clear or until lesion failed to respond. All lesions ulcerated\nhaemangiomas healed after an average 3 treatment. Both the physician and parental perception of\nimprovement were analysed based on three parameters, which include reduction in redness,\nthickness and size. All the haemangiomas showed significant reduction in size, thickness and colour.\nLess than 1% of patients had atrophic scaring. We conclude that the flashlamp-pulsed dye laser may\nsuccessfully prevent enlargement and promote involution of superficial haemangiomas with minimal\nadverse effect. Therapy is most appropriate for patients with ulcerated haemangiomas and\nhaemangiomas at sites of potential functional impairment.\n\n\n\nKeywords Infantile haemangiomas, 585 nm Pulse dye laser\n\n\n\nCorrespondence\nBKI Sabeera\nInstitute of Paediatrics, Kuala Lumpur Hospital\nE-mail : dr_sabeera@yahoo.com\n\n\n\n1Institute of Paediatrics, Kuala Lumpur Hospital\n2Department of Dermatology, Kuala Lumpur Hospital\n\n\n\nIntroduction\nHaemangiomas are common vascular neoplasms,\nwith approximately 2.6% incidence in neonates1.\nThe rapid proliferation of the endothelial cells is\ncharacteristic of haemangiomas which often leads\nto rapid growth in the first few months after birth,\nand may ulcerate or obstruct a vital organ or\nfunction. The majority will regress spontaneously\nafter 18 months of life. The attitude of \u2018wait and\nsee\u2019 policy is frequently recommended, whereas in\ncase of complications, steroids or surgical therapy\nare applied2,3. Meanwhile, the application of the\nflashlamp-pumped pulsed dye laser (FPDL) has\nbecome a standard therapy for haemangiomas in\nm a ny centre4 , 5 , 6. By selective phototherm o ly s i s ,\n\n\n\nlaser irradiation destroys a superficial layer of blood\nvessels in the haemangiomas.\n\n\n\nThis seems to prevent further proliferation in the\nhaemangiomas which clinically may lead to a slow\nproliferation or may stop of the tumour growth7. We\nshare the rev i ew of forty three complicated\nchildhood haemangiomas, who underwent the\nFPDL therapy at our department from December\n1999 to December 2003. The objective of the\nreview is to determine the response or outcome and\nthe side effects of FPDL.\n\n\n\nMaterials and methods \nThis is a retrospective review of children with\ncomplicated haemangiomas who had FPDL therapy\nat our department over a 4 year period, from\nDecember 1999 to December 2003. The data was\ncollected from the laser unit and counter checked\nwith the patients\u2019 medical records. Pre and post\nlaser digital photographs of each patient we r e\nr ev i ewed from the computerized photogr a p h s\nfolders.\n\n\n\n\n\n\n\n\n16 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nComplicated haemangiomas in this study include: \n\n\n\n(i) haemangiomas located on the head and neck \nregion which obstruct vital organs or functions \ne.g. ophthalmic problems related to periorbital \nlesions. \n\n\n\n(ii) haemangiomas that ulcerate and/or bleed \n(iii) rapidly proliferating haemangiomas at the \n\n\n\nmacular stage (head & neck region). \n\n\n\nThe indications of laser in this group of patients are\nshown in Figure 1.\n\n\n\nPatients had photographs taken prior to each FPDL\nt h e r a py. FPDL therapy is done as a day care\nprocedure by the \u2018Laser team\u2019 consisting laser\nsurgeon, paediatric dermatologist, anaesthetist and\nlaser nurse at 4 to 8 weekly intervals. The procedure\nis done under general anaesthesia (GA). SPTL1b\nwith the following parameters were most frequently\nused; fluence: 5.5-7J/cm2 ; spot size: 7mm and\nduration: 0.45s. After FPDL patients are observed\nin the paediatric wards before discharging home.\n\n\n\nResponses to therapy was done by analysing three\nparameters including: Reduction of (i) redness (ii)\nthickness and (iii) size of haemangiomas. First,\nparental views on the reduction of redness of the\nhaemangiomas were assessed as slight, mild,\nmoderate and marked reduction. \n\n\n\nSecond, the thickness of the haemangiomas before\nand after FPDL was recorded in millimetres.\n\n\n\nThe thickness was grouped into flat lesions, lesions\nthan 3mm, and lesions >3mm. Last, the reduction in\nthe sizes of the haemangiomas were recorded in\ncentimetres and grouped into 0 to 5cm, 6 to 10cm\nand >10cm.\n\n\n\nTreatment is continued until the haemangiomas had\npartial or complete response or parentral request for\ndiscontinuation of therapy.\n\n\n\nThe short and long term complications we r e\nrecorded. Long term complications were obtained\nafter a minimum of 6 months period following the\nlast laser therapy. And the maximum period in this\nreview was 2 years post laser therapy. Data was\ntabulated and analysed accordingly.\n\n\n\nResults \nThere were forty three haemangiomas observed in\n33 children who were either referred from private or\ngovernment paediatrician or dermatologist. There\nwere 82% female and 18% male (female to male\nratio; 4.5: 1), with 42% being Chinese, 35% Malays\nand 23% Indians. \n\n\n\nFifty percent of haemangiomas were noticed at\nbirth, and another 50% by the first 4 weeks of life.\nAge of presentation to us is shown on Figure 2. The\nmean age of presentation is at 4 months.  60% of the\npatients presented before the age of 6 months,\nduring the rapid proliferative phase of\nhaemangioma. The oldest patient in this series is 12\nyears old.\n\n\n\nFigure 1 Common indications of laser therapy\n\n\n\n\n\n\n\n\n17MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nSixty percent of the haemangiomas were superficial\nand 40% were mixed. Eight percent haemangiomas\nwere observed on the head and neck region of\nwhich; 63% periorbital, 12% on the cheek, 10%\nperioral and rest forehead and scalp. Seven percent\nwere present on the buttock, 7% on the trunk, and\n6% on the extremities. \n\n\n\nThe most common complication were ulceration\nand bleeding (40%), followed by compromised\nvision (36%). 24% were noted at the rapid\nproliferating stage, and there was a concern of vital\n\n\n\no rgan obstruction. Two patients had laser for\nr egr owth after stopping the systemic steroid\ntherapy. 40% of patients had systemic and 2 had\nreceived intralesional steroid prior to FPDL\n\n\n\nThe mean age of first laser treatment was at 5\nmonths. Figure 3 shows the number of FPDLs\nr e c e ived by patients in this series. 4 lesions\nresponded to one laser session and there was one\nlesion which responded only after 12 sessions. The\nmean number was 3 for each patient before any\ndesired clinical response was seen. \n\n\n\nFigure 2 Age of presentation in months\n\n\n\nFigure 3 Number of FPDL received by patients\n\n\n\n\n\n\n\n\n18 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nThe response was assessed by the reduction in\ncolour, thickness and size. Tables 1,2,3 and 4 are the\ns u m m a ry of the response and outcome of the\nFPDL.\n\n\n\nThe use of general anaesthesia is not without any\nrisks, and needs proper assessment of patient. The\nshort term complications were pain in all patients\nand  transient blister in 20%. The long term\ncomplications include 37% with either hypo or\nhyperpigmentation, (5%) atrophic scaring, (9%)\nwith textural changes.\n\n\n\nFigure 4 1a & b: Pictures of perioricular haemangioma pre and post 4FPDLs.\n2 a & b: Haemangioma on the left cheek pre and post 5 FPDLs.\n\n\n\n1a 1b 2a 2b\n\n\n\nFigure 6 1 a, b, c & d: Complete resolution after 12 sessions of FPDL.\n\n\n\n1a 1b 1c 1d\n\n\n\nFigure 5 1 a & b: Pictures of scalp haemangioma pre and post 5 FPDLs.\n\n\n\n1a 1b\n\n\n\nFigure 7 Complete resolution of ulcerated haemangioma after 3 sessions of FPDL.\n\n\n\n\n\n\n\n\n19MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nDiscussion\nHaemangiomas may be complicated by medical and\npsychological issues that can be overwhelming to\nthe patient\u2019s family as well as humbling to the\nphysician. There is tremendous degree of variation\nin the rate, duration, and degree of growth, as well\nas the rate of involution. The clinical heterogeneity\nand \u2018auto-involutive\u2019 nature, makes the treatment\ncontroversial. Therefore, treatment must be highly\nindividualized taking into account; age, anatomical\nsite, size, rate of growth, and other factors, always\nweighing potential risks and benefits8.\n\n\n\nSince the study by Sherwood and Tan9 of the\nsuccessful treatment of a haemangioma of the\nfinger with the FPDL, several authors have reported\nequally successful results10. FPDL has proved to be\na safe and effective treatment modality for Port\nwine stain, in treating small vessels found in\nchildhood Port wine stains11.\n\n\n\nWe reviewed complicated haemangiomas in this\nseries, which would not reflect the tru e\ndemographic features of haemangiomas of infancy.\n\n\n\nThe demographic feature of this series, with respect\nto sex ratio and age of onset is similar to other\nstudies12. More Chinese than Malays were noted as\ncompared to the attendance at our depart m e n t\n(public sector healthcare) where Malays represent\n50%, Chinese (30%) and Indians (20%). Most\nChinese patients are referred from the private sector\nfor laser treatment. \n\n\n\nAlthough all regions of the body can be affected by\nhaemangiomas, eighty percent localised on the\nhead, with 63% at periorbital region, giving rise to\n\n\n\nvisual compromise. This figure is comparable with\nanother study1 3. Superficial haemangiomas are\nmore common than mixed ones14.\n\n\n\nUse of lasers to treat haemangiomas must be\ndivided into three separate indications: (i) treatment\nof ulcerated haemangiomas, (ii) treatment of\nproliferative phase3 and (iii) treatment of residual\ntelangiectases.\n\n\n\nUlceration is the most frequent indication for FPDL\nin this series. The ophthalmic compromise during\nthe proliferative phase is the second most common\nindication followed by rapid proliferation and re-\ngrowth after cessation of systemic steroid. \n\n\n\nSeventy five percent of these haemangiomas had\nmore than 75% reduction in redness similar to the\nstudy by Landhaler et al where 198 patients with\nhaemangiomas were treated, and 74% of these\npatients had 75% or greater lightening of their\nlesions with no evidence of permanent scaring13.\nFlat lesions responded to FPDL completely. Nearly\n90% of haemangiomas with 3mm and less in\nthickness responded much better to FPDL treatment\nand involuted more completely. The size of the\nhaemangiomas remained the same. Our study\ndemonstrates a better outcome in the superficial\nhaemangiomas group. Treatment of mixe d\nhaemangiomas has been the source of some\ncontroversy in the literature14.\n\n\n\nBleeding from ulcerated haemangiomas responded\nc o m p l e t e ly after one laser whereas ulceration\nhealed after a mean of 3 FPDLs. This observation is\nsimilar to a study by Hans Peter et al13.\n\n\n\nTable 1 Characteristics of the haemangiomas\n\n\n\nIndicator\n\n\n\nSize\n\n\n\nThickness\n\n\n\nColour\n\n\n\nCharacteristics\n\n\n\n0-5cm\n6-10cm\n>10cm\n\n\n\nFlat\n<3mm\n> 3mm\n\n\n\nBright red\nViolaceous\n\n\n\nN=43\n\n\n\n36 (83)\n5 (12)\n2 (5)\n\n\n\n2 (5)\n35 (81)\n\n\n\n6 (14)\n\n\n\n40 (93)\n3 (7)\n\n\n\nTable 2 Reduction in the redness of the haemangiomas after\nFPDL\n\n\n\nIndicator\n\n\n\nReduction of \nredness\n(Parental\nperception)\n\n\n\nResponse\n\n\n\nSlight (<25%)\n\n\n\nMild (26-50%)\n\n\n\nModerate (51-75%)\n\n\n\nMarked (>75%)\n\n\n\nNumber, N=40(%)\n\n\n\n0\n\n\n\n3 (7)\n\n\n\n7 (18)\n\n\n\n30 (75)\n\n\n\n\n\n\n\n\n20 MJD 2010 December Vol 25\n\n\n\nM a l aysian Journal of D e rm a t o l og y\n\n\n\nBesides the risk of GA, the morbidity of the long\nt e rm complications should be considered. T h e\npercentage of transient hypopigmentation and\nhyperpigmentation in our series was 10% and 8%\nrespectively compared to 2.6% and 1% in another\nseries. Higher percentage of both pigmentation can\nbe explained by the type 3 or 4 skin type in our\nseries. The hypopigmentation or hyperpigmentation\nis a transient phenomena and these patients need\nlong term follow up. Atrophic scaring was noted in\n4.5% compared to 0.1% in the above study15.\n\n\n\nConclusion \nTreatment with FPDL is safe and effective for\nulcerated haemangiomas. FPDL should be offered\nto infants with proliferative haemangiomas on the\nhead and neck region which may compromise\nvision or other vital organs or structures. This mode\nof therapy may further help in slowing the process\nof proliferation of the haemangiomas. We\nrecommend early treatment, especially in\np r o blematic lesions (around eyes, ears, nose,\ngenital, anal region) where early treatment can\nprevent disfigurement or other complications.\n\n\n\nReferences\n\n\n\n1. 1. Ceisler EJ, Santos L, Blei F. Pe r i o c u l a r\nHemangiomas: What Every Physician Should Know.\nPediatric Dermatology 2004;21:1-9\n\n\n\n2. Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R,\nMallory SB. Guidelines of care of hemangiomas of\ninfancy. J Am Acad Dermatol. 1997;37:4-10\n\n\n\n3. Bruckner AL, Frieden IJ. Hemangiomas in infancy. J\nAm Acad Dermatol. 2003;48:477-493\n\n\n\n4. Barlow RJ, Walker NPJ, Markey AC. Treatment of\nproliferative haemangiomas with the 585nm pulsed dye\nlaser. Br J Dermatol. 1996;134:700-704\n\n\n\n5. Frieden IJ. Pulsed dye laser treatment of hemangiomas\nof infancy: indications and complications. Pediatric\nDermatology. 2001;18:27\n\n\n\n6. Cantatore JL, Kriegel DA. Laser surgery: An approach\nto the pediatric patients. J Am Acad Derm a t o l .\n2004;50:12\n\n\n\n7. Staudt A, Baumler W, Hohenleutner U, Landthaler M.\nTreatment of childhood haemangioma with the\nflashlamp-pumped pulsed dye laser- A 10 ye a r s\nexperience. Pediatric Dermatology 2004;21:402-410\n\n\n\n8. Haggstrom A N, Frieden IJ. Haemangiomas: Pa s t ,\npresent, and future. J Am Acad Dermatol 2004;51(1):1\n\n\n\n9. S h e r wood KA, Tan OT. Treatment of a capillary\nhemangioma with FPDL. J Am Acad Derm a t o l .\n1990;22:136-137\n\n\n\n10. Ashinoff R, Geronemus RG. Capillary hemangiomas\nand treatment with the FPDL. Arch Derm a t o l .\n1991;127:202-205\n\n\n\n11. Garden JM, Bakus A D, Paller AS. Treatment of\ncutaneous hemangiomas by the FPDL: Prospective\nanalysis. J Padiatr. 1992;120:555-560\n\n\n\n12. Chiller KG, Passaro D, Frieden IJ. Haemangiomas of\nInfancy: Clinical Characteritics, Morphology Subtypes,\nand Their Relationship to Race, Ethnicity and Sex.\nAchieves of Dermatology. 2002; 138:1567-1576\n\n\n\n13. M a rgitta P, Carsten P, Hans Peter B. FPDL for\nhemangiomas in infancy: Tx of Superficial vs Mixed\nHemangiomas. A r c h ives of Derm a t o l og y. 2000;\n136:628-632\n\n\n\n14. Kim HJ, Colombo M, Frieden IJ. Ulcerated\nhaemangiomas: Clinical characteristics and response to\ntherapy. J Am Acad Dermatol. 2001;44:46\n\n\n\n15. Levine VJ, Geronemus RG. Adverse effects associated\nwith 577/585nm PDL in Tx of vascular lesions: study\nof 500 patients.  J Am Acad Dermatol. 1996;32:613-\n617\n\n\n\n16. E m i ly J. Ceisler, Francine Blei. Pe r i o c u l a r\nHemangiomas: What Every Physician Should Know.\nPediatric Dermatology 2004;21:1-9\n\n\n\n17. Ilona J. Frieden et al. Guidelines of care of\nhemangiomas of infa n cy. J Am Acad Derm a t o l .\n1997;37:4-10\n\n\n\n18. nna L. Bru c k n e r, Ilona J. Frieden, A u r o r a .\nHemangiomas in infa n cy. J Am Acad Derm a t o l .\n2003;48:477-93\n\n\n\n19. R . J. Barlow, NPJ Wa l ker et al. Treatment of\nproliferative haemangiomas with the 585nm pulsed dye\nlaser. Br J Dermatol. 1996;134:700-704\n\n\n\n20. Ilona J. Frieden et al. Pulsed dye laser treatment of\nhemangiomas of infa n cy: indications and\ncomplications. Pediatric Dermatology. 2001;18:27\n\n\n\n21. Julie L. Cantatore. Laser surgery: An approach to the\npediatric patients. J Am Acad Dermatol. 2004;50:12\n\n\n\n22. Treatment of childhood haemangioma with the\nflashlamp-pumped pulsed dye laser- A 10 ye a r s\nexperience. Pediatric Dermatology 2004;21:402-410\n\n\n\n23. Ilona J. Frieden. Haemangiomas: Past, present, and\nfuture. J Am Acad Dermatol 2004;51(1):1\n\n\n\n24. S h e r wood KA, Tan OT. Treatment of a capillary\nhemangioma with FPDL. J Am Acad Derm a t o l .\n1990;22:136-137\n\n\n\n25. Ashinoff R et al. Capillary hemangiomas and treatment\nwith the FPDL. Arch Dermatol. 1991;127:202-205\n\n\n\n26. Jerome M, Amy S Paller et al. Treatment of cutaneous\nhemangiomas by the FPDL: Prospective analysis. J\nPadiatr. 1992;120:555-60\n\n\n\n27. Kararina G. Chiller, Ilona J. Frieden. Haemangiomas of\nInfancy: Clinical Characteritics, Morphology Subtypes,\nand Their Relationship to Race, Ethnicity and Sex.\nAchieves of Dermatology. 2002; 138:1567-1576\n\n\n\n28. Hans Peter et al. FPDL for hemangiomas in infancy: Tx\nof Superficial vs Mixed Hemangiomas. Archives of\nDermatology. 2000; 136:628-632\n\n\n\n29. Ilona J. Frieden et al. Ulcerated haemangiomas:\nClinical characteristics and response to therapy. J Am\nAcad Dermatol. 2001;44:6\n\n\n\n30. Vicki J. Levine MD et al. Adverse effects associated\nwith 577/585nm PDL in Tx of vascular lesions: study\nof 500 patients. J Am Acad Dermatol. 1996;32:613-\n617.\n\n\n\n\n\n\n\n\n\n"
"\n\nMalaysian Journal of Dermatology\n\n\n\n38 \u2022   MJD 2012 Dec Vol 29\n\n\n\nSatya Wydya Yenny, \nWahyu Lestari\n\n\n\nA Study Comparing the Use\nof 10% L-Ascorbic Acid and\n10% Zinc Sulfate Solution\nin the Treatment of Melasma\n\n\n\nAbstract\nBackground Melasma is a hypermelanosis which is difficult to treat. There are \n\n\n\nseveral treatment options for melasma and one of them is topical therapy using 10% \n\n\n\nL-Ascorbic acid and 10% Zinc sulfate. \n\n\n\nAim  To compare the efficacy and side effects of 8 weeks 10% L-Ascorbic acid solution \n\n\n\nwith 10% Zinc sulfate on melasma.\n\n\n\nMethods  This is an observational study with cross sectional design and single-blind, \n\n\n\ncomparing the left and right side of the faces sequentially (right-left comparison study) \n\n\n\nwith each treatment 10% L-Ascorbic acid  and 10% Zinc sulfate applied at night. In \n\n\n\nthe morning and afternoon patients uses sunscreen SPF 30. Only new patients with \n\n\n\nmelasma seen at Dermatology Polyclinic Dr M Djamil Hospital Padang from March \n\n\n\n2012 to May 2012 were included in this study.\n\n\n\nResults 20 melasma patients were studied. Their ages range from 25-54 years. 12 (60%) \n\n\n\nhad combination triggering factors. All patients had epidermal type of melasma with \n\n\n\n65% located over the centrofacial and 35% on the malar zones. After 2 months of \n\n\n\ntreatment there was  significant improvement of melasma treated with 10% Zinc \n\n\n\nsulfate  and 10% L-Ascorbic acid with a P value of <0.05. Minimal side effects were \n\n\n\nfound with Zinc sulfate.\n\n\n\nConclusion Improvement of melasma was noted with both topical 10% L-Ascorbic \n\n\n\nacid and 10% Zinc sulfate but minimal side effects were noted with the use of 10%  \n\n\n\nZinc sulfate.\n\n\n\nKeywords: Melasma, 10% L-Ascorbic acid, 10% Zinc sulphate\n\n\n\nCorrespondence\nWahyu Lestari\nDepartment of Dermatovenereology, Medical Faculty of Andalas University\nDr. M. Djamil Hospital Padang / Indonesia\nEmail: Mulia_1@yahoo.com\n\n\n\nDERMATOLOGY THERAPEUTICS - ORIGINAL ARTICLE\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n39MJD 2012 Dec Vol 29   \u2022\n\n\n\nIntroduction\nMelasma, also called the \u2018mask of pregnancy\u2019 and \ncloasma, comes from the Greek \u2018melas\u201d which means \nblack, is hypermelanosis with light brown to dark brown \n(sometimes grayish or blue), irregular shaped on the sun-\nexposed areas, which develop slowly and symmetrically.1-3 \nMelasma is more common in individuals from tropical \ncountries including Indonesia. Melasma affects mainly \nwomen, and only about 10% in man. Generally, melasma \nis noted in adult, middle age and fertile woman.\n\n\n\nMelasma is a cosmetic problem, especially in women, \nbecause of its location on the face.4 Rizal Y, et al. (Indonesia, \n2008) reported 405 cases of melasma in the Polyclinic of \nDermato-Venereology Dr. M. Djamil Hospital Padang \nfrom 2001-2006. There were 8 male and 397 female \npatients.5 Melasma can affect all races, but particularly in \nindividuals with skin type IV-VI.1\n\n\n\nThe exact cause is unknown. The various precipitating \nfactors include genetic influences, exposure to ultraviolet \nradiation, pregnancy, oral contraceptive, estrogen-\nprogesterone therapy, thyroid dysfunction, cosmetics and \nphotosensitizing and antiseizure medicine. Aetiology is \nunknown in a third of patients with melasma.1-3 Diagnosis \nis based on symptoms and physical examination using \nWood\u2019s lamp and rarely by histopathologic examination. \nSkin biopsy performed for histopathologic examination \non the face should pay attention to the aesthetic aspect \nto prevent new complaint from the patients.1-3 Current \ntreatments include the routine use of broad-spectrum \nsunscreens4 and skin lightening agents which aim to slow \nthe proliferation of melanocytes, inhibit the formation \nof melanosomes and stimulate the degradation of \nmelanosomes.4-6\n\n\n\nL-Ascorbic acid 10% affects the monopherase activity \nof tyrosinase via its ability to reduce the enzymatically \ngenerated in the production or synthesis of melanin. This \nprovide photo protection, preventing the absorption of \nUV radiation and antioxidants. Topical 10% Ascorbic acid \nhas been shown to reduce the effect of 52% of erythema \ncaused by UVB. Several studies have reported minimal \nside effects in the form of erythema which clears within \n1-2 weeks, but L-Ascorbic acid is more expensive.7 \n\n\n\nTopical 10% Zinc sulfate has anti-inflammatory effect. \nTopical Zinc ions have been reported to have antioxidant \neffects which then provide skin photoprotection. Several \nstudies have reported no side effects after use of 10% Zinc \nsulfate and the price is more economical than the other \ndrug for depigmentation.7,8 Sharquie KE, (Iraq, 2008) \nreported the use of 10% solution Zinc sulfate 2 times a day \nfor 2 months for the treatment of melasma in 28 patients. \nThe MASI score was reduced from 9.45 to 4.70.9 \n\n\n\nIn this study, our aim was to compare the efficacy of 10% \nsolution of  L-Ascorbic acid and 10% solution Zinc sulfate \nin patients with melasma.\n\n\n\nPatients and methods\nThe study was conducted at the Polyclinic of Dermato-\nVenereology Dr. M. Djamil Hospital Padang from March \n2012 to May 2012. Diagnosis was based on anamnesis and \nphysical examination. All patients had informed consent \nand explanation about the possible side effects from the \nmedications. Inclusion criteria were adult women, aged \n25-59 years with melasma. Exclusion criteria included \npregnancy, lactation, hormonal contraceptive users, a \nmalignancy of the face, history of hypersensitivity to 10% \nL-Ascorbic acid and 10% Zinc sulfate and had received \nany other form of treatment (less than 1 month ago).\n\n\n\nA full history was taken from each patient, including \npersonal history (age, sex, marital state, and occupation), \nfamily history, duration of melasma, relation to \npregnancy, usage of oral contraceptive pills, relation to \nsun exposure, and previous therapy. Clinical examination \nand photographs of faces (left and right) were performed \nbefore and at the end of treatment. \n\n\n\nThe melasma area and severity index (MASI) score was \ncalculated for each patient at baseline, every 2 weeks, and \nat the end of the 8-week follow-up period to accurately \nassess the severity of melasma before, during, and after \ntreatment. The MASI is calculated on the basis of the area \nof involvement, darkness of melasma, and homogeneity \nof hyperpigmentation.\n\n\n\nFour areas on the face were evaluated: forehead (f ), right \nmalar (rm), left malar (lm), and chin (c), which represented \n30%, 30%, 30%, and 10% of the facial skin, respectively. \nThe area (A) of involvement in each of these four areas \nwas given a numerical value 0 to 6 (0, no involvement; \n1, 1-9%; 2, 10-29%; 3, 30-49%; 4, 50-69%; 5, 70-89%; 6, \n90-100%).\n\n\n\nThe severity of melasma was based on two factors: \ndarkness (D) and homogeneity (H). These parameters \nwere measured on a scale of 0 to 4 (0, absent; 1, slight; \n2, mild; 3, marked; 4, maximum). Melasma area severity \nindex scores were then calculated for each half of the face \nby using the following equation7:\n\n\n\n0.15 (HF + DF) + 0.15 AF (DMR + HMR) AMR + 0.15 \n(DML + HML) AML + 0.05 (HC + DC) AC.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40 \u2022   MJD 2012 Dec Vol 29\n\n\n\nGlobal evaluation of improvement in response to therapy \nwas done by the patient at baseline, every 2 weeks and at \nthe end of treatment (8 weeks) and was scored as marked \n(>75% improvement), good (50% to <75% improvement), \nmoderate (25% to <50% improvement), or mild (<25% \nimprovement).7 All side effects, including erythema, \nburn, and itching, were registered. Reduction of  \u2265 40% \nof the value of MASI was taken as improvement, while \nreduction  of  <40% was classified as no improvement \n(nominal scale). \n\n\n\nClinical, Wood\u2019s lamp examination and digital photographs \n(frontal, right, and left views) were taken before starting \ntreatment (baseline) and for every 2 weeks of the study \nand 2 weeks after the end of the treatment (8 weeks).7-9 \nThe Wood\u2019s light examination (nominal scale) enhanced \npigment differences between melasma and normal skin \ncolor.10,11  \n\n\n\nEach patient received 10% Zinc sulfate (Brataco\u00ae \npharmaceutical, 10% Zinc sulfate solution was prepared \nby dissolving 10 g of Zinc sulfate crystals (ZnSO4 _7H2O) \nin 100mL of distilled water) drug A, on the right face and \n\n\n\n10% L-Ascorbic acid  (Skinnase\u00ae pharmaceutical) drug \nB, on the left face and a sunscreen. The medication was \napplied on the face once daily at night, while the sunscreen \nwas applied in the morning and afternoon. Participants \nwere asked to record the side effects that arose and given \nan appointment card which contained the schedule for \nthe next visit (every 2 weeks). Informed consent was \nobtained before treatment. The study was conducted after \nobtaining approval from the Ethics Committee of Dr. M. \nDjamil Hospital Padang.\n\n\n\nStatistical Analysis \nStatistical analyses was used for all parameters. A \nWilcoxons test was used to compare the mean of MASI \nchange resulting from treatment. A p-value of less than \n0.05 was considered significant.\n\n\n\nResults and Discussion\nA. Demographic data \nTwenty women were enrolled in this study with age \nranging from 25 to 54 years, with a majority (35%) of \npatients in the 35-39 age groups (Table 1).\n\n\n\nTable 1  Patients\u2019 demographic data.\n\n\n\nAge Group\n\n\n\n25-29 year\n\n\n\n30-34 year\n\n\n\n35-39 year\n\n\n\n40-44 year\n\n\n\n45-49 year\n\n\n\n50-54 year\n\n\n\n55-59 year\n\n\n\nOccupation\n\n\n\nHouse wife\n\n\n\nGovernment employee\n\n\n\nSelf employed\n\n\n\nOthers\n\n\n\nNumber\n\n\n\n1\n\n\n\n3\n\n\n\n7\n\n\n\n4\n\n\n\n3\n\n\n\n2\n\n\n\n-\n\n\n\n6\n\n\n\n7\n\n\n\n7\n\n\n\n-\n\n\n\n%\n\n\n\n5\n\n\n\n15\n\n\n\n35\n\n\n\n20\n\n\n\n15\n\n\n\n10\n\n\n\n-\n\n\n\n30\n\n\n\n35\n\n\n\n35\n\n\n\n-\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n41MJD 2012 Dec Vol 29   \u2022\n\n\n\nTable 2  Characteristics of aggravating factors for melasma.\n\n\n\nTable 3  Pattern of melasma and Wood\u2019s lamp examination.\n\n\n\nCharacteristics\n\n\n\nHistory of hormonal contraception\n\n\n\nYes\n\n\n\nNo\n\n\n\nAggravating factors\n\n\n\nSun exposure\n\n\n\nHormonal contraception\n\n\n\nCosmetics\n\n\n\nGenetics\n\n\n\nCombined\n\n\n\nPatient characteristic\n\n\n\nPattern of melasma\n\n\n\n- Centrofacial\n\n\n\n- Malar\n\n\n\n- Mandibular\n\n\n\nMelasma type (Wood\u2019s lamp)*\n\n\n\n- Epidermal\n\n\n\n- Dermal\n\n\n\n- Mixed\n\n\n\nMelasma type (Wood\u2019s lamp)**\n\n\n\n- Epidermal \n\n\n\n- Dermal\n\n\n\n- Mixed\n\n\n\nNumber\n\n\n\n12\n\n\n\n8\n\n\n\n4\n\n\n\n-\n\n\n\n4\n\n\n\n-\n\n\n\n12\n\n\n\nNumber\n\n\n\n13\n\n\n\n7\n\n\n\n-\n\n\n\n16\n\n\n\n-\n\n\n\n4\n\n\n\n16\n\n\n\n1\n\n\n\n3\n\n\n\n%\n\n\n\n60\n\n\n\n40\n\n\n\n20\n\n\n\n-\n\n\n\n20\n\n\n\n-\n\n\n\n60\n\n\n\nPercentage \n\n\n\n65\n\n\n\n35\n\n\n\n-\n\n\n\n80\n\n\n\n-\n\n\n\n20\n\n\n\n80%\n\n\n\n5%\n\n\n\n15%\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42 \u2022   MJD 2012 Dec Vol 29\n\n\n\nTable 4  Evaluation of response to treatment of melasma with 10% L-Ascorbic acid and 10% Zinc sulfate.\n\n\n\nBefore therapy\n\n\n\nAscorbic acid 10% \n\n\n\nZinc sulfate 10%\n\n\n\nAfter therapy\n\n\n\n(2 weeks)\n\n\n\nAscorbic acid 10%\n\n\n\nZinc sulfate 10%\n\n\n\n(4 weeks)\n\n\n\nAscorbic acid 10% \n\n\n\nZinc sulfate 10%\n\n\n\n(6 weeks)\n\n\n\nAscorbic acid 10%\n\n\n\nZinc sulfate 10%\n\n\n\n(8 weeks)\n\n\n\nAscorbic acid 10%\n\n\n\nZinc sulfate 10%\n\n\n\nExcellent\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nGood\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nModerate\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n9\n\n\n\n9\n\n\n\n15\n\n\n\n16\n\n\n\n16\n\n\n\n17\n\n\n\nMild\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n11\n\n\n\n11\n\n\n\n5\n\n\n\n4\n\n\n\n4\n\n\n\n3\n\n\n\nWorst\n\n\n\n20\n\n\n\n20\n\n\n\n20\n\n\n\n20\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\n-\n\n\n\nCharacteristics Clinical response\n\n\n\nTable 5  MASI score and  treatment with 10% Ascorbic acid (drug 1, left face) and 10%  \nZinc sulfate (drug 2, right face).\n\n\n\nDay\n\n\n\nDay 0\n\n\n\nDay 14\n\n\n\nDay 28\n\n\n\nDay 42\n\n\n\nDay 56\n\n\n\nGroup\n\n\n\nDrug 1\nDrug 2\n\n\n\nDrug 1\nDrug 2\n\n\n\nDrug 1\nDrug 2\n\n\n\nDrug 1\nDrug 2\n\n\n\nDrug 1\nDrug 2\n\n\n\nAverage \nScore \n\n\n\n11.23\n10.35\n\n\n\n10.67\n9.14\n\n\n\n7.49\n6.57\n\n\n\n5.12\n5.02\n\n\n\n4.34\n4.06\n\n\n\nSD \n\n\n\n3.42\n3.65\n\n\n\n2.98\n2.86\n\n\n\n2.42\n2.02\n\n\n\n2.54\n1.98\n\n\n\n1.23\n1.04\n\n\n\nP \n\n\n\n0.1\n\n\n\n0.1\n\n\n\n0.08\n\n\n\n0.06\n\n\n\n0.05\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n43MJD 2012 Dec Vol 29   \u2022\n\n\n\n1. Before Treatment\n\n\n\n2. After Day 28\n\n\n\n3. After Day 56 \n\n\n\n10% Ascorbic acid : left face 10% Zinc sulfate : right face\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44 \u2022   MJD 2012 Dec Vol 29\n\n\n\n60% (n=12) had a combination of  aggravating factors. \nGuinot C, et al. (Tunisia, 2010) reported that 60% of \nmelasma appeared at the age of 30 years and the most \ncommon precipitating factors were sun exposure, \npregnancy and oral hormonal contraception.13\n\n\n\nMajority (65%) of the  patients in this study have \ncentrofacial patterns of melasma which is similar with \nother reports and the mandibular type is noted to be \nrare.13,14 Our study did not have  any patients with \nmandibular type. \n\n\n\nThe results of Wood\u2019s lamp examination showed that at \nthe beginning of the study there were 16 patients (60%) \nwith epidermal melasma and mixed type4.  This is similar \nwith previous studies with epidermal melasma being \nmore common, approximately 72%.14 After 8 weeks of \ntreatment, 1 patient (5%) had dermal and 3 patients \n(15%) had mixed type. In this study, 1 patient with mixed \ntype resulted into a dermal type probably indicating \ntreatment success in removing epidermal melasma.  This \nsuggests that there is a reduction and or disappearance of \nthe epidermal component, although this difference was \nnot significant in both groups.\n\n\n\nSeveral studies have reported topical treatment of melasma \nusing these medications removing only the epidermal \ncomponent.14 No improvement of melasma with 10% \nL-Ascorbic acid and 10% Zinc sulfate were noted at 2 \nweeks therapy. After 4 weeks there was mild to moderate \nimprovement. However, after 6 weeks treatment, there \nwas moderate improvement in both treatment sites. \nAfter 2 months of treatment there was significantly more \nimprovement with 10% L- Ascorbic acid as compared to \nZinc sulfate 10%(p <0.05).\n\n\n\nUp to day 28 of therapy, there was no significant difference \nbetween  10% L-Ascorbic acid and 10% Zinc sulfate (mean  \nof  10% L-Ascorbic acid was 7.49\u00b12.42 and the mean 10% \nZinc sulfate was 6.57\u00b12.02 (Table 5)).