bluuebunny/crossref_metadata_2025_split huggingface dataset:
BG01 Confirming small nuclear ribonucleoprotein polypeptide E as a cause of nonsyndromic hypotrichosis
Authors: Poudel Pratima , Haider Zahra , Ryan Gavin , Ogboli Malobi , Moss Celia 
Published: June 2023

Abstract
Hereditary nonsyndromic hypotrichosis comprises at least 15 genetically distinct but phenotypically overlapping disorders. Affected individuals generally have hair at birth, which sheds during infancy or childhood. Severity ranges from partial alopecia to complete loss of scalp and body hair, with phenotypic variability between and within families. Genetic testing is essential for accurate diagnosis and counselling. We describe a case where several factors contributed to a delay in genetic diagnosis. A female child of nonconsanguineous White parents was born at term with normal hair that started to shed at 2 weeks of age. By 6 weeks of age, there was a complete absence of scalp, eyelash and eyebrow hair. There was no relevant family history apart from atopy. On examination at 3.3 years of age, she had total alopecia apart from some hairs in the external auditory canals. Nails, teeth and sweating were normal. She appeared developmentally normal and healthy apart from mild eczema with persistent erythema on both cheeks. The differential diagnosis included autoimmune alopecia and genetic nonsyndromic hypotrichosis. She was recruited to the 100 000 Genomes Project, but primary analysis did not identify any causative variants. Reanalysis using a limited gene-agnostic approach identified heterozygosity for the c.1A&gt;G; p.(Met1?) variant in small nuclear ribonucleoprotein polypeptide E (SNRPE) that was not present in parents. This variant is not present in the gnomAD population database and is predicted to alter the initiation codon of SNRPE. It has been reported de novo in a British girl with sparse scalp hair and eyelashes and absent eyebrows, and in eight affected members of a Spanish family whose phenotypes ranged from sparse eyebrows and eyelashes to complete alopecia (Pasternack SM, Refke M, Paknia E et al. Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal dominant hypertrichosis simplex. Am J Hum Genet 2013; 92:81–7). This condition has been designated hypotrichosis type 11. SNRPE encodes a core protein of U small nuclear ribonucleoproteins, which are essential to the removal of introns from pre-mRNA and thus critical for the post-transcriptional modification of RNA. In our case, review of the primary analysis showed that the incorrect gene panel was applied (‘familial cicatricial alopecia’ instead of ‘nonsyndromic hypotrichosis’) and that SNRPE was listed as ‘amber’ for hypotrichosis, meaning ‘moderate evidence for this gene–disease association and should not yet be used for genome interpretation’. Genomics England has now incorporated nonsyndromic hypotrichosis into the ‘ectodermal dysplasia’ panel, with SNRPE now listed as ‘green’ for hypotrichosis 11, meaning a ‘high level of evidence for this gene–disease association’. This case emphasizes the importance of revisiting negative results as knowledge evolves.
BG03 The first case of Haim–Munk syndrome in the UK
Authors: McCarthy Rebecca , Gnanappiragasam Dushyanth , Scorer Matthew , Taylor Marisa , O’Toole Edel 
Published: June 2023