\n\n\n\nOn day 56 of therapy, there were significant differences: \n10% L-Ascorbic acid was 4.34\u00b11.23 and the 10% Zinc \nsulfate  4.06\u00b11.04.  It appears that 10% Zinc sulfate gave \nbetter results than 10% Ascorbic acid.\n\n\n\nSharquie KE, et al. (Iraq, 2008) reported the treatment of \nmelasma with 10% solution Zinc sulfate twice daily for \n2 months for treatment of melasma. The MASI scores \ndecreased from 9.45 to 4.70 after treatment. Side-effects \nappeared in 3 patients with a mild stinging sensation.12   \nAnother study reported the use of Ascorbic acid with \niontophoresis in 29 patients for 12 weeks. The MASI score \ndecreased from 4.8 to 2.78 after treatment. Side-effects \nsuch as itching, erythema and burning occured in some \npatients.6  Ochiai Y, et al. (Japan, 2006) reported the use of \nAscorbic acid for treatment of hyperpigmentation. After \n3 weeks there was suppression of the elevated intracellular \nperoxide after UVB irradiation, and enhanced cellular \ntolerance against UVB and reactive oxygen species such \nas hydrogen peroxide and tert-butyl hydroperoxide. \nAscorbic acid reduced the production of interleukin-1a \nand prostaglandin E2 in UVB-irradiated keratinocytes \nand suppressed melanocyte proliferation in conditioned \nculture medium prepared from UVB-irradiated \nkeratinocytes.13\n\n\n\nConclusions\nBoth 10% L-Ascorbic acid and 10% Zinc sulfate reduced \nthe MASI score in melasma patients although 10% Zinc \nsulfate gave better results with minimal side effects.  Clinical \nimprovement was noticed after 1 month of treatment \nbased on reduction in the MASI score. Side effects in \npatients treated with 10% L-Ascorbic acid included \nredness and pain, whereas 10% Zinc sulfate only caused a  \nmild itch which resolved within a week. However, further \nresearch is needed using a larger number of patients and a \nlonger observation period.\n\n\n\nAcknowledgement\nWe would like to thank Skinnase\u00ae pharmacy for their \nsupport.\n\n\n\nTrout CR, Levine N, Chang MW. Disorders of pigmentation. In 1. \n: Bolognia JL, Jorizzo JL, Rapini R, editor. Dermatology. 2nd ed, \nvol 1, London, Mosby, 2004: 975-1004.\nSoepardiman L. Kelainan Pigmen. In : Djuanda A, Hamzah 2. \nM, Aisah S editor. Ilmu penyakit kulit dan kelamin. 5th ed. \nJakarta, FKUI, 2007: 289-99.\nLapeere H, Boone B, Schepper SD, Verhaeghe E, Ongenae K, 3. \nGeel NV, Lambert J. Brochez L. Naeyaert JM. Hypomelanoses \nand hypermelanoses. In : Wolff K, Goldsmith LA, Katz SI, \nGilchrest BA, Paller AS, Leffel DJ eds. Dermatology in general \nmedicine, 7th ed, vol 1, New York : Fitzpatrick, Mc Graw Hill, \nMedical Publishing Division, 2008 : 622-40.\n\n\n\nRizal Y, Lestari S. Insidens Melasma incident from 2001-2006 4. \nin polyclinic and venereal clinic RSUP Dr. M. Djamil Padang. \nDV Indonesia 2008; 35: 56-9.\nOdom RB, James WD. Disturbances of pigmentation. Disease of 5. \nthe skin clinical dermatology. 10th Ed; New York; WB Saunders \nComp, 2006: 217-25.\nRendom M, Berneburg M, Arellano I, Picardo M. Treatment of 6. \nmelasma. JAAD 2006; 54:S272-81.\nA. Katsambas, Ch. Antoniou. Melasma. Classification and 7. \ntreatment. JEADV 1995;4: 217-23.\nPearl E, Grimes. Melasma. Etiologic and Therapeutic 8. \nconsiderations. Arch Dermatol 1995; 131: 1453-7.\n\n\n\nReference\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n45MJD 2012 Dec Vol 29   \u2022\n\n\n\nLorizzo M, Tosti A, Padova MPD. Melasma. Tosti A, Grimes 9. \nPE, Padova MPD. Color atlas of chemical peels. London; \nSpringer;149-59.\nKimberly A. Cayce; Amy J. McMichael; Steven R. Feldman. 10. \nHyperpigmentation: An Overview of the Common Afflictions. \nDermatol Nurs.  2004; 16(5): 401-16.\nGuinot C, Latreille J, Dhaoui MA, Youssef S. Aggravating 11. \nfactors for melasma: a prospective study in 197 Tunisian \npatients. JEADV 2010; 24: 1060 \u2013 9.\n\n\n\nSharquie KE, Mashhadani SA, Salman HA. Topical 10% Zinc 12. \nSulfate Solution for Treatment of Melasma. Dermatol Surg \n2008; 36: 1346-9.\nOchiai, Kaburagi S, Obayashi K, Ujiie k, Hashimoto S, Okano 13. \nY. A new lipophilic pro-vitamin C, tetra-isopalmitoyl Ascorbic \nacid (VC-IP), prevents UV-induced skin pigmentation through \nits anti-oxidative properties. J Dermatol Sc. 2006; 44: 37-44.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46 \u2022   MJD 2012 Dec Vol 29\n\n\n\nAsmah J.\n\n\n\nAcne Management Clinical \nPractice Guideline (CPG)  \n\n\n\nThe Acne Management Clinical Practice Guideline (CPG) was launched on 5th June 2012 in Institut Perubatan \nRespiratori (IPR), Kuala Lumpur by Dato\u2019 Dr Zaininah Mohd. Zain, the Director of Kuala Lumpur Hospital \non behalf of the Director General of Health, Dato\u2019 Dr Hasan Abdul Rahman.\n\n\n\nThis is the first evidence based CPG launched for dermatology under the guidance of Health Technology \nAssessment Section, Ministry of Health. The CPG was developed for almost 3 years as all evidence had to be \nreviewed thoroughly. The development committee also had to assess its relevance in Malaysian Health Care \nsystem. It serves as a guide for local doctors especially in primary care to optimize treatment before referral \nis made to a dermatologist or plastic surgeon for other specific treatment or management.\n\n\n\nThis topic was initially chosen as acne is a common problem among adolescents and young adults. It has a \nwide spectrum of clinical severity with different types of treatment modalities. There is also a wide variation \nin the prescribing patterns; hence the treatment may not be standardized to our expectation. It also provides \na very good reference for medical students to improve their knowledge. \n\n\n\nThe development committee consists of a group of dermatologists, Datin Dr Asmah Johar (Chairperson), \nDr. Noor Zalmy Azizan, Dr. Chang Choong Chor, Dr. Ng Ting Guan, Dr. Lee Yin Yin and other relevant \npersonnel involved were Ass. Prof. Dr. Leelavathi Muthupalaniappen (Family Medicine Specialist), Dr. \nNorraliza Md. Zain (Family Medicine Specialist), Dr. Siti Irma Fadhilah Ismail (Clinical Psychologists), Dr. \nZahara Abdul Manaf (Dietitian), Ms Lui Wei Qi (Pharmacist), Dr. Mohd. Aminuddin Mohd. Yusof (Public \nHealth Physician) and Mariammah Krishnasamy (Scientific Officer). \n\n\n\nThe review committee consists of senior dermatologist, Datuk Dr. Roshidah Baba, Head of Dermatology \nServices (Chairperson), Puan Sri Datuk Dr. Suraiya H. Hussein, Dr. Choon Siew Eng, Dr. Pubalan Muniandy, \nDr. Rohna Ridzwan, Dr. Ting Hoon Chin, Dr. Mohd. Noh Idris, Dr. Mardziah Alias and other members include \nDr. Suraya Yusoff (Psychiatrist) and Datin Dr. Rugayah Bakri (from Health Technology Assessment). \n\n\n\nThe CPG addresses on various sections including recently updated and more established acne pathophysiology, \nrisk and aggravating factors including the role of diet and supplements and quality of life assessment. For \ndermatologists, it offers a good review on pharmacology and non-pharmacology treatment response up to \n31st July 2011. \n\n\n\nCorrespondence\nDr Asmah Johar \nDepartment of Dermatology, Hospital Kuala Lumpur\nE-mail: asdr2001@hotmail.com\n\n\n\nANNOUNCEMENT - ADMINISTRATIVE UPDATE\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n47MJD 2012 Dec Vol 29   \u2022\n\n\n\nThis CPG has an important \nguide on appropriate \ntreatment algorithm, \nrecommendations and a \nquick reference. Provision \nof well designed training \nmodule for implementation \nand patient information \nleaflet will encourage \nutilization of CPG. \nDownload is available from \nthe Ministry of Health \nwebsite.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48 \u2022   MJD 2012 Dec Vol 29\n\n\n\n2013\nCONTINUOUS PROFESSIONAL DEVELOPMENT \u2013 CME \n\n\n\nAmerican Academy\nof Dermatology\nAnnual Meeting \nOrganizers American Academy of Dermatology\n\n\n\nVenue Miami, Florida\n\n\n\nDate March 1-5, 2013\n\n\n\nProgram www.aad.org\nwebsite\n\n\n\nThe International Affairs Committee of the American Academy \n\n\n\nof Dermatology (AAD) offers attendance scholarships to two \n\n\n\n(2) young dermatologists per country to attend the AAD\u2019s 2013 \n\n\n\nAnnual Meeting, March 1-5, 2013 in Miami, Florida. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n49MJD 2012 Dec Vol 29   \u2022\n\n\n\nAmerican Academy\nof Dermatology\nAnnual Meeting \n\n\n\nMALAYSIAN HISTORY\n\n\n\nPublication in \nDermatology\nfrom Malaysia\n\n\n\nTitle\n\n\n\nJernel Dermatologi Malaysia, Volume 1\nNow also known as Malaysian Journal of Dematology\n\n\n\nChief Editor\n\n\n\nFounding editor Chow Kim Weng followed by Rosidah Baba, \n\n\n\nMardziah Omar, Najeeb Safdar, Henry Foong and currently \n\n\n\nRohna Ridzwan\n\n\n\nPublisher\n\n\n\nPublished for Persatuan Dermatologi Malaysia  \n\n\n\n(Dermatological Society of Malaysia), 1987\n\n\n\nKDN 1505(6813)/10\n\n\n\nISSN 1511-5356 (YEAR 1999)\n\n\n\nSynopsis\n\n\n\nJernel Dermatologi Malaysia is currently known as Jurnal \n\n\n\nDermatologi Malaysia according to the updated Malay \n\n\n\nthesaurus. The journal is written in English, published \n\n\n\nannually but as off 2009, there are 2 issues published yearly. \n\n\n\nInitial paper written focus on review article by invitation \n\n\n\nonly, case reports and case series. With the inception of post-\n\n\n\ngraduate training for Masters in Advance Dermatology in \n\n\n\nMalaysia, original papers and clinical trials were written to be \n\n\n\nshared not only among Malaysian community but also to those \n\n\n\nin Western Pacific Region after it was accepted by Western \n\n\n\nPacific Research Index Medicus in November 2010.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50 \u2022   MJD 2012 Dec Vol 29\n\n\n\nTitle\n\n\n\nDermatologi Asas\n\n\n\nAuthor\n\n\n\nBA Adam\n\n\n\nPublisher\n\n\n\nUniversiti Malaya\n1991\n\n\n\nSynopsis\n\n\n\nMalay textbook in Dermatology for \nmedical students and medical officers.\n\n\n\nTitle\n\n\n\nConsensus statement -\nThe Management of \nPsoriasis\n\n\n\nAuthor\n\n\n\nChow Kim Weng &nd the team from \nMalaysian Dermatological Society \n\n\n\nEditor\n\n\n\nAcademy Medicine of Malaysia\n1996 \n\n\n\nSynopsis\n\n\n\nGuideline of psoriasis care for Malaysian \ndermatologists.\n\n\n\nTitle\n\n\n\nCurrent treatment in \nDermatology \n\n\n\nAuthor\n\n\n\nAdam, Basheer A\n\n\n\nPublisher\n\n\n\nUniversiti Malaya\n1994\n\n\n\nSynopsis\n\n\n\nDermatology Textbook in English for \nmedical students and medical officers.\n\n\n\nTitle\n\n\n\nA Guidebook on \nHistological Diagnosis\nof Inflammatory Skin \nDiseases  \n\n\n\nEditor\n\n\n\nP ]ayalakshmi, H H Suraiya, A Kreetharan\n\n\n\nPublished\n\n\n\n2001\n\n\n\nSynopsis\n\n\n\nThis book is to be commended for the \nMedical Officer or GP confronted with a \npatient with a skin disease and could also \nbe useful for the 1st year trainee specialist \nin dermatology.\n\n\n\nTitle\n\n\n\nContact & Occupational Dermatitis -\nLecture Notes for Beginners\n\n\n\nAuthor\n\n\n\nRohna Ridzwan\n\n\n\nPublisher\n\n\n\nSelf\n2012\nISBN 978-967-10420-1-4\n\n\n\nSynopsis\n\n\n\nQuick hand book for primary, secondary and tertiary dermatology care providers \nto recognising and managing contact and occupational dermatitis.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n51MJD 2012 Dec Vol 29   \u2022\n\n\n\nTitle\n\n\n\nProblem Orientated Atlas of \nDermatology for Primary Care \nProviders \n\n\n\nAuthor\n\n\n\nRohna Ridzwan, Nik Malihan, Noor Kaslina, Wahidah, \n\n\n\nNurhayati Mokhty\n\n\n\nPublisher\n\n\n\nSelayang Hospital\n\n\n\n2004\n\n\n\nISBN 983-420140-0-6\n\n\n\nSynopsis\n\n\n\nProblem orientated approach to diagnosing skin lesions \n\n\n\naccording to sites and characteristic of skin lesion.\n\n\n\nTitle\n\n\n\nDoc, patients\u2019 outcome is in your hands.\nImprove your clinical skill with \ndermatology clinical skill test kit \n\n\n\nAuthor\n\n\n\nRohna Ridzwan\n\n\n\nPublisher\n\n\n\nSelf\n\n\n\n2011 \n\n\n\nISBN 978-967-10420-0-7\n\n\n\nSynopsis\n\n\n\nSkin slides with multiple choice questions. Patients\u2019 outcome \n\n\n\ncan be predicted by the diagnosis chosen by the doctor.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52 \u2022   MJD 2012 Dec Vol 29\n\n\n\nTitle\n\n\n\nHow nurses can uphold corporate values -\nIn dermatology setting \n\n\n\nAuthor\n\n\n\nRohna Ridzwan, Riza & Team\n\n\n\nPublisher\n\n\n\nSelayang Hospital\n\n\n\n2004\n\n\n\nISBN 983-42140-1-4\n\n\n\nSynopsis\n\n\n\nThis book aid nurses to prioritize scheduling of patients with\n\n\n\nskin diseases, being professional, courteous and caring to\n\n\n\npatients in the clinic, ward and in day care centre.\n\n\n\nTitle\n\n\n\nAdverse drug reactions involving skin, \nliver & kidney -\nwhat health care providers should know \n\n\n\nEditor\n\n\n\nRohna Ridzwan, Tan Soek Siam, Ghazali TV Ahmad Kutty\n\n\n\nPublisher\n\n\n\nMinistry of Health, Malaysia\n\n\n\n2006  \n\n\n\nISBN 983-42140-2-2\n\n\n\nSynopsis\n\n\n\nThis book alert first line health providers on the early signs of \n\n\n\nadverse drug reactions and reduce delay in therapy.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n53MJD 2012 Dec Vol 29   \u2022\n\n\n\nTitle\n\n\n\nRahsia Jerawat Terbongkar -\nBagaimana Mengawal Jerawat\nDalam Masa 60 Hari\n\n\n\nAuthor\n\n\n\nHasseenah Hassan\n\n\n\nPublisher\n\n\n\nSelf\n\n\n\n2012 \n\n\n\nEbook available through http://www.drhasseenah.com/jerawa\n\n\n\nSynopsis\n\n\n\nControlling acne written in Malay by a private clinician \n\n\n\npractising aesthetic medicine.\n\n\n\nTitle\n\n\n\nPenyakit Kulit Kanak-Kanak\n\n\n\nAuthor\n\n\n\nWan Ghazali Wan Mohamed\n\n\n\nPublisher\n\n\n\nKuala Lumpur; Dewan Bahasa Pustaka\n2002, 2006\nISBN 9836271961\n\n\n\nSynopsis\n\n\n\nMalay textbook on skin diseases in children for the general \npublic especially parents and kindergarten supervisor.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54 \u2022   MJD 2012 Dec Vol 29\n\n\n\ncontents\nGENERAL DERMATOLOGY\n\n\n\nReview Article\nEpidemiology of Skin Diseases from \nthe Spectrum of Dermatitis and \nEczema\nAgnieszka D, Radoslaw S\n\n\n\nOriginal Article\nA 10-Year Retrospective Review of \nNon-Scarring Alopecia in a Tertiary \nHospital in Malaysia\nYin YL, Chew KL\n\n\n\nOriginal Article\nA 7-Year Retrospective Review of \nSkin Cancer at University Malaya \nMedical Centre: A Tertiary Centre \nExperience \nCh\u2019ng CC, Wong SM, Yin YL et al\n\n\n\nCase Report\nSquamous cell carcinoma arising \nfrom linear porokeratosis in a young \nChinese man\nYin YL, Chew KL, Koh CK et al\n \nCase Report\nPseudocyst of ear \nSumit Kaur\n\n\n\nPAEDIATRIC DERMATOLOGY\n    \nCase Report\nA case of cutaneous and \nparavertebral infantile \nhaemangioma\nNg SY, Sabeera BKI\n\n\n\nCase Report\nA rare case of suspected dystrophic \nepidermolysis bullosa pruriginosa\nSatya WY, Yuanita\n \n\n\n\nDERMATOLOGY THERAPEUTICS\n\n\n\nOriginal Article\nComparative study treatment of \nMelasma using 10% L-Ascorbic acid \nand 10% Zinc sulfate solution\nSatya WY, Wahyu L\n\n\n\nANOUNCEMENT \n\n\n\nNew CPG \nAcne management clinical\npractice guideline\nAsmah J\n\n\n\nCPD\n2013 AAD Annual Meeting\n\n\n\nMalaysian History\nPublication in Dermatology\nfrom Malaysia\n\n\n\n1\n\n\n\n12\n\n\n\n16\n\n\n\n23\n\n\n\n27\n\n\n\n30\n\n\n\n33\n\n\n\n38\n\n\n\n46\n\n\n\n48\n\n\n\n49\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\n\n"
"\n\n\n\n\n\nMalaysian Journal of\n\n\n\nMJD 2019 Dec Vol 43\n\n\n\nDermatologyMalaysian Journal of\n\n\n\nNotice to Authors\n\n\n\nDermatology\n\n\n\nThe Malaysian Journal of Dermatology welcome \nmanuscripts on all aspects of cutaneous medicine and \nsurgery in the form of original articles, research papers, case \nreports and correspondence. Contributions are accepted \nfor publication on condition that they are submitted \nexclusively to the Malaysian Journal of Dermatology. The \nPublisher and Editors cannot be held responsible for errors \nor any consequences arising from the use of information \ncontained in this journal; the views and opinions expressed \ndo not necessarily reflect those of the publisher and Editors, \nneither does the publication of advertisements constitute \nany endorsement by the publisher.\n\n\n\nManuscripts should be submitted via email to:\ntanwooichiang@yahoo.com\n\n\n\nQuestions regarding the Malaysian Journal of Dermatology\ncan be sent to: \ntanwooichiang@yahoo.com\n\n\n\nContributions should be written for one of the following \ncategories:\n\n\n\nCase Report*\nA report of 400-600 words, illustrated by no more than \nthree illustrations. This category offers a means for rapid \ncommunication about a single subject.\n\n\n\nCommentary*\nAn editorial 700-1200 words in length with approximately \nfive references. The author may express his or her opinion \nwithout complete documentation.\n\n\n\nClinicopathological Challenge*\nA photographic essay that includes both clinical and \npathological photographs in color. The diagnosis and \nlegends for the photographs should be listed after the \nreferences in the article. The article should be no more than \n2-3 pages in length.\n\n\n\nCorrespondence*\nLetters to the editor and short notes. Contributions should \nnot exceed 600 words, 2 figures, and 10 references.\n\n\n\nDermatological Surgery\nAn article relating to the surgical aspects of treatment. \nArticle types may include Review, Report or Case Report \nFormat.\n\n\n\nOriginal Article\nAn original article including, whenever possible, an \nIntroduction, Materials and Methods, Results, Comment \nand References. A Structured Abstract of not more than 240 \nwords must be included. It should consist of five paragraphs, \nlabelled Background, Methods, Results, Discussion and \nConclusion. It should describe the problem studies, how \nthe study was performed, the main results, and what the \nauthor(s) concluded from the results.\n\n\n\nReview\nBy invitation only. A major didactic article that clarifies \nand summarizes the existing knowledge in a particular \nfield. It should not be an exhaustive review of the literature, \nand references should not exceed 100 in number. Tables, \ndiagrams, and selected figures are often helpful. The length \nis left to the judgment of the author, although it generally \nshould not exceed 5000 words. Topics may include updates \nin clinically relevant basic science and cutaneous biology.\n\n\n\n*No abstract required\n\n\n\nManuscripts should include a title page bearing the title of \nthe paper, the author(s)\u2019 name(s), degrees, and affiliation(s), \nthe category of the article, the number of figures and tables, \nand three key words for indexing purposes. The name and \nfull postal address (including a street address), phone and fax \nnumbers and an email address of the corresponding author \nwho will be responsible for reading the proofs must also \nbe given on the title page. The author(s) must also declare \nany affiliation or significant financial involvement in any \norganizations or entity with a direct financial interest in the \nsubject matter or materials discussed in the manuscript on \nthis page.\n\n\n\nAll measurements should be according to the metric system. \nIf confusion could result, please include other measurement \nsystems in parentheses.\n\n\n\nRefer to patients by number or letters; names or initials \nshould not be used.\n\n\n\nReferences\nReferences must be listed in the order in which they appear \nin the manuscript. References from journals should include: \n(1) name(s) followed by the initials of the author(s), up to \nsix authors: if more than six authors, include the first six \nauthors followed by et al.; (2) title of paper; (3) title of the \njournal as abbreviated in the Index Medicus; (4) year of \npublication; (5) volume number; (6) first and final page \nnumbers of the article.\n\n\n\nFor example:\nAmbrose D, Gangaram HB, Hussein SH. Sporotrichosis: A \nHospital Kuala Lumpur experience. Malaysian J Dermatol \n2006;19:52-5.\n\n\n\nReferences to books should include: (1) author(s) or \neditor(s); (2) chapter (if any) book titles; (3) edition, \nvolume, etc.; (4) place of publication; (5) publisher; (6) \nyear; (7) page(s) referred to.\n\n\n\nFor example:\nFoong HBB. Transcontinental Dermatology: Virtual \nGrand Rounds. In: Wootton R and Oakley A, editors. \nTeledermatology. London. Royal Society of Medicine \n2002. p.127-34.\n\n\n\nThe author is responsible for the accuracy and completeness \nof all references; incomplete references may result in a \ndelay to publication.\n\n\n\nTables should be typed, double-spaced with a heading, \neach on a separate sheet, and should only include essential \ninformation. Drawings, graphs, and formulas should be \nsubmitted on separate pages.\n\n\n\nSend illustrations as tiff or jpeg files. In the case of \nphotomicrographs, the stain type and original magnification \nshould be stated. Each figure should bear a reference \nnumber corresponding to a similar number in the text.\n\n\n\nTo minimise the publication time of your manuscript it \nis important that all electronic artwork is supplied to the \nEditorial Office in the correct format and resolution.\n\n\n\nDisclaimer\nThe Publisher and Editors cannot be held responsible \nfor errors or any consequences arising from the use of \ninformation contained in this journal; the views and opinions \nexpressed do not necessarily reflect those of the publisher \nand Editors, neither does the publication of advertisements \nconstitute any endorsement by the publisher and Editors of \nthe products advertised.\n\n\n\n\n\n\n\n\nMJD 2019 Dec Vol 43\n\n\n\nMalaysian Journal of Dermatology\n\n\n\nREVIEW ARTICLE \n\n\n\n2 Vitiligo: Recent Advances in Pathogenesis and \nTherapy    \n\n\n\n Tang JJ\n\n\n\nORIGINAL ARTICLE\n\n\n\n11 Impact of Cutaneous Lupus Erythematosus on \nQuality of Life and Its Association with Anxiety \nand Depression   \n\n\n\n Kiing JW, Muniandy P\n\n\n\n21 Increased Risk of Non-alcoholic Fatty Liver \nDisease, Diabetes Mellitus and Hypertension \nin Patients with Plaque Psoriasis Compared to \nPatients with Generalized Pustular Psoriasis\n\n\n\n Wong KW, Choon SE, Tey KE, Abu Bakar K, Baherin \nH, Abdul Halim AZS\n\n\n\n29  Sexually Transmitted Infections in a State General \nHospital in Peninsular Malaysia\n\n\n\n Ramalingam R\n\n\n\n\n\n\n\nCASE REPORT \n\n\n\n36 Condylomata Acuminata in Children: Sexual Abuse \nor Not? A Case Series\n\n\n\n Wee AL\n\n\n\n39  Identification of p.Gly221_Gln231del, FS7X EDA \nMutation in 3 Siblings from a Malaysian Family of \nIndian Ethnicity Diagnosed with XLHED\n\n\n\n Tang MM, Oh GGK, Surana U, Pramano ZAD, Leong \nKF\n\n\n\n43  Epidermodysplasia Verruciformis: A Rare Case \nReport\n\n\n\n Verma V, Kar S, Patrick S, Gangane N, Bonde P, Ramteke \nK\n\n\n\n46  A Case of Devastating Ocular Sequelae of Stevens-\nJohnson Syndrome\n\n\n\n Rajandran S, Mohd Razali K, Mustapha M\n\n\n\n49  Light Chain Myeloma-associated Systemic Nodular \nCutaneous Amyloidosis \u2013 A Case Report and Review \nof Literature\n\n\n\n Ramalingam R\n\n\n\n54  Five Cases of Melanoma Presenting Over a Year in a \nSingle Institution\n\n\n\n Lim SZ, Keating RE, Toh YF, Chew MF, Kwan ZL\n\n\n\n58  Bags of Worms\n Low QJ, Cheo SW, Lim TH, Ab Latif LS, Yap EWY\n\n\n\nCLINICOPATHOLOGICAL CHALLENGE  \n\n\n\n60 A Case of Persistent Flexural Hyperpigmentation\n Tan CH, Lim J H-L\n\n\n\nRETRACTION NOTE \n\n\n\nACKNOWLEDGEMENT\n\n\n\nM A L A Y S I A N  J O U R N A L  O F  D E R M A T O L O G Y\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n1MJD 2019 Dec Vol 43\n\n\n\nEditor-in-Chief\nDr Tan Wooi Chiang\nMRCP, Adv M Derm\nGeorgetown, Penang\n\n\n\nCo-Editor \nDr Tang Min Moon\nMRCP, M Adv Derm\nWilayah Persekutuan Kuala Lumpur\n\n\n\nFounding Editor \nDr Steven Chow Kim Weng\nFRCP\nWilayah Persekutuan Kuala Lumpur\n\n\n\nEditorial Office\nDepartment of Dermatology (105)\nHospital Pulau Pinang\nJalan Residensi, \n10990 Georgetown, Penang\n\n\n\nExecutive Committee\nChan Lee Chin, MMed - President\nNoor Zalmy Azizan, Adv M Derm - Vice President\nSabeera Begum, MMed - Secretary\nTan Wooi Chiang, Adv M Derm - Treasurer\nAgnes Heng Yoke Hui, MRCP - Past President\nDr Tang Jyh Jong, Adv M Derm - Committee \nMember\nDr Peter Ch\u2019ng Wee Beng, Adv M Derm - \nCommittee Member\n\n\n\nPublished by Dermatological Society of Malaysia twice a year from year 2009 (June and December issues)\n\n\n\nPrinted by Vanda Dynamic Enterprise\n723E, 1st Floor, Vanda Business Park, Jalan Sungai Dua, 11700 Penang\nTel : 04-6584515 / 04-6578515 Fax : 04-6584505\n\n\n\n\u00ae2019 Persatuan Dermatologi Malaysia. All rights reserved.\nNo part of this journal can be reproduced without the written permission from editorial board.\n\n\n\nDr Teoh Tze Yuen, Adv M Derm - \nCommittee Member\nDr. Sharifah Rosniza Syed Nong Chek, \nAdv M Derm - Committee Member\n\n\n\nDermatological Society of Malaysia\n(Rumah Dermatology)\nG1, Medical Academics of Malaysia, 210, \nJalan Tun Razak, 50400 Kuala Lumpur, \nMalaysia\n\n\n\nDermatological Society of Malaysia  |  Persatuan Dermatologi Malaysia\n\n\n\nEditorial Board\nDr Henry Foong Boon Bee FRCP, FAMM                          \nIpoh, Perak\n\n\n\nDr Agnes Heng Yoke Hui MRCP                                  \nIpoh, Perak\n\n\n\nDr Chan Lee Chin MMed                                       \nGeorgetown, Penang\n\n\n\nDr Chang Choong Chor MRCP, Adv M Derm                            \nWilayah Persekutuan Kuala Lumpur \n\n\n\nAssoc Prof Dr Norashikin Shamsudin FRCP, \nAdv M Derm \nSerdang, Selangor\n\n\n\nAssoc Prof Dr Adawiyah Jamil MMed,     \nAdv M Derm      \nWilayah Persekutuan Kuala Lumpur\n\n\n\nAssoc Prof Dr Felix Yap Boon Bin MRCP, \nAdv M Derm \nWilayah Persekutuan Kuala Lumpur       \n\n\n\nDr Tang Jyh Jong MRCP, Adv M Derm                              \nIpoh, Perak\n\n\n\nDr Tarita Taib MMed, Adv M Derm                             \nSelayang, Selangor\n\n\n\nDr Ch\u2019ng Chin Chwen MRCP, Adv M Derm            \nWilayah Persekutuan Kuala Lumpur\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n2 MJD 2019 Dec Vol 43\n\n\n\nREVIEW\n\n\n\nVitiligo: Recent Advances in Pathogenesis and Therapy          \nJyh Jong Tang, AdvMDerm \n\n\n\nDepartment of Dermatology, Raja Permaisuri Bainun Hospital, Perak, Malaysia\n\n\n\nSummary\nVitiligo is an acquired pigmentary disorder with an estimated worldwide prevalence of 1-2%. \nVitiligo is clinically characterised by the development of white macules due to the loss of functioning \nmelanocytes in the skin or hair, or both. Two forms of the disease are well recognised: segmental \nand non-segmental vitiligo (the commonest form). This disorder can be psychologically devastating \nand stigmatising especially in dark skinned individuals. Hence, recognising this condition and early \ninitiation of treatment is important to ensure the success of therapy. Over the last decade, significant \nprogress has been made in understanding the pathogenesis of vitiligo. It is now theorized that vitiligo \nis a dynamic interplay between genetic, environmental factors, melanocyte oxidative stress, innate and \nadaptive immune responses.  One of the most important advances is the demonstration of the key role \nof the interferon gamma (INF-g)/Janus kinase (JAK)/CXCL10 pathway in the depigmentation process \nof vitiligo. Every component of this pathway represents a potential therapeutic target. This has leads \nto the discovery of emerging treatment such as janus kinase inhibitors in the management of vitiligo. \n\n\n\nKey words: Vitiligo, Segmental vitiligo, Non-segmental vitiligo, Janus kinase inhibitor,\n\n\n\nCorresponding Author\nDr Tang Jyh Jong\nDepartment of Dermatology, Hospital Raja Permaisuri \nBainun, Jalan Hospital, 30450 Ipoh, Perak\nEmail: tangjyhjong@gmail.com\n\n\n\nIntroduction\nVitiligo is an acquired chronic depigmenting disorder \nresulting from loss of epidermal melanocytes. It \nis a common pigmentary disorder affecting 1-2% \nof worldwide population.1 There is no sex or race \npredilection but usually begins in childhood or \nyoung adulthood. Half of the patients acquire this \ncondition before the age of 20 years. Vitiligo can \ncause significant psychosocial impact due to the \ncontrast between depigmented and normal skin. \nIndividuals with darker skin usually face more \nstigmatization, discrimination, and possibly major \npsychosocial problems. \n\n\n\nClassification\nBased on revised classification VGICC 2012,2 \nvitiligo can be classified into the following groups \ntwo major forms\u2014namely, non-segmental vitiligo \nand segmental vitiligo. Non-segmental vitiligo is the \ncommonest form of vitiligo and is characterised by \nsymmetrical and bilateral white patches. Different \nclinical subtypes have been described, including \ngeneralised, acrofacial and universalis types, all \nwith a bilateral distribution. \n\n\n\nVitiligo vulgaris or generalised vitiligo is the \ncommonest type of vitiligo with symmetrical \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n3MJD 2019 Dec Vol 43\n\n\n\ndistribution of the depigmentation and involvement \nof multiple sites especially periorificial, extensors, \nbony prominences and distal digits.3 Acrofacial \nvitiligo is a subtype of vitiligo vulgaris which \ninvolves face, distal digits of hands and feet. It \nmay later involve other body sites, resulting in \ntypical vitiligo vulgaris. Vitiligo universalis is a rare \nsubtype and is the most extensive form of the vitiligo \nwith complete or near complete depigmentation \nof the skin (80\u201390% of body surface), but some \npigmentation may be still present. \n\n\n\nSegmental vitiligo is less common than non-\nsegmental vitiligo and is characterized by unilateral \npatch of depigmentation which frequently affects \nthe face. It progresses quickly over 6 months to 2 \nyears but typically stabilizes without treatment. It \nis associated with early leukotrichia. The unilateral \npatch of depigmentation may be arranged in a linear \nor block-like pattern.4 The percentage of SV is higher \nin children compared to adults suggesting a mosaic \nskin developmental predisposition.5 Mixed vitiligo \nis a recently described subtype with segmental \ninvolvement preceding typical generalized vitiligo.6 \nThis subtype usually seen in paediatric group and \nthe presence of leukotrichia and halo nevi have been \nnoted as predictors of passage to mixed vitiligo in \npatients with SV.6 \n\n\n\nUnclassified vitiligo refers to focal cutaneous or \nmucosal vitiligo which is defined as a small isolated \npatch that does not fit a segmental distribution, and \nhas not evolved after a period of at least 2 years.3 \n\n\n\nAssociated Autoimmune Diseases\nVitiligo has been associated with an increased \nfrequency of autoimmune diseases. An \nepidemiological survey in the UK and North \nAmerica revealed that 19\u00b74% of patients with \nvitiligo aged more than 20 years had clinical history \n\n\n\nof autoimmune thyroid disease compared with \n2\u00b739% of the overall white population of the same \nage.7 Association of vitiligo with other autoimmune \ndiseases, such as rheumatoid arthritis, psoriasis, \nadult-onset diabetes mellitus, Addison\u2019s disease, \npernicious anaemia, alopecia areata, systemic lupus \nerythematosus, and atopic background has been \nshown in various studies although the frequency \nvaried.8,9,10 The association between vitiligo and \nthese autoimmune diseases has not yet been \nfully explained, but most likely related to shared \nunderlying genetic susceptibility to autoimmune \ndiseases. \n\n\n\nGenetic\nThe genetic origin of vitiligo is supported by \nfamilial occurrence of vitiligo. First-grade relatives \nhave a 6\u20138% risk of developing vitiligo while \nthe risk increases to 23% in monozygotic twins.7 \nVitiligo is inherited in a polygenic pattern with \napproximately 50 genetic loci as important risk \nfactors that contribute to vitiligo.11 The majority of \nthese genes are immunoregulatory genes confirming \nan important role for the immune system in vitiligo \npathogenesis. Some of these genes encode for \ninnate immunity (IFIH1, CASP7, NLRP1, TICAM1 \nand others) while others are involved in mediating \nadaptive immunity (CTLA4, CD80, HLA, GZMB, \nFOXP3 and others).12 \n\n\n\nApart from immune genes, there is a small subset of \ngene expressed in melanocytes supporting a role for \nintrinsic defect of melanocytes in initiating disease.  \nSeveral of these genes encode for proteins or \nenzymes that may serve as autoantigens (e.g., TYR, \nPMEL, MC1R, OCA2), while others are involved \nin the regulation of melanocyte development and \nsurvival (e.g., ZMIZ1), cell death during oxidative \nstress (e.g., RNASET2), and apoptosis (e.g., \nFGFR1OP, RERE, CASP7 GZMB).13 In addition, \nthe association of XPB1 with vitiligo supports a \nrole for the unfolded protein response pathway \nin pathogenesis which may also be important in \ninitiating inflammation.11,14\n\n\n\nEnvironmental triggers\nPhenolic and catecholic chemicals such as \nmonobenzyl ether of hydroquinone, rhododendrol \n4-tert-butylphenol, 4-tert-butylcatechol which can \nbe found in adhesive resins, industrial oils, paints, \nadhesives and hair dyes have been shown to trigger \nthe depigmentation in vitiligo.15,16,17,18,19,20 Skin \ntrauma (Koebner phenomenon) and ultraviolet \nradiation are also known environmental trigger for \nvitiligo.\n\n\n\nRevised Classification of Vitiligo Global \nIssues Consensus Conference 2012 (VGICC)\n1. Segmental\n2. Non segmental\n\n\n\n\u2022 Generalised (Vulgaris)\n\u2022 Acrofacial\n\u2022 Universalis\n\u2022 Mucosal (> 1 sites)\n\u2022 Mixed\n\n\n\n3. Unclassified\n\u2022 Focal\n\u2022 Mucosal (1 site)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n4 MJD 2019 Dec Vol 43\n\n\n\nPathogenesis\nOver the last decade, significant progress has been \nmade in understanding the pathogenesis of vitiligo. \nIt is now theorized that vitiligo is a dynamic interplay \nbetween genetic, environmental factors, melanocyte \noxidative stress, innate and adaptive immune \nresponses.21 Intrinsic defects in melanocytes that \nexhibit an elevated cellular stress response may \ntrigger disease through innate inflammation leading \nto autoimmune attack of epidermal melanocytes \nby cytototoxic T cells.22 The process begin with \nunfolded protein response and overproduction \nof reactive oxygen species (ROS) which lead to \noxidative stress in vulnerable melanocyte.  Stressed \nmelanocytes will then secrete heat shock proteins, \nespecially heat shock protein (HSP) 70 which have \nbeen found to be elevated in the skin of patients \nwith vitiligo and correlated with active disease.23\n\n\n\nDysregulated innate activation in response to \nmelanocyte stress will then recruit innate populations \nlike natural killer cells and inflammatory dendritic \ncells.12 Antigen presenting cells migrate out of the \nskin to draining lymph nodes to present melanocyte \nantigens to T cells and activate autoreactive CD8 +T \ncells which ultimately causes the final destruction of \nepidermal melanocytes.12 IFN-\u03b3 is required for the \nrecruitment of melanocyte-specific, autoreactive \nCD8 + T cells to the skin. Janus kinase (JAK)\u2013signal \ntransducer and activator of transcription (STAT) \nsignaling is essential to transmit extracellular \nsignals of IFN-\u03b3 to the nucleus. IFN- \u03b3 binds to \nJAK receptors (JAK1 and JAK2), which activate \nSTAT1 and produce the chemokine CXCL10, which \nproceeds to bind to the CXCR3 receptor on CD8 \ncytotoxic T cells.24,25,26,27\n\n\n\nThe interferon-\u03b3/CXCL10/CXCR3 pathway plays \nan important role in triggering the autoimmune \nmelanocytic destruction. Hence, blocking IFN-\u03b3/\nCXCL10/CXCR3 and JAK-STAT pathway is a \nviable new treatment strategy and it can open the \nsearch for more targeted therapy in vitiligo. The \nexpression of additional cytokines, including tumor \nnecrosis factor \u03b1, interleukin (IL)-6, and IL-17 has \nbeen reported in patients with vitiligo. However, \ntheir functional role is still unclear. 12\n\n\n\nClinical Markers of Disease Activity \nThe most extensively characterized clinical markers \nof active, progressive disease include the Koebner \nphenomenon, trichrome lesions, inflammatory \nlesions and confetti-like depigmentation. Koebner \n\n\n\nphenomenon is defined as the development of \nlesions at the site of traumatized, uninvolved skin. \nThose with greater body surface involvement and \nearlier age of involvement have a higher risk of \nthe Koebner phenomenon.28 Trichrome lesions \nhave 3 colors consisting of depigmented lesional \nskin, normally pigmented skin, and an intervening \nzone of hypopigmented skin usually at the border. \nThis lesion has been associated with active, rapidly \nprogressing disease.29 \n\n\n\nInflammatory vitiligo is a rare presentation \ncharacterized by erythema, scale and pruritus \nwithin the depigmented lesions especially at the \nlesional border. The inflammatory phase may be \nshort-lived, but associate with rapid enlargement \nof depigmentation. An infiltrate of lymphocytes \nand macrophages with concomitant disappearance \nof melanocytes has been reported in this form of \nvitiligo.30 Confetti-like depigmentation has been \nrecently described as a marker of rapidly progressive \nvitiligo.31 These lesions are characterized by \nnumerous clusters of small, 1 to 5-mm depigmented \nmacules, often located  at the periphery of existing \nlesions. The small lesions enlarge, and rapidly \ncoalesce and form larger, more typical lesions of \nvitiligo.32 It is important to recognize the signs \nof vitiligo activity as it is helpful in choosing the \nchoice of therapy. Stable disease can usually be \ntreated with topicals and phototherapy but patients \nwith active disease may also need to be treated \nwith systemic agents such as oral corticosteroids to \nstabilize their disease.\n\n\n\nDiagnosis\nVitiligo is usually a clinical diagnosis. Diagnosis \ncan be made by thorough history and examination \nfollowed by Wood\u2019s lamp examination which \nreveals a chalky white enhancement of depigmented \nskin. The differential diagnosis of vitiligo includes \nprogressive macular hypomelanosis, tinea \nversicolor, pityriasis alba, leprosy hypopigmented \nmycosis fungoides and nevus depigmentosus. \nHistopathologic examination may sometimes be \nnecessary to confirm the diagnosis of vitiligo. \nVitiligo lesion shows complete or near-complete \nloss of epidermal pigmentation with an absence \nof melanocytes at the basal layer.33 Early lesions \nwill show subtle interface dermatitis consisting of \nCD81 cytotoxic T cells infiltrating the epidermis \nwith the expanding edges of active lesions showing \nperivascular and perifollicular lymphocytic \ninfiltrate.12\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n5MJD 2019 Dec Vol 43\n\n\n\nTreatment\nOne of the biggest challenges in the management \nof patients with vitiligo is delayed in seeking \ntreatment. Patients are often told by their primary \ncare physician that vitiligo \u2018\u2018isn\u2019t a big deal,\u2019\u2019 and \nthere is \u2018\u2018nothing that can be done for it,\u2019\u2019 and they \n\u2018\u2018should just learn to live with it\u2019\u2019 This is a disservice, \nas the patients often arrive in a dermatologist\u2019s clinic \ndiscouraged after years of disease progression. \nOptimal treatment of vitiligo patients involved three \nobjectives: first, halting the disease progression; \nthen, allowing complete repigmentation of lesional \nareas; and, finally, preventing relapses.34\n\n\n\nA. Halting Disease Progression\n\n\n\nThe initial step in the management of vitiligo is to \nhalt or decrease the progression of active vitiligo. \nAn active vitiligo is characterized by history of rapid \nonset and ongoing extension of depigmented lesions \nor presence of Koebner phenomenon, trichrome \nlesions, inflammatory lesions, and confetti-like \ndepigmentation.  \n\n\n\nThere are 2 options of systemic medical therapy \nwhich can be used to halt disease progression: 1) \nSystemic steroids 2) Oral Methotrexate.\n\n\n\nSystemic steroids\nThere are few different regimes of systemic steroid \nused to arrest spreading vitiligo and to induce \nrepigmentation: daily oral low dose, high-dose \npulsed therapy or mini-pulsed regimen. Low-\ndose oral prednisolone (0.3 mg/kg) taken daily \nfor 2 months35 and a high dose of intravenous \nmethylprednisolone (8 mg/kg) administered on \n3 consecutive days36 were reported to halt disease \nprogression in more than 85% of cases and to induce \nsome repigmentation in more than 70% of cases. \nOral mini-pulsed steroid has been used widely to halt \ndisease activity while reducing potential side effects \nof steroid. Oral betamethasone or dexamethasone \nusing 5 mg twice a week on 2 consecutive days \nfor 3 months to 6 months has been shown to halt \nthe disease progression in more than 85% of cases \nbut a marked repigmentation was only observed \nin less than 7% of cases.37,38 Side effects such as \nweight gain, insomnia, acne, agitation, menstrual \ndisturbance and hypertrichosis ranged from 12% \nto 69%.37,38 Relapses after discontinuation of the \nsystemic steroid are not rare and therefore the use \nof such regime must be individualised based on the \nrisk and the benefit. \n \n\n\n\nMethotrexate \nThe efficacy of methotrexate (10 mg per week) was \ncomparable with oral mini-pulsed dexamethasone \n(5 mg per week with 2.5 mg taken on 2 consecutive \ndays) as demonstrated in a prospective randomized \nopen-label study in 52 vitiligo patients.39 Both \ndrugs had also a similar reduction in vitiligo disease \nactivity score. However, the data evaluating the use \nof methotrexate in vitiligo still remain limited. \n\n\n\nB. Repigmentation Therapies \n\n\n\nTopical Corticosteroids \nTopical corticosteroids remain as first line treatments \nfor small and localized vitiligo. The effectiveness \nof topical steroid for localized vitiligo has been \nconfirmed in a meta-analysis. However, low potent \ntopical corticosteroids has no therapeutic effect on \nvitiligo.40 Steroid-induced repigmentation occurs in \na perifollicular pattern and from the margins of the \nlesions usually within 1 to 4 months of treatment. \nProlonged use of topical steroid can associate \nwith epidermal atrophy, steroid induced acne, \nrosacea, telangiectasia, ecchymoses and striae. It \nis recommended to use topical steroids on limited \nskin areas to minimize the incidence of these side \neffects; Treatment-free period (treatment for 6 to \n8 weeks followed by a treatment-free interval of \nseveral weeks) or intermittent therapy (3 weeks \non and 1 week off or 5 days a week)  have been \nused to reduce the side effects. If there is no visible \nimprovement after 3 months, topical steroid should \nbe discontinued.34\n\n\n\nTopical Calcineurin Inhibitors \nTacrolimus 0.1% and pimecrolimus 1% have been \nshown to be comparable to clobetasol propionate \n0.05% in inducing repigmentation in vitiligo.41,42,43 \nFacial lesions responded faster and better compared \nwith non-facial lesions. Twice-daily application of \n0.1% tacrolimus provided better results compared \nwith once-daily applications.44 \n\n\n\nOther Topical Treatments \nTopical vitamin D analogues as monotherapy or \ncombined with phototherapy has not been shown to \nbe beneficial in treating vitiligo.45,46 The data on the \nuse of topical antioxidants for treating vitiligo is still \nlimited and remains controversial even though the \nrationale for using topical antioxidants in vitiligo is \nstrong.34 \n\n\n\nPhototherapy\nPhototherapy has long been used as an efficacious \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n6 MJD 2019 Dec Vol 43\n\n\n\ntreatment to induce repigmentation in vitiligo. \nNarrow-band UVB (NB-UVB) is the phototherapy \nof choice and is usually carried out two to three \ntimes weekly. Vitiligo usually requires several \nmonths of treatment with phototherapy before \nrepigmentation is observed. Hence patients need \nto be informed about the length of the treatment to \navoid premature discontinuation of the treatment \nas many expect to observe rapid repigmentation.  \n\n\n\nResponse to phototherapy is better on areas, \nsuch as the face while the response is generally \npoor for area such as hands and feet. Majority of \npatients will show signs of repigmentation (Figure \n1a-f) but only a small minority of patients have \ncomplete repigmentation.47 In addition, the patient \nshould be informed about the risk of relapse after \ndiscontinuation of phototherapy. \n\n\n\nFigure 1 (a) Baseline vitiligo vilgaris involving chest; (b) Near complete repigmentation after 12 months \nof  phototherapy with NBUVB twice a week; (c) Baseline segmental vitiligo vulgaris involving left hand; \n(d) Significant repigmentation after 6 months of phototherapy with NBUVB twice a week; (e) Baseline \nsegmental vitiligo involving left forehead and periorbital region; (f) Significant repigmentation after 6 months \nof phototherapy with NBUVB twice a week\n\n\n\na\n\n\n\nc\n\n\n\ne\n\n\n\nb\n\n\n\nd\n\n\n\nf\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n7MJD 2019 Dec Vol 43\n\n\n\nAbout half of patients will develop vitiligo lesions in \nrepigmented skin within the first year if phototherapy \nis discontinued.48,49 Hence,  phototherapy can be \ncontinued for a maximum of 1\u20132 years provided \nthe repigmentation continues.22 The combination of \nNB-UVB with topical corticosteroids and topical \ncalcineurin inhibitors has also been shown to \nincrease repigmentation rates.50 Photochemotherapy \nor PUVA shows less repigmentation compared with \nNB-UVB and is associated with higher side effects.51 \n\n\n\nAlthough 308-nm excimer laser may show faster \nrepigmentation compared with NB-UVB, there was \nno significant differences for \u226550% repigmentation \nbetween an excimer laser or NB-UVB.53 Side effects \nof phototherapy include dose-dependent burning \nof the skin and hyperpigmentation of the skin. \nThe risk of skin cancer development is correlated \nwith an increased number of phototherapy \nsessions especially for photochemotherapy but the \ncarcinogenic risk of NB-UVB treatment is less \nevident.53 No consensus exists on the maximum \nnumber of NB-UVB treatments considered to be \nsafe in vitiligo.22\n\n\n\nC. Preventing Vitiligo Relapses \n\n\n\nAfter successful repigmentation, the rate of \nrelapse in vitiligo patches is approximately 40%.54 \nThe use of biweekly application of tacrolimus \nointment 0.1% has been shown to be efficacious \nin reducing risk of depigmentation as compared \nto placebo (9.7% versus 40%, p=0.0075) in a \nprospective randomized study on 35 patients with \n72 non-segmental vitiligo lesions who achieved at \nleast 75% of repigmentation after phototherapy, \ntopical treatment, or a combination approach.55 \nThis maintenance treatment is only proposed in \npatients who had relapses after having achieved \nrepigmentation and it can be continued for at least 6 \nmonths without any sign of disease activity.34\n\n\n\nD. Other Treatment\n\n\n\nCosmetic: Camouflage\nA wide range of cosmetic products (including cover \ncreams, self-tanners) can be used as camouflage the \nvitiligo. This can reduce the negative impact of the \ndisease and social stress related to vitiligo. \n\n\n\nDepigmentation\nDepigmentation of the remaining pigmented \nareas can be considered in patients with vitiligo \nuniversalis or extensive vitiligo involving body \nsurface area 50 to 60% or disfiguring refractory \n\n\n\nvitiligo on the face or the hands. Various methods \nof depigmentation exist such as bleaching creams \n(e.g., monobenzyl ether of hydroquinone), laser \ntreatment, or cryotherapy. Monobenzyl ether of \nhydroquinone requires a relatively long duration \nof treatment up to 12-month period to achieve \nsatisfactory depigmentation. Multiple sessions are \nalso required for laser and cryotherapy induced \ndepigmentation.22\n\n\n\nSurgery\nDifferent melanocytes transplantation techniques \nhave been developed and is divided into cellular \ngraft transplantation and tissue grafting (e.g., \npunch grafting, split-thickness grafting, epidermal \nblister grafting). Melanocytes transplantation is \nmost effective in patients with stable segmental \nvitiligo.56 In patients with non-segmental vitiligo, \nmelanosytes transplantation has a higher chance of \nrepigmentation if the disease is stable for at least \n1\u20132 years and absence of Koebner phenomenon.22 \n\n\n\nCellular grafting (Noncultured epidermal \nsuspension) demonstrates superior extent and \nquality of pigmentation compared with other \nsurgical techniques and it is now considered the \ncriterion standard for vitiligo grafting worldwide.56\n\n\n\nPotential Emerging Medical Treatments \n\n\n\nA. Afamelanotide \nAfamelanotide is a melanocortin-1 receptor \nagonist, an endogenous peptide that stimulates \nmelanocyte proliferation and melanogenesis.57 A \nprospective randomized trial showed beneficial \nresult when afamelanotide (administrated monthly \nby subcutaneous implants) was combined with \nUVB (repigmentation rate of 48.64% at day 168) \ncompared with UVB alone (repigmentation rate \nof 33.26%). The result was better in dark-skinned \npatients The most frequent side effects were \nnausea, fatigue, erythema and hyperpigmentation.57 \nHowever, additional study is required to determine \nthe indications and the limitations of afamelanotide \nin the treatment of vitiligo. \n\n\n\nB. Janus Kinase Inhibitors \nRecent advances in the understanding of the \npathophysiology of vitiligo foster new therapeutic \nopportunities. One of the most important advances \nis the demonstration of the key role of the interferon \ngamma (INF-g)/Janus kinase (JAK)/CXCL10 \npathway in the depigmentation process of vitiligo. \nEvery component of this pathway represents a \npotential therapeutic target. Two JAK inhibitors, \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n8 MJD 2019 Dec Vol 43\n\n\n\ntofacitinib and ruxolitinib have been investigated in \nseparate case studies in which oral administration \nresulted in significant to complete repigmentation \nof vitiligo lesions and their discontinuation resulted \nin recurrence of depigmentation.58,59,60 Topical \nruxolitinib 1.5%  has shown efficacy in a 12-patient, \n20-week, open label study while a 32-week \nextension of this study with the same methodology \nshowed a statistically significant mean improvement \nin the overall Vitiligo Area Scoring Index score at \nweek 52.61,62 JAK inhibitors has been shown to have \nsynergistic effect with low-level light and therefore \nit may become an adjunct to phototherapy for \nvitiligo.63\n\n\n\nConclusion \nVitiligo is a common pigmentary disorder with \na large signifcant impact on patients\u2019 quality of \nlife, and therefore it should not be dismissed as \n\u2018\u2018simply cosmetic.\u2019\u2019 Distinct subtypes of vitiligo \nand lesion patterns are important to recognize \nbecause they influence prognosis through disease \nactivity, progression, and treatment responses. \nRecent understanding in the pathogenesis of vitiligo \nand risk factors for disease opens the interesting \nperspectives for innovative treatment strategies.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReference\n\n\n\n1. 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Topical 0.05% clobetasol \npropionate versus 1% pimecrolimus ointment in vitiligo. \nEur J Dermatol 2005;15:88-91.\n\n\n\n44. Radakovic S, Breier-Maly J, Konschitzky R, Kittler H, \nSator P, Hoenigsmann H et al. Response of vitiligo to \nonce- vs. twice-daily topical tacrolimus: a controlled \nprospective, randomized, observer-blinded trial. J Eur \nAcad Dermatol Venereol 2009;23:951-3.\n\n\n\n45. Chiaverini C, Passeron T, Ortonne JP. Treatment of vitiligo \nby topical calcipotriol. J Eur Acad Dermatol Venereol \n2002;16:137-8.\n\n\n\n46. Ada S, Sahin S, Boztepe G, Karaduman A, K\u00f6lemen. No \nadditional effect of topical calcipotriol on narrow-band \nUVB phototherapy in patients with generalized vitiligo. \nPhotodermatol Photoimmunol Photomed 2005;21:79-83.\n\n\n\n47. Anbar TS, Westerhof W, Abdel-Rahman AT, El- Khayyat \nMA. Evaluation of the effects of NB-UVB in both \nsegmental and nonsegmental vitiligo affecting different \nbody sites. 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Long-term results of noncultured epidermal cellular \ngrafting in vitiligo, halo naevi, piebaldism and naevus \ndepigmentosus. Br J Dermatol 2010;163:1186-93.\n\n\n\n57. Lim HW, Grimes PE, Agbai O, Hamzavi I, Henderson M, \nHaddican M et al. Afamelanotide and narrowband UV-B \nphototherapy for the treatment of vitiligo: a randomized \nmulticenter trial. JAMA Dermatol 2015;151:42-50.\n\n\n\n58. Damsky W, King BA. JAK inhibitors in dermatology: \nThe promise of a new drug class. J Am Acad Dermatol \n2017;76:736-44.\n\n\n\n59. Craiglow BG, King BA. Tofacitinib citrate for the \ntreatment of vitiligo: A pathogenesis-directed therapy. \nJAMA Dermatol 2015;151:1110-2.\n\n\n\n60. Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio \nG, Clynes R et al. Rapid skin repigmentation on oral \nruxolitinib in a patient with coexistent vitiligo and alopecia \nareata (AA). J Am Acad Dermatol 2016;74:370-1.\n\n\n\n61. Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H, \nTurkowski Y et al. Treatment of vitiligo with the topical \nJanus kinase inhibitor ruxolitinib. J Am Acad Dermatol \n2017;76:1054-60.e1.\n\n\n\n62. Joshipura D, Alomran A, Zancanaro P, Rosmarin D. \nTreatment of vitiligo with the topical Janus kinase inhibitor \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n10 MJD 2019 Dec Vol 43\n\n\n\nruxolitinib: a 32-week open-label extension study with \noptional narrow-band ultraviolet. B. J Am Acad Dermatol \n2018;78(6):1205\u20137.e1.\n\n\n\n63. Liu LY, Strassner JP, Refat MA, Harris JE, King BA et al. \nRepigmentation in vitiligo using the Janus kinase inhibitor \ntofacitinib may require concomitant light exposure. J Am \nAcad Dermatol 2017;77:675-82.e1.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n11MJD 2019 Dec Vol 43\n\n\n\nORIGINAL ARTICLE\n\n\n\nImpact of Cutaneous Lupus Erythematosus on Quality of Life and Its \nAssociation with Anxiety and Depression         \nJiu Wen Kiing, MRCP, Pubalan Muniandy, FRCP \n\n\n\nDepartment of Dermatology, Sarawak General Hospital, Kuching, Sarawak, Malaysia\n\n\n\nAbstract\nIntroduction:\nCutaneous Lupus Erythematosus (CLE) is believed to have a negative impact on patient\u2019s quality of \nlife (QOL) and psychosocial perspective. To determine the impact of CLE on patient\u2019s QOL and its \nassociation with anxiety and depression. \n\n\n\nMethods:\nThis was a cross sectional study done at a tertiary center, Sarawak General Hospital (SGH), \nKuching. There were 185 patients with CLE specific lesions, aged 18 and above, recruited into the \nstudy from January till December 2018. Patients were examined clinically and administered self-\nreported questionnaires including Dermatology Life Quality Index (DLQI) and Hospital Anxiety and \nDepression Scale (HADS).\n\n\n\nResults:\nThe female to male ratio was 7:1. The mean age of onset was 32.7 years. 62.7% of subjects had acute \ncutaneous lupus erythematosus (ACLE), 30.8% had chronic cutaneous lupus erythematosus (CCLE) \nand 6.5% had subacute cutaneous lupus erythematosus (SCLE). There were 48.7% CLE subjects with \nsignificant impairment in QOL. \u2018Embarrassment\u2019, \u2018social/leisure\u2019 and \u2018work/school\u2019 were interfered \nmost in patients\u2019 life. There were 42.2% patients with borderline anxiety or anxiety, whereas 29.8% \npatients had borderline depression or depression. Disease severity was significantly associated with \nhigher risk of anxiety and depression. \n\n\n\nConclusion:\nImpairment of QOL is common among CLE patients, particularly SCLE and CCLE subtypes with the \nmost commonly affected domain being \u2018embarrassment\u2019, \u2018social/leisure\u2019 and \u2018work/school\u2019. Anxiety \nand depression are common among CLE patients. Therapeutic approach should include managing the \npoor QOL and mood problems of the patients while treating CLE.\n\n\n\nKey words: Cutaneous Lupus Erythematosus, Quality of Life, Anxiety, Depression\n\n\n\nCorresponding Author\nDr Kiing Jiu Wen\nDepartment of Dermatology, Sarawak General Hospital, \nJalan Hospital, 93586 Kuching, Sarawak \nE-mail: rolandk_01@hotmail.com\n\n\n\nIntroduction\nCutaneous Lupus Erythematosus (CLE) has \nsignificant impact on quality of life whereby at least \nan estimated 50% of the patients have a moderate, \nvery large, or extremely large effect on quality of \nlife.1 Furthermore, CLE has significant impact on \npsychiatric disorders. According to the research \ndone by Jalenques et al., patients with skin restricted \nlupus had a high prevalence of several psychiatric \ndisorders including anxiety, depression, suicide risk \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n12 MJD 2019 Dec Vol 43\n\n\n\nand alcohol dependence.2 This study will elucidate \nclearly the impact of CLE on quality of life and \npsychological issues among CLE patients in a \ntertiary setting in Malaysia.\n\n\n\nMaterials and Methods\n\n\n\nStudy design \nWe performed a cross-sectional, single centre study \nbetween 1st January 2018 and 31st December 2018. \nThe study was conducted at the dermatology clinic, \nrheumatology clinic and medical ward in Sarawak \nGeneral Hospital, which was the only tertiary \nreferral center for dermatology service in Kuching, \nSarawak, Malaysia. The target population included \npatients aged 18 years old and above, who had been \ndiagnosed to have either chronic cutaneous lupus \nerythematosus (CCLE), subacute cutaneous lupus \nerythematosus (SCLE) or acute cutaneous lupus \nerythematosus (ACLE) on clinico-pathological \ncorrelation and who were followed up between 1st \nJanuary 2018 and 31st December 2018. \n\n\n\nThe diagnosis of CLE was confirmed by a senior \nconsultant dermatologist after reviewing the \nsubjects\u2019s clinical finding, histopathological \nfinding including immunofluorescence study and \nautoimmune serology markers. They were recruited \nfrom the dermatology clinic, rheumatology clinic \nor medical ward, Sarawak General Hospital. We \nexcluded those patients who were not able to \ncomplete the DLQI and HADS questionnaires \nand those presenting with LE-nonspecific lesion. \nPatient\u2019s demographic data, diagnosis, skin \ninvolvement, CLASI, DLQI and Hospital Anxiety \nAnd Depression Scales (HADS) were collected \nduring the study. \n\n\n\nIn patients with more than one CLE subtypes, the \nrespective subtype that was initially diagnosed \nwas defined as the main diagnosis in the analysis. \nFor the patients with more than one CLE subtypes \nsimultaneously, the form with the higher risk of \ndeveloping systemic manifestation was defined as \nthe main diagnosis (ACLE>SCLE>CCLE). \n\n\n\nStudy analysis and Ethical consideration\nSPSS statistical packages version 23.0 was used \nfor data collection and transformation. A SPSS \ndatabase was designed to enable a consistent, \ndetailed statistical analysis of the DLQI, CLASI \nand HADS. Each parameter was assigned a specific \nname in the SPSS, and a standard coding plan for \nthe numerical values was developed. The database \n\n\n\nwas analyzed with Fisher\u2019s exact test to adjust \nsmall case numbers. According to the respective \nquestion analyzed, a Kruskal-Wallis test, a Mann-\nWhitney U test, or an analysis of variance (one-way \nANOVA with scheffe post hoc test) were applied. \nP-values <0.05 were considered significant. Means \nwere presented with standard deviations. This study \nwas approved by the Medical Research and Ethics \nCommittee, Ministry of Health, Malaysia (NMRR-\n18-153-39665).\n\n\n\nResults\n\n\n\nDemographic characteristics\n185 patients participated in this study. Out of 185 \npatients, 161 (87.0%) were females and 24 (13.0%) \nwere males. The female to male ratio was 7:1. The \nyoungest was 18.0 years, whereas the oldest was \n97.0 years. The mean age of the subjects at the time \nof participation was 42.7 years with the median age \nof 41.0 years. Regarding the subjects\u2019 education \nlevels, 103 subjects (55.7%) had obtained secondary \nschool education level and 49 subjects (26.5%) had \nobtained post-secondary school education level. \nHowever, there were 27 subjects (14.6%) with \nlower education level and the remaining 6 subjects \n(3.2%) had not received any formal education. Our \ndata showed that 53.0% of the subjects were from \n\u2018lower\u2019 and \u2018lower middle income\u2019 group consisting \nof 98 subjects, whereas the other 47.0% of the \nsubjects were from \u2018upper middle\u2019 and \u2018high income\u2019 \ngroup with 87 subjects. 117 subjects (63.2%) were \nmarried, 53 subjects (28.6%) were single, and 15 \nsubjects (8.1%) were divorced or widowed. The \nmean age of onset of CLE among the study subjects \nwas (mean\u00b1SD) 32.7\u00b114.6 years old, ranged 9-96 \nyears old. Majority of the patients denied smoking \nduring the disease onset (n=161, 87%). \n\n\n\nClinical characteristics\nAmong those study subjects (n=185), 116 (62.7%) \npatients were diagnosed to have ACLE (86 patients \nwith localized and 30 patients with generalized \nform), 12 (6.5%) patients were diagnosed to have \nSCLE (all are papulosquamous form) and 57 \n(30.8%) patients were diagnosed to have CCLE \n(24 patients with localized DLE, 32 patients with \ngeneralized form of DLE and 1 patient with LE \npanniculitis).  As all of our patients were Asian, \nthus our patients had skin phototype of III (n=77, \n41.6%), IV (n=105, 56.8%) or V (n=3, 1.6%). Our \nstudy subjects were mainly SLE patients with the \nnumber of 139 patients (75.1%), whereas the other \n46 (24.9%) patients had CLE without systemic \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n13MJD 2019 Dec Vol 43\n\n\n\ninvolvement. The mean body surface area affected \nwas 4.8% (\u00b18.2) and it ranged from minimum 4.0% \nto maximum 90.0%. 181 (97.8%) patients had \nlesions over visible areas such as scalp, face, and \nupper chest, whereas the other 4 (2.2%) patients had \nlesions over the covered areas.\n \nSeverity of cutaneous involvement\nAmong the 185 subjects, the total CLASI activity \nand damage mean score was 3.3\u00b14.7 and 6.5\u00b18.4 \nrespectively. The total CLASI activity score was \nfound to be statistically significant higher in patients \nwith SCLE (mean\u00b1SD; 11.3\u00b17.3), followed by \npatients with CCLE (mean\u00b1SD; 4.0\u00b14.9) and ACLE \n(mean\u00b1SD; 2.1\u00b13.2) (p=0.000). Patients with CCLE \nwere observed to have statistically significant \nhigher CLASI damage score (mean\u00b1SD; 11.7\u00b19.5), \nfollowed by patients with SCLE (mean\u00b1SD; 9\u00b17.5) \nand ACLE (mean\u00b1SD; 3.7\u00b16.4) (p=0.000).\n \nThe CLASI activity score was observed to be \nstatistically significant higher in patients who had \never smoked (mean\u00b1SD; 5.7\u00b16.3) than in CLE \npatients who had never smoked (mean\u00b1SD; 2.9\u00b14.3) \n(p=0.005), whereas the CLASI damage score was \nstatistically significant higher in CLE patients who \nhad ever smoked (mean\u00b1SD; 11.0\u00b19.6) than in CLE \npatients who had never smoked (mean\u00b1SD; 5.8\u00b18.0) \n(p=0.003). The CLASI damage scores correlated \nwith CLASI activity scores (r=0.304, p=0.002).\n\n\n\nDLQI and CLE\nThere were 51.3% (n=95) of subjects with small or \nno effect at all on the patient\u2019s life. The remaining \n48.7% (n=90) of the subjects had moderate effect \n(22.7%, n=42), very large effect (22.2%, n=41) or \nextremely large effect (3.8%, n=7). Among patients \nwith ACLE, there were 44.9% (n=52) patients with \na moderate to extremely large effect on quality of \nlife.\n \nThe effect was observed to be greater in patients \nwith SCLE and CCLE with 66.7% (n=8) and 52.7% \n(n=30) respectively, with a moderate to extremely \nlarge effect on quality of life. The mean DLQI score \nwas 6.7 (SD\u00b16.2) for the whole study subjects and it \nranged from minimal score 0 to maximum score 27. \nThe mean DLQI score was statistically significant \nhigher among patients with SCLE (mean\u00b1SD; \n11.9\u00b19.4), which was followed by CCLE (mean\u00b1SD; \n7.7\u00b16.5) and ACLE (mean\u00b1SD; 5.7\u00b15.4) (p=0.017).