Abstract
Haim–Munk syndrome (HMS) and Papillon–Lefevre syndrome (PLS) are rare, autosomal recessive palmoplantar keratodermas (PPKs) characterized by PPK and periodontal inflammation. They are phenotypic variants of clinically related syndromes caused by homozygous or compound heterozygous mutations in cathepsin C (CTSC) on chromosome 11q14. Specific features of HMS include pes planus, radiographic deformity of the fingers, arachnodactyly, acro-osteolysis and onychogryphosis. In contrast, PLS can be associated with neurological disorders, calcification of the dura mater, hyperhidrosis and susceptibility to infection. Fewer than 100 cases of HMS have been reported, the majority of which have come from the Cochin region of India. We describe the case of a phenotypic presentation of HMS, with a novel mutation in CTSC. To our knowledge, this is the first case of HMS in the UK. The patient was a 14-year-old male, born in Gujarat, India, to consanguineous, healthy parents. He migrated to the UK in his early teens and was referred for a specialist opinion of symptoms of ichthyosis and PPK, which had been present from the age of 8 years. He was treated with acitretin in India, before moving to the UK. Physical examination revealed transgradient PPK, generalized mild ichthyosis, periodontal inflammation, dystrophic fingernails and toenails, and marked deformities of the fingers, including contractures, subluxation and swan-neck deformities, with a degree of arthritis. Bilateral hand radiographs showed slender, long bones, with extension/flexion deformities at several sites but no erosions. Laboratory investigations revealed low iron, folate and vitamin D levels. Based on the clinical and radiographic findings, a diagnosis of HMS was made. The patient was continued on acitretin, soap substitutes, regular emollients, iron, folate and vitamin D supplementation and referred to occupational therapy for hand splinting. Next-generation sequencing identified an autosomal recessive, homozygous c.901G&gt;A (p.Gly301Ser) variant of CTSC. A total of 75 mutations, in a diverse range of ethnic groups, have been reported in CTSC; the majority (97%) is reported in PLS. The variant seen in our patient has previously been reported in PLS; however, to our knowledge, it has not been associated with the HMS phenotype. This case details the first homozygous c.901G&gt;A CTSC variant in a patient with HMS. To date, the genotype–phenotype correlations in PLS and HMS have not been established, largely due to the rarity of these conditions. This report adds to existing literature and expands on the understanding of clinical findings associated with CTSC mutations.
BG11 Palmoplantar keratoderma with mutations in filaggrin and desmoglein-1 genes
Authors: McCarthy Rebecca L , O’Toole Edel 
Published: June 2023

Abstract
Hereditary palmoplantar keratoderma (PPK) has many forms, and genetic testing can help distinguish diagnoses. This case demonstrates a presentation of PPK with an altered phenotype caused by a mutation in FLG. The patient was a 23-year-old woman referred with PPK since the age of 6 years. She reported dry skin on the back of her hands from infancy and no other dermatological conditions. She denied plantar pain except when there were fissures in the callus. There was no relevant past medical history, but a significant family history of individuals with PPK and curly hair, and sudden infant death (SID) in two siblings. Physical examination revealed focal plantar keratoderma bilaterally, curly hair, mild tongue leukokeratosis and generally dry skin on both legs. She had palmar hyperlinearity, small calluses on the palms and normal nails. She declined a skin biopsy. The patient was referred to cardiology to rule out cardiomyopathy associated with a desmoplakin variant. She had an unremarkable transthoracic echocardiography and cardiac magnetic resonance imaging. Twelve-lead electrocardiography showed sinus rhythm with biphasic T-wave in V2 and inverted V1. Clinically arrhythmogenic right ventricular cardiomyopathy (ARVC) was ruled out; however, given her significant family history of SID and PPK, panel testing for genes associated with ARVC was performed, which revealed a heterozygous variant of uncertain significance in MYBPC3 (p.Val639lle). This variant did not explain the patient’s PPK; therefore, a PPK panel was performed. Next-generation sequencing identified a heterozygous DSG1 [c430A&gt;T p.(Arg.144*)] pathogenic variant and a heterozygous FLG [c2282_2285del p.(Ser761Cysfs*36)] pathogenic variant. The patient’s PPK was more severe on the plantar surface of the feet than one might expect with a DSG1 variant. This case demonstrates the interaction between two genetic variants known to be associated with skin conditions. Ichthyosis vulgaris is caused by FLG variants. Patients with heterozygous FLG variants are less severely affected and have reduced penetrance compared to homozygotes. Meanwhile, heterozygous pathogenic variants in DSG1 are associated with keratosis palmoplantaris striata I (MIM148700). We hypothesize that the coexistence of FLG and DSG1 variants may contribute to a more extensive keratoderma phenotype than usually seen with DSG1 variants. This case contributes to our understanding of PPK, demonstrates the value of genetic testing in dermatological conditions and describes a unique phenotype in the presence of multiple genetic variants. Further research is required to better understand the interaction between variants in PPK pathogenesis.
BG13 A rare case of Muir–Torre syndrome
Authors: Ashcroft Samuel , De Mozzi Paola 
Published: June 2023