\n\n\n\nFactors related to quality of life among study \nsubjects\nAmong study subjects, we analyzed the clinical \n\n\n\nand demographic factors ( including age, gender, \nincome, education level, marital status, presence \nor absence of SLE, CLE subtypes, disease severity, \npercentages of body surface area involvement, \nvisible body lesions, disease duration and smoking \nhistory) to  determine association with poor \nquality of life, as determined by DLQI. There was \nno statistically significant difference in term of \nDLQI scoring between male and female subjects \n(p=0.232).\n \nThe age of the subjects had a weak negative linear \nrelationship with the DLQI scoring as it showed \nthat the older subjects tended to score lower \nDLQI scores (r=-0.155, p=0.035). There was no \nstatistically significant difference in term of DLQI \nscoring among the different household income \n(p=0.463) and different education level (p=0.235). \nFurthermore, factors such as marital status, presence \nor absence of SLE, presence of visible body lesions, \nsmoking status and disease duration were not \nstatistically significant in affecting the mean DLQI \nscoring (p=0.423, p=0.083, p=0.547, p=0.266 \nand p=0.183 respectively). CLE subtypes was \nstatistically significant in affecting the DLQI mean \nscoring with SCLE subtypes with the highest score, \nfollowed by CCLE then ACLE (p=0.017). There \nwere mild to moderate positive linear relationship \nbetween the DLQI and the CLASI scores (r=0.390, \np=0.000 for CLASI total scores; r=0.304, p=0.000 \nfor CLASI activity scores; r=0.296, p=0.000 for \nCLASI damage scores). When the disease severity \nwas taken into account, the mean DLQI scores was \n6.1 (moderate effect on QOL) in patients with mild \ndisease, 10.6 (moderate effect on QOL) in patients \nwith moderate disease and 16.8 (very large effect on \nQOL) for those patients with severe disease. \n\n\n\nThere was weak positive linear relationship between \nthe percentage of body surface area affected by the \nCLE and DLQI mean score (r=0.372 and p=0.000). \nAs for the domains studied by the DLQI, the \ndomains concerning embarrassment (mean\u00b1SD; \n0.9\u00b11.0), social/leisure (mean\u00b1SD; 0.9\u00b11) and \nwork/school (mean\u00b1SD; 0.9\u00b11.2) were interfered \nmost in the patients\u2019 life due to the disease. The least \naffected domain in quality of life among the patients \nwas sexual life (mean\u00b1SD; 0.2\u00b10.6) (Table 1).\n  \nHADS and CLE\nThe overall mean total anxiety score (HADS-A) for \nall study subjects was 6.8\u00b13.7 (Mean\u00b1SD) and the \noverall mean total depression score (HADS-D) was \n5.5\u00b13.8 (Mean\u00b1SD). There were 57.8% (n=107) of \npatients who scored \u2018normal\u2019, 25.4% (n=47) scored \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n14 MJD 2019 Dec Vol 43\n\n\n\n\u2018borderline abnormal\u2019 and 16.8% (n=31) scored \n\u2018abnormal\u2019 in the HADS-A. On the other hand, there \nwere 70.3% (n=130) of the patients scored \u2018normal, \n16.8% (n=31) scored \u2018borderline abnormal\u2019 and \n13% (n=24) scored \u2018abnormal\u2019 in HADS-D. There \nwere relatively higher number of patients found to \nhave anxiety (HADS-A score\u226511) in SCLE group \n(33.3%, n=4), followed by CCLE group (17.5%, \nn=10) then ACLE group (14.7%, n=17).\n\n\n\nThere was statistically significant higher number of \npatients found to have depression (HADS-D\u226511) in \nSCLE group (25%, n=3), followed by CCLE group \n(15.8%, n=9) then ACLE group (10.3%, n=12) \n(p=0.043). Among the difference CLE subtypes, \nSCLE group scored the highest mean HADS-A \nscore (8.8), followed by CCLE (7.0) and then ACLE \n(6.4). On the other hand, CCLE group scored the \nhighest mean HADS-D score (6.5), followed by \nSCLE (5.8) and then ACLE (4.9). The difference in \nmean HADS-D scoring was statistically significant \n(p=0.015). \n\n\n\nFactors related to anxiety and depression among \nstudy subjects\nWe had analyzed the clinical and demographic \nfactors (including age, gender, income, education \nlevel, marital status, presence or absence of SLE, \ndisease severity, percentage of body surface area \ninvolvement, visible body lesions, disease duration \nand smoking history) as well as DLQI of the study \nsubjects to determine association with anxiety and \ndepression, as determined by HADS. There was \nstatistically significant weak negative correlation \nbetween the age of the subjects and the total anxiety \nscore (r=-.0.208, p=0.05).\n \nHowever the correlation between the age of the \nsubjects and the total depression score was very weak \nand statistically insignificant (r=-0.056, p=0.449). \nOverall, the mean total anxiety score was higher \nfor female subjects (6.9) than male subjects (6.2), \nbut the difference was not statistically significant \n(p=0.441). However the mean total depression \nscore was higher for male subjects (6.8) than female \nsubjects (5.3), but the difference was also not \nstatistically significant (p=0.088). The household \nincome of the subjects did not have statistically \nsignificant influence in total anxiety and depression \nscoring (p=0.217 and p=0.129 respectively).\n \nThere was no statistically significant difference \namong different education level groups in term of \ntotal anxiety and total depression scoring (p=0.388 \n\n\n\nand p=0.118 respectively). Single and divorcee/\nwidow/widower had statistically significant higher \ntotal anxiety score compared to married patients \n(p=0.007). Single and divorcee/widow/widowers \nwere also found to have statistically significant \nhigher total depression score compared to married \npatients (p=0.04). There was no statistically \nsignificant difference in anxiety scoring between the \npatient with underlying SLE and those without SLE \n(p=0.973). The difference between SLE and those \nwithout SLE in term of total depression scoring was \nnot statistically significant (p=0.077).\n \nThe correlation between the CLASI activity and \nthe total anxiety score (r=0.102, p=0.169) and the \ncorrelation between the CLASI activity and the \ntotal depression score (r=0.067, p=0.361) were very \nweak and statistically insignificant. The CLASI \ndamage score was found to have weak correlation \nwith the total anxiety score and statistically tested \nsignificant (r=0.179, p=0.015). The CLASI damage \nscore was also found to have correlation with \nthe total depression score and statistically tested \nsignificant (r=0.230, p=0.002). Body surface area \nhad statistically significant weak correlation with \nthe total anxiety score (r=0.245, p=0.001) and total \ndepression score (r=0.242, p=0.001).\n \nThere was no statistically significant difference in \ntotal anxiety score between the subjects with visible \nskin lesions and the subjects without visible skin \nlesions (p=0.989). There was also no statistically \nsignificant difference in term of total depression \nscore between the subjects with visible skin lesions \nand the subjects without visible skin lesions \n(p=0.586).\n \nThere was no statistically significant correlation \nbetween the duration of symptoms and the total \nanxiety (r=-0.093, p=0.208) or total depression \nscore (r=-0.073, p=0.322). Smoking status did not \nstatistically affect the total anxiety and depression \nscore (p=0.758 and p=0.110 respectively). There \nwas statistically significant correlation between \nthe DLQI mean score and the total anxiety score \n(r=0.538, p=0.000). There was also statistically \nsignificant correlation between the DLQI mean \nscore and the total depression score (r=0.382, \np=0.000) (Table 2).\n\n\n\nDiscussion\nDLQI is the first dermatology-specific health-related \nquality-of-life (HRQoL) instrument developed \nby Finlay and Kahn in 1994.3 DLQI is a self-\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n15MJD 2019 Dec Vol 43\n\n\n\nTable 1. Variables associated with quality of life impairment measured on the Dermatology Life Quality Index \n(DLQI)\n\n\n\nVariables DLQI Score (Mean\u00b1SD) P-Value\nDemographic variables\nAge (years) NA p=0.035*\n\n\n\nr=-0.155\nGender Male: 7.9\u00b16.5\n\n\n\nFemale: 6.5\u00b16.2\np=0.232\u02b7\n\n\n\nHousehold income Low income: 8.1\u00b17.4\nLower middle: 6.2\u00b15.6\nUpper middle: 6.4\u00b15.9\nHigh income: 5.8\u00b15.6\n\n\n\np=0.463 \u0368\n\n\n\nEducation level No education: 2.2\u00b11.7\nPrimary school: 6.9\u00b16.4\n\n\n\nSecondary school: 6.9\u00b16.5\nPost-secondary: 6.9\u00b15.7\n\n\n\np=0.235 \u0368\n\n\n\nMarital status Single: 7.3\u00b15.7\nMarried: 6.4\u00b16.3\n\n\n\nDivorcee/Widow/Widower: 6.4\u00b17.3\n\n\n\np=0.423 \u0368\n\n\n\nDisease variables\nDisease duration (months) NA p=0.183*\n\n\n\nr=-0.098\nCLASI activity Mild: 6.1\u00b15.7\n\n\n\nModerate: 10.6\u00b17.9\nSevere: 16.8\u00b17.9\n\n\n\np=0.003 \u0368 \n\n\n\nCLASI damage NA p=0.000*\nr=0.296\n\n\n\nCLASI total score NA p=0.000*\nr=0.390\n\n\n\nBSA(%) NA p=0.000*\nr=0.372\n\n\n\nVisible body lesions Yes: 6.7\u00b16.3\nNo: 4.5\u00b13.7\n\n\n\np=0.547\u02b7\n\n\n\nSmoker Yes: 8.3\u00b17.5\nNo: 6.5\u00b16.0\n\n\n\np=0.266\u02b7\n\n\n\nSLE Yes: 6.1\u00b15.6\nNo: 8.4\u00b17.5\n\n\n\np=0.083\u02b7\n\n\n\nCLE subtypes ACLE: 5.7\u00b15.4\nSCLE: 11.9\u00b19.4\nCCLE: 7.7\u00b16.5\n\n\n\np=0.017 \u0368\n\n\n\n*p values were calculated by using Spearman\u2019s Rank-Order Correlation. \u02b7p values were calculated by using Mann-Whitney U test. \u0368 p \nvalues were calculated by using Kruskal-Wallis test. NA=Not applicable. r=Spearman correlation coefficient.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n16 MJD 2019 Dec Vol 43\n\n\n\nTable 2. Variables associated with mood impairment measured on the HADS\n\n\n\nVariables Anxiety Score\n(Mean\u00b1SD)\n\n\n\nP-Value Depression Score \n(Mean\u00b1SD)\n\n\n\nP-Value\n\n\n\nDemographic variables\nAge (years) NA p=0.005*\n\n\n\nr=-0.208\nNA p=0.449*\n\n\n\nr=-0.056\nGender Male: 6.2\u00b13.3\n\n\n\nFemale: 6.9\u00b13.7\np=0.441\u02b7 Male: 6.8\u00b14.0\n\n\n\nFemale: 5.3\u00b13.8\np=0.088\u02b7\n\n\n\nHousehold income Low income: 6.8\u00b13.9\nLower middle: 6.9\u00b13.9\nUpper middle: 7.3\u00b13.8\nHigh income: 5.8\u00b13.0\n\n\n\np=0.217 \u0368 Low income: 5.7\u00b13.6\nLower middle: 6.3\u00b14.1\nUpper middle: 5.2\u00b14.0\nHigh income: 4.4\u00b13.5\n\n\n\np=0.129 \u0368\n\n\n\nEducation level No education: 5.3\u00b13.7\nPrimary school: 6.7\u00b14.3\n\n\n\nSecondary school: 6.7\u00b13.8\nPost-secondary: 7.2\u00b13.2\n\n\n\np=0.388 \u0368 No education: 6.5\u00b15.9\nPrimary school: 6.7\u00b13.7\n\n\n\nSecondary school: 5.5\u00b13.9\nPost-secondary: 4.7\u00b13.3\n\n\n\np=0.118 \u0368\n\n\n\nMarital status Single: 7.9\u00b13.2\nMarried: 6.2\u00b13.8\n\n\n\nDivorcee/Widow/Widower: \n7.4\u00b14.0\n\n\n\np=0.007 \u0368 Single: 6.2\u00b13.4\nMarried: 5.0\u00b14.0\n\n\n\nDivorcee/Widow/Widower: \n6.1\u00b13.2\n\n\n\np=0.040 \u0368\n\n\n\nDisease variables\nDisease duration \n(months)\n\n\n\nNA P=0.208*\nr=-0.093\n\n\n\nNA p=0.322*\nr=-0.073\n\n\n\nCLASI activity Mild: 6.6\u00b13.5\nModerate: 8.4\u00b15.2\n\n\n\nSevere: 9.8\u00b11.9\n\n\n\np=0.065 \u0368 Mild: 5.3\u00b13.8\nModerate: 7.0\u00b13.7\n\n\n\nSevere: 8.3\u00b14.6\n\n\n\np=0.093 \u0368 \n\n\n\nCLASI damage NA p=0.015*\nr=0.179\n\n\n\nNA p=0.002*\nr=0.230\n\n\n\nCLASI total score NA p=0.001*\nr=0.232\n\n\n\nNA p=0.001*\nr=0.242\n\n\n\nBSA(%) NA p=0.001*\nr=0.245\n\n\n\nNA p=0.001*\nr=0.242\n\n\n\nVisible body lesions Yes: 6.8\u00b13.7\nNo: 7.0\u00b14.6\n\n\n\np=0.989\u02b7 Yes: 5.4\u00b13.8\nNo: 6.3\u00b13.4\n\n\n\np=0.586\u02b7\n\n\n\nSmoker Yes: 7.1\u00b13.6\nNo: 6.7\u00b13.7\n\n\n\np=0.758\u02b7 Yes: 6.7 \u00b14.0\nNo: 5.3\u00b13.8\n\n\n\np=0.110\u02b7\n\n\n\nSLE Yes: 6.8\u00b13.7\nNo: 6.8\u00b13.7\n\n\n\np=0.973\u02b7 Yes: 5.2\u00b13.8\nNo: 6.3\u00b13.9\n\n\n\np=0.077\u02b7\n\n\n\nCLE subtypes ACLE: 6.5\u00b13.5\nSCLE: 8.8\u00b14.8\nCCLE: 7.0\u00b13.8\n\n\n\np=0.202 \u0368 ACLE: 4.9\u00b13.8\nSCLE: 5.8\u00b14.2\nCCLE: 6.5\u00b13.7\n\n\n\np=0.015 \u0368\n\n\n\nDLQI NA p=0.000*\nr=0.538\n\n\n\nNA p=0.000*\nr=0.382\n\n\n\n*p values were calculated by using Spearman\u2019s Rank-Order Correlation. \u02b7p values were calculated by using Mann-Whitney U test. \u0368 p \nvalues were calculated by using Kruskal-Wallis test. NA=Not applicable. r=Spearman correlation coefficient.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n17MJD 2019 Dec Vol 43\n\n\n\nTable 3. Comparing DLQI mean score among CCLE, SCLE and ACLE\n\n\n\nTable 4. Comparing the DLQI performance among study subjects with different subtypes of CLE\n\n\n\nTable 5. The mean score of the DLQI and each component of the DLQI\n\n\n\nDLQI\n(Mean\u00b1SD)\n\n\n\nCCLE \nPresent study\n\n\n\n(n=57)\n7.7\u00b16.5\n\n\n\nBatalla et al 2013, Spain\n(n=29)\n\n\n\n6.8\u00b16.8\n\n\n\nSCLE Present study\n(n=12)\n\n\n\n11.9\u00b19.4\n\n\n\nBatalla et al 2013, Spain\n(n=4)\n\n\n\n5.8\u00b13.7\n\n\n\nACLE Present study\n(n=116)\n\n\n\n5.7\u00b15.4\n\n\n\nBatalla et al 2013, Spain\n(n=3)\n\n\n\n17.7\u00b16.1\n\n\n\nDLQI Performance Among Study Subjects (number, percentages)\nNo impact Slight impact Moderate \n\n\n\nimpact\nLarge impact Extremely \n\n\n\nlarge impact\nACLE Present study\n\n\n\n(n=116)\n36(31) 28(24.1) 26(22.4) 25(21.6) 1(0.9)\n\n\n\nBatalla et al 2013, Spain\n(n=3)\n\n\n\n0(0) 0(0) 0(0) 2(66.7) 1(33.3)\n\n\n\nSCLE Present study\n(n=12)\n\n\n\n1(8.3) 3(25) 3(25) 2(16.7) 3(25)\n\n\n\nBatalla et al 2013, Spain\n(n=4)\n\n\n\n1(25) 0(0) 0(0) 3(75) 0(0)\n\n\n\nCCLE Present study\n(n=57)\n\n\n\n10(17.5) 17(29.8) 13(22.8) 14(24.6) 3(5.3)\n\n\n\nBatalla et al 2013, Spain\n(n=34)\n\n\n\n9(26.5) 9(26.5) 6(17.6) 8(23.5) 2(5.9)\n\n\n\nQuestionnaire DLQI Mean Score\nFerraz LB et al 2005, Brazil (n=71) Present study (n=185)\n\n\n\nDLQI 6.5 6.7\nSymptoms 1.18 0.82\n\n\n\nEmbarrassment 1.00 0.88\nDaily Activities 0.51 0.80\n\n\n\nClothes 0.72 0.63\nSocial/Leisure 1.15 0.87\n\n\n\nSports 0.25 0.82\nWork/School 0.49 0.86\nRelationships 0.17 0.43\n\n\n\nSexual life 0.11 0.22\nTreatment 0.79 0.37\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n18 MJD 2019 Dec Vol 43\n\n\n\nadministered 10 items questionnaire which covers \nsymptoms and feeling, daily activities, leisure, work \nand school, personal relationship and treatment. We \nselected DLQI as our study tool because it has been \naccepted as the standard to measure HRQoL for \ndermatology patients by physicians and researchers \nand it may serve as a historical comparator. Our \nstudy showed the overall mean DLQI score was \n6.7 which was comparable with the study done \nby Ferraz LB et al. They evaluated the QOL in 71 \npatients with lupus erythematosus and skin lesions \nand found out that the mean DLQI score was 6.5.4 \nOur study showed that CCLE group had higher \nmean DLQI score compared to ACLE group which \ncould be explained due to the difference in the \nspectrum of the cutaneous lesions, in which DLE \nlesions tend to have worse cosmetic effect, whereas \nacute LE lesions are fleeting and disappear without \nscars and pigmentary disturbances.\n \nFurthermore, preoccupation with a serious systemic \ndisease in patients with SLE could minimize the \nattention given to the cutaneous lesions and lead \nto better adaptation to the disease and small impact \non the QOL compared to the DLE group.5 SCLE \nwas found to have higher DLQI mean score as they \nhad higher CLASI activity mean score (11.3\u00b17.3) \ncompare to other subtypes in our study and this \ninfers that they causing more impairment in QOL \nto the patients. On the other hand, CCLE group \n(majority were DLE) who had the highest CLASI \ndamage mean score (11.7\u00b19.5) but had lower DLQI \nmean score than the SCLE because majority of these \npatients were in remission without symptoms after \ntreatment and with scarring and dyspigmentation as \nsequelae.\n \nDue to chronicity of the CCLE, there was a possibility \nthat most of these groups of patient had accepted and \nadapted to their appearance. Regarding the domains \nstudied by the DLQI, the first three domains with \nthe highest score in our study were \u2018embarrassment\u2019 \n(Mean score: 0.9), \u2018social/leisure\u2019 (Mean score: 0.9) \nand \u2018work/school\u2019 (Mean score: 0.9). The cutaneous \n\u2018symptoms\u2019were not the major concern in our study \nwhich may be due to the fact that large proportion of \nour CLE patients were already on treatment during \nthe time of recruitment. Furthermore, as large \nproportion of our study subjects were SLE patients \n(n=139, 75.1%) who had more concern about their \nserious systemic disease rather than the transient \nskin lesions, the dermatological \u2018symptoms\u2019 could \nalways be ignored by them.\n \n\n\n\nIn view of CLE occurring over sun-exposed \nareas, a majority of patients will feel embarrassed \nbecause of the visible lesions. Furthermore, they \nmay also withdraw themselves from society due to \nembarrassment including avoidance from social and \nleisure activity and work or school. Factors such as \ncosmetic considerations, concern for subsequent \nflares, and impaired outdoor activities can \nsignificantly reduce quality of life even when lupus \ndisease becomes less active. The younger patients \ntend to score higher DLQI mean score compared to \nthe older patients. This could be explained due to \nyounger patients being more concerned with their \nappearance. \n\n\n\nThe comparison between our study and other \nresearch studies are shown in the following tables \n(Table 3, Table 4, Table 5, and Table 6). Although \nin the past, many researches were done to assess the \nimpairment of QOL due to lupus using DLQI as an \nassessment tool, but there were some deficiencies \nin the DLQI assessment tool as it did not include \nthe assessment of anxiety and depression. In order \nto screen the anxiety and depression of the patients, \nZigmond AS and Snaith RP had developed HADS \nin 1983.6 HADS is a validated, useful psychiatric \nscreening tool and performs well in assessing \nthe symptom severity of anxiety disorders and \ndepression in both somatic, psychiatric and primary \ncare patients and in the general population.7 We \nfound out that younger age group patients tend \nto score higher HADS-A (r=-0.208, p=0.05) and \nHADS-D (r=-0.056, p=0.449). \n\n\n\nA Danish nationwide cohort study showed that the \nrisk of depression was more pronounced in patients \ndiagnosed with CLE or SLE < 50 years of age, \nespecially for CLE.11 The Danish study showed that \nthe adjusted hazard ratios (HRs) were 3.15 (95% \nCI, 2.02\u20134.92) and 2.28 (95% CI, 1.60\u20133.25) for \npatients with CLE and SLE < 50 years of age.11 A \ncross-sectional study from USA which was done \non patient with chronic cutaneous lupus showed \nthat patients aged less than 60 years, tended to have \nhigher risk of depression (p<0.001).12 This could \nbe explained with younger patients having more \nconcern with their physical symptoms and lesions \ncompared to older patients. Married patients had \nsignificantly lower HADS-A (p=0.007) and lower \nHADS-D (p=0.040) scoring compared to single, \ndivorcee or widowed patients. The study from \nUSA showed married subjects or subjects with \na partner have a lower risk of depression.12  This \ncould be explained by married patients being able \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n19MJD 2019 Dec Vol 43\n\n\n\nto share their disease burden with their spouses. \nFurthermore, married patients can get their mental \nsupport from their spouse. CLASI damage score \nwas found statistically significant to correlate \nwith HADS-A (p=0.015, r=0.179) and HADS-D \n(p=0.002, r=0.230) scoring, but not CLASI activity \nscore. \n\n\n\nIt could be postulated that lupus associated skin \ndamage is more worrisome to patients compared to \nlupus associated active inflammatory skin. Lupus \nassociated skin damage is a permanent effect on the \nskin with scarring and dyspigmentation whereas \nlupus associated active inflammatory skin such \nas malar rash is fleeting and transient in nature \nwith no scarring. Percentage of body surface area \ninvolvement was found significantly to correlate \nwith HADS-A (p=0.001, r=0.245) and HADS-D \n(p=0.001, r=0.242). The higher the body surface \narea affected by lupus, the more worrisome to the \npatient leading to depression and anxiety. Our study \nshowed that DLQI score had significant correlation \nwith the HADS-A (p=0.000, r=0.538) and HADS-D \n(p=0.000, r=0.382) score. This finding was \ncomparable with the study done by Ali FM and co-\nworkers.8\n\n\n\nThe limitation of our current study is due to the cross-\nsectional study design which allows for correlation \n\n\n\nbut not causation. Our study is a single centre study, \nwhich may not reflect the actual characteristic of the \nlocal population, even though the study was done in \na large tertiary hospital. As our study centre is at a \ntertiary hospital, receiving referrals with severe CLE \ncases from other district hospitals or polyclinics, \nthe severity of quality of life may be overestimated \nin CLE patients. Furthermore, this study recruited \nlarger proportion of SLE patients who presented \nwith mild malar rashes from the rheumatology \nclinic who were already on treatments for their \nserious systemic disease, thus severity of quality \nof life may be significantly underestimated in these \ngroup of patients. \n\n\n\nIn order to better understand the disease impact \non quality of life and its association with anxiety \nand depression, future longitudinal and multicentre \nstudies including control group will lead to better \nunderstanding of the disease and its impact on \nquality of life.  Our current study design focused \non correlating the potential subject\u2019s demographic \nbackground or the severity of CLE with the patient\u2019s \nQOL (DLQI) and mood disorders via screening \ntest (HADS). Hence, our current study cannot \ndifferentiate between the mood disorders related to \nthe neuropsychiatric manifestation of SLE, mood \ndisorders due to steroid related psychosis and mood \ndisorders due to physical illness.\n \n\n\n\nTable 6. Factors associated with Quality of Life tested in various studies\n\n\n\nTest Parameters Correlation with Quality of Life\nPresent Study\n\n\n\n(n=185)\nBatalla et al \n2013, Spain\n\n\n\n(n=36)\n\n\n\nFerraz LB et \nal 2005, Brazil \n\n\n\n(n=71)\n\n\n\nKlein R et al \n2011, California \n\n\n\n(n=157)\n\n\n\nVasquez R et \nal 2013, Dallas \n\n\n\n(n=91) & \nPhiladelphia \n\n\n\n(n=157)\nAge Negative \n\n\n\ncorrelation\n- No correlation Negative \n\n\n\ncorrelation\n-\n\n\n\nGender No - - Female was \nassociated with \n\n\n\npoor QOL\n\n\n\nFemale was \nassociated with \n\n\n\npoor QOL\nSLE status No No No - Yes\n\n\n\nDisease duration No No No No -\nCLE subtypes Yes - - No No\n\n\n\nSmoking status No - - - No\nEducation level No - - - Yes\n\n\n\nIncome No - - - Yes\nBSA Yes No - Yes Yes\n\n\n\nDisease severity Yes No - Yes Yes\nVisible skin lesions No No - Yes -\nType of treatments Yes \n\n\n\n(Only in topical \ntreatment)\n\n\n\nNo - - -\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n20 MJD 2019 Dec Vol 43\n\n\n\nConclusion\nIn conclusion, 48.7% of the CLE patients have \nimpairment of quality of life due to the disease, \nparticularly in the SCLE and CCLE subtypes. We \nshould focus on patient\u2019s \u2018embarrassment\u2019, \u2018social/\nleisure\u2019 and \u2018work/school\u2019 domains as these aspects \nare affected most in our study. Factors such as \nyounger age group, CLE subtypes, body surface area \nand disease severity are associated with impairment \nof quality of life. There are 42.2% of CLE patients \nwith anxiety disorder and 29.8% of CLE patients \nwith some depression. Factors such as younger age \ngroup, marital status, CLASI damage, body surface \narea and CLE subtypes are associated with mood \nimpairment measured on the HADS.\n \nIt is imperative that in the management of lupus \naffecting the skin, the onus is on the healthcare \nprovider to elucidate measures in QOL affecting \nthese patients. Outcomes on quality of life would \nbe a significant indicator in successful wholesome \nmanagement of the patient. The treating clinician \nshould be aware of the factors mentioned above \nand a management plan be devised to improve the \nquality of life and treat the symptoms of anxiety \nand depression via a multidisciplinary approach \ninvolving psychiatrist, patient support groups, \nsocial workers, counselor and dermatologist. It is \nbest if a longitudinal, multicenter study at point \nof first contact in patients with SLE be assessed in \ndetermining the findings of this study. \n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Batalla A, Garcia-Doval I, Pe\u00f3n G, de La Torre C. A \nquality-of-life study of cutaneous lupus erythematosus. \nActas Dermosifiliogr 2013;104:800-6.\n\n\n\n2. Jalenques I, Rondepierre F, Massoubre C, Haffen E, \nGrand JP, Labeilla B et al. High prevalence of psychiatric \ndisorders in patients with skin-restricted lupus: a case-\ncontrol study. Br J Dermatol 2016;174:1051-60. \n\n\n\n3. Tamar Nijsten. Dermatology life quality index: time to \nmove forward. J Invest Dermatol 2012;132:11-13. \n\n\n\n4. Ferraz LB, Almeida FA, Vasconcellos MR, Faccina \nAS, Ciconelli RM, Ferraz MB. The impact of lupus \nerythematosus cutaneous on the quality of life: the \nBrazilian-Portuguese version of DLQI. Qual Life Res \n2006;15:565-70.\n\n\n\n5. Martins PR, Skare T, Ferrari TA, Silva AP, Alessio BF. \nComparative analysis of the quality of life of patients \nwith discoid lupus erythematosus and systemic lupus \nerythematosus with skin injuries. An Bras Dermatol \n2012;87:326-8.\n\n\n\n6. Zigmond AS, Snaith RP. The hospital anxiety and \ndepression scale. Acta Psychiatr Scand 1983;67:361-70.\n\n\n\n7. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The \nvalidity of the Hospital Anxiety and Depression Scale. An \nupdate literature review. J Psychosom Res 2002;52:69-77.\n\n\n\n8. Ali FM, Johns N, Salek S, Finlay AY. Correlating the \nDLQI with psychiatric measures: a systematic review. Clin \nDermatol 2018;36:691-7.\n\n\n\n9. Klein R, Moghadam-Kia S, Taylor L, Coley C, Okawa \nJ, LoMonico J et al. Quality of life in cutaneous lupus \nerythematosus. J Am Acad Dermatol 2011;64:849-58.\n\n\n\n10. Vasquez R, Wang D, Tran QP, Adams-Huet B, Chren MM, \nCostner MI et al. A multi-center, cross-sectional study on \nquality of life in cutaneous lupus erythematosus patients. \nBr J Dermatol 2013;168:145-53.\n\n\n\n11. Hesselvig JH, Egeberg A, Kofoed K, Gislason G, Dreyer \nL. Increased risk of depression in patients with cutaneous \nlupus erythematosus and systemic lupus erythematosus: \na Danish nationwide cohort study. Br J Dermatol \n2018;179:1095-101.\n\n\n\n12. Hong J, Aspey L, Bao G, Haynes T, Lim SS, Drenkard \nC. Chronic Cutaneous Lupus Erythematosus: Depression \nBurden and Associated Factors. Am J Clin Dermatol \n2019;20:465-75.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n21MJD 2019 Dec Vol 43\n\n\n\nORIGINAL ARTICLE\n\n\n\nIncreased Risk of Non-alcoholic Fatty Liver Disease, Diabetes Mellitus \nand Hypertension in Patients with Plaque Psoriasis Compared to \nPatients with Generalized Pustular Psoriasis         \nKit Wan Wong1, MRCP, Siew Eng Choon2, FRCP, Kwee Eng Tey1, MRCP, Khatijah Abu Bakar3, MRad, Hartini Baherin3, \nMMed, Ahmad Zuhri Shin bin Abdul Halim3, MB.BCh.BAO \n\n\n\n1Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Johor Bahru, Malaysia\n2Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor \nBahru, Malaysia\n3Department of Radiology, Hospital Sultanah Aminah Johor Bahru, Johor Bahru, Malaysia\n\n\n\nAbstract\nIntroduction:\nPsoriasis is a chronic systemic inflammatory disease with multiple comorbidities. We aim to study \nthe clinical characteristics and prevalence of comorbidities among patients with the most common \nsubtype, plaque psoriasis (PsO) as compared to the rarer subtype, generalized pustular psoriasis (GPP).\n\n\n\nMethods:\nA cross-sectional study involving 50 subjects with PsO and 50 with GPP. History taking, clinical \nexamination and screening for comorbidities were done.\n\n\n\nResults:\nMajority of the patients were Malay, followed by Chinese, Indian and others. Male to female ratio \nwas 1.2:1.0 for PsO and 1.0:2.1 for GPP. Comorbidities detected include obesity (24% in PsO, 20% in \nGPP), hypertension (38% in PsO, 44% in GPP), dyslipidemia (54% in both PsO and GPP), diabetes \nmellitus (30% in PsO, 20% in GPP), metabolic syndrome (40% in PsO, 46% in GPP), coronary artery \ndisease (2% in PsO, 10% in GPP), cerebrovascular disease (2% in PsO), chronic kidney disease (6% \nin PsO, 8% in GPP), non-alcoholic fatty liver disease (NAFLD) (58% in PsO, 34% in GPP), psoriatic \narthritis (20% in PsO, 26% in GPP) and depression (4% in PsO, 12% in GPP). After adjusting for \nconfounding factors, NAFLD, diabetes mellitus and hypertension were found to be significantly \nhigher in PsO. \n\n\n\nConclusion:\nPrevalence of comorbidities is high in both PsO and GPP but higher in PsO as compared to GPP. The \nsignificantly higher prevalence of NAFLD, diabetes mellitus and hypertension in PsO needs to be \nreplicated by further studies.\n\n\n\nKey words: Psoriasis, Plaque psoriasis, Pustular psoriasis, Systemic inflammation, Comorbidities, Coronary artery disease, \nCerebrovascular disease, Hypertension, Diabetes mellitus, Obesity, Dyslipidemia, Metabolic syndrome\n\n\n\nCorresponding Author\nDr Wong Kit Wan\nDepartment of Dermatology, Hospital Sultanah Aminah \nJohor Bahru, Jalan Abu Bakar, 80000 Johor Bahru, \nMalaysia \nEmail: w_kitwan@yahoo.com\n\n\n\nIntroduction\nPsoriasis is a chronic systemic inflammatory \ndisease with multiple comorbidities.1 There are \nfive main clinical subtypes of psoriasis: plaque, \nguttate, inverse, pustular and erythrodermic. Plaque \npsoriasis, which is also known as psoriasis vulgaris \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n22 MJD 2019 Dec Vol 43\n\n\n\n(PsO), is the most common variant, making up about \n90 percent of cases. Malaysian Psoriasis Registry \n2007-2016 reported that out of 15,794 patients who \nwere notified to the registry during that period, \nplaque psoriasis (85.1%) was the commonest \nclinical type of psoriasis in adult patients. This was \nfollowed by guttate psoriasis (2.9%), erythrodermic \npsoriasis (1.7%), pustular psoriasis (1.0%), flexural \npsoriasis (0.4%) and palmoplantar nonpustular \npsoriasis (0.4%).2 \n\n\n\nPsO is manifested by sharply demarcated, scaly, red \nlesions most often on the elbows, knees, scalp, hands \nand feet. There is also the rarer pustular variant, \nwhich is subdivided into generalized and localized \nforms. Generalized forms of pustular psoriasis \ninclude acute generalized pustular psoriasis (GPP), \npustular psoriasis of pregnancy, and infantile \nand juvenile pustular psoriasis. Localized forms \ninclude acrodermatitis continua of Hallopeau and \npalmoplantar pustular psoriasis. GPP is characterized \nby abrupt onset episodes of skin erythema and sterile \npustules covering most of the body. These episodes \nare often recurrent. The pustular lesions can cause \na burning sensation and involve mucosal surfaces \nin addition to the skin. The von Zumbusch type of \nGPP is the most classical form, with abrupt onset \nof painful skin lesions, fever and chills. Febrile, \nacute illness usually accompanies flares, which can \nbe severe and in some cases even life-threatening. \nTriggers include stress, bacterial or viral infections, \ndrug exposure, menses and pregnancy. In addition, \npatients with a prior history of psoriasis have been \nreported to develop GPP with immune-suppressant \nweaning.3 \n\n\n\nPsoriasis has been associated with comorbidities \nsuch as psoriatic arthritis, metabolic syndrome, \ninflammatory bowel disease (IBD), uveitis and \npsychological or psychiatric disorders such as \ndepression.4 Metabolic syndrome as a whole and \nits individual components, have been associated \nwith psoriasis.5-6. More recent studies have also \nshown an increased prevalence of celiac disease, \nnon-alcoholic fatty liver disease (NAFLD) and \nchronic kidney disease in patients who suffer from \npsoriasis.7-10 Additionally, a population-based study \ndocumented a threefold increased risk of lymphoma \ncompared with the general population.11\n\n\n\nComorbidities are also common in Malaysians with \npsoriasis. From the Malaysian Psoriasis Registry \n2007-2016, adult psoriasis patients were found to \nhave hypertension (26.3%), dyslipidemia (18.5%), \n\n\n\ndiabetes mellitus (17.4%), ischaemic heart disease \n(5.6%), and cerebrovascular disease (1.6%). 33.1% \nof them were overweight and 23.6% were obese.2 In \n2014, Choon et al published a review of the clinical \nprofile, comorbidities and outcomes of patients \nwith adult-onset generalized pustular psoriasis \nin Johor.12 Of the 101 patients with documented \ncomorbid conditions in this study, 64.4% had at \nleast one comorbid condition. Hypertension (26 \ncases), hyperlipidemia (26 cases) and diabetes \nmellitus (24 cases) were the three commonly \nassociated conditions. Other comorbidities included \nnine cases of ischaemic heart disease; four hepatitis \nB infection; three cases each of asthma and \ntuberculosis; two cases each of fatty liver, peptic \nulcer disease, congestive heart failure, Parkinson\u2019s \ndisease, syphilis and retroviral infection; and one \ncase each of Down\u2019s syndrome, thyrotoxicosis, \nbreast carcinoma, meningioma and cerebrovascular \naccident. \n\n\n\nAs of to date, there is a lack of data comparing \nthe demography and prevalence of comorbidities \nin the different subtypes of psoriasis. With this in \nmind, this study aims to determine and compare \nthe clinical characteristics and prevalence of \ncomorbidities among patients with PsO, which is \nthe most common variant of psoriasis and GPP, the \nrarer, but most severe and life-threatening variant. \n\n\n\nMaterials and Methods\nThis is a cross-sectional study of patients aged 18 \nand above with dermatologist-diagnosed PsO or \nGPP attending the dermatology clinic, Hospital \nSultanah Aminah Johor Bahru. Patients were \nrecruited by convenience sampling of the first 50 \nconsecutive PsO and 50 consecutive GPP seen \nin the dermatology clinic between 1st May 2018 \nand 31st August 2018. Patients with localized \npustular psoriasis such as acrodermatitis continua \nof Hallopeau and palmoplantar pustulosis are \nexcluded, unless complicated by at least one \nepisode of GPP. Patients who were pregnant were \nalso excluded from this study.\n\n\n\nHistory taking and physical examination were done \nfor all the patients. Examination of the subjects \nincluded anthropometric measurements (weight, \nheight and waist circumference). The body mass \nindex (BMI) was calculated as weight (kg)/[height \n(m)]2. The waist circumference was measured at the \nlevel of the most upper part of the hipbone without \ncompression on the skin. Blood pressure was \nmeasured after a 5-minute rest in sitting position. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n23MJD 2019 Dec Vol 43\n\n\n\nThe severity of psoriasis was assessed using Body \nSurface Area (BSA). BSA is accepted as severe \nin patients with BSA >30%, moderate in patients \nwith BSA >10-30% and mild in patients with BSA \n\u226410%.13 Grading of severity for each patient was \ntaken at its worst available in their medical records. \nImpact of psoriasis on quality of life was assessed \nusing Dermatology Life Quality Index (DLQI) \nand International Physical Activity Questionnaire \n(IPAQ).\n\n\n\nPatients were screened actively for the presence of \ncomorbidities. If they had already been formally \ndiagnosed as having the condition, relevant clinical \ninformation was extracted from their medical \nrecords accordingly. Venous blood sampling was \ndone for fasting blood glucose, HbA1c, fasting \nlipid profile, liver and renal function test. Urine \nsamples were collected for detection of urine \nmicro-albuminuria. Ultrasound for each patient was \nperformed by a trained radiologist or registrar to \nlook for fatty liver and renal parenchymal disease. \nMetabolic syndrome was diagnosed using the most \nrecent Joint Interim Statement (JIS) 2009 definition \nby the IDF International Diabetes Federation \nTask Force.14 Patients were identified as having \nmetabolic syndrome if they had three or more out \nof the five following diagnostic criteria: 1) waist \ncircumference \u2265 90 cm for men and \u2265 80 cm for \nwomen; 2) elevated triglycerides  \u2265 1.7 mmol/l or \nspecific treatment for this lipid anomaly; 3) reduced \nconcentration of HDL cholesterol < 1.0 mmol/l \nfor men and < 1.3 mmol/l for women or specific \ntreatment for this lipid anomaly; 4) systolic blood \npressure  \u2265 130 mmHg or diastolic blood pressure \n\u2265 85 mmHg or treatment of previously diagnosed \nhypertension; 5) fasting plasma glucose \u2265 5.6 \nmmol/l or use of medication for hyperglycemia. \nAs for coronary artery disease and cerebrovascular \naccident, patients were asked whether they have \nhistory of typical symptoms and were diagnosed by \npositive findings (electrocardiogram, exercise stress \ntest, echocardiogram or coronary angiogram for \ncoronary artery disease and computed tomography \nor magnetic resonance imaging for cerebrovascular \naccident). History taking and physical examination \nwere done for screening of psoriatic arthritis and \nlymphoma. Patients were assessed using the two-\nquestion screening test for depression and if they \nanswered yes to one or both questions, they would \nthen be referred to the psychiatrist for further \nassessment.15 \n\n\n\nThe patients\u2019 demographic profile, clinical \n\n\n\ncharacteristics and comorbidities were analyzed \nusing statistical analysis SPSS v 20.0.\n\n\n\nResults\nTable 1 shows the demographic profile and clinical \ncharacteristics of the study population. Majority \nof the patients were Malay, followed by Chinese, \nIndian and others, but ethnic distribution among \nboth groups was similar. Male to female ratio was \n1.2:1.0 for PsO and 1.0:2.1 for GPP. There was no \nsignificant difference in the age of onset among \npatients with PsO and GPP in our cohort.\n\n\n\nIn both groups of patients, most of them were non-\nsmokers and teetotalers. About half of the patients \nhave low level of physical activities. Those with \nGPP were noted to be more inactive, with double \nthe numbers of patients in the GPP group having \nlow physical activity as compared to those with \nPsO. Majority had severe disease with BSA>30% \nin both groups of patients. About a quarter of the \npatients had received phototherapy before and a \ntotal of 77% of them had required systemic therapy \nfor treatment of psoriasis (60% for PsO and 94% \nfor GPP). The most common systemic therapy \nreceived was methotrexate, followed by acitretin \nand cyclosporine. 20% of the patients had received \nbiologics therapy before (14% for PsO and 26% for \nGPP).\n\n\n\nMore than half of the patients were overweight or \nobese, and there was no significant difference in \nthe body mass index profile in both groups (P = \n0.672). The most prevalent comorbidity detected \nwas dyslipidemia, followed by non-alcoholic fatty \nliver disease (NAFLD), metabolic syndrome, \nhypertension, diabetes mellitus, psoriatic arthritis, \ndepression, chronic kidney disease, coronary artery \ndisease and cerebrovascular disease.\n\n\n\nTable 2 shows the distribution and association \nbetween type of psoriasis and comorbidities. \nAfter adjusting for age of onset, gender, ethnicity, \nduration of diagnosis, severity of psoriasis, obesity, \nsmoking status, exercise level and family history of \neach comorbidity; NAFLD, diabetes mellitus and \nhypertension were found to be significantly higher \nin PsO. \n\n\n\nDiscussion\nPsoriasis is a common chronic inflammatory \ndisease worldwide, affecting men and women of all \nages and ethnic origins. The median age of onset of \npsoriasis in our patients was 29.04 years, which is \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n24 MJD 2019 Dec Vol 43\n\n\n\nTable 1. Demographic Profile and Clinical Characteristics of Study Population (N=100)\n\n\n\nCharacteristics All (N=100);\nn (%)\n\n\n\nType of psoriasis\nP-valuePsO (n=50); \n\n\n\nn (%)\nGPP (n=50);\n\n\n\nn (%)\nAge, years:\nMedian (IQR) 45.04 (32.02\u201359.02) 39.75 (28.56\u201352.71) 47.67 (36.06\u201360.79)   0.017\nRange 19.00\u201382.50 19.00\u201375.75 23.67\u201382.50\nGender:\nMale 43 (43.0) 27 (54.0) 16 (32.0)   0.026\nFemale 57 (57.0) 23 (46.0) 34 (68.0)\nEthnicity:\nMalay 51 (51.0) 27 (54.0) 24 (48.0)   0.926\nChinese 29 (29.0) 14 (28.0) 15 (30.0)\nIndian 15 (15.0)   7 (14.0)   8 (16.0)\nOthers   5 (5.0)   2 (4.0)   3 (6.0)\nDuration of diagnosis, \nyears:\n<10 years 42 (42.0) 24 (48.0) 18 (36.0)   0.011\n10\u201320 years 38 (38.0) 22 (44.0) 16 (32.0)\n>20 years 20 (20.0)   4 (8.0) 16 (32.0)\nAge of onset of psoriasis, \nyears:\nMedian 29.04 25.33 31.46   0.826\nIQR 21.29-42.48 21.10-42.44 21.92-42.63\nBMI:\nUnderweight (<18.5)   6 (6.0)   3 (6.0)   3 (6.0)   0.672\nNormal (18.5-24.9) 40 (40.0) 17 (34.0) 23 (46.0)   \nOverweight (25.0-30.0) 32 (32.0) 18 (36.0) 14 (28.0)\nObese (>30.0) 22 (22.0) 12 (24.0) 10 (20.0)\nSmoking status:\nNon-smoker (<100 \ncigarettes in lifetime) 71 (71.0) 32 (64.0) 39 (78.0)   0.287\n\n\n\nFormer smoker \n(stopped >6 months) 12 (12.0)   7 (14.0)   5 (10.0)\n\n\n\nCurrent smoker 17 (17.0) 11 (22.0)   6 (12.0)\nAlcohol status:\nNever 79 (79.0) 37 (74.0) 42 (84.0)   0.456\nFormer   9 (9.0)   6 (12.0)   3 (6.0)\nCurrent 12 (12.0)   7 (14.0)   5 (10.0)\nExercise:\nLow 45 (45.0) 15 (30.0) 30 (60.0)   0.001\nModerate 40 (40.0) 22 (44.0) 18 (36.0)\nHigh 15 (15.0) 13 (26.0)   2 (4.0)\nSeverity of psoriasis\n(at its worst):\nMild (BSA \u2264 10%) 29 (29.0) 19 (38.0) 10 (20.0)   0.049\nModerate \n(BSA > 10% - 30%) 19 (19.0) 11 (22.0)   8 (16.0)\n\n\n\nSevere (BSA > 30%) 52 (52.0) 20 (40.0) 32 (64.0)\nSystemic treatment: 77 (77.0) 30 (60.0) 47 (94.0) <0.001\nPast therapy*:\nPhototherapy 24 (24.0) 11 (22.0) 13 (26.0)   0.640\nCyclosporin 29 (29.0)   6 (12.0) 23 (46.0) <0.001\nAcitretin 45 (45.0)   6 (12.0) 39 (78.0) <0.001\nMethotrexate 66 (66.0) 29 (58.0) 37 (74.0)   0.091\nBiologic 20 (20.0)   7 (14.0) 13 (26.0)   0.134\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n25MJD 2019 Dec Vol 43\n\n\n\nCurrent therapy*:\nTopical 35 (35.0) 24 (48.0) 11 (22.0)   0.006\nPhototherapy   3 (3.0)   2 (4.0)   1 (2.0) >0.995\nMethotrexate 33 (33.0) 19 (38.0) 14 (28.0)   0.288\nAcitretin 16 (16.0)   2 (4.0) 14 (28.0)   0.001\nCyclosporin   5 (5.0)   1 (2.0)   4 (8.0)   0.362\nSecukinumab   5 (5.0)   1 (2.0)   4 (8.0)   0.362\nAdalimumab   3 (3.0)   1 (2.0)   2 (4.0) >0.995\nUstekinumab   2 (2.0)   1 (2.0)   1 (2.0) >0.995\nComorbidity*:\nHypertension 41 (41.0) 19 (38.0) 22 (44.0) 0.542\nDyslipidaemia 54 (54.0) 27 (54.0) 27 (54.0) >0.995\nObesity 22(22.0) 12 (24.0) 10 (20.0) 0.630\nDiabetes mellitus 25 (25.0) 15 (30.0) 10 (20.0) 0.251\nMetabolic syndrome 43 (43.0) 20 (40.0) 23 (46.0) 0.545\nNon-alcoholic fatty liver \ndisease 46 (46.0) 29 (58.0) 17 (34.0) 0.017\n\n\n\nPsoriatic arthritis 23 (23.0) 10 (20.0) 13 (26.0) 0.477\nChronic kidney disease 7 (7.0) 3 (6.0) 4 (8.0) 0.696\nCerebrovascular accident 1 (1.0) 1 (2.0) 0 (0.0) NA\nCoronary artery disease 6 (6.0) 1 (2.0) 5 (10.0) 0.128\nLymphoma 0 (0.0) 0 (0.0) 0 (0.0) NA\nDepression 8 (8.0) 2 (4.0) 6 (12.0) 0.159\nFamily history*:\nPsoriasis 39 (39.0) 19 (38.0) 20 (40.0)   0.838\nHypertension 67 (67.0) 36 (72.0) 31 (62.0)   0.288\nDyslipidaemia 50 (50.0) 29 (58.0) 21 (42.0)   0.110\nObesity 34 (34.0) 14 (28.0) 20 (40.0)   0.205\nDiabetes mellitus 55 (55.0) 27 (54.0) 28 (56.0)   0.841\nMetabolic syndrome   5 (5.0)   2 (4.0)   3 (6.0) >0.995\nNon-alcoholic fatty liver \ndisease   3 (3.0)   1 (2.0)   2 (4.0) >0.995\n\n\n\nPsoriatic arthritis   6 (6.0)   1 (2.0)   5 (10.0)   0.204\nChronic kidney disease   7 (7.0)   3 (6.0)   4 (8.0) >0.995\nCerebrovascular accident 31 (31.0) 10 (20.0) 21 (42.0)   0.017\nCoronary artery disease 38 (38.0) 20 (40.0) 18 (36.0)   0.680\nLymphoma   4 (4.0)   1 (2.0)   3 (6.0)   0.617\nDepression   8 (8.0)   5 (10.0)   3 (6.0)   0.715\nSmoker 60 (60.0) 29 (58.0) 31 (62.0)   0.683\nAlcohol abuse 19 (19.0) 10 (20.0) 9 (18.0)   0.799\n\n\n\nIQR = Interquartile range, reported as 25th percentile-75th percentile; Range is reported as minimum\u2013maximum.\nNA = Not analyzed\n*One patient may have multiple treatments/comorbidities/family history of comorbidities; the percentage reported is based \non total patients in each group. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n26 MJD 2019 Dec Vol 43\n\n\n\nTable 2. The Distribution and Association between Subtype of Psoriasis and Comorbidities\n\n\n\nComorbidities Frequency Prevalence among GPP vs PsO\nGPP\n\n\n\nn=50 (%)\nPsO\n\n\n\nn=50 (%)\nCrude OR \n(95% CI)\n\n\n\nP-value Adjusted \nOR*\n\n\n\n(95% CI)\n\n\n\nP-value\n\n\n\nHypertension 22 (44.0) 19 (38.0) 1.28\n(0.58, 2.85)\n\n\n\n0.542 0.09\n(0.01, 0.93)\n\n\n\n0.043\n\n\n\nDyslipidaemia 27 (54.0) 27 (54.0) 1.00\n(0.46, 2.20)\n\n\n\n>0.995 0.69\n(0.24, 1.98)\n\n\n\n0.486\n\n\n\nDiabetes mellitus 10 (20.0) 15 (30.0) 0.58\n(0.23, 1.46)\n\n\n\n0.251 0.15\n(0.03, 0.78)\n\n\n\n0.023\n\n\n\nMetabolic syndrome 23 (46.0) 20 (40.0) 1.28\n(0.58, 2.82)\n\n\n\n0.545 0.52\n(0.15, 1.88)\n\n\n\n0.322\n\n\n\nNon-alcoholic fatty liver \ndisease\n\n\n\n17 (34.0) 29 (58.0) 0.37\n(0.17, 0.84)\n\n\n\n0.017 0.23\n(0.07, 0.71)\n\n\n\n0.011\n\n\n\nChronic kidney disease 4 (8.0) 3 (6.0) 1.36\n(0.29, 6.43)\n\n\n\n0.696 0.82\n(0.08, 8.59)\n\n\n\n0.869\n\n\n\nPsoriatic arthritis 13 (26.0) 10 (20.0) 1.41\n(0.55, 3.59)\n\n\n\n0.477 1.22\n(0.36, 4.12)\n\n\n\n0.748\n\n\n\nOR = Odds ratio; CI = Confidence interval.\nEach comorbidity comparison was made in isolation of the other comorbidity.\nCoronary artery disease, cerebrovascular accident, lymphoma and depression were not included in the analysis since there \nis small (\u22642) cell observation.\n*Adjusted for age of onset, gender, ethnicity, duration of diagnosis, severity, obesity, smoking status, exercise level and \nfamily history of each comorbidity.\n\n\n\nconsistent with other studies that reported psoriasis \ngenerally appearing at age 20 to 39 years.16 There \nwas a female preponderance in our cohort of GPP \npatients, which is in accordance to the findings of \nmajority in other regions.17\n\n\n\nEvidence increasingly suggest that there is a relation \nbetween psoriasis and multiple comorbidities, \nwhich have led to the recognition of psoriasis as \na disorder with important health implications that \nextend beyond the skin. Epidemiological studies \nhave established these associations and increasingly, \nresearchers are determining the directionality \nof the associations and the role of psoriasis as an \nindependent risk factor for these outcomes.\n\n\n\nWe found that the prevalence of comorbidities \nis high in both PsO and GPP.  After adjusting \nfor confounding factors of age of onset, gender \nand duration of disease, we found no significant \ndifference in the prevalence of comorbidities \nbetween mild to moderate and severe psoriasis in \nboth groups. The relationship between severity \nof psoriasis and comorbidities varies in different \nstudies. Gisondi et al. had also found no correlation \nbetween severity of psoriasis and the prevalence of \nmetabolic syndrome.18 However, systematic review \nand meta-analysis of observational studies have \n\n\n\nfound that patients with more severe psoriasis have \ngreater odds of metabolic syndrome than those with \nmilder psoriasis.19\n\n\n\nAfter controlling for age of onset, gender, ethnicity, \nduration of diagnosis, severity of psoriasis, obesity, \nsmoking status, exercise level and family history of \neach comorbidity; NAFLD,20,21 diabetes mellitus22 \nand hypertension23 were found to be significantly \nhigher in PsO. This may be explained by the \npresence of persistent inflammation in PsO which \nis absent in GPP, as its presentation is acute and \nepisodic.\n\n\n\nPrevalence of metabolic syndrome including \nits individual disease of obesity, dyslipidaemia, \ndiabetes mellitus and hypertension is found to be \nhigh in both our cohort of psoriasis patients. Other \ncase-control studies have also demonstrated an \nincreased prevalence of these diseases in psoriasis \npatients as compared to the general population.24,25\n\n\n\nProinflammatory cytokines which occurs in chronic \ninflammation in psoriasis are linked to augmentation \nof atherogenesis and peripheral insulin resistance, \nand thus leads to hypertension and diabetes mellitus \nType 2.25 Increasing associations between psoriasis \nand metabolic syndrome, and its components \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n27MJD 2019 Dec Vol 43\n\n\n\nsuch as diabetes mellitus Type 2, hypertension, \ndyslipidemia and obesity have now been \nrecognized.4 Gelfand et al. were the first to consider \npsoriasis as an independent factor of cardiovascular \nrisk aggravation.26 A local study on comorbidities \nassociated with psoriasis which compiled data from \nthe Malaysia Psoriasis Registry was published by \nM B Mazlin et al in 2012. The study concluded \nthat comorbidities which increase the risk of \ncardiovascular disease are common among adult \npatients with psoriasis in Malaysia.27\n\n\n\nStudies have shown that cardiovascular disease \nrisk is higher in patients with personal and family \nhistory of classic risk factors.28 Interestingly, 6 \npatients in our cohort had an established diagnosis \nof coronary artery disease where 5 out of the 6 are \nfrom GPP group. The only patient who has coronary \nartery disease in the PsO group has a family history \nof coronary artery disease, whereas all 5 of the \npatients in the GPP group do not have positive \nfamily history. They however, have multiple other \nconventional cardiovascular risk factors such \nas smoking, diabetes mellitus, dyslipidaemia, \nhypertension and obesity. In our study, the P-value \nfor the association between coronary artery disease \nwith psoriasis was not significant and the numbers \nwere too small for further multivariate analysis \nadjusting for confounding factors. Further study \nwith larger sample size is suggested to look at the \nassociation between coronary artery disease and the \ndifferent subtypes of psoriasis, in particular GPP. \n\n\n\nOther than the role of chronic inflammation, \ngenetic factors are also considered to play a role \nin the development of metabolic syndrome in \nthose affected by psoriasis.29,30 A significant role \nis also played by life style, including improper \nnutrition, physical inactivity, stress, smoking and \nconsumption of alcohol, which leads to obesity \nand development of metabolic syndrome. Overall \nprevalence of metabolic syndrome among adults \nin Malaysia lies between 25-40%31, and prevalence \nof metabolic syndrome is found to be increased \nin psoriasis patients with significant OR ranging \nfrom 1.3 to 5.9.32,33 The prevalence of metabolic \nsyndrome among 212 psoriasis patients seen at a \nlocal tertiary referral public hospital was 55.7%, \nhigher when compared with normal Malaysian \npopulation (OR=3.56, 95% Cl 2.60 to 4.88).34\n\n\n\nRecognizing and managing comorbidities are \ncrucial in the management of patients with psoriasis \nas it lessens disease severity, impacts the choice \n\n\n\nof treatment and reduces risks of the associated \ncomorbidities. The knowledge that psoriasis can \nbe associated with multiple comorbidities that \nhave significant impact not only on morbidity \nand mortality but also on healthcare utilization, \nshould lead us to early diagnosis and aggressive \nmanagement of not only the psoriasis but also \nits associated comorbidities. Recognizing and \naddressing comorbidities are crucial to effectively \nand safely treating patients with psoriasis because \nthese comorbidities often have implications on \nquality of life and also therapy selection. \n\n\n\nLimitation\nSingle centre study and small sample size. This study \nwas done using convenience sampling, thus there \ncould be potential bias due to under-representation \nof subgroups in the sample. \n\n\n\nConclusion\nPsoriasis is associated with numerous comorbidities. \nPrevalence of comorbidities is high in both PsO \nand GPP but higher in PsO as compared to GPP. \nThe significantly higher prevalence of NAFLD, \ndiabetes mellitus and hypertension in PsO needs to \nbe replicated by further studies. \n\n\n\nTo the best of our knowledge, this study is among \nthe first to compare the clinical characteristics and \nprevalence of comorbidities among patients with \ndifferent subtypes of psoriasis, adjusting for potential \nconfounders. It is hoped that findings from our study \nwill contribute towards knowledge, recognition and \nmanagement of psoriasis and its comorbidities, as \nwell as aid in future research efforts.\n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper. \n\n\n\nReferences\n\n\n\n1. Sch\u00f6n MP, Boehncke WH. Psoriasis. N Engl J Med \n2005;352:1899-912.\n\n\n\n2. Robinson S, Kwan Z, Ramalingam R, Yeoh CA, Voo MSY, \nSaaya NN et al. Annual Report of the Malaysian Psoriasis \nRegistry 2007-2016, Kuala Lumpur, Malaysia 2018.\n\n\n\n3. Milner JD. Autoinflammatory Diseases Affecting \nPredominantly the Skin. In: Stiehm\u2019s Immune Deficiencies. \nSan Diego, CA: Elsevier Inc. 2014;27:585-90.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n28 MJD 2019 Dec Vol 43\n\n\n\n4. Oliveira Mde F, Rocha Bde O, Duarte GV. 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Actas Dermatosifiliogr. 2016;107:823-\n9.\n\n\n\n11. Gelfand JM, Berlin J, Van Voorhees A, Margolis DJ. \nLymphoma rates are low but increased in patients with \npsoriasis: results from a population-based cohort study in \nthe United Kingdom. Arch Dermatol. 2003;134:595-8.\n\n\n\n12. Choon SE1, Lai NM, Mohammad NA, Nanu NM, Tey \nKE, Chew SF. Clinical profile, morbidity, and outcome of \nadult-onset generalized pustular psoriasis: analysis of 102 \ncases seen in a tertiary hospital in Johor, Malaysia. Int J \nDermatol. 2014;53;676-84.\n\n\n\n13. Malaysia Health Technology Assessment Section \n(MaHTAS), Ministry of Health Malaysia, Clinical Practice \nGuideline on Management of Psoriasis Vulgaris, MOH/P/\nPAK/266.13(gu) June 2013; 30 Dec 2019, Available from: \nhttp://www.moh.gov.my/\n\n\n\n14. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman \nJI, Donato KA et al. Harmonizing the metabolic syndrome: \na joint interim statement of the International Diabetes \nFederation Task Force on Epidemiology and Prevention; \nNational Heart, Lung, and Blood Institute; American \nHeart Association; World Heart Federation; International \nAtherosclerosis Society; and International Association for \nthe Study of Obesity. Circulation. 2009;120:1640-5. \n\n\n\n15. Arroll B, Khin N, Kerse N. Screening for depression in \nprimary care with two verbally asked questions: cross \nsectional study. BMJ 2003;327:1144-6. \n\n\n\n16. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; \nIdentification and Management of Psoriasis and \nAssociated ComorbidiTy (IMPACT) project team. Global \nepidemiology of psoriasis: a systematic review of incidence \nand prevalence. J Invest Dermatol 2013;133:377-85.\n\n\n\n17. Twelves S, Mostafa A, Dand N, Burri E, Farkas K, \nWilson R et al. Clinical and genetic differences between \npustular psoriasis subtypes. J Allergy Clin Immunol \n2019;143:1021-6.\n\n\n\n18. Gisondi P, Tessari G, Conti A, Piaserico S, Schianchi S, \nPeserico A et al. Prevalence of metabolic syndrome in \npatients with psoriasis: a hospital-based case-control \nstudy. Br J Dermatol. 2007;157:68-73.\n\n\n\n19. Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis \nand metabolic syndrome: a systematic review and meta-\nanalysis of observational studies. J Am Acad Dermatol \n2013;68:654-62.\n\n\n\n20. Miele L, Vallone S, Cefalo C, La Torre G, Di Stasi C, \nVecchio FM et al. Prevalence, characteristics and severity \n\n\n\nof non-alcoholic fatty liver disease in patients with chronic \nplaque psoriasis. J Hepatol 2009;51:778-86.\n\n\n\n21. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-\nalcoholic fatty liver disease in patients with chronic plaque \npsoriasis. J Hepatol 2009;51:758-64.\n\n\n\n22. Shapiro J, Cohen AD, David M, Hodak E, Chodik G, \nViner A et al. The association between psoriasis, diabetes \nmellitus and artherosclerosis in Israel: A case-control \nstudy. J Am Acad Dermatol 2007;56:629-34.\n\n\n\n23. Armstrong AW, Harskamp CT, Armstrong EJ. The \nassociation between psoriasis and hypertension: \na systematic review and meta-analysis of observational \nstudies. J Hypertens 2013;31:433-43.\n\n\n\n24. Salunke AS, Nagargoje MV, Belgaumkar VA, Tolat SN, \nChavan RB. Association of Metabolic Syndrome in \nChronic Plaque Psoriasis Patients and their Correlation \nwith Disease Severity, Duration and Age: A Case Control \nStudy from Western Maharashtra. J Clin Diagn Res. \n2017;11:WC06\u2013WC10.\n\n\n\n25. Henseler T, Christophers E. Disease concomitance \nin psoriasis. Journal of the American Academy of \nDermatology 1995;32:982-6.\n\n\n\n26. Gelfand JM, Troxel AB, Lewis JD, Kurd SK, Shin DB, \nWang X et al. The risk of mortality in patients with \npsoriasis: results from a population-based study. Arch \nDermatol 2007;143:1493-9.\n\n\n\n27. Mazlin MB, Chang CC, Baba R. Comorbidities associated \nwith psoriasis \u2013 Data from the Malaysia Psoriasis Registry. \nMed J Malaysia 2012;67:518-21.\n\n\n\n28. Mahyoodeen NG, Crowther NJ, Tikly M. Double trouble: \npsoriasis and cardiometabolic disorders. Cardiovasc J Afr \n2018;29:189-94.\n\n\n\n29. Quaranta M, Burden AD, Griffiths CE, Worthington J, \nBarker JN, Trembath RC et al. Differential contribution of \nCDKAL1 variants to psoriasis, Crohn\u2019s disease and type II \ndiabetes. Genes Immun. 2009;10:654-8. \n\n\n\n30. Wolf N, Quaranta M, Prescott NJ, Allen M, Smith R, \nBurden AD et al. Psoriasis is associated with pleiotropic \nsusceptibility loci identified in type II diabetes and Crohn \ndisease. J Med Genet 2008;45:114-6. \n\n\n\n31. Lim KG, Cheah WK. A review of metabolic \nsyndrome research in Malaysia. Med J Malaysia \n2016;71(Suppl1):20-8. \n\n\n\n32. Love TJ, Qureshi AA, Karlson EW, Gelfand JM, Choi HK. \nPrevalence of the metabolic syndrome in psoriasis: results \nfrom the National Health and Nutrition Examination \nSurvey 2003-2006. Arch Dermatol 2011;147:419-24.\n\n\n\n33. Prey S, Paul C, Bronsard V, Puzenat E, Gourraud PA, \nAractingi S. Cardiovascular risk factors in patients with \nplaque psoriasis: a systematic review of epidemiological \nstudies. J Eur Acad Dermatol Venereol 2010;24(suppl \n2):23-30.\n\n\n\n34. Tan WC (2013). Risk of metabolic syndrome in multi-\nethnic Malaysian psoriasis patients (unpublished advanced \nmaster\u2019s thesis). Universiti Kebangsaan Malaysia, Kuala \nLumpur, Malaysia.  \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n29MJD 2019 Dec Vol 43\n\n\n\nORIGINAL ARTICLE\n\n\n\nSexually Transmitted Infections in a State General Hospital in \nPeninsular Malaysia         \nRajalingam Ramalingam, AdvMDerm \n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia\n\n\n\nAbstract\nIntroduction: \nSexually transmitted infections (STIs) continue to be a cause of concern in Malaysia, especially since \nmany of them increase the risk of Human Immunodeficiency Virus (HIV) transmission. Not all STIs \nare notifiable by law, resulting in an incomplete epidemiological picture of STIs in our hospital, a \ntertiary dermatology referral center for the state of Pahang in Peninsula Malaysia. \n\n\n\nMethods: \nThis is a single-center, retrospective audit of 159 patients with 174 STIs who attended the Dermatology \noutpatient clinic in Hospital Tengku Ampuan Afzan (HTAA), Malaysia between 2008 and 2018. \n\n\n\nResults: \nOut of 159 patients with 174 STIs, 61% were men, 66.7% Malay, 64.2% heterosexual and 37.1% \nhad multiple sexual partners at the time of diagnosis. The mean age of patients was 36.6 years, the \nyoungest being 15 years old with almost two-thirds (60.4%) aged between 21 and 40. More than half \n(52.8%) were married at the time of diagnosis, including 64.5% of women. Almost a quarter (22.6%) \nof women were pregnant upon diagnosis. Past STIs were reported by 14.4% of patients while 19.5% \nhad more than one STI at the time of diagnosis. The commonest STI was genital warts (55.8%), \nfollowed by all stages of syphilis (24.1%), with more than half (54.8%) being late latent syphilis. \nOther STIs encountered include herpes genitalis (8.6%), gonorrhea (7.5%), chancroid (2.3%), HIV \n(1.2%) and chlamydia (0.6%). \n\n\n\nConclusions: \nGenital wart was the commonest STI encountered in our center. Most patients were men, Malay, \nmarried, heterosexual and aged between 21 and 40 years old.\n\n\n\nKey words: Sexually transmitted infections, Syphilis, Gonorrhea, Genital warts, Chancroid, Herpes genitalis, Pahang, Malaysia\n\n\n\nCorresponding Author\nDr Rajalingam Ramalingam\nDepartment of Dermatology, Hospital Tengku Ampuan \nAfzan, Jalan Tanah Putih, 25100 Kuantan, Pahang, \nMalaysia. \nEmail: raj.blueheart@gmail.com \n\n\n\nIntroduction\nSexually transmitted infections (STIs) are bacterial, \nviral and parasitic diseases that are transmitted \nvia sexual contact. They continue to be a cause of \nconcern in Malaysia, especially since most of them \nincrease susceptibility to Human Immunodeficiency \nVirus (HIV) infection,1,2 HIV virus shedding3 as well \nas result in unfavorable and even deadly sequelae \nsuch as pelvic inflammatory disease, ectopic \npregnancy, perinatal or congenital infections, \ninfertility and cervical or anal cancer,4 all of which \nfurther overwhelm an already strained national \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n30 MJD 2019 Dec Vol 43\n\n\n\nhealthcare system. \n\n\n\nMany factors, largely social and psychological, \nundermine the continued scourge of STIs worldwide, \nincluding Malaysia. They include a general lack of \nawareness and education regarding STIs and their \nprevention,5 intoxication by alcohol and illicit \ndrugs,6 social media platforms that influence sexual \nrisk-taking behaviors,7 international and local \nrural-to-urban human migration,8,9 transgenderism \nand other sexual identities,10,11 and the prevalence \nof commercial sex workers.12 Unless these issues \nare scrutinized and promptly addressed, we will \nlikely see a resurgence of not only STIs but also \nan uncontrolled epidemic of HIV and acquired \nimmunodeficiency syndrome (AIDS).