Abstract
Muir–Torre syndrome is a rare variant of hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. It is caused by a defect in mismatch repair genes, which are most commonly inherited in an autosomal dominant fashion. It is characterized clinically by sebaceous neoplasms of the skin associated with at least one visceral malignancy, with colon cancer being the most frequent. The most common genetic defects responsible are in MLH1, MSH2 and MSH6, which results in an increased frequency of unrepaired base mismatching during DNA replication and subsequent microsatellite instability, predisposing to cancer. We present a case of a 59-year-old man with a history of colon cancer who was referred with a rapidly growing irregular nodule on his lower back for the past 2 months, concerning for an amelanocytic melanoma. An excision biopsy was arranged, and subsequent histology demonstrated a sebaceoma. Immunohistochemistry for mismatch repair genes showed loss of expression for MSH2 and MSH6. Upon further questioning, it was found that he had a strong family history of colon cancer (father, brother and two sisters), and he developed colon cancer at 36 years of age, which was treated with a pancolectomy. Genetic testing revealed a mutation in MSH2. Given this history, annual follow-up was arranged for skin surveillance.
BH04 Review of a dermatology nurse-led hair service
Authors: Mowbray Megan , Christie Emma 
Published: June 2023

Abstract
In 2017, our department was faced with a significant delay in new patient waiting times for the tertiary hair and nails clinic. A nurse-led service was developed to relieve this pressure. Within 18 months, the waiting list was much more manageable at less than 12 weeks, an improvement that has been maintained. The nurse-led service was designed predominantly to see and treat patients with alopecia areata. We present details of the nurse training and clinic setup. Three years after the setup of the nurse-led hair clinic, we reviewed this service. The aims of this review were to assess the capacity of the nurse-led hair clinic, the clinical outcome and the psychological impact. A review of all patients seen between November 2021 and October 2022 is presented. The total number of patients seen was 130. The majority had focal alopecia areata (90%). Clinical outcome measures were recorded using the Severity of Alopecia Tool score and Alopecia Areata Investigator Global Assessment. Psychological outcome measures were assessed using the Dermatology Life Quality Index and a patient questionnaire. The majority (72%) were treated with intralesional triamcinolone; 5% received a wig. The aim is to treat and discharge, while enabling easy access back into the service. It was hoped that this pathway would alleviate patient anxiety on discharge. All patients reported that they found it easy/very easy to be referred correctly by their general practitioner. The majority of returning patients had been given a clear explanation of the rereferral process on discharge. All reported an excellent or good service. More than 90% answered positively when asked whether the nurse listened, addressed fears/concerns and provided adequate verbal and written information. Sixty-two per cent remember being signposted to a relevant support group and all were satisfied with their treatment. We will present written information provided by the patients on what they found most useful about the clinic and how the clinic could be improved. We show the success of a nurse-led service that has addressed capacity issues and clinical management and provides emotional support. The detail presented will be sufficient to guide other departments on training and clinic setup when developing such a service.
BH07 The socioeconomic burden of alopecia areata
Authors: Montgomery Kerry , Zucchelli Fabio , Clayton Julie , Messenger Andrew , Harries Matthew 
Published: June 2023