\n\n\n\nIn our country, not all STIs are notifiable by law, thus \nthe true impact of STIs on the growing burden of \nHIV/AIDS and long-term clinical complications is \nnot known. While nationwide epidemiological data \nmay be available for STIs, the same cannot be said \nabout regional centers, such as our hospital, which \nis a tertiary dermatology referral center for the state \nof Pahang in Peninsula Malaysia. Hence, we sought \nto determine the local epidemiology of STIs in our \ncenter, especially with regards to non-notifiable STIs, \nwith the hope that it may encourage enhancements \nin clinical and public health management guidelines \nas well as community intervention. \n\n\n\nMaterials and Methods  \nThis is a single-center, retrospective audit of \n159 patients with 174 STIs who attended our \nDermatology outpatient clinic between 2008 and \n2018. The list of all outpatients and inpatients \nwith STIs was readily available in the department \ncensus. Subsequently, the respective case-notes \nwere traced and reviewed before demographic data \nand other variables were recorded. The data were \nthen analyzed using Microsoft Office Excel 2018. \n\n\n\nResults\nA total of 159 patients were confirmed to have \nSTIs, of which 97 (61.0%) were men, resulting \nin a male:female ratio of 1.56:1. The mean age \nof patients was 36.6 years, the youngest being 15 \nyears old, the oldest 81, and with almost two-thirds \n(60.4%) aged between 21 and 40. In fact, 35.2% \nwere aged between 21 and 30 years old. Malays \nwere the predominant ethnicity with STIs, affecting \n106 (66.7%) individuals, followed by 38 (23.9%) \nChinese, 8 (5.0%) Indians and 7 (4.4%) of other \nethnicities. More than half of the patients (52.8%) \n\n\n\nwere married at the time of diagnosis, including \n64.5% of women and 45.4% of men. Almost a \nquarter (22.6%) of women were pregnant at the time \nof diagnosis. \n\n\n\nMost patients were heterosexual (102, 64.2%), while \n14 (8.8%) and 5 (3.1%) patients were homosexual \nand bisexual, respectively. Thirty-eight (23.9%) of \npatients did not state their sexual orientation. More \nthan a third (37.1%) of the patients were having \nmultiple partners at the time of diagnosis, while \nsix (3.8%) reported being regularly intoxicated \nwith illicit drugs and/or alcohol during sex. Past \nSTIs were reported by 23 (14.5%) of patients while \n31 (19.5%) had more than one STI at the time of \ndiagnosis. These results are illustrated in Table 1 \nbelow.\n\n\n\nMore than half of the 174 cases of STIs, or 97 \n(55.8%), was genital warts, as depicted in Figure 1 \nbelow, out of which 48 (49.5%) were penile warts, \n40 (41.2%) vulvovaginal warts and 13 (13.4%) \nanal/perianal warts. There were two patients with \ncondylomata accuminata, involving the anal and \nvulvovaginal regions each. Syphilis was the second \nmost common STI seen in our center, affecting 42 \npatients (24.1%), out of which 23 (54.8%) had late \nlatent syphilis, 12 (28.6%) had early latent syphilis, \n6 (14.3%) had secondary syphilis and 1 (2.4%) had \nprimary syphilis. Herpes genitalis was the third most \ncommon STI, affecting 15 (8.6%) patients, followed \nby 13 (7.5%) cases of gonorrhea, 4 (2.3%) cases of \nchancroid, 2 (1.2%) HIV and 1 (0.6%) chlamydia. \n\n\n\nMost of the STIs showed almost equal gender \npreponderance, except syphilis which affected \nthree times more men compared to women, and \ngonorrhea which affected twelve times as many \nmen compared to women. Genital warts was the \nonly STI where there were more married than \nsingle individuals, but this difference was not \nstatistically significant (P=0.061). Gonorrhea, on \nthe other hand, significantly affected more single \nindividuals compared to those who were married \n(P=0.0047). Gonorrhea also significantly affected \nmore homosexual individuals compared to other \nSTIs (P=0.007). These results are shown in greater \ndetail in Table 2 below.\n\n\n\nDiscussion\nSTIs are a big health concern to a developing \nnation like Malaysia because it affects the most \nproductive as well as reproductive age bracket \nof 21- to 40-year-olds.13 With acute infection and \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n31MJD 2019 Dec Vol 43\n\n\n\nFigure 1. Types of Sexually Transmitted Infection in our Dermatology Clinic\n\n\n\nTable 1. Demographic Pattern of the 159 Patients with Sexually Transmitted Infections\n\n\n\nSTI: sexually transmitted infection; NS: not specified\n\n\n\nN (%)\nGender Male\n\n\n\nFemale\n97 (61.0)\n62 (39.0)\n\n\n\nEthnicity Malay\nChinese\n\n\n\nIndian\nOthers\n\n\n\n106 (66.7)\n38 (23.9)\n8 (5.0)\n7 (4.4)\n\n\n\nAge group (years) 0 \u2013 20\n21 \u2013 40\n41 \u2013 60\n60 \u2013 80\n\n\n\n81 \u2013 100\n\n\n\n15 (9.4)\n96 (60.4)\n29 (18.2)\n18 (11.3)\n1 (0.6)\n\n\n\nSexual orientation Heterosexual\nHomosexual\n\n\n\nBisexual\nNS\n\n\n\n102 (64.2)\n14 (8.8)\n5 (3.1)\n\n\n\n38 (23.9)\nMarital status Married\n\n\n\nSingle\n84 (52.8)\n75 (47.2)\n\n\n\nMultiple partners Yes\nNo\n\n\n\n59 (37.1)\n100 (62.9)\n\n\n\nDrug/alcohol intoxication Yes\nNo\n\n\n\n6 (3.8)\n153 (96.2)\n\n\n\nPast STI Yes\nNo\n\n\n\n23 (14.5)\n136 (85.5)\n\n\n\nTwo or more STI coinfection Yes\nNo\n\n\n\n31 ((19.5)\n128 (80.5)\n\n\n\nPregnant at time of diagnosis (N=62) Yes\nNo\n\n\n\n14 (22.6)\n48 (77.4)\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n32 MJD 2019 Dec Vol 43\n\n\n\nG\nen\n\n\n\nita\nl W\n\n\n\nar\nts\n\n\n\nSy\nph\n\n\n\nili\ns\n\n\n\nH\ner\n\n\n\npe\ns \n\n\n\nG\nen\n\n\n\nita\nlis\n\n\n\nG\non\n\n\n\nor\nrh\n\n\n\nea\nC\n\n\n\nha\nnc\n\n\n\nro\nid\n\n\n\nH\nIV\n\n\n\nC\nhl\n\n\n\nam\nyd\n\n\n\nia\n\n\n\nN\n97\n\n\n\n42\n15\n\n\n\n13\n4\n\n\n\n2\n1\n\n\n\nG\nen\n\n\n\nde\nr \n\n\n\n(%\n)\n\n\n\nM\nal\n\n\n\ne\nFe\n\n\n\nm\nal\n\n\n\ne\nM\n\n\n\nal\ne:\n\n\n\nFe\nm\n\n\n\nal\ne\n\n\n\n56\n (5\n\n\n\n7.\n7)\n\n\n\n41\n (4\n\n\n\n2.\n3)\n\n\n\n1.\n36\n\n\n\n:1\n\n\n\n32\n (7\n\n\n\n6.\n2)\n\n\n\n10\n (2\n\n\n\n3.\n8)\n\n\n\n3.\n2:\n\n\n\n1\n\n\n\n7 \n(4\n\n\n\n6.\n7)\n\n\n\n8 \n(5\n\n\n\n3.\n3)\n\n\n\n1:\n1.\n\n\n\n14\n\n\n\n12\n (9\n\n\n\n2.\n3)\n\n\n\n1 \n(7\n\n\n\n.7\n)\n\n\n\n12\n:1\n\n\n\n2 \n(5\n\n\n\n0.\n0)\n\n\n\n2 \n(5\n\n\n\n0.\n0)\n\n\n\n1:\n1\n\n\n\n2 \n(1\n\n\n\n00\n.0\n\n\n\n)\n0 -\n\n\n\n1 \n(1\n\n\n\n00\n.0\n\n\n\n)\n0 -\n\n\n\nE\nth\n\n\n\nni\nci\n\n\n\nty\n (%\n\n\n\n)\nM\n\n\n\nal\nay\n\n\n\nC\nhi\n\n\n\nne\nse\n\n\n\nIn\ndi\n\n\n\nan\nO\n\n\n\nth\ner\n\n\n\ns\n\n\n\n57\n (5\n\n\n\n8.\n8)\n\n\n\n32\n (3\n\n\n\n3.\n0)\n\n\n\n6 \n(6\n\n\n\n.2\n)\n\n\n\n2 \n(2\n\n\n\n.1\n)\n\n\n\n30\n (7\n\n\n\n1.\n4)\n\n\n\n6 \n(1\n\n\n\n4.\n3)\n\n\n\n2 \n(4\n\n\n\n.8\n)\n\n\n\n4 \n(9\n\n\n\n.5\n)\n\n\n\n10\n (6\n\n\n\n6.\n7)\n\n\n\n4 \n(2\n\n\n\n6.\n7)\n\n\n\n0\n1 \n\n\n\n(6\n.7\n\n\n\n)\n\n\n\n12\n (9\n\n\n\n2.\n3)\n\n\n\n0\n1 \n\n\n\n(7\n.7\n\n\n\n)\n0\n\n\n\n2 \n(5\n\n\n\n0.\n0)\n\n\n\n1 \n(2\n\n\n\n5.\n0)\n\n\n\n0\n1 \n\n\n\n(2\n5.\n\n\n\n0)\n\n\n\n1 \n(5\n\n\n\n0.\n0)\n\n\n\n0 0\n1 \n\n\n\n(5\n0.\n\n\n\n0)\n\n\n\n1 \n(1\n\n\n\n00\n.0\n\n\n\n)\n0 0 0\n\n\n\nM\ned\n\n\n\nia\nn \n\n\n\nag\ne \n\n\n\n(y\nea\n\n\n\nrs\n) (\n\n\n\nra\nng\n\n\n\ne)\n32\n\n\n\n.0\n15\n\n\n\n \u2013\n 6\n\n\n\n8\n40\n\n\n\n.0\n19\n\n\n\n \u2013\n 8\n\n\n\n0\n34\n\n\n\n.0\n17\n\n\n\n \u2013\n 8\n\n\n\n1\n27\n\n\n\n.0\n19\n\n\n\n \u2013\n 4\n\n\n\n0\n30\n\n\n\n.0\n23\n\n\n\n \u2013\n 7\n\n\n\n3\n22\n\n\n\n.5\n20\n\n\n\n \u2013\n 2\n\n\n\n5\n27 -\n\n\n\nA\nge\n\n\n\n g\nro\n\n\n\nup\n (y\n\n\n\nea\nrs\n\n\n\n) (\n%\n\n\n\n)\n\u22642\n\n\n\n0\n21\n\n\n\n-4\n0\n\n\n\n41\n-6\n\n\n\n0\n61\n\n\n\n-8\n0\n\n\n\n>8\n0\n\n\n\n9 \n(9\n\n\n\n.3\n)\n\n\n\n63\n (6\n\n\n\n4.\n9)\n\n\n\n19\n (1\n\n\n\n9.\n6)\n\n\n\n6 \n(6\n\n\n\n.2\n)\n\n\n\n0\n\n\n\n4 \n(9\n\n\n\n.5\n)\n\n\n\n17\n (4\n\n\n\n0.\n5)\n\n\n\n10\n (2\n\n\n\n3.\n8)\n\n\n\n11\n (2\n\n\n\n6.\n2)\n\n\n\n0\n\n\n\n1 \n(6\n\n\n\n.7\n)\n\n\n\n9 \n(6\n\n\n\n0.\n0)\n\n\n\n4 \n(2\n\n\n\n6.\n7)\n\n\n\n0\n1 \n\n\n\n(6\n.7\n\n\n\n)\n\n\n\n2 \n(1\n\n\n\n5.\n4)\n\n\n\n11\n (8\n\n\n\n4.\n6)\n\n\n\n0 0 0\n\n\n\n0\n3 \n\n\n\n(7\n5.\n\n\n\n0)\n0\n\n\n\n1 \n(2\n\n\n\n5.\n0)\n\n\n\n0\n\n\n\n1 \n(5\n\n\n\n0.\n0)\n\n\n\n1 \n(5\n\n\n\n0.\n0)\n\n\n\n0 0 0\n\n\n\n0\n1 \n\n\n\n(1\n00\n\n\n\n.0\n)\n\n\n\n0 0 0\nSe\n\n\n\nxu\nal\n\n\n\n o\nri\n\n\n\nen\nta\n\n\n\ntio\nn \n\n\n\n(%\n)\n\n\n\nH\net\n\n\n\ner\nos\n\n\n\nex\nua\n\n\n\nl\nH\n\n\n\nom\nos\n\n\n\nex\nua\n\n\n\nl\nB\n\n\n\nis\nex\n\n\n\nua\nl\n\n\n\nN\nS\n\n\n\n61\n (6\n\n\n\n2.\n9)\n\n\n\n6 \n(6\n\n\n\n.2\n)\n\n\n\n2 \n(2\n\n\n\n.1\n)\n\n\n\n28\n (2\n\n\n\n8.\n9)\n\n\n\n26\n (6\n\n\n\n1.\n9)\n\n\n\n5 \n(1\n\n\n\n1.\n9)\n\n\n\n4 \n(9\n\n\n\n.5\n)\n\n\n\n7 \n(1\n\n\n\n6.\n7)\n\n\n\n13\n (8\n\n\n\n6.\n7)\n\n\n\n0 0\n2 \n\n\n\n(1\n3.\n\n\n\n3)\n\n\n\n7 \n(5\n\n\n\n3.\n8)\n\n\n\n4 \n(3\n\n\n\n0.\n8)\n\n\n\n0\n2 \n\n\n\n(1\n5.\n\n\n\n4)\n\n\n\n3 \n(7\n\n\n\n5.\n0)\n\n\n\n1 \n(2\n\n\n\n5.\n0)\n\n\n\n0 0\n\n\n\n0\n2 \n\n\n\n(1\n00\n\n\n\n.0\n)\n\n\n\n0 0\n\n\n\n1 \n(1\n\n\n\n00\n.0\n\n\n\n)\n0 0 0\n\n\n\nM\nar\n\n\n\nita\nl s\n\n\n\nta\ntu\n\n\n\ns (\n%\n\n\n\n)\nM\n\n\n\nar\nrie\n\n\n\nd\nSi\n\n\n\nng\nle\n\n\n\n57\n (5\n\n\n\n8.\n8)\n\n\n\n40\n (4\n\n\n\n1.\n2)\n\n\n\n17\n (4\n\n\n\n0.\n5)\n\n\n\n25\n (5\n\n\n\n9.\n5)\n\n\n\n7 \n(4\n\n\n\n6.\n7)\n\n\n\n8 \n(5\n\n\n\n3.\n3)\n\n\n\n2 \n(1\n\n\n\n5.\n4)\n\n\n\n11\n (8\n\n\n\n4.\n6)\n\n\n\n1 \n(2\n\n\n\n5.\n0)\n\n\n\n3 \n(7\n\n\n\n5.\n0)\n\n\n\n0\n2 \n\n\n\n(1\n00\n\n\n\n.0\n)\n\n\n\n0\n1 \n\n\n\n(1\n00\n\n\n\n.0\n)\n\n\n\nM\nul\n\n\n\ntip\nle\n\n\n\n p\nar\n\n\n\ntn\ner\n\n\n\ns (\n%\n\n\n\n)\nYe\n\n\n\ns\nN\n\n\n\no\n37\n\n\n\n (3\n8.\n\n\n\n1)\n60\n\n\n\n (6\n1.\n\n\n\n8)\n15\n\n\n\n (3\n5.\n\n\n\n7)\n27\n\n\n\n (6\n4.\n\n\n\n3)\n6 \n\n\n\n(4\n0.\n\n\n\n0)\n9 \n\n\n\n(6\n0.\n\n\n\n0)\n7 \n\n\n\n(5\n3.\n\n\n\n8)\n6 \n\n\n\n(4\n6.\n\n\n\n2)\n2 \n\n\n\n(5\n0.\n\n\n\n0)\n2 \n\n\n\n(5\n0.\n\n\n\n0)\n1 \n\n\n\n(5\n0.\n\n\n\n0)\n1 \n\n\n\n(5\n0.\n\n\n\n0)\n0\n\n\n\n1 \n(1\n\n\n\n00\n.0\n\n\n\n)\nPr\n\n\n\neg\nna\n\n\n\nnc\ny \n\n\n\n(%\n)\n\n\n\nN\nYe\n\n\n\ns\nN\n\n\n\no\n\n\n\n41\n12\n\n\n\n (2\n9.\n\n\n\n3)\n29\n\n\n\n (7\n0.\n\n\n\n7)\n\n\n\n10\n1 \n\n\n\n(1\n0.\n\n\n\n0)\n9 \n\n\n\n(9\n0.\n\n\n\n0)\n\n\n\n8\n1 \n\n\n\n(1\n2.\n\n\n\n5)\n7 \n\n\n\n(8\n7.\n\n\n\n5)\n\n\n\n1 0\n1 \n\n\n\n(1\n00\n\n\n\n.0\n)\n\n\n\n2 0\n2 \n\n\n\n(1\n00\n\n\n\n.0\n)\n\n\n\n0 0 0\n\n\n\n0 0 0\n\n\n\nTa\nbl\n\n\n\ne \n2.\n\n\n\n D\nem\n\n\n\nog\nra\n\n\n\nph\nic\n\n\n\n C\nha\n\n\n\nra\nct\n\n\n\ner\nis\n\n\n\ntic\n o\n\n\n\nf P\nat\n\n\n\nie\nnt\n\n\n\ns a\ncc\n\n\n\nor\ndi\n\n\n\nng\n to\n\n\n\n v\nar\n\n\n\nio\nus\n\n\n\n S\nex\n\n\n\nua\nlly\n\n\n\n T\nra\n\n\n\nns\nm\n\n\n\nitt\ned\n\n\n\n In\nfe\n\n\n\nct\nio\n\n\n\nns\n\n\n\nH\nIV\n\n\n\n: h\num\n\n\n\nan\n im\n\n\n\nm\nun\n\n\n\nod\nefi\n\n\n\nci\nen\n\n\n\ncy\n v\n\n\n\niru\ns;\n\n\n\n N\nS:\n\n\n\n n\not\n\n\n\n sp\nec\n\n\n\nifi\ned\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n33MJD 2019 Dec Vol 43\n\n\n\nchronic sequelae come greater health and economic \nburden. Compared to other centers in Malaysia \nand in various Asian countries (Table 3), we only \nrecorded a small number of STIs despite the long \nstudy period. This is because most cases of STIs \nare managed at the primary care level or are self-\ntreated with over-the-counter medication.14 Only \ncases with complications, that are non-responsive \nto conventional treatment, or that require treatment \nnot readily available at a primary care facility, get \nreferred to our dermatology clinic. Hence, our data \ncannot truly represent the true landscape of STI \nin the state, let alone the country. This is further \ncompounded by the fact that not all STIs need to \nbe notified under the law, thus the exact burden \nof STI among the population of Pahang cannot be \nconfidently ascertained. Perhaps administrative or \ninstitution-based notification of STIs can be a step \nin the right direction in gauging the true burden \nof the diseases and subsequently, in formulating \ncomprehensive community intervention programs. \n\n\n\nAnother possible reason for the small number \nof patients in our cohort is the lack of awareness \namong healthcare providers of the myriad \npresentations of STIs which can masquerade as \nurinary tract infection, inflammatory bowel disease, \nuveitis, oropharyngitis or even cutaneous adverse \ndrug reactions. This unfortunately leads to delayed \nor incorrect diagnoses, and the inappropriate use \nof antimicrobials.15-18 The \u201csyndromic approach\u201d \nof treatment still adopted by some primary care \nclinics also contributes to the superfluous abuse of \nantibiotics in the management of STIs.\n\n\n\nAlmost a quarter of women were pregnant upon \ndiagnosis, and this can lead to potentially life-\nthreatening perinatal and congenital complications \nwith the added risk of long-term clinical sequelae, \ndepending on the type of STI. More alarming was \nthe finding that close to a third of women with \ngenital warts were also pregnant at the time of \ndiagnosis. Neonates of mothers who have not been \ntreated risk developing respiratory papillomatosis \nduring delivery.19 It is well established that human \npapillomavirus (HPV) infection causes cervical \ncancer, hence the importance of eradicating genital \nwarts. However, there is also mounting evidence \nlinking HPV infection to anal, vulvovaginal and \npenile carcinoma20-26 in addition to oropharyngeal \nsquamous cell carcinoma.27-29 As such, these \ndevastating cancers are potentially preventable by \nsimilar preventive strategies used for the control \nand management of cervical cancer, which includes \n\n\n\nquality sex education, promotion and provision of \ncondoms, screening pap smears, male circumcision \nand HPV vaccination. HPV vaccination, introduced \nin Malaysia since 2010, has already been proven \nto reduce the prevalence of vaccine-type HPV \ninfections and HPV-related cancers in many \ncohorts.30-36 Nevertheless, in our country, the \nvaccine is only made available for women aged \n13 years old as part of the national immunization \nprogram. Further discussion may be warranted \nshould the preventive indication of the vaccine be \nalso considered for other high-risk groups.\n\n\n\nStudies among Malaysian youth demonstrated \nthat sexual health awareness was still less than \nsatisfactory.36,37 Many of these youths agree that sex \neducation should be introduced into the Malaysian \nschool education system.38 The abuse of alcohol \nand other intoxicating illicit drugs coupled with \nthis insufficient awareness poses an increased risk \nof contracting STIs.39,40 Thus, strategies to curb the \nprevalence of STIs should also include an action \nplan to address and tackle substance abuse. \n\n\n\nLimitations of the Study\nA small and single-center cohort may not be \nrepresentative of the true epidemiology of STI in \nthe state, and data analysis could be biased. \n\n\n\nConclusion\nThe three commonest STIs in our center were genital \nwarts, syphilis and herpes genitalis. Most patients \nwere married heterosexual men aged between 21 \nand 40 years old. \n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of the \ndepartment of Dermatology of Hospital Tengku \nAmpuan Afzan, Kuantan, Pahang, Malaysia for \ntheir hard work in compiling the relevant records. \nWe would also like to thank the Director-General \nof Health, Malaysia, for his permission to publish \nthis article.\n\n\n\nReferences\n\n\n\n1. Sexton J, Garnett G, R\u00f8ttingen J. Meta-analysis and meta-\nregression in interpreting study variability in the impact \nof sexually transmitted diseases on susceptibility to HIV \ninfection. Sex Transm Dis 2005;32:351-7.\n\n\n\n2. Galvin SR, Cohen MS. The Role of Sexually Transmitted \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n34 MJD 2019 Dec Vol 43\n\n\n\nDiseases in HIV Transmission. 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Am J Clin Pathol \n2015;144:771-81.Ta\n\n\n\nbl\ne \n\n\n\n3.\n E\n\n\n\npi\nde\n\n\n\nm\nio\n\n\n\nlo\ngy\n\n\n\n o\nf S\n\n\n\nex\nua\n\n\n\nlly\n T\n\n\n\nra\nns\n\n\n\nm\nitt\n\n\n\ned\n In\n\n\n\nfe\nct\n\n\n\nio\nns\n\n\n\n in\n v\n\n\n\nar\nio\n\n\n\nus\n A\n\n\n\nsi\nan\n\n\n\n C\nou\n\n\n\nnt\nrie\n\n\n\ns\n\n\n\nA\nl-F\n\n\n\nou\nza\n\n\n\nn \nA\n\n\n\n, e\nt a\n\n\n\nl41\n\n\n\n(2\n00\n\n\n\n2)\nK\n\n\n\nuw\nai\n\n\n\nt\nN\n\n\n\n=4\n,0\n\n\n\n14\n\n\n\nM\now\n\n\n\nla\n M\n\n\n\nR\n, e\n\n\n\nt a\nl42\n\n\n\n(2\n00\n\n\n\n3-\n20\n\n\n\n11\n)\n\n\n\nB\nan\n\n\n\ngl\nad\n\n\n\nes\nh\n\n\n\nN\n=3\n\n\n\n0,\n15\n\n\n\n1\n\n\n\nH\nar\n\n\n\niy\nad\n\n\n\nur\nai\n\n\n\n H\nR\n\n\n\n, e\nt a\n\n\n\nl13\n\n\n\n(2\n01\n\n\n\n5-\n20\n\n\n\n16\n)\n\n\n\nK\nua\n\n\n\nla\n L\n\n\n\num\npu\n\n\n\nr, \nM\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\nN\n=1\n\n\n\n,3\n61\n\n\n\nC\nha\n\n\n\nk \nM\n\n\n\n, e\nt a\n\n\n\nl43\n\n\n\n(2\n01\n\n\n\n7)\nH\n\n\n\non\ng \n\n\n\nK\non\n\n\n\ng,\n C\n\n\n\nhi\nna\n\n\n\nN\n=1\n\n\n\n2,\n93\n\n\n\n3\n\n\n\nSi\nng\n\n\n\nh \nSK\n\n\n\n, e\nt a\n\n\n\nl44\n\n\n\n(2\n01\n\n\n\n3-\n20\n\n\n\n17\n)\n\n\n\nG\nor\n\n\n\nak\nhp\n\n\n\nur\n, I\n\n\n\nnd\nia\n\n\n\nN\n=9\n\n\n\n40\n\n\n\nO\nur\n\n\n\n S\ntu\n\n\n\ndy\n(2\n\n\n\n00\n8-\n\n\n\n20\n18\n\n\n\n)\nK\n\n\n\nua\nnt\n\n\n\nan\n, M\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\nN\n=1\n\n\n\n59\n\n\n\nM\nal\n\n\n\ne:\nFe\n\n\n\nm\nal\n\n\n\ne \nra\n\n\n\ntio\n2.\n\n\n\n4:\n1\n\n\n\n2.\n57\n\n\n\n:1\n2.\n\n\n\n56\n:1\n\n\n\n1.\n64\n\n\n\n:1\n2.\n\n\n\n64\n:1\n\n\n\n1.\n56\n\n\n\n:1\nM\n\n\n\nea\nn \n\n\n\nag\ne \n\n\n\n(y\nea\n\n\n\nrs\n)\n\n\n\nN\nA\n\n\n\n30\n.9\n\n\n\n32\n.1\n\n\n\nN\nA\n\n\n\n28\n.5\n\n\n\n36\n.6\n\n\n\nM\nos\n\n\n\nt c\nom\n\n\n\nm\non\n\n\n\n \nse\n\n\n\nxu\nal\n\n\n\nly\n tr\n\n\n\nan\nsm\n\n\n\nitt\ned\n\n\n\n \nin\n\n\n\nfe\nct\n\n\n\nio\nns\n\n\n\n (%\n)\n\n\n\n1.\n N\n\n\n\nSU\n (5\n\n\n\n4.\n8%\n\n\n\n)\n2.\n\n\n\n G\non\n\n\n\nor\nrh\n\n\n\nea\n (3\n\n\n\n4.\n6%\n\n\n\n)\n3.\n\n\n\n G\nen\n\n\n\nita\nl h\n\n\n\ner\npe\n\n\n\ns \n(4\n\n\n\n.1\n%\n\n\n\n)\n4.\n\n\n\n C\nha\n\n\n\nnc\nro\n\n\n\nid\n (3\n\n\n\n.4\n%\n\n\n\n)\n5.\n\n\n\n G\nen\n\n\n\nita\nl w\n\n\n\nar\nts\n\n\n\n (2\n.3\n\n\n\n%\n)\n\n\n\n6.\n S\n\n\n\nyp\nhi\n\n\n\nlis\n (0\n\n\n\n.8\n%\n\n\n\n)\n\n\n\n1.\n N\n\n\n\nSU\n (3\n\n\n\n1.\n4%\n\n\n\n)\n2.\n\n\n\n G\non\n\n\n\nor\nrh\n\n\n\nea\n (2\n\n\n\n7.\n8%\n\n\n\n)\n3.\n\n\n\n S\nyp\n\n\n\nhi\nlis\n\n\n\n (1\n8.\n\n\n\n1%\n)\n\n\n\n4.\n G\n\n\n\nen\nita\n\n\n\nl s\nca\n\n\n\nbi\nes\n\n\n\n \n(6\n\n\n\n.6\n%\n\n\n\n)\n5.\n\n\n\n C\nha\n\n\n\nnc\nro\n\n\n\nid\n (5\n\n\n\n.3\n%\n\n\n\n)\n6.\n\n\n\n G\nen\n\n\n\nita\nl h\n\n\n\ner\npe\n\n\n\ns \n(4\n\n\n\n.8\n%\n\n\n\n)\n\n\n\n1.\n G\n\n\n\nen\nita\n\n\n\nl w\nar\n\n\n\nts\n (3\n\n\n\n0.\n2%\n\n\n\n)\n2.\n\n\n\n S\nyp\n\n\n\nhi\nlis\n\n\n\n (2\n1.\n\n\n\n7%\n)\n\n\n\n3.\n G\n\n\n\non\nor\n\n\n\nrh\nea\n\n\n\n (1\n3.\n\n\n\n8%\n)\n\n\n\n4.\n G\n\n\n\nen\nita\n\n\n\nl h\ner\n\n\n\npe\ns \n\n\n\n(1\n1.\n\n\n\n4%\n)\n\n\n\n5.\n N\n\n\n\nSU\n (7\n\n\n\n.9\n%\n\n\n\n)\n\n\n\n1.\n N\n\n\n\nSU\n (4\n\n\n\n5.\n2%\n\n\n\n)\n2.\n\n\n\n G\nen\n\n\n\nita\nl w\n\n\n\nar\nts\n\n\n\n \n(1\n\n\n\n5.\n5%\n\n\n\n)\n3.\n\n\n\n G\non\n\n\n\nor\nrh\n\n\n\nea\n (1\n\n\n\n2.\n3%\n\n\n\n)\n4.\n\n\n\n S\nyp\n\n\n\nhi\nlis\n\n\n\n (8\n.6\n\n\n\n%\n)\n\n\n\n5.\n G\n\n\n\nen\nita\n\n\n\nl h\ner\n\n\n\npe\ns \n\n\n\n(5\n.8\n\n\n\n%\n)\n\n\n\n6.\n T\n\n\n\nric\nho\n\n\n\nm\non\n\n\n\nia\nsi\n\n\n\ns \n(2\n\n\n\n.5\n%\n\n\n\n)\n\n\n\n1.\n G\n\n\n\nen\nita\n\n\n\nl h\ner\n\n\n\npe\ns \n\n\n\n(2\n4.\n\n\n\n0%\n)\n\n\n\n2.\n G\n\n\n\nen\nita\n\n\n\nl w\nar\n\n\n\nts\n \n\n\n\n(2\n3.\n\n\n\n5%\n)\n\n\n\n3.\n T\n\n\n\nric\nho\n\n\n\nm\non\n\n\n\nia\nsi\n\n\n\ns \n(1\n\n\n\n2.\n3%\n\n\n\n)\n4.\n\n\n\n N\nSU\n\n\n\n (1\n0.\n\n\n\n6%\n)\n\n\n\n5.\n C\n\n\n\nha\nnc\n\n\n\nro\nid\n\n\n\n (8\n.4\n\n\n\n%\n)\n\n\n\n6.\n S\n\n\n\nyp\nhi\n\n\n\nlis\n (5\n\n\n\n.7\n%\n\n\n\n)\n\n\n\n1.\n G\n\n\n\nen\nita\n\n\n\nl w\nar\n\n\n\nts\n \n\n\n\n(5\n5.\n\n\n\n8%\n)\n\n\n\n2.\n S\n\n\n\nyp\nhi\n\n\n\nlis\n (2\n\n\n\n4.\n1%\n\n\n\n)\n3.\n\n\n\n G\nen\n\n\n\nita\nl h\n\n\n\ner\npe\n\n\n\ns \n(8\n\n\n\n.6\n%\n\n\n\n)\n4.\n\n\n\n G\non\n\n\n\nor\nrh\n\n\n\nea\n (7\n\n\n\n.5\n%\n\n\n\n)\n5.\n\n\n\n C\nha\n\n\n\nnc\nro\n\n\n\nid\n (2\n\n\n\n.3\n%\n\n\n\n)\n\n\n\n*N\nSU\n\n\n\n: n\non\n\n\n\n-s\npe\n\n\n\nci\nfic\n\n\n\n u\nre\n\n\n\nth\nrit\n\n\n\nis\n; N\n\n\n\nA\n: n\n\n\n\not\n a\n\n\n\nva\nila\n\n\n\nbl\ne\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n35MJD 2019 Dec Vol 43\n\n\n\n19. 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A cross-sectional study to explore \npostgraduate students\u2019 understanding of and beliefs \nabout sexual and reproductive health in a public \nuniversity, Malaysia. Reprod Health 2015;12:77.\n\n\n\n38. Mutalip SSM, Mohamed R. Sexual Education in \nMalaysia: Accepted Or Rejected? Iran J Public Health \n2012;41:34-9.\n\n\n\n39. Nordin RB, Isa AR, Abdullah MR. Prevalence of \nSexually Transmitted Diseases among New Female \nDrug Abusers in a Rehabilitation Centre. Malaysian J \nMed Sci 2001;8:9-13.\n\n\n\n40. Dembo R, Belenko S, Childs K, Wareham J. Drug Use \nand Sexually Transmitted Diseases among Female and \nMale Arrested Youths. J Behav Med 2009:32:129-41.\n\n\n\n41. Al-Fouzan A, Al-Mutairi N. Overview of Incidence of \nSexually Transmitted Diseases in Kuwait. Clin Dermatol \n2004;22:509-12.\n\n\n\n42. Mowla MR. Recent trends in sexually transmitted \ninfections: The Bangladesh experience. J Am Acad \nDermatol 2017;5812:AB216.\n\n\n\n43. Chak M, Lui R. Hong Kong STD/AIDS Update \n2017;23:Quarter 4. \n\n\n\n44. Singh SK, Kumar N, Gupta AK, Mohan L, Sushantika, \nMohammad A. An epidemiological study of sexually \ntransmitted diseases cases at STD clinic, Gorakhpur. Int \nJ Res Dermatol 2018;4:185-9.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n36 MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nCondylomata Acuminata In Children: Sexual Abuse or Not?  A Case \nSeries         \nWee Ai Leen, MRCPCH \n\n\n\nDepartment of Paediatric, Hospital Tuanku Ja\u2019afar Seremban, Negeri Sembilan, Malaysia\n\n\n\nSummary\nDiagnosing and treating anogenital warts is a reasonably easy and straightforward process. However, \nit is a difficult task for the practitioner to decide whether the anogenital warts is a result of sexual abuse \nor not; particularly without a forthcoming and clear-cut history and physical examination. Reported \nand discussed here is a series of cases I encountered and managed in 2 centres in Malaysia.  \n\n\n\nKey words: Condylomata acuminata, Anogenital warts, Sexual abuse\n\n\n\nCorresponding Author\nDr Wee Ai Leen\nDepartment of Paediatric, Hospital Tuanku Ja\u2019afar \nSeremban, Jalan Rasah, 70300, Seremban, Negeri \nSembilan\nEmail: weeaileen78@yahoo.com \n\n\n\nIntroduction\nCondylomata acuminata or anogenital warts caused \nby human papillomavirus (HPV) is the commonest \nsexually transmitted infection (STI). The approach \nto children with anogenital warts in the context of \nsexual abuse is a challenge in clinical practice.1 \nCondylomata acuminata in children can be, but not \nnecessarily, an indicator of child sexual abuse.2 \n\n\n\nCase Series\nReported here is a series of 6 cases of anogenital \nwarts in children diagnosed and managed in two \ndifferent hospitals for the past 30 months. The ages \nof onset ranged from 7 months to 4.2 years; two \nboys and four girls. Three mothers had history of \nanogenital warts before. Screening for infectious \ndiseases including Human Immunodeficiency \nVirus (HIV), Hepatitis B, Hepatitis C and syphilis \nwere all negative. Only one out of the 6 cases had \npositive history of sexual abuse. However, she had \nno evidence of genital trauma or hymen rupture. \nAll patients (where possible and age appropriate), \ntheir parents and caretakers went through thorough \nhistory taking and physical examinations. They \nwere evaluated by paediatricians well versed with \nmanaging child sexual abuse cases. All of them \nwere treated with one or more of these modalities \nincluding topical imiquimod and cryotherapy. Table \n1 summarises the details of the patients. \n\n\n\nDiscussion\nEstablishing the diagnosis of anogenital warts is \nfairly straightforward and can be done by clinical \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n37MJD 2019 Dec Vol 43\n\n\n\n1 2 3 4 5 6\nAge of onset \n(months)\n\n\n\n24 24 7 50 18 8\n\n\n\nAge at 1st \nconsultation\n(months)\n\n\n\n29 27 15 52 18 14\n\n\n\nGender Boy Girl Boy Girl Girl Girl\nInfectious screen Negative Negative Negative Negative Negative Negative\nMother HPV status No Yes Yes No No Yes\nSexual abuse No No No Yes No No\nTreatment modalities:\n1.Cryotherapy\n2.Imiquimod\n\n\n\n1 1 1 1 & 2 2 2\n\n\n\nResolution Yes Yes Yes Yes Yes Yes\n\n\n\nTable 1. Summary of Cases\n\n\n\nappearance mainly. It is neither possible nor \nbeneficial to assess with certainty the origin of HPV \ninfection in children with anogenital warts because \nboth the HPV genotyping and the infection\u2019s \nclinical features does not allow the identification of \nthe mode of transmission as sexual or otherwise.1 \nApart from sexual abuse, anogenital warts in young \nchildren may be transmitted by perinatal exposure, \nhetero-inoculation, autoinoculation and indirect \nfomite transmission.2,3,4 \n\n\n\nThe approach to a child presenting with anogenital \nwarts can be challenging and require a tedious \nprocess, in particular attempting to exclude child \nsexual abuse. If practitioner does not investigate \nfurther, he/she risks missing a case of child sexual \nabuse.3 On the other hand, if he/she reports all cases \nof anogenital warts without evidence/ suspicion, \nparents/ caregivers may potentially suffer false \naccusation and its possible consequences including \n\n\n\nIn the same review paper, there was also a guidelines \nfor follow up screening in children who have \nanogenital warts but not reported as suspected child \n\n\n\nlosing their children\u2019s custody.3 \n\n\n\nThe diagnosis of child sexual abuse includes \nobtaining a complete and meticulous interview with \nthe primary caregivers (usually parents), child and \nthorough physical examinations. Ideally, they should \nbe referred to and managed by a doctor specially \ntrained in child sexual abuse. The probability of \nchild sexual abuse appears to be higher in children \nmore than 4 years old presenting with anogenital \nwarts.1,3 This was also witnessed in this case series \nas the only case of child sexual abuse is the only \npatient who was above 4 years of age. Sinclair KA \net al suggested that any child more than 4 years old \npresenting with anogenital warts should be reported \nto the Child Protection Services; apart from other \nfindings such as child\u2019s behaviour suggests abuse \nand finding of a sexually transmitted infection in \naddition to HPV3 (Table 2). \n\n\n\nsexual abuse3 (Table 3). Fairly similar approach was \nmentioned in an older article.4\n\n\n\nTable 2. Findings in a Child Who Has Anogenital Warts That Require a Report to Child Protective Services\n\n\n\n\u2022\t Parents suspect abuse\n\u2022\t Child discloses abuse\n\u2022\t Child\u2019s behaviour suggests abuse\n\u2022\t Physical examination suggest abuse\n\u2022\t Finding of a sexually transmitted infection in addition to HPV\n\u2022\t Any child older than 48 months of age\n\n\n\nExceptions: Adolescents who report consensual sexual activity with an appropriate-age peer & severely immunosuppresse \nchildren who have multiple warts at other sites with no other findings of abuse\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n38 MJD 2019 Dec Vol 43\n\n\n\nTable 3. Follow up Screening for Sexual Abuse in Children Who Have Anogenital Wart Not Reported as \nSuspected Child Sexual Abuse\n\n\n\nTreatment may not be necessary as 75% of \nanogenital warts resolve spontaneously within few \nmonths in immunocompetent children.3 Treatment \nmay be desired in long lasting cases or when warts \nare causing symptoms such as pain with defaecation, \nitching or bleeding.3 Non-surgical approaches \ninclude those that cause non-specific tissue \ndestruction (e.g. podophyllin, podofilox) and topical \nimmunomodulators (e.g. imiquimod). Physical \ntherapies include liquid nitrogen cryotherapy, \nelectrodessication and pulsed dye laser.3 Selection \nof treatment modality depends largely on the age \nand tolerability of the child. \n\n\n\nConclusion\nThis series of cases once again showed that in older \nchildren presenting with anogenital warts, there is \nhigher probability of child sexual abuse, consistent \nwith several previous reports and reviews.  \nAnogenital warts in a child does not equate to sexual \nabuse. Non-sexual transmissions of HPV should be \nactively sought and strongly considered as long as \nthere is no other concomitant STI, history of sexual \nabuse, evidence of genital trauma or hymen rupture.     \n\n\n\nHistory:\n\u2022\t New caretaker concerns about abuse\n\u2022\t New disclosure by the child\n\u2022\t Symptoms of anal/ genital trauma or infection (vaginal discharge, vaginal/ anal bleeding or \n\n\n\npain)\n\u2022\t Behaviours (non-specific but often seen in child sexual abuse cases)\n\n\n\n\uf0fc\tUnusual fears\n\uf0fc\tSleep disturbances\n\uf0fc\tChange in school performance\n\uf0fc\tAnger or acting out \n\n\n\n\u2022\t Behaviours (more specific for child sexual abuse)\n\uf0fc\tSexual knowledge unusual for age of child\n\uf0fc\tActing out sexual acts with peers\n\uf0fc\tInappropriate exposure or excessive touching of genitalia of self or others\n\n\n\nExamination Findings:\n\u2022\t Trauma to genitalia/ anal area\n\u2022\t Trauma to skin in area of breast e.g. bite marks\n\u2022\t Trauma to the mouth or pharynx e.g. bruising of tongue or palate\n\n\n\nLaboratory Testing:\n\u2022\t Confirmed sexually transmitted infection\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health, Malaysia for permission to \npublish this paper.\n\n\n\nReferences\n\n\n\n1. Costa-Silva M, Fernandes I, Rodrigues AG, Lisboa \nC. Anogenital warts in pediatric population. An Bras \nDermatol 2017;92:675-81.\n\n\n\n2. Bussen S, Sutterlin M, Schmidt U, Bussen D. Anogenital \nWarts in Childhood- Always a Marker for Sexual Abuse? \nGeburtshilfe Frauenheilkd 2012;72:43-8.\n\n\n\n3. Sinclair KA, Woods CR, Sinal SH. Venereal Warts in \nChildren. Pediatr Rev. 2011;32:115-21.\n\n\n\n4. Jayasinghe Y, Garland SM. Genital warts in children: what \ndo they mean? Arch Dis Child 2006;91:696-700.\n\n\n\n5. Horror G. Ano-Genital Warts in Children: Sexual Abuse or \nNot? J Pediatr Health Care 2004;18:165-70.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n39MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nIdentification of p.Gly221_Gln231del, FS7X EDA mutation in 3 siblings \nfrom a Malaysian family of Indian ethnicity diagnosed with XLHED         \nMin Moon Tang1, AdvMDerm, Glenda Guek Khim Oh2,3, BSc, Uttam Surana4,5, PhD, Zacharias Aloysius Dwi Pramano3, \nMD, PhD, Kin Fon Leong6, MRCPCH \n\n\n\n1Department of Dermatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n2Australian Research Council Centre of Excellence in Plant Energy Biology, University of Western Australia, Perth, \nAustralia\n3National Skin Centre, Singapore\n4Institute of Molecular and Cellular Biology (IMCB), Agency of Science, Technology and Research (A*STAR), Singapore\n5Singapore Bioprocessing Technology Institute, Singapore\n6Paediatric Dermatology Unit, Paediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia\n\n\n\nSummary\nHypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by hypohidrosis, \nhypotrichosis and hypodontia.1 HED is a consequence of mutations in any one of numerous genes \nencoding proteins of the tumor necrosis factor-\u03b1 (TNF\u03b1) related pathway, specifically the ectodysplasin \nA (EDA) signalling pathway that is essential in the development of embryonic ectoderm.1 Here we \nreport the genetic study of HED that affects three Indian orphans who were siblings from Malaysia.  \n\n\n\nKey words: Hypohidrotic ectodermal dysplasia (HED), X-linked HED\n\n\n\nCorresponding Author\nDr Tang Min Moon\nDepartment of Dermatology, Hospital Kuala Lumpur, \nJalan Pahang, 50586 Kuala Lumpur, Malaysia\nEmail: minmoon2005@yahoo.com \n\n\n\nIntroduction\nHypohidrotic ectodermal dysplasia (HED) is a \ngenetic disorder characterized by hypohidrosis, \nhypotrichosis and hypodontia.1 HED is a \nconsequence of mutations in any one of numerous \ngenes encoding proteins of the tumor necrosis \nfactor-\u03b1 (TNF\u03b1) related pathway, specifically \nthe ectodysplasin A (EDA) signalling pathway \nthat is essential in the development of embryonic \nectoderm.1 These proteins play important roles in the \nsignal transduction from ectoderm to mesenchyme \nin the fetus particularly for the differentiation of \nectoderm-derived structures like eccrine sweat \nglands, teeth, hair, skin, and/or nails. Here we report \nthe genetic study of HED that affects three Indian \norphans who were siblings from Malaysia.\n\n\n\nCase Report\nJ1, J2 and J3, all males, aged 4, 7 and 11 years \npresented to the dermatology clinic for xerosis and \neczema with suspected syndromic facial figures. No \ngross abnormality was noted at birth. There were \nno documentations of delay in their developmental \nmilestones. However, all of them had history of \nlack of sweating with a few hospitalizations for \nhyperthermia, recurrent respiratory tract infections \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n40 MJD 2019 Dec Vol 43\n\n\n\nand asthma. They were left at the orphanage \nfor 4 years by their parents, who were in a non-\nconsanguineous marriage. The family tree was \nshown in Figure 1.\n\n\n\nPhysical examination revealed all of them had \nheights and weights below the third centile. They \nhad eczema and xerosis. Their scalp hair was thin \nand sparse. They had reduced number of wide-\nspaced peg-shaped teeth (Figure 2a-f). The nails \nwere normal. Examination of other systems were \nnormal.\n\n\n\nUnfortunately, the parents could not be traced for \nfurther exploration of family history. Despite that, \nour provisional diagnosis was X-linked HED. After \nobtaining informed consent according to the local \nmedical ethics guidelines, peripheral blood samples \n(3 ml) were obtained from all three patients in \nEDTA-containing tubes. Genomic DNA was isolated \nfrom these samples using E.Z.N.A Blood DNA Kit \n(Omega Bio-tek, Norcross, Georgia, USA). The \nthree genes, namely EDA1, EDAR and EDARADD \nwere screened for mutation.  Direct sequencing of \npurified PCR products were performed using Big \nDye Terminator Sequencing Kit (Version 3.0) and \nanalysed on the ABI 3700 DNA sequencing system \n(both from PE Applied Biosystems, Foster City, CA). \nSequence comparisons and analyses were performed \nusing Basic Local Alignment Search Tool (BLAST) \nfrom the National Centre for Biotechnology \nInformation (NCBI). The results revealed that all \nof them carried a 35-bp deletion in exon 5 of EDA \nresulting in 11 amino acid deletion (Figure 2g-j), \nfollowed by a frame shift and premature stop codon, \nEDA c.663_697del (p.Gly221_Gln231delfxTer27). \nNo mutation was found in EDAR and EDARADD. \n\n\n\nFigure 1. Family tree of the three siblings which \nshowed that only males were affected.\n\n\n\nDiscussion\nA spot diagnosis is possible in HED in \nthe presence of hypotrichosis, hypodontia \ntogether with history of hypohidrosis. To \nconfirm the diagnosis, the demonstration of \nmutation at ligand-ectodysplasin A(EDA, \nXq13.1, OMIM#300451), ectodysplasin A-A1 \nreceptor(EDAR, 2q13, type 10A-OMIM#129490 \nand 10B-OMIM#224900) or EDAR-associated \ndeath domain protein(EDARADD, 1q42-q43, type \n11A-OMIM#614940 and 11B-OMIM#614941) \nis  required.1 The most frequent variant of HED \nis results from mutations in EDA located on the \nlong arm of chromosome X.  Hence \u201cfull blown\u201d \nsymptoms of HED are seen in hemizygous males \nwhile heterozygous females may present with \nmild or negligible symptoms. To date, about 314 \nmutations were reported in EDA gene which included \nmissense/nonsense, splicing, small insertions, small \ndeletions, small indels, gross deletions and gross \ninsertions.1 \n  \nTo the best of our knowledge, our case reported \nhere is probably the fourth case associated with \nEDA c.663_697del(p.Gly221_Gln231delfxTer27). \nThe other 3 cases were reported by the Oregon \nHealth Sciences University (2 cases)2,3 and in China \n(1 case)4. The mutation is predicted to produce a \ntruncated EDA with a change in the collagen domain \nand the absence of the entire TNF homology domain. \nEven if the truncated EDA produced survives from \ndegradation, it is unable to bind to EDAR. As \nconsequence, the initiation of various downstream \nsignalling pathways cannot take place, resulting \nin defective development of structures such as the \nteeth, hair and skin.\n\n\n\nManagement of HED includes avoidance of \nhyperthermia, the frequent use of emollients for the \nxerosis and eczema as well as individualized dental \nprosthesis. Prenatal intraamniotic administration \nof recombinant protein that includes the receptor-\nbinding domain of EDA reported by Schneider et \nal5 has shed some light on the genetic treatment for \nXLHED. As this treatment is at the research stage \nand not widely available, genetic counselling to the \naffected family remains indispensable.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director \nGeneral of Health Malaysia for the permission to \n\n\n\n11 7 4\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n41MJD 2019 Dec Vol 43\n\n\n\npublish this paper.\n\n\n\nFigure 2. (a&d \u2013 J3; b&e \u2013 J2 and c&f- J3) Clinical features of all three siblings presented with xerosis, thin and \nsparse hair as well as peg-shaped teeth; (g-i) Direct sequencing of the amplicons showed that all three siblings \ncarried a 35-bp deletion in exon 5 of EDA resulting in 11 amino acid deletion, followed by a frame shift and \npremature stop codon, EDA c.663_697del (p.Gly221_Gln231delfxTer27).\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n42 MJD 2019 Dec Vol 43\n\n\n\nReferences\n\n\n\n1. Reyes-Reali, Mendoza-Ramos MI, Garrido-Guerrero E, \nM\u00e9ndez-Catal\u00e1 CF, M\u00e9ndez-Cruz AR, Pozo-Molina G. \nHypohidrotic ectodermal dysplasia: clinical and molecular \nreview. Int J Dermatol 2018;57:965-72\n\n\n\n2. Schneider P, Street SL, Gaide O, Hertig S, Tardivel A, \nTschopp J et al. Mutations leading to X-linked hypohidrotic \nectodermal dysplasia affect three major functional \ndomains in the tumor necrosis factor family member \nectodysplasin-A. J Biol Chem 2001;276:18819-27.\n\n\n\n3. Monreal AW, Zonana J, Ferguson B. Identification of a \nnew splice form of the EDA1 gene permits detection of \nnearly all X-linked hypohidrotic ectodermal dysplasia \nmutations. Am J Hum Genet 1998;63:380-9.\n\n\n\n4. He F, Wang H, Zhang X, Gao Q, Guo F, Chen C. \nConservation analysis and pathogenicity prediction \nof mutant genes of ectodysplasin a. BMC Med Genet \n2018;19:209.\n\n\n\n5. Schneider H, Faschingbauer F, Schuepbach-Mallepell S, \nK\u00f6rber I, Wohlfart S, Dick A et al. Prenatal Correction of \nX-Linked Hypohidrotic Ectodermal Dysplasia. N Engl J \nMed 2018;378:1604-10.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n43MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nEpidermodysplasia Verruciformis - A Rare Case Report         \nVarsha Verma1, MBBS, Sumit Kar1, MD, Safa Patrick1, MBBS, Nitin Gangane, MD, PhD, Pooja Bonde, MBBS, Komal \nRamteke, MBBS \n\n\n\n1Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, \nWardha, Maharashtra, India\n2Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra, India\n\n\n\nSummary\nEpidermodysplasia verruciformis (EV) is a rare disease characterized by verrucous skin lesions \nand macules resembling pityriasis versicolor. It is caused by human papillomavirus (HPV) mostly \ndue to subtypes 5 and 8. We hereby present a case of an 18-year-old boy  with a 6-year history of \nasymptomatic raised lesions on hands, forearms, legs and feet with multiple flat light colored lesions \non the trunk, face and back. His elder sister had also similar skin lesions since early childhood. He also \nhad plane warts and verruca vulgaris like lesions over both dorsum of hands, forearms, legs and feet \nand multiple pityriasis versicolor like lesions over face, back and chest. Skin biopsy from the warty \nlesion present on the extensor surface of left forearm was consistent with EV. Hence we report this \ncase with rare presentation.  \n\n\n\nKey words: Epidermodysplasia verruciformis, Pityriasis versicolor, Human papilloma virus\n\n\n\nCorresponding Author\nDr Sumit Kar\nDepartment of Dermatology, Venereology & Leprosy, \nMahatma Gandhi Institute of Medical Sciences. \nSewagram, Maharashtra, 442102 India\nEmail: karmgims@gmail.com \n\n\n\nIntroduction\nEpidermodysplasia verruciformis (EV) is a rare \ndisease characterized by verrucous skin lesions \nand macules resembling pityriasis versicolor. It is \ncaused by human papillomavirus (HPV) mostly \ndue to subtypes 5 and 8.1 EV has a tendency to \nprogress to squamous cell carcinomas. In 1922, \nLewandowsky and Lutz has first described this \nentity.2 Its transmission through a recessive gene \nwas proposed by Cockayne.3 There is mutations \nin the epidermodysplasia verruciformis 1 and \nepidermodysplasia verruciformis 2 genes located \non chromosome 17q25.4 We are hereby reporting \na patient with verrucous skin lesions and pityriasis \nversicolor like hypopigmented macules over trunk \nand face.\n\n\n\nCase Report\nAn 18-year-old boy presented with a 6-year history \nof asymptomatic raised lesions on hands, forearms, \nlegs and feet. He also had multiple flat light-colored \nlesions on the trunk, face and back. His elder sister \nalso had similar skin lesions since early childhood. \nThe patient was born of non-consangouis marriage.  \nThe sister was also called upon for examination \nbut she couldn\u2019t follow up because the sister was \nmarried and stay far away. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n44 MJD 2019 Dec Vol 43\n\n\n\nOn examination, he had multiple plane warts and \nverruca vulgaris like lesions over both dorsum of \nhands, forearms, legs and feet. He also had multiple \nhypopigmented pityriasis versicolor like lesions \nover face, back and chest (Figure 1 a, b, c & d).\n \nSkin biopsy from the warty lesion present on \nthe extensor surface of left forearm revealed \nhyperkeratosis, irregular acanthosis, and an \n\n\n\nDiscussion\nEV presents with widespread and persistent human \npapilloma virus infection. It has been postulated \nthat there occurs defective presentation of viral \nantigens on the surface of keratinocytes which \nis responsible for selective loss of T-lymphocyte \nimmune response against human papilloma virus, \nleading to widespread infection.5\n\n\n\nIt is postulated that properly functioning zinc \nhomeostasis plays a role in preventing viral \nreplication.3 Due to mutation in EVER genes in EV, \n\n\n\nFigure 1 (a) Multiple Plane warts like lesion over dorsum of hands; (b) Pityriasis versicolor like lesions over \nface; (c)  Multiple verruca vulgaris like lesions over both legs; (d) Pityriasis versicolor like lesions over back.\n\n\n\nenlarged vacuolated cells suggestive of koilocytes. \nAlso, there were features of dysplasia. Skin biopsy \nfrom hypopigmented macules was also done which \nshowed features of Pityriasis versicolor. These \nhistopathological features were consistent with EV. \nLaboratory evaluation revealed slight lymphopenia \nand mild eosinophilia. A serological test for human \nimmunodeficiency virus was negative. We started \nhim on acitretin 25mg/day. Follow up is awaited.\n \n\n\n\nthere is impaired synthesis of EVER proteins. Also, \nZnT-1/EVER complex get affected which causes \nincreased zinc level in the cytoplasm and excessive \nreplication of EV HPV.6 It has been reported in \npatients with immunodeficiency as well and hence \nit is not purely a genetic disease.\n\n\n\nThere are two clinical forms of this disease. First one \nis flat hypopigmented or hyperpigmented macules \nor patches resembling pityriasis versicolor. These \nlesions are of benign nature. They usually occur \nat trunk, neck and extremities while the verrucous \n\n\n\na\n\n\n\nc\n\n\n\nb\n\n\n\nd\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n45MJD 2019 Dec Vol 43\n\n\n\nlesions have more malignant nature. They most \ncommonly occur at sun exposed surface like face, \nhands and feet.\n \nSkin malignancy develops in around 30\u201360% of \nindividuals. Squamous cell carcinoma and Bowen\u2019s \ndisease are the common malignancies reported. \nAdnexal carcinoma7 and sebaceous carcinoma4 are \nalso reported, but are rare.\n \nTreatment includes Several nonsurgical treatment \nmodalities including oral and topical retinoids, \ninterferon, immunotherapy, electrodesiccation \nand cryotherapy. However, all of these treatments \nhave either been ineffective or have had temporary \nresults. These lesions generally require surgical \nexcision and reconstruction of the defects. Surgical \ntreatment included complete excision and defect \nreconstruction with split-thickness or full-thickness \nskin grafts or local flaps.8\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nReferences\n\n\n\n1. G\u00fcl U, Kili\u00e7 A, G\u00f6n\u00fcl M, Cakmak SK, Bayis SS. Clinical \naspects of epidermodysplasia verruciformis and review of \nthe literature. Int J Dermatol 2007;46:1069-72.\n\n\n\n2. Lewandowsky F, Lutz W. Ein Fall einer bisher nicht \nbeschriebenen Hauterkrankung (Epidermodysplasia \nverruciformis) Arch Dermatol Syphilol 1922;141:193-203.\n\n\n\n3. Kali\u0144ska-Bienias A, Kowalewski C, Majewski S. The \nEVER genes - the genetic etiology of carcinogenesis in \nepidermodysplasia verruciformis and a possible role in \nnon-epidermodysplasia verruciformis patients. Postepy \nDermatol Alergol 2016;33:75-80.\n\n\n\n4. Kambhampati SB, Vinay K, De D, Handa S, Gaspar \nBL, Saikia UN. Sebaceous cell carcinoma developing \nin epidermodysplasia verruciformis. Indian J Dermatol \nVenereol Leprol 2016;82:433-5.\n\n\n\n5. S\u00e1 NB, Guerini MB, Barbato MT, Di Giunta G, Nunes DH. \nEpidermodysplasia verruciformis: Clinical presentation \nwith varied forms of lesions. An Bras Dermatol \n2011;86:S57-60.\n\n\n\n6. Lazarczyk M, Favre M. Role of Zn2+ ions in host-virus \ninteractions. J Virol 2008;82:11486-94.\n\n\n\n7. Sri JC, Dubina MI, Kao GF, Rady PL, Tyring SK, Gaspari \nAA. Generalized verrucosis: A review of the associated \ndiseases, evaluation, and treatments. J Am Acad Dermatol \n2012;66:292-311.  \n\n\n\n8. Emsen IM, Kabalar ME. Epidermodysplasia verruciformis: \nAn early and unusual presentation. Can J Plast Surg \n2010;18:21-4.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n46 MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nA Case of Devastating Ocular Sequelae of Stevens-Johnson \nSyndrome         \nSatheitra Rajandran1, 2, MD, Kursiah Mohd Razali1, MS Ophthal, Fellowship in Cornea Diseases, Mushawiahti Mustapha2, \nMS Ophthal, Fellowship in vitreoretinal diseases \n\n\n\n1Department of Ophthalmology, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia\n2Department of Ophthalmology, Hospital Canselor Tunku Muhriz, Kuala Lumpur, Malaysia\n\n\n\nSummary\nStevens-Johnson syndrome is a life-threatening severe drug adverse event that commonly seen to have \nocular involvement. Here we report a case of a lady who developed Stevens-Johnson syndrome after \nconsuming a type of non-steroidal anti-inflammatory drug and had severe lid margin cicatrization \nand ocular surface abnormalities which lead to recurrent persistent cornea epithelial defect causing \nirreversible blindness years after the first manifestation  \n\n\n\nKey words: Stevens-Johnson syndrome, Cornea epithelium, Amnion\n\n\n\nCorresponding Author\nDr Satheitra Rajandran\n124, Jalan Foo Win Yin, Taman Canning, 31400 Ipoh, \nPerak\nEmail: satheitra@gmail.com \n\n\n\nIntroduction\nStevens\u2013Johnson syndrome (SJS) is a type IV \ndelayed hypersensitivity that leads to severe systemic \nmucocutaneous reactions. It is characterized \nby severe blistering epidermal detachment and \nhemorrhagic erosions.1,2 It can also affect the \nmucocutaneous junction of the ocular surface.\n\n\n\nOcular manifestations during the acute stage are \ninflammatory conjunctivitis, corneal or conjunctival \nepithelial defects, pseudomembrane formation and \nlid margin keratinization. Chronic ocular sequelaes \ninclude symblepharon, lid cicatrical changes \n(entropion, distichiasis), cornea limbal stem cell \ndeficiency, persistent cornea epithelial defects and \ncornea conjunctivalization.3 Severe cases can lead \nto cornea perforation and blindness. The severity \nof the ocular involvement at the acute stage is the \ncontributing factor to the frequency and severity of \nthe chronic ocular sequelae.4\n\n\n\nCase Report\nA 31-year-old lady developed mucocutaneous rashes \nover the oral cavity, perianal and genital region after \ningesting mefenamic acid, a type of non steroidal \nanti- inflammatory drug. She was diagnosed with \nStevens-Johnson syndrome complicated with acute \nhepatitis. She was referred to ophthalmology team \nfor both eye discharge, redness and pain. Upon \nassessment, the visual acuity was 6/36 in both eyes. \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n47MJD 2019 Dec Vol 43\n\n\n\nOcular examinations showed pseudomembranous \nconjunctivitis with almost total cornea epithelial \ndefects bilaterally. She was treated as severe ocular \nSJS with lubricants antibacterial, and steroid \neye drops. Amniotic membrane transplantation \n(AMT) was planned however due to her unstable \nsystemic medical condition it was then deferred. \nSubsequently 4 weeks later, AMT was performed \nto her right eye in view of non healing epithelial \ndefect. After the operation, conjunctival and the \n\n\n\nShe was seen by oculoplastic team and planned \nfor bilateral lower lid posterior lamellar grafting \nwith buccal mucosa. However, the patient refused \nfor intervention. She was then monitored and co-\nmanaged for symptomatic treatment by both cornea \nand oculoplastic team with long term steroid and \nintensive lubricants.\n\n\n\nA year after the initial presentation, she presented \nwith sudden onset of left eye pain and redness. \nVisual acuity reduced from 6/9 to 6/60. Examination \nrevealed diffuse conjunctival hyperemia, \npseudomembrane on both upper and lower \npalpebral conjunctiva, epithelial defect centrally \noverlying the old cornea scar, 360 degrees cornea \nconjunctivalization and central cornea thinning. \nFigure 1b. She had left eye infective conjunctivitis \nwhich subsequently resolved, but the epithelial \ndefect persisted. \n\n\n\nAMT was performed twice however the epithelial \ndefect on the left eye did not heal. She was then \ncounselled for lateral tarsorrhaphy, for which she \nwas not keen. Her left eye condition progressively \nworsened as she developed a descemetocele which \nthen perforated (Figure 1c). \n\n\n\nDiscussion\nOcular involvement in SJS needs to be tackled \nas early as possible and intensively to preserve \n\n\n\nFigure 1(a) Scarring of palpebral conjunctiva; (b) Cornea opacity with central thinning, and cornea \nvascularization; (c) Left eye cornea perforation.\n\n\n\ncornea epithelial defects healed and both eye\u2019s \nvisual acuity improved to 6/9.\n\n\n\nDuring her subsequent follow ups, noted that she \ndeveloped chronic ocular SJS sequelaes such \nas lower lid cicatrical entropion with trichiasis, \nobliteration of lower lid punctum, palpebral \nconjunctival scarring Figure 1a, shortening of the \nlateral fornix at both eyes.\n\n\n\nthe vision and prevent severe vision threatening \nchronic complications. The primary outcome can \nbe measured by assessing the severity of ocular \ninvolvement in acute phases. According to Power \nclassification, they can be graded into mild, moderate \nand severe based on the extent of involvement of the \nconjunctiva and cornea.5\n\n\n\nGregory et al proposed another grading system to \nguide when urgent amniotic membrane transplant \n(AMT) is indicated. Cases which has either cornea \nepithelial defect, or lid margin staining more than \n1/3 of its length, or more than 1 cm of bulbar/\npalpebral conjunctiva belongs to the severe group \nwhere urgent AMT is indicated. The study showed \nexcellent results where all the patients from severe \nand extremely severe groups had BCVA 20/20 and \nonly mild dry eye problem and scarring sequelae.6 \n\n\n\nAMT can be repeated for every 10-14days as \nindicated.7 \n\n\n\nSystemic pulse steroid given alone at the onset \nof disease, or in combination with intravenous \nimmunoglobulin shown to reduce the severity of \nillness and the severity of ocular inflammation and \nsubsequent complications.8, 9\n\n\n\nBased on the grading stated above, this patient fell \nin the severe category of ocular SJS who are more \nprone to have severe chronic ocular complications. \n\n\n\na b c\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n48 MJD 2019 Dec Vol 43\n\n\n\nAfter a superimposed infection on the left eye, the \nocular surface abnormalities worsened leading to \na persistent non healing left eye epithelial defect \nwhich did not respond to the intensive treatment and \nrepeated amniotic membrane transplantation. This \ncould be attributed to limbal stem cell deficiency, \nand to the constant erosion of the cornea by the \nmisdirected lashes.\n\n\n\nWe also witnessed a better outcome of visual \nacuity and milder chronic sequelae in right eye \nwhich underwent AMT early during the acute \nstage, compared to the left eye which had a more \naggressive course.\n\n\n\nThis patient refused surgical intervention of the \nlid margin which could have prevented the severe \ncomplications of cornea perforation and blindness.\n\n\n\nConclusion\nIn conclusion, ophthalmologist play a great role in \nthe co-management of SJS with ocular involvement. \nEarly staging and aggressive management are very \nimportant to prevent sequelaes which might lead to \ndevastating ocular complications in future.\n\n\n\nConflict of Interest Declaration \nThe author has no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\nReferences\n\n\n\n1. Wolf R, Davidovici B. Severe cutaneous adverse drug \nreactions: Who should treat, where and how: Facts and \ncontroversies. Clin Dermatol 2010;28:344-8. \n\n\n\n2. Lihite R, Lahkar M, Borah A, Hazarika D, Singh S. A study \non drug induced Stevens-Johnson Syndrome (SJS), Toxic \nEpidermal Necrolysis (TEN) and SJS-TEN overlap in a \ntertiary care hospital of Northeast India. J Young Pharm \n2016;8:146-50.\n\n\n\n3. Chan F, Benson MD, Plemel DJA, Mahmood MN, Chan \nSM. A diagnosis of Stevens-Johnson Syndrome (SJS) \nin a patient presenting with superficial keratitis. Am J \nOphthalmol Case Rep. 2018;11:167-9.\n\n\n\n4. Saka B, Akakpo AS, Teclessou JN, Mahamadou G, \nMouhari-Toure A, Dzidzinyo K et al. Ocular and \nMucocutaneous Sequelae among Survivors of Stevens-\nJohnson Syndrome and Toxic Epidermal Necrolysis in \nTogo. Dermatol Res Pract. 2019; 2019:4917024.\n\n\n\n5. Power WJ, Ghoraishi M, Merayo-Lloves J, Neves \nRA, Foster CS. Analysis of the acute ophthalmic \nmanifestations of the erythema multiforme/ Stevens-\nJohnson syndrome/toxic epidermal necrolysis disease \nspectrum. Ophthalmology 1995;102:1669-76.\n\n\n\n6. Gregory DG. New Grading System and Treatment \nGuidelines for the Acute Ocular Manifestations of Stevens-\nJohnson Syndrome. Ophthalmology 2016;123:1653-8.\n\n\n\n7. Gregory DG. Treatment of Acute Stevens Johnson \nSyndrome and Toxic Epidermal Necrolysis Using \nAmniotic Membrane: A Review of 10 Consecutive Cases. \nOphthalmology 2011;118:908-14.\n\n\n\n8. Aihara M, Kano Y, Fujita H, Kambara T, Matsukura S, \nKatayama I et al. Efficacy of additional i.v. immunoglobulin \nto steroid therapy in Stevens-Johnson syndrome and toxic \nepidermal necrolysis. J Dermatol 2015;42:768-77.\n\n\n\n9. Araki Y, Sotozono C, Inatomi T, Ueta M, Yokoi N, \nUeda E et al. Successful treatment of Stevens-Johnson \nsyndrome with steroid pulse therapy at disease onset. Am J \nOphthalmol. 2009;147:1004-11.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n49MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nLight Chain Myeloma-associated Systemic Nodular Cutaneous \nAmyloidosis \u2013 A Case Report and Review of Literature         \nRajalingam Ramalingam, AdvMDerm \n\n\n\nDepartment of Dermatology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia\n\n\n\nSummary\nSystemic amyloidosis is characterized by extracellular deposition of insoluble fibrillar protein called \namyloid, in various tissues and organs, including the skin, and complicates about 10% of multiple \nmyeloma cases. It can present with a variety of cutaneous signs and symptoms which physicians \nand dermatologists should be aware of, as a high index of suspicion of an underlying hematological \nmalignancy can lead to prompt diagnosis and early intervention. While nodular amyloidosis is \ncategorized as a primary localized cutaneous amyloidosis, to the best of our knowledge, systemic \nnodular amyloidosis has not been reported before, especially in association with multiple myeloma. \nHence, this case report aims to highlight this condition as well as some of the other cutaneous lesions \nencountered in systemic amyloidosis, with the hope that it increases awareness among healthcare \nproviders.\n\n\n\nKey words: Cutaneous amyloidosis, Systemic amyloidosis, Nodular amyloidosis, Multiple myeloma, Paraproteinemia, Malaysia\n\n\n\nIntroduction\nMultiple myeloma is a neoplastic proliferation \nof a single clone of plasma cells that produces \na monoclonal immunoglobulin. It encompasses \napproximately 1% of all malignant tumors and \n10-15% of hematologic cancers.1 Up to 20% of \ncases of multiple myeloma is due to light chain \nimmunoglobulins. Amyloidosis on the other hand, \nis the extracellular deposition of insoluble fibrillar \nprotein called amyloid, in various tissues and organs, \nincluding the skin. Light chain amyloidosis (AL) is \nthe most common form of systemic amyloidosis and \ncomplicates about 10% of cases of multiple myeloma. \nLiterature categorizes nodular amyloidosis as \nprimary localized cutaneous amyloidosis (PLCA), \nand to the best of our knowledge, a systemic form of \nnodular amyloidosis has never been reported before, \nespecially in association with multiple myeloma. \nThus, this case report hopes to not only highlight \nthis unusual presentation in our patient, but also to \nincrease awareness of the cutaneous manifestations \nof systemic amyloidosis among healthcare providers \nin order to facilitate prompt diagnosis and early \nintervention.\n\n\n\nCase Report\nA 52-year-old indigenous man with no medical \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n50 MJD 2019 Dec Vol 43\n\n\n\nproblems, complained of progressive lethargy, \nanorexia, bone pain and significant weight loss \nover a one-month period, eventually rendering \nhim bed-bound. He gave no other symptoms \nsuch as prolonged fever, cough, night sweats, \ngastrointestinal, genitourinary or neurological \nsymptoms. He did, however, notice a painless, \nskin-colored, nodular eruption over his head and \nneck about a month prior to his illness. He had no \ncontact with anyone suffering from tuberculosis or \nleprosy, and there was no significant family history. \nHe earned a living gathering rattan from the forest. \n\n\n\nExamination of the skin revealed multiple firm, non-\ntender, skin-colored subcutaneous nodules over his \n\n\n\nBlood investigations revealed normochromic \nnormocytic anemia with a hemoglobin level of 5.6 \ng/dL, normal total white cell count of 10 x109/L, \nnormal platelet count of 387 x109/L, elevated \nerythrocyte sedimentation rate (135 mm/hour), \n\n\n\nFigure 1. (a) \u2013 (d) Clinical presentation of the patient showed mutiple skin-colored subcutaneous nodules over \nthe face, forehead, scalp and periorbital region. \n\n\n\nface, neck and scalp. These nodules were ranged in \nsize from half a centimeter to one centimeter across, \nwith a few coalescing into vague plaques (Figure 1, \na-c). No ecchymosis, blisters or skin fragility were \nnoted. He was found to be pale, with no jaundice, \nmildly dehydrated and cachexic. He also had non-\ntender hepatomegaly of 4 fingerbreadths below \nthe right subcostal margin, and splenomegaly of \n3 fingerbreadths medially below the left subcostal \nmargin. Otherwise, the abdomen was soft and non-\ntender. No lymphadenopathy was appreciated, and \nexamination of the cardiovascular, respiratory and \nneurological systems were normal.  Our differential \ndiagnoses included nodular amyloidosis, cutaneous \nsarcoidosis and histoid leprosy. \n\n\n\nrenal impairment (blood urea 14.5 mmol/L, serum \ncreatinine 197 mmol/L), hypoalbuminemia (25 \ng/dL) with raised globulin level (69 g/L), raised \nliver alanine aminotransferase (88 U/L with \nelevated alkaline phosphatase (190 U/L). He also \n\n\n\na\n\n\n\nc\n\n\n\nb\n\n\n\nd\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n51MJD 2019 Dec Vol 43\n\n\n\nhad hypercalcemia (corrected serum calcium 3.83 \nmmol/L). There was 1+ proteinuria and peripheral \nblood smear showed rouleaux formation and the \npresence of occasional neoplastic plasma cells. \nChest, skull and long bone radiography revealed \nmultiple lytic lesions. \n\n\n\nFurther investigation revealed that more than 60% \nof bone marrow cells was made up of atypical \nplasma cells in sheets and clusters. Immunoglobulin \nG kappa paraprotein was found in both serum and \nurine protein electrophoresis. Histopathology of a \nsubcutaneous nodule showed masses of amorphous \neosinophilic material in the dermis and subcutaneous \ntissue which stained positive for Congo Red, and \nwhich, under polarized light, showed an apple-green \nbirefringence (Figure 2, a-c). These findings were in \nkeeping with cutaneous nodular amyloidosis. Thus, \na diagnosis of light chain myeloma-associated \nsystemic nodular cutaneous amyloidosis was made.\n\n\n\nFigure 2. (a) \u2013 (c) Histology of the skin biopsy \nrevealed masses of amorphous eosinophilic material \nin the dermis and subcutaneous tissue which stained \npositive for Congo Red.\n\n\n\nHe was promptly rehydrated, prescribed \nintravenous bisphosphonates and urgently referred \nto our hematology and nephrology colleagues. \nNevertheless, despite early intervention and \naggressive measures, he unfortunately succumbed \nto his illness in less than a week of hospitalization \nfrom overwhelming sepsis and deteriorating organ \nfunction.\n\n\n\nDiscussion \nMultiple myeloma is a neoplastic proliferation \nof a single clone of plasma cells that produces \na monoclonal immunoglobulin. It comprises \nabout 1% of all malignant tumors and 10-15% \nof hematologic cancers1. Light chain myeloma \naccounts for up to 20% of cases of myeloma and \nis characterized by the presence of only a light \nchain in the serum or urine, and lacking expression \nof the immunoglobulin heavy chain. Amyloidosis \nis characterized by extracellular deposition of \ninsoluble fibrillar protein called amyloid, in various \ntissues and organs. Light chain amyloidosis (AL) is \nthe most common form of systemic amyloidosis and \ncomplicates about 10% of multiple myeloma cases. \n\n\n\nNo matter the underlying cause, systemic amyloidosis \ncan present with a multitude of cutaneous signs and \nsymptoms that a dermatologist should be aware of. \nPetechiae, purpura and ecchymoses, often deemed \nclassic signs of systemic amyloidosis, is due to \ndeposits in dermal capillary walls, leading to wall \nfragility and subsequent bleeding,2 oftentimes \nlocated around the orbits (racoon eyes).3,4 In advanced \ndisease, amyloid can be deposited in the dermis, \nadipocytes, glands, vessels and hair follicles,5,6 \nand this presents clinically as non-pruritic, waxy, \ntranslucent papulonodular masses, mainly around \nthe eyes, mouth and mucocutaneous junctions,5 \nas demonstrated in our patient. Other cutaneous \nmanifestations that have been reported include \n\n\n\na: H&E x20\n\n\n\nc: Congo Red x100\n\n\n\nb: H&E x100\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n52 MJD 2019 Dec Vol 43\n\n\n\nalopecia,7 cutis laxa,8 bullae,9 cutaneous ulceration10 \nand nail dystrophy.11 In AA amyloidosis, where \nserum amyloid A is found in the amyloid, typically \nhas no macroscopic involvement of the skin,12 while \nin dialysis-associated beta 2 microglobulin-derived \namyloidosis, lichenoid plaques,13 flaccid plaques,14 \npapules on the arms and trunk,15 subcutaneous \nnodules on the buttocks16 and lingual papules13 have \nbeen reported. Thus, it is not impossible to determine \nthe most likely type of systemic amyloidosis given \nthe clinical presentation. Occasionally, systemic \nAL amyloidosis with amyloid deposition around \nindividual elastic fibers (amyloid elastosis), \ndermal appendages and blood vessel walls can \nmanifest as a sclerodermatous facial appearance, a \npseudoxanthoma elasticum-like appearance on the \nneck, cutaneous papulonodules, livedo reticularis-\nlike changes on the trunk, Raynaud phenomenon, \nblood vessel thromboses and nephrotic syndrome.17 \n\n\n\nTraditionally, nodular amyloidosis is categorized \nas primary localized cutaneous amyloidosis \n(PLCA),18,19 thus, to the best of our knowledge, \nsystemic nodular amyloidosis has not been \nreported before, especially in association with \nmultiple myeloma. Despite being made up of \nlight chain immunoglobulins (AL amyloid), it is \nnot said to be associated with any hematological \ndisorders.2 Nevertheless, systemic involvement \nmust be aggressively ruled out as cutaneous nodular \namyloidosis may be the first manifestation of \nhematological malignancy-associated systemic AL \namyloidosis20 and carries a poor prognosis.21 Rarely, \nnodular amyloidosis has been reported in association \nwith CREST syndrome,22 where it usually presents \nas single or multiple waxy nodules with or without \nepidermal atrophy, mainly in the extremities of the \nlimbs23 but can also appear on the nose, eyelids, \ntrunk and genitalia.24,25\n\n\n\nConclusion\nHence, we can appreciate the myriads of ways \nsystemic amyloidosis can present, frequently \nmimicking other more common dermatoses. A high \nindex of suspicion of an underlying hematological \nmalignancy, especially multiple myeloma, can aid \nthe attending dermatologist and physician in making \na prompt diagnosis, particularly when encountering \na patient with similar cutaneous features.