Abstract
It is widely acknowledged that alopecia areata (AA) can have a significant impact on psychosocial wellbeing and daily functioning. Individuals with AA often seek treatments or products to promote hair regrowth or use strategies to conceal their hair loss, which results in a financial cost to the individual. The current study aimed to examine the socioeconomic burden of AA, to understand the wider impact of the condition. A total of 829 UK-based participants completed an online survey. Demographic and condition-specific data were collected, alongside spending on AA-related products and services over the preceding year, and AA-associated work absenteeism and presenteeism. Participants predominantly identified as female (85.9%) and White (92.7%), with a mean age of 42.7 years and median duration of AA of 10.94 years. The median expense on AA-related products and services over the preceding year was £840. Wigs incurred the greatest cost to individuals (median £700). Although accessed by approximately 10% of participants, private dermatology and mental health services also incurred significant costs, when used. Over half of the sample also reported that the products and services they used made their quality of life a little or much better. Using hierarchical regression analysis, sex and AA symptoms uniquely predicted higher financial burden, with females and those with more severe AA spending a greater proportion of their disposable income on AA-related products and services. Lower disposable income also predicted greater financial burden from spending. Regarding work absenteeism, 21% of participants reported being signed off work due to AA since their diagnosis, and over the preceding 7 days, 10.5% of those in employment (n = 525) reported missing &gt; 1 h of work due to AA. Of 154 participants claiming work-related benefits, 33 said their reason for claiming was connected to their AA. The presenteeism findings suggest, on average, a minimal effect of AA on participants’ work productivity in the preceding 7 days, with those more recently diagnosed reporting lower productivity. The findings suggest that products/services to manage the aesthetic consequences of hair loss from AA are costly yet broadly valued by individuals. It is concerning that those with lower disposable income spent proportionately more on AA products and services, implying these individuals consider this spending as essential. The other risk factors identified in the findings also require consideration by health providers, commissioners and policymakers when designing services to support the wellbeing of people living with AA.
Funding: this study was funded by Pfizer Inc.
BH09 Patient experience of off-label Janus kinase inhibitor use for alopecia areata in a cohort of 34 patients from a single UK practitioner: exploring changing trends in healthcare provision and access to drug treatments
Authors: Ryan Sarah , Ascott Anna , Farrant Paul 
Published: June 2023

Abstract
We present data from a UK cohort of patients with alopecia areata (AA) who have sought Janus kinase inhibitor (JAKi) treatments prior to National Health Service funding. We have explored referral methods, access to consultations, and shared care in monitoring and acquisition of medication both from the UK and abroad. We have looked at the drugs and dosage, adjuvant therapies and response to treatment, and report data on side-effects and reasons for changing drugs or stopping treatment. Thirty-four patients (25 adults and nine children) self-referred to a UK-based private hair clinic for JAKi treatment over a period of 36 months. The median age of patients was 40 years (interquartile range 18–50). The patients sought treatment from a wide geographical area in the UK, with one patient living 400 miles from the clinic. Seventeen (50%) and 14 (41%) patients were prescribed baricitinib and tofacitanib, respectively, with three (9%) patients prescribed both. Nineteen (56%) patients had severe alopecia with &gt; 95% hair loss. Social media, in particular a closed Facebook group, was an important source of referral and information on sourcing medication from abroad. Nine per cent of consultations were virtual (telephone/video). The cost of treatment varied from £100 per month to £1400, with a large difference between UK-sourced medication and that from abroad. Eight (24%) patients showed no scalp regrowth response to first-line treatment, despite dose escalation, with one subsequently experiencing total hair regrowth on swapping to a different JAKi class. One patient had to stop treatment after developing breast cancer. JAKi are an exciting and emerging treatment for AA that are yet to be widely prescribed by UK practitioners. However, the response to JAKi is not universal. Owing to the cost of private prescription, patients are choosing to source JAKi from abroad. Our study presents data on how the alopecia community has helped inform patients about treatment access.
BI01 Disseminated Nannizziopsis fungal infection in a kidney transplant recipient: iguanas, immunosuppression or international travel?
Authors: Cernova Jeva , Haddad Salma , Goldsmith Portia , Mabayoje Diana , Lambourne Jonathan , Melzer Mark , Magdi Yaqoob , Byrne Conor , Harwood Catherine 
Published: June 2023

Abstract
Transplant waiting list demographics are changing profoundly in some parts of the UK, partly due to trends in global migration. This has significant implications for the spectrum of post-transplant skin malignancies and skin infections presenting to dermatologists. We present a kidney transplant recipient born in Nigeria who developed disseminated infection with Nannizziopsis spp., an emerging pathogenic fungus in humans and reptiles. A 64-year-old man from Nigeria who received a kidney transplant 10 months earlier was referred to our 2-week-wait skin cancer clinic with a 4-cm tender, ulcerated nodule on his left thigh that had been present for 2 months. He was being investigated for possible pulmonary Aspergillus infection and also had a fluctuant subcutaneous mass over the right tibia with suspected osteomyelitis. On examination, he had a similar plaque on his right hand, fluctuant subcutaneous nodules of his left flank and left upper arm, a 20-cm fluctuant swelling over his right tibia and a 2-cm plaque of his hard palate. Skin biopsy from the left flank and thigh showed suppurative granulomatous inflammation and fungal hyphae in the dermis and macrophages with septation and 45° branching. β-D-Glucan was positive and molecular identification revealed Nannizziopsis spp. Magnetic resonance imaging of the head did not show evidence of central nervous system infection. He was treated with intravenous amphotericin B for 2 months and subsequent oral posaconazole with resolution of skin and lung infection. Nannizziopsis is a genus of fungi that usually infects reptiles such as iguanas, geckos and chameleons, snakes, turtles and crocodiles. It causes cutaneous and musculoskeletal granulomatous infections which can be rapidly fatal. Fewer than 20 human cases have been reported, mostly related to travel to West Africa. Almost all infections are in immunocompromised individuals and species of Nannizziopsis reported to affect humans are generally different from those identified in animals. Our patient denied contact with reptiles, but he had travelled to Nigeria before his transplant where he probably acquired a latent infection that reactivated post-transplant. This case illustrates the importance of biopsy and culture of atypical skin lesions, particularly in immunocompromised patients. With the rising global migration and travel, such infections are likely to be seen more frequently in the UK, and both residential and travel history may be relevant. Finally, zoonotic infections are increasing globally as interspecies barriers break down. Although there is not enough evidence to caution against ownership of exotic pets in immunocompromised individuals, animal sources of rare infections should always be considered in this patient group.
BI03 (P76) Management of aciclovir-resistant mucocutaneous herpes simplex virus infection: a systematic review
Authors: Castillo Valladares Herbert , Rudd Nora , Leslie Kieron 
Published: June 2023

Abstract
Aciclovir resistance results in immunocompromised hosts due to long-term antiviral therapy and ongoing viral replication. Aciclovir resistance in herpes simplex virus (HSV) poses a major concern, as this can lead to chronic and recalcitrant infection that significantly impacts on quality of life. While different treatment options exist, there are currently no standardized clinical treatment guidelines for mucocutaneous aciclovir-resistant (ACV-R) HSV infection. This systematic review seeks to identify safe and effective treatments for mucocutaneous ACV-R HSV infection. For this systematic review, PubMed/MEDLINE and Embase were searched in September 2022 for all articles published between 1 January 1980 and 1 September 2022. Studies were included if they described the use of medications for the treatment of mucocutaneous ACV-R HSV infection. From the initial search that yielded 1066 studies, 86 met the inclusion criteria and were selected. Of the 86 studies, six were clinical trials and 80 were case reports/series. A total of 318 patients were included in our review. Foscarnet [intravenous (IV) and topical] was studied in five clinical trials and 25 case reports/series, leading to complete response in most patients, with adverse effects including renal toxicity and electrolyte abnormalities. Vidarabine (IV) was found to be inferior to foscarnet in a clinical trial and reported in two case reports. Common side-effects included nausea, anaemia and renal impairment. Trifluridine (topical) was studied in a clinical trial and a case report, showing complete response in some patients. Cidofovir (IV, topical, intralesional) was studied in 21 case reports/series, showing complete response in most patients, with renal impairment as the most common adverse effect. Imiquimod (topical) was studied in eight case reports/series, showing complete response and no side-effects. Pritelivir (oral) was reported in two case reports/series, showing complete response and no side-effects. Combination treatment was reported in 10 case reports/series with variable clinical response. Our review also identified reports of less widely used treatments. These include artesunate, zidovudine, varicella-zoster virus vaccine, leflunomide and surgical excision, which achieved variable response rates but have not been widely studied. While foscarnet and cidofovir have the most robust evidence, IV administration of these agents is associated with significant side-effects and may be limiting. Intralesional and topical formulations of cidofovir, trifluridine and imiquimod are alternative options appropriate for outpatient management. Pritelivir is a novel and promising treatment of mucocutaneous ACV-R HSV infection.