\n\n\n\nDeclaration of Conflict of Interest\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nWe, the authors, would like to thank the staff of \nthe departments of Dermatology and Pathology of \nHospital Tengku Ampuan Afzan, Kuantan, Pahang, \nMalaysia for their hard work in assisting in this \nendeavor. We would also like to thank the Director-\nGeneral of Health, Malaysia, for his permission to \npublish this article.\n\n\n\nReferences\n\n\n\n1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri \nSA, Stein H et al. WHO Classification of Tumours of \nHaemopoietic and Lymphoid Tissues, Fourth Edition \n(2008); WHO press.\n\n\n\n2. Breathnach S. M. Amyloid and amyloidosis. J Am Acad \nDermatol 1988;18:1-16.\n\n\n\n3. Levine N. Bluish discoloration of periorbital area. Eyelid \npurpura and patient\u2019s medical history lead to diagnosis. \nGeriatrics 2004;59:20.\n\n\n\n4. Loo H, Forman WB, Levine MR, Crum ED, Rassiga \nAL. Periorbital ecchymoses as the initial sign in multiple \nmyeloma. Ann Ophthalmol 1982;14:1066-8.\n\n\n\n5. Fernandez-Flores A. Cutaneous Amyloidosis: A Concept \nReview. Am J Dermatopathol 2012;34: 1-14.\n\n\n\n6. Lee DD, Huang CY, Wong CK. Dermatopathologic \nfindings in 20 cases of systemic amyloidosis. Am J \nDermatopathol 1998;20:438-42.\n\n\n\n7. Lutz ME, Pittelkow MR. Progressive generalized alopecia \ndue to systemic amyloidosis. J Am Acad Dermatol \n2002;46:434-6.\n\n\n\n8. Dicker TJ, Morton J, Williamson RM, Chick J. Myeloma-\nassociated systemic amyloidosis presenting with acquired \ndigital cutis laxa-like changes. Australas J Dermatol \n2002;43:144-6.\n\n\n\n9. Wang XD, Shen H, Liu ZH. Diffuse haemorrhagic bullous \namyloidosis with multiple myeloma. Clin Exp Dermatol \n2008;33:94-6.\n\n\n\n10. Alhaddab M, Srolovitz H, Rosen N. Primary systemic \namyloidosis presenting as extensive cutaneous ulceration. \nJ Cutan Med Surg 2006;10:253-6.\n\n\n\n11. Mancuso G, Fanti PA, Berdondini RM. Nail changes as \nthe only skin abnormality in myeloma-associated systemic \namyloidosis. Br J Dermatol 1997;137:471-2.\n\n\n\n12. Rubinow A, Cohen AS. Skin involvement in generalized \namyloidosis. A study of clinically involved and uninvolved \nskin in 50 patients with primary and secondary amyloidosis. \nAnn Intern Med 1978;88:781-5.\n\n\n\n13. Uenotsuchi T, Imafuku S, Nagata M, Kiryu H, Morita K, \nKoga T et al. Cutaneous and lingual papules as a sign of \nbeta 2 microglobulin-derived amyloidosis in a longterm \nhemodialysis patient. Eur J Dermatol 2003;13:393-5.\n\n\n\n14. Kiuru-Enari S, Keski-Oja J, Haltia M. Cutis laxa \nin hereditary gelsolin amyloidosis. Br J Dermatol \n2005;152:250-7.\n\n\n\n15. Sato KC, Kumakiri M, Koizumi H, Ando M, Ohkawara \nA, Fujioka Y et al. Lichenoid skin lesions as a sign of \nbeta 2-microglobulin-induced amyloidosis in a long-term \nhaemodialysis patient. Br J Dermatol 1993;128:686-9.\n\n\n\n16. Shimizu S, Yasui C, Yasukawa K, Nakamura H, Shimizu \nH, Tsuchiya K. Subcutaneous nodules on the buttocks \nas a manifestation of dialysis-related amyloidosis: a \nclinicopathological entity? Br J Dermatol 2003;149:400-4.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n53MJD 2019 Dec Vol 43\n\n\n\n17. Sepp N, Pichler E, Breathnach SM, Fritsch P, Hintner \nH. Amyloid elastosis: analysis of the role of amyloid P \ncomponent. J Am Acad Dermatol 1990;22:27-34.\n\n\n\n18. Ashurst P. Nodular cutaneous amyloidosis. Br J Dermatol \n1971;84:94.\n\n\n\n19. Chapel TA, Birmingham DJ, Malinowski YE. Nodular \nprimary localized cutaneous amyloidosis. Arch Dermatol \n1977;113:1248-9.\n\n\n\n20. Gr\u00fcnewald K, Sepp N, Weyrer K, Lhotta K, Feichtinger \nH, Konwalinka G et al. Gene rearrangement studies in \nthe diagnosis of primary systemic and nodular primary \nlocalized cutaneous amyloidosis. J Invest Dermatol \n1991;97:693-6.\n\n\n\n21. Moon AO, Calamia KT, Walsh JS. Nodular amyloidosis: \nreview and long-term follow-up of 16 cases. Arch \nDermatol 2003;139:1157-9.\n\n\n\n22. Summers EM, Kendrick CG. Primary localized cutaneous \nnodular amyloidosis and CREST syndrome: a case report \nand review of the literature. Cutis 2008;82:55-9.\n\n\n\n23. Love WE, Miedler JD, Smith MK, Mostow EN, Cooper \nKD, Gilliam AC. The spectrum of primary cutaneous \nnodular amyloidosis: two illustrative cases. J Am Acad \nDermatol 2008;58:S33-S35.\n\n\n\n24. Evers M, Baron E, Zaim MT, Han A. Papules and \nplaques on the nose. Nodular localized primary cutaneous \namyloidosis. Arch Dermatol 2007;143:535-40.\n\n\n\n25. Northcutt AD, Vanover MJ. Nodular cutaneous \namyloidosis involving the vulva. Case report and literature \nreview. Arch Dermatol 1985;121:518-21.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n54 MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nFive Cases of Melanoma Presenting ver a year in a Single Institution         \nSheng Zheng Lim1,2, MBBS, Rebecca Emily Keating1,3, MBBS, Yen Fa Toh, MPath4, Man Fong Chew, MPath4, Zhenli \nKwan, AdvMDerm, FRCP1 \n\n\n\n1Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n2Newcastle University Medicine Malaysia, Johor, Malaysia \n3Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom\n4Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia\n\n\n\nSummary\nAccording to the World Cancer Research Fund International, malignant melanoma (MM) is the \n19th most common cancer for both genders. However, there is limited documentation of malignant \nmelanomas in the Asian population and the clinical presentation of melanomas in non-Caucasians is \nnot very well-understood. Hence, we evaluated the clinical presentation, management and outcome \nof five patients diagnosed with melanoma over the span of one year in a single urban Malaysian \ninstitution.   \n\n\n\nKey words: Melanoma, Malaysia, Skin Cancer, Acral lentiginous melanoma, Asian\n\n\n\nCorresponding Author\nDr Kwan Zhenli\nDivision of Dermatology, Department of Medicine, \nFaculty of Medicine, University of Malaya, \nKuala Lumpur, Malaysia\nEmail: zhenli@ummc.edu.my \n\n\n\nIntroduction\nAccording to the World Cancer Research Fund \nInternational, malignant melanoma (MM) is the \n19th most common cancer for both genders. In \n2018, there were approximately 300,000 new cases \nof MM, with Australia having the highest rate, \nfollowed by New Zealand.1 The most common \nhistological subtype in Caucasian patients is \nsuperficial spreading melanoma. However, in Asian \nmelanoma patients, the predominant subtype is \nacral lentiginous melanoma (ALM).2 Cormier at al. \nestablished that the anatomical location of lesions \ndiffers significantly in non-white patients, with \nsoles and subungual areas being common sites, \nresulting in delayed detection and advanced stages \non presentation. There is limited documentation \nof malignant melanomas in the Asian population \nand the clinical presentation of melanomas in non-\nCaucasians is not very well-understood.3 The aim of \nour case series is to strengthen the existing although \nlimited literature on malignant melanoma in Asian \npopulations. Hence, we evaluated the clinical \npresentation, management and outcome of five \npatients diagnosed with melanoma over the span of \none year in a single urban Malaysian institution. \n\n\n\nCase Reports\nIn 2018, there were 5 cases of MM who presented \nat the University of Malaya Medical Centre \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n55MJD 2019 Dec Vol 43\n\n\n\nN\no.\n\n\n\nA\nge\n\n\n\n \n(y\n\n\n\nea\nrs\n\n\n\n)\nG\n\n\n\nen\nde\n\n\n\nr\nE\n\n\n\nth\nni\n\n\n\nci\nty\n\n\n\nTy\npe\n\n\n\nPr\nes\n\n\n\nen\nta\n\n\n\ntio\nn\n\n\n\nL\noc\n\n\n\nat\nio\n\n\n\nn\nSi\n\n\n\nze\n (c\n\n\n\nm\n)\n\n\n\nB\nre\n\n\n\nsl\now\n\n\n\n \nth\n\n\n\nic\nkn\n\n\n\nes\ns \n\n\n\n(m\nm\n\n\n\n)\n\n\n\nA\nJC\n\n\n\nC\n \n\n\n\nst\nag\n\n\n\nin\ng\n\n\n\nD\nur\n\n\n\nat\nio\n\n\n\nn \nof\n\n\n\n le\nsi\n\n\n\non\nTr\n\n\n\nea\ntm\n\n\n\nen\nt\n\n\n\nO\nut\n\n\n\nco\nm\n\n\n\ne\n\n\n\n1\n79\n\n\n\nM\nal\n\n\n\ne\nC\n\n\n\nhi\nne\n\n\n\nse\n \n\n\n\nA\nLM\n\n\n\nFu\nng\n\n\n\nat\nin\n\n\n\ng \nm\n\n\n\nas\ns \n\n\n\nR\nig\n\n\n\nht\n \n\n\n\nlit\ntle\n\n\n\n \nfin\n\n\n\nge\nr \n\n\n\n1.\n3 \n\n\n\nx \n1.\n\n\n\n2 \nx \n\n\n\n0.\n1 \n\n\n\n3.\n0\n\n\n\nT3\nb\n\n\n\nN\n2b\n\n\n\n M\n0 \n\n\n\n(S\nta\n\n\n\nge\n II\n\n\n\nIC\n)\n\n\n\n1 \nm\n\n\n\non\nth\n\n\n\nA\nm\n\n\n\npu\nta\n\n\n\ntio\nn \n\n\n\nof\n \n\n\n\nrig\nht\n\n\n\n li\nttl\n\n\n\ne \nfin\n\n\n\nge\nr  \n\n\n\nSu\ncc\n\n\n\num\nbe\n\n\n\nd \nto\n\n\n\n m\net\n\n\n\nas\nta\n\n\n\ntic\n \n\n\n\nhe\npa\n\n\n\nto\nce\n\n\n\nllu\nla\n\n\n\nr \nca\n\n\n\nrc\nin\n\n\n\nom\na \n\n\n\n2\n74\n\n\n\nM\nal\n\n\n\ne \nC\n\n\n\nhi\nne\n\n\n\nse\n \n\n\n\nA\nLM\n\n\n\n \nFu\n\n\n\nng\nat\n\n\n\nin\ng \n\n\n\nm\nas\n\n\n\ns\nR\n\n\n\nig\nht\n\n\n\n b\nig\n\n\n\n \nto\n\n\n\ne \n3.\n\n\n\n5 \nx \n\n\n\n2.\n5 \n\n\n\nx \n2.\n\n\n\n3\n6.\n\n\n\n0\nT4\n\n\n\nb\nN\n\n\n\n2b\n M\n\n\n\n0 \n(S\n\n\n\nta\nge\n\n\n\n II\nIC\n\n\n\n)\n\n\n\n3 \nm\n\n\n\non\nth\n\n\n\ns\n \n\n\n\nR\nig\n\n\n\nht\n b\n\n\n\nig\n to\n\n\n\ne \nR\n\n\n\nay\n\u2019s\n\n\n\n a\nm\n\n\n\npu\nta\n\n\n\ntio\nn,\n\n\n\n \npe\n\n\n\nm\nbr\n\n\n\nol\niz\n\n\n\num\nab\n\n\n\nO\nng\n\n\n\noi\nng\n\n\n\n tr\nea\n\n\n\ntm\nen\n\n\n\nt \nw\n\n\n\nith\n p\n\n\n\nem\nbr\n\n\n\nol\niz\n\n\n\num\nab\n\n\n\n3\n68\n\n\n\nM\nal\n\n\n\ne \nIn\n\n\n\ndi\nan\n\n\n\nA\nLM\n\n\n\n \nPi\n\n\n\ngm\nen\n\n\n\nte\nd \n\n\n\nm\nac\n\n\n\nul\ne \n\n\n\nw\nith\n\n\n\n \npa\n\n\n\nra\nlle\n\n\n\nl r\nid\n\n\n\nge\n p\n\n\n\nat\nte\n\n\n\nrn\n o\n\n\n\nn \nde\n\n\n\nrm\nos\n\n\n\nco\npy\n\n\n\nLe\nft \n\n\n\nso\nle\n\n\n\n \n0.\n\n\n\n7 \nx \n\n\n\n0.\n5 \n\n\n\nx \n0.\n\n\n\n1\n0.\n\n\n\n2\nT1\n\n\n\na \nN\n\n\n\n0 \nM\n\n\n\n0 \n(S\n\n\n\nta\nge\n\n\n\n IA\n)\n\n\n\n1 \nye\n\n\n\nar\n  \n\n\n\nW\nid\n\n\n\ne \nlo\n\n\n\nca\nl \n\n\n\nex\nci\n\n\n\nsi\non\n\n\n\n a\nnd\n\n\n\n fu\nll-\n\n\n\nth\nic\n\n\n\nkn\nes\n\n\n\ns s\nki\n\n\n\nn \ngr\n\n\n\naf\nt\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n w\n\n\n\nel\nl, \n\n\n\non\n \n\n\n\nsu\nrv\n\n\n\nei\nlla\n\n\n\nnc\ne\n\n\n\n4 \n50\n\n\n\nM\nal\n\n\n\ne \nM\n\n\n\nal\nay\n\n\n\nN\nM\n\n\n\nN\nod\n\n\n\nul\nes\n\n\n\n w\nith\n\n\n\n c\non\n\n\n\nta\nct\n\n\n\n \nbl\n\n\n\nee\ndi\n\n\n\nng\n a\n\n\n\nris\nin\n\n\n\ng \nfr\n\n\n\nom\n \n\n\n\npr\ne-\n\n\n\nex\nis\n\n\n\ntin\ng \n\n\n\nlo\nng\n\n\n\n-\nst\n\n\n\nan\ndi\n\n\n\nng\n p\n\n\n\nig\nm\n\n\n\nen\nte\n\n\n\nd \npa\n\n\n\ntc\nh\n\n\n\nB\nac\n\n\n\nk \n4.\n\n\n\n7 \nx \n\n\n\n2.\n6 \n\n\n\nx \n0.\n\n\n\n3\n3.\n\n\n\n5\nT3\n\n\n\na \nN\n\n\n\n0 \nM\n\n\n\n0 \n(S\n\n\n\nta\nge\n\n\n\n II\nA\n\n\n\n)\n1 \n\n\n\nm\non\n\n\n\nth\nW\n\n\n\nid\ne \n\n\n\nlo\nca\n\n\n\nl \nex\n\n\n\nci\nsi\n\n\n\non\n a\n\n\n\nnd\n sp\n\n\n\nlit\n-\n\n\n\nth\nic\n\n\n\nkn\nes\n\n\n\ns s\nki\n\n\n\nn \ngr\n\n\n\naf\nt\n\n\n\nPr\nes\n\n\n\nen\nte\n\n\n\nd \nw\n\n\n\nith\n \n\n\n\nbi\nla\n\n\n\nte\nra\n\n\n\nl a\nxi\n\n\n\nlla\nry\n\n\n\n \nly\n\n\n\nm\nph\n\n\n\n n\nod\n\n\n\nes\n o\n\n\n\nn \nsu\n\n\n\nrv\nei\n\n\n\nlla\nnc\n\n\n\ne \n10\n\n\n\n \nm\n\n\n\non\nth\n\n\n\ns a\nfte\n\n\n\nr i\nni\n\n\n\ntia\nl \n\n\n\nsu\nrg\n\n\n\ner\ny,\n\n\n\n p\nla\n\n\n\nnn\ned\n\n\n\n fo\nr \n\n\n\nax\nill\n\n\n\nar\ny \n\n\n\ncl\nea\n\n\n\nra\nnc\n\n\n\ne \n5\n\n\n\n65\nM\n\n\n\nal\ne \n\n\n\nC\nhi\n\n\n\nne\nse\n\n\n\nA\nLM\n\n\n\nPa\ntc\n\n\n\nh \nw\n\n\n\nith\n ir\n\n\n\nre\ngu\n\n\n\nla\nr \n\n\n\nbo\nrd\n\n\n\ner\ns a\n\n\n\nnd\n d\n\n\n\niff\ner\n\n\n\nen\nt \n\n\n\nco\nlo\n\n\n\nur\ns, \n\n\n\nar\nea\n\n\n\n o\nf \n\n\n\nre\ngr\n\n\n\nes\nsi\n\n\n\non\n\n\n\nLe\nft \n\n\n\nso\nle\n\n\n\n \n(h\n\n\n\nee\nl)\n\n\n\n1.\n6 \n\n\n\nx \n1.\n\n\n\n2  \n0.\n\n\n\n5\nT1\n\n\n\na \nN\n\n\n\n0 \nM\n\n\n\n0 \n(S\n\n\n\nta\nge\n\n\n\n IA\n)\n\n\n\nFe\nw\n\n\n\n y\nea\n\n\n\nrs\nW\n\n\n\nid\ne \n\n\n\nlo\nca\n\n\n\nl \nex\n\n\n\nci\nsi\n\n\n\non\n a\n\n\n\nnd\n fu\n\n\n\nll-\nth\n\n\n\nic\nkn\n\n\n\nes\ns s\n\n\n\nki\nn \n\n\n\ngr\naf\n\n\n\nt\n\n\n\nR\nec\n\n\n\nov\ner\n\n\n\ned\n w\n\n\n\nel\nl, \n\n\n\non\n \n\n\n\nsu\nrv\n\n\n\nei\nlla\n\n\n\nnc\ne\n\n\n\nTa\nbl\n\n\n\ne \n1.\n\n\n\n D\nes\n\n\n\ncr\nip\n\n\n\ntio\nn \n\n\n\nof\n m\n\n\n\nel\nan\n\n\n\nom\na \n\n\n\nca\nse\n\n\n\ns s\nee\n\n\n\nn \nin\n\n\n\n th\ne \n\n\n\nU\nni\n\n\n\nve\nrs\n\n\n\nity\n o\n\n\n\nf M\nal\n\n\n\nay\na \n\n\n\nM\ned\n\n\n\nic\nal\n\n\n\n C\nen\n\n\n\ntre\n D\n\n\n\ner\nm\n\n\n\nat\nol\n\n\n\nog\ny \n\n\n\ncl\nin\n\n\n\nic\n in\n\n\n\n 2\n01\n\n\n\n8\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n56 MJD 2019 Dec Vol 43\n\n\n\nDermatology Clinic (Table 1). All the patients were \nmale and mean age at diagnosis was 67.2 years old \n(range from 50 to 79 years). Most of the patients \nwere of ethnic Chinese background (60%, n=3) \nwhile another 20% (n=1) were Malay and Indian \nrespectively. Four of the cases were acral lentiginous \nmelanoma (ALM) and one was nodular melanoma \n(NM). Two of the patients presented with a fungating \nmass on the digit, necessitating amputation. Lymph \nnode involvement was detected during the staging \nof these two patients as well as in another gentleman \nwho had NM on his back. One patient has since \nsuccumbed while another is surviving with ongoing \npembrolizumab treatment. An increased Breslow \nthickness is related with poorer melanoma-specific \nsurvival.4 The mean Breslow thickness for our \npatients is 2.64 mm (range from 0.2 to 6 mm).\n\n\n\nFigure 1. Patient 3 demonstrated a parallel ridge \npattern indicative of melanoma on dermoscopic \nexamination of his left sole\n\n\n\nFigure 2. Patient 2 presented with a fungating mass \nover his right big toe\n\n\n\nDiscussion\nPrevious retrospective analyses from our centre \nreported that the frequency of melanoma among \npatients with skin cancer ranged from 0.9% to \n11.6%.5,6 Although basal cell carcinomas and \nsquamous cell carcinomas are far more common, \nmelanomas pose a distinctive challenge due to \nrelated morbidity and mortality. Half of the patients \nwith melanoma between 2004 and 2010 presented \nwith the acral lentiginous type.5 Our findings were \nconsistent with the previous data. It is interesting to \nnote the preponderance of ethnic Chinese as acral \nmelanomas are not associated with sun exposure \nand therefore the Fitzpatrick skin phototype would \nbe less likely to pose as a risk factor.7 \n\n\n\nWe found that patients with acral melanoma who \nwere detected early when the lesion was either a \nmacule or patch, demonstrated superior outcomes. \nFor patient number 3, the melanoma was an \nincidental finding during a routine check-up for \nother dermatological conditions. Dermoscopy \nwas invaluable in determining the diagnosis in \nthis patient. Efforts to increase awareness about \nthe different presentations of skin cancer as well \nas improving dermoscopy skills would aid early \ndiagnosis and prompt management of melanomas \nin our patient population. \n\n\n\nDespite advancements in melanoma treatment \nparticularly for targeted therapy, surgical \nmanagement remains the mainstay. Therefore, it \nis imperative to work in multidisciplinary teams to \nprovide optimal management.\n\n\n\nConclusion\nThe majority of our MM patients were elderly \nChinese gentlemen, whose tumours were located \non the lower extremities. ALM is the most common \nMM subtype in the Asian population. These patients \ntypically present late and the delayed diagnosis is \noften associated with poorer outcomes.4 Knowledge \nof the unique features of melanoma in our population \nis key to fashioning targeted interventions.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health, Malaysia for permission to publish this \npaper.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n57MJD 2019 Dec Vol 43\n\n\n\nReferences\n\n\n\n1. Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal \nA. Global cancer statistics 2018: GLOBOCAN estimates \nof incidence and mortality worldwide for 36 cancers in 185 \ncountries. CA Cancer J Clin 2018;68:394-424.\n\n\n\n2. Chang JW, Guo J, Hung CY, Lu S, Shin SJ, Quek R et \nal. Sunrise in melanoma management: Time to focus \non melanoma burden in Asia. Asia Pac J Clin Oncol \n2017;13:423-7.\n\n\n\n3. Cormier JN, Xing Y, Ding M, Lee JE, Mansfield PF, \nGershenwald JE et al. Ethnic Differences Among \nPatients with Cutaneous Melanoma. Arch Intern Med \n2006;166:1907-14.\n\n\n\n4. Higgins S, Nazemi A, Feinstein S, Chow M, Wysong A. \nClinical Presentations of Melanoma in African Americans, \nHispanics, and Asians. Dermatol Surg 2019;45:791-801.\n\n\n\n5. Ch\u2019ng CC, Wong SM, Lee YY, Rokiah I, Pailoor J. A 7-year \nretrospective review of skin cancer at University Malaya \nMedical Centre: a tertiary centre experience. Malaysian J \nDermatol 2012;29:16-22.\n\n\n\n6. Han WH, Yong SS, Tan LL, Toh YF, Chew MF, Pailoor JC \net al. Characteristics of skin cancers among adult patients \nin an urban Malaysian population. Australas J Dermatol \n2019;60:e327-9.\n\n\n\n7. Bradford PT, Goldstein AM, McMaster ML, Tucker MA. \nAcral lentiginous melanoma: incidence and survival \npatterns in the United States, 1986-2005. Arch Dermatol \n2009;145:427-34.\n\n\n\n \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n58 MJD 2019 Dec Vol 43\n\n\n\nCASE REPORT\n\n\n\nBags of Worms         \nQin Jian Low1, MRCP, Seng Wee Cheo1, MRCP, Tzyy Huei Lim1, MRCP, Laili Suriani Ab. Latif2, M.Med (Radiology), \nWen Yee Evelyn Yap3, AdvMDerm \n\n\n\n1Department of Internal Medicine, Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia. \n2Department of Radiology, Hospital Pakar Sultanah Fatimah Muar, Johor, Malaysia.\n3Department of Dermatology, Hospital Pakar Sultanah Fatimah, Muar, Johor, Malaysia.\n\n\n\nSummary\nNeurofibromatosis type 1 is commonly associated with peripheral nerve sheath tumor.  Plexiform \nneurofibroma is an uncommon variant of neurofibromatosis type 1. It is usually diagnosed during \nchildhood and found in approximately 30% of patients with neurofibromatosis type 1 (NF1).1 It \nusually involves multiple nerve fascicles with serpiginous growth and significant vascularity1. There \nis a significant risk of eventual malignant transformation from plexiform neurofibromas.1   \n\n\n\nKey words: Plexiform neurofibromatosis, Neurofibromatosis type 1.\n\n\n\nCorresponding Author\nLow Qin Jian\nDepartment of Internal Medicine, Hospital Sultanah \nNora Ismail, Jalan Korma, Taman Soga, 83000 Batu \nPahat, Johor, Malaysia \nEmail: lowqinjian@moh.gov.my \n\n\n\nCase Report \nA 14-year-old male patient presented with enlarging \nskin swelling over his right hand since birth. He \nwas investigated for vascular malformation initially \nand subsequently referred to the dermatology \nteam. There was a grossly enlarged blackish, cystic \nswelling involving the span of his entire right hand. \nMagnetic resonance imaging of his right hand/\nforearm along with histopathological findings \nconfirmed the diagnosis of plexiform neurofibroma \nwithout malignant transformation. He underwent \ndebulking surgery for cosmetic reason and remains \nasymptomatic during his follow-ups. \n\n\n\nFigure 1. Dorsal aspect of right hand showing \nplexiform neurofibromatosis\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n59MJD 2019 Dec Vol 43\n\n\n\nFigure 2. Palmar aspect of right hand showing \nplexiform neurofibromatosis\n\n\n\nDiscussion \nIn plexiform neurofibromas, multiple nerve \nfascicles are usually involved with serpiginous \ngrowth and vascularity.1 This can lead to chronic \n\n\n\nFigure 3. MRI of the right hand\nA:  Cor T1 WI showing multilobulated conglomerate \n\n\n\nhypo/isointense mass at the palmar aspect of the \nright hand\n\n\n\nB:  Axial T2WI showing target sign at the ventral \naspect of the hand\n\n\n\nC:  Sagittal T2FS images showing corresponding \nhyperintense conglomerate mass at the palmar \naspect of the right hand with target sign\n\n\n\nD:  Post contrast study right hand in T1FS coronal \nview\n\n\n\npain with especially if there is progressive growth \nalong the spinal column that may compress on the \nspinal cord.2 Surgical resection is often considered \nfor debulking of a specific area of a large lesion for \nexample, when it is impinging on a spinal cord or \nairway.3 Some may consider surgical resection for \ncosmetic reasons.3 There is no specific medical \ntreatment for neurofibromas. \n\n\n\nClinical trials with mammalian target of rapamycin \n(mTOR) inhibitor sirolumus and pirfenidone \nhave not shown benefit.4 Imatinib and pegylated \ninterferon has resulted in shrinkage of plexiform \nneurofibromas in a limited number of patients with \nplexiform neurofibromas.4 There has been evidence \nthat selumetinib (oral selective mitogen-activated \nprotein kinase (MAPK) kinase (MEK) inhibitor) \ncan lead to tumor regression in mouse model of \nNF1.5 Malignant transformation of plexiform \nneurofibromas may take place. They can develop \ninto malignant peripheral nerve sheath tumors \n(MPNST).1 This MPNST are treated as malignant \nsoft tissue sarcomas where surgical resection and \nadjunctive chemo-radiation therapy is considered. \n\n\n\nConclusion\nPlexiform neurofibromas are pathognomonic for \nneurofibromatosis type 1. MRI images with typical \nsigns can be helpful in making this diagnosis. \n\n\n\nAcknowledgement\nThe authors would like to thank the Director General \nof Health of Malaysia for the permission to publish \nthis paper.\n\n\n\nReferences\n\n\n\n1. Serletis D, Parkin P, Bouffet E, Shroff M, Drake JM, \nRutka JT. Massive plexiform neurofibromas in childhood: \nnatural history and management issues. J Neurosurg \n2007;106:363.\n\n\n\n2. Gutmann DH, Recent insights into neurofibromatosis type \n1: clear genetic process. Arch Neurol 1998;55:778-80.\n\n\n\n3. Dunn GP, Spiliopoullos K, Plotkin SR, Hornicek FJ, \nHarmon DC, Delaney TF et al. Role of resection of \nmalignant peripheral nerve sheath tumors in patients with \nneurofibromatosis type 1. J Neurosurg 2013;118:142-8. \n\n\n\n4. Robertson KA, Nalepa G, Yang FC, Bowers DC, Ho \nCY, Hutchins GD et al. Imatinib mesylate for plexiform \nneurofibromas in aptients with neurofibromatosis type 1: a \nphase 2 trial. Lancet Oncol 2012;13:1218-24.\n\n\n\n5. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim \nA et al. Activity of Selumetinib in neurofibromatosis Type \n1- Related Plexiform Neurofibromatosis. N Engl J Med \n2016;375:2550-60.\n\n\n\nA\n\n\n\nC\n\n\n\nB\n\n\n\nD\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n60 MJD 2019 Dec Vol 43\n\n\n\nCLINICOPATHOLOGICAL CHALLENGE\n\n\n\nA Case of Persistent Flexural Hyperpigmentation         \nChee Hian Tan, MMed, Hua-Liang Joel Lim, MMed \n\n\n\nNational Skin Centre, Singapore\n\n\n\nCorresponding Author\nChee Hian Tan  \nNational Skin Centre, 1, Mandalay Road, 308205 \nSingapore\nEmail: tan.cheehian@gmail.com\n\n\n\nClinical History\nA 45-year-old Chinese lady presented with a \nyear\u2019s duration of mildly pruritic hyperpigmented \nmacules and patches that were persistent and \nprogressive. Lesions appeared over the groin folds, \nwith subsequent involvement of bilateral inguinal \nfolds, left axilla and left inframammary region (Fig. \n1). There was no preceding rash. She did not take \nany new medications nor was there any contactant \nexposure. A punch biopsy of the skin lesion on the \ninguinal fold was performed (Fig. 2).\n\n\n\nQuestions\n\n\n\nQuestion 1: What is your diagnosis?\na. Acanthosis nigricans \nb. Pigmented contact dermatitis \nc. Lichen planus pigmentosus inversus \nd. Erythema dyschromicum perstans\ne. Post inflammatory hyperpigmentation \n\n\n\nQuestion 2: What is the investigation of choice?\na. Patch test\nb. Serum glucose\nc. Skin biopsy\nd. Skin scraping for fungal elements\ne. Wood\u2019s lamp examination \n\n\n\nFigure 1 (a). Clinical photos showing brownish, \nelliptical and irregular macules and patches in a \nlinear fashion on the patient in (a) left inframammary \nregion.\n\n\n\na\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n61MJD 2019 Dec Vol 43\n\n\n\nAnswers\nQuestion 1: C\nQuestion 2: C\n\n\n\nDiscussion\nLichen planus pigmentosus (LPP) is a rare variant \nof lichen planus (LP), possibly first described \nin 1935 under the name \u201clichens atypiques ou \n\n\n\ninvisible pigmentogenes\u201d in the French literature.1 \nIt is characterized by acquired dark brown to gray \nmacular pigmentation located on sun-exposed areas, \ncommonly found in dark-skinned individuals.1 Pock \net al2 subsequently proposed the term LPP-inversus \nin 2001 when he described 7 patients with striking \npredominance of lesions in an intertriginous \nlocation suggesting that the underlying pathogenic \n\n\n\nFigure 1 (b, c). Clinical photos showing brownish, elliptical and irregular macules and patches in a linear \nfashion on the patient in (b) left axilla, and (c) left inguinal fold. \n\n\n\nFigure 2 (a, b). Skin biopsy specimen using Haematoxylin-eosin (H&E) stain, with (a) 4x, and (b) 20x \nmagnification views. (a) There is epidermal atrophy with effacement of rete ridge pattern and intense lichenoid \ndermatitis. (b) There is basal vacuolar alteration with scattered apoptotic basal keratinocytes. A moderately \ndense lichenoid infiltrate of lymphocytes and eosinophils is seen. Pigment incontinence and melanophages are \nseen admixed within the inflammatory infiltrate.\n\n\n\nb c\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n62 MJD 2019 Dec Vol 43\n\n\n\nprocesses could have been related to koebnerization. \nTo date, there are only about 30 cases reported \ninternationally.3\n\n\n\nIn LPP, there is rapid and intense lichenoid reaction \ngiving rise to an intensive hydropic degeneration of \nbasal keratinocytes without compensatory increased \nproliferation of keratinocytes.1,2 This would explain \nthe relatively asymptomatic nature of skin lesions \nthat are often flat and non-palpable with no evidence \nof erythema. LPP needs to be differentiated from \nLP, especially the variant of atrophic LP. Clinically, \natrophic LP presents as violaceous annular plaques \ncomprising hyperpigmented atrophic centers and \nraised borders, with a predilection for lower limbs. \nOn histology, the atrophic centre shows a thinned \nepidermis, with loss of rete ridges and dermal \nfibrosis.4 \n\n\n\nIn this patient with circumscribed hyperpigmented \nmacules and patches in the flexures, the absence \nof preceding inflammatory dermatosis, trauma \nor contactant use excludes post-inflammatory \nhyperpigmentation and pigmented contact \ndermatitis. Other differential diagnoses to consider \nwould then include acanthosis nigricans (AN), and \nerythema dyschromicum perstans (EDP). \n\n\n\nAN can be differentiated from LPP clinically \nand histologically. AN is characterized by \nhyperpigmented and thickened plaques with a \nvelvety texture and epidermal change. Histologically, \nthere is no dermal inflammation in AN with \northokeratosis, papillomatosis and increased basal \npigmentation. \n\n\n\nEDP and LPP were thought to be the same condition \nin the past. However, Vega et al5 described clinical \ndifferences between the two conditions, such as \n(i) gray-blue hyperpigmented macules in EDP \n(compared with black-brown macules in LPP); (ii) \nelevated erythematous border in early EDP lesions; \n(iii) absence of pruritus in EDP. Histologically, \nSanchez et al6 identified a deeper extension of \ndermal infiltration and pigmentation in EDP. It is the \npresence of melanophages in deeper layers of the \ndermis that gives the bluish gray colour to the lesions \nin EDP (compared with LPP where melanophages \nare found in the superficial layer).\n\n\n\nThe clinical course of LPP-inversus can vary. \nThere have been reports of cases in which lesions \ndisappear spontaneously over weeks to months.1,3 \nManagement of LPP-inversus includes avoidance \n\n\n\nof exacerbating factors such as tight clothing,1,3 and \ntopical treatment1,3 with medium to high potency \ncorticosteroids or calcineurin inhibitors.\n\n\n\nConflict of Interest Declaration\nThe authors have no conflict of interest to declare.\n\n\n\nAcknowledgement\nNil\n\n\n\nReferences \n\n\n\n1. Robles-Mendez JC, Rizo-Frias P, Herz-Ruelas ME, Pandya \nAG, Ocampo Candiani J. Lichen planus pigmentosus \nand its variants: review and update. Int J Dermatol \n2018;57:505-14.\n\n\n\n2. Pock L, Jelinkova L, Drlik L, Abrhamova S, Vojtechovska \nS, Sezemska D et al. Lichen planus pigmentosus-inversus. \nJ Eur Acad Dermatol Venerol 2001;15:452-4.\n\n\n\n3. Chen S, Sun W, Zhou G, Chen S, Lu X. Lichen planus \npigmentosus-inversus: report of three Chinese cases and \nreview of published work. J Dermatol 2015;42:77-80.\n\n\n\n4. Kim BS, Seo SH, Jang BS, Kim MB, Oh CK, Kwon YW \net al. A case of annular atrophic lichen planus. J Eur Acad \nDermatol Venereol 2007;21:989-90.\n\n\n\n5. Vega ME, Waxtein L. Arenas R, Hojyo T, Dominguez-\nSoto L. Ashy dermatosis and lichen planus pigmentosus: \na clinicopathologic study of 31 cases. Int J Dermatol \n1992;31:90-4.\n\n\n\n6. Sanchez NP, Pathak MA, Sato SS, Sanchez JL, Mihm \nMC, Fitzpatrick TB. Circumscribed dermal melaninoses: \nclassification, light, histochemical, and electron \nmicroscopic studies on three patients with the erythema \ndyschromicum perstans type. Int J Dermatol 1982;21:25-\n31.   \n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n63MJD 2019 Dec Vol 43\n\n\n\nRETRACTION NOTE\nThis retracts the article \u201cPsychological Impact, Self-perception and the Contributing Factors in \nPatients with Androgenetic Alopecia\u201d in Malaysian Journal of Dermatology 2018, volume 41 on \npage 39-46.\n\n\n\nThis article has been retracted due to violation of Malaysian Journal of Dermatology\u2019s publication \nprinciple as part of the content has been duplicated and published elsewhere. All authors Kim Fong Ng, \nNorazirah Mohd Nor, Mazlin Baseri, Adawiyah Jamil, Shamsul Azhar Shah apologize to the Editors and \nreaders for this unintentional mistake done.\n\n\n\n\n\n\n\n\nMalaysian Journal of Dermatology\n\n\n\n64 MJD 2019 Dec Vol 43\n\n\n\nACKNOWLEDGEMENT\nDec Issue 2019\n\n\n\nThe Editorial Board of The Malaysian Journal of Dermatology gratefully acknowledge the following\nindividuals for reviewing the papers submitted for publication:\n\n\n\n1. Assoc Professor Dr Adawiyah Jamil\n2. Dr Agnes Heng Yoke Hui\n3. Dr Ch\u2019ng Chin Chwen\n4. Dr Chang Choong Chor\n5. Dr Chong Yew Thong\n6. Dr Dawn Ambrose\n7. Assoc Professor Dr Felix Yap Boon Bin\n8. Dr Heah Sheau Szu\n9. Dr Henry Foong Boon Bee\n10. Dr Khor Yek Huan\n11. Dr Kwan Zhenli\n12. Dr Lee Bang Rom\n13. Dr Leong Kin Fon\n14. Dr Ng Su Yuen\n15. Dr Ng Ting Guan\n16. Dato\u2019 Dr Noor Zalmy Azizan\n17. Associate Professor Dr Norashikin Bt Shamsudin\n18. Dr Oh Hoey Hoey\n19. Dr Rajalingam Ramalingam\n20. Dr Sabeera Begum\n21. Dr Tang Jyh Jong\n22. Dr Wee Ai Lian\n\n\n\n\